bluuebunny/crossref_metadata_2025 huggingface dataset:
His bundle pacing preserves left ventricular ejection fraction in patients with conduction disease and high risk of development pacing induced cardiomyopathy
Authors: Mizner J , Curila K , Stros P , Prochazkova R , Vesela J , Karch J , Herman D , Osmancik P , Widimsky P
Published: November 2020

Background

His bundle pacing (HBP), contrary to right ventricular myocardial pacing (RVP), offers the most physiological activation of both ventricles and may not lead to pacing induced cardiomyopathy. The change in myocardial structure in failing heart due to myocardial pacing should be reflected in plasmatic levels of collagen metabolism biomarkers and inflammation markers.

Purpose

To compare a difference in the left ventricular ejection fraction (LVEF) and levels of selected biomarkers between two groups: HBP and RVP (preferably septal).

Methods

Eighty-six patients with conduction disease indicated to permanent cardiac pacing were randomized to HBP or RVP. Only high-risk patients for pacing induced cardiomyopathy development were included. Blood sampling and echocardiography were performed on the consequent day and 180 days after the pacemaker implantation. The measured biomarkers were: matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), galectin-3 (GAL3), ST2/IL-33R (ST2/IL) and TGF-beta 1 (TGFβ1). Statistical analysis included Students t-test, Fishers exact test and Chi-squared test. The p<0.05 was considered to be statistically significant.

Results

First group included 39 patients with HBP (selective or non-selective His bundle capture) and 47 patients with RVP. Both groups were similar with respect to gender, LVEF, QRS duration and the baseline levels of evaluated biomarkers. In both groups, there was a high burden of ventricular pacing after 6 months (above 90%) (p = NS). The ejection fraction of the left ventricle did not change in the HBPgroup (60 vs 60%, p=0,3), but it decreased significantly in the RVP group (59 vs 56%, p=0,004). The decline in the LVEF of at least 5% occurred in 12 patients (26%) from RVP group, compared to 3 patients (8%) in HBP group (p=0,03). The blood levels of dMMP-9 (p=0,02), TIMP-1 (p=0,003), ST2/IL (p=0,003) and TGFβ1 (p=0,021) declined significantly after 180 days in the HBP group, decline of Galectin 3 was nonsignificant. In the RVP group, there was a significant decline in blood levels of MMP-9 (p=0,014), TIMP-1 (p=0,001) and ST2/IL (p= 0,04), decline of Galectin 3 and TGFβ1 was nonsignificant. The biomarker level difference was not statistically significant between the two groups.

Conclusion

His bundle pacing, contrary to right ventricular myocardial pacing, preserves LVEF in patients with high risk of pacing induced cardiomyopathy development.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Charles University research programme. Q38. UNCE/MED/002
The challenge of education in conduction system pacing: results from single or dual operators
Authors: Zanon F , Marcantoni L , Pastore G , Baracca E , Roncon L
Published: November 2020

Background

The his bundle pacing (HBP) and Left bundle branch pacing (LBBp) techniques are quickly increasing in the cardiovascular interest being the most physiological mode of pacing. Education in these new conduction system pacing (CSP) is mandatory in the modern EP programs. Achieving acceptable implant success rate, together with electrical parameters adequacy is required.

Objective

The aim of the study was to compare clinical and technical outcomes in 2 groups of patients, those implanted by a single operator with large expertise in CSP and those implanted by two operators (one of them during his learning curve).

Methods

Data from 255 consecutive patients (mean age 78±9 years; 186 males) who underwent successful HBP or LBBp implants were collected and analyzed. The operators were classified as expert after performing more than 50 procedures. Baseline caracteristics were not significantly different between the two groups.

Results

After a mean follow-up of 20±10months, we found that there were no differences between patients implanted by 1 single expert operator and 2 operators (1 beginner during his learning cirve supervised by 1 expert operator) in terms of clinical end point (composite of death or heart failure hospitalizations) and technical end point (need for surgical revision of the implant for reason other than battery replacement). Fluoroscopy time (16±17 min vs 9.8±11 min; p 0.004) and procedural time (113±48 min vs 16±17 min; p 0.003) were significantly prolonged when the implant was performed by 2 operators.

