Progressive Heart Failure Death Research Articles

Atrial fibrillation and risk of progressive heart failure in patients with preserved ejection fraction heart failure.

Understanding of the pathophysiology of progressive heart failure (HF) in patients with heart failure with preserved ejection fraction (HFpEF) is incomplete. We sought to identify factors differentially associated with risk of progressive HF death and hospitalization in patients with HFpEF compared with patients with HF and reduced ejection fraction (HFrEF). Prospective cohort study of patients newly referred to secondary care with suspicion of HF, based on symptoms and signs of HF and elevated natriuretic peptides (NP), followed up for a minimum of 6years. HFpEF and HFrEF were diagnosed according to the 2016 European Society of Cardiology guidelines. Of 960 patients referred, 467 had HFpEF (49%), 311 had HFrEF (32%), and 182 (19%) had neither. Atrial fibrillation (AF) was found in 37% of patients with HFpEF and 34% with HFrEF. During 6years follow-up, 19% of HFrEF and 14% of HFpEF patients were hospitalized or died due to progressive HF, hazard ratio (HR) 0.67 (95% CI: 0.47-0.96; P=0.028). AF was the only marker that was differentially associated with progressive HF death or hospitalization in patients with HFpEF HR 2.58 (95% CI: 1.59-4.21; P<0.001) versus HFrEF HR 1.11 (95% CI: 0.65-1.89; P=0.7). De novo patients diagnosed with HFrEF have greater risk of death or hospitalization due to progressive HF than patients with HFpEF. AF is associated with increased risk of progressive HF death or hospitalization in HFpEF but not HFrEF, raising the intriguing possibility that this may be a novel therapeutic target in this growing population.

Incidence of cardiovascular events in patients with atrial fibrillation anticoagulated with rivaroxaban after 2.5 years of follow-up: not all is stroke or bleeding

Abstract Introduction Atrial fibrillation (AF) is not a benign arrhythmia, but is associated with an increase in mortality, above all related to the risk of suffering thromboembolic events, mainly stroke. The use of oral anticoagulants (OAC) reduces this risk, but increases the risk of serious bleeding. The DOACs have been shown to be superior to the classic vitamin K antagonists (VKAs). It is not as well known whether AF is associated with an increase in other serious cardiac events. Purpose The objective of this analysis was to assess the incidence of stroke, major bleeding, total mortality and major adverse cardiac events [MACE, defined as cardiac mortality (including death for coronary events, progressive heart failure death and sudden cardiac death), coronary revascularization, myocardial infarction] in a contemporary series of patients with AF anticoagulated with rivaroxaban. Methods To do this, we have analyzed a series of 1,433 patients with AF, anticoagulated with rivaroxaban for at least the previous 6 months, consecutively included in the first half of year 2017 in 79 Spanish centers (EMIR study), and followed for 2.5 years. Results Mean age was 74.2±9.7 years, 44.5% being women. Prevalence of diabetes was 27.1%, chronic renal failure 16.1%, coronary heart disease 16.4% and heart failure 22.7%. 2MACE score was 1.8±1.4, CHA2DS2-VASc was 3.5±1.5 and HAS-BLED 1.6±1.0. 77.1% of patients received 20 mg/ day of rivaroxaban and 22.9% 15 mg/day. After a follow-up of 2.5 years, the annual rate (events/100 patients/year) of myocardial infarction was 0.16 (all non-STEMI), coronary revascularization 0.28, cardiac death 0.63 (sudden 0.16, heart failure 0.41, other 0.06), overall MACE 1.07 and overall mortality 2.73, while the incidence of stroke was 0.57 / 100 patients / year (ischemic 0.35, haemorrhagic 0.22) and major bleeding 1.04 (gastrointestinal 0.63, intracranial 0.28). Conclusion In a current series of patients with AF anticoagulated with rivaroxaban, the incidence of embolic and hemorrhagic complications and mortality are low, while the incidence of serious cardiac events is significant, being overall similar to that of stroke and major bleeding. Attention must be paid to the prevention and diagnosis of these problems. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Bayer Hispania

Very long-term survival and late sudden cardiac death in cardiac resynchronization therapy patients.

