'Hot phase' clinical presentation in arrhythmogenic cardiomyopathy.

AIMS: The aim of this study is to evaluate the clinical features of patients affected by arrhythmogenic cardiomyopathy (AC), presenting with chest pain and myocardial enzyme release in the setting of normal coronary arteries ('hot phase'). METHODS AND RESULTS: We collected detailed anamnestic, clinical, instrumental, genetic, and histopathological findings as well as follow-up data in a series of AC patients who experienced a hot phase. A total of 23 subjects (12 males, mean age at the first episode 27 ± 16 years) were identified among 560 AC probands and family members (5%). At first episode, 10 patients (43%) already fulfilled AC diagnostic criteria. Twelve-lead electrocardiogram recorded during symptoms showed ST-segment elevation in 11 patients (48%). Endomyocardial biopsy was performed in 11 patients, 8 of them during the acute phase showing histologic evidence of virus-negative myocarditis in 88%. Cardiac magnetic resonance was performed in 21 patients, 12 of them during the acute phase; oedema and/or hyperaemia were detected in 7 (58%) and late gadolinium enhancement in 11 (92%). At the end of follow-up (mean 17 years, range 1-32), 12 additional patients achieved an AC diagnosis. Genetic testing was positive in 77% of cases and pathogenic mutations in desmoplakin gene were the most frequent. No patient complained of sustained ventricular arrhythmias or died suddenly during the 'hot phase'. CONCLUSION: 'Hot phase' represents an uncommon clinical presentation of AC, which often occurs in paediatric patients and carriers of desmoplakin gene mutations. Tissue characterization, family history, and genetic test represent fundamental diagnostic tools for differential diagnosis.

Assessing pediatric ileocolonic Crohn's disease activity based on global MR enterography scores.

OBJECTIVES: This study was aimed at correlating a magnetic resonance index of activity (MaRIA) and a magnetic resonance enterography global score (MEGS) with activity indexes in a paediatric population with Crohn's disease (CD). METHODS: This retrospective study included 32 paediatric patients (median age 14.5 years, 18 male) with proven CD who underwent magnetic resonance enterography (MRE). A correlation analysis was performed on the MRE-based scores, the simplified endoscopic score for CD (SES-CD), the paediatric Crohn's disease activity index (PCDAI), and C-reactive protein (CRP) levels. Based on PCDAI, comparison of both global MaRIA and MEGS was made between patients with mild and moderate/severe disease activity. RESULTS: Global MaRIA correlated with SES-CD (r = 0.70, p = 0.001) and PCDAI (r = 0.42, p = 0.016). MEGS correlated with PCDAI (r = 0.46, p = 0.007) and CRP levels (r = 0.35, p = 0.046). MEGS differed significantly (p = 0.027) between patients grouped by clinical disease severity. CONCLUSIONS: MRE-based global scores correlated with clinical indexes of CD activity. Therefore, they represent a potential useful tool to predict CD activity and severity, as well as a possible promising alternative to endoscopy, to monitor paediatric patients with CD during their follow-up. KEY POINTS: • MRE is widely used to for accurate assessment of CD. • Global MaRIA and MEGS have been suggested as indicators of CD activity. • Paediatric studies comparing MRE-based global scores with clinical CD activity are lacking. • Such scores can serve as predictors of CD activity/severity in paediatric patients. • MRE offers an alternative to clinical score/endoscopy for paediatric CD monitoring.

Arrhythmic Mitral Valve Prolapse and Sudden Cardiac Death.

