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Background: Health-related quality of life (HQOL) enhancement is a major objective of valvular surgery (VS), but assessments have been limited primarily to generic measures that may not be optimally responsive to intervention. Disease-specific instruments have been used in heart failure (HF), commonly associated with valve disease, but have been neither validated nor routinely applied among patients undergoing VS., Methods and Results: We administered the Minnesota Living with Heart Failure (MLHFQ) and SF-36 questionnaires preoperatively (T(0)) to 50 patients undergoing VS and at 1 (T(1)) and 6 months (T(2)) after VS. Performance of MLHFQ was evaluated and compared with SF-36. MLHFQ completion rates were >98% (NS vs. SF-36); Cronbach's alpha was > or = 0.9 (total score, dimensions), supporting internal reliability. Confirmatory factor analysis verified good model fit for physical/emotional domain items (relative chi-squares < 3.0, critical ratios > 2.0, both instruments), supporting structural validity. Spearman coefficients correlating MLHFQ with parallel SF-36 domains were moderate to high (0.6-0.9; P < or = .001: T(0)-T(2)), supporting convergent validity. Baseline HQOL was poorest in patients with HF (P < or = .05 [both instruments]), supporting criterion validity. Responsiveness (proportional HQOL change scores: T(0) vs. T(2)) to VS was greater with MLHFQ vs. SF-36 (P < or = .002)., Conclusions: Among patients undergoing VS, the MLHFQ is highly acceptable and maintains good psychometric properties, comparing favorably with SF-36. These findings suggest its utility for measuring disease-specific HQOL changes after VS.

Background: Community patients with heart failure (HF) are older, less often treated by HF specialists, and have more comorbidity than those in randomized clinical trials. These differences might affect beta-blocker prescribing in HF., Methods: To explore patterns of beta-blocker prescribing for HF in the community and their association with outcomes, we determined carvedilol doses at end titration in 4113 patients from a community-based beta-blocker HF registry according to physician and patient characteristics, HF severity, and rates of hospitalization and death., Results: Female sex, age > or = 65 years, and left ventricular ejection fraction > or = 35% were associated with lower beta-blocker doses. Average daily dose of beta-blocker was lower with worse baseline New York Heart Association class. More patients of cardiologists achieved carvedilol doses > or = 25 mg twice daily, whereas in those of noncardiologists lower doses were more common. Relative risk of HF hospitalizations or all-cause death was significantly lower with higher doses of beta-blocker., Conclusions: Beta-blocker dosing in community HF appears lower than in randomized clinical trials, especially when prescribed by noncardiologists. At all doses, patients taking the beta-blocker carvedilol have a lower incidence of death and HF hospitalization than those discontinuing it, regardless of physician type in the community setting.

Heart failure (HF) in the community differs meaningfully from that in clinical trials, particularly the higher prevalence of patients with preserved left ventricular (LV) ejection fraction (EF) typically excluded from clinical trials, thus limiting knowledge of their responsiveness to beta-blocker therapy. From a community-based registry of 4,280 patients with HF starting treatment with the beta blocker carvedilol, we compared characteristics, carvedilol titration, and outcomes of patients according to LVEF >40% or <40% (as in clinical trials) and across the spectrum of LVEF <21%, 21% to 30%, 31% to 40%, and >40%. Patients with preserved EF (LVEF >40%) were older and more often women and hypertensive. Lower LVEF was associated with worse functional class and more HF hospitalizations in the previous year. Carvedilol dose decreased with increasing LVEF. Hospitalization rates for HF related inversely to LVEF before starting carvedilol therapy and decreased from the previous year in all LVEF groups during follow-up. Although 1-year mortality rate decreased from 8% with LVEF < or =20% to 6% with LVEF >40%, adjusted hazard ratios were not significantly different across LVEF groups. Thus, characteristics of community patients with HF vary across the spectrum of LVEF. Patients with HF and preserved EF treated with carvedilol in the community improve symptomatically and experience fewer HF hospitalizations after initiating carvedilol. In conclusion, without a control group, the effect of carvedilol on outcomes is not conclusive and trials of carvedilol in patients with HF and preserved EF should be undertaken.

