Heart Failure Hospitalization Research Articles

Guidelines, heart failure and the elderly

Heart failure (HF) guidelines have recently introduced several innovations in pharmacological therapeutic options. Specifically, for HF with reduced ejection fraction, an intensive therapeutic strategy of early initiation and rapid up-titration of guideline-directed medical therapy is now recommended in all patients to reduce the risk of HF rehospitalization or death. In clinical practice, however, this approach is not always feasible in the elderly population due to the coexistence of multiple geriatric conditions such as frailty, comorbidities in addition to the risk of adverse drug effects, general prescribing inertia and the unmet need for close follow-up during drug up-titration. As for HF with preserved ejection fraction, sodium-glucose cotransporter 2 inhibitors have been shown to significantly reduce the composite outcome of HF hospitalization and cardiovascular mortality. However, these drugs have not yet been proven effective in some cardiomyopathies, as these were not included in clinical trials. This review aims to provide a critical analysis of current HF guidelines, illustrating their limits in real-world applicability through a cardio-geriatric lens reinterpretation of recent evidence.

Contemporary epidemiology of hospitalised heart failure with reduced versus preserved ejection fraction in England: a retrospective, cohort study of whole-population electronic health records.

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.

Sodium-glucose cotransporter 2 inhibitors in cardiocerebrovascular disease

Cardiovascular disease is a leading cause of global mortality, necessitating effective strategies for prevention and treatment. The cardiovascular disease continuum concept highlights the progression from risk factors such as hypertension and diabetes mellitus to advanced stages, including heart failure (HF) and death. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, initially developed to manage diabetes, have emerged as effective therapies across all stages of the cardiovascular disease continuum. Numerous cardiovascular outcome trials demonstrate that SGLT2 inhibitors significantly reduce major adverse cardiovascular events and hospitalizations for HF in patients with and without established atherosclerotic cardiovascular disease. Notably, SGLT2 inhibitors have shown remarkable benefits in reducing HF risk, even in patients without diabetes, including those with HF and preserved ejection fraction. Furthermore, recent studies in post–myocardial infarction patients suggest potential benefits in reducing hospitalizations for HF. Despite their widespread use, the precise mechanisms by which SGLT2 inhibitors confer cardiovascular protection remain unclear, suggesting the need for further investigation. In conclusion, SGLT2 inhibitors have revolutionized cardiovascular disease management, offering significant therapeutic potential across a broad spectrum of patients, and are expected to play an increasingly prominent role in both the prevention and treatment of cardiovascular disease.

Association Between Clonal Hematopoiesis of Indeterminate Potential and Cardiovascular Outcomes in Patients With Acute Coronary Syndrome Who Have Quit Smoking: Study Design of a Prospective Cohort Study

Abstract Despite quitting smoking, patients with acute coronary syndrome (ACS) still have an increased risk of cardiovascular events. Clonal hematopoiesis of indeterminate potential (CHIP), which may be induced by smoking, has been identified to be associated with the development of coronary artery disease. However, it is unclear whether CHIP has a detrimental effect on the poor prognosis of ACS patients even after smoking cessation. This single-center, prospective cohort study will recruit 1,029 ACS patients undergoing complete percutaneous coronary intervention. The enrolled patients will be categorized into 3 groups based on their smoking status at admission: current smoker, non-smoker, and previous smoker. Previous smokers are defined as patients who have quit smoking for at least 1 year before experiencing the index ACS event. Whole-exome sequencing will be performed to identify the occurrence of CHIP in each patient. The primary endpoint is major adverse cardiovascular and cerebrovascular events, defined as a composite of cardiac death, non-fatal myocardial infarction, ischemia-driven revascularization, hospitalization for heart failure, and ischemic stroke. The association between CHIP and the primary endpoint will be determined by using Cox proportional hazard regression. This study aims to investigate the association among smoking cessation, CHIP, and the prognosis of ACS patients to provide new insights into the impact of CHIP on ACS patients, particularly among those who have quit smoking. The results will be published following the STROBE in a peer-reviewed scientific journal (Trial registration number: NCT04987268).

Uptitration of Sacubitril/Valsartan and Outcomes in Patients With Heart Failure - Insight From the REVIEW-HF Registry.

