cardiovascular-agents and Hypertrophy--Left-Ventricular

Heart failure (HF) is one of the major challenges in the management of diabetes patients. Among subjects with diabetes, up to 20% could have HF. Conversely, diabetes prevalence in HF patients varies greatly from more than 10% up to 50%. When it is present, the risk of mortality and rehospitalization increases substantially. In addition, current evidence points to an increased risk of atrial fibrillation and sudden cardiac death in patients with diabetes. The inter-relation between diabetes cardiomyopathy, left ventricular hypertrophy, coronary artery disease and renal dysfunction indicates complex and intricate pathways. Despite the great value of clinical assessment and echocardiography, there is insufficient data to suggest systematic screening for HF in asymptomatic patients with diabetes. There is little evidence to indicate that improved glycaemic control improves HF outcome in this population. In the case of established HF, the general guidelines apply in diabetes patients. However, recent advances concerning glucose-lowering treatment in patients with cardiovascular disease suggest that the choice of glucose-lowering agent is of crucial interest and should be based on the patient's phenotype. New drug classes, such as SGLT2 inhibitors, seem to be of particular benefit in these patients. In the future, new personalized strategies should aim at not only good control of the glycaemic level but also the reduction and possibly the prevention of HF onset.

Topics: Atrial Fibrillation; Cardiovascular Agents; Death, Sudden, Cardiac; Diabetes Complications; Diabetic Cardiomyopathies; Heart Failure; Humans; Hypertrophy, Left Ventricular; Hypoglycemic Agents; Prevalence; Risk; Sodium-Glucose Transporter 2 Inhibitors

A series of hemodynamic and pathological responses occur in chronic aortic regurgitation, which eventually result in myocardial fibrosis and irreversible left ventricular dysfunction. According to guidelines, valvular surgery is recommended with the development of symptoms, left ventricular systolic dysfunction, or left ventricular dilatation. The optimal timing of surgical intervention has recently been questioned with documentation of irreversible myocardial damage resulting in incomplete left ventricular recovery and adverse clinical outcomes after surgery. Recognizing the shortcomings of the guidelines, we performed a comprehensive review on the novel diagnostic methods that have been shown to improve the detection of subclinical ventricular dysfunction in chronic aortic regurgitation and to improve prediction of outcomes.

Topics: Aged; Aortic Valve Insufficiency; Asymptomatic Diseases; Cardiovascular Agents; Chronic Disease; Disease Progression; Early Diagnosis; Female; Fibrosis; Heart Valve Prosthesis Implantation; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Myocardium; Predictive Value of Tests; Recovery of Function; Time Factors; Time-to-Treatment; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

Heart failure (HF) is a systemic disease that can be divided into HF with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). HFpEF accounts for over 50% of all HF patients and is typically associated with high prevalence of several comorbidities, including hypertension, diabetes mellitus, pulmonary hypertension, obesity, and atrial fibrillation. Myocardial remodeling occurs both in HFrEF and HFpEF and it involves changes in cardiac structure, myocardial composition, and myocyte deformation and multiple biochemical and molecular alterations that impact heart function and its reserve capacity. Understanding the features of myocardial remodeling has become a major objective for limiting or reversing its progression, the latter known as reverse remodeling (RR). Research on HFrEF RR process is broader and has delivered effective therapeutic strategies, which have been employed for some decades. However, the RR process in HFpEF is less clear partly due to the lack of information on HFpEF pathophysiology and to the long list of failed standard HF therapeutics strategies in these patient's outcomes. Nevertheless, new proteins, protein-protein interactions, and signaling pathways are being explored as potential new targets for HFpEF remodeling and RR. Here, we review recent translational and clinical research in HFpEF myocardial remodeling to provide an overview on the most important features of RR, comparing HFpEF with HFrEF conditions.

Topics: Animals; Cardiovascular Agents; Drug Design; Heart Failure; Humans; Hypertrophy, Left Ventricular; Molecular Targeted Therapy; Myocardium; Recovery of Function; Signal Transduction; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

Interactions between the heart and the kidneys are increasingly acknowledged among both cardiologists and nephrologists. The term cardiorenal syndrome now applies to the bidirectional nature of how disease in one organ system affects the function of the other organ system. Cardiovascular disease is a major threat to patients with chronic kidney disease, while renal dysfunction is prevalent in patients with cardiac disease and is a significant predictor of prognosis in cardiac patients. Still, renal patients with cardiac disease have largely been excluded from the clinical trials that have been the basis of modern cardiologic treatment. In this review, the current understanding of the pathophysiological mechanisms involved in the cardiorenal syndrome and potential therapeutic implications will be summarized from a nephrologist's point of view. Probably, fragile cardiorenal patients will benefit from an enhanced collaboration between cardiologists and nephrologists to secure the best treatment given under safe conditions.

Topics: Acute Disease; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Arteriosclerosis; Biomarkers; Cardio-Renal Syndrome; Cardiovascular Agents; Chronic Disease; Diuretics; Hemodynamics; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertrophy, Left Ventricular; Mineralocorticoid Receptor Antagonists; Risk Factors

Left ventricular hypertrophy (LVH) is a cardiovascular complication highly prevalent in patients with chronic kidney disease (CKD) and end-stage renal disease. LVH in CKD patients has generally a negative prognostic value, because it represents an independent risk factor for the development of arrhythmias, sudden death, heart failure and ischemic heart disease. LVH in CKD patients is secondary to both pressure and volume overload. Pressure overload is secondary to preexisting hypertension, but also to a loss of elasticity of the vessels and to vascular calcifications, leading to augmented pulse pressure. Anemia and the retention of sodium and water secondary to decreased renal function are responsible for volume overload, determining a hyperdynamic state. In particular, the correction of anemia with erythropoietin in CKD patients is advantageous, since it determines LVH reduction. Other risk factors for LVH in CKD patients are documented: some are specific to CKD, as mineral metabolism disorders (hypocalcemia, hyperphosphatemia, low serum vitamin D levels and secondary hyperparathyroidism), others are non-traditional, such as increased asymmetric dimethylarginine, oxidative stress, hyperhomocysteinemia and endothelial dysfunction that, in turn, accelerates the process of atherogenesis, triggers the inflammation and pro-thrombotic state of the glomerular and the vascular endothelium and aggravates the process of both CKD and LVH.

Topics: Anemia; Cardiovascular Agents; Cardiovascular System; Chronic Disease; Early Diagnosis; Early Medical Intervention; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney; Kidney Diseases; Kidney Function Tests; Metabolism; Risk Factors; Severity of Illness Index; Vascular Resistance; Water-Electrolyte Imbalance

Heart failure with preserved ejection fraction (HF-PEF) is the clinical syndrome of heart failure associated with normal or near-normal systolic function. Because inhibition of the adrenergic and renin-angiotensin-aldosterone systems has been so effective in the treatment of systolic heart failure, these same therapies have been the subject of recent clinical trials of HF-PEF. In this review, we examine the current evidence about treatment of HF-PEF, with particular emphasis on reviewing the literature for large-scale randomized clinical studies. The lack of significant benefit with neurohormonal antagonism in HF-PEF suggests that this condition might not involve neurohormonal activation as a critical pathophysiologic mechanism. Perhaps heart failure as we traditionally think of it is the wrong paradigm to pursue as we try to understand this condition of volume overload known as HF-PEF.

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Biphenyl Compounds; Calcium Channel Blockers; Cardiovascular Agents; Digitalis Glycosides; Exercise; Exercise Tolerance; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertrophy, Left Ventricular; Irbesartan; Mineralocorticoid Receptor Antagonists; Randomized Controlled Trials as Topic; Renin-Angiotensin System; Stroke Volume; Tetrazoles; Ventricular Dysfunction, Left; Verapamil

We focus on the molecular and cellular basis of the improvement in myocardial energetics, which might represent an attractive therapeutic option in some forms of acute and chronic heart disease.. Myocardial dysfunction, whether related to left ventricular hypertrophy, heart failure or myocardial ischaemia, is frequently associated with impairment of myocardial energy balance. It is now apparent that this energetic impairment plays a pivotal role, not only in the evolution and outcomes of these disorders but also frequently in their pathogenesis. Despite the fact that energetic impairment may arise for many complex reasons, and the difficulty both in assessing the impairment in vivo and in determining its precise mechanism(s), a number of drugs have become available for treatment of ischaemia and heart failure, as well as potentially for limitation of pathological left ventricular hypertrophy, which act primarily by altering myocardial metabolism so as to improve energetic status. Recent studies with perhexiline and trimetazidine, agents which induce a 'metabolic shift' from long-chain fatty acid to glucose utilization, have demonstrated the utility of this therapeutic principle.. There is ongoing need for more complete mechanistic understanding of the 'metabolic agents', as well as for the large-scale clinical trials of their impact on health outcomes.

Topics: Acetanilides; Amiodarone; Cardiovascular Agents; Heart Failure; Humans; Hypertrophy, Left Ventricular; Myocardial Ischemia; Myocardial Perfusion Imaging; Myocardial Reperfusion; Myocardium; Perhexiline; Piperazines; Ranolazine; Trimetazidine; Vasodilator Agents

LA-419, currently being developed by Lacer SA, is a thiol-containing analog of isosorbide mononitrate that is undergoing assessment in clinical trials for the treatment of chronic ischemic cardiovascular disorders. The compound was originally designed to have a reduced tendency toward tolerance sensitivity - a major limitation of established organic nitrate compounds. The rationale behind the drug design was to include an antioxidant moiety in the drug structure to combat the contribution of oxidative stress in tolerance induction. The compound is at an early stage of development, but has already provided some surprising data. First, LA-419 does not appear to require the nitroxy ester moiety for activity and its actions might not be mediated only by nitric oxide release. Second, unlike conventional nitrates, LA-419 is active in platelets, suggesting a potential role as an antithrombotic agent. Third, LA-419 has a profound impact on left ventricular hypertrophy, making the drug a plausible candidate for several additional potential therapeutic opportunities. In addition, LA-419 has demonstrated potential in the treatment of glaucoma and intestinal disorders. At the time of publication, LA-419 was in phase II clinical trials in patients with chronic ischemic cardiovascular disorders.

Topics: Animals; Antioxidants; Cardiovascular Agents; Cardiovascular Diseases; Disease Models, Animal; Drug Tolerance; Fibrinolytic Agents; Humans; Hypertrophy, Left Ventricular; Isosorbide Dinitrate; Myocardial Ischemia; Nitric Oxide Donors; Patents as Topic; Structure-Activity Relationship; Treatment Outcome

The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study is the first, and, so far, the only endpoint trial in patients with hypertension and left ventricular hypertrophy (LVH) to show a divergent therapeutic outcome of one treatment modality over another with equivalent blood pressure control. The purpose of this article is to review post hoc sub-analyses of LIFE study data and other clinical studies that offer some insight into possible treatment-related differences contributing to the superior stroke outcome of losartan versus atenolol beyond blood pressure reduction.. Relevant randomized clinical trials and review articles were identified through a MEDLINE search of English-language articles published between 1990 and 2006 using the search terms losartan, atenolol, LIFE, hypertension, and LVH. Articles describing major clinical studies, new data, or mechanisms pertinent to the LIFE study were selected for review.. Differences in blood pressure or in the distribution of add-on medications were not evident between study groups in the LIFE study. Thus, the observed outcomes benefits favoring losartan may involve other possible mechanisms, including differential effects of losartan and atenolol on LVH regression, left atrial diameter, atrial fibrillation, brain natriuretic peptide, vascular structure, thrombus formation/platelet aggregation, serum uric acid, albuminuria, new-onset diabetes, and lipid metabolism. Alternative explanations for the LIFE study findings have also been put forward, including the choice of atenolol as an appropriate active comparator and differential effects between treatment groups on central pulse pressure. Additional clinical trials are needed to determine if the beneficial effects of losartan seen in LIFE are shared by other inhibitors of the renin-angiotensin system.. Sub-analyses of the LIFE study data suggest that losartan's stroke benefit may arise from a mosaic of mechanisms rather than a single action. Further studies are expected to continue to delineate the mechanisms of differential responses to treatments in LIFE.

