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Implantable cardioverter-defibrillators (ICDs) improve outcomes in patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤35%. Less is known about whether outcomes varied between the 2 noninvasive imaging modalities used to estimate LVEF—2-dimensional echocardiography (2DE) and multigated acquisition radionuclide ventriculography (MUGA)—which use different principles (geometric vs count-based, respectively). The purpose of this study was to examine whether the effect of ICD on mortality in patients with HF and LVEF ≤35% varied on the basis of LVEF measured by 2DE or MUGA. Of the 2521 patients with HF with LVEF ≤35% in the Sudden Cardiac Death in Heart Failure Trial, 1676 (66%) were randomized to either placebo or ICD, of whom 1386 (83%) had LVEF measured by 2DE (n = 971) or MUGA (n = 415). Hazard ratios (HRs) and 97.5% confidence intervals (CIs) for mortality associated with ICD were estimated overall, checking for interaction, and within the 2 imaging subgroups. Of the 1386 patients in the present analysis, all-cause mortality occurred in 23.1% (160 of 692) and 29.7% (206 of 694) of patients randomized to ICD or placebo, respectively (HR 0.77; 97.5% CI 0.61–0.97), which is consistent with that in 1676 patients in the original report. HRs (97.5% CIs) for all-cause mortality in the 2DE and MUGA subgroups were 0.79 (0.60–1.04) and 0.72 (0.46–1.11), respectively (P =.693 for interaction). Similar associations were observed for cardiac and arrhythmic mortalities. We found no evidence that in patients with HF and LVEF ≤35%, the effect of ICD on mortality varied by the noninvasive imaging method used to measure LVEF. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2006.12.020 Byline: J. Edwin Atwood (a), Jonathan N. Myers (e), X. Charlene Tang (d), Domenic J. Reda (d), Steven N. Singh (b), Bramah N. Singh (c) Abstract: Therapy for chronic atrial fibrillation (AF) focuses on rate versus rhythm control, but little is known about the effects of common therapeutic interventions on exercise tolerance in AF. Author Affiliation: (a) Walter Reed Army Medical Center, Washington, DC (b) Department of Veterans Affairs Medical Center, Washington, DC (c) Department of Veterans Affairs Medical Center, Los Angeles, CA (d) Department of Veterans Affairs Medical Center, Hines, IL (e) Department of Veterans Affairs Medical Center, Palo Alto, CA Article History: Received 12 April 2006; Accepted 17 December 2006 Article Note: (footnote) This study was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development (Washington, DC), Berlex Laboratories (Montville, IL) and Wyeth-Ayerst Laboratories (Philadelphia, PA).

Background: Controlled clinical trial data are lacking for cardiac resynchronization therapy (CRT) outcomes in patients with advanced heart failure (HF) from reduced left ventricular ejection fraction (HFrEF) and intermittent atrial fibrillation or flutter (IAF/AFL).Objective: The purpose of this study was to describe CRT outcomes in patients with IAF/AFL and advanced HF.Methods: HF outcomes in patients in the COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure) trial with New York Heart Association class III or IV HFrEF, left ventricular ejection fraction ≤0.35, sinus rhythm at randomization, and no history of baseline arrhythmia were compared with those with a history of IAF/AFL.Results: In those with no history of baseline arrhythmia (n = 887), compared with optimal pharmacological therapy (OPT) with no CRT, the CRT + OPT arms exhibited a significant reduction in the end points of death or any hospitalization (hazard ratio [HR] 0.73 [95% Confidence Interval (CI): 0.60 to 0.89]; P = .002) and death or HF hospitalization (HR 0.53 [95% CI: 0.41 to 0.68]; P < .001). In contrast, in the IAF/AFL subgroup (n = 293), CRT did not result in improved outcomes compared with OPT (death or any hospitalization: HR 1.16 [95% CI: 0.83 to 1.63]; P = .38; death or HF hospitalization: HR 0.97 [95% CI: 0.64 to 1.46]; P = .88). The interaction between history of AF/AFL and CRT was statistically significant for both outcomes (P < .05).Conclusion: In the COMPANION trial, patients with moderate to severe HFrEF and a history of IAF/AFL had no benefit from CRT. [ABSTRACT FROM AUTHOR]

