benzofurans and Heart-Failure

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Topics: Animals; Benzofurans; Heart Failure; Humans; Hypertension; Kidney; Molecular Structure; Molecular Targeted Therapy; Piperazines; Potassium; Potassium Channel Blockers; Potassium Channels, Inwardly Rectifying

Topics: Animals; Aspartic Acid Endopeptidases; Benzazepines; Benzofurans; Drug Design; Endothelin-Converting Enzymes; Glycopeptides; Heart Failure; Humans; Hypertension; Metalloendopeptidases; Mice; Mice, Knockout; Myocardial Infarction; Organophosphonates; Phenylalanine; Tetracyclines; Tetrazoles

The advent of direct-acting antiviral therapy for hepatitis C virus (HCV) has generated tremendous interest in transplanting organs from HCV-infected donors. We conducted a single-arm trial of orthotopic heart transplantation (OHT) from HCV-infected donors into uninfected recipients, followed by elbasvir/grazoprevir treatment after recipient HCV was first detected (NCT03146741; sponsor: Merck). We enrolled OHT candidates aged 40-65 years; left ventricular assist device (LVAD) support and liver disease were exclusions. We accepted hearts from HCV-genotype 1 donors. From May 16, 2017 to May 10, 2018, 20 patients consented for screening and enrolled, and 10 (median age 52.5 years; 80% male) underwent OHT. The median wait from UNOS opt-in for HCV nucleic-acid-test (NAT)+ donor offers to OHT was 39 days (interquartile range [IQR] 17-57). The median donor age was 34 years (IQR 31-37). Initial recipient HCV RNA levels ranged from 25 IU/mL to 40 million IU/mL, but all 10 patients had rapid decline in HCV NAT after elbasvir/grazoprevir treatment. Nine recipients achieved sustained virologic response at 12 weeks (SVR-12). The 10th recipient had a positive cross-match, experienced antibody-mediated rejection and multi-organ failure, and died on day 79. No serious adverse events occurred from HCV transmission or treatment. These short-term results suggest that HCV-negative candidates transplanted with HCV-infected hearts have acceptable outcomes.

Topics: Adult; Aged; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; Female; Genotype; Graft Rejection; Heart Failure; Heart Transplantation; Heart-Assist Devices; Hepacivirus; Hepatitis C; Humans; Imidazoles; Male; Middle Aged; Postoperative Period; Quinoxalines; RNA, Viral; Sulfonamides; Sustained Virologic Response; Time Factors; Tissue and Organ Procurement; Treatment Outcome; Viral Load; Waiting Lists

The effects of amiodarone by injection have been studied in 100 patients. 50% of these patients were in cardiac failure. Amiodarone was given intravenously over 30 seconds in a dose of 300 mg; in 15 of the patients a further dose of 150 mg was given after ten minutes. Amiodarone was found to be particularly effective in the tachy-arrhythmias (90% successful) in which it brought about slowing (18 cases out of 30) or conversion (17 cases out of 30). Just as good results were obtained for the atrial tachycardias (90% success rate) and in the junctional tachycardias. This treatment is less effective for atrial flutter (50% successful) and for ventricular arrhyrthmia, in which the success rate was only 60%. It is possible to use the defibrillator after amiodarone has been administered. This drug is well tolerated, and no increase in cardiac failure has been noted in these patients. There does remain, however, the possibility of hypotension and perhaps of circulatory collapse, which is rapidly reversable; this is probably due to vasodilator activity. Intracavitary studies in 8 patients have shown that amiodarone causes slowing of sino-atrial and of atrio-ventricular conduction. Amiodarone may equally worsen a distal conduction defect. The uses for this anti-arrhythmic drug, which is particularly effective at the atrial level, are discussed in this paper.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzofurans; Clinical Trials as Topic; Depression, Chemical; Drug Tolerance; Female; Heart Block; Heart Conduction System; Heart Failure; Heart Rate; Humans; Injections, Intravenous; Male; Middle Aged

