lisinopril and Ventricular-Dysfunction--Left

Congestive heart failure is a pathologic condition characterized by progressive decrease in left ventricular contractility and consequent decline of cardiac output. There is convincing clinical and experimental evidence that the renin-angiotensin system (RAS) and its primary effector peptide, angiotensin II, are linked to the pathophysiology of interstitial fibrosis, cardiac remodeling, and heart failure. In addition to the traditional endocrine or circulating RAS, an active tissue RAS has been characterized. Tissue angiotensin-converting enzyme and locally synthesized angiotensin II, for example, by chymase, exert local trophic effects that modulate gene expression, which regulates growth and proliferation in both myocytes and nonmyocytes. The existence of the tissue RAS offers an opportunity for targeted imaging, which may be of considerable value for guiding medical therapy.

Topics: Animals; Diagnostic Imaging; Gene Expression Regulation, Enzymologic; Heart Failure; Humans; Lisinopril; Myocardium; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Ventricular Dysfunction, Left

Ventricular remodeling indicates a dynamic process, starting with and after acute myocardial infarction, as a result of structural and functional modifications which involve acutely and chronically both the infarcted and noninfarcted zones of the left ventricle. The most effective way to prevent or minimize post-MI cardiac remodeling is to limit the extent of the initial insult. This can be partly achieved by early myocardial reperfusion obtained by different strategies including thrombolysis. In 6405 patients of the GISSI-3 trial, 2D echocardiographic studies were available at predischarge, at 6 weeks and at 6 months after the infarction. The increase in left ventricular volumes over time was reduced by 6-week lisinopril treatment. Patients randomized to lisinopril had smaller volume also at 6 months, after withdrawal of treatment at 6 weeks. Important prognostic indications can also be derived from predischarge echocardiography, since larger quartiles of left ventricular volumes and lower quartile of ejection fraction indicates higher risk of mortality and non-fatal congestive heart failure in the 6 months after the index event, even in the relatively low risk general population of infarcts of the GISSI-3.

Topics: Angiotensin-Converting Enzyme Inhibitors; Clinical Trials as Topic; Humans; Lisinopril; Myocardial Infarction; Myocardium; Prognosis; Ultrasonography; Ventricular Dysfunction, Left; Ventricular Function, Left

Trastuzumab (TZB) is an established therapy for HER2-positive breast cancer. The use of TZB is commonly associated with cardiotoxicity manifesting as asymptomatic decrease in left ventricular ejection fraction (LVEF) or overt heart failure. Several studies demonstrated favorable effects of angiotensin-converting enzyme (ACE) inhibitors and β-blockers (BBs) in the prevention of chemotherapy-induced cardiotoxicity. We hypothesize that patients, randomized to receive an ACE inhibitor or a BB during trastuzumab therapy for breast cancer, will maintain a higher LVEF than patients randomized to placebo.. We designed a prospective, multicenter, randomized, phase II placebo-controlled clinical trial to evaluate the effects of an ACE inhibitor (lisinopril) and a BB (carvedilol phosphate-extended release) on cardiotoxicity in patients with breast cancer who are receiving adjuvant or neoadjuvant TZB therapy. The primary objectives include (1) comparison of incidence of cardiotoxicity and (2) comparison of LVEF as a continuous variable in between the arms. Cardiotoxicity was defined as an absolute decrease in LVEF from baseline of ≥10% at follow-up or an absolute decrease of ≥5% in LVEF from baseline for individuals with <50% LVEF at follow-up. The target accrual is 468 participants, representing patients both with and without anthracycline exposure. The enrollment is completed. The trial is co-sponsored by University of South Florida and National Cancer Institute. The LVEF is being evaluated by echocardiography or multigated acquisition scan.. If we can demonstrate that the use of an ACE inhibitor or a BB can reduce the degree of TZB-induced cardiotoxicity, it is hoped that patients will receive complete and uninterrupted TZB therapy for breast cancer without compromising cardiac function.

Topics: Adrenergic alpha-1 Receptor Antagonists; Adult; Angiotensin-Converting Enzyme Inhibitors; Antineoplastic Agents; Breast Neoplasms; Carbazoles; Cardiotoxicity; Carvedilol; Dose-Response Relationship, Drug; Female; Humans; Lisinopril; Middle Aged; Propanolamines; Prospective Studies; Stroke Volume; Trastuzumab; Treatment Outcome; Ventricular Dysfunction, Left

