BACKGROUND AND AIMS:The prediction of the first major arrhythmic event (MAE) is still an unmet need in the recently defined scenario of non-dilated left ventricular cardiomyopathy (NDLVC). METHODS:A cohort of 337 patients with NDLVC and no history of MAE was retrospectively identified at two large centres. Patient-tailored diagnostic workup included cardiac magnetic resonance (CMR), endomyocardial biopsy, and genetic testing. The primary endpoint was the occurrence of the first MAE, including sustained ventricular tachycardia (VT), ventricular fibrillation, or appropriate implantable cardioverter-defibrillator therapy, by 60-month follow-up. A pool of 216 NDLVC patients from 11 European centres served as a validation cohort. RESULTS:In the study cohort (mean age 37 ± 15 years, 62% male), the mean left ventricular ejection fraction (LVEF) was 52 ± 8%, and 79% of patients had late gadolinium enhancement (LGE) at baseline CMR. By 60-month follow-up, 51 patients (15%) experienced a MAE. The primary endpoint was predicted by male sex [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.3-4.4, P = .007], baseline non-sustained VT (HR 3.1, 95% CI 1.7-5.6, P < .001), LVEF < 45% (HR 5.5, 95% CI 2.7-11.0, P < .001), septal (HR 2.0, 95% CI 1.0-4.0, P = .046) and ring-like pattern of LGE (HR 1.3, 95% CI .6-2.6, P = .54), pathogenic/likely pathogenic variants in guideline-defined high-risk genes (HR 4.6, 95% CI 2.3-9.1, P < .001), and biopsy/CMR-proven myocardial inflammation (HR 15.7, 95% CI 6.1-40.3, P < .001). The results were confirmed in the validation cohort (Uno's C-index 0.81, 95% CI .75-.88). A novel risk score was subsequently derived. CONCLUSIONS:In NDLVC, male sex, non-sustained VT, LVEF < 45%, septal and ring-like LGE, high-risk genotypes, and myocardial inflammation predicted the first episode of MAE by 60 months.

AIMS:Interleukin-1 (IL-1) plays a central role in myocardial inflammation and adverse remodelling. However, the long-term clinical impact of IL-1 blockade in myocarditis and inflammatory cardiomyopathy (Infl-CMP), particularly according to treatment exposure and discontinuation, remains unclear. We evaluated time-dependent outcomes in patients treated with the IL-1 receptor antagonist anakinra. METHODS AND RESULTS:We included 42 consecutive patients with definite myocarditis or Infl-CMP diagnosed by cardiac magnetic resonance either with or without endomyocardial biopsy. Mean age was 46 ± 17 years, 60% were male, and mean left ventricular ejection fraction (LVEF) at presentation was 43 ± 16%. Patients received anakinra (100 mg/day) for a median of 11 months and were followed for 51 ± 20 months. The primary endpoint was major adverse events (MAE), defined as cardiac death, heart transplantation, major ventricular arrhythmias, hospitalization for acute heart failure, or recurrent myocarditis. Time-updated Kaplan-Meier analysis showed a significant reduction in MAE during anakinra treatment compared with both pre-treatment and post-discontinuation phases (log-rank P < .001). Events were rare during active treatment, whereas most deaths (7/8) and all major ventricular arrhythmias occurred outside the treatment phase. Recurrent myocarditis was reduced during therapy (1/42 vs 9/32 pre-treatment; P = .002) and reappeared after discontinuation (3/37). Cardiac-related hospitalizations decreased during treatment and increased thereafter. These changes were paralleled by improvements in troponin, LVEF (≥5% in one-third), cardiac magnetic resonance inflammatory abnormalities, and arrhythmic burden. Outcomes differed according to aetiology. CONCLUSION:Anakinra was associated with a marked reduction in MAE during active treatment, with re-emergence after discontinuation, supporting a potential role for sustained IL-1 blockade in selected high-risk patients.

