ICD Implantation Research Articles

Abstract 4136643: Automated cardiac arrest detection using a photoplethysmography wristband: Evaluation of the time to detection of the circulatory arrest event

Introduction: Out-of-hospital cardiac arrest survival depends on immediate recognition and early cardiopulmonary resuscitation. For victims of unwitnessed cardiac arrest, accounting for 30-50% of cases worldwide, survival chances are dismal as help often comes too late. Automated cardiac arrest detection and alarming would offer a solution to shorten treatment delays. Within the DETECT project, a wristband with the functionality of automated cardiac arrest detection is developed. During the DETECT-1 study, we developed a photoplethysmography (PPG) algorithm to detect circulatory arrest in patients with induced circulatory arrest. Research question: In this sub analysis of the DETECT-1 study, we aim to study the delay between the actual circulatory arrest and the algorithms’ cardiac arrest alarm. Methods: Patients undergoing circulatory arrest induction during transcatheter aortic valve implantation (TAVI), subcutaneous ICD (S-ICD) implantation or ventricular tachycardia (VT) ablation wore a PPG wristband. Continuous ECG and arterial blood pressure data were collected as reference standard. PPG data were used to develop a circulatory arrest detection algorithm in three training iterations and one validation. Time to detection was defined as the difference between the algorithm’s cardiac arrest alarm and the circulatory arrest annotated based on the arterial blood pressure data. Results: The validation set consisted of 86 patients (77 TAVI, 3 S-ICD, 6 VT ablation) with 97 induced circulatory arrest events of which 95 were correctly identified by the algorithm (sensitivity 97% [95% CI 90-100%]). The median time to circulatory arrest detection was -1 second (IQR -2 – 0). In total, 50 (53%) events were detected before the annotated time (median; -1 sec), 33 (35%) events were detected at t=0, and 12 (13%) events were detected after the annotation (median; +2 sec). A total of 65 (68%) induced circulatory arrest events were detected within one second before and after the annotated start time of the circulatory arrest. Return of PPG pulsations were detected in all patients, with a median of 4 seconds (IQR 3 – 7) after pulsations returned (Figure 1 and 2). There were no differences in detection time between the three subgroups. Conclusion: The PPG algorithm detects the induced circulatory arrest events directly when blood pressure lowers. Further research is needed to validate the circulatory arrest detection algorithm and detection interval in spontaneous cardiac arrest.

Abstract 4122035: The Distinct Natural History, Phenotype Spectrum, Familial Penetrance and Clinical Outcomes in Desmin ( DES )-Associated Cardiomyopathy

Background: Pathogenic/likely pathogenic variants (P/LP) in the desmin ( DES ) gene cause heterogeneous cardiomyopathy and skeletal myopathy phenotypes. Research Questions: Limited data suggest that patients with P/LP DES variants have a high incidence of major adverse cardiac events (MACEs), including cardiac conduction disease requiring pacemaker implantation (CCD-PM), sustained ventricular arrhythmias (VA), and heart failure (HF) events (HF hospitalization, heart transplant, HF-related death). However, small cohort sizes have limited full clinical characterization. Aims: We aimed to describe the natural history, phenotype spectrum, familial penetrance and MACE in patients with P/LP DES variants identified via clinical genetic testing. Methods: We conducted a systematic review and individual patient data meta-analysis of cardiac and skeletal myopathy phenotypes and MACE (CCD-PM, VA and HF events) in patients with P/LP DES variants by retrieving publications from Medline (PubMed) and Embase. Diagnosis of cardiomyopathy or MACE were both considered evidence of cardiac involvement. Results: Out of 4,212 screened records, 72 met inclusion criteria. In total, 230 patients were included (52.6% male, 52.2% probands, median age: 31 years at first evaluation [22.0; 42.8]). Eighty-five (37.0%) patients showed isolated cardiac involvement, 89 (38.7%) cardiac and skeletal muscle involvement, 39 (17.0%) only skeletal muscle involvement, and 17 (7.4%) had neither phenotype. Overall, 130 (56.5%) patients were diagnosed with a cardiomyopathy and 134 (57.4%) patients developed MACE (96 [41.7%] had CCD-PM, 36 [15.7%] sustained VA, and 43 [18.7%] HF events). Familial cardiac disease penetrance was 69.1% (76/110) in relatives with P/LP DES variants. Out of 40 patients who presented with isolated CCD-PM phenotype, 18 (45.0%) were diagnosed with a cardiomyopathy after 6 [2.0; 16.0] years of follow-up. In multivariable analysis, male sex and non-missense variants were associated with higher risk of sustained VA (HR 2.71, p=0.008, and HR 4.62, p<0.001, respectively) and HF events (HR 2.63, p=0.005, and HR 2.79, p=0.015). Conclusions: DES cardiomyopathy demonstrates a distinct natural history, characterized by high familial penetrance and a high MACE burden. Male patients and those carrying non-missense variants are at higher risk for sustained VA events and may benefit from primary preventive ICD implantation even in the absence of severe LV systolic dysfunction.

Rates of and Indications for Subcutaneous ICD Extraction: A Multihospital Healthcare System Analysis.

