Heart failure etiologies and clinical factors precipitating for worsening heart failure: Findings from BIOSTAT-CHF

BackgroundKnowledge on the association between heart failure (HF) etiologies, precipitant causes and clinical outcomes may help in ascertaining patient's risk and in selecting tailored therapeutic strategies.MethodsThe prognostic value of both HF etiologies and precipitants for worsening HF were analyzed using the index cohort of BIOSTAT-CHF. The studied HF etiologies were: a) ischemic HF; b) dilated cardiomyopathy; c) hypertensive HF; d) valvular HF; and e) other/unknown. The precipitating factors for worsening HF were: a) atrial fibrillation; b) non-adherence; c) renal failure; d) acute coronary syndrome; e) hypertension; and f) Infection. The primary outcome was the composite of all-cause death or HF hospitalization.ResultsAmong 2465 patients included in the study, 45% (N = =1102) had ischemic HF, 23% (N = =563) dilated cardiomyopathy, 15% (N = =379) other/unknown, 10% (N = =237) hypertensive and 7% (N = =184) valvular HF. Patients with ischemic HF had the worst prognosis, whereas patients with dilated cardiomyopathy had the best prognosis. From the precipitating factors for worsening HF, renal failure was the one independently associated with worse prognosis (adjusted HR (95%CI) = =1.48 (1.04–2.09), p < 0.001). We found no interaction between HF etiologies and precipitating factors for worsening HF with regard to the study outcomes (p interaction > 0.10 for all). Treatment up-titration benefited patients regardless of their underlying etiology or precipitating cause (p interaction > 0.10 for all).ConclusionsIn BIOSTAT-CHF, patients with HF of an ischemic etiology, and those with worsening HF precipitated by renal failure (irrespective of the underlying HF etiology), had the highest rates of death and HF hospitalization, but still benefited equally from treatment up-titration.     

Safety and Efficacy of Istaroxime 1.0 and 1.5 µg/kg/min for Patients With Pre-Cardiogenic Shock

IntroductionIstaroxime was shown, in a small study, to increase systolic blood pressure (SBP) in patients with pre-cardiogenic shock (CS) due to acute heart failure (AHF).ObjectivesIn the current analysis, we describe the effects of 2 doses of istaroxime 1.0 (Ista-1) and 1.5 µg/kg/min (Ista-1.5).MethodsThe target dose of istaroxime, administered in a double-blind, placebo-controlled fashion, was 1.5 µg/kg/min in the first cohort (n = 24), and it was reduced to 1.0 µg/kg/min in subsequent patients (n = 36).ResultsIsta-1 was associated with numerically larger effects on SBP area under the curve, with a 93.6% relative increase from baseline during the first 6 hours with Ista-1 vs 39.5% for Ista-1.5, and with a 49.4% and 24.3% relative increase, respectively, at 24 hours. Compared to placebo, Ista-1.5 had more worsening HF events until day 5 and fewer days alive out of hospital (DAOH) through day 30. Ista-1 had no worsening HF events, and DAOH to day 30 were significantly increased. Effects on echocardiographic measures were similar, although decreases in left ventricular end systolic and diastolic volumes were numerically larger in the Ista-1 group. Ista-1, but not Ista-1.5, showed numerically smaller creatinine increases and larger decreases in natriuretic peptides as compared to placebo. There were 5 serious adverse events in Ista-1.5 (4 of which were cardiac) but only 1 in Ista-1.ConclusionsIn patients with pre-CS due to AHF, istaroxime 1.0 µg/kg/min induced beneficial effects on SBP and DAOH. Clinical benefits appear to be reached at dosages less than 1.5 ug/kg/min.     

Adverse Renal Response to Decongestion in the Obese Phenotype of Heart Failure With Preserved Ejection Fraction

