Non-Ischemic Scar Underlines Ventricular Arrhythmias in Kearns-Sayre Syndrome

Kearns-Sayre syndrome (KSS) is a rare mitochondrial disease in which cardiac involvement has been associated with poor prognosis. Although the most common clinical manifestation is progressive conduction system impairment, patients can suffer from ventricular arrhythmias. Yet, they show a high prevalence of sudden cardiac death, whose etiopathological mechanism is not completely understood. Cardiac magnetic resonance is a rising tool to detect subclinical heart involvement in many heart diseases and was recently able to detect nonischemic scar, which is an arrhythmogenic substrate, in patients affected by KSS

Ventricular arrhythmias in young competitive athletes: Prevalence, determinants, and underlying substrate

Whether ventricular arrhythmias (VAs) represent a feature of the adaptive changes of the athlete's heart remains elusive. We aimed to assess the prevalence, determinants, and underlying substrates of VAs in young competitive athletes.Background--Whether ventricular arrhythmias (VAs) represent a feature of the adaptive changes of the athlete's heart remains elusive. We aimed to assess the prevalence, determinants, and underlying substrates of VAs in young competitive athletes. Method and Results--We studied 288 competitive athletes (age range, 16-35 years; median age, 21 years) and 144 sedentary individuals matched for age and sex who underwent 12-lead 24-hour ambulatory electrocardiographic monitoring. VAs were evaluated in terms of number, complexity (ie, couplet, triplet, or nonsustained ventricular tachycardia), exercise inducibility, and morphologic features. Twenty-eight athletes (10%) and 13 sedentary individuals (11%) showed > 10 isolated premature ventricular beats (PVBs) or 651 complex VA (P=0.81). Athletes with > 10 isolated PVBs or 651 complex VA were older (median age, 26 versus 20 years; P=0.008) but did not differ with regard to type of sport, hours of training, and years of activity compared with the remaining athletes. All athletes with > 10 isolated PVBs or 651 complex VA had a normal echocardiographic examination; 17 of them showing > 500 isolated PVBs, exercise-induced PVBs, and/or complex VA underwent additional cardiac magnetic resonance, which demonstrated nonischemic left ventricular late gadolinium enhancement in 3 athletes with right bundle branch block PVBs morphologic features. Conclusions--The prevalence of > 10 isolated PVBs or 651 complex VA at 24-hour ambulatory electrocardiographic monitoring did not differ between young competitive athletes and sedentary individuals and was unrelated to type, intensity, and years of sports practice. An underlying myocardial substrate was uncommon and distinctively associated with right bundle branch block VA morphologic features

Coronary Collateral Circulation: A New Predictor of Mortality in Heart Transplant Recipients With Allograft Vasculopathy

Background: Coronary collateral arteries (CCAs) are anastomotic channels between vessels; although beneficial in atherosclerosis, their role in heart transplantation (HT) recipients is underinvestigated. CCAs initially develop as microcirculation and cardiac allograft vasculopathy (CAV), promoting immune-dependent proliferative angiogenic response, and play a role in their development. In our hypothesis, ischemia induced by coronary microvascular dysfunction (CMD) triggers the development of CCAs, which are, in turn, less functional as affected by CAV themselves. Methods: One hundred twenty-one patients receiving HT at our institution were retrospectively evaluated and were included if transthoracic echocardiography with coronary flow velocity reserve (CFVR) assessment and coronary angiography were performed. CMD was defined as CFVR of ≤2.5. Patients with CAV were enrolled, and their angiograms were reviewed to evaluate the presence of CCAs. Cardiovascular mortality was assessed as the main clinical outcome. Results: Forty patients were found to have CCAs. Patients with CCAs have lower CFVR than those without CCAs (2.22 ± 0.72 versus 2.69 ± 0.92;P = 0.003), reflecting in different rates of CMD in the 2 groups (72.5% versus 37%; P < 0.001). CMD is associated with higher CAV grades (P < 0.001), which are also associated with CCAs (P < 0.001). Patients with poorly developed CCAs have lower CFVR (P < 0.001). At multivariable analysis, CMD (P = 0.008) and higher CAV grades (P = 0.005) are independent predictors of CCAs. During the median follow-up time of 10.2 (6.6-13.3) y, patients with CCAs have been found to have higher mortality than those without CCAs (57.5% versus 32.1%; P = 0.007). CCAs are associated with a lower probability of survival also in patients with CMD (P < 0.001) and are independent predictors of mortality (P < 0.001). Conclusions: Our results demonstrate an interplay between CAV, CMD, and CCAs. We confirm that CAV is associated with CMD, and we show, for the first time, that CMD is associated with CCAs. CCAs are pathophysiologically associated with more severe graft vasculopathy and independently predict mortality after HT

