Heart Failure Group Research Articles

8 DIFFERENCES BETWEEN PATIENTS HOSPITALIZED FOR PAROXYSMAL ATRIAL FIBRILLATION AND HEART FAILURE WITH PRESERVED, MIDLY-REDUCED, AND SEVERELY-REDUCED EJECTION FRACTION

Abstract Introduction Paroxysmal atrial fibrillation (PAF), is a very common cardiac arrhythmya in patients with heart failure (HF). In the last five years we observed many patients with AF. Aim of this observation was to evaluate differences on clinical outcomes of a paroxysmal AF episode on patients with preserved (HFpEF), mildly reduced (HFmrEF), or severely-reduced (HFrEF) ejection fraction. Methods 439 patients consecutively hospitalized in our Cardiology Unit from January 2017 to January 2022 for paroxysmal AF were retrospectively evaluated. Of them, 201 presented without heart failure, 59 with a previously known HFpEF, 49 patients with HFmrEF, and 130 patients with HFrEF. For each patient, demographic and clinical characteristics, comorbidities, instrumental data and clinical outcomes (percentage of cardioverted arrhythmia, length of hospitalization) were collected. To examinate the correlations between characteristics of patients and clinical outcomes, chi-square or Pearson test were performed. Results patients with AF and HF were significantly older rather than AF patients without HF. No significantly differences we found between the three HF groups. The three groups of AF patients with HF presented more comorbidities rather than AF patients without HF. The duration of hospitalization were significantly longer for AF patients with HF rather than AF no-HF patient, without differences between the three goups . Percentage of cardioverted AF were significantly higher in no-HF patients rather than in HFrEF, but not in HFpEF and HFmrEF patients . In no-HF and in HF groups, age and length of hospitalizations were significantly correlated, but no differences we found between the groups. In the three HF groups, number of comorbidity were inversely correlated with percentage of cardioversion, but not in no-HF group. Age was significantly correlated with failure in attemps of cardioversion, without differences between HF and no-HF patients. Conclusions our hospitalized patients for a newly onset AF and HF presented worse clinical outcomes rather AF patients without HF. This worsening clinical outcome, seem at least in part due to differences on age and comorbidities between the three groups, whereas cardiac systolic function seems not been significantly related with worse clinical outcomes.

192 GLP1-RA AND HEART FAILURE-RELATED OUTCOMES IN PATIENTS WITH AND WITHOUT HISTORY OF HEART FAILURE: A SYSTEMATIC REVIEW AND METANALYSIS

Abstract Background GLP1-receptor agonists (GLP1-ra) are recently developed anti-diabetic drugs which have shown promising results in phase-3 cardiovascular (CV) outcomes trials in diabetic patients, demonstrating a reduction in major adverse cardiovascular events (MACE) and, possibly, in heart failure (HF) hospitalizations. However, whether these medications improve such outcomes in patients with a history of HF remains unknown. Methods All randomized, placebo-controlled trials of GLP1-ra (and predefined/post-hoc analysis) reporting CV outcomes stratified by HF history were searched in Pubmed from inception to August 31st, 2022. The primary outcome was HF hospitalizations. Secondary outcomes included MACE, CV death and a composite of HF hospitalization and CV death. The analysis was performed after stratifying for HF history. Odds-ratio (OR) and 95% confidence interval (CIs) were used as effect estimated and calculated via a random-effects model. P for interaction between subgroups were calculated via meta-regression analysis and a level of p<0.10 was considered as significant. Results Data from 6 trials and a total of 40300 patients (n=20127 GLP1-ra group, n=20173 placebo group) were included. GLP1-ra reduced HF hospitalizations in patients without HF history (OR 0.71, 95% CI 0.51-0.99) but had neutral effect on those with previous HF (OR 1.04, 95% CI 0.88–1.22, p-interaction=0.089). CV death was also reduced by intervention only in the group without history of HF (OR 0.81, 95% CI 0.71–0.92), as well as the composite of HF hospitalizations and CV death (OR 0.80, 95% CI 0.72–0.90). Indeed, no difference between treatment arms was found in the HF group for CV death (OR 0.99, 95% CI 0.82–1.18, p-interaction=0.18) and the composite of HF hospitalization or CV death (OR 1.02 95%CI 0.89–1.18, p-interaction=0.073). MACE reduction was similar in patients with (OR 0.87 95% CI 0.72–1.06) and without HF history (OR 0.84 95% CI 0.76–0.93, p-interaction = 0.75). Conclusion GLP1-ra do not reduce HF hospitalization and CV death in patients with history of HF, as the benefit on cardiovascular outcomes provided by this anti-diabetic class of drugs seems to be mainly limited to patients without HF history. Future studies focused on HF patients are needed to confirm such findings and clarify the limited efficacy of GLP1-ra in this relevant group of patients.