BackgroundPatients with heart failure (HF) with preserved ejection fraction (HFpEF) and obesity display a number of pathophysiologic features that may render them more or less vulnerable to negative effects of decongestion on renal function, including greater right ventricular remodeling, plasma volume expansion and pericardial restraint. We aimed to contrast the renal response to decongestion in obese compared to nonobese patients with HFpEFMethods and ResultsNational Institutes of Health heart failure network studies that enrolled patients with acute decompensated HFpEF (EF ≥ 50%) were included (DOSE, CARRESS, ROSE, and ATHENA). Obese HFpEF was defined as a body mass index ≥ 30 kg/m². Compared to nonobese HFpEF (n = 118), patients with obese HFpEF (n = 214) were an average of 9 years younger (71 vs 80 years,< 0.001), were more likely to have diabetes (64% vs 31%, P< 0.001) but had less atrial fibrillation (56% vs 75%, P< 0.001). Renal dysfunction (glomerular filtration rate < 60 mL/min/1.73m²) was present in 82% of patients, and there was no difference at baseline between obese and nonobese patients. Despite similar weight loss through decongestive therapies, obese patients with HFpEF demonstrated greater rise in creatinine (Cr) and decline in glomerular filtration rate, with a 2-fold higher incidence of mild worsening renal function (rise in Cr ≥ 0.3 mg/dL) (28 vs 14%, P = 0.008) and a substantially greater increase in severe worsening of renal function (rise in Cr > 0.5 mg/dL) (9 vs 0%, P = 0.002).ConclusionsDespite being nearly a decade younger, obese patients with HFpEF experience greater deterioration in renal function during decongestion than do nonobese patients with HFpEF. Further study to elucidate the complex relationships between volume distribution, cardiorenal hemodynamics and adiposity in HFpEF is needed.     

Worsening renal function and prognosis in heart failure: systematic review and meta-analysis

BackgroundRenal impairment is associated with increased mortality in heart failure (HF). Recently, reports suggest that worsening renal function (WRF) is another predictor of clinical outcome in HF. The present study was designed to establish the proportion of patients with HF that exhibits (WRF) and the associated risk for mortality and hospitalization by conducting a systematic review and meta-analysis.Methods and ResultsA systematic search of MEDLINE revealed 8 studies on the relationship between WRF and mortality in 18,634 patients with HF. The mortality risk associated with WRF was estimated using random-effects meta-analysis. WRF was defined as an increase in serum creatinine ≥0.2 mg/dL or a corresponding decrease in estimated glomerular filtration rate ≥5 mL·min·1.73 m². Subgroup analysis included differentiation between in- and out-hospital patients, degree of WRF and time until end point occurrence. WRF developed in 4,734 (25%) patients and was associated with a higher risk for mortality (odds ratio [OR] = 1.62; 95% confidence interval [CI] 1.45–1.82, P < .001) and hospitalization (OR = 1.30, 95% CI 1.04–1.62, P = .022). The severity of WRF was also associated with greater mortality. Patients with impaired renal function at baseline were more prone to progressive renal function loss.ConclusionsWRF predicts substantially higher rates of mortality and hospitalization in patients with HF.     

Liver Function,In-Hospital,and Post-Discharge Clinical Outcome in Patients With Acute Heart Failure—Results From the Relaxin for the Treatment of Patients With Acute Heart Failure Study

BackgroundElevated plasma concentrations of liver function tests are prevalent in patients with chronic heart failure (HF). Little is known about liver function in patients with acute HF. We aimed to assess the prevalence and prognostic value of serial measurements of liver function tests in patients admitted with acute decompensated HF.MethodsWe investigated liver function tests from all 234 patients from the Relaxin for the Treatment of Patients With Acute Heart Failure study at baseline and during hospitalization. The end points were worsening HF through day 5, 60-day mortality or rehospitalization, and 180-day mortality.ResultsMean age was 70 ± 10 years, 56% were male, and most patients were in New York Heart Association functional class III/IV (73%). Abnormal liver function tests were frequently found for alanine transaminase (ALT; 12%), aspartate transaminase (AST; 21%), alkaline phosphatase (12%), and total bilirubin (19%), and serum albumin (25%) and total protein (9%) were decreased. In-hospital changes were very small. On a continuous scale, baseline ALT and AST were associated with 180-day mortality (hazard ratios [HRs; per doubling] 1.52 [P = .030] and 1.97 [P = .013], respectively) and worsening HF through day 5 (HRs [per doubling] 1.72 [P = .005] and 1.95 [P = .008], respectively). Albumin was associated with 180-day mortality (HR 0.86; P = .001) but not with worsening HF (HR 0.95; P = .248). Total protein was associated with only worsening HF (HR 0.91; P = .004).ConclusionsAbnormal liver function tests are often present in patients with acute HF and are associated with an increased risk for mortality, rehospitalization, and in-hospital worsening HF.     

