Diagnosis Of Heart Failure Research Articles

Value-based versus usual care for heart failure patients leads to reduction in cost, hospital admissions and improved survival

Abstract Background OptumCare (OC) in our city, Nevada established a heart failure (HF) program comprised of a team of outpatient cardiologists including two who are board certified in advanced heart failure. Referred patients are enrolled in the HF program once HF is diagnosed by a cardiologist. Patients are managed by an interdisciplinary team of cardiologists, advanced practice clinicians (APC), registered nurse case managers (RNCM), and a social worker. Patients at higher risk for HF admissions are enrolled in remote patient telemonitoring. In contrast, OC in Arizona utilizes a "usual" care approach of fee-for-service contracted cardiology groups to manage HF patients in outpatient and in-patient settings. Purpose A head-to-head comparison was performed between the cohort of patients enrolled in HF program in OC Nevada (treatment group) and patients with HF diagnosis in OC Arizona (control group). The groups were compared on the following measures: medical cost, hospital admissions, and survival rates. Methods In this retrospective study, a 1:1 iterative propensity score (PS) matching was performed to closely approximate patient demographics and comorbidities, which resulted in 818 matched pairs (total n=1,636) of the patients with program enrollment or 1st HF diagnosis between March 1, 2019 and June 30, 2022. For Difference-in-Difference Analysis (Diff-in-Diff), generalized linear models were used on PS matched data to test the difference in difference in medical cost and utilizations changes between control and treatment group over a six month period. Log-Binomial regression was used to estimate the relative risk of post period 30-day readmission and hospice enrollment. Kaplan Meier Estimator was used to test the difference in survival rates over time. Results Average age of patients was 77.6 years old, and 49% were female. The treatment group resulted in significantly lower overall medical costs per member per month (PMPM), significantly less emergency room (ER) visits, less acute hospital and skilled nursing facility (SNF) admissions, and shorter overall hospital length of stays. The control group was twice as likely to be readmitted to the hospital. Lastly, the treatment group had a significantly better survival rate than the control group. 19% of the patients in the control group expired within 12 months of enrollment vs. 10% of the patients in the treatment group expired during the same time period. Average survival was 142 days in the control group vs. 200 days in the treatment group. Conclusions A value-based care approach involving a multidisciplinary team in an outpatient-based cardiology HF program resulted in statistically significant improvement in medical costs, acute care visits/admissions, and survival rates compared to "usual" care approach for HF patients.

Predicting heart failure in cancer survivors: use of polygenic risk vs clinical score

Abstract Background The risk of heart failure (HF) is increased among cancer survivors, but predicting individual HF risk is difficult. Polygenic risk scores (PRS) for HF prediction summarize the combined effect of multiple genetic variants, specific to the individual. We sought to compare clinical HF prediction models with PRS in both cancer- and non-cancer populations. Methods Cancer and HF diagnoses were identified in the UK-Biobank from International Classification of Diseases (ICD)-10 codes. HF risk was calculated using the Atherosclerosis Risk in Communities score (ARIC-HF). PRS-HF was calculated using the Global Biobank Meta-analysis Initiative. The predictive performance of ARIC-HF and PRS-HF were compared using the area under the curve (AUC) in both cancer- and non-cancer populations. Results After excluding 2,644 participants with HF prior to consent, we identified 440,813 non-cancer participants (mean age 57 years, 53% female) and 43,720 cancer survivors (mean age 60 years, 65% female). Both ARIC-HF and PRS-HF were significant predictors for HF occurrence after adjustment for chronic kidney disease, overall health rating and total cholesterol level. The PRS-HF performed poorly in predicting HF among cancer (AUC: 0.552) and non-cancer populations (AUC: 0.571). However, the ARIC-HF predicted HF incidence in the non-cancer population (AUC: 0.806) and a reasonable performance among the cancer population (AUC: 0.748). Conclusions Prediction of HF occurrence in cancer survivors based on conventional risk factors is superior to PRS. However, both models demonstrate suboptimal discriminative capabilities in forecasting HF, emphasizing the imperative for the development of a cancer-specific HF predictive model.

Cardiovascular events and consequent risk of death in hematopoietic stem cell transplant recipients

Abstract Background Hematopoietic stem cell transplant (HSCT) represents a potentially curative approach for various hematologic cancers and bone marrow disorders. Advancements in safety and efficacy have broadened the application of HSCT to older individuals and those with concurrent medical conditions predisposing them to cardiovascular (CV) issues. Despite the significant survival benefits offered by HSCT, it is accompanied by both short- and long-term complications, leading to considerable morbidity and mortality. CV complications, including heart failure, arrhythmias, acute thrombosis, pulmonary hypertension, and pericardial effusions, are among the potential adverse events following HSCT. Aim for the present registry is to determine how much CV complications are related to short-term survival in patients after HSCT. Methods Observational, monocentric cohort study consecutively enrolling all patients undergoing HSCT from 2019 to 2023. Inclusion criteria was >18 years, autologous or allogeneic HSCT, and written informed consent for the participation in the study. All patients underwent a complete cardiological examination, including 12-lead ECG, echocardiography, and cardiac biomarkers, before HSCT, and after 2,6 and 12-months. CV-related adverse events were defined as systolic dysfunction (even asymptomatic), thromboembolism (both VTE and PE), stroke, arrhythmias, pericarditis and hypertensive crises. Results 91 patients (34% female; mean age 54 +/- 12 years) were followed-up for a median of 2 years after HSCT. Major risk factors' prevalence was overall low (hypertension 28%, dyslipidaemia 33%, diabetes 9%, and only 11 patients (12%) had a positive history for CV events (6 atrial fibrillation, 4 coronary heart disease, 1 stroke) before HSCT. During follow-up, 26 patients (29%) experienced at least one CV-related adverse event, of which 7 (8%) were serious enough to require an hospital admission. CV adverse events included 5 new heart failure diagnosis, 5 new atrial fibrillation diagnosis, 10 episodes of VTE/PE, 4 pericarditis, one stroke and one hypertensive crisis. Twenty of all CV-related adverse events were reported within the first six months after HSCT (77%). Having a CV-related AE within the first six months after HSCT is associated with an increased risk of all-cause death (39% vs. 17%; log-rank p=.01; Figure 1). Conclusions CV-related adverse events are common in patients undergoing HSCT and strikes an overall young and healthy population. Having a CV-related adverse event in the six months following HSCT is a heavy prognostic factor for all-cause mortality. Therefore, an optimal prevention strategy including arrhythmia monitoring, echocardiographic follow-up and guideline-driven thromboembolic prophilaxis could improve patients' survival after HSCT.Figure 1

