Temporal shift in heart failure diagnoses among hospitalized patients within a large US integrated health system

Comparison of Medication Practices in Patients With Heart Failure and Preserved Versus Those With Reduced Ejection Fraction (from the Cardiovascular Research Network [CVRN

BackgroundDiabetes mellitus (DM), chronic kidney disease (CKD), and heart failure (HF) are pathophysiologically linked and increasing in prevalence in Asian populations, but little is known about the interplay of DM and CKD on outcomes in HF. ObjectivesThis study sought to investigate outcomes in patients with heart failure with preserved ejection fraction (HFpEF) vs heart failure with reduced ejection fraction (HFrEF) in relation to the presence of DM and CKD. MethodsUsing the multinational ASIAN-HF registry, we investigated associations between DM only, CKD only, and DM+CKD with: 1) composite of 1-year mortality or HF hospitalization; and 2) Kansas City Cardiomyopathy Questionnaire scores, according to HF subtype. ResultsIn 5,239 patients with HF (74.6% HFrEF, 25.4% HFpEF; mean age 63 years; 29.1% female), 1,107 (21.1%) had DM only, 1,087 (20.7%) had CKD only, and 1,400 (26.7%) had DM+CKD. Compared with patients without DM nor CKD, DM+CKD was associated with 1-year all-cause mortality or HF hospitalization in HFrEF (adjusted HR: 2.07; 95% CI: 1.68-2.55) and HFpEF (HR: 2.37; 95% CI: 1.40-4.02). In HFrEF, DM only and CKD only were associated with 1-year all-cause mortality or HF hospitalization (both HRs: 1.43; 95% CI: 1.14-1.80), while in HFpEF, CKD only (HR: 2.54; 95% CI: 1.46-4.41) but not DM only (HR: 1.01; 95% CI: 0.52-1.95) was associated with increased risk (interaction P < 0.01). Adjusted Kansas City Cardiomyopathy Questionnaire scores were lower in patients with DM+CKD (HFrEF: mean 60.50, SEM 0.77, HFpEF: mean 70.10, SEM 1.06; P < 0.001) than with no DM or CKD (HFrEF: mean 66.00, SEM 0.65; and HFpEF: mean 75.80, SEM 0.99). ConclusionsCombined DM and CKD adversely effected outcomes independently of HF subtype, with CKD a consistent predictor of worse outcomes. Strategies to prevent and treat DM and CKD in HF are urgently required.

Aldosterone blockade has been shown to be effective in reducing total mortality in patients with severe heart failure due to systolic left ventricular dysfunction and in patients with heart failure post myocardial infarction. Increasing evidence suggests that aldosterone blockade alone and or in conjunction with an angiotensin converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) with or without a thiazide diuretic may also prevent target organ damage (TOD) in patients with hypertensive heart disease (HHD) independent of its effects on blood pressure. Aldosterone blockade may be of especial value in patients with resistant hypertension, visceral obesity, and sleep apnea. Aldosterone blockade prevents myocardial fibrosis and improves echocardiographic indices of diastolic function in patients with heart failure and a normal left ventricular ejection fraction (HFNEF). Its effects on cardiovascular mortality and hospitalization for heart failure in HFNEF are currently under investigation. Aldosterone blockade has also been shown to be beneficial in preventing experimental atherosclerosis and in limiting experimental stroke, although not as yet in man. Although aldosterone may cause serious hyperkalemia this is unlikely in patients with normal renal function. Nevertheless careful selection of patients and serial monitoring of serum potassium, especially in patients with chronic kidney disease, is essential if one is to obtain benefit from this strategy. The risk/benefit of aldosterone blockade alone and or in combination with an ACE-I or ARB with or without a thiazide diuretic in patients with HHD will however require further large scale prospective randomized study.