Background: Energy levels for electrocardioversion in atrial fibrillation (AF) have been empiric, and the influence of antiarrhythmic therapy compared with placebo is largely unknown. Objective: The purpose of this study was to determine systematically the energy levels for electrocardioversion in patients with persistent AF and to define the influence of antiarrhythmic therapy. Methods: Patients (n = 665) with persistent AF were randomized to amiodarone, sotalol, or placebo. Rate control, if necessary, was achieved with digoxin, diltiazem, or verapamil. Among the 665 patients, 504 who did not achieve sinus rhythm at day 28 had electrocardioversion systematically by a prespecified four-step protocol as follows: monophasic shocks—100, 200, 360, 360 J; or biphasic shocks—150, 175, 200, 200 J sequentially. Energy levels and shock waveforms (monophasic/biphasic) for successful electrocardioversion (sinus rhythm for at least 1 minute) and use of antiarrhythmic therapy and calcium channel blockers were recorded. Results: Electrocardioversion was successful in 371 (71.6%) of 504 patients: 72%, 73.5%, and 67.9% for patients assigned to amiodarone, sotalol, and placebo, respectively. Overall, after adjustments for age, body mass index (BMI), history of AF, shock waveforms, left atrial size, and ejection fraction, both amiodarone (odds ratio [OR]: 2.16, 95% confidence interval [CI]: 1.24–3.77, P <.01) and sotalol (OR: 1.92, 95% CI: 1.11–3.33, P = .02) significantly facilitated successful electrocardioversion compared with placebo. Calcium channel blockers had no effect on the success rate of electrocardioversion. Success of electrocardioversion was associated with lower BMI, AF history ≤1 year, and older age. Compared with placebo, patients taking amiodarone were significantly more likely to achieve successful electrocardioversion in step 1 (OR: 2.73, 95% CI: 1.11–6.74, P = .03) and step 3 (OR: 1.86, 95% CI: 1.00–3.44, P = .05) but not in steps 2 and 4. Sotalol was superior to placebo in step 4 (OR: 2.58, 95% CI: 1.02–6.52, P = .05) and trended in step 2 (OR: 1.7, 95% CI: 0.98–3.07, P = .06). Successful electrocardioversion was seen in 11%, 29%, 38%, and 29% in steps 1, 2, 3, and 4, respectively. Compared with monophasic shocks, biphasic shocks achieved higher success rates for step 1 (P <.001) and step 2 (P <.01), respectively. Antiarrhythmic therapy did not influence the total number of energy steps used for the patients with successful electrocardioversion. However, biphasic shocks, lower BMI, and AF duration ≤1 year were associated with less energy step used for successful cardioversion. Conclusion: Amiodarone and sotalol facilitated successful electrocardioversion, which could be achieved in a stepwise fashion. Upon achievement of successful electrocardioversion, amiodarone is superior to placebo, and sotalol has a lesser effect. Antiarrhythmic drugs had no effect on the total number of energy step use in patients who had successful electrocardioversion. Calcium channel blockers had no influence on the success rate in achieving sinus rhythm. Successful electrocardioversion was associated with lower BMI and AF history ≤1 year. Lower energy use was associated with biphasic shocks, lower BMI, and AF duration ≤1 year. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to determine quality of life (QOL) and exercise performance (EP) in patients with persistent atrial fibrillation (AF) converted to sinus rhythm (SR) compared with those remaining in or reverting to AF. Background: Restoration of SR in patients with AF improving QOL and EP remains controversial. Methods: Patients with persistent AF were randomized double-blind to amiodarone, sotalol, or placebo. Those not achieving SR at day 28 were cardioverted and classified into SR or AF groups at 8 weeks (n = 624) and 1 year (n = 556). The QOL (SF-36), symptom checklist (SCL), specific activity scale (SAS), AF severity scale (AFSS), and EP were assessed. Results: Favorable changes were seen in SR patients at 8 weeks in physical functioning (p < 0.001), physical role limitations (p = 0.03), general health (p = 0.002), and vitality (p < 0.001), and at 1 year in general health (p = 0.007) and social functioning (p = 0.02). Changes in the scores for SCL severity (p = 0.01), functional capacity (p = 0.003), and AFSS symptom burden (p < 0.001) at 8 weeks and in SCL severity (p < 0.01) and AF symptom burden (p < 0.001) at 1 year showed significant improvements in SR versus AF. Symptomatic patients were more likely to have improvement. The EP in SR versus AF was greater from baseline to 8 weeks (p = 0.01) and to 1 year (p = 0.02). The EP correlated with physical functioning and functional capacity except in the AF group at 1 year. Conclusions: In patients with persistent AF, restoration and maintenance of SR was associated with improvements in QOL measures and EP. There was a strong correlation between QOL measures and EP. [Copyright &y& Elsevier]

