bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic utility of cardiopulmonary exercise testing indices in arrhythmogenic right ventricular cardiomyopathy
Authors: Adigun R , Brady P , Sommers V , Chahal A , Masood M , Jaliparthy K , Karim S , Khan N , Sherif A , Lin G 
Published: November 2020

Abstract

Introduction
Cardiopulmonary exercise testing (CPET) has an established role in the clinical evaluation of exercise intolerance and in the risk stratification of patients with heart failure. There is limited data assessing its prognostic utility in the evaluation of patients with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC). The predisposition of patients with ARVC for ventricular arrhythmias and sudden cardiac death has led to recommendations for exercise restrictions and limits our understanding of how the impairment in oxygen extraction and cardiac output impact disease progression and outcomes in these patients.

Purpose
We examined the association between CPET indices and event free survival (time to mortality or cardiac transplantation) in patients with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC).

Methods
Patients with definite ARVC based on 2010 task force criteria and genetically positive were enrolled into our institutional ARVC registry. 43 patients underwent CPET and have been included in our analyses. Indications for testing included: Evaluation of exercise-induced palpitations/arrhythmias or syncope (37%), pharmacotherapy optimization (28%), heart failure evaluation (19%), and ARVC management decisions (16%). CPET data (peak oxygen consumption (pVO2), respiratory exchange ratio (RER), and ventilatory efficiency (VE/VCO2) were assessed in patients at time of initial evaluation. Median follow-up time was 4.9 years (IQR 9 years).

Results
126 patients were studied (age 43.7+ 15 yrs; 41% women; LVEF 57+ 11%; 15% with LVEF &lt;50%) and 43 underwent CPET evaluation. 41 patients (95%) performed at near maximal effort (RER &gt;1) and no fatal events were reported during testing. During the follow up period, the outcome (death or cardiac transplantation) occurred in 31 patients. On Kaplan Meier analysis, pVO2 ≤14 mL/kg/min was associated with worse outcomes (unadjusted p&lt;0.001). Peak oxygen consumption (pVO2) ≤14 mL/kg/min and ventilatory efficiency (VE/VCO2) &gt;34 were associated with shorter event free survival (HR 5.58, p=0.002 and HR 5.56 p=0.005, respectively). After adjusting for age, sex, and right ventricular function, the association between peak oxygen consumption (pVO2) and event free survival remained significant (p=0.02).

Conclusions
In patients with ARVC, peak oxygen consumption (pVO2) was a prognostic indicator of worse outcomes. Our findings suggest a potential role for pVO2 in disease surveillance and early assessment for advanced heart failure therapies.
Figure 1. KM plot pVO2 & event free survival

Funding Acknowledgement
Type of funding source: Other. Main funding source(s): Mayo Clinic
Inhibition of CD44 attenuates pressure overload-induced cardiac and lung inflammation, fibrosis, and heart failure progression
Authors: Weng X , Yue W , Shang L , Wang D , Xu Y , Chen Y , Ge J 
Published: November 2020

Abstract

Background
Inflammation contributes to heart failure (HF) development and progression. CD44 is a member of the hyaluronate receptor family of cell adhesion molecules, which regulates tissue inflammation and fibrosis through modulating macrophage and lymphocyte migration and homing in several diseases. Here we evaluated the role and cellular mechanism of CD44 in regulating transverse aortic constriction (TAC)-induced HF development and progression in mice.

Methods and results
C57/B6 background CD44 KO and wild type mice (6–8 weeks) were subjected to TAC to evaluate the effect of CD44 on the development of TAC-induced LV hypertrophy and cardiac dysfunction. Due to the rapid response to TAC, Balb/c mice (6–8 weeks) were used to determine the effect of CD44 on the progression of TAC-induced congestive heart failure. We found that CD44 expression is dramatically increased in left ventricular (LV) tissues obtained from HF patients and mice. While CD44 gene knockout (KO) has no detectable effect on cardiac structure and function under control conditions, CD44 KO mice were protected from TAC-induced LV inflammation, fibrosis, hypertrophy, dysfunction, and lung remodeling as compared with wild type mice. In addition, we found that inhibition of CD44 signaling with blocking antibodies (Abs) significantly attenuated the transition from LV failure to lung remodeling, and right ventricular hypertrophy in mice with existing HF.

