Marrick Kukin

Double-Blind, Placebo-Controlled Study of the Long-term Efficacy of Carvedilol in Patients With Severe Chronic Heart Failure

BACKGROUNDnClinical trials have shown that beta-adrenergic blocking drugs are effective and well tolerated in patients with mild to moderate heart failure, but the utility and safety of these drugs in patients with advanced disease have not been evaluated.nnnMETHODS AND RESULTSnWe enrolled 56 patients with severe chronic heart failure into a double-blind, placebo-controlled study of the vasodilating beta-blocker carvedilol. All patients had advanced heart failure, as evidenced by a mean left ventricular ejection fraction of 0.16 +/- 0.01 and a mean maximal oxygen consumption of 13.6 +/- 0.6 mL.kg-1.min-1 despite digitalis, diuretics, and an angiotensin-converting enzyme inhibitor (if tolerated). After a 3-week, open-label, up-titration period, 49 of the 56 patients were assigned (in a double-blind fashion using a 2:1 randomization) to receive either carvedilol (25 mg BID, n = 33) or matching placebo (n = 16) for 14 weeks, while background therapy remained constant. Hemodynamic and functional variables were measured at the start and end of the study. Compared with the placebo group, patients in the carvedilol group showed improved cardiac performance, as reflected by an increase in left ventricular ejection fraction (P = .005) and stroke volume index (P = .010) and a decrease in pulmonary wedge pressure, mean right atrial pressure, and systemic vascular resistance (P = .003, .002, and .017, respectively). In addition, compared with placebo, patients treated with carvedilol benefited clinically, as shown by an improvement in symptom scores (P = .002), functional class (P = .013), and submaximal exercise tolerance (P = .006). The combined risk of death, worsening heart failure, and life-threatening ventricular tachyarrhythmia was lower in the carvedilol group than in the placebo group (P = .028), but carvedilol-treated patients had more dizziness and advanced heart block.nnnCONCLUSIONSnCarvedilol produces clinical and hemodynamic improvement in patients who have severe heart failure despite treatment with angiotensin-converting enzyme inhibitors.

Metoprolol Reverses Left Ventricular Remodeling in Patients With Asymptomatic Systolic Dysfunction The REversal of VEntricular Remodeling with Toprol-XL (REVERT) Trial

Background— There are no randomized, controlled trial data to support the benefit of &bgr;-blockers in patients with asymptomatic left ventricular systolic dysfunction. We investigated whether &bgr;-blocker therapy ameliorates left ventricular remodeling in asymptomatic patients with left ventricular systolic dysfunction. Method and Results— Patients with left ventricular ejection fraction <40%, mild left ventricular dilation, and no symptoms of heart failure (New York Heart Association class I) were randomly assigned to receive extended-release metoprolol succinate (Toprol-XL, AstraZeneca) 200 mg or 50 mg or placebo for 12 months. Echocardiographic assessments of left ventricular end-systolic volume, end-diastolic volume, mass, and ejection fraction were performed at baseline and at 6 and 12 months. The 149 patients randomized to the 3 treatment groups (200 mg, n=48; 50 mg, n=48; and placebo, n=53) were similar with regard to all baseline characteristics including age (mean, 66 years), gender (74% male), plasma brain natriuretic peptide (79 pg/mL), left ventricular end-diastolic volume index (110 mL/m2), and left ventricular ejection fraction (27%). At 12 months in the 200-mg group, there was a 14±3 mL/m2 decrease (least square mean±SE) in end-systolic volume index and a 6±1% increase in left ventricular ejection fraction (P<0.05 versus baseline and placebo for both). The decrease in end-diastolic volume index (14±3) was different from that seen at baseline (P<0.05) but not with placebo. In the 50-mg group, end-systolic and end-diastolic volume indexes decreased relative to baseline but were not different from what was seen with placebo, whereas ejection fraction increased by 4±1% (P<0.05 versus baseline and placebo). Conclusion— &bgr;-Blocker therapy can ameliorate left ventricular remodeling in asymptomatic patients with left ventricular systolic dysfunction.

Beta-blockers for primary prevention of heart failure in patients with hypertension insights from a meta-analysis.

