bluuebunny/crossref_metadata_2025 huggingface dataset:
1445Physical activity and long-term mortality risk in Israeli older adults with and without cardiovascular disease
Authors: Gerber Y , Shaked O , Cohen G , Goshen A , Shimony T , Shohat T
Published: October 2019

Background

Physical activity (PA) is a known protective factor among both general population and cardiovascular disease (CVD) patients. Yet, only a few cohort studies assessed the role of PA among older adult populations, characterized by high CVD prevalence rates.

Objectives

To evaluate the association between PA levels and all-cause mortality among Israeli older adults, and to assess whether it differs by baseline CVD status.

Methods

Participants were drawn from the National Health and Nutrition Survey of Older Adults Aged 65+ (“Mabat-Zahav”), conducted by the Israel Center for Disease Control between July 2005 and December 2006. Clinical, behavioral, and psychosocial data were collected via interview at study entry; a detailed PA questionnaire was also administered, through which participants were classified as sufficiently-active, insufficiently-active, and inactive, according to the American College of Sports Medicine classification. Mortality data (last follow-up, December 2016) were obtained from the Israeli Ministry of Health. Inverse probability weighted Cox proportional hazards models, based on propensity score, were constructed to assess the adjusted association between PA categories and mortality.

Results

Of the 1799 participants (mean [SD] age, 74.6 [6.2] years; 647 [36%] with a history of CVD), 559 (31%) were sufficiently-active, 506 (28%) were insufficiently-active and 734 (41%) were inactive. During a mean follow-up period of 9.0 years, 684 participants (38%) died. PA and mortality demonstrated an inverse dose-response relationship in both CVD and non-CVD groups, with no CVD-by-PA interaction detected on multiplicative-scale (P=0.70) or additive-scale (P=0.58). Notably, inactive non-CVD subjects had comparable risk to CVD patients who were sufficiently active (Figure).

Physical activity and mortality

Conclusions

In a nationally-based cohort of subjects aged 65 years and over, PA was inversely associated with mortality risk. CVD patients who preformed sufficient PA had a comparable mortality risk to inactive subjects free of CVD. These findings illustrate the importance of PA in the older adult population.
2139Left atrial dysfunction assessed by strain correlates with symptoms and severity of aortic stenosis
Authors: Santoro C , Pardo A , Hinojar R , Garcia A , Salido L , Gonzalez-Gomez A , Jimenez-Nacher J J , Marco Del Castillo A , Abellas M , Hernandez-Antolin R , Zamorano J L , Fernandez-Golfin C
Published: October 2019

Background

Aortic stenosis (AS) results in high pressure afterload causing detrimental effect especially on the left chambers. Structural and functional changes of the left ventricle (LV) usually corresponds to concomitant remodelling of the left atrium (LA). However, how this pressure afterload specifically affects LA function and whether the study of LA function could help in stratifying patients with different degree of AS it is not known.

Purpose

We aim to evaluate the differences in LA and LV function according different degree of AS by standard and speckle tracking echocardiographic.

Methods

From January 2016 to May 2018 we recruited 135 patients referring to our echo-lab with diagnosis of AS (mean age 79.5±4.4; 60/55% female). We divided this population according to AS severity in patients with moderate AS, severe asymptomatic and severe symptomatic AS and matched with 35 control group with no aortic stenosis (n=45, mean age: 77.6±4.5). All patients underwent standard and 2-dimensional speckle tracking echocardiography computing global longitudinal strain (GLS) of LV and peak atrial strain of LA (PALS).

Results

In all patients PALS was a good predictor of E/e' ratio after correction for LV EF and age (p<0.001, β: −0.48). LVEF and GLS progressively decreased together with worsening of AS degree, as well as parameters of geometry and function of LA (Table1). By excluding patients with LV dysfunction the reduction gradient of parameters of LA geometry and function was still present. However, when severe symptomatic with asymptomatic severe AS are compared, no difference in E/e' ratio was found while both GLS and PALS were significantly reduced (both p<0.0001).

Variables Overall population (180) Control (45) Moderate AS (45) Severe asympt AS (45) Severe sympt. AS (45) p LVEF 65.0±11.1 67.7±5.6 69.4±8.5 66.1±10.7 59.5±13.5 0.0001 GLS −20.4±4.1 −23.1±2.4 −21.5±2.9 −21.4±3.2 −17.1±4.3 0.0001 LA vol index 41.6±21.5 28.2±10.4 40.1±19.7 39.8±16.7 52.3±24.9 0.0001 LA strain 23.6±10.9 30.8±10.3 27.8±9.2 24.4±9.7 15.2±7.1 0.0001 LA reservoir 46.4±15.9 51.9±11.5 53.0±15.0 48.3±14.1 37.2±16.1 0.0001 Ee' ratio 14.8±7.0 9.6±2.7 13.7±6.3 15.4±6.2 19.3±7.2 0.0001

Conclusions

LA function seems to progressively decrease according to the degree of AS, independently from LV function. Significant difference was found between parameters of LA remodelling and dysfunction between symptomatic and asymptomatic AS patients. The assessment of LA function by strain may help stratify the patients with AS, identifying those who need intensive medical/surgical treatment.
2204Predicting the trajectory of depression following an acute coronary syndrome: the role of resilience
Authors: Smith J H C , Toukhsati S , Francis A J P , Stavropoulos V , Hare D L
Published: October 2019

Background

Depression is common in patients following an Acute Coronary Syndrome (ACS) substantially increases the risk of future events and mortality. Post-ACS depression typically resembles one of four longitudinal trajectories: chronic; absent; recovered, or delayed depression. Early identification of a patient's post-ACS depression trajectory will improve risk stratification, treatment implementation and risk management.

