Heart Failure Hospitalization-free Survival Research Articles

Hemoglobin Level Can Predict Heart Failure Hospitalization in Patients with Advanced Heart Failure Awaiting Heart Transplantation without Inotropes or Mechanical Circulatory Support.

Although anemia is a common comorbidity that often coexists with heart failure (HF), its clinical impact in patients with advanced HF remains unclear. We investigated the impact of hemoglobin levels on clinical outcomes in patients with advanced HF listed for heart transplantation without intravenous inotropes or mechanical circulatory support.We retrospectively reviewed the clinical data of patients listed for heart transplantation at our institute who did not receive intravenous inotropes or mechanical circulatory support between 2011 and 2022. We divided the patients into those with hemoglobin levels lower or higher than the median value and compared the composite of all-cause death and HF hospitalization within 1 year from the listing date.We enrolled consecutive 38 HF patients (27 males, 49.1 ± 10.8 years old). The median hemoglobin value at the time of listing for heart transplantation was 12.9 g/dL, and 66.7% of the patients had iron deficiency. None of the patients in either group died within 1 year. The HF hospitalization-free survival rate was significantly lower in the lower hemoglobin group (40.9% versus 81.9% at 1 year, P = 0.020). Multivariate Cox proportional hazards model analysis showed that hemoglobin as a continuous variable was an independent predictor for HF hospitalization (odds ratio 0.70, 95% confidence interval 0.49-0.97, P = 0.030).Hemoglobin level at the time of listing for heart transplantation was a predictor of hospitalization in heart-transplant candidates without intravenous inotropes or mechanical circulatory support.

Personalized lifetime prediction of survival and treatment benefit in patients with heart failure with reduced ejection fraction: The LIFE-HF model.

Although trials have proven the group-level effectiveness of various therapies for heart failure with reduced ejection fraction (HFrEF), important differences in absolute effectiveness exist between individuals. We developed and validated the LIFEtime-perspective for Heart Failure (LIFE-HF) model for the prediction of individual (lifetime) risk and treatment benefit in patients with HFrEF. Cox proportional hazards functions with age as the time scale were developed in the PARADIGM-HF and ATMOSPHERE trials (n = 15 415). Outcomes were cardiovascular death, heart failure (HF) hospitalization or cardiovascular death, and non-cardiovascular mortality. Predictors were age, sex, New York Heart Association class, prior HF hospitalization, diabetes mellitus, extracardiac vascular disease, systolic blood pressure, left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide, and glomerular filtration rate. The functions were combined in life-tables to predict individual overall and HF hospitalization-free survival. External validation was performed in the SwedeHF registry, ASIAN-HF registry, and DAPA-HF trial (n = 51 286). Calibration of 2- to 10-year risk was adequate, and c-statistics were 0.65-0.74. An interactive tool was developed combining the model with hazard ratios from trials to allow estimation of an individual's (lifetime) risk and treatment benefit in clinical practice. Applying the tool to the development cohort, combined treatment with a mineralocorticoid receptor antagonist, sodium-glucose cotransporter 2 inhibitor, and angiotensin receptor-neprilysin inhibitor was estimated to afford a median of 2.5 (interquartile range [IQR] 1.7-3.7) and 3.7 (IQR 2.4-5.5) additional years of overall and HF hospitalization-free survival, respectively. The LIFE-HF model enables estimation of lifelong overall and HF hospitalization-free survival, and (lifetime) treatment benefit for individual patients with HFrEF. It could serve as a tool to improve the management of HFrEF by facilitating personalized medicine and shared decision-making.

Design and results of aCRT MID-Q study: Adoption of adaptive CRT in patients with normal AV conduction and moderately wide left bundle branch block

