Myocardial phenotype changes in heart failure: cellular and subcellular adaptations and their functional significance.
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Cardiomegaly↗
Biomedical subjects
H Just
Publications and source records attributed to H Just.
Pathophysiology and treatment of congestive heart failure.
Pharmacotherapy of heart failure is likely to be most efficacious when individually tailored to the prevailing pathophysiological derangements. Their diagnostic definition and understanding of the mechanisms involved affords the greatest opportunity for their correction and retardation of further progression of the syndrome, together with related improvements in quality of life, reduction of morbid cardiovascular events and improvement in prognosis. Four approaches may be identified, each of which allows rational therapeutic intervention. The disordered contractile geometry of the failing ventricle gives rise to increased ventricular wall tension and myocardial hypertrophy. The phenotype change largely responsible for this progression may be retarded, halted, or even reversed by a reduction of the elevated ventricular pressure and volume induced by diuresis and/or systemic vasodilatation. Knowledge of the subcellular changes responsible for electromechanical coupling and subsequent myocardial cell contraction in the various stages of heart failure is still incomplete. Pharmacotherapeutic interventions with positive inotropic agents have not been universally clinically efficacious, though the digitalis glycosides and, more recently, drugs that increase the sensitivity of the contractile proteins to calcium appear to afford further opportunity as they do not increase myocardial energy expenditure. In this regard, reduction in heart rate is a major determinant of myocardial contractile performance. Vascular stiffness and reduced vasodilator capacity are intrinsic accompaniments of congestive heart failure and exert deleterious effects on the heart by increasing preload and afterload and on the regional circulations by reducing blood flow. The mechanisms responsible include increased activity of the sympathoadrenal and renin-angiotensin-aldosterone systems, as well as reduction of endothelium-derived relaxing factor and increased stiffness of the vascular wall due to oedema.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood Vessels↗
Reflex versus tonic vagal activity as a prognostic parameter in patients with sustained ventricular tachycardia or ventricular fibrillation.
BACKGROUND: The autonomic nervous system has been demonstrated to play a decisive role in the genesis of sudden cardiac death. The loss of protective vagal reflexes, in particular, appears to be associated with an increased incidence of malignant ventricular tachyarrhythmias. Two clinically applicable methods for assessment of cardiac autonomic control have been developed: determination of heart rate variability and evaluation of baroreflex sensitivity. METHODS AND RESULTS: To compare the potential predictive value of both methods, two groups of patients were studied. Group 1 comprised 14 postinfarction patients who had experienced at least one episode of ventricular fibrillation or sustained ventricular tachycardia and who were studied after this event. Group 2 consisted of 14 postinfarction patients without tachyarrhythmic events after their infarct. Both groups were carefully matched with respect to age, sex, infarct location, extent of coronary artery disease, left ventricular ejection fraction, blood pressure, and heart rate at rest. Heart rate variability was assessed from 24-hour Holter recordings, and baroreflex sensitivity was determined by means of the phenylephrine method. Indices of heart rate variability were not significantly different between the two groups (SD of the mean RR interval, 84 +/- 30 milliseconds versus 103 +/- 20 milliseconds; proportion of adjacent RR intervals > 50 milliseconds different, 2.8 +/- 3.2% versus 5.0 +/- 4.1% in group 1 versus 2). Baroreflex sensitivity, however, showed a striking difference: Group 1 patients had a mean value of 1.75 +/- 1.63 ms/mm Hg compared with 9.17 +/- 5.40 ms/mm Hg in group 2 (P = .0002). Eleven of 14 group 1 patients had a baroreflex sensitivity < or = 3.0 ms/mm Hg. By contrast, only 1 of 14 group 2 patients had such a depressed value. CONCLUSIONS: The results of this study indicate that postmyocardial infarction patients who develop life-threatening ventricular tachyarrhythmias, compared with carefully matched postinfarction patients without major arrhythmic episodes, differ strikingly in terms of baroreflex sensitivity but not in terms of heart rate variability. This finding may have implications for the risk stratification of postinfarction patients and may lead to a differential therapeutic strategy based on autonomic testing.
Baroreflex↗
Coronary atherosclerotic wall thickening and vascular reactivity in humans. Elevated high-density lipoprotein levels ameliorate abnormal vasoconstriction in early atherosclerosis.