Long-term outcomes in women diagnosed with heart failure in connection to delivery

Abstract Background Heart failure (HF) among young patients may be from various causes, often triggered by heightened physical demands like pregnancy. Data regarding outcomes of women diagnosed with HF in conjunction to pregnancy and delivery are varied. There remains a notable gap in understanding the outcomes observed in women diagnosed with heart failure in conjunction with delivery. Also, long-term follow-up studies are crucial to elucidate the impact of pregnancy-associated HF on future cardiovascular. Purpose To study the interplay between pregnancy, HF, and subsequent cardiovascular risk. Method Using the personal identification numbers (PINs) that all individuals in Sweden have enables linkage of data between different registers. Data from the National Patient Register (NPR), Swedish Medical Birth Register (MBR) and the Cause of Death Register were also used. All women 18 to 50 years of age registered in the in MBR in the period 1st January 1997 to 31st December 2019 were included. Women with first-time HF in relation to delivery were identified using the international classification code for diseases (ICD-10) I50, I42, I43 and 090.3 together with co-morbidities. Every patient was compared with 5 controls without HF from the Total Population Register matched on age at delivery and calendar year of delivery. Outcomes: all-cause mortality, and any cardiovascular disease (CVD) diagnosed during the observation time. Results A total of 286 cases and 1,430 controls were included. The prevalence of comorbidities at baseline for both patients and controls was low; congenital heart disease (1.4%, vs. 0%), pulmonary hypertension (1.0% vs. 0%), valvular heart disease (5.9% vs. 0%), myocardial infarction 0.7% vs. 0%), arrhythmia (5.9% vs. 0%), hypertension (6.3 % vs. 0.1%), (all p<0.05). Preeclampsia prior to HF diagnosis had 31% of patients vs. 0.2% of controls (p<0.001). Patients exhibited higher mortality rates at 4.9% during median follow up 9.0 (IQR 5.6-13.0) years vs. 0.3%, median follow up 9.4 (6.2-13.5) years and hazard ratios (HR) for all-cause mortality HR (95% CI) of 18.20 (5.99 - 55.31) (p<0.001) compared to controls. During median follow up of 3.2 (0.0-9.2) years 60.1% of patients were diagnosed with CVD both at in-/out-patient settings compared with 4.1% in controls during 9.4 (5.8-13.5) years of follow up. Comparing patients with controls the HR (95% CI) was 22.24 (16.50 - 29.96) p<0.0001 for CVD diagnosis during follow-up, see Figure 1. Conclusion In conjunction with delivery, and in the years thereafter, women with heart failure diagnosis had more than eighteen times higher risk of mortality than women without heart failure. The risk of CVD event in the heart failure group is highest in conjunction with delivery. Figure 1. Cumulative incidence functions for all-cause mortality, CVD in- or out-patient visit adjusted for death as competing risk, comparing cases with controls.

Recent Advances in the Wearable Devices for Monitoring and Management of Heart Failure.

Heart failure (HF) is an acute and degenerative condition with high morbidity and mortality rates. Early diagnosis and treatment of HF can significantly enhance patient outcomes through admission and readmission reduction and improve quality of life. Being a progressive condition, the continuous monitoring of vital signs and symptoms of HF patients to identify any deterioration and to customize treatment regimens can be beneficial to the management of this disease. Recent breakthroughs in wearable technology have revolutionized the landscape of HF management. Despite the potential benefits, the integration of wearable devices into HF management requires careful consideration of technical, clinical, and ethical challenges, such as performance, regulatory requirements and data privacy. This review summarizes the current evidence on the role of wearable devices in heart failure monitoring and management, and discusses the challenges and opportunities in the field.

