Heterogeneous sympathetic innervation in German shepherd dogs with inherited ventricular arrhythmia and sudden cardiac death

BACKGROUND: Recently, a colony of German shepherd dogs with inherited spontaneous cardiac arrhythmias and associated sudden death has been developed and characterized. Due to the median age of onset of the arrhythmia (4.5 months), the tendency for the arrhythmia to occur during REM sleep or after exercise, and the absence of structural heart disease, we hypothesized a developmental abnormality of the sympathetic innervation to the heart. METHODS AND RESULTS: We studied 11 dogs from this colony, ranging in age from 6 months to 6 years, and four 7-month-old German shepherd dogs unrelated to the colony as controls. We imaged the distribution of functional myocardial sympathetic innervation and perfusion with [123I]metaiodobenzylguanidine (MIBG) and 201Tl, respectively. Sympathetic nerve distribution was evaluated morphologically by immunocytochemical localization of tyrosine hydroxylase. All of the hearts showed evidence of a regional decrease in MIBG uptake, ranging from 5.3% to 53.4% of the myocardium, whereas control dogs showed homogeneous MIBG uptake. Immunocytochemical studies on sections from regions with decreased MIBG uptake showed a striking paucity of nerves compared with regions with normal MIBG uptake, confirming denervation. When the dogs were grouped into those with (n=6) and without (n=5) evidence of ventricular tachycardia on ambulatory ECG, the group with ventricular tachycardia showed 35+/-16.5% denervation, whereas the group without ventricular tachycardia showed 12+/-5.6% denervation (P<.02). CONCLUSIONS: Abnormal heterogeneous sympathetic innervation exists in these dogs with inherited ventricular arrhythmia and sudden cardiac death. Mechanisms relating the presence and extent of regional denervation to the incidence of ventricular arrhythmia remain to be defined.     

Postinfarction use of beta-blockers in elderly patients

beta-Adrenoceptor antagonists (beta-blockers) reduce mortality and recurrent myocardial infarction (MI) in older patients after both Q-wave MI and non-Q-wave MI. The effects of beta-blockers are to: (i) reduce complex ventricular arrhythmias, including ventricular tachycardia; (ii) increase the ventricular fibrillation threshold; (iii) reduce myocardial ischaemia; (iv) decrease sympathetic tone; (v) markedly attenuate the circadian variation of complex ventricular arrhythmias: (vi) abolish the circadian variation of myocardial ischaemia; and (vii) abolish the circadian variation of sudden cardiac death or MI. beta-Blockers reduce mortality in patients with MI and complex ventricular arrhythmias. In addition, they are excellent antianginal agents. Older persons with hypertension who have had an MI should be treated initially with a beta-blocker. beta-Blockers reduce mortality in patients with: (i) diabetes mellitus who have had an MI; (ii) MI and congestive heart failure with an abnormal or normal left ventricular ejection fraction; and (iii) MI and an asymptomatic abnormal left ventricular ejection fraction. Severe congestive heart failure, severe peripheral arterial disease with threatening gangrene, greater than first degree atrioventricular block, hypotension, bradycardia, lung disease with bronchospasm, and bronchial asthma are contraindications to treatment with beta-blockers.     

Action of clonidine on the baroreceptor pathway and medullary sites mediating vagal bradycardia

In anaesthetized dogs, clonidine (10 mug/kg i.v.) increased the spontaneous firing of the carotid sinus nerve and decreased blood pressure and heart rate. After transection of the spinal cord, clonidine decreased heart rate and this bradycardia was abolished by selective baroreceptor denervation. Clonidine (1 mug/kg) injected into the vertebral artery of anaesthetized dogs, pretreated with a beta-adrenoceptor blocking agent (S 2395: 50 mug/kg i.v.) potentiated the bradycardia induced by stimulation of the carotid sinus nerve but did not change the hypotension and bradycardia produced by stimulation of the nucleus tractus solitarius or of the nucleus ambiguus. In anaesthetized cats with bilateral destruction of nuclei tractus solitarii, clonidine (10 mug/kg i.v.) decreased blood pressure and heart rate. Clonidine (2 mug/kg), injected into the vertebral artery of anaesthetized dogs pretreated with a beta-adrenergic blocking agent (S 2395: 50 mug/kg i.v.) or guanethidine, induced a bradycardia but the discharges of the carotid sinus nerve were not increased. Selective baroreceptor denervation abolished this bradycardia. In conclusion, these experiments provide direct evidence that the central facilitory effect of clonidine on baroreceptor impulses play a role in the bradycardic effect of the drug. This facilitation is likely localized in the nucleus tractus solitarius at the first synapse of baroreceptor fibres. The vagally mediated bradycardia can be explained by an increase in baroreceptor discharges and by the central facilitation of baroreceptor impulses. The site of the hypotensive effect of clonidine did not seem to be localized in the nucleus tractus solitarius.     