Guideline-directed medical therapy has become an important component of heart failure (HF) therapy, with sacubitril/valsartan as one of the recommended drugs; however, the real-world prognostic implications of sacubitril/valsartan uptitration are unclear. Patients with HF newly initiated on sacubitril/valsartan were registered in a retrospective multicenter study (REVIEW-HF). In all, 995 patients were divided into 3 groups according to the maximum dose achieved: high dose, sacubitril/valsartan 400 mg; intermediate dose, sacubitril/valsartan 200-<400 mg; and low dose, sacubitril/valsartan <200 mg. A total of 397 (39.9%) patients received high-dose sacubitril/valsartan; they had a significantly lower risk of mortality or HF hospitalization than patients in the low-dose (hazard ratio [HR] 0.39; 95% confidence interval [CI] 0.29-0.53; P<0.001) and intermediate-dose (HR 0.64; 95% CI 0.45-0.94; P=0.03) groups. In the multivariable Cox regression model, higher systolic blood pressure and maintained geriatric nutritional risk index were significantly associated with a higher incidence of achieving a high dose of sacubitril/valsartan. Patients who did not receive high-dose sacubitril/valsartan experienced more hypotension during the follow-up period, whereas hyperkalemia, severe renal events, and angioedema did not differ across the achieved dose classifications. Patients who achieved sacubitril/valsartan uptitration had a better prognosis than those who did not. Before sacubitril/valsartan uptitration, patients need to monitor blood pressure closely to prevent worsening events.

O USO DOS INIBIDORES DO COTRANSPORTADOR DE SÓDIO-GLICOSE-2 (SGLT2) NA INSUFICIÊNCIA CARDÍACA: UMA REVISÃO BIBLIOGRÁFICA

Heart failure (HF) is not a single pathological diagnosis, but a clinical syndrome caused by a structural and/or functional abnormality of the heart, resulting in elevated intracardiac pressure or inadequate cardiac output at rest or during exercise. It is a common clinical condition found in various healthcare settings, with a vast socio-economic impact. In Brazil, HF is the leading cardiovascular cause of hospital morbidity. Thus, heart failure studies play a crucial role in the development of new drugs, enabling significant improvements in the efficacy, safety and tolerability of treatment, as well as the personalization of care for individual patients. Recent advances in pharmacotherapy have led to the evolution of new therapeutic agents with a decrease in hospitalization and mortality rates in HF. The 2023 update of the European Society of Cardiology (ESC) guidelines recommends (class IA) the administration of sodium-glucose transporter 2 inhibitors (SGLT2i) for patients with heart failure with preserved ejection fraction (HFpEF) and mildly reduced EF (HFpEF). This study aims to analyze the use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in heart failure. In order to arrive at these topics, articles were collected from the PUBMED and SCIELO databases, and an analysis was carried out based on the material found in order to be able to explain the information relevant to the topic.

Evaluating the budget impact of Empagliflozin in managing heart failure with reduced ejection fraction: Proposing strategic policies for Malaysian public healthcare.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors such as Empagliflozin, are increasingly recommended as part of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) in many developed nations. This recommendation is based on robust clinical evidence showing that adding Empagliflozin to GDMT improves heart failure symptoms, clinical outcomes, functional status, and overall quality of life. In Malaysia, where healthcare is predominantly public and heavily subsidized, the introduction of new treatments can significantly impact costs, requiring detailed economic assessments. This study evaluates the budget impact of incorporating Empagliflozin into GDMT for HFrEF from the perspective of the public healthcare system. A five-year budget impact model was developed, integrating local data such as population, drug use, costs, clinical outcomes, and healthcare expenses. In the current scenario (GDMT alone), the projected five-year expenditure is MYR 6.12 billion (USD 3.92 billion). With Empagliflozin, the total cost rises by 0.71% to MYR 6.16 billion (USD 3.95 billion), driven by drug acquisition costs of MYR 160.12 million (USD 102.64 million) and adverse event costs of MYR 211,543 (USD 135,604). However, these costs are offset by savings from reduced HF hospitalizations, fewer cardiovascular deaths, and improved renal outcomes. Sensitivity analysis identified hospitalization costs, the price of Empagliflozin, and cardiovascular deaths in diabetic patients as key factors influencing the budget impact. Policymakers can improve the affordability of Empagliflozin through strategies like price negotiations, cost-sharing, and focusing on high-risk groups to optimize healthcare expenditure while ensuring effective treatment access.

Vericiguat Global Study in Participants with Chronic Heart Failure: Design of the VICTOR trial.