142 ADVANCED HEART FAILURE IN PATIENTS WITH ARRHYTHMOGENIC CARDIOMYOPATHY

Abstract Background Arrhythmogenic Cardiomyopathy (ACM) is a primary disease of the heart muscle, characterized by fibro-fatty myocardial replacement. Improvements in the clinical diagnosis and antiarrhythmic therapy, including the use of the defibrillator (ICD) and endo-epicardial catheter ablation, have increased the survival of these patients, who experience late complications such as advanced heart failure, which sometimes requires cardiac transplantation. Aim of the study To evaluate clinical, instrumental and genetic features of patients affected with ACM who developed heart failure (HF) and to sought for possible predictive factors of HF. Methods From the entire cohort of probands and family members followed at the Cardiomyopathy unit of our University (555 patients), 34 patients (29%), both probands (n= 26, 77%) and family members who experienced HF (6%) were selected (24 males, 71%). Their anamnestic, clinical, and instrumental data were compared with those without episodes of HF (n-HF). Results The mean age at diagnosis in HF cohort was 45.2 (±18) years. In 14 patients (41%) HF was the first symptom that led to diagnosis. According to 2010 TFC 30 patients (88%) had a definite diagnosis of ACM. The most frequently observed phenotype was the biventricular ACM (n=27, 79%). A disease-related genetic variant was found in 18 (53%) and DSP was the more common disease-gene, accounting for 24% of cases. The mean duration of follow-up was 12.6 (±11.0) years (min-max, 1-20 years). During this period a total of 14 subjects (41.2%) experienced life-threatening arrhythmias (LTA), while 13 patients (38.2%) died, of whom 11 (84.6%) because of refractory HF. Eighteen patients (53%) underwent cardiac transplantation (mean age 43±17 years), approximately 4 (±3.5) years after the onset of symptoms. Comparison with the n-HF cohort of ACM patients showed a significant difference on presence of T-wave inversion (TWI) in V1-V3 (p=0.001), TWI in V4-V6 (p=0.010), low QRS voltages both in precordial and limb leads (both p<0.001) and presence of left bundle-branch block and right bundle-branch block (both p<0.001). Regarding CMR, HF cohort was characterized by a significantly more dilated right and left ventricle EDV (both p<0.001), EF reduction (both p<0.001), presence of wall motion alterations (respectively, p=0.007 and p<0.001) and LGE (respectively, p=0.002 and p=0.005) compared to n-HF group. Regarding outcomes evaluation, the HF group showed more frequently LTA (HF=41.2% vs n-HF 21.5%, p=0.008). Finally, the presence of right bundle-branch block at ECG (OR=20.562, CI 1.884-224.413, p=0.013) and of impaired RV ejection fraction (OR=0.821, CI 0.719-0.937, p=0.004) were found to be independent predictors of HF. Conclusions Heart failure is a rare complication in patients affected with ACM, with a prevalence of 6% in our study. The mean age of onset of HF was 45.2 (±18) years. Furthermore, 18 patients (53%) had an unfavorable progression to heart transplantation. The presence of right bundle branch block at ECG and an impaired CMR RV-EF were found to be predictors of HF. Our results suggest the importance of scheduling a close follow-up in ACM patients who show initial signs and/or symptoms of HF, taking into consideration the fast rate of progression to refractory HF, once established.

Validation of the Meta-Analysis Global Group in Chronic Heart Failure risk score for the prediction of 1-year mortality in a Chinese cohort.

The Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score was developed in 2013 to predict survival in heart failure (HF) patients. However, it has yet to be validated in a Chinese population. Our study aimed to investigate the ability of the score to predict 1-year mortality in a Chinese population. Consecutive patients with HF were retrospectively selected from the inpatient electronic medical records of the cardiology department in a regional hospital in China. A total integer score was calculated for each enrolled patient based on the value of each risk factor in the MAGGIC scoring system. Each enrolled patient was followed for at least 1 year. The observational endpoint of this study was all-cause mortality. The predictive ability of the MAGGIC score was assessed by comparing observed and predicted mortality within 1 year. Between January 2018 and December 2020, a total of 635 patients were included in the study: 57 (9.0%) of whom died within 1 year after discharge. The average age of all patients was 74.6 ± 11.2 years, 264 of them (41.6%) were male, and the average left ventricular ejection fraction was 50.7% ± 13.2%. The area under the receiver operating characteristic curve was 0.840 (95% confidence interval: 0.779, 0.901), which indicated a fair discriminatory ability of the score. The Hosmer-Lemeshow test result ( χ2 = 12.902, degree of freedom = 8, P = 0.115) indicated that the MAGGIC score had good calibration. The decision curve analysis showed that the MAGGIC score yielded a good clinical net benefit and net reduction in interventions. This validation of the MAGGIC score showed that it has a good ability to predict 1-year mortality in Chinese patients with HF after discharge. Due to regional and inter-hospital differences, external validation studies need to be further confirmed in other centers.

Diagnostic utility of total NT-proBNP testing by immunoassay based on antibodies targeting glycosylation-free regions of NT-proBNP.

