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OBJECTIVE: Implantable cardiac defibrillators (ICD) implantation in the very elderly remains controversial. We aimed to describe the experience and outcome of patients over 80 years old implanted with an ICD in Belgium. METHODS: Data were extracted from the national QERMID-ICD registry. All implantations performed in octogenarians between February 2010 and March 2019 were analysed. Data on baseline patient characteristics, type of prevention, device configuration and all-cause mortality were available. To determine predictors of mortality, multivariable Cox proportional hazard regression modelling was performed. RESULTS: Nationwide, 704 primo ICD implantations were performed in octogenarians (median age 82, IQR 81-83 years; 83% male and 45% secondary prevention). During a mean follow-up of 3.1 ± 2.3 years, 249 (35%) patients died, of which 76 (11%) within the first year after implantation. In multivariable Cox regression analysis age (HR = 1.15, P = 0.004), oncological history (HR = 2.43, P = 0.027) and secondary prevention (HR = 2.23, P = 0.001) were independently associated with 1-year mortality. A better preserved left ventricular ejection fraction (LVEF) was associated with a better outcome (HR = 0.97, P = 0.002). Regarding overall mortality multivariable analysis withheld age, history of atrial fibrillation, centre volume and oncological history as significant predictors. Higher LVEF was again protective (HR = 0.99, P = 0.008). CONCLUSIONS: Primary ICD implantation in octogenarians is not often performed in Belgium. Among this population, 11% died within the first year after ICD implantation. Advanced age, oncological history, secondary prevention and a lower LVEF were associated with an increased one-year mortality. Age, low LVEF, atrial fibrillation, centre volume and oncological history were indicative of higher overall mortality.

Background Ventricular arrhythmia (VT/VF) can complicate acute myocardial ischemia (AMI). Regional instability of repolarization during AMI contributes to the substrate for VT/VF. Beat-to-beat variability of repolarization (BVR), a measure of repolarization lability increases during AMI. We hypothesized that its surge precedes VT/VF. We studied the spatial and temporal changes in BVR in relation to VT/VF during AMI. Methods In 24 pigs BVR was quantified on 12-lead electrocardiogram (ECG) recorded at a sampling rate of 1kHz. AMI was induced in 16 pigs by percutaneous coronary artery occlusion (MI), while 8 underwent sham-operation (Sham). Changes in BVR were assessed at 5-minutes after occlusion, 5- and 1-minute pre-VF in animals that developed VF and matched time points in pigs without VF. Serum troponin and ST deviation were measured. After 1-month, magnetic resonance imaging and VT induction by programmed electrical stimulation were performed. Results During AMI, BVR increased significantly in inferior-lateral leads correlating with ST-deviation and troponin increase. BVR was maximal 1-minute pre-VF (3.78±1.36 vs 5-minutes pre-VF: 1.67±1.56, P < 0.0001). After 1-month, BVR was higher in MI than sham and correlated with the infarct size (1.43±0.50, vs 0.57±0.30, P = 0.009). VT was inducible in all MI animals and the ease-of-induction correlated with BVR. Conclusion BVR increased during AMI and temporal BVR changes predicted imminent VT/VF supporting a possible role in monitoring and early-warning systems. BVR correlated to arrhythmia vulnerability suggesting utility in risk stratification post-AMI.