Purpose

To explore whether stable psychosocial traits, such as resilience, predict the trajectory of depression one month and 6 months following an ACS admission.

Method

Consecutive adult ACS patients (STEMI/NSTEMI) admitted to a large general hospital completed the Cardiac Depression Scale (CDS) and the Sense of Coherence scale during their admission, then one and six months following discharge.

Results

132 ACS in-patients (males = 111; mean age = 63.13±13.47) satisfied enrolment criteria. Unconditional linear latent growth modelling identified a 3-class model for the trajectory of depression post-ACS (increasing depression; consistent non-depressed; decreasing non-depressed). For the increasing depression class, resilience at baseline was significant and negative compared to the consistent class, b=−0.06, Wald chi square (1) = 4.42, p=0.036 and the decreasing class, b=−0.09, Wald chi square (1) = 7.20, p=0.007.

Conclusions

Patients who reported lower levels of resilience during an ACS admission were significantly more likely to experience initially high levels of depressive symptoms (CDS ≥85) that exceeded the clinically relevant cut-off (CDS ≥95) at 6 months post-discharge. This study suggests that screening for resilience and depression will improve risk stratification for persistent and delayed depression post-ACS.
2212Body mass index and its association to cardiovascular outcomes in patients with stable coronary heart disease - experiences from the STABILITY study
Authors: Held C , Hadziosmanovic N , Hagstrom E , Hochman J S , Stewart R A H , White H D , Wallentin L
Published: October 2019

Background

Obesity, assessed as body mass index (BMI), is an established risk factor for development of coronary heart disease (CHD). However, in patients with heart failure and atrial fibrillation there is an “obesity paradox” with better prognosis among obese patients. The association between BMI and cardiovascular outcomes in patients with stable CHD is unclear.

Methods

The prospective STABILITY trial included 15,828 patients with stable CHD with a follow-up of 3–5 years (median 3.7) on optimal secondary preventive treatment. BMI and waist circumference were measured at baseline (n=15,785). All cardiovascular outcomes were centrally adjudicated. Associations between obesity indices and outcomes were evaluated by multivariable Cox regression analyses with adjustments for age, sex, study treatment, and clinical risk factors.

Results

Mean age was 64 years and 19% were females. In total, 3250 (20.9%) patients had BMI <25, 6628 (42.8%), BMI >25 and <30 and 5614 (36.3%), BMI >30. Underweight (BMI <18.5) was seen in 79 patients. Most risk markers (diabetes, hypertension, and levels of inflammatory biomarkers and triglycerides) showed a graded association with higher BMI. The frequency of smoking and levels of HDL, GDF-15 and NT-proBNP were higher at lower BMI. Lower BMI was associated with an increased risk of MACE, total and CV death, and heart failure (Figure). Higher BMI was associated with increased risk of the same outcomes and also with MI. BMI was not associated with the risk of stroke. There was no interaction with age, sex, diabetes or type of MI (type 1 vs type 2–5). Associations between waist circumference and outcomes were weaker and not significant in the fully adjusted model.

Figure 1

Conclusion

In patients with stable CHD on optimal secondary prevention BMI had a U-shaped association with the risk of MACE, death, and heart failure and a linear association with the risk of MI. The lowest risk for MACE was seen for BMI between 25 and 30, considered as overweight. The findings do not support current recommendations to achieve an ideal BMI of 20–25 for weight adjustments in patients with CHD.

Acknowledgement/Funding

The original STABILITY study was funded by GlaxoSmithKline
2226The randomised study of epicardial application of hydrogel with amiodarone for prevention of postoperative atrial fibrillation in patients after coronary artery bypass grafting
Authors: Bockeria O , Shvartz V A , Kanametov T
Published: October 2019

The purpose of our study was to evaluate safety and efficacy of local epicardial application of amiodarone - releasing hydrogel in the prevention of postoperative atrial fibrillation (AF) in patients undergoing coronary artery bypass grafting (CABG).

Material and methods

We present an open prospective randomised study, in which 60 patients (47 male), mean age of 62±8,5 were included. Baseline clinical, laboratory and instrumental characteristics were similar in all patients. Patients didn't have any arrhythmic complains or previously registered AF. All patients underwent elective CABG and were randomised into two groups: Group #1 (n=30) - had the amiodarone-releasing hydrogel application before chest closure, and Group #2 (n=30) regular CABG surgery, no local application. We used 60 mg of amiodarone in hydrogel. This dose was experimentally determined during previously performed animal study. Heart rhythm control was monitored continuously during first 5 postoperative days and occasionally (mornings and evenings) the remaining days before the discharge. The local ethics committee approved this study design.

Results

The incidence of postoperative AF occurrence was significantly lower in Group #1: AF was registered in 3.3% cases versus 37% of patients from Group #2 (p<0.001). There was slight increase of PQ interval duration in Group #1 - 0.14 sec (0.12; 0.16), which however was significantly higher then in Group #2 - 0.12 (0.12; 0.14), (p<0.01). QRS and QT intervals were similar in both groups without significant difference.

There were no complications associated with the application procedure neither during postoperative period, such as AV block, infection or life-threatening situations.

