Prevalence and clinical correlates of exercise-induced ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy.

Exercise has a deleterious effect on the phenotypic expression of arrhythmogenic right ventricular cardiomyopathy (ARVC) and increases the risk of sudden death. The aim of the study was to determine the prevalence and correlates of exercise-induced arrhythmias during exercise tolerance test (ETT) in patients with ARVC. Between 2010 and 2019, 30 (47% males, mean age 42 ± 12 years) consecutive patients with a definite diagnosis of ARVC underwent a full genotypic and phenotypic characterization at our center. Exercise-induced arrhythmic response (EIAR) was defined by the development of complex or repetitive ventricular arrhythmias after stage 2 of exercise. A heart rate ≥ 85% of predicted was achieved by 23 (77%) patients. In 16 (53%) cases, a desmosomal pathogenic variant was found [most commonly PKP2 (n = 7) and DSP (n = 3)]. In 12 (40%) cases, an EIAR was observed. In 2 (6%) patients, ETT was interrupted due to the onset of ventricular tachycardia (sustained with a LBBB/inferior axis pattern in one case, and non-sustained LBBB/superior axis pattern in the other). Mean body surface area (BSA)-indexed left ventricular (LV) end-diastolic volumes (EDV) were higher in the EIAR group (92 ± 12 ml/m2 vs 80 ± 7 ml/m2, p = 0.002), as well as right ventricular EDV/BSA (110 ± 18 ml/m2 vs 91 ± 27 ml/m2, p = 0.04). Subepicardial/mid-wall LV late gadolinium enhancement (LGE) was more common in the EIAR group (67% vs 22%, p = 0.01). ARVC patients commonly exhibit exercise-induced ventricular arrhythmias. Patients with more significant RV remodeling and LV involvement (based on the presence of LV dilatation and LGE) appear more susceptible to exercise-induced arrhythmias.

Clinical effectiveness of a dedicated cardiac resynchronization therapy pre-assessment clinic incorporating cardiac magnetic resonance imaging and cardiopulmonary exercise testing on patient selection and outcomes.

BACKGROUND: Pre-procedural assessment of patients undergoing cardiac resynchronization therapy (CRT) is heterogenous and patients implanted with unfavorable characteristics may account for non-response. A dedicated CRT pre-assessment clinic (CRT PAC) was developed to standardize the review process and undertake structured pre-procedural evaluation. The aim of this analysis was to determine the effectiveness on patient selection and outcomes. METHODS: A prospective database of consecutive patients attending the CRT PAC between 2013 and 2018 was analyzed. Pre-operative assessment included cardiac magnetic resonance (CMR) and cardiopulmonary exercise testing (CPET). Patients were considered CRT responders based on improvement in clinical composite score (CCS) and/or reduction in left ventricular end-systolic volume (LVESV) ≥ 15% at 6-months follow-up. RESULTS: Of 252 patients reviewed in the CRT PAC during the analysis period, 192 fulfilled consensus guidelines for implantation. Of the patients receiving CRT, 82% showed improvement in their CCS and 57% had a reduction in LVESV ≥ 15%. The presence of subendocardial scar on CMR and a peak VO2 ≤ 12 ml/kg/min on CPET predicted CRT non-response. Two patients were unsuitable for CRT as they had end-stage heart failure and died during follow-up. The majority of patients initially deemed unsuitable for CRT did not suffer from unexpected hospitalization for decompensated heart failure or died from cardiovascular disease; only 8 patients (13%) received CRT devices during follow-up because of symptomatic left ventricular systolic impairment. CONCLUSION: A dedicated CRT PAC is able to appropriately select patients for CRT. Pre-procedural investigation/imaging can identify patients unlikely to respond to, or may not yet be suitable for CRT.

Cardiac magnetic resonance in patients with ARVC and family members: the potential role of native T1 mapping.