: ObjectivesThe purpose of this study was to assess the effect of oral azimilide dihydrochloride (AZ) 100 mg versus placebo on the onset, termination, and prevalence of atrial fibrillation (AF) in a subpopulation of patients in the Azimilide Postinfarct Survival Evaluation (ALIVE) trial.: BackgroundPrevious clinical trials have demonstrated the antiarrhythmic effects of AZ in patients with AF. Azimilide was investigated for its effects on mortality in patients with depressed left ventricular (LV) function after recent myocardial infarction (MI) and in a subpopulation of patients with AF.: MethodsA total of 3,381 post-MI patients with depressed LV function were enrolled in this randomized, placebo-controlled, double-blind study of AZ 100 mg on all-cause mortality. A total of 93 patients had AF on the baseline 12-lead electrocardiogram (ECG). An additional 27 patients developed AF after initially being in sinus rhythm at randomization. These patients were identified through 12-lead ECGs obtained during routine visits at week 2, months 1, 4, 8, and 12.: ResultsPatients with AF at baseline had a higher mortality than those without AF (p = 0.0006). Among AF patients, there was no difference in mortality between AZ patients and placebo patients (p = 0.82). Fewer AZ patients developed AF than placebo patients (p = 0.04). More AZ patients than placebo patients converted to sinus rhythm, but this difference did not achieve statistical significance (p = 0.076). Over one-year follow-up, more AZ patients were in sinus rhythm than placebo patients (p = 0.04).: ConclusionsAzimilide was safe and effective AF therapy in patients with depressed LV function after an MI. [Copyright &y& Elsevier]

The Sotalol-Amiodarone Fibrillation Efficacy Trial (SAFE-T) is a randomized, double-blind, multicenter, placebo-controlled trial in which the effects of sotalol and amiodarone in maintaining stability of sinus rhythm are being examined in patients with persistent atrial fibrillation at 20 Veterans Affairs medical centers. The time to the occurrence of atrial fibrillation or flutter in patients with atrial fibrillation converted to sinus rhythm is the primary outcome measure, with a number of parameters as secondary end points. SAFE-T had randomized 665 patients when enrollment terminated on October 31, 2001. Follow-up of patients continued until October 31, 2002, for a maximum period of 54 months and a minimum period of 12 months for all patients. [Copyright &y& Elsevier]

Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce sudden cardiac death and all-cause mortality. They also may have direct antiarrhythmic properties. We retrospectively analyzed the data from the Multicenter UnSustained Tachycardia Trial (MUSTT), to determine the effects of ACE inhibitors on inducibility of sustained ventricular tachycardia and on sudden cardiac death and overall mortality in 2,087 patients with prior myocardial infarction, nonsustained ventricular tachycardia, and depressed left ventricular function. Results of electrophysiologic testing were compared by use of ACE inhibitors at baseline, and outcomes were compared between the 564 patients prescribed ACE inhibitors at discharge and the 1,523 patients who did not receive treatment. The inducibility of sustained ventricular tachycardia during electrophysiologic testing did not differ by baseline ACE inhibitor use (unadjusted p = 0.75). Patients discharged from hospital on ACE inhibitors had a lower ejection fraction, more extensive coronary artery disease, and fewer previous revascularizations at baseline. After adjustments for differences in baseline factors and initial hospitalization variables, there were no significant differences in total mortality (p = 0.47) or arrhythmic death or cardiac arrest (p = 0.51) with ACE inhibitor use at discharge over a median 43 months of follow-up. [ABSTRACT FROM AUTHOR]