Conclusions
These data identify an important role of CD44 in attenuating cardiac and lung inflammation, fibrosis, HF development, and HF progression, suggesting that inhibition of CD44 signaling may be useful in preventing and treating HF.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): Chinese National Natural Science Foundation Grants and American Heart Association
Event-prediction of right ventricular to pulmonary circulation coupling measured during exercise in patients with heart failure
Authors: Sugimoto T , Boveri S , Bandera F , Barletta M , Alfonzetti E , Guazzi M 
Published: November 2020

Abstract

Background
Right ventricular (RV) contractile function and its coupling with pulmonary circulation (PC) stratify the pattern of clinical phenotypes in heart failure (HF) but its predictive role when measured during exercise is undefined. This study sought to investigate the prognostic impact of RV to PC coupling during exercise in HF patients of any left ventricular ejection fraction (LVEF) categorization.

Methods
218 HF patients with reduced (n=120), mid-range (n=55), and preserved (n=43) EF and 51 patients with noncardiac dyspnea underwent exercise with gas exchange analysis combined with echocardiography for assessment of RV-PC coupling assessed by the TAPSE/PASP ratio and left atrial (LA) strain (as a mediator of RV to PC uncoupling).

Results
TAPSE was negatively correlated with PASP (R=−0.31 and −0.31, P&lt;0.001) both at rest and during exercise. TAPSE/PASP was positively correlated with LA strain (R=0.58 and 0.59, P&lt;0.001) and cardiac output (R=0.28 and 0.58, P&lt;0.001) both at rest and during exercise. The severity of mitral regurgitation was also associated with TAPSE/PASP and LA strain both at rest and during exercise (P for trend &lt;0.001). There was significant difference in peak VO2 and the minute ventilation-carbon dioxide production slope among 3 groups divided by tertile of TAPSE/PASP at exercise. During 5 years follow up, 48 HF patients with reduced (n=34), mid-range (n=8), and preserved (n=6) EF had the composite end point. The age and gender adjusted hazard ratio for the events in HF patients with TAPSE/PASP at exercise &lt;0.33, derived by ROC curve (AUC=0.71, P&lt;0.05), was 2.9 (95% CI: 1.5 to 5.5, figure).

Conclusions
The impaired RV to PC coupling by TAPSE/PASP ratio during exercise predicts prognosis in patients with HF. The cutoff of 0.33 overlaps with the threshold observed to be predictive at rest in various reports across HF populations. These data further emphasize the usefulness of assessing RV to PC uncoupling in cardiac failure during various clinical conditions.

Funding Acknowledgement
Type of funding source: None
Impact of catheter ablation on HFpEF in people with comorbid atrial fibrillation and HFpEF using invasive haemodynamic testing
Authors: Sugumar H , Nanayakkara S , Vizi D , Chieng D , Leet A , Mariani J , Taylor A , Kalman J , Kistler P , Ling L 
Published: November 2020

Abstract

Background
The impact of catheter ablation (CA) for atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF) is unknown.

Objectives
To determine whether CA for AF reverses adverse haemodynamic changes associated with HFpEF.

Methods
Consecutive consenting patients with EF ≥50% scheduled for index CA underwent baseline exercise right heart catheterisation (exRHC), cardiac output (CO) measurement, cardiac MRI, echocardiogram, QOL questionnaires and BNP testing. HFpEF was defined by resting pulmonary capillary wedge pressure (PCWP) ≥15mmHg or peak exercise PCWP ≥25 mmHg during exRHC. Patients with HFpEF were offered follow-up exRHC ≥6 months post-CA.

Results
Of 252 patients scheduled for CA between April 2017 and Sept 2019, 131 (51.9%) qualified for inclusion, 65 (49.6%) consented to exRHC and 11 (16.9%) were excluded due to a subsequent decrease in EF (10) and uncontrolled hypertension (1). Fifty-four underwent exRHC, with 35 (65%) meeting criteria for HFpEF. Of them 26 (74.3%) who underwent CA, 20 (77%) had a follow up exRHC at 12±6 months follow-up, showing an overall decrease in peak exercise PCWP from 30.3±4.2 to 26.8±4.7 mmHg (p&lt;0.05). Patients without arrhythmia recurrence showed significant improvements in peak exercise PCWP (29.2±3.7 to 22.9±2.0 mmHg (p&lt;0.01). Their cardiac output increased from 10.3±3.0 to 12.1±4.0 mmHg p=0.1), and BNP decreased from (94.6±101.6 to 38.0±34.0 mmHg (p=0.06),whereas those with arrhythmia recurrence did not. Overall, 9 patients (45.0%) no longer met criteria for HFpEF.