The subcutaneous implantable cardioverter defibrillator (S-ICD) is an alternative to a transvenous ICD in patients who meet the criteria for ICD implantation without concurrent need for cardiac pacing. The objective of this study is to examine the rates of and indications for S-ICD removal and extraction. A retrospective analysis of all patients who underwent S-ICD implantation between 2010 and 2022 at a single multihospital healthcare system was performed. The primary endpoint was S-ICD removal or extraction. Patient and device characteristics were abstracted from the electronic medical record. Univariate and multivariate analyses were completed to determine factors associated with S-ICD extraction. A total of 372 patients (69.5% male; 48.6 ± 14.4 years old) underwent S-ICD implantation during the study period. There were 22 (5.9%) patients (81.8% male; 52.1 ± 13.2 years old) who underwent S-ICD extraction over a median follow-up period of 4.4 [2.0-6.5] years. The median length of time between implantation and extraction was 39.6 [8.3-64.6] months. The most common indications for S-ICD extraction were the need for bradycardia pacing (frequency among extractions, 18.2%), infection (22.7%), and inappropriate shocks due to oversensing (22.7%). A smoking history and higher body mass index were independently associated with S-ICD extraction. The overall rate of S-ICD extraction over 4.4 [2.0-6.5] years was 5.9%, with the most common indications for extraction being the need for bradycardia pacing, infection, and inappropriate shocks due to oversensing. A smoking history and high body mass index are associated with increased rates of S-ICD extraction. With appropriate patient selection for the S-ICD, the need to remove the device after implantation is low.

Late gadolinium enhancement on cardiac MRI: A systematic review and meta-analysis of prognosis across cardiomyopathies

BackgroundLate gadolinium enhancement (LGE) on cardiac MRI has been shown to predict adverse outcomes in a range of cardiac diseases. However, no study has systematically reviewed and analyzed the literature across all cardiac pathologies including rare diseases. MethodsPubMed, EMBASE and Web of Science were searched for studies evaluating the relationship between LGE burden and cardiovascular outcomes. Outcomes included all-cause mortality, MACE, sudden cardiac death, sustained VT or VF, appropriate ICD shock, heart transplant, and heart failure hospitalization. Only studies reporting hazards ratios with LGE as a continuous variable were included. ResultsOf the initial 8928 studies, 95 studies (23,313 patients) were included across 19 clinical entities. The studies included ischemic cardiomyopathy (7182 patients, 33 studies), hypertrophic cardiomyopathy (5080 patients, 17 studies), non-ischemic cardiomyopathy not otherwise specified (2627 patients, 11 studies), and dilated cardiomyopathy (2345 patients, 14 studies). Among 42 studies that quantified LGE by percent myocardium, a 1 % increase in LGE burden was associated with life-threatening ventricular arrhythmias (LTVA) with a pooled hazard ratio of 1.04 (CI 1.02–1.05), and MACE with a pooled hazard ratio of 1.06 (CI 1.04–1.07). The risk of these events was similar across disease types, with minimal heterogeneity. ConclusionsDespite mechanistic differences myocardial injury, LGE appears to have a fairly consistent, dose-dependent effect on risk of LTVA, MACE, and mortality. This data can be applied to derive a patient's absolute risk of LTVA, and therefore can be clinically useful in informing decisions on primary prevention ICD implantation irrespective of the disease etiology.

Prolonged ventricular activation time as a novel biomarker identifying burn-out phase of hypertrophic cardiomyopathy

Abstract Background Patients with hypertrophic cardiomyopathy (HCM) classically have preserved systolic function and decreased left ventricular end-diastolic volume. However, in a small sub-population, patients paradoxically develop systolic dysfunction, left ventricular dilatation, and ventricular wall thinning, which is known as end-stage hypertrophic cardiomyopathy or "burned-out cardiomyopathy’. Although an electrocardiogram (ECG) is a pivotal tool in HCM, its role in the detection of burned-out HCM has not been investigated. Purpose We assessed the ventricular activation time (VAT), an ECG marker of the duration of ventricular depolarization, as a predictive tool in the detection of the HCM burn-out phase. Methods We prospectively studied consecutive patients diagnosed with HCM via echocardiography at our medical center between 2017 and 2022. The ECG, along with echocardiography, was performed on the same day as the diagnosis. VAT was measured in milliseconds between the onset of the QRS complex to the peak or R wave on the V5 and V6 precordial ECG lead. HCM burn-out phase was supported when the left ventricular ejection fraction (LVEF) was below 50%, measured with echocardiography. Statistical analysis was performed using the SPSS software. Results Forty-five patients with HCM were studied, and their mean age was 51, while 78% (35/45) were male. Echocardiography data upon diagnosis revealed a mean maximum wall thickness of 19 (±3mm) and a mean left ventricular ejection fraction of 65% (±5%). Left ventricular outflow obstruction was present in 31% (14/45). During the study, 24% (11/45) presented atrial fibrillation, 44% (20/45) had an ICD implantation, and 22% (10/45) progressed to the burn-out phase of HCM. HCM patients who presented atrial fibrillation (63±31 vs. 46±14msec, p=0.018) or burn-out phase (65±32 vs. 46±13msec, p=0,009) had a significantly higher VAT than those subsets without. Notably, there was a significant positive relationship between VAT a burn-out phenotype (r=0,385, p=0.009). HCM patients with greater VAT also had a significantly higher risk of presenting a larger left atrial diameter (r=0,295, p=0.048), an increased left ventricular end-diastolic diameter (r=0.306, p=0.041), and a trend of presenting a lower LVEF (r=-0,262, p=0.082). Finally, we revealed a positive relationship between VAT and atrial fibrillation incidence (r=0,352, p=0.018). Conclusion Prolongation of VAT predicts the incidence of burn-out stage in patients with HCM and atrial fibrillation. Therefore, it seems to be a promising, inexpensive ECG marker for HCM progression and severity. Our findings emphasize the pivotal role of the ECG as a useful and inexpensive tool in the diagnostic follow-up of HCM.