In the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial, the soluble guanylate cyclase stimulator vericiguat reduced the risk of hospitalization for heart failure (HHF) or cardiovascular death in patients with heart failure (HF) and reduced ejection fraction (HFrEF) with recent worsening HF. The effect of vericiguat in patients with HFrEF without recent worsening HF remains unknown. The VICTOR (Vericiguat Global Study in Participants with Chronic Heart Failure) trial was designed to assess the efficacy and safety of vericiguat in patients with ejection fraction ≤40% without recent worsening HF on a background of current foundational HFrEF therapy. The primary endpoint for VICTOR is time to first event for the composite of HHF or cardiovascular death. The trial will also assess the effect of vericiguat on time to cardiovascular death, time to HHF, total HHF, and all-cause death. As an event-driven trial, at least 1080 primary events are expected, but follow-up will continue until the targeted number of at least 590 cardiovascular deaths has been reached. Approximately 6000 participants will be randomized to vericiguat or placebo. VICTOR is the first large event-driven HFrEF trial performed in the contemporary era of quadruple foundational guideline-directed medical therapy, in a compensated ambulatory HF population. VICTOR will add important information to the evidence of the effects of vericiguat across the spectrum of patients with HFrEF.

Impact of sex-specific thresholds for low flow in assessment of prognosis in concordantly and discordantly graded aortic valve stenosis.

Sex-specific low flow was recently defined as stroke volume index (SVi) ≤40 ml/m² in men and ≤32 ml/m² in women. We tested the prognostic association of these cut-offs in patients with aortic stenosis (AS) with concordantly and discordantly graded AS (CGASEL and DGASEL) based on pressure recovery adjusted aortic valve area (energy loss, EL). Data from 1351 patients with asymptomatic AS, peak jet velocity <4m/s and preserved left ventricular ejection fraction enrolled in the Simvastatin and Ezetimibe in AS study was used. DGASEL was defined as EL <1.0 cm² with mean aortic gradient <40 mmHg, and CGASEL as EL ≥1.0 cm² with mean aortic gradient <40mmHg. Patients were further grouped into normal and low flow. Outcome was combined all-cause death and hospitalization for heart failure. CGASEL with normal/low flow was present in 915/253 patients, and DGASEL with normal/low flow in 57/126 patients. During median 4.3 years follow-up, event-free survival was lower in patients with DGASEL irrespective of flow compared to CGASEL with normal flow (p<0.05). In Cox regression analysis, DGASEL with normal or low flow were both associated with increased risk of all-cause death and hospitalization for heart failure after adjustment for age, sex, heart rate, randomized study treatment, hypertension, aortic valve replacement and aortic valve calcification (p<0.05). No survival difference was found between patients with normal vs. low flow within groups of DGASEL or CGASEL. Identification of low flow by the proposed sex-specific thresholds of SVi needs more prognostic validation before application in clinical practice.

Transcatheter Valve Replacement in Severe Tricuspid Regurgitation.

Severe tricuspid regurgitation is associated with disabling symptoms and an increased risk of death. Data regarding outcomes after percutaneous transcatheter tricuspid-valve replacement are needed. In this international, multicenter trial, we randomly assigned 400 patients with severe symptomatic tricuspid regurgitation in a 2:1 ratio to undergo either transcatheter tricuspid-valve replacement and medical therapy (valve-replacement group) or medical therapy alone (control group). The hierarchical composite primary outcome was death from any cause, implantation of a right ventricular assist device or heart transplantation, postindex tricuspid-valve intervention, hospitalization for heart failure, an improvement of at least 10 points in the score on the Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ-OS), an improvement of at least one New York Heart Association (NYHA) functional class, and an improvement of at least 30 m on the 6-minute walk distance. A win ratio was calculated for the primary outcome by comparing all possible patient pairs, starting with the first event in the hierarchy. A total of 267 patients were assigned to the valve-replacement group and 133 to the control group. At 1 year, the win ratio favoring valve replacement was 2.02 (95% confidence interval [CI], 1.56 to 2.62; P<0.001). In comparisons of patient pairs, those in the valve-replacement group had more wins than the control group with respect to death from any cause (14.8% vs. 12.5%), postindex tricuspid-valve intervention (3.2% vs. 0.6%), and improvement in the KCCQ-OS score (23.1% vs. 6.0%), NYHA class (10.2% vs. 0.8%), and 6-minute walk distance (1.1% vs. 0.9%). The valve-replacement group had fewer wins than the control group with respect to the annualized rate of hospitalization for heart failure (9.7% vs. 10.0%). Severe bleeding occurred in 15.4% of the valve-replacement group and in 5.3% of the control group (P = 0.003); new permanent pacemakers were implanted in 17.4% and 2.3%, respectively (P<0.001). For patients with severe tricuspid regurgitation, transcatheter tricuspid-valve replacement was superior to medical therapy alone for the primary composite outcome, driven primarily by improvements in symptoms and quality of life. (Funded by Edwards Lifesciences; TRISCEND II ClinicalTrials.gov number, NCT04482062.).

