Intensity of Guideline-Directed Medical Therapy for Coronary Heart Disease and Ischemic Heart Failure Outcomes

PurposeThe impact of guideline-directed medical therapy for coronary heart disease in those hospitalized with acute heart failure is unknown.MethodsWe studied guideline-directed medical therapies for coronary disease: angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), beta-adrenoreceptor antagonists, antiplatelet agents or anticoagulants, and statins. Using inverse probability of treatment weighting the propensity score, we examined associations of guideline-directed medical therapy intensity (categorized as low [0-1], high [2-3], or very high [4] number of drugs) with mortality in 1873 patients with angina, troponin elevation, or prior myocardial infarction.ResultsAt discharge, 0-1, 2-3, and 4 medications were prescribed in 467 (25%), 705 (38%), and 701 (37%) patients, respectively. Relative to those prescribed 0-1 drugs (reference), all-cause mortality was lower with 2-3 (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.28-0.84, P = 0.009) or all 4 drug classes (HR 0.56, 95% CI 0.33-0.96, P = 0.034) over 181-365 days, with similar reductions present from 0-180 days. In those with heart failure with preserved ejection fraction, mortality trended lower with 2-3 drug classes (HR 0.43, 95% CI 0.18-1.02, P = 0.054) and was significantly reduced with 4 drugs (HR 0.32, 95%CI 0.12-0.84, P = 0.021) during 0-180 day follow-up. In heart failure with reduced ejection fraction, all-cause mortality was reduced during both 0-180 and 181-365 days when discharged on 2-3 (HR 0.30 for 181-365 days, 95%CI 0.14-0.64, P = 0.002) or all 4 drug classes (HR 0.43, 95%CI 0.19-0.95, P = 0.038).ConclusionsIncreasing guideline-directed medical therapy intensity for coronary heart disease resulted in lower mortality in patients with acute ischemic heart failure with both preserved and reduced ejection fractions.     

In-Hospital and Three-Year Outcomes of Heart Failure Patients in South India: The Trivandrum Heart Failure Registry

Background

Long-term data on outcomes of participants hospitalized with heart failure (HF) from low- and middle-income countries are limited.

Hydrogen- and Methane-Based Breath Testing and Outcomes in Patients With Heart Failure

BackgroundRecent evidence endorses gut microbiota dysregulation in the pathophysiology of heart failure (HF). Small intestinal bacterial overgrowth (SIBO) might be present in HF and associated with poor clinical outcomes. Lactulose breath testing is a simple noninvasive test that has been advocated as a reliable indicator of SIBO. In patients with HF, we aimed to evaluate the association with clinical outcomes of the exhaled hydrogen (H₂) and methane (CH₄) concentrations through the lactulose breath test.Methods and ResultsWe included 102 patients with HF in which lactulose SIBO breath tests were assessed. Cumulative gas was quantified by the area under the receiver operating characteristic curve of CH₄ (AUC-CH₄) and H₂ (AUC-H₂). Clinical end points included the composite of all-cause death with either all-cause or HF hospitalizations, recurrent all-cause hospitalizations, and recurrent HF hospitalizations. Medians (interquartile ranges) of AUC-H₂ and AUC-CH₄ were 1290 U (520-2430) and 985 U (450-2120), respectively. In multivariable analysis, AUC-H₂ (per 1000 U) was associated with all-cause death/all-cause hospitalization (hazard ratio [HR] 1.21, 95% CI 1.04–1.40; P = .012), all-cause death/HF hospitalization (HR 1.20, 95% CI 1.03–1.40; P = .021), and an increase in the rate of recurrent all-cause (incidence rate ratio [IRR] 1.31, 95% CI 1.14–1.51; P < .001) and HF (IRR 1.41, 95% CI 1.15–1.72; P = .001) hospitalizations. AUC-CH₄ was not associated with any of these end points.ConclusionsAUC-H₂, a safe and noninvasive method for SIBO estimation, is associated with higher risk of long-term adverse clinical events in patients with HF. In contrast, AUC-CH₄ did not show any prognostic value.     