Impact of Mental Stress and Anger on Indices of Diastolic Function in Patients With Heart Failure

BackgroundUnder controlled conditions, mental stress can provoke decrements in ventricular function, yet little is known about the effect of mental stress on diastolic function in patients with heart failure (HF).Methods and ResultsTwenty-four patients with HF with ischemic cardiomyopathy and reduced ejection fraction (n = 23 men; mean left ventricular [LV] ejection fraction 27 ± 9%; n = 13 with baseline elevated E/e’) completed daily assessment of perceived stress, anger, and negative emotion for 7 days, followed by a laboratory mental stress protocol. Two-dimensional Doppler echocardiography was performed at rest and during sequential anger recall and mental arithmetic tasks to assess indices of diastolic function (E, e’, and E/e’). Fourteen patients (63.6%) experienced stress-induced increases in E/e', with an average baseline to stress change of 6.5 ± 9.3, driven primarily by decreases in early LV relaxation (e’). Age-adjusted linear regression revealed an association between 7-day anger and baseline E/e’; patients reporting greater anger in the week before mental stress exhibited higher resting LV diastolic pressure.ConclusionsIn patients with HF with reduced ejection fraction, mental stress can provoke acute worsening of LV diastolic pressure, and recent anger is associated with worse resting LV diastolic pressure. In patients vulnerable to these effects, repeated stress exposures or experiences of anger may have implications for long-term outcomes.     

Prognostic value of hemodynamics and comorbidities in pulmonary hypertension due to advanced heart failure

BackgroundThe prognostic predictors of pulmonary hypertension (PH) due to advanced heart failure (HF) have yet to be explored.ObjectivesTo examine the prognostic value of hemodynamics and comorbidities in this patient group.MethodsWe retrospectively enrolled consecutive patients with PH due to advanced HF diagnosed by echocardiography and right heart catheterization. Follow-up was performed every 6 months ± 2 weeks. Primary endpoints were all-cause mortality and heart or lung transplantation.ResultsIn total, 92 patients were included. The mean age was 46.82 years and mean left ventricular ejection fraction (LVEF) was 26.63%. During a median follow-up time of 9.72 months, 66 patients (71.7%) met primary endpoints. Pulmonary arterial compliance (PAC) was a significant predictor for primary endpoints and patients burdened with more than 3 comorbidities had worse prognoses (P = 0.0114).ConclusionsIn these patients, PAC can be a potential prognostic predictor and patients with a higher comorbidity burden have worse outcomes.     

Prognostic Interplay Between COVID-19 and Heart Failure With Reduced Ejection Fraction

BackgroundCOVID-19 may negatively impact the prognosis of patients with chronic HFrEF and vice versa.MethodsThis study included 2 parallel analyses of patients in the United States who were in the TriNetX health database and who underwent polymerase chain reaction testing for SARS-CoV-2 as an inpatient or outpatient between January and September of 2020. Analysis A included patients with positive tests for COVID-19 and compared patients with histories of worsening heart failure with reduced ejection fraction (HFrEF) (hospitalization due to heart failure (HF) or IV diuretic use during the prior 12 months), HFrEF without worsening, and no prior HF. Analysis B included patients with histories of HFrEF and compared patients with positive vs negative COVID-19 tests. Outcomes included mortality and worsening HF. In both analyses, prespecified subgroup analyses were stratified by inpatient vs outpatient settings of the COVID-19 tests.ResultsIn Analysis A, of 99,052 patients with positive COVID-19 tests, 514 (0.5%) and 524 (0.5%) patients had histories of worsening HFrEF and HFrEF without worsening, respectively. After adjustment, compared to patients without HF, worsening HFrEF (risk ratio [RR] 1.42, 95% CI 1.10–1.83; P< 0.001) and HFrEF without worsening (RR 1.33, 95% CI 0.96–1.84; P= 0.06) were associated with higher 30-day mortality rates. Excess risk of mortality tended to be pronounced in patients initially diagnosed with COVID-19 as outpatients (P for interaction, 0.12 and 0.006, respectively). In Analysis B, of 14,838 patients with HFrEF tested for COVID-19, 1038 (7.0%) had positive tests. After adjustment, testing positive was associated with excess 30-day mortality risk (RR 1.67, 95% CI 1.38–2.02; P< 0.001) and worsening HF (RR 1.33, 95% CI 1.17–1.51; P< 0.001). Mortality risk was nominally more pronounced among patients presenting as outpatients (P for interaction 0.07).ConclusionIn this large cohort of patients tested for COVID-19, among patients testing positive, a history of HFrEF with or without worsening was associated with excess mortality rates, particularly among patients diagnosed with COVID-19 as outpatients. Among patients with established HFrEF, compared with testing negative, testing positive for COVID-19 was independently associated with higher risk of death and worsening HF.     

