Right Ventricular Dysfunction During Endurance Exercise as Determined by Pressure-Volume Analysis.

A 37-year-old athlete completed invasive endurance (90 km) bicycle exercise testing for right ventricular pressure-volume analysis. Increased right ventricular afterload caused declines in ventricular-arterial coupling and cardiac output, causing increased arteriovenous oxygen difference to maintain oxygen uptake. These findings demonstrate effects of changes in right ventricular performance on exercise capacity. (Level of Difficulty: Intermediate.).

Natural History of Patients Postacute Coronary Syndrome Based on Heart Failure Status.

The natural history of patients hospitalized for acute coronary syndrome (ACS) with pre-existing versus (vs) de novo heart failure (HF) has not been previously reported over an extended duration of follow-up. The IMPROVE-IT trial enrolled 18,144 patients hospitalized for ACS and randomized them to combination simvastatin (40 mg)/ezetimibe (10 mg) vs simvastatin (40 mg). Subjects were divided into 3 groups: pre-existing HF (i.e., defined by past medical history), de novo HF (i.e., defined by Killip class II or greater during index admission), and no HF. The final analytical cohort included 14,792 patients (82%) with HF status recorded at baseline. In total, 790 patients (5.3%) reported a pre-existing diagnosis of HF and 1374 patients (9.3%) experienced de novo HF. Patients with pre-existing or de novo HF were older, more likely to be woman, and had a greater prevalence of atrial fibrillation and diabetes mellitus. The incidences of death/HF-hospitalizations at 5 years were 32%/20% for pre-existing HF, 18%/7% for de novo HF, and 8%/3% for no HF. After adjusting for potential confounders, a history of pre-existing or de novo HF was independently associated with increased risk of death (pre-existing HF: hazard ratio [HR] 1.93, 95% confidence interval [CI] 1.68 to 2.22, p < 0.001; de novo HF: HR 1.51, 95% CI 1.33 to 1.72, p < 0.001) and hospitalizations for HF (pre-existing HF: HR 2.96, 95% CI 2.36 to 3.71, p < 0.001; de novo HF: HR 1.88, 95% CI 1.49 to 2.38, p < 0.001). There was no interaction among baseline HF status (i.e., pre-existing or de novo), lipid lowering therapy (i.e., simvastatin/ezetimibe vs simvastatin alone), and clinical outcomes. In conclusion, patients hospitalized for ACS with pre-existing or de novo HF were older and had a greater burden of medical co-morbidities. In conclusion, HF was independently associated with increased risk of long-term morbidity and mortality with the pre-existing HF cohort demonstrating the highest overall risk.

Post-Traumatic Stress Disorder and Heart Failure in Men Within the Veteran Affairs Health System.

Patients with post-traumatic stress disorder (PTSD) are at risk of multiple co-morbidities and are more likely to develop incident heart failure with reduced ejection fraction (HFrEF). The relation of PTSD with clinical outcomes in HFrEF is not established. US veterans diagnosed with HFrEF from January 2007 to January 2015 and treated nationwide in the Veterans Affairs (VA) Health System were included in the study. Patients with HFrEF were identified through International Classification of Diseases, Ninth Revision (ICD-9) codes. Mortality data were obtained from the VA's death registry. We compared characteristics of patients with HFrEF with and without PTSD. We identified 111,970 VA patients with HFrEF and 11,039 patients with concomitant PTSD (9.9%). Patients with PTSD and HFrEF tended to be younger (64 vs 69 years) and have a higher rate of coronary artery disease (73% vs 64%), chronic obstructive pulmonary disease (42% vs 31%), and hypertension (80% vs 64%, p <0.01 for all variables). Patients with PTSD and HFrEF were more commonly on a high-dose ß blocker (70% vs 68%, p <0.01) and angiotensin-converting enzyme inhibitors (96% vs 93%, p <0.01). PTSD was associated with significantly increased mortality at 7 years compared with patients with heart failure without PTSD (adjusted 1.54, 95% confidence interval 1.30 to 1.82, p <0.01). In conclusion, nearly 10% of veterans with HFrEF have PTSD. Patients with HFrEF with PTSD have a higher burden of co-morbidities, and PTSD is associated with a higher rate of all-cause death. Our findings support greater attention to the treatment of patients with PTSD and the causes associated with the poor outcomes.

Is Time of the Essence? The Impact of Time of Hospital Presentation in Acute Heart Failure: Insights From ASCEND-HF Trial.

