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Background: The aims of this study were to describe the prevalence of QRS prolongation and abnormal QRS morphology in patients with heart failure and preserved ejection fraction (HF-PEF) and to examine the relationship between these QRS abnormalities and clinical outcomes.Methods and Results: We categorized patients in the Irbesartan in Heart Failure with Preserved Ejection Fraction trial (I-PRESERVE) according to QRS duration <120 vs. ≥120 ms and QRS morphology: normal, left bundle branch block (LBBB), and right bundle branch block (RBBB) or other non-specific intra-ventricular conduction defect (IVCD). The outcomes examined were the composite of cardiovascular death or heart failure hospitalization (and its components) and all-cause mortality. Of the 4128 patients enrolled in I-PRESERVE, 3754 were included in the present analyses. A total of 606 patients had a QRS duration ≥120 ms, 302 had LBBB and 742 had RBBB/IVCD. Patients with an abnormal QRS had evidence of more severe heart failure [lower left ventricular ejection fraction, lower estimated glomerular filtration rate, higher N-terminal pro-B-type natriuretic peptide (NT-proBNP)] and worse clinical status (higher New York Heart Association functional class and greater use of diuretics). Both abnormalities of QRS duration and QRS morphology were associated with worse outcomes. The rates of the composite outcome were: 6.0 and 9.3 per 100 patient years in the <120 ms and ≥120 ms groups, respectively [adjusted hazard ratio (HR) 1.32, 95% confidence interval (CI) 1.11-1.57; P = 0.002) and 6.0, 7.7 and 8.7 per 100 patient years in the normal, non-LBBB and LBBB groups, respectively (adjusted HR 1.19, 95% CI 1.00-1.42, P = 0.046; and HR 1.31, 95% CI 1.03-1.66, P = 0.026, respectively, compared with normal). The heightened risk related to QRS abnormalities persisted after adjustment for other prognostic variables, including NT-proBNP.Conclusion: We found that both prolongation of QRS duration and abnormal QRS morphology were associated with a high risk of fatal and non-fatal adverse outcomes in heart failure with preserved ejection fraction. [ABSTRACT FROM AUTHOR]

Aims: To compare surgical outcomes for a simple purse string method of laparoscopic hernia (LH) repair with a traditional open inguinal hernia (OH) repair in children in a single center.Materials and Methods: Following ethical approval, a retrospective review of all children undergoing LH repair from January 2010 to December 2013 versus a historic cohort of all OH repairs between January 2010 and December 2011 was conducted. LH repair was performed by a simple purse string technique using nonabsorbable braided suture. Groups were compared using the independent t test or the Mann-Whitney test as appropriate.Results: One hundred three patients (23 females, 80 males) underwent LH repair over the 4-year period compared with 151 (25 females, 126 males) OH procedures in the first 2 years. Median age in the LH group was 0.56 years (range, 0.04-14.7 years) compared with 0.52 years (range, 0.04-13.47 years) in the OH group (P = .81). In the LH group the intended operation was bilateral in 18 (17.4%); 85 were clinically unilateral, but at operation a contralateral patent processus vaginalis was repaired in 26 (30.5%). Median operative time was 50.5 minutes (range, 20-95 minutes) in the LH group and 20 minutes (range, 10-90 minutes) in the OH cohort (P < .0001). Recurrence rate was 2.9% in the LH group and 3.9% in the OH group, and overall complication rates were 7.8% and 9.9%, respectively.Conclusions: LH repair yields similar results to OH repair; however, the operation time is significantly longer. All complication rates were statistically similar on balance. Almost one-third of LH procedures resulted in concurrent detection and repair of a contralateral patent processus vaginalis at laparoscopy. [ABSTRACT FROM AUTHOR]