Prevalence and risk factors associated with decompensated heart failure after successful elective cardioversion for atrial fibrillation and atrial flutter

Study objectiveTo determine the incidence of and risk factors for HF after successful electrical and ablative cardioversion (CV) of atrial fibrillation (AF) and atrial flutter (AFL). DesignRetrospective cohort study. SettingSingle center academic institution. ParticipantsSeven hundred fifty-five patients underwent successful elective CV from July 1, 2018 to May 20, 2019. Patients presenting in arrhythmias other than AF or AFL, those who developed HF due to alternative etiologies, and those who developed arrhythmia recurrence within 30 days were excluded. Medical records of the remaining 451 patients were reviewed before and after CV. Main outcomes measuredDevelopment of heart failure despite sinus rhythm following CV and the risk factors associated with this outcome. ResultsThirty-three (7.3 %) of 451 patients who met inclusion criteria for our study developed new or worsening HF symptoms while maintaining sinus rhythm (SR) after successful CV. Symptoms were reported an average of 5.1 days following CV (range 0–17 days, SD 4.71). Following a multivariate stepwise logistic regression model, prior HF hospitalization (OR 3.91, 95 % CI 1.82–8.39), BMI (OR 1.06, 95 % CI 1.02–1.11), and valve disease (OR 2.51, 95 % CI 1.12–5.60) remained significant risk factors, and anti-arrhythmic drug (AAD) use was marginally significant (OR 2.02, 95 % CI 0.95–4.31). ConclusionDespite maintenance of SR, 7.3 % of patients developed decompensated HF in the 30 days following successful CV of AF or AFL, indicating this complication may be more frequent than previously believed. Predictors of HF post-CV included elevated BMI, valve disease, previous HF hospitalization, and prior AAD use.

Comparative Influences of Beta blockers and Verapamil on Cardiac Outcomes in Hypertrophic Cardiomyopathy

Guidelines recommend β blockers (BBs) as first-line therapy in symptomatic patients with hypertrophic cardiomyopathy (HCM) and nondihydropyridine calcium channel blockers, particularly, verapamil, as the second-line therapy, despite the absence of comparison trials between those 2 drugs. Because deleterious effects of verapamil have been reported in this setting, the present analysis aimed to evaluate the prognostic impact of BBs and verapamil in a cohort of patients with HCM. From a nationwide cohort of 1,434 patients with a diagnosis of HCM included in the French prospective observational REgistry of hypertrophic cardioMYopathy (REMY), we retrospectively analyzed patients with sarcomeric HCM included in the 3 largest centers and treated either with BBs or verapamil. Patients with a cardiac defibrillator or a pacemaker or who underwent a procedure of atrial fibrillation or septal ablation were excluded. The primary end point was the composite of cardiovascular death, hospitalization for heart failure, and hospitalization for atrial fibrillation. Of 600 patients with HCM, 544 (91%) were treated with BBs and 56 (9%) with verapamil. At inclusion, the 2 groups were comparable concerning the presence/amplitude of obstruction and sudden cardiac death risk factors. At up to 8 years of follow-up (median 3.9 years, interquartile range 2.1 to 5.8), no significant differences were observed in the primary end point (132 [24%] vs 10 [18%] under BBs or verapamil, respectively, hazard ratio 1.84, 95% confidence interval 0.94 to 3.63). In conclusion, in a real-world cohort of low-risk patients with HCM, verapamil therapy was not associated with a higher incidence of adverse events than β-blocker therapy.

Lung Ultrasound in the Acute Phase of ST-Segment-Elevation Acute Myocardial Infarction: 1-Year Prognosis and Improvement in Risk Prediction.