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

Detection and risk stratification of cardiac amyloidosis patients by integration of imaging and non-imaging data using a machine learning approach

Abstract Background With the advent of amyloid-targeting therapies, early and reliable diagnosis as well as precise risk estimation of cardiac amyloidosis (CA) have become of substantial importance. While the current diagnostic approach relies on difficult-to-standardize, visual interpretation of 99mTc-scintigraphy, risk assessment is largely based on a combination of blood and imaging parameters. Purpose Aim of this study is to assess the possibility of machine learning-based integration of scintigraphy, echocardiography, and non-imaging parameters such as blood parameters and comorbidities for the detection and risk stratification of patients with CA. Methods This study included all patients who underwent 99mTc-scintigraphy at a university affiliated tertiary care centre between 2010 and 2023. Two machine learning models were developed, and the relative predictive importance of their parameters were assessed (Figure 1): First, a model to detect patients with CA-suggestive uptake (Perugini grade 2/3) on 99mTc-scintigraphy scans; Second, a model to assess the risk of patients with CA-suggestive uptake for future heart failure hospitalization (HFH). A total of 58 features were extracted from electronic health records including blood, echocardiographic, demographic parameters and comorbidities. Scintigraphy imaging features were extracted from the raw imaging data using a deep learning approach. For the time to HFH prediction, a random survival forest machine learning model was employed. Results Overall, 12 380 consecutively enrolled patients were included, 279 (2.3%) of which were affected by CA-suggestive uptake. The machine learning model showed higher accuracy for the detection of CA (AUC 0.96 [95% CI 0.95-0.97], sensitivity 0.78 [95% CI 0.77-0.80] and specificity 0.99 [95% CI 0.99-0.99]. In the outcome analysis, the machine model showed good accuracy in predicting future HFH (C-index 0.71 [95% CI 0.68-0.75]). Parameter importance for the time to event analysis revealed right ventricular diameter, previous diagnosis of chronic heart failure and creatine kinase as the three most important predictors (Figure 2). Conclusions Detection of patients with cardiac amyloidosis and their risk estimation for heart failure can be aided using machine learning-based integration of imaging and non-imaging data. Our findings may guide novel approaches for assessing disease progression and treatment response.

Usefulness of preoperative NT-proBNP for prediction of acute heart failure, perioperative myocardial infarction/injury and mortality after non-cardiac surgery

Abstract Background Predicting cardiac complications after non-cardiac surgery is challenging. Purpose to determine the predictive accuracy of N-Terminal Pro–B-Type Natriuretic Peptide (NT-proBNP) and, to assess the utility of existing NT-proBNP cutoffs of the 2021 ESC Guidelines for the diagnosis of acute and chronic heart failure for prediction of postoperative acute heart failure (pAHF), perioperative myocardial infarction/injury (PMI) and mortality following non-cardiac surgery. Methods we prospectively determined preoperative NT-proBNP concentrations in consecutive patients at high cardiac risk undergoing inpatient non-cardiac surgery. Uni- and multivariable regression models were constructed to test the association between NT-proBNP concentrations and the outcomes (pAHF, PMI, 30-day and one-year mortality), using NT-proBNP as a continuous variable. We further stratified NT-proBNP into 5 categories according to guidelines (<125 pg/ml, 125 to 299pg/ml, 300 to 900 pg/ml, 901 to 1800pg/ml and >1800 pg/ml). Receiver operating characteristic curves were constructed to determine the predictive value of NT-proBNP. Results Among the 2,334 cases included, pAHF occurred in 83 (3.6%), PMI in 381 (17%), 45 (2.5%) patients died within 30 days and 179 (10%) within one year. After adjusting for confounders, NT-proBNP concentrations were independent predictors of pAHF (adjusted hazard ratio [aHR] 1.8 [95%CI, 1.5-2.1], p<0.001), PMI (aHR 1.3 [95%CI, 1.2-1.4],p<0.001) and 30 day/one year mortality (aHR 1.6[95%CI, 1.3-2.0], p<0.001)/aHR 1.5 [95%CI 1.4-1.7], p<0.001). By quintiles, higher the NT-proBNP levels were strongly associated with adverse outcome (Figure). Accuracy of preoperative NT-proBNP for prediction of pAHF was excellent (area under the curve [AUC] 0.825) and better than accuracy of the Revised Cardiac Risk Index score (AUC 0.692, p<0.001), whereas accuracy of NT-proBNP for prediction of PMI (AUC 0.654) and mortality (AUC 0.787) was only moderate. Conclusion NT-proBNP concentrations are independent predictors of pAHF, PMI and short and long-term mortality following non-cardiac surgery. Stratifying NT-proBNP concentrations using current recommended cut-offs could help to further determine the magnitude of the risk, mainly of pAHF.

The role of malnutrition and dependence on outside help in hospitalized elderly patients with decompensated heart failure