Shear wave elastography (SWE) has been proposed as a novel noninvasive method for the assessment of myocardial stiffness, a relevant determinant of diastolic function. It is based on tracking the propagation of shear waves, induced, for instance, by mitral valve closure (MVC), in the myocardium. The speed of propagation is directly related to myocardial stiffness, which is defined by the local slope of the nonlinear stress-strain relation. Therefore, the operating myocardial stiffness can be altered by both changes in loading and myocardial mechanical properties.This study sought to evaluate the capability of SWE to quantify myocardial stiffness changes in vivo by varying loading and myocardial tissue properties and to compare SWE against pressure-volume loop analysis, a gold standard reference method.In 15 pigs, conventional and high-frame rate echocardiographic data sets were acquired simultaneously with pressure-volume loop data after acutely changing preload and afterload and after inducting an ischemia/reperfusion (I/R) injury.Shear wave speed after MVC significantly increased by augmenting preload and afterload (3.2 ± 0.8 m/s vs 4.6 ± 1.2 m/s and 4.6 ± 1.0 m/s, respectively; P = 0.001). Preload reduction had no significant effect on shear wave speed compared to baseline (P = 0.118). I/R injury resulted in significantly higher shear wave speed after MVC (6.1 ± 1.2 m/s; P 0.001). Shear wave speed after MVC had a strong correlation with the chamber stiffness constant β (r = 0.63; P 0.001) and operating chamber stiffness dP/dV before induction of an I/R injury (r = 0.78; P 0.001) and after (r = 0.83; P 0.001).Shear wave speed after MVC was influenced by both acute changes in loading and myocardial mechanical properties, reflecting changes in operating myocardial stiffness, and was strongly related to chamber stiffness, invasively derived by pressure-volume loop analysis. SWE provides a novel noninvasive method for the assessment of left ventricular myocardial properties.

Ischemic heart disease is the most common cause of lethal ventricular arrhythmias and sudden cardiac death (SCD). In patients who are at high risk after myocardial infarction, implantable cardioverter defibrillators are the most effective treatment to reduce incidence of SCD and ablation therapy can be effective for ventricular arrhythmias with identifiable culprit lesions. Yet, these approaches are not always successful and come with a considerable cost, while pharmacological management is often poor and ineffective, and occasionally proarrhythmic. Advances in mechanistic insights of arrhythmias and technological innovation have led to improved interventional approaches that are being evaluated clinically, yet pharmacological advancement has remained behind. We review the mechanistic basis for current management and provide a perspective for gaining new insights that centre on the complex tissue architecture of the arrhythmogenic infarct and border zone with surviving cardiac myocytes as the source of triggers and central players in re-entry circuits. Identification of the arrhythmia critical sites and characterisation of the molecular signature unique to these sites can open avenues for targeted therapy and reduce off-target effects that have hampered systemic pharmacotherapy. Such advances are in line with precision medicine and a patient-tailored therapy. ispartof: CELLS vol:10 issue:10 ispartof: location:Switzerland status: published

Background Myocardial infarction (MI) results in a regional scar, with a border zone (BZ) of surviving myocytes interspersed with fibrosis providing an anatomical substrate for re-entry. Heterogeneous repolarization within the BZ may add a functional component aggravating re-entrant arrhythmias. Purpose We studied BZ heterogeneity and developed novel methodology for high resolution mapping of local in vivo activation-repolarization intervals (ARI) within the BZ and for studying the relation to cellular action potential (AP) profiles of cells isolated from the BZ. Methods Anterior-septal myocardial infarction was induced in 5 domestic pigs by 120-minute occlusion of the left anterior descending artery followed by reperfusion (18.9±4.7% of the left ventricle). After 1-month, electro-anatomical mapping was performed. Contact mapping was used to define the BZ (bipolar voltage 0.5–1.5mV). A non-contact recording of a 64-electrode array was translated to 2048 non-contact electrograms distributed over the LV. The non-contact electrograms were processed to determine the ARIs using a custom-made algorithm, validated against monophasic action potential recordings. After 2–4 days recovery, single cardiomyocytes were enzymatically isolated from the anterior-septal BZs and remote regions. Cardiomyocytes were field stimulated at 1Hz at 37°C and cellular AP duration (APD) was optically recorded (fluorescent voltage-sensitive dye Di-8-Annepps). Results In vivo, regional ARIs tended to be longer in the BZs than remote. ARI heterogeneity, quantified as the standard deviation of ARIs in a neighborhood of 1cm radius, was increased in the BZ (anterior BZ: 3.4±1.0 ms, P=0.052, septal BZ: 3.6±1.7 ms, P=0.027 vs remote: 2.0±0.5 ms). Cellular APD was measured in large population samples (>100 cells per region in each pig) and was longer in BZ myocytes compared to the remote region. Cellular APD heterogeneity, measured as the standard deviation within cell population samples pooled by region per animal, was increased in the BZ (anterior BZ: 105.9±17.0 ms, P=0.0010; septal BZ: 98.1±20.8 ms, P=0.0127 vs remote: 73.9±8.6 ms). Cell APD correlated to in vivo ARI (R2=0.34, P=0.021) and cellular heterogeneity correlated strongly with in vivo heterogeneity (R2=0.67, P=0.002). Conclusion In the BZ of MI, in vivo regional heterogeneity adds a functional substrate for re-entry that may result from heterogeneous cellular remodeling and increased cell-cell APD variability. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): KU Leuven BOF-C1 “Blood pressure induced premature ventricular beats as triggers for ventricular arrhythmia in ischemic cardiomyopathy”