Lung ultrasound (LUS) has emerged as a useful tool in the acute phase of patients admitted for ST-segment-elevation myocardial infarction. However, its long-term significance remains uncertain, and risk scores do not include LUS findings as a predictor. This study aims to assess the 1-year prognostic value of LUS and its ability to enhance existing risk scores. This is a multicenter prospective cohort study involving 373 patients with ST-segment-elevation myocardial infarction. LUS was performed during the first 24 hours after angiography. LUS results were assessed both as a categorical (wet/dry lung) and continuous variable (LUS score). The primary end point comprised the following major adverse cardiovascular events: all-cause mortality or hospitalization for heart failure, acute coronary syndrome, or stroke within 1 year. We also evaluated whether LUS could enhance the predictive value of the GRACE (Global Registry of Acute Coronary Events) score. Major adverse cardiovascular events occurred in 51 (13.7%) patients over a median follow-up of 368 days. After multivariate analysis, the LUS score was an independent predictor (hazard ratio [HR], 1.06 [95% CI, 1.01-1.10]; P=0.009] for each additional B-line), whereas the categorical classification was an independent predictor in patients with ST-segment-elevation myocardial infarction Killip I (HR, 3.12 [95% CI, 1.34-7.31]; P=0.009). Incorporating LUS into GRACE resulted in a net reclassification index of 31.6% and a significant increase in the area under the curve; GRACE alone scored 0.705 compared with GRACE+LUS 0.791 (P=0.002). Detecting B-lines on LUS at the acute phase predicts major adverse cardiovascular events at 1 year in patients with ST-segment-elevation myocardial infarction and enhances the predictive value of the GRACE score. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04526535.

Sodium-glucose cotransporter-2 inhibitors in acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trials.

We aimed to assess the efficacy and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus placebo, initiated within the hospitalization period, in addition to habitual treatment, for treating adult patients with confirmed acute myocardial infarction (AMI). We also conducted subgroup analysis by diabetes mellitus (DM) status and type of AMI. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs). The primary outcome was hospitalization for heart failure (HF). The secondary outcomes were all-cause death, cardiovascular death, and serious adverse events (AEs). We pooled risk ratios (RR) with a 95% confidence interval (CI) for binary outcomes. The between-study variance was assessed using tau2 statistics. We included five RCTs, encompassing 11,211 patients. SGLT2i significantly reduced the risk of hospitalization for HF compared to placebo (RR 0.73; 95% CI [0.61, 0.88]). However, the risk of all-cause death (RR 1.05; 95% CI [0.78, 1.41]) and cardiovascular death (RR 1.04; 95% CI [0.84, 1.29]) was similar between the groups, as well as the risk of serious AEs (RR 1.01; 95% CI [0.90, 1.14]). In the subgroup analysis by DM status and type of AMI, there were no significant subgroup differences for the outcomes of hospitalization for HF and all-cause death. In patients with AMI, treatment with SGLT2i is safe and significantly reduces the risk of hospitalization for HF, but it has no impact on all-cause death and cardiovascular death compared to placebo.

Integrated, person-centred care for patients with complex cardiovascular disease, diabetes mellitus and chronic kidney disease; a randomized trial

Abstract Background Patients with cardiovascular disease (CVD), diabetes mellitus (DM), and chronic kidney disease (CKD) often experience fragmented care, which negatively impacts outcomes and health-related quality of life (HRQoL). This study assessed whether multidisciplinary, person-centred care at an integrated clinic improves clinical outcomes and HRQoL. Methods This prospective, open, blinded-endpoint trial (CareHND; NCT03362983) included 131 patients with CVD, DM, and CKD stages 3–4, most of whom were enrolled during or shortly after acute hospitalization. The intervention group received person-centred care from cardiologists, nephrologists, endocrinologists, and specialist nurses at an integrated clinic; the control group received traditional care from separate specialists. Primary disease progression outcome was the composite of major adverse renal and cardiovascular events (MARCE) including death, heart failure (HF) readmission, myocardial infarction, PCI/CABG, acute or end-stage kidney failure, or TIA/stroke at 2 years. Co-primary person-centred outcomes was self-reported HRQoL by RAND-36. Results In a pre-specified interim analysis, patients randomized to integrated care had lower eGFR and higher NT-proBNP than traditional care. Follow-up ranged from 2.0 to 5.7 years. Kaplan-Meier analysis showed no difference in MARCE between groups. Cox-regression adjusting for baseline differences, indicated a trend towards reduced HF hospitalisations for integrated care (HR 0.53; CI 0.28–1.01; P = 0.054). Integrated care improved Role Physical and Social Function scores, and self-rated health (P = 0.021, P = 0.019, and P = 0.011, respectively). Conclusions Integrated care improved several dimensions of HRQoL but did not improve MARCE compared to traditional care in this small trial. We observed a trend towards reduced HF hospitalizations. Overall, integrated care presents a promising alternative.

