Heart Failure Symptoms Research Articles

Development and validation of a prognostic score integrating remote heart failure symptoms and clinical variables for mortality risk prediction after myocardial infarction. The PragueMi score

Abstract Background While heart failure (HF) symptoms are associated with adverse prognosis after myocardial infarction (MI), they are not routinely used for patients’ stratification. Purpose The primary objective of this study was to develop and validate a score to predict mortality risk after MI, combining remotely recorded HF symptoms and clinical risk factors, and to compare it against the guideline-recommended GRACE score. Methods A cohort study design using prospectively collected data from consecutive patients hospitalized for MI at a large tertiary heart centre between June 2017 and September 2022 was used. Results Data from 1,135 patients (aged 64±12 years, 26.7% women), were split into derivation (70%) and validation cohort (30%). Components of the 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ) questionnaire and clinical variables were used as possible predictors. The best model included the following variables – age, heart failure history, admission creatinine and heart rate, ejection fraction at hospital discharge, and HF symptoms 1 month after discharge including walking impairment, leg swelling, and change in HF symptoms. Based on these variables, the PragueMi score was developed. In the validation cohort, the PragueMi score showed superior discrimination to the GRACE score for 6 months (AUC 90.1, 95% CI 81.8-98.4 vs. 77.4, 95% CI 62.2-92.5, p=0.04) and 1-year risk prediction (AUC 89.7, 95% CI 83.5-96.0 vs. 76.2, 95% CI 64.7-87.7, p=0.004). Conclusion The PragueMi score combining heart failure symptoms and clinical variables performs better than the currently recommended GRACE score.

Cardiac magnetic resonance T1 imaging for the diagnosis of cardiac amyloidosis among patients with symptomatic heart failure

Abstract Background Cardiac amyloidosis (CA) is a significant cause of heart failure in elderly patients. However, specific signs in cardiac imaging are lacking, hence bone scintigraphy in combination with screening for monoclonal protein, or myocardial biopsy is required for the diagnosis. Cardiac magnetic resonance (CMR) imaging with T1 mapping is a promising diagnostic tool, which may allow to differentiate causes of left ventricular (LV) hypertrophy, particularly CA. Purpose The aim of this study was to test the diagnostic accuracy of T1 mapping for the diagnosis of CA in elderly patients with symptomatic heart failure and red flags for CA. Methods We prospectively enrolled 120 patients aged above 60 years with symptomatic heart failure NYHA II-IV, LV ejection fraction ≥ 40%, increased LV wall thickness of ≥ 12 mm end-diastolic on echocardiography, and elevated cardiac biomarkers (N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥ 1,000 ng/L, high-sensitivity cardiac troponin T (hs-cTnT) ≥ 14 ng/L). All patients underwent standardized quantitative CMR with a 3.0T scanner. 99mTc-DPD bone scintigraphy, blood screening for monoclonal protein, and, where applicable, cardiac biopsy, were performed as reference methods in all patients. Primary endpoint was diagnostic accuracy of native T1 mapping for the diagnosis of CA. Results 112 patients were included in the final analysis. Median age was 81.0 years (interquartile range 74.0–85.0 years), and 45% were female. CA was diagnosed in 38 patients (34%), of which 32 suffered from a Transthyretin (ATTR) and 6 patients from light chain (AL) amyloidosis. The areas under the receiver operating characteristic curves for native T1 were 0.713, 0.772, 0.836 for global, septal short-axis (SAX), and septal 4-chamber (4Ch) view measurements. The corresponding value of extracellular volume fraction (ECV) was 0.904 (Figure 1). Based on these results, we developed a new diagnostic algorithm for the diagnosis of CA including T1 septal 4Ch and ECV, with a sensitivity and positive predictive value of both 92.9% and a specificity and negative predictive value of 95.8% (Figure 2). Thereby, contrast application can be avoided in 33% of patients. A definite diagnosis could be provided in 81%. Conclusion CMR with T1 imaging provides a high diagnostic accuracy to diagnose CA in patients with symptomatic heart failure at risk for CA. These data may help to identify underlying causes in heart failure which require specific treatment. An earlier diagnosis of CA may improve outcome of these patients.Figure 1Figure 2

Protein signatures associated with methylation patterns of heart failure phenotypes

Abstract Introduction The heart failure (HF) syndrome is highly susceptible to the exposome. The interplay between DNA methylation (DNAm), surrogate for exposomal influences, and the plasma proteome in the progression and development of phenotypes of heart failure is unclear. We investigated the relation between methylation patterns of HF phenotypes and proteins signatures. Methods Individuals with symptomatic HF (stage C/D with HFpEF, HFmrEF and HFrEF) of the MyoVasc cohort (N=3,289) were investigated. EDTA-Plasma and DNA were extracted from peripheral blood and stored in -80°C. DNAm was measured using the Infinium MethylationEPIC v2.0 methylation array. Concentrations for 538 proteins were measured using an immuno-qPCR assay in EDTA plasma. Multivariable regression models adjusted for age and sex were used to assess the relationship between DNAm signatures and individual proteins in each phenotype. Ridge-regularized linear regression was used to generate a phenotype-specific protein-signature in relation to each methylation signature, linear regression to estimate links between protein signatures and cardiovascular traits and Cox regression relate protein signatures to clinical outcome. Results Data from 1,317 individuals with symptomatic HF were analyzed. After FDR adjustment, 310 proteins were significantly related to HFpEF methylation signature, 314 to HFmrEF and 266 to HFrEF. Of associated proteins, 49.9% (198) were found in all phenotypes, 8.82% (35) only in HFpEF, 12.1% (48) in HFmrEF and 4.79% (19) in HFrEF. Tumor necrosis, arterial hypertension and T-cell regulation pathways were enriched in all three phenotypes. NT-proBNP had the strongest association with HFrEF (β=0.95 [0.82-1.08], p<0.0001) followed by presence of plaques in carotid artery and C-reactive protein, while left ventricular mass (LVM) had stronger association with HFpEF (β=0.22 [0.11-0.33], p=0.0001). All three signatures were associated with worsening of HF (HFpEF: HR=1.93 [1.61-2.30], p<0.0001; HFmrEF: HR=1.63 [1.29-2.04], p<0.0001; HFrEF: HR=1.64 [1.38-1.95], p<0.0001) and all-cause death in HF (HFpEF: HR=1.93 [1.65-2.26], p<0.0001; HFmrEF: HR=1.95 [1.58-2.42], p<0.0001; HFrEF: HR=2.24 [1.86-2.69], p<0.0001). Methylation-associated protein signatures had stronger associations with clinical outcome than the methylation signatures themselves (p < 0.01). Conclusion This study revealed protein signatures associated with methylation patterns of HF phenotypes that shared common and unique features for HF phenotypes. Important common pathways were enriched in tumour necrosis, arterial hypertension and regulation of T cells. However, important differences between phenotypes were also revealed, e.g. NT-proBNP was strongly associated with the HFrEF protein signature and LVM with the HFpEF signature. The methylation-associated protein signatures emphasise the possible exposomal influence on HF syndrome.