The N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) is a widely used heart failure (HF) biomarker. Commercial NT-proBNP immunoassays detect only a subfraction of endogenous NT-proBNP, as the antibodies target a region of NT-proBNP that could be glycosylated at Ser44. The diagnostic utility of immunoassays measuring total NT-proBNP remains unclear. NT-proBNP was measured in 183 HF and 200 non-HF patients diagnosed by two independent cardiologists blinded to NT-proBNP results. Plasma samples either non-treated or treated with a mixture of glycosidases were analyzed by the Elecsys proBNP II assay (Roche Diagnostics, based on antibodies targeting a glycosylated region of NT-proBNP) and the SuperFlex NT-proBNP assay (PerkinElmer, based on antibodies targeting regions of NT-proBNP that are free of O-glycans). The diagnostic accuracy of the two assays was analyzed by comparison of ROC curves. The ROC-AUC for the proBNP II assay was 0.943(95% CI 0.922-0.964) for NT-proBNP measured in untreated samples and 0.935 (0.913-0.958) for NT-proBNP measured in glycosidase-treated samples. The SuperFlex NT-proBNP assay in untreated samples gave a ROC-AUC of 0.930 (95% CI 0.907-0.954). The median percentage of non-glycosylated NT-proBNP to total NT-proBNP was 1.5-1.6-fold lower in the non-HF group compared to that in the HF group. The clinical value of total NT-proBNP for HF diagnosis was similar to the subfraction of NT-proBNP that was non-glycosylated at Ser44. The lower percentage of non-glycosylated NT-proBNP to total NT-proBNP in non-HF patients suggests that total NT-proBNP might be more sensitive in individuals without current or prior symptoms of HF.

Predictors of 6-Minute Walk Distance Among Aging Adults With Chronic Cardiopulmonary, Metabolic, and Renal Diseases

ABSTRACT Background The 6-minute walk test is a widely used measure of physical function in healthy people and patients with chronic conditions. Few reports have compared 6-minute walk distance (6MWD) across different conditions, and limited knowledge is available about how common covariates [age, sex, body mass index (BMI)] differentially affect 6MWD. Our purposes were to examine the 6MWD in persons with chronic conditions, compare walk distances with healthy controls, and identify predictors of 6MWD. Methods Data were aggregated from previous studies. Participants with primary diagnoses of heart failure (HF), chronic obstructive pulmonary disease (COPD), type 2 diabetes, chronic kidney disease, and peripheral artery disease (PAD) were included. Univariate and multivariate general linear models were used to estimate the impact of each condition on the 6MWD. Results The sample included 429 adults (48% female) aged 63 ± 9 years. Participants with HF, COPD, and PAD walked shorter distances than healthy controls (all P < 0.01). Predictors differed by group. In the HF group, age, Black race, and male sex negatively affected 6MWD. In the type 2 diabetes group, older age and high BMI were associated with shorter distances walked. In the chronic kidney disease group, higher BMI, Black race, and male sex negatively impacted 6MWD. No covariates were associated with 6MWD in the PAD, COPD, or control groups. Conclusion We found wide variation in common, nondisease-specific predictors of the 6MWD and significantly lower 6MWDs compared with healthy controls. Our findings add to our knowledge of 6MWD among aging adults with common chronic diseases.

Exertional dyspnea responses to the Dyspnea Challenge in heart failure: Comparison to chronic obstructive pulmonary disease

BackgroundIn heart failure (HF), exertional dyspnea is a common symptom, but validated field-based tests for its measurement are limited. The Dyspnea Challenge is a two-minute uphill treadmill walk designed to measure exertional dyspnea in cardiopulmonary disease. ObjectivesThe purpose of this study was to establish the test-retest reliability of the Dyspnea Challenge in HF and to compare the exercise responses to a group with chronic obstructive pulmonary disease (COPD). MethodsThe study was an experimental, single-blind, randomized, multi-site project that recruited individuals with HF (New York Heart Association I-III) and COPD (Global Initiative for Chronic Obstructive Lung Disease II-IV). Participants completed two visits. On the first visit, participants performed two six-minute walk tests (6MWT), followed by two to three Dyspnea Challenges to calculate treadmill speed and gradient. At Visit Two, participants performed two separate Dyspnea Challenges, with one including measures of pulmonary gas exchange and central hemodynamics. ResultsTwenty-one individuals with HF (10 female; 66±11years; ejection fraction:45.3 ± 6.1%; six-minute distance(6MWD) 520 ± 97 m), and 25 COPD (11 female; 68 ± 10 yr; forced expiratory volume in 1 s:47.6 ± 11.5%; 6MWD: 430 ± 101 m). Intraclass correlation coefficients demonstrated excellent test-retest reliability for HF (0.94, P<.01) and COPD (0.95, P<.01). While achieving similar end-exercise exertional dyspnea intensities (P=.60), the HF group walked at a higher average speed (4.2 ± 0.8 vs. 3.5 ± 0.8km·h−1) and gradient (10.3 ± 2.8 vs. 9.6 ± 2.8%) and a greater oxygen uptake (P<.01) and ventilation (P<.01) than those with COPD. While achieving similar cardiac outputs (P=.98), stroke volumes (P=.97), and heart rates (P=.83), those with HF displayed a larger arteriovenous oxygen difference (P<.01), while those with COPD exhibited greater decreases in inspiratory capacity (P=.03), arterial oxygen saturation (P=.02), and breathing reserve (P<.01). ConclusionsThe Dyspnea Challenge is a reliable test-retest measure of exertional dyspnea in HF. Typical to their pathologies, HF seemed limited by an inadequate modulation of cardiac output, while ventilatory constraints hampered those with COPD.

Identification and verification of immune-related biomarkers and immune infiltration in diabetic heart failure.