Conclusions

Skill acquisition in physiological pacing (both HBP and LBBp) is a nowadays process which cannot put patient's safety at risk. Our experience shows that clinical and technical outcomes were equivalent when the implant was performed by an expert operator or a beginner operator supervised by 1 expert operator. Fluoroscopy time and duration of the procedure were significantly prolonged by the presence of a trainees.

Kaplan Meyer curves

Funding Acknowledgement

Type of funding source: None
Mortality and readmission in non-ischemic compared with ischemic cardiomyopathies after implantable cardioverter-defibrillator implantation
Authors: Freeman J , Bjerre J , Parzynski C , Minges K , Ahmad T , Desai N , Enriquez A , Spatz E , Friedman D , Curtis J , Hlatky M , Higgins A
Published: November 2020

Background/Introduction

Uncertainty remains regarding the benefit of primary prevention ICDs overall in contemporary practice, and particularly in those with NICM compared with ICM.

Purpose

To evaluate the contemporary risk of death and readmission following following implantable cardioverter-defibrillator (ICD) implantation in patients with non-ischemic cardiomyopathies (NICM) compared with ischemic cardiomyopathies (ICM) in a large nationally representative cohort in the United States.

Methods

We used data from the American College of Cardiology (ACC) National Cardiovascular Data Registry (NCDR) ICD Registry linked with Medicare claims from April 1, 2010 to December 31, 2013 to establish a cohort of NICM and ICM patients with a left ventricular ejection fraction ≤35% who received a de novo, primary prevention ICD. We compared mortality, all-cause readmission, and heart failure readmission using Kaplan-Meier curves and Cox proportional hazard regressions models. We also evaluated temporal trends in mortality.

Results

Among 31,044 NICM and 68,458 ICM patients with a median follow up of 2.4 years, one-year mortality was significantly higher in ICM patients (12.3%) compared with NICM (7.9%, p<0.001). The higher mortality in ICM patients remained significant after adjustment for covariates (hazard ratio (HR) 1.40; 95% confidence interval (CI) 1.36 to 1.45), and was consistent in subgroup analyses. These findings were consistent across the duration of the study. ICM patients were also significantly more likely to be readmitted for all causes (adjusted HR 1.15, CI 1.12 to 1.18) and for heart failure (adjusted HR 1.25, CI 1.21 to 1.31).

Conclusions

The risks of mortality and hospital readmission after primary prevention ICD implantation were significantly higher in patients with ICM compared with NICM, and these findings were consistent across all patient subgroups tested and over the duration of the study.

Funding Acknowledgement

Type of funding source: None
Outcomes of cardiac resynchronization therapy with or without a defibrillator in patients with nonischemic cardiomyopathy in Korea: a nationwide cohort study
Authors: Yang P.S , Kang Y , Park H.D , Sung J.H , Joung B
Published: November 2020

Background

Randomized control trials comparing the effectiveness of cardiac resynchronization therapy devices, with (CRT-D) or without (CRT-P) a defibrillator, are scarce in heart failure patients. Patients with nonischemic dilated cardiomyopathy (NICM) may be at lower risk for ventricular arrhythmias compared with those with ischemic cardiomyopathy. In addition, NICM has been identified as a predictor of positive response to CRT. The aim of this study was to investigate the impact of an additional implantable cardioverter-defibrillator over CRT in Korean patients with NICM.

Methods

During the period from January 1, 2008 to December 31, 2017, 533 NICM patients (mean age, 65.7±12.2 years, male 53.6%) with newly-implanted CRT-P (n=71) or CRT-D (n=462) who were aged 19 years or older were identified by 50-percents random sampling from the Korean National Health Insurance Service database.

Results

Compared with patients receiving CRT-P, those receiving CRT-D were younger (65.3±12.3 vs. 68.3±11.6 years, p=0.038), more likely to be male (56.1% vs. 38.0%, p=0.005), and have an admission history of congestive heart failure (93.9% vs. 87.3%, p=0.041). Over the mean follow-up period of 21 months,114 cases in the CRT-D group and 24 cases in the CRT-P group died, with annualized mortality rates of 14.9 and 17.2 per 100 person-years, respectively. Kaplan-Meier estimates of event-free survival showed that there was no difference in mortality between CRT-D and CRT-P groups (p=0.343). In multivariate analysis, factors associated with mortality were chronic kidney disease, atrial fibrillation, and older age. With regard to death or heart failure hospitalization, heart failure death, and non-cardiac death, there were no difference between the two groups.