Ventricular arrhythmias in syndrome of balloon deformity of mitral valve. Definition of possible high risk group

Twenty patients clinically identified as having balloon deformity of the mitral valve were studied to assess the incidence of ventricular arrhythmias. Echocardiography and phonocardiography were used to confirm the nature of the mitral valve lesion. Continuous 24-hour electrocardiograms were obtained from all patients and analysed by a computer and 2 observers. One patient has ventricular fibrillation and 3 patients had ventricular tachycardia. There was a high incidence of other less severe forms of ventricular arrhythmias. Eight patients had inferolateral ST and T wave abnormality on the resting electrocardiogram, and were described as having the ausculatatory-electrocardiographic variant of the balloon mitral valve syndrome. The occurrence of serious ventricular arrhythmias (ventricular fibrillation and tachycardia) was significantly more frequent in this group. This raises the possibility that the resting electrocardiogram may identify those patients with balloon deformity of the mitral valve who are at risk from sudden death.     

Tachyarrhythmias in old age

The electrocardiograms of 1,171 patients above the age of 65 in a predominantly geriatric institution were reviewed to determine the incidence of tachyarrhythmias. Data on the overall incidence and the individual types of arrhythmias are presented. Atrial fibrillation was the most common arrhythmia observed, followed by atrial flutter and supraventricular tachycardia. Atrial fibrillation often was associated with other evidence of myocardial damage. The significance of sinus bradycardia and grade I A-V block in the pathogenesis of atrial fibrillation and the significance of the tachyarrhythmias are discussed.     

An activator/repressor dual system allows tight tetracycline-regulated gene expression in budding yeast

OBJECTIVES: This study sought to determine the prevalence and significance of nonsustained ventricular tachycardia (NSVT) in patients with premature ventricular contractions (PVCs) and heart failure treated with vasodilator therapy. BACKGROUND: Heart failure patients with ventricular arrhythmia and NSVT have a significantly increased risk of premature cardiac death. Recently there has been the question of whether these arrhythmias are expressions of a severely compromised ventricle or are they independent risk factors. We, therefore, determined the prevalence and significance of NSVT in patients with PVCs and heart failure and on vasodilator therapy. METHODS: Twenty-four hour ambulatory recordings were done at randomization, at 2 weeks, at months 1, 3, 6, 9 and 12 and then every 6 months in 674 patients with heart failure and on vasodilator therapy. The median period of follow-up was 45 months (range 0 to 54). RESULTS: Nonsustained ventricular tachycardia was present in 80% of all patients. Patients without (group 1) and with (group 2) NSVT were balanced for variables: age, etiology of heart disease, New York Heart Association (NYHA) functional class, use of amiodarone and diuretics and left ventricular diameter by echocardiogram. However, group 1 patients had significantly less beta-adrenergic blocking agent use and higher ejection fraction (EF) (p < 0.002 and p < 0.001, respectively). Survival analysis for all deaths showed a greater risk of death among group 2 patients (p=0.01). Similarly, sudden death was increased in group 2 patients (p=0.02, risk ratio 1.8). After adjusting for the above variables, only EF (p=0.001) and NYHA class (p=0.01) were shown to be independent predictors of survival. Nonsustained ventricular tachycardia showed a trend (p=0.07) as an independent predictor for all-cause mortality but not for sudden death. Only EF was an independent predictor for sudden death. CONCLUSIONS: Nonsustained ventricular tachycardia is frequently seen in patients with heart failure and may be associated with worsened survival by univariate analysis. However, after adjusting other variables, especially for EF, NSVT was not an independent predictor of all-cause mortality or sudden death. These results have serious implications in that suppression of these arrhythmias may not improve survival.     