Complications after cardiac implantable electronic devices in patients with severe mental illness: a Danish nationwide study

Abstract Background Patients with mental illness experience higher rates of postoperative complications and mortality across several types of surgery, but knowledge is lacking in relation to cardiac implantable electronic device (CIED) implantations. Purpose Our study aimed to investigate the 7-day, 30-day, and 90-day postoperative complication rate and mortality in patients with severe mental illness compared to the general population. Methods All adult patients in Denmark with a first-time pacemaker or ICD implantation during the study period from July 1995 to December 2022 were identified using the Danish nationwide registers. Severe mental illness was defined as having a preexisting diagnosis of schizophrenia and other non-affective psychotic disorders, bipolar affective disorders or major depressive disorder. Postoperative complications were obtained as diagnosis codes possibly relating to device implantation and categorized into seven types of complications: arterial thrombosis, venous thrombosis, pneumothorax, bleeding, infection, device function problem, and death. Stratified logistic regression analyses adjusted for sex and age were used to calculate the odds of postoperative complications within 7, 30, and 90 days of device implantation. Results Among 108,790 patients who had a de novo pacemaker or ICD implantation the mean age was 73.5 (± 12.8), 37.5% were women and 3,393 (3.1%) of the patients had preexisting severe mental illness. In total, 10,690 (9.8%) patients had one or more complications within 90 days. The number of patients with severe mental illness who experienced a complication were 407 (12.0%) while it was 10,283 (9.8%) of those without severe mental illness. Odds of death (OR 1.57, 95% CI: 1.03-2.29) were higher in patients with severe mental illness 7 days postoperatively, and 30 days postoperatively odds of venous thromboembolism (OR: 1.69, 95% CI: 1.05-2.56) and death (OR: 1.62, 95% CI: 1.29-2.01) were higher in patients with severe mental illness. 90 days postoperatively odds of venous thrombosis (OR: 1.95, 95% CI: 1.37-2.70), infection (OR: 1.45, 95% CI: 1.16-1.79), and death (OR: 1.40, 95% CI: 1.19-1.65) were higher in patients with severe mental illness compared to patients without severe mental illness, while the odds of pneumothorax were lower at all three time points for patients with severe mental illness (OR 7-days: 0.49, 95% CI: 0.21-0.95). The odds of arterial thrombosis, bleeding and device function problems were similar between the two groups at all three time points. Conclusion Severe mental illness was associated with increased risk of several types of complications and death following CIED implantation. This indicates that further care and attention is needed to ensure adequate treatment of patients with severe mental illness suffering from cardiac arrhythmias.Forest plot, SMI: severe mental illness

Myocarditis prognostic score: a new risk assessment tool in patients with myocarditis

Abstract Background Myocarditis is an inflammatory disease of the myocardium with multiple causes and evolutions. The aim of our study was to design a prognostic multiparametric score in patients with myocarditis, to identify those at higher risk of adverse cardiovascular events (AE). Methods A prospective study was performed enrolling 98 patients with myocarditis: 72 M, 26 F; median age 27 [IQR 20–40]. Patients were divided into 2 groups: complicated (CM) and uncomplicated myocarditis (UM). Six months after hospital admission, cardiac magnetic resonance (CMR) and cardiological consultation were repeated. AE (death, hospitalization for heart failure, heart transplant, ICD implantation, heart failure development) were evaluated at 6 months and after 3 years. Results We found 67 UM and 31 CM. AE were significantly higher in patients with complicated myocarditis. We found a significant correlation between AE and reduced left ventricular ejection fraction (LVEF) at hospital admission, increased GLS, septal LGE at CMR, longer persistence time of increased troponin, LGE extension progression or persistence 6-month CMR. A myocarditis prognostic score was developed on the basis of these parameters. A score ≥ 5 showed higher sensitivity (100%) and specificity (87%) - AUC 1, to identify AE in patients with myocarditis. A score between 3 and 4 showed high sensitivity but low specificity. A score ≤ 2 was associated with low probability of events. Conclusion Our study confirms the high probability of AE in patients with CM and it suggests a myocarditis prognostic score to identify patients at higher risk of AE.

Can variants of genes associated with familial heart block predict conduction disease in the general population? A UK Biobank study.