Heart failure (HF) clinical trials suggest different responses of blacks and whites to beta-blockers. Differences between clinical trial and community settings may also have an impact. The Carvedilol Heart Failure Registry (COHERE) observed experience with carvedilol in 4280 patients with HF in a community setting. This analysis compares characteristics, outcomes, and carvedilol dosing of blacks and whites in COHERE. Compared with whites (n=3433), blacks (n=523) had more severe HF symptoms despite similar systolic function. At similar carvedilol maintenance doses, symptoms improved in 33% of blacks vs 28% of whites, while worsening in 10% and 11%, respectively (both nonsignificant), and HF hospitalization rates were reduced comparably in both groups (-58% vs -56%, respectively; both P<.001). Incidence and hazard ratios of death were similar in blacks and whites (6.9% vs 7.5%, hazard ratio 1.2 vs 1.0, P=.276). Thus carvedilol was similarly effective in blacks and whites with HF in the community setting, consistent with carvedilol clinical trials.

The major advances in our understanding and management of heart failure (HF) in recent decades have not fully benefited all segments of our population. HF still represents a growing epidemic, especially for African-Americans, in whom the burden of HF is even greater. The recently reported beneficial effects of the fixed combination of isosorbide dinitrate and hydralazine (ISDN+HYD) in the African-American Heart Failure Trial (A-HeFT), has led to both the FDA approval of this agent and its endorsement by the latest HF guidelines. The properties of ISDN+HYD are well known as its components are mature agents, readily available in generic formulations that have been used for decades in other indications. However, fixed-dose ISDN+HYD represents the first drug to undergo targeted clinical development and to be approved for use in a specific ethnic group. As such, A-HeFT and the approval of ISDN+HYD represent landmark events that merit further scrutiny.

Risk factors for outcomes in heart failure (HF) were derived from populations in clinical trials, at hospital discharge, or in localized geographic or socioeconomic strata before the widespread use of beta blockers. This study observed 4,280 patients in a community-based HF registry for 1 year after completing carvedilol titration. Independent risk factors for death, hospitalization for HF, or hospitalization for cardiovascular reasons other than HF were first identified by age-, gender-, and race-adjusted analyses, then by multivariate analysis adjusted simultaneously for all factors. Over this period, 7% of patients died, 11% were hospitalized for HF, 12% were hospitalized for other cardiovascular reasons, and 27% had > or =1 of these events. The most significant outcome predictors were New York Heart Association class III or IV, history of hospitalization for HF or other cardiovascular reasons, and angina pectoris, all associated with increased odds of having an adverse outcome (all p < or =0.001). The left ventricular ejection fraction was not a significant outcome predictor by multivariate analysis. The odds ratio for an adverse outcome was significantly reduced for patients with hypertensive or idiopathic causes of HF and for those whose physicians had graduated from medical school > or =24 years earlier compared with <14 years earlier (all p <0.005). In conclusion, easily obtained historical information predicts clinical outcomes in patients with HF in the year after initiating carvedilol. In this unselected community population, these historical factors were better predictors of risk than the left ventricular ejection fraction.

Women and the elderly are underrepresented in clinical trials of heart failure (HF). The authors analyzed, by sex and age groups, a registry of 4280 community patients initiating carvedilol for HF. Women (n=1485) were older than men (n=2793) and had worse functional class with higher left ventricular ejection fraction and blood pressure. Women also had more HF hospitalizations, less use of angiotensin-converting enzyme inhibitors, and lower doses of carvedilol. Nevertheless, during 1-year follow-up, both groups experienced greater than 40% reductions in HF hospitalizations (P<.001), with mortality of 7.3% in women vs 9.1% in men (P=.085). With increasing age, left ventricular ejection fraction, blood pressure, and functional class increased, whereas angiotensin-converting enzyme inhibitor use and carvedilol doses decreased. HF hospitalizations fell at least 40% in all age groups after starting carvedilol (P<.001). Characteristics of women and the elderly with HF in the community suggest increased risk, but both populations respond well after initiating carvedilol.

