Background Optimal management of direct oral anticoagulants (DOAC) prior to implantation of cardiac implantable electronic devices (CIED) remains controversial. Objective To determine whether a strategy of minimal interruption of DOAC before cardiac CIED implantation is associated with improved clinical outcomes compared to uninterrupted DOAC use. Methods The electronic clinical records of 310 patients who were on DOAC and underwent CIED implantation were evaluated. The patients were separated into 2 groups: patients in Group 1 had minimal DOAC interruption (DOAC held < 24 h before procedure), while patients in Group 2 continued DOAC before procedure. Resumption of DOAC in both groups was on the same day of the procedure or the next morning at the operator's discretion. Clinically significant pocket hematoma and thromboembolic events were compared. Results Among the 310 patients, 71 (22.9%) of them had DOAC held < 24 h before procedure, while DOAC was continued without interruption in 239 (77.1%) in the periprocedural period. Clinically significant pocket hematomas were found in 1 patient (1.4%) in the DOAC interrupted group and 24 (10.0%) in the DOAC continuous group (p = 0.046). Low thromboembolic events were observed in both groups: 0 in the minimally interrupted group and 1 (0.4%) in the un-interrupted group (p > 0.05). Conclusion The bleeding risk in our cohort of patients who underwent CIED implantation with the uninterrupted DOAC approach is higher than previously reported in the literature. A minimally interrupted approach appears to mitigate this risk without significantly increasing the risk of thromboembolism.

Aims:Pulsed field ablation for atrial fibrillation offers shorter procedural times and improved safety compared with thermal ablation, but the optimal anaesthesia strategy remains uncertain. Most centres in the USA use general anaesthesia with endotracheal intubation, whereas monitored anaesthesia care without endotracheal intubation may be a safe and efficient alternative. Objectives:To compare procedural efficiency and safety between monitored anaesthesia care and general anaesthesia for pulsed field ablation. Methods and results:Consecutive adults who underwent pulsed field ablation for atrial fibrillation between 2024 and 2025 at Marshfield Clinic Health System were included. The anaesthesia approach was determined by operator preference. Procedural times, medication use, complications, and patient tolerance were recorded prospectively. Among 200 patients, 100 received monitored anaesthesia care without endotracheal intubation, and 100 received general anaesthesia. The mean age was 67 years, 42% were female, and the mean body mass index was 33 kilograms per square metre. Monitored anaesthesia care shortened case duration (77 vs. 95 min; P < 0.001) and laboratory time (118 vs. 153 min; P = 0.002) and required fewer adjunct medications (P < 0.001). Twenty-five procedures (25%) were challenging due to cough or motion but were all completed safely. Complications occurred in one monitored anaesthesia care case and six general anaesthesia cases (P = 0.054). Pulmonary vein isolation was achieved in all patients. Conclusion:Monitored anaesthesia care without endotracheal intubation was safe, efficient, and resource-sparing compared with general anaesthesia for pulsed field atrial fibrillation ablation.

