Heart Failure Admissions Research Articles

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.

Long-term outcomes after transcatheter aortic valve implantation: derivation and validation of the long-TAVI prediction model

Abstract Background Identification of high-risk individuals after transcatheter aortic valve implantation (TAVI) is essential to personalized care. Established risk models require a plethora of variables, fail to account for biomarker dynamics and imaging parameters, mostly focus on the short term, and offer limited predictive performance. Purpose We aimed to develop an easily applicable prediction model for long-term mortality or heart failure (HF) admission following TAVI. Methods Patients undergoing TAVI at a high-volume university centre in the United Kingdom (n = 990) were recruited into a prospective cohort study. Enrolled patients were divided into a development cohort (07/2007 – 12/2016) and a validation cohort (01/2017 – 11/2018) and followed for up to 15.1 (median 5.3, interquartile range [IQR] 2.8 – 7.4) years. Patient characteristics along with pre- and post-procedural imaging results and brain natriuretic peptide (BNP) levels before the procedure and at 3 months were recorded. A clinical risk score for long-term mortality and HF admission (i.e., Long-TAVI risk score) was derived using Cox regression and evaluated using time-dependent area under the receiver operating characteristics curve (AUC). Results Age at presentation was 79.8 (standard deviation [SD] 8.9) years, 961 (99.0%) patients had signs of heart failure, left ventricular ejection fraction was 52 (SD 11.2), and pre-TAVI BNP levels were 298.0 (interquartile range [IQR] 159.0 – 571.5) pg/mL. High BNP levels at presentation (higher vs. lower than 400 pg/mL: HR 1.50, 95% CI 1.17 – 1.92, P < 0.001) and dynamic changes in BNP with the first 3 months (low/high vs. low/low: 2.61, 95% CI 1.17 – 5.86, P = 0.020; high/high vs. low/low: 2.41, 95% CI 1.26 – 4.64, P = 0.008) were independent predictors mortality or HF admission. The simple 8-item Long-TAVI score accounts for periprocedural BNP dynamics and shows good discrimination (AUC 0.76, 95% CI 0.72 – 0.79) and calibration in the development cohort performing similarly well in the external validation cohort (AUC 0.70, 95% CI 0.63 – 0.77). Long-TAVI significantly outperformed the logistic EURO score (AUC 0.56, 95% CI 0.52 – 0.59, P < 0.001). Conclusion Both pre-TAVI BNP levels and periprocedural BNP trajectories are independently associated with long-term outcomes after TAVI. Accounting for clinical characteristics, imaging parameters, and circulating BNP levels, the newly developed Long-TAVI risk score achieves high performance and provides the first prediction model for long-term mortality or HF admission. Long-TAVI represents a novel tool for personalized risk assessment in patients undergoing TAVI.Correlation at baseline A) and FUP B)Score performance A) and risk groups B)

Prognostic determinants in patients with heart failure with reduced ejection fraction after a first hospitalisation for acute heart failure. COMFE registry

Abstract Introduction The clinical characteristics and determinants for prognosis of patients with a first hospitalisation for heart failure (HF) with reduced left ventricular ejection fraction (LVEF <40%) are poor described and show heterogeneous results that need major investigation. Purpose The aim of our study was to identify the clinical characteristics, prognosis and their main determinants in a prospective registry of patients with HF and reduced LVEF with a first hospital admission for acute heart failure, prognosis and their main determinants in a prospective registry in these patients. Methods We carried out a prospective registry in 2 University Hospitals of patients admitted to cardiology department due to first-time HF hospitalisation with reduced LVEF. 231 admitted consecutively between March 2021 and September 2022 were included, with a mean follow-up of 381 days. Continuous variables were represented as median (interquartile range) and categorical variables as percentage %. A multivariate logistic regression was performed in which age, sex, comorbidities, treatment, rhythm at discharge and improvement in LVEF were included; and using the Wald method, the predictors of rehospitalization and/or death were identified. Data were analysed using SPSS v. 25.0. Results The main baseline characteristics are shown in Table 1. The population had a median age of 71 years, 75% were men, with a high prevalence of arterial hypertension (HBP) (69%) and hyperlipidemia (57%). Quadruple therapy (Na-Glucose cotransporter 2 inhibitor [SGLT2i], Beta-Blocker, mineralocorticoid receptor antagonist [MRA] and angiotensin receptor-neprilysin inhibitor [ARNI], angiotensin converting enzyme inhibitor [ACEi] or Angiotensin-II receptor blocker [ARB]) was achieved in 57% at discharge. The dynamics of NTproBNP was studied from admission to completed up-titration, observing an average reduction of 37% and 32% met the criteria for improved LVEF after. The etiology is described in Figure 1a, with ischemic heart disease being the most represented (31%). Multivariate Cox regression for the combined event of readmission/death from any cause showed that treatment with SGLT2i (OR 0,48 [CI 95%: 0,23-0,98 p:0,04]) and Beta-Blocker (OR 0,35 [CI 95%: 0,14-0,87 p:0,02]) at discharge and improved LVEF (OR 0,33 [CI 95%: 0,15-0,72 p:0,006]) were protective predictors against the event; but diabetes mellitus (DM) was a predictor of a worse prognosis (OR 2,9 [CI 95%: 1,52-5,5 p:0,001]) Fig. 1b. Conclusions Patients with a first admission for HF with reduced LVEF constitute a heterogeneous clinical group. Improvement in LVEF after drug up-titration and treatment with SGLT2i and Beta-blocker are independently associated with a better prognosis. Our findings may have implications for their clinical management.Table 1Figure 1

Ablation strategy for patients with atrial fibrillation and heart failure - a Danish nationwide cohort study