BACKGROUND: Mitral valve prolapse (MVP) may present with ventricular arrhythmias and sudden cardiac death (SCD) even in the absence of hemodynamic impairment. The structural basis of ventricular electric instability remains elusive. METHODS AND RESULTS: The cardiac pathology registry of 650 young adults (≤40 years of age) with SCD was reviewed, and cases with MVP as the only cause of SCD were re-examined. Forty-three patients with MVP (26 females; age range, 19-40 years; median, 32 years) were identified (7% of all SCD, 13% of women). Among 12 cases with available ECG, 10 (83%) had inverted T waves on inferior leads, and all had right bundle-branch block ventricular arrhythmias. A bileaflet involvement was found in 70%. Left ventricular fibrosis was detected at histology at the level of papillary muscles in all patients, and inferobasal wall in 88%. Living patients with MVP with (n=30) and without (control subjects; n=14) complex ventricular arrhythmias underwent a study protocol including contrast-enhanced cardiac magnetic resonance. Patients with either right bundle-branch block type or polymorphic complex ventricular arrhythmias (22 females; age range, 28-43 years; median, 41 years), showed a bileaflet involvement in 70% of cases. Left ventricular late enhancement was identified by contrast-enhanced cardiac magnetic resonance in 93% of patients versus 14% of control subjects (P<0.001), with a regional distribution overlapping the histopathology findings in SCD cases. CONCLUSIONS: MVP is an underestimated cause of arrhythmic SCD, mostly in young adult women. Fibrosis of the papillary muscles and inferobasal left ventricular wall, suggesting a myocardial stretch by the prolapsing leaflet, is the structural hallmark and correlates with ventricular arrhythmias origin. Contrast-enhanced cardiac magnetic resonance may help to identify in vivo this concealed substrate for risk stratification.

Real-life experience with liver iron concentration R2 MRI measurement in patients with hemoglobinopathies: baseline data from LICNET.

BACKGROUND: Real-life data on the use of R2 MRI for the assessment of liver iron concentration (LIC) remain limited. METHODS: We conducted a cross-sectional analysis on 363 patients (mean age 35.6 yr, 44.1% men) with hemoglobinopathies (204 ß-thalassemia major [TM], 102 ß-thalassemia intermedia [TI], and 57 sickle cell disease [SCD]) that were evaluated with R2 MRI as part of LICNET, an MRI network of 13 Italian treatment centers. RESULTS: The mean LIC was 7.8 mg/g (median: 4.0), with high LIC (>7 mg/g) noted in both transfused (TM, TI 37%; SCD 38%) and non-transfused (TI 20%) patients. Ferritin levels correlated with LIC in both transfused (TM, TI, SCD) and non-transfused (TI) patients (P < 0.001), although lower values predicted high LIC in non-transfused patients (1900 vs. 650 ng/mL in TM vs. non-transfused TI). A correlation between LIC and ALT levels was only noted in HCV-negative patients (rs = 0.316, P < 0.001). The proportion of patients with high LIC was significantly different between iron chelators used (P = 0.023), with the lowest proportion in deferasirox (30%) and highest in deferiprone (53%)-treated patients. CONCLUSIONS: High LIC values persist in subgroups of patients with hemoglobinopathy, warranting closer monitoring and management optimization, even for non-transfused patients with relatively low ferritin levels.

Relationship between T-wave inversion and transmural myocardial edema as evidenced by cardiac magnetic resonance in patients with clinically suspected acute myocarditis: clinical and prognostic implications.

BACKGROUND: The pathophysiologic mechanisms and the prognostic meaning of electrocardiographic (ECG) T-wave inversion (TWI) occurring in a subgroup of patients with clinically suspected acute myocarditis remain to be elucidated. Contrast-enhanced cardiac magnetic resonance (CMR) offers the potential to identify myocardial tissue changes such as edema and/or fibrosis which may underlie TWI. METHODS AND RESULTS: We studied 76 consecutive patients (median age 34years) with clinically suspected acute myocarditis, using a comprehensive CMR protocol which included T2 weighted sequences for myocardial edema. At the time of CMR, TWI was observed in 21 (27%) patients. There was a statistically significant association of TWI with the median number of left ventricular (LV) segments showing both any pattern of myocardial edema (transmural and non-transmural) [5 (3-7) vs. 3 (2-4); p=0.015] and myocardial late-gadolinium-enhancement [4 (3-7) vs. 3 (2-4); p=0.002]. Transmural myocardial edema involving ≥2 LV segments was found in 17/21 (81%) patients with TWI versus 13/55 (24%) patients without TWI (p<0.001) and remained the only independent predictor of TWI at multivariable analysis (OR=9.96; 95%CI=2.71-36.6; p=0.001). Overall, topographic concordance between the location of TWI across the ECG leads and the regional distribution of transmural myocardial edema was 88%. There was no association between acute TWI and reduced LV ejection fraction (<55%) at 6-months of follow-up. CONCLUSIONS: This is the first study to demonstrate an association between LV transmural myocardial edema as evidenced by CMR sequences and TWI in clinically suspected acute myocarditis. As an expression of reversible myocardial edema, development of TWI during the acute disease phase was not a predictor of LV systolic dysfunction at follow-up.