OBJECTIVESnThis study sought to evaluate the efficacy of beta-blockers (BBs) for primary prevention of heart failure (HF) in patients with hypertension.nnnBACKGROUNDnThe American College of Cardiology/American Heart Association staging for HF classifies patients with hypertension as stage A HF, for which BBs are a treatment option. However, the evidence to support this is unknown.nnnMETHODSnWe conducted a MEDLINE/EMBASE/CENTRAL search of randomized controlled trials that evaluated BB as first-line therapy for hypertension with follow-up for at least 1 year and with data on new-onset HF. The primary outcome was new-onset HF. Secondary outcomes were all-cause mortality, cardiovascular mortality, myocardial infarction, and stroke.nnnRESULTSnAmong the 12 randomized controlled trials, which evaluated 112,177 patients with hypertension, BBs reduced blood pressure by 12.6/6.1 mm Hg when compared with placebo, resulting in a 23% (trend) reduction in HF risk (p = 0.055). When compared with other agents, the antihypertensive efficacy of BBs was comparable, which resulted in similar but no incremental benefit for HF risk reduction in the overall cohort (risk ratio: 1.00; 95% confidence interval: 0.92 to 1.08), in the elderly (> or =60 years) or in the young (<60 years). Analyses of secondary outcomes showed that BBs confirmed similar but no incremental benefit for the outcomes of all-cause mortality, cardiovascular mortality, and myocardial infarction but increased stroke risk by 19% in the elderly.nnnCONCLUSIONSnIn hypertensive patients, primary prevention of HF is strongly dependent on blood pressure reduction. When compared with other antihypertensive agents, there was similar but no incremental benefit of BBs for the prevention of HF. However, given the increased risk of stroke in the elderly, BBs should not be considered as first-line agents for prevention of HF.

Malnutrition as Assessed by Nutritional Risk Index is Associated with Worse Outcome in Patients Admitted with Acute Decompensated Heart Failure: An ACAP-HF Data Analysis:

Malnutrition is common at hospital admission and tends to worsen during hospitalization. This controlled population study aimed to determine if serum albumin or moderate and severe nutritional depletion by Nutritional Risk Index (NRI) at hospital admission are associated with increased length of hospital stay (LOS) in patients admitted with acute decompensated heart failure (ADHF). Serum albumin levels and lymphocyte counts were retrospectively determined at hospital admission in 1740 consecutive patients admitted with primary and secondary diagnosis of ADHF. The Nutrition Risk Score (NRI) developed originally in AIDS and cancer populations was derived from the serum albumin concentration and the ratio of actual to usual weight, as follows: NRI = (1.519 × serum albumin, g/dL) + {41.7 × present weight (kg)/ideal body weight(kg)}. Patients were classified into four groups as no, mild, moderate or severe risk by NRI. Multiple logistic regressions were used to determine the association between nutritional risk category and LOS. Three hundred and eighty-one patients (34%) were at moderate or severe nutritional risk by NRI score. This cohort had lower BMI (24 ± 5.6 kg/m2), albumin (2.8±0.5 g/dL), mean NRI (73.5±9) and lower eGFR (50±33 mL/min per 1.73 m2). NRI for this cohort, adjusted for age, was associated with LOS of 10.1 days. Using the Multiple Logistic regression module, NRI was the strongest predictor for LOS (OR 1.7, 95% CI: 1.58–1.9; P=0.005), followed by TIMI Risk Score [TRS] (OR 1.33, 95% CI: 1.03–1.71; P=0.02) and the presence of coronary artery disease (OR 2.29, 95%CI: 1.03–5.1; P=0.04). Moderate and severe NRI score was associated with higher readmission and death rates as compared to the other two groups. Nutritional depletion as assessed by Nutritional Risk Index is associated with worse outcome in patients admitted with ADHF. Therefore; we recommend adding NRI to further risk stratify these patients.

Ablation vs Medical Therapy in the Setting of Symptomatic Atrial Fibrillation and Left Ventricular Dysfunction