Abstract Introduction Atrial fibrillation (AF) patients with heart failure (HF) face increased risks of AF recurrence and HF admission. Catheter ablation (CA) is a recognized treatment option. Due to observed atrial remodelling and fibrosis associated with ventricular remodelling in HF patients, it could be suggested that a more comprehensive ablation strategy should be applied for these patients. Purpose To examine the risk of AF recurrence and HF admission by ablation strategy for patients with AF and HF. Method This nationwide cohort study was conducted using real-life data from Danish healthcare registries. All patients above 18 years of age, with a diagnosis of AF and HF that underwent first-time CA from January 1st 2010 to December 31st 2018, were identified and included at the date of ablation. Exposure of interest was ablation strategy - pulmonary vein isolation (PVI) or additional ablation to PVI (PVI plus). PVI plus was defined as either roofline, mitral linear ablation, posterior wall isolation, complex fractionated atrial electrograms or ganglionated plexi ablation. Primary endpoint was HF admission and AF recurrence after a 3-months blanking period. AF recurrence was defined by a composite endpoint of first-reached endpoint of either use of antiarrhythmic drugs, AF admission, electrical cardioversions, or AF re-ablation. The relative rates of recurrent AF and HF admission by ablation strategy (PVI or PVI plus) were examined by Cox proportional models using PVI as reference. The analyses were adjusted for clinically important baseline characteristics including age, sex, AF type (paroxysmal or persistent), diagnosis-to-ablation time, procedural year, body mass index, size of left atrium, as well as co-morbidities such as ischemic heart disease, chronic obstructive pulmonary disease, chronic kidney disease, hypertension, and diabetes. Results The study cohort consisted of 1,270 patients diagnosed with AF and HF undergoing first-time CA, of which 1,119 (88%) received PVI and 151 (12%) received PVI plus. 80% where males in both groups. Median age was 62 for the PVI group and 64 for the PVI plus group. Severely enlarged left atrium, ischemic heart disease and use of amiodarone were more prevalent in the PVI plus group compared to the PVI group (Table 1). The relative risk of recurrent AF showed a hazard ratio of 1.02 (95% CI: 0.77-1.37) for the PVI plus group compared to the PVI group, and for HF admission the hazard ratio was 0.95 (95% CI: 0.55-1.65) for the PVI plus group compared to the PVI group (Figure 1). Conclusion No significant differences in AF recurrence and HF admission were observed between PVI and PVI plus strategy in AF and HF patients in this observational study. With a diagnosis-to-ablation time exceeding 3 years, it could be argued that advanced atrial remodelling may diminish the impact of reverse atrial remodelling after catheter ablation, irrespective of the ablation strategy employed.Table 1Figure 1

Angiotensin receptor-neprilysin inhibitor (Sacubitril/Valsartan) in cancer therapy-related cardiac dysfunction: real-world experience from a nurse-led cardio-oncology clinic

Abstract Introduction Cancer therapy-related cardiac dysfunction (CTRCD) is a common toxicity amongst patients receiving anti-cancer treatment1. Angiotensin receptor-neprilysin inhibitor (ARNI) Sacubitril/Valsartan is recommended to reduce Heart Failure (HF) admissions and cardiovascular mortality2. However, patients with active cancer were excluded from the key trials of ARNI. This study aims to provide a real-world experience of ARNI prescription and management from the perspective of a nurse-led Cardio-Oncology clinic. Methods This is a single centre, retrospective, observational cohort study performed at a Cardio-Oncology specialist centre between the period of 2021 to 2024. Adult cancer patients receiving anti-cancer therapy were included if they had symptomatic HF or asymptomatic CTRCD, were initiated on ARNI and followed up in the nurse-led Cardio-Oncology clinic. Results Twenty-nine patients were started on ARNI (see Figure 1). The mean age of the patients was 66+11 years and 17 (59%) were male. Cardiovascular risk factors were common: hypertension (45%), hyperlipidaemia (35%), diabetes mellitus (21%), and smoking (17%). Haematological and breast malignancies were most common (31% and 21% respectively), followed by gynaecological malignancies (14%). Twenty-one (72%) were treated with cytotoxic chemotherapy including 10 (35%) received anthracyclines. Five (17%) patients received human epidermal growth factor receptor 2 (HER2) targeted therapies, 3 (10%) were on tyrosine kinase inhibitors, and 2 (7%) received immunotherapy. Twenty-five (86%) patients presented with symptomatic HF while 4 (14%) had asymptomatic CTRCD. The median N-terminal-pro B-type natriuretic peptide (NTproBNP) level was elevated at 1325(806-4330)ng/L. Thirteen (45%) patients tolerated the maximum dose of 200mg twice daily, while 16 (56%) could only tolerate middle and lowest dosages. ARNI dose up titration to the maximum tolerated dose took 26 (15-79) days. Twenty-eight (97%) patients were on beta blockers, 26 (90%) received SGLT2 inhibitors, 25 (86%) on mineralocorticoid receptor antagonists, and 10 (35%) patients required diuretics. The most common side effect was symptomatic hypotension in 11 (38%) patients. Two (7%) had hyperkalemia, 1 (3%) acute kidney injury following initiation, and 1 (3%) had dizziness without significant hypotension. Nine (31%) required dose reduction allowing ARNI to be continued, while 3 (10%) patients had to permanently discontinue ARNI. There were no cardiovascular deaths, cancer deaths or HF admissions. Conclusion The Cardio-Oncology nurse-led clinic permits rapid up-titration of ARNI to target dosages in patients with CTRCD, resulting in significant improvements in cardiac function. The nurse lead clinic education, support and side effect management allowed uninterrupted continuation of cancer treatment. Whether this approach translates into be better cardiac and cancer outcomes requires further study.