U-Shaped Relationship of Sodium-to-chloride Ratio on admission and Mortality in Elderly Patients with Heart Failure: A Retrospective Cohort Study

Serum sodium and chloride have clinical significance in the prognosis of heart failure. Little is known regarding the prognostic value of sodium-to-chloride (Na/Cl) ratio in patients with heart failure. This study sought to investigate the association between Na/Cl ratio on admission and mortality risk of elderly patients with acute heart failure in a retrospective cohort. We included 1819 patients (aged over 60) from the Zigong Heart Failure Study. Patients were grouped according to Na/Cl ratio and followed up for all-cause mortality at 3 months. Restricted cubic spline, cox proportional hazard regression and Kaplan-Meier curve were used to examine the correlation between serum Na/Cl ratio on admission and mortality risk. Restricted cubic spline analysis suggested a U-shaped association between Na/Cl ratio on admission and 3 months mortality risk (P nonlinearity <0.001), with the nadir of risk at 1.34. After adjustment for multivariate, patients with Na/Cl ratio <1.3 or ≥ 1.4 had hazard ratios for mortality of 3.58 (95% CI, 1.63-7.84) and 2.66 (95% CI, 1.23-5.72) compared with those with Na/Cl ratio of 1.3-1.4. The cumulative hazard of mortality estimates significantly differed across Na/Cl ratio groups (log-rank P<0.001). Subgroup analysis showed there were no interactions with absent or present of hyponatremia and hypochloremia (P for interaction all >0.05). Both low and high Na/Cl ratios were associated with an increased mortality risk in elderly patients with acute heart failure. Further studies need to verify these 2 biochemical phenotypes and develop corresponding treatment strategies.     

The long-term impact of the angiotensin-converting enzyme inhibitor trandolapril on mortality and hospital admissions in patients with left ventricular dysfunction after a myocardial infarction: follow-up to 12 years.

AIMS: To investigate the long-term benefits of treatment with angiotensin-converting enzyme (ACE)-inhibitors in patients with myocardial infarction (MI) and left ventricular dysfunction (LVD). METHODS AND RESULTS: In the trandolapril cardiac evaluation (TRACE) study, 1749 patients with LVD (ejection fraction< or =35%) were randomized to trandolapril (n=876) or placebo (n=873) 3-7 days post-MI. Enrolment lasted from 1990 to 1994; on-treatment follow-up ranged from 2 to 4 years. At study closure, all patients were recommended continued ACE-inhibitor use. National registries were used to track deaths and hospitalizations until 2002. Mortality was analysed with Cox proportional hazard models and hospitalization with Poisson regression models (models adjusted for observation time). Over 10-12 years of follow-up, a total of 1283 deaths and 9220 hospitalizations were registered. Compared with the placebo group, the trandolapril group had a significantly reduced risk of all-cause mortality (relative risk 0.89, 95% CI 0.80-0.99, P=0.03), all-cause hospitalizations (rate ratio 0.92, 95% CI 0.88-0.96, P<0.001), and cardiovascular hospitalizations (rate ratio 0.95, 95% CI 0.91-1.00, P=0.047), including congestive heart failure hospitalizations (rate ratio 0.85, 95% CI 0.77-0.93, P<0.001). CONCLUSION: In patients with LVD, use of trandolapril shortly after an MI for 2-4 years has long-term benefits. The beneficial effect on mortality and hospitalization rates is maintained for at least 10-12 years.     

Digoxin use and heart failure outcomes: results from the Valsartan Heart Failure Trial (Val-HeFT)

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 β-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.     

eGFR and Outcomes in Patients with Acute Decompensated Heart Failure with or without Elevated BUN

Background and objectives

In patients with heart failure, the association of renal dysfunction and BUN levels with outcomes is unclear. The aim of our study was to investigate the association between the eGFR at discharge and outcomes in patients with heart failure with or without an elevated BUN level at discharge.

