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.

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.

[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.

[CME-ECG 70: Chest Pain in a Young Patient - Differential Diagnoses beyond the Acute Coronary Syndrome]. / CME-EKG 70: 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. 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.

[CME-EKG 69/Answers: Sinus Pauses in Long-Term Monitoring]. / CME-EKG 69/Antworten: Sinuspausen im Monitoring.

CME-EKG 69/Answers: Sinus Pauses in Long-Term Monitoring Abstract. While the indication for a pacemaker therapy in patients with high-degree AV block or symptomatic bradycardias is straightforward in most cases, intermittent oligo- and asymptomatic sinus bradycardias and pauses turn out to be more challenging. In this case report potential causes, diagnostic steps and possible therapies will be discussed.

[CME-EKG 69: Sinus Pauses in Long-Term Monitoring]. / CME-EKG 69: Sinuspausen im Monitoring CME-Fragen.

CME-EKG 69: Sinus Pauses in Long-Term Monitoring Abstract. While the indication for a pacemaker therapy in patients with high-degree AV block or symptomatic bradycardias is straightforward in most cases, intermittent oligo- and asymptomatic sinus bradycardias and pauses turn out to be more challenging. In this case report potential causes, diagnostic steps and possible therapies will be discussed.

[CME ECG 68/Answers: Gender Specificities in Heart Rhythm Disorders]. / CME-EKG 68/Antworten: Der Einfluss des Geschlechts bei Herzrhythmusstörungen.

CME ECG 68/Answers: Gender Specificities in Heart Rhythm Disorders Abstract. Sex differences in heart rhythm disorders have been described, especially due to differences of hormone status in women and men. In general, women do have a higher baseline heart rate than men and shorter refractory periods of most structures in the conduction system, except the ventricles. This is particularly apparent in paroxysmal supraventricular tachycardias. The incidence of a dual AV nodal physiology is the same in both sexes. However, an AV-nodal reentry tachycardia is much more frequent in women than in men. The embryonal disposition for an accessory pathway, as well as the resultant AV reentry tachycardia is more common in men than in women. Focal atrial tachycardias do not reveal a clear dominance between the sexes. Knowledge about sex-related differences in heart rhythm disorders are relevant for its diagnostics. Therefore, important aspects will be discussed in this article.

[CME ECG 68: Gender Specificities in Heart Rhythm Disorders]. / CME-EKG 68: Der Einfluss des Geschlechts bei Herzrhythmusstörungen.

CME ECG 68: Gender Specificities in Heart Rhythm Disorders Abstract. Sex differences in heart rhythm disorders have been described, especially due to differences of hormone status in women and men. In general, women do have a higher baseline heart rate than men and shorter refractory periods of most structures in the conduction system, except the ventricles. This is particularly apparent in paroxysmal supraventricular tachycardias. The incidence of a dual AV nodal physiology is the same in both sexes. However, an AV-nodal reentry tachycardia is much more frequent in women than in men. The embryonal disposition for an accessory pathway, as well as the resultant AV reentry tachycardia is more common in men than in women. Focal atrial tachycardias do not reveal a clear dominance between the sexes. Knowledge about sex-related differences in heart rhythm disorders are relevant for its diagnostics. Therefore, important aspects will be discussed in this article.

[CME ECG 67/Answers: Arrhythmia on Exertion]. / CME-EKG 67/Antworten: Arrhythmie bei Belastung.

CME ECG 67/Answers: Arrhythmia on Exertion Abstract. Ventricular tachycardias are potentially life-threatening cardiac arrhythmias with a heart rate >100 beats/min, originating from the specific conduction system below the His or the ventricular myocardium. The morphology of the surface ECG can provide valid information about the underlying mechanism and the associated cardiac disorder. The according pathomechanism is of paramount importance for further management. This article is intended to provide an insight into the various causes and treatment options as well as the differential diagnosis of ventricular tachycardias.

Impact of Genetic Variant Reassessment on the Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy Based on the 2010 Task Force Criteria.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy, which is associated with life-threatening ventricular arrhythmias. Approximately 60% of patients carry a putative disease-causing genetic variant, but interpretation of genetic test results can be challenging. The aims of this study were to systematically reclassify genetic variants in patients with ARVC and to assess the impact on ARVC diagnosis. METHODS: This study included patients from the Multicenter Zurich ARVC Registry who hosted a genetic variant deemed to be associated with the disease. Reclassification of pathogenicity was performed according to the modified 2015 American College of Medical Genetics criteria. ARVC diagnosis (categories: definite, borderline, possible) based on the 2010 Task Force Criteria was reclassified after genetic readjudication. RESULTS: In 79 patients bearing 80 unique genetic variants, n=47 (58.8%) genetic variants were reclassified, and reclassification was judged to be clinically relevant in n=33 (41.3%). Variants in plakophilin-2 (PKP2) were shown to reclassify less frequently as compared with other genes (PKP2, n=1, 8.3%; desmosomal non-PKP2, n=20, 66.7%; nondesmosomal, n=26, 68.4%; P=0.001for overall comparison; PKP2 versus desmosomal non-PKP2, P=0.001; PKP2 versus nondesmosomal, P<0.001). Genetic reclassification impacted ARVC diagnosis. Eight patients (10.1%) were downgraded from definite to borderline/possible disease at the time of initial genetic testing as well as last follow-up, respectively. Separate genetic reclassification in family members led to downgrading of n=5 (38.5%) variants. CONCLUSIONS: Given that approximately half of genetic variants were reclassified, with 10.1% of patients losing their definite disease status, accurate determination of variant pathogenicity is of utmost importance in the diagnosis of ARVC.

[CME ECC 67: Arrhythmia on Exertion]. / CME-EKG 67: Arrhythmie bei Belastung.

CME ECC 67: Arrhythmia on Exertion Abstract. Ventricular tachycardias are potentially life-threatening cardiac arrhythmias with a heart rate >100 beats/min, originating from the specific conduction system below the His or the ventricular myocardium. The morphology of the surface ECG can provide valid information about the underlying mechanism and the associated cardiac disorder. The according pathomechanism is of paramount importance for further management. This article is intended to provide an insight into the various causes and treatment options as well as the differential diagnosis of ventricular tachycardias.

[CME ECC 65: The Athlete's ECG]. / CME-EKG 65: Das Sportler-EKG CME-Fragen.

CME ECC 65: The Athlete's ECG Abstract. Regular, intensive training in athletes causes a modulation of the heart due to higher vagal tone and emerging hypertrophy. To assess these changes, which can be seen in an athlete's ECG as well, an international group of experts constituted contemporary standards for ECG interpretation in athletes, the "Seattle Criteria" which are discussed in this article: Athletes often have a physiologic sinus bradycardia with a heart rate between 30 and 60 bpm and a pronounced respiratory arrhythmia. A junctional rhythm with retrograde depolarisation of the atria frequently occurs as well, especially at rest. Early repolarisation is also an occasional phenomenon in athletes. Depending on its morphology and the history of the athlete it may be regarded as physiologic. This article shall help to evaluate an athlete's ECG in a physician's routine.