Prognostic implications of N-terminal pro-brain natriuretic peptide in patients with Non-ST segment elevation myocardial infarction

Abstract Background Limited data exist regarding prognostic implications of N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) in patients with non-ST segment elevation myocardial infarction (NSTEMI) who underwent percutaneous coronary intervention (PCI). Objectives The current study sought to evaluate the prognostic implications of NT-proBNP in patients with NSTEMI who underwent PCI. Methods Among a total of 13,104 patients from a nationwide, multicenter, and prospective registry of the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH), a total of 3,083 patients with NSTEMI who underwent PCI were selected. The selected patients were classified according to the initial NT-proBNP value (cut-off value of NT-proBNP, 700 pg/ml). Primary endpoint was major adverse cardiovascular events (MACE) at 3 years, a composite of all-cause death, recurrent myocardial infarction (MI), unplanned repeat revascularization, and admission for heart failure. Results Among the study population, 1,813 patients (58.8%) were in the low NT-proBNP group (<700 pg/ml) and 1,270 patients (41.2%) were in the high NT-proBNP group (≥700 pg/ml). The high NT-proBNP group showed significantly higher risk of MACE than the low NT-proBNP group (29.5% vs 12.3%; adjusted hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.39-2.07; P<0.001), mainly driven by higher risk of cardiac death or admission for heart failure (15.6% vs. 2.2%; adjusted HR, 2.98; 95% CI, 2.03-4.40; P<0.001). These results were consistent after confounder adjustment by propensity score matching (HR, 1.56; 95% CI, 1.21-2.02; P=0.001) and inverse probability weighting analysis (HR, 1.54; 95% CI, 1.19-2.00; P=0.001). Conclusion In patients with NSTEMI who underwent PCI, elevated initial NT-proBNP level was associated with higher risk of MACE at 3 years, mainly driven by the higher risk of cardiac death or admission for heart failure. The current results suggest that the initial NT-proBNP level may have a clinically significant prognostic value in NSTEMI patients undergoing PCI.

Dynamics and prognostic role of persistent angina in chronic coronary syndrome with clinical, angiographic and stress CMR evidence of ischemia

Abstract Background In patients with established chronic coronary syndrome (CCS), the significance of myocardial ischemia is a controversial issue. Persistent angina within the first year after treatment intervention has ranged widely in previous studies and its association with subsequent hard clinical events is unclear. We aim to evaluate the long-term dynamics of angina class and the prognostic role of persistent angina in symptomatic chronic coronary syndrome (CCS) patients with abnormal stress cardiovascular magnetic resonance (CMR) and altered angiography. Methods We analyzed 486 CCS patients with Canadian Cardiovascular Society angina class ≥2, perfusion deficit in stress CMR and severe lesions in angiography submitted to treatment intervention (medical therapy plus, if feasible, CMR-guided revascularization). The dynamics and association of persistent angina at 6 months post-intervention with subsequent cardiac death, myocardial infarction, and admission for heart failure were investigated. Results All patients displayed angina class ≥2 (mean: 2.7±0.7), abnormal stress CMR (mean ischemic burden: 6.2±3 segments) and severe angiographic lesions. Most underwent CMR-guided revascularization (n=392, 81%). The angina resolution rate was 78% at 6 months, and 79%, 77%, and 75% at 1, 2, and 5 years respectively. Compared with medical treatment alone, CMR-guided revascularization was associated with less persistent angina (19% vs. 35%; HR 0.42 [0.2–0.7]; p=0.003). During an 8.3-year median follow-up, persistent angina was independently associated with higher subsequent cardiac death rates (18% vs. 4%; HR 10.9 [4.1–29.2]; p<0.001), myocardial infarction (24% vs. 6%; HR 5.8 [3.2–10.4]; p<0.001), and admission for heart failure (31% vs. 14%; HR 2.7 [1.7–4.2]; p<0.001). Conclusions In CCS patients with robust diagnostic evidence by symptoms, stress CMR and angiography, sustained improvement of anginal symptoms can be achieved in most patients after treatment intervention. Angina resolution is more frequent in patients treated with CMR-guided revascularization and is associated with fewer cardiac events.Central Figure.Persistent angina and MACE risk

Prognostic implications of microvascular resistance reserve in symptomatic patients with intermediate coronary stenosis

Abstract Background Microvascular resistance reserve (MRR) is a novel index reflecting coronary microcirculatory function, irrespective of epicardial coronary artery stenosis. There is limited evidence regarding whether MRR can be an independent prognostic tool in patients with stable ischemic heart disease (IHD). Objective To evaluate clinical outcomes according to MRR in patients with stable IHD accompanied with or without significant epicardial coronary artery stenosis. Methods The current study included 547 consecutive patients undergoing systematic echocardiographic and invasive physiologic assessment for suspected stable IHD. Significant epicardial coronary artery stenosis was defined as fractional flow reserve (FFR)≤0.80. Coronary microvascular dysfunction (CMD) was defined as MRR≤3.0. Primary outcome was major adverse cardiovascular event (MACE), a composite of cardiovascular death, myocardial infarction, repeat revascularization, and admission for heart failure. Results Among the total patients, 172 patients (31.4%) had FFR≤0.80 and 200 patients (36.6%) had CMD defined by MRR≤3.0. MRR showed no significant correlation with FFR (R=-0.031, P=0.469), however, it was significantly correlated with index of microcirculatory resistance (R=-0.353, P<0.001), NT-proBNP (R=-0.296, P<0.001), left ventricular filling pressure (E/e’) (R=-0.224, P<0.001), and diastolic dysfunction grade (P<0.001). During median follow-up of 3.3 years (interquartile range from 2.0 to 4.5 years), MRR was significantly associated with MACE risk (HR 1.23 per-1 decrease, 95% CI 1.12-1.36, P<0.001). CMD defined by MRR≤3.0 was associated with an increased MACE risk in both FFR>0.80 (41.0% vs. 26.0%; HRadj 1.59, 95% CI 1.07-2.35, P=0.021) and FFR≤0.80 (34.7% vs. 14.8%; HRadj 2.32, 95% CI 1.12-4.82, P=0.024) groups. Conclusion Decreased MRR was associated with the presence of cardiac diastolic dysfunction as well as with increased left ventricular filling pressure. The presence of CMD defined by MRR was independently associated with the risk of a composite of cardiovascular death, myocardial infarction, repeat revascularization, and admission for heart failure in patients with stable IHD, irrespective of significant epicardial coronary artery stenosis.