Behçet's disease is a chronic inflammatory vasculitis. Vascular involvement is one of the major complications of Behçet's disease, during the course of the disease. Previous studies showed that ACE inhibitors and statins may improve endothelial functions in endothelial dysfunction. The aim of our study is to compare the effects of atorvastatin and lisinopril to placebo on endothelial dysfunction in patients with Behçet's disease.. We prospectively studied 92 (48 female) Behçet's patients who were diagnosed according to the International Study Group criteria. Endothelial dysfunction was evaluated by brachial artery flow-mediated dilatation (FMD) method using high-resolution vascular ultrasound device at baseline and after for 3-month therapy. Patients were consecutively randomized into three groups as (atorvastatin (n = 31), lisinopril (n = 31), and placebo groups (n = 30). Patients in atorvastatin group received 20 mg atorvastatin, lisinopril group received 10 mg lisinopril per day, and placebo group received placebo per day for 3 months.. The baseline characteristics of patients were similar among three groups; however, high-sensitive C-reactive protein (hs-CRP) levels were lower in atorvastatin group than placebo group. A significant improvement in FMD was observed in both atorvastatin (5.0 ± 1.4 vs. 12.8 ± 3.6%, P < 0.001) and lisinopril groups (5.0 ± 1.2 vs. 11.4 ± 5.0%, P < 0.001). Partial significant enhancement was observed in placebo group (4.9 ± 1.1% vs. 5.7 ± 1.0, P = 0.002). However, it was lower than the cutoff value for endothelial dysfunction.. These findings suggest that atorvastatin and lisinopril improve endothelial functions in Behçet's disease patients. However, large studies are needed to determine the long-term effects of atorvastatin and lisinopril therapy.

Topics: Adult; Anticholesteremic Agents; Antihypertensive Agents; Atorvastatin; Behcet Syndrome; Double-Blind Method; Endothelium, Vascular; Female; Heptanoic Acids; Humans; Lisinopril; Male; Placebo Effect; Pyrroles; Treatment Outcome; Ultrasonography; Ventricular Dysfunction, Left

In arterial hypertension, left ventricular hypertrophy (LVH) includes myocyte hypertrophy and fibrosis, which leads to LV diastolic dysfunction and, finally, heart failure. In spontaneously hypertensive rats, myocardial fibrosis was regressed and LV diastolic function was improved by treatment with the angiotensin-converting enzyme inhibitor lisinopril. Whether this holds true for patients with hypertensive heart disease was addressed in this prospective, randomized, double-blind trial.. A total of 35 patients with primary hypertension, LVH, and LV diastolic dysfunction were treated with either lisinopril (n=18) or hydrochlorothiazide (HCTZ; n=17). At baseline and after 6 months, LV catheterization with endomyocardial biopsy, Doppler echocardiography with measurements of LV peak flow velocities during early filling and atrial contraction and isovolumic relaxation time, and 24-hour blood pressure monitoring were performed. Myocardial fibrosis was measured by LV collagen volume fraction and myocardial hydroxyproline concentration. With lisinopril, collagen volume fraction decreased from 6.9+/-0.6% to 6. 3+/-0.6% (P:<0.05 versus HCTZ) and myocardial hydroxyproline concentration from 9.9+/-0.3 to 8.3+/-0.4 microg/mg of LV dry weight (P:<0.00001 versus HCTZ); this was associated with an increase in the early filling and atrial contraction LV peak flow velocity ratio from 0.72+/-0.04 to 0.91+/-0.06 (P:<0.05 versus HCTZ) and a decrease in isovolumic relaxation time from 123+/-9 to 81+/-5 ms (P:<0.00002 versus HCTZ). Normalized blood pressure did not significantly change in either group. No LVH regression occurred in lisinopril-treated patients, whereas with HCTZ, myocyte diameter was reduced from 22. 1+/-0.6 to 20.7+/-0.7 microm (P:<0.01 versus lisinopril).. In patients with hypertensive heart disease, angiotensin-converting enzyme inhibition with lisinopril can regress myocardial fibrosis, irrespective of LVH regression, and it is accompanied by improved LV diastolic function.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Cardiomyopathies; Double-Blind Method; Female; Fibrosis; Humans; Hydrochlorothiazide; Lisinopril; Male; Middle Aged; Myocardium; Prospective Studies; Ventricular Dysfunction, Left

Ventricular remodeling indicates a dynamic process, starting with and after acute myocardial infarction, as a result of structural and functional modifications which involve acutely and chronically both the infarcted and noninfarcted zones of the left ventricle. The most effective way to prevent or minimize post-MI cardiac remodeling is to limit the extent of the initial insult. This can be partly achieved by early myocardial reperfusion obtained by different strategies including thrombolysis. In 6405 patients of the GISSI-3 trial, 2D echocardiographic studies were available at predischarge, at 6 weeks and at 6 months after the infarction. The increase in left ventricular volumes over time was reduced by 6-week lisinopril treatment. Patients randomized to lisinopril had smaller volume also at 6 months, after withdrawal of treatment at 6 weeks. Important prognostic indications can also be derived from predischarge echocardiography, since larger quartiles of left ventricular volumes and lower quartile of ejection fraction indicates higher risk of mortality and non-fatal congestive heart failure in the 6 months after the index event, even in the relatively low risk general population of infarcts of the GISSI-3.