Relationship between electrocardiographic findings and cardiac magnetic resonance phenotypes in arrhythmogenic cardiomyopathy

Background-\u2014The new designation of arrhythmogenic cardiomyopathy defines a broader spectrum of disease phenotypes, which include right dominant, biventricular, and left dominant variants. We evaluated the relationship between electrocardiographic findings and contrast-enhanced cardiac magnetic resonance phenotypes in arrhythmogenic cardiomyopathy. Methods and Results-\u2014We studied a consecutive cohort of patients with a definite diagnosis of arrhythmogenic cardiomyopathy, according to 2010 International Task Force criteria, who underwent electrocardiography and contrast-enhanced cardiac magnetic resonance. Both depolarization and repolarization electrocardiographic abnormalities were correlated with the severity of dilatation/dysfunction, either global or regional, of both ventricles and the presence and regional distribution of late gadolinium enhancement. The study population included 79 patients (60% men). There was a statistically significant relationship between the presence and extent of T-wave inversion across a 12-lead ECG and increasing values of median right ventricular (RV) end-diastolic volume (P55 ms in the right precordial leads (V1-V3) was associated with higher RV volume (P=0.014) and lower RV ejection fraction (P=0.053). Low QRS voltages in limb leads predicted the presence (P=0.004) and amount (P<0.001) of left ventricular late gadolinium enhancement. Conclusions-\u2014The study results indicated that electrocardiographic abnormalities predict the arrhythmogenic cardiomyopathy phenotype in terms of severity of RV disease and left ventricular involvement, which are among the most important determinants of the disease outcome

332 Clinical and prognostic significance of junctional late gadolinium enhancement in patients with non-ischaemic cardiomyopathy

Abstract Aims Pulmonary hypertension (PH) carries a poor prognosis in patients with non-ischaemic dilated cardiomyopathy (NIDC). Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) evaluation can identify myocardial abnormalities. In particular, junctional LGE is already an established marker of adverse right ventricular (RV) remodelling in patients with pre-capillary PH. This study sought to assess the prevalence of junctional LGE by CMR in NIDC, its relationship with hemodynamic parameters and, moreover, its prognostic significance. Methods and results Patients with NIDC who underwent right heart catheterization (RHC) and CMR within 3 months in a tertiary hospital were enrolled. Patients with acute heart failure were excluded. Among others, RV and left ventricular (LV) volumes, junctional LGE at CMR, pulmonary artery pressure (PAP) and pulmonary capillary wedge pressure (PCWP) at RHC were tabulated. Pulmonary hypertension was defined accordingly to current Guidelines (median PAP at RHC ≥ 25 mmHg). The primary endpoint consisted of heart failure (HF) hospitalization during follow-up. A total of 188 patients [median age 49 (SD 15), 71% males] were evaluated. At morpho-functional CMR evaluation, most subjects (76%) had important systolic dysfunction (LV EF ≤ 35%). Junctional LGE was observed in 83 (44%) patients. Among patients with junctional LGE, 21 had LGE confined only to the junctional region, while 61 had also mid-wall interventricular septal stria and 21 a mid-wall stria in the lateral free LV wall. Patients with junctional LGE had lower RV EF (49% vs. 56%, P &lt; 0.001) and LV EF (27% vs. 30%, P = 0.012) when compared to those without junctional LGE although no differences in LV and RV dimensions were found. RHC showed PH in 83 patients (44%). Patients with junctional LGE showed a worse hemodynamic profile in terms of PH (55% vs. 36%; P = 0.011) and increase in PCWP (PCWP &gt; 15 mmHg in 60% vs. 42%; P = 0.015) compared to subjects without junctional LGE. Among 79 patients with PH and PCWP &gt; 15 mmHg, 75 (95%) had a combined post capillary and pre-capillary PH (diastolic pressure gradient ≥7 mmHg). Univariate analysis showed that junctional LGE was associated with a worse hemodynamic profile; on multivariable model, RV EF was significantly associated with the presence of junctional LGE (OR: 0.91; 95% CI: 0.87–0.96, P &lt; 0.001). During a median follow-up of 58 months, 33 patients (18%) died or underwent heart transplantation/ventricular assist device implantation, 17% in the junctional LGE group vs. 18% among those without junctional LGE. Thirty-eight patients (20%) had at least one episode of HF, 22 among junctional LGE group and 16 in control group (27% vs. 15%, P = 0.056). When adjusted for age, junctional LGE resulted a significant determinant of HF hospitalization (OR: 2.13, 95% CI: 1.02–4.44, P = 0.044). Conclusions Junctional LGE is detectable in almost half of NIDC patients and it is related to a worse haemodynamic profile, characterized by PH and elevated PCWP. Moreover, after adjustment for age, it was a significant determinant of HF hospitalization during follow-up in our population. Junctional LGE can therefore represent a useful prognostic tool, as marker of adverse ventricular remodelling likely related to ventricular interdependence