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.

Longitudinal changes in the prevalence of indicators for the precursor stage B of heart failure: results of the STAAB study

Abstract Background The ACC/AHA guidelines on heart failure (HF) use selected echocardiographic signs of structural heart disease (SHD) as well as NT-proBNP levels to define the precursor stage B of heart failure in asymptomatic individuals. Purpose To study the change in prevalence over time of echocardiographic signs of SHD or elevated NT-proBNP levels in clinically inapparent individuals of the general population. Methods The STAAB study investigates precursor stages of HF in the general population of a medium-sized city in Germany (source population 124,297 inhabitants as of 2011 census). Participants, stratified for sex and age (30-79 years), were recruited between 12/2013 and 10/2017 from the source population if they had no preceding HF diagnosis and were followed for 2-4 years. Echocardiographic signs of SHD were (for exact definitions see table): left ventricular (LV) hypertrophy, LV dilation, reduced LV ejection fraction. Subjects with history of myocardial infarction, significant LV valve disease or symptomatic HF (Framingham criteria) were excluded. Results Of 4,965 subjects included at baseline, 3,684 (74.2%; mean age 55.2 years, 52.7% women) with at least one paired measurement were analysed. The changes observed over time in the prevalence of echocardiographic signs of SHD and elevated NT-proBNP levels are displayed in the table. Prevalences of echocardiographic signs of SHD increased (significantly for LVEF and LV dilation, trend for LV hypertrophy). Addition of NT-proBNP increased the cross-sectional prevalences, but not the change in prevalence of potential HF precursor stages. Conclusion The net incidence of clinically inapparent echocardiographic signs of SHD increased over time at a rate consistent with the prevalence observed for clinically apparent HF in the general population. Of note, not all echocardiographic findings will eventually result in symptomatic HF, and the classification is influenced by measurement errors. However, our data support the concept of HF precursor stages.

Monocytic mitochondrial dysfunction and impaired monocytic bioenergetic profile in patients with heart failure symptoms in post-COVID syndrome

Abstract Introduction/Purpose Approximately 35% of COVD-19 patients have persistent symptoms similar to congestive heart failure. The so called post-Covid syndrome, which includes symptoms such as dyspnea and angina pectoris, is presumably associated to cellular metabolism and oxidative stress, yet whether mitochondrial function is impaired in post-COVID patients is still unclear. We thus investigated the mitochondrial function in monocytes of symptomatic post-COVID patients compared to matched controls. Methods Patients with persisting cardiac symptoms in their daily activities and diagnosed with post-COVID syndrome (n=14) were recruited and matched with unaffected controls (n=10) for age, sex and cardiovascular risk factors. Structural heart disease was excluded through cardiac work-up (echocardiography, functional stress testing and when necessary coronary angiography). Primary monocytes were isolated using negative selection method. The bioenergetic status of the monocytes was assessed using the Agilent Seahorse XF Cell Mito Stress Test without and after modulation of reactive oxygen species (ROS) by buthionine sulfoximine (BSO). Results CD14++ monocytes isolated from post-COVID patients showed non-significantly increased basal proton leak (p=0.57), reduced maximal respiration, and reserved respiratory capacity (p=0.19) compared to controls. Induction of additional oxidative stress by ROS modulation revealed a significantly impaired bioenergetic profile of monocytes in terms of reduction of basal respiration (3-fold, p=0.0005), maximal respiration (4-fold, p=0.004) and spare respiratory capacity (5-fold, p=0.008). Conclusions We demonstrated an impaired bioenergetic profile of CD14++ monocytic mitochondria in patients suffering from heart failure symptoms following COVID-19 infection. Whether the findings provide a novel biomarker for measuring systemic oxidative stress conditions or whether there is a direct link between symptoms of post-COVID disease and monocytic function needs to be addressed in further studies.

Functional status is associated with mean right atrial pressure derived from cardiac MRI