Topics: Angiotensin-Converting Enzyme Inhibitors; Clinical Trials as Topic; Humans; Lisinopril; Myocardial Infarction; Myocardium; Prognosis; Ultrasonography; Ventricular Dysfunction, Left; Ventricular Function, Left

Arterial hypertension may be associated with altered left ventricular filling dynamics. The specific goal of this study was to evaluate whether short-term administration of the ACE inhibitor lisinopril in hypertensive patients with an altered diastolic pattern induced an improvement of left ventricular dynamics, assessed by the echocardio-Doppler technique, independently of effects on left ventricular mass. In a double-blind cross-over study 39 essential hypertensive patients with a ratio of peak early to peak atrial velocity (E/A) < 1 were randomized, after a run-in period of 2 weeks without any antihypertensive treatment, to receive lisinopril (20 mg once a day) and placebo for 4 weeks, respectively. At the end of both the run-in and the treatment periods, blood pressure and heart rate were measured and an echocardio-Doppler examination was carried out. The echocardio-Doppler evaluation was performed both at rest and at the peak of a hand-grip test (3 min at 30% of maximal strength). Left ventricular dimensions were obtained from two-dimensionally guided M-mode tracings using the criteria of the American Society of Echocardiography. Left ventricular peak filling rates and filling rate integrals were measured by a pulsed Doppler technique. Lisinopril caused a significant reduction in systolic and diastolic blood pressure at rest (-13/-9 mmHg vs baseline values, p < 0.05; -6/-4 mmHg vs placebo values, p < 0.05) and during isometric exercise (-17/-9 mmHg vs baseline period, p < 0.05; -6/-5 mmHg vs placebo, p < 0.05). Lisinopril did not induce any significant change in left ventricular structure and systolic function. All the left ventricular filling parameters considered (E velocity, A velocity, E/A ratio) both at rest and during isometric exercise did not significantly differ after lisinopril treatment when compared to those obtained in basal conditions and after placebo administration. This double-blind cross-over study demonstrates that short-term afterload reduction induced by lisinopril does not modify altered diastolic dynamics in hypertensive patients. Diastolic dysfunction of the left ventricle is a complex process influenced by a number of functional and structural factors and apparently cannot be significantly improved by short-term blood pressure reduction by antihypertensive therapy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Coronary Circulation; Cross-Over Studies; Diastole; Double-Blind Method; Echocardiography; Female; Humans; Hypertension; Lisinopril; Male; Middle Aged; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left

This 6-month follow-up analysis sought to assess whether the early reduction of mortality obtained with a 6-week treatment course of lisinopril or glyceryl trinitrate, or both, in unselected patients with acute myocardial infarction outlasts therapy and is still present after 6 months. The primary outcome of the 6-month follow-up was the combined end point of mortality and severe left ventricular dysfunction.. The assumption was that the early benefit on remodeling processes may be maintained over a longer period of time, even in the absence of treatment.. A total of 19,394 patients with acute myocardial infarction were randomized within 24 h of onset of symptoms to a 6-week treatment course of oral lisinopril or open control and, according to a 2 x 2 factorial design, to glyceryl trinitrate or open control. Randomized treatments were stopped after 6 weeks in the absence of specific indications, and the patients were followed up for 6 months.. At 6 months, among patients randomized to lisinopril, 18.1% died or developed severe ventricular dysfunction versus 19.3% of those randomized to no lisinopril (2p = 0.03). No difference was found between patients with and without glyceryl trinitrate therapy (18.4% vs. 18.9%, 2p = 0.39).. Although the systematic administration of glyceryl trinitrate started early and continued for 6 weeks after acute myocardial infarction does not yield evidence of benefit, early treatment with lisinopril appears to improve prognosis. This effect seems to carry over the first 6 months from randomization, even after treatment withdrawal.