BackgroundSub-analysis of the adaptive CRT (aCRT) trial demonstrated the potential benefits of the aCRT algorithm over conventional echo-guided bi-ventricular (BiV) pacing in patients with left bundle branch block (LBBB) with moderately wide QRS (120–149 ms) and normal atrioventricular (AV) conduction. MethodsAdoption of Adaptive CRT in Patients with Left Bundle Branch Block and Moderately Wide QRS (aCRT MID-Q, UMIN Clinical Trials Registry Number: 000022452) was a multicenter, prospective, randomized, double-blind study designed to investigate the superiority of the aCRT pacing algorithm compared to echo-guided BiV pacing in patients with moderately wide LBBB and normal AV conduction. The primary endpoint was the improvement in clinical composite score (CCS) at 6 months; the secondary endpoints were changes in left ventricular (LV) end-systolic volume, LV ejection fraction, New York Heart Association classification, 6-min walk distance, and quality of life from baseline to 6 months post-randomization; heart failure administration; all-cause mortality; and cardiac mortality within 12 months. ResultsThe trial was terminated prematurely after enrollment of 39 patients (aCRT arm; n = 17, echo-guided BiV arm; n = 22) because of lower than expected enrollment. In the intention-to-treat analysis, the improvement of CCS was achieved in 10 patients (59%) in the aCRT arm (n = 17) and 16 patients (73%) in the echo-guided BiV arm (n = 22, p = 0.36). For the secondary endpoint, only 6-min walk distance was significantly greater in the aCRT arm than in the echo-guided BiV arm, and no difference was observed in the echocardiographic parameters. Heart failure hospitalization-free survival was also not significantly different (p = 0.91). There was no death during the follow-up. ConclusionsImprovement of CCS was similarly observed after aCRT and echo-guided BiV in CRT recipients with moderately wide LBBB and normal AV conduction. A prospective study is needed to explore the impact of CRT and pacing algorithm on Japanese patients with moderately wide LBBB.

Differential Prognostic Impact of Resting Heart Rate in Older Compared With Younger Patients With Chronic Heart Failure—Insights From TIME-CHF

BackgroundThere is little information regarding the prognostic role of resting heart rate (HR) in older compared with younger patients with chronic heart failure (HF). Methods and ResultsIn patients enrolled in the Trial of Intensified Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) with sinus rhythm, effects of baseline HR (≥70 vs <70 beats/min [bpm]) on 18-month outcomes were compared between older (≥75 years; n = 186) and younger (<75 years; n = 141) patients. Older patients with lower (61 ± 6 bpm) and higher (83 ± 9 bpm) HR had similar left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) functional class, N-terminal pro–B-type natriuretic peptide (NT-proBNP), and survival and HF hospitalization–free survival. In contrast, younger patients with higher HR (81 ± 7 bpm) had higher NT-proBNP and NYHA functional class, lower LVEF, and a higher risk of death (hazard ratio 4.01 [95% confidence interval (CI) 1.17 −13.69]; P = .02) and death or HF hospitalization (hazard ratio 2.35 [95% CI 1.01–5.50]; P = .04) than those with lower HR (62 ± 5 bpm), with the association between higher HR and survival remaining significant after adjustment for NYHA functional class, LVEF, and NT-proBNP. ConclusionsIn contrast to HF patients aged <75 years, we found no association between HR and worse outcomes in HF patients aged ≥75 years.

Echocardiography-guided left ventricular lead placement for cardiac resynchronization therapy in ischemic vs nonischemic cardiomyopathy patients

Echocardiography-guided (EG) left ventricular (LV) lead placement at the site of latest mechanical activation improves outcome in heart failure (HF) patients receiving a cardiac resynchronization therapy (CRT)-defibrillator (CRT-D). The purpose of this study was to examine the effect of a strategy of EG LV lead placement in each of ischemic (ICM) vs nonischemic (NICM) cardiomyopathy patients. Patients enrolled in the Speckle Tracking Assisted Resynchronization Therapy for Electrode Region (STARTER) prospective, randomized trial who were treated with a CRT-D device (108 EG strategy and 75 routine strategy) were followed to the end-points of death, appropriate CRT-D therapy, or HF hospitalization. Of the patients enrolled in STARTER, 115 had ICM and 68 had NICM. Over mean follow-up of 3.7 ± 2.1 years, 62 patients died, 40 received appropriate CRT-D therapy, and 67 had HF hospitalizations. Compared to NICM patients, patients with ICM had worse survival (P = .0003), worse survival free from implantable cardioverter-defibrillator therapy (P = .004), and survival free from HF hospitalization (P = .0001). A strategy of EG LV lead placement improved the outcome of CRT-D therapy-free survival primarily in ICM patients and the outcome of HF hospitalization-free survival in both ICM and NICM patients. Achieving LV resynchronization was most critical in ICM patients in whom arrhythmic and HF outcomes improve with resynchronization to levels comparable to those of NICM patients. A strategy of EG LV lead placement improves HF-free survival equally in ICM and NICM patients and CRT-D therapy-free survival more favorably in ICM patients to levels comparable to those of NICM patients.