Abstract Introduction Despite recent achievement in the diagnosis and treatment of heart failure, the prognosis for disease remains unfavorable especially in elderly patients. It has been recently actively proposed to introduce a comprehensive geriatric assessment to determine the group of adverse outcome and frailty, however the assessment of geriatric syndromes in acute decompensated heart failure (ADHF) among hospitalized patients is poor. Aim To assess the prognostic role of malnutrition and dependence on outside help in hospitalized elderly patients with ADHF. Materials and methods The study included 60 patients over 75 years old who were hospitalized for ADHF. The median [IQR] age was 83.0 [77.0-87.0] years, 41.7% (n=25) were men. The preserved left ventricular ejection fraction (LVEF) prevailed – 51.2% (n=22), moderately reduced and low LVEF – 23.3% (n=10) and 25.6% (n=11), respectively. Total/severe dependence on outside help was determined with Barthel Index of ≤60 points, malnutrition – with a Mini Nutritional Assessment Scale of <17 points, sarcopenia with SARC-F ≥4 points. At discharge, all patients underwent bioimpedance analysis of body composition (BIA). The primary endpoint was hospital mortality. Results 48.3% (n=29) of hospitalized elderly patients with ADHF had total/severe dependence on outside help. This group of patients had a higher risk of malnutrition (OP 2.01, 95% CI 1.49-2.83, p=0.04) and sarcopenia (OP 8.25, 95% CI 1.55-44.02, p=0.01). Elderly patients with ADHF and malnutrition had a more severe functional class (NYHA III-IV) than patients without malnutrition (97.1% vs. 66.7%, respectively, p=0.02). There were no differences in ADHF phenotypes depending on the presence of malnutrition. The ability to self-serve according to Barthel Index has positively correlated with the BIA Index (r=0.483, p=0.04). The risk of sarcopenia on the SARC-F scale has negatively correlated with fat, lean and active cell mass according to BIA (r=-0.538, r=-0.599 and r=-0.532, respectively, p<0.05). Elderly patients with ADHF and a combination of total/severe dependence on outside help and malnutrition (27.9%, n=12) had higher inflammation level (neutrophil-lymphocytic index 5.6 [2.6-7.7] vs. 3.9 [2.0-6.0], p=0.03, respectively) and the need for longer intravenous diuretic therapy (OP 4.38, 95% CI 1.21-15.81, p=0.03) compared with patients without these disorders (72.1%, n=31), The primary endpoint was reached by 4 patients, in 100% of cases there was a combination of total/severe dependence on outside help and malnutrition. Conclusion The combination of total/severe dependence on outside help and malnutrition is an unfavorable prognostic marker of hospital mortality in hospitalized elderly patients with ADHF. A comprehensive geriatric assessment and determination of body composition can identify a risk group for an adverse outcome.

Sex-specific prognostic implications of new-onset atrial fibrillation in patients treated with dual chamber pacemakers

Abstract Background Right ventricular pacing induces ventricular dyssynchrony, which over time may result in left ventricular dysfunction, increased left ventricular filling pressures, and ensuing left atrial dilatation, with increased risk of atrial arrhythmias. Atrial fibrillation (AF) prior to device implant is associated with worse prognosis, but the prognostic effects of new-onset AF during pacemaker treatment are less well described. Purpose To describe risk factors, incidence, and prognostic effects of new-onset AF after treatment is initiated with a dual chamber pacemaker. To evaluate mortality and risk of heart failure diagnosis or hospitalisation for heart failure in patients who develop AF, compared to those who do not develop AF. Methods All patients without pre-existing heart failure or atrial fibrillation, who received a dual chamber pacemaker at a large-volume tertiary care center during the period 2005–2020 were included. Data was crossmatched between the national pacemaker registry, the population registry and national disease registries. The primary outcome was 10-year mortality, and the secondary outcome was new-onset heart failure. Results 37127 patients were included in the study, of which 14760 (30%) were female. Median age was 76.4 years [interquartile range, IQR, 68.0–83.1] and the most common indication for pacemaker implant was AV block (57.7%), see Table 1. Overall, 10-year survival was higher for female patients, compared to male patients, p<0.0001 (see Kaplan-Meier curve in Figure 1A). Patients who developed new-onset AF had more comorbidities, were slightly older and a higher percentage were men. During follow-up 3661 (9.9%) developed atrial fibrillation within two years (9.1% of female and 10.3% of male patients, p<0.001), at a median of 291 [88–461] days after implant. In multivariable Cox regression analysis with new-onset AF as time dependent covariable and adjusted for clinically relevant covariables, AF was an independent predictor of higher all-cause mortality (HR 1.43 [1.37–1.49], p<0.0001). Risk factors for new-onset AF included increasing age, male sex, hypertension, malignancy, diabetes, chronic obstructive lung disease, chronic renal disease, and sick sinus syndrome indication (all p<0.01). In separate analyses for men and women, the risk factors and magnitude of odds ratios were the same. Conclusion In patients treated with dual chamber pacemakers due to bradycardia or AV block, development of new-onset AF within two years was associated with a higher 10-year mortality. The risk of developing AF was higher for men, but the negative prognostic effect was more pronounced for women.Figure 1A.-B. K-M survival curves

REDUCE-HF: a stronger heart go a long way

Abstract Introduction/Purpose Heart failure (HF) is a serious cardiovascular condition with a significant global health concern. The risk of heart failure rehospitalisation is high globally and locally, the 30-day HF readmission was about 32% from a local study (1). The study aims to adopt an intensive treatment strategy similar to Strong-HF trial (2) and evaluate rapid up-titration of guideline directed medical therapy (GDMT) and close follow-up will improve patients' outcomes after acute heart failure (AHF). Objectives The Reduction of Decompensation and Unnecessary Cardiac failure Emergency admissions: ambulatory Heart Failure service model (REDUCE-HF) is a non-randomised prospective study evaluating clinical outcome of patients discharged from AHF. Exclusion criteria included primary valvular disorders, end-stage renal failure and metastatic cancer. After HF discharge, eligible patients were recruited into our REDUCE-HF program irrespective of LVEF. They were subsequently managed in our ambulatory HF centre within two weeks, where intensive up-titration of GDMT and close follow-up would be proceeded. The data of our service model will be compared with our 5-year historical cohort. Primary outcome comprised of all-cause mortality and heart failure hospitalisation. Secondary outcome will be comparison of clinical and functional status at baseline and 3-month on follow up. Results Between October 2022, and December 2023, 245 patients were successfully recruited into our REDUCE-HF service model. Historical cohort of 6867 patients with primary diagnosis of acute heart failure were served as control (usual care pathway), data extracted from 2018 to 2022. Their mean age was 67.8+/-12.2 and 72.2%were male. 60% of them were HFrEF (EF<=40%) and 28% were ischaemic cardiomyopathy. The mean follow up period was 3 months. At 90 days, REDUCE-HF cohort group has shown much lower all-cause mortality than usual care group (2.5% vs 9.3%, HR 0.26, 95% CI 0.18-0.41, p<0.001). There was a much lower incidence of heart failure hospitalisation in REDUCE-HF group as compared to control (8.6% vs 13.1%, HR 0.65; 95% CI 0.55 to 0.74, p<0.01). In secondary outcome, there was significant reduction of NT-ProBNP of 45.2% (from 4229 to 2319pg/m, p<0.001), tremendous increment of 6-minute walk test (from 211 to 250m, p<0.001) and remarkable improvement of KCCQ score from 55.1 to 86.7, p<0.001. The overall LVEF was significantly increased from 39% to 44%, p<0.05. The positive outcome were attributed to good adherence to GDMT: ACEi/ARB/ARNI 91%, Betablocker 90.3%, MRA 72.4% and SGLT2i 95.5%. Conclusion The REDUCE-HF ambulatory service model has been proven effective in reducing mortality, decompensation and preventing unnecessary heart failure hospitalisation in this prospective study. By intervening proactively, this model not only enhances the quality of life but also hold promise in alleviating the burden of in-patient services on heart failure.