Topics: Administration, Cutaneous; Adult; Age Factors; Aged; Angiotensin-Converting Enzyme Inhibitors; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Lisinopril; Male; Middle Aged; Myocardial Infarction; Nitroglycerin; Prognosis; Sex Factors; Time Factors; Treatment Outcome; Vasodilator Agents; Ventricular Dysfunction, Left

This study examined the effects of lisinopril on diastolic function in 12 normotensive patients (mean age 72 years) with symptomatic congestive heart failure, intact left ventricular systolic function and abnormal diastolic function secondary to ischaemic heart disease in a placebo-controlled double blind crossover study, with each treatment dosed orally for 5 continuous weeks. Compared to placebo, lisinopril significantly decreased blood pressure, increased plasma renin activity without altering heart rate or plasma norepinephrine. There was no statistically significant improvement with lisinopril in radionuclide derived peak filling rate and time to peak filling rate, in Doppler echocardiographic measurements of the ratio of peak flow velocity in early diastole to the peak flow velocity of atrial contraction (E:A ratio) and in visual analogue scales of symptoms. Thus, although angiotension converting enzyme inhibitors may have an established role in the treatment of heart failure secondary to left ventricular systolic dysfunction, its use in patients with isolated diastolic dysfunction remains unclear.

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Cross-Over Studies; Diastole; Double-Blind Method; Female; Heart Failure; Humans; Lisinopril; Male; Middle Aged; Prospective Studies; Ventricular Dysfunction, Left

Aim of the METR study - to assess effect of antihypertensive therapy with fixed combination of angiotensin converting enzyme inhibitor lisinopril (10 mg) and calcium antagonist amlodipine (5 mg) on parameters of arterial wall stiffness and central hemodynamics in patients with stage I-II essential hypertension (EH) and functional class II-III ischemic heart disease. Combination therapy was associated with persistent lowering of central arterial pressure, decrease of augmentation index and other parameters of arterial wall stiffness, and reduction of left ventricular myocardial mass. These changes have a potential to lower risk of cardiovascular complications and improve prognosis of patients with EH.

Topics: Aged; Amlodipine; Antihypertensive Agents; Aorta; Blood Pressure; Drug Combinations; Essential Hypertension; Female; Heart Ventricles; Hemodynamics; Humans; Hypertension; Lisinopril; Male; Middle Aged; Organ Size; Prognosis; Vascular Stiffness; Ventricular Dysfunction, Left

Graves hyperthyroidism is commonly seen in clinical practice and Takotsubo stress cardiomyopathy is an increasingly recognized cardiac complication of physical or emotional stress. We report the rare case of a patient with Graves hyperthyroidism that was complicated by severe biventricular takotsubo cardiomyopathy, which was demonstrated on heart catheterization. After appropriate pharmacologic treatment of her hyperthyroidism, she had complete resolution of her cardiomyopathy.

Topics: Adult; Carbazoles; Carvedilol; Drug Therapy, Combination; Electrocardiography; Female; Graves Disease; Humans; Hyperthyroidism; Lisinopril; Methimazole; Propanolamines; Takotsubo Cardiomyopathy; Thyroid Function Tests; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right

Topics: Anthracyclines; Antibiotics, Antineoplastic; Benzazepines; Cardiotoxicity; Dietary Supplements; Drug Therapy, Combination; Female; Humans; Ivabradine; Lisinopril; Middle Aged; Treatment Outcome; Ventricular Dysfunction, Left; Vitamins

Left ventricular hypertrabeculation (LVHT), also known as noncompaction, has been previously reported in a female patient with Turner syndrome (TS) with X0-karyotype, but has not been described in a male patient with a Turner mosaic.. In a 45-year-old man with short stature, facial dysmorphism, cryptorchism, hypospadia, but normal intellectual performance, TS was diagnosed upon cytogenetic evaluation and fluorescence in-situ hybridization revealing the karyotype mos45,X(28)/46,X,+mar(21)/47,X, + 2 mar(1). During an episode of heart failure at age 41 LVHT was detected in the posterolateral region on echocardiography also showing a slightly dilated left ventricle, severely reduced systolic function, and a moderate mitral and tricuspid insufficiency. On cardiac MRI LVHT was additionally seen in the lateral and anterior regions. Under adequate therapy, heart failure completely resolved but LVHT persisted.. LVHT may also occur in association with a mosaic TS with male phenotype. In such patients LVHT may not be accompanied by other congenital cardiac abnormalities but may be associated with severe cardiomyopathy resulting in rhythm abnormalities and heart failure.