The prevalence of heart failure with preserved ejection fraction (HFpEF) is increasing because of an aging population and an unhealthy, sedentary lifestyle, predisposing to diabetes, obesity, dyslipidemia, hypertension, and chronic kidney disease. A substantial proportion of patients with HFpEF exhibits coronary microvascular disease (CMD), and the combination of CMD with left ventricular diastolic dysfunction is associated with worse outcomes. Distinct patient clusters within HFpEF populations are based on clinical and biomarker profiles, each with unique prognoses and comorbidity patterns. Most patients with HFpEF present with multiple comorbidities, adding to the disease's complexity. Since risk factors directly affect the coronary microvasculature-and considering the bidirectional paracrine signaling between cardiomyocytes and the microvasculature-there is significant pathophysiological overlap between HFpEF and CMD. Therefore, in this review, we aim to summarize epidemiological evidence for the overlap in patients with CMD and HFpEF, identify shared biomarkers pathophysiological pathways underlying the co-occurrence of CMD and HFpEF, and discuss how cardiometabolic interventions may simultaneously address both CMD and HFpEF. Established and emerging treatments for HFpEF and CMD target these shared mechanisms. A deeper understanding of these interrelated pathways may pave the way for novel therapeutic strategies to alleviate the burden of HFpEF and refine patient management.

Clinical characteristics and prognosis of heart failure in elderly patients

Failing Hypertensive Heart: a Question of Altered Telomere Biology?

Summary : Lifelong exercise training maintains a youthful compliance of the left ventricle (LV), whereas a year of exercise training started later in life fails to reverse LV stiffening, possibly because of accumulation of irreversible advanced glycation end products. Alagebrium is a novel drug that breaks advanced glycation end product crosslinks and improves LV stiffness in aged animals. In this study, the authors prescribed alagebrium (200 mg daily) or placebo combined with aerobic exercise training or contact control in healthy, sedentary older individuals for 1 year. The authors evaluated overall cardiac function by the use of several modalities, including invasive pressure–volume measurements, exercise testing, and cardiac MRI before and after the training. To the authors’ knowledge, this is the first study to evaluate the effects of alagebrium and exercise training in healthy aged humans. After intervention, exercise training significantly increased exercise capacity, LV mass, and LV end-diastolic volume. Conversely, alagebrium had little effect on exercise capacity or LV geometry. However, alagebrium showed a modest improvement in LV stiffness compared with placebo. This favorable effect of alagebrium on LV stiffness was most prominent in individuals with combined alagebrium and exercise training. Conclusions : Alagebrium had no effect on hemodynamics, LV geometry, or exercise capacity in healthy, previously sedentary seniors. However, it did show a modestly favorable effect on age-associated LV stiffening.1 Summary : Maximum oxygen consumption (peak VO2) and efficiency of ventilation (VE) during exercise (VE/VCO2 slope) are known to stratify adults in heart failure for 1-year survival. On the basis of adult data, a recent American Heart Association scientific statement suggested that peak VO2<50% predicted for age and sex should be considered substantial impairment in exercise performance in children with heart disease and therefore a class I indication for heart transplant listing. This single-center study examined the association of …

Age-Related Characteristics and Outcomes of Patients With Heart Failure With Preserved Ejection Fraction

Sodium-glucose co-transporter 2 inhibitors in heart failure with preserved ejection fraction: reasons for optimism.

Hypertension is a major risk factor for cardiovascular morbidity and mortality. The presence of hypertension more than doubles the risk for coronary heart disease, including acute myocardial infarction and sudden death, and more than triples the risk of congestive heart failure as well as strokes. Patients with high blood pressure frequently have abnormalities of cardiac structure or function, including left ventricular hypertrophy, systolic and diastolic dysfunction and in extreme cases, overt heart failure. There may also be concomitant or related coronary heart disease and an increased risk of arrhythmias and sudden death. Many of these factors are inter-related and their individual contributions are difficult to quantify. There is, however, some debate as to whether ‘hypertensive cardiomyopathy’ exists as a separate entity specific to hypertension. The term ‘cardiomyopathy’, however, would normally be reserved for intrinsic myocardial disease, where underlying causes such as hypertension and coronary artery disease have been excluded. Therefore, the preferred term should perhaps be ‘hypertensive heart disease’, and given the many mechanisms by which the heart may be abnormal in hypertension, the term ‘hypertensive heart disease’ is probably not so controversial. The purpose of this review is to describe the various mechanisms whereby the heart is abnormal in hypertension and to discuss the possibility of a discrete entity called hypertensive cardiomyopathy.