Small, single-center studies suggest that catheter ablation of atrial fibrillation (AF) can improve ventricular function and reduce symptoms in patients with left ventricular (LV) dysfunction. However, ablation has not been compared with a pharmacologic strategy for AF. The authors evaluated patients with AF and symptomatic LV dysfunction (ejection fraction < or =45%) referred for pulmonary vein isolation (PVI). They compared these patients with a matched cohort treated medically for AF and LV dysfunction via a retrospective case-control method. Fifteen patients (14 men, 56+/-11 years, 10 [67%] paroxysmal AF) with AF for 4+/-3 years underwent PVI. Baseline ejection fraction was 37%+/-6% and New York Heart Association (NYHA) class was 2.0+/-1.0. Fifteen controls (13 men, 63+/-14 years, 11 [73%] paroxysmal AF) with AF for 5+/-4 years were treated medically for AF. Baseline ejection fraction was 34%+/-11% and NYHA class was 2.0+/-0.7. The groups were similar in all respects. During a follow-up of 16+/-13 months after complete PVI, ejection fraction improved (P=.001) to 50%+/-13% and normalized in 8 patients (53%). NYHA class improved to 1.3+/-0.5 (P=.01). In the medically treated group, after follow-up of 16+/-12 months, no improvement in ejection fraction (36%+/-12%) or NYHA class (1.8+/-0.7) was seen. Compared with pharmacologic therapy, PVI significantly improved LV function and NYHA class in patients with AF and symptomatic LV dysfunction. These provocative findings provide potent rationale for a randomized clinical trial comparing ablation with pharmacologic therapy.

Prognosis and response to therapy of first inpatient and outpatient heart failure event in a heart failure clinical trial: MADIT‐CRT

Hospitalization for worsening heart failure (HF) is known to increase mortality and morbidity risk and has been frequently used as an endpoint in randomized clinical trials. Whether outpatient management of HF exacerbation carries similar prognostic and therapeutic information is less well known, but could be important for the design of trials that use HF hospitalization as an endpoint.

Right Ventricular Dysfunction is a Strong Predictor of Developing Atrial Fibrillation in Acutely Decompensated Heart Failure Patients, ACAP-HF Data Analysis

BACKGROUNDnHeart failure and atrial fibrillation (AFib) are the twin epidemics of modern cardiovascular disease. The incidence of new-onset AFib in acute decompensated heart failure (ADHF) patients is difficult to predict and the short- and long-term outcomes of AFib in a cohort of patients admitted with ADHF are unknown.nnnMETHODS AND RESULTSnA total of 904 patients admitted with ADHF were studied. Incidence of AFib on admission was recorded and a multivariate analysis was performed using echocardiographic parameters to specify the predictors of AFib incidence in this cohort. In 904 ADHF patients (57% male, mean age 69 ± 14 years), 81% had history of hypertension, 40% were diabetics, and 51% were smokers. A total of 63% of the patients had known heart failure (HF) with mean ejection fraction of 34% ± 21%, and 33% of the patients had ischemic cardiomyopathy as the etiology of HF. Echocardiographic parameters were: left atrial (LA) diameter 4.5 ± 0.8 cm, left ventricular end-systolic 4.1 ± 1.3 cm, left ventricular end-diastolic 5.3 ± 1.1 cm. Right ventricular dysfunction (RVD) was present in 34% of the patients. A total of 191 (21%) patients subsequently developed AFib with two thirds of the cases occurring in patients with RVD. Using a univariate analysis, older age (OR 1.02; P < .0001), history of HF (OR 2.93; P < .0001), LA dilation (OR 1.58; P < .0001), the presence of left ventricular hypertrophy (OR 3.01, P < .0001), and RVD (OR 4.93; P < .00001) were the strongest predictors for AFib. Controlling for LA size and left ventricular hypertrophy using a forward stepwise regression, RVD remained the strongest predictor (OR 4.45; P < .0001). Patients with RVD had more events (cardiac readmission and mortality) than those with normal RV (56% versus 38%; P < .00001), notably; all-cause mortality was 4.7%/year in the abnormal RV group versus 2.9%/year in the normal RV group; P < .05. RV function analyses by echocardiography further risk stratified these patients based on their rhythm categorizing those patients with abnormal RV and AFib as the ones with the worse prognosis.nnnCONCLUSIONnRV dysfunction is a strong predictor for developing AFib in acutely decompensated systolic failure patients. Patients with AFib and RVD have the worse outcome specially when is combined with LV dysfunction, therefore; evaluation of RV function may substantiate the difference in HF prognosis.

Pathway for the management of acute heart failure.

Acute heart failure poses a major healthcare problem. Recent guidelines for heart failure address management of outpatient chronic heart failure but do not address inpatient management. We present a unique, simple, yet comprehensive pathway that focuses on the differential diagnosis of new-onset heart failure and acute decompensation of chronic heart failure. An algorithm is presented for the optimal management of the patient with chronic heart failure who presents to the emergency room with acute symptomatic decompensation. The treatment algorithm provides recommendations for daily management and adjustments of therapy, which is primarily focused on a safe and rapid diuresis to the point of discharge from the acute care setting.