Background: beta-Blockers reduce morbidity and mortality rates in heart failure (HF) clinical trials, but it is unknown whether these findings persist in the community setting., Methods: A registry was created to survey tolerability and outcomes during initiation and 1-year follow-up of beta-blocker treatment with carvedilol in patients with HF treated by cardiologists (CARD) and primary care physicians (PCP) in the community., Results: A total 4280 patients were enrolled (3121 by 259 CARD, 1159 by 129 PCP). Patient age averaged 67 +/- 13 years; 35% were women and 12% were black. The left ventricular ejection fraction averaged 31 +/- 12; New York Heart Association class was II-III in 86% and IV in 3%. Patients of PCP had higher left ventricular ejection fraction, were older, and more frequently were female, black, diabetic, hypertensive, and in New York Heart Association class III/IV. Minimal difficulty titrating carvedilol was noted by >80% of CARD and PCP. Significantly more CARD-treated patients reached carvedilol doses of 25 mg twice daily (49% vs 27%). Kaplan-Meier all-cause mortality rate was 8.5% at 1 year and did not differ between CARD-treated and PCP-treated patients (8.2% vs 9.3%, P =.254). At least one HF hospitalization occurred in 11% of patients during follow-up, compared with 28% in the preceding year., Conclusions: Community-based physicians use carvedilol with success approaching that of clinical trials. Overall mortality rates and HF hospitalizations were in the same low range as in clinical trials. Thus, it appears that results of clinical trials with carvedilol for HF can be translated to the community setting.

Background: Clinical trials do not represent community settings, making widespread implementation of evidence-based medicine problematic. New heart failure treatments are an example, as results comparable to those of clinical trials have not been observed in the community. Alternatives to clinical trials could provide useful complementary information., Objectives and Methods: To review the clinical trials and community experiences in heart failure management by searching Pubmed with key words "observational studies," "clinical trials," and "heart failure," to present the preliminary results of a community-based heart failure registry as a complementary database, and to assess the potential value and limitations of the registry approach., Results: Recent advances in the treatment of heart failure led to guidelines using clinical trial evidence as the rationale for transferring newer therapeutic technologies to the community practice setting. Implementation of such guidelines is slow, reflecting concerns over applicability of clinical trial results to the community setting. A community-based registry of beta-blocker treatment for heart failure showed outcomes comparable to those of clinical trials, despite significant differences between physicians and their patients in these settings., Conclusion: Registries can complement clinical trials to expedite technology transfer to the community setting.

New treatments have improved outcomes in heart failure (HF), but applicability of these advances may be limited in African Americans. Analysis of previous trials has shown that a combination of hydralazine (H) plus isosorbide dinitrate (ISDN) may be especially beneficial in African Americans with HF. The African American Heart Failure Trial (A-HeFT) is a double-blind, randomized, and placebo-controlled trial in African American patients with stable NYHA Class III-IV HF while on standard therapy. Randomization to addition of BiDil, a fixed combination of H+ISDN, or placebo, will be stratified for beta-blocker usage, and all patients will be treated and followed until the last patient entered has completed six months of follow-up. The primary efficacy endpoint will be a composite score including quality of life, deaths, and hospitalizations for HF. At least 600 patients will be randomized. The first patient was randomized in June, 2001. Besides additional testing of H+ISDN in HF, A-HeFT will be the first HF trial aimed at a subgroup of African American patients, as well as the first to use a new composite HF score as its primary efficacy endpoint.