BACKGROUND: Abnormal vascular reactivity represents a fundamental disturbance in vascular biology with the development of atherosclerosis. Because endothelial vasodilator function plays a pivotal role in controlling vasomotor tone, we hypothesized that atherosclerotic wall thickening might directly interfere with deficient endothelium-mediated dilation and thereby contribute to the abnormal reactivity of atherosclerotic arteries in vivo. METHODS AND RESULTS: In 26 patients without focal stenoses in the left anterior descending coronary artery, acetylcholine (0.036 to 3.6 micrograms/mL) was infused into the artery to evaluate endothelium-mediated vasodilation. Segmental vasomotor responses to acetylcholine were correlated with the local extent of atherosclerotic wall thickening quantitated by intracoronary ultrasound examination. Seventeen of the patients also underwent cold pressor testing to assess the vasoreactivity to sympathetic activation. The response of coronary artery segments to acetylcholine varied from 35% dilation to 52% constriction and demonstrated a segmental pattern, with dilation and constriction observed in different segments of the same artery. The vasomotor response to acetylcholine was closely correlated with the extent of local atherosclerotic wall thickening (r = -.82, P < .0001). Over the entire range of atherosclerotic wall thickening, segments from patients with elevated high-density lipoprotein (HDL) cholesterol serum levels (> 75th percentile) demonstrated a significantly blunted constrictor response to acetylcholine (P < .01 at the maximal acetylcholine concentration) compared with segments from patients with HDL cholesterol < 75th percentile. The degree of constriction or dilation in response to the acetylcholine infusion correlated with the response to cold pressor testing (r = .75, P < .0001). Again, the cold pressor test-induced constrictor response was significantly (P < .05) blunted in segments from patients with elevated HDL cholesterol serum levels compared with those from patients with HDL cholesterol < 75th percentile despite equal degrees of atherosclerotic wall thickening. CONCLUSIONS: Coronary vasomotor responses to the endothelium-dependent dilator acetylcholine and to sympathetic stimulation by cold pressor test correlate with local atherosclerotic wall thickening. Thus, the degree of abnormal local vascular reactivity is closely related to the extent of atherosclerotic "plaque load" in human epicardial arteries in vivo. Elevated HDL cholesterol serum levels ameliorate abnormal vasoconstriction at any given extent of atherosclerotic wall thickening, suggesting that HDL cholesterol exerts a beneficial effect on abnormal vascular reactivity, a fundamental functional disturbance associated with coronary atherosclerosis.
Acetylcholine↗
Open infarct artery, late potentials, and other prognostic factors in patients after acute myocardial infarction in the thrombolytic era. A prospective trial.
BACKGROUND: Successful reperfusion of the infarct-related artery in patients with acute myocardial infarction has been shown to reduce in-hospital as well as 1-year mortality. Besides the thrombolysis-induced myocardial salvage, there is increasing evidence that an open infarct-related artery results in increased electrical stability of the heart and that this effect is at least in part responsible for the favorable long-term outcome of these patients. The exact incidence of arrhythmic events during the first year after myocardial infarction and the predictive value of different risk factors for these complications, however, have not been determined in patients in the thrombolytic era. METHODS AND RESULTS: A total of 173 patients with acute myocardial infarction, 51% treated with thrombolysis, were prospectively entered into the study. At the time of hospital discharge, signal-averaged ECG, Holter monitoring, radionuclide angiography, coronary angiography, and levocardiography were performed in all patients. An open infarct-related artery was documented in 136 patients. The overall incidence of late potentials was 24% (41 patients). By multivariate analysis, an occluded infarct-related artery (P = .04) and the presence of regional wall motion abnormalities (P = .02) were the strongest independent predictors for the development of a late potential. Residual ischemia was treated by either percutaneous transluminal coronary angioplasty or surgery in 86 of 173 patients (50%). Seventy percent of the patients received beta-blocker therapy. During a mean follow-up of 12 +/- 5 months, 7 patients died suddenly or had ventricular fibrillation documented, while only 2 developed sustained monomorphic ventricular tachycardia. Overall 1-year mortality was 4.1%. Multivariate analysis revealed only an occluded infarct-related artery as an independent predictor of arrhythmic complications (P = .017). CONCLUSIONS: In patients with acute myocardial infarction treated according to contemporary therapeutic guidelines, with a large proportion of individuals undergoing coronary artery revascularization, a low incidence of arrhythmic events, particularly of ventricular tachycardia, was observed in the first year after the index infarction. The presence or absence of an open infarct-related artery was the strongest independent predictor of these events, whereas other traditional risk factors, such as late potentials, were less helpful in identifying patients prone to sudden death. These findings emphasize the importance of the open artery hypothesis in patients recovering from acute myocardial infarction.
