Real World Data from Catheter Ablation of Ventricular Tachycardias and Premature Ventricular Complexes in a Tertiary Care Center.

Background: Catheter ablation in patients with ventricular arrhythmias (VA), such as ventricular tachycardias (VT) or frequent premature ventricular complexes (PVC), is increasingly considered an effective and safe therapy when performed in experienced centers. This study sought to determine acute success rates and complication rates of ablation procedures for patients with VA in a Swiss tertiary care center. Methods: All patients who underwent ablation therapy for VT and PVC at the University Heart Center in Zurich, Switzerland, between March 2012 and April 2017 were included in this analysis. Results: A total of 120 patients underwent catheter ablation for VT and PVC (69 and 51, respectively). Seventy percent of patients were male, and the mean age was 55.3 years. The most common indication for ablation was high PVC burden (47.5%), followed by paroxysmal VT (38.3%), ICD shocks (23.3%), incessant VT (12.5%), electrical storm (7.5%), and syncope (3.3%). Acute success rates for VT and PVC ablations were 94.2% and 92.2%, respectively. Rates for complications (including major and minor) for VT and PVC were 10.1% and 7.8%, respectively. Complications occurred only in patients with structural heart disease; no complications were noted in structurally normal hearts. Conclusions: Our results suggest that catheter ablation for VT and PVC has high acute success rates with a reasonable risk for complications in the setting of tertiary care centers, comparable to those reported in other studies.

Right heart strain in arrhythmogenic right ventricular cardiomyopathy: Implications for cardiovascular outcome.

INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by progressive myocardial dysfunction and associated with an increased risk of major cardiovascular events. AIMS: To determine right heart strain (ventricular and atrial global longitudinal strain (RVGLS and RAGLS)) in patients with definite ARVC and its association with adverse events during follow-up. METHODS: RVGLS and RAGLS were analysed in focused right heart apical views from 70 patients using TomTec ImageArena and association with a composite endpoint (sustained ventricular arrhythmia and cardiovascular death) was determined. RESULTS: Over a median follow-up duration of 4.9 years, 26 (37%) patients met the endpoint. RVGLS was significantly impaired in the event group (-11.5 [-13.3 - -10.2]%) versus the no-event group (-15.8 [-17.1 - -14.5]%, P < 0.001), and so was RAGLS (22.8 [21.4 - 27.4]% vs. 31.5 [25.1 - 39.6]%, respectively, P < 0.001). In Cox regression, RVGLS (HR 1.36, P < 0.001) and RAGLS (HR 0.92, P = 0.002) were associated with higher risk of adverse events. In multivariable Cox regression models, RVGLS and RAGLS remained independent of and were incremental to age, gender, and conventional RV parameters, and model fit was improved when RVGLS and RAGLS were applied together rather than alone. CONCLUSIONS: RVGLS and RAGLS are more impaired in patients with adverse events and associated with adverse events independent of age, gender, and conventional RV parameters. When RVGLS and RAGLS are applied together, prediction models are improved suggesting that right heart strain may form part of the echocardiographic routine protocol in patients with ARVC.

[Pregnancy Management in a Patient with Long QT Syndrome Type 2 (LQT2) carrier of the variant KCNH2: Trp100X].

INTRODUCTION: Long QT syndrome (LQTS) is a congenital ion channel disorder causing prolonged ventricular repolarization and presents on surface ECG with a prolonged QTc interval. This condition predisposes to ventricular arrhythmias and also sudden cardiac death. LQTS without appropriate therapy during pregnancy and the postnatal phase poses an additionally increased risk of sudden cardiac death due to physiological changes associated with gestation. We present a case report of a 30-year-old pregnant woman with known long QT syndrome Type 2 (LQT2) and discuss the management in cardiological practice.

The effect of first step right atrial mapping (FRAM) on ablation duration and fluoroscopy exposure during cavotricuspid isthmus ablation of atrial flutter.