Hemodynamic Effects of Late Sodium Current Inhibitors in a Swine Model of Heart Failure

ObjectivesTo evaluate possible treatment-related hemodynamic changes, we administered ranolazine or mexiletine to swine with heart failure (HF) and to controls.BackgroundRanolazine and mexiletine potently inhibit depolarizing late Na⁺ current (I_Na,late) and Na⁺ entry into cardiomyocytes_. Blocking Na⁺ entry may increase forward-mode Na/Ca exchange and reduce cellular Ca⁺² load, further compromising systolic contraction during HF.Methods and ResultsAnesthetized tachypaced HF swine received ranolazine (n = 9) or mexiletine (n = 7) as boluses, then as infusions; the same experiments were performed in 10 nonpaced controls. The swine with HF had characteristic elevated left ventricular end-diastolic pressure (LVEDP) and reduced maximal left ventricular pressure rise (+dP/dt_max) and left ventricular peak systolic pressure (LVSP). No significant change occurred after ranolazine dosing for any parameter: LVEDP, +dP/dt_max, LVSP, heart rate, maximal LV pressure fall rate (–dP/dt_max), or time constant for isovolumic relaxation. Similar results seen in additional swine with HF: 7 were given mexiletine, and 7 others were given ranolazine after a 27% rate decrement to maximize I_Na,late. Patch-clamped HF cardiomyocytes confirmed drug-induced I_Na,late blockade.ConclusionsRanolazine or mexiletine blocking I_Na,late neither worsened nor improved hemodynamics during advanced HF. Although results must be clinically confirmed, they suggest inhibition of I_Na,late by ranolazine or mexiletine may not exacerbate HF in patients.     

A New Monitoring Method for the Estimation of Body Fluid Status by Digital Weight Scale Incorporating Bioelectrical Impedance Analyzer in Definite Heart Failure Patients

BackgroundThis pilot study examined the feasibility of monitoring changes in body weight and body-fat percentage (BF%) using commercially available digital weight scale incorporating bioelectrical impedance analyzer (HBF-352-W, Omron Healthcare Co, Kyoto, Japan) to estimate changes in body fluid status in definite heart failure (HF) patients during follow-up.Methods and ResultsA total of 64 patients completed a prospective study (June 2003-December 2006). During the study period, 38 patients developed worsening HF over a mean duration of 34 ± 3 days from the most recent visit with clinical stability to the time of worsening HF status. Of these, 32 patients (84%) showed an increase in body weight concurrent with a decrease in BF% during deterioration. During recovery (n = 35), all but 1 patient showed a decrease in body weight concurrent with an increase in BF%. Combined monitoring of both body weight and BF% provides quite excellent predictive accuracy (70%, 95% CI 59–81%) for identifying worsening HF status when compared with a sole body weight monitoring (56%, 95% CI 44–68%]) (cutoff point of body weight gain ≥1.5 kg).ConclusionsNew monitoring method reported here is an effective tool for specifically detecting fluid weight gain at deterioration in definite HF patients.     

The Influence of Renal Function on Clinical Outcome and Response to β-Blockade in Systolic Heart Failure: Insights From Metoprolol CR/XL Randomized Intervention Trial in Chronic HF (MERIT-HF)