Increased matrix metalloprotease 9 (MMP9) after myocardial infarction (MI) exacerbates ischemia-induced chronic heart failure (CHF). Autophagy is cardioprotective during CHF; however, whether increased MMP9 suppresses autophagic activity in CHF is unknown. This study aimed to determine whether increased MMP9 suppressed autophagic flux and MMP9 inhibition increased autophagic flux in the heart of rats with post-MI CHF. Sprague-Dawley rats underwent either sham surgery or coronary artery ligation 6-8 wk before being treated with MMP9 inhibitor for 7 days, followed by cardiac autophagic flux measurement with lysosomal inhibitor bafilomycin A1. Furthermore, autophagic flux was measured in vitro by treating H9c2 cardiomyocytes with two independent pharmacological MMP9 inhibitors, salvianolic acid B (SalB) and MMP9 inhibitor-I, and CRISPR/cas9-mediated MMP9 genetic ablation. CHF rats showed cardiac infarct, significantly increased left ventricular end-diastolic pressure (LVEDP), and increased MMP9 activity and fibrosis in the peri-infarct areas of left ventricular myocardium. Measurement of the autophagic markers LC3B-II and p62 with lysosomal inhibition showed decreased autophagic flux in the peri-infarct myocardium. Treatment with SalB for 7 days in CHF rats decreased MMP9 activity and cardiac fibrosis but increased autophagic flux in the peri-infarct myocardium. As an in vitro corollary study, measurement of autophagic flux in H9c2 cardiomyocytes and fibroblasts showed that pharmacological inhibition or genetic ablation of MMP9 upregulates autophagic flux. These data are consistent with our observations that MMP9 inhibition upregulates autophagic flux in the heart of rats with CHF. In conclusion, the results in this study suggest that the beneficial outcome of MMP9 inhibition in pathological cardiac remodeling is in part mediated by improved autophagic flux.

Topics: Animals; Autophagy; Benzofurans; Cell Line; Disease Models, Animal; Fibroblasts; Fibrosis; Heart Failure; Male; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Mice; Myocytes, Cardiac; Rats, Sprague-Dawley; Signal Transduction; Ventricular Function, Left; Ventricular Remodeling

Qiliqiangxin capsule (QLQX), composed of 11 herbs, is an effective traditional Chinese medicine (TCM) that has been widely used for treatment of chronic heart failure (CHF) in China. In the Chinese pharmacopoeia (Ch.P.) only astragaloside was described as the marker component to control the quality of QLQX, which could not reflect the overall effectiveness.. The aim of this work was to investigate the quality markers (Q-markers) of QLQX based on the association of the pharmacodynamics (PD) of inhibitory effect on activated renin-angiotensin-aldosterone system (RAAS) and the pharmacokinetics (PK) of bioactive compounds according to the Q-marker theory.. The contents of astragaloside, calycosin-7-glucoside, sinapine, ginsenoside Rb1, ginsenoside Rb2, ginsenoside Rg1, salvianolic acid A, salvianolic acid B, danshensu, rosmarinic acid, formononetin, aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypacoitine were determined by an HPLC-MS/MS method both in QLQX preparation and in the plasma of CHF rats administered intragastrically with QLQX. The effect of lowering angiotensin II (Ang II) production by QLQX was assayed by ELISA. The association between PK and PD was explored and the bioactive compounds with higher content in vitro and better exposure in vivo, which were closely related to the inhibitory effect on the activated RAAS, were identified as Q-markers of QLQX for CHF treatment.. The contents of 17 constituents were in the order of salvianolic acid B > danshensu > ginsenoside Rb1 > sinapine > benzoylmesaconine > astragaloside > benzoylhypacoitine > ginsenoside Rb2 > salvianolic acid A > ginsenoside Rg1 > calycosin-7-glucoside > rosmarinic acid > formononetin > benzoylaconine > hypaconitine > aconitine > mesaconitine in QLQX preparation. PK and PD association study of 14 bioactive compounds of QLQX showed the maximum effect (E. Astragaloside, calycosin-7-glucoside, sinapine and ginsenoside Rg1 are suitable as the Q-markers of QLQX for CHF treatment, which have higher content in vitro, finer exposure in vivo and a direct correlation with the inhibitory effect on activated RAAS.