Adult↗
Adjunctive intracoronary infusion of antithrombin III during percutaneous transluminal coronary angioplasty. Results of a prospective, randomized trial.
BACKGROUND: Heparin needs the plasma protein antithrombin III to function as an inhibitor of thrombin, and local antithrombin III deficiency might therefore limit the antithrombotic effectiveness of heparin during percutaneous transluminal coronary angioplasty. METHODS AND RESULTS: In the present double-blind study, 615 consecutive patients undergoing percutaneous transluminal coronary angioplasty (PTCA), of a total of 713 stenoses, were prospectively randomized to receive a bolus injection of 15,000 U heparin followed by a continuous intracoronary infusion via the guiding catheter of either 250 U heparin per minute or 250 U heparin plus 25 U antithrombin III per minute during the procedure. Four clinical variables, 19 lesion-specific characteristics, and 16 procedure-related variables were evaluated. Procedural success was assessed by quantitative angiography; procedure-related ischemic complications were analyzed during in-hospital follow-up. Procedural success rates (< 50% final diameter stenosis and no major ischemic complication) were similar, with 85% in the heparin group (n = 324 patients) and 83% in the heparin+antithrombin III group (n = 291 patients). Percent diameter stenosis after PTCA was 39 +/- 18% in the heparin group and 40 +/- 20% in the heparin+antithrombin III group (NS). There were no differences between the two groups with respect to PTCA-related acute vessel occlusion, angiographic evidence of intracoronary thrombus formation, post-procedure creatine kinase increase, Q-wave myocardial infarction, or emergency coronary artery bypass surgery. High-risk subgroup analysis revealed no beneficial effect of adjunctive intracoronary antithrombin III in any of the analyzed subgroups. In addition, although risk stratification according to the criteria of the American College of Cardiology/American Heart Association Task Force classification proved to be very useful for the entire study population, no beneficial effect of intracoronary antithrombin III infusion was observed in any of the different risk groups. CONCLUSIONS: Compared with heparin alone, adjunctive intracoronary antithrombin III therapy does not appear to have any beneficial effect on procedural outcome as well as type and frequency of acute complications during PTCA even in subgroups of patients with a high risk for thrombotic complications. Thus, a local deficiency of antithrombin III does not play a major role for the failure of heparin to abolish thrombotic complications during PTCA.
Aged↗
Relation between myocardial function and expression of sarcoplasmic reticulum Ca(2+)-ATPase in failing and nonfailing human myocardium.
Expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase was shown to be reduced in failing human myocardium. The functional relevance of this finding, however, is not known. We investigated the relation between myocardial function and protein levels of SR Ca(2+)-ATPase in nonfailing human myocardium (8 muscle strips from 4 hearts) and in myocardium from end-stage failing hearts with dilated (10 muscle strips from 9 hearts) or ischemic (7 muscle strips from 5 hearts) cardiomyopathy. Myocardial function was evaluated by the force-frequency relation in isometrically contracting muscle strip preparations (37 degrees C, 30 to 180 min-1). In nonfailing myocardium, twitch tension rose with increasing rates of stimulation and was 76% higher at 120 min-1 compared with 30 min-1 (P < .02). In failing myocardium, there was no significant increase in average tension at stimulation rates above 30 min-1. At 120 min-1, twitch tension was decreased by 59% (P < .05) in dilated cardiomyopathy and 76% (P < .05) in ischemic cardiomyopathy compared with nonfailing myocardium. Protein levels of SR Ca(2+)-ATPase, normalized per total protein or per myosin, were reduced by 36% (P < .02) or 32% (P < .05), respectively, in failing compared with nonfailing myocardium. SR Ca(2+)-ATPase protein levels were closely related to SR Ca2+ uptake, measured in homogenates from the same hearts (r = .70, n = 16, and P < .005).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Gene expression of the cardiac Na(+)-Ca2+ exchanger in end-stage human heart failure.