BackgroundIn older adults with atrial fibrillation (AF), the presence of comorbid chronic kidney disease (CKD) may be more challenging for optimal disease management, influence stroke prophylaxis with oral anticoagulation, and impact bleeding risk. We examined the prevalence and burden of CKD in older patients with AF, patterns of anticoagulation prescribing according to CKD stage, and major bleeding events.MethodsPatients aged 65 years and older with AF were enrolled in a cohort study from clinics in Massachusetts and Georgia between 2016 and 2018. Kidney function was assessed with estimated glomerular filtration rate (GFR) values at study enrollment. Anticoagulation therapy with direct acting oral anticoagulation therapy (DOAC) or warfarin; and major bleeding events were ascertained from medical records. Cox proportional hazards model was used to estimate the multivariable adjusted risk of two-year major bleeding events.ResultsParticipants' (n = 1,244) mean age was 75 years; 48% were women, and 86% were White. Overall, 25% had a normal GFR, 44%, 28%, and 3% had mild, moderate, and severe CKD/kidney failure, respectively. Patients with severe CKD/kidney failure were more likely to be the oldest participants, dependent in their instrumental activities of daily living, and had the highest burden of frailty, multimorbidity, and polypharmacy. Approximately 44% of patients with normal GFR and 39% of those with mild CKD were prescribed a DOAC, while a majority of those with severe CKD/kidney failure (69%) were prescribed warfarin. Overall, 8% (n = 105) experienced a major bleeding event over the 2-year follow-up. After adjusting for sociodemographic, psychosocial, geriatric, and clinical variables, patients with severe CKD/kidney failure (HR: 2.81 [95% CI:1.10-7.17]) had a higher bleeding risk than those with a normal GFR.ConclusionsIn managing older patients with AF and comorbid CKD, healthcare providers should be increasingly aware of the increased burden of frailty, dependence for care, multimorbidity, polypharmacy, and the high risk of major bleeding especially among those with severely impaired kidney function. This finding emphasizes the need for a more holistic and multidisciplinary approach to stroke prophylaxis in older adults with AF and comorbid CKD.

Despite lack of concrete evidence, right ventricular thrombus is generally considered to be a contraindication for intracardiac lead placement. We present a case of successful placement of a right ventricular defibrillator lead and left bundle branch pacing lead and atrioventricular node ablation in a patient with chronic right ventricle thrombus.

Background: Physical activity (PA) restriction is a recommended intervention for patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), due to strong associations of PA history with disease, and the known risk of arrhythmic events in affected patients from tertiary referral centers. However, in patients with secondary findings of genetic risk for ARVC, the association of PA exposure with disease expression is unknown. Hypothesis: Among individuals with incidentally identified pathogenic or likely pathogenic (P/LP) variants in desmosome genes (PKP2, DSP, DSG2, DSC2), clinical evidence of disease will be associated with higher pre-diagnostic PA exposure. Methods: The MyCode (MC) cohort included individuals with P/LP variants in desmosome genes, discovered via population genomic screening of 175,000 individuals; the Johns Hopkins (JH) disease-based cohort included ARVC probands and family members with single P/LP variants enrolled in the JH ARVC Registry. The ARVC task force criteria (TFC) status of each patient was defined based on most recent clinical evaluation. Recreational PA history from age 10 to time of diagnosis (TFC+) or survey (TFC-) was self-reported through structured phone interview and each activity was assigned a metabolic equivalent score. Results: The MC cohort was older, more female-predominant, had a lower proportion of PKP2 variants, and had less disease than the JH cohort (Figure; all p<0.001). As expected, MET-hrs/year of exercise prior to presentation was significantly higher in affected vs. unaffected patients in the JH cohort. In contrast, no association between PA history and disease expression was observed in MC (p=0.42). Conclusions: The MyCode cohort demonstrated both a paucity of clinically evident disease and a lack of obvious association of exercise with disease expression. These findings may be seen as reassuring in the management of patients with secondary ARVC genetic findings, but additional data are needed.

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Slow conduction within the myocardium can be a substrate for ventricular tachycardia. Signal-averaged electrocardiogram (SAECG) is a method to identify slow conduction manifested as late potential. For arrhythmogenic right ventricular cardiomyopathy (ARVC), late potentials were included in the 1994 diagnostic criteria as a minor criterion,1 which was based on an early experience examining 12 patients with ARVC.2 Later, in a comparison of 87 ARVC probands to 103 controls, abnormal SAECG (any 1 of 3 components) was reported to have sensitivity of 69% and specificity of 95% in diagnosing ARVC.

