Utility of Left and Right Ventricular Strain in Arrhythmogenic Right Ventricular Cardiomyopathy: A Prospective Multicenter Registry.

BACKGROUND: Imaging evaluation of arrhythmogenic right ventricular cardiomyopathy (ARVC) remains challenging. Myocardial strain assessment by echocardiography is an increasingly utilized technique for detecting subclinical left ventricular (LV) and right ventricular (RV) dysfunction. We aimed to evaluate the diagnostic and prognostic utility of LV and RV strain in ARVC. METHODS: Patients with suspected ARVC (n = 109) from a multicenter registry were clinically phenotyped using the 2010 ARVC Revised Task Force Criteria and underwent baseline strain echocardiography. Diagnostic performance of LV and RV strain was evaluated using the area under the receiver operating characteristic curve analysis against the 2010 ARVC Revised Task Force Criteria, and the prognostic value was assessed using the Kaplan-Meier analysis. RESULTS: Mean age was 45.3±14.7 years, and 48% of patients were female. Estimation of RV strain was feasible in 99/109 (91%), and LV strain was feasible in 85/109 (78%) patients. ARVC prevalence by 2010 ARVC Revised Task Force Criteria is 91/109 (83%) and 83/99 (84%) in those with RV strain measurements. RV global longitudinal strain and RV free wall strain had diagnostic area under the receiver operating characteristic curve of 0.76 and 0.77, respectively (both P<0.001; difference NS). Abnormal RV global longitudinal strain phenotype (RV global longitudinal strain > -17.9%) and RV free wall strain phenotype (RV free wall strain > -21.2%) were identified in 41/69 (59%) and 56/69 (81%) of subjects, respectively, who were not identified by conventional echocardiographic criteria but still met the overall 2010 ARVC Revised Task Force Criteria for ARVC. LV global longitudinal strain did not add diagnostic value but was prognostic for composite end points of death, heart transplantation, or ventricular arrhythmia (log-rank P=0.04). CONCLUSIONS: In a prospective, multicenter registry of ARVC, RV strain assessment added diagnostic value to current echocardiographic criteria by identifying patients who are missed by current echocardiographic criteria yet still fulfill the diagnosis of ARVC. LV strain, by contrast, did not add incremental diagnostic value but was prognostic for identification of high-risk patients.

The Cardiovascular Physical Examination - Is It Still Relevant?

Advances in technology have reshaped the practice of medicine. These changes have greatly benefited our patients. However, in the setting of these advances, the importance of basic clinical tools is more pertinent than ever. Despite the growing reliance on technology, the physical exam remains valuable and cost effective, often enabling the well-trained clinician to arrive at the diagnosis, rapidly and accurately. The physical exam must not become a relic of a distant past. We aim to investigate current competency and proficiency, proposals for change in teaching curriculums, and the relationship with technology such as hand-held echocardiography. A skillful exam provides both emotional and intellectual satisfaction. It may be a lost art but it is well worth the effort to restore.

2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy: Executive summary.

Arrhythmogenic cardiomyopathy (ACM) is an arrhythmogenic disorder of the myocardium not secondary to ischemic, hypertensive, or valvular heart disease. ACM incorporates a broad spectrum of genetic, systemic, infectious, and inflammatory disorders. This designation includes, but is not limited to, arrhythmogenic right/left ventricular cardiomyopathy, cardiac amyloidosis, sarcoidosis, Chagas disease, and left ventricular noncompaction. The ACM phenotype overlaps with other cardiomyopathies, particularly dilated cardiomyopathy with arrhythmia presentation that may be associated with ventricular dilatation and/or impaired systolic function. This expert consensus statement provides the clinician with guidance on evaluation and management of ACM and includes clinically relevant information on genetics and disease mechanisms. PICO questions were utilized to evaluate contemporary evidence and provide clinical guidance related to exercise in arrhythmogenic right ventricular cardiomyopathy. Recommendations were developed and approved by an expert writing group, after a systematic literature search with evidence tables, and discussion of their own clinical experience, to present the current knowledge in the field. Each recommendation is presented using the Class of Recommendation and Level of Evidence system formulated by the American College of Cardiology and the American Heart Association and is accompanied by references and explanatory text to provide essential context. The ongoing recognition of the genetic basis of ACM provides the opportunity to examine the diverse triggers and potential common pathway for the development of disease and arrhythmia.