BACKGROUND:The relationship between intercalated disc abnormalities (IDAs) and arrhythmias in inflammatory cardiomyopathy (ICM) remains incompletely understood. OBJECTIVES:This study presents a pilot research that aimed to: 1) investigate the link between IDAs and arrhythmias in humans with ICM; and 2) compare findings in humans and mice with experimental autoimmune myocarditis (EAM). METHODS:Humans with ICM (N = 316) investigated for either genetic or autoimmune IDAs were identified at a referral center. Ultrastructural analysis on biobanked tissue was performed to determine the average intercellular cleft width (ICW) between cardiac myocytes. IDA+ cases were compared with IDA- control subjects matched 1:1 by age, sex, and race/ethnicity. The primary endpoint was the occurrence of clinically demanding supraventricular or ventricular arrhythmias, recorded either by Holter electrocardiography or implanted devices during a 24-month prospective follow-up. The relationships between ICW and arrhythmias were compared in humans and male mice with EAM (n = 12). RESULTS:Of 316 humans with ICM (mean age 45 ± 15 years, 63% male), 70 (22%) were IDA+ and 107 (34%) had arrhythmias on admission. IDA+ patients had greater ICW than control subjects (44 ± 8 nm vs 28 ± 4 nm; P < 0.001) and higher incidence of clinically demanding arrhythmias both at presentation (31 of 70 vs 9 of 70; P < 0.001) and during follow-up (44 of 70 vs 10 of 70; P < 0.001). In a multivariable model, IDAs predicted the occurrence of major ventricular arrhythmias by 24 months (HR: 3.0; 95% CI: 1.4-6.4; P = 0.004). In mice, arrhythmias were documented in 7 of 12 EAM cases and 0 of 6 control animals (P = 0.038). Increased ICW was found in close relationship with arrhythmias in both species (humans: 32 of 44 with vs 4 of 52 without arrhythmias; P < 0.001; mice: 7 of 8 with vs 0 of 4 without arrhythmias; P = 0.010), as well as with abnormal ventricular electrograms on viable murine myocardial tissue (5 of 6 vs 0 of 6; P = 0.015). CONCLUSIONS:As a shared trait between genetic and autoimmune ICM, IDAs are linked to arrhythmias in humans and find promising applications in the EAM mouse model.

OBJECTIVES:Cardiovascular involvement in systemic lupus erythematosus (SLE) is frequent, but little is known about possible distinctive traits of SLE-related myocarditis (myoSLE) in comparison with patients with SLE (onlySLE) or myocarditis alone (onlyMyo). METHODS:A retrospective analysis was performed comparing patients with myoSLE (n = 25) from three centres with consecutive patients with onlySLE (n = 279) and onlyMyo (n = 88). SLE patients were dichotomized by disease duration ≤1 vs >1 year into recent onlySLE/early myoSLE vs longstanding onlySLE/late myoSLE. Further stratification into disease duration of 1-5, 5-10 and >10 years was also performed. SLE disease activity index 2000 (SLEDAI-2K) was used to estimate disease activity. Myocarditis was diagnosed through biopsy or MRI. RESULTS:Women were significantly more frequent among myoSLE than among onlyMyo (72% vs 43%; P = 0.013). Compared with onlyMyo, myoSLE patients had a higher frequency of conduction abnormalities (22% vs 5%; P = 0.046) and presented with numerically higher frequencies of left ventricular function compromise (48% vs 30%), along with higher pro-brain natriuretic peptide levels. Inflammation markers were higher in myoSLE compared with onlyMyo and with patients with onlySLE with >10 years of disease duration. SLEDAI-2K was significantly higher in late myoSLE than in longstanding onlySLE. Antiphospholipid syndrome was more frequent in myoSLE than in onlySLE. Multivariate analysis showed an association among myoSLE, anti-β-2-glycoprotein I antibodies (aB2GPI, P = 0.014) and a higher number of involved British Isles Lupus Assessment Group domains in patient history (P = 0.003). CONCLUSION:myoSLE has unique clinical traits compared with other forms of myocarditis and is associated with aB2GPI and a more severe SLE course.