Mechanisms promoting the transition from hypertensive heart disease to heart failure with preserved ejection fraction are poorly understood. When inappropriate for salt status, mineralocorticoid (deoxycorticosterone acetate) excess causes hypertrophy, fibrosis, and diastolic dysfunction. Because cardiac mineralocorticoid receptors are protected from mineralocorticoid binding by the absence of 11-beta hydroxysteroid dehydrogenase, salt-mineralocorticoid-induced inflammation is postulated to cause oxidative stress and to mediate cardiac effects. Although previous studies have focused on salt/nephrectomy in accelerating mineralocorticoid-induced cardiac effects, we hypothesized that hypertensive heart disease is associated with oxidative stress and sensitizes the heart to mineralocorticoid, accelerating hypertrophy, fibrosis, and diastolic dysfunction. Cardiac structure and function, oxidative stress, and mineralocorticoid receptor-dependent gene transcription were measured in sham-operated and transverse aortic constriction (studied 2 weeks later) mice without and with deoxycorticosterone acetate administration, all in the setting of normal-salt diet. Compared with sham mice, sham plus deoxycorticosterone acetate mice had mild hypertrophy without fibrosis or diastolic dysfunction. Transverse aortic constriction mice displayed compensated hypertensive heart disease with hypertrophy, increased oxidative stress (osteopontin and NOX4 gene expression), and normal systolic function, filling pressures, and diastolic stiffness. Compared with transverse aortic constriction mice, transverse aortic constriction plus deoxycorticosterone acetate mice had similar left ventricular systolic pressure and fractional shortening but more hypertrophy, fibrosis, and diastolic dysfunction with increased lung weights, consistent with heart failure with preserved ejection fraction. There was progressive activation of markers of oxidative stress across the groups but no evidence of classic mineralocorticoid receptor-dependent gene transcription. Pressure-overload hypertrophy sensitizes the heart to mineralocorticoid excess, which promotes the transition to heart failure with preserved ejection fraction independently of classic mineralocorticoid receptor-dependent gene transcription.