Relationship between chronic obstructive pulmonary disease and heart failure hospitalization in patients with atrial fibrillation: the Fushimi AF Registry

Abstract Background Chronic heart failure and chronic obstructive pulmonary disease (COPD) are both common diseases and often co-exist. Patients with COPD are at increased risk for hospitalizations due to cardiovascular diseases. However, in patients with atrial fibrillation (AF), the relationship between COPD and the risk of heart failure (HF) hospitalization remains unclear. Purpose The purpose of this study was to investigate the relationship between COPD and HF hospitalization in AF patients. Methods The Fushimi AF Registry, a community-based prospective survey, was designed to enroll all of the AF patients in Fushimi-ku, Japan. Fushimi-ku is densely populated with a total population of 283,000 and is assumed to represent a typical urban community in Japan. We started to enroll patients from March 2011, and follow-up data were available for 4,496 patients by the end of February 2022. We compared patients with and without COPD with regard to clinical background and HF hospitalization during follow-up period. Results In this cohort, the proportion of pre-existing HF among patients with COPD was 30.1%, and the proportion of COPD among patients with pre-existing HF was 5.9%. Of 4,496 patients, 238 (5.3%) patients had COPD (COPD; the mean age 75.6 years, female 20.6%), and the remaining 4,258 patients did not (Non-COPD; the mean age 73.5 years, female 41.6%). Patients with COPD were older than those without COPD. However, the proportions of patients with pre-existing HF, previous stroke, vascular disease, cardiomyopathy, coronary artery disease (CAD), diuretic use, renal dysfunction, diabetes mellitus (DM) and hypertension were comparable. During the median follow-up period of 1,824 days, the incidence of HF hospitalization was significantly higher in COPD than in Non-COPD (COPD vs. Non-COPD; 4.85% vs. 3.01% per person-year: p&amp;lt;0.01). In multivariate analysis adjusted by sex, age (≥ 75 years), heart disease (combined by heart failure, vascular disease, cardiomyopathy and CAD), renal dysfunction, DM, hypertension and diuretic use, COPD was an independent risk factor for HF hospitalization (hazard ratio (HR) 1.54, 95% confidence interval (CI) 1.15-2.07, P&amp;lt;0.01) (Figure 1). When we analyzed patients without pre-existing HF, the incidence of HF hospitalization was also significantly higher in COPD than in Non-COPD (COPD vs. Non-COPD; 2.87% vs. 1.75% per person-year: p=0.02). In multivariate analysis after adjusting for the same factors, COPD was an independent risk factor for HF hospitalization (HR 1.63, 95% CI 1.05-2.53, P=0.03) (Figure 2). Conclusion In patients with AF, COPD was the risk of HF hospitalization. The results were consistent in AF patients without pre-existing HF.

Impact of diabetes on vascular endothelial growth factor D and cardiovascular mortality in patients with suspected or known coronary artery disease: the ANOX study

Abstract Background Vascular endothelial growth factor D (VEGF-D) is a secreted glycoprotein that can induce lymphangiogenesis and angiogenesis. We recently demonstrated that serum levels of VEGF-D are independently associated with all-cause mortality in patients with suspected or known coronary artery disease (CAD). However, the impact of diabetes mellitus (DM) on the association between VEGF-D and cardiovascular (CV) mortality in those patients is unclear. Methods Serum VEGF-D levels were measured in 2418 patients with suspected or known CAD undergoing elective coronary angiography. The primary outcome was CV death. The secondary outcomes were all-cause death, major adverse CV events (MACE) defined as a composite of CV death, nonfatal myocardial infarction, and nonfatal stroke, and heart failure (HF) hospitalization. Patients were divided into 2 groups according to the presence (DM, n=1087) or absence (non-DM, n=1331) of DM, and followed up over a 6-year period. Results During the follow-up, 166 (81 DM and 85 non-DM) patients died from CV disease, 536 (284 DM and 252 non-DM) patients died from any cause, 297 (156 DM and 141 non-DM) patients developed MACE, and 268 (131 DM and 137 non-DM) patients developed HF hospitalization. After adjustment for potential clinical confounders and established CV biomarkers (i.e., N-terminal pro-brain natriuretic peptide, high-sensitivity cardiac troponin I, and high-sensitivity C-reactive protein), VEGF-D levels were significantly associated with all-cause death (hazard ratio [HR] for 1-SD increase, 1.20; 95% confidence interval [CI], 1.08–1.33) and HF hospitalization (HR, 1.23; 95% CI, 1.08–1.40), but not with CV death (HR, 1.18; 95% CI, 0.98–1.43) or MACE (HR, 1.11; 95% CI, 0.96–1.28), in DM patients, while VEGF-D levels were significantly associated with CV death (HR, 1.24; 95% CI, 1.08–1.43) and MACE (HR, 1.16; 95% CI, 1.03–1.32), but not with all-cause death (HR, 1.10; 95% CI, 0.99–1.22) or HF hospitalization (HR, 1.13; 95% CI, 0.99–1.28), in non-DM patients. The addition of VEGF-D levels to the model with potential clinical confounders and established CV biomarkers did not improve the prediction of CV death (P=0.92 for continuous net reclassification improvement [NRI], P= 0.32 for integrated discrimination improvement [IDI]), all-cause death (P=0.098 for NRI, P=0.12 for IDI), MACE (P=0.80 for NRI, P=0.53 for IDI) or HF hospitalization (P=0.96 for NRI, P=0.39 for IDI) in DM patients, whereas the addition of VEGF-D levels significantly improved the prediction of CV death (P=0.002 for NRI, P=0.03 for IDI) and all-cause death (P&amp;lt;0.001 for NRI, P=0.02 for IDI), but not that of MACE (P=0.11 for NRI, P= 0.09 for IDI) or HF hospitalization (P=0.89 for NRI, P=0.83 for IDI), in non-DM patients. Conclusions In patients with suspected or known CAD, the VEGF-D level independently predicted CV mortality in non-DM, but not in DM patients. The association between VEGF-D and CV mortality was attenuated in the presence of DM.