Predictors of heart failure hospitalization after surgery in patients with primary mitral regurgitation: the relevance of left atrial coupling index

Abstract Background and Aims The main indications for surgery in patients with primary mitral regurgitation (PMR) include the presence of symptoms, left ventricular dysfunction (LVEF ≤60%) and dilation (LVESD ≥ 40 mm), but novel markers are needed to detect early myocardial damage. Our aim was to explore the impact of echocardiographic parameters on the incidence of heart failure (HF) hospitalizations after surgery in our cohort of patients with PMR. Methods Retrospective analysis of a prospective cohort of patients with PMR who underwent mitral valve surgery in a tertiary care center from 2014 to 2022. Echocardiographic parameters measured prior to surgery were analyzed. The primary outcome was HF admissions during follow-up. Results 349 patients were included. The mean age was 69 (12) years and 55.9% were male. During a mean follow up of 3.28 (2) years, 13 patients (3.7%) were admitted due to HF. Variables significantly associated with HF admissions were: female gender, atrial fibrillation prior to surgery, LVEF, LV end-diastolic volume index, LV global longitudinal strain, left atrial coupling index [LACI] (end-diastolic left atrial volume/end-diastolic LV volume), TAPSE and right ventricular-arterial coupling. In a multivariable logistic regression analysis, the only independent predictors of HF admissions were female gender (OR 5.68), LVEF (OR 0.93) and LACI (1.87) (p<0.05). Conclusions In our cohort of patients with PMR, apart from LVEF, LACI was the only echocardiographic parameter independently associated with HF hospitalizations after surgery. This easy to obtain echocardiographic parameter, which takes into account the interrelation between LA and LV compliance, could help guide patients’ management in this setting.Table 1

Sodium-glucose co-transporter-2 inhibitors : a potential cardioprotective agent?

Abstract Background Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are one of the cornerstones in the treatment of patients with heart failure (HF) , regardless the ejection fraction (EF) or the presence of diabetes mellitus (DM). Other types of medications used in the treatment of heart failure , like angiotensin converting enzyme inhibitors (ACEi) or beta-blockers (BB) have shown some degree of cardioprotection in high risk patients receiving cardiotoxic chemotherapy, but data on SGLT2i are very limited. Purpose To examine the possible differences in the development of anthracycline cardiotoxicity in diabetic patients receiving SGLT2i compared to those who don’t. Methods We retrospectively analysed the data from the oncological as well as hematological patients of our hospital. Group 1 (SGLT2) included patients with cancer who received anthracycline treatment and diabetes on treatment with SGLT2i. Group 2 (control) included patients with cancer who received anthracycline treatment and diabetes but with treatment other than SGLT2i. We recorded the basic demographic parameters, the development of cardiotoxicity (heart failure incidence, heart failure admissions, new cardiomyopathy [>10% decline in ejection fraction to <50%], and clinically significant arrhythmias) as well as the abnormal levels of troponin I (tnI) and natriuretic peptides (NTproBNP). Results Age, sex, ethnicity, cancer type, cancer stage, and other cardiac risk factors were similar between groups. The mean duration of the follow up was 2 years. In the SLT2 group were included 86 patients and in the control group 97. The rates of the cardiotoxicity events were recorded as follow : (SGLT2 vs control) Heart failure (7.4% vs 31.9%, p<0.01), heart failure admissions (3.4% vs 12.3%, p<0.05), new cardiomyopathy (6.1% vs 27.2%, p<0.05), arrhythmias (2.7% vs 24.3%, p<0.01), abnormal tnI levels (4.2% vs 14.7% , p< 0.01), abnormal NTproBNP levels (6.4% vs 30.9%, p<0.01) Conclusions SGLT2 inhibitors were associated with lower rate of cardiac events among patients with cancer and DM who were treated with anthracyclines. Further studies are needed in order to test the possible cardioprotective effects of SGLT2 inhibitors in patients at high cardiac risk treated with anthracyclines.

Cardiac resynchronization therapy in adult congenital heart disease: single center cohort study

Abstract Introduction Cardiac resynchronization therapy (CRT) is a recommended therapeutic measure for patients with heart failure. Heart failure is a major morbidity amongst patients with adult congenital heart disease (ACHD). However, the data on the efficacy and safety of CRT amongst ACHD is limited. Methods Data was analyzed from a retrospective cohort of patients with a known diagnosis of ACHD and implantation of CRT between 2015-2022. The primary outcome was echocardiographic response to CRT. This was defined as either:1) an increase in systemic ventricular ejection fraction (EF) of ≥5% in patients with EF <50% (therapeutic) or 2) maintenance of EF in patients with EF≥50% (preventative). Secondary outcomes included change in QRS duration, heart failure admissions, death and CIED (cardiovascular implantable electronic devices) infection during follow up. The outcomes were also assessed by subgroup of systemic left or right ventricle systemic ventricle. Results Our cohort included 46 patients, 96% male and average age was 54±14 years. 26 patients had a systemic left ventricle (56.6%) and 20 patients had a systemic right ventricle (44.4%). The indication for CRT implantation was 1) Reduced EF with wide QRS (n=10, 22%), 2) Reduced EF and RV (right ventricular) pacing (n=22, 49%), and 3) Normal EF with RV pacing (n=14, 33%). 25 patients (55%) had an implanted defibrillator at baseline. Primary outcome amongst patients with preserved EF at baseline was achieved in 22/32 patients (68.7%) and was achieved in 12/14 patients (85.7%) amongst patients with reduced EF at baseline. During follow up, QRS duration was shortened in 68.7%, 13 patients had heart failure admissions (30%), 4 patients underwent heart transplants/mechanical support device implantation (8.6%), death occurred in 11 patients (24%) and 3 had CIED infection (7%). There was no significant difference in complication or efficacy rates between the left systemic and right systemic group. Conclusion CRT is effective in patients with ACHD both as a therapeutic and as a preventative measure for heart failure. There was no difference in clinical response to CRT between patients with SRV compared to SLV. The percentage of patients with a safety outcome was relatively high in this subpopulation due to advanced ACHD.