Heart failure is common, complex, and often associated with coexisting chronic medical conditions and a high mortality. We aimed to assess the epidemiology of people admitted to hospital with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), including the period covering the COVID-19 pandemic, which was previously not well characterised. In this retrospective, cohort study, we used whole-population electronic health records with 57 million individuals in England to identify patients hospitalised with heart failure as the primary diagnosis in any consultant episode of an in-patient admission to a National Health Service (NHS) hospital. We excluded individuals with less than 1 year of medical history records in primary or secondary care; admissions to NHS hospitals for which less than 10% of heart failure cases were linkable to the National Heart Failure Audit (NHFA); individuals younger than 18 years at the time of the heart failure hospitalisation; and patients who died in hospital during the index heart failure admission. For patients with new onset heart failure, we assessed incidence rates of 30-day and 1-year all-cause and cause-specific (cardiovascular, non-cardiovascular, and heart failure-related) emergency rehospitalisation and mortality after discharge, and dispensed guideline-recommended medical therapy (GRMT). Follow-up occurred from the index admission to the earliest occurrence of the event of interest, death, or end of data coverage. We estimated adjusted hazard ratios (HRs) to compare HFrEF with HFpEF. We computed population-attributable fractions to quantify the percentage of outcomes attributable to coexisting chronic medical conditions. Among 233 320 patients identified who survived the index heart failure admission across 335 NHS hospitals between Jan 1, 2019, and Dec 31, 2022, 101 320 (43·4%) had HFrEF, 71 910 (30·8%) had HFpEF, and 60 090 (25·8%) had an unknown classification. In patients with new onset heart failure, there were reductions in all-cause 30-day (-5·2% [95% CI -7·7 to -2·6] in 2019-22) and 1-year rehospitalisation rates (-3·9% [-6·6 to -1·2]). Declining 30-day rehospitalisation rates affected patients with HFpEF (-4·8% [-9·2 to -0·2]) and HFrEF (-6·2% [-10·5 to -1·6]), although 1-year rates were not statistically significant for patients with HFpEF (-2·2% [-6·6 to 2·3] vs -5·7% [-10·6 to -0·5] for HFrEF). There were no temporal trends in incidence rates of 30-day or 1-year mortality after discharge. The rates of all-cause (HR 1·20 [1·18-1·22]) and cause-specific rehospitalisation were uniformly higher in those with HFpEF than those with HFrEF. Patients with HFpEF also had higher rates of 1-year all-cause mortality after discharge (HR 1·07 [1·05-1·09]), driven by excess risk of non-cardiovascular death (HR 1·25 [1·21-1·29]). Rates of rehospitalisation and mortality were highest in patients with coexisting chronic kidney disease, chronic obstructive pulmonary disease, dementia, and liver disease. Chronic kidney disease contributed to 6·5% (5·6-7·4) of rehospitalisations within 1 year for HFrEF and 5·0% (4·1-5·9) of rehospitalisations for HFpEF, double that of any other coexisting condition. There was swift implementation of newer GRMT, but markedly lower dispensing of these medications in patients with coexisting chronic kidney disease. Rates of rehospitalisation in patients with heart failure in England have decreased during 2019-22. Further population health improvements could be reached through enhanced implementation of GRMT, particularly in patients with coexisting chronic kidney disease, who, despite being at high risk, remain undertreated. Wellcome Trust, Health Data Research UK, British Heart Foundation Data Science Centre.

Background: One of uremic toxins, indoxyl sulfate (IS) is related to the progression of chronic kidney disease (CKD) and the worse cardiovascular outcomes. We have previously reported the relationship between IS levels and the severity of chronic heart failure (CHF), but the question arises as to whether the treatment of uremic toxin is beneficial in patients with CHF. This study aimed to elucidate whether the treatment with the oral adsorbent which reduces uremic toxin improved the cardiac function of the patients with CHF. Methods: First of all, we retrospectively enrolled 49 patients with both CHF and stage ≤3 CKD in our institute compared with the healthy subjects without CHF or CKD in the resident cohort study of Arita. Secondly, we retrospectively enrolled 16 CHF outpatients with stage 3-5 CKD. They were treated with and without the oral adsorbent of AST-120 for one year termed as the treatment and control groups, respectively. We underwent both blood test and echocardiography before and after the treatment. Results: First of all, among 49 patients in CHF patients, plasma IS levels increased to 1.38 ± 0.84 μg/ml from the value of 0.08 ± 0.06 μg/ml in Arita-cho as a community-living matched with gender and eGFR of CHF patients. We found both fractional shortening (FS) and E/e’, an index of diastolic function were decreased (25.0 ± 12.7%) and increased (13.7 ± 7.5), respectively in CHF patients compared with the value of FS and E/e’ in Arita-cho (FS: 41.8 ± 8.3%, E/e’: 8.8 ± 2.1). Secondly, in the treatment group, the plasma IS levels and the serum creatinine and brain natriuretic peptide levels decreased (1.40 ± 0.17 to 0.92 ± 0.15 μg/ml; p&lt;0.05, 1.91 ± 0.16 to 1.67 ± 0.12 mg/dl; p&lt;0.05, 352 ± 57 to 244 ± 49 pg/ml; p&lt;0.05, respectively) and both FS and E/e’ were improved following the treatment with AST-120 (28.8 ± 2.8 to 32.9 ± 2.6%; p&lt;0.05, 18.0 ± 2.0 to 11.8 ± 1.0; p&lt;0.05). However, these parameters did not change in the control group. Conclusions: The treatment to decrease the blood levels of uremic toxins improved not only renal dysfunction but cardiac systolic and diastolic dysfunction in patients with chronic heart failure. Oral adsorbents might be a new treatment of heart failure especially with diastolic dysfunction.