The very long-term outcome of patients who survive the first few years after receiving cardiac resynchronization therapy (CRT) has not been well described thus far. We aimed to provide long-term outcomes, especially with regard to the occurrence of sudden cardiac death (SCD), in CRT patients without (CRT-P) and with defibrillator (CRT-D). A total of 1775 patients, with ischaemic or non-ischaemic dilated cardiomyopathy, who were alive 5 years after CRT implantation, were enrolled in this multicentre European observational cohort study. Overall long-term mortality rates and specific causes of death were assessed, with a focus on late SCD. Over a mean follow-up of 30 months (interquartile range 10-42 months) beyond the first 5 years, we observed 473 deaths. The annual age-standardized mortality rates of CRT-D and CRT-P patients were 40.4 [95% confidence interval (CI) 35.3-45.5] and 97.2 (95% CI 85.5-109.9) per 1000 patient-years, respectively. The adjusted hazard ratio (HR) for all-cause mortality was 0.99 (95% CI 0.79-1.22). Twenty-nine patients in total died of late SCD (14 with CRT-P, 15 with CRT-D), corresponding to 6.1% of all causes of death in both device groups. Specific annual SCD rates were 8.5 and 5.8 per 1000 patient-years in CRT-P and CRT-D patients, respectively, with no significant difference between groups (adjusted HR 1.0, 95% CI 0.45-2.44). Death due to progressive heart failure represented the principal cause of death (42.8% in CRT-P patients and 52.6% among CRT-D recipients), whereas approximately one-third of deaths in both device groups were due to non-cardiovascular death. In this first description of very long-term outcomes among CRT recipients, progressive heart failure death still represented the most frequent cause of death in patients surviving the first 5 years after CRT implant. In contrast, SCD represents a very low proportion of late mortality irrespective of the presence of a defibrillator.

Prevalence and Predictors of Sepsis Death in Patients With Chronic Heart Failure and Reduced Left Ventricular Ejection Fraction.

BackgroundNoncardiovascular death is increasingly common in people with chronic heart failure (CHF), yet its causes remain poorly characterized. We aimed to define the prevalence of sepsis death in people with CHF and to ascertain its risk marker profile.Methods and ResultsWe conducted a prospective cohort study of 1802 patients with CHF and left ventricular ejection fraction ≤45% attending CHF clinics in 4 United Kingdom hospitals between 2006 and 2014. Mode of death was defined over a 10.3‐year follow‐up period (mean 4 years). Competing risk regression defined mode‐specific hazard ratios for sepsis, other noncardiovascular, progressive heart failure, and sudden cardiac death in relation to established heart failure prognostic markers. Of 737 deaths, 173 (23.5%) were due to sepsis; respiratory tract infections accounted for 69.9% (n=121) of these events. Those who died from sepsis were older, had higher platelet counts, and had a higher prevalence of chronic obstructive pulmonary disease than those who died from other causes. Sepsis death was independently associated with older age (hazard ratio=1.05; 95% confidence interval 1.03‐1.07), greater prevalence of chronic obstructive pulmonary disease (2.43; 1.74‐3.40), male sex (1.73; 1.16‐2.60), lower log serum vitamin D (0.68; 0.49‐0.95), and higher platelet count (1.002; 1.000‐1.005) than nonsepsis death. Established heart failure prognostic markers exhibited different patterns of association with sepsis death, other noncardiovascular death, progressive heart failure death, and sudden cardiac death.ConclusionsSepsis is a major contributor to death in people with CHF and has a different risk marker profile from other modes of death, suggesting that it may be amenable to targeted preventative strategies.

Ambulatory heart rate range predicts mode-specific mortality and hospitalisation in chronic heart failure

ObjectiveWe aimed to define the prognostic value of the heart rate range during a 24 h period in patients with chronic heart failure (CHF).MethodsProspective observational cohort study of 791 patients...

The Utility of Galectin-3 for Predicting Cause-Specific Death in Hospitalized Patients With Heart Failure