Abstract Although there is a large body of literature linking atrial fibrillation (AF) to adverse clinical outcomes, little is known with regards to the potential links between health-related quality of life (HRQoL) and AF related clinical events. To address this gap, individuals with AF aged ≥ 65 years were recruited from clinics in Massachusetts and Georgia between 2016-18 and followed until 2020. HRQoL was assessed via the Atrial Fibrillation Effect on Quality of Life (AFEQT). The AFEQT is a validated HRQoL measure that quantifies the effect of AF on patients’ daily life on a scale of 0 to 100. AFEQT scores < 80 indicated poor HRQoL and ≥ 80 indicated good HRQoL. The clinical events included major bleeding, stroke, and death. Of the 1,244 participants, the mean age was 75.5 (SD: 7.1), 49% identified as female, 13% were non-White, and 57% were married. After 2 years, 105 major bleeding events (49% poor HRQoL), 19 strokes (42% poor HRQoL) and 108 deaths (59% poor HRQoL) occurred. Our composite outcome included 200 participants (53% poor HRQoL). After adjusting for key covariates, poor HRQoL was associated with an increased risk of our composite outcome (adjusted hazard ratio [AHR]= 1.34, 95% CI: 1.00, 1.80) and death (AHR= 1.58, 95% CI: 1.05, 2.38). We found no significant differences between poor and good HRQoL in major bleeding and strokes. HRQoL is important when assessing health of AF patients. Health providers who treat patients with AF should consider HRQoL when evaluating the risk of death and other adverse outcomes.

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia associated with significant health ramifications, including an elevated susceptibility to ischemic stroke, heart disease, and heightened mortality. Photoplethysmography (PPG) has emerged as a promising technology for continuous AF monitoring for its cost-effectiveness and widespread integration into wearable devices. Our team previously conducted an exhaustive review on PPG-based AF detection before June 2019. However, since then, more advanced technologies have emerged in this field. This paper offers a comprehensive review of the latest advancements in PPG-based AF detection, utilizing digital health and artificial intelligence (AI) solutions, within the timeframe spanning from July 2019 to December 2022. Through extensive exploration of scientific databases, we have identified 59 pertinent studies. Our comprehensive review encompasses an in-depth assessment of the statistical methodologies, traditional machine learning techniques, and deep learning approaches employed in these studies. In addition, we address the challenges encountered in the domain of PPG-based AF detection. Furthermore, we maintain a dedicated website to curate the latest research in this area, with regular updates on a regular basis.

Endurance and frequent exercise are associated with earlier onset of arrhythmogenic right ventricular cardiomyopathy (ARVC) and ventricular arrhythmias (VA) in desmosomal gene variant carriers. Individuals with the pathogenic c.40_42del; p.(Arg14del) variant in the PLN gene are frequently diagnosed with ARVC or dilated cardiomyopathy (DCM). The aim of this study was to evaluate the effect of exercise in PLN p.(Arg14del) carriers. In total, 207 adult PLN p.(Arg14del) carriers (39.1

Background: Exercise is associated with sustained ventricular arrhythmias (VA) in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) but is not included in the ARVC risk calculator ( arvcrisk.com ). The objective of this study is to quantify the influence of exercise at diagnosis on incident VA risk and evaluate whether the risk calculator needs adjustment for exercise. Methods: We interviewed ARVC patients without sustained VA at diagnosis about their exercise history. The relationship between exercise dose 3 years preceding diagnosis (average METh/wk) and incident VA during follow-up was analyzed with time-to-event analysis. The incremental prognostic value of exercise to the risk calculator was evaluated by Cox models. Results: We included 176 patients (male, 43.2%; age, 37.6±16.1 years) from 3 ARVC centers, of whom 53 (30.1%) developed sustained VA during 5.4 (2.7–9.7) years of follow-up. Exercise at diagnosis showed a dose-dependent nonlinear relationship with VA, with no significant risk increase <15 to 30 METh/wk. Athlete status, using 3 definitions from literature (>18, >24, and >36 METh/wk), was significantly associated with VA (hazard ratios, 2.53–2.91) but was also correlated with risk factors currently in the risk calculator model. Thus, adding athlete status to the model did not change the C index of 0.77 (0.71–0.84) and showed no significant improvement (Akaike information criterion change, <2). Conclusions: Exercise at diagnosis was dose dependently associated with risk of sustained VA in ARVC patients but only above 15 to 30 METh/wk. Exercise does not appear to have incremental prognostic value over the risk calculator. The ARVC risk calculator can be used accurately in athletic patients without modification.