Abstract Background Right atrial pressure (RAP) is a key metric in haemodynamic assessment. Elevated RAP is associated with poor prognosis in heart failure and pulmonary hypertension and physiologically with fluid overload. RAP can be measured invasively or non-invasively, but Cardiac MRI (CMR) currently cannot estimate RAP. Purpose To develop a model to estimate RAP from CMR from paired right heart catheter (RHC) and CMR assessments. Assess correlation to WHO functional status prior to prospective clinical validation studies. Methods Patients were recruited to a registry of those referred for assessment of dyspnoea between 2012 and 2020. Inclusion criteria were age >18 years, signs and symptoms of heart failure and adequate CMR image quality. Patients diagnosed with pulmonary arterial hypertension were excluded. RHC and CMR were performed on the same day. CMR 2- and 4- chamber cines were used to measure chamber dimensions, strain, ejection fraction and stroke volume with operator reviewed AI contours in MASS research software. Pearson’s product-moment correlation coefficient (r ) was used to assess relationships between CMR metrics and invasive mRAP. Variables were then included in stepwise multiple linear regression models to predict mRAP. These were compared with receiver-operator curve analysis and DeLong’s test. Kruskal-Wallis test compared median mRAP between WHO functional class groups. Results The cohort of 672 patients was divided based upon invasive mRAP ≤ 8mmHg (44%) and mRAP > 8mmHg (56%). Higher mRAP was associated with increased age, male sex and a higher diastolic blood pressure but there was no difference in rates of heart failure types although the majority had preserved ejection fraction (51% vs 52%) with few having reduced ejection fraction (4.1% vs 8%). Right atrial (RA) dimensions, strain and ejection fraction had the strongest correlation with mRAP with moderate correlation to right ventricular (RV) measurements. Multivariable models contained simple RA dimensions (model 1), RA dimensions and strain (model 2), RA and RV dimensions (model 3) and RA end systolic volume corrected for body mass index and sex (model 4). All models had similar predictive capability (Figure 1 Panel A). RA end systolic volume was isolated in model 1 as the only variable required for mRAP prediction (coefficient = 0.06, p < 0.001). Using a threshold of mRAP >8mmHg ROC analysis demonstrated an area under the curve of 0.78 (95% Confidence interval 0.75 to 0.81) (Figure 1 Panel B). Worse WHO functional Class at time of assessment was significantly associated with increased CMR derived mRAP (P<0.001) (Figure 2). Conclusions mRAP can be estimated with moderate confidence from CMR RA end systolic volume. Limited available clinical data suggest functional status may be predicted by CMR derived mRAP. Further studies on wider populations are required to validate this model externally, refine it and determine its prognostic clinical significance.

Potential hematopoietic effects of SGLT2 inhibitors in patients with cardiac amyloidosis

Abstract Introduction Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have been revealed to have potential hematopoietic effects in patients with heart failure (HF), leading to an improvement in clinical outcome. However, these benefits have not been studied in patients with cardiac amyloidosis (CA), despite CA often causing symptoms of heart failure (HF) and contributing to an iron-deficient state, which further complicates by limiting erythropoiesis and lowering haemoglobin and haemotocrit levels. We aimed to determine the potential of SGLT2i in improving haematological parameters and functional capacity (FC) in amyloidosis patients. Methods A prospective analysis was conducted to compare the effects of SGLT2i in a cohort of patients who received the best medical therapy (BMT) alongside SGLT2i (n=20), as opposed to patients receiving only BMT without SGLT2i (n=20). All of patients underwent blood testing and cardiopulmonary exercise testing (CPET) at baseline and after 6 months (IQR:5.0 – 6.0). Results The SGLT2i-based therapy resulted in a significant improvement and difference in hematological parameters upon follow-up assessment compared to the control group. In the SGLT2i group, the mean haemoglobin level increased from 13.3 g/dL to 14.5 g/dL, whereas in the control group, it decreased from 12.7 g/dL to 10.9 g/dL (P < 0.001). Furthermore, the haematocrit difference showed a significant increase in the SGLT2i group (+3.8%) compared to a decrease in the control group (-4.4%) (P < 0.001). Additionally, the iron status improved in the SGLT2i-treated group (+6.7 µg/dL) compared to a decrease in the control group (-14.9 µg/dL), although the difference was significant only with a p-value of 0.034. However, neither group demonstrated significant improvement nor regression in CPET parameters. The peak oxygen consumption (peak VO2, (ml/min)/kg) showed no significant change in either group (P = 0.286), as well as VE/VCO2 slope (P = 0.295). Conclusions Treatment with SGLT2i could be utilized in the treatment of patients with amyloidosis. This potential benefit in improving hematological parameters warrants further investigation and consideration in clinical practice.

Protease-activated receptor 2 (PAR2) inhibition reduces complement-associated cardiac remodelling in obesity-related heart failure

Abstract Background and Aims Obesity is considered a major risk factor for the development of heart failure (HF) due to lipid accumulation, oxidative stress and inflammation which results in cardiac remodeling. Protease activated receptor 2 (PAR2) has been linked to various cardiovascular and inflammatory diseases. The role of PAR2 has not yet been studied in obesity-related HF. Methods In the experimental mouse study, we used 1-year-old ApoE knockout (ApoE-/-) and ApoE PAR2 double knockout (ApoE-/-PAR2-/-) mice with a C57BL/6J background on a high fat (HF) diet (n=5/ group). Cell culture experiments were performed with human primary cardiac fibroblasts and HepG2 hepatocytes. Patients (n=50) included in the clinical study had a BMI > 25kg/m², symptoms of heart failure (HF), coronary angiography (CA) that excluded coronary artery disease (CAD) and endomyocardial biopsy (EMB) that confirmed the absence of active myocarditis or primary cardiac amyloidosis. Patients were divided into PAR2low (n=22) and PAR2high (n=22) based on the median PAR2 expression measured via qPCR in the EMB of the cohort, and six patients served as healthy controls. Results Evaluation of endomyocardial biopsies (EMB) from overweight/ obese non-ischemic cardiomyopathy (NICM) patients with heart failure (HF) (n=44) revealed that a reduced cardiac PAR2 expression is associated with less cardiac C3 (p≤0.054), C4 (p≤0.041) and C5 gene expression (p≤0.045), as well as plasma levels of complement C3 (1.1g/l± 0.7 vs 2.1g/l±0.2; p≤0.016) and C5b-9 (303.4ng/ml± 215.7 vs 992.7ng/ml± 756.2; p≤0.0002) and as a result, better systolic function i.e. LVEF (46.1%±17.1 vs 36.8%±15.2; p≤0.046) and LV GLS (-14.9%± 5.7 vs -9.5%± 4.6; p≤0.009), less cardiac remodeling and damage. Correspondingly, aged ApoE-/-PAR2-/-mice on a Western diet showed less hepatic and cardiac complement expression (i.e. C1q, C3, C4, C5, C9), cardiac C3 deposition (p≤0.047) and C5b-9 plasma levels (p≤0.049), as well as less cardiac necrosis (p≤0.046) and lower BNP (p≤0.016) than ApoE-/-. PAR2 overexpression in human cardiac fibroblasts (HCFs) independently enhanced and PAR2 antagonism reduced interferon γ (IFNγ)-mediated STAT1-dependent complement C3, C4 and C5 expression. Conclusions Protease-activated receptor 2 regulates complement-mediated cardiac damage and remodeling in HF. The PAR2-IFNγ/STAT1/C3-C4-C5 complement-axis might be a promising prognostic and therapeutic approach to identify and treat high-risk cases of HF in overweight/obese patients.