According to 5 days ECG monitoring, the average heart rate in the Group #1 was 59 (52; 60) beats per min versus 69 beats per min (65; 75) in Group #2 (p<0.001). Temporary atrial or atrio-ventricular pacing used for correction of the heart rate if required in both groups. By the time of discharge none of the patients required permanent cardiac pacing. The length of stay in Group #1 was significantly shorter: 6 (6; 7) days versus 8 (8; 9) days (p<0,001).

Among all studied parameters, amiodarone-releasing hydrogel application and older age were statistically significant in postoperative AF occurrence (p<0.01). According to the Cox regression model amiodarone-releasing hydrogel application decreases the incidence of postoperative AF by 18,9 folds. The older age instead increases the incidence of postoperative AF by 1,2 folds.

Conclusions

The local epicardial amiodarone (60 mg) application in hydrogel before chest closure is a safe procedure. This approach showed it's effectiveness in AF prevention in patient undergoing elective CABG.
2230Results from the CAMI1 Study: selective CRP apheresis as a new treatment option in acute myocardial infarction
Authors: Garlichs C , Torzewski J , Sheriff A , Pfluecke C , Darius H , Lehrke S , Horstkotte J , Heigl F , Ince H , Mitzner S , Nordbeck P , Butter C , Zaenker M , Ries W
Published: October 2019

Background

Inflammation is increasingly recognized as an important pathogenic feature in cardiovascular disease. In patients with STEMI, C-reactive protein (CRP), the prototype human acute phase protein, is a marker of poor prognosis and independently predicts 30-day mortality. In STEMI, CRP may indeed be intimately involved in myocardial damage by activating the complement system in the ischemic tissue. In animal experiments, CRP removal after STEMI reduces infarct size and results in a significantly better left ventricular ejection fraction (LVEF). Recently, in the multi-center matched-control pilot study on CRP apheresis in Acute Myocardial Infarction (CAMI1), a newly designed CRP adsorber has been demonstrated to efficiently and selectively lower CRP plasma levels in humans. Here, we present preliminary data of the ongoing trial.

Methods

Up to the present day, 67 STEMI patients were enrolled in the study following complete coronary revascularization. 32 patients received CRP apheresis, whereas 35 patients treated by standard protocols served as controls. CRP apheresis started 24±12 h and 48±12 h after onset of symptoms. In case of a rapid increase in CRP plasma levels following the 2nd session, a 3rd session was carried out another 24 h later. In each apheresis session, 6000 ml plasma was treated via peripheral venous access. Primary study endpoint was myocardial infarction size as determined by Cardiac Magnetic Resonance Imaging (MRI) 5±3 days after STEMI.

Results

Apheresis sessions were well tolerated with no relevant side effects. Peak CRP plasma levels after STEMI ranged from 12 mg/l to 279 mg/l. The peak CRP level after AMI can be calculated precisely with at 2–3 CRP quantifications during the first 24 h after the onset of symptoms. The regression coefficient for this analysis is 0.95. This mathematical step allows for the comparison of the CRP-apheresis group and the controls on the basis of their individual CRP peak levels. The statistical evaluation shows that the apheresis patients no longer correlate with the control with regard to the endpoints infarct size, LVEF, longitudinal strain and circumferential strain. They perform significantly better at all endpoints. The CRP apheresis reduced the development of myocardial damage.

Conclusions

Here, an unequivocal association between infarct size and CRP is demonstrated for the first time. CRP apheresis following STEMI is feasible and safe. Our preliminary results in a small cohort show a significant beneficial effect of CRP apheresis on myocardial infarction size and wall motion. Selective CRP apheresis may emerge as a new therapeutic approach in the treatment of acute myocardial infarction.
2285Increased risk of out-of-hospital cardiac arrest associated with psychiatric disorders
Authors: Barcella C A , Mohr G H , Kragholm K , Christensen D M , Polcwiartek C , Wissenberg M , Lippert F K , Torp-Pedersen C , Kessing L V , Gislason G H , Soendergaard K B
Published: October 2019

Introduction

Patients with psychiatric disorders are at high risk of cardiovascular morbidity and mortality; yet, the risk of out-of-hospital cardiac arrest (OHCA) compared to the general population remains unknown.

Purpose

We investigated whether the presence and severity of different psychiatric disorders were associated with a higher risk of OHCA.

Methods

We conducted a case-control study matching all adult patients with OHCA of presumed cardiac cause between 2001 and 2014 with up to nine controls from the entire Danish population on age, sex and ischemic heart disease (IHD). Patients with psychiatric disorders were identified using in- and out-patient hospital diagnoses – both primary and secondary - before index date. We identified six mutually exclusive psychiatric disorders that were separately examined: personality disorders, anxiety, substance-related mental disorders, depression, bipolar disorder and schizophrenia. The risk of OHCA associated with the six psychiatric disorders was evaluated by conditional logistic regression adjusting for comorbidities, concomitant pharmacotherapy, socioeconomic status and marital status.

Results

We included 32,447 OHCA cases matched with 291,999 controls from the general population. Overall, the median age was 72 years, 67% were male and 29% had IHD prior to index date. All the six psychiatric disorders examined were more common among cases than controls; depression was the most common psychiatric disorders in both groups: 5.0% among cases and 2.8% among controls. Concurrently, all six psychiatric disorders were associated with significantly higher odds of OHCA: personality disorders (odds ratio (OR) 1.30 [95% confidence interval (CI) 1.06–1.60], anxiety OR 1.26 [95% CI 1.15–1.39], substance induced-mental disorders OR 2.36 [95% CI 2.17–2.57], depression OR 1.27 [95% CI 1.19–1.35], bipolar disorder OR 1.32 [95% CI 1.16–1.50] and schizophrenia OR 1.80 [95% CI 1.58–2.05] (Figure). The association persisted unaffected when we studied psychiatric patients neither exposed to antipsychotics nor to antidepressants. We observed a trend towards a stronger association when we stratified according to the severity of the psychiatric disorder (Figure). Severe disorders where classified as at least one hospitalization for the specific psychiatric illness as primary diagnosis during the five years prior to index date.