Non-viral myocarditis is rare but relatively more frequent in patients with systemic autoimmune diseases (such as systemic lupus erythematosus, SLE, and allied conditions) than in the general population. In rare cases, mRNA-based vaccines can also trigger non-viral myocarditis. Limited data are available about the cardiac safety of mRNA vaccines in this subset of patients. Here, we report data from a third-level hospital on long-term safety, leveraging on a previously described cohort of 13 consecutive patients with SLE, Undifferentiated (UCTD) and Mixed Connective Tissue disease (MCTD), and a history of myocarditis, who had received anti-COVID-19 vaccination between April 2021 and January 2022. Demographics and clinical data (including validated clinometric for SLE) were collected at baseline, at the first available visit following the primary vaccination cycle, after an additional 12 months, and at the last available follow-up after at least 36 months. Twelve patients, seven females, ten with SLE, one MCTD, and one UCTD, had a median follow-up of 41 (35–45) months. One patient was lost at follow-up. No disease flare or sign of myocarditis recurrence were observed. At last visit, all patients were in a low disease activity state (LLDAS), and all but one were in remission, according to the Definition of Remission in SLE (DORIS) criteria. No significant variations in disease activity or damage accrual nor in markers of inflammation and myocardial injury were observed. Our data suggest that mRNA-based anti-COVID-19 vaccines in patients with previous autoimmune myocarditis in the context of SLE and allied conditions have a good long-term safety profile.

BACKGROUND:Nondilated left ventricular cardiomyopathy (NDLVC) is a highly heterogeneous and unexplored category of cardiomyopathies introduced in the 2023 European Society of Cardiology (ESC) guidelines. This study aims to identify factors associated with adverse remodeling in a large multicentre cohort of patients with NDLVC. METHODS:A total of 432 patients with NDLVC (63.4% male, mean age 39.4 ± 14.6 years) with multiparametric characterization were enrolled from January 2010 to May 2023 in 2 high-volume Italian centres. Diagnosis followed ESC criteria. Endpoints were worsening of left ventricular ejection fraction (LVEF) ≥ 10% from the baseline value (or group W), evolution to dilated cardiomyopathy (DCM) (or group E), and the concomitant occurrence of both (or group W + E), assessed at the latest available echocardiographic evaluation. RESULTS:During a median follow-up of 77 months (interquartile range [IQR]: 48-109), 27.3% of patients experienced worsening LVEF, 28.9% progressed to DCM, and 18.3% reached the combined W + E endpoint. A multivariable model including positive genetic testing associated to myocardial inflammation, family history of cardiomyopathies or sudden cardiac death, intraventricular conduction delay, baseline echocardiographic LVEF < 45%, a ring-like late gadolinium enhancement on cardiac magnetic resonance, and nonsustained ventricular tachycardia at baseline had the strongest discrimination power for predicting worsening LVEF (area under the curve [AUC] of 0.8; 95% confidence interval [CI], 0.75-0.86), evolution to DCM (AUC 0.78; 95% CI, 0.73-0.84) and the combined W + E (AUC 0.84; 95% CI, 0.79-0.89). Negative genetic testing reduced the risk across all the endpoints (odds ratio [OR], 0.2; 95% CI, 0.1-0.4; P < 0.001; OR, 0.2; 95% CI, 0.1-0.4; P < 0.001 and OR, 0.1; 95% CI, 0.04-0.3; P < 0.001, respectively). CONCLUSIONS:In this large NDLVC cohort, in which 38% of patients showed an adverse remodelling over long-term follow-up, a multiparametric approach integrating deep phenotyping and genetics effectively identified high-risk patients.