In older patients with atrial fibrillation (AF), physical, cognitive, and psychosocial limitations are prevalent. The prognostic value of these conditions for major bleeding is unclear. To determine whether geriatric conditions are prospectively associated with major bleeding in older patients with AF on anticoagulation. Multicenter cohort study with 2-year follow-up from 2016 to 2020 in Massachusetts and Georgia from cardiology, electrophysiology, and primary care clinics. Diagnosed with AF, age 65 years or older, CHA2DS2-VASc score of 2 or higher, and taking oral anticoagulant (n=1,064). A total of 6507 individuals were screened. A six-component geriatric assessment of frailty, cognitive function, social support, depressive symptoms, vision, and hearing. Main outcome was major bleeding adjudicated by a physician panel. At baseline, participants were, on average, 75.5 years old and 49% were women. Mean CHA2DS2-VASc score was 4.5 and the mean HAS-BLED score was 3.3. During 2.0 (± 0.4) years of follow-up, 95 (8.9%) participants developed an episode of major bleeding. After adjusting for key covariates and accounting for competing risk from death, cognitive impairment (hazard ratio [HR] 1.62, 95% confidence interval [CI]: 1.02–2.56) and frailty (HR 2.77, 95% CI 1.38–5.58) were significantly associated with the development of major bleeding. In older patients with AF taking anticoagulants, cognitive impairment and frailty were independently associated with major bleeding.

Introduction: Psychosocial impairments (i.e., depression or anxiety) and geriatric impairments are prevalent among older patients with atrial fibrillation (AF) and adversely impact their long-term outcomes. However, little is known about the association between symptoms of anxiety or depression and various impairments associated with older age. Hypothesis: We hypothesize that depression and anxiety would be associated with frailty, cognitive impairment, and low quality of life among older adults with AF. Methods: We analyzed data from the Systemic Assessment of Geriatric Elements-AF study. Participants with AF aged 65 years and older, with a CHA 2 DS 2 -VASc≥2, were recruited from multiple clinics in Georgia and Massachusetts. Patient Health Questionnaire-9 and the Generalized Anxiety Disorder-7 Scale were used to assess depression and anxiety symptoms, respectively. We used a GEE model to examine the association between depression and anxiety at baseline with our principal study outcomes over a 2-year follow-up period. Results: 972 participants (mean age 74 years; 48 % female; 87 % were non-Hispanic White) were included in this study. Participants who met the criteria for anxiety (29%) or depression (26%) at baseline, as compared to those without, were more likely to be frail ( OR = 2.20, 95% CI: 1.58-3.05; OR [OR] = 4.32, 95% CI: 3.16-5.90, respectively) and to have a lower AF related quality of life over 2 years ( OR= 3.21, 95% CI: 2.52-4.11; OR= 3.71, 95% CI: 2.94-4.69, respectively). However, there was no association between depression or anxiety and cognitive impairment. Conclusions: Anxiety and depression in older adults with AF were associated with increased risk of frailty and decreased AF related quality of life. As such, addressing mental health needs of older adults may improve their clinical outcomes and quality of life.