Conclusions

Common psychiatric disorders including personality disorders, anxiety, substance-related mental disorders, depression, bipolar disorder and schizophrenia are significantly associated with higher odds of OHCA. These findings provide a rationale for early cardiovascular risk factor screening and, potentially, management among psychiatric patients to identify patients at high risk of OHCA.

Acknowledgement/Funding

ESCAPE-NET project
2396Long-term follow-up of patients with tetralogy of Fallot and implantable cardioverter defibrillator
Authors: Waldmann V , Bouzeman A , Marquie C , Labombarda F , Koutbi R , Sellal J M , Fauchier L , Mondoly P , Pasquie J L , Anselme F , Eschalier R , Iserin L , Thambo J B , Combes N , Marijon E
Published: October 2019

Background

Ventricular arrhythmias and sudden death are potential late complications in patients with tetralogy of Fallot. Data regarding the value of implantable cardioverter defibrillators (ICD) are scarce in this population.

Purpose

To assess long-term rates of appropriate ICD therapies and ICD-related complications in a large registry of ICD recipients with tetralogy of Fallot.

Methods

The DAI-T4F study is an ongoing national French registry including all patients with tetralogy of Fallot and ICD (NCT03837574). Information have been collected prospectively since 2010 with annual update. Baseline patient characteristics and clinical events during follow-up were analyzed with central adjudication. Cox proportional hazard models were used to identify factors associated with appropriate ICD therapies and complications.

Results

A total of 134 patients (median age 41.7 years, 70.7% males) were enrolled. The median (IQR) follow-up duration was 6.1 (2.7–10.2) years. ICDs were implanted for primary prevention in 47 (35.1%) patients and for secondary prevention in 87 (64.9%) patients. Overall, 14 (29.8%) and 45 (51.7%) patients received at least one appropriate ICD therapy in primary and secondary prevention, respectively, giving annual incidences of 5.5% and 7.1% (p=0.06). Patients with altered left ventricle ejection fraction (LVEF) at inclusion ≤35% experienced less appropriate ICD therapies (HR=0.31, 95% CI: 0.11–0.86, p=0.02), whereas a history of sustained or non-sustained ventricular arrhythmia (HR=2.7, 95% CI: 1.2–3.9, p=0.03) was positively associated with appropriate therapies. Fifty-seven (42.5%) patients had ICD-related complications, including 32 (24.2%) inappropriate ICD shocks, 22 (16.4%) significant lead dysfunction, 14 (10.4%) device infection, and 5 (3.7%) generator dysfunction/recall. History of supraventricular arrhythmias (HR=2.2, 95% CI: 1.2–3.7, p=0.01) and congestive heart failure (HR=2.0, 95% CI: 1.2–3.6, p=0.01) were both associated with a higher risk of complications. During follow-up, 7 (5.2%) patients underwent cardiac transplantation and 12 (9.0%) patients died, mainly from progressive heart failure (n=5). Only one sudden death due to electrical storm was recorded.

Figure 1

Conclusions

Appropriate therapies are frequent in patients with tetralogy of Fallot and ICDs, including in primary prevention. The relatively important proportion of ICD-related complication highlights the need for improving risk stratification in this population, considering associated conditions in the individual benefit-risk equation.
2397Lesion-specific risk for sudden cardiac death or life-threatening ventricular arrhythmias in adult congenital heart disease
Authors: Gallego Garcia De Vinuesa P , Gonzalez Garcia A E , Avila P , Alonso A , Garcia Hamilton D , Peinado R , Dos Subira L , Pijuan-Domenech A , Rueda Soriano J , Rodriguez-Puras M J , Garcia-Orta R , Martinez-Quintana E , Bermejo J , Fernandez-Aviles F , Oliver J M
Published: October 2019

Background

Risk models for primary prevention strategies in adult congenital heart disease (ACHD) must incorporate the heterogeneous risk for sudden cardiac death (SCD) and life-threatening ventricular arrhythmias (LTVA) as stratified by underlying lesion.

Objectives

To determine lesion-specific risk for SCD and LTVA in ACHD.

Methods

We analyzed 3311 ACHD patients (50% males) prospectively followed-up for 37510 person/years. SCD cases were confirmed by means of the Spanish National Death Registry. In addition, we identified all cases of resuscitated cardiac arrest or ventricular tachycardia requiring cardioversion. According to the incidence rate of the composite end-point of SCD and LTVA, lesions were stratified into four groups of risk. Cumulative freedom from SCD or LTVA in patients at high, moderate, low and very low risk were compared by using Cox regression model with left truncation. The c-index of this lesion-specific risk stratification was calculated by using the β-coefficients. The discriminative ability of this lesion-specific risk stratification was also tested in an external cohort of 203 SCD-LTVA cases and 2287 controls from 20 different centers.