Cardiac rupture in acute myocardial infarction: a cardiac magnetic resonance study.

AIMS: We assessed the feasibility of cardiac magnetic resonance (CMR) and the role of myocardial strain in the diagnostic work-up of patients with acute myocardial infarction (AMI) and a clinical suspicion of cardiac rupture (CR). METHODS AND RESULTS: Consecutive patients with AMI complicated by CR who underwent CMR were enrolled. Traditional and strain CMR findings were evaluated; new parameters indicating the relative wall stress between AMI and adjacent segments, named wall stress index (WSI) and WSI ratio, were analysed. A group of patients admitted for AMI without CR served as control. 19 patients (63% male, median age 73 years) met the inclusion criteria. Microvascular obstruction (MVO, P = 0.001) and pericardial enhancement (P < 0.001) were strongly associated with CR. Patients with clinical CR confirmed by CMR exhibited more frequently an intramyocardial haemorrhage than controls (P = 0.003). Patients with CR had lower 2D and 3D global radial strain (GRS) and global circumferential strain (in 2D mode P < 0.001; in 3D mode P = 0.001), as well as 3D global longitudinal strain (P < 0.001), than controls. The 2D circumferential WSI (P = 0.010), as well as the 2D and 3D circumferential (respectively, P < 0.001 and P = 0.042) and radial WSI ratio (respectively, P < 0.001 and P: 0.007), were higher in CR patients than controls. CONCLUSION: CMR is a safe and useful imaging tool to achieve the definite diagnosis of CR and an accurate visualization of tissue abnormalities associated with CR. Strain analysis parameters can give insights into the pathophysiology of CR and may help to identify those patients with sub-acute CR.

New-Onset Exertional Dyspnea in a Young Patient With Previous Blunt Chest Trauma.

CASE PRESENTATION: A 16-year-old male patient was admitted to our Cardiology Department for new-onset exertional dyspnea (NYHA functional class II-III). He had no family history of cardiovascular diseases, no cardiovascular risk factors, and an unremarkable medical history, except for a blunt chest trauma after a motorbike accident 2 years earlier.

Clinical profile and long-term follow-up of a cohort of patients with desmoplakin cardiomyopathy.

BACKGROUND: Desmoplakin (DSP) genetic variants have been reported in arrhythmogenic cardiomyopathy with particular regard to predominant left ventricular (LV) involvement. OBJECTIVE: The purpose of this study was to improve our understanding of clinical phenotype and outcome of DSP variant carriers. METHODS: The clinical picture and outcome of 73 patients (36% probands) harboring a pathogenic/likely pathogenic DSP variant were evaluated. RESULTS: The phenotype during follow-up (mean 11 years; range 1-39 years) changed in 25 patients (35%), arrhythmogenic LV cardiomyopathy (ALVC) forms being the most frequent (n = 26 [36%]), followed by biventricular (BIV; n = 20 [27%]) and arrhythmogenic right ventricular cardiomyopathy (ARVC; n = 16 [22%]) forms. Major ventricular arrhythmias were detected in 21 patients (29%), and they were more common in ARVC (n = 6, 56%) and BIV forms (n = 8, 40%) than in ALVC forms (n = 4, 15%). In patients with ALVC, major ventricular arrhythmias occurred in the setting of a normal/mildly reduced systolic function. Heart failure (HF) occurred in 6 patients (8%); none affected with ALVC. Females showed more commonly LV involvement, while ARVC forms were more frequently detected in males (21 [61%] vs 15 [38%]; P = .147). Males showed a higher incidence of major ventricular arrhythmias (18 [52%] vs 9 [24%]; P = .036), HF (11 [31%] vs 1 [3%]; P = .004), and cardiac death (11 [31%] vs 0 [0%]; P < .001). CONCLUSION: The clinical phenotype in pathogenic/likely pathogenic DSP variant carriers is wide. Although most patients show LV involvement, 16 (22%) has right ventricular abnormalities in keeping with a "classical" arrhythmogenic cardiomyopathy form. In ALVC, HF and major ventricular arrhythmias seem less common than in right ventricular and BIV variants. Females show more frequently LV involvement and a better outcome.