Diabetic heart failure (DHF) or cardiomyopathy is a common complication of diabetes; however, the underlying mechanism is not clear. In the present study, the authors searched for differentially expressed genes associated with DHF and the molecular types of immune cells based on bioinformatics. The RNA expression dataset of DHF was obtained from the NCBI Gene Expression Omnibus (GEO) database. After preprocessing the data, the differentially expressed genes (DEGs) between the DHF group and the non-diabetic heart failure (NHF) group were screened and intersected with immune-related genes (IRGs) in the ImmPort database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the DAVID tool. The ssGSEA algorithm was used to evaluate immune infiltration of the heart tissue in each group. In addition, the protein-protein interaction (PPI) network and miRNA-mRNA network were constructed using the STRING online website and Cytoscape program. Finally, validation analysis was performed using animal models. Eight immune-related core genes were identified. GO and KEGG showed that core genes were mainly enriched in angiogenesis and cytokine-cytokine receptor interaction. Immune infiltration results showed that activated dendritic cells, central memory CD4 T cells, central memory CD8 T cells, myeloid-derived suppressor cells (MDSCs), neutrophils, and regulatory T cells may be involved in DHF. Neutrophils may play a key role in the pathogenesis of HF in diabetes. Immune-related core genes and immune infiltrating cells provide a new perspective on the pathogenesis of DHF.

Abstract 13319: Cryoaballoon Ablation in Patients With Atrial Fibrillation and Heart Failure - Insights From Ongoing POLAR-HF Trial

Background Atrial Fibrillation (AF) and heart failure (HF) often co-exist and increase cardiovascular mortality. Radiofrequency ablation is safe and effective in patients with AF and HF. There is evidence for a reduction in mortality in treated patients (CASTLE, NEJM 2019), and the European Society of Cardiology recommends catheter ablation (class 1A), particularly in patients with tachycardiomyopathy. However, there is no large-scale prospective study evaluating efficacy and safety of cryoballoon pulmonary vein isolation (cryoPVI) in patients with AF and HF. Objective Prospective comparison of cryoPVI in patients with and without HF (defined as LVEF ≤ 40%) regarding efficacy and safety. Methods POLAR-HF trial is an investigator-initiated, single-center, prospective, non-inferiority, interventional study. Follow-up was performed at 3, 6 and 12, 18 and 24 months after ablation. Endpoints were: symptomatic AF recurrence for efficacy and bleeding, stroke or death for safety. Periprocedural parameters were observed. Results: We analyzed 668 consecutive patients who underwent cryoPVI. Of these 581 had normal LVEF (age 69±10 years, CHA2DS2-VASc Score 2.7±1.5, 54% male) while 87 patients (13%) suffered from HF (age 70±10 years, CHA2DS2-VASc Score 3.3±1.4, 70% male). After 24 months primary efficacy endpoint occurrence was similar in normal LVEF and HF group (34.1 % vs. 35.6%, P=0.66, Figure). Safety endpoint occurred in form of pericardial effusion or transient phrenic nerve injury in six patients with normal LVEF (1.2%) and none in HF group. No deaths or strokes were observed in either group. Conclusion The interim results of the POLAR-HF study suggest that cryoPVI is a safe and effective ablation method for patients with atrial fibrillation and heart failure.

Abstract 12677: Intensive Cardiac Rehabilitation Outcomes in Patients With Heart Transplant

INTRODUCTION Heart Transplant (HT) is gold standard for patients with Heart failure (HF) with end stage disease, however it requires ideal post-surgical recovery which includes medications &amp; Cardiac Rehabilitation (CR). Clinical trials have shown that CR can reduce morbidity &amp; mortality, increase exercise tolerance and reduce psychological symptoms in patients with HT. Intensive Cardiac rehabilitation (ICR) has proven benefits for patients with HF but the outcomes of ICR in patients with HT are unknown. Methods: Retrospective cohort study of 1413 patients from Jan-2016 to Dec-2020. ICR sessions consists of 4-hours two times per week for 9-weeks of lifestyle modification aiming at high fiber low fat diet, peer support, exercise and stress reduction.Patients were divided into two groups: 18 patients in HT group and 1395 patients in HF group. Primary endpoints were change in body mass index (BMI), exercise minutes per week (EMW) and depression scores (CESD). Secondary endpoints includes change in blood pressure (BP), cholesterol (chol), low density lipoprotein (ldl), high density lipoprotein (hdl), triglycerides (tgl) and health status (SF-36 physical &amp; mental composite scores). T test was used to compare variables between two groups. Linear regression was used to adjust for difference in baseline variables. Results: Table 1 explains baseline characteristics and demographics of both groups. Table 2 shows outcomes of both groups pre and post-ICR. Conclusions: Significant Improvement in ICR outcomes were achieved for both groups. There is no difference among groups when improvements were compared with each other except for chol which has improved more in patients with HF.