Long-Term Results of Intensified, N-Terminal-Pro-B-Type Natriuretic Peptide–Guided Versus Symptom-Guided Treatment in Elderly Patients With Heart Failure

Background— Therapy guided by N-terminal-pro-B-type natriuretic peptide (NT-proBNP) levels may improve outcomes in patients with chronic heart failure (HF), especially in younger patients with reduced left ventricular ejection fraction. It remains unclear whether treatment effects persist after discontinuation of the NT-proBNP–guided treatment strategy. Methods and Results— Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure randomized 499 patients with HF aged ≥60 years with left ventricular ejection fraction ≤45% to intensified, NT-proBNP–guided versus standard, symptom-guided therapy into prespecified age groups (60–74 and ≥75 years) during 18 months. A total of 329 patients (92%) alive at 18 months agreed to long-term follow-up. HF medication was intensified to a larger extent in the NT-proBNP–guided group. During long-term, NT-proBNP–guided therapy did not improve hospital-free (primary end point: hazard ratio, 0.87; 95% confidence interval, 0.71–1.06; P =0.16) or overall survival (hazard ratio, 0.85; 95% confidence interval, 0.64–1.13; P =0.25) but did improve HF hospitalization-free survival (hazard ratio, 0.70; 95% confidence interval, 0.55–0.90; P =0.005). Patients aged 60 to 74 years had benefit from NT-proBNP–guided therapy on the primary end point and HF hospitalization-free survival, whereas patients aged ≥75 years did not ( P &lt;0.10 for interaction). In landmark analysis, there was no regression to the mean after cessation of the NT-proBNP–guided strategy. More intensified HF medication at month 12 was associated with better long-term HF hospitalization-free and overall survival. Conclusions— Intensified, NT-proBNP–guided therapy did not improve the primary end point compared with symptom-guided therapy but did improve HF hospitalization-free survival. Within the subgroup of patients aged 60 to 74 years, it improved clinical outcome including the primary end point. These effects did not disappear after cessation of the NT-proBNP–guided strategy on the long-term. This is possibly attributable to a more intensified HF medical therapy in the NT-proBNP–guided group. Clinical Trial Registration— URL: http://www.isrctn.org . Unique identifier: ISRCTN43596477.

N‐terminal pro brain natriuretic peptide‐guided management in patients with heart failure and preserved ejection fraction: findings from the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME‐CHF)

To assess the effects of an NT-proBNP-guided medical management on 18-month outcomes in patients with heart failure (HF) and preserved LVEF ( HFpEF). Patients with HFpEF (LVEF >45%; n = 123) and HF with reduced LVEF (HFrEF; LVEF ≤45%; n = 499) with age ≥60 years, NYHA class ≥ II, and elevated NT-proBNP (>400 ng/L or >800 ng/L depending on age) were randomized to medical therapy titrated only to reduce symptoms to NYHA ≤II (symptom-guided) or also to reduce NT-proBNP below the inclusion threshold (NT-proBNP-guided) during a 6-month period. Patients were followed for an additional 12 months. Despite similar treatment escalation, NT-proBNP reduction and symptom relief were less in HFpEF than in HFrEF. Hospitalization-free survival at 18 months was worse in HFpEF than in HFrEF (P = 0.02), while survival and HF hospitalization-free survival did not differ. Among HFpEF patients, NT-proBNP reduction and symptom relief were similar in the symptom-guided (n = 59) and NT-proBNP-guided (n = 64) group despite more aggressive treatment in the NT-proBNP-guided group. In contrast to effects in HFrEF, NT-proBNP-guided management tended to worsen 18-month outcomes in HFpEF, with P-values for the interactions between LVEF stratum and management strategy of 0.2 for hospitalization-free survival, 0.03 for survival, and 0.01 for HF hospitalization-free survival. Outcomes in HFpEF were not better than in HFrEF, and opposite effects of NT-proBNP-guided management were observed in HFpEF compared with HFrEF. These preliminary findings suggest that, in contrast to HFrEF, NT-proBNP-guided therapy may not be beneficial in HFpEF. Trial registration ISRCTN43596477.

Differential prognostic impact of heart rate in younger and older patients with chronic heart failure