Conclusions

Among Asian patients with NICM with indications for CRT, death, death or heart failure hospitalization, heart failure death, and non-cardiac death were not different between CRT-D and CRT-P groups.

Funding Acknowledgement

Type of funding source: None
AV delay optimisation in LV only CRT: constant fusion pacing is easier in patients with first degree AV block
Authors: Vacarescu C , Luca C.T , Petrescu L , Ionac A , Mornos C , Goanta E.V , Crisan S , Lazar M.A , Cozma D
Published: November 2020

Background

LV only pacing is non-inferior to BiV pacing, and recent publications showed that DDD CRT without RV lead is safe in patients with normal atrioventricular (AV) conduction, although there are no device algorithms available for fusion pacing and PR interval variability is understudied in this population.

Purpose

To analyse AV behaviour in patients with DDD CRT and the impact to effective fusion maintenance.

Methods

Consecutive patients with right atrium/left ventricle leads DDD CRT pacing system were included. Prospective data were collected at every 6 months follow-up visits: device interrogation, exercise test (ET), echocardiography. CRT assessment during ET analysed loss of LV capture with special focus on maintaining constant fusion pacing during exercise. We defined 2 groups of patients: longer PR interval patients (200–250 ms) and normal PR interval patients (<200 ms). In case of LV loss of capture or unsatisfactory LV fusion pacing, device reprogramming was performed individualised for each patient and BB/ivabradine dose titration was done to achieve stability of PR spontaneous interval. Patients were rescheduled in no later one month to be reassessed by ET.

Results

55 patients (29 male) aged 62±11 y.o. were included, 36 patients with normal PR and 19 patients with longer PR. During follow-up (45±19 months), a total of 235 ETs were performed with mean exercise load 118±35 watts. In the normal PR group, 14 patients (39%) had inadequate pacing or loss of LV capture during ET due to physiological shortening of PR interval vs. 4 patients (21%) in the longer PR group. Loss of LV capture by exceeding maximum tracking rate (MTR) was noted in 6 patients (17%) with normal PR vs. 2 patients (11%) with long PR. Post ET device optimisation included: reprogramming rate adaptive AV interval (23±8 ms decrease in normal PR patients vs. 12±7 ms in longer PR patients, p<0.0001) and individualised programming of MTR. BB/ivabradine optimisation was performed in 32% of patients with normal PR vs. 13% of patients with longer PR.

Conclusions

A lower rate of optimisations after ET was needed in patients with a slightly longer AV conduction to achieve stability of fusion pacing DDD CRT, without device algorithms. Larger studies are needed to assess AV conduction variability and the benefits of fusion pacing CRT in patients with longer PR interval.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): University of Medicine and Pharmacy “Victor Babes”, Timisoara; Timisoara Institute of Cardiovascular Diseases
Change in QRS area by cardiac resynchronization therapy is associated with clinical outcomes and echocardiographic response
Authors: Ghossein M.A , Van Stipdonk A.M.W , Plesinger F , Kloosterman M , Salden O.A.E , Wouters P , Meine M , Maass A.H , Prinzen F.W , Vernooy K
Published: November 2020

Background

Cardiac Resynchronization Therapy (CRT) is the cornerstone of treatment in patients with dyssynchronous heart failure. Recently, baseline QRS area proved to predict outcomes after CRT better than QRS duration and morphology.

Purpose

It was the aim of the study to investigate whether the change in QRS area (ΔQRS area) by CRT-pacing further improves the prediction of CRT outcomes.

Methods

We conducted a retrospective analysis on 1,299 patients, who were included in a CRT-registry from three Dutch University hospitals with both pre- (baseline) and post-implantation 12-lead ECGs. ΔQRS area and ΔQRS duration were defined as the decrease in their respective values after CRT. Optimal cut offs for ΔQRS area and ΔQRS duration by means of Youden indices were found at 62μVs and −11ms, respectively. Primary endpoint was a combination of all-cause mortality, heart transplantation, and left ventricular assist device implantation. Secondary endpoint was the relative reduction in left ventricular end-systolic volume (LVESV), and echocardiographic response being defined as ≥15% LVESV reduction.