OBJECTIVES: As the largest acute heart failure (AHF) trial conducted to date, the global ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial database presented an opportunity to systematically describe the relationship among time of hospital presentation, clinical profile, inpatient management, and outcomes among patients admitted with AHF. BACKGROUND: Time of hospital presentation has been shown to impact outcomes among patients hospitalized with many conditions. However, the association among time of presentation and patient characteristics, management, and clinical outcomes among patients hospitalized with AHF has not been well characterized. METHODS: A post hoc analysis of the ASCEND-HF trial was performed, which enrolled 7,141 patients hospitalized for AHF. Patients were divided based on when they presented to the hospital; regular hours were defined as 9 am to 5 pm, Monday through Friday, and off hours were defined as 5 pm to 9 am, Monday through Friday and weekends. Clinical characteristics and outcomes were compared by time of presentation. RESULTS: Overall, 3,298 patients (46%) presented during off hours. Off-hour patients were more likely to have orthopnea (80% vs. 74%, respectively) and rales (56% vs. 49%, respectively) than regular-hour patients. Off-hour patients were more likely to receive intravenous (IV) nitroglycerin (18% vs. 11%, respectively) and IV loop diuretics (92% vs. 86%, respectively) as initial therapy and reported greater relief from dyspnea at 24 h (odds ratio [OR]: 1.14; 95% confidence interval [CI]: 1.04 to 1.24; p = 0.01) than regular-hour patients. After adjustment, off-hour presentation was associated with significantly lower 30-day mortality (OR: 0.74; 95% CI: 0.57 to 0.96; p = 0.03) and 180-day mortality (hazard ratio [HR]: 0.82; 95% CI: 0.72 to 0.94; p = 0.01) but similar 30-day rehospitalization rates (p = 0.40). CONCLUSIONS: In this AHF trial, patients admitted during off hours exhibited a distinct clinical profile, experienced greater dyspnea relief, and had lower post-discharge mortality than regular-hour patients. These findings have implications for future AHF trials.

Hospitalization for Recently Diagnosed Versus Worsening Chronic Heart Failure: From the ASCEND-HF Trial.

BACKGROUND: It is unclear how patients hospitalized for acute heart failure (HF) who are long-term chronic HF survivors differ from those with more recent HF diagnoses. OBJECTIVES: The goal of this study was to evaluate the influence of HF chronicity on acute HF patient profiles and outcomes. METHODS: The ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial randomized 7,141 hospitalized patients with acute HF with reduced or preserved ejection fraction (EF) to receive nesiritide or placebo in addition to standard care. The present analysis compared patients according to duration of HF diagnosis before index hospitalization by using pre-specified cutoffs (0 to 1 month [i.e., "recently diagnosed"], >1 to 12 months, >12 to 60 months, and >60 months). RESULTS: Overall, 5,741 (80.4%) patients had documentation of duration of HF diagnosis (recently diagnosed, n = 1,536; >1 to 12 months, n = 1,020; >12 to 60 months, n = 1,653; and >60 months, n = 1,532). Across HF duration groups, mean age ranged from 64 to 66 years, and mean ejection fraction ranged from 29% to 32%. Compared with patients with longer HF duration, recently diagnosed patients were more likely to be women with nonischemic HF etiology, higher baseline blood pressure, better baseline renal function, and fewer comorbidities. After adjustment, compared with recently diagnosed patients, patients with longer HF duration were associated with more persistent dyspnea at 24 h (>1 to 12 months, odds ratio [OR]: 1.20; 95% confidence interval [CI]: 0.97 to 1.48; >12 to 60 months, OR: 1.34; 95% CI: 1.11 to 1.62; and >60 months, OR: 1.31; 95% CI: 1.08 to 1.60) and increased 180-day mortality (>1 to 12 months, hazard ratio [HR]: 1.89; 95% CI: 1.35 to 2.65; >12 to 60 months, HR: 1.82; 95% CI: 1.33 to 2.48; and >60 months, HR: 2.02; 95% CI: 1.47 to 2.77). The influence of HF duration on mortality was potentially more pronounced among female patients (interaction p = 0.05), but did not differ according to age, race, prior ischemic heart disease, or ejection fraction (all interactions, p ≥ 0.23). CONCLUSIONS: In this acute HF trial, patient profile differed according to duration of the HF diagnosis. A diagnosis of HF for ≤1 month before hospitalization was independently associated with greater early dyspnea relief and improved post-discharge survival compared to patients with chronic HF diagnoses. The distinction between de novo or recently diagnosed HF and worsening chronic HF should be considered in the design of future acute HF trials. (A Study Testing the Effectiveness of Nesiritide in Patients With Acute Decompensated Heart Failure; NCT00475852).