Assessing one-year risk of heart failure following first time myocardial infarction and subsequent five-year mortality risk: a nationwide study of 34,401 patients

Abstract Introduction A comprehensive understanding of the post-myocardial infarction (MI) trajectory leading to heart failure (HF) and its profound impact on long-term mortality is imperative for effective secondary prevention and risk assessment. Methods We conducted a registry-based nationwide cohort study of all Danish patients with a first MI during 2014 to 2020. Excluding patients with prior HF, individuals were followed for one year post-MI, assessing HF incidence through hospital admissions and visits to elective HF ambulatory clinics. Among those who survived one year, long-term mortality 1-6 years post-index MI was assessed using landmark analysis and Cox proportional hazards models adjusting for age, gender and comorbidities and hazard. Patients were categorized into three groups: not HF, referred for elective HF outpatient follow-up, and acute admission for HF. Results Among 34,301 individuals with a first MI and surviving the first year (median age 67.5, and 66.9 % male), 3.3 % were admitted acute for HF while 11.2 % had an elective HF outpatient follow-up within one year of the MI event (see Figure 1a). We observed a significant association between acute HF admissions post-MI and increased five-year mortality risk (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.40-1.90, p-value <0.001, see Figure 1b) (absolute 5-year risk: 18.4 %). In contrast, the five-year mortality risk for patients with elective outpatient HF follow-up was comparable to that of individuals without HF (HR 1.06 [0.94-1.19], p-value 0.34) (absolute 5-year risk: 9.6 vs 8.5 %). Conclusion Our findings suggest that acute admission for HF after a first time MI occur in 3.3 % of the patients with a subsequent significantly increased mortality risk compared to patients that do not develop clinical HF. Admission for HF in patients with a first time MI should be considered as a relatively rare but fatal complication.

Heart failure and advanced chronic kidney disease: differences in characteristics, treatment and outcomes in patients with glomerular filtration rate greater or less than 30 ml/minute/m2

Abstract Introduction Heart failure (HF) is a serious health problem and continues to have a high mortality and incidence of decompensation, despite advances in its management. Chronic kidney disease (CKD) is very prevalent in patients with HF, hinders their treatment and worsens their prognosis, especially when it is advanced CKD (glomerular filtration rate-GFR <30 ml(min/m2). It is important to know the differential characteristics of these patients to improve their management. Purpose To analyze in a contemporary registry of HF patients followed in specialized HF units in Spain the differences in clinical characteristics and treatment between patients with HF and advanced CKD. Methods We analyzed data from the registry of the SEC-Excelente-IC quality accreditation program of the Spanish Society of Cardiology, with 1716 patients with HF included between 2019 and 2021 by 45 specialized HF units accredited by the SEC. Patients were included consecutively in two 1-month cutoffs (March and October) in that period. The clinical and demographic characteristics and comorbidities of the patients were compared according to GFR < or > 30ml/min/m2. Results Of the 1,716 patients, 11.1% had a GFR<30 and 88.9% >30 mL/min/m2. Figure 1 shows the main clinical characteristics and comorbidities of the 2 groups. Median LVEF was similar in both groups: 42 (30-58) vs 38% (29-54). The group with advanced CKD was older (77±9.6 vs 70.5±12.6 years; p<0.001), had greater HF severity (more admissions for HF in the last year, worse NYHA functional class and longer evolution time), and a higher prevalence of coronary heart disease, hypertension, diabetes mellitus, cognitive impairment, anemia, iron deficiency and hyponatremia. There were no differences in sex, BMI, serum potassium or other comorbidities (Figure 1). Figure 2 shows the treatment received in each group. Patients with GFR <30 received in a significantly lower proportion all drugs for HF (p<0.001), except diuretics and potassium binders (ACEI/ARA, sacubitril-valsartan, MRA, beta-blockers, digoxin and SLGT2 inhibitors), and less cardiac rehabilitation (5.2 vs 10.4%; p=0.029). Incidence of one-year mortality was significantly higher in patients with GFR<30 ml/min/m2 (37.2 vs 14.4 per 100 persons-year, p<0.001), as were HF hospitalizations (61.3 vs 33.0; p<0.001) and HF decompensations without hospitalization (24.1 vs 11; p<0.001). Conclusions In our contemporary cohort of real-life HF patients, the prevalence of advanced CKD was 11.1%. These patients had a higher severity of HF, despite which, the utilization of HF drugs, including SGLT2 inhibitors was much lower than in those with GFR >30 ml/min/m2. One-year mortality, HF hospitalization and HF decompensations were almost 3-times higher. This treatment trend needs to be modified to improve the prognosis of these patients.