BACKGROUND: Sympathetic activation in ischemic heart disease can cause lethal arrhythmias. These often are preceded by premature ventricular complexes (PVCs), which at the cellular level could result from delayed afterdepolarizations. OBJECTIVE: The purpose of this study was to identify and map vulnerable areas for arrhythmia initiation after myocardial infarction (MI) and to explore the link between PVCs and cellular events. METHODS: Anterior-septal wall MI was induced by 120 minutes of coronary occlusion followed by reperfusion (27 MI and 16 sham pigs). After 4 weeks, EnSite™ electroanatomic mapping combined with imaging was performed to precisely locate PVC sites of origin and subsequently record monophasic action potentials. Cardiomyocytes were isolated from different regions to study regional cellular remodeling. Isoproterenol was used as a surrogate for adrenergic stimulation both in vivo and in cardiomyocytes. RESULTS: PVCs originated from the MI border zone (BZ) and occurred at discrete areas with clusters of PVCs within the BZ. At these sites, frequent delayed afterdepolarizations and occasional associated spontaneous action potentials translating to a PVC were present. Cardiomyocytes isolated from the MI BZ exhibited more spontaneous action potentials than cardiomyocytes from remote regions. Sensitivity to adrenergic stimulation was increased in MI, in vivo and in cardiomyocytes. In awake, freely moving MI animals, frequent PVCs, ventricular arrhythmia, and sudden cardiac death occurred spontaneously at moderately elevated heart rates. CONCLUSION: Post-MI, arrhythmias initiate from discrete vulnerable areas within the BZ, where delayed afterdepolarizations, related to increased adrenergic response of BZ cardiomyocytes, can generate PVCs. ispartof: HEART RHYTHM vol:18 issue:11 pages:1976-1987 ispartof: location:United States status: published

Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): BV is supported by a research grant of the Frans Van de Werf Fund for Clinical Cardiovascular Research. Introduction COVID-19 can be related with a poor clinical outcome. ECG abnormalities in COVID-19 have been widely described, but literature on the predictive value of a 12-lead ECG at hospital admission and normalization of these abnormalities after infection is limited. Purpose To describe the predictive value of ECG abnormalities on admission and after recovery of COVID-19. Methods After informed consent patients older than 18 years admitted with COVID-19 between March and July 2020 were included in a prospective registry. Diagnosis was confirmed by PCR-assay or based on suggestive clinical and radiological presentation. Demographic and clinical data were collected by review of the electronic medical record. All ECGs from admission until last follow-up were assessed lead by kead for repolarization abnormalities. The index ECG was defined as first ECG available after admission, a post-COVID ECG was obtained after hospital discharge in the absence of acute pathology. Minor abnormalities included iso-electric T-waves and ST-depression ≤2 mm. Major abnormalities were ST-depression >2 mm, ST-elevation, biphasic T-waves and T-wave inversion. Myocardial regions were defined as anterior (V1-V4), lateral (I, aVL, V5, V6) and inferior (II, III, aVF). Patients with a ventricular pacemaker were excluded. Results A total of 283 patients were included, median age 65 years and 64.7% were male. The 30-day mortality rate was 20.5%. In 96.8% of patients an ECG was available within 48 hours after admission. Repolarization abnormalities were observed in 48.8% of patients. In 27.2% this was limited to minor abnormalities. Abnormal repolarization was related to age, cardiovascular medical history, renal function, high-sensitive troponin-T and NT-proBNP levels. There were no significant differences in clinical presentation, ICU admission, need for ventilation or ECMO. On Kaplan-Meier analysis (figure) the presence (p A post-COVID ECG was available in 172 patients (60.8%), the median time between index and post-COVID ECG was 63.3 days. There was 1 new first-degree AV-block and 1 new RBBB. Repolarization abnormalities were present in 32 patients (11.3%); however, only 3 patients (1.7%) had new abnormalities, 2 of whom died during further follow-up. Conclusions The extent of repolarization abnormalities on an ECG at admission for COVID-19 is an independent predictor of 30-day mortality. New ECG abnormalities after COVID-19 infection are uncommon but may be associated with adverse outcome. Abstract Figure.