Background: Patients with heart failure and preserved ejection fraction (HFpEF) have a poor prognosis, and no therapies have been proven to improve outcomes. It has been proposed that heart failure, including HFpEF, represents overlapping syndromes that may have different prognoses. We present an exploratory study of patients enrolled in the Irbesartan in Heart Failure with Preserved Ejection Fraction Study (I-PRESERVE) using latent class analysis (LCA) with validation using the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Preserved study to identify HFpEF subgroups.Methods and Results: In total, 4113 HFpEF patients randomized to irbesartan or placebo were characterized according to 11 clinical features. The HFpEF subgroups were identified using LCA. Event-free survival and effect of irbesartan on the composite of all-cause mortality and cardiovascular hospitalization were determined for each subgroup. Subgroup definitions were applied to 3203 patients enrolled in CHARM-Preserved to validate observations regarding prognosis and treatment response. Six subgroups were identified with significant differences in event-free survival (P < 0.001). Clinical profiles and prognoses of the six subgroups were similar in CHARM-Preserved. The two subgroups with the worst event-free survival in both studies were characterized by a high prevalence of obesity, hyperlipidaemia, diabetes mellitus, anaemia, and renal insufficiency (Subgroup C) and by female predominance, advanced age, lower body mass index, and high rates of atrial fibrillation, valvular disease, renal insufficiency, and anaemia (Subgroup F).Conclusion: Using a data-driven approach, we identified HFpEF subgroups with significantly different prognoses. Further development of this approach for characterizing HFpEF subgroups is warranted. [ABSTRACT FROM AUTHOR]

The article focuses on the benefits of irbesartan in the management of patients with heart failure and preserved ejection fraction. I-PRESERVE (Irbesartan in Heart Failure with Preserved Ejection Fraction Trial) patients' N-terminal pro-brain natriuretic peptide was measured by the authors for their study. They discovered that significant interaction was seen between irbesartan's effect and median split of baseline NT-proBNP, all-cause mortality and the heart failure composite outcome.

Several retrospective studies have raised concerns regarding digoxin therapy in select subgroups of heart failure patients. To assess the impact of digoxin therapy on outcomes in the current era of heart failure therapy, the authors analyzed data representing 5010 patients enrolled in the Valsartan Heart Failure Trial (Val-HeFT) to examine the relationship of baseline digoxin use and all-cause mortality, first morbid event, and heart failure hospitalizations. At baseline, 3374 patients (67%) were receiving digoxin therapy and 1636 (33%) were not. Patients receiving digoxin had features of worse heart failure with higher New York Heart Association class and lower blood pressure, ejection fraction, and b-blocker use (32.1% vs 40.8%). Digoxin use was associated with worse mortality (21.1 vs 15.0%, P<.001), first morbid event (34.6 vs 21.7, P<.001), and HF hospitalization rate (19.1 vs 10.1%, P<.001). After adjustment for baseline group differences including medical therapy and baseline rhythm, patients receiving digoxin remained at a higher risk for all-cause mortality (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.05-1.57), first morbid event (HR, 1.35; 95% CI, 1.15-1.59), and heart failure hospitalization (HR, 1.41; 95% CI, 1.12-1.78). These results remained materially unchanged with propensity matched analysis. No benefit with digoxin use was observed in this study, underscoring the need to reassess the role of digoxin in the contemporary management of heart failure. [ABSTRACT FROM AUTHOR]

It is unknown whether statin use improves survival in patients with advanced chronic heart failure (HF) receiving cardiac resynchronization therapy (CRT). The authors retrospectively assessed the effect of statin use on survival in patients with advanced chronic HF receiving CRT alone (CRT-P) or CRT with implantable cardioverter-defibrillator therapy (CRT-D) in 1520 patients with advanced chronic HF from the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial database. Six hundred three patients (40%) were taking statins at baseline. All-cause mortality was 18% in the statin group and 22% in the no statin group (hazard ratio [HR] 0.85; confidence interval (CI), 0.67–1.07; P=.15). In a multivariable analysis controlling for significant baseline characteristics and use of CRT-P/CRT-D, statin use was associated with a 23% relative risk reduction in mortality (HR, 0.77; CI, 0.61–0.97; P=.03). Statin use is associated with improved survival in patients with advanced chronic HF receiving CRT. No survival benefit was seen in patients receiving statins and optimal pharmacologic therapy without CRT. [ABSTRACT FROM AUTHOR]