Left ventricular (LV) involvement in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) is not evaluated in the revised Task Force Criteria, possibly leading to underdiagnosis. This study explored the diagnostic role of myocardial native T1 mapping in patients with ARVC and their first-degree relatives. Thirty ARVC patients (47% males, mean age 45 ± 27 years) and 59 first-degree relatives not meeting diagnostic criteria underwent CMR with native T1 mapping. C MR was abnormal in 26 (87%) patients with ARVC. The right ventricle was affected in isolation in 13 (43%) patients. Prior to T1 mapping assessment, 2 (7%) patients exhibited isolated LV involvement and 11 (36%) patients showed features of biventricular disease. Left ventricular involvement was manifest as detectable LV late gadolinium enhancement (LGE) in 12 out of 13 cases. According to pre-specified inter-ventricular septal (IVS) T1 mapping thresholds, 11 (37%) patients revealed raised native T1 values including 5 out of the 17 patients who would otherwise have been classified as exhibiting a normal LV by conventional imaging parameters. Native septal T1 values were elevated in 22 (37%) of the 59 first-degree relatives included. Biventricular involvement is commonly observed in ARVC; native myocardial T1 values are raised in more than one third of patients, including a significant proportion of cases that would have been otherwise classified as exhibiting a normal LV using conventional CMR techniques. The significance of abnormal T1 values in first-degree relatives at risk will need validation through longitudinal studies.

Electrocardiographic differentiation between 'benign T-wave inversion' and arrhythmogenic right ventricular cardiomyopathy.

AIMS: To characterize the most common electrocardiographic (ECG) abnormalities in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), including anterior T-wave inversion (TWI) and to compare the characteristics of TWI in patients with ARVC and in a cohort of young healthy athletes and sedentary individuals. METHODS AND RESULTS: The study population consisted of 162 patients with a definite diagnosis of ARVC and 129 young controls with anterior TWI. Cardiac disease was excluded in all controls after a comprehensive diagnostic work-up. The ECG was abnormal in 131 patients with ARVC (81%). Abnormalities included anterior TWI (n = 82, 51%), QRS duration ratio V2:V5 >1.2 (n = 51, 31%), prolonged terminal S wave activation duration in V2 >55 ms (n = 42, 26%), inferior TWI (n = 30, 18%), and lateral TWI (n = 26, 16%). The J-point preceding anterior TWI was <0.1 mV in 80/82 (98%) patients with ARVC and in 98 (76%) controls. Among the ARVC patients with anterior TWI, 62 (77%) showed at least one additional abnormal feature, most commonly QRS duration ratio V2:V5 > 1.2 (52%) and inferior or lateral TWI (47%). CONCLUSION: The ECG is frequently abnormal in patients with ARVC and anterior TWI is the most common feature. Anterior TWI is usually accompanied by other abnormalities in ARVC, which are uncommon in healthy individuals. J point <0.1 mV preceding anterior TWI is not specific to ARVC and is observed in the majority of healthy individuals, including athletes, indicating a limited role for differentiating physiology or normal variants from ARVC.

Percutaneous Revascularization for Ischemic Ventricular Dysfunction: Rationale and Design of the REVIVED-BCIS2 Trial: Percutaneous Coronary Intervention for Ischemic Cardiomyopathy.

OBJECTIVES: Evaluate whether PCI in combination with optimal medical therapy (OMT) will reduce all-cause death and hospitalization for HF compared to a strategy of OMT alone. BACKGROUND: Ischemic cardiomyopathy (ICM) is the most common cause of heart failure (HF) and is associated with significant mortality and morbidity. Surgical revascularization has been shown to improve long-term outcomes in some patients, but surgery itself carries a major early hazard. Percutaneous coronary intervention (PCI) may allow a better balance between risk and benefit. METHODS: REVIVED-BCIS2 is a prospective, multi-center, open-label, randomized controlled trial, funded by the National Institute for Health Research in the United Kingdom. Follow-up will be for at least 2 years from randomization. Secondary outcomes include left ventricular ejection fraction (LVEF), quality of life scores, appropriate implantable cardioverter defibrillator therapy and acute myocardial infarction. Patients with LVEF ≤35%, extensive coronary disease and demonstrable myocardial viability are eligible for inclusion and those with a myocardial infarction within 4 weeks, decompensated HF or sustained ventricular arrhythmias within 72 h are excluded. A trial of 700 patients has more than 85% power to detect a 30% relative reduction in hazard. RESULTS: A total of 400 patients have been enrolled to date. CONCLUSIONS: International guidelines do not provide firm recommendations on the role of PCI in managing severe ICM, because of a lack of robust evidence. REVIVED-BCIS2 will provide the first randomized data on the efficacy and safety of PCI in ICM and has the potential to inform guidelines pertaining to both revascularization and HF. (Study of Efficacy and Safety of Percutaneous Coronary Intervention to Improve Survival in Heart Failure [REVIVED-BCIS2]; NCT01920048) (REVascularisation for Ischaemic VEntricular Dysfunction; ISRCTN45979711).