ObjectivesGalectin-3 has been shown to be involved in the process of cardiac fibrosis and to predict adverse events in heart failure (HF), but the association of galectin-3 with cause-specific death has not been well established. The purpose of this study was to investigate the prognostic value of baseline galectin-3 for all-cause, cardiovascular (CV), and in-hospital death in patients with HF. Methods and ResultsFrom March 2009 to April 2013, we consecutively measured galectin-3 in a large cohort of 1,440 hospitalized patients with HF. Cox proportional hazards regression, discrimination, and reclassification analyses were used to evaluate the association between galectin-3 and death. During a median follow-up of 582 days, 283 deaths were identified, of which 64 were patients who died during hospitalization. Compared with the lowest galectin-3 tertile, the highest 2 tertiles were significantly associated with all-cause, CV, and progressive HF death, but not significant for sudden and in-hospital death when analyzed by multivariable Cox regression. The utility of combining galectin-3 and N-terminal pro–B-type natriuretic peptide was assessed by dichotomizing these 2 biomarkers according to their median values. The highest risk of death due to all-cause, CV, and progressive HF was observed when both biomarkers were elevated after adjustment for established risk factors. Addition of galectin-3 to the prediction model for all-cause and CV death significantly improved discrimination and reclassification. ConclusionsGalectin-3 independently predicted death and added additional prognostic value beyond established risk factors in hospitalized patients with HF. The utility of galectin-3 alone as a risk predictor was not strong enough to assess sudden or in-hospital death.

Most Important Outcomes Research Papers on Device Therapies for Cardiomyopathies

Disorders of the cardiac muscle or cardiomyopathies are a broad, yet collectively common, group of conditions. Despite the heterogeneous etiologies, mode of death from these conditions is remarkably similar - progressive decline in cardiac function leading to intractable heart failure (HF) and sustained ventricular arrhythmias resulting in sudden cardiac death (SCD). Nearly 50% of patients die within 5 years of a HF diagnosis.1 Indeed, in the United States, HF alone is thought to cause 55,000 deaths per year2 and further contribute to 1 in 9 deaths overall.1 However, while advanced HF and the risk of SCD were once thought to be untreatable, technological advances has seen the emergence of device therapies as viable treatment options. Specifically, implantable cardioverter-defibrillator (ICD) therapy for treatment of ventricular arrhythmias, cardiac resynchronization therapy (CRT) for restoring cardiac synchrony and mechanical efficiency, and ventricular assist device (VAD) therapy to temporarily or permanently replace the function of the failing heart, have all emerged as highly efficacious therapies. The expanding use of device therapies, however, poses many challenges. First, while the indications for these devices are well summarized in clinical guidelines,3,4 considerable hurdles remain in ensuring eligible patients receive these therapies.5 By the same token, establishing the safety and effectiveness of these therapies in populations that are found in clinical practice, yet commonly excluded from trials, such as the elderly6 and uncommon forms of cardiomyopathies,7 is a high priority. Second, rapid dissemination of technologies frequently results in disparities in care. Indeed, age, gender, and racial disparities, in both receipt of these devices and outcomes following implantation, have been well documented. Whether these disparities have persisted, and the potential causative mechanisms underlying these disparities, however, are uncertain.8,9 Third, these devices are not without significant untoward effects; understanding …

Temporal Trends in Treatment and Outcomes for Advanced Heart Failure With Reduced Ejection Fraction From 1993–2010

Background— Randomized trials have demonstrated the efficacy of several new therapies for heart failure (HF) with reduced ejection fraction over the preceding 2 decades. This study investigates whether these therapeutic advances have translated into improvement in outcomes for patients with advanced HF referred to a heart transplant center. Methods and Results— Patients with HF (n=2507) referred to a single university center were analyzed in three 6-year eras during which medical and device therapies were evolving: 1993 to 1998 (era 1), 1999 to 2004 (era 2), and 2005 to 2010 (era 3). Impaired hemodynamics and comorbidities were more frequent at time of referral in later eras, whereas other HF severity parameters where similar or improved. Successive eras had greater usage of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, aldosterone antagonists, implantable cardioverter defibrillators, and cardiac resynchronization therapy, consistent with evolving evidence and guideline recommendations over the study period. All-cause mortality and sudden death were significantly lower in era 2 and 3 compared with era 1. After multivariable risk adjustment, era 3 had significantly decreased 2- and 3-year all-cause mortality risk and significantly decreased 1- and 3-year sudden death risk compared with era 1. However, progressive HF death and the combined outcome of mortality/urgent transplant/ventricular assist device were modestly increased in the latter eras. Conclusions— Over the past 2 decades, patients with advanced HF referred to and managed at a tertiary university referral center have benefited from advances in HF medications and devices, as evidenced by improvements in overall survival and sudden death risk.