Background: Approximately 50% of patients with heart failure have a left ventricular ejection fraction of at least 45%, but no therapies have been shown to improve the outcome of these patients. Therefore, we studied the effects of irbesartan in patients with this syndrome. Methods: We enrolled 4128 patients who were at least 60 years of age and had New York Heart Association class II, III, or IV heart failure and an ejection fraction of at least 45% and randomly assigned them to receive 300 mg of irbesartan or placebo per day. The primary composite outcome was death from any cause or hospitalization for a cardiovascular cause (heart failure, myocardial infarction, unstable angina, arrhythmia, or stroke). Secondary outcomes included death from heart failure or hospitalization for heart failure, death from any cause and from cardiovascular causes, and quality of life. Results: During a mean follow-up of 49.5 months, the primary outcome occurred in 742 patients in the irbesartan group and 763 in the placebo group. Primary event rates in the irbesartan and placebo groups were 100.4 and 105.4 per 1000 patient-years, respectively (hazard ratio, 0.95; 95% confidence interval [CI], 0.86 to 1.05; P=0.35). Overall rates of death were 52.6 and 52.3 per 1000 patient-years, respectively (hazard ratio, 1.00; 95% CI, 0.88 to 1.14; P=0.98). Rates of hospitalization for cardiovascular causes that contributed to the primary outcome were 70.6 and 74.3 per 1000 patient-years, respectively (hazard ratio, 0.95; 95% CI, 0.85 to 1.08; P=0.44). There were no significant differences in the other prespecified outcomes. Conclusions: Irbesartan did not improve the outcomes of patients with heart failure and a preserved left ventricular ejection fraction. (ClinicalTrials.gov number, NCT00095238.) N Engl J Med 2008;359:2456-67. [ABSTRACT FROM AUTHOR]

Abstract: Background: We describe the baseline characteristics of subjects randomised in the largest placebo-controlled, morbidity-mortality trial to date in patients with heart failure and preserved ejection fraction — the irbesartan in heart failure with preserved systolic function trial (I-PRESERVE). Methods and results: 4133 patients with a mean age of 72 years (a third were 75 years or older) were randomised and 60% were women. The mean (SD) LVEF was 59 (9)% and almost 80% of patients were in NYHA Class III or IV. Approximately 80% of patients were also overweight or obese. Heart failure was reported by investigators to have a hypertensive aetiology in 64% of patients. Prior myocardial infarction was relatively uncommon (24%), as was coronary revascularisation (13%). Atrial fibrillation and diabetes each occurred in between a quarter and a third of patients. The following treatments were used at baseline: diuretic 83%, beta-blocker 59%, calcium channel blocker 40%, ACE inhibitor 25%, spironolactone 15% and digoxin 14%. Conclusions: Patients in I-PRESERVE are broadly representative of those seen in epidemiological studies and, because of this, the results of this trial should be generally applicable to “real world” patients with heart failure and preserved ejection fraction. [Copyright &y& Elsevier]

Background: We determined whether low-dose oral enoximone could wean patients with ultra-advanced heart failure (UA-HF) from intravenous (IV) inotropic support. Chronic parenteral inotropic therapy in UA-HF is costly and requires an indwelling catheter. An effective and safe oral inotrope would have value. Methods: In this placebo-controlled study, 201 subjects with UA-HF requiring IV inotropic therapy were randomized to enoximone or placebo. Subjects receiving intermittent IV inotropes were administered study medication of 25 or 50 mg 3 times a day (tid). Subjects receiving continuous IV inotropes were administered 50 or 75 mg tid for 1 week, which was reduced to 25 or 50 mg tid. The ability of subjects to remain alive and free of inotropic therapy was assessed for up to 182 days. Results: Thirty days after weaning, 51 (51%) subjects on placebo and 62 (61.4%) subjects in the enoximone group were alive and free of IV inotropic therapy (unadjusted primary end point P = 0.14, adjusted for etiology P = .17). At 60 days, the wean rate was 30% in the placebo group and 46.5% in the enoximone group (unadjusted P = .016) Kaplan-Meier curves demonstrated a trend toward a decrease in the time to death or reinitiation of IV inotropic therapy over the 182-day study period (hazard ratio 0.76 [95% CI 0.55-1.04]) and a reduction at 60 days (0.62 [95% CI 0.43-0.89], P = .009) and 90 days (0.69 [95% CI 0.49-0.97], P = .031) after weaning in the enoximone group. Conclusions: Although there was no benefit over placebo in weaning patients from IV inotropes from 0 to 30 days, the EMOTE data suggest that low-dose oral enoximone can be used to wean a modest percentage of subjects from IV inotropic support for up to 90 days after initiation of therapy. [Copyright &y& Elsevier]