T1 and T2 Mapping in Recognition of Early Cardiac Involvement in Systemic Sarcoidosis.

Purpose To determine whether quantitative tissue characterization with T1 and T2 mapping supports recognition of myocardial involvement in patients with systemic sarcoidosis. Materials and Methods Fifty-three consecutive patients with a biopsy-proven extracardiac diagnosis of systemic sarcoidosis (21 men; median age, 45 years; interquartile range, 22 years) and 36 normotensive previously healthy control subjects (14 men; median age, 43 years; interquartile range, 18 years) underwent cardiovascular magnetic resonance imaging, which was performed to assess cardiac function and late gadolinium enhancement, and T1 and T2 mapping. A follow-up substudy was performed in 40 patients (mean follow-up interval, 144 days ± 35 [standard deviation]); of these 40 patients, 18 underwent anti-inflammatory treatment for systemic symptoms. Binary logistic regression and receiver operating characteristic curve analyses were used to assess discrimination between health and disease; Wilcoxon signed rank test was used to assess the effect of treatment. Results When compared with control subjects, patients had higher ventricular volume, higher myocardial native T1 and T2, and lower longitudinal strain and ejection fraction (P < .05 for all). Myocardial native T1 and T2 had higher discriminatory accuracy (area under the receiver operating characteristic curve [AUC]: 0.96 and 0.89, respectively) for separation between control subjects and patients when compared with the standard diagnostic criteria (AUC < 0.67). Native T1 was the independent discriminator between health and disease (specificity, 90%; sensitivity, 96%; accuracy, 94%). There was a significant reduction of native T1 and T2 in the patients who underwent treatment (z score: -3.72 and -2.88; P < .01) but not in the patients who did not (z score, -1.42 and -1.38; P > .15). Conclusion Quantitative myocardial tissue characterization with T1 and T2 mapping may enable noninvasive recognition of cardiac involvement and activity of myocardial inflammation in patients with systemic sarcoidosis. Future studies will be performed to confirm their role in risk stratification and guidance of clinical management. © RSNA, 2017 Online supplemental material is available for this article.

Clinical Differentiation Between Physiological Remodeling and Arrhythmogenic Right Ventricular Cardiomyopathy in Athletes With Marked Electrocardiographic Repolarization Anomalies.

BACKGROUND: Physiological cardiac adaptation to regular exercise, including biventricular dilation and T-wave inversion (TWI), may create diagnostic overlap with arrhythmogenic right ventricular cardiomyopathy (ARVC). OBJECTIVES: The goal of this study was to assess the accuracy of diagnostic criteria for ARVC when applied to athletes exhibiting electrocardiographic TWI and to identify discriminators between physiology and disease. METHODS: The study population consisted of athletes with TWI (n = 45), athletes without TWI (n = 35), and ARVC patients (n = 35). Subjects underwent electrocardiography (ECG), signal-averaged electrocardiography (SAECG), echocardiography, cardiac magnetic resonance imaging (CMRI), Holter monitoring, and exercise testing. RESULTS: There were no electrical, structural, or functional cardiac differences between athletes exhibiting TWI and athletes without TWI. When athletes were compared with ARVC patients, markers of physiological remodeling included early repolarization, biphasic TWI, voltage criteria for right ventricular (RV) or left ventricular hypertrophy, and symmetrical cardiac enlargement. Indicators of RV pathology included the following: syncope; Q waves or precordial QRS amplitudes <1.8 mV; 3 abnormal SAECG parameters; delayed gadolinium enhancement, RV ejection fraction ≤45%, or wall motion abnormalities at CMRI; >1,000 ventricular extrasystoles (or >500 non-RV outflow tract) per 24 h; and symptoms, ventricular tachyarrhythmias, or attenuated blood pressure response during exercise. Nonspecific parameters included the following: prolonged QRS terminal activation; ≤2 abnormal SAECG parameters; RV dilation without wall motion abnormalities; RV outflow tract ectopy; and exercise-induced T-wave pseudonormalization. CONCLUSIONS: TWI and balanced biventricular dilation are likely to represent benign manifestations of training in asymptomatic athletes without relevant family history. Diagnostic criteria for ARVC are nonspecific in such individuals. Comprehensive testing using widely available techniques can effectively differentiate borderline cases.