Prognostic Significance of Feature-Tracking Right Ventricular Global Longitudinal Strain in Non-ischemic Dilated Cardiomyopathy.

Aims: Left ventricular global longitudinal strain (GLS) by cardiac magnetic resonance feature tracking (CMR-FT) analysis has shown an incremental prognostic value compared to classical parameters in non-ischemic dilated cardiomyopathy (NICM). However, less is known about the role of right ventricular (RV) GLS. Our objective was to evaluate the prognostic impact of RV-GLS by CMR-FT analysis in a population of NICM patients. Methods: In this multicenter study, we examined NICM patients evaluated with a comprehensive CMR-FT study. Major cardiac events (MACEs) were considered as the study primary outcome measure and were defined as a composite of (a) cardiovascular death, (b) cardiac transplant or destination therapy ventricular assist device, (c) hospitalization for life-threatening ventricular arrhythmias or implantable cardiac defibrillator appropriate intervention. Heart failure (HF) related events, including hospitalizations and life-threatening arrhythmia-related events were considered as secondary end-points. Receiver operating time-dependent analysis were used to calculate the possible additional effect of RV-GLS to standard evaluation. Results: We consecutively enrolled 273 patients. During a median follow-up of 39 months, 41 patients (15%) experienced MACEs. RV-GLS and LV late gadolinium emerged as the strongest prognostic CMR-FT variables: their association provided an estimated 3-year MACEs rate of 29%. The addition of RV-GLS significantly improved the prognostic accuracy in predicting MACEs with respect to the standard evaluation including LGE (areas under the curve from 0.71 [0.66-0.82] to 0.76 [0.66-0.86], p = 0.03). On competing risk analysis, RV-GLS showed a significant ability to reclassify overall both HF-related and life-threatening arrhythmia-related events, regardless of LV and RV ejection fraction. Conclusions: In NICM patients, RV-GLS showed a significant prognostic role in reclassifying the risk of MACEs, incremental with respect to standard evaluation with standard prognostic parameters.

Relationship Between Electrocardiographic Findings and Cardiac Magnetic Resonance Phenotypes in Arrhythmogenic Cardiomyopathy.

Background The 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 We 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 ( P<0.001) and decreasing values of RV ejection fraction ( P<0.001). The extent of T-wave inversion to lateral leads predicted a more severe RV dilatation rather than a left ventricular involvement because of the leftward displacement of the dilated RV , as evidenced by contrast-enhanced cardiac magnetic resonance. A terminal activation delay of >55 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 The 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.

Diagnostic value and prognostic implications of early cardiac magnetic resonance in survivors of out-of-hospital cardiac arrest.