Aerobic exercise training and general health status in ambulatory heart failure patients with a reduced ejection fraction-Findings from the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION)trial.

BACKGROUND: Although aerobic exercise improves quality of life as assessed by a disease-specific instrument in ambulatory HF patients with a reduced ejection fraction (EF), the impact of an exercise intervention on general health status has not been previously reported. METHODS: A secondary analysis was performed of the HF-ACTION trial (ClinicalTrials.gov Number: NCT00047437), which enrolled 2331 medically stable outpatients with HF and an EF ≤35% and randomized them to aerobic exercise training, consisting of 36 supervised sessions followed by home-based training versus usual care for a median follow-up of 30 months. The EuroQOL 5-dimension questionnaire (EQ-5D) was administered to study participants at baseline, 3 months, and 12 months. EQ-5D includes functional dimensions (ie, mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), which were mapped to corresponding utility scores (ie, 0=death and 1=perfect health), and a visual analogue scale (VAS) ranging from 0 (ie, "worst imaginable health state") to 100 (ie, "best imaginable health state"). RESULTS: Study participants had a median (25th, 75th) age of 59 (51, 68) years and 71% were male. A history of ischemic heart disease was reported in 51% of participants and the EF was 25% (20%, 30%). Baseline VAS and mapped utility scores were 65±19 and 0.81±0.14. Exercise training led to an improvement in VAS score compared with usual care from baseline to 3 months (exercise training: 6±17 vs usual care: 3±20; P <.01) although there were no further significant changes at 12 months. Aerobic exercise training did not favorably change mapped utility scores over either timeframe. After multivariable adjustment, lower mapped utility (hazard ratio [HR] 1.19 per 0.1 decrease, 95% CI 1.09-1.29; P < .0001) and VAS scores (HR 1.05 per 10 point decrease, 95% CI 1.02-1.08; P < .01) at baseline were associated with increased risk of death or hospitalization. CONCLUSION: Ambulatory HF patients with a reduced EF had impaired health status at baseline which was associated with increased morbidity and mortality, in part mitigated by a structured aerobic exercise regimen.

Body Weight Change During and After Hospitalization for Acute Heart Failure: Patient Characteristics, Markers of Congestion, and Outcomes: Findings From the ASCEND-HF Trial.

OBJECTIVES: This study sought to examine the relationships between in-hospital and post-discharge body weight changes and outcomes among patients hospitalized for acute heart failure (AHF). BACKGROUND: Body weight changes during and after hospitalization for AHF and the relationships with outcomes have not been well characterized. METHODS: A post hoc analysis was performed of the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide and Decompensated Heart Failure) trial, which enrolled patients admitted for AHF regardless of ejection fraction. In-hospital body weight change was defined as the difference between baseline and discharge/day 10, whereas post-discharge body weight change was defined as the difference between discharge/day 10 and day 30. Spearman rank correlations of weight change, urine output (UOP), and dyspnea relief as assessed by a 7-point Likert scale are described. Logistic and Cox proportional hazards regression was used to evaluate the relationship between weight change and outcomes. RESULTS: Study participants with complete body weight data (n = 4,172) had a mean age of 65 ± 14 years, and 66% were male. Ischemic heart disease was reported in 60% of patients and the average ejection fraction was 30 ± 13%. The median change in body weight was -1.0 kg (interquartile range: -2.1 to 0.0 kg) at 24 h and -2.3 kg (interquartile range: -5.0 to -0.7 kg) by discharge/day 10. At hour 24, there was a weak correlation between change in body weight and UOP (r = -0.381), and minimal correlation between body weight change and dyspnea relief (r = -0.096). After risk adjustment, increasing body weight during hospitalization was associated with a 16% increase per kg in the likelihood of 30-day mortality or HF readmission for patients showing weight loss ≤1 kg or weight gain during hospitalization (odds ratio per kg increase 1.16, 95% confidence interval [CI]: 1.09 to 1.27; p < 0.001). Among the subset of patients experiencing >1-kg increase in body weight post-discharge, increasing body weight was associated with higher risk of 180-day mortality (hazard ratio per kg increase 1.16; 95% CI: 1.09 to 1.23; p < 0.001). CONCLUSIONS: A substantial number of patients experienced minimal weight loss or frank weight gain in the context of an AHF trial, and increasing body weight in this subset of patients was independently associated with a worse post-discharge prognosis.