Background: Hydralazine and isosorbide dinitrate combination (H+ISDN), angiotensin-converting enzyme inhibitors, and beta-blockers have improved outcomes in heart failure (HF). Analysis of previous trials has shown that H+ISDN appears especially beneficial in African American patients., Methods and Results: The African-American Heart Failure Trial (A-HeFT) is double-blind, placebo-controlled, and includes African American patients with stable New York Heart Association Class III-IV HF on standard therapy. Patients must have prior HF-related events and left ventricular ejection fraction (LVEF) < or = 35% or LVEF <45% with left ventricular internal diastolic dimension >2.9 cm/m(2). Randomization to addition of placebo or BiDil (Nitro Med, Inc., Bedford, MA), a fixed combination of H+ISDN, is stratified for beta-blocker usage. All patients are treated and followed until the last patient entered completes 6 months of follow-up. The primary efficacy endpoint is a composite score including quality of life, death, and hospitalization for HF. At least 600 patients will be randomized; the first was randomized in June 2001., Conclusions: In addition to providing additional information on BiDil efficacy in HF, A-HeFT is the first HF trial aimed at a selected subgroup of patients and the first to use a new composite HF score as its primary efficacy endpoint.

Background: The success of beta-blocking agents in clinical trials of heart failure (HF) has led to a widespread call for their increased use, which assumes these agents will perform as well in the usual care setting. Given the traditional contraindication of the use of beta-blocking agents in HF, and their perception as difficult to use in HF, observing how they perform in the usual care setting could be critical in accelerating their widespread application. Carvedilol is the only beta-blocking agent currently approved in the United States for use in HF., Methods: The Coreg (brand of carvedilol; SmithKline Beecham Pharmaceuticals, Philadelphia, PA) Heart Failure Registry (COHERE) is intended to collect data on outcomes and other clinical variables in a typical HF population and to observe experience with carvedilol in the hands of community practitioners. COHERE does not include any specific patient selection or exclusion criteria. The decision to use carvedilol is entirely at the discretion of the participant physician, based on evidence of HF as judged by assessments the practitioner usually uses. All patients will be followed for 1 year, with information on outcomes and other clinical variables collected and analyzed at baseline, the end of titration, and at 6 and 12 months after reaching the maximum tolerated dose. About 600 participant physicians selected to be as representative as possible of the community practice setting will enroll approximately 6,000 patients., Conclusions: COHERE will be the first and largest prospective observational experience with a new treatment, ie, carvedilol, in patients with HF managed in the usual care setting and should provide valuable information about this new treatment in this environment compared with the more rigid clinical trials setting.

The dose requirements and duration of effect of transdermal nitroglycerin in patients with heart failure are not clearly established. In a first series of eight patients with chronic heart failure we gave transdermal nitroglycerin in incremental doses until pulmonary capillary wedge pressure fell at least 30% within 4 hr in three consecutive patients. Thus we found that a single dose of 60 mg/24 hr (120 cm2) was the minimal effective dose. Transdermal nitroglycerin or placebo was then given as a single application of 60 mg/24 hr in random double-blind fashion to 15 additional patients with heart failure (eight received transdermal nitroglycerin and seven received placebo), and hemodynamics were monitored for up to 24 hr. After administration of transdermal nitroglycerin, the control pulmonary capillary wedge pressure of 22 +/- 7 mm Hg fell by 6 +/- 6 mm Hg at 2 hr (p less than .05) and reached maximal reduction of 8 +/- 6 mm Hg (p less than .01) at 4 hr. The reduction in wedge pressure remained significant through 12 hr but was no longer statistically significant by 18 hr after administration of the drug. Transdermal nitroglycerin also significantly reduced pulmonary arterial and right atrial pressures as well as pulmonary vascular resistance from 4 through 12 hr but did not affect systemic hemodynamics. No significant hemodynamic changes occurred after administration of placebo. Thus transdermal nitroglycerin is an effective vasodilator in patients with heart failure, but a dose of at least 60 mg/24 hr is needed. Even with this dose, hemodynamic effects do not last beyond 18 hr, suggesting altered absorption or development of tolerance.