OBJECTIVES:To analyse clinical features and biomarkers associated with primary heart involvement (pHI) confirmed at cardiac magnetic resonance (CMR) in a monocentric cohort of SSc patients. METHODS:A retrospective study. SSc patients who underwent CMR for clinically suspected pHI were identified. SSc-pHI at CMR was defined by the presence of at least one abnormality among: non-ischaemic late gadolinium enhancement (LGE), myocardial oedema (STIR), increased extracellular volume (ECV), native T1 or T2-mapping. Clinical, laboratory and instrumental features were compared between pHI-SSc and non-pHI-SSc patients, and between CMR-positive and CMR-negative patients. RESULTS:259 SSc patients (females 89.6%; median age 49 [39-61] years) were included. CMR was performed in 56 (21%) and pHI detected in 37 patients (14%). At univariate analysis, age at SSc onset, diffuse cutaneous subset, increased inflammatory markers and cardiac enzymes, interstitial lung disease (ILD) and myositis were significantly associated with SSc-pHI at CMR; an inverse correlation emerged with anti-centromere antibodies, VEDOSS and female gender. At multivariate analysis, increased troponin T(TnT) [OR 14.108, CI 2.772-71.808, P = 0.014], CRP [OR 11.237, CI 2.265-55.763, P = 0.0031] and the presence of ILD [OR 6.275, CI 1.240-31.763, P = 0.0264] were significantly associated with a positive CMR for SSc-pHI. Considering the 56 patients who underwent CMR, arrhythmias at 24 h-ECG-Holter were associated at univariate analysis to the presence of SSc-pHI at CMR [OR 3.75, CI 1.041-13.5, P = 0.04]. CONCLUSION:This retrospective analysis identified biomarkers and disease features associated with SSc-pHI confirmed at CMR. Our preliminary data suggest that increased serum levels of TnT and CRP, as well as the presence of ILD and arrhythmias might be considered as red flags suggesting to promptly proceed with a comprehensive cardiac evaluation, including CMR, to diagnose SSc-pHI.

Pentraxin 3 (PTX3) is an acute phase protein produced in various tissues in response to microbial and sterile stimuli, which regulates the inflammation outcomes. PTX3 has not been investigated in myocarditis. Our aim was to assess circulating and cardiac tissue expression of PTX3 in 55 patients with myocarditis proven by magnetic resonance and/or endomyocardial biopsy. A major proportion of patients with myocarditis displayed significantly increased plasma PTX3 levels as compared with controls (26/30 vs. 0/10), with higher diagnostic yield than conventional biomarkers in the study group. Cardiac tissue analysis revealed PTX3 expression in all patients (40/40), with viral myocarditis exhibiting higher signal intensity than autoimmune myocarditis, and with a predominant localization in cardiomyocytes. Abnormal plasma PTX3 was associated with systolic dysfunction and heart failure at presentation. Interestingly, patients who recovered by 12 months had higher baseline PTX3 levels. Our preliminary data support the potential use of PTX3 as a biomarker in myocarditis.