Conclusion
There is a high prevalence of HFpEF in people referred for AF ablation. Successful CA for AF reverses the adverse haemodynamic changes associated with HFpEF
Changes in PCWP following AF ablation

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): NHMRC, NHF, RACP
Left ventricular remodelling pattern and prognostic relevance in patients with STEMI treated with primary percutaneous coronary intervention
Authors: Chimed S , Van Der Bijl P , Lustosa R , Montero J.M , Marsan N.A , Delgado V , Bax J.J 
Published: November 2020

Abstract

Background
Left ventricular (LV) remodelling after ST-segment elevation myocardial infarction (STEMI) is a complex pathological process which has been associated with long-term cardiovascular adverse events. The current definition of LV remodelling is usually based on the change in LV end-diastolic volume (LVEDV). An increase in LVEDV, however, may also be considered an adaptive response to maintain effective LV ejection fraction (LVEF) in LV remodelling.

Purpose
To reclassify post-infarct LV remodelling according to the change in LVEDV and LVEF from baseline and to determine the prognostic relevance of integrated LV remodelling and systolic function groups.

Methods
A total of 1859 patients with STEMI who received primary percutaneous coronary intervention (PCI) and guideline-directed medical treatment, were retrospectively evaluated. Four LV remodelling subgroups were identified, based on the change in LVEDV and LVEF from baseline to 6 months post-infarct. ≥20% increase in LVEDV, compared to baseline, was defined as LV dilatation, while any increase or decrease in LVEF compared to baseline was used to categorise remodelling further according to systolic function. Study endpoints were all-cause mortality and the composite of all-cause mortality and heart failure (HF) hospitalisation.

Results
The mean age of the study population was 60±11 years and the majority were men (76.4%). 402 patients showed LVEDV≥20% and LVEF increase (Group 1), 952 patients LVEDV≤20% and LVEF increase (Group 2), 325 patients LVEDV≤20% and LVEF decrease (Group 3) and 180 patients LVEDV≥20% and LVEF decrease (Group 4). During a median follow-up of 89 (IQR 64; 113) months, all-cause mortality occurred in 256 patients (13.8%), HF hospitalisation in 40 patients (2.2%) and the composite endpoint in 279 patients (15.0%). All-cause mortality was significantly higher in Group 4 (21.7%, chi-square p=0.002) compared to other groups (15.4% in Group, 12.9% in Group 2 and 9.8% in Group 3). The composite endpoint was also significantly more frequent in Group 4 (25.6%, chi-square p&lt;0.001) compared with the other groups (16.2% in Group 1, 13.8% in Group 2 and 11.4% in Group 3). Mean survival time (Figure 1A) and event-free survival time for the composite endpoint (Figure 1B) were significantly lower in Group 4 (122 months 95% CI 115–128, p=0.004 and 117 months 95% CI 110–124, p&lt;0.001, respectively) compared to other groups.

Conclusion
Patients with LVEDV≥20% and a LVEF decrease at 6 months after STEMI experienced all-cause mortality and the composite endpoint of all-cause mortality and HF hospitalisation more frequently compared to other LV remodelling groups. Patients with an increase in LVEDV and a decrease in LVEF 6 months after STEMI, may benefit from careful surveillance and preventative strategies.
KM comparison for study endpoints.

Funding Acknowledgement
Type of funding source: None
Time, magnitude and patterns of left ventricular remodeling after MitraClip implantation: clinical implications
Authors: Carrabba N , Migliorini A , Berteotti M , Fumagalli C , Taddei A , Vannini M , Cerillo A , Cerillo A , Stefano P , Marchionni N , Valenti R 
Published: November 2020

Abstract

Background
The reverse left ventricular remodeling (LV-R) is well known phenomenon that may occurs in a wide spectrum of heart disease, generally associated with an improvement of prognosis. Recently, conflicting data are reported from two randomized trials assessing prognosis after MitraClip implantation.

Purpose
To assess time, magnitude and pattern of LV-R and its relationship with outcome, and to assess the role of ejection fraction (EF) in selection of patients for MitraClip procedure.