Data published by this laboratory indicated that the beta adrenergic blocking drugs timolol and propranolol exerted equivalent beta blocking and antihypertensive actions in patients with mild essential hypertension, but that whereas cardiac output fell acutely with both drugs, it returned to normal after 5 wk of treatment with timolol, but remained depressed after propranolol. This preliminary observation needed further confirmation in a larger series of patients. In this study, 11 patients with initial diastolic blood pressures between 90 and 125 mm Hg were given timolol for 5 wk. Hemodynamic measurements were made before and at the end of treatment. Mean heart rate fell from 76.8 to 64.3 bpm (p less than 0.001), and blood pressure was reduced from 179.4/99 mm Hg to 167.4/93.3 mm Hg (less than 0.02). Cardiac output averaged 6.29 L/min before timolol, and fell to 5.95 L/min (NS) after treatment. Stroke volume increased significantly, while total peripheral resistance was unchanged. These results confirm our earlier observations that timolol is an effective beta adrenergic blocking drug with antihypertensive action that does not reduce cardiac output significantly when given chronically. This drug merits further evaluation in other cardiovascular disorders since it may have advantages over other beta adrenergic blocking drugs.

Current heart failure therapy has included both stimulation and inhibition of beta-adrenergic receptors. Full beta-agonists have not been clinically effective because of side effects or loss of efficacy over the long term. Full beta-antagonists are effective in selected patients but are not tolerated in others because of cardiac depression. Partial beta-antagonists (beta-blockers with weak intrinsic sympathomimetic activity) do not possess sufficient agonist activity to counteract their own cardiac depressant action. Partial beta-agonists produce mild beta-antagonism, but not enough to offset their overall cardiac stimulating property. The partial beta-agonists have been clinically effective in some patients with heart failure and appear to be a potentially useful and unique class of agents because of their ability to modulate cardiac beta-receptors in such a way as to avoid an excessive response to endogenous or exogenous stimuli.

Although the beneficial effects of treating hypertension remain firmly established, concern has recently arisen that certain antihypertensive drugs may adversely modify cardiovascular risk factors. Equipotent blood pressure-lowering agents may also have differing effects on cardiac structure and function. Thus, established approaches to antihypertensive therapy are being questioned and revised or new approaches are being suggested.

Vasodilators are gaining importance in management of congestive heart failure. The short-acting varieties are often helpful in severe or refractory cases, and several agents show promise for long-term therapy. An understanding of the chain of events that occurs in congestive heart failure and of the corrective hemodynamic effects of the different vasodilators is essential for proper use of these agents.

Minoxidil, a potent predominant arterial dilator, improves hemodynamics over the short term in patients with heart failure. In random double-blind fashion 17 patients with chronic left heart failure were given minoxidil (nine patients) or placebo (eight patients) in addition to digoxin and diuretics for 3 months. Cardiac index and heart rate increased and mean arterial pressure and systemic vascular resistance fell within 4 hr of minoxidil administration. Right heart and pulmonary arterial pressures were unchanged over the short term but rose after long-term minoxidil. After 3 months of minoxidil treatment, systemic vascular resistance was still reduced (11.7 +/- 6.3[SD] vs 17.1 +/- 3.1 U at baseline; p less than .05). Hemodynamics were similar at baseline and remained unchanged during placebo treatment. Mean left ventricular ejection fraction rose from 29.6 +/- 17.7% to 42.7 +/- 22.3% (p less than .05) after 3 months of minoxidil treatment (this result was influenced largely by responses in two patients), and remained unchanged (at 25.1 +/- 16.6%) after 3 months of placebo. Exercise duration and maximal oxygen uptake during exercise were unchanged during minoxidil or placebo treatment. Total clinical events, including increased need for diuretics, angina, ventricular arrhythmias, worsening heart failure, and death were all more frequent during minoxidil vs placebo administration (21 vs seven total events; p less than .01). Thus, despite improving hemodynamics and left ventricular function, long-term minoxidil administration was associated with a poorer clinical course in patients with chronic left ventricular failure. Furthermore, this experience demonstrates that improvement of left ventricular function alone cannot be reliably interpreted as proof of clinical efficacy of therapeutic interventions in patients with heart failure.