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Atenolol; Atrial Fibrillation; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Cardiovascular Agents; Cohort Studies; Drug Utilization; Endothelium, Vascular; Follow-Up Studies; Heart Atria; Humans; Hypertension; Hypertrophy, Left Ventricular; Losartan; Models, Biological; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Platelet Aggregation; Platelet Aggregation Inhibitors; Protein Precursors; Randomized Controlled Trials as Topic; Research Design; Risk; Risk Factors; Stroke; Thrombosis; Treatment Outcome

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers; Cardiovascular Agents; Clinical Trials as Topic; Coronary Disease; Defibrillators, Implantable; Diabetes Complications; Disease Progression; Female; Follow-Up Studies; Health Surveys; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Mass Screening; Middle Aged; Multicenter Studies as Topic; Natriuretic Peptide, Brain; Pacemaker, Artificial; Practice Guidelines as Topic; Prevalence; Severity of Illness Index; Stroke Volume; Systole; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Remodeling

To review the antihypertensive, cardiovascular and pleiotropic effects of angiotensin-receptor blockers (ARBs).. ARBs are the most recently approved class of antihypertensive agents. They selectively block the angiotensin II type 1 receptor, thus inhibiting most of the deleterious effects of angiotensin II. In addition to blood-pressure control, other benefits may be gained using ARBs. This is because the renin-angiotensin system plays a crucial role in circulatory homoeostasis, and in patients with atherosclerosis, diabetes or hypertension, angiotensin II contributes to the pathophysiology of disease. Evidence-based medicine includes well-controlled studies with mortality and morbidity endpoints in patients with a variety of conditions including hypertension, type 2 diabetes, stroke, renal disease, heart failure, left-ventricular hypertrophy and coronary heart diseases. In addition to these hard endpoints, it has been shown that treatment with ARBs prevents the development of type 2 diabetes, ameliorates coronary and peripheral vascular endothelial dysfunction and decreases plasma levels of several markers of vascular inflammation.. ARBs are first-line agents for the treatment of hypertension and cardiovascular diseases. Blocking the renin-angiotensin system with these agents has special advantages due to specific vascular and antiatherosclerotic effects, which contribute to a better cardiovascular and renal protection in patients at risk from or with cardiovascular disease.

Topics: Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Cardiovascular Agents; Cardiovascular Diseases; Cerebrovascular Disorders; Coronary Disease; Diabetes Mellitus, Type 2; Endothelium, Vascular; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Diseases

The main goal of current antihypertensive therapy is to achieve a lowering of intra-arterial pressure by various mechanisms. A plethora of data suggests that this reduces cardiovascular morbidity and mortality due to stroke, heart failure and to a lesser extent, ischemic heart disease. Early cardiac manifestations of chronic hypertension, left ventricular hypertrophy (LVH) and diastolic dysfunction (CHF-D) confer additional risk of cardiovascular morbidity and mortality in patients with hypertension. Regression of left ventricular (LV) mass with antihypertensive therapy is associated with improved diastolic function and overall reduction in cardiovascular events, and this benefit may be independent of actual lowering of arterial pressure. Antihypertensive therapy should therefore be geared to both lower arterial blood pressure and specifically reverse pathophysiologic processes that promote LVH and CHF-D. Emerging therapies accomplish this without specifically affecting blood pressure. Therefore, future treatments for hypertension may require a combination of drugs performing complimentary tasks in lowering arterial pressure and reversing maladaptive physiologic and genetic processes causing hypertensive heart disease. This review summarizes the current and emerging approaches to the treatment of individuals with hypertensive heart disease.

Topics: Antihypertensive Agents; Cardiac Output, Low; Cardiovascular Agents; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Ventricular Dysfunction, Left

The association between chronic kidney disease and cardiovascular death is accounted for, in part, by higher rates of serious arrhythmias. Research shows an independent relationship between worsened renal function and atrial fibrillation, heart block, ventricular tachycardia, ventricular fibrillation, and asystole. These higher rates also associate with underlying structural heart disease including left ventricular hypertrophy, cardiac fibrosis, valvular disease, and left ventricular systolic and diastolic dysfunction. In addition, chronic intermittent ischemia is implicated in the arrhythmias observed during hemodialysis. The superimposed conditions of acidosis and fluxes in both potassium and magnesium also contribute to higher rates of arrhythmias. Baseline estimated glomerular filtration rate is linked to worsened outcomes and increased defibrillation thresholds in patients receiving implantable cardioverter defibrillators. Preventive strategies include meticulous management of electrolytes, baseline treatment for cardiovascular disease, and when indicated, implantable cardioverter defibrillators. Future research into the mechanisms and prevention of sudden cardiac death in patients with chronic kidney disease is warranted.

Topics: Adrenergic beta-Antagonists; Arrhythmias, Cardiac; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Heart Function Tests; Humans; Hypertrophy, Left Ventricular; Kidney Diseases; Kidney Function Tests; Outcome Assessment, Health Care; Risk Factors

Recent studies call into question the necessity of hypertrophic growth of the heart as a "compensatory" response to hemodynamic stress. These findings, coupled with recent progress in dissecting the molecular bases of hypertrophy, raise the prospect of suppressing hypertrophy without provoking circulatory insufficiency. In this article, we focus on signaling pathways that hold promise as potential targets for therapeutic intervention. We also summarize observations from animal models and clinical trials that suggest benefit from an antihypertrophic strategy.

Topics: Adaptation, Physiological; Animals; Arrhythmias, Cardiac; Calcium; Cardiac Output; Cardiovascular Agents; Cell Size; Clinical Trials as Topic; Heart Diseases; Heart Failure; Humans; Hypertrophy, Left Ventricular; Ion Channels; Mechanoreceptors; Muscle Proteins; Myocytes, Cardiac; Pressure; Ventricular Remodeling

Topics: Arrhythmias, Cardiac; Cardiomyopathy, Hypertrophic, Familial; Cardiovascular Agents; Death, Sudden, Cardiac; Dyspnea; Heart Septum; Humans; Hypertrophy, Left Ventricular; Pacemaker, Artificial; Prevalence

Although the past number of years have seen a substantial improvement in the therapeutic approaches for the treatment of heart failure, mortality rates continue to be high. Moreover, the incidence of heart failure is expanding rapidly. Sodium-hydrogen exchange (NHE) is a key target for the treatment of heart failure. NHE is a major mechanism for intracellular pH regulation in most cell types, including the cardiac cell. Seven isoforms of NHE have been identified so far although cardiac cells possess primarily the ubiquitous NHE-1 subtype. NHE-1 is a major contributor to ischaemic and reperfusion injury and NHE-1 inhibitors exert marked cardioprotective effects, particularly when administered before ischaemia, findings which have now been extended to clinical trials. It is emerging that NHE-1 also contributes to chronic maladaptive myocardial responses to injury (myocardial remodelling) and may contribute to the development of heart failure. Experimental studies using both in vitro approaches as well as animal models of heart failure have consistently demonstrated a beneficial effect of NHE-1 inhibitors in terms of inhibition of hypertrophy in response to various stimuli as well as inhibiting heart failure after coronary artery ligation. These effects occurred independently of any infarct size reducing effects of NHE-1 inhibitors or on any direct effects on afterload thus indicating a direct effect on the myocardial remodelling process. In fact, it appears that NHE-1 may represent a common downstream mediator for various hypertropic factors such as angiotensin II, endothelin-1 and beta(1) adrenergic receptor activation. NHE-1 inhibition, therefore, represents a potentially effective new therapeutic approach for the treatment of heart failure.

Topics: Animals; Cardiomegaly; Cardiovascular Agents; Drug Design; Drug Evaluation, Preclinical; Gene Expression Regulation; Heart Failure; Humans; Hypertrophy, Left Ventricular; Ion Transport; Myocardial Ischemia; Myocardial Reperfusion Injury; Rats; Sodium; Sodium-Hydrogen Exchangers; Ventricular Remodeling

One of the aims of transplantation is to restore the potential for a full life to individuals with ESRD. To obtain this strategies that allow better and longer allograft function and a reduction in adverse events that lead to premature death are required. To this end, the recommendations below showed reduce cardiovascular disease and help present and future transplant recipients live a full life. Focusing on traditional risk factors (hypertension, hyperlipidemia, discontinuation of smoking, and prevention and treatment of diabetes mellitus) in patients at risk and striving for the recommended targets will have the greatest clinical benefit. These strategies should begin in the pre-dialysis and dialysis phases in order to reduce the cumulative burden of disease. Failing this, early and hopefully pre-emptive transplantation should be the goal.

Topics: Arteriosclerosis; Aspirin; Cardiovascular Agents; Cardiovascular Diseases; Comorbidity; Cost-Benefit Analysis; Diabetes Mellitus; Heart Function Tests; Humans; Hyperlipidemias; Hypertension; Hypertrophy, Left Ventricular; Hypoglycemic Agents; Hypolipidemic Agents; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Life Expectancy; Pancreas Transplantation; Postoperative Complications; Prevalence; Renal Dialysis; Risk Reduction Behavior; Smoking Cessation; Treatment Outcome

Cardiomyopathies have either a primary (without associated anomalies) or a secondary origin. They are classified in three groups according to their anatomy and function: hypertrophic, dilated or restrictive. We review here the relevant diagnostic points of each type as well as their treatment. Restrictive cardiomyopathies, arrhythmogenic right ventricle, non compaction and Uhl's anomaly will not be dealt with in detail as they are very seldom in children.

Topics: Cardiac Surgical Procedures; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Child; Death, Sudden, Cardiac; Diagnosis, Differential; Electrocardiography; Genetic Predisposition to Disease; Humans; Hypertrophy, Left Ventricular; Incidence

Heart failure is a changing paradigm. The hemodynamic model, which served our needs well from the 1950s through the early 1980s, has now been largely abandoned, except for the management of decompensated patients in the hospital. The pathophysiology is exceedingly complex and involves structural changes, such as loss of myofilaments, apoptosis and disorganization of the cytoskeleton, as well as disturbances in Ca(2+) homeostasis, alteration in receptor density, signal transduction, and collagen synthesis. A more contemporary working hypothesis is that heart failure is a progressive disorder of left ventricular remodeling, usually resulting from an index event, that culminates in a clinical syndrome characterized by impaired cardiac function and circulatory congestion. This change in the framework of our understanding of the pathophysiology of heart failure is predicated on the results of numerous clinical trials conducted during the past 20 years. New therapies are now evolving that are designed to inhibit neuroendocrine and cytokine activation, whereas drugs specifically designed to heighten cardiac contractility and "unload" the left ventricle have proven to be unhelpful in long-term management of patients with chronic heart failure. However, the hemodynamic model is still relevant for patients in the hospital with decompensated heart failure, where positive inotropic drugs and vasodilators are still widely used. The modern treatment of chronic heart failure is now largely based on the neurohormonal hypothesis, which states that neuroendocrine activation is important in the progression of heart failure and that inhibition of neurohormones is likely to have long-term benefit with regard to morbidity and mortality. Thus, the evolution of treatment for chronic heart failure as a result of clinical trials has provided much enlightenment for our understanding of the fundamental biology of the disorder, a reversal of the usual flow of information from basic science to clinical investigation.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Cardiovascular Agents; Chronic Disease; Diuretics; Heart Conduction System; Heart Failure; Hormones; Humans; Hypertrophy, Left Ventricular; Myocardial Contraction; Myocardium; Vasodilator Agents; Ventricular Dysfunction, Left; Ventricular Remodeling

Topics: Antihypertensive Agents; Arterioles; Arteriosclerosis; Basement Membrane; Bone Remodeling; Calcinosis; Calcium; Cardiovascular Agents; Cardiovascular Diseases; Chronic Kidney Disease-Mineral and Bone Disorder; Diagnostic Tests, Routine; Disease Progression; Humans; Hyperparathyroidism; Hypertension; Hypertrophy, Left Ventricular; Kidney Transplantation; Osteoblasts; Renal Dialysis; Uremia; Vascular Diseases; Venules; Vitamin D

Topics: Anemia; Cardiovascular Agents; Combined Modality Therapy; Drug Therapy, Combination; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Myocardial Ischemia; Renal Dialysis

Topics: Cardiotonic Agents; Cardiovascular Agents; Cardiovascular Diseases; Clinical Trials as Topic; Cost-Benefit Analysis; Fibrinolytic Agents; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Sociology

Structural and biochemical modifications of the myocardium (remodeling) occur after acute myocardial infarction. An important part of this process of myocardial remodeling takes place in the interstitial compartment which is composed mainly of fibrillar collagen. These remodeling changes are associated with modifications in left ventricular geometry and function that could be deleterious and have significant clinical manifestations. Some salutary effects of the treatment are related to modifications of the process of interstitial remodeling. Clinical studies with calcium channel antagonists, nitrates and, specially converting enzyme inhibitors have shown significant improvement in the degree of ventricular dilation, hemodynamics and exercise tolerance as a compared to placebo treated patients. Ongoing clinical studies will provide us with more definite information on the effects of converting enzyme inhibitors on long term prognosis as well as on myocardial remodeling after acute myocardial infarction.