Aim: To investigate the clinical significance of right atrial mapping prior to cavotricuspid isthmus (CTI) ablation in patients with typical atrial flutter (AFL). Methods: Clinical and ablation parameters were retrospectively assessed and compared in patients undergoing CTI ablation with or without a first-step right atrial mapping (FRAM) by using the CARTO 3D mapping system. Results: CTI block by radiofrequency ablation (RFA) was achieved in all 143 patients. In the FRAM group there was a shorter ablation duration and fluoroscopy exposure compared with the non-FRAM group. CHA2DS2-VASc score was associated with higher ablation durations, more ablation applications and increased fluoroscopy exposure. Body mass index (BMI) was associated with longer ablation duration and more ablation applications. Furthermore, patients with reduced left ventricular ejection fraction (LVEF) had longer ablation durations and more fluoroscopy exposure. One patient in the non-FRAM group developed cardiac effusion after ablation. None of the patients had recurrence after 6 months of follow-up. Conclusions: Patients with high BMI, high CHA2DS2-VASc score and reduced LVEF may benefit from the FRAM approach by reducing ablation duration, number of ablation applications and fluoroscopy exposure.

Evolution and triggers of defibrillator shocks in patients with arrhythmogenic right ventricular cardiomyopathy.

INTRODUCTION: Implantable cardioverter-defibrillators (ICDs) can prevent sudden cardiac death due to ventricular arrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). The aim of our study was to assess the cumulative burden, evolution and potential triggers of appropriate ICD shocks during long-term follow-up, which may help to reduce and further refine individual arrhythmic risk in this challenging disease. METHODS: This retrospective cohort study included 53 patients with definite ARVC according to the 2010 Task Force Criteria from the multicentre Swiss ARVC Registry with an implanted ICD for primary or secondary prevention. Follow-up was conducted by assessing all available patient records from patient visits, hospitalisations, blood samples, genetic analysis, as well as device interrogation and tracings. RESULTS: Fifty-three patients (male 71.7%, mean age 43±2.2 years, genotype positive 58.5%) were analysed during a median follow-up of 7.9 (IQR 10) years. In 29 (54.7%) patients, 177 appropriate ICD shocks associated with 71 shock episodes occurred. Median time to first appropriate ICD shock was 2.8 (IQR 3.6) years. Long-term risk of shocks remained high throughout long-term follow-up. Shock episodes occurred mainly during daytime (91.5%, n=65) and without seasonal preference. We identified potentially reversible triggers in 56 of 71 (78.9%) appropriate shock episodes, the main triggers representing physical activity, inflammation and hypokalaemia. CONCLUSION: The long-term risk of appropriate ICD shocks in patients with ARVC remains high during long-term follow-up. Ventricular arrhythmias occur more often during daytime, without seasonal preference. Reversible triggers are frequent with the most common triggers for appropriate ICD shocks being physical activity, inflammation and hypokalaemia in this patient population.

A Novel Heterozygous Desmoplakin Variant Causes Cardiocutaneous Syndrome with Arrhythmogenic Cardiomyopathy and Palmoplantar Keratosis.

Cardiocutaneous syndrome (CCS) is often caused by genetic variants in desmoplakin (DSP) in the presence of thick calluses on the hands and soles of the feet (palmoplantar keratoderma) in combination with arrhythmogenic cardiomyopathy. In this case report, we describe a 58-year-old man presenting with a history of cardiomyopathy with recurrent sustained ventricular tachycardia and palmoplantar keratosis. The cardiological evaluation showed biventricular cardiomyopathy, and repeated genetic testing identified a novel DSP variant. Repeated genetic testingis clinically meaningful in patients with a high probability of a specific inherited cardiac disease, such as CCS, particularly if molecular screening has been performed in the pre-NGS era with an incomplete NGS panel or outdated technology as presented in this case report.

Distinctive characteristics of His bundle potentials in patients with atrioventricular nodal reentrant tachycardia.