Objective: We wanted to develop a new method for processing dense spatially sampled unipolar electrograms, that yields physiological spatial distributions in activation-repolarization intervals.Background: Spatial heterogeneity in repolarization plays an important role in genesis and sustainment of cardiac arrhythmias. Reliable determination of repolarization times at high resolution on electrograms remains a difficult task. Methods: The new method describes the electrical activity on the heart's surface in terms of a physical electric field (E-field). Activation and repolarization times are calculated using an amplitude weighted average on QRS and T-waves. Activation-recovery intervals (ARI) obtained with this E-field method were validated against action potential durations (APD90) from monophasic action potential measurements. Relevance of the method was shown by calculating dense spatial distributions of beat-to-beat variability of repolarization (BVR) in myocardial infarction (MI).Results: E-field waveforms were more spatially homogeneous than the unipolar electrograms. The ARI strongly correlated with the APD90 (r2=0.94; p

Introduction: The impact of gender on ICD implantation practice and survival remain a topic of controversy. We analysed differences between men and women in patients implanted with an ICD in Belgium. Methods: The Belgian governmental health care institution (RIZIV/INAMI) keeps track of every ICD implantation by a digital registry. Participation is mandatory for reimbursement. From this registry, we analysed all new ICD implantations between 01/02/2010 and 31/01/2019 in Belgian patients. We compared men with women for baseline patient characteristics. We used a Chi 2 test for categorical variables (NYHA class, primary vs secondary prevention, underlying heart disease, type of device, QRS duration, presence of atrial fibrillation, diabetes and other comorbidity, center volume, population density and average income of the area of residency) and a Mann-Whitney U test for continuous variables [age and ejection fraction(EF)]. We used the Bonferroni method to correct for multiple testing. Secondly, we performed a Kaplan-Meier analysis. At last, we performed a multivariate logistic regression for 3-year and total mortality. Results: Only 3146 (20.8%) on 14747 implantations were in women. Women were significantly younger and had a better EF compared to men. Except for oncological history, women had less comorbidities (table 1). More women functioned in NYHA class > II and had a QRS > 150ms, which was consistent with a higher CRT-D vs VVI/DDD ratio. Kaplan-Meier showed a survival benefit in women (log-rank, p= Conclusions: Only a minority of patients implanted with a new ICD in Belgium are women. Their clinical profile differs from men. Their long-term survival is better, which can in part be explained by differences in indications and comorbidities.