Patients with congestive heart failure frequently have ventricular arrhythmias on ambulatory electrocardiographic recordings and sudden cardiac death is seen in almost 50% of such patients. Many antiarrhythmic agents have been approved to suppress the arrhythmia in an effort to improve survival. Some sodium-channel blockers not only failed to improve survival but have been shown to be harmful. This led to the development of potassium-channel blockers, such as d-sotalol, amiodarone, dofetilide, and azimilide. d-Sotalol was associated with excess mortality in patients with left ventricular dysfunction; amiodarone seems to be potentially beneficial; and dofetilide has a neutral effect on mortality. The Sudden Cardiac Death Heart Failure Trial (SCD HEFT) is testing the implantable cardioverter defibrillator (ICD) against amiodarone and placebo. The ICDs appear to be superior to antiarrhythmic drugs in certain high-risk patients, although not proved in unstratified patients with heart failure. [ABSTRACT FROM AUTHOR]

Analyzes the effects of the antiarrhythmic drug d-sotalol in patients with congestive heart failure. Mechanism of action; Assessment of hemodynamic variables; Absence in changes in blood pressure and right atrial pressure; Decrease in cardiac index; Inadequate hemodynamic actions.

Background: The deleterious effects of discontinuation of digoxin on outcomes in ambulatory patients with chronic heart failure (HF) with reduced ejection fraction (HFrEF) receiving angiotensin-converting enzyme inhibitors are well-documented.Objectives: The authors sought to determine the relationship between digoxin discontinuation and outcomes in hospitalized patients with HFrEF receiving more contemporary guideline-directed medical therapies including beta-blockers and mineralocorticoid receptor antagonists.Methods: Of the 11,900 hospitalized patients with HFrEF (EF ≤45%) in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 3,499 received pre-admission digoxin, which was discontinued in 721 patients. Using propensity scores for digoxin discontinuation, estimated for each of the 3,499 patients, a matched cohort of 698 pairs of patients, balanced on 50 baseline characteristics (mean age 76 years; mean EF 28%; 41% women; 13% African American; 65% on beta-blockers) was assembled.Results: Four-year post-discharge, digoxin discontinuation was associated with significantly higher risks of HF readmission (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 1.05 to 1.39; p = 0.007), all-cause readmission (HR: 1.16; 95% CI: 1.04 to 1.31; p = 0.010), and the combined endpoint of HF readmission or all-cause mortality (HR: 1.20; 95% CI: 1.07 to 1.34; p = 0.002), but not all-cause mortality (HR: 1.09; 95% CI: 0.97 to 1.24; p = 0.163). Discontinuation of digoxin was associated with a significantly higher risk of all 4 outcomes at 6 months and 1 year post-discharge. At 30 days, digoxin discontinuation was associated with higher risks of all-cause mortality (HR: 1.80; 95% CI: 1.26 to 2.57; p = 0.001) and the combined endpoint (HR: 1.36; 95% CI: 1.09 to 1.71; p = 0.007), but not of HF readmission (HR: 1.19; 95% CI: 0.90 to 1.59; p = 0.226) or all-cause readmission (HR: 1.03; 95% CI: 0.84 to 1.26; p = 0.778).Conclusions: Among hospitalized older patients with HFrEF on more contemporary guideline-directed medical therapies, discontinuation of pre-admission digoxin therapy was associated with poor outcomes. [ABSTRACT FROM AUTHOR]