Abstract Background Progressive familial heart block is a genetic disease that can present with worsening cardiac conduction disease (CCD) and risk of life-threatening bradycardia. The prevalence, penetrance, and expressivity of known rare pathogenic/likely pathogenic variants (P/LP) in the general population is unclear. In addition, the role of common genetic variation in this phenotypic expression is unknown. Understanding this is essential for patient management in clinic. Purpose 1). To investigate the prevalence of variants linked with early-onset CCD and phenotypic expression in a large biobank. 2). To investigate whether a PR interval polygenic risk score (PRS) improves risk prediction. Methods Early-onset conduction disease P/LP or variants of uncertain significance (VUS) were identified from ClinVar, genetic testing reports at a teaching hospital (6 variants), and the literature, mapping to 22 genes. From the full UK Biobank prospective cohort, 469,511 participants passed genetic quality control and were assigned to P/LP, VUS, or genotype negative (G-) groups, using whole exome sequencing analysed with bcftools. A PR-PRS was constructed using weights from a published meta-analysis excluding UKB data. The primary outcome was CCD (atrioventricular (AV) block, bundle branch block, pacemaker or ICD implantation) and secondary outcomes were high-grade AV block or pacemaker insertion, compared with lifetime risk Cox proportional hazards controlled for sex and age as a timescale. Results 55% of participants were female, 95% had European ancestry, and average age at censor was 71 years. There were 25 P/LP carriers, and 8,862 with a VUS, in 6 genes (MYH7, SCN5A, TNNI3K, TRPM4, TTN, and LMNA). Major demographic factors were the same between groups. CCD was significantly more prevalent in P/LP individuals (28% vs 5.8% in VUS vs 5.5% in G-; p<0.001) with a hazard ratio of HR 6.47 [95% CI=3.09-13.6] vs G-. This was driven by AV block and pacemaker implantation (HR 23.2 [95% CI=8.69-61.8] and 13.4 [95% CI=6.01-29.8], respectively). Results were similar in an unrelated subset and controlling for ischaemic heart disease and heart failure. The 7 P/LP individuals with conduction disease were mostly linked to a single LMNA variant (4 out of 6 carriers with penetrant disease). In the full cohort, the PR-PRS was predictive of CCD (HR=1.07 [95% CI=1.06-1.08]), AV block (HR=1.09 [95% CI=1.06-1.13]), and pacemaker implantation (HR=1.04 [95% CI=1.02-1.06]). When combined with P/LP status, both PR-PRS (HR=1.07 [95% CI=1.06-1.08]) and P/LP (HR=6.42 [95% CI=3.06-13.5]) were independent predictors of CCD. Conclusion(s) Rare variant carrier status predicts a 6.5-fold increased lifetime risk of CCD, a 23-fold increased risk of AV block and 13-fold risk for pacemaker requirement. However, phenotypic expression for some variants is highly variable. A PR-PRS captures risk independent of P/LP variants and warrants further investigation with updated PRS construction methods.

Revisiting risk stratification in hypertrophic cardiomyopathy after the recent guidelines - LGE remains tough to beat

Abstract Background and Objectives Over the last decades, the recommendation for ICD implantation for the primary prevention of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) has been evolving. Late gadolinium enhancement (LGE) has been incorporated in the guidelines as a risk factor to be considered for ICD implantation. The aims of this study were: 1) assess the evolution of accuracy and discriminative ability of the different guidelines (ESC 2014, ESC 2022, ESC 2023, ACC 2011 and ACC 2020) in predicting SCD; and 2) to understand whether LGE can further help in the risk stratification of SCD. Methods We conducted an international multicentric retrospective analysis of HCM patients undergoing cardiac magnetic resonance (CMR) for diagnostic confirmation and/or risk stratification. Eligibility criteria for ICD according to the ESC 2014 (HCM), ESC 2022 (Ventricular arrhythmias VAs), ESC 2023 (Cardiomyopathies), ACC 2011 and ACC 2020 (both HCM guidelines) was determined for each patient. Our primary endpoint was a composite of SCD, appropriate ICD discharge and sustained VT. Results We included a total of 530 patients (median age was 49 (IQR 35-61), 57% male). Over a median follow-up of 3.8 (IQR 1.6 – 7.0) years, 27 events occurred (13 SCDs, 8 appropriate ICD discharges and 6 sustained VAs). The diagnostic accuracy statistics of the European and the American societies guidelines have evolved similarly over time: sensitivity and PPV increased, NPV remained high and discriminative ability also increased (see Figure). However, the concordance in risk assessment is only moderate between the ESC 2022 and ACC 2020 (κ = 0.60 (95%CI: 0.54–0.67); p < 0.001) or the ESC 2023 and ACC 2020 guidelines (κ = 0.56 (95%CI: 0.49–0.62); p < 0.001). LGE was present in 80% of patients. Median LGE% was 3.2% (IQR 0.5 – 8.4%) and remained an independent predictor of arrhythmic events after adjustment to known confounders (aHR of 1.09 per 1% increase in LGE% [95% CI 1.05 – 1.12; p < 0.001]). The Youden test showed a best cut-off for LGE burden of 7.1%. Further risk stratification could be reached by employing LGE% as an arbiter. Irrespectively of the guideline publisher, in patients with any recommendation for ICD (classes IIa and IIb), the absence of LGE identified patients with no arrhythmic events during follow-up (see Figure). Conclusions Current guidelines have shown increased sensitivity, PPV and discriminative power when compared with older counterparts. LGE burden remains an independent risk factor for arrhythmic events and although extensive LGE burden has been included in the risk stratification for ICD implantation, further stratification can be accomplished for ICD recommendation, since this seems to be a predictor stronger than clinical parameters.

Elevated cancer biomarkers in patients with severe heart failure could be a potential predictor of mortality during LVAD support