Results

71 patients experienced an event (53 SCD, 18 LTVA). Patients at highest risk (incidence rate >1%) were those with Rastelli procedure, severe coronary abnormalities, complex Fallot and cyanotic patients, either Eisenmenger or non-Eisenmenger; at moderate risk (incidence rate 0.25–1.0%) non-complex Fallot, Mustard/Senning repair, Fontan procedures and congenitally corrected transposition; at low risk (incidence rate 0.1–0.25%) Ebstein anomaly and left heart lesions; and at very low risk (incidence rate <0.1%) left-to-right shunts and right ventricular outflow lesions. The discriminative ability in a multicenter external cohort was excellent (c-index ranged from 0.748 to 0.819 by center).

Lesion-specific risk and C-index

Conclusions

A lesion-specific risk stratification based on the incidence rate of SCD and LTVA was performed and validated. This approach could result in a more individualized risk assessment.

Acknowledgement/Funding

Instituto de Salud Carlos III, Ministerio de Economía y Competividad, Spain (Exp PI14/02099 and PI17/01327) and co-financed by FEDER
2402Reduced heart rate variability is linked to clinical status in patients with a systemic right ventricle
Authors: Zandstra T E , Kies P , Man S , Maan A C , Bootsma M , Vliegen H W , Schalij M J , Jongbloed M R M
Published: October 2019

Background

Adult patients with congenital heart disease and a systemic right ventricle (sRV) are prone to develop heart failure. Decreased heart rate variability (HRV), a measure of autonomic dysfunction, is associated with morbidity and mortality in patients with congestive heart failure. The standard deviation of all intervals between normal sinus beats (SDNN) is a HRV parameter commonly reported as an indicator of autonomic function in these patients. Data about HRV and its clinical implications in patients with a sRV are scarce.

Purpose

To compare HRV parameters between patients with a sRV and healthy controls, and to assess their association with clinical status.

Methods

All available 24-hour Holter monitoring records of sRV patients under follow-up in our center and one record per healthy control subject were analysed. Holters with non-sinus rhythm were excluded. Time and frequency domain parameters were calculated and compared between both groups. Clinical landmarks such as arrhythmias or an episode of congestive heart failure, which occurred up until the time of the ambulatory ECG, were combined in a clinical event score. Determinants of SDNN were investigated with mixed model linear regression in the patients and with multivariate linear regression in the controls. Baseline characteristics, medication use, global longitudinal strain, validity as measured with bicycle exercise testing, and the clinical event score were taken into account.

Results

113 Holters of 43 patients and 39 Holters of healthy controls were analysed. The patient group included 30 patients (70%) late after Mustard or Senning correction for transposition of the great arteries, and 13 patients with congenitally corrected transposition of the great arteries (30%). Age and gender were comparable in patients and controls. Several HRV parameters were significantly worse in patients compared with controls, including SDNN (138 in patients vs. 161 in controls, p=0.021). In the patients, clinical event score was the only significant determinant of a lower SDNN (p<0.001). In the controls, age was the only significant determinant of a lower SDNN (p=0.039).

Conclusion

Contrary to the healthy population, in patients with a sRV, HRV is associated with clinical status rather than age. This indicates that disease progression affects autonomic function more than ageing in this group. Further research is needed to clarify the relation between clinical outcome and autonomic function in sRV patients.

Acknowledgement/Funding

The Department of Cardiology of the LUMC received research grants from Medtronic, Biotronik, Boston Scientific and Edwards Lifesciences
2403Experience with the wearable cardioverter-defibrillator by disease etiology: results from the wearit-II registry
Authors: Kutyifa V , Vermilye K , Zareba W , McNitt S , Goldenberg I
Published: October 2019

Background

The use of the wearable cardioverter-defibrillator (WCD) in patients with non-ischemic cardiomyopathy has been less characterized.

Objective

We aimed to characterize WCD use and outcomes for patients with ischemic or non-ischemic cardiomyopathy, enrolled in the WEARIT-II Registry.

Methods

In WEARIT-II, we stratified 1,732 patients into ischemic (n=805) and non-ischemic etiology (n=927). WCD wear time, arrhythmia events during WCD use, and implantable cardioverter-defibrillator (ICD) implantation rates, or ejection fraction (EF) improvement at the end of WCD were evaluated for etiology subgroups.

Results

The WCD median wear time was higher in patients with non-ischemic cardiomyopathy (93 vs. 87 days, p=0.003), however daily use was similar (22.4 vs. 22.6 hours, p=0.07). There were 24 ischemic patients (3%) with sustained VT/VF events compared to 10 patients (1%) with non-ischemic cardiomyopathy (p=0.013). About 2/3 of these events were treated with WCD shock in ischemic patients, half of them in the non-ischemic group (1.9% vs. 0.4%). Atrial arrhythmias were frequent in both groups (3.1% vs. 3.1%, p=0.06). At the end of WCD use, 36% of the non-ischemic patients were implanted with an ICD compared to 42% in ischemic (p=0.01), likely due to the lower rate of sustained ventricular arrhythmias (Figure).

Figure 1

Conclusions

In WEARIT-II, patients with non-ischemic cardiomyopathy had longer WCD use than ischemic patients with good compliance. The rate of sustained ventricular arrhythmia events was lower in non-ischemic patients avoiding the need for an ICD implantation in more patients compared to ischemic, following a time period of risk stratification.