Background: Heart failure complicated by atrial fibrillation (AF) is associated with excessive mortality and morbidity. The aim of the study was to determine the role of amiodarone or implantable cardioverter/defibrillator (ICD) in patients with AF and heart failure. Methods: Patients were determined to be in sinus rhythm (SR) or AF on the baseline electrocardiogram. Mortality, ICD discharge, or change in rhythm was assessed. Results: Of the 2521 patients at baseline, 2328 were in SR and 173 were in AF. Overall, after adjusting for differences in baseline variables, there was no difference in mortality between patients with SR and patients with AF (P = .98), nor within assigned groups: placebo (P) (P = .82), amiodarone (A) (P = .68), and ICD (P = .40). For patients with SR, ICD decreased mortality (P vs ICD, P = .004; A vs ICD, P = .004; P vs A, P = .75). For patients with AF, there were no differences in mortality among groups (P vs ICD, P = .99; A vs ICD, P = .88; P vs A, P = .88). Of patients with SR at baseline, 11% (264) developed AF by any electrocardiogram during follow-up (P 12%, A 8%, ICD 15%; A vs P, P = .019; A vs ICD, P = .001; P vs ICD, P = .044). Of patients with AF, 70% (121) developed SR during follow-up (P 66%, A 67%, ICD 75%, all P = not significant against each other). Any ICD shock was seen in 52% (34) of patients with AF vs 30% (222) of patients with SR (P = .001). Inappropriate shocks were seen in 37% (24) of patients with AF vs 14% (107) of patients with SR (P = .001). Appropriate shocks were more often seen in AF vs SR (P = .03). Conclusion: After adjustments for baseline differences, patients with AF and patients with SR have similar overall mortality rates. Compared to P or A, ICD improves survival in patients with SR, but may not in patients with AF. Amiodarone is effective in reducing new AF, but not in converting AF to SR. Implantable cardioverter/defibrillator, inappropriate, and appropriate shocks were more often seen in AF than in SR. [Copyright &y& Elsevier]

Background: National guidelines recommend that systolic blood pressure (SBP) in patients with heart failure with reduced ejection fraction (HFrEF) and hypertension be maintained below 130 mm Hg.Objectives: This study sought to determine associations of SBP <130 mm Hg with outcomes in patients with HFrEF.Methods: Of the 25,345 patients in the Medicare-linked OPTIMIZE-HF registry, 10,535 had an ejection fraction (EF) ≤40%. Of these, 5,615 had stable SBP (≤20 mm Hg admission to discharge variation), and 3,805 (68%) had a discharge SBP <130 mm Hg. Propensity scores for SBP <130 mm Hg, estimated for each of the 5,615 patients, were used to assemble a matched cohort of 1,189 pairs of patients with SBP <130 versus ≥130 mm Hg, balanced on 58 baseline characteristics (mean age 76 years; mean EF 28%, 45% women, 13% African American). This process was repeated in 3,946 patients, after excluding 1,669 patients (30% of 5,615) with a discharge SBP <110 mm Hg and assembled a second matched balanced cohort of 1,099 pairs of patients with SBP 110 to 129 mm Hg versus ≥130 mm Hg.Results: Thirty-day all-cause mortality occurred in 7% and 4% of matched patients with SBP <130 mm Hg versus ≥130 mm Hg, respectively (hazard ratio [HR]: 1.76; 95% confidence interval [CI]: 1.24 to 2.48; p = 0.001). HRs (95% CIs) for all-cause mortality, all-cause readmission, and HF readmission at 1 year, associated with SBP <130 mm Hg, were 1.32 (1.15 to 1.53; p < 0.001), 1.11 (1.01 to 1.23; p = 0.030), and 1.24 (1.09 to 1.42; p = 0.001), respectively. HRs (95% CIs) for 30-day and 1-year all-cause mortality associated with SBP 110 to 129 mm Hg (vs. ≥130 mm Hg) were 1.50 (1.03 to 2.19; p = 0.035), and 1.19 (1.02 to 1.39; p = 0.029), respectively.Conclusions: Among hospitalized older patients with HFrEF, SBP <130 mm Hg is associated with poor outcomes. This association persisted when the analyses were repeated after excluding patients with SBP <110 mm Hg. There is an urgent need for randomized controlled trials to evaluate optimal SBP reduction goals in patients with HFrEF. [ABSTRACT FROM AUTHOR]