Thirty patients with acute myocardial infarction (AMI) treated with intracoronary streptokinase (7 X 10(5) +/- 3 X 10(5) IU) followed by 10 days of intravenous heparin (800 to 1,500 IU/hour) therapy were prospectively studied by serial 2-dimensional echocardiography for left ventricular (LV) thrombus. Within the first 24 hours, evidence of a thrombolytic state appeared as indicated by fibrin and fibrinogen degradation products (123 +/- 45 mg/dl at 24 hours). Throughout the course of this study partial thromboplastin times were maintained within therapeutic range (40 to 100 seconds). Apical LV thrombus developed in 8 of 30 patients (27%). Apical thrombus developed within 24 hours in 3 patients with anterior AMI and persisted through day 10. By day 10, apical thrombus developed in 3 additional patients with anterior AMI and 2 patients with inferior AMI. In these patients, anterior AMI and apical dysfunction were significant (p less than 0.01 for both) determinants of LV thrombus formation. Hence, the incidence of LV thrombus in patients treated with streptokinase/heparin is similar to that reported earlier in comparable patients not receiving thrombolytic therapy.

The factors that might activate the renin-angiotensin system in treated heart failure were explored. Serum Na+ correlated inversely with plasma renin activity. The degree of congestive heart failure measured by right atrial pressure, pulmonary capillary wedge pressure, cardiac index, and systemic vascular resistance did not correlate with plasma renin activity. Similarly, renal function as measured by blood urea nitrogen, creatinine, and urinary Na+ excretion did not correlate with plasma renin activity. In a prospectively screened group, seven patients with congestive heart failure who were found to be hyponatraemic had plasma renin activities greater than 15 ng/ml per h. Serial determinations in one patient showed plasma renin activity to vary inversely with the serum Na+. It is concluded that serum sodium can be used to identify those patients with congestive heart failure who have a high plasma renin activity. The value of identifying these high renin heart failure patients was seen in their response in four cases to specific therapy with a converting enzyme inhibitor.

Indoramin is an alpha 1-adrenergic antagonist vasodilator of potential value in heart failure. We measured hemodynamics and exercise capacity in 12 patients with heart failure, before and after 1 week of indoramin dosing, 75 mg b.i.d. Maximal hemodynamic effects 2 hours after the first dose of indoramin consisted of reduced mean systemic arterial pressure from 96.0 +/- 15.3 to 87.9 +/- 15.3 mm Hg (P less than 0.05) and pulmonary wedge pressure from 23.6 +/- 7.8 to 16.9 +/- 6.6 mm Hg (P less than 0.001). Heart rate, cardiac index, and total systemic resistance did not change acutely after indoramin, but after 1 week mean systemic arterial pressure was still reduced whereas cardiac index fell from 2.69 +/- 0.38 to 2.32 +/- 0.44 L/min/m2 (P less than 0.05) and total systemic resistance rose from 20.4 +/- 2.8 to 21.9 +/- 4.0 U (P less than 0.1). After 1 week maximal exercise oxygen uptake fell from 16.8 +/- 5.6 to 12.5 +/- 3.5 ml/min/kg (P less than 0.02). This limited observation suggests that indoramin is a predominant venodilator acutely in patients with heart failure but that despite this effect it may worsen functional capacity and hemodynamics during continuous dosing in these patients.