Effect of adding nitroglycerin to early diuretic therapy on the morbidity and mortality of patients with chronic kidney disease presenting with acute decompensated heart failure.

Abstract Background: Loop diuretics are considered first-line therapy for patients with acute decompensated heart failure (ADHF). Adding nitroglycerin (NTG) to diuretic therapy for alleviation of acute shortness of breath has been advocated in our institution. We evaluated the benefits of adding NTG to diuretics in the emergency department for patients with ADHF and chronic kidney disease (CKD). Methods: 430 consecutive patients with ADHF who were admitted with a chief complaint of dyspnea were included in this retrospective study. Patients were divided into 3 groups. Group A patients were treated with neither diuretics nor NTG; Group B patients were treated with diuretics only; and Group C patients were treated with both diuretics and NTG. Estimated glomerular filtration rate (GFR) was calculated according to the Cockcroft-Gault formula. Follow-up was 36 ± 9 (mean ± standard deviation [SD]) months. Primary endpoints were readmission rate at 30 days and mortality at 24 months. Results: 430 patients were included in this study (42% men; age, 69 ± 14 [mean ± SD] years); mean New York Heart Association class was 2.4 ± 0.7 (mean ± SD) and mean ejection fraction was 28% ± 17% (mean ± SD). Group A included 257 (59%) patients, Group B had 127 (29%) patients, and Group C had 46 (11%) patients. Group C patients were older (mean age, 72 ± 13 years) with lower body mass index (26 ± 7 kg/m2), lower estimated GFR (55.8 ± 38 mL/min per 1.73 m2), higher B-type natriuretic peptide levels (1112 ± 876 pg/mL; P = nonsignificant [NS]), and higher systolic and diastolic blood pressures on admission (P = 0.001). The primary endpoint was assessed as a composite of all-cause mortality and ADHF readmission seen in 143 (56%) Group A patients, 68 (53%) Group B patients, and 22 (48%) Group C patients (P = NS). At 30 days there were 53 (12%) readmissions—26 in Group A, 20 in Group B, and 7 in Group C (P = NS). However, survival at 24 months was higher in Group C (87%) compared with Groups A (79%) and B (82%) (P = 0.002). Using the Cox proportional-hazards regression module, early administration of NTG and Lasix (95% confidence interval [CI], 1.06–1.62; P = 0.01) followed by CKD stage (95% CI, 1.00–1.35; P = 0.04) were the only predictors for survival. Conclusion: There is a role for early administration of NTG in addition to diuretic therapy in patients admitted to the emergency department with ADHF, with resultant decreased length of stay and a trend toward a decrease in the composite endpoint of all-cause mortality and ADHF readmission. The mortality benefit at 2 years reported in our study is thought-provoking and raises a premise to be proven in randomized clinical trials.

Novel pathway for sudden cardiac death prevention.

Sudden cardiac death is one of the leading causes of death in the United States, accounting for an estimate 350,000 deaths each year. The US Congress passed a resolution in late September 2008 designating October as National Sudden Cardiac Arrest Awareness Month. In an effort to raise awareness for preventing unnecessary deaths because of sudden cardiac death, the resolution calls upon the people of the United States to observe this month with appropriate programs and activities. The response from our institute was to develop a novel pathway named ESCAPE-which is an evidence-based novel pathway for low Ejection fraction and Sudden Cardiac death Awareness and Prevention Eligibility. The main objective of this program is to demonstrate that implementing a simple novel pathway for primary prevention of sudden cardiac arrest leads to an increase in the number of patients with low ejection fraction (<or=35%) referred for implantable cardioverter defibrillators therapy. The key difference of our pathway compared with prior reported algorithms is that it is initiated at imaging laboratories. The registry will consist of consecutive patients presenting to our imaging laboratories (the echocardiography, the nuclear, and the cardiac catheterization laboratories). The ESCAPE pathway defines patients management based upon 3 key parameters: left ventricular ejection function, heart failure functional class, and an evidence of a prior myocardial infarction or coronary artery disease. We hope that this new novel pathway will help to bridge the gap between the complex guidelines and the actual clinical practice and will help to save many lives.