BackgroundLimited information is available on the risk and impact of renal dysfunction on the response to β-blockade and mode of death in systolic heart failure (HF).Methods and ResultsRenal function was estimated with glomerular filtration rate (eGFR) using the simplified Modification of Diet in Renal Disease (MDRD) equation. Patients from the Metoprolol CR/XL Controlled Randomized Intervention Trial in Chronic HF (MERIT-HF) were divided into 3 renal function subgroups (MDRD formula): eGFR_MDRD > 60 (n = 2496), eGFR_MDRD 45 to 60 (n = 976), and eGFR_MDRD < 45 mL/min per 1.73m² body surface area (n = 493). Hazard ratio (HR) was estimated with Cox proportional hazards models adjusted for prespecified risk factors. Placebo patients with eGFR < 45 had significantly higher risk than those with eGFR > 60: HR for all-cause mortality, 1.90 (95% confidence interval [CI], 1.28 to 2.81) comparing placebo patients with eGFR < 45 and eGFR > 60, and for the combined end point of all-cause mortality/hospitalization for worsening HF (time to first event): HR, 1.91 (95% CI, 1.44 to 2.53). No significant increase in risk with deceased renal function was observed for those randomized to metoprolol controlled release (CR)/extended release (XL) due to a highly significant decrease in risk on metoprolol CR/XL in those with eGFR < 45. For total mortality, metoprolol CR/XL vs placebo: HR, 0.41 (95% CI. 0.25 to 0.68; P < .001) in those with eGFR < 45 compared with HR, 0.71 (95% CI, 0.54 to 0.95; P < .021) for those with eGFR > 60; corresponding data for the combined end point was HR, 0.44 (95% CI, 0.31 to 0.63; P < .0001) and HR, 0.75 (0.62 to 0.92; P = .005, respectively; P = .095 for interaction by treatment for total mortality; P = .011 for combined end point). Metoprolol CR/XL was well tolerated in all 3 renal function subgroups.ConclusionsRenal function as estimated by eGFR was a powerful predictor of death and hospitalizations from worsening HF. Metoprolol CR/XL was at least as effective in reducing death and hospitalizations for worsening HF in patients with eGFR < 45 as in those with eGFR > 60.     

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.     

Inotrope Use and Outcomes Among Patients Hospitalized for Heart Failure: Impact of Systolic Blood Pressure,Cardiac Index,and Etiology

BackgroundInotropes are widely used in hospitalized systolic heart failure (HF) patients, especially those with low systolic blood pressure (SBP) or cardiac index. In addition, inotropes are considered to be harmful in nonischemic HF.Methods and ResultsWe examined the association of in-hospital inotrope use with (1) major events (death, ventricular assist device, or heart transplant) and (2) study days alive and out of hospital during the first 6 months in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness, which excluded patients with immediate need for inotropic therapy. Predefined subgroups of interest were baseline SBP <100 versus ≥100 mm Hg, cardiac index <1.8 vs ≥1.8 L min⁻¹ m⁻², and ischemic versus nonischemic HF etiology. Inotropes were frequently used in both the <100 mm Hg (88/165 [53.3%]) and the ≥100 mm Hg (106/262 [40.5%]) SBP subgroups and were associated with higher risk for major events in both subgroups (adjusted hazard ratio [HR] 2.85, 95% confidence interval [CI] 1.59–5.12 [P < .001]; and HR 1.86, 95% CI 1.02–3.37 [P = .042]; respectively). Risk with inotropes was more pronounced among those with cardiac index ≥1.8 L min⁻¹ m⁻² (n = 114; HR 4.65, 95% CI 1.98–10.9; P < .001) vs <1.8 L min⁻¹ m⁻² (n = 82; HR 1.48, 95% CI 0.61–3.58; P = .39). Event rates were higher with inotropes in both ischemic (n = 215; HR 2.64, 95% CI 1.49–4.68; P = .001) and nonischemic (n = 216; HR 2.19, 95% CI 1.18–4.07; P = .012) patients. Across all subgroups, patients who received inotropes spent fewer study days alive and out of hospital.ConclusionsIn the absence of cardiogenic shock or end-organ hypoperfusion, inotrope use during hospitalization for HF was associated with unfavorable 6-month outcomes, regardless of admission SBP, cardiac index, or HF etiology.     