Topics: Animals; Cardiovascular Agents; Heart Aneurysm; Heart Failure; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Myocardial Infarction; Myocardium

The presence and extent of left ventricular hypertrophy (LVH) is a major determinant of symptoms in patients with hypertrophic cardiomyopathy (HCM). There is increasing evidence to suggest that myocardial energetic impairment represents a central mechanism leading to LVH in HCM. There is currently a significant unmet need for disease-modifying therapy that regresses LVH in HCM patients. Perhexiline, a potent carnitine palmitoyl transferase-1 (CPT-1) inhibitor, improves myocardial energetics in HCM, and has the potential to reduce LVH in HCM.. The primary objective is to evaluate the effects of perhexiline treatment on the extent of LVH, in symptomatic HCM patients with at least moderate LVH.. RESOLVE-HCM is a prospective, multicenter double-blind placebo-controlled randomized trial enrolling symptomatic HCM patients with at least moderate LVH. Sixty patients will be randomized to receive either perhexiline or matching placebo. The primary endpoint is change in LVH, assessed utilizing cardiovascular magnetic resonance (CMR) imaging, after 12-months treatment with perhexiline.. RESOLVE-HCM will provide novel information on the utility of perhexiline in regression of LVH in symptomatic HCM patients. A positive result would lead to the design of a Phase 3 clinical trial addressing long-term effects of perhexiline on risk of heart failure and mortality in HCM patients.

Topics: Adult; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Double-Blind Method; Echocardiography; Female; Humans; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging; Male; Perhexiline; Prospective Studies

Trimetazidine is a metabolic anti-ischemic agent, which increases the tolerance of cardiomyocytes to ischemia. However, few studies have explored the effect of trimetazidine on ventricular remodeling in coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) with left ventricular hypertrophy (LVH).. It is a randomized, placebo-controlled trial, and we propose to recruit one hundred and twenty-four CAD patients undergoing PCI with LVH during a 12-month period. They will be randomized to receive either trimetazidine (35 mg twice a day) or placebo in the following 12 months after PCI. Blood tests, echocardiography, symptom of angina and major adverse cardiovascular events (MACEs) will be collected at follow-up visit at 3 and 12 months. The primary end point will be the left ventricular remodeling measured by left ventricular mass index (LVMI) at 3- and 12-month follow-up compared with the baseline. The secondary end points will be the symptom of angina assessed by Seattle Angina Questionnaire, myocardial ischemia measured by 6-min walk test and exercise electrocardiography test, as well as MACEs (defined as a composite of death, myocardial infarction, stroke, recurrent angina, re-hospitalization, change of viable myocardium).. This study aims to demonstrate the effect of trimetazidine on left ventricular remodeling and myocardial ischemia in CAD patients undergoing PCI with LVH. Trimetazidine treatment is likely to improve the left ventricular remodeling, symptoms of angina and myocardial ischemia. It might also reduce the risk of MACEs in CAD patients undergoing PCI with LVH.. http://www.chictr.org.cn, Chinese Clinical Trial Registry (ChiCTR1800017876). Registered on 19 Aug 2018.

Topics: Adolescent; Adult; Aged; Cardiovascular Agents; China; Coronary Artery Disease; Female; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Percutaneous Coronary Intervention; Prospective Studies; Randomized Controlled Trials as Topic; Recovery of Function; Time Factors; Treatment Outcome; Trimetazidine; Ventricular Function, Left; Ventricular Remodeling; Young Adult

Alamandine is the newest identified peptide of the renin-angiotensin system (RAS) and has protective effects in the cardiovascular system. Although the involvement of classical RAS components in the genesis and progression of cardiac remodeling is well known, less is known about the effects of alamandine. Therefore, in the present study we investigated the effects of alamandine on cardiac remodeling induced by transverse aortic constriction (TAC) in mice. Male mice (C57BL/6), 10-12 wk of age, were divided into three groups: sham operated, TAC, and TAC + ALA (30 µg/kg/day alamandine for 14 days). The TAC surgery was performed under ketamine and xylazine anesthesia. At the end of treatment, the animals were submitted to echocardiographic examination and subsequently euthanized for tissue collection. TAC induced myocyte hypertrophy, collagen deposition, and the expression of matrix metalloproteinase (MMP)-2 and transforming growth factor (TGF)-β in the left ventricle. These markers of cardiac remodeling were reduced by oral treatment with alamandine. Western blotting analysis showed that alamandine prevents the increase in ERK1/2 phosphorylation and reverts the decrease in 5'-adenosine monophosphate-activated protein kinase (AMPK)α phosphorylation induced by TAC. Although both TAC and TAC + ALA increased SERCA2 expression, the phosphorylation of phospholamban in the Thr17 residue was increased solely in the alamandine-treated group. The echocardiographic data showed that there are no functional or morphological alterations after 2 wk of TAC. Alamandine treatment prevents myocyte hypertrophy and cardiac fibrosis induced by TAC. Our results reinforce the cardioprotective role of alamandine and highlight its therapeutic potential for treating heart diseases related to pressure overload conditions.

Topics: AMP-Activated Protein Kinases; Animals; Aorta; Calcium-Binding Proteins; Cardiovascular Agents; Collagen; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Heart Ventricles; Hypertrophy, Left Ventricular; Ligation; Male; Matrix Metalloproteinase 2; Mice, Inbred C57BL; Oligopeptides; Oxidative Stress; Phosphorylation; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Signal Transduction; Transforming Growth Factor beta; Ventricular Function, Left; Ventricular Remodeling

Many studies have shown the beneficial effects of aconite water-soluble alkaloid extract (AWA) in experimental models of heart disease, which have been ascribed to the presence of aconine, hypaconine, talatisamine, fuziline, neoline, and songorine. This study evaluated the effects of a chemically characterized AWA by chemical content, evaluated its effects in suprarenal abdominal aortic coarctation surgery (AAC)-induced chronic heart failure (CHF) in rats, and revealed the underlying mechanisms of action by proteomics.. Rats were distributed into different groups: sham, model, and AWA-treated groups (10, 20, and 40 mg/kg/day). Sham rats received surgery without AAC, whereas model rats an AWA-treated groups underwent AAC surgery. after 8 weeks, the treatment group was fed AWA for 4 weeks, and body weight was assessed weekly. At the end of the treatment, heart function was tested by echocardiography. AAC-induced chronic heart failure, including myocardial fibrosis, cardiomyocyte hypertrophy, and apoptosis, was evaluated in heart tissue and plasma by RT-qPCR, ELISA, hematoxylin and eosin (H&E) staining, Masson's trichrome staining, TUNEL staining, and immunofluorescence staining of α-SMA, Col Ⅰ, and Col Ⅲ. Then, a proteomics approach was used to explore the underlying mechanisms of action of AWA in chronic heart failure.. AWA administration reduced body weight gain, myocardial fibrosis, cardiomyocyte hypertrophy, and apoptosis, and rats showed improvement in cardiac function compared to model group. The extract significantly ameliorated the AAC-induced altered expression of heart failure markers such as ANP, NT-proBNP, and β-MHC, as well as fibrosis, hypertrophy markers MMP-2 and MMP-9, and other heart failure-related factors including plasma levels of TNF-α and IL-6. Furthermore, the extract reduced the protein expression of α-SMA, Col Ⅰ, and Col Ⅲ in the left ventricular (LV), thus inhibiting the LV remodeling associated with CHF. In addition, proteomics characterization of differentially expressed proteins showed that AWA administration inhibited left ventricular remodeling in CHF rats via a calcium signaling pathway, and reversed the expression of RyR2 and SERCA2a.. AWA extract exerts beneficial effects in an AAC-induced CHF model in rats, which was associated with an improvement in LV function, hypertrophy, fibrosis, and apoptotic status. These effects may be related to the regulation of calcium signaling by the altered expression of RyR2 and SERCA2a.

Topics: Aconitum; Animals; Apoptosis; Calcium Signaling; Cardiovascular Agents; Chronic Disease; Disease Models, Animal; Fibrosis; Heart Failure; Hypertrophy, Left Ventricular; Myocytes, Cardiac; Plant Extracts; Rats, Sprague-Dawley; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Solubility; Solvents; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling; Water

Topics: Acute Coronary Syndrome; Adult; Cardiac Catheterization; Cardiovascular Agents; Cardiovascular Diseases; Combined Modality Therapy; Coronavirus Infections; COVID-19; Diabetes Mellitus, Type 2; Diagnosis, Differential; Extracorporeal Membrane Oxygenation; Female; Heart Failure; Heart Transplantation; Humans; Hyperlipidemias; Hypertension; Hypertrophy, Left Ventricular; Immunosuppressive Agents; Intra-Aortic Balloon Pumping; Kidney Transplantation; Male; Middle Aged; Pandemics; Pericarditis; Pneumonia, Viral; Postoperative Complications; Respiration, Artificial; Respiratory Distress Syndrome; Shock, Cardiogenic

Topics: AMP-Activated Protein Kinases; Animals; Arterial Pressure; Cardiovascular Agents; Disease Models, Animal; Energy Metabolism; Fatty Acids; Glucose; Hypertension; Hypertrophy, Left Ventricular; Metformin; Myocardium; Oxidation-Reduction; Oxidative Stress; Rats, Inbred SHR; Rats, Inbred WKY; TOR Serine-Threonine Kinases; Ventricular Function, Left; Ventricular Remodeling

This study aimed to investigate the effects and molecular mechanisms of ivabradine in preventing cardiac hypertrophy in an established transverse aortic constriction (TAC) mouse model. A total of 56 male C57BL/6 mice were randomly assigned into the following seven groups (8 mice per group): sham, TAC model, Iva-10 (10 mg/kg/day ivabradine), Iva-20 (20 mg/kg/day ivabradine), Iva-40 (40 mg/kg/day ivabradine), Iva-80 (80 mg/kg/day ivabradine), and Rap (rapamycin, a positive control). Echocardiography and left ventricular hemodynamics were performed. Hematoxylin-eosin (H&E), Masson's trichome staining, and TUNEL assays were conducted to evaluate cardiac hypertrophy, fibrosis, and apoptosis, respectively. Western blotting was performed to detect the expression of proteins related to the PI3K/Akt/mTOR/p70S6K pathway. Ivabradine could effectively improve left ventricular dysfunction and hypertrophy induced by TAC in a dose-independent manner. Moreover, no obvious change in heart rate (HR) was observed in the TAC and Rap groups, whereas a significant decrease in HR was found after ivabradine treatment (P < 0.05). Cardiac hypertrophy, fibrosis, and apoptosis induced by TAC were notably suppressed after either rapamycin or ivabradine treatment (P < 0.05). Ivabradine and rapamycin also decreased the expression of PI3K/Akt and mTOR induced by TAC. Ivabradine improved cardiac hypertrophy and fibrosis as well as reduced cardiomyocyte apoptosis via the PI3K/Akt/mTOR/p70S6K pathway in TAC model mice.

Topics: Animals; Aortic Diseases; Apoptosis; Cardiovascular Agents; Constriction, Pathologic; Disease Models, Animal; Hypertrophy, Left Ventricular; Ivabradine; Male; Mice; Mice, Inbred C57BL; Myocytes, Cardiac; Pressure; Ventricular Dysfunction, Left

Heart failure-associated morbidity and mortality is largely attributable to extensive and unregulated cardiac remodelling. Roselle (Hibiscus sabdariffa) calyces are enriched with natural polyphenols known for antioxidant and anti-hypertensive effects, yet its effects on early cardiac remodelling in post myocardial infarction (MI) setting are still unclear. Thus, the aim of this study was to investigate the actions of roselle extract on cardiac remodelling in rat model of MI. Male Wistar rats (200-300 g) were randomly allotted into three groups: Control, MI, and MI + Roselle. MI was induced with isoprenaline (ISO) (85 mg/kg, s.c) for two consecutive days followed by roselle treatment (100 mg/kg, orally) for 7 days. Isoprenaline administration showed changes in heart weight to body weight (HW/BW) ratio. MI was especially evident by the elevated cardiac injury marker, troponin-T, and histological observation. Upregulation of plasma levels and cardiac gene expression levels of inflammatory cytokines such as interleukin (IL)-6 and IL-10 was seen in MI rats. A relatively high percentage of fibrosis was observed in rat heart tissues with over-expression of collagen (Col)-1 and Col-3 genes following isoprenaline-induced MI. On top of that, cardiomyocyte areas were larger in heart tissues of MI rats with upregulation of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) gene expression, indicating cardiac hypertrophy. Interestingly, roselle supplementation attenuated elevation of plasma troponin-T, IL-6, IL10, and gene expression level of IL-10. Furthermore, reduction of cardiac fibrosis and hypertrophy were observed. In conclusion, roselle treatment was able to limit early cardiac remodelling in MI rat model by alleviating inflammation, fibrosis, and hypertrophy; hence, the potential application of roselle in early adjunctive treatment to prevent heart failure.