Background: In patients with chronic heart failure (HF), high heart rate (HR) is a marker of poor prognosis, and HR reduction is associated with improved outcomes. However, these data are based on trials including relatively young patients (typically less than 75 years), and there is little information regarding the prognostic role of HR in older HF patients. Accordingly, the aim of the present study was to compare the relationship between HR and outcomes in younger (age <75 years) and older (age ≥75 years) patients with chronic HF. Methods: Patients enrolled in the randomized, controlled multicenter Trial of Intensified Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) with sinus rhythm and without any device (pacemaker, defibrillator) throughout the trial were included in this post-hoc analysis. The effects of baseline HR (≥70 vs. <70 beats per minute (bpm) on 18 months outcomes (survival, HF hospitalization-free survival) were compared between younger (n=141, age 69±4 years) and older (n=186, age 82±4 years) patients. Results: Younger patients with higher baseline HR (n=86; HR 81±7 bpm) had worse left ventricular ejection fraction (LVEF; p=0.01), worse NYHA class (p=0.006) and higher N-terminal-pro-B-type natriuretic peptide (NT-proBNP; p=0.003) than those with lower HR (n=55; HR 62±5 bpm) but groups did not differ in terms of management strategy allocation (NT-proBNP-guided vs. symptom-guided). Survival and HF hospitalization-free survival at 18 months were worse in those with higher compared to those with lower HR [hazard ratio = 4.01 (95% CI, 1.17 -13.69), p= 0.02 and hazard ratio=2.35 (95% CI, 1.01-5, 50), p= 0.04; respectively], even after adjustment for LVEF, NYHA class, and NT-proBNP. In contrast, older patients with lower (n=77; HR 61±6 bpm) and higher (n=109; HR 83±9 bpm) baseline HR did not differ in terms of LVEF, NYHA class, NT-proBNP, and management strategy, and outcomes did not differ between those with higher and lower HR [for survival hazard ratio= 0.87 (95% CI, 0.47-1.61), p= 0.66 and HF hospitalization-free survival hazard ratio =0.84 (95% CI, 0.52-1.34), p= 0.46]. In older patients, the relationship between HR and outcomes was similar across LVEF categories (>45% and ≤45%) and was not influenced by betablocker use (p value for interaction > 0.33 for all endpoints). Conclusion: In accordance with previous data, we observed better outcomes in younger patients with chronic HF with lower HR compared to those with higher HR. In contrast, an association between HR and outcomes was not seen in older patients with chronic HF.

Summary of ‘Hot Line’ sessions presented at the European Society of Cardiology Congress 2008: August 30, 2008 to September 3, 2008, Munich, Germany

The European Society of Cardiology Congress, the largest medical meeting in Europe, was held August 30, 2008, to September 3, 2008, in Munich, Germany. Among the conference's main sessions, workshops and symposia, several ‘Hot Line’ sessions presented new scientific data and study results. The following are a summary of these Hot Line sessions. Brunner-La Rocca and colleagues presented results from TIME-CHF [Trial of Intensified (BNP-guided) versus standard (symptom-guided) Medical therapy in Elderly patients with Congestive Heart Failure], which aimed to compare intensified BNP-guided therapy to standard symptom-guided therapy on 18-month outcome. They also assessed whether or not there was a difference in response to such therapy in patients ≥75 years old (n=289) compared to those b75 years of age (n=210). It was found that intensified, BNP-guided therapy did not improve the primary endpoint of all-cause hospitalization free survival overall; however, it did improve the more disease-specific endpoint of heart failure hospitalization free survival. Response to therapy differed significantly between age groups with those b75 years of age showing reduced mortality and improved hospitalization survival while those ≥75 years old showing no benefit on outcome and less improvement in quality of life. The BEAUTIFUL (morBidity–mortality EvAlUaTion of the IF inhibitor ivabradine in patients with CAD and left

Aldosterone Synthase Promoter Polymorphism Predicts Outcome in African Americans With Heart Failure: Results From the A-HeFT Trial

We sought to evaluate the effect of the aldosterone synthase promoter polymorphism on heart failure outcomes for subjects in the African American Heart Failure Trial (A-HeFT). Genetic heterogeneity modulates clinical outcomes in subjects with heart failure (HF); however, little data exist in African American populations. A common polymorphism exists in the promoter region of the aldosterone synthase gene (CYP11B2) at position -344 (T/C). The -344C allele, associated with higher aldosterone synthase activity, has been linked to hypertension; however, its impact on outcomes in HF is unknown. A total of 354 subjects from A-HeFT participated in the GRAHF (Genetic Risk Assessment of Heart Failure in African Americans) substudy and were genotyped for the aldosterone synthase polymorphism. Patients were followed prospectively, and event-free survival (freedom from death and HF hospitalization) compared by CYP11B2 genotype. Of the cohort, 218 patients were TT, 114 CT, and 22 patients were CC. Baseline etiology, blood pressure, and functional class were not significantly different among the 3 cohorts. The C allele was associated with significantly poorer HF hospitalization-free survival with the best survival among TT subjects, intermediate for heterozygotes, and the poorest for CC homozygotes (p = 0.018), and a higher rate of death (% death TT/TC/CC = 1.8/3.5/18.2, p = 0.001). The TT genotype, more prevalent in blacks, was associated with greater impact of fixed combination of isosorbide dinitrate and hydralazine on the primary composite end point (p = 0.01). The aldosterone synthase promoter -344C allele linked to higher aldosterone levels is associated with poorer event-free survival in blacks with HF. The role of aldosterone receptor antagonists in diminishing this apparent genetic risk remains to be explored.