Topics: Aconitine; Angiotensin II; Animals; Benzofurans; Biomarkers; Chromatography, High Pressure Liquid; Chronic Disease; Drugs, Chinese Herbal; Ginsenosides; Heart Failure; Isoflavones; Male; Medicine, Chinese Traditional; Quality Control; Rats, Sprague-Dawley; Tandem Mass Spectrometry

Heart failure(HF) is a dangerous disease that affects millions of patients. Radix Salvia is widely used in Chinese clinics to treat heart diseases. Salvianolic acid B(SalB) is the major active component of Radix Salvia. This study investigated the mechanisms of action and effects of SalB on HF in an experimental mouse model of HF.. We created a mouse model of HF by inducing pressure overload with transverse aortic constriction(TAC) surgery for 2 weeks and compared among 4 study groups: SHAM group (n = 10), TAC group (n = 9), TAC+MET group (metprolol, positive drug treatment, n = 9) and TAC+SalB group (SalB, 240 mg•kg-1•day-1, n = 9). Echocardiography was used to evaluate the dynamic changes in cardiac structure and function in vivo. Plasma brain natriuretic peptide (BNP) concentration was detected by Elisa method. In addition, H9C2 rat cardiomyocytes were cultured and Western blot were implemented to evaluate the phosphorylation of ERK1/2, AKT, and protein expression of GATA4.. SalB significantly inhibited the phosphorylation of Thr202/Tyr204 sites of ERK1/2, but not Ser473 site of AKT, subsequently inhibited protein expression of GATA4 and plasma BNP(P < 0.001), and then inhibited HF at 2 weeks after TAC surgery.. Our data provide a mechanism of inactivating the ERK1/2/GATA4 signaling pathway for SalB inhibition of the TAC-induced HF.

Topics: Animals; Aorta, Thoracic; Benzofurans; Blood Pressure; Cell Line; Disease Models, Animal; Drugs, Chinese Herbal; GATA4 Transcription Factor; Heart Failure; Heart Ventricles; Male; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Signal Transduction

In the failing human heart, altered Ca2+ homeostasis causes contractile dysfunction. Because Ca2+ and Na+ homeostasis are intimately linked through the Na+/Ca2+ exchanger, we compared the regulation of [Na+]i in nonfailing (NF) and failing human myocardium.. [Na+]i was measured in SBFI-loaded muscle strips. At slow pacing rates (0.25 Hz, 37 degrees C), isometric force was similar in NF (n=6) and failing (n=12) myocardium (6.4+/-1.2 versus 7.2+/-1.9 mN/mm2), but [Na+]i and diastolic force were greater in failing (22.1+/-2.6 mmol/L and 15.6+/-3.2 mN/mm2) than in NF (15.9+/-3.1 mmol/L and 3.50+/-0.55 mN/mm2; P<0.05) myocardium. In NF hearts, increasing stimulation rates resulted in a parallel increase in force and [Na+]i without changes in diastolic tension. At 2.0 Hz, force increased to 136+/-17% of the basal value (P<0.05), and [Na+]i to 20.5+/-4.2 mmol/L (P<0.05). In contrast, in failing myocardium, force declined to 45+/-3%, whereas [Na+]i increased to 27.4+/-3.2 mmol/L (both P<0.05), in association with significant elevations in diastolic tension. [Na+]i was higher in failing than in NF myocardium at every stimulation rate. [Na+]i predicted in myocytes from Na+ (pipette)-contraction relations was 8.0 mmol/L in NF (n=9) and 12.1 mmol/L in failing (n=57; P<0.05) myocardium at 0.25 Hz. Reverse-mode Na+/Ca2+ exchange induced significant Ca2+ influx in failing but not NF myocytes, compatible with higher [Na+]i in failing myocytes.. Na+i homeostasis is altered in failing human myocardium. At slow heart rates, the higher [Na+]i in failing myocardium appears to enhance Ca2+ influx through Na+/Ca2+ exchange and maintain sarcoplasmic reticulum Ca(2+) load and force development. At faster rates, failing myocytes with high [Na+]i cannot further increase sarcoplasmic reticulum Ca2+ load and are prone to diastolic Ca2+ overload.