Abstract Introduction Owing to increasing numbers of heart failure patients a search for new biomarkers predicting prognosis is desirable. Background The purpose of this study was to analyze levels of cancer biomarkers in patients with severe heart failure before or after left ventricular assist device (LVAD) implantation and estimate its impact on survival during LVAD support. Methods We retrospectively analyzed data of all consecutive 168 LVAD recipients (92.8%- male, mean age 53.3 years ( median - 56.6, SD 12.0 ), median INTERMACS profile- 3.0, ischemic etiology of heart failure- 52.4%, 41.0% post CRT-D and 54.8% post ICD implantation, 36.9 post IABP, 5.4% post ECMO%, 11.9% post CABG and 8.9% post other cardiac surgery before LVAD implantation) implanted with continuous-flow LVAD (59.5%-HeartMate3, 35.1%- HeartWare, 5.4%-Heart Mate II) in our institution within years 2009-2023. Among comorbidities 63% of patients had atrial fibrillation or flutter, 41.6%- diabetes, 37.5%- arterial hypertension, 48.8%-renal failure, 7.1% pulmonary obstructive disease, 56.5% had pulmonary hypertension with mean pulmonary artery pressure above 25 mm Hg in right heart catheterization and 47% of patients had a history of cardiac arrest or sustained ventricular arrythmia before LVAD implantation. The overall mortality was 44.0 %. 31% patients were transplanted during LVAD support and in 4 patients (2.3%) LVAD was explanted or deactivated. Patient were followed to death, heart transplantation, LVAD explantation or the end of observation in our institution. Mean time of LVAD support was 885 days (1-2570). 23% of patients had right ventricular failure (RVF) early post LVAD implantation while 7.7% had late form of RVF. Results Serum concentrations of cancer biomarkers: carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, carbohydrate antigen(CA)-125 and alpha fetoprotein (AFP) taken before (56 patients -33.3%) or after (24 patients-14.3%) LVAD implantation were analyzed. Mean values, rate of abnormal results and correlation of abnormal results of CEA, CA19-9, CA-125, AFP with mortality during LVAD support were depicted in Table 1. No statistically significant correlations were found between levels of abovementioned cancer biomarkers and mortality though a trend towards increased mortality could be observed for abnormal results of CEA and Ca 19-9 taken before LVAD implantation. No malignant neoplasms were found in all analyzed patients except of one in whom a recurrence of lymphoma was found 2 months after LVAD implantation. Conclusions Patients with severe heart failure before and after LVAD implantation may present abnormal values of cancer biomarkers despite no found neoplasms. Our observation suggests that elevated cancer biomarker levels could predict mortality in heart failure patients after LVAD implantation. Further research is needed to confirm this thesis and investigate mechanisms of this phenomenon.

Unravelling cardiomyopathies: a comprehensive analysis of phenotypic diversity, endomyocardial biopsy patterns, and the impact of Gremlin-1 on clinical prognosis

Abstract Background Cardiomyopathies are the main cause of progressive heart failure (HF) and despite outstanding advances of diagnostics and therapies, mortality remains high.1,2 The current phenotype-based classification of non-ischemic cardiomyopathies (NICM) is based on a clinical workflow including endomyocardial biopsy (EMB).3-5 Inflammation and fibrosis are essentially involved in progression of HF and lead to development of adverse cardiovascular (CV) events.6,7 The diagnostic algorithm facilitates risk stratification of HF patients but nonetheless risk factors often remain inapparent prior to disease incidence. Objective In this study we investigate EMB patters in patients with NICM and elucidate alterations associated with phenotypic diversity and progression of HF. Methods We prospectively enrolled patients with HF due to NICM in a large-scale all-comers cohort (n=703). All patients underwent guideline-based phenotypic classification including EMB, and RNA data were acquired alongside histological analyses within the myocardium. We then performed a ten-year follow-up to screen for disease progression. Results A guideline-based classification of patients with NICM resulted in a phenotyping of aetiological risk groups (Figure 1A). We found that characteristic expression of fibroinflammatory mediators within the myocardium occurred in patients with symptomatic NICM (Figure 1B). We found that elevated expression of Gremlin-1 (Grem), a potent downstream profibrotic mediator of TGFß pathway, was associated with pro-fibrotic cardiac remodelling (Figure 1C). Further, Gremlin-1 was associated with a significant decrease of left ventricular functional capacity and inversely correlated with late gadolinium enhancement (LGE) (Figure 1D&E). Moreover, the expression of Gremlin-1 was enriched with pro-fibrotic and inflammatory RNA signalling pathways hinting at underlying pathophysiological cascades (Figure 2A&B). Most strikingly, the expression of Gremlin-1 was independently associated with an increased CV risk during the ten-year follow-up (Figure 2C). Thus, patients with Gremlin-1+ EMB were at elevated risk to suffer from all-cause mortality and number of patients eligible for ICD implantation was critically enhanced in patients with Gremlin-1+ EMB (Figure 2D-F). In addition, the estimation of an elevated CV risk by machine learning including Gremlin-1 improved the ten-year risk stratification among all patients with NICM (Figure 2G). Thus, Gremlin-1 was associated with cardiac remodelling and disease activity in HF patients (Figure 2H). Conclusion Our results unveiled that Gremlin-1 is associated with inflammation and cardiac remodelling in patients with symptomatic cardiomyopathy and patients with Gremlin-1+ EMB are at elevated risk to develop adverse CV events. Thus, the histological evaluation of Gremlin-1 may help to identify pathophysiological cascades and improve early risk discrimination and management of HF patients.Figure 1Figure 2

Automated cardiac arrest DETECTion incorporated into a wristband: validation of a photoplethysmography algorithm in patients with spontaneous and induced cardiac arrest