Cites information on the Prospective Randomized Amlodipine Survival Evaluation (PRAISE) trial study which investigated the effect which amlodipine has on patients with advanced heart failure. Details on the PRAISE trial; Information on the participants in the study; Concern regarding calcium antagonists in heart disease patients; In-depth look at the results of the study.

Background: In patients with heart failure and preserved ejection fraction, little is known about the characteristics of, and outcomes in, those with and without diabetes mellitus.Methods: We examined clinical and echocardiographic characteristics and outcomes in the I-Preserve trial (Irbesartan in Heart Failure With Preserved Ejection Fraction) according to history of diabetes mellitus. Cox regression models were used to estimate hazard ratios for cardiovascular outcomes adjusted for known predictors, including age, sex, natriuretic peptides, and comorbidity. Echocardiographic data were available in 745 patients and were additionally adjusted for in supplementary analyses.Results: Overall, 1134 of 4128 patients (27%) had diabetes mellitus. Compared with those without diabetes mellitus, they were more likely to have a history of myocardial infarction (28% versus 22%), higher body mass index (31 versus 29 kg/m2), worse Minnesota Living With Heart Failure score (48 versus 40), higher median N-terminal pro-B-type natriuretic peptide concentration (403 versus 320 pg/mL; all P<0.01), more signs of congestion, but no significant difference in left ventricular ejection fraction. Patients with diabetes mellitus had a greater left ventricular mass and left atrial area than patients without diabetes mellitus. Doppler E-wave velocity (86 versus 76 cm/s; P<0.0001) and the E/e' ratio (11.7 versus 10.4; P=0.010) were higher in patients with diabetes mellitus. Over a median follow-up of 4.1 years, cardiovascular death or heart failure hospitalization occurred in 34% of patients with diabetes mellitus versus 22% of those without diabetes mellitus (adjusted hazard ratio, 1.75; 95% confidence interval, 1.49-2.05), and 28% versus 19% of patients with and without diabetes mellitus died (adjusted hazard ratio, 1.59; confidence interval, 1.33-1.91).Conclusions: In heart failure with preserved ejection fraction, patients with diabetes mellitus have more signs of congestion, worse quality of life, higher N-terminal pro-B-type natriuretic peptide levels, and a poorer prognosis. They also display greater structural and functional echocardiographic abnormalities. Further investigation is needed to determine the mediators of the adverse impact of diabetes mellitus on outcomes in heart failure with preserved ejection fraction and whether they are modifiable.Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00095238. [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]

We sought to identify the clinical characteristics and outcomes of patients who had advanced heart failure and nonfatal myocardial infarction (MI) in the β-Blocker Evaluation of Survival Trial (BEST) and to investigate whether bucindolol alters the risk of developing nonfatal MI. Of the 2,708 patients enrolled in the study, 142 had suspected MI and 69 had confirmed MI; there were 860 deaths overall. The rate of nonfatal MI in the BEST was low over the 4.1 years of follow-up (4.8% had suspected events and 2.4% had adjudicated events) and was similar to that in high-risk populations. Cox''s proportional hazard model with 23 prespecified candidate variables associated advanced age, heart failure symptoms, male gender, ischemic etiology, diabetes, and hypertension with nonfatal MI or cardiovascular death. The 2-year mortality rate was 56% for the cohort that had suspected nonfatal MI versus 30% for the cohort that did not (p = 0.01). Likewise, the risk of hospitalization for congestive heart failure was twofold greater. Beta-blocker therapy with bucindolol resulted in a 52% decrease in suspected nonfatal MI (2.9% vs 5.5%, p = 0.001). In conclusion, nonfatal MI occurs at low rates but increases the risks for mortality and hospitalization in patients who have advanced heart failure. Beta-blocker therapy with bucindolol appears to attenuate the risk of nonfatal MI in this population. [Copyright &y& Elsevier]