Machine learning for prediction of incident heart failure and heart failure hospitalisation: multi-cohort development, validation and association with clinical phenotypes

Abstract Background Delayed heart failure (HF) diagnosis is associated with adverse outcomes and costs of hospitalisation.(1,2) Whilst previous tools have been developed to predict incident HF,(3) risk of HF incidence may correlate poorly with risk of HF hospitalisation, which may be more important in targeting diagnostics. Purpose To develop and validate a novel decision support tool for prediction of incident HF and HF hospitalisation, and investigate association of score with HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). Methods We developed the models (FIND-HF) in UK primary care health record data from individuals aged ≥40 years without known HF (Jan 2, 1998 to Feb 28, 2022), randomly divided into training (80%) and testing (20%) datasets. We evaluated logistic regression and supervised machine learning models for prediction of 1- and 5- year HF and HF hospitalisation risk in the testing dataset with internal bootstrap validation. Models were externally validated for HF hospitalisation in data from a Taiwanese university hospital. Association of FIND-HF score with HF phenotypes of HFpEF and HFrEF was assessed in two prospective cohorts, the MATCH registry of patients diagnosed with HFrEF and the FIND-AF cohort of individuals at higher predicted risk of atrial fibrillation who underwent echocardiography. Results Of 565 284 UK individuals (mean age 68.9 (SD 12.2) years, 49.2% women), incidence of HF and HF hospitalisation was 1.1% and 0.5% at 1-year, and 6.6% and 3.4% at 5-years, respectively. Prediction performance was superior for machine learning algorithms compared with logistic regression, with best performance for XGBoost (area under receiver operating characteristic curve (AUROC) at 1 and 5-years: 0.755 and 0.723 for incident HF, and 0.738 and 0.711 for incident HF hospitalization). On external validation in 106,026 individuals in Taiwan (mean age 64.7 (SD 10.6) years, 52.8 % women), HF hospitalisation incidence was 0.71%, and 2.46% at 1- and 5- years, respectively, and discrimination performance was excellent (AUROC at 1- and 5-years: 0.834 and 0.843). When the FIND-HF score was applied to individuals in the MATCH cohort (n = 133, mean age 69.0 (SD 11.7) years, 38.3% women) and FIND-AF cohort (n = 82, mean age 71.6 (SD 7.5) years, 50.0% women), the distribution of score to clinical phenotypes demonstrated a binomial distribution (Figure 1), and likelihood of HFpEF diagnosis correlated with the numeric score (Figure 2). Conclusions The machine learning FIND-HF decision support tool can accurately identify individuals at risk of incident HF and HF hospitalisation, to enable new approaches for early detection and prevention. The variation of score amongst high risk individuals with different HF clinical phenotypes emphasizes the distinct pathophysiological pathways but shared adverse outcome profile across the HF syndrome.Figure 1Figure 2

Comparing de novo heart failure and acute decompensated heart failure using a proteomic approach

Abstract Background Acute heart failure (HF) is defined as new or worsening symptoms of HF and stands as the most common cause of unscheduled hospital admission in patients above the age of 65. Acute HF can be classified into de novo HF (DNHF), defined as no previous history of HF, and acutely decompensated HF (ADHF), defined as worsening symptoms of HF in individuals with a prior diagnosis of HF. Clinically, it is relevant to distinguish ADHF from DNHF as they differ regarding aetiology, comorbidities, mortality, and morbidity. The aim of this study was to compare DNHF and ADHF using a proteomic approach. Method Using a proximity extension assay in a Swedish HF cohort, a total of 324 individuals hospitalized for acute HF underwent proteomic analysis of 92 proteins. The population was categorized into DNHF and ADHF, subsequently comparing normally distributed proteins using an independent samples t-test. Non-normally distributed proteins were compared using the Mann-Whitey U-test. To adjust for multiple testing, Benjamini Hochberg method was applied with a false discovery rate of 5%. Fold change was calculated by subtracting the mean or median protein concentration in ADHF from DNHF. As protein concentrations are expressed on a log2-scale, the difference between the groups equals the fold change. Proteins were considered differentially expressed at a fold change threshold of 1.15. The proteins that met a cut-off, were thereafter analysed with a pathway enrichment analysis using Reactome (only a corrected p-value ≤0.05 was considered significant). Results Complete data was available for n=317 (30.3% women; mean age 74.6) individuals (Table 1). After FDR adjustment, differential protein expression analysis yielded 56 differentially expressed proteins. After applying the fold change threshold, 51 proteins were significantly up regulated in ADHF compared to DNHF and one (Paraoxonase 3) was significantly downregulated. The most prominently up-regulated protein was fatty acid binding protein-4 (FABP4) (fold change 1.68, p <0.001). The largest number of proteins were related to neutrophil degranulation (Figure 1). Conclusion In patients hospitalized for acute HF, we identified several common pathways of the proteins differentially expressed in DNHF compared with ADHF. Neutrophil degranulation was related to the largest number of proteins. The most prominently up regulated protein was FABP4. These findings may inspire future investigation into the different underlying molecular mechanisms in ADHF and DNHF and reveal potentially different targets of treatment between the two conditions.Figure 1.Pathway enrichment analysis