Topics: Benzofurans; Calcium; Cells, Cultured; Culture Techniques; Electric Conductivity; Electric Stimulation; Fluorescent Dyes; Heart Failure; Homeostasis; Humans; Ion Transport; Kinetics; Middle Aged; Myocardial Contraction; Myocardium; Ouabain; Phthalic Acids; Sodium

Topics: Aspartic Acid Endopeptidases; Benzazepines; Benzhydryl Compounds; Benzofurans; Endothelin Receptor Antagonists; Endothelin-1; Endothelin-Converting Enzymes; Endothelins; Enzyme Inhibitors; Heart Failure; Humans; Metalloendopeptidases; Organophosphonates; Pyrimidines; Vascular Diseases; Vasoconstrictor Agents

The purpose of this study was to determine whether Angiotensin II (Ang II) contributes to the regulation of resting hemodynamics via Ang II type 1 (AT1) receptors in awake dogs with coronary microembolization-induced heart failure. Six dogs were surgically instrumented for measurement of systemic hemodynamics and for coronary microembolization. The acute hemodynamic effects of a selective AT1-receptor antagonist, GR138950 (1 mg/kg, i.v.), were determined before and after congestive heart failure (CHF). GR138950 had no effects on hemodynamics before CHF Daily coronary microembolizations (through the previously implanted coronary catheter) resulted in CHF, as documented by hemodynamic measurements, a slight but significant increased Ang II plasma level (17.4 +/- 1.6 vs. 23 +/- 1.0 pg/ml; p < 0.05), and characteristic clinical signs of CHF. After CHF, GR138950 significantly increased left ventricular dP/dt(max) (LVdP/dt(max)) from 1,754 +/- 68 to 2,347 +/- 114 mm Hg/s and decreased LV systolic pressure (LVSP) from 118 +/- 5 to 101 +/- 7 mm Hg; meanwhile, heart rate (from 132 +/- 4 to 102 +/- 6 beats/min) and LV end-diastolic pressure (LVEDP; from 17 +/- 3 to 9 +/- 1.5 mm Hg) were significantly decreased. Mean arterial pressure (MAP) was not affected. The peak effects occurred 90 min after administration. Thus Ang II contributes significantly to resting hemodynamics via AT1 receptors in this CHF model; that is, the specific AT1 blocker inhibits the negative inotropic actions of Ang II in the CHF state.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Benzofurans; Blood Pressure; Coronary Disease; Dogs; Embolism; Female; Heart Failure; Heart Rate; Male; Receptors, Angiotensin

Five cases of amiodarone-induced syncope due to torsades de pointes or ventricular fibrillation are described. Amiodarone was used for recurrent supraventricular tachycardia in four cases and frequent ventricular extra systoles complicating congenital QT prolongation in the remaining case. Each was associated with a marked prolongation in the QTc interval following amiodarone. Three cases had had a previous history of life-threatening ventricular arrhythmias secondary to anti-arrhythmic drugs. Hypokalemia may have been a contributory factor in two. The clinical features, predisposing factors, and treatment are discussed.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Benzofurans; Drug Therapy, Combination; Electrocardiography; Female; Heart Arrest; Heart Failure; Humans; Long QT Syndrome; Tachycardia

Topics: Amiodarone; Benzofurans; Child, Preschool; Electrocardiography; Heart Defects, Congenital; Heart Failure; Humans; Male; Tachycardia