Acknowledgement/Funding

WEARIT-II was funded by an unrestricted research grant from ZOLL Inc.
P1230Impact of regulated junctophilin-2 clustering at axial tubule junctions on atrial excitation-contraction coupling and therapeutic implications
Authors: Brandenburg S , Pawlowitz J , Eikenbusch B , Kohl T , Sossalla S , Hasenfuss G , Wehrens X H T , Kohl P , Rog-Zielinska E A , Lehnart S E
Published: October 2019

Objectives

Atrial dysfunction is highly prevalent and known to significantly aggravate heart failure. While rapid excitation-contraction (EC) coupling depends on axial tubule junctions in atrial myocytes (AMs), the mechanisms leading to atrial loss-of-function remain unclear. Junctophilin-2 (JP2), a tail-anchored protein of the sarcoplasmic reticulum, stabilizes the integrity of ventricular Ca2+ release units, which is disrupted in ventricular myocytes by reduced JP2 expression or proteolysis. Here we aim to characterize the abundance and subcellular localisation of JP2 in AMs, to assess the impact of decreased JP2 expression on atrial remodelling, and to investigate the potential to correct JP2 expression and atrial dysfunction.

Results

We identified 5-fold lower JP2 levels in atrial compared to ventricular tissue in mouse and human hearts by SDS-PAGE. Surprisingly, in AMs, this resulted in subcellular expression of large JP2 clusters at axial tubule junctions together with highly phosphorylated ryanodine receptor (RyR2) channels visualized by STED superresolution microscopy. Importantly, left atrial hypertrophy induced by aortic pressure overload led to an additional strong decrease in JP2 expression compared to sham control, disrupted junctional RyR2 clustering and EC-coupling. This loss-of-function mechanism was confirmed by conditional shRNA-mediated JP2 knockdown. Quantitative image analysis after atrial JP2 knockdown showed a 50% decrease in area overlap between RyR2 and JP2 in AMs (JP2 knockdown 0.03±0.003 μm2 vs. control 0.06±0.004 μm2, p<0.001), and a ∼2-fold increased Ca2+ spark frequency, consistent with decreased left atrial fractional shortening (JP2 knockdown 12.9±0.8% vs. control 16.5±0.9%, p<0.01). Whereas atrial-ventricular dysfunction due to aortic pressure overload resulted in 40% mortality, additional JP2 knockdown exacerbated mortality to 100% (n: 10 control vs. 9 JP2 knockdown mice). In contrast, transgenic JP2 overexpressor mice showed greatly improved atrial contractility without mortality after induced aortic pressure overload (n: 21 control vs. 16 JP2 overexpressor mice). JP2-OE not only augmented atrial RyR2-clustering, but induced the de-novo biogenesis of large poly-adic junctional membrane complexes, which were resolved by STED microscopy via high-resolution cholesterol-based membrane staining in live AMs and electron tomography.

Conclusions

Nanoscale imaging identifies a new subcellular mechanism of significantly limited atrial JP2 protein expression in large clusters at axial tubule junctions. In atrial hypertrophy, JP2 is further decreased with junctional RyR2 cluster disruption leading to impaired Ca2+ release and decreased contractility. Importantly, JP2 overexpression effectively protected from atrial dysfunction, providing a novel therapeutic rationale for atrial cardiomyopathies.
P1233Differential effects of five risk variants for atrial fibrillation at the 4q25 region on L-type calcium current and transient inward currents in human atrial myocytes
Authors: Tarifa C , Herraiz-Martinez A , Llach A , Jimenez-Sabado V , Colino H , Lozano-Velazquez E , Franco D , Rosello E , Rodriguez-Font E , Cinca J , Hove-Madsen L
Published: October 2019

Background

An increasing number of single nucleotide polymorphisms (SNPs) at the chromosomal region 4q25 have been associated with risk of atrial fibrillation (AF) and we have recently reported that carriers of the rs13143308 risk variant have an increased incidence of spontaneous calcium release-induce transient inward currents (ITI). However, it is not known if different 4q25 variants have similar effects.

Purpose

This study aimed to compare the effects of five SNPs at 4q25 on L-type calcium current (ICa) and ITI frequency, features that are altered in patients with AF.

Methods

To avoid confounding effects of AF on calcium homeostasis, atrial samples from 63 patients without AF were genotyped and divided into groups according to the genotype of the SNPs rs1448818, rs6817105, rs13143308, rs6843082, rs3853443 ordered according to their location and identified by the three last digits + an R for risk or N for normal variants. ICa density and ITI frequency were measured with perforated patch clamp technique in atrial myocytes from these patients.

Results

Three SNPs 818, 308 and 443 segregated independently of the genotype at the other loci. The 105 and 082 loci always co-segregated with 308 but never together. The ICa density was smaller in carriers of 818R and 443N variants (−1.6±0.3pA/pF, p=0.01) or 818N and 443R variants (−1.6±0.4pA/pF, p=0.02) than in patients with 818N and 443N variants (−3.2±0.4pA/pF), independently of the genotype at 105, 308 and 082 (these loci did not affect ICa). In contrast, to this, the ITI frequency was increased only in myocytes from patients carrying 105R, 308R and 082N (1.4±0.2events/min, p<0.001) or 105N, 308R and 082R (1.6±0.5events/min, p=0.002) when compared to patients with 105N, 308N and 082N (0.36±0.09events/min) independently of the genotypes at 818 and 443, or when compared to patients without risk at any of the five loci (0.55±0.30events/min). The table shows schematically the qualitative effects of the different risk variants.