Background: A lower heart rate is associated with better outcomes in patients with heart failure (HF) with reduced ejection fraction (EF). Less is known about this association in patients with HF with preserved ejection fraction (HFpEF).Objectives: The aims of this study were to examine associations of discharge heart rate with outcomes in hospitalized patients with HFpEF.Methods: Of the 8,873 hospitalized patients with HFpEF (EF ≥50%) in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 6,286 had a stable heart rate, defined as ≤20 beats/min variation between admission and discharge. Of these, 2,369 (38%) had a discharge heart rate of <70 beats/min. Propensity scores for discharge heart rate <70 beats/min, estimated for each of the 6,286 patients, were used to assemble a cohort of 2,031 pairs of patients with heart rate <70 versus ≥70 beats/min, balanced on 58 baseline characteristics.Results: The 4,062 matched patients had a mean age of 79 ± 10 years, 66% were women, and 10% were African American. During 6 years (median 2.8 years) of follow-up, all-cause mortality was 65% versus 70% for matched patients with a discharge heart rate <70 versus ≥70 beats/min, respectively (hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.80 to 0.93; p < 0.001). A heart rate <70 beats/min was also associated with a lower risk for the combined endpoint of HF readmission or all-cause mortality (HR: 0.90; 95% CI: 0.84 to 0.96; p = 0.002), but not with HF readmission (HR: 0.93; 95% CI: 0.85 to 1.01) or all-cause readmission (HR: 1.01; 95% CI: 0.95 to 1.08). Similar associations were observed regardless of heart rhythm or receipt of beta-blockers.Conclusions: Among hospitalized patients with HFpEF, a lower discharge heart rate was independently associated with a lower risk of all-cause mortality, but not readmission. [ABSTRACT FROM AUTHOR]

Objectives: The analysis goal was to estimate incremental cost-effectiveness ratios (ICERs) for the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial patients who received cardiac resynchronization therapy (CRT) via pacemaker (CRT-P) or pacemaker-defibrillator (CRT-D) in combination with optimal pharmacological therapy (OPT) relative to patients with OPT alone. Background: In the COMPANION trial, CRT-P and CRT-D reduced the combined risk of all-cause mortality or first hospitalization among patients with advanced heart failure and intraventricular conduction delays, but the cost effectiveness of the therapy remains unknown. Methods: In this analysis, intent-to-treat trial data were modeled to estimate the cost effectiveness of CRT-D and CRT-P relative to OPT over a base-case seven-year treatment episode. Exponential survival curves were derived from trial data and adjusted by quality-of-life trial results to yield quality-adjusted life-years (QALYs). For the first two years, follow-up hospitalizations were based on trial data. The model assumed equalized hospitalization rates beyond two years. Initial implantation and follow-up hospitalization costs were estimated using Medicare data. Results: Over two years, follow-up hospitalization costs were reduced by 29% for CRT-D and 37% for CRT-P. Extending the cost-effectiveness analysis to a seven-year base-case time period, the ICER for CRT-P was $19,600 per QALY and the ICER for CRT-D was $43,000 per QALY relative to OPT. Conclusions: For the COMPANION trial patients, the use of CRT-P and CRT-D was associated with a cost-effectiveness ratio below generally accepted benchmarks for therapeutic interventions of $50,000 per QALY to $100,000 per QALY. This suggests that the clinical benefits of CRT-P and CRT-D can be achieved at a reasonable cost. [Copyright &y& Elsevier]