Results

The primary endpoint occurred in 408 patients (31%). ΔQRS area was superior to ΔQRS duration for the primary and secondary endpoints. Primary endpoint analysis showed a lower risk in the ΔQRS area ≥62μVs than in the <62μVs group (HR 0.43; 0.33–0.56, p<0.001). In the multivariable analysis, both baseline QRS area and ΔQRS area remained significantly associated with both primary and secondary endpoints. Clinical outcome (left panel of figure) and echocardiographic response (right panel) were significantly worse in patients with baseline QRS area <109μVs (group 3) than in those with QRS area ≥109μVs. Within the latter group, outcomes were significantly better in patients with ΔQRS area ≥62μVs (group 1) as compared to ΔQRS area <62μVs (group 2) (figure). Baseline QRS duration and ΔQRS duration were not independently associated with both clinical outcome and echocardiographic response.

Conclusion

The combination of baseline QRS area and ΔQRS area has a stronger association with CRT response than baseline QRS area alone, and (Δ)QRS duration. These results suggest that especially in patients with a good electrical substrate (large baseline QRS area) it is worthwhile to adjust CRT to achieve the largest decrease in QRS area.

Funding Acknowledgement

Type of funding source: None
Transvenous lead extraction: procedural outcomes and in-hospital mortality in octogenarian patients
Authors: Giannotti Santoro M , Segreti L , Zucchelli G , Barletta V , Di Cori A , De Lucia R , Fiorentini F , Canu A , Viani S , Bongiorni M.G
Published: November 2020

Background

Managing elderly patients with infection or malfunction deriving from a cardiac implantable electronic device (CIED) may be challenging. The aim of this study was to evaluate safety and efficacy of mechanical transvenous lead extraction (TLE) in elderly patients.

Methods

Patients who had undergone TLE in single tertiary referral center were divided in two groups (Group 1: ≥80 years; group 2:<80 years) and their acute and chronic outcomes were compared. All patients were treated with manual traction or mechanical dilatation.

Results

Our analysis included 1316 patients (group 1: 202, group 2: 1114 patients), with a total of 2513 leads extracted. Group 1 presented more comorbidities and more pacemakers, whereas the dwelling time of the oldest lead was similar, irrespectively of patient's age. In group 1 the radiological success rate for lead was higher (99.0% vs 95.9%; P<0.001) and the fluoroscopy time lower (13.0 vs 15.0 minutes; P=0.04) than in group 2. Clinical success was reached in 1273 patients (96.7%), without significant differences between groups (group 1: 98.0% vs group 2: 96.4%; P=0.36). Major complications occurred in 10 patients (0.7%) without significative differences between patients with more or less than 80 years (group 1: 1.5% vs group 2: 0.6%; P=0.24). In the elderly group no in-hospital mortality occurred (0.0% vs 0.5%; P=0.42).

Conclusions

Mechanical TLE in elderly patients is a safe and effective procedure. In the over-80s, a comparable incidence of major complications with younger patients was observed, with at least a similar efficacy of the procedure and no procedural-related deaths.

Funding Acknowledgement

Type of funding source: None
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

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 <50%) and 43 underwent CPET evaluation. 41 patients (95%) performed at near maximal effort (RER >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<0.001). Peak oxygen consumption (pVO2) ≤14 mL/kg/min and ventilatory efficiency (VE/VCO2) >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

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

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<0.001) both at rest and during exercise. TAPSE/PASP was positively correlated with LA strain (R=0.58 and 0.59, P<0.001) and cardiac output (R=0.28 and 0.58, P<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 <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 <0.33, derived by ROC curve (AUC=0.71, P<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

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<0.05). Patients without arrhythmia recurrence showed significant improvements in peak exercise PCWP (29.2±3.7 to 22.9±2.0 mmHg (p<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

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<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<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

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

Background

Elderly >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

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 <0.05 in the study population AND gnomAD NFE AF <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

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: <120mmHg, ≥120mmHg and <130mmHg, ≥130mmHg and <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 <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 <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)
A comparison of machine learning models for predicting rehospitalisation and death after a first hospitalisation with heart failure
Authors: Jones Y , Hillen N , Friday J , Pellicori P , Kean S , Murphy C , Cleland J
Published: November 2020

Background

Many machine learning models exist, including Multilayer Perceptron (MLP), Random Forest algorithm (RF), Support Vector Machine (SVM), and Gradient Boosted Machine (GBM), but their value for predicting outcome in patients with heart failure has not been compared.