Performance of an automated echocardiographic artificial intelligence model. to detect subclinical heart failure with preserved ejection fraction (HFpEF) in community-dwelling older adults

Abstract Background Heart failure (HF) with preserved Ejection Fraction (HFpEF) is common among older adults and associated with a high burden of morbidity and mortality. Early identification of subclinical HFpEF, defined by abnormalities in cardiac structure and function without symptoms of HF, can prompt early initiation of evidence-based therapies to prevent HFpEF. However, scalable strategies for the identification of subclinical HFpEF are lacking. Purpose To evaluate the performance of a validated, automated echocardiographic artificial Intelligence algorithm (Ultromics, UK) to identify subclinical HFpEF among community-dwelling individuals without HF. Methods The study included participants of the Dallas Hearts and Minds Study without HF who underwent cardiovascular phenotyping with resting and exercise echocardiography and maximal cardiopulmonary exercise testing. The resting apical 4C echocardiographic images were analyzed by the AI echo algorithm to identify the HFpEF phenotype (AI-HFpEF). Subclinical HFpEF was defined by E/e’ >14 and Peak exercise oxygen uptake (VO2peak) <25th percentile for the cohort. The performance of the AI algorithm to detect subclinical HFpEF was determined using the area under the receiver operating curve and decision curve analysis and was compared with the previously validated H2FpEF score. The association between the AI-HFpEF phenotype and the presence of subclinical HFpEF, VO2peak, exercise E/e’, left ventricular strain, and left atrial strain was assessed using multivariable-adjusted logistic and linear regression models. Results The study included 511 participants (mean age: 61 y, 57% women, mean VO2peak = 16.9 ml/kg/min). Using the AI echo algorithm, subclinical HFpEF was detected in 10% of participants (n=76), and 10% were non-diagnostic. The participants with (vs. without) AI-HFpEF phenotype were older and had a higher burden of CVD risk factors, left ventricular hypertrophy, and left atrial dilation. Subclinical HFpEF, as defined by the gold standard criteria, was present in 5.3% of participants. The AUROC for diagnosis of subclinical HFpEF using the AI-HFpEF algorithm was 0.85 vs. 0.78 by the H2FpEF score (see Figure). In the adjusted analysis, the AI-HFpEF phenotype was significantly associated with greater odds of subclinical HFpEF by exercise and echocardiographic phenotyping criteria, higher E/e’ with exercise, lower VO2 peak, and worse LV and LA strain (see Table). In decision curve analysis, the AI-HFpEF algorithm identified 23 additional cases of subclinical HFpEF per 1000 screened participants compared with the H2FpEF score. Conclusion The AI-HFpEF algorithm can reliably identify community-dwelling individuals with subclinical HFpEF characterized by diastolic dysfunction at rest or exercise and impaired exercise capacity. Future studies are needed to assess the utility of the AI-HFpEF algorithm in screening for subclinical HFpEF in health systems.

High-Intensity interval training improves global longitudinal strain in patients with metabolic syndrome and high risk of heart failure

Abstract Background Metabolic syndrome (MS) has been associated with the development of myocardial dysfunction which can lead to heart failure (HF). It is possible to detect early signs of myocardial dysfunction by assessing the global longitudinal strain (GLS) in a transthoracic echocardiography. A reduced GLS is considered as a predictor of HF development. Preventive strategies are recommended in patients with MS to avoid the progression to HF. Although exercise improves cardiovascular and metabolic health in MS patients, it is unknown whether exercise can affect the evolution of GLS in a group of patients with MS who are under medical treatment. Purpose To assess the prevalence of myocardial dysfunction (i.e., reduced GLS) in a heterogeneous group of patients with MS who are under medical treatment, and to test in these patients if 16 weeks of high-intensity interval training (HIIT) can improve the GLS. Methods Seventy-seven volunteers with MS and without signs or symptoms of HF were randomized in one of two 16-week intervention: i). HIIT in stationary bikes 3 sessions/week, 50 minutes/session + medical treatment (HIIT group), or ii). medical treatment (CONTROL). Maximal oxygen consumption (VO2max), and GLS together with rutinary echocardiographic parameters were assessed before and after intervention. The effect of HIIT compared to CONTROL was analyzed by a split-plot ANOVA to compare the effects of time (pre vs. post) and group (HIIT vs. CONTROL), and the interaction between the two factors. Results Before intervention 48.9% of participants from the HIIT group, and 46.7% from the CON group had a reduced GLS (i.e., >17% for men and >18% for women). However, none of them had a reduced left ventricular ejection fraction (LVEF), signs of diastolic dysfunction or an abnormal VO2max (less than 80% of predicted VO2max). After the 16-week intervention, only individuals from the HIIT group improved their VO2max (time*group P<0.001). LVEF did not improve in any of the experimental groups (time P=0.278) HIIT group improved their GLS by 0.51%, whereas CONTROL group improved it by 0.05% without reaching statistical significance (time*group P=0.186). However, a subgroup analysis of GLS conducted among the participants from the HIIT group discriminated by their pre-intervention values (GLS normal or reduced), showed that individuals with reduced GLS improved significantly by 1,41% (P=0.001) whereas those with a normal GLS improved by 0.14% without reaching statistical significance (P=0.736, time*group P=0.009). Conclusions Myocardial dysfunction assessed by GLS is present in MS even in the absence of symptoms, diastolic dysfunction, or reductions in the LVEF. HIIT can reduce the risk of HF development by improving GLS in patients with MS and early signs of myocardial dysfunction.A. Overall changes in GLSB. Subgroup analysis of GLS pre vs. post