Topics: Adrenergic alpha-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Carbazoles; Cardiomyopathy, Dilated; Cardiotonic Agents; Carvedilol; Digoxin; Diuretics; Echocardiography; Furosemide; Heart Ventricles; Humans; Lisinopril; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Mosaicism; Phenotype; Propanolamines; Spironolactone; Turner Syndrome; Ventricular Dysfunction, Left

To investigate whether the combination of exercise training with the angiotensin-converting enzyme inhibitor lisinopril will have an additional beneficial effect on left ventricular function in spontaneously hypertensive rats.. Twelve-week-old male rats were assigned to treadmill running (Ht-Ex; 20 m/min at 5 degrees grade, 1 h/day, 5 days/week), or lisinopril treatment (Ht-Lis; 15 mg/kg per day by gavage), or treadmill running while treated with lisinopril (Ht-ExLis), and were compared with a sedentary group (Ht-Sed). Age-matched and sex-matched Wistar-Kyoto rats were controls.. After 10 weeks of experimentation, left ventricular morphology and function were assessed from M-mode echocardiograms and transmitral Doppler spectra [early (E) and atrial peak velocities (A), their ratio (E/A), and E-wave deceleration time (Edec time) and slope (Edec slope)].. Ht-Sed exhibited prominent concentric left ventricular hypertrophy with systolic and diastolic dysfunctions evidenced by a significantly reduced fractional shortening (%FS) and 'pseudonormalization' of left ventricular filling, characterized by an apparently normal E/A ratio despite an underlying left ventricular relaxation abnormality. Exercise training did not significantly alter left ventricular morphology or function. Lisinopril alone attenuated left ventricular hypertrophy and enhanced diastolic function but had no significant effect on systolic function. Combining exercise training with lisinopril treatment increased %FS by 25%, decreased the E/A ratio and Edec slope by 35% and 37%, respectively, and increased Edec time by 82%.. Our results provide experimental evidence that lisinopril administration, when combined with moderate exercise training, is more promising in attenuating cardiac dysfunction than either agent alone in hypertension of a genetic origin.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Combined Modality Therapy; Hypertension; Hypertrophy, Left Ventricular; Lisinopril; Male; Physical Conditioning, Animal; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Ventricular Dysfunction, Left

The brain renin-angiotensin system contributes significantly to progressive left ventricular (LV) dysfunction in rats after myocardial infarction (MI). The present study evaluated the effects of central versus peripheral plus central angiotensin-converting enzyme (ACE) blockade on sympathetic activity, and LV anatomy and function after MI.. Wistar rats were treated for 4 weeks after MI with the lipophilic ACE inhibitor trandolapril at 5 mg/kg/day or the hydrophilic blocker lisinopril at 50 mg/kg/day by once daily subcutaneous injection, or with a central infusion of lisinopril at 0.1 mg/kg/day.. At 24 hours after the last dose, subcutaneous trandolapril caused 70% to 80% ACE inhibition in both brain and kidneys; lisinopril caused 10% to 20% less. Central infusion of lisinopril caused 70% inhibition of brain ACE and minimal (6%) inhibition in the kidneys. All three treatments similarly improved sympathetic reactivity and arterial baroreflex function. All three treatments lowered cardiac Ang I and II, and similarly attenuated the increases in LV end diastolic pressure, circumference, and fibrosis. Both subcutaneous treatments further decreased LV peak systolic pressure and dP/dt max, whereas icv lisinopril caused no change.. Despite marked differences in the extent of peripheral blockade, all three treatments similarly affected sympathetic activity and decreased cardiac Ang II, preload and remodeling after MI. One may speculate that central and peripheral ACE-mediated mechanisms are sequential and therefore only minor additional effects of peripheral ACE blockade are noted.

Topics: Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Baroreflex; Brain; Fibrosis; Hemodynamics; Indoles; Infusions, Intravenous; Injections, Subcutaneous; Kidney; Lisinopril; Male; Myocardial Infarction; Myocardium; Rats; Rats, Wistar; Renin-Angiotensin System; Sympathetic Nervous System; Ventricular Dysfunction, Left

In addition to the absolute magnitude of left ventricular (LV) mass (LVM), the geometric pattern of the left ventricle might help explain the different tendency toward LV hypertrophy (LVH) regression seen under effective therapy in chronic hemodialysis patients.. Forty-five hemodialyzed uremic subjects, 17 patients with concentric LVH and 28 patients with eccentric LVH, were followed up with yearly echocardiography over 3 years while on monotherapy with angiotensin-converting enzyme (ACE) inhibitors. Predialysis blood pressure (BP) and percentage of interdialytic weight gain recorded during the month the echocardiographic study was performed were retrieved and averaged. Any adverse cardiovascular events occurring during the 3-year follow-up period also were recorded.. Significant regression of LVH (P = 0.0028) was observed in the group as a whole during the 3 years on ACE-inhibitor therapy, mainly accounted for by a reduction in pulse pressure (PP; r = 0.45; P = 0.0017). After subgrouping patients according to LV geometry, an LVM reduction was observed only in the 17 patients with concentric LVH (P = 0.0003), whereas no difference was detected in subjects with eccentric LVH despite the same degree of BP reduction and hemoglobin level and Kt/V increases in both groups. Moreover, a greater incidence of cardiovascular events was observed in patients with eccentric LVH than in those with concentric LVH during the 3-year follow-up period.. The most important finding of this study is that eccentric LVH seems to be less responsive to ACE-inhibitor treatment and is associated with a greater incidence of adverse cardiovascular events compared with concentric LVH. Furthermore, the decrease in PP appears to be the main predictor of LVH regression in chronic hemodialysis patients on ACE-inhibitor therapy.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiovascular Diseases; Drug Administration Schedule; Echocardiography; Female; Follow-Up Studies; Humans; Hypertension; Hypertrophy, Left Ventricular; Lisinopril; Male; Middle Aged; Renal Dialysis; Risk Factors; Uremia; Ventricular Dysfunction, Left; Ventricular Remodeling