Background: Current guidelines encourage adults with atrial fibrillation (AF) to engage in regular physical activity. However, little is known about the association between meeting the recommended level of regular physical activity and clinical outcomes among older adults with AF. Objective: To examine the association between meeting the recommended level of physical activity and clinical outcomes including mortality, stroke, and major bleeding. Methods: We used data collected from the Systemic Assessment of Geriatrics Elements (SAGE)-AF study which include patients with AF (≥65 years) and a CHA 2 DS 2 -VASc score ≥2. Participants were recruited from several clinics in Massachusetts and Georgia. We used the Minnesota Leisure Time Physical Activity questionnaire to examine if participants met the recommended level of physical activity (i.e. at least 500 metabolic equivalent task (MET)-minutes per week). A multivariable cox regression model was used to examine the association between meeting the recommended level of physical activity and our clinical outcomes while controlling for several potentially confounding variables. Results: A total of 1,244 participants (average age 75 years; 49% male; 85 % non-Hispanic White) were included in this study. Nearly one-half of participants engaged in regular physical activity. Meeting the recommended level of physical activity was associated with improved survival (adjusted HR (aHR) = 0.60, 95% CI = 0.38-0.96). However, engaging in regular physical activity was not significantly associated with reduced risk of stroke or major bleeding ( aHR = 1.37, 95% CI = 0.51-3.69; aHR = 0.86, 95% CI = 0.56-1.33, respectively ), although we may have lacked power for these associations, therefore, these results should be interpreted with caution. Conclusions: Meeting the recommended level of physical activity among older adults with AF significantly reduces the risk of mortality. Clinicians and health care providers should promote and encourage engagement in physical activity and tailor interventions to address barriers of engagement to improve patient survival.

BACKGROUND:In managing older adults with atrial fibrillation (AF), their symptomatology impacts their well-being and may inform treatment decision-making. We examined AF symptom perception, its impact on quality of life (QoL), and its relation to treatment strategies in older adults with AF.METHODS:Data were obtained from older adults with AF enrolled in a multicenter study conducted at clinic sites in Massachusetts and Georgia between 2016 and 2018. Participants were stratified into three age groups: 65-74 (youngest-old), 75-84 (middle-old), and ≥85 (oldest). Perception of AF symptoms was assessed by participant self-report during their clinic visit and at study enrollment by the Atrial Fibrillation Effect on Quality-of-Life Questionnaire which assessed cardiac-specific and non-specific, non-cardiac AF symptoms and their impact on QoL. Treatment strategies (rate or rhythm control) utilized were ascertained from electronic medical records.RESULTS:Among the 1184 participants (mean age 75 years, 48% women, 86% Non-Hispanic White), 51% were aged 65-74 years, 36% were 75-84 years, and 13% were ≥ 85 years. The most commonly reported AF symptoms were non-specific, non-cardiac symptoms (fatigue, dyspnea, lightheadedness) with similar prevalence and impact on QoL in all age groups. Cardiac-specific AF symptoms (palpitations, irregular heartbeat, pause in heart activity) were less prevalent, but most commonly reported by the youngest participants (65-74 years), who endorsed considerable impact of these symptoms on their QoL. Overall, those who reported experiencing any AF symptoms during their clinic visit were more likely to have received rhythm compared with rate control (OR: 1.56; 95% CI: 1.18-2.04) with similar findings for all age groups except those aged ≥85 years.CONCLUSIONS:Our findings suggest a high prevalence of non-specific, non-cardiac symptoms among older adults with AF and that cardiac-specific AF symptoms may exert considerable impact on their QoL. The presence of any AF symptoms may drive more rhythm control in a majority of older adults.