Abstract 9820: Heart Failure at Admission in Patients With ST-Elevation Myocardial Infarction. Registry ARGEN-IAM-ST

Introduction: Heart failure (HF) is a frequent complication of ST-elevation myocardial infarction (STEMI). Despite advances in the management of STEMI, when associated with HF, its prognosis continues to be ominous. Knowing the reality and the management of these patients is a necessity that will guide us for future strategies. Objective: To evaluate incidence, associated factors, relationship with reperfusion strategies, treatment at admission, and evolution of patients (pts) with STEMI who present HF at admission. Material and Method: Data from the National Registry of ST-Elevation Myocardial Infarction of Argentina (ARGEN-IAM-ST) were analyzed from 1/1/2016 to 9/30/2020. Based on Killip and Kimball variable at admission, the population was divided into 2 groups, those pts with Killip and Kimball equal to 1 were grouped as pts without HF (noHF) at admission and those with Killip and Kimball greater to 1 as with HF at admission. Demographic characteristics, clinical, electrocardiographic, laboratory variables, and admission treatment were compared. Hospital mortality was compared. Results: 3,174 pts were analyzed. Pts with HF were 22.31%. Mean age (noHF vs HF) was 59.80 years (SD±11.45) and 64.01 years (SD±12.14), p&lt;0.0001; predominance of women in HF (24.50% vs 18.50%, p&lt;0.001). The baselines characteristics can be seen in Table 1. Reperfusion strategy was less used in HF group [87.57% vs 92.58%, OR 0.56 (95%CI 0.43-0.74), p&lt;0.001] and its success was less frequent (Table 2). Pharmacological treatment is shown in Figures 1 and 2. Mortality was 3.00% in noHF vs 28.39% in HF, p&lt;0.001. In the multivariate analysis, the variables associated with changes in mortality are described in Table 3; HF was associated with an increase in mortality. Conclusions: Pts with STEMI associated with HF at admission are a different group with a higher risk. The reperfusion strategy and certain pharmacological treatments on admission are less frequent in these pts.

Abstract 10494: Proteomic Assessment of Novel Kidney Function Biomarkers in Heart Failure: A Community Study

Introduction: Heart failure (HF) is a complex syndrome with high mortality often associated with impaired kidney function. Estimated glomerular filtration rate (eGFR) is central to kidney function assessment in HF. However, novel proteins related to kidney function (lipocalin 2 [LCN2], macrophage inhibitory cytokine 1 [MIC1], T cell immunoglobulin and mucin domain 1 [TIM1]) may improve risk stratification of HF patients, beyond eGFR. Their prognostic contribution remain to be fully explored. Hypothesis: Proteomic assessment of kidney function biomarkers improves risk stratification in HF. Methods: Clinical data and biospecimens were collected from a HF community cohort in Southeastern Minnesota from 2003-2012. Serum creatinine was measured in 1,388 patients and eGFR was calculated with the 2021 Chronic Kidney Disease (CKD) Epidemiology Collaboration equation. CKD was defined as an eGFR &lt;60 mL/min/1.73m 2 . Plasma proteins were measured using the SomaLogic aptamer-based technology SomaScan®. In HF patients with and without CKD, Cox proportional hazard models were used to estimate the association between kidney function biomarkers and mortality, after adjustment for Meta-Analysis Global Group in Chronic HF (MAGGIC) risk score. Results: At HF index, patients were on average 75±13 years of age and 48% female. Patients had a median eGFR of 57 mL/min/1.73m 2 and 64% had CKD. Adjusted geometric mean levels of LCN2, MIC1, and TIM1 levels were 20-30% higher in patients with CKD. Patients with CKD were at higher risk of dying (HR 1.6, 95% CI 1.4-1.8). Patients with above median levels of LCN2, TIM1, MIC1 were at higher risk of dying, irrespective of CKD (See Figure). Conclusions: In a HF community cohort, several novel kidney function biomarkers provided further risk stratification in patients with and without CKD.

Abstract 12075: Extracellular Vesicle Cargo Long-Noncoding RNAs Are Dynamic Biomarkers in Acute Decompensated Heart Failure

Introduction: Acute decompensation is associated with increased long-term mortality in patients with heart failure (HF). Biomarkers of acute HF that are dynamic during decongestion may provide physiologic insight for this observation. We hypothesized that long-noncoding RNAs (lncRNAs) and mRNAs in extracellular vesicles (EVs) not only mark different types of HF, but also may be dynamically altered with decongestion across physiologically important pathways. Methods: RNA sequencing was performed on plasma-derived EVs in acute HF patients (7 HFpEF; 7 HFrEF) at hospital admission (V1) and at discharge (V2) along with 9 controls without HF. Differential expression analysis was performed using DESeq2 across groups and time-points. Transcripts were prioritized by fold change (±1.5) and statistical significance (&lt;5% FDR). We subsequently validated targets in EVs from 182 additional patients (24 control; 86 HFpEF; 72 HFrEF). Results: Between HF and control patients, 138 lncRNAs and 147 mRNAs were different (Fig a,b). LncRNAs were confirmed to be exclusively present in EVs. Of 13 targets investigated in our validation cohort, 5 lncRNAs and 6 mRNAs were significantly different between control and HF (age, sex-adjusted; Fig c). Pairwise comparisons between EV RNAs at hospital admission versus decongestion revealed a significant change in 4 lncRNAs (Fig d,e ) that was independent of weight change during hospitalization. Notably, distinct fragments derived from these transcripts were noted in HF versus control groups. Conclusions: The plasma EV transcriptome is significantly altered in patients with acute HF. Plasma EV-derived lncRNA fragments demarcate congestion and decongestion better than mRNAs, may be markers for pathophysiologically relevant pathways independent of volume status, and may provide additional prognostic information.