Associations of Cardiac myosin binding protein C to Troponin I in patients with chronic heart failure during exercise. A substudy of the SMARTEX-HF trial

Abstract Aim Cardiac myosin binding protein C (cMyC) has shown promise being more sensitive than cardiac troponins, rising faster after myocardial infarction[i]. Its association to hs-cTnI in heart failure patients during physical activity is not known. The aim of this study was to assess the association between a novel biomarker: cMyC and the clinically used high sensitivity cardiac Troponin I (hs-cTnI) during a 12-week exercise training program in patients with chronic symptomatic heart failure with reduced ejection fraction (HFrEF). The changes of biomarkers in plasma levels in an intervention group, performing structured exercise programs, were compared to those in a control group, instructed to perform regular recommended exercise (RRE) according to current guidelines. Methods and results This was a post hoc analysis of the SMARTEX-HF trial in 215 patients with symptomatic heart failure (HF) with Left Ventricular Ejection Fraction (LVEF) <35% and NYHA II-III. The patients were randomly assigned to High Intensity Interval Training (HIIT, n=77), Moderate Continuous Training (MCT, n=65) or RRE, (n=73) for 12 weeks. Measurements and clinical data were acquired before and after the 12-week intervention. In 191 patients, plasma was available for hs-cTnI testing and in 189 patients plasma was available for cMyC testing. Due to the lack of a normal distribution, the values were log transformed. There was a significant association of change in log hs-cTnI and change in log cMyC (Pearson correlation R=0.52 (95% CI 0.37- 0.66) p<0.001) (Figure 1). For any 10% increase in cMyC level, the ratio of the hs-cTnI level increased with approximately 5% (Figure 2). There was no association between the levels of cMyC at baseline and change in hs-cTnI at 12 weeks. Conclusion Changes in levels of the novel biomarker cMyC was significantly associated with hs-cTnI plasma levels in patients with symptomatic chronic HFrEF during a structured 12 week exercise training program. Being more sensitive, it may indicate a role as a future marker of subclinical myocardial damage.Models with adjustmentsMarginal effect at the mean

Serum expression of mirnas in obese and lean patients with heart failure

Abstract Background Heart Failure (HF) is a progressive disease that results in increased morbidity and mortality, and clinical studies have demonstrated that body mass index (BMI) is an independent risk factor for the development of HF. Evidence has suggested that human obesity is associated with reduced mortality among patients with HF, a clinical phenomenon known as the "Obesity Paradox." MicroRNAs (miRNAs) have been underscored for their pivotal regulatory roles in numerous diseases, particularly in the context of HF. Nevertheless, our understanding of the impact of these miRNAs on obesity in conjunction with HF remains limited. Purpose The objective of this study was to evaluate the serum expression of miRNAs in obese and lean patients with HF and establish the relationship between these miRNAs and BMI. Additionally, we explored this association within two distinct phenotypes: HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Methods Sixty-five patients with symptomatic HF (all NYHA >/=II, mean-LVFE 44.4 %), 29 lean (BMI= 25.87 ± 2.52 Kg/m2) and 36 obese (BMI= 34.52 ± 4.15 Kg/m2), were prospectively evaluated by clinical, laboratory and echocardiographic analyses. Serum expression of miRNAs was assessed by the TaqMan OpenArray Human MicroRNA system, a polymerase chain reaction-based quantitative platform that contains 754 microRNAs in a microfluidic platform. Results Among the studied miRNAs, seventeen were upregulated and one downregulated in obese HF patients compared to lean HF patients (Figure 1A). Ten miRNAs were differentially expressed in the serum of obese HFpEF patients compared to lean HFrEF patients (Figure 1B) and five were differentially expressed in the serum of obese HFpEF patients when compared to lean HFpEF patients (Figure 1C). miR-132 was upregulated in obese patients with HFrEF and HFpEF compared to lean patients, whereas miR-1291 was downregulated only in obese patients with HFpEF. Correlation analysis demonstrated a positive association between BMI and miR-132 (r=0.502; p=0.001), miR-148b (r=0.510; p<0.001), miR-103a-3p (r=0.373; p =0.011) and miR-374b-5p (r=0.325; p=0.034) in HF patients and gene set enrichment analysis identified seventy-nine potential target genes common to at least three of these four miRNAs, with the EIF4E3 and TRA2B genes common to the four miRNAs. Conclusions Our study reveals a profile of miRNAs that are differentially expressed in obese patients with HF when compared to lean patients with HF. Furthermore, four of these miRNAs showed a positive correlation with BMI in patients with HF. Although the literature indicates that miR-132 presents reduced expression in obesity models, our study identified increased serum expression of this miRNA, suggesting that it might be a potential "missing link" in the obesity paradox in patients with HF. Further studies with a larger sample are needed to confirm and explore the mechanisms linking these miRNAs to the obesity paradox.

Tafamidis for the treatment of transthyretin cardiac amyloidosis (ATTR-CM) - Real-world data from a tertiary center