A U-shaped relationship between LVEF and the risk of heart failure hospitalization: a large hospital-based cohort study

Abstract Background Left ventricular ejection fraction (LVEF) is a frequently used metric for quantifying left ventricular function. Previous studies found a U-shaped relationship between LVEF and long-term survival. However, the association between the spectrum of LVEF and heart failure (HF) hospitalization remains unclear. Purpose We aim to investigate the distribution of HF hospitalizations across the spectrum of LVEF using a large hospital-based cohort. Methods Consecutive participants who underwent echocardiography (2002-2021) in a tertiary medical center in Taiwan were included. LVEF was measured by echocardiography using biplane Simpson’s method and was categorized into intervals of 5% from &amp;lt;20% to ≥70%. The study outcome was HF hospitalization by linking to the National Health Insurance Registry Database. Cox proportional hazards regression was used for analyses with adjustment for age, sex, hypertension, diabetes, hyperlipidemia, coronary artery disease, and history of HF. We used restricted cubic splines to demonstrate the distribution of HF hospitalizations across the spectrum of LVEF. Results 94,762 participants (age 59.7 ± 18.1, men 51.4%) were included. Adjusted hazard ratios (HR) for HF hospitalizations showed a U-shaped relationship between LVEF and the risk of incident HF hospitalization with a nadir of risk at LVEF of 60-70%. (Figure) Compared with the reference group (LVEF: 60-65%), subjects with LVEF&amp;gt; 70% had an HR of 1.49 (95% confidence interval [CI]: 1.21-1.84), and those with LVEF of 50-55% had an HR of 1.93 (95% CI: 1.68-2.22). Similar results with a nadir at 60-70% could be observed irrespective of different age groups defined by the World Health Organization (WHO), sex, with or without hypertension or diabetes. Conclusions A U-shaped relationship between LVEF and the risk of incident HF hospitalization can be observed, with a nadir at LVEF of 60-70%. LVEF ≥ 70% may be defined as supranormal LVEF that necessitates further HF treatment.Figure

Effect of renin-angiotensin system inhibitors in elderly patients with heart failure and reduced ejection fraction