Cryoballoon ablation for atrial fibrillation in patients with heart failure with mildly reduced and preserved ejection fraction.

Limited data are available on the outcomes of cryoballoon ablation (CBA)-based pulmonary vein isolation (PVI) for atrial fibrillation (AF) in patients with heart failure (HF) with preserved ejection fraction (HFpEF) and mildly reduced ejection fraction (HFmrEF). The present study aimed to evaluate the safety and effectiveness of CBA in such patients. Consecutive patients with AF referred for CBA-based PVI from two highly experienced electrophysiology centres were included in this retrospective study. Of 651 patients undergoing CBA, 471 cases were divided into four groups: No HF (n=255), HFpEF (n=101), HFmrEF (n=78), and HF with reduced ejection fraction (n=37). Similar early recurrence of atrial arrhythmia was found among groups (16.2% vs. 15.4% vs. 14.9% vs. 12.2%, P=0.798), and no significant difference of long-term sinus rhythm (SR) maintenance was identified among the HFmrEF, HFpEF, and No HF groups (71.8% vs. 75.2% vs. 79.6%, P=0.334). CBA is safe for patients with HFmrEF and HFpEF with similar complications compared with the No HF group (3.8% vs. 4.0% vs. 3.1%, P=0.814). The reassessment of cardiac function after CBA showed that patients with HF indicated beneficial outcomes. Left atrial diameter (LAD) and left ventricular ejection fraction were significantly improved in the HFmrEF group. There were 41.6% of patients in the HFpEF group who were completely relieved from HF. LAD and New York Heart Association (NYHA) were associated with recurrence in the HFpEF and HFmrEF groups, and the maintenance of SR was an independent predictor of NYHA improvement for all HF groups. Patients with HFmrEF and HFpEF could benefit from CBA with high SR maintenance and significant HF improvement.

Prognostic Significance of Percutaneous Coronary Intervention for First Acute Myocardial Infarction with Heart Failure: Five-Year Follow-Up Results

The study aimed to investigate the incidence and influencing factors of heart failure after 5 years of percutaneous coronary intervention (PCI) for first acute myocardial infarction. A total of 1235 patients, diagnosed as acute myocardial infarction and treated with PCI in Beijing Anzhen Hospital, Capital Medical University, from January 1, 2014, to December 31, 2014, were enrolled. Based on the exclusion criteria, 671 patients were followed up to obtain echocardiographic results 5 years after the onset of myocardial infarction (from January 1, 2019, to December 31, 2019). Of 671 patients, 62 were lost to follow-up. Finally, 609 patients were recruited in this study. According to the results of the echocardiographic examination, patients were divided into a heart failure group (n = 97) (LVEF < 50%) and a nonheart failure group (n = 512) (LVEF ≥ 50%). The clinical characteristics were compared between the two groups, and the influencing factors of heart failure after 5 years of PCI in patients with acute myocardial infarction were analyzed using logistic regression and receiver-operating characteristic (ROC) analyses. Of 609 patients, 97 had heart failure within 5 years after PCI for first myocardial infarction, with an incidence of 15.9%. Multivariate regression analysis finally examined the predictors related to the occurrence of heart failure, including age (aOR, 1.008; 95% confidence interval (CI), 1.054-1.123; P ≤ 0.001), peak troponin I level (aOR, 1.020; 95% CI, 1.006-1.034; P = 0.004), left ventricular ejection fraction (LVEF) (during admission) (aOR, 0.908; 95% CI, 0.862-0.956; P ≤ 0.001), and left ventricular end-diastolic dimension (LVEDD) (at admission) (aOR, 1.136; 95% CI, 1.016-1.271; P = 0.025). In this study, the incidence of heart failure (LVEF < 50%) in patients with acute myocardial infarction who underwent PCI was 15.9% at a five-year follow up. Age, peak troponin I level, and LVEDD (at admission) were risk factors for heart failure, while LVEF (at admission) of patients during hospitalization was a protective factor for heart failure.

Performance of the heart failure risk scores in predicting 1year mortality and short-term readmission of patients.

The aim of this study was to assess the performance of these main scores in predicting prognosis in patients with heart failure (HF). A total of 2008 patients who were admitted to the Fourth People's Hospital of Zigong, Sichuan, from December 2016 to June 2019 and diagnosed with HF were included in the study. We compared the prognostic predictive performance of Seattle Heart Failure Model (SHFM), Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC-HF) risk score, Get With the Guidelines-Heart Failure programme (GWTG-HF), Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND) risk scores, the Acute Decompensated Heart Failure National Registry (ADHERE) model, Barcelona Bio-Heart Failure (BCN-Bio-HF) risk calculator, and Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico-Heart Failure (GISSI-HF) for the endpoints. The primary endpoint was 1year all-cause mortality and the secondary endpoint was the incidence of 28day readmission post-discharge. At 1year follow-up, 44 (2.21%) patients with HF died. Discrimination analyses showed that all risk scores performed reasonably well in predicting 1year mortality, with areas under the receiver operating characteristic curve (AUCs) fluctuating between 0.757 and 0.822. GISSI-HF showed the best discrimination with the AUC of 0.822 (0.768-0.876), followed by MAGGIC-HF, BCN-Bio-HF, ASCEND, SHFM, GWTG-HF, and ADHERE with AUCs of 0.819 (0.756-0.883), 0.812 (0.758-0.865), 0.802 (0.742-0.862), 0.787 (0.725-0.849), 0.762 (0.684-0.840), and 0.757 (0.681-0.833), respectively. All risk scores were similarly predictive of 28day emergency readmissions, with AUCs fluctuating between 0.609 and 0.680. Overestimation of mortality occurred in all scores except the ASCEND. The risk scores remained with good prognostic discrimination in patients with biventricular HF and in the subgroup of patients taking angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker. Currently assessed risk scores have limited clinical utility, with fair accuracy and calibration in assessing patients' 1year risk of death and poor accuracy in assessing patients' risk of readmission. There is a need to incorporate more patient-level information, use more advanced technologies, and develop models for different subgroups of patients to achieve more practical, innovative, and accurate risk assessment tools.