Regadenoson stress echocardiography: a road ahead

Abstract Introduction Drugs used in stress echocardiography (SE) have important limitations due to side effects and contraindications. Since its approval in 2008, Regadenoson has seen a significant increase in usage. This is largely attributed to its good safety profile and diagnostic accuracy, making it the preferred drug for stress tests in many European centers. However, despite its expanding use and major advantages, current guidelines don't place it as the first choice for SE, probably because the reported experience with this drug remains limited. The aim of the present study was to assess the safety and short-medium term prognosis of patients who underwent Regadenoson SE. Methods Retrospective observational study. Patients who underwent Regadenoson SE between 2017 and 2023 were included. Safety was assessed by monitoring immediate adverse effects following Regadenoson infusion and the need for using an antidote (Aminophylline). A positive test result was defined by the occurrence of any of the following: wall motion abnormalities, left ventricle dilatation, electrocardiographic changes or symptoms of ischemia. During the follow up, we registered the incidence of ischaemic events (admission for unstable angina, acute myocardial infarction (AMI) or cardiovascular (CV) death) and other CV events such as admission for heart failure (HF) and stroke. Additionally, we evaluated patients in both groups who underwent coronary angiography (by computerized tomography or coronary catheterization) during the follow up period. The groups with negative SE (NSE) and positive SE (PSE) were compared. Results The total number of patients was 344, with a median follow up of 29 months. Basal population characteristics and events by group (NSE and PSE) are shown in Figure 1. We needed to use the antidote in only one case, because of ventricular bigeminism, with no other major adverse effects reported. SE was positive in 37 (11%) patients. In this group, patients were more likely to present ischaemic events (16% vs. 3%, p<0.01) and admissions for HF (24% vs. 5%, p <0.01), compared to the NSE one. In those who underwent coronary angiography, revascularization was needed in 14 patients of the PSE group, and only in 7 of the NSE group (38% vs 2%, p < 0.05). The indications for these last cases were persistent angina in 5 patients (2 of them with history of coronary artery disease) and revascularization following an AMI in 2 patients. (Figure 2). Conclusions The probability of an ischaemic event after a negative Regadenoson SE remains very low, unlike positive studies. Regadenoson SE showed to be both safe in assessing ischemic cardiomyopathy and very useful for its prognostic value. These findings encourage its expanding use in the stress echo lab.

Pathogenic cardiomyopathy gene variants inform prognosis in atrial fibrillation: results from exome sequencing in over 17,000 patients in TIMI trials

Abstract Background Rare genetic variants in cardiomyopathy genes are associated with risk of atrial fibrillation (AF), even in the absence of overt ventricular dysfunction. Data on clinical outcomes for rare genetic variant carriers among patients with AF remain sparse. Purpose We aimed to study the prognostic implication of rare pathogenic/likely pathogenic (PLP) variants for dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC) in patients with AF from large, well-phenotyped randomized clinical trials. Methods and results Rare variants were called using exome sequencing data in 5 large clinical trials from the TIMI study group (ENGAGE-AF, FOURIER, SAVOR, PEGASUS, DECLARE). PLP variants for cardiomyopathy were identified using phenotype- and gene-specific curation of protein-truncating variants and high-confidence variant classifications from the ClinVar database. In 17,190 patients with a history of AF, we identified 421 (2.4%) PLP variant carriers (age 67±10, 35% women) and 16,769 (97.6%) pts without PLP variants (age 70±9, 36% women). Among these individuals, we identified 265 DCM carriers (1.5%), 106 (0.6%) HCM carriers and 54 (0.3%) ARVC carriers. In this cohort, 9,275 (54%) had a history of heart failure (HF) and 2,991 (17.4%) prior ischemic stroke. Over 2.5 years median follow-up, 1,365 pts (7.9%) were hospitalized for HF, 599 (3.5%) had an ischemic stroke, and 1147 (6.7%) died of cardiovascular causes. In logistic regression analyses adjusting for age, sex, trial, and principal components of ancestry, PLP variants were significantly associated with a history of HF (OR 1.66, p<0.0001), most notably for DCM variants (OR 1.97, 1.48-2.62, p<0.0001). PLP variants were independently associated with incident HF admissions (adj HR 1.75, 1.39-2.29, p<0.0001), most notably for HCM (adj HR 2.59, 1.68-3.99, p<0.0001) and ARVC variants (adj HR 2.50, 1.34-4.66, p=0.004). The increased risk of HF admissions remained consistent in patients with (adj HR 1.49, 1.11-2.00, p=0.009) and those without (adj HR 1.88, 1.00-3.54, p=0.049) a history of HF. PLP variants were also associated with higher risk of cardiovascular death (adj HR 1.46, 1.06-2.02, p=0.02), most notably for DCM variants (adj HR 1.77, 1.21-2.58, p=0.003). In contrast, PLP variants were not associated with history of ischemic stroke at baseline (adj OR 0.99, p=0.96) nor with incident ischemic stroke (adj HR 0.95, p=0.84). Conclusion In patients with AF, rare cardiomyopathy gene variants are associated with increased risks of HF and of cardiovascular death, but not stroke. These results, collected from large well-phenotyped randomized clinical trials, demonstrate an important prognostic implication for rare genetic variants for CMP in pts with AF.

The association between endogenous erythropoietin levels and the risk of heart failure in a Chinese community-based population

Abstract Background Patients with heart failure (HF) often have elevated endogenous erythropoietin (EPO) levels, which are associated with disease severity and prognosis. Previous studies have indicated that in the special population elevated endogenous EPO levels are associated with HF and cardiovascular death. However, whether endogenous EPO levels are associated with the risk of HF in the general population remains to be elucidated. Purpose Our study aims to investigate the association between endogenous EPO levels and the risk of HF admission in the general population. Methods We conducted a prospective cohort study on subjects from a Beijing community in China who had no history of stroke or myocardial infarction. Endogenous EPO levels were measured at baseline for all participants. The endpoint of interest was admission with HF. Cox proportional hazard regression models were used to analyze the relationship between endogenous EPO levels and the occurrence of the endpoint. Results A total of 4870 participants were included. Among all participants, the mean (±SD) age was 56.72 ± 8.78 years, with 1802 (37.0%) being men. The median (interquartile range, IQR) EPO level was 13.19 (9.47-18.20) IU/L. During a mean 9.57-year follow-up, a total of 176 (3.6%) subjects experienced heart failure. Subjects were grouped in quintiles according to baseline endogenous EPO levels. Higher and lower endogenous EPO levels were both associated with increased risk of HF (Figure 1A). The Kaplan–Meier curves showed significant differences in cumulative hazards of heart failure among EPO quintiles (log-rank test: P＜0.05) (Figure 1B). After adjusting for covariates, including demographics, traditional risk factors for cardiovascular disease, renal function, and hemoglobin levels, and using the middle quintile (Q3) (11.72-14.94IU/L) of EPO levels as a reference, we found that the highest quintile (Q5) (>19.86 IU/L) was associated with a 159% increased risk of HF admission (HR 2.59, 95% CI 1.57-4.28, P = 0.0002). Similarly, the lowest quintile (Q1) (<8.66 IU/L) was associated with a 94% increased risk (HR 1.94, 95% CI 1.11-3.41, P = 0.0210) (Table 1). Conclusion There exists a "U-shaped" relationship between endogenous EPO levels and HF admission in the general population. Both higher and lower endogenous EPO levels were associated with an increased risk of HF admission in the community population. These findings differ from previous studies, so further research may be needed to explore the underlying pathophysiological mechanisms of endogenous EPO and HF.