Abstract Background Although survival from out-of-hospital cardiac arrest (OHCA) has improved, this does not apply to unwitnessed cases, as the arrest is often recognized too late. Automated cardiac arrest detection and alarming using a wristband is a promising technology to facilitate early assistance after cardiac arrest in a home setting. In the DETECT-1 study, a photoplethysmography(PPG) algorithm for circulatory arrest detection has been developed in patients with induced circulatory arrest. Purpose To assess the performance of the developed PPG algorithm for circulatory arrest detection in: 1) patients with spontaneous cardiac arrest; 2) subjects with induced circulatory arrest using blood pressure cuff inflation. Methods We selected patients with episodes of spontaneous cardiac arrest who participated in the DETECT-1 study and patients/healthy subjects with short-lasting induced circulatory arrest using blood pressure cuff inflations from the DETECT-1 and DETECT-2 studies. The DETECT-1 study included patients who underwent transcatheter aortic valve implantation (TAVI), subcutaneous ICD implantation, or ventricular tachycardia ablation. Included patients wore the PPG-wristband during the procedure. Continuous ECG and invasive blood pressure data were collected as reference standard. The DETECT-2 study included healthy volunteers who wore the PPG-wristband during physical exercise. Sensitivity for spontaneous and induced circulatory arrest and false positive alarms were assessed using the previously developed algorithm for circulatory arrest detection. All episodes were analyzed as individual events. Results A total of 39 individuals were included; nine patients with spontaneous cardiac arrests during TAVI and 20 subjects with 116 induced circulatory arrests. Of the patients with spontaneous cardiac arrest, two had ventricular fibrillation, five had pulseless electrical activity (figure), and two had asystole. Eight out of nine cardiac arrest events were detected by the circulatory arrest detection algorithm (sensitivity 89% [95% CI 51-99%]). Of the subjects with induced circulatory arrests, the PPG algorithm detected 114 induced circulatory arrests, yielding a sensitivity of 98% (95% CI 93-100%). In the entire group, there were no false positive alarms during 60 recording hours. Conclusions Automated cardiac arrest detection using a PPG-wristband is feasible with excellent sensitivity for both spontaneous and induced circulatory arrest. False positive alarms were absent in this controlled setting. Further study is warranted to assess algorithm performance in a larger sample of spontaneous cardiac arrests, and false positive alarms during daily life use. If available, automated cardiac arrest detection and alarming has the potential to markedly increase survival from OHCA in a home setting.Episode of spontaneous cardiac arrest

Echocardiographic evaluation of cardiac remodelling in a cohort of patients with heart failure and reduced ejection fraction treated with dapagliflozin

Abstract Background Several mechanisms have been proposed to explain SGLT2 inhibitors’ (SGLT2i) beneficial effects in patients with heart failure (HF), but their exact mode of action in this setting is not fully understood. Pivotal randomised clinical trials regarding this class of drugs in HF setting have not reported echocardiographic data regarding potential cardiac positive remodelling. Objectives To assess the effects of dapagliflozin treatment initiation on cardiac remodelling in patients with HF and reduced ejection fraction (HFrEF), with a focus on left ventricular performance and atrial volumetry. Methods In this retrospective observational study, we analysed data from 94 patients with HFrEF in whom dapagliflozin had been prescribed as part of HF treatment optimization. Inclusion criteria were: age > 18 years; ongoing optimal medical therapy (OMT) for HF according to 2021 ESC HF guidelines (except for SGLT2i); transthoracic echocardiogram within 30 days of baseline assessment demonstrating a left ventricular (LV) ejection fraction (EF) <40%; comprehensive assessment at 6 months with clinical, laboratory and echocardiographic data. Results Patients (mean age 71.7 ± 9.8, 76% males, coronary artery disease as HFrEF main aetiology in 66%) showed significant cardiac remodelling after dapagliflozin initiation, specifically in terms of stroke volume index (SVi, +9.7 ml/m2, p<0.001), LVEF (+5.1%, p<0.001), LV end-diastolic volume (LV EDV) index (-8.4 ml/m2, p<0.001), left atrial (LA) volume index (-3.9 ml/m2, p=0.026), and LV mass index (LVMi, -12.9 gr/m2, p=0.004). BNP tended to significantly decrease (-168.6 ng/L, p=0.025). Percentage of patients with an indication for ICD implantation in primary prevention went from 36.2% to 8.5%, p<0.001. We did not observe significant differences in terms of mitral regurgitation (MR) grading at follow-up (in particular, the proportion of patients with severe MR remained approximately stable: 7% vs 4%, p=0.86). We did not observe any change in diastolic function measured by E/e’ ratio (mean difference -0.6; 95% CI -2.2 to 0.9, p=0.41). Conclusions Treatment with dapagliflozin resulted in positive remodelling in our cohort of patients with HFrEF in terms of chamber volumes, contractility parameters (and this was not explained by an improvement in MR severity) and LVMi. There was a significant decrease in natriuretic peptide as well as in the proportion of patients with primary prevention ICD indication. Our findings highlight the need of further data to fully elucidate the exact mechanism that leads to LA and LV positive remodelling with SGLT2i.Figure 1.Change in TTE Parameters

Automated cardiac arrest detection using a photoplethysmography wristband: algorithm performance in relation to sex, skin color type and arm hair density

Abstract Background While survival from witnessed out-of-hospital cardiac arrest (OHCA) has improved, this is not the case for unwitnessed cardiac arrest as the event goes unnoticed. Automated cardiac arrest detection and alerting through a wristband is considered a promising technique also facilitating early assistance for this large group. In the DETECT-1 study, a photoplethysmography(PPG) algorithm for circulatory arrest detection was developed in patients with induced circulatory arrest. However, patient characteristics, such as skin color and arm hair density, can influence the accuracy of the PPG signal. Thus, we performed further analyses to study the effect of patient characteristics on the algorithm’s performance. Purpose To assess the performance of the developed PPG algorithm for cardiac arrest detection in relation to sex, skin color type and arm hair density. Methods Patients who underwent short-lasting circulatory arrest induction during transcatheter aortic valve implantation, ventricular tachycardia ablation or subcutaneous ICD implantation wore a PPG wristband during the procedure. Continuous ECG and invasive blood pressure recordings served as reference standards. A PPG algorithm for circulatory arrest detection was developed. The algorithm’s performance was assessed in subgroups based on sex, skin color type (according to the Fitzpatrick scale), and arm hair density. The sensitivity for the detection of circulatory arrest and false positive alarms were compared between the different subgroups. Results In total, 151 patients were included in the current analysis. Analyzed data consisted of 159 hours of PPG data including 176 induced circulatory arrest events. The population consisted of 57 (38%) females and 94 (62%) males. The sensitivity for circulatory arrest detection was 100% in the female group vs. 98% in the male group (p=ns); false positive alarms occurred in 4 females and 9 males, resulting in a positive predictive value (PPV) of 94% and 92% (p=ns), respectively. Within the skin color subgroup analysis, 114 (75%) patients had skin color type I or II, and 37 (25%) patients had a skin color type III, IV, V or VI. There were no differences in sensitivity (p=ns) and PPV (p=ns) in the skin color subgroup (table 1). The population consisted of 106 (71%) patients with nil or sparse arm hair density, 43 (29%) patients with moderate or dense arm hair density, and 2 not reported. There were no differences in sensitivity (p=ns) and PPV (p=ns) within the arm hair density subgroup (table 1). Conclusions Automated cardiac arrest detection using a smartwatch is feasible and its accuracy is not affected by sex, skin color type or arm hair density in this study. Further study is needed to assess performance of the algorithm in a larger sample size and a more diverse study population. If proven to be effective, automated cardiac arrest detection has the potential to improve survival from OHCA.Sensitivity/PPV for arrest detection