An insight into transcatheter aortic valve implantation-a perspective from multidetector-computed tomography.

Transcatheter aortic valve implantation (TAVI) has now become an acceptable alternative to surgical aortic valve replacement for patients with severe aortic stenosis at high risk. The early enthusiasm for this technology has not diminished but rather has developed at an unprecedented rate over the last decade. Alongside the developments in implantation technique, transcatheter design, and postprocedural care, cardiac imaging modalities have also had to concurrently evolve to meet the perpetual demand for lower peri- and postprocedural complication rates. Although transthoracic and transesophageal echocardiography remain vital in patient's selection and periprocedural guidance, there is now emerging evidence that indicates that multidetector-computed tomography (MDCT) may also have an equally important role to play. The aim of the current review is to examine the modern role of MDCT in assessing patients with aortic stenosis being considered for TAVI.

A simultaneous X-Ray/MRI and noncontact mapping study of the acute hemodynamic effect of left ventricular endocardial and epicardial cardiac resynchronization therapy in humans.

BACKGROUND: Cardiac resynchronization therapy (CRT) using endocardial left ventricular (LV) pacing may be superior to conventional CRT. We studied the acute hemodynamic response to conventional CRT and LV pacing from different endocardial sites using a combined cardiac MRI and LV noncontact mapping (NCM) protocol to gain insights into the underlying mechanisms. METHODS AND RESULTS: Fifteen patients (age, 63 ± 10 years; 12 men) awaiting CRT were studied in a combined x-ray and MRI laboratory. Delayed-enhancement cardiac magnetic resonance was performed to define areas of myocardial fibrosis. Patients underwent an electrophysiological study incorporating endocardial and epicardial LV pacing. Acute hemodynamic response was measured using a pressure wire within the LV cavity to derive LV dP/dt max. NCM was used to define areas of slow conduction. There was a significant improvement in all LV pacing modes versus baseline (P<0.001). LV endocardial CRT from the best endocardial site was superior to conventional CRT, with a 79.8 ± 49.0% versus 59.6 ± 49.5% increase in LV dP/dt max of from baseline (P<0.05). The hemodynamic benefits of pacing were greater when LV stimulation was performed outside of areas of slow conduction defined by NCM (P<0.001). Delayed-enhancement cardiac magnetic resonance was able to delineate zones of slow conduction seen with NCM in ischemic patients but was unreliable in nonischemic patients. CONCLUSIONS: Endocardial LV pacing appears superior to conventional CRT, although the optimal site varies between subjects and is influenced by pacing within areas of slow conduction. Delayed-enhancement cardiac magnetic resonance was a poor predictor of zones of slow conduction in nonischemic patients.

Prevalence of desmosomal protein gene mutations in patients with dilated cardiomyopathy.