Cardiopulmonary and Noninvasive Hemodynamic Responses to Exercise Predict Outcomes in Heart Failure

BackgroundAn impaired cardiac output response to exercise is a hallmark of chronic heart failure (HF). We determined the extent to which noninvasive estimates of cardiac hemodynamics during exercise in combination with cardiopulmonary exercise test (CPX) responses improved the estimation of risk for adverse events in patients with HF.Methods and ResultsCPX and impedance cardiography were performed in 639 consecutive patients (mean age 48 ± 14 years), evaluated for HF. Clinical, hemodynamic, and CPX variables were acquired at baseline and subjects were followed for a mean of 460 ± 332 days. Patients were followed for the composite outcome of cardiac-related death, hospitalization for worsening HF, cardiac transplantation, and left ventricular assist device implantation. Cox proportional hazards analyses including clinical, noninvasive hemodynamic, and CPX variables were performed to determine their association with the composite endpoint. There were 113 events. Among CPX variables, peak oxygen uptake (VO₂) and the minute ventilation (VE)/carbon dioxide production (VCO₂) slope were significant predictors of risk for adverse events (age-adjusted hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.05–1.11 for both; P < .001). Among hemodynamic variables, peak cardiac index was the strongest predictor of risk (HR 1.08, 95% CI 1.0–1.16; P = .01). In a multivariate analysis including CPX and noninvasively determined hemodynamic variables, the most powerful predictive model included the combination of peak VO₂, peak cardiac index, and the VE/VCO₂ slope, with each contributing significantly and independently to predicting risk; an abnormal response for all 3 yielded an HR of 5.1 (P < .001).ConclusionsThese findings suggest that noninvasive indices of cardiac hemodynamics complement established CPX measures in quantifying risk in patients with HF.     

Intracardiac impedance monitors hemodynamic deterioration in a chronic heart failure pig model

Introduction: A large number of heart failure (HF) patients benefit from cardiac resynchronization therapy. Measurements of intrathoracic impedance (ITZ) by implantable devices correlate with intrathoracic fluid content and are used for monitoring lung edema formation in HF patients. However, intrathoracic fluid is only an indirect parameter of cardiac function. We hypothesized that changes in intracardiac impedance correlate with left ventricular (LV) volume changes. Therefore, measurements of intracardiac impedance between a right ventricular lead and a LV lead may be used to monitor long-term changes of LV function.
Methods and Results: HF was successfully induced in nine mini-pigs by continuous high-rate pacing. Hemodynamic parameters as well as intracardiac impedance and ITZ were measured before HF induction and after 20 ± 5 days of high-rate pacing. After the pacing period, we found a significant deterioration of hemodynamics, reflected by a reduction of ejection fraction from 71±11% to 48±7% and an increase of LV end diastolic pressure (EDP) from 12 ± 4 mmHg to 26 ± 8 mmHg. Worsening of cardiac function correlated with a significant >30% decrease of end diastolic intracardiac impedance, in accordance with a >20% increase of end diastolic volume (EDV). ITZ decreased by more than 8%. We observed a significant inverse correlation between end diastolic intracardiac impedance and EDP (r =−0.81, P < 0.001).
Conclusions: In this animal model, changes of intracardiac impedance revealed hemodynamic deterioration as reflected by EDV and EDP pressure. Thus, intracardiac impedance is a promising new application to monitor heart failure status within implantable devices.     

Age-Related Maximum Heart Rate Among Ischemic and Nonischemic Heart Failure Patients Receiving β-Blockade Therapy

BackgroundEquations to predict maximum heart rate (HR_max) in heart failure (HF) patients receiving β-adrenergic blocking (BB) agents do not consider the cause of HF. We determined equations to predict HR_max in patients with ischemic and nonischemic HF receiving BB therapy.Methods and ResultsUsing treadmill cardiopulmonary exercise testing, we studied HF patients receiving BB therapy being considered for transplantation from 1999 to 2010. Exclusions were pacemaker and/or implantable defibrillator, left ventricle ejection fraction (LVEF) >50%, peak respiratory exchange ratio (RER) <1.00, and Chagas disease. We used linear regression equations to predict HR_max based on age in ischemic and nonischemic patients. We analyzed 278 patients, aged 47 ± 10 years, with ischemic (n = 75) and nonischemic (n = 203) HF. LVEF was 30.8 ± 9.4% and 28.6 ± 8.2% (P = .04), peak VO₂ 16.9 ± 4.7 and 16.9 ± 5.2 mL kg^?1 min^?1 (P = NS), and the HR_max 130.8 ± 23.3 and 125.3 ± 25.3 beats/min (P = .051) in ischemic and nonischemic patients, respectively. We devised the equation HR_max = 168 ? 0.76 × age (R² = 0.095; P = .007) for ischemic HF patients, but there was no significant relationship between age and HR_max in nonischemic HF patients (R² = 0.006; P = NS).ConclusionsOur study suggests that equations to estimate HR_max should consider the cause of HF.     