Topics: Adolescent; Adult; Aged; Amiodarone; Benzofurans; Female; Heart Failure; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Thyroid Hormones; Thyrotropin; Thyrotropin-Releasing Hormone

Topics: Amiodarone; Benzazepines; Benzofurans; Diltiazem; Drug Interactions; Drug Therapy, Combination; Female; Heart Failure; Humans; Hypotension; Middle Aged; Myocardial Contraction; Sinoatrial Node

The role that the new antiarrhythmic agents, such as verapamil and amiodarone, might play in the therapeutic strategy of tachycardia-induced fetal heart failure remains to be determined.

Topics: Adult; Amiodarone; Benzofurans; Female; Fetal Diseases; Fetal Heart; Heart Failure; Heart Rate; Humans; Infant, Newborn; Male; Maternal-Fetal Exchange; Pregnancy; Tachycardia; Verapamil

Amiodarone is a cardiac antiarrhythmic agent now undergoing clinical trials in the United States. Its most important side effect is pulmonary toxicity, which may present radiographically in two forms. One is similar to eosinophilic pneumonia with peripheral alveolar opacities but without any of the laboratory or pathologic findings. A second presentation is as a bilateral interstitial pattern resembling interstitial pulmonary edema. This is often mistaken for heart failure in the clinical and radiographic setting. Amiodarone also causes a phospholipidosis of the liver, which is usually asymptomatic but on occasion may present as hepatitis. On abdominal CT the liver will have an abnormally high attenuation (80-140 HU), which appears to be due to accumulation of an amiodarone metabolite in hepatocytes. This appearance is usually distinguishable from the other causes of increased hepatic attenuation by virtue of other CT criteria and clinical history. However, from a radiographic standpoint alone, the combination of acute congestive heart failure and an abnormally dense liver may result in at least an initial misdiagnosis of advanced primary hemochromatosis.

Topics: Aged; Amiodarone; Benzofurans; Chemical and Drug Induced Liver Injury; Female; Heart Failure; Humans; Liver; Liver Diseases; Lung; Pulmonary Fibrosis; Radiography

Reports of pulmonary infiltrates in patients taking amiodarone, initiated the study of 69 patients for pulmonary toxicity using serial chest roentgenograms (CXRs), pulmonary function tests (PFTs), and symptoms before and during therapy. Mean PFTs did not significantly change from their baseline normal values, but 10 percent of patients had a greater than or equal to 15 percent fall in total lung capacity, and 28 percent a greater than or equal to 15 percent fall in diffusion capacity (DCO) following treatment. Initial abnormalities in pulmonary function or CXR were predictive of risk of developing pulmonary toxicity. Degree of exposure to amiodarone (dose plus duration) correlated only weakly with development of pulmonary toxicity, which could occur in patients taking relatively small doses of the drug. Pulmonary complications of amiodarone are common, in most cases reversible, and often confused with congestive heart failure or pneumonia. Patients should be evaluated before treatment by assessing symptoms, CXRs, and DCO. Patients with initial abnormalities in these parameters, particularly both CXR and DCO abnormalities, should be considered for alternative therapy.

Topics: Adult; Aged; Amiodarone; Benzofurans; Diagnosis, Differential; Female; Follow-Up Studies; Heart Failure; Humans; Infections; Lung; Lung Diseases; Male; Middle Aged; Prospective Studies; Pulmonary Diffusing Capacity; Pulmonary Ventilation; Radiography; Respiratory Function Tests; Risk; Total Lung Capacity