Abstract Introduction Tafamidis 61mg was shown to be the first treatment to reduce cardiovascular hospitalizations and to improve survival in patients with Transthyretin Amyloid Cardiomyopathy (ATTR-CM). Real-world data on the efficacy of transthyretin (TTR) stabilizers in patients with Heart Failure (HF) due to ATTR-CM is scarce. Purpose We aimed to assess the use of tafamidis in our center, that features a dedicated Cardiomyopathy Clinic. Methods We conducted an all-comers single-centre prospective study of consecutive patients with symptomatic HF due to ATTR-CM followed up to November 2023. As per site protocol, the diagnosis was established according to the ESC algorithm and all patients were assessed at least twice yearly. Disease management plans include HF treatment tailored to ATTR-CM (CHAD-STOP) and treatment with disease-modifying tafamidis 61mg. The latter is considered in patients who meet the local protocol criteria, including key inclusion criteria - NYHA class I-II - and none of the exclusion criteria - e.g. estimated glomerular filtration rate (GFR) <25mL/min. The primary endpoint was time to cardiovascular hospitalization or all-cause death. Results A total 226 ATTR-CM patients were identified, of whom 181 had a follow-up of at least 6 months and were included in the analysis (mean age 84 ± 7 years; 81% males, 16% hATTR-CM). Overall, there were 84 patients treated with tafamidis. Compared to non-treated patients, those receiving tafamidis were younger (mean age 83 vs. 86 years, p=0.007), more often with a lower NYHA functional class (e.g., NYHA I-II: 92 vs. 62%; p<0.001), scored higher on performance scales (e.g., Karnovsky >70: 67 vs 33%; p<0.001), and had less comorbidities (e.g., GFR: 40 vs. 30mL/min; p<0.001). Over a median follow-up of 16 months, 68 (37.6%) patients met the primary endpoint (49.5% vs. 22.6%, respectively; p<0.001). In multivariate analysis, treatment with tafamidis was an independent predictor of the primary endpoint (HR 0.24; 95%CI 0.13-0.43; p<0.001), adjusted for NYHA functional class (HR for NYHA I-II vs. III-IV: 0.54; 95%CI 0.32-0.92; p=0.023), NT-proBNP (HR 1.83; 95%CI 1.09-3.08; p=0.023) and high-sensitivity Troponin T (HR per 10 units: 1.01; 95%CI 1.01-1.02; p=0.024). These findings were consistent in multivariate analysis with any combination of the prior variables with either creatinine, GFR, albumin, or TTR type (wild-type vs. mutated). These results were primarily driven due to association of tafamidis treatment with increased survival. Conclusion The use of tafamidis in a cohort of patients with symptomatic HF and ATTR-CM was shown to be independently associated with reduced cardiovascular hospitalization or all-cause death. The effect had a similar magnitude of effect to that of the ATTR-ACT trial, suggesting that our local protocol based on the key criteria from this trial may allow for appropriate patient selection.

A comparative analysis of conventional echocardiographic findings among different heart failure stages and phenotypes: insights from the national echocardiographic society registry

Abstract Background The contemporary conceptualization of heart failure (HF) encompasses four developmental stages (at risk for HF, pre-HF, symptomatic HF, and advanced HF) and three distinct HF phenotypes categorized by left ventricular ejection fraction (LVEF) (HFpEF, HFmrEF, HFrEF). However, there is a need for a more comprehensive understanding of echocardiographic similarities and differences among pre-HF stages and various HF phenotypes. Material and Methods Our national echocardiographic society conducted a multicenter HF screening initiative. General practitioners in 13 primary care centers utilized the original mobile phone app to determine referrals for transthoracic echocardiography and N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing in individuals without a prior HF diagnosis. The 2021 ESC guidelines' algorithms were used to diagnose HF phenotypes and 2016 EACVI/ASA recommendation² to assess diastolic function. This study defined "heart stress" (elevated NT-proBNP in asymptomatic individuals with risk factors, regardless of structural heart disease or cardiac dysfunction) and "patients at risk for HF" (normal NTproBNP and at least one HF risk factor). All patients were categorized into six groups: (I) no HF, no risk, (II) at risk for HF, (III) heart stress, (IV) HFpEF, (V) HFmrEF, and (VI) HFrEF. Echocardiographic findings were compared among groups (II) to (VI), using ANOVA, Kruskal-Wallis and Chi-squared test, when needed. Results In a cohort of 930 outpatients (mean age 66±11 years, 61% female), 34.2% were diagnosed with HF, 22.3% experienced heart stress, 37.8% were at risk for HF, and 12.8% had neither HF nor risk factors (Figure). While NT pro BNP showed progressive increase, LVEF showed a progressive decline across the groups, reaching its lowest in HFrEF patients (Table). Simultaneously, left ventricular mass index (LVMi), left atrial volume index (LAVi), and maximal velocity of tricuspid regurgitation (TR Vmax) significantly increased in a stepwise manner. Variations in predominant LV geometry were significant across groups (p<0.001): normal LV geometry in those without HF (60.8%), concentric LV remodeling in at-risk patients (38.6%), normal LV geometry in heart stress (49%), concentric LV hypertrophy (LVH) in HFpEF (27.7%), eccentric LVH in HFmrEF (42.3%), and both concentric and eccentric LVH in HFrEF (43.3% each). Diastolic dysfunction increased prevalence across the groups (12.9% vs 24.7% vs 37.6% vs 19.6% vs 51.1%, p<0.001). Remarkably, HFmrEF group had the highest proportion of undetermined diastolic function (14.7% vs 23.1% vs 27.9% vs 50% vs 26.7%, p<0.001). Conclusions The mobile phone app used in primary care setting allowed identification of significant number of individuals in the pre-HF stages, warranting further investigation. Distinct echocardiographic differences in pre-HF stages and HF phenotypes provide valuable insights for early detection and tailored treatments.

Prevalence and outcomes of American Heart Association stages of heart failure in an adult brazilian population of the ELSA-Brasil study