BACKGROUND AND AIMS:Contemporary multicentre data on clinical and diagnostic spectrum and outcome in myocarditis are limited. Study aims were to describe baseline features, 1-year follow-up, and baseline predictors of outcome in clinically suspected or biopsy-proven myocarditis (2013 European Society of Cardiology criteria) in adult and paediatric patients from the EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry. METHODS:Five hundred eighty-one (68.0% male) patients, 493 adults, median age 38 (27-52) years, and 88 children, aged 8 (3-13) years, were divided into 3 groups: Group 1 (n = 233), clinically suspected myocarditis with abnormal cardiac magnetic resonance; Group 2 (n = 222), biopsy-proven myocarditis; and Group 3 (n = 126) clinically suspected myocarditis with normal or inconclusive or no cardiac magnetic resonance. Baseline features were analysed overall, in adults vs. children, and among groups. One-year outcome events included death/heart transplantation, ventricular assist device (VAD) or implantable cardioverter defibrillator (ICD) implantation, and hospitalization for cardiac causes. RESULTS:Endomyocardial biopsy, mainly right ventricular, had a similarly low complication rate in children and adults (4.7% vs. 4.9%, P = NS), with no procedure-related death. A classical myocarditis pattern on cardiac magnetic resonance was found in 31.3% of children and in 57.9% of adults with biopsy-proven myocarditis (P < .001). At 1-year follow-up, 11/410 patients (2.7%) died, 7 (1.7%) received a heart transplant, 3 underwent VAD (0.7%), and 16 (3.9%) underwent ICD implantation. Independent predictors at diagnosis of death or heart transplantation or hospitalization or VAD implantation or ICD implantation at 1-year follow-up were lower left ventricular ejection fraction and the need for immunosuppressants for new myocarditis diagnosis refractory to non-aetiology-driven therapy. CONCLUSIONS:Endomyocardial biopsy was safe, and cardiac magnetic resonance using Lake Louise criteria was less sensitive, particularly in children. Virus-negative lymphocytic myocarditis was predominant both in children and adults, and use of immunosuppressive treatments was low. Lower left ventricular ejection fraction and the need for immunosuppressants at diagnosis were independent predictors of unfavourable outcome events at 1 year.

Objectives: Myocarditis is an overlooked manifestation of anti-synthetase syndrome (ASS). Our study describes the clinical and instrumental features of ASS myocarditis and evaluates the performance of cardiac MRI (CMRI) with mapping techniques in assisting diagnosis of ASS myocarditis. Methods: Data from patients with ASS were retrospectively analysed. CMRI data for patients diagnosed with myocarditis, including late gadolinium enhancement (LGE), T2 ratio, T1 mapping, extracellular volume (ECV) and T2 mapping, were reviewed. Myocarditis was defined by the presence of symptoms and/or signs suggestive for heart involvement, including increased high-sensitive troponin T (hs-TnT) and/or N-terminal pro-brain natriuretic peptide (NT-proBNP), and at least an instrumental abnormality. The clinical features of patients with ASS with and without myocarditis were compared. A P-value of <0.05 was considered statistically significant. Results: Among a cohort of 43 patients with ASS [median age 58 (48.0-66.0) years; females 74.4%; anti-Jo1 53.5%], 13 (30%) were diagnosed with myocarditis. In 54% of those 13 patients, myocarditis was diagnosed at clinical onset. All patients with ASS with myocarditis had at least one CMRI abnormality: increased ECV in all cases, presence of LGE in 91%, and increased T1 and T2 mapping in 91%. The 2009 Lake Louise criteria (LLC) were satisfied by 6 patients, and the 2018 LLC by 10 patients. With the updated LLC, the sensitivity for myocarditis improved from 54.6% to 91.0%. Patients with ASS with myocarditis were more frequently males (53% vs 13%; P = 0.009) with fever (69% vs 17%; P = 0.001), and had higher hs-TnT [88.0 (23.55-311.5) vs 9.80 (5.0-23.0) ng/l; P < 0.001], NT-proBNP [525.5 (243.5-1575.25) vs 59.0 (32.0-165.5; P = 0.013) pg/ml; P = 0.013] and CRP [7.0 (1.7-15.75) vs 1.85 (0.5-2.86) mg/l; P = 0.011] compared with those without myocarditis. Conclusion: In ASS, myocarditis is frequent, even at clinical onset. Patients with ASS with myocarditis frequently presented with fever and increased CRP, suggesting the existence of an inflammatory phenotype. The use of novel CMRI mapping techniques may increase diagnostic sensitivity for myocarditis in ASS.