Design, setting, participants, & measurements

Of 4842 patients enrolled in the Acute Decompensated Heart Failure Syndromes Registry, 4449 patients discharged alive after hospitalization for acute decompensated heart failure were investigated to assess the association of eGFR in the context of serum BUN level at discharge with all-cause mortality. The enrolled patients were divided into four groups on the basis of the discharge levels of eGFR (<45 or ≥45 ml/min per 1.73 m²) and BUN (≥25 or <25 mg/dl). The median follow-up period after discharge was 517 (381–776) days.

Results

The all–cause mortality rate after discharge was 19.1%. After adjustment for multiple comorbidities, an eGFR<45 ml/min per 1.73 m² was associated with a significantly higher risk of all-cause mortality in patients with a BUN≥25 mg/dl (hazard ratio, 1.58; 95% confidence interval, 1.33 to 1.88; P<0.001) but not in patients with a BUN<25 mg/dl (hazard ratio, 0.97; 95% confidence interval, 0.76 to 1.26; P=0.84) relative to those with an eGFR≥45 ml/min per 1.73 m² and a BUN<25 mg/dl. Among patients with an eGFR≥45 ml/min per 1.73 m², a BUN≥25 mg/dl was associated with a significantly higher risk of all-cause mortality than a BUN<25 mg/dl (hazard ratio, 1.34; 95% confidence interval, 1.04 to 1.73; P=0.02).

Conclusions

We showed that elevation of BUN at discharge significantly modified the relation between eGFR at discharge and the risk of all-cause mortality after discharge, suggesting that the association between eGFR and outcomes may be largely dependent on concomitant elevation of BUN.     

Plasma Volume Status and Its Association With In-Hospital and Postdischarge Outcomes in Decompensated Heart Failure

BackgroundPrior analyses suggest an association between formula-based plasma volume (PV) estimates and outcomes in heart failure (HF). We assessed the association between estimated PV status by the Duarte-ePV and Kaplan Hakim (KH-ePVS) formulas, and in-hospital and postdischarge clinical outcomes, in the ASCEND-HF trial.Methods and ResultsThe KH-ePVS and Duarte-ePV were calculated on admission. We assessed associations with in-hospital worsening HF, 30-day composite cardiovascular mortality or HF rehospitalization and 180-day all-cause mortality. There were 6373 (89.2%), and 6354 (89.0%) patients who had necessary characteristics to calculate KH-ePVS and Duarte-ePV, respectively. There was no association between PV by either formula with in-hospital worsening HF. KH-ePVS showed a weak correlation with N-terminal prohormone BNP, and with measures of decongestion such as body weight change and urine output (r < 0.3 for all). Duarte-ePV was trending toward an association with worse 30-day (adjusted odds ratio 1.07, 95% confidence interval [CI] 1.00–1.15, P = .058), but not 180-day outcomes (adjusted hazard ratio 1.03, 95% CI 0.97–1.09, P = .289). A continuous KH-ePVS of >0 (per 10-unit increase) was associated with improved 30-day outcomes (adjusted odds ratio 0.75, 95% CI 0.62–0.91, P = .004). The continuous KH-ePVS was not associated with 180-day outcomes (adjusted hazard ratio 1.05, 95% CI 0.98–1.12, P = .139).ConclusionsBaseline PV estimates had a weak association with in-hospital measures of decongestion. The Duarte-ePV trended toward an association with early clinical outcomes in decompensated HF, and may improve risk stratification in HF.     

Continuous Ambulatory Peritoneal Dialysis and Clinical Outcomes in Patients With Refractory Congestive Heart Failure

Introduction and objectives

Peritoneal dialysis has been proposed as a therapeutic alternative for patients with refractory congestive heart failure. The objective of this study was to assess its effect on long-term clinical outcomes in patients with advanced heart failure and renal dysfunction.

Methods

A total of 62 patients with advanced heart failure (class III/IV), renal dysfunction (glomerular filtration<60 mL/min/1.73 m²), persistent fluid congestion despite loop diuretic treatment and at least 2 previous hospitalizations for heart failure were invited to participate in a continuous ambulatory peritoneal dialysis program. Of these, 34 patients were excluded and adjudicated as controls. The most important reasons for exclusion were refusal to participate, inability to perform the technique and abdominal wall defects. The primary endpoint was all-cause mortality and the composite of death/readmission for heart failure. To account for baseline imbalance, a propensity score was estimated and used as a weight in all analyses.