Predictors for short-term progressive heart failure death in New York Heart Association II patients implanted with a cardioverter defibrillator—the EVADEF study

Sudden cardiac death (SCD) is the predominant cause of mortality in patients with mild heart failure (HF). This 2-year follow-up, multicenter, cohort study aimed to assess the extent to which implantable cardioverter defibrillators (ICDs), by reducing SCD, lead to predominant progressive HF death in mildly symptomatic HF patients at baseline in daily medical practice. Between June 2001 and June 2003, 1,030 New York Heart Association II patients received an ICD in 22 French centers. Sudden cardiac death and progressive HF mortality rates were assessed using competing risk methodology, and predictors for progressive HF at baseline were tested in a multivariate regression model. During a mean follow-up of 22 +/- 6 months, 114 deaths occurred: 12 (10.5%) due to SCD and 52 (45.6%) due to progressive HF (24-month cause-specific mortality rates of 1.2% [95% CI 0.6-1.9] and 5.4% [95% CI 4.0-6.8], respectively). Diuretics use (hazard ratio [HR] 2.8, 95% CI 1.5-5.5, P = .002), history of atrial fibrillation (HR 2.09, 95% CI 1.2-3.65, P = .01), and low ejection fraction (HR 2.7, 95% CI 1.4-4.8, P = .0008) were independent predictors for progressive HF death, whereas beta-blocker therapy was a protector (HR 0.6, 95% CI 0.3-0.9, P = .04). Half of the patients (48%) who died from progressive HF within 2 years of ICD implant initially presented with enlarged QRS (> or =120 milliseconds). Because of ICD efficiency, progressive HF is the main cause of death within 2 years of implant, although these patients are only mildly symptomatic at implantation. In addition to optimal pharmacologic therapy, these results raise the question of systematically implanting ICDs with cardiac resynchronization therapy in patients with electrical asynchronism at baseline.

Diuretic Use, Progressive Heart Failure, and Death in Patients in the DIG Study

Background Nonpotassium-sparing diuretics (NPSDs), have been associated with increased sudden cardiac death (SCD) and progressive heart failure (HF) death in HF patients. Methods and Results In 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). Conclusion NPSDs 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.

Mode of Death From Congestive Heart Failure: Implications for Clinical Management

The care of the end-stage patient has not been extensively studied, and little is known about best care practices. Therefore, using new definitions for mode of death due to heart failure, we performed a retrospective chart review of records from a university-based heart failure disease management program to characterize the population of patients dying from heart failure and to define clinical predictors that identify patients who will likely die of metabolic and/or progressive causes. Of 74 deaths recorded over a 60-month period, 17.6% and 21.3% were deemed to be metabolic or progressive, respectively. Utilization of resources was considerable, and only a small number of patients died while in hospice. Patients who required continuous inotropic support and those with preexisting renal failure were at highest risk for non-sudden cardiac death. We conclude that prospective identification of patients at risk for metabolic and progressive heart failure death is possible. The numbers of these patients is likely to increase in an era of implantable cardioverter-defibrillators. Intervention studies designed to evaluate and improve strategies that emphasize symptom control should target this group.

Predicting death due to progressive heart failure in patients with mild-to-moderate chronic heart failure

ObjectivesThe aim of this study was to explore the value of noninvasive predictors of death/mode of death in ambulant outpatients with chronic heart failure (HF). BackgroundMortality in chronic HF remains high, with a significant number of patients dying of progressive disease. Identification of these patients is important. MethodsWe recruited 553 ambulant outpatients age 63 ± 10 years with symptoms of chronic HF (New York Heart Association functional class, 2.3 ± 0.5) and objective evidence of left ventricular dysfunction (ejection fraction <45%, cardiothoracic ratio >0.55, or pulmonary edema on chest radiograph). After 2,365 patient-years of follow-up, 201 patients had died, with 76 events due to progressive HF. ResultsIndependent predictors of all-cause mortality assessed with the Cox proportional hazards model were as follows: a low standard deviation of all normal-to-normal RR intervals (SDNN); lower serum sodium and higher creatinine levels; higher cardiothoracic ratio; nonsustained ventricular tachycardia; higher left ventricular end-systolic diameter; left ventricular hypertrophy; and increasing age. Independent predictors of death specific to progressive HF were SDNN, serum sodium and creatinine levels. The hazard ratio of progressive HF death for a 10% decrease in SDNN was 1.06 (95% confidence interval [CI], 1.01 to 1.12); for a 2 mmol/l decrease in serum sodium, 1.22 (95% CI, 1.08 to 1.38); and for a 10 μmol/l increase in serum creatinine, 1.14 (95% CI, 1.09 to 1.19) (all p < 0.01). ConclusionsIn ambulant outpatients with chronic HF, low serum sodium and SDNN and high serum creatinine identify patients at increased risk of death due to progressive HF.