Abstract Aims Heart failure (HF) has a major impact on public health, affecting up to 2% of adult population. HF staging is helpful in capturing pre-clinical disease and its progression to advanced stages. We aimed to determine the prevalence and mortality of HF stages in the participants of a Brazilian adult cohort. Methods The ELSA-Brasil cohort comprises 15,105 adult public servants from 6 Brazilian capitals. In the initial evaluation of the study (2008-2010), ELSA carried out interviews and clinical, laboratory, and cardiovascular ancillary tests. In this analysis, we included participants who had electrocardiogram and echocardiogram performed at baseline visit, and additional information regarding risk factors and functional capacity. The HF stages were defined based on AHA guidelines criteria as follow: Stage 0 was defined as a healthy individual with no risk factors for heart failure. Stage A (at risk for HF) included those without cardiac structural or functional abnormality but with any of the following conditions: systemic hypertension; diabetes mellitus, obesity, history of myocardial revascularization, history of rheumatic fever, and seropositivity for Chagas’ disease. Stage B (pre-HF) was defined as asymptomatic participants with history of myocardial infarction or any major abnormalities on ECG or echocardiogram. Stage C (symptomatic HF) included participants with a clinical history of HF, or HF symptoms in the presence of structural heart disease (defined as in Pre-HF stage). Considering the community-dwelling profile of the sample, we did not expect to have advanced heart failure patients in our sample. Results We included the 3,267 participants (61±9 years; 53% women) with baseline data. Prevalences of HF stages were stage 0: 938 (29%) A: 1,385 (42%), B: 651 (28%) and C: 293 (9%), with different distribution between sexes (p<0.001). Older participants had higher prevalences of stages B and C (p<0.001), with the prevalence of stage C increasing from 1.8% at 35-44 years to 12.2% at 65-74 years. After 12 years of follow-up, total mortality rates of HF stages were Stage 0: 4%; A:10%. B: 16%, and C: 26%, and respective Cox proportional hazard ratios [95% CI] adjusted for age and sex were A: 1.94 [1.3-2.8], B:2.78 [1.9-4.1], and C: 5.39 [3.6-8.1] compared to stage 0. Conclusions The prevalence of HF in Brazilians reflects what is described in international literature, with a large proportion of individuals in pre-symptomatic stages. A notable shift in the sample toward pre-symptomatic and symptomatic HF occurred gradually and persistently across the age span studied. Mortality rates increase incrementally across the HF stages. This information is important for understanding and planning health policies for this syndrome.

Health-related quality of life disparity in cardiac sarcoidosis versus other myocardial diseases

Abstract Background Sarcoidosis, a systemic inflammatory disorder, can manifest as progressive inflammatory heart disease, termed cardiac sarcoidosis (CS). Despite advances in treatment, the impact of CS on health-related quality of life (HRQoL) remains incompletely understood. This study aimed to compare HRQoL between patients with CS and those with non-inflammatory cardiomyopathies, namely dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Purpose To assess and compare HRQoL across patients with cardiac sarcoidosis and non-inflammatory cardiomyopathies. Methods A total of 240 CS patients (86% response rate), 96 DCM patients (55% response rate), and 81 HCM patients (65% response rate) completed the RAND-36 general health-related questionnaire, comprising eight dimensions. Patients listed for transplantation were excluded. Clinical data were obtained from the Finnish myocardial inflammatory diseases registry for CS patients and from medical records in hospitals for HCM and DCM patients. Results Median age ranged from 56 to 59 years across the groups. Unlike DCM, which typically presents with heart failure symptoms, a substantial proportion (82%) of CS patients presented with advanced atrioventricular block or ventricular arrhythmias, while HCM cases were often incidentally detected or identified through family screening. Most CS patients (94%) had implanted pacemakers or ICDs, compared to a lower proportion in HCM (26%) and DCM (63%). DCM patients exhibited a higher prevalence of impaired LVEF (<50%) compared to CS and HCM patients. Functional impairment, as measured by NYHA class, was most pronounced in DCM patients. CS patients experienced more adverse events between diagnosis and the study entry, particularly sustained ventricular tachycardia/ventricular fibrillation. However, heart failure hospitalizations did not significantly differ between groups. Table 1 presents a comparative analysis of patient-reported outcomes across four functional and mental dimensions to assess the relative burden of disease among patients with CS, HCM, and DCM. While the functional dimensions in CS exhibited disparities from both HCM and DCM, no significant differences were observed in the mental dimensions between CS and HCM. CS patients reported lower scores in the domains of role physical, and general health compared to either HCM or DCM counterparts. Conclusion Patients with CS demonstrated significantly poorer HRQoL compared to those with non-inflammatory cardiomyopathies. This underscores the substantial burden of disease associated with CS and highlights the importance of comprehensive management strategies to address both clinical and quality of life aspects in affected individuals.

Sex differences in paediatric onset hypertrophic cardiomyopathy

Abstract Background Hypertrophic Cardiomyopathy (HCM) is a heterogeneous disease characterised by age related incomplete penetrance and variable long term outcomes. Sex differences have been described in both the clinical phenotype and natural history of adults with the disease, which have been attributed to both biological (eg sex hormone effect) and non-biological (eg societal and cultural effects) factors. It is unknown if similar sex differences exist in childhood-onset HCM. Purpose This study aimed to investigate the influence of biological sex on the clinical characteristics and outcomes of children with HCM. Methods Retrospective cohort study from an international registry of patients diagnosed under the age of 18 years with HCM. Patients with syndromic disease (RASopathy syndromes, inborn errors of metabolism, neuromuscular disease) were excluded. Sex differences in baseline characteristics and clinical outcomes were described. Primary outcomes were all-cause mortality or cardiac transplantation, Major Arrhythmic Cardiac Event (MACE) and heart failure event (defined as heart failure death or cardiac transplantation) Results Of 1262 patients, 851 (67.4%) were male (median age 11 yrs (IQR 7.4, 14.4) vs 11.1 (IQR 6.9, 14.0) in females, p=0.0312). Female patients were more likely to have a sarcomeric variant identified (n=208, 85.6% vs 388 (79.4%), p=0.041) despite equivalent genetic testing utilisation between sexes. Female patients were more likely to have severe heart failure symptoms (NYHA 3 or 4) (n=19, 6.1% vs n=20, 2.5% p value 0.030) but there was no difference in the proportion on medical therapy (male n=328, 39.7%, female n=167, 41.8, p value 0.476). The clinical phenotype in terms of degree of hypertrophy, left atrial size and left ventricular outflow tract gradient did not differ by sex. Over a median follow up of 5.2 years (IQR 2.4, 9.9) all-cause mortality or cardiac transplantation did not vary by sex but females were more likely to experience a heart failure event (females 0.6/100,000 pt years (95% CI 0.39-0.92) vs males 0.32/100,000 pt years (95% CI 0.21 – 0.50), hazard ratio 1.89, p value 0.0467). The incidence of MACE did not differ by sex but there was a trend towards higher implantable cardioverter defibrillator implantation in females (n=123, 30.7% vs n=210, 25.4%, p value 0.051). Conclusions For the first time, this study has shown sex differences in paediatric-onset hypertrophic cardiomyopathy. Despite no difference in baseline clinical phenotype, young female patients are more likely to experience heart failure symptoms and heart failure events over follow up. Further studies are required to explore the underlying mechanisms for these observed differences.Table summarising outcomes by sexSurvival free from heart failure