Results

The peritoneal dialysis (n=28) and control groups (n=34) were alike in all baseline covariates. During a median follow-up of 16 months, 39 (62.9%) died, 21 (33.9%) patients were rehospitalization for heart failure, and 42 (67.8%) experienced the composite endpoint. In the propensity score-adjusted models, peritoneal dialysis (vs control group) was associated with a substantial reduction in the risk of mortality using complete follow-up (hazard ratio=0.40; 95% confidence interval, 0.21-0.75; P=.005), mortality using days alive and out of hospital (hazard ratio=0.39; 95% confidence interval, 0.21-0.74; P=.004) and the composite endpoint (hazard ratio=0.32; 95% confidence interval, 0.17-0.61; P=.001).

Conclusions

In refractory congestive heart failure with concomitant renal dysfunction, peritoneal dialysis was associated with long-term improvement in clinical outcomes.     

Activities of Daily Living and Outcomes in Patients with Advanced Heart Failure

BackgroundFunctional debility is associated with worse outcomes in the general heart failure population, but the prevalence of difficulty with activities of daily living and clinical significance once patients develop advanced heart failure requires further examination.MethodsThis was a population-based, retrospective cohort study of Olmsted County, Minnesota adults with advanced heart failure from 2007-2018. Difficulty with 9 activities of daily living was assessed by questionnaire. Predictors of difficulty were assessed by a proportional odds model. Associations of difficulty with activities of daily living with mortality and hospitalization were examined using Cox and Andersen-Gill models.ResultsAmong 765 patients with advanced heart failure, 565 (73.9%) reported difficulty with activities of daily living at diagnosis. Of those, 257 (45%) had moderate and 148 (26%) had severe difficulty. Independent predictors of difficulty included female sex (odds ratio [OR] 1.73; 95% confidence interval [CI], 1.26-2.36; P = .001), older age (OR per 10-year increase 1.17; 95% CI, 1.05-1.31; P = .005), dementia (OR 1.85; 95% CI, 1.06-3.24; P = .031), depression (OR 1.75; 95% CI, 1.28-2.40; P = .001), and morbid obesity (OR 1.49; 95% CI, 1.04-2.13; P = .031). Estimated 2-year mortality was 61.5%, 64.2%, and 67.6% in patients with no/minimal, moderate, and severe difficulty, respectively. The adjusted hazard ratios (95% CI) for death were 1.08 (0.90-1.28) and 1.17 (0.95-1.43) for moderate and severe difficulty, respectively, vs no/minimal difficulty (P = .33). There were no statistically significant associations of difficulty with activities of daily living and hospitalization risks.ConclusionsMost patients with advanced heart failure have difficulty completing activities of daily living and are at high risk of mortality regardless of impairment in activities of daily living.     

Right Ventricular Free Wall Strain and Effect of Defibrillator Implantation in Patients With Nonischemic Systolic Heart Failure

BackgroundPatients with nonischemic systolic heart failure have an increased risk of malignant ventricular arrhythmias and sudden cardiovascular death. Because the risk is less pronounced than for patients with ischemic cause of heart failure more discriminating tools are needed to identify patients most likely to benefit from implantable cardioverter-defibrillator (ICD) implantation. Right ventricular (RV) dysfunction is associated with a worse prognosis, but whether RV free wall strain (RV-FWS) measured with echocardiography can identify the patients most likely to benefit from ICD implantation is not known.Methods and ResultsIn this extended follow-up analysis of the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) trial, RV-FWS was measured with echocardiography in 445 patients before randomization. RV dysfunction was defined as an RV-FWS of greater than –20%. The primary end point was all-cause mortality. The median RV-FWS was –18% (quartiles –23% to –14%), and RV dysfunction was measured in 255 patients (57%). During a median follow-up of 5.7 years, 170 patients (38%) died. There was a statistically significant interaction between RV dysfunction and the effect of ICD implantation (P = .003), also after adjusting for known cardiovascular risk factors (P = .01). ICD implantation significantly decreased all-cause mortality in patients with RV dysfunction (hazard ratio 0.54, 95% confidence interval 0.36-0.80, P = .002), but not in patients with normal RV function (hazard ratio 1.34, 95% confidence interval 0.84-2.12, P = .22).ConclusionsIn patients with nonischemic systolic heart failure, RV dysfunction on echocardiography was associated with a greater effect of ICD implantation and could be used to select patients with benefit from ICD treatment.     