BACKGROUND: Idiopathic dilated cardiomyopathy is a familial disorder in 25% to 50% of patients, but the genetic basis in the majority of cases remains unknown. Genes encoding desmosomal proteins, currently regarded as synonymous with another disorder, arrhythmogenic right ventricular cardiomyopathy, are known to cause left ventricular dysfunction, but their importance in unselected patients with unequivocal dilated cardiomyopathy is unknown. The objective of this study was to determine the prevalence of mutations in 5 desmosomal protein genes in patients with dilated cardiomyopathy. METHODS AND RESULTS: We studied 100 unrelated patients with idiopathic dilated cardiomyopathy consecutively referred to a dedicated cardiomyopathy unit. Patients underwent clinical evaluation, ECG, echocardiography, exercise testing, 24-hour ambulatory ECG monitoring, and mutation screening of 5 genes implicated in arrhythmogenic right ventricular cardiomyopathy: plakoglobin, desmoplakin, plakophilin-2, desmoglein-2, and desmocollin-2. Of the 100 patients (mean age at evaluation, 46.8+/-13.8 years; range, 17.0 to 72.8 years; male sex, 63%), 5 were found to carry pathogenic desmosomal protein gene mutations. An additional 13 patients had sequence variants of uncertain pathogenic significance and were excluded from further comparative analysis. Patients harboring desmosomal gene mutations had a phenotype indistinguishable from the 82 noncarriers, with the exception of exercise-induced ventricular ectopy, which was more frequent in the desmosomal mutation carriers (P=0.033). None of the 5 carriers of desmosomal mutations fulfilled current diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy, but 1 had fibrofatty change in the left ventricle at autopsy. CONCLUSIONS: Heart failure caused by a dilated, poorly contracting left ventricle and arrhythmogenic right ventricular cardiomyopathy have been considered distinct clinicopathologic entities. This study suggests that both clinical presentations can be caused by mutations in desmosomal protein genes.

A cardiac sonographer led follow up clinic for heart valve disease.

INTRODUCTION: This study describes the effect of introducing a cardiac sonographer led follow up clinic for patients with stable heart valve disease. The 2 years before and after the instigation of the valve clinic were audited. MATERIALS AND METHODS: The clinic was conducted in a single centre and undertaken in the cardiology department of a district general hospital. 382 patients, with 397 clinically significant valve lesions, but for whom surgery was not yet indicated but follow up required, were seen in a cardiac sonographer run clinics. These patients no longer attended a medical follow up clinic unless there was clinical or echocardiographic deterioration. Effectiveness was judged by the percentage treated according to current best practice guidelines, the number of echocardiograms performed and the number of hospital out patient visits attended. In addition mortality data for the subjects in the clinic was collected. RESULTS: The proportion followed up according to best practice guidelines rose from 157 (41%) to 354 (92%) (p<0.01). The total number of echocardiograms performed fell from 807 to 550. Total number of out patient visits fell from 998 to 31. 11 patients died in the two year study period, none from progressive valve disease. DISCUSSION: This study demonstrates that a protocol driven sonographer led heart valve disease follow up clinic, significantly improved the quality of follow up while bringing about a major reduction in out patients visits, without compromising patient safety.

Regional ventricular dynamics during acute coronary occlusion: a comparison of invasive with non-invasive echocardiographic markers to detect and quantify myocardial ischaemia-observations made during off-pump coronary surgery.

OBJECTIVES: To investigate the performance of non-invasive markers used in stress echocardiography to detect the presence and depth of myocardial ischaemia. We therefore sought to compare these non-invasive markers during acute coronary occlusion in humans. METHODS: 27 patients with stable angina and normal LV cavity size were studied during off-pump coronary artery bypass grafting to the left anterior descending coronary artery using transoesophageal echocardiography and simultaneous high fidelity LV pressure. Regional power development of the anterior wall was plotted throughout the cardiac cycle, allowing the measurement of its time course, peak value and time integral (intrinsic work). Regional effective myocardial work was calculated and its reduction during acute occlusion was used as the invasive standard for ischaemic dysfunction. RESULTS: In all patients acute coronary occlusion led to a delay in the onset of regional wall thickening which persisted after aortic valve closure. These time intervals of myocardial thickening had the highest qualitative concordance with the gold standard of a fall in effective work. Regression models identified three significant predictors of the depth of myocardial ischaemia; the interval from Q wave to the onset of regional thickening, duration of post-ejection thickening and peak thickening rate. Objective wall thickening and thinning rates were not significant predictors. CONCLUSIONS: The regional timing of myocardial thickening and peak thickening rate accurately predicted the presence and indicated the depth of local ischaemia during acute coronary occlusion. These markers may complement subjective wall motion scores aimed at predicting the presence of epicardial coronary artery disease. CONDENSED ABSTRACT: We compared non-invasive markers commonly used in stress echocardiography using measurements of the fall in regional myocardial work with coronary occlusion as a standard. 27 patients were studied using transoesophageal echocardiography and simultaneous high fidelity left ventricular pressure during off-pump coronary surgery. Delayed myocardial thickening had the highest qualitative concordance with the gold standard of a fall in effective work, while regression models identified three significant predictors; the interval Q wave to the onset of regional thickening, duration of post-ejection thickening and peak thickening rate. These markers may complement current non-invasive indices of ischaemia during clinical stress testing.