We sought to describe the dosages of angiotensin-converting enzyme (ACE) inhibitor prescribed to elderly patients with heart failure at hospital discharge, the factors associated with dosing level, and the association of these dosages with 1-year outcomes.. Demographic, procedural, and medication data were collected retrospectively from medical records at 18 Connecticut hospitals. Information on mortality and readmission was obtained from the Health Care Financing Administration administrative databases. Dosages of ACE inhibitor were grouped into 3 categories: dosages recommended in practice guidelines or higher (target dose), dosages used in clinical trials but lower than guideline recommendations (subtarget dose), and dosages lower than those used in clinical trials (low dose).. A total of 554 patients, 65 years old or less with confirmed heart failure and systolic dysfunction, were prescribed an ACE inhibitor at discharge. Target, subtarget, and low doses were given in 19%, 63%, and 18% of the patients, respectively. Few demographic or clinical factors were related to lower dosages. Both subtarget and target doses of ACE inhibitors were associated with a significantly lower adjusted 1-year mortality (relative risk 0.67, P =.04; relative risk 0.51, P =.02, respectively) compared with low doses of ACE inhibitors.. In a representative elderly cohort of patients with heart failure with systolic dysfunction, the majority (82%) were discharged on doses of ACE inhibitors consistent with those used in clinical trials. We observed a dose-response relationship between higher doses and lower mortality. Future studies will need to determine whether this association is causal.

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Captopril; Enalapril; Female; Heart Failure; Humans; Lisinopril; Male; Retrospective Studies; Treatment Outcome; Ventricular Dysfunction, Left

Topics: Angiotensin-Converting Enzyme Inhibitors; Heart Failure; Humans; Lisinopril; Primary Health Care; Randomized Controlled Trials as Topic; Ventricular Dysfunction, Left

To determine the effect of preoperative therapy with angiotensin-converting enzyme (ACE) inhibitors on clinical outcome after cardiovascular surgery.. Inception cohort.. A tertiary care 54-bed cardiothoracic ICU.. All admissions to an ICU over a 42-month period after cardiovascular surgery.. Extraction of preoperative, operative, and ICU data from a database.. Incidence of acute organ dysfunction, length of mechanical ventilation, ICU stay, and death after cardiovascular surgery.. The study cohort consisted of four groups: normal or moderately impaired left ventricular function control (group A, n=6,400); normal or moderately impaired left ventricular function treated with ACE inhibitors (group B, n=1,375); severe left ventricular dysfunction control (group C, n=1,905); and severe left ventricular dysfunction treated with ACE inhibitors (group D, n=1,650). The incidence of three or more organ dysfunction was similar on comparison of group A vs group B (5% vs 6%) or group C vs group D (15% vs 13%). There were no differences in the total duration of mechanical ventilation or length of stay in the ICU in group A vs group B or group C vs group D. Death occurred in 2% of groups A and B, and at 6% in groups C and D. Preoperative severe left ventricular dysfunction in both groups C and D was associated with an increased incidence of three or more organ dysfunction, duration of mechanical ventilation, length of stay in ICU, and death after surgery. Multivariate analysis indicated that therapy with ACE inhibitors did not affect the clinical outcome after cardiovascular surgery.. Preoperative therapy with ACE inhibitors did not influence the clinical outcome after cardiac surgery. It is unlikely that therapy with ACE inhibitors can alter the clinical sequelae of cardiopulmonary bypass and cardiac surgical procedures performed in high-risk patients because of underlying severe left ventricular dysfunction.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Captopril; Cardiopulmonary Bypass; Cardiovascular Diseases; Cardiovascular Surgical Procedures; Case-Control Studies; Electrocardiography; Enalapril; Female; Follow-Up Studies; Hospital Mortality; Humans; Incidence; Intra-Aortic Balloon Pumping; Lisinopril; Male; Middle Aged; Multiple Organ Failure; Postoperative Complications; Preoperative Care; Retrospective Studies; Treatment Outcome; Ventricular Dysfunction, Left