AbstractAimsLittle is known about patients with right bundle branch block (RBBB)-ventricular tachycardia (VT) and arrhythmogenic cardiomyopathy (ACM). Our aims were: (i) to describe electrocardiogram (ECG) characteristics of sinus rhythm (SR) and VT; (ii) to correlate SR with RBBB-VT ECGs; and (iii) to compare VT ECGs with electro-anatomic mapping (EAM) data.Methods and resultsFrom the European Survey on ACM, 70 patients with spontaneous RBBB-VT were included. Putative left ventricular (LV) sites of origin (SOOs) were estimated with a VT-axis-derived methodology and confirmed by EAM data when available. Overall, 49 (70%) patients met definite Task Force Criteria. Low QRS voltage predominated in lateral leads (n = 37, 55%), but QRS fragmentation was more frequent in inferior leads (n = 15, 23%). T-wave inversion (TWI) was equally frequent in inferior (n = 28, 42%) and lateral (n = 27, 40%) leads. TWI in inferior leads was associated with reduced LV ejection fraction (LVEF; 46 ± 10 vs. 53 ± 8, P = 0.02). Regarding SOOs, the inferior wall harboured 31 (46%) SOOs, followed by the lateral wall (n = 17, 25%), the anterior wall (n = 15, 22%), and the septum (n = 4, 6%). EAM data were available for 16 patients and showed good concordance with the putative SOOs. In all patients with superior-axis RBBB-VT who underwent endo-epicardial VT activation mapping, VT originated from the LV.ConclusionsIn patients with ACM and RBBB-VT, RBBB-VTs originated mainly from the inferior and lateral LV walls. SR depolarization and repolarization abnormalities were frequent and associated with underlying variants.

Over recent years, preclinical and clinical evidence has implicated myocardial inflammation (M-Infl) in the pathophysiology and phenotypes of traditionally genetic cardiomyopathies. M-Infl resembling myocarditis on imaging and histology occurs frequently as a clinical manifestation of classically genetic cardiac diseases, including dilated and arrhythmogenic cardiomyopathy. The emerging role of M-Infl in disease pathophysiology is leading to the identification of druggable targets for molecular treatment of the inflammatory process and a new paradigm in the field of cardiomyopathies. Cardiomyopathies constitute a leading cause of heart failure and arrhythmic sudden death in the young population. The aim of this review is to present, from bedside to bench, the current state of the art about the genetic basis of M-Infl in nonischemic cardiomyopathies of the dilated and arrhythmogenic spectrum in order to prompt future research towards the identification of novel mechanisms and treatment targets, with the ultimate goal of lowering disease morbidity and mortality.

Aims:Clinical features and risk stratification of patients with viral myocarditis (VM) complicated by ventricular arrhythmias (VA) are incompletely understood. We aim to describe arrhythmia patterns and outcomes in patients with VM and early-onset VA.Methods and results:We present a single-centre study, enrolling patients with VM proven by endomyocardial biopsy, and evidence of VA within 24 h of hospitalization. The incidence of major adverse events (MAE), including all-cause death, severe heart failure, advanced atrioventricular blocks, or major VA, was evaluated during a 24-month follow-up (FU) and compared with a matched group of virus-negative myocarditis. Of patients with VM (n = 74, mean age 47 ± 16 years, 66% males, and left ventricular ejection fraction 51 ± 13%), 20 (27%) presented with major VA [ventricular tachycardia/ventricular fibrillation (VT/VF)], and 32 (44%) had polymorphic VA. Patients with polymorphic VA more commonly had evidence of ongoing systemic infection (24/32 vs. 10/42, P = 0.004) and experienced greater occurrence of MAE at discharge (15/32 vs. 2/42, P < 0.001). However, the incidence of MAE during FU was higher in patients with monomorphic VA compared to those with polymorphic VA (17/42 vs. 2/28, P = 0.002). Patients with monomorphic VA displayed frequently signs of chronic cardiomyopathy and had outcomes comparable with virus-negative myocarditis (log rank P = 0.929). Presentation with VT/VF was independently associated with MAE [at discharge: hazard ratio (HR) 4.7, 95% confidence interval (CI) 1.6-14.0, P = 0.005; during FU: HR 6.3, 95% CI 2.3-17.6, P < 0.001].Conclusion:In patients with VM, polymorphic VA point to ongoing systemic infection and early adverse outcomes, whereas monomorphic VA suggest chronic cardiomyopathy and greater incidence of MAE during FU. Presentation with VT/VF is independently associated with MAE.