Prospective assessment of risk factors for appropriate ICD intervention in patients with ischemic cardiomyopathy: results of PARCADIA trial

Abstract Background There is still a big unmet need for better risk stratification tools to identify patients at high risk for sudden cardiac death in the era of primary prevention ICD therapy. Scar burden on late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging may be a risk marker for the prediction of ventricular arrhythmia in post-myocardial infarction (MI) patients. Purpose The aim of the PARCADIA trial was to assess whether scar characteristics, determined via LGE-CMR, or other baseline risk markers are associated with appropriate ICD therapy. Methods In this prospective, multi-center, clinical trial, we enrolled post-MI patients with an indication for de novo primary prevention ICD. Main exclusion criteria were indication for cardiac resynchronization therapy and NYHA class IV. Prior to the ICD implantation, LGE-CMR was performed to analyze the amount of scar tissue (LGE core mass + grey zone mass) and LV function / volumes. A 24h Holter recording was performed to collect information on potential triggers like premature ventricular beats (PVB) and sympathetic-vagal balance based on heart rate variability (HRV). Follow-ups were performed in-office every 6 months, including remote monitoring. Appropriate ICD therapy was used as primary endpoint and adjudicated by a clinical event committee. Results 199 patients were enrolled at 5 investigational sites in Europe. Patients mean age was 64.3 years, with a mean LVEF of 27.7 %, timing from the index MI was 9.1 years, and 42.7% received a primary PCI on index MI. After a median follow-up duration of 47.7 months, 23.1% of patients received appropriate ICD therapy. In 135 patients (67.8%), quality of LGE-CMR was sufficient for detailed analysis. The mean LGE core mass (20.5 vs. 19,7 g) and grey zone mass (10.5 vs. 11.4 g) was not different in patients with or without appropriate ICD therapy, also not when corrected for LV mass. However, LVEF (28.5 vs. 32.9 %) was lower, while diastolic myocardial mass (141 vs. 125 g), and end-diastolic volume (265.0 vs. 226.7 ml) were significantly higher in patients with appropriate ICD therapy. On 24h Holter the mean PVB burden (3695 vs. 1643 beats), and non-sustained ventricular tachycardia (12 vs. 0.9), were higher in patients with appropriate ICD therapy, while the HRV (96.1 vs. 113.1 SDNN) was lower. In univariate analysis the variables LVEF, timing to index MI, primary PCI on index MI, PVB burden and HRV appeared to be predictors for appropriate ICD intervention, while in multivariate analysis LVEF and PVB burden remained predictive. Conclusion In post-MI patients with appropriate ICD therapy, scar burden was not different from patients without appropriate ICD therapy. Only LVEF and PVB burden were independent predictors of increased arrhythmogenicity. Improved CMR analysis on scar characteristics (conduction channels) to identify potential arrhythmogenic regions might be the topic for future research.

Hypertrophic Cardiomyopathy as a Form of Heart Failure with Preserved Ejection Fraction: Diagnosis, Drugs, and Procedures.

Hypertrophic cardiomyopathy (HCM) is a complex and heterogeneous cardiac disorder characterized by cardiac hypertrophy disproportionate to loading stimuli (e.g. hypertension or aortic stenosis). Diagnosing HCM requires a thorough examination of clinical symptoms, with echocardiography as the key initial imaging tool. Multimodality imaging further supports diagnosis, helps assess left ventricular outflow obstruction, and aids in risk stratification for sudden cardiac death. The cornerstone of HCM management remains pharmacological therapy with β-blockers and calcium channel blockers serving as first-line agents to alleviate symptoms and reduce left ventricular outflow tract obstruction. More recently, cardiac myosin inhibitors have revolutionized the treatment paradigm for obstructive HCM. Procedural interventions such as septal reduction therapy are reserved for refractory cases. Genetic testing and risk stratification for sudden cardiac death play a critical role in treatment decisions, guiding further testing in first-degree relatives and ICD implantation in high-risk individuals. Exercise recommendations have evolved based on recent data, challenging traditional restrictions and emphasizing individualized plans.

A manual synchronous low energy shock impedance as a predictor of successful defibrillation testing during subcutaneous ICD implantation.