Genetic and phenotypic architecture of biventricular trabeculation

Abstract Introduction Cardiac trabeculae form a network of muscular strands that line the inner surfaces of the heart, and their development involves molecular pathways that regulate structural complexity. Excessive or hypertrabeculation occurs as part of normal variation in apparently healthy individuals, as an adaptation to altered loading conditions, and is observed in patients with cardiomyopathies (CMs) and heart failure (HF). Purpose In adults, trabeculation is not a prognostic factor independent of the underlying myocardial disease but may play a role in the natural history of ventricular remodelling. We sought to (i) understand the genetic and non-genetic determinants of trabeculation, (ii) understand its role in the causality of disease, and (iii) evaluate trabeculation as a biomarker for diagnosis and stratification. Methods We report genes with a burden of rare variants and novel common variant associations across the allele frequency spectrum for biventricular trabecular morphology in 47,803 participants of the UK Biobank using fractal dimension analysis of cardiac imaging (Figure 1). We assessed environmental modifiers of trabecular morphology, correlation with cardiac traits, phenome-wide association studies, and the relationship with the progression of CMs and HF. Results We identified a burden of trabeculation-associated rare variants in genes that regulate myocardial contractility and cardiac development and GWAS identified novel loci near genes implicated in CMs, conduction traits, and signalling pathways that define the early development of trabeculation. For example, we identified 56 genes with a burden of rare variants and 68 novel loci from GWAS (e.g., CASQ2, CACNA1C, MYBPC3, MYH7, NKX2-5, NOTCH1, TBX20) for the left ventricle. The strongest imaging relationships with trabeculation were with measures of volume and strain. Modifiers of trabeculation included African ancestry, alcohol intake, and physical activity. Carriers of CM-associated pathogenic variants had increased trabeculation. Of participants with CM reported after imaging, 25% had hypertrabeculation on imaging and hypertrabeculation was a risk factor for a subsequent diagnosis of HF (HR=1.3), mitral valve disorders (HR=1.4), bundle branch block (HR=1.2). Comparisons of biventricular trabeculation showed similarities in trabeculation across the ventricles in CM. Reduced right ventricular trabeculation and end-diastolic volume associated with Type-2 diabetes. Conclusions These data provide new insights into the mechanisms that regulate structural complexity in the heart. Changes in trabeculation may occur early in the pathogenesis of heart disease, can be modified by genes regulating pathways outside the sarcomere, and causality depends on the underlying cardiomyopathic substrate. Trabeculation progresses with cardiovascular disease, is a useful marker of remodelling, and identifies novel genetic modifiers of ventricular complexity.Figure 1

Real-world eligibility for GLP1-ra therapy in a cohort of heart failure patients

Abstract Background GLP1-ra have demonstrated substantial cardiovascular (CV) benefits in diabetic and, more recently, non-diabetic patients, however their use in heart failure (HF) patients is still limited. Purpose To evaluate real-word eligibility to GLP1-ra in a cohort of HF patients. Methods Demographic and clinical data from HF patients evaluated at a single center HF unit from August 1st 2021 to November 29th 2023 were automatically retrieved from the electronic health record (EHR). Patients were deemed eligible to GLP1-ra based on (1) absence of ongoing treatment with GLP1-ra and (2) either having type 2 diabetes mellitus (T2DM) or satisfying the inclusion criteria of the SELECT trial or those of the STEP-HFpEF trial, which were adapted according to the available information. A sensitivity analysis lowering the body mass-index cut-off to >= 27 kg/m2 also for the STEP-HFpEF trial was performed. Results 1754 patients with an established diagnosis of HF were included; median age was 78.3 (IQR 70.7-83.8) years and 697 patients were female (39.7%). 6 patients had type 1 diabetes mellitus. Among the remaining 1749 patients, 633 (36.2%) patients had T2DM and 14 were already treated with GLP1-ra. Among 1116 patients without diabetes, 302 (27.1%) were eligible to receive GLP1-ra according to the inclusion criteria of the SELECT or STEP-HFpEF trials. 226 (20.2%) satisfied the SELECT trial inclusion criteria and among them 100 (44.8%) had HF with reduced ejection fraction, whereas 136 patients (12.2%) were eligible to receive GLP1-ra according to the STEP-HFpEF trial. Changing the BMI cut-off to >= 27 kg/mq, as in the SELECT trial, 219 patients (19.6%) according to the STEP-HFpEF inclusion criteria and 344 (30.8%) overall were found to be eligible for GLP1-ra therapy. Conclusion Real-word eligibility to GLP1-ra may reach up to 55% of HF patients according to diabetes status or trial inclusion criteria.