The CO2 rebreathing method, a noninvasive indirect Fick procedure, has been previously validated in normal subjects at supine rest and during exercise. In the present study 29 nearly simultaneous measurements of cardiac output were made by CO2 rebreathing and dye dilution in 17 patients with cardiovascular disease, 11 with hypertension, and six with congestive heart failure. Cardiac output at supine rest averaged 5.52 +/- 0.31 L. per minute by CO2 and 5.62 +/- 0.32 L. per minute by dye dilution (r = 0.93). Successive cardiac output measurements by rebreathing varied 6.0 +/- 1.1 per cent (r = 0.96) and by dye dilution, 6.5 +/- 0.9 per cent. Changes in cardiac output during exercise or after beta-adrenergic blockade were reflected by the CO2 method. It is concluded that the CO2 method provides reliable measurements of cardiac output both at rest and during exercise in patients with hypertension or congestive heart failure. Further validation of the method is needed in various disease states before it can be widely applied.

Trimazosin is a new quinazoline derivative vasodilator previously thought to act primarily on resistance vessels. Vasodilators characteristically improve hemodynamics in patients with left ventricular failure. Trimazosin in single oral doses of 100 to 300 mg was given to 6 patients with class III-IV congestive heart failure due to ischemic or primary cardiomyopathy and hemodynamics were monitored for 4 hr. Onset of action was apparent at 1 hr, with peak effects occurring at 1 to 3 hr and significant effects persisting at 4 hr. At peak, mean systemic arterial pressure fell from 91.2 +/- 4.8 (SEM) to 82.5 +/- 2.5 mm Hg (p less than 0.05), heart rate was unchanged, and cardiac index (by dye dilution) was up to 2.12 +/- 0.27 from 1.76 +/- 0.33 L/min/m2 (NS). Right heart pressures (by Swan-Ganz catheterization) were reduced, right atrial, 11.3 +/- 2.1 to 8.7 +/- 1.6 mm Hg (p less than 0.02), mean pulmonary arterial pressure, 40.7 +/- 4.6 to 33.8 +/- 4.8 mm Hg (p less than 0.01), and pulmonary arterial wedge, 30.7 +/- 4.5 to 23.8 +/- 5.0 mm Hg (p less than 0.01). Forearm venous capacitance, by occlusion plethysmography, increased from 0.83 +/- 0.18 ml/100 gm to 1.12 +/- 0.22 ml/100 gm after trimazosin (p less than 0.01). Trimazosin is an orally effective vasodilator that acts on both resistance and capacitance vessels in patients with congestive heart failure.

Symptoms of congestive heart failure occur most commonly during exercise, but cardiac performance is usually quantitated at rest. The relation between exercise capacity and measurements of cardiac performance at rest is little known. Treadmill exercise was performed in 21 patients with heart failure due to cardiomyopathy. Exercise duration averaged 9.1 +/- 0.7 (standard error of the mean) minutes (normal value 12 or more minutes) and did not correlate with resting ejection fraction of 26.4 +/- 2.7 percent (r = -0.06). Left ventricular diastolic dimension of 6.6 +/0 0.2 cm, mean velocity of circumferential fiber shortening and ratio of preejection period to left ventricular ejection time did not correlate with treadmill time (r = -0.03). Repeat studies after treatment of heart failure also failed to show correlations between changes in exercise capacity and changes in left ventricular performance at rest. Thus, measures of left ventricular performance obtained at rest do not accurately reflect exercise tolerance and symptomatic status of patients with congestive heart failure.