Effects of magnesium sulfate and lidocaine in the treatment of ventricular arrhythmias in experimental amitriptyline poisoning in the rat

OBJECTIVES: Amitriptyline poisoning is associated with ventricular arrhythmias. Standard treatment is sodium bicarbonate but further intervention may be necessary. The present study compared the actions of lidocaine and magnesium sulfate on ventricular tachycardia induced by amitriptyline. DESIGN: Nonrandomized, controlled, intervention trial. SETTING: University laboratory. SUBJECTS: Thirty male Wistar rats anesthetized with pentobarbital and mechanically ventilated. INTERVENTIONS: After pretreatment with norepinephrine, the animals were subjected to a continuous infusion of amitriptyline. After the appearance of ventricular tachycardia, they were treated with magnesium sulfate (45 mg/kg + 15 mg/kg/min) or lidocaine (1 mg/kg + 0.5 mg/kg/min) or glucose infusion as a control. MEASUREMENTS AND MAIN RESULTS: In the group treated with magnesium sulfate, electrocardiogram tracings demonstrated that nine of ten animals converted from ventricular tachycardia to sinus rhythm compared with one of ten in both the lidocaine- and glucose-treated groups (p < .001). The animals treated with magnesium sulfate also had a significantly longer total time in sinus rhythm (10.0 +/- 1.6 mins) than those rats treated with lidocaine (1.7 +/- 1.5 mins) or glucose (1.5 +/- 1.5 mins). Magnesium sulfate significantly decreased blood pressure and heart rate, but no severe hemodynamic side effects were observed. CONCLUSIONS: Magnesium sulfate is effective in converting ventricular tachycardia in hyperadrenergic amitriptyline poisoning. In contrast, lidocaine had no effect on arrhythmias.     

Fish, fish oils, arrhythmias and sudden death

Cardiovascular morbidity and mortality is relatively low in individuals with a high consumption of fish oils containing omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid). This has been mainly attributed to the anti atherogenic and anti thrombotic effects of these oils. However, recent evidence suggests that fish and fish oils may also prevent malignant ventricular arrhythmias and sudden cardiac death. Several animal experiments have shown that fish oils can reduce the incidence of ischaemia induced ventricular tachycardia and fibrillation. Observational studies in humans have shown that there is a connection between the intake of omega-3 fatty acids and a lower risk of sudden cardiac death. Some trials suggest that fish oils can prevent ventricular arrhythmias in humans. It is possible that the effect of fish oils on arrhythmias is independent of their anti atherogenic and anti thrombotic activities. There is also some evidence that these oils affect ion fluxes in cardiomyocytes.     

Effects of guan-fu base a on experimental cardiac arrhythmias and myocardial contractility

Guan-fu base A (GFA) is a terpenoid alkaloid isolated from the tuber of Aconitum coreanum in our institute. GFA (20-30 mg.L-1) reduced the ventricular tachycardia (VT) and ventricular fibrillation (VF) rate induced by K(+)-free and high Ca2+ solution in Langendorf heart of rats. Pretreatment of conscious rats with GFA 2.5-10 mg.kg-1 iv, increased the amount of beiwutine necessary to produce arrhythmias. Ouabain-induced VT in conscious dogs was reverted to sinus rhythm in 1-2 min by iv GFA 9-10 mg.kg-1. GFA 10-20 mg.kg-1 iv was also found to be effective in protecting anesthetized dogs from atrial fibrillation induced by topical application of ACh. GFA 10 mg.kg-1 iv obviously decreased heart rate and prolonged the P-R interval, but slightly affected the myocardial contractility in anesthetized dogs. GFA showed no obvious effect on stroke volume and cardiac output in conscious dogs. In conclusion, GFA showed therapeutic and prophylactic effect on different models of experimental arrhythmias without causing marked effect on myocardial contractility.     

Morphine effects on the cardiovascular system of awake, freely behaving rats

The effects of small, i.v. infusion of morphine on the heart rate was studied in unanesthetized rats. A dose-response study indicated that all values of morphine between 5 and 1000 mug/kg resulted in a transient bradycardia. In addition, morphine doses above 20 mug/kg induced cardiac irregularities including atrial fibrillation, atrioventricular block and temporary cardiac arrest. When morphine was delivered daily over a period of eight weeks, cardiac responding (first arrhythmias and then the bradycardia) became tolerant at a time when catatonia was still present. These results indicate that in an unanesthetized rat, profound cardiovascular effects are seen to very small, mug range, doses of morphine.     