Background: Stroke prevention with oral anticoagulation (OAC) is a mainstay therapy in atrial fibrillation (AF) but is associated with increased bleeding. Identifying health determinants that contribute to this risk is essential to minimizing these adverse events and evaluating the risk benefit of OAC in an individual patient. This study examines the association between the seven cardiovascular risk factors (blood pressure, cholesterol, smoking status, physical activity, glucose, BMI, and diet) from the American Heart Association’s (AHA) Life’s Simple 7 (LS7) and major bleeding in older individuals with AF on OAC. Methods: In this multicenter prospective cohort study, we enrolled 1064 patients who were 65 years old and above, had non-valvular AF, and on OAC and followed them for 2 years. Based on AHA’s LS7 criteria, each risk factor was graded on a 3-point scale: 0 points (poor), 1 point (intermediate), and 2 points (ideal). Patients were separated into poor (0-6 pts), intermediate (7-9 pts), or ideal (10-14 pts) cohorts based on their aggregate score. Cox models were used to assess the relationship between the aggregate cohort scores and major bleeding as well as each individual cardiovascular risk factor score and major bleeding. Results: Our 1064 patients were separated into poor (n=242), intermediate (n=581) and ideal (n=241) cardiovascular health cohorts. There was a total of 95 major bleeding events, 8.93% of patients who had a major bleed, and a crude rate of 4.68 major bleeding events per 100 person-years. Compared to the ideal group, patients in the poor (HR, 2.29; 95% CI, 1.13 to 4.65) and intermediate groups (HR, 2.17; 95% CI, 1.14 to 4.14) were more likely to have a major bleeding event. Additionally, patients with poor smoking status (HR, 2.78; 95% CI, 1.29 to 5.98) or physical activity (HR, 1.66; 95% CI, 1.07 to 2.59) were significantly more likely to have a major bleeding event than those in the intermediate and ideal categories. Conclusions: In older adults with AF on OAC, poor cardiovascular health, smoking, and poor physical activity are all associated with a higher risk of major bleeding. Further investigation is needed to determine if smoking cessation and physical activity can lead to clinically meaningful reduction in bleeding events.

Background:Little is known about online health information-seeking behavior among older adults with atrial fibrillation (AF) and its association with self-reported outcomes. Objective:To examine patient characteristics associated with online health information seeking and the association between information seeking and low AF-related quality of life and high perceived efficacy in patient-physician interaction. Methods:We used data from the SAGE-AF (Systematic Assessment of Geriatric Elements in AF) study, which includes older participants aged ≥65 years with AF and a CHA2DS2-VASc risk score ≥2. To assess online health information seeking, participants who reported using the Internet were asked at baseline if they used the Internet to search for advice or information about their health in the past 4 weeks (not at all vs at least once). Atrial Fibrillation Effect on Quality of Life and Perceived Efficacy in Patient-Physician Interactions questionnaires were used to examine AF-related quality of life (QOL) and patient-reported confidence in physicians. Logistic regression models were used to examine demographic and clinical factors associated with online health information seeking and associations between information seeking and low AF-related QOL (AFEQT <80) and high perceived efficacy for patient-physician interactions (PEPPI ≥45). Results:A total of 874 online participants (mean age 74.5 years, 51% male, 91% non-Hispanic White) were studied. Approximately 60% of participants sought health information online. Participants aged 74 years or older and those on anticoagulation were less likely, while those with a college degree were more likely, to seek online health information after adjusting for potential confounders. Participants who sought health information online, compared to those who did not, were significantly more likely to have a low AF-related QOL, but less likely to self-report confidence in patient-physician interaction (aOR = 1.56, 95% CI: 1.15-2.13; aOR = 0.68, 95% CI: 0.49-0.93, respectively). Conclusion:Clinicians should consider barriers to patient-physician interaction in older adults who seek health information online, encourage shared decision-making, and provide patients with a list of online resources for AF in addition to disease education plans to help patients manage their health.

BACKGROUND:There is limited evidence guiding the selection between subcutaneous and transvenous implantable cardioverter-defibrillators (ICDs) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) at risk for sudden death. OBJECTIVES:This study aimed to compare clinical and quality-of-life outcomes between transvenous and subcutaneous ICDs among patients with ARVC. METHODS:Patients with a subcutaneous ICD (n = 57) were matched to patients with a transvenous ICD (n = 88) based on sex, proband status, primary prevention or secondary prevention, monomorphic ventricular tachycardia before implantation, and year of implantation. Appropriate therapy for ventricular arrhythmia, inappropriate shocks, and complications were compared. Quality-of-life surveys were conducted annually. RESULTS:The matched cohort (median age of 35 years, 43% men, 78% proband, and 37% secondary prevention device) were prospectively followed for 5.1 ± 2.5 years. No significant difference was observed in the rate of appropriate ICD shocks. The subcutaneous group had more inappropriate shocks (23% vs 10%) and fewer procedure-related complications (4% vs 14%) than the transvenous group (P < 0.05). The association between ICD type and the composite of inappropriate shock and complication was not statistically significant (subcutaneous vs transvenous adjusted HR: 1.43; 95% CI: 0.72-2.84). A subcutaneous ICD was associated with more body image concerns and range of motion than a transvenous ICD (P < 0.05). CONCLUSIONS:In patients with ARVC receiving an ICD, the risk of inappropriate shocks from a subcutaneous ICD should be balanced against the significant vascular complication risk from a transvenous ICD. Patients with a subcutaneous ICD had more concerns for body image and range of motion.