In order to evaluate the effects of amiodarone on thyroid function in chronically treated patients, 43 consecutive patients, who had been taking a mean weekly dose of 1420 +/- 488 mg for more than 9 months (mean 16.5 months), were studied. In a first evaluation, three patients with hypothyroidism and two with hyperthyroidism were discovered. In the remaining 38 patients, mean T4 (131 +/- 38 nmol/L) and rT3 (0.85 +/- 0.3 nmol/L) levels were significantly higher than reference values (p less than 0.05 and p less than 0.001, respectively), and mean T3 levels (1.89 +/- 0.73 nmol/L) were significantly lower (p less than 0.001). Thirteen patients showed hyperresponsiveness to thyrotropin-releasing hormone (TRH) stimulation testing. In a second evaluation, performed 12 to 18 months later, two new cases of hypothyroidism were discovered. T3 levels showed significantly lower values (p less than 0.02) than in the first evaluation, whereas basal thyroid-stimulating hormone levels and levels 30 and 60 minutes after TRH stimulation were significantly higher than those in the first evaluation (p less than 0.001). Five new hyperresponders to TRH were found. In the present series, the progressive appearance of clinical thyroid dysfunction with an elevated total incidence (16%) is demonstrated. Moreover, a progressively high prevalence of hyperresponsiveness to TRH stimulation is shown. These findings indicate that chronic amiodarone administration may carry a high risk of thyroid dysfunction.

Topics: Adult; Aged; Amiodarone; Benzofurans; Chronic Disease; Coronary Disease; Female; Follow-Up Studies; Goiter; Heart Failure; Heart Valve Diseases; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Thyroid Function Tests; Thyroid Gland

Myocardial size and contractility were measured by gated radionuclide ventriculography in 70 patients before and a mean of 66 days after beginning amiodarone therapy. The mean dose of amiodarone at the time of the second study was 481 mg. The mean left ventricular (LV) ejection fraction (EF) increased slightly, from 40% to 43% (p = 0.001). The mean right ventricular EF remained unchanged (38% to 39%, difference not significant [NS]). The LV end-diastolic volume (count-based method) increased by 9% (p = 0.01), but no change could be demonstrated for end-systolic volume (4%, NS). The LV stroke volume increased 19% (p = 0.001), but cardiac output remained unchanged (5%, NS) because the heart rate decreased by 9 beats/min (p = 0.001). The right ventricular end-diastolic volume increased by 12% (p = 0.01) and end-systolic volume increased by 11% (p = 0.03). Stroke volume increased by 18% (p = 0.005). There was no significant correlation between the change in LVEF and the pre-amiodarone LVEF, the time interval between studies, or with indexes of amiodarone effect (change in heart rate, QRS, QTc, TSH, amiodarone dosage). In 5 patients (7%), LVEF decreased significantly, requiring discontinuation of amiodarone therapy in 1 patient. At the time of the second study congestive heart failure was manifest in 19%, and there was a trend suggesting that congestive heart failure was more likely if the initial LVEF was less than or equal to 35% (p = 0.10). Thus, amiodarone may rarely adversely affect contractility, although myocardial contractility is typically unchanged. There is an associated small increase in the size of both ventricles.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Cardiac Output; Female; Heart; Heart Diseases; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Myocardial Contraction; Radionuclide Imaging; Stroke Volume

Topics: Amiodarone; Anemia, Hemolytic; Benzofurans; Cardiac Complexes, Premature; Heart Failure; Humans; Male; Middle Aged; Pulmonary Alveoli; Pulmonary Fibrosis

Fifteen patients aged 59.3 +/- 11.5 years (mean +/- standard deviation [SD]) had recurrent symptomatic ventricular tachycardia (VT) refractory to at least 2 conventional antiarrhythmic drugs. All patients had organic heart disease; 4 had an acute myocardial infarction. The mean ejection fraction was 0.30 +/- 0.09. TWelve patients had overt congestive heart failure. Five had bundle branch block. Before treatment with intravenous amiodarone, the patients had had 6 to 40 episodes of symptomatic VT over 1 to 8 days of hospitalization. All patients received an initial bolus of 5 mg of amiodarone/kg over 15 minutes. Seven patients also received a continuous infusion of 600 to 1,000 mg of amiodarone over 12 to 24 hours. Additional doses depended on the patients' clinical responses. In 11 of 15 patients, antiarrhythmic drugs that had failed to suppress VT were continued during administration of amiodarone. In 12 of 15 patients acute control of VT was obtained with intravenous administration of amiodarone either alone or in combination with previously ineffective drugs. Three patients continued to have frequent episodes of VT while being treated with intravenous amiodarone. Mobitz type I atrioventricular block developed in 1 patient. No patient had high degree atrioventricular block, symptomatic hypotension, or a clinically apparent worsening of congestive heart failure. The use of intravenous amiodarone represents a significant advance in the acute treatment of frequent life-threatening VT refractory to other drugs. With appropriate monitoring, it can be used safely in patients with congestive heart failure, bundle branch block, or acute myocardial infarction.