Bronchodilator response to salbutamol after chronic dosing with salmeterol or placebo

OBJECTIVES: We report the occurrence of cardiac events during long-term follow-up in patients with hypertrophic cardiomyopathy (HCM) after cardioverter-defibrillator implantation. BACKGROUND: The identification of patients at high risk for sudden death and the prevention of recurrence of sudden death in HCM represents a difficult problem. METHODS: We retrospectively analyzed the occurrence of cardiac events during follow-up of 13 patients with HCM who received an implantable cardioverter-defibrillator (ICD) because of aborted sudden death (n = 10) or sustained ventricular tachycardia (n = 3) (group I). Findings were compared with those in 215 patients with an ICD and other structural heart disease or idiopathic ventricular fibrillation (group II). RESULTS: After a mean (+/-SD) follow-up period of 26+/-18 months, 2 of 13 patients in group I received appropriate shocks. The calculated cumulative incidence of shocks was 21% in group I and 66% in group II after 40 months (p < 0.05). We observed a low incidence of recurrence of ventricular tachycardia/fibrillation during follow-up in patients with HCM. No deaths occurred. CONCLUSIONS: Our data suggest that ventricular tachyarrhythmias may not always be the primary mechanism of syncope and sudden death in patients with HCM. The ICD seems to have a less important impact on prognosis in patients with HCM than in patients with other etiologies of aborted sudden death.     

Pediatric use of intravenous amiodarone: efficacy and safety in critically ill patients from a multicenter protocol

OBJECTIVE: The purpose of this study was to analyze the efficacy and safety of intravenous amiodarone in young patients with critical, drug-resistant arrhythmias. BACKGROUND: Intravenous amiodarone has been investigated in adults since the early 1980s. Experience with the drug in young patients is limited. A larger pediatric study group was necessary to provide responsible guidelines for the drug's use before its market release. METHODS: Eight centers obtained institutional approval of a standardized protocol. Other centers were approved on a compassionate use basis after contacting the primary investigator (J.C.P). RESULTS: Forty patients were enrolled. Standard management in all failed. Many patients had early postoperative tachyarrhythmias (25 of 40), with early successful treatment in 21 (84%) of 25. Twelve patients had ventricular tachyarrhythmias: seven had successful therapy, and six died, none related to the drug. Eleven patients had atrial tachyarrhythmias: 10 of 11 had immediate success, but 3 later died. Fourteen patients had junctional ectopic tachycardia, which was treated with success (sinus rhythm or slowing, allowing pacing) in 13 of 14, with no deaths. Three other patients had supraventricular tachycardias, with success in two and no deaths. The average loading dose was 6.3 mg/kg body weight, and 50% of patients required a continuous infusion. Four patients had mild hypotension during the amiodarone bolus. One postoperative patient experienced bradycardia requiring temporary pacing. There were no proarrhythmic effects. Deaths (9 [23%] of 40) were not attributed to amiodarone. CONCLUSIONS: Intravenous amiodarone is safe and effective in most young patients with critical tachyarrhythmia. Intravenous amiodarone can be lifesaving, particularly for postoperative junctional ectopic tachycardia, when standard therapy is ineffective.     

Coronary occlusion site as a determinant of the cardiac rhythm effects of atropine and vagotomy

We have previously demonstrated that atropine pretreatment increases the incidence of fatal ventricular arrhythmias induced by left anterior descending coronary artery (LAD) occlusion. The purpose of the present study was to determine whether the deleterious effect of atropine also applies to arrhythmias induced by right coronary artery (RCA) occlsusion. Occlusion of the RCA resulted in ventricular arrhythmias in all 20 animals studied, followed by ventricular fibrillation in three animals (15 per cent). Right coronary occlusion also resulted in bradycardia (-30.3 +/- 5.1 beats per minute) and hypotension (-23.1 +/- 4.9 mm. Hg). Pretreatment of 15 animals with atropine caused no significant increase in the incidence of ventricular fibrillation (i.e., 20 per cent). In addition, atropine pretreatment had no effect on the fall in heart rate and hypotension associated with RCA ligation. Sectioning the vagus nerves produced results similar to atropine pretreatment with the exception that a significant portion of the bradycardia was prevented. These results indicate that the increase in deaths after atropine observed in animals undergoing experimental LAD occlusion in not demonstrated with RCA occlusion. The results also indicate that the potential for deleterious effects of atropine in acute infarction might depend on the anatomic location of the involved myocardium.     