Impact on healthcare costs of adding telemedicine to a multidisciplinary disease management program for heart failure: a sub-analysis of the iCOR trial

Abstract Background Impact of telemedicine on heart failure outcomes has shown conflicting results. Little is known about the effect of these programs on mid-term healthcare costs. Purpose To evaluate the cost-efficacy of a comprehensive telemonitoring program within the vulnerable post-discharge period after an acute heart failure admission. Methods The insuficiència cardiaca Optimizació Remota (iCOR) trial was a single-centre, randomized, open-label study designed to evaluate the efficacy of the addition of telemonitoring and teleintervention to a specialized multidisciplinary nurse-led heart failure (HF) program. Adult patients with a recent hospital admission for acute HF and an acceptable social support and cognitive ability were recruited. This sub-analysis evaluates the effect of telemedicine on mid-term healthcare costs, including clinical events, drugs and devices, technology purchase and maintenance, outpatient care, days of hospitalization, procedures and complementary tests. t-test via bootstrap estimation is used to compare differences between the telemedicine (TM) and the usual care (UC) groups. Results 81 patients were assigned to the TM group and 97 patients to the UC group. Mean age was 74 years, more than 50% had HF with preserved ejection fraction and 25% were frail. Baseline characteristics were well-balanced between groups. Among the TM subgroup, adherence was very high (< 1% of missed biometric daily transmissions). During 6 months of follow-up, mean total healthcare cost per patient was 7949 euros (€) in the UC cohort and 4383 € in the TM cohort (relative risk reduction [RRR] of 45%; between-group differences 3546 €, 95% confidence interval 627-6464 €, bootstrap achieved significance level 0.022). This result was consistent across several subgroups (age, sex, frailty, left ventricular ejection fraction, educational level) and mainly driven by a 63% RRR in costs of hospitalization (which accounted for two-thirds of the total costs) in the TM cohort. 20 patients required HF admissions in the TM group, compared to 51 patients in the TM group (p < 0.001). This was associated with a 59% RRR in the need for diagnostic procedures. Total number of days of hospitalization per patient decreased from 12.2 in the UC group to 4.2 days in the TM group (p = 0.003), impelled by a reduction in HF and cardiovascular days of hospital stay. On the contrary, ambulatory care costs increase two-fold in the TM group compared to UC group. Nevertheless, these costs only accounted for a 19% of the total costs. Cost of devices needed to implement TM supposed 698 € per patient. Use of TM was associated with a 355 € increase in the cost of ambulatory neurohormonal treatment for HF. Conclusions TM implementation during the vulnerable phase after an acute HF admission was associated to a 45% RR reduction in mean total healthcare cost per patient. This result was driven by an almost two-thirds decrease in costs of hospitalization.UC and TM total healthcare costs

The impact of peptide receptor radionucleotide therapy with Lutetium-177 DOTATATE on cardiac metastases in neuroendocrine tumors

Abstract Background Cardiac metastasis from neuroendocrine tumors (NET) is rare and has been thought to potentially result in life threatening sequalae. Peptide receptor radionucleotide therapy (PRRT), such as Lutetium-177 (Lu-177) DOTATATE, has been validated as effective treatment for patients with NET who have progressed on somatostatin analogue (SSA) therapy and more recently suggested for use in SAA-naïve higher risk grade 2 and grade 3 NETs. However, Lu-177 DOTATATE therapy has been found to have potentially serious adverse effects both locally and systemically. Overall, the clinical significance of cardiac metastasis of NET, as well as the safety and efficacy of Lu-177 DOTATATE in this cohort, has not been thoroughly evaluated. Purpose This study assessed the outcomes and clinical consequences of cardiac metastatic involvement in patients with NET. Furthermore, this study investigated the safety of Lu-177 DOTATATE therapy in patients with cardiac metastases from NET. Methods All patients who underwent 68Ga-DOTATATE positron emission tomography for evaluation of NET across three tertiary centers between 2016 and 2022 were retrospectively evaluated. Patients with evidence of cardiac metastasis were further evaluated. Baseline characteristics, treatment modality, and clinical outcomes including mortality, arrhythmia or conduction disease, carcinoid heart disease, and heart failure admissions were recorded. Patients with cardiac metastases were grouped and compared based on therapeutic modality (conservative therapy with surveillance or SSA, Lu-177 DOTATATE therapy, or surgical resection of metastases). Results From 3253 patients with NET, 51 patients were identified to have cardiac metastases (mean age 66.7 ± 12.2 years, 54% male). Three patients underwent surgical resection of cardiac metastases, and in two of whom this was concomitant while undergoing valve surgery for carcinoid heart disease. Patients with cardiac metastasis had significantly higher mortality than patients without cardiac metastasis (HR 2.12, 95%CI 1.00 – 4.52, p = 0.049, Figure 1A). Median follow-up from diagnosis of cardiac metastasis was 3.64 years [IQR 1.59 – 5.64]. There was no significant difference in clinical outcomes between patients that received Lu-177 DOTATATE therapy (n = 27) and conservative therapy (n = 21). Specifically, there was no significant difference in mortality risk at five years post the diagnosis of cardiac metastasis between these groups (p = 0.47, Figure 1B). Conclusion Patients with cardiac metastasis from NETs have worse clinical outcomes than NET patients without cardiac metastatic involvement. Lu-177 DOTATATE therapy appears to be safe in patients with cardiac metastasis from NET.Figure 1AFigure 1B