Methods and results
Among 47 patients treated with MitraClip for severe mitral regurgitation (MR), 2 switched to surgical intervention. All patients underwent echo before, at discharge, 1 and 6-month after procedure (age 78.2±8.3 years, NYHA 3.74±0.44, LV EF 36.5±12.8%, logistic EuroSCORE I 22.41±8.4, STS-PROM 4.6±1.9, functional MR 82%). From baseline to 6-month reverse LV-R was defined as a ≥15% decrease in LV end-systolic volume (LVESV) and an adverse LV-R as a increase of ≥10% in LVESV, respectively. At 6-month, sustained reduction of MR ≤2 was observed in all patients, but 2; reverse LV-R occurred in 51% (23), adverse LV-R in 18% (8) and no LV-R in 31% (14) patients. In a multivariate regression model, baseline LVEDV were a strong independent predictor of reverse LV remodeling [β −0.564, 95% CI: −0.363 to −0.074; P=0.004], whereas baseline LVEF was not (P=0.126). Furthermore, an LVEDV ≤130 mL was strongly associated with reverse remodeling with an OR: 0.796 (CI: 0.052–0.792, P=0.022). During follow-up (17.5±9.3 months), in adverse/no LV-R patients mortality for any cause and hospitalization for heart failure (HF) occurred in 50% vs. 95.7% (log-rank, P value= 0.006). By Cox analysis, adverse LV-R was strongly associated with mortality for any cause and hospitalization for HF with adjusted OR of 5.6 (95% CI: 1.65–19.00, P=0.006). Finally, combining adverse/no LV-R together the risk of mortality for any cause and hospitalization for HF increased with adjusted OR of 10.08 (95% CI: 1.29–78.6, P=0.027).

Conclusion
The half of real-world patients undergoing percutaneous mitral valve repair for severe MR showed reverse remodeling. However, there was a half of patients in whom afterload mismatch resulted in early and sustained adverse and no remodeling associated with subsequently high mortality and recurrence of HF. Baseline larger LV volumes rather than EF may help us to refine selection patients for MitraClip procedure, avoiding futility.

Funding Acknowledgement
Type of funding source: None
Chronic heart failure in octogenarians. Temporal trends in clinical characteristics, treatment and outcomes over two decades in a nationwide cardiology registry
Authors: De Maria R , Gori M , Marini M , Gonzini L , Benvenuto M , Cassaniti L , Municino' A.M , Navazio A , Ammirati E , Gorini M , Leonardi G , Pagnoni N , Montagna L , Midi P , Iacoviello M 
Published: November 2020

Abstract

Background
Elderly &gt;80 years represent the most rapidly expanding population segment in Europe. Chronic heart failure (CHF) affects over 10% of this group and generates a major M&M burden. We analyzed the temporal trends in characteristics, therapy and outcomes over two decades in octogenarians enrolled in our nationwide registry.

Methods
According to the recruitment epoch, among 14.283 CHF patients first enrolled in the registry since 1–1999 through 5–2018, we divided those aged 80+ (2520,17.6%) into 3 cohorts: 1999–2005 (547, 10%); 2006–2011 (659, 16.5%); 2012–2018 (1314, 14.1%). We analyzed trends over time in characteristics, therapy, 1-year all-cause mortality and proportion admitted to hospital.

Results
From 1999 to 2018 the proportion of 80+ CHF patients (60% men, 84±3 years, LVEF 41±1%, HFrEF 49%) rose from 10% to 24%. Across the 3 epochs (Table 1) we observed a shift towards the HFpEF phenotype with an increase in its driving factors (obesity, diabetes, hypertension, AFib). At the same time, the proportion treated with recommended therapies rose. Cumulative 1-year mortality did not differ across the 3 epochs (Fig.1 top), whereas the proportion of 80+ hospitalized overall, for CV causes and for decompensated HF, declined (Fig. 1 bottom).

Conclusions
During 20 years, the clinical characteristics of octogenarians enrolled in a nationwide CHF registry have deeply changed, reflecting demographic variations, the evolution of CV risk factors and improved management. There was a consistent implementation of BB, MRA and devices. Survival of 80+ remained stable, but the proportion of those hospitalized for CV causes, and specifically decompensated HF, declined. These data suggest that cardiologists' input may contribute to decrease the socioeconomic burden of CHF in the elderly.

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): Fondazione per il Tuo cuore – Heart Care Foundation (HCF) ONLUS
Precision medicine: myocardial fibrosis burden and genotype predict outcome in non-ischemic dilated cardiomyopathy (DCM)
Authors: Kayvanpour E , Sedaghat-Hamedani F , Levinson R.T , Li D , Miersch T , Gi W.T , Grabe N , Lahrmann B , Taeger T , Frankenstein L , Uhlmann L , Herpel E , Katus H.A , Saez-Rodriguez J , Meder B 
Published: November 2020

Abstract

Introduction
Myocardial fibrosis occurs during pathological remodeling of the heart and can be associated with worse outcome in affected patients. Genetic background is also known to affect patients' survival. In this study we sought to estimate patients' overall fibrosis burden by combining independent modalities including left ventricular endomyocardial biopsy (LV-EMB), circulating biomarkers, and cMRI. We also aimed to use patients' genetics information to predict outcome. Furthermore, we investigated the correlation between cardiac fibrosis and genetic variations to detect novel susceptibility loci for fibrosis in DCM.