The relationship between QT intervals and mortality in ambulant patients with chronic heart failure. The united kingdom heart failure evaluation and assessment of risk trial (UK-HEART)

Mortality in patients with heart failure remains high and is difficult to predict. QT interval parameters on a 12-lead ECG have been shown to predict arrhythmic events in patients with a variety of myocardial diseases. There is some, but not consistent, evidence that QT interval parameters may act as predictors of mortality, in particular sudden death, in patients with heart failure. In an adequately powered prospective study we have studied QT interval parameters in patients with stable chronic heart failure in order to determine whether they are predictive of all-cause mortality or mode of death. Five hundred and fifty-four ambulant outpatients with chronic heart failure were recruited. A 12-lead ECG, chest radiograph, echocardiogram, 24 h ambulatory electrocardiogram and serum for biochemical analysis were obtained at baseline. Patients were followed for 471+/-168 days. QT intervals were measured in all leads blinded to patient's characteristics and outcome, were corrected for heart rate, and the maximum QT intervals, and QT dispersion (range of QT intervals) were determined. The same parameters were determined for JT intervals. The primary end-point was all-cause mortality, secondary end-points were sudden cardiac death and death due to progressive heart failure. Multivariate analysis with the Cox's proportional hazards model was used to determine which variables were independently related to outcome. Four hundred and ninety-five patients had analysable ECGs at study entry and of these 71 died during follow-up. The heart rate corrected QT dispersion and maximum QT interval were significant univariate predictors of all-cause mortality (P=0.026 and <0.0001 respectively), and also of sudden death and progressive heart failure death, but were not related to outcome in the multivariate analysis. The independent predictors of all-cause mortality were cardiothoracic ratio (P=0.0003), creatinine (P=0.0009), heart rate (P=0.007), echocardiographically derived left ventricular end-diastolic dimension (P=0.007) and ventricular couplets on 24 h electrocardiographic monitoring (P=0.015). In an adequately powered prospective study none of the QT or JT parameters were shown to be independent predictors of outcome in patients with mild to moderate congestive heart failure. These variables do not therefore add to the prognostic information which can be gained from simple radiographic, biochemical, echocardiographic and Holter data in this group of patients.

Heart Rate Is a Marker of Amiodarone Mortality Reduction in Severe Heart Failure

Objectives. The impact of amiodarone on mortality in patients with severe congestive heart failure (CHF) (New York Heart Association functional classes II [advanced], III and IV; left ventricular ejection fraction <35%) in the Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA) trial was analyzed in relation to initial mean baseline heart rate (BHR) and its change after 6 months of follow-up.Background. Trials of amiodarone therapy in CHF have produced discordant results, suggesting that the effect is not uniform in all patient subgroups with regard to survival.Methods. The present analysis was carried out in 516 patients randomized to receive amiodarone, 300 mg/day (n = 260), or nonantiarrhythmic therapy (n = 256, control group) and followed up for 2 years. Survival was evaluated for patients with a BHR ≥90 beats/min (control: n = 132; amiodarone: n = 122) and <90 beats/min (control: n = 124; amiodarone: n = 138). Survival was also analyzed according to heart rate reduction at 6 months for 367 patients.Results. For patients with a BHR ≥90 beats/min, amiodarone therapy reduced mortality to 38.4% compared with 62.4% in control patients (relative risk [RR] 0.55, 95% confidence interval [CI] 0.35 to 0.95, p < 0.002). Both sudden death (RR 0.46, 95% CI 0.24 to 0.90, p < 0.02) and progressive heart failure death (RR 0.60, 95% CI 0.30 to 1.03, p < 0.06) were reduced, and functional capacity was improved. In patients with a BHR <90 beats/min, amiodarone did not alter survival. Among 367 patients who completed 6 months of follow-up, amiodarone reduced 2-year mortality only in those with a BHR ≥90 beats/min, which was reduced at 6 months.Conclusions. Elevated rest heart rates in severe CHF identify a subgroup of patients who benefit from treatment with amiodarone. Amiodarone-induced heart rate slowing may be an important benefit for patients.(J Am Coll Cardiol 1997;29:1199–205)