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

AIMS: 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). METHODS AND RESULTS: 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 6 years. 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 6 years 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). CONCLUSIONS: 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.

Reduction of heart failure guideline-directed medication during hospitalization: prevalence, risk factors, and outcomes.

AIMS: Optimal management of heart failure with reduced ejection fraction (HFrEF) includes titration of guideline-directed medical therapy (GDMT) to the highest tolerated dose within the licensed range. During hospitalization, GDMT doses are often significantly altered, although it is unknown whether the cause of hospitalization influences this. METHODS AND RESULTS: We recruited 711 people with stable HFrEF from specialist heart failure clinics and prospectively assessed events occurring during first unplanned hospitalization. Dose changes of ACE inhibitors or angiotensin receptor blockers (ACEi/ARB), beta-blockers, mineralocorticoid receptor antagonists, and loop diuretics were recorded during 414 hospitalizations, categorized as due to decompensated heart failure, other cardiovascular causes, infection, or other non-cardiovascular causes. Most hospitalizations resulted in no change to GDMT. ACEi/ARB dose was reduced in 21% of hospitalizations and was more common during non-cardiovascular hospitalization (25.4% vs. 13.9%; P = 0.005). ACEi/ARB dose reduction was associated with older age and lower left ventricular ejection fraction at study recruitment, and poorer renal function, lower systolic blood pressure, higher serum potassium, and less frequent care from a cardiologist during admission. People experiencing ACEi/ARB reduction had worse age-adjusted survival after discharge, without differences in heart failure re-hospitalization. De-escalation of beta-blockers occurred in 8% of hospitalizations, most often due to other non-cardiovascular causes; this was not associated with post-discharge survival or re-hospitalization with heart failure. CONCLUSIONS: De-escalation of HFrEF GDMT is more common during non-cardiovascular hospitalization and for ACEi/ARB is associated with reduced survival. Post-discharge care plans should include robust plans to consider re-escalation of GDMT in these cases.

Diabetes mellitus and the causes of hospitalisation in people with heart failure.

INTRODUCTION: Diabetes mellitus (DM) is associated with increased risk of hospitalisation in people with heart failure and reduced ejection fraction (HFrEF). However, little is known about the causes of these events. METHODS: Prospective cohort study of 711 people with stable HFrEF. Hospitalisations were categorised by cause as: decompensated heart failure; other cardiovascular; infection or other non-cardiovascular. Rates of hospitalisation and burden of hospitalisation (percentage of follow-up time in hospital) were compared in people with and without DM. RESULTS: After a mean follow-up of 4.0 years, 1568 hospitalisations occurred in the entire cohort. DM (present in 32% [n=224]) was associated with a higher rate (mean 1.07 vs 0.78 per 100 patient-years; p<0.001) and burden (3.4 vs 2.2% of follow-up time; p<0.001) of hospitalisation. Cause-specific analyses revealed increased rate and burden of hospitalisation due to decompensated heart failure, other cardiovascular causes and infection in people with DM, whereas other non-cardiovascular causes were comparable. Infection made the largest contribution to the burden of hospitalisation in people with and without DM. CONCLUSIONS: In people with HFrEF, DM is associated with a greater burden of hospitalisation due to decompensated heart failure, other cardiovascular events and infection, with infection making the largest contribution.

Infection-Related Hospitalization in Heart Failure With Reduced Ejection Fraction: A Prospective Observational Cohort Study.

BACKGROUND: Hospitalization is a common adverse event in people with heart failure and reduced ejection fraction, yet is often not primarily due to decompensated heart failure (HF). We investigated the long-term prognosis following infection-related hospitalization. METHODS: We conducted a prospective observational cohort study of 711 people with heart failure and reduced ejection fraction recruited from 4 specialist HF clinics in the United Kingdom. All hospitalization episodes (n=1568) were recorded and categorized as primarily due to decompensated HF, other cardiovascular disease, infection-related, or other noncardiovascular disease. Survival was determined after the first hospitalization. RESULTS: During 2900 patient-years of follow-up, there were a total of 14 686 hospital days. At least one hospitalization occurred in 467 people (66%); 25% of first hospitalizations were primarily due to infection and these were not associated with typical signs including tachycardia and pyrexia. Compared with other categories of hospitalization, infection-related was associated with older age, lower serum albumin, higher blood neutrophil counts, and greater prevalence of chronic obstructive pulmonary disease at recruitment. Median survival after first infection-related hospitalization was 18.6 months, comparable to that after first decompensated HF hospitalization, even after age-sex adjustment. The burden of all-cause rehospitalization was comparable irrespective of the category of first hospitalization, but infection more commonly caused re-hospitalization after index infection hospitalization. CONCLUSIONS: Infection is a common driver of hospitalization in heart failure and reduced ejection fraction and often presents without classical signs. It is associated with high mortality rates, comparable to decompensated HF, and a major burden of rehospitalization caused by recurrent episodes of infection.