Topics: Animals; Atrial Natriuretic Factor; Cardiovascular Agents; Collagen Type I; Collagen Type III; Disease Models, Animal; Fibrosis; Heart Ventricles; Hibiscus; Hypertrophy, Left Ventricular; Inflammation Mediators; Interleukin-10; Interleukin-6; Isoproterenol; Male; Myocardial Infarction; Myocytes, Cardiac; Natriuretic Peptide, Brain; Rats, Wistar; Troponin T; Ventricular Function, Left; Ventricular Remodeling

Patients with left ventricular hypertrophy (LVH) have reportedly higher than normal mortality and incidences of cardiovascular events. Coronary microvascular pathophysiology also appears to differ from other populations. Such coronary microcirculation dysfunctions are considered strong causes of cardiac events. We compare the functional improvement of myocardial ischemia between LVH patients and other patients after successful coronary artery bypass surgery (CABG) using coronary flow velocity reserve (CFVR) by transthoracic echo cardiography. Patients who underwent isolated coronary artery bypass surgery, including left anterior descending artery (LAD) revascularization via "in situ" internal thoracic artery (ITA) between June 2008 and July 2017 (n = 155), were retrospectively reviewed. ITA grafts were patent in postoperative graft evaluation in all patients. CFVR was evaluated pre- and postoperatively, and data were compared between patients with severe LVH group and those without (non-LVH group). Preoperative mean CFVR was 1.77 ± 0.75 in LVH group and 1.91 ± 0.63 in non-LVH group (P = 0.188). After the operation, ITA to LAD graft patency was confirmed in all patients. Postoperative CFVR was 2.23 ± 0.70 in LVH group and 2.85 ± 0.71 in non-LVH group, respectively (P = 0.002). Significant difference was observed between the 2 groups. CFVR values improved after ITA to LAD bypass grafting in both LVH and non-LVH groups, but postoperative CFVR was significantly lower in patients with severe LVH than in patients without. Myocardial ischemia may exist in patients with LVH, despite patent graft, due to microvascular dysfunction. Comprehensive treatment, including long-term oral medication to improve microvascular dysfunction, is necessary for patients with LVH.

Topics: Aged; Blood Flow Velocity; Cardiovascular Agents; Coronary Artery Bypass; Coronary Artery Disease; Coronary Circulation; Echocardiography, Doppler; Female; Humans; Hypertrophy, Left Ventricular; Male; Microcirculation; Middle Aged; Recovery of Function; Retrospective Studies; Severity of Illness Index; Treatment Outcome; Vascular Patency

Prolonged exercise and exercise training can adversely affect cardiac function in some individuals. QiShenYiQi Pills (QSYQ), which are a compound Chinese medicine, have been previously shown to improve pressure overload-induced cardiac hypertrophy. We hypothesized that QSYQ can ameliorate as well the fatigue-induced cardiac hypertrophy. This study was to test this hypothesis and underlying mechanism with a focus on its role in energy regulation. Male Sprague-Dawley rats were used to establish exercise adaptation and fatigue model on a motorized rodent treadmill. Echocardiographic analysis and heart function test were performed to assess heart systolic function. Food-intake weight/body weight and heart weight/body weight were assessed, and hematoxylin and eosin staining and immunofluorescence staining of myocardium sections were performed. ATP synthase expression and activity and ATP, ADP, and AMP levels were assessed using Western blot and ELISA. Expression of proteins related to energy metabolism and IGF-1R signaling was determined using Western blot. QSYQ attenuated the food-intake weight/body weight decrease, improved myocardial structure and heart function, and restored the expression and distribution of myocardial connexin 43 after fatigue, concomitant with an increased ATP production and a restoration of metabolism-related protein expression. QSYQ upgraded the expression of IGF-1R, P-AMPK/AMPK, peroxisome proliferator-activated receptor-γ coactivator-1α, nuclear respiratory factor-1, P-phosphatidylinositol 3-kinase (PI3K)/PI3K, and P-Akt/Akt thereby attenuated the dysregulation of IGF-1R signaling after fatigue. QSYQ relieved fatigue-induced cardiac hypertrophy and enhanced heart function, which is correlated with its potential to improve energy metabolism by regulating IGF-1R signaling.

Topics: Adenosine Triphosphate; Animals; Cardiovascular Agents; Cell Line; Disease Models, Animal; Drugs, Chinese Herbal; Energy Metabolism; Fatigue; Hypertrophy, Left Ventricular; Male; Myocytes, Cardiac; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; Receptor, IGF Type 1; Signal Transduction; Ventricular Function, Left; Ventricular Remodeling

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Drug Therapy, Combination; Heart Failure; Humans; Hypertrophy, Left Ventricular; Mineralocorticoid Receptor Antagonists; Recovery of Function; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

Oxidative stress results in mtDNA damage and contributes to myocardial cell death. mtDNA repair enzymes are crucial for mtDNA repair and cell survival. We investigated a novel, mitochondria-targeted fusion protein (Exscien1-III) containing endonuclease III in myocardial ischemia-reperfusion injury and transverse aortic constriction (TAC)-induced heart failure. Male C57/BL6J mice (10-12 wk) were subjected to 45 min of myocardial ischemia and either 24 h or 4 wk of reperfusion. Exscien1-III (4 mg/kg ip) or vehicle was administered at the time of reperfusion. Male C57/BL6J mice were subjected to TAC, and Exscien1-III (4 mg/kg i.p) or vehicle was administered daily starting at 3 wk post-TAC and continued for 12 wk. Echocardiography was performed to assess left ventricular (LV) structure and function. Exscien1-III reduced myocardial infarct size ( P < 0.01) at 24 h of reperfusion and preserved LV ejection fraction at 4 wk postmyocardial ischemia. Exscien1-III attenuated TAC-induced LV dilation and dysfunction at 6-12 wk post-TAC ( P < 0.05). Exscien1-III reduced ( P < 0.05) cardiac hypertrophy and maladaptive remodeling after TAC. Assessment of cardiac mitochondria showed that Exscien1-III localized to mitochondria and increased mitochondrial antioxidant and reduced apoptotic markers. In conclusion, our results indicate that administration of Exscien1-III provides significant protection against myocardial ischemia and preserves myocardial structure and LV performance in the setting of heart failure. NEW & NOTEWORTHY Oxidative stress-induced mitochondrial DNA damage is a prominent feature in the pathogenesis of cardiovascular diseases. In the present study, we demonstrate the efficacy of a novel, mitochondria-targeted fusion protein that traffics endonuclease III specifically for mitochondrial DNA repair in two well-characterized murine models of cardiac injury and failure.

Topics: Animals; Apoptosis; Apoptosis Regulatory Proteins; Cardiovascular Agents; Disease Models, Animal; DNA Damage; DNA, Mitochondrial; Fibrosis; Heart Failure; Hypertrophy, Left Ventricular; Male; Mice, Inbred C57BL; Mitochondria, Heart; Myocytes, Cardiac; Oxidative Stress; Recombinant Fusion Proteins; Signal Transduction; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

Left ventricular (LV) dysfunction develops during LV hypertrophy and particularly during tachycardia. Thus we investigated the effects of heart rate (HR) reduction with ivabradine, an I. Eight chronically instrumented pigs receiving continuous angiotensin II infusion during 28days to induce chronic hypertension and LV hypertrophy. Measurements were performed at Days 0 and 28 after stopping angiotensin II infusion in the presence and absence of ivabradine.. At Day 0, reducing HR from 75±3 to 55±2beats/min with ivabradine did not affect LV twist but slowed LV untwist along with an increase in LV end-diastolic pressure. At Day 28, LV posterior and septal wall thickness as well as the estimated LV mass increased, indicating LV hypertrophy. LV twist and untwist were significantly reduced by 33±4% from 16±1° and 32±6% from -154±9°/s, respectively, showing global LV systolic and diastolic dysfunction. In this context, ivabradine decreased HR by 25% from 86±5beats/min and significantly improved LV twist from 11±1 to 14±1° and LV untwist from -104±8 to -146±5°/s.. Administration of ivabradine during chronic hypertension and LV hypertrophy improved LV twist and untwist. This further supports the beneficial effect of this drug on both LV systolic and diastolic function during the development of LV hypertrophy.

Topics: Animals; Benzazepines; Cardiovascular Agents; Chronic Disease; Female; Hypertension; Hypertrophy, Left Ventricular; Ivabradine; Swine; Ventricular Dysfunction, Left

This study aims to contribute to the improvement of treatment protocols for patients with dilated cardiomyopathies (DCMs) in Brazzaville. We conducted a prospective analytical study at the University Hospital in Brazzaville between 1 January 2014 and 30 June 2015. All patients hospitalized with heart failure (HF) associated with DCM in the Department of Cardiology were included in the study. The study involved 100 patients. Hospitalization rate for DCM was 32.1%: 38 men (38%) and 62 women (62%) with an average age of 52.9 ± 17.1 years. Seventy two patients had comprehensive heart failure (72%). ECG showing normal sinus rhythm (95%) objectified left ventricular hypertrophy (40%), left bundle-branch block (16%), atrial fibrillation (5%). Mean left ventricular ejection fraction (EF) was 33.4 ± 6.8% and left ventricle end-diastolic diameter was 65.5 ± 7.0 mm. Treatment was based on loop diuretic (100%), ACE Inhibitors, Angiotensin II Receptor Blockers (ARBs) (100%), beta blocker (38%), digitalis (30%), anti-aldosterone (16%) and anti-vitamin K (11%). After 12-month follow-up period, overall case-fatality rate was 9%, readmission rate was 12% and the rate of patient lost-to-follow-up was 41%. This study shows that DCM is frequent and it is one of the leading causes of heart failure. The short follow-up period and the high rate of people lost to follow up do not enable assessment of survival rate of patients at our Department.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Bundle-Branch Block; Cardiomyopathy, Dilated; Cardiovascular Agents; Congo; Electrocardiography; Female; Follow-Up Studies; Heart Failure; Hospitalization; Hospitals, University; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Patient Readmission; Prospective Studies; Stroke Volume; Young Adult

In this study, we examined whether aspirin could inhibit cardiac hypertrophy.. We utilized cultured neonatal mouse cardiomyocytes and mice for the study and subjected to cardiomyocyte immunochemistry, qRT-PCR, and immunoblotting analysis. The cardiac function was measured using M-mode echocardiography.. Ten μM aspirin significantly inhibited Ang II-induced increase in cardiomyocyte size, the mRNA, and protein levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC) (P < 0.05). Meantime, consistent with the result in vitro, the increase in HW/BW ratio, the mRNA, and protein levels of ANP, BNP, and β-MHC could be reduced by aspirin in vivo (P < 0.05). Analysis of cardiac function revealed that mouse hearts treated with Ang II displayed thickening of the ventricular walls, left ventricular end-diastolic dimensions, and left ventricular end-systolic dimensions were significantly decreased (P < 0.05), whereas interventricular septal thickness at end-diastole, interventricular septal thickness at end-systole, posterior wall thickness in diastole, and posterior wall thickness in systole were markedly increased (P < 0.05), which could be reversed by aspirin (P < 0.05). Moreover, aspirin blunted the increase inCa(2+) and inhibited the calcineurin activity and NFAT dephosphorylation caused by Ang II (P < 0.05).. Aspirin inhibited cardiac hypertrophy in vitro and in vivo through inhibition of the Ca(2+)/calcineurin-NFAT signaling pathway. Therefore, these findings suggested that aspirin might become a therapeutic option to reduce cardiac hypertrophy.