Validation of peak exercise oxygen consumption and the Heart Failure Survival Score for serial risk stratification in advanced heart failure

The Heart Failure Survival Score (HFSS) and peak exercise oxygen consumption (VO2) accurately assess mortality in ambulatory patients who have advanced heart failure and are referred for initial cardiac transplant evaluation. We investigated the prognostic value of the HFSS and peak VO2 when applied serially to these patients. This study included 227 adults (mean age +/- SD 52 +/- 10 years old) who presented for reevaluation >60 days after initial evaluation (352 +/- 238 days). The HFSS was determined from mean arterial blood pressure, heart rate, left ventricular ejection fraction, serum sodium, peak VO2, heart failure etiology, and width of QRS complex. Survival without reevaluation, United Network of Organ Sharing 1 transplant, or left ventricular assist device was determined by the Kaplan-Meier method with censoring at United Network of Organ Sharing 2 transplant. Survival differed by HFSS stratum (p <0.001) and by peak VO2 stratum (p <0.001). Patients whose HFSS or peak VO2 deteriorated from low risk to medium or high risk had lower survival rates than did patients whose values remained at low risk (p <0.01 and p <0.001, respectively). Patients who started at medium or high risk and improved to low risk tended to have higher survival rates than those who remained medium or high risk (p = 0.06 and p <0.16, respectively). Patients who improved to low risk had a 1-year survival rate of 72% for HFSS and peak VO2. However, patients who improved to low risk and were treated with beta blockers had a 1-year survival rate (89% for HFSS and 83% for peak VO2) comparable to that after transplant (84%). Peak VO2 and the HFSS can be successfully used for serial evaluation of mortality risk in ambulatory patients who have advanced heart failure.     

The Israel Nationwide Heart Failure Survey: Sex Differences in Early and Late Mortality for Hospitalized Heart Failure Patients

BackgroundCurrent data on the influence of sex on the prognosis of heart failure (HF) are conflicting, possibly owing to the use of different end points and a heterogeneous heart failure population in earlier studies. We sought to evaluate the effect of sex on the risk of early and late mortality outcomes after hospitalization for acute heart failure.Methods and ResultsThe prospective cohort study population comprised 2,212 hospitalized patients with acute HF enrolled in a multicenter national survey in Israel. Cox proportional-hazards regression modeling was used to evaluate the effect of sex on the risk of early (≤6 months) and late (>6 months to 4 years) mortality after the index hospitalization. Among the study patients, 998 (45%) were women. Women with HF displayed significantly different clinical characteristics compared with men, including older age, higher frequency of HF with preserved ejection fraction and hypertensive heart disease, and lower percentage of coronary artery disease (all P < .001). The fully adjusted multivariable analyses for mortality outcomes showed that women tended toward an increased risk for early (≤6 months) mortality (hazard ratio [HR] 1.16, 95% confidence interval [CI] 0.96–1.41; P = .13), whereas men had significantly increased risk for late (>6 months) mortality (HR 1.25, 95% CI 1.09–1.43; P = .001).ConclusionsThere are important differences in the clinical characteristics and the short- and long-term outcomes between men and women hospitalized with acute HF after adjusting for multiple confounding variables.     