Characteristics of ischaemic human myocardium: a transoesophageal echocardiographic and voltammetric microelectrode study.

Delayed local myocardial power development (primary asynchrony) has been suggested as a marker of ischaemic ventricular dysfunction in humans. However, to prove this, microcirculatory perfusion, microcirculatory oxygenation, and intrinsic mechanical function of the same asynchronous myocardial segment should be studied simultaneously before and after revascularisation. We performed a prospective intraoperative study of 15 patients (age 67 [SD 5] years) at baseline and 30 min after left anterior descending artery grafting. Local tissue perfusion and oxygenation of the anterior left ventricular wall were quantified with a voltammetric microelectrode technique. Transesophageal M-mode echocardiograms and simultaneous high-fidelity left ventricular pressure were measured. Eight patients showed primary asynchrony and 7 did not. Patients with primary asynchrony had local mechanical depression with lower resting values of myocardial work and peak power which increased with surgery. In this group, resting perfusion consistently increased with surgery (32.1 [13] to 54 [31] ml min(-1) 100 g(-1), P < 0.05). In the remaining patients, local work and power were normal, and resting perfusion was consistently higher (90 [9] Ml min(-1) 100 g(-1), P < 0.05 vs primary asynchrony), and fell with surgery. Local tissue oxygen tension was similar in both groups (38 vs 44 mmHg) and did not change with surgery. In patients with chronic coronary artery disease, microcirculatory perfusion, but not pO2, is reduced in regions showing primary asynchrony and impaired mechanical function. Abnormalities in both mechanical function and perfusion normalise within 30 min of revascularisation. These data provide further evidence that primary asynchrony is not only a marker of chronic ischemic ventricular dysfunction, but is associated with a modified contraction pattern in which normal oxygen tension coexists with reduced perfusion.

Chronic stable ischaemia protects against myocyte damage during beating heart coronary surgery.

OBJECTIVES: Many patients with coronary artery disease demonstrate chronic resting ischaemic myocardial dysfunction. We have investigated whether this ischaemia influences the myocardial damage caused by the period of coronary occlusion involved in beating heart surgery. METHODS: Thirty-three patients with chronic stable angina and normal left ventricular ejection fraction were studied. To make our model clinically appropriate, we included patients with a wide range of ischaemic times, ages and in a subset of 10 patients a surgical preconditioning protocol. Myocyte injury was assessed from venous Troponin T release measured on days 1, 2, and 3. We used intraoperative transoesophageal M mode echocardiograms and simultaneous high-fidelity left ventricular pressure to assess whether patients were demonstrating the functional effects of ischaemia (asynchronous regional contraction with reduced mechanical function). RESULTS: Patients demonstrated the functional effects of resting ischaemia and 17 did not. Patients with resting ischaemia had lower preoperative values of regional peak power and work and all three variables increased significantly with surgery. Venous Troponin T levels at 48 and 72 h postoperatively were lower in those with preoperative resting ischaemia (median (interquartile range) 0.13 (0.08-0.20) vs 0.21 (0.13-0.69) for 48 h and 0.10 (0.08-0.19) vs 0.26 (0.12-0.51) for 72 h). Stepwise multiple linear regression of total postoperative troponin release (measured as the area under the curve of troponin release) demonstrated two independent determinants (R squared for model 0.40): longer ischaemic time, and increasing values of cycle efficiency. The surgical ischaemic preconditioning protocol and preoperative collaterals were not independent determinants. CONCLUSIONS: In patients with chronic coronary artery disease, stable preoperative ischaemia may thus represent a naturally occurring form of myocardial protection, whose presence reduces Troponin T release after beating heart surgery. This protection is different in nature from classical ischaemic preconditioning.