Methods
A total number of 542 DCM patients were included. Collagen volume fraction (CVF) was automatically estimated from biopsies. 13 circulating fibrosis biomarkers were measured using Human Magnetic Luminex Screening Assays, and the cMRIs were screened for presence of LGE. Whole exome sequencing (WES) was performed in 410 patients of the cohort using illumina HiSeq 2000. Common (MAF ≥0.05 in the study population OR gnomAD NFE AF ≥0.01) and non-common missense variants (MAF &lt;0.05 in the study population AND gnomAD NFE AF &lt;0.01) in 42 DCM genes were tested for associations with end points using single variants and burden analyses respectively. Analyses were adjusted for age and sex and performed using R and SKAT. End points were all-cause mortality and a composite of heart failure (HF) associated events.

Results
The median follow-up time was 43.2 months (2084 patient-years). Sixty-two patients reached the composite end point and 55 died. LV-EMB proved to be a safe procedure with a total complication rate of 2.3%. Machine learning based characterization of biopsies was highly accurate. Although the 3 different modalities did not significantly correlate with one another, the extent of CVF, levels of MMP-2, TIMP-1, OPN, and GDF-15, and presence of LGE were each significantly associated with worse outcome. Four possible susceptibility loci for cardiac fibrosis in DCM were introduced and underwent eQTL analyses. Rare missense variants in a list of 11 DCM-related genes showed to be associated with the 2 outcome measures or fibrosis burden.

Conclusions
LV-EMB, fibrosis biomarkers, and cMRI likely capture different aspects of a detrimental fibrosis process and may be combined to estimate patients' prognosis and monitor therapeutic success. Phenotype-genotype association studies help elucidate novel disease pathomechanisms and individualize patients' treatment.

Funding Acknowledgement
Type of funding source: Other. Main funding source(s): German Centre for Cardiovascular Research: DZHK
Long-term systolic blood pressure and all-cause mortality in heart failure with preserved ejection fraction: an analysis of the TOPCAT trial
Authors: Huang P , Liu C 
Published: November 2020

Abstract

Background
Lower systolic blood pressure (SBP) at admission or discharge was associated with poor outcomes in patients with heart failure and preserved ejection fraction (HFpEF). However, the optimal long-term SBP for HFpEF was less clear.

Purpose
To examine the association of long-term SBP and all-cause mortality among patients with HFpEF.

Methods
We analyzed participants from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study. Participants had at least two SBP measurements of different times during the follow-up were included. Long-term SBP was defined as the average of all SBP measurements during the follow-up. We stratified participants into four groups according to long-term SBP: &lt;120mmHg, ≥120mmHg and &lt;130mmHg, ≥130mmHg and &lt;140mmHg, ≥140mmHg. Multivariable adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause mortality associated with SBP level. To assess for nonlinearity, we fitted restricted cubic spline models of long-term SBP. Sensitivity analyses were conducted by confining participants with history of hypertension or those with left ventricular ejection fraction≥50%.

Results
The 3338 participants had a mean (SD) age of 68.5 (9.6) years; 51.4% were women, and 89.3% were White. The median long-term SBP was 127.3 mmHg (IQR 121–134.2, range 77–180.7). Patients in the SBP of &lt;120mmHg group were older age, less often female, less often current smoker, had higher estimated glomerular filtration rate, less often had history of hypertension, and more often had chronic obstructive pulmonary disease and atrial fibrillation. After multivariable adjustment, long-term SBP of 120–130mmHg and 130–140mmHg was associated with a lower risk of mortality during a mean follow-up of 3.3 years (HR 0.65, 95% CI: 0.49–0.85, P=0.001; HR 0.66, 95% CI 0.50–0.88, P=0.004, respectively); long-term SBP of &lt;120mmHg had similar risk of mortality (HR 1.03, 95% CI: 0.78–1.36, P=0.836), compared with long-term SBP of ≥140mmHg. Findings from restricted cubic spline analysis demonstrate that there was J-shaped association between long-term SBP and all-cause mortality (P=0.02). These association was essentially unchanged in sensitivity analysis.

Conclusions
Among patients with HFpEF, long-term SBP showed a J-shaped pattern with all-cause mortality and a range of 120–140 mmHg was significantly associated with better outcomes. Future randomized controlled trials need to evaluate optimal long-term SBP goal in patients with HFpEF.

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): China Postdoctoral Science Foundation Grant (2019M660229 and 2019TQ0380)