A prediction model for major adverse cardiovascular events in patients with heart failure based on high-throughput echocardiographic data.

Heart failure (HF) is a serious end-stage condition of various heart diseases with increasing frequency. Few studies have combined clinical features with high-throughput echocardiographic data to assess the risk of major cardiovascular events (MACE) in patients with heart failure. In this study, we assessed the relationship between these factors and heart failure to develop a practical and accurate prognostic dynamic nomogram model to identify high-risk groups of heart failure and ultimately provide tailored treatment options. We conducted a prospective study of 468 patients with heart failure and established a clinical predictive model. Modeling to predict risk of MACE in heart failure patients within 6 months after discharge obtained 320 features including general clinical data, laboratory examination, 2-dimensional and Doppler measurements, left ventricular (LV) and left atrial (LA) speckle tracking echocardiography (STE), and left ventricular vector flow mapping (VFM) data, were obtained by building a model to predict the risk of MACE within 6 months of discharge for patients with heart failure. In addition, the addition of machine learning models also confirmed the necessity of increasing the STE and VFM parameters. Through regular follow-up 6 months after discharge, MACE occurred in 156 patients (33.3%). The prediction model showed good discrimination C-statistic value, 0.876 (p < 0.05), which indicated good identical calibration and clinical efficacy. In multiple datasets, through machine learning multi-model comparison, we found that the area under curve (AUC) of the model with VFM and STE parameters was higher, which was more significant with the XGboost model. In this study, we developed a prediction model and nomogram to estimate the risk of MACE within 6 months of discharge among patients with heart failure. The results of this study can provide a reference for clinical physicians for detection of the risk of MACE in terms of clinical characteristics, cardiac structure and function, hemodynamics, and enable its prompt management, which is a convenient, practical and effective clinical decision-making tool for providing accurate prognosis.

Serum myostatin level is associated with myocardial scar burden by SPECT myocardial perfusion imaging

BackgroundMyostatin is a negative regulator of skeletal muscle and myocardial mass. The relationship between myocardial ischemia and scar burden and levels of myostatin has not been established. MethodsWe enrolled symptomatic patients with heart failure (HF) with a left ventricular ejection fraction (LVEF) < 45 % and controls (LVEF ≥ 45 %). Serum levels of myostatin were measured. Single-photon emission computed tomography (SPECT) imaging was interpreted, and summed scores of 17 stress and rest image segments in 5-point scale produced the summed stress score (SSS) and summed rest score (SRS), respectively. The summed difference score (SDS) was calculated as the difference between the SSS and SRS. ResultsNinety-six patients with HF and 103 controls were enrolled. The levels of myostatin were higher in the HF group. In linear regression analysis, myostatin level was positively correlated with SSS (β coefficient = 6.840, p = 0.013) and SRS (β coefficient = 5.557, p = 0.026), but not correlated with SDS. The areas under the receiver operating characteristic curves of myostatin levels for SSS ≥ 8 and SSS ≥ 13 were 0.6813 ± 0.04854 (p < 0.001) and 0.7498 ± 0.04402 (p < 0.001), respectively. ConclusionSerum levels of myostatin were correlated with the extent of myocardial scarring as defined by SPECT imaging. Serum levels of myostatin may be a predictor of myocardial scar burden.

Multiparametric CMR tissue characterization differentiates pathological from physiological phenotypes