Risk variant rs1448818C rs6817105C rs13143308T rs6843082T rs3853445C ICa Decreased Unchanged Unchanged Unchanged Decreased ITI Unchanged Increased Increased Increased Unchanged

Conclusion

Different SNPs at the chromosomal region 4q25 are associated with differential pathological changes in intracellular calcium homeostasis. Risk variants at rs1448818 or rs3853445 cause loss of ICa without affecting ITI frequency while a risk variant at rs13143308 elevates the ITI frequency without affecting ICa. These findings afford a framework for stratification of pharmacological therapy based on the functional effects of the 4q25 risk variants

Acknowledgement/Funding

SAF2017-88019; Marato2015-20-30; SGR2017-1769; CIBERCV
P1237Left ventricular myocardial work characteristics and CRT response in patients with LBBB according to Strauss criteria and ESC 2013 definition
Authors: Kostyukevich M V , Van Der Bijl P , Vo N M , Ajmone Marsan N , Delgado V , Bax J J
Published: October 2019

Background

The impact of left bundle branch block (LBBB) on left ventricular (LV) myocardial work may vary according to the specific definition of a LBBB. Quantification of the interplay between LV myocardial work and the underlying electrical dyssynchrony may improve our understanding of cardiac resynchronization therapy (CRT) response.

Objective

To evaluate the impact of LBBB, defined according to Strauss and ESC 2013 ECG criteria, as well as non-LBBB morphologies on different LV myocardial work indices and response to CRT.

Methods

LBBB was defined according to the Strauss criteria and ESC 2013 guidelines on heart failure. LV myocardial constructive and wasted work (CW and WW) were derived from pressure-strain loop analysis integrating valvular opening and closing times, speckle tracking strain echocardiography and noninvasive blood pressure measurement. LV myocardial work efficiency (WE) was calculated from the ratio of constructive work, divided by the sum of constructive and wasted work. CRT response was defined as a decrease in LV end-diastolic volume (EDV) ≥15% at 6 months' follow-up.

Results

Patients were divided into 3 groups: 1) LBBB according to Strauss criteria (group 1, n=109, age 64±10 years), 2) LBBB according to ESC 2013 criteria (group 2, n=22, age 64±10 years) and 3) non-LBBB (group 3, n=44, age 69±10 years). Patients from group 1 were 4.2 times more likely to respond to CRT than patients from group 3 (odds ratio [OR] 4.182; 95% confidence interval [CI], 1.999–8.750; p<0.001), whereas CRT response between groups 2 and 3 did not differ significantly (OR 1.100; 95% CI 0.387–3.124; p=0.859). Patients in group 1, were characterized by significantly lower WE, compared to groups 2 and 3 (67.6±9.9 mmHg% vs. 72.7±9.7 mmHg% and 75.4±9.6 mmHg%, respectively; p<0.001) as well as higher WW (313.2±144.9 mmHg% vs. 215.1±102.5 mmHg% and 229.0±113.5 mmHg%, respectively; p<0.001). There was no significant difference in CW between any of the groups (811.6±353.4 mmHg% vs. 798.6±440.6 mmHg% and 893.6±420.2 mmHg% respectively for groups 1, 2 and 3; p=0.447).

Conclusion

Patients with a LBBB according to Strauss criteria had a higher probability of response to CRT, compared to those with a LBBB defined by ESC 2013 guidelines criteria or with non-LBBB morphology. This is reflected in a greater amount of wasted work and more impaired LV myocardial work efficiency at baseline in patients with LBBB satisfying Strauss criteria, compared to the other two groups, representing the substrate for CRT.

Acknowledgement/Funding

Study was supported by ESC Research grant 2018
P1247FLNC pathogenic variants in patients with various cardiomyopathies:prevalence and genotype-phenotype correlations
Authors: Ader F , De Groote P , Reant P , Dupin-Deguine D , Rambaud C , Khraiche D , Pruny J F , Mathieu Dramard M , Troadec Y , Gouya L , Jeunemaitre X , Van Maldergem L , Villard E , Charron P , Richard P
Published: October 2019

Background/Introduction

Pathogenic variants FLNC encoding filamin C have been firstly reported to cause myopathies, and were recently linked to isolated cardiac phenotypes.However, few data on phenotype-genotype correlation are available.

Purpose

Our aim was to estimate the prevalence of FLNC pathogenic variants in cardiomyopathies and to study the relations between phenotype and genotype.

Methods

DNAs from a cohort of 1150 unrelated index-patients with an isolated cardiomyopathy (700 hypertrophic, 300 dilated, 50 restrictive cardiomyopathies, and 100 left ventricle non-compactions) have been sequenced on a custom panel of 52 cardiomyopathy disease-causing genes.

Results

A FLNC pathogenic variant was identified in 28 patients corresponding to a prevalence ranging from 1 to 8% depending on the cardiomyopathy subtypes. Truncating variants were always identified in patients with dilated cardiomyopathy, while missense or in-frame variants were found in other phenotypes. This work reported for the first time a left ventricular non-compaction associated with FLNC pathogenic variant.

In the cohort, nine patients (32%) were implanted with an automatic defibrillator. In 7 families (25%), history of sudden cardiac death (SCD) before 50 years was reported. A personal or family history of sudden cardiac death (SCD) was significantly higher in patients with truncating variants than in patients carrying missense variants (p=0.01). Four patients died of cardiac cause including 3 from SCD and 1 from heart failure.

Conclusion

This work highlights the role of FLNC in cardiomyopathies. A correlation between the type of the variant and the cardiomyopathy subtype was observed as well as with SCD risk. These new data should be taken into consideration for patient's management and primary prevention of sudden cardiac death.