Right Ventricular Ejection Fraction and Beta-Blocker Effect in Heart Failure With Reduced Ejection Fraction

BackgroundA low right ventricular ejection fraction (RVEF) is a marker of poor outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Beta-blockers improve outcomes in HFrEF, but whether this effect is modified by RVEF is unknown.Methods and ResultsOf the 2798 patients in Beta-Blocker Evaluation of Survival Trial (BEST), 2008 had data on baseline RVEF (mean 35%, median 34%). Patients were categorized into an RVEF of less than 35% (n = 1012) and an RVEF of 35% or greater (n = 996). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) within each RVEF subgroup and formally tested for interactions between bucindolol and RVEF. The effect of bucindolol on all-cause mortality in 2008 patients with baseline RVEF (HR 0.88, 95% CI 0.75–1.02) is consistent with that in 2798 patients in the main trial (HR 0.90, 95% CI 0.78–1.02). Bucindolol use was associated with a lower risk of all-cause mortality in patients with an RVEF of 35% or greater (HR 0.70, 95% CI 0.55–0.89), but not in those with an RVEF of less than 35% (HR 1.02, 95% CI 0.83–1.24, P for interaction = .022). Similar variations were observed for cardiovascular mortality (P for interaction = .009) and sudden cardiac death (P for interaction = .018), but not for pump failure death (P for interaction = .371) or HF hospitalization (P for interaction = .251).ConclusionsThe effect of bucindolol on mortality in patients with HFrEF was modified by the baseline RVEF. If these hypothesis-generating findings can be replicated using approved beta-blockers in contemporary patients with HFrEF, then RVEF may help to risk stratify patients with HFrEF for optimization of beta-blocker therapy.     

The Relationship Between Valproate and Lamotrigine/Levetiracetam Use and Prognosis in Patients With Epilepsy and Heart Failure: A Danish Register-Based Study

ObjectiveTo compare the hazard for all-cause mortality and mortality due to heart failure (HF) between valproate (VPA) and levetiracetam (LEV)/lamotrigine (LTG) users in patients aged ≥ 65 with comorbidities of epilepsy and HF.MethodsThis was a cohort study using Danish registers during the period from January 1996 to July 2018. The study population included new users of LTG, LEV or VPA. A Cox regression model was used to compute crude and adjusted hazard ratios for the outcome, using an intention-to-treat approach. Average treatment effects (eg, 1-year absolute risks), risk differences and the ratio of risks were computed using the G-formula based on a Cox regression model for the outcomes at the end of the follow-up period.ResultsWe included 1345 subjects in the study population. VPA users (n = 696), when compared to LTG/LEV users (n = 649), had an increased hazard of mortality due to HF (hazard ratio [HR] 2.39; 95% CI 1.02–5.60) and to all-cause mortality (HR 1.37; 95% CI 1.01–1.85) in both crude and adjusted analyses. The 1-year absolute risks for all-cause mortality were 29% (95% CI 25%–33%) and 22% (95% CI 18%–26%) for VPA and LTG/LEV users. For mortality due to HF, 1-year absolute risks were 5% (95% CI 3%–7%) and 2% (95% CI 1%–4%) for VPA and LTG/LEV users. The average risk ratio, with LTG/LEV as the reference group, was 1.31 (95% CI 1.02–1.71) for all-cause mortality and 2.35 (95% CI 1.11–5.76) for HF mortality.ConclusionIn older people with HF and epilepsy, treatment with VPA was associated with a higher risk of all-cause and HF mortality compared to treatment with LTG and LEV.     

Association of diastolic dysfunction and outcomes in ambulatory older adults with chronic heart failure

BACKGROUND: Studies of patients with heart failure and preserved systolic function report variable outcomes compared with those of patients with impaired systolic function. OBJECTIVE: To study outcomes of diastolic (vs systolic) heart failure in older adults with chronic heart failure. METHODS: Patients were ambulatory chronic heart failure patients 65 years and older (N = 3984) who participated in the Digitalis Investigation Group trial. Of these, 3405 had systolic heart failure (ejection fraction < or =45%) and 579 had diastolic heart failure (ejection fraction >45%). By using a 1:1 match by age, sex, and race, 571 diastolic heart failure patients were matched with 571 systolic heart failure patients. Kaplan-Meier survival analyses and multivariable Cox proportional hazard analyses were used to estimate the risk of various outcomes between the groups. RESULTS: During the 1044 mean days of follow up, compared with 41% of systolic heart failure patients, 27% of diastolic heart failure patients died (p <.001). Presence of diastolic heart failure was independently associated with a 27% decreased risk of all-cause death (adjusted hazard ratio [HR] = 0.73; 95% confidence interval [CI], 0.58-0.91) and a 32% reduction in risk of hospitalization due to heart failure (adjusted HR = 0.68; 95% CI, 0.52-0.88). There was no difference in overall hospitalization between the groups. However, compared with systolic heart failure patients, diastolic heart failure patients were more likely to be hospitalized due to noncardiovascular causes (adjusted HR = 1.38; 95% CI, 1.02-1.88). CONCLUSIONS: Older adults with diastolic heart failure had lower risk of all-cause mortality and heart failure-related hospitalizations, but higher risk of noncardiovascular hospitalization.     