The regulation of cytosolic Ca2+ concentration during excitation-contraction coupling is altered in the failing human heart. Previous studies have focused on disturbances in Ca2+ release and reuptake from the sarcoplasmic reticulum (SR), whereas functional studies of the cardiac Na(+)-Ca2+ exchanger, another important determinant of myocyte homeostasis, are lacking for the failing human heart. Using a cardiac Na(+)-Ca2+ exchanger cDNA recently cloned from a guinea pig cDNA library, we investigated the gene expression of the cardiac Na(+)-Ca2+ exchanger in relation to the SR Ca(2+)-ATPase. Expression of both genes was quantified in left ventricular myocardium from 24 failing human cardiac explants and 7 control heart samples in relation to beta-myosin heavy chain mRNA by slot blot analysis. Compared with patients with nonfailing hearts, patients with dilated cardiomyopathy (DCM, n = 13) showed a 55% increase in Na(+)-Ca2+ exchanger mRNA levels (P < .05 versus control value) and a 41% increase in patients with coronary artery disease (CAD, n = 11). In the same hearts, SR Ca(2+)-ATPase mRNA levels were decreased by 50% in DCM and by 45% in CAD (P < .05 for both versus control value). There was a positive correlation between Na(+)-Ca2+ exchanger and SR Ca(2+)-ATPase mRNA levels both in normal and failing human hearts, albeit with different slopes and intercepts of the regression line. The Na(+)-Ca2+ exchanger protein levels as assessed by Western blot analysis and normalized to beta-myosin heavy chain protein were increased in DCM and CAD (P < .05 and P < .01 versus control value, respectively), whereas SR Ca(2+)-ATPase protein levels were reduced (P < .05 for both groups versus control values). Thus, the Na(+)-Ca2+ exchanger gene expression is enhanced in failing human hearts and may, in part, compensate for the depressed SR function with regard to diastolic Ca2+ removal.
Adult↗
Increased angiotensin-I converting enzyme gene expression in the failing human heart. Quantification by competitive RNA polymerase chain reaction.
Local activation of the components of the renin angiotensin system in the heart is regarded as an important modulator of cardiac phenotype and function; however, little is known about their presence, regulation, and potential activation in the human heart. To investigate the gene expression of major angiotensin-II-forming enzymes in left ventricles of normal (n = 9) and failing human hearts (n = 20), we established a competitive RNA-polymerase chain reaction (PCR) for mRNA quantification of angiotensin-I converting enzyme (ACE) and human heart chymase. For each gene, competitor RNA targets with small internal deletions were used as internal standards to quantify the original number of transcripts and to control reverse transcription and PCR. In PCR, each target and the corresponding competitor were amplified by competing for the same primer oligonucleotides. The variability of ACE RNA-PCR was 11% indicating a high reproducibility of this method. In addition, ACE mRNA levels obtained by competitive RNA-PCR correlated favorably with traditional slot blot hybridization (r = 0.69, n = 10; P < 0.05). Compared with nonfailing hearts, the number of ACE transcripts referred to 100 ng of total RNA was increased threefold in patients with chronic heart failure (4.2 +/- 2.5 vs. 12.8 +/- 6 x 10(5); P < 0.0005). In contrast, no significant difference was found in chymase gene expression between normal and failing hearts. Thus, the expression of the cardiac ACE but not of human heart chymase is upregulated in failing human heart indicating an activation of the cardiac renin-angiotensin system in patients with advanced heart failure.
Adult↗
Drug-induced torsade de pointes. Incidence, management and prevention.