BACKGROUND: His bundle (HB) potentials vary in amplitude and duration in patients with and without slow pathways. The aim of this study was to determine the characteristics of HB potentials and to elucidate whether they can provide clues for identification of slow pathway (SP). METHODS: The present research prospectively studied the electrophysiological findings of 162 patients with symptomatic atrioventricular nodal reentrant tachycardia (AVNRT) due to slow-fast or fast-slow type and atrioventricular reentrant tachycardia (AVRT). Maximal HB potential (HBmax, HB with the highest amplitude) among HB cloud was recorded in both groups. For AVNRT patients, the following were measured: (1) AH interval at the "jump" during programmed atrial stimulation (A2H2, taken as a reflection of SP conduction time); (2) Distance from HBmax to the successful SP ablation site (HBmax-ABL) and from HBmax to the ostium of coronary sinus (HBmax-CSO). RESULTS: HBmax was 0.29 ± 0.10 mV in AVNRT patients, whereas it was 0.17 ± 0.05 mV in AVRT group (p < 0.0001). Likewise, the HBmax duration was 22 ± 5 ms in AVNRT group and 16 ± 3 ms in AVRT group (p < 0.0001). The area under the receiver operating characteristic curve of HBmax amplitude in AVNRT patients was 0.86 and the optimal HBmax cut-off to predict AVNRT was ≥ 0.22 mV with a sensitivity of 0.78 and specificity of 0.84. HBmax-CSO was positively correlated with HBmax-ABL, and HBmax-ABL was positively correlated with A2H2. CONCLUSIONS: HBmax amplitudes were higher and durations longer in patients with AVNRT, as compared to those with AVRT. Moreover, the distance between HBmax and successful ablation site was positively correlated with the SP conduction time and with the distance from HBmax to the CSO.

Catecholaminergic Polymorphic Ventricular Tachycardia: Multiple Clinical Presentations of a Genetically Determined Disease.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare, inherited heart rhythm disorder that is caused by variants in genes responsible for cardiac calcium homeostasis. The aim of this study was to analyze different genotype-specific clinical manifestations of this disease. METHODS AND RESULTS: We analyzed five CPVT cases from our institution in the context of specific patient characteristics and genotype-phenotype correlations. In this cohort, three of the index patients were male. The median age at diagnosis was 11 (11-30) years, and median age at disease onset was 12 (12-33) years. Four index patients suffered from syncope, while one female index patient suffered from out-of-hospital cardiac arrest. Two index patients experienced concomitant atrial flutter and atrial fibrillation. Three patients received an implantable cardioverter defibrillator and one patient received an event recorder. All index patients had causative genetic variants in the RYR2-gene. CONCLUSIONS: This study presents various phenotypic presentations of patients with CPVT harboring different pathogenic variants in the RYR2 gene, some of which have not previously been described in published studies. Syncope was the most prevalent symptom on admission. Adjustment of beta-blocker therapy may be necessary due to side effects. Moreover, our work further highlights the common occurrence of atrial tachyarrhythmias in these patients.

Biventricular Arrhythmogenic Cardiomyopathy Associated with a Novel Heterozygous Plakophilin-2 Early Truncating Variant.

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is a hereditary condition that can cause sudden cardiac death in young, frequently athletic individuals under the age of 35 due to malignant arrhythmias. Competitive and endurance exercise may hasten the onset and progression of ARVC, leading to right ventricular dysfunction and potentially fatal ventricular arrhythmias earlier in life. In this article, we present a novel, pathogenic, early truncating heterozygous variant in the PKP2 gene that causes biventricular arrhythmogenic cardiomyopathy and affects a family, of which the only member with the positive phenotype is a competitive endurance athlete.

A comparative study on the analysis of hemodynamics in the athlete's heart.

The pathophysiological mechanisms underlying the development of the athlete's heart are still poorly understood. To characterize the intracavitary blood flows in the right ventricle (RV) and right-ventricular outflow tract (RVOT) in 2 healthy probands, patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and 2 endurance athletes, we performed 4D-MRI flow measurements to assess differences in kinetic energy and shear stresses. Time evolution of velocity magnitude, mean kinetic energy (MKE), turbulent kinetic energy (TKE) and viscous shear stress (VSS) were measured both along the whole RV and in the RVOT. RVOT regions had higher kinetic energy values and higher shear stresses levels compared to the global averaging over RV among all subjects. Endurance athletes had relatively lower kinetic energy and shear stresses in the RVOT regions compared to both healthy probands and ARVC patients. The athlete's heart is characterized by lower kinetic energy and shear stresses in the RVOT, which might be explained by a higher diastolic compliance of the RV.

Programmed Ventricular Stimulation as an Additional Primary Prevention Risk Stratification Tool in Arrhythmogenic Right Ventricular Cardiomyopathy: A Multinational Study.