Introduction: According to guidelines ICD implantation should not be performed in patients with an expected survival less than 1 year. We investigated how useful validated risk scores are to predict 1-y mortality after ICD implantation in patients with ischemic heart disease (IHD). Methods: The QERMID-ICD registry, managed by the Belgian health authorities, contains data of all patients implanted with an ICD. Participation is mandatory for reimbursement. We analyzed all new implantations between 01/02/2010 and 31/01/2018 in Belgian IHD patients. Data is available about age, gender, ejection fraction (EF), NYHA class, type of prevention, type of device, QRS duration, center volume, comorbidities and socio-economic status based on the area of residency. We performed a Cox proportional hazard regression and applied a modified version of the MADIT- (Goldenberg et al., JACC 2008) risk score (reported renal failure instead of BUN > 26mg%) and AAACC (Nevzorov et al., JCE 2018) risk score (no data on anemia, so AACC score) to predict 1-y mortality. Results: On a total of 6320 IHD patients, the 1-y mortality was 5.7%. Patients who died within 1 year were significantly older (70.9 vs 65.9 years), had a worse EF (28.7 vs 31.5%) and differed in most comorbidities. In the Cox model age, worse EF, secondary prevention, VVI/DDD devices, atrial fibrillation, COPD, neurological antecedents and renal failure were independent predictors of 1-y mortality (table 1). Area under ROC was comparable for the modified Goldenberg and AACC score (0.647 vs 0.652). With a cut-off of 5 on the modified Goldenberg and 7 on the AACC-score a positive predictive value (PPV) of respectively 15.5% an 17.4% and negative predictive value of 94.2% and 94.7% were obtained. Conclusion: Despite significant differences in baseline characteristics, selection of patients not suitable for ICD implantation (because of high 1-y mortality risk) can only be slightly improved by using simple risk scores due to their low PPV.

Introduction In Belgium ICD implantation is restricted to 23 centers. A previous analysis of our group based on aggregated results per center showed that 3y mortality varied significantly between centers ranging from 7.5 to 23.4%. Multivariate analysis demonstrated that volume, infection rate and a higher proportion of implantations in primary prevention were predictors of 3y-mortality. These findings needed to be confirmed on a patient level since they could be caused by inter-patient rather than inter-hospital differences. Methods The QERMID-ICD database is a retrospective database of all patients implanted with an ICD in Belgium managed by the governmental health care institution (RIZIV/INAMI). Participation is mandatory for reimbursement. We analyzed data of 9896 new implantations performed between 2010 and 2016. Following patient characteristics were available: demographics (gender, NYHA class, primary vs secondary prevention, underlying heart disease, type of device, QRS duration, age and ejection fraction (EF)), comorbidities (atrial fibrillation, diabetes, COPD, neurological disease, oncological disease and renal failure), volume of center (low < median of 65 primo-implantations/year vs high >65 implantations/year) and the average income of the arrondissement in which the patient lived (low income < p25, median p25-p75, high > p75). The primary endpoint was 3y-mortality. Chi-squared test and Mann-Whitney U test with correction for multiple testing were used and multivariate logistic regression was performed to determine the corrected odds ratio for 3-year mortality. Finally, Kaplan-Meier survival analysis was performed. Results Low volume centers treated different patients than high volume centers. They implant more primary prevention (66.5 vs. 61.6%), more often patients with ischemic cardiomyopathy (49.8 vs 47.9%), less often arrhythmogenic heart disease (13.2 vs 16.6%) and patients with more co-morbidities and from communities with lower average income. High volume centers used more cardiac resynchronization therapy (26.8 vs 22.5%) despite no difference in QRS width. 1 and 3-y mortality were significantly higher in the low volume centers, respectively 5.6 vs. 4.4% and 16 vs. 11.1%. This was also confirmed in Kaplan Meier survival analysis. In multivariate logistic regression underlying heart disease, income, age, EF, NYHA class, CRT, indication and most comorbidities were significantly associated with mortality, but center volume remained an independent risk factor for 3-y mortality (OR = 0.749 (0.702–0.937), p Conclusion Patients treated in low and high-volume centers in Belgium are different. However, there remained an association between volume and mortality of centers when controlling for these differences. Further research to elucidate if this association is due to statistical limitations of our analysis, referral bias or differences in quality of care is necessary. Funding Acknowledgement Type of funding source: None