Torsade de pointes is a particular form of polymorphic ventricular tachycardia causing few haemodynamic symptoms, but carries a poor prognosis because of recurrence and sudden death in up to 31% of patients. A wide range of agents have been shown to aggravate and even to cause torsade de pointes by prolonging the QT interval or increasing QT dispersion. For the majority of substances the incidence of torsade de pointes remains unclear, but is of the order of 3 to 15% for a wide range of agents. Elicitation of proarrhythmia by drug-induced QT prolongation is mainly based on increased cellular excitability and/or abnormal dispersion of ventricular repolarisation. Torsade de pointes has been shown to be related to bradycardia-dependent early after-depolarisations and/or increased dispersion of repolarisation. Clinically, patients with predisposing factors prior to medication should be considered at risk of drug-mediated proarrhythmia. Typically, torsade de pointes occurs during the first days of antiarrhythmic therapy. During this phase, QT interval measurement and assessment of the QTc time should be performed frequently. Phases of bradycardia or occurrence of ventricular extra beats with a long coupling interval may be of help to identify patients at high risk of proarrhythmic events. As a first attempt in managing this arrhythmia, magnesium sulphate has been shown to be effective in many patients. In case of recurrence of torsade de pointes, the use of a temporary pacemaker with pacing at about 100 to 120 beats/min is the therapy of choice until the causative agent has been completely eliminated.
Anti-Arrhythmia Agents↗
[Amiodarone and verapamil/quinidine in treatment of patients with chronic atrial fibrillation].
Rapid, reliable and safe reestablishment of sinus rhythm is the major aim of pharmacologic treatment in patients with chronic atrial fibrillation. The mainstay of therapy in this arrhythmia has been quinidine. More recently, amiodarone was shown in noncomparitive studies to be superior to class IA agents under certain conditions. In 40 patients with atrial fibrillation persisting for 4 weeks up to 2 years, the efficacy and safety of either quinidine and verapamil (days 1 to 3, quinidine 1,500 mg/day; days 4 to 6, quinidine 1,500 mg+verapamil 240 mg/day) or amiodarone therapy (days 1 to 3, amiodarone 1,200 mg/day intravenously; days 4 to 14, amiodarone 800 mg/day orally) were randomly examined. Responders continued on their effective medication for 3 months. Thereafter, all patients were treated with a fixed regimen of quinidine (480 mg/day) plus verapamil (240 mg/day) for up to 2 years. During atrial fibrillation, quinidine reduced mean ventricular cycle length by 40 ms (-5%), quinidine and verapamil increased mean cycle length by 57 ms (8%) and amiodarone by 192 ms (28%, p < 0.01). In addition, quinidine and verapamil had a characteristic "rate-smoothing" effect on atrioventricular conduction during atrial fibrillation. The rhythm was converted to sinus rhythm after quinidine in 5 (25%) of 20 patients and after the combination of quinidine and verapamil in 11 (55%) of 20 patients. Amiodarone restored sinus rhythm in 12 (60%) of 20 patients. Overall, a shorter duration of atrial fibrillation (p < 0.05) and a smaller left atrial size (p < 0.01) were predictive of successful conversion of the arrhythmia.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Role of calcium antagonists in progression of arteriosclerosis. Evidence from animal experiments and clinical experience. Part II. Clinical experience with preventive effects of calcium channel blockers in atheromatous coronary artery disease.
Experimental evidence for antiatheromatous of effects of calcium antagonists has been impressive. Clinical experience has, in contrast, been more difficult to obtain. Primary prevention with calcium antagonists has not been studied due to obvious difficulties. Secondary prevention, however, has been investigated: Several studies have addressed influence of calcium antagonists upon atheromatous arterial wall changes as demonstrated by quantitative coronary angiocardiography. A review of these studies reveals considerable methodological problems. For nifedipine it could be demonstrated, however, that the occurrence of "new lesions" can be retarded to a certain extent (3-6). Nicardipine has been studied, but the preventive effect reported cannot be considered valid, because distribution of risk factors to the study groups was not statistically homogeneous. Another approach has been the application of calcium antagonists to patients with acute myocardial infarction. Here, vascular and myocardial effects come into play. In non-Q-wave, i.e. not transmural infarction, the calcium antagonist diltiazem definitely has preventive effects as regards re-infarction (2). The large multicenter post-myocardial infarction trial MDPIT showed an improvement of cardiac envent rate and re-infarction. This effect was seen only if pulmonary congestion was not present. Calcium antagonists have negative effects if cardiac failure is present. Verapamil was shown to have beneficial effects in acute myocardial infarction in the large DAVIT trials. Here again, the effect was only seen if heart failure was not present. Otherwise negative results were recorded. Nifedipine demonstrated only borderline myocardial protective effects in acute myocardial infarction (7). We conclude that calcium antagonists have vascular and myocardial protective effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Calcium Channel Blockers↗
[Continuous molsidomine infusions in patients with unstable angina pectoris and acute myocardial infarct].