Topics: Angiotensin II; Animals; Animals, Newborn; Aspirin; Atrial Natriuretic Factor; Calcineurin; Calcium; Calcium Signaling; Cardiovascular Agents; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Gene Expression Regulation; Hypertrophy, Left Ventricular; Male; Mice; Myocytes, Cardiac; Myosin Heavy Chains; Natriuretic Peptide, Brain; NFATC Transcription Factors; Phosphorylation; Stroke Volume; Ventricular Function, Left

Nitric oxide synthase uncoupling occurs under conditions of oxidative stress modifying the enzyme's function so it generates superoxide rather than nitric oxide. Nitric oxide synthase uncoupling occurs with chronic pressure overload, and both are ameliorated by exogenous tetrahydrobiopterin (BH4)-a cofactor required for normal nitric oxide synthase function-supporting a pathophysiological link. Genetically augmenting BH4 synthesis in endothelial cells fails to replicate this benefit, indicating that other cell types dominate the effects of exogenous BH4 administration. We tested whether the primary cellular target of BH4 is the cardiomyocyte or whether other novel mechanisms are invoked.. Mice with cardiomyocyte-specific overexpression of GTP cyclohydrolase 1 (mGCH1) and wild-type littermates underwent transverse aortic constriction. The mGCH1 mice had markedly increased myocardial BH4 and, unlike wild type, maintained nitric oxide synthase coupling after transverse aortic constriction; however, the transverse aortic constriction-induced abnormalities in cardiac morphology and function were similar in both groups. In contrast, exogenous BH4 supplementation improved transverse aortic constricted hearts in both groups, suppressed multiple inflammatory cytokines, and attenuated infiltration of inflammatory macrophages into the heart early after transverse aortic constriction.. BH4 protection against adverse remodeling in hypertrophic cardiac disease is not driven by its prevention of myocardial nitric oxide synthase uncoupling, as presumed previously. Instead, benefits from exogenous BH4 are mediated by a protective effect coupled to suppression of inflammatory pathways and myocardial macrophage infiltration.

Topics: Animals; Anti-Inflammatory Agents; Biopterins; Cardiovascular Agents; Cytokines; Cytoprotection; Disease Models, Animal; GTP Cyclohydrolase; Humans; Hypertrophy, Left Ventricular; Inflammation Mediators; Macrophages; Mice, Transgenic; Myocytes, Cardiac; Nitric Oxide; Nitric Oxide Synthase; Oxidation-Reduction; Signal Transduction; Superoxides; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

Therapeutic strategies aimed at increasing hydrogen sulfide (H2S) levels exert cytoprotective effects in various models of cardiovascular injury. However, the underlying mechanism(s) responsible for this protection remain to be fully elucidated. Nuclear factor E2-related factor 2 (Nrf2) is a cellular target of H2S and facilitator of H2S-mediated cardioprotection after acute myocardial infarction. Here, we tested the hypothesis that Nrf2 mediates the cardioprotective effects of H2S therapy in the setting of heart failure.. Mice (12 weeks of age) deficient in Nrf2 (Nrf2 KO; C57BL/6J background) and wild-type littermates were subjected to ischemic-induced heart failure. Wild-type mice treated with H2S in the form of sodium sulfide (Na2S) displayed enhanced Nrf2 signaling, improved left ventricular function, and less cardiac hypertrophy after the induction of heart failure. In contrast, Na2S therapy failed to provide protection against heart failure in Nrf2 KO mice. Studies aimed at evaluating the underlying cardioprotective mechanisms found that Na2S increased the expression of proteasome subunits, resulting in an increased proteasome activity and a reduction in the accumulation of damaged proteins. In contrast, Na2S therapy failed to enhance the proteasome and failed to attenuate the accumulation of damaged proteins in Nrf2 KO mice. Additionally, Na2S failed to improve cardiac function when the proteasome was inhibited.. These findings indicate that Na2S therapy enhances proteasomal activity and function during the development of heart failure in an Nrf2-dependent manner and that this enhancement leads to attenuation in cardiac dysfunction.

Topics: Animals; Cardiovascular Agents; Disease Models, Animal; Endoplasmic Reticulum Stress; Heart Failure; Hydrogen Sulfide; Hypertrophy, Left Ventricular; Male; Mice, Inbred C57BL; Mice, Knockout; Myocardial Ischemia; Myocardium; NF-E2-Related Factor 2; Oxidative Stress; Proteasome Endopeptidase Complex; Signal Transduction; Sulfides; Time Factors; Ventricular Function, Left

Metabolism remodeling has been recognized as an early event following cardiac pressure overload. However, its temporal association with ventricular hypertrophy has not been confirmed. Moreover, whether trimetazidine could favorably affect this process also needs to be determined. The aim of the study was to explore the temporal changes of myocardial metabolism remodeling following pressure-overload induced ventricular hypertrophy and the potential favorable effect of trimetazidine on myocardial metabolism remodeling.. A rat model of abdominal aortic constriction (AAC)-induced cardiac pressure overload was induced. These rats were grouped as the AAC (no treatment) or TMZ group according to whether oral trimetazidine (TMZ, 40 mg/kg/d, for 5 days) was administered. Changes in cardiac structures were sequentially evaluated via echocardiography. The myocardial ADP/ATP ratio was determined to reflect the metabolic status, and changes in serum neuropeptide Y systems were evaluated.. Myocardial metabolic disorder was acutely induced as evidenced by an increased ADP/ATP ratio within 7 days of AAC before the morphological changes in the myocardium, accompanied by up-regulation of serum oxidative stress markers and expression of fetal genes related to hypertrophy. Moreover, the serum NPY and myocardial NPY-1R, 2R, and 5R levels were increased within the acute phase of AAC-induced cardiac pressure overload. Pretreatment with TMZ could partly attenuate myocardial energy metabolic homeostasis, decrease serum levels of oxidative stress markers, attenuate the induction of hypertrophy-related myocardial fetal genes, inhibit the up-regulation of serum NPY levels, and further increase the myocardial expression of NPY receptors.. Cardiac metabolic remodeling is an early change in the myocardium before the presence of typical morphological ventricular remodeling following cardiac pressure overload, and pretreatment with TMZ may at least partly reverse the acute metabolic disturbance, perhaps via regulation of the NPY system.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Aorta, Abdominal; Arterial Pressure; Cardiovascular Agents; Constriction; Disease Models, Animal; Energy Metabolism; Gene Expression Regulation; Hypertrophy, Left Ventricular; Male; Myocardium; Neuropeptide Y; Oxidative Stress; Rats, Wistar; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Receptors, Neuropeptide Y; Signal Transduction; Trimetazidine; Ventricular Function, Left; Ventricular Remodeling

Mineralocorticoid receptor(MR) antagonism reduces sudden cardiac death in heart failure, but the underlying mechanism remains poorly understood. Concurrent treatment with an MR antagonist during rapid ventricular pacing (RVP) prevents development of adverse ventricular electrophysiological remodeling, interstitial fibrosis, inflammatory cytokine gene activation, and ventricular tachyarrhythmia inducibility without diminishing the extent of systolic dysfunction. We hypothesized that attenuating preexistent inflammatory pathways and myocardial fibrosis with eplerenone after systolic heart failure is established by rapid pacing can reduce electrical activation delays and arrhythmia vulnerability.. Dogs subjected to RVP for 8 weeks in the absence or presence of eplerenone treatment during the final 4 weeks of pacing were assessed by echocardiography, electrophysiology study,ventricular fibrosis measurements, and inflammatory cytokine mRNA expression analysis. Eplerenone reversed preexistent ventricular activation delays, interstitial fibrosis, inflammatory cytokine (interleukin-6, tumor necrosis factor-α) gene overexpression, and arrhythmia vulnerability in ventricular paced dogs with heart failure. Eplerenone failed to improve left ventricular systolic dysfunction or chamber enlargement. A correlation between severity of fibrosis and ventricular arrhythmia inducibility was found.. MR antagonism regresses rapid pacing-induced electrical delays, inflammatory cytokine gene activation, and fibrosis in heart failure. Ventricular arrhythmia vulnerability in heart failure is correlated with extent of fibrosis and electrical activation delays during premature excitation.

Topics: Action Potentials; Animals; Anti-Inflammatory Agents; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Cardiovascular Agents; Disease Models, Animal; Dogs; Eplerenone; Fibrosis; Heart Failure; Hypertrophy, Left Ventricular; Inflammation Mediators; Interleukin-6; Male; Mineralocorticoid Receptor Antagonists; Myocardium; Spironolactone; Time Factors; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

We report a familial form of ventricular non compaction in a mother and two of her sons. It was a young man of 25 years who presented with NYHA stage III dyspnea and a cough with bloody sputum. The clinical examination found left ventricular failure. The echocardiogram done showed left ventricular dilatation with large trabeculae separated by deep intertrabecular recesses in both ventricles suggestive of a non-biventricular compaction. It was possible to note from the family screening by echocardiography of the mother and half-brother a left ventricular non compaction while they were asymptomatic. Thus we concluded a familial form of ventricular non-compaction. This is the first familial case described in Senegal.

Topics: Adult; Barth Syndrome; Cardiovascular Agents; Developing Countries; Echocardiography; Electrocardiography; Female; Heart Failure; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Senegal; Stroke Volume; Ultrasonography, Doppler, Color; Vitamin K; Young Adult

Cardiac fibrosis is a hallmark of heart disease and plays a vital role in cardiac remodeling during heart diseases, including hypertensive heart disease. Hexarelin is one of a series of synthetic growth hormone secretagogues (GHSs) possessing a variety of cardiovascular effects via action on GHS receptors (GHS-Rs). However, the role of hexarelin in cardiac fibrosis in vivo has not yet been investigated. In the present study, spontaneously hypertensive rats (SHRs) were treated with hexarelin alone or in combination with a GHS-R antagonist for 5 wk from an age of 16 wk. Hexarelin treatment significantly reduced cardiac fibrosis in SHRs by decreasing interstitial and perivascular myocardial collagen deposition and myocardial hydroxyproline content and reducing mRNA and protein expression of collagen I and III in SHR hearts. Hexarelin treatment also increased matrix metalloproteinase (MMP)-2 and MMP-9 activities and decreased myocardial mRNA expression of tissue inhibitor of metalloproteinase (TIMP)-1 in SHRs. In addition, hexarelin treatment significantly attenuated left ventricular (LV) hypertrophy, LV diastolic dysfunction, and high blood pressure in SHRs. The effect of hexarelin on cardiac fibrosis, blood pressure, and cardiac function was mediated by its receptor, GHS-R, since a selective GHS-R antagonist abolished these effects and expression of GHS-Rs was upregulated by hexarelin treatment. In summary, our data demonstrate that hexarelin reduces cardiac fibrosis in SHRs, perhaps by decreasing collagen synthesis and accelerating collagen degradation via regulation of MMPs/TIMP. Hexarelin-reduced systolic blood pressure may also contribute to this reduced cardiac fibrosis in SHRs. The present findings provided novel insights and underscore the therapeutic potential of hexarelin as an antifibrotic agent for the treatment of cardiac fibrosis.

Topics: Animals; Blood Pressure; Cardiovascular Agents; Collagen Type I; Collagen Type III; Disease Models, Animal; Fibrosis; Gene Expression Regulation; Heart Diseases; Hydroxyproline; Hypertension; Hypertrophy, Left Ventricular; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Myocardium; Oligopeptides; Rats; Rats, Inbred SHR; Rats, Wistar; Receptors, Ghrelin; RNA, Messenger; Time Factors; Tissue Inhibitor of Metalloproteinase-1; Ventricular Dysfunction, Left; Ventricular Function, Left

Detection of cardiac recovery that allows long-term cardiac stability after ventricular assist device (VAD) explantation is a major goal. After normalization of ventricular diameters during unloading, the pre-explant left ventricular ejection fraction (LVEF) allows the detection of patients with the potential to remain stable after VAD explantation. However, some patients with LVEF >45 before VAD explantation show early recurrence of heart failure (HF). We aimed to find out if unstable improvement can be recognized before VAD explantation.. Among 96 patients weaned from VADs since 1995, a relatively homogenous group of 53 patients with nonischemic chronic cardiomyopathy (CCM) was selected for the study. The pre-explant stability of major parameters of LV function, size, and geometry that were measured by echocardiography during serial "off-pump" trials was tested for relationship with cardiac stability after VAD explantation. LVEF, systolic peak wall motion velocity (Sm), end-diastolic diameter (LVEDD), end-diastolic relative wall thickness (RWT(ED)) and end-diastolic short/long-axis ratio (S/L(ED)) were selected for evaluation. In postweaning unstable patients, the selected parameters showed relevant instability already before VAD explantation during the time period between best cardiac improvement and VAD explantation and also during the final off-pump trial just before VAD explantation. For all parameters, there were significant differences (P<0.05) in pre-explant changes between patients with and without postweaning cardiac stability. Using the optimal cutoff values obtained from receiver-operating characteristic analysis, we found for our selected parameters predictive values for postexplant cardiac stability of ≥1 year, ≥3 years, and ≥5 years, ranging between 94 and 100, 92, and 100, and 78 and 100, respectively. Using for all parameter changes the cutoff value of 10, we found similar predictive values for cardiac stability of ≥1 year, ≥3 years, and ≥5 years, ranging between 93 and 97, 90 and 96, and 83 and 92, respectively.. Our results strongly suggest the possibility to improve the prediction of postexplant transplant/VAD-free outcome in CCM patients with cardiac improvement during VAD support by analyzing the pre-explant stability of several LV off-pump echocardiographic parameters during serial off-pump trials.