A double-blind, randomized study was designed to evaluate the efficacy of oral propafenone and oral quinidine in suppressing premature ventricular complexes (PVCs). Twenty-five men were studied for 3 weeks. Twelve were randomized to the quinidine group and 13 to the propafenone group. Small doses of the drugs were administered for 1 week (200 mg of quinidine every 6 hours or 300 mg of propafenone every 12 hours) and large doses were administered for another week (400 mg of quinidine every 6 hours or 300 mg of propafenone every 8 hours). Strict criteria were used to define responders to antiarrhythmic therapy. For more than 85% reduction in total PVCs per hour: During the low-dose week, 36% in the quinidine group and 50% in the propafenone group were responders (difference not significant [NS]), while during the high-dose week 33% and 64% were responders (NS). For more than 95% reduction of ventricular couplets per hour: During the low-dose week, 45% in each group were responders, while during the high-dose week, 56% and 60% were responders (NS). For 100% abolition of ventricular tachycardia (VT) beats per 24 hours: During the low-dose week, 60% in the quinidine group and 56% in the propafenone group were responders (NS); during the high-dose week 80% and 67% were responders (NS). There was no significant difference in the 2 groups in incidence of side effects. This study shows comparable efficacy and tolerance of propafenone and quinidine for the control of ventricular arrhythmias in ambulatory patients with diverse forms of heart diseases.

Resting hemodynamics improve during vasodilator administration in patients, with congestive heart failure (CHF), but the effects of these agents on exercise is unknown. Twenty-two patients with class II or III CHF performed bicycle exercise to symptomatic maximum before and 90 minutes after random double-blind administration of oral hydralazine (100 mg) and isosorbide dinitrate (40 mg) (11 patients, group 1) or placebo (11 patients, group 2). Exercise duration was unchanged after treatment in either group. Maximal oxygen consumption changed insignificantly in both groups, from 12.6 +/- 1.2 (SEM) to 13.6 +/- 1.6 ml/kg/min in group 1, and from 11.7 +/- 1.4 to 13.4 +/- 1.7 ml/kg/min in group 2. Maximal cardiac index was unchanged in both group 1 (4.00 +/- 0.33 to 4.41 +/- 0.29 l/min/m2) and group 2 (4.11 +/- 0.43 to 4.14 +/- 0.42 l/min/m2). Systemic vascular resistance at peak exercise was also unchanged in both group 1 (14.1 +/- 1.6 to 11.8 +/- 1.0 units) and group 2 (14.7 +/- 1.6 to 13.5 +/- 1.6 units). at submaximal exercise (300 kilopond-meters/min), however, cardiac index after treatment increased in group 1 (0.51 +/- 0.18 l/min/m2, p less than 0.05) and systemic vascular resistance decreased (-3.3 +/- 1.3 units, p less than 0.05), but were unchanged in group 2. Thus, although vasodilators do not improve maximal exercise capacity acutely, they can improve hemodynamics at lower work loads which may, therefore, be better tolerated in patients with CHF.

Vasodilators used in chronic congestive heart failure are not optimal in that nitrates are predominant venodilators, prazosin is associated with tolerance development, and hydralazine produces chronic toxicity. Therefore, we studied the acute hemodynamic effects of a single dose of minoxidil in 18 patients with chronic left ventricular failure caused by ischemic or primary cardiomyopathy. Peak effects were observed 5 hours after single oral doses of minoxidil, averaging 15.3 +/- 1.4 mg (SEM). Heart rate rose slightly, from 85.4 +/- 2.9 to 90.9 +/- 3.2 beats/min, after minoxidil (p less than 0.02) and mean arterial pressure fell slightly, from 88.0 +/- 2.3 to 84.9 +/- 2.5 mm Hg (p less than 0.05). Cardiac index increased from 2.34 +/- 0.l4 to 2.95 +/- 0.29 l/min/m2 after minoxidil (p less than 0.02) and systemic vascular resistance fell from 19.6 +/- 1.5 to 15.0 +/- 1.3 units (p less than 0.01). Minoxidil did not affect right atrial, pulmonary arterial and pulmonary wedge pressures. Hemodynamic effects of minoxidil persisted for at least 8 hours after a single dose. Minoxidil appears to be an effective arterial dilating agent in patients with heart failure and resembles hydralazine in its actions. Because of its potency, prolonged duration of action and relatively low toxicity, minoxidil may be a useful vasodilator for heart failure. However, its long-term effect must be further evaluated.