HomeJournal of the American Heart AssociationVol. 11, No. 13Predicting Heart Failure in Arrhythmogenic Right Ventricular Cardiomyopathy Open AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toOpen AccessEditorialPDF/EPUBPredicting Heart Failure in Arrhythmogenic Right Ventricular Cardiomyopathy Weijia Wang, MD, MPH and Hugh Calkins, MD Weijia WangWeijia Wang https://orcid.org/0000-0002-9435-0145 , Division of Cardiology, Department of Medicine, , Johns Hopkins University, , Baltimore, , MD, and Hugh CalkinsHugh Calkins * Correspondence to: Hugh Calkins, MD, Division of Cardiology, Department of Medicine, Johns Hopkins University, 600 N. Wolfe Street, Sheikh Zayed Tower 7125R, Baltimore, MD 21287. Email: E-mail Address: [email protected] https://orcid.org/0000-0002-9262-9433 , Division of Cardiology, Department of Medicine, , Johns Hopkins University, , Baltimore, , MD, Originally published29 Jun 2022https://doi.org/10.1161/JAHA.122.026874Journal of the American Heart Association. 2022;11:e026874This article is a commentary on the followingNovel Risk Prediction Model to Determine Adverse Heart Failure Outcomes in Arrhythmogenic Right Ventricular CardiomyopathyOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: June 29, 2022: Ahead of Print Since its recognition, arrhythmogenic right ventricular cardiomyopathy (ARVC) has been characterized as a heart muscle disease with high risk of ventricular arrhythmia. Much of the effort has been focused on the arrhythmogenic aspect of the disease, including the risk stratification for sudden death1 and intervention to mitigate the risk for lethal arrhythmia such as exercise reduction,2 medication,3 and ablation.4 The heart failure aspect of the disease had been largely neglected until Gilotra et al5 reported that heart failure was present in 49% of patients with ARVC, with exertional dyspnea and fatigue being the most common symptoms. Also, classic left‐sided heart failure signs such as orthopnea, paroxysmal nocturnal dyspnea, and pulmonary rales are usually absent. It was reported that patients with heart failure had higher odds of being a woman, having more severe right ventricular dysfunction, having hypertension, and having negative T waves in precordial leads V4 through V6. The predictors of end‐stage heart failure remained unknown in ARVC. In this context, Chen et al drew our attention again to heart failure in ARVC by presenting a prediction model for adverse heart failure outcomes in ARVC in this issue of the Journal of the American Heart Association (JAHA).6This was a multicenter study with patients from ARVC registries in Fuwai Hospital, China (n=290) and University Heart Center, Switzerland (n=99). ARVC probands without end‐stage heart failure at enrollment were included. The primary end point was heart transplant or death from heart failure. The least absolute shrinkage and selection operator method and Cox regression analysis was used to develop the model. The average age was 38 years with 65% being men. After ≈5 years of follow‐up, 48 (12%) patients reached the primary end point (29 transplants, 19 heart failure deaths). The final model included 4 variables: left ventricular ejection fraction, tricuspid regurgitation, creatinine, and atrial fibrillation. The model performed well in internal bootstrap validation, with excellent discrimination (C‐index of 0.92) and good calibration across high‐ and low‐risk population as well as long and short follow‐up. A user‐friendly web‐based calculator was also provided.This is the first risk prediction model for heart failure adverse outcomes in ARVC. With the use of widely available clinical and laboratory data, this work enables clinicians to conveniently estimate the risk for development end‐stage heart failure and need of transplant. This would remind providers to start or intensify neurohormonal therapies and facilitate early referral to heart failure providers. There are a few caveats to be kept in mind in the interpreting of the results. First, patients