Background: We examined whether a fixed dose of both isosorbide dinitrate and hydralazine provides additional benefit in blacks with advanced heart failure, a subgroup previously noted to have a favorable response to this therapy. Methods: A total of 1050 black patients who had New York Heart Association class III or IV heart failure with dilated ventricles were randomly assigned to receive a fixed dose of isosorbide dinitrate plus hydralazine or placebo in addition to standard therapy for heart failure. The primary end point was a composite score made up of weighted values for death from any cause, a first hospitalization for heart failure, and change in the quality of life. Results: The study was terminated early owing to a significantly higher mortality rate in the placebo group than in the group given isosorbide dinitrate plus hydralazine (10.2 percent vs. 6.2 percent, P=0.02). The mean primary composite score was significantly better in the group given isosorbide dinitrate plus hydralazine than in the placebo group (–0.1±1.9 vs. –0.5±2.0, P=0.01; range of possible values, –6 to +2), as were its individual components (43 percent reduction in the rate of death from any cause [hazard ratio, 0.57; P=0.01] 33 percent relative reduction in the rate of first hospitalization for heart failure [16.4 percent vs. 22.4 percent, P=0.001], and an improvement in the quality of life [change in score, –5.6±20.6 vs. –2.7±21.2, with lower scores indicating better quality of life; P=0.02; range of possible values, 0 to 105]). Conclusions: The addition of a fixed dose of isosorbide dinitrate plus hydralazine to standard therapy for heart failure including neurohormonal blockers is efficacious and increases survival among black patients with advanced heart failure. N Engl J Med 2004;351:2049-57. [ABSTRACT FROM AUTHOR]

Background: Inotropic therapy, other than with digitalis glycosides, has had limited success in patients with chronic congestive heart failure. We investigated whether vesnarinone, a new positive inotropic agent, reduces morbidity and mortality and improves the quality of life of patients with symptomatic heart failure. Methods: Patients receiving concomitant therapy with digoxin (87 percent) and an angiotensin-converting-enzyme inhibitor (90 percent) who had ejection fractions of 30 percent or less were randomly assigned to receive double-blinded therapy with 60 mg of vesnarinone per day, 120 mg of vesnarinone per day, or placebo. After 253 patients had been enrolled, randomization to the 120-mg vesnarinone group had to be stopped because of a significant increase in early mortality in this group. Thereafter, patients were randomly assigned only to 60 mg of vesnarinone per day (a total of 239 patients) or placebo (a total of 238 patients). Results: Significantly fewer patients in the group receiving 60 mg of vesnarinone than in the group receiving placebo (26 vs. 50 patients; P = 0.003) died or had worsening heart failure during the six-month study period. The reduction in risk was 50 percent (95 percent confidence interval, 20 to 69 percent). Similarly, there was a 62 percent reduction (95 percent confidence interval, 28 to 80 percent) in the risk of dying from any cause among the patients receiving vesnarinone. Furthermore, quality of life improved to a greater extent in the vesnarinone group than in the placebo group over 12 weeks (P = 0.008). The principal side effect associated with vesnarinone was reversible neutropenia, which occurred in 2.5 percent of the patients. Conclusions: Six months of therapy with 60 mg of vesnarinone per day resulted in lower morbidity and mortality and improved the quality of life of patients with congestive heart failure. However, a higher dose of vesnarinone (120 mg per day) increased mortality, suggesting that this drug has a narrow therapeutic range; the long-term effects of vesnarinone are unknown. (N Engl J Med 1993;329:149-55.) [ABSTRACT FROM AUTHOR]