ACE inhibitors exert both acute and chronic beneficial effects on cardiac function (e.g remodelling, diastolic dysfunction). We have previously reported that the ACE inhibitor captopril induces selective left ventricular (LV) relaxant effects in the isolated ejecting guinea pig heart. The aim of the present study was to further investigate the mechanism of the captopril-induced changes in early LV relaxation by comparing the effects of two sulphydryl and two non-sulphydryl containing ACE inhibitors in the same experimental preparation. Isolated ejecting guinea pig hearts were studied under conditions of constant loading and heart rate. LV pressure was monitored by a 2F micromanometer-tipped catheter transducer inserted in the LV cavity. The sulphydryl-containing ACE inhibitors captopril and zofenaprilat enhanced early LV relaxation, whereas the non-sulphydryl-containing ACE inhibitors lisinopril and quinaprilat did not. The effects of captopril and zofenaprilat were attenuated both by the nitric oxide-scavenger haemoglobin and the bradykinin B2-kinin receptor antagonist HOE 140. Neither the oxygen free-radical scavenger superoxide dismutase nor the sulphydryl-containing compound N-acetyl cysteine administered together with lisinopril had any effect on LV relaxation. These data demonstrate that inhibition of intra-cardiac ACE activity may acutely modulate LV relaxation through increased activity of the bradykinin-nitric oxide pathway. The presence of a sulphydryl group on the relevant ACE inhibitor appears to be essential for this LV relaxant effect.

Topics: Acetylcysteine; Angiotensin-Converting Enzyme Inhibitors; Animals; Bradykinin; Bradykinin Receptor Antagonists; Captopril; Diastole; Female; Free Radical Scavengers; Guinea Pigs; Heart Ventricles; Hemoglobins; Isoquinolines; Lisinopril; Male; Muscle Relaxation; Nitric Oxide; Receptor, Bradykinin B2; Simethicone; Stroke Volume; Sulfhydryl Compounds; Superoxide Dismutase; Systole; Tetrahydroisoquinolines; Ventricular Dysfunction, Left

To assess the effect of ACE-inhibition on left ventricular filling and wall motion in patients with a clinical diagnosis of heart failure.. Prospective examination of left ventricular systolic and diastolic function using M mode echocardiography and pulsed and continuous wave Doppler before and three weeks after starting an ACE inhibitor.. A tertiary referral centre for cardiac disease equipped with non-invasive facilities.. 30 outpatients with a clinical diagnosis of heart failure in whom treatment with an ACE inhibitor was started; age 61 (SD 11) years; 27 male; 3 female; 21 healthy controls of similar age.. Left ventricular cavity was dilated both at end systole and end diastole, and fractional shortening reduced. Although mean isovolumetric relaxation time (IVRT) and transmitral E (early) to A (late) filling velocity (E/A) ratio were not different from normal, a value of 1.0 on the normal frequency plot of the E/A ratio divided the patients bimodally into two groups: 20 patients (group A) with E/A ratio > 1.0 and 10 patients (group B) < 1.0. In group A patients, IVRT was short as was transmitral E wave deceleration time compared to normal (P < 0.001), fulfilling the criteria of restrictive left ventricular physiology. Left ventricular wall motion during IVRT was coordinate and left ventricular end diastolic pressure was raised on the apex-cardiogram (P < 0.001). In group B, E wave deceleration time was longer, relaxation incoordinate, and apexcardiogram normal. With an ACE inhibitor: in group A, left ventricular dimensions fell at end diastole (P < 0.05) and end systole (P < 0.01) but fractional shortening did not change; long axis total excursion (P < 0.01) and peak rate of shortening (P < 0.05) both increased; IVRT increased (P < 0.001) with the appearance of markedly incoordinate wall motion, minor axis lengthening, and long axis shortening (P < 0.001 for both); A wave amplitude also consistently increased (P < 0.001); finally, transmitral E wave velocity fell and A wave velocity increased. ACE inhibition did not alter any of the left ventricular minor and long axis or transmitral Doppler variables in patients in group B.. Patients with a clinical diagnosis of heart failure differ in their presentation and response to ACE inhibition according to baseline haemodynamics. In restrictive left ventricular physiology, ACE inhibition reduces cavity size and prolongs IVRT, compatible with a fall in left atrial pressure. At the same time, ventricular relaxation becomes very delayed and incoordinate, greatly reducing early diastolic left ventricular filling velocity. Thus ACE inhibition unmasks major diastolic abnormalities in patients with restrictive left ventricular disease.