Background: Several clinical and observational studies have established that exercise capacity and activity status are strong predictors of cardiovascular and overall mortality. We aimed to evaluate the relationship between exercise tolerance test (ETT) indices and occurrence of coronary heart disease (CHD), in patients with heterozygous Familial Hypercholesterolemia (eFH). Methods: During 1987–1997, we enrolled 639 cardiovascular disease-free patients with heterozygous eFH; 58 (9%) patients were excluded since they had a positive ETT. A fatal or non-fatal CHD event was the end point. Cox proportional hazards models were applied to evaluate the association between the investigated outcome and ETT indices. Results: During the follow-up (1987–2002), 53 (18%) men and 34 (10%) women developed a CHD event (11 were fatal). The age-adjusted event rate was 87 events per 2915 person-years (3%). Statistical analysis revealed that exercise capacity (hazard ratio=0.82, P<0.001), heart rate recovery at 1 min (hazard ratio=0.91, P<0.05), and peak pulse pressure levels (hazard ratio=1.03, P<0.001), were predictors of CHD, after controlling for several potential confounders. Conclusion: Decreased exercise capacity, a delayed decrease in heart rate during the first minute of graded exercise, and increased peak pulse pressure are strong predictors of coronary events in patients with eFH. Physical activity should be strongly recommended in these patients. [Copyright &y& Elsevier]

Although the value of heart rate variability (HRV) for risk stratification after acute myocardial infarction has been demonstrated, the value of low HRV as a predictor of sudden cardiac death in patients with ischemic cardiomyopathy has not been shown convincingly to date. We retrospectively analyzed electrocardiographic data from 179 patients in the Veterans Affairs’ Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure to determine if HRV (expressed as the SD of the normal-to-normal RR intervals [SDNN]) would be useful as a predictor of overall mortality and sudden death. Because our goal was to identify high-risk patients, we compared patients in the lowest quartile of HRV with the remaining patients. Among the 127 patients meeting inclusion criteria, SDNN <65.3 ms (the lowest quartile) was the sole independent factor predictive of survival in a multivariate model (p = 0.0001). A Cox proportional-hazards model revealed that each increase of 10 ms in SDNN conferred a 20% decrease in risk of mortality (p = 0.0001). Furthermore, patients with SDNN <65.3 ms had a significantly increased risk of sudden death (p = 0.016). Thus, HRV was the sole independent predictor of overall mortality and was significantly associated with sudden death in this population. [Copyright &y& Elsevier]

: ObjectivesWe investigated the acute and long-term hemodynamic and neurohumoral effects of the vasopeptidase inhibitor omapatrilat in human heart failure.: BackgroundAngiotensin-converting enzyme (ACE) inhibition constitutes a major advance in the treatment of chronic heart failure (CHF). Simultaneous inhibition of both neutral endopeptidase and ACE with omapatrilat may represent a new treatment strategy in CHF.: MethodsThree hundred and sixty-nine patients with symptomatic heart failure were randomized to double-blind treatment with omapatrilat (first 190 patients: 2.5 mg, 5 mg or 10 mg; last 179 patients: 2.5 mg, 20 mg or 40 mg once daily) for 12 weeks.: ResultsAcutely, the 10 mg, 20 mg and 40 mg doses of omapatrilat produced greater reductions in pulmonary capillary wedge pressure (PCWP), systolic blood pressure (SBP) and systemic vascular resistance compared with 2.5 mg. Higher doses were associated with greater increases in vasodilator and natriuretic peptides, in addition to ACE inhibition. After 12 weeks, omapatrilat 20 mg and 40 mg showed greater falls from baseline in PCWP (40 mg: 0 h to 12 h average change −7.3 ± 0.8 mm Hg) and SBP (40 mg: −11.7 ± 1.7 mm Hg) than 2.5 mg (both p < 0.01 vs. 2.5 mg). The incidence of adverse experiences and patient withdrawal were similar in all groups.: ConclusionsIn CHF, the acute hemodynamic benefit seen with higher doses of omapatrilat was associated with increases in plasma vasodilator and natriuretic peptide levels in addition to ACE inhibition. After 12 weeks, the hemodynamic benefit was maintained. Omapatrilat may be a promising new agent in CHF. [Copyright &y& Elsevier]