Topics: Adolescent; Adult; Aged; Cardiovascular Agents; Combined Modality Therapy; Device Removal; Female; Heart Failure; Heart-Assist Devices; Humans; Hypertrophy, Left Ventricular; Kaplan-Meier Estimate; Male; Middle Aged; Organ Size; Prognosis; Proportional Hazards Models; Recovery of Function; Recurrence; Retrospective Studies; Stroke Volume; Treatment Outcome; Ultrasonography; Ventricular Dysfunction, Left; Ventricular Function, Left; Young Adult

Topics: Animals; Cardiovascular Agents; Drug Chronotherapy; Humans; Hypertrophy, Left Ventricular; Sleep; Ventricular Remodeling

Chronic treatment with suprapharmacologic doses of peroxisome proliferator-activated receptor (PPAR) agonists has a known potential for causing left ventricular hypertrophy (LVH). The mechanism by which LVH develops is not well understood nor are biomarkers of it well characterized. Natriuretic peptides are important regulators of cardiac growth, blood volume, and arterial pressure and may be useful biomarkers of LVH and hemodynamic changes that precede it. We measured amino-terminal pro-atrial natriuretic peptide (NTproANP), amino-terminal pro-brain natriuretic peptide (NTproBNP), and cardiac troponin I (cTnI) concentrations in serum and plasma, as well as transcripts in left ventricular heart tissue for atrial natriuretic peptide precursor (Nppa), brain natriuretic peptide precursor (Nppb), and myosin heavy chain-beta (Myh7) as potential biomarkers of LVH induced by a PPARalpha/gamma dual agonist in Sprague-Dawley rats. We used magnetic resonance imaging, echocardiography, and hemodynamics to identify structural and functional cardiovascular changes related to the biomarkers. Heart-to-brain weight ratios (HW:BrW) were correlated with NTproANP, NTproBNP, and cTnI concentrations in serum as well as fold change in expression of Nppa and Nppb. LVH was characterized by increased left ventricular wall thickness and inner diameter, increased cardiac output, decreased arterial blood pressure, and increased heart rate. In these studies, each end point contributed to the early detection of LVH, the ability to monitor its progression, and demonstrated the ability of NTproANP concentration in serum to predict LVH and hemodynamic changes.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Cardiovascular Agents; Disease Models, Animal; Echocardiography; Female; Heart; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging; Male; Myocardium; Natriuretic Peptide, Brain; Organ Size; Peptide Fragments; Phenylpropionates; PPAR alpha; PPAR gamma; Rats; Rats, Sprague-Dawley; Signal Transduction; Thiophenes; Troponin T

Ginsenoside Rg(1) (Rg(1)), one of the active components of Panax ginseng, has been reported to promote endogenous nitric oxide (NO) production in some tissues, and to inhibit left ventricular (LV) hypertrophy in rats. This study aimed to investigate whether Rg(1)-induced inhibition of rat LV hypertrophy is mediated by NO-production. Rat LV hypertrophy was induced by abdominal aorta coarctation. Rg(1) 15 mg/kg/d, L-arginine 200 mg/kg/d, and the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine-methyl ester (L-NAME) 100 mg/kg/d used with the same dose of L-arginine or Rg(1) were given starting from 1 d after surgery for 21 consecutive days. LV hypertrophy was evidenced by determining LV weight and mRNA expression of atrial natriuretic peptide, a marker of cardiac hypertrophic response, as well as by histopathology. Rg(1) and L-arginine administration significantly reduced the elevated LV hypertrophic parameters independent of LV systolic pressure changing, and ameliorated the histopathology of LV myocardium and LV diastolic function. All the beneficial effects of Rg(1) and L-arginine were abolished or blunted by L-NAME. Further to examine the role of NO in Rg(1) inhibition on LV hypertrophy, expression of endothelial NOS was determined at the transcript levels. In our experimental conditions endothelial NOS mRNA expression in LV tissue was lowered by abdominal aorta coarctation, and upregulated by Rg(1) administration. These results demonstrate that Rg(1)-induced protection against LV hypertrophy elicited by abdominal aorta coarctation in rats is mediated, at least in part, via endogenous NO production and release.

Topics: Abdomen; Animals; Aortic Coarctation; Arginine; Atrial Natriuretic Factor; Cardiovascular Agents; Disease Models, Animal; Endothelium; Ginsenosides; Heart Ventricles; Hypertrophy, Left Ventricular; Male; Myocardium; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Organ Size; Panax; Phytotherapy; Random Allocation; Rats; Rats, Sprague-Dawley; RNA, Messenger

Myocardial hypertrophy has been recognized to be an adaptive response to a variety of external stimuli (e.g., myocardial infarction, pressure overload, catecholamine treatment, endocrine disorders) that are involved in several subcellular factors that mediate signaling pathways, from external stimuli to nuclear protein synthesis. Glycogen synthase kinase-3beta (GSK-3beta) is one of the subcellular factors that regulate nuclear transcription factors, such as activated T-cell (NFAT) proteins, that are related to gene programming during cardiac hypertrophy. On the other hand, GSK-3beta, known as a regulator of cardiomyocyte growth in Wnt signaling of cardiogenesis, is involved in beta-catenin degradation. Inhibition of GSK-3beta has been reported to induce cardiac hypertrophy. Tateishi et al. demonstrated in an aortic constriction-induced acute hypertrophy model using 6-week-old Wister rats that if GSK-3b is inhibited by LiCl up-regulated beta-catenin expression and additional hypertrophy were observed. They suggested that Li(2+) had an additive effect on pressure overload-induced hypertrophy through the GSK-3beta-beta-catenin pathway. Their article provides promising information on the mechanism of hypertrophic myocyte growth during acute pressure overload.

Topics: Animals; Aorta, Abdominal; Atrial Natriuretic Factor; beta Catenin; Blood Pressure; Cardiovascular Agents; Disease Models, Animal; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Hypertension; Hypertrophy, Left Ventricular; Ligation; Lithium Chloride; Phosphorylation; Protein Kinase Inhibitors; Rats; RNA, Messenger; Serine; Time Factors

A large number of diverse signaling molecules in cell and animal models participate in the stimulus-response pathway through which the hypertrophic growth of the myocardium is controlled. However, the mechanisms of signaling pathway including the influence of lithium, which is known as an inhibitor of glycogen synthase kinase-3beta, in pressure overload hypertrophy remain unclear. The aim of our study was to determine whether glycogen synthase kinase-3beta inhibition by lithium has acute effects on the myocyte growth mechanism in a pressure overload rat model.. First, we created a rat model of acute pressure overload cardiac hypertrophy by abdominal aortic banding. Protein expression time courses for beta-catenin, glycogen synthase kinase-3beta, and phosphoserine9-glycogen synthase kinase-3beta were then examined. The rats were divided into four groups: normal rats with or without lithium administration and pressure-overloaded rats with or without lithium administration. Two days after surgery, Western blot analysis of beta-catenin, echo-cardiographic evaluation, left ventricular (LV) weight, and LV atrial natriuretic peptide mRNA levels were evaluated.. We observed an increase in the level of glycogen synthase kinase-3beta phosphorylation on Ser 9. A significant enhancement of LV heart weight (P < 0.05) and interventricular septum and posterior wall thickness (P < 0.05) with pressure-overloaded hypertrophy in animals treated with lithium were also observed. Atrial natriuretic peptide mRNA levels were significantly increased with pressure overload hypertrophy in animals treated with lithium.. We have shown in an animal model that inhibition of glycogen synthase kinase-3beta by lithium has an additive effect on pressure overload cardiac hypertrophy.

Topics: Animals; Aorta, Abdominal; Atrial Natriuretic Factor; beta Catenin; Blood Pressure; Blotting, Western; Cardiovascular Agents; Disease Models, Animal; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Hypertension; Hypertrophy, Left Ventricular; Ligation; Lithium Chloride; Male; Phosphorylation; Polymerase Chain Reaction; Protein Kinase Inhibitors; Rats; Rats, Wistar; RNA, Messenger; Serine; Time Factors; Ultrasonography

The study was designed to examine the effects of polydatin on ventricular remodeling induced by isoproterenol in mice and by abdominal aortic banding in rats. Polydatin reduced cardiac weight indexes in mice and rats, lowered the contents of cyclic AMP and angiotensin II in mice. It also decreased the size of cardiomyocyte, the levels of aldosterone, tumor necrosis factor-α, angiotensin II and endothelin-1, reduced ventricular collagen volume and decreased blood pressure in rats. The results demonstrate that polydatin has the beneficial effects on attenuating ventricular remodeling, which are associated with its inhibiting the activation of neurohormone, especially in rennin-angiotensin-aldosterone system.

Topics: Aldosterone; Angiotensin II; Animals; Aorta, Abdominal; Blood Pressure; Cardiovascular Agents; Collagen; Cyclic AMP; Drugs, Chinese Herbal; Endothelin-1; Fallopia japonica; Glucosides; Heart; Hypertrophy, Left Ventricular; Isoproterenol; Male; Mice; Myocytes, Cardiac; Organ Size; Phytotherapy; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System; Stilbenes; Tumor Necrosis Factor-alpha; Ventricular Remodeling

α-Sulfone-α-piperidine and α-tetrahydropyranyl hydroxamates were explored that are potent inhibitors of MMP's-2, -9, and -13 that spare MMP-1, with oral efficacy in inhibiting tumor growth in mice and left-ventricular hypertrophy in rats and in the bovine cartilage degradation ex vivo explant system. α-Piperidine 19v (SC-78080/SD-2590) was selected for development toward the initial indication of cancer, while α-piperidine and α-tetrahydropyranyl hydroxamates 19w (SC-77964) and 9i (SC-77774), respectively, were identified as backup compounds.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Biological Availability; Cardiovascular Agents; Cartilage, Articular; Cattle; Crystallography, X-Ray; Humans; Hydroxamic Acids; Hypertrophy, Left Ventricular; Macaca fascicularis; Matrix Metalloproteinase Inhibitors; Mice; Mice, Nude; Models, Molecular; Molecular Structure; Piperidines; Pyrans; Rats; Structure-Activity Relationship; Sulfones; Xenograft Model Antitumor Assays

1. The role of growth hormone (GH) in cardiac remodelling and function in chronic and persistent pressure overload-induced left ventricular hypertrophy has not been defined. The aim of the present study was to assess short-term GH treatment on left ventricular function and remodelling in rats with chronic pressure overload-induced hypertrophy. 2. Twenty-six weeks after induction of ascending aortic stenosis (AAS), rats were treated with daily subcutaneous injections of recombinant human GH (1 mg/kg per day; AAS-GH group) or saline (AAS-P group) for 14 days. Sham-operated animals served as controls. Left ventricular function was assessed by echocardiography before and after GH treatment. Myocardial fibrosis was evaluated by histological analysis. 3. Before GH treatment, AAS rats presented similar left ventricular function and structure. Treatment of rats with GH after the AAS procedure did not change bodyweight or heart weight, both of which were higher in the AAS groups than in the controls. After GH treatment, posterior wall shortening velocity (PWSV) was lower in the AAS-P group than in the control group. However, in the AAS-GH group, PWSV was between that in the control and AAS-P groups and did not differ significantly from either group. Fractional collagen (% of total area) was significantly higher in the AAS-P and AAS-GH groups compared with control (10.34 +/- 1.29, 4.44 +/- 1.37 and 1.88 +/- 0.88%, respectively; P < 0.05) and was higher still in the AAS-P group compared with the AAS-GH group. 4. The present study has shown that short-term administration of GH to rats with chronic pressure overload-induced left ventricular hypertrophy induces cardioprotection by attenuating myocardial fibrosis.