Topics: Adult; Aged; Amiodarone; Benzofurans; Female; Heart Block; Heart Failure; Humans; Infusions, Parenteral; Injections, Intravenous; Long-Term Care; Male; Middle Aged; Recurrence; Sinoatrial Node; Tachycardia

Fourteen patients with congestive heart failure due to chronic Chagas' disease had hemodynamic studies before and 20, 40 and 60 minutes and 24 hours after intravenous amiodarone. Amiodarone was given initially as a bolus (5 mg/kg); after 1 hour a continuous infusion was maintained for 24 hours (total dose 900 to 1,050 mg). During the first hour of observation, heart rate and cardiac index decreased and mean right atrial, left ventricular end-diastolic pressures and pulmonary and systemic vascular resistances increased. Except for heart rate and mean right atrial pressure, all hemodynamic variables returned to control values at 24 hours. Thus, myocardial depression occurred with a dose of 5 mg/kg within the first hour of intravenous administration. Amiodarone must be cautiously administered by bolus, especially in patients with cardiac failure.

Topics: Adult; Amiodarone; Benzofurans; Blood Pressure; Cardiac Output; Chagas Cardiomyopathy; Female; Heart Failure; Heart Rate; Hemodynamics; Humans; Infusions, Parenteral; Male; Middle Aged; Time Factors; Vascular Resistance

Amiodarone was used to treat cardiac arrhythmias that had been refractory to conventional medical therapy. The first 70 consecutive patients treated with amiodarone in this study had at least 6 months of follow-up (range 6 to 24, mean 11) and form the basis for this report. Sixty-six patients were treated for ventricular arrhythmias and four for supraventricular tachycardias. Amiodarone therapy consisted of a loading dose of 600 mg orally twice a day for 7 days, and 600 mg daily thereafter. Doses were reduced only if side effects occurred. Because of frequent side effects, the dose was reduced from 572 +/- 283 mg per day (mean +/- standard deviation) at 45 days to 372 +/- 174 mg per day at 6 months. With a mean follow-up of 11 months in the 54 patients who continued to take amiodarone, only 4 patients had ventricular fibrillation. Three additional patients experienced recurrent sustained ventricular tachycardia in long-term follow-up. All 70 patients had extensive clinical and laboratory evaluation in follow-up. Side effects were common, occurring in 93% of patients. Thirteen patients (19%) had to discontinue the medication because of severe side effects. Fifty-six patients had gastrointestinal side effects, most commonly constipation. All patients but 1 eventually developed corneal microdeposits, and 43 patients were symptomatic. Cardiovascular side effects were uncommon. Symptomatic pulmonary side effects occurred in seven patients, with unequivocal pulmonary toxicity occurring in five. Neurologic side effects, most commonly tremor and ataxia, occurred in 52 patients. Thyroid dysfunction occurred in 3 patients, and 32 patients had cutaneous abnormalities. Miscellaneous other side effects occurred in 32 patients. Amiodarone appears to be useful in the management of refractory arrhythmias. Because virtually all patients develop side effects when given a maintenance daily dose of 600 mg, lower maintenance doses should be used. It is unknown if the more severe side effects are dose-related. Amiodarone is difficult to administer because of its narrow toxic-therapeutic range and prolonged loading phase. More importantly, the first sign of antiarrhythmic failure may be manifest as sudden cardiac death.