Topics: Angiotensin-Converting Enzyme Inhibitors; Captopril; Echocardiography; Enalapril; Female; Heart Failure; Humans; Lisinopril; Male; Middle Aged; Signal Processing, Computer-Assisted; Ventricular Dysfunction, Left

This study was undertaken to assess whether the converting enzyme inhibitor lisinopril, and the long-acting nitrate, isosorbide-5-mononitrate, affect left ventricle dysfunction and anatomical remodelling in rats with myocardial infarction. Lisinopril, isosorbide-5-mononitrate or vehicle were given to rats (n = 10-14 per group) immediately after coronary artery occlusion (by an intravenous bolus) and then for nine weeks (in drinking water). At the end of the study, left ventricular pressures were measured, the heart arrested in diastole, and infarct size, left ventricular chamber volume and wall thicknesses measured. Lisinopril significantly lowered systemic blood pressure and left ventricular systolic pressure in rats with small (< 15% scarred tissue of the left ventricle) and large (> 15%) infarcts; the weight of the left ventricle (including the septum) was reduced by 24% and 28% in animals with small and large infarcts, respectively. Lisinopril lowered left ventricular end-diastolic pressure (by 33% and 39%) and chamber volume (by 4% and 34%) in rats with small and large infarcts, respectively, compared with controls (NS). The combined anatomical and hemodynamic changes led to a reduction of the circumferential wall stress by 20% and 44% in lisinopril-treated rats with small and large infarcts, respectively (NS). No significant changes were seen in the nitrate-treated hearts compared with controls. Lisinopril, given early after myocardial infarction and continued for nine weeks, significantly affected cardiac hemodynamics and ventricular weights in rats with infarcts of different sizes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Disease Models, Animal; Follow-Up Studies; Hemodynamics; Isosorbide Dinitrate; Lisinopril; Male; Myocardial Infarction; Organ Size; Rats; Vasodilator Agents; Ventricular Dysfunction, Left

The serum concentrations of two procollagen-derived peptides, procollagen type III amino terminal peptide (PIIIP) and procollagen type I carboxy terminal peptide (PIP), have been proposed as useful markers of the tissue synthesis of collagen type III and type I, respectively. Therefore, this study was designed to evaluate fibrogenic activity in patients with essential hypertension by measuring serum PIIIP and PIP. Furthermore, since hypertensive heart disease is characterized by myocardial accumulation of collagen type III and type I, a second aim of the study was to assess whether some relation exists between the serum concentrations of PIIIP and PIP and several parameters of left ventricular anatomy and function in hypertensive patients.. The study was performed in 50 patients with never-treated essential hypertension and in 30 normotensive control subjects. Measurements were repeated in 43 hypertensive patients after 6 months of treatment with the angiotensin-converting enzyme inhibitor lisinopril. The serum concentrations of PIIIP and PIP were measured by specific radioimmunoassay. Two-dimensional, targeted M-mode and Doppler ultrasound recordings were obtained in every subject to determine several parameters of the left ventricle anatomy and function. Ambulatory ECG monitoring was performed in each patient, and the recorded ventricular arrhythmias were categorized according to Lown-Wolf classification. Baseline serum PIIIP and PIP were increased (P < .001) in hypertensive patients as compared with normotensive subjects. An inverse correlation was found between serum PIIIP and the ratio between maximal early transmitral flow velocity and maximal late transmitral flow velocity measured during diastole (r = .3786, P < .01) in the group of hypertensive patients. Serum PIP was correlated directly with the left ventricular mass index (r = .3277, P < .05) in the group of hypertensive patients. Serum PIP concentrations increased in parallel with the increase in the grade of ventricular arrhythmias in the group of hypertensive patients. Treated patients attained normalization in blood pressure, amelioration of diastolic filling, regression of left ventricular mass index, and a diminution in the number of daily ventricular extrasystoles. In addition, serum PIIIP and PIP concentrations decreased significantly (P < .001) to normal values in patients treated with lisinopril.. These findings suggest that tissue synthesis of collagen type III and type I is abnormally increased in essential hypertension and can be normalized by treatment with lisinopril. On the other hand, our results suggest that serum PIIIP and PIP are related to several anatomic and functional alterations of the hypertensive left ventricle. Serum procollagen peptide measurements may therefore provide indirect diagnostic information on the myocardial fibrosis associated with arterial hypertension.

Topics: Collagen; Echocardiography; Electrocardiography, Ambulatory; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Lisinopril; Male; Middle Aged; Peptide Fragments; Procollagen; Renin-Angiotensin System; Ventricular Dysfunction, Left