Sudden cardiac death and the use of implantable cardioverter-defibrillators in pediatric patients. The Pediatric Electrophysiology Society

BACKGROUND: During the past decade, the implantable cardioverter-defibrillator (ICD) has emerged as the primary therapeutic option for survivors of sudden cardiac death (SCD). Investigation of the clinical efficacy of these devices has primarily assessed outcome in adults with coronary artery disease. The purpose of this cooperative, international study was to evaluate the impact of ICDs on the pediatric population of SCD survivors, based on an analysis of the clinical characteristics and outcomes of young patients who underwent ICD implantation following an episode of life-threatening ventricular tachycardia or resuscitation from SCD. METHODS AND RESULTS: An initial data base, established by contacting the manufacturers of the various commercially and investigationally available devices, identified 177 patients who were less than 20 years of age at the time of initial implantation of an ICD. With this data base as a reference, detailed responses were subsequently obtained from physicians involved in the care of 125 (71%) of these patients. The patients ranged in age from 1.9 to 19.9 years (mean, 14.5 +/- 4 years) and weighted 9.7-117 kg (mean, 44.6 +/- 14 kg). Of the 125 patients, 76% were survivors of SCD, 10% had drug refractory ventricular tachycardia, and 10% had syncope with heart disease and inducible sustained ventricular tachyarrhythmias. The most common types of associated cardiovascular disease were hypertrophic and dilated cardiomyopathies (54%), primary electrical diseases (26%), and congenital heart defects (18%). Ventricular function was abnormal in 46% of the patients. During a mean follow-up of 31 +/- 23 months, at least one ICD discharge occurred in 85 of the 125 (68%) patients. Seventy-three patients (59%) received at least one appropriate ICD discharge, and 25 patients (20%) had one or more spurious or indeterminate discharges. Duration of follow-up > 24 months (p = 0.001) and inducibility of a sustained ventricular arrhythmia (p = 0.05) were correlated with appropriate ICD discharges. There were nine deaths during the study period: five sudden, two due to recurrent ventricular arrhythmias, and two related to congestive heart failure. Abnormal ventricular function (p = 0.002) and prior ICD discharge (p = 0.01) were univariate correlates of patient mortality; by multivariate logistic regression, abnormal ventricular function was the only significant correlate of death (p = 0.005). By actuarial analysis, the estimated overall post-ICD implant survival rates at 1, 2, and 5 years were 95%, 93%, and 85%, respectively. The corresponding sudden death-free survival rates were 97%, 95%, and 90%. CONCLUSIONS: Pediatric patients resuscitated from SCD appear to remain at risk for recurrence of life-threatening tachyarrhythmias. During a mean follow-up of 31 months, the ICD provided an effective therapy for such arrhythmias in the majority of patients in this study. Following ICD implant, impaired ventricular function was the primary factor correlated with mortality. The patterns of ICD discharge observed in young patients and, thus, inferred risk of recurrent life threatening arrhythmias are similar to those of adult survivors of SCD. Thus, the use of ICDs in pediatric patients, with implant selection criteria similar to adults, appears valid.     

Arrhythmias after acute myocardial infarction. Evaluation and management of rhythm and conduction abnormalities

Patients with myocardial infarction can experience a wide range of arrhythmias and conduction abnormalities, from transient and relatively innocuous sinus bradycardia to life-threatening ventricular fibrillation. This nut-and-bolts article covers all the possibilities, emphasizing the clinical significance of the various arrhythmias and their evaluation and treatment. Also included are indications for temporary and permanent pacemaker placement based on the revised ACC/AHA guidelines.     

Radiofrequency treatment of tachyarrhythmias in children and adolescents

INTRODUCTION: Radiofrequency ablation has been extensively used in adults to treat supraventricular and ventricular tachycardia. In children and adolescents few data are available on its safety and efficacy. METHODS: 28 patients (mean age 12.8) with symptomatic tachyarrhythmias underwent catheter ablation; 21 children had atrioventricular accessory pathways (11 right connections, 9 lef connections and one midseptal pathway), 3 had intranodal tachycardia, 2 had ventricular tachycardia and 2 had atrial tachycardia. Only four patients had associated structural anomalies. RESULTS: Success rate was 71.4% (20 patients). The success per cents in each group were: in intranodal tachycardias 100%; we failed in the two patients with ventricular tachycardias; in accessory pathways 76.1% and 50% in atrial tachycardia. There were no recurrences of arrhythmia in a mean chase period of 24 months (12-46). Major complications were only observed in one patient who developed a Wallenberg syndrome after ablation. CONCLUSIONS: Radiofrequency catheter ablation appears to be a safe and effective method to treat arrhythmias in children and adolescents, which in most cases can supersede surgery. Alow incidence of complications is reported, although long term damage on endocardial structures remains yet to be determined.     