Abstract Background More than half of the patients admitted for acute decompensated heart failure (ADHF) in Japan are over 80 years of age. Both Japanese and European heart failure guidelines recommend the use of renin-angiotensin system inhibitors (RASIs) in patients with heart failure with reduced ejection fraction (HFrEF). However, there is a paucity of data on the effect of RASIs in elderly patients with HFrEF, because elderly patients have been excluded from large clinical trials. Purpose The purpose of the current study was to clarify the effect of RASIs in elderly patients with HFrEF. Methods This was a post-hoc analysis of a prospective, observational, multicentre cohort study that enrolled consecutive patients admitted with ADHF to 19 secondary and tertiary hospitals in Japan between October 2014 and March 2016. Patients who were ≥ 80 years old, with left ventricular ejection fraction (LVEF) &amp;lt; 40% and discharged alive were included in the present study. RASIs were defined as either ACE inhibitors or angiotensin II receptor blockers. The primary endpoint was a composite of all-cause death and heart failure (HF) hospitalisation. Results Among 518 patients enrolled, 288 patients received RASIs at discharge and 230 patients did not. The median follow-up period was 335 days (interquartile range; 124 – 499 days). Patients receiving RASIs were younger (85.7 ± 4.4 vs. 86.5 ± 4.4 years of age, p=0.03), had a higher body mass index (BMI; 21.4 ± 3.3 vs. 20.6 ± 3.7 kg/m², p=0.01) and better renal function (eGFR; 45.4 ± 21.5 vs. 38.2 ± 19.2 ml/min/1.73m², p&amp;lt;0.001). Patients receiving RASIs had a higher LVEF (30.9 ± 6.3 vs. 28.5 ± 7.1%, p&amp;lt;0.001). The use of beta-blockers at discharge was more prevalent in patients receiving RASIs (77.8% vs. 60.4%, p&amp;lt;0.001), but the use of mineralocorticoid receptor antagonists was not (50.0% vs. 42.2%, p=0.08). The cumulative incidence of all-cause death or HF hospitalisation one year after discharge was significantly lower in patients receiving RASIs (40.1% vs. 59.5%, p&amp;lt;0.001). Even after adjusting for confounders, the risk of a composite of all-cause death and HF hospitalisation was significantly lower in patients receiving RASIs (adjusted hazard ratio 0.59, 95% confidence interval 0.45-0.77, p&amp;lt;0.001). There was no interaction between the effect of RASIs and subgroup factors such as age, BMI, dementia, malignancy, frailty, and renal function. Conclusion Use of RASIs at discharge was associated with lower incidence of all-cause death or HF hospitalisation in elderly patients with HFrEF.

Impact of a clinician-to-clinician electronic consultation program in heart failure patients with previous hospitalization. Implications for heart failure multidisciplinary management

Abstract Background A clinician-to-clinician electronic consultation (e-consultation) programme may not only improve the accessibility to care but may also impact patient outcomes, particularly in heart failure (HF) patients with a previous episode of hospitalization (HFH), group of patients associated with a worse outcome. Purpose To evaluate the impact of an outpatient care management programme that includes a clinician-to-clinician e-consultation on delay time in care, hospital admissions, and mortality in a high-risk group of patients with heart failure (HF) and previous episodes of HF hospitalization (HFH). Materials and methods We selected 6444 HF patients who visited the cardiology service at least once between 2010 and 2021. Of these, 4146 were attended in e-consultation, and 2230 had previous HFH (Fig 1a). Using an interrupted time series regression model, we analysed the impact of incorporating e-consultation into the healthcare model in the group of patients with HFH and evaluated the elapsed time to cardiology care, HF, cardiovascular (CV), and all-cause hospital admissions and mortality, calculating the incidence relative risk (iRR). We performed a multivariate logistic regression for each of these outcomes in both groups. Results Patients with HFH had a higher prevalence of men (P &amp;lt; 0.001) but had a similar age (P = 0.267) compared to patients without HFH. Patients with HFH had a higher prevalence of diabetes (P &amp;lt; 0.001), ischaemic heart disease (P = 0.036), and peripheral arterial disease (P = 0.008) (Fig 1b). In the group of patients with HFH, the introduction of e-consult substantially decreased waiting times to cardiology care (8.6 [8.7] vs. 55.4 [79.9] days, P &amp;lt; 0.001) (Fig 2a). In that group of patients, after e-consult implantation, hospital admissions for HF were reduced (iRR [95%CI]: 0.837 [0.840–0.833]), 0.900 [0.862–0.949] for CV and 0.699 [0.678–0.726] for all-cause hospitalizations (Fig 2b). There was also lower mortality (iRR [95%CI]: 0.715 [0.657–0.798] due to HF, 0.737 [0.764–0.706] for CV and 0.687 [0.652–0.718] for all-cause) (Fig 2c). The improved outcomes after e-consultation implementation were significantly higher in the group of patients with previous HFH. The multivariate analyses showed a higher risk of hospitalizations in men, patients with HFH, and those who required more emergency department assistance (Fig 2d). Conclusions In patients with HFH, an outpatient care programme that includes an e-consultation significantly reduced waiting times to cardiology care and was safe, with a lower rate of hospital admissions and mortality in the first year. Our results may have implications for optimize the heart failure care organization.Figure 1Figure 2