Quadriceps Strength and Mortality in Older Patients With Heart Failure

BackgroundThis study was performed to test the hypothesis that low quadriceps isometric strength (QIS) is associated with greater risk of mortality and has the additive prognostic significance to the severity of heart failure (HF) and gait speed in older patients with HF.MethodsA retrospective cohort study was performed in 1273 patients ≥ 60 years of age with HF (mean age 75 ± 8 years, 59.1% men); all of whom were evaluated during hospitalization for usual gait speed and maximal QIS. The QIS was expressed relative to body mass (% BM). The endpoint was all-cause mortality.ResultsOver a median follow-up period of 1.59 years (interquartile range, 0.58 to 3.42 years), 224 patients died. The cutoff value based on the Youden index for the QIS discriminating those at high risk of mortality was 36.2% BM for overall, and we defined less than this cutoff point of QIS as low QIS. After adjustment for the HF risk score, the hazard ratio in low QIS was 1.55 for overall (95% confidence interval [CI], 1.17-2.06). The addition of low QIS to the HF risk score and gait speed was associated with significant increases in both net reclassification improvement (NRI, 0.239 for overall; 95% CI, 0.096-0.381) and integrated discrimination improvement (IDI, 0.004 for overall; 95% CI, 0.001-0.009) for all-cause mortality.ConclusionLow QIS was strongly associated with poor prognosis and showed complementary prognostic predictive capability to the HF risk score and gait speed in older patients with HF.     

Association between Respiratory Failure and Clinical Outcomes in Patients with Acute Heart Failure: Analysis of 5 Pooled Clinical Trials

BackgroundDespite a temporal increase in respiratory failure in patients hospitalized with acute heart failure (HF), clinical trials have largely not reported the incidence or associated clinical outcomes for patients requiring mechanical ventilation.Methods and ResultsAfter pooling 5 acute HF clinical trials, we used multivariable logistic regression adjusted for demographics, comorbidities, examinations, and laboratory findings to assess associations between mechanical ventilation and clinical outcomes. Among the 8296 patients, 210 (2.5%) required mechanical ventilation. Age, sex, smoking history, baseline ejection fraction, HF etiology, and the proportion of patients randomized to treatment or placebo in the original clinical trial were similar between groups (all, P > 0.05). Baseline diabetes mellitus was more common in the mechanical ventilation group (P = 0.02), but other comorbidities, including chronic lung disease, were otherwise similar (all P > 0.05). HF rehospitalization at 30 days (12.7% vs 6.6%, P < 0.001) and all-cause 60-day mortality (33.3% vs 6.1%, P < 0.001) was higher among patients requiring mechanical ventilation. After multivariable adjustment, mechanical ventilation use was associated with an increased 30-day HF rehospitalization (odds ratio 2.03; 95% confidence interval, 1.29-3.21, P = 0.002), 30-day mortality (odds ratio 10.40; 95% confidence interval, 7.22-14.98, P < 0.001), and 60-day mortality (odds ratio 7.68; 95% confidence interval, 5.50-10.74, P < 0.001). The influence of mechanical ventilation did not differ by HF etiology or baseline ejection fraction (both, interaction P > 0.20).ConclusionsRespiratory failure during an index hospitalization for acute HF was associated with increased rehospitalization and all-cause mortality. The development of respiratory failure during an acute HF admission identifies a particularly vulnerable population, which should be identified for closer monitoring.