Ankyrin-B dysfunction predisposes to arrhythmogenic cardiomyopathy and is amenable to therapy.

Arrhythmogenic cardiomyopathy (ACM) is an inherited arrhythmia syndrome characterized by severe structural and electrical cardiac phenotypes, including myocardial fibrofatty replacement and sudden cardiac death. Clinical management of ACM is largely palliative, owing to an absence of therapies that target its underlying pathophysiology, which stems partially from our limited insight into the condition. Following identification of deceased ACM probands possessing ANK2 rare variants and evidence of ankyrin-B loss of function on cardiac tissue analysis, an ANK2 mouse model was found to develop dramatic structural abnormalities reflective of human ACM, including biventricular dilation, reduced ejection fraction, cardiac fibrosis, and premature death. Desmosomal structure and function appeared preserved in diseased human and murine specimens in the presence of markedly abnormal ß-catenin expression and patterning, leading to identification of a previously unknown interaction between ankyrin-B and ß-catenin. A pharmacological activator of the WNT/ß-catenin pathway, SB-216763, successfully prevented and partially reversed the murine ACM phenotypes. Our findings introduce what we believe to be a new pathway for ACM, a role of ankyrin-B in cardiac structure and signaling, a molecular link between ankyrin-B and ß-catenin, and evidence for targeted activation of the WNT/ß-catenin pathway as a potential treatment for this disease.

2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is an arrhythmogenic disorder of the myocardium not secondary to ischemic, hypertensive, or valvular heart disease. ACM incorporates a broad spectrum of genetic, systemic, infectious, and inflammatory disorders. This designation includes, but is not limited to, arrhythmogenic right/left ventricular cardiomyopathy, cardiac amyloidosis, sarcoidosis, Chagas disease, and left ventricular noncompaction. The ACM phenotype overlaps with other cardiomyopathies, particularly dilated cardiomyopathy with arrhythmia presentation that may be associated with ventricular dilatation and/or impaired systolic function. This expert consensus statement provides the clinician with guidance on evaluation and management of ACM and includes clinically relevant information on genetics and disease mechanisms. PICO questions were utilized to evaluate contemporary evidence and provide clinical guidance related to exercise in arrhythmogenic right ventricular cardiomyopathy. Recommendations were developed and approved by an expert writing group, after a systematic literature search with evidence tables, and discussion of their own clinical experience, to present the current knowledge in the field. Each recommendation is presented using the Class of Recommendation and Level of Evidence system formulated by the American College of Cardiology and the American Heart Association and is accompanied by references and explanatory text to provide essential context. The ongoing recognition of the genetic basis of ACM provides the opportunity to examine the diverse triggers and potential common pathway for the development of disease and arrhythmia.

Epsilon wave: A review of historical aspects.

The epsilon wave of the electrocardiogram (ECG) together with fragmented QRS (fQRS), the terminal conduction delay, incomplete right bundle branch block (IRBBB) and complete/advanced RBBB (CRBBB) of peripheral origin are part of a spectrum of ventricular depolarization abnormalities of arrhythmogenic cardiomyopathy(AC). Although the epsilon wave is considered a major diagnostic criterion for AC since 2010 (AC Task Force Criteria), its diagnostic value is limited because it is a sign of the later stage of the disease. It would be more appropriate to say that the epsilon wave is a "hallmark" of AC, but is of low diagnostic sensitivity. Although the epsilon wave has high specificity for AC, it can be present in other pathological conditions. In this update we will cover the nomenclature, association with disease states and electrocardiographic aspects of the epsilon wave.