Incidence of 1-year mortality, heart failure admissions and decompensation in patients with heart failure followed in HF units in Spain. Differences according to type of units

Abstract Introduction Heart failure is a serious health problem and continues to have a high mortality and incidence of decompensation, despite advances in its management. The introduction of specific multidisciplinary HF units has improved the management of patients with this disease, thanks to better organization and management of available diagnostic and therapeutic resources. The HF Association of the ESC and the Spanish Society of Cardiology have defined 3 types of HF units (community, specialized, and advanced) according to their structure, complexity, and portfolio of services. Purpose To analyze in a contemporary registry of patients with HF followed up in HF units in Spain whether the results in terms of mortality and HF decompensations during follow-up are similar or different between the 3 types of units. Methods We analyzed data from the registry of the SEC-Excelente-IC quality accreditation program of the Spanish Society of Cardiology, with 1,716 patients with HF included between 2019 and 2021 by 45 SEC-accredited HF units. Patients were included consecutively in two 1-month cutoffs (March and October) in that period. Units were defined as community, specialized, and advanced according to ESC HFA and SEC criteria. We compared the incidence of death, HF admissions and total decompensations at 1-year follow-up between community and specialized/advanced units. Results Of the 1716 patients, 55.5% were treated in community units, 65.9% in advanced units, and 20.9% in advanced HF units. Figure 1 shows the main characteristics and treatment used in the 3 types of units. The community units treated older patients and more HFpEF, and the use of NRA and AID was lower, with no differences in the remaining characteristics, comorbidities, or treatments (Figure 1). Figure 2 shows the incidence of events at 1 year. Total mortality was 27.5% in community and 15.5% in specialized/advanced (p<0.001). HF admissions (39.7 vs 29.2%; p=0.019), HF decompensations without admission (16.4 vs 11.3%; p=0.074), total decompensations (56.1 vs 40.5%; p=0.003), and combined HF death/admissions (45.2 vs 31.4%; p=0.005) were statistically higher in community units. Control in specialized/advanced units was an independent protector factor for all events (mortality: HR 0.59, 0.43-0.82; p=0.002; HF admissions: HR 0.61, 0.42-0.90; p=0.012; total HF decompensations: HR 0.58, 0.42-0.81; p=0.001). Conclusions One-year prognosis of HF patients continues to be poor, with high rates of mortality and decompensations. Patients attended in community HF units was significantly worse in our country during the study period. Although this may be due in part to the small differences between the characteristics of the patients followed in the different types of units, it seems necessary to improve the network organization of HF care with the aim of achieving greater equity in the treatment of HF in Spain.

Liver function tests in patients receiving high-intensity care after hospital admission for acute heart failure: the STRONG-HF trial

Abstract Background/Introduction Episodes of acute heart failure (AHF) unfavorably affect extra-cardiac organs such as the liver due to altered hemodynamics and neurohormonal activation. In AHF, elevated levels of levels of alanine aminotransferase (ALT) and total bilirubin (tBil) may reflect congestion and impaired liver function, while lower levels of ALT (which is also produced in muscle cells) correlate with malnutrition and sarcopenia. Thus, the clinical importance of these markers in AHF and the post-discharge period is unclear. Purpose To assess circulating concentrations of ALT and tBil in patients with AHF before discharge and during high-intensity care (HIC) vs usual care follow-up in association with clinical outcomes. Methods ALT and tBil concentrations were measured 1-2 days before discharge in patients hospitalized for AHF (baseline), and again after 90 days of either HIC or usual care according to the STRONG-HF protocol. Baseline values and changes in ALT and tBil were analyzed in association with the primary outcome of all-cause death or HF readmission by day 180. Results At baseline, the median (Q1-Q3) concentrations of ALT and tBil were 21 (15-32) U/L and 14 (10-21) umol/L, respectively. Lower levels of both ALT and tBil were associated with female sex, Black race, lower BMI, higher LVEF, lower hemoglobin, lower creatinine and less frequent atrial fibrillation/flutter, while there were no significant associations with age. Patients with lower ALT, but not tBil, were more likely to have edema, elevated JVP and orthopnea, and used higher loop diuretic doses and less beta-blockers, pre-randomization (Figure, panel A). ALT was inversely associated with risk for the primary outcome (HR 0.81 [95%CI 0.65,1.00) per log increment, p=0.05), while there was no association with risk for tBil (HR 1.04 [95%Ci 0.84-1.28], p=0.73) (Figure, panel B). After 90 days, ALT and tBil concentrations were lower than at baseline, with a greater reduction in tBil in the HIC group vs usual care group (mean -1.7 [95%CI -3.0,-0.4] umol/L, p=0.01), while there was no significant between-group differences in ALT changes (mean -0.6 [95%CI -4.7,3.4] U/L, p=0.75) (Figure, panel C). The treatment effect of HIC over usual care on the primary outcome was consistent across the range of baseline ALT (P-interaction=0.30) and tBil (P-interaction=0.80) (Figure, panel D). Conclusion Contrary to our hypothesis of higher liver function tests with hepatic congestion in AHF, lower ALT was associated with more congestion and worse outcomes among patients hospitalized for AHF in STRONG-HF. There was no prognostic value from tBil levels. This suggests that ALT may be a marker of sarcopenia in these patients. Importantly, the beneficial effect of HIC on clinical outcomes is consistent irrespective of ALT and tBil levels at discharge.Figure