Arrhythmogenic Right Ventricular Cardiomyopathy: Characterization of Left Ventricular Phenotype and Differential Diagnosis With Dilated Cardiomyopathy

Background This study assessed the prevalence of left ventricular (LV) involvement and characterized the clinical, electrocardiographic, and imaging features of LV phenotype in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Differential diagnosis between ARVC-LV phenotype and dilated cardiomyopathy (DCM) was evaluated. Methods and Results The study population included 87 ARVC patients (median age 34\ua0years) and 153 DCM patients (median age 51\ua0years). All underwent cardiac magnetic resonance with quantitative tissue characterization. Fifty-eight ARVC patients (67%) had LV involvement, with both LV systolic dysfunction and LV late gadolinium enhancement (LGE) in 41/58 (71%) and LV-LGE in isolation in 17 (29%). Compared with DCM, the ARVC-LV phenotype was statistically significantly more often characterized by low QRS voltages in limb leads, T-wave inversion in the inferolateral leads and major ventricular arrhythmias. LV-LGE was found in all ARVC patients with LV systolic dysfunction and in 69/153 (45%) of DCM patients. Patients with ARVC and LV systolic dysfunction had a greater amount of LV-LGE (25% versus 13% of LV mass; P<0.01), mostly localized in the subepicardial LV wall layers. An LV-LGE 6520% had a 100% specificity for diagnosis of ARVC-LV phenotype. An inverse correlation between LV ejection fraction and LV-LGE extent was found in the ARVC-LV phenotype (r=-0.63; P<0.01), but not in DCM (r=-0.01; P=0.94). Conclusions LV involvement in ARVC is common and characterized by clinical and cardiac magnetic resonance features which differ from those seen in DCM. The most distinctive feature of ARVC-LV phenotype is the large amount of LV-LGE/fibrosis, which impacts directly and negatively on the LV systolic function

Morphofunctional abnormalities of mitral annulus and arrhythmic mitral valve prolapse

Background\u2014Arrhythmic mitral valve prolapse (MVP) is characterized by myxomatous leaflets and left ventricular (LV) fibrosis of papillary muscles and inferobasal wall. We searched for morphofunctional abnormalities of the mitral valve that could explain a regional mechanical myocardial stretch. Methods and Results\u2014Thirty-six (27 female patients; median age: 44 years) arrhythmic MVP patients with LV late gadolinium enhancement on cardiac magnetic resonance and no or trivial mitral regurgitation, and 16 (6 female patients; median age: 40 years) MVP patients without LV late gadolinium enhancement were investigated by morphofunctional cardiac magnetic resonance. Mitral annulus disjunction (median: 4.8 versus 1.8 mm; P1.5 (22 [61%] versus 4 [25%]; P=0.016) were higher in MVP patients with late gadolinium enhancement than in those without. A linear correlation was found between mitral annulus disjunction and curling (R=0.85). A higher prevalence of auscultatory midsystolic click (26 [72%] versus 6 [38%]; P=0.018) was also noted. Histology of the mitral annulus showed a longer mitral annulus disjunction in 50 sudden death patients with MVP and LV fibrosis than in 20 patients without MVP (median: 3 versus 1.5 mm; P<0.001). Conclusions\u2014Mitral annulus disjunction is a constant feature of arrhythmic MVP with LV fibrosis. The excessive mobility of the leaflets caused by posterior systolic curling accounts for a mechanical stretch of the inferobasal wall and papillary muscles, eventually leading to myocardial hypertrophy and scarring. These mitral annulus abnormalities, together with auscultatory midsystolic click, may identify MVP patients who would need arrhythmic risk stratification