BACKGROUND: A novel risk calculator based on clinical characteristics and noninvasive tests that predicts the onset of clinical sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been proposed and validated by recent studies. It remains unknown whether programmed ventricular stimulation (PVS) provides additional prognostic value. METHODS: All patients with a definite ARVC diagnosis, no history of sustained VAs at diagnosis, and PVS performed at baseline were extracted from 6 international ARVC registries. The calculator-predicted risk for sustained VA (sustained or implantable cardioverter defibrillator treated ventricular tachycardia [VT] or fibrillation, [aborted] sudden cardiac arrest) was assessed in all patients. Independent and combined performance of the risk calculator and PVS on sustained VA were assessed during a 5-year follow-up period. RESULTS: Two hundred eighty-eight patients (41.0±14.5 years, 55.9% male, right ventricular ejection fraction 42.5±11.1%) were enrolled. At PVS, 137 (47.6%) patients had inducible ventricular tachycardia. During a median of 5.31 [2.89-10.17] years of follow-up, 83 (60.6%) patients with a positive PVS and 37 (24.5%) with a negative PVS experienced sustained VA (P<0.001). Inducible ventricular tachycardia predicted clinical sustained VA during the 5-year follow-up and remained an independent predictor after accounting for the calculator-predicted risk (HR, 2.52 [1.58-4.02]; P<0.001). Compared with ARVC risk calculator predictions in isolation (C-statistic 0.72), addition of PVS inducibility showed improved prediction of VA events (C-statistic 0.75; log-likelihood ratio for nested models, P<0.001). PVS inducibility had a 76% [67-84] sensitivity and 68% [61-74] specificity, corresponding to log-likelihood ratios of 2.3 and 0.36 for inducible (likelihood ratio+) and noninducible (likelihood ratio-) patients, respectively. In patients with a ARVC risk calculator-predicted risk of clinical VA events <25% during 5 years (ie, low/intermediate subgroup), PVS had a 92.6% negative predictive value. CONCLUSIONS: PVS significantly improved risk stratification above and beyond the calculator-predicted risk of VA in a primary prevention cohort of patients with ARVC, mainly for patients considered to be at low and intermediate risk by the clinical risk calculator.

Tissue Doppler echocardiography and outcome in arrhythmogenic right ventricular cardiomyopathy.

AIMS: This study aimed at investigating whether tissue Doppler imaging (TDI) is associated with adverse events in arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS AND RESULTS: Transthoracic echocardiography was performed in 72 patients with definite (n = 63) or borderline (n = 9) ARVC diagnosed according to the 2010 Task Force Criteria and included in the prospective Zurich ARVC registry. Myocardial peak systolic tissue velocity (S') was measured by TDI at lateral tricuspid (tricuspid S'), medial mitral (septal S'), and lateral mitral annulus (lateral S'). Association of echocardiographic parameters with outcome was assessed by univariable Cox regression. During a median follow-up of 4.9 ± 2.6 years, 6 (8.3%) patients died of cardiovascular cause or received heart transplantation and 21 (29.2%) patients developed sustained ventricular arrhythmia. Tricuspid, septal, and lateral S' were lower in patients who died (p = 0.001; p < 0.001; p = 0.008; respectively), while tricuspid and septal S' were lower in those with ventricular arrhythmia (p = 0.001; p = 0.008; respectively). There was a significant association of tricuspid, septal, and lateral S' with mortality (HR = 1.61, p = 0.011; HR = 2.15, p = 0.007; HR = 1.67, p = 0.017; respectively), while tricuspid and septal S' were associated with ventricular arrhythmia (HR = 1.20, p = 0.022; HR = 1.37, p = 0.004; respectively). Kaplan-Meier analyses demonstrated a higher freedom from mortality with tricuspid S' >8 cm/s (p = 0.001) and from ventricular arrhythmia with S' >10.5 cm/s (p = 0.021). CONCLUSIONS: This study demonstrates that TDI provides information on the ARVC phenotype, is associated with adverse events in ARVC patients, and differentiates between patients with and without adverse events.

Novel Risk Prediction Model to Determine Adverse Heart Failure Outcomes in Arrhythmogenic Right Ventricular Cardiomyopathy.