Sudden death in hypertrophic myocardiopathy]

Hypertrophic cardiomyopathy is the most common cause of sudden death in young individuals who are otherwise healthy. Risk of sudden death is highest in patients who are between 14 and 35 years old. Several mechanisms are involved in sudden death: ventricular arrhythmias, supraventricular arrhythmias leading to cardiac collapse, bradycardias and severe ischemia. Many studies have analyzed how to identify high risk patients. The factors that best identify high risk patients are: previous history of sudden death or syncope, induction in adults of sustained ventricular arrhythmias, the presence of non-sustained ventricular tachycardia in symptomatic patients, the presence of ischemia associated with hypotension in children, the presence of mutations in the beta-myosin heavy chain together with a family history of sudden death and a poor left ventricular ejection fraction. Risk stratification should be done on an individualized basis. In those patients in whom a high risk for sudden arrhythmic death is suspected, the only current effective treatment is the implantable defibrillator.     

"The athlete's heart": most common electrocardiographic findings

The morphological and functional cardiac adaptations induced by physical training may be reflected in several athlete's electrocardiographic variants. Rhythm and heart rate disturbances are the most common findings, and sinus bradycardia is the most frequent adaptation. Non-specific intraventricular conduction delay and incomplete right bundle branch block are also frequent, but other bundle branch and fascicular blocks are extremely rare. While the atrioventricular conduction may be prolonged, the occurrence of first degree and type I second degree atrioventricular blocks depends on the individual's susceptibility. Advanced second and third degree atrioventricular blocks are exceptional, and when present, the possibility of underlying heart disease must be excluded. High QRS voltage is more frequent in male athletes, but its correlation with left ventricular hypertrophy is low. The ST segment elevation in the so called "early repolarization" pattern is typical of the athlete's electrocardiogram. Vagotonic or high T wave voltages and U waves are also frequent when sinus bradycardia is present. Tachyarrhythmias and increased automatism arrhythmias are rare and usually benign. The increased vagal tone is responsible for the suppression of the physiological and ectopic pacemakers. While Wolff-Parkinson-White syndrome per se does not exclude an athlete from sports activity, the risk of a sudden death makes it mandatory to perform an exhaustive cardiac evaluation. We may conclude that no sport can be considered arrhythmogenic or as a predisposing factor for malignant ventricular arrhythmias.     

Pharmacological profile of valsartan, a non-peptide angiotensin II type 1 receptor antagonist. 5th communication: hemodynamic effects of valsartan in dog heart failure models

Hemodynamic effects of valsartan ((S)-N-valeryl-N-?[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]meth yl?valine, CAS 137862-53-4, CGP 48933), a non-peptide angiotensin II type 1 receptor antagonist were examined in dogs with heart failure induced acutely by coronary artery ligation and chronically by rapid-ventricular pacing. Coronary artery ligation induced decrease in cardiac output and increase in left ventricular end-diastolic pressure. Valsartan at 10 mg/kg i.v. reduced blood pressure, heart rate, left ventricular pressure, left ventricular end-diastolic pressure and total systemic resistance. Similar changes were observed with enalaprilat at 0.1 mg/kg i.v. Rapid left ventricular pacing for 2 weeks reduced cardiac contractility. Valsartan, administered at a dose of 100 mg/kg/d p.o. for 2 weeks, lowered left ventricular end-diastolic pressure. Valsartan reduced preload and afterload in these two dog heart failure models.     

The current role of amiodarone in patients with congestive heart failure

Amiodarone in low to moderate doses is generally safe in controlling arrhythmias in patients with congestive heart failure (CHF). However, its role is uncertain, because it did not affect the overall mortality rate in three out of four large-scale studies. Whether some subgroups might benefit is a matter of speculation. In patients with sustained ventricular tachycardia, or in those who have survived an episode of sudden death, implantation of a cardioverter-defibrillator may be a better strategy.