The concept of “diastolic” heart failure grew out of the observation that many patients who have the symptoms and signs of heart failure had an apparently normal left ventricular (LV) ejection fraction. Thus it was assumed that since systolic function was “preserved” the problem must lie in diastole, although it is not clear by whom or when this assumption was made. Nevertheless, many guidelines followed on how to diagnose “diastolic” heart failure backed up by indicators of diastolic dysfunction derived from Doppler echoardiography. Diastolic heart failure is associated with a lower annual mortality rate of approximately 8% as compared to annual mortality of 19% in heart failure with systolic dysfunction, however, morbidity rate can be substantial. Thus, diastolic heart failure is an important clinical disorder mainly seen in the elderly patients with hypertensive heart disease. Early recognition and appropriate therapy of diastolic dysfunction is advisable to prevent further progression to diastolic heart failure and death. There is no specific therapy to improve LV diastolic function directly. Medical therapy of diastolic dysfunction is often empirical and lacks clear-cut pathophysiologic concepts. Nevertheless, there is growing evidence that calcium channel blockers, beta-blockers, ACE-inhibitors and ARB as well as nitric oxide donors can be beneficial. Treatment of the underlying disease is currently the most important therapeutic approach.

In Canada, the incidence of heart failure (HF) among adults ≥40 years has increased from 521 per 100,000 to 601 per 100,000 from 2013 to 2023, and is expected to rise further in the coming decades. HF is the second leading cause of death in Canada, with an age standardized all-cause mortality rate of 5,761 per 100,000 compared to people without HF at 913 per 100,000. HF with preserved ejection fraction (HFpEF), defined as the clinical syndrome of HF with left-ventricular ejection fraction (LVEF) ≥50%, comprises approximately half of all HF diagnoses. Contemporary data published this year suggests one- and five-year mortality rates for HFpEF are similar to those seen in heart failure with reduced ejection fraction (HFrEF). The Canadian Cardiovascular Society (CCS) endorses the universal definition of HF, which classifies HFpEF as having an LVEF cutoff of 50% and emphasizes markers of increased left ventricular (LV) filling pressures as a reflection of the underlying pathophysiology. HFpEF is associated with both functional and structural cardiac abnormalities, including diastolic dysfunction, ventricular and atrial remodelling, LV hypertrophy, and fibrosis.5 In addition, systemic inflammation, endothelial dysfunction, altered myocardial energetics, and abnormalities in skeletal muscle are increasingly recognized as important contributors to HFpEF pathophysiology and serve as therapeutic targets. Comorbid conditions including type 2 diabetes mellitus (T2DM), obesity, atrial fibrillation, chronic kidney disease, pulmonary hypertension, obstructive sleep apnea, and iron deficiency have been associated with the development and progression of HFpEF. Furthermore, there is growing interest in identifying distinct HFpEF phenotypes to better characterize patient populations beyond their comorbid conditions, with the aim of personalizing prognosis and treatment options. In a recent study, three distinct HFpEF phenotypes were identified, including a younger group with primarily New York Heart Association (NYHA) II symptoms, a higher prevalence of smoking, and a lower prevalence of diabetes and chronic kidney disease; another consisting of older age individuals (mean age 77 years), predominantly women with atrial fibrillation and chronic kidney disease; and a third group of intermediate age (mean age 66 years) with a very high prevalence of obesity and diabetes, greater functional impairment, and elevated inflammatory markers. Notably, the patients in this latter phenotype, with a very high prevalence of obesity and diabetes, were most likely to be hospitalized for HF along with having an overall mortality risk comparable to those patients classified in the older, atrial fibrillation, chronic kidney disease phenotype, despite their younger age.