Background Patients with arrhythmogenic right ventricular cardiomyopathy are at risk for life-threatening ventricular tachyarrhythmias, but progressive heart failure (HF) may occur in later stages of disease. This study aimed to characterize potential risk predictors and develop a model for individualized assessment of adverse HF outcomes in arrhythmogenic right ventricular cardiomyopathy. Methods and Results Longitudinal and observational cohorts with 290 patients with arrhythmogenic right ventricular cardiomyopathy from the Fuwai Hospital in Beijing, China, and 99 patients from the University Heart Center in Zurich, Switzerland, with follow-up data were studied. The primary end point of the study was heart transplantation or death attributable to HF. The model was developed by Cox regression analysis for predicting risk and was internally validated. During 4.92±3.03 years of follow-up, 48 patients reached the primary end point. The determinants of the risk prediction model were left ventricular ejection fraction, serum creatinine levels, moderate-to-severe tricuspid regurgitation, and atrial fibrillation. Implantable cardioverter-defibrillators did not reduce the occurrence of adverse HF outcomes. Conclusions A novel risk prediction model for arrhythmogenic right ventricular cardiomyopathy has been developed using 2 large and well-established cohorts, incorporating common clinical parameters such as left ventricular ejection fraction, serum creatinine levels, tricuspid regurgitation, and atrial fibrillation, which can identify patients who are at risk for terminal HF events, and may guide physicians to assess individualized HF risk and to optimize management strategies.

Right atrial strain and cardiovascular outcome in arrhythmogenic right ventricular cardiomyopathy.

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by progressive fibro-fatty infiltration of the myocardium and associated with adverse cardiovascular (CV) events. This study aims to examine right atrial (RA) deformation in ARVC and understand its association with CV outcomes. METHODS AND RESULTS: RA strain was determined in 50 patients with definite ARVC, compared with a matched control group of 50 healthy individuals, and analysed for outcome association over a median follow-up duration of 5 years. A subgroup of 30 ARVC patients with normal RA volume (ARVC-N group) was compared with 30 matched controls (Control-N), and the outcome was analysed separately. RA reservoir, conduit, and pump strain were significantly impaired in ARVC vs. control. Similar observations were made in the N-ARVC subgroup. Reservoir strain was associated with an increased risk of atrial arrhythmia (AA) [hazard ratio (HR) 0.88, P < 0.01] and CV events (HR 0.92, P < 0.01). Conduit strain also predicted AA (HR 1.02, P < 0.01), while pump strain predicted CV events (HR 1.09, P = 0.02). Reservoir strain improved the fitness of bivariable models for the association of RV end-diastolic area index, RV fractional area change, and RV global longitudinal strain with CV events. CONCLUSION: ARVC patients display impaired RA strain even when RA volume is normal. Reservoir and pump strain are associated with an increased risk of CV events. Reservoir strain improved model fitness for the association of RVGLS and other echocardiographic parameters with CV events.

Predictors of left atrial fibrosis in patients with atrial fibrillation referred for catheter ablation.

BACKGROUND: Left atrial (LA) fibrosis in patients with atrial fibrillation (AF) is associated with an increased risk of AF recurrence after catheter ablation. Therefore, we searched for clinical risk factors that confer an increased risk of LA fibrosis, which can influence the treatment strategy. METHODS: We included 94 patients undergoing 3-dimensional electroanatomical voltage mapping-guided catheter ablation of AF. LA low-voltage areas during sinus rhythm as a surrogate parameter of fibrosis were measured with the CARTO3 mapping system and adjusted for LA volumes obtained by computed tomography. Blood tests including N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) and echocardiographic parameters of left ventricular function were also analyzed. RESULTS: Patients were 62.5 ± 11.4 years old, and 29% were female. LA fibrosis was present in 65%, with 50% having a fibrotic area > 5% (≥ Utah-Stage 1). Mean left ventricular ejection fraction (LVEF) was 53.9 ± 10.5%. Patients with LA fibrosis had higher NT-proBNP levels (869 ± 1056 vs. 552 ± 859 ng/L, p = 0.001) and larger LA volumes (body surface area-corrected 63.3 ± 19.3 vs. 80 ± 27.1 mL/m2, p = 0.003). In univariable analyses, LA fibrosis was significantly associated with female gender, older age, increased LA volumes, hypertension, statin therapy, higher NT-proBNP values, and echocardiographic E/e'. In bivariable analyses, higher NT-proBNP, echocardiographic parameters of diastolic dysfunction, female gender, older age, and higher DR-FLASH scores remained as independent predictors of LA fibrosis. CONCLUSIONS: In this single-center longitudinal study, surrogate parameters of elevated left-sided cardiac filling pressures such as higher NT-proBNP levels and higher echocardiographic E/e' values as well as female gender independently predicted the prevalence of LA fibrosis in patients referred for catheter ablation of AF.