who met the study end point already had suffered advanced heart failure at enrollment (70% New York Heart Association class ≥3 at age 38, left ventricular ejection fraction 39.69±13.30%, NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide] 2289.5 pg/mL). It would be obvious that these individuals were at high risk for end‐stage heart failure, which may explain the excellent model performance and the high incidence of end‐stage heart failure observed. In practice, risk prediction would be most valuable for patients without heart failure symptoms to direct preventative interventions. Second, right ventricular dysfunction is a key feature of ARVC and has been associated with heart failure severity.5 However, its prevalence was not reported. Right ventricular function was not included among the prespecified predictors. Prior ventricular arrhythmia (another disease feature of ARVC) was not included, despite repeated ventricular arrhythmia and defibrillator shocks having been which has been shown to worsen heart failure.5 Both right ventricular function and recurrent ventricular arrhythmias would at least deserve exploration during model development. Third, it is notable that more than one‐third of patients were not on a beta blocker, and no mention at all was made of how many patients, if any, were on an angiotensin‐converting enzyme inhibitor. Fourth, although difference by genotype was observed (18% of DSP carriers reaching end point versus 3% of PKP2 carriers), genotype was not included in the model because of the limited genetic testing rate. Furthermore, it is well known that exercise restriction after diagnosis of ARVC dramatically reduces the risk of heart failure and transplant.7 But there was no mention as to whether the patients in this study restricted exercise. Finally, external validation would be required to be assess the generalizability of the model.The authors are to be congratulated for this important work in risk‐stratifying heart failure outcomes in ARVC and reminding us once again of the importance of heart failure in patients with ARVC. Future efforts need to be directed at better defining methods to reduce heart failure risk of patients with ARVC, and especially those determined to be at high risk of developing heart failure.DisclosuresDr Calkins is a consultant for Medtronic Inc., Biosense Webster, Pfizer, StrideBio, and Abbott; receives research support from Boston Scientific Corp; and receives research support from Medtronic, Biosense Webster, Farapulse, and Adagio. Dr Wang has no disclosures to report.Footnotes* Correspondence to: Hugh Calkins, MD, Division of Cardiology, Department of Medicine, Johns Hopkins University, 600 N. Wolfe Street, Sheikh Zayed Tower 7125R, Baltimore, MD 21287. Email: [email protected]eduFor Disclosures, see page 2.See Article by Chen et al.References1 Cadrin‐Tourigny J, Bosman LP, Nozza A, Wang W, Tadros R, Bhonsale A, Bourfiss M, Fortier A, Lie ØH, Saguner AM, et al. A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy. Eur Heart J. 2019; 40:1850–1858. doi: 10.1093/eurheartj/ehz103CrossrefMedlineGoogle Scholar2 Wang W, Orgeron G, Tichnell C, Murray B, Crosson J, Monfredi O, Cadrin‐Tourigny J, Tandri H, Calkins H, James CA. Impact of exercise restriction on arrhythmic risk among patients with arrhythmogenic right ventricular cardiomyopathy. J Am Heart Assoc. 2018; 7:e008843. doi: 10.1161/JAHA.118.008843LinkGoogle Scholar3 Ermakov S, Gerstenfeld EP, Svetlichnaya Y, Scheinman MM. Use of flecainide in combination antiarrhythmic therapy in patients with arrhythmogenic right ventricular cardiomyopathy. 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Published on behalf of the American Heart Association, Inc., by Wiley BlackwellThis is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.https://doi.org/10.1161/JAHA.122.026874PMID: 35766273 Originally publishedJune 29, 2022 Keywordsarrhythmogenic right ventricular cardiomyopathyheart failureEditorialsPDF download SubjectsArrhythmiasCardiomyopathy