Abstract Background An abnormal increase of cardiomyocyte mass of the left ventricle is observed in physiological and pathological phenotypes of hypertrophy. Aims To apply CMR tissue characterization using native T1/T2 and post-contrast T1 mapping and identify tissue phenotypes corresponding to physiological and pathological hypertrophy, in athletes and heart failure (HF), respectively. Methods/Results 187 individuals were prospectively enrolled, in 4 groups: Athletes (n=56, 32±13 years), HF with and without preserved ejection fraction (HFpEF: n=49, 62±12 years; HFrEF: n=49, 54±16 years, H2FpEF-score: 4.8 [3–9]), and healthy controls (n=33, 41±13.7 years). All participants underwent cardiopulmonary exercise testing and a multiparametric CMR study to assess morphology/function, T2, native T1, extracellular volume fraction (ECV), and intracellular lifetime of water (a marker of cardiomyocyte diameter). As expected, LVEF varied significantly among groups (Athletes: 64.7±6.1%, HFpEF: 59.3±10.7%, HFrEF: 29.4±8.5%, and controls: 65.4±4.3%, p&amp;lt;0.001) and was markedly reduced in HFrEF. Both LV mass index (Athletes: 64.1±15.8 g/m2, HFpEF: 62.3±24 g/m2, HFrEF: 79.5±36.7 g/m2, and controls: 42±9.2 g/m2, p&amp;lt;0.001) and cardiomyocyte mass index (calculated as (1 − ECV) x LV mass/BSA) (Athletes: 47.9±13.1 g/m2, HFpEF: 42.2±17.2 g/m2, HFrEF: 55.69±24.70 g/m2, and controls: 30.7±6.9 g/m2, p&amp;lt;0.001, Fig. 1A) were elevated in athletes and HF, compared to controls. Athletes and HFpEF patients showed concentric LV remodeling, while the eccentric LV remodeling was observed in HFrEF (Fig. 1B). In the HF groups NT-proBNP was elevated (Athletes: 34.6±16.8 ng/dL, HFpEF: 473.2±700.1 ng/dL, HFrEF: 1,365.3±1,772 ng/dL, and controls: 34.3±29 ng/dL, p&amp;lt;0.005), and adjusted maximum oxygen consumption was markedly reduced (Athletes: 49.4±9.3 mL/kg/min, HFpEF: 18.3±5.5 mL/kg/min, HFrEF: 17.1±4.2 mL/kg/min, and controls: 30.3±10.2 mL/kg/min, p&amp;lt;0.005). ECV was larger in both HF groups (athletes: 0.27±0.04, HFpEF: 0.31±0.05, HFrEF: 0.32±0.04, and controls: 0.26±0.02, p&amp;lt;0.001). The intracellular lifetime of water was longer among athletes compared to controls and shorter in HFrEF compared to HFpEF (Athletes: 0.17±0.07, HFpEF: 0.15±0.05, HFrEF: 0.13±0.05, and controls: 0.14±0.05, p&amp;lt;0.001). Native T1 was reduced in athletes compared to controls and elevated in the HF groups (Athletes: 1,173.4±63.2 ms, HFpEF: 1,262.8±62.4 ms, HFrEF: 1,275.1±59.9 ms, and controls: 1,212.78±76.01 ms, p&amp;lt;0.001). Lastly, the an increased T2 was indicative of edema in HF patients (Fig. 2). Conclusions In a prospective observational study with CMR T1/T2 mapping, physiological hypertrophy is characterized by increased cardiomyocyte diameter, normal ECV, and a decrease in native T1, due to the larger cardiomyocyte volume. In contrast, with pathological hypertrophy in HF, is associated with an increased and an above-normal native T1. Cardiomyocyte diameter appears reduced in HFrEF compared to HFpEF, reflecting the transition to an eccentric LV shape. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The São Paulo Research Foundation

Comparing the findings and diagnostic accuracy of cardiac magnetic resonance imaging in patients with biopsy confirmed acute myocarditis presenting with infarct-like and heart failure symptoms

Abstract Introduction Cardiac magnetic resonance imaging (CMR) is considered the reference imaging modality in providing a non-invasive diagnosis of acute myocarditis (AM), as it allows for the detection of myocardial injury associated with AM. However, the diagnostic accuracy and pattern of CMR findings appear to differ according to clinical presentation. Methods This is a retrospective cross-sectional study. Consecutive adult patients presenting to a single tertiary centre in South Africa between August 2017 and November 2021 with endomyocardial biopsy (EMB) confirmed AM presenting with infarct-like (IL) or heart failure (HF) symptoms who had undergone CMR were included. Results Thirty-eight patients were enrolled. Twenty-two presented with IL symptoms and sixteen with HF symptoms. On CMR, the IL group had significantly higher ejection fractions of both ventricles (LVEF 54.3±14.9% vs 35.4±14.0%, p&amp;lt;0.001; RVEF 56.8±10.9% vs 43.6±18.6%, p=0.03), despite similar end diastolic dimensions (LVEDVi 83.2±30.9 ml/m2 vs 104.4±38.0 ml/m2, p=0.07; RVEDVi 74.4±22.1 ml/m2 vs 85.8±29.9 ml/m2, 0=0.19). Myocardial oedema was detected more frequently on T2-weighted imaging (90.9% vs 62.5%, p=0.05) and in more myocardial segments (3.0 (IQR 2.0–4.0) vs 1.0 (IQR 0–1.0), p 0.003) in the IL group. Despite no significant difference in the prevalence of late gadolinium enhancement (LGE) between the two groups (95.5% vs 68.8%, p=0.06), the IL group had LGE detectable in significantly more ventricular segments (4.5 (IQR 2.3–6.0) vs 2.0 (IQR 0–3.3), p=0.01) and in a different distribution. The sensitivity of the original Lake Louise Criteria (LLC) was 90.9% in IL patients and 56.3% in HF patients, which improved to 95.5% and 68.8% with the updated LLC respectively. Conclusion The pattern of CMR findings and its diagnostic accuracy appears to differ in AM patients presenting with IL and HF symptoms. Although the sensitivity of the LLC improved with the addition of parametric mapping in the HF group, it remained lower than that of the IL group, and suggests that EMB should be strongly considered in patients with clinically suspected AM presenting with HF. Funding Acknowledgement Type of funding sources: None.