Atypical Presentation of Multiple Myeloma: From Heart Failure to Multiple Myeloma

Multiple myeloma (MM) is a hematological malignancy commonly associated with bone pain, hypercalcemia, and renal failure. However, its presentation can occasionally mimic other medical conditions, which may delay diagnosis. This case report describes a patient who was initially diagnosed and treated for heart failure but was later found to have MM, highlighting the importance of considering MM in the differential diagnosis of heart failure. A 56-year-old lady presented with recurrent episodes of shortness of breath, orthopnea, paroxysmal nocturnal dypsnea and bilateral lower limb swelling which she had been treated for decompensated heart failure with optimal therapy. She denied any family history of cardiovascular disease personal history of underlying medical condition and was a nonsmoker. This patient was diagnosed with multiple myeloma and probability of concomitant cardiac amyloidosis and commenced on bortezomib, thalidomide and dexamethasone (VTD) regime and standard optimal therapy of heart failure but her condition deteriorated. After a few days of starting chemotherapy, patient demised despite all the resuscitative effort. Multiple myeloma is common hematological malignancy with its distinct clinical features of “CRAB”, however, more attention and alertness should also be exercised by clinicians as to be able to diagnose it early.

The effect of Trimetazidine on the left ventricular global longitudinal strain assessed by cardiac magnetic resonance in stable angina patients with previous myocardial infarction and left ventricular

Abstract Introduction Trimetazidine (TMZ) is an anti-ischemic metabolic agent that is indicated in adults as add-on therapy for the symptomatic treatment of patients with stable angina pectoris (SA). Global left ventricular (LV) systolic function is an important predictor of outcomes in patients after myocardial infarction (MI). Cardiac magnetic resonance (CMR) imaging has now evolved into a major tool for the evaluation of patients with LV dysfunction, providing precise measurements of ejection fraction (EF) and viability assessment but also now allowing assessment of global longitudinal strain (GLS) from standard cine CMR images. We hypothesized that the use of TMZ 80 mg as an anti-ischemic agent in patients with SA, history of MI, reduced EF and in the presence of viable myocardium may produce an early modification of GLS. Methods TRIM-AZ - was a non-interventional, prospective Azerbaijan study to analyze the capacity of short-term therapy with TMZ 80 mg on LV GLS evaluated by CMR in patients with previous MI. Patients with a confirmed diagnosis of heart failure (HF) with impaired LV systolic function and SA in the presence of viable myocardium were included. The treatment of all patients was optimized according to the latest ESC guidelines before entry in the study. Patients were randomized into two groups, one received TMZ 80 mg on top of guidelines directed medical therapies, and the other was the control group. A CMR as well as a transthoracic echography were performed for all patients at the inclusion visit and 8 weeks later. Results 52 patients were included in the study, 30 patients in the TMZ group and 22 in the control group,. At baseline, the mean age was 62±7 years , 63% were smokers, 60% hypertensive, 60% diabetics, 48% had a family history of MI, 12% had typical symptoms of SA while 88% had atypical form (e.g. like shortness of breath). All patients received baseline therapy with ARNI/ACE-i, SGLT2 inhibitors, beta-blockers, MRA, ASA, and statin. 8 weeks after the initiation of TMZ, there were no significant changes in LVEF assessed both by Echo and CMR (29,8%±3,2% vs 30,1%±3,5% by echo in TMZ group; 31,3%±2,7% vs 31,6%±2,7% by echo in the control group; 25,9%±3,1% vs 26,9±4,1% by CMR in TMZ group; 26,9%±2,1% vs 30,1%±2,3% by CMR in the control group), however GLS was significantly improved in TMZ group (-9,9%±1,1% to -12,7%±1,2%, p=0,00), but not in control group (-9,3%±1,3% vs -10,3%±1,4% p=0,3). No adverse event related to TMZ use was reported during the study. Conclusion These findings suggest that the use of trimetazidine in patients with stable angina , previous MI and heart failure in the presence of viable myocardium could improve the left ventricular global longitudinal strain assessed by CMR.

A streamlined protocol for exercise right heart catheterisation for the diagnosis of heart failure with preserved ejection fraction

Abstract Background Heart failure with preserved ejection fraction (HFpEF) can be a challenging diagnosis. The gold standard diagnostic test is exercise right heart catheterisation (eRHC), with HFpEF confirmed if pulmonary capillary wedge pressure (PCWP) >15mmHg at rest or ≥25mmHg with exercise. However, many centres do not perform eRHC and the current, well-established, nine-minute eRHC protocol can be time consuming and costly. Purpose We sought to determine whether an abbreviated 3-minute eRHC protocol is sufficient for accurate diagnosis of HFpEF, thus allowing simplification, reduced patient risk and costs, and broader uptake of eRHC across centres. Methods Patients undergoing eRHC between 09/09/2008 and 18/07/2023 at a tertiary hospital in Australia were retrospectively analysed. Haemodynamic measurements at three minutes of exercise were correlated with peak measurements. Results Overall cohort of n=532, with a mean age of 64 ± 12 years, and 60% female. Compared to PCWP ≥25mmHg at peak exercise, measurement of PCWP at 3 minutes yielded an area under the receiver-operating characteristic curve of 0.92±0.01, P<0.0001. PCWP ≥25mmHg at 3 minutes has a high specificity (97%) but moderate sensitivity (65%) for diagnosis of HFpEF; PCWP ≥21 mmHg at 3 minutes has good specificity (83%) and sensitivity (85%) for predicting peak PCWP ≥25mmHg. Using the 3-minute protocol with PCWP cut-off of 21mmHg, 86% of participants were correctly diagnosed (Figure 1). There were strong positive correlations in PCWP (R2=0.6922), cardiac output (R2=0.5543) and pulmonary vascular resistance (R2=0.6516) between 3 minutes and peak exercise (Figure 2). Conclusions Abbreviated 3-minute eRHC protocol has good diagnostic potential in HFpEF, with strong correlations in haemodynamics, when compared to peak exercise. This suggests that simplification of the current HFpEF protocol to 3 minutes exercise could be a valid strategy to enable improved uptake and maximise resource utilisation while maintaining diagnostic accuracy.Figure 1.Sankey plot of PCWP valuesFigure 2.Haemodynamics during eRHC