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Corneal Diseases; Digitalis Glycosides; Drug Interactions; Dyspnea; Epididymitis; Follow-Up Studies; Heart Failure; Humans; Hypotension, Orthostatic; Liver Function Tests; Male; Pulmonary Fibrosis; Stroke Volume; Thyrotropin

We evaluated the electrophysiologic effects of amiodarone and its ability to control ventricular arrhythmia in a selected group of 51 patients with refractory sustained ventricular arrhythmia. Amiodarone in doses of 400 to 800 mg/day prolonged refractoriness in the atria, atrioventricular (AV) node, and ventricle as well as conduction through the AV node and His-Purkinje system. Although it had no effect on measurements of sinus nodal function (sinus nodal recovery time and sinoatrial conduction time), it prolonged the sinus cycle length and 2 patients required a permanent pacemaker for symptomatic sinus bradycardia. Amiodarone did not alter the ease of inducibility in any consistent manner, and only 5 of 43 patients (12%) who had inducible ventricular tachycardia before amiodarone therapy had none induced during amiodarone treatment. The clinical effectiveness of amiodarone could be evaluated in 46 patients followed up for 8.6 +/- 6 months (range 0.5 to 22). It provided effective therapy in 23 patients (50%), partly effective therapy in 13 (28%), and was ineffective in 10 (22%). Adverse effects were noted in 28 of 51 patients (55%), and in 11 of these (22%) the drug had to be discontinued because of adverse effects. We conclude that amiodarone is a useful agent for the treatment of refractory sustained ventricular arrhythmia. Its use should be reserved for patients with life-threatening sustained arrhythmia because of the significant incidence of adverse effects. Furthermore, good clinical response can be observed in patients receiving amiodarone in spite of continued inducibility.

Topics: Adolescent; Adult; Aged; Amiodarone; Benzofurans; Cardiac Pacing, Artificial; Chemical and Drug Induced Liver Injury; Corneal Diseases; Electrophysiology; Female; Heart Conduction System; Heart Failure; Humans; Male; Middle Aged; Myocardial Contraction; Peripheral Nervous System Diseases; Photosensitivity Disorders; Pulmonary Fibrosis; Stroke Volume; Tachycardia; Ventricular Fibrillation

Six patients are presented who developed pulmonary infiltrates of undetermined origin while being treated for severe ventricular arrhythmias with amiodarone hydrochloride. Biopsy material was available in four patients and revealed interstitial or alveolar fibrosis and pneumonitis. Four patients recovered and two died of severe cardiopulmonary decompensation; all of the patients who recovered received corticosteroid therapy. Pulmonary fibrosis is a previously unreported complication of amiodarone therapy.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Coronary Disease; Female; Heart Failure; Humans; Lung; Male; Middle Aged; Myocardial Infarction; Pneumonia; Pulmonary Fibrosis

Topics: Aged; Amiodarone; Angina Pectoris; Arrhythmias, Cardiac; Benzofurans; Coronary Disease; Dipyridamole; Electrocardiography; Female; Heart Failure; Heart Function Tests; Humans; Hypertension; Male; Middle Aged

Topics: Adult; Antihypertensive Agents; Benzofurans; Child; Child, Preschool; Diagnosis, Differential; Digoxin; Drug Synergism; Electrocardiography; Female; Heart Failure; Heart Rate; Humans; Infant; Infant, Newborn; Male; Prenylamine; Tachycardia; Time Factors

Topics: Adult; Amiodarone; Animals; Benzofurans; Dogs; Echocardiography; Heart; Heart Failure; Humans; Injections, Intravenous; Middle Aged

Topics: Anti-Arrhythmia Agents; Antihypertensive Agents; Arrhythmias, Cardiac; Benzofurans; Female; Heart Aneurysm; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction

Topics: Benzofurans; Coronary Artery Disease; Coumarins; Heart Failure; Humans