Greater Body Mass Index Is Associated With Poorer Cognitive Functioning in Male Heart Failure Patients

BackgroundHeart failure (HF) and obesity are associated with cognitive impairment. However, few studies have investigated the relationship between adiposity and cognitive functioning in HF for each sex, despite observed sex differences in HF prognosis. We tested the hypothesis that greater body mass index (BMI) would be associated with poorer cognitive functioning, especially in men, in sex-stratified analyses.Methods and ResultsParticipants were 231 HF patients (34% female, 24% nonwhite, average age 68.7 ± 7.3 years). Height and weight were used to compute BMI. A neuropsychology battery tested global cognitive function, memory, attention, and executive function. Composites were created using averages of age-adjusted scaled scores. Regressions adjusting for demographic and medical factors were conducted. The sample was predominantly overweight/obese (76.2%). For men, greater BMI predicted poorer attention (ΔR² = 0.03; β = −0.18; P = .01) and executive function (ΔR² = 0.02; β = −0.13; P = .04); these effects were largely driven by men with severe obesity (BMI ≥40 kg/m²). BMI did not predict memory (P = .69) or global cognitive functioning (P = .08). In women, greater BMI was not associated with any cognitive variable (all P ≥ .09).DiscussionHigher BMI was associated with poorer attention and executive function in male HF patients, especially those with severe obesity. These patients may therefore have more difficulties with the HF treatment regimen and may have poorer outcomes.     

Clinical Course of Patients With Worsening Heart Failure With Reduced Ejection Fraction

Background

Epidemiology of patients with worsening heart failure and reduced ejection fraction (HFrEF) in the real-world setting is not well described.

Diuretic use, progressive heart failure, and death in patients in the DIG study

BackgroundNonpotassium-sparing diuretics (NPSDs), have been associated with increased sudden cardiac death (SCD) and progressive heart failure (HF) death in HF patients.Methods and ResultsIn 6797 Digitalis Investigation Group study patients, risk ratios were calculated for death, cardiovascular death (CVD), death from worsening HF, SCD, and HF hospitalization among those taking a potassium-sparing (PSD), NPSD, or no diuretic. Compared with not taking diuretic, risk of death (relative risk [RR] 1.36, 95% confidence interval [CI] 1.17–1.59, P < .0001), CVD (RR = 1.38, 95% CI 1.17–1.63, P = .0001), progressive HF death (RR = 1.41, 95% CI 1.06–1.89, P = .02), SCD (RR = 1.67, 95% CI 1.23–2.27, P = .001), and HF hospitalization (RR = 1.68, 95% CI 1.41–1.99, P < .0001) were increased with NPSD. There was no significant difference in any end point for patients taking only PSD compared to no diuretic. PSD only subjects were less likely than NPSD subjects to be hospitalized for HF (RR = 0.71, 95% CI 0.52–0.96, P = .02).ConclusionNPSDs are associated with increased risk of death, CVD, progressive HF death, SCD, and HF hospitalization. A randomized trial is needed to assess the role of NPSDs versus PSDs in HF patients.     

Aberrant central nervous system responses to the Valsalva maneuver in heart failure

Heart failure (HF) is associated with aberrant autonomic nervous system (ANS) activity, with altered responses to blood pressure and breathing challenges that appear to reflect abnormal central nervous system function. The authors used functional magnetic resonance imaging (fMRI) to determine whether the Valsalva maneuver, an ANS challenge, would show abnormal responses in ANS regulatory areas of the brain in HF. Brain fMRI signal changes in 5 HF patients (left ventricular ejection fraction, 0.15+/-0.08; age, 50+/-10 years) and 14 controls (age, 47+/-11 years) were assessed during 3 successive Valsalva maneuvers. The hypothalamus, hippocampus, putamen, amygdala, mid-cingulate, right insula, and cerebellar cortex showed exaggerated and phase-shifted fMRI responses in HF; other areas showed inverted signals from those found in controls. Central ANS control areas have altered phase, extent, and direction of responses to Valsalva maneuvers in a small sample of HF patients. These findings suggest that therapeutics that address neuroprotective aspects may be useful interventions for the condition.