BACKGROUND: In patients who survived out-of-hospital cardiac arrest (OHCA), it is crucial to establish the underlying cause and its potential reversibility. OBJECTIVE: The purpose of this study was to assess the incremental diagnostic and prognostic role of early cardiac magnetic resonance (CMR) in survivors of OHCA. METHODS: Among 139 consecutive OHCA patients, the study enrolled 44 patients (median age 43 years; 84% male) who underwent coronary angiography and CMR ≤7 days after admission. The CMR protocol included T2-weighted sequences for myocardial edema and late gadolinium enhancement (LGE) sequences for myocardial fibrosis. RESULTS: Coronary angiography identified obstructive coronary artery disease in 18 of 44 patients in whom CMR confirmed the diagnosis of ischemic heart disease by demonstrating subendocardial or transmural LGE. The presence of myocardial edema allowed differentiation between acute myocardial ischemia (n = 12) and postinfarction myocardial scar (n = 6). Among the remaining 26 patients without obstructive coronary artery disease, CMR in 19 (73%) showed dilated cardiomyopathy in 5, myocarditis in 4, mitral valve prolapse associated with LGE in 3, ischemic scar in 2, idiopathic nonischemic scar in 2, arrhythmogenic cardiomyopathy in 1, hypertrophic cardiomyopathy in 1, and takotsubo cardiomyopathy in 1. In this subgroup of 26 patients, 6 (23%) had myocardial edema. During mean follow-up of 36 ± 17 months, all 18 patients with myocardial edema had an uneventful outcome, whereas 9 of 26 (35%) without myocardial edema experienced sudden arrhythmic death (n = 1), appropriate defibrillator interventions (n = 5), and nonarrhythmic death (n = 3; P = .006). CONCLUSION: In survivors of OHCA, early CMR with a comprehensive tissue characterization protocol provided additional diagnostic and prognostic value. The identification of myocardial edema was associated with a favorable long-term outcome.

Nonischemic Left Ventricular Scar as a Substrate of Life-Threatening Ventricular Arrhythmias and Sudden Cardiac Death in Competitive Athletes.

BACKGROUND: The clinical profile and arrhythmic outcome of competitive athletes with isolated nonischemic left ventricular (LV) scar as evidenced by contrast-enhanced cardiac magnetic resonance remain to be elucidated. METHODS AND RESULTS: We compared 35 athletes (80% men, age: 14-48 years) with ventricular arrhythmias and isolated LV subepicardial/midmyocardial late gadolinium enhancement (LGE) on contrast-enhanced cardiac magnetic resonance (group A) with 38 athletes with ventricular arrhythmias and no LGE (group B) and 40 healthy control athletes (group C). A stria LGE pattern with subepicardial/midmyocardial distribution, mostly involving the lateral LV wall, was found in 27 (77%) of group A versus 0 controls (group C; P<0.001), whereas a spotty pattern of LGE localized at the junction of the right ventricle to the septum was respectively observed in 11 (31%) versus 10 (25%; P=0.52). All athletes with stria pattern showed ventricular arrhythmias with a predominant right bundle branch block morphology, 13 of 27 (48%) showed ECG repolarization abnormalities, and 5 of 27 (19%) showed echocardiographic hypokinesis of the lateral LV wall. The majority of athletes with no or spotty LGE pattern had ventricular arrhythmias with a predominant left bundle branch block morphology and no ECG or echocardiographic abnormalities. During a follow-up of 38±25 months, 6 of 27 (22%) athletes with stria pattern experienced malignant arrhythmic events such as appropriate implantable cardiac defibrillator shock (n=4), sustained ventricular tachycardia (n=1), or sudden death (n=1), compared with none of athletes with no or LGE spotty pattern and controls. CONCLUSIONS: Isolated nonischemic LV LGE with a stria pattern may be associated with life-threatening arrhythmias and sudden death in the athlete. Because of its subepicardial/midmyocardial location, LV scar is often not detected by echocardiography.

Morphofunctional Abnormalities of Mitral Annulus and Arrhythmic Mitral Valve Prolapse.

BACKGROUND: Arrhythmic 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: Thirty-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; P<0.001), end-systolic mitral annular diameters (median: 41.2 versus 31.5; P=0.004) and end-diastolic mitral annular diameters (median: 35.5 versus 31.5; P=0.042), prevalence of posterior systolic curling (34 [94%] versus 3 [19%]; P<0.001), and basal to mid LV wall thickness ratio >1.5 (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: Mitral 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.