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Adult↗
[Effects of intravenous administration of nitroglycerin and SIN-1 or molsidomine on epicardial arterial diameter in patients with stable coronary heart disease].
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Coronary Circulation↗
[Use of enoximone in patients with acute and subacute heart failure in the intensive care unit].
The phosphodiesterase inhibitor enoximone has both vasodilating and positive inotropic pharmacological properties. The balance between vasodilation and positive inotropism may be different between the various types of heart failure as well as the various stages of heart failure. Therefore, we investigated the effect of intravenous application of enoximone (1 mg/kg body weight) in a cohort of patients (n = 10) suffering from acute or subacute heart failure mainly due to ischemia or hypoxia. All patients had high left ventricular filling pressure, low cardiac output and were pretreated with intravenous dobutamine. Enoximone increased cardiac output from 3.2 +/- 1.2 to 5.5 +/- 2.2 l/min, increased heart rate from 94 +/- 20 to 100 +/- 18 beats/min, decreased systemic peripheral resistance from 1770 +/- 861 to 931 +/- 340 dyn.sec.cm-5 and decreased pulmonary wedge pressure from 24 +/- 5 to 20 +/- 6 mmHg, significantly. However, systolic aortic pressure, systolic pulmonary pressure and right atrial pressure were not significantly altered. We conclude that in a selected group of patients enoximone-given intravenously and acutely in the intensive care unity-can induce beneficial effects on central hemodynamics without critical falls in perfusion pressure.
Aged↗
[Stucture and function of the endothelium in cardivascular diseases. Introduction to the theme].
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Animals↗
Endothelial dysfunction in chronic heart failure. Experimental and clinical studies.
The endothelium plays an important role in the control of human vascular tone by releasing endothelium-derived nitric oxide. Therefore, endothelial dysfunction could be involved in the increased peripheral vasoconstriction of patients with chronic congestive heart failure (CHF). To investigate endothelial function in humans in vivo, agents such as acetylcholine are used to stimulate the release of endothelium-derived nitric oxide (EDRF). Conversely, N-mono-methyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthesis from L-arginine decreases forearm blood flow by inhibiting the basal release of nitric oxide. Consistent with experimental studies, the blood flow response to acetylcholine is blunted in patients with chronic heart failure as compared to healthy age-matched volunteers. In contrast, the decrease in blood flow induced by L-NMMA appears to be exaggerated in CHF. The blood flow response to nitroglycerin or sodium nitroprusside, endothelium-independent vasodilators, is usually preserved in patients with chronic, non-edematous heart failure, indicating a normal response of the vascular smooth muscle of resistance vessels to exogenous nitric oxide. In contrast, the dilator response of the radial artery diameter to nitroglycerin and flow-dependent dilation are impaired in patients with chronic heart failure, indicating that the abnormal flow-mediated relaxation of large arteries may be due to both endothelial and vascular smooth muscle alterations. Thus, impaired endothelium-dependent dilation of peripheral resistance vessels emerges in chronic heart failure, suggesting a reduced release of nitric oxide upon stimulation. Thus, endothelial dysfunction may be involved in the impaired vasodilator capacity in the peripheral circulation, e.g. during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Arginine↗
Effect of sotalol on heart rate variability assessed by Holter monitoring in patients with ventricular arrhythmias.
Reduced vagal activity has been demonstrated to be associated with an increased risk of sudden death. Assessing the heart rate variability as a measure of the autonomic control of the heart has been established as a useful tool for the risk stratification of patients after myocardial infarction. In the current study, heart rate variability assessed by time- and frequency-domain measures was determined from Holter recordings before and during treatment with sotalol in 28 patients with chronic ventricular arrhythmias. The heart rate variability at baseline was independent of the presence or absence of spontaneous arrhythmias and of left ventricular function. Therapy with sotalol produced a significant improvement over control values in indices of parasympathetic tone (root mean square of the difference in successive RR intervals, proportion of adjacent RR intervals different by > 50 msec, high-frequency power spectrum). This improvement was not related to drug-induced changes in the mean heart rate or the suppression of ventricular ectopic activity. These effects on heart rate variability may contribute significantly to the overall efficacy profile of sotalol.
Adult↗