Acknowledgement/Funding

La ligue contre la Cardiomyopathie
P1249Prognostic impact of sarcopenia on major adverse cardiovascular outcomes in coronary artery disease patients undergoing successful percutaneous coronary intervention
Authors: Kang D O , Park S Y , Park Y , Jang W Y , Kim W , Choi B G , Na J O , Choi C U , Kim E J , Rha S.-W , Park C G , Hong S.-J , Seo H S
Published: October 2019

Background

Sarcopenia is an emerging marker of frailty. Its prognostic impact on atherosclerotic cardiovascular disease (ASCVD) requires further investigation.

Purpose

We investigated the long-term prognostic impact of computed tomography (CT)-determined sarcopenia in patients with coronary artery disease (CAD).

Methods

Total 475 CAD patients those who underwent successful percutaneous coronary intervention (PCI) and performed CT scan within 30 days of PCI were enrolled. The cross-sectional area of skeletal muscle at the first lumbar vertebra (L1) level was measured. Sarcopenia was defined as L1 skeletal muscle index of less than 34.60 cm2/m2 for men and of less than 25.90 cm2/m2 for women. Primary outcome was 3-year all-cause mortality and secondary outcome was 3-year major adverse cardiovascular event (MACE), a composite of all-cause mortality, any myocardial infarction, and repeat revascularization.

Results

Sarcopenia was present in 214 (45.1%) of 475 patients. The incidence of 3-year all-cause mortality and MACE was significantly higher in patients with sarcopenia than in those without sarcopenia (17.7% vs. 5.7%, p<0.001; and 35.0% vs. 11.2%, p<0.001, respectively). In the fully adjusted multivariable analysis, sarcopenia was an independent predictor of higher risk of 3-year all-cause mortality (odds ratio [OR]: 2.98; 95% confidence interval [CI]: 1.35 to 6.58, p=0.007) and MACE (OR: 4.39; 95% CI: 2.49 to 7.73, p<0.001). The results were consistent after propensity-score matched analysis with 100 pairs of study population (C-statistics = 0.868).

Kaplan–Meier analysis of 3-year outcomes Overall population PSM population Sarcopenia (n=214) No sarcopenia (n=261) Log-rank p-value Sarcopenia (n=100) No sarcopenia (n=100) Log-rank p-value All-cause mortality 36 (17.7) 14 (5.7) <0.001 19 (20.0) 7 (7.7) 0.013 Non-fatal MI 12 (6.6) 5 (2.0) 0.021 6 (7.0) 2 (2.3) 0.134 Repeat revascularization 32 (20.3) 14 (6.2) <0.001 17 (23.3) 8 (8.0) 0.027 Total MACEs 68 (35.0) 27 (11.2) <0.001 36 (39.3) 14 (15.4) 0.001 Data are expressed as n (%). MACE = major adverse cardiovascular event; MI = myocardial infarction; PSM = propensity-score matched.

Clinical impact of sarcopenia on CAD

Conclusion

Sarcopenia is a useful predictor of adverse clinical outcomes in patients with CAD undergoing PCI. CT-determined sarcopenia may further aid in risk stratification and decision-making for patients with established ASCVD.

Acknowledgement/Funding

National Research Foundation of Korea (NRF-2016R1A2B3013825), Ministry of Future Creation and Science of Korea (2018K000255)
P1252Diagnostic performance of quantitative flow ratio from coronary angiography versus fractional flow reserve from computed tomography
Authors: Emori H , Kubo T , Tanigaki T , Kawase Y , Shiono Y , Shimamura K , Sobue Y , Matsuo Y , Hirata T , Kitabata H , Ota H , Ino Y , Okubo M , Matsuo H , Akasaka T
Published: October 2019

Background

QFR and FFRCT are recently developed, less-invasive techniques for functional assessment of coronary artery disease.

Objectives

We compared the diagnostic performance between fractional flow reserve derived from computed tomography (FFRCT) and quantitative flow ratio (QFR) derived from coronary angiography, using FFR as the standard reference.

Methods

We measured FFRCT, QFR and FFR in 152 patients (233 vessels) with stable coronary artery disease.

Results

QFR was highly correlated with FFR (r=0.78, p<0.001), while FFRCT was moderately correlated with FFR (r=0.63, p<0.001). Both QFR and FFRCT showed good agreements with FFR, presenting small values of mean difference and root-mean-squared deviation (FFR -QFR: 0.02±0.09 and FFR -FFRCT: 0.03±0.11). The AUC of QFR was significantly greater than that of 3D-QCA-derived %DS (0.93 vs. 0.78; difference: 0.15; 95% CI: 0.09 to 0.20; p<0.001). The AUC of FFRCTwas significantly greater than that of CCTA-derived %DS (0.82 vs. 0.70; difference: 0.12; 95% CI: 0.05 to 0.19; p<0.001). The AUC of QFR was significantly greater than that of FFRCT (0.93 vs. 0.82; difference: 0.11; 95% CI: 0.05 to 0.16; p<0.001). The sensitivity, specificity, positive predictive value, and negative predictive valueof QFR ≤0.80 for predicting FFR ≤0.80 were 90%, 82%, 81%, and 90%, respectively. Those of FFRCT ≤0.80 for predicting FFR ≤0.80 were 82%, 70%, 70%, and 82%, respectively. The diagnostic accuracy of QFR ≤0.80 for predicting FFR ≤0.80 was 85% [95% confidence interval: 81% to 89%], while that of FFRCT≤0.80 for predicting FFR ≤0.80was 76% [95% confidence interval: 70% to 80%].

Figure 1. Comparison of FFR ≤0.80 predictors

Conclusions

Both QFR and FFRCTpossessed the ability to accurately evaluate the functional severity of coronary stenosis.