Topics: Animals; Aorta; Aortic Diseases; Cardiovascular Agents; Chronic Disease; Constriction, Pathologic; Disease Models, Animal; Echocardiography; Fibrosis; Human Growth Hormone; Hypertrophy, Left Ventricular; Injections, Subcutaneous; Male; Myocardial Contraction; Myocardium; Rats; Rats, Wistar; Recombinant Proteins; Time Factors; Ventricular Function, Left; Ventricular Remodeling

We investigated the effects of iptakalim, a new ATP-sensitive potassium channel (K(ATP)) opener providing endothelial protection, on the progression of cardiac hypertrophy to failure in a rat model of pressure overloading caused by abdominal aortic banding (AAB). Endothelial dysfunction is central to cardiac hypertrophy and failure induced by pressure overload. It would be useful to clarify whether iptakalim could prevent this.. The effects of pressure overload were assessed in male Sprague-Dawley rats 6 weeks after AAB using progression of cardiac hypertrophy to heart failure as the endpoint. The AAB-treated rats had significantly elevated blood pressure, systolic and diastolic cardiac dysfunction, evidence of left ventricular hypertrophy (LVH), and transition to heart failure. LVH was characterized by increases in the ratios of heart and left ventricular weights to body weight, increased myocyte cross-sectional areas, myocardial and perivascular fibrosis, and elevated cardiac hydroxyproline. These could be prevented by treatment with iptakalim at daily oral doses of 1, 3, and 9 mg/kg for 6 weeks. Progression to cardiac failure, demonstrated by increases in relative lung and right ventricular weights, cardiac function disorders and overexpression of atrial and B-type natriuretic peptide mRNA, could also be prevented. The downregulated nitric oxide signalling system was enhanced, whereas the upregulated endothelin signalling system was inhibited, resulting in normalization of the balance between these two systems.. Iptakalim protected the endothelium and prevented progression of cardiac hypertrophy to failure induced by a pressure overload.

Topics: Animals; Aorta, Abdominal; Atrial Natriuretic Factor; Blood Pressure; Cardiovascular Agents; Disease Models, Animal; Disease Progression; Dose-Response Relationship, Drug; Endothelin-1; Endothelium, Vascular; Fibrosis; Heart Failure; Heart Rate; Hydroxyproline; Hypertension; Hypertrophy, Left Ventricular; KATP Channels; Male; Myocardium; Natriuretic Peptide, Brain; Nitric Oxide; Propylamines; Rats; Rats, Sprague-Dawley; Signal Transduction; Time Factors; Ventricular Remodeling

Oxidative stress followed by abnormal signalling can play a critical role in the development of long-term, high blood pressure-induced cardiac remodelling in heart failure (HF). Since oxidative stress-induced poly(ADP-ribose)polymerase (PARP) activation and cell death have been observed in several experimental models, we investigated the possibility that inhibition of nuclear PARP improves cardiac performance and delays transition from hypertensive cardiopathy to HF in a spontaneously hypertensive rat (SHR) model of HF.. SHRs were divided into two groups: one received no treatment (SHR-C) and the other (SHR-L) received 5 mg/kg/day L-2286 (PARP-inhibitor) orally for 46 weeks. A third group was a normotensive age-matched control group (CFY) and a fourth was a normotensive age-matched group receiving L-2286 treatment 5 mg/kg/day (CFY+L). At the beginning of the study, systolic function was similar in both CFY and SHR groups. In the SHR-C group at the end of the study, eccentric hypertrophy with poor left ventricular (LV) systolic function was observed, while PARP inhibitor treatment preserved systolic LV function. Due to these favourable changes, the survival rate of SHRs was significantly improved (P < 0.01) by the administration of the PARP inhibitor (L-2286). The PARP inhibitor used did not affect the elevated blood pressure of SHR rats, but moderated the level of plasma-BNP (P < 0.01) and favourably influenced all the measured gravimetric parameters (P < 0.05) and the extent of myocardial fibrosis (P < 0.05). The inhibition of PARP increased the phosporylation of Akt-1/GSK-3beta (P < 0.01), ERK 1/2 (P < 0.01), and PKC epsilon (P < 0.01), and decreased the phosphorylation of JNK (P < 0.05), p-38 MAPK (P < 0.01), PKC pan betaII and PKC zeta/lambda (P < 0.01), and PKC alpha/betaII and delta (P < 0.05).. These data demonstrate that chronic inhibition of PARP induces long-term favourable changes in the most important signalling pathways related to oxidative stress. PARP inhibition also prevents remodelling, preserves systolic function, and delays transition of hypertensive cardiopathy to HF in SHRs.

Topics: Administration, Oral; Animals; Blood Pressure; Cardiovascular Agents; Disease Models, Animal; Disease Progression; Enzyme Inhibitors; Extracellular Signal-Regulated MAP Kinases; Fibrosis; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Heart Failure; Hypertension; Hypertrophy, Left Ventricular; Isoenzymes; JNK Mitogen-Activated Protein Kinases; Male; Myocardium; Natriuretic Peptide, Brain; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Piperidines; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Protein Kinase C; Proto-Oncogene Proteins c-akt; Quinazolines; Rats; Rats, Inbred SHR; Signal Transduction; Time Factors; Ventricular Function, Left; Ventricular Remodeling

Topics: Animals; Cardiovascular Agents; Disease Progression; Endothelin-1; Endothelium, Vascular; Fibrosis; Heart Failure; Hemodynamics; Humans; Hypertension; Hypertrophy, Left Ventricular; KATP Channels; Mice; Myocardium; Nitric Oxide; Propylamines; Signal Transduction; Ventricular Remodeling

Tumor necrosis factor (TNF)-alpha is a proinflammatory cytokine that has been implicated in the pathogenesis of heart failure. In contrast, we have recently shown that myocardial levels of TNF-alpha are acutely elevated in the aortocaval (AV) fistula model of heart failure. Based on these observations, we hypothesized that progression of adverse myocardial remodeling secondary to volume overload would be prevented by inhibition of TNF-alpha with etanercept. Furthermore, a principal objective of this study was to elucidate the effect of TNF-alpha inhibition during different phases of the myocardial remodeling process. Eight-week-old male Sprague-Dawley rats were randomly divided into the following three groups: sham-operated controls, untreated AV fistulas, and etanercept-treated AV fistulas. Each group was further subdivided to study three different time points consisting of 3 days, 3 wk, and 8 wk postfistula. Etanercept was administered subcutaneously at 1 mg/kg body wt. Etanercept prevented collagen degradation at 3 days and significantly attenuated the decrease in collagen at 8 wk postfistula. Although TNF-alpha antagonism did not prevent the initial ventricular dilatation at 3 wk postfistula, etanercept was effective at significantly attenuating the subsequent ventricular hypertrophy, dilatation, and increased compliance at 8 wk postfistula. These positive adaptations achieved with etanercept administration translated into significant functional improvements. At a cellular level, etanercept also markedly attenuated increases in cardiomyocyte length, width, and area at 8 wk postfistula. These observations demonstrate that TNF-alpha has a pivotal role in adverse myocardial remodeling and that treatment with etanercept can attenuate the progression to heart failure.

Topics: Animals; Aorta, Abdominal; Arteriovenous Fistula; Cardiovascular Agents; Cell Size; Collagen; Compliance; Disease Models, Animal; Disease Progression; Etanercept; Heart Failure; Hypertrophy, Left Ventricular; Immunoglobulin G; Injections, Subcutaneous; Male; Myocardial Contraction; Myocytes, Cardiac; Rats; Rats, Sprague-Dawley; Receptors, Tumor Necrosis Factor; Time Factors; Tumor Necrosis Factor-alpha; Venae Cavae; Ventricular Function, Left; Ventricular Pressure; Ventricular Remodeling

Topics: Cardiovascular Agents; Death, Sudden, Cardiac; Diabetes Mellitus, Type 2; Humans; Hyperkalemia; Hypertension; Hypertrophy, Left Ventricular; Hypoglycemic Agents; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Risk Factors; Sulfonylurea Compounds

A 64-year-old male was observed as an outpatient with atypical, non-exercise-induced chest pain and palpitations. He had arterial hypertension and marked concentric left ventricular hypertrophy. After 2.5 years of antihypertensive drug therapy the patient's blood pressure had returned to normal, but his left ventricular hypertrophy was unchanged.. Electrocardiography, transthoracic echocardiography, myocardial perfusion scintigraphic imaging, measurement of alpha-galactosidase A activity, gene sequencing, brain MRI, carotid artery ultrasonography, biochemical renal evaluation and cardiac Doppler tissue imaging.. Cardiac Fabry's disease.. Losartan, hydrochlorothiazide, low-dose aspirin and bisoprolol. The patient is expected to begin enzyme replacement therapy.

Topics: alpha-Galactosidase; Cardiovascular Agents; Echocardiography; Electrocardiography; Enzyme Therapy; Fabry Disease; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged

The management of asymptomatic severe mitral regurgitation remains controversial. The aim of this study was to evaluate the outcome of a watchful waiting strategy in which patients are referred to surgery when symptoms occur or when asymptomatic patients develop left ventricular (LV) enlargement, LV dysfunction, pulmonary hypertension, or recurrent atrial fibrillation.. A total of 132 consecutive asymptomatic patients (age 55+/-15 years, 49 female) with severe degenerative mitral regurgitation (flail leaflet or valve prolapse) were prospectively followed up for 62+/-26 months. Patients underwent serial clinical and echocardiographic examinations and were referred for surgery when the criteria mentioned above were fulfilled. Overall survival was not statistically different from expected survival either in the total group or in the subgroup of patients with flail leaflet. Eight deaths were observed. Thirty-eight patients developed criteria for surgery (symptoms, 24; LV criteria, 9; pulmonary hypertension or atrial fibrillation, 5). Survival free of any indication for surgery was 92+/-2% at 2 years, 78+/-4% at 4 years, 65+/-5% at 6 years, and 55+/-6% at 8 years. Patients with flail leaflet tended to develop criteria for surgery slightly but not significantly earlier. There was no operative mortality. Postoperative outcome was good with regard to survival, symptomatic status, and postoperative LV function.. Asymptomatic patients with severe degenerative mitral regurgitation can be safely followed up until either symptoms occur or currently recommended cutoff values for LV size, LV function, or pulmonary hypertension are reached. This management strategy is associated with good perioperative and postoperative outcome but requires careful follow-up.

Topics: Aged; Atrial Fibrillation; Cardiovascular Agents; Case Management; Comorbidity; Disease Progression; Disease-Free Survival; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Hypertrophy, Left Ventricular; Life Tables; Male; Middle Aged; Mitral Valve Insufficiency; Mitral Valve Prolapse; Prospective Studies; Survival Analysis; Time Factors; Treatment Outcome; Ultrasonography; Ventricular Dysfunction, Left

The objective was to assess the cardiac effects of growth hormone (GH) therapy. Anthracycline-treated childhood cancer survivors frequently have reduced left ventricular (LV) wall thickness and contractility, and GH therapy may affect these factors.. We examined serial cardiac findings for 34 anthracycline-treated childhood cancer survivors with several years of GH therapy and baseline cardiac z scores similar to those of a comparison group (86 similar cancer survivors without GH therapy).. LV contractility was decreased among GH-treated patients before, during, and after GH therapy (-1.08 SD below the age-adjusted population mean before therapy and -1.88 SD 4 years after therapy ceased, with each value depressed below normal). Contractility was higher in the control group than in the GH-treated group, with this difference being nearly significant. The GH-treated children had thinner LV walls before GH therapy (-1.38 SD). Wall thickness increased during GH therapy (from -1.38 SD to -1.09 SD after 3 years of GH therapy), but the effect was lost shortly after GH therapy ended and thickness diminished over time (-1.50 SD at 1 year after therapy and -1.96 SD at 4 years). During GH therapy, the wall thickness for the GH-treated group was greater than that for the control group; however, by 4 years after therapy, there was no difference between the GH-treated group and the control group.. GH therapy among anthracycline-treated survivors of childhood cancer increased LV wall thickness, but the effect was lost after therapy was discontinued. The therapy did not affect the progressive LV dysfunction.

Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Body Height; Cardiovascular Agents; Child; Child, Preschool; Enalapril; Female; Heart Ventricles; Hemodynamics; Human Growth Hormone; Humans; Hypertrophy, Left Ventricular; Hypopituitarism; Infant; Male; Myocardial Contraction; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Survivors; Ultrasonography; Ventricular Dysfunction, Left

Congestive heart failure (CHF) results in decreased cardiac sympathetic innervation.. The purpose of this study was to test the hypothesis that therapy with the vasopeptidase inhibitor omapatrilat (OMA) attenuates cardiac neuronal remodeling in CHF.. We induced CHF in dogs with rapid ventricular pacing for 5 weeks with (CHF+OMA group, n = 8) or without (CHF group, n = 10) concomitant OMA treatment (10 mg/kg twice daily). Cardiac catheterization and echocardiography were performed to determine cardiac structure and hemodynamic parameters. Myocardial nerve density was determined by immunocytochemical staining with anti-growth associated protein 43 (GAP43) and anti-tyrosine hydroxylase (TH) antibodies. Seven normal dogs were used as histologic controls.. In the CHF group, ascites developed in 3 dogs and 4 dogs died, compared with no ascites or death in the CHF+OMA group (P = .07). In the 6 CHF dogs that survived, all had atrial fibrosis, severely depressed left ventricular systolic function, and increased atrial and ventricular chamber size. OMA treatment decreased the atrial and ventricular chamber sizes and the degree of atrial fibrosis. Most CHF dogs showed severe myocardial denervation, although some showed normal or abnormally high nerve counts. OMA treatment prevented heterogeneous reduction of nerve density. The left ventricular TH-positive nerve densities were 128 +/- 170 microm(2)/mm(2), 261 +/- 185 microm(2)/mm(2), and 503 +/- 328 microm(2)/mm(2) (P < .05), and the atrial GAP43-positive nerve densities were 1,683 +/- 1,365 microm(2)/mm(2), 305 +/- 368 microm(2)/mm(2), and 1,278 +/- 1,479 microm(2)/mm(2) (P < .05) for the control, CHF, and CHF+OMA groups, respectively.. CHF results in heterogeneous cardiac denervation. Long-term OMA treatment prevented the reduction of nerve density and promoted beneficial cardiac structural remodeling.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Cardiovascular Agents; Disease Models, Animal; Dogs; Heart Atria; Heart Failure; Heart Ventricles; Hypertrophy, Left Ventricular; Male; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue; Pyridines; Renin; Stroke Volume; Thiazepines; Ventricular Dysfunction, Left; Ventricular Pressure; Ventricular Remodeling

We tested the hypothesis that induction of chronic bradycardia would trigger an upregulation of key growth factors and receptors, which would then lead to angiogenesis and improve coronary reserve in the left ventricle after myocardial infarction.. Bradycardia was induced in rats by administering alinidine via osmotic pumps beginning 1 day after coronary artery ligation. Echocardiographic analysis was conducted before and after treatment. Morphometric analysis was used in perfusion-fixed hearts to document arteriolar and capillary growth. Western blots were used to evaluate growth factor and receptor changes. During the first week of treatment, vascular endothelial growth factor (VEGF), VEGF receptor 1 (Flt-1), and basic fibroblast growth factor proteins were higher in the treated group, whereas VEGF receptor 2 (Flk-1), angiopoietin-1, and angiopoietin-2 were not affected by treatment. After 3 weeks, VEGF protein remained elevated, and bradycardia was associated with a higher capillary length density in the border (40%) and remote (14%) regions and a higher arteriolar length density in the septum (62%), despite a greater increase in left ventricular mass. Although arteriolar length density increased in all size classes, the greatest increase occurred in the smallest (terminal) arterioles. This vascular growth was associated with a 23% greater coronary reserve. Echocardiography revealed a smaller increase in ventricular volume and a greater preservation of ejection fraction in rats treated with bradycardia.. Pharmacologic induction of bradycardia enhances vascularity and coronary reserve, preserves function of surviving myocardium, and therefore, is a noninvasive, therapeutic avenue that provides an alternative to gene therapy.

Topics: Angiopoietin-1; Angiopoietin-2; Animals; Bradycardia; Cardiovascular Agents; Clonidine; Coronary Vessels; Drug Evaluation, Preclinical; Extracellular Matrix Proteins; Fibroblast Growth Factor 2; Heart Ventricles; Hypertrophy, Left Ventricular; Ligation; Male; Models, Animal; Myocardial Infarction; Myocytes, Cardiac; Neovascularization, Physiologic; Rats; Rats, Sprague-Dawley; Stroke Volume; Ultrasonography; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor Receptor-2

Topics: Aortic Valve Insufficiency; Cardiovascular Agents; Chronic Disease; Humans; Hypertrophy, Left Ventricular; Practice Guidelines as Topic; Systole; United States; Ventricular Dysfunction, Left

Interferon-alpha (IFN-alpha) has been widely used for treatment of chronic hepatitis C in Japan. In general, cardiovascular adverse reactions are rare in association with IFN-alpha therapy. Here, a 64-year-old man with chronic active hepatitis C complained of fatigue, palpitation and depression, and developed atrial fibrillation with prominent negative T waves during IFN-alpha therapy. Echocardiogram showed septal and apical hypertrophy. Three days after discontinuation of IFN-alpha, subjective symptoms and atrial fibrillation subsided. It is unclear whether or not IFN-alpha induced the giant negative T waves with apical hypertrophy. We might observe the developing course of hepatitis C virus (HCV)-related myocardial hypertrophy by chance. Cardiovascular toxicity should be carefully monitored during IFN-alpha therapy even in patients with minor cardiac disease, such as premature ventricular contracture (PVC) and mild hypertension.

Topics: Antihypertensive Agents; Antiviral Agents; Atrial Fibrillation; Atrial Premature Complexes; Cardiovascular Agents; Electrocardiography; Hepatitis C, Chronic; Humans; Hypertension; Hypertrophy, Left Ventricular; Interferon alpha-2; Interferon-alpha; Male; Middle Aged; Recombinant Proteins; Tachycardia; Ultrasonography

The present study examined the ability of dual-chamber (DDD) pacing to improve symptoms and exercise tolerance in patients with non-obstructive hypertrophic cardiomyopathy (HNCM). Seven patients with HNCM who had failed to benefit from pharmacotherapy participated in the study. The New York Heart Association (NHYA) functional class status and exercise tolerance, which was determined by the treadmill exercise test, were recorded and an echocardiographic observation was performed before, and 1 week, 3 months and 1 year after the implantation of a permanent DDD pacemaker. The atrioventricular delay (AVd) was determined by measuring the point of peak rapid filling velocity and maximum cardiac output (CO). Two patients were not implanted with a permanent pacemaker because their CO and blood pressure decreased or because palpitation occurred during temporary pacing. The ratio between early and late peaks of flow velocity (1.56, 1.21,0.95, and 0.86 before implantation and 1 week, 3 months and 1 year after implantation, respectively); deceleration time (ms: 263.2, 217.6, 204.6, 187.0); peak filling rate (ml/s: 146.2, 204.0, 233.2, 243.6); NYHA functional class status (2.0, 1.8, 1.6, 1.4); and exercise tolerance (s: 203, 264, 403, 480) were significantly improved after implantation. However, left ventricular dimension, percent fractional shortening, ejection fraction, acceleration time and the isovolumic relaxation time were not changed significantly. In conclusion, DDD pacing improved symptoms and the NYHA functional class status, which is associated with improvement of left ventricular diastolic function. It is proposed that DDD pacing would be useful in patients not only with obstructive but also non-obstructive hypertrophic cardiomyopathy refractory to medical treatment, depending on the careful selection of subjects.

Topics: Aged; Cardiac Pacing, Artificial; Cardiovascular Agents; Diastole; Drug Resistance; Echocardiography; Echocardiography, Doppler; Exercise Test; Exercise Tolerance; Female; Follow-Up Studies; Heart Failure; Heart Ventricles; Hemodynamics; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Severity of Illness Index; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Pressure

Omapatrilat is a newly developed vasopeptidase inhibitor that inhibits both angiotensin-converting enzyme (ACE) and neutral endopeptidase and has potent antihypertensive efficacy. However, the specific effect of omapatrilat on cardiac function and left ventricular hypertrophy with hypertension remains controversial. Therefore, we investigated the effect of omapatrilat on blood pressure, cardiac hypertrophy, and cardiac function in spontaneously hypertensive rats (SHR). Studies were performed in SHR that received vehicle (n = 9), omapatrilat (n = 10), or fosinopril (ACE inhibitor, n = 7) by daily gavage for 56 days. Systolic blood pressure (SBP) and mean blood pressure (MBP) were measured by tail plethysmography. Left ventricular fractional shortening and left ventricular mass were measured by echocardiography at day 56. Omapatrilat and fosinopril significantly decreased SBP and MBP from day 1 through day 56, and omapatrilat markedly reduced SBP and MBP compared with fosinopril from day 21 to day 56. Although both omapatrilat and fosinopril decreased left ventricular mass and left ventricular mass-to-body weight ratio with increased LV fractional shortening, omapatrilat had a more potent effect on the reduction of left ventricular mass and improvement of cardiac function. This study shows that in SHR, omapatrilat mediated a potent and stable antihypertensive effect and a reduction in left ventricular mass with improvement of cardiac function, compared with ACE inhibition alone.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Cardiovascular Agents; Endocardium; Fosinopril; Hemodynamics; Hypertension; Hypertrophy, Left Ventricular; Male; Pyridines; Rats; Rats, Inbred SHR; Thiazepines; Ventricular Function, Left

Topics: Angina, Unstable; Cardiovascular Agents; Female; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Middle Aged; Shock, Cardiogenic; Ventricular Outflow Obstruction

Excess cardiovascular morbidity and mortality among African (black) Americans remains an important yet unexplained public health problem. One possible explanation proposes that intrinsic or acquired abnormalities in coronary vascular reactivity and endothelial function result in excess ischemia among black Americans. To examine this hypothesis, we subjected 80 individuals with normal coronary arteries to invasive testing of coronary artery and microvascular relaxation using intracoronary infusions of acetylcholine and adenosine, a Doppler tipped intracoronary guide wire, and quantitative coronary angiography. We measured the percent increase in coronary blood flow and epicardial diameter after graded infusion of intracoronary acetylcholine and in coronary blood flow after intracoronary adenosine in 31 normotensive subjects (10 black, 21 white) and 49 hypertensive subjects with left ventricular hypertrophy (25 black, 24 white). Categorical and multivariate analyses revealed that in response to intracoronary adenosine and acetylcholine, the depression in endothelium-independent and -dependent microvascular relaxation during peak agonist effect was largely related to the presence of chronic hypertension and left ventricular hypertrophy. Normotensive subjects demonstrated no intrinsic racial differences in conduit and resistance vessel vasoreactivity. In response to maximal infusion of acetylcholine, epicardial coronary arteries constricted similarly in black and white subjects with hypertensive left ventricular hypertrophy and dilated similarly in normotensive black and white subjects. Thus, our study shows that in a cohort of black and white subjects referred for coronary arteriography because of chest pain, African American race is not associated with excess intrinsic or acquired depression in coronary vascular relaxation during the peak effect of the endothelium-dependent and -independent agonists acetylcholine and adenosine, after adjustment for the presence of left ventricular hypertrophy.

Topics: Adenosine; Adult; Black People; Cardiovascular Agents; Cohort Studies; Coronary Circulation; Coronary Vessels; Endothelium, Vascular; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Infusions, Intra-Arterial; Male; Middle Aged; Muscle Relaxation; Prospective Studies; White People

Topics: Cardiovascular Agents; Humans; Hypertension; Hypertrophy, Left Ventricular; Ventricular Dysfunction, Left

Left ventricular failure has been subdivided into different forms. Systolic pump failure (= systolic dysfunction) and diastolic filling failure (= diastolic dysfunction) are important entities in the overall framework of heart failure. The clinical patterns of both are presented in light of 2 case reports: systolic dysfunction involves the combination of left ventricular failure, cardiomegaly and depressed systolic ejection fraction. Diastolic dysfunction is accompanied by pulmonary congestion in the presence of a normal or only slightly enlarged ventricle and a normal ejection fraction. Prognosis of systolic dysfunction is poor, with a 5-year survival rate of 40%, compared to 70% in patients with isolated diastolic dysfunction. Medical treatment of systolic dysfunction is based primarily on ACE-inhibitors followed by diuretics and digitalis. Betablockers in low doses and spironolactone can provide additional benefit. Calcium channel blockers are rarely indicated, due to their negative inotropic effects. In patients with diastolic dysfunction, however, they are the first choice because of their positive lusitropic effect on relaxation and ventricular filling. ACE-inhibitors are suitable in hypertensive heart disease, while diuretics and betablockers are second line drugs. Digitalis should be avoided since worsening of diastolic function may occur.

Topics: Cardiovascular Agents; Diastole; Drug Therapy, Combination; Heart Failure; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Stroke Volume; Systole; Ventricular Function, Left