Vagal Mediation of Low-Frequency Heart Rate Variability During Slow Yogic Breathing.

OBJECTIVE: Changes in heart rate variability (HRV) associated with breathing (respiratory sinus arrhythmia) are known to be parasympathetically (vagally) mediated when the breathing rate is within the typical frequency range (9-24 breaths per minute [bpm]; high-frequency HRV). Slow yogic breathing occurs at rates below this range and increases low-frequency HRV power, which may additionally reflect a significant sympathetic component. Yogic breathing techniques are hypothesized to confer health benefits by increasing cardiac vagal control, but increases in low-frequency HRV power cannot unambiguously distinguish sympathetic from parasympathetic contributions. The aim of this study was to investigate the autonomic origins of changes in low-frequency HRV power due to slow-paced breathing. METHODS: Six healthy young adults completed slow-paced breathing with a cadence derived from yogic breathing patterns. The paced breathing took place under conditions of sympathetic blockade, parasympathetic (vagal) blockade, and placebo. HRV spectral power was compared under 11 breathing rates during each session, in counterbalanced order with frequencies spanning the low-frequency range (4-9 bpm). RESULTS: HRV power across the low-frequency range (4-9 bpm) was nearly eliminated (p = .016) by parasympathetic blockade (mean (SD) spectral power at breathing frequency = 4.1 (2.1)) compared with placebo (69.5 (8.1)). In contrast, spectral power during sympathetic blockade 70.2 (9.1) and placebo (69.5 (8.1)) was statistically indistinguishable (p = .671). CONCLUSIONS: These findings clarify the interpretation of changes in HRV that occur during slow-paced breathing by showing that changes in low-frequency power under these conditions are almost entirely vagally mediated. Slow-paced breathing is an effective tool for cardiac vagal activation.

High incidence of ST-T changes in women during tilt-table testing.

INTRODUCTION: We have observed electrocardiographic (ECG) changes primarily in women during tilt table testing. METHODS: We reviewed 12 lead ECGs during tilt studies between 2012 and 2016 for changes in ST segments and T waves during tilt table testing. Patients with distinctly abnormal baseline ECGs were excluded. RESULTS: Of the 180 tilt studies, 117 (65%) were in women. There were 32 patients with ECG changes during tilting. Of these, 28 (87.5%) were in women with an average age of 45years. None had a history of CAD or exertional chest pain. Echocardiograms were available in 21 of the 28 women with tilt induced ECG changes and all were normal. ECG changes during tilt table testing were found in 4/64 (6.25%) of men. The occurrence of ST-T wave changes during tilt testing was significantly higher among women compared to men, with a p value of 0.008. Of the 28 women with ECG changes during tilt, 11 had T wave inversions alone. ST segment depression alone was noted in 7 women. There were 10 women who had both ST segment depression and T wave inversions. Changes occurred immediately upon tilting in 6. In the remaining, they occurred at an average of 4.8±4min after tilting. The slight increase in heart rate in patients with ECG changes was similar to that in the patients without new ECG changes. The ECG changes were not related to the presence of syncope. CONCLUSIONS: ECG changes during the testing was observed at a relatively high incidence primarily in women. The clinical significance of these repolarization changes during tilt testing is unknown. These ECG changes during tilt testing may correlate with the high incidence of false positive ECGs in women during exercise testing but do not necessarily indicate the presence of ischemic coronary disease. Additional research is needed to explain this phenomenon.

Risk Stratification in Arrhythmic Right Ventricular Cardiomyopathy Without Implantable Cardioverter-Defibrillators.

OBJECTIVES: The primary objective of this study is risk stratification of patients with arrhythmic right ventricular cardiomyopathy (ARVC). BACKGROUND: There is a need to identify those who need an automatic implantable defibrillator (ICD) to prevent sudden death. METHODS: This is an analysis of 88 patients with ARVC from three centers who were not treated with an ICD. RESULTS: Risk factors for subsequent arrhythmic deaths were pre-enrollment sustained or nonsustained ventricular tachycardia (VT) and decreased left ventricular function. CONCLUSION: These factors serve as proposed guidelines for implantation of an ICD in patients with ARVC to prevent sudden death.