Changes in Exercise Capacity and Ventricular Function in Arrhythmogenic Right Ventricular Cardiomyopathy: The Impact of Sports Restriction during Follow-Up.

(1) Background: Physical exercise has been suggested to promote disease progression in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). We aimed to investigate the exercise performance and ventricular function of ARVC patients during follow-up, while taking into account their adherence to exercise restriction recommendations. (2) Methods: This retrospective study included 49 patients (33 male, 67%) who had an exercise test at baseline and after 4.2 ± 1.6 years. Of the 49 ARVC patients, 27 (55%) were athletes, while 22 (45%) were non-athletes. Of the athletes, 12 (44%) continued intensive sports activity (non-adherent), while 15 (56%) stopped intensive physical activity upon recommendation (adherent). The maximum workload in Watts (W), percentage of the target workload (W%), and double product (DP) factor were measured for all patients. (3) Results: The non-adherent cohort had a significant decrease in physical performance (W at baseline vs. follow-up, p = 0.012; W% at baseline vs. follow-up, p = 0.025; DP-factor at baseline vs. follow-up, p = 0.012) over time. Left ventricular (LV) function (LV ejection fraction at baseline vs. follow-up, p = 0.082) showed a decreasing trend in the non-adherent cohort, while the performance of the adherent cohort remained at a similar level. (4) Conclusions: If intensive sports activities are not discontinued, exercise capacity and left ventricular function of athletes with ARVC deteriorates during follow-up. All patients with ARVC need to strictly adhere to the recommendation to cease intense sports activity in order to halt disease progression.

[CME-ECG 70: Chest Pain in a Young Patient - Differential Diagnoses beyond the Acute Coronary Syndrome]. / CME-EKG 70/Antworten: Thoraxschmerzen bei einem jungen Patienten ­ Differenzialdiagnosen neben dem akuten Koronarsyndrom.

CME-ECG 70: Chest Pain in a Young Patient - Differential Diagnoses beyond the Acute Coronary Syndrome Abstract. CME-ECG 70: Chest Pain in a Young Patient - Differential Diagnoses beyond the Acute Coronary Syndrome Older patients with chest pain and typical ECG changes are most likely to be diagnosed with cardiovascular diseases. However, younger patients with similar symptoms may reveal different disease patterns. In this case report, differential diagnoses and diagnostic steps, with particular attention to the ECG, will be discussed.

Novel plasma biomarkers predicting biventricular involvement in arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease characterized by fibrofatty replacement of the myocardium and ventricular arrhythmias. Biventricular involvement in ARVC may lead to heart failure. This study aimed to investigate the role of plasma biomarkers soluble (s)ST2, Galectin-3 (Gal-3) and GDF-15 in predicting biventricular involvement and adverse outcomes in ARVC. METHODS AND RESULTS: ARVC patients from 2 independent cohorts, were studied. The Bejing (Chinese) cohort (n = 108) was the discovery cohort, whereas the Zurich (Swiss) cohort (n = 47) served as validation. All patients had a definite ARVC diagnosis at time of blood withdrawal. Biomarkers were independently correlated with NT-proBNP and left ventricular (LV)-function. ARVC patients with LV involvement had higher levels of sST2 and GDF-15 as compared to controls and patients with isolated right ventricle (RV) involvement. sST2 and GDF-15 were significantly correlated with late gadolinium enhancement in CMR and with adverse heart failure outcomes. Gal-3 was elevated in ARVC patients with and without LV involvement. The combined use of the three biomarkers (sST2, GDF-15 and NT-proBNP) showed the best performance in predicting LV involvement in both cohorts. Plasma drawn from the coronary arteries and coronary sinus indicated a transmyocardial elevation of sST2, but no transmyocardial gradient of GDF-15. After heart transplantation, both sST2 and GDF-15 returned to near-normal levels. CONCLUSION: Our study showed that sST2 and GDF-15 may predict biventricular involvement in ARVC. The combined use of sST2, GDF-15 and NT-proBNP showed the best prediction of biventricular involvement in ARVC.