Exploring the long-term effects of dapagliflozin in patients with stable acute myocardial infarction and preserved ejection fraction through a propensity score matching study

Abstract Background and Aims The recent Emmy trial underscored notable improvements in cardiac structure and function among post-acute myocardial infarction (AMI) patients treated with Empagliflozin, compared to those receiving a placebo. However, limitations such as a small sample size and a short follow-up period hindered the assessment of potential differences in actual clinical events between the groups. Consequently, our study aimed to evaluate the long-term outcomes, survival rates, rates of major adverse cardiovascular events (MACE), and heart failure (HF) incidence in patients with preserved ejection fraction (EF) who experienced AMI and underwent successful percutaneous coronary intervention (PCI), comparing those who received early initiation of Dapagliflozin with those who did not. Methods Data from the Taipei Medical University Research Database in Taiwan identified 7,081 inpatients who met the criteria of AMI status post successful PCI, with a left ventricular ejection fraction (LVEF) greater than 50% and absence of clinical symptoms indicative of heart failure. Exclusion criteria included individuals with a pre-existing diagnosis of heart failure before the index AMI episode and those with an LVEF below 50%, resulting in the exclusion of 357 patients from our study. The study subjects were then divided into two groups: those treated with Dapagliflozin and those not treated with Dapagliflozin, with matching for age, diabetes mellitus, and chronic kidney disease in a 1:2 ratio. Results The cohort study included of 756 patients who met the criteria of this study, among whom 252 were Dapagliflozin users and 504 were not. Over a 7-year follow-up period, Kaplan-Meier survival analyses revealed a significant reduction in cardiovascular mortality and all-cause mortality among Dapagliflozin users compared to non-users (p < 0.01). However, no significant differences were observed in heart failure, recurrent AMI, or stroke during the follow-up. Multivariate Cox analysis indicated the use of Dapagliflozin (hazard ratio = 0.310, 95% confidence interval = 0.188-0.510, p < 0.001) and age of diagnosis (hazard ratio = 1.063, 95% confidence interval =1.045-1.081, p < 0.001) were both independent predictors of all cause death. Conclusions In patients with stabilized AMI, the use of Dapagliflozin was associated with a decreased risk of all-cause death, especially cardiovascular mortality. However, there were no significant differences observed in the rates of heart failure, recurrent AMI, or stroke over the seven-year follow-up period.Baseline characteristicsKaplan–Meier curves of all cause death

Prognostic and diagnostic implications of impaired rest and exercise-stress left atrial compliance in heart failure with preserved ejection fraction: Insights from the HFpEF Stress Trial

Abstract Background With emerging therapies, early diagnosis of heart failure with preserved ejection fraction (HFpEF) comes to the fore. Whilst the reference standard of exercise-stress right heart catheterisation is well established, the clinical routine struggles between feasibility of exercise-stress and diagnostic accuracy of available tests. Methods The HFpEF Stress Trial (DZHK-17) prospectively enrolled 75 patients with exertional dyspnoea and echocardiographic signs of diastolic dysfunction (E/e’>8) who underwent simultaneous rest and exercise-stress echocardiography and RHC. HFpEF was defined according to pulmonary capillary wedge pressure (HFpEF: PCWP rest: ≥15mmHg stress: ≥25mmHg). Patients were classified as non-cardiac dyspnoea (NCD) in the absence of HFpEF and cardiovascular disease. LA compliance was defined as reservoir strain (Es)/(E/e’). Follow-up was conducted after 4 years to evaluate cardiovascular hospitalisation (CVH). Results The final study population included 68 patients (HFpEF n=34 and NCD n=34) of which 23 reached the clinical endpoint, 1 Patient was lost to follow-up. Patients with HFpEF according to the HFA-PEFF score (≥5 points) had significantly lower LA compliance at rest (p<0.001) compared to patients with a score ≤4. LA compliance at rest outperformed E/e’ (AUC 0.78 vs 0.87, p=0.024) and showed a statistical trend to outperform Es (AUC 0.79 vs 0.87, p=0.090) for the diagnosis of HFpEF. LA compliance at rest predicted CVH (HR 2.83, 95% CI 1.70-4.74, p<0.001) irrespective of concomitant atrial fibrillation. Conclusions LA compliance at rest can be obtained from clinical routine imaging and bears strong diagnostic and prognostic accuracy. Addition of LA compliance can improve the role of echocardiography as the primary test and gatekeeper.