Changes in the diagnostic landscape of transthyretin amyloid cardiomyopathy (ATTR-CM): a comparison of tests ordered and test Intervals in 2020 Q4 and 2023 Q4

Abstract Background Transthyretin Amyloid Cardiomyopathy (ATTR-CM) is a genetic disease caused when misfolded transthyretin protein is deposited in the myocardium. Amyloidosis driven stiffness in heart muscles results in heart failure symptoms. ATTR-CM is underdiagnosed, requiring specialized tests to identify the condition. Purpose This paper examines and compares diagnostic tests and the time intervals between rounds of testing conducted to identify ATTR-CM in 2020 Q4 and 2023 Q4 in France (FR), Germany (DE), Italy (IT), Spain (ES) and the United Kingdom (UK). Methods A multi-centre online medical chart review was performed between November and December 2020, with 210 (FR: 46, DE: 40, IT: 43, ES: 42, UK: 39) cardiologists/internists providing data on 320 (FR: 71, DE: 63, IT: 64, ES: 63, UK: 59) patients diagnosed with ATTR-CM; and between October and November 2023, with 225 (FR: 45, DE: 48, IT: 48, ES: 45, UK: 39) cardiologists/Internists providing data on 780 (FR: 151, DE: 163, IT: 172, ES: 175, UK: 119) patients. Participants were screened for ATTR-CM patient management. We analysed the diagnostic tests ordered and tracked the intervals between batteries of tests to understand how the timing of diagnosis has changed across the EU4+UK. Results The average number of ATTR-CM diagnostic tests received by reported patients rose from 5.9 in 2020 to 7.4 in 2023, with ECHO with strain imaging (87%), Genetic tests (78%), Cardiac MRI (74%), Laboratory tests (67%), and Scintigraphy tests (65%) as the top 5 tests in Q4 2023. There was a notable increase in the use of ECHO with strain imaging, Laboratory tests, and Scintigraphy tests recorded in the Spanish patient cohort (p<0.01). Reported patients in Italy, Spain & UK received an increased average number of tests (p<0.05) [Table 1]. The recorded interval between the 1st and 2nd test batteries remained consistent between Q4 2020 and Q4 2023 (4.8-4.9 wks.), but the interval between the 2nd to 3rd rounds increased from 4.3 to 5.0 weeks. Timings between batteries increased in the France, Germany, Italy and UK data. Reported patients in Germany continue to experience the shortest intervals between batteries of tests (4.1 wks. between 1st and 2nd; 4.4 wks. between 2nd and 3rd batteries). Between Q4 2020 and Q4 2023, reported patients in Spain had an increase in the average number of tests received from 5.2 to 7.2, and were the only group with decreased time intervals (7.3 to 4.5 wks. between 1st and 2nd; 5.8 to 5.1 wks. between 2nd and 3rd batteries) Conclusion Results indicate that the use of certain diagnostic tests as well as the number of tests used to diagnose ATTR-CM has increased, however, intervals between testing batteries have also increased. This suggests that the increase in the number of tests used to diagnose ATTR-CM is possibly negating the necessity for more frequent testing. Further research in needed to confirm this and assess its impact on early detection of ATTR-CM.Table 1:Diagnostic Procedures by RegionTable 2:Testing battery intervals

No improvement in atrial arrhythmia rates in patients on baroreflex activation therapy

Abstract Background Atrial arrhythmias encompass a wide range of abnormal cardiac rhythms including atrial fibrillation, atrial flutter, and atrial tachycardia. Patients with heart failure with reduced ejection fraction (HFrEF) have increased risk of atrial arrhythmias, ultimately leading to increased morbidity. Baroreflex Activation Therapy (BAT) employs an implantable device to increase parasympathetic nervous system activity by stimulating the carotid baroreceptors thereby reducing afterload and heart failure symptoms. In our prior study, BAT therapy has been shown to reduce hospitalization rates in patients with HFrEF. However, the effects of BAT on atrial arrhythmia has never been studied. Objective In this study, we analyzed the effects of BAT on atrial arrhythmia rates in patients with HFrEF. Methods Patients with HFrEF with BAT therapy for at least 12-months at a hospital were retrospectively studied. Inclusion criteria includes implantable cardioverter-defibrillator (ICD) placement of at least 12-months pre- and post-BAT therapy. Additionally, patients diagnosed with atrial arrhythmias prior to the study timeline were excluded. Atrial arrhythmia rates 6 and 12-months pre-BAT therapy and 6 and 12-months post-BAT therapy were compared. Atrial arrhythmia episodes were recorded through ICD interrogation every 1-3 months in the clinic. Of the 31 identified patients on BAT therapy, 11 patients fit the inclusion criteria. For the 11 patients in the study, 3 identified as female and 8 identified as male, 6 identified as white, 4 identified as Hispanic, and 1 identified as African-American with a mean age of 59.8 ± 17.4 years. The average left ventricular ejection fraction pre-BAT therapy was 23.8 ± 10.8%. Results The mean average atrial arrhythmia rates for 6-month pre-BAT therapy and 6-month post-BAT therapy were 0.12/month ± 0.40 and 1.32/month ± 2.76 respectively (p=0.18), suggesting no differences in atrial arrhythmia rates at 6-months with BAT therapy. The mean average atrial arrhythmia rates for 12-month pre-BAT therapy and 12-month post-BAT therapy were 0.11/month ± 0.35 and 2.40/month ± 5.84 respectively (p=0.22), suggesting no differences in atrial arrhythmia rates at 12-months with BAT therapy. Conclusion Although BAT therapy has been shown to decrease hospitalization rates, BAT therapy is not associated with decreased atrial arrhythmia rates at 6 months and 12 months.