Aim

To predict rehospitalisation (all-cause) and death (all-cause) at 1-, 3- and 12 months after discharge from a first hospitalisation for heart failure using four machine learning models.

Methods

The National Health Service Greater Glasgow and Clyde Health Board serves a population of ∼1.1 million. We obtained de-identified administrative data, including investigations, diagnosis and prescriptions, linked to hospital admissions and deaths for anyone with a diagnosis of vascular disease or heart failure or prescribed loop diuretics, statins or neuro-endocrine antagonists at any time between 1st January 2010 and 1st June 2018. Patients who were under 18 or had no prior hospitalisation for heart failure were excluded. Four ML algorithms using 46 variables were applied.

Results

Of 360,000 people who met the above criteria between 2010–2018, 6,372 had a hospitalisation for heart failure prior to 1st January 2010 and 8,304 had a first hospitalisation for heart failure thereafter. Between 2010 and 2018 there were 3,086 re-hospitalisations over 24 hours and 3,706 patients died, with 5,070 patients experiencing the composite outcome.

GBM and RF consistently outperformed MLP and SVM when comparing AUC, sensitivity and specificity combined, with GBM performing best in all scenarios. Since GBM and RF are both tree-based models, and with SVM and MLP regularly reporting very poor sensitivity or specificity despite a similar AUC to the others, this suggests that SVM and MLP may be suffering from overfitting and might perform better in larger data-sets.

Both GBM and RF work by ordering variables, so the final model can be used to determine the most important prediction variables. Age, number of times a blood sample was taken out of hospital, length of stay, social deprivation index and haemoglobin concentration consistently ranked amongst the most important variables. Models predicted all 1-month events better than later events.

Conclusions

Some, but not all, ML models applied to this data-set predicted rehospitalisation and death with great accuracy for up to 3 months after a first hospitalisation for heart failure. The models identified several important prognostic variables that are currently seldom collected in clinical research registries but perhaps should be.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Medical Research Council
Biomarkers associated with poor prognosis in patients with end-stage heart failure
Authors: Szczurek W , Gasior M , Skrzypek M , Romuk E , Szygula Jurkiewicz B
Published: November 2020

Background

Despite advances in the treatment, end-stage heart failure (HF) is a disease with a severe prognosis, showing an annual mortality rate of 30 to 50%. Due to a poor prognosis in this population of patients, it is necessary to accurately stratify the risk of death, including simple and effective prognostic markers.

Objective

This study aimed to determine biomarkers associated with mortality in patients with end-stage HF.

Material and methods

The study was a prospective analysis of optimally treated patients with end-stage HF, who were hospitalised at the Cardiology Department between 2016 and 2018. At the time of enrollment to the study routine laboratory tests, cardiopulmonary exercise tests, echocardiography and right heart catheterization were performed in all patients. Human Interleukin 33 (IL-33) and IL-1 Receptor Like 1 (IL1RL1) were measured by sandwich enzyme-linked immunosorbent assay (ELISA) with the commercially available kit (Human Il-33 and IL1RL1 ELISA kit, SunRedBio Technology Co, Ltd, Shanghai, China). Plasma concentration of N-terminal brain natriuretic peptide (NT-proBNP) was measured using a commercially available kit (Human NTproBNP ELISA kit, Roche Diagnostics, Mannheim, Germany). The endpoint was all-cause mortality during a one-year follow-up. The Medical University of Silesia's local Institutional Review Board approved the study protocol, and all patients provided informed consent.

Results

The final study group consisted of 282 patients (87.6% males, median age 57.0 years). One-year mortality rate in the analysed population was 28%. In a multivariate analysis, independent risk factors of death included NT-proBNP [Hazard Ratio (HR) 1.056 (95% Confidence Interval (CI): 1.024–1.089); P<0.001], sodium [HR 0.877 (95% CI: 0.815–0.944); p<0.001], IL33 [HR 0.977 (95% CI: 0.965- 0.989); p<0.001] and IL1RL1 [HR 1.015 (95% CI: 1.008–1.023); p<0.001) serum levels.

Conclusions

Our study showed that lower sodium and IL-33 levels, as well as higher NT-proBNP and IL1RL1 levels are associated with an increased risk of death in patients with end-stage HF during a one-year follow-up.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Medical University of SIlesia, Katowice, Poland