Guidelines recommend defibrillation testing (DFT) during subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation. Implant position, patient characteristics and device factors, such as shock impedance, influence defibrillation success. To evaluate the shock impedance, a manual synchronous 10J shock (low energy synchronous shock [LESS]) can be delivered, without the need to induce ventricular fibrillation (VF). To compare LESS and DFT impedance values and to evaluate the diagnostic accuracy of LESS impedance for predicting a successful DFT during S-ICD implantation. Consecutive S-ICD implantations were included. Shock impedances were compared by paired t-tests. Univariate analysis was performed to investigate factors associated with successful DFT. A prediction model of successful DFT based on LESS impedance was assessed by logistic regression. Receiver operating characteristic (ROC) curve, area under the ROC curve and the Hosmer-Lemeshow tests were used to evaluate the accuracy of LESS impedance. Sixty patients were included (52±14years; 69% male). LESS and DFT impedance values were highly correlated (r2=0.97, p<.01). Patients with a failed first shock had higher body mass index (BMI) (30±3vs. 25.7±4.3, p=.014), higher mean LESS (120±35Ω vs. 86.±23Ω, p=.0013) and DFT impedance (122±33Ω vs. 87±24Ω, p=.0013). ROC analysis showed that LESS impedance had a good diagnostic performance in predicting a successful conversion test (AUC 84% [95% CI: 0.72-0.92]) with a cutoff value of <94Ω to identify a successful DFT (sensitivity 71%, specificity 73%). LESS impedance values without the need to induce VF can intraoperatively predict a successful DFT.

Electrogram-guided Bachmann bundle area pacing to correct interatrial block: Initial experience, safety, and feasibility

BackgroundA lack of standard Bachman Bundle(BB) capture criteria has affected the clinical impact of Bachmann Bundle Area Pacing(BBAP) in patients with inter-atrial block(IAB). ObjectiveWe evaluated the feasibility and safety of electrogram guided BBP using sheath assisted, stylet-driven atrial lead implantation. MethodsPatients with a baseline IAB undergoing dual chamber PPI or ICD implantation were enrolled in a single center,prospective study. BBAP was attempted in all patients with the aid of a Selectra 3D S-40 delivery sheath and Solia S-60 pacing lead. BB capture was confirmed using a combination of fluoroscopy,P wave morphology,and electrophysiological criteria. These included the recording of a high frequency BB potential and a transition between non-selective(NS) to selective(S) BB capture during threshold testing. Procedure-related complications,lead parameters,and P wave morphology were assessed at implantation and follow up. ResultsPermanent BBAP was successful in 32 of the 36(88.9%) enrolled patients. Baseline P wave duration was 148.5+16.1ms. Among patients who underwent successful BBP, the final paced P wave duration was 117.8+19.6ms. There was a correction of the partial or complete interatrial block in 22(91.7%) and 6(75.0%) patients, respectively. BB potentials were recorded in 83.3% of all study patients.A transition from NS to S-BB capture could be demonstrated during threshold testing in 22(87.5%) patients. The only major complications were 2 BBAP lead dislodgements within 24 hours and a rise in pacing impedance at 3 weeks in 1 patient. ConclusionBBAP is feasible in a high percentage of patients and is associated with stable capture thresholds during follow up.

Ventricular stimulation in patients with myotonic dystrophy type 1 may not predict future ventricular arrhythmias

Myotonic dystrophy type 1 (DM1) is associated with progressive conduction disease. Furthermore, DM1 patients are at risk ventricular arrhythmias (VAs), although prediction remains difficult. The 2022 Heart Rhythm Expert Consensus Statement gives a IIb recommendation to the use of electrophysiology study (EPS) to risk-stratify patients for VAs. The utility of EPS in predicting the development of VAs, however, has not been explored in this patient population. The study sought to examine the natural history of DM1 patients with positive and negative ventricular stimulation (v-stim) during EPS. Patients with a history of DM1 undergoing EPS with associated v-stim from 2008 to present were retrospectively identified. From 2008 to 2022, 26 consecutive DM1 patients presented for EPS with v-stim. Four v-stim protocols were positive for sustained or hemodynamically significant ventricular tachycardia (VT), one of which was induced with 600 doubles, the others with triple extrastimuli. A total of 22 of 26 subjects received a device implant, with 18 receiving permanent pacemakers and 4 implantable cardioverter-defibrillators. All 4 of the patients with positive v-stims underwent ICD implantation. After a mean of 5.7 years of follow-up, 7 patients had sustained VT, 6 of whom had negative v-stims. Of the 4 patients with positive v-stims, only 1 developed sustained VT in follow-up. Other than baseline QT interval at time of EPS, no baseline characteristics were significantly different between patients with and without subsequent VT. In this single center, v-stim in DM1 patients did not predict clinical VAs, as a vast majority of DM1 patients who developed VAs had negative v-stims.

Recent insights in striated muscle laminopathies.

To highlight recent insights in different aspects of striated muscle laminopathies (SMLs) related to LMNA mutations. Clinical and genetic studies allow better patient management and diagnosis, with confirmation of ventricular tachyarrhythmias (VTA) risk prediction score to help with ICD implantation and development of models to help with classification of LMNA variants of uncertain significance. From a pathophysiology perspective, characterization of lamin interactomes in different contexts revealed new lamin A/C partners. Expression or function modulation of these partners evidenced them as potential therapeutic targets. After a positive phase 2, the first phase 3 clinical trial, testing a p38 inhibitor targeting the life-threatening cardiac disease of SML, has been recently stopped, thus highlighting the need for new therapeutic approaches together with new animal and cell models. Since the first LMNA mutation report in 1999, lamin A/C structure and functions have been actively explored to understand the SML pathophysiology. The latest discoveries of partners and altered pathways, highlight the importance of lamin A/C at the nuclear periphery and in the nucleoplasm. Modulation of altered pathways allowed some benefits, especially for cardiac involvement. However, additional studies are still needed to fully assess treatment efficacy and safety.