Clinical Presentation and Outcomes by Sex in Arrhythmogenic Right Ventricular Cardiomyopathy: Findings from the North American ARVC Registry.

BACKGROUND: Sex differences in clinical presentation and outcomes of hereditary arrhythmias are commonly reported. We aimed to compare clinical presentation and outcomes in men and women with arrhythmogenic right ventricular cardiomyopathy (ARVC) enrolled in the North American ARVC Registry. METHODS: A total of 125 ARVC probands (55 females, mean age 38 ± 12; 70 males, mean age 41 ± 15) diagnosed, as either "affected" or "borderline" were included. Baseline clinical characteristics and time-dependent outcomes including syncope, ventricular tachycardia (VT), fast VT (>240 bpm), ventricular fibrillation (VF), and death were compared between males and females. RESULTS: The percentage of ARVC subjects diagnosed as "affected" (84% vs. 89%; P = 0.424) or "borderline" (16% vs. 11%; P = 0.424) was similar between females and males. Among the baseline characteristics, inverted T-waves in V2 trended to be more common in women (P = 0.09), whereas abnormal signal-averaged ECGs (SAECGs; P < 0.001) and inducible VT/VF (P = 0.026) were more frequent in men. During a mean follow-up of 37 ± 20 months, the probability of ICD-recorded VT/VF or death was not significantly different between men and women (P = 0.456). However, there was a trend toward lower risk of fast VT/VF or death in women compared to men (hazard ratio 0.41, 95% CI 0.151-1.113, P = 0.066). Abnormal SAECG and evidence of intramyocardial fat by cardiac MRI was associated with adverse outcomes in men (P = 0.006 and 0.02 respectively). CONCLUSION: In the North American ARVC Registry, we found similar frequency of "affected" and "borderline" subjects between men and women. Sex-related differences were observed in baseline ECG, SAECG, Holter-recorded ventricular arrhythmias, and VT inducibility. Men showed a trend toward greater risk of fast VT than women.

Arrhythmogenic Phenotype in Dilated Cardiomyopathy: Natural History and Predictors of Life-Threatening Arrhythmias.

BACKGROUND: Patients with dilated cardiomyopathy (DCM) may present with ventricular arrhythmias early in the disease course, unrelated to the severity of left ventricular dysfunction. These patients may be classified as having an arrhythmogenic DCM (AR-DCM). We investigated the phenotype and natural history of patients with AR-DCM. METHODS AND RESULTS: Two hundred eighty-five patients with a recent diagnosis of DCM (median duration of the disease 1 month, range 0 to 7 months) and who had Holter monitoring at baseline were comprehensively evaluated and followed for 107 months (range 29 to 170 months). AR-DCM was defined by the presence of ≥1 of the following: unexplained syncope, rapid nonsustained ventricular tachycardia (≥5 beats, ≥150 bpm), ≥1000 premature ventricular contractions/24 hours, and ≥50 ventricular couplets/24 hours, in the absence of overt heart failure. The primary end points were sudden cardiac death (SCD), sustained ventricular tachycardia (SVT), or ventricular fibrillation (VF). The secondary end points were death from congestive heart failure or heart transplantation. Of the 285 patients, 109 (38.2%) met criteria for AR-DCM phenotype. AR-DCM subjects had a higher incidence of SCD/SVT/VF compared with non-AR-DCM patients (30.3% vs 17.6%, P=0.022), with no difference in the secondary end points. A family history of SCD/SVT/VF and the AR-DCM phenotype were statistically significant and cumulative predictors of SCD/SVT/VF. CONCLUSIONS: One-third of DCM patients may have an arrhythmogenic phenotype associated with increased risk of arrhythmias during follow-up. A family history of ventricular arrhythmias in DCM predicts a poor prognosis and increased risk of SCD.