Background:Acute myocarditis (AM) is thought to be a rare cardiovascular complication of COVID-19, although minimal data are available beyond case reports. We aim to report the prevalence, baseline characteristics, in-hospital management, and outcomes for patients with COVID-19–associated AM on the basis of a retrospective cohort from 23 hospitals in the United States and Europe.Methods:A total of 112 patients with suspected AM from 56 963 hospitalized patients with COVID-19 were evaluated between February 1, 2020, and April 30, 2021. Inclusion criteria were hospitalization for COVID-19 and a diagnosis of AM on the basis of endomyocardial biopsy or increased troponin level plus typical signs of AM on cardiac magnetic resonance imaging. We identified 97 patients with possible AM, and among them, 54 patients with definite/probable AM supported by endomyocardial biopsy in 17 (31.5%) patients or magnetic resonance imaging in 50 (92.6%). We analyzed patient characteristics, treatments, and outcomes among all COVID-19–associated AM.Results:AM prevalence among hospitalized patients with COVID-19 was 2.4 per 1000 hospitalizations considering definite/probable and 4.1 per 1000 considering also possible AM. The median age of definite/probable cases was 38 years, and 38.9% were female. On admission, chest pain and dyspnea were the most frequent symptoms (55.5% and 53.7%, respectively). Thirty-one cases (57.4%) occurred in the absence of COVID-19–associated pneumonia. Twenty-one (38.9%) had a fulminant presentation requiring inotropic support or temporary mechanical circulatory support. The composite of in-hospital mortality or temporary mechanical circulatory support occurred in 20.4%. At 120 days, estimated mortality was 6.6%, 15.1% in patients with associated pneumonia versus 0% in patients without pneumonia (P=0.044). During hospitalization, left ventricular ejection fraction, assessed by echocardiography, improved from a median of 40% on admission to 55% at discharge (n=47;P<0.0001) similarly in patients with or without pneumonia. Corticosteroids were frequently administered (55.5%).Conclusions:AM occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia.

BACKGROUND:Predictors of major adverse cardiovascular events (MACE) in patients with undefined left ventricular arrhythmogenic cardiomyopathy (ULVACM) have not been described. OBJECTIVES:The purpose of this study was to investigate the prognostic value of genetic testing and histology in a cohort of ULVACM patients. METHODS:We identified 313 patients with ULVACM defined by new-onset ventricular arrhythmia (VA), nonischemic pattern of late gadolinium enhancement limited to the left ventricle (LV), and no severe dilated cardiomyopathy (LV ejection fraction ≥40%) from a retrospective multicenter registry. Patients undergoing next generation sequencing (NGS) for cardiomyopathy genes and endomyocardial biopsy (EMB) were compared with subjects without these studies. The primary endpoint was the occurrence of MACE, defined as the composite of cardiac death, heart transplantation, and malignant VA (ventricular tachycardia, ventricular fibrillation, appropriate implantable cardioverter-defibrillator treatment), at 60 months after clinical presentation. RESULTS:Of the whole cohort (age 46 ± 14 years, 63% men, LV ejection fraction 55% ± 7%), 160 (51%) and 198 patients (63%), respectively, underwent NGS and EMB. NGS identified pathogenic or likely-pathogenic cardiomyopathy variants (pathogenic variants/likely pathogenic variants) in 25 of 160 cases (16%). EMB showed active myocardial inflammation (AM) in 102 of 198 patients (52%), 47 of whom (46%) received immunosuppressive therapy. After 58-month median follow-up, 93 of 313 patients (30%) experienced MACE. On multivariable analysis, presentation with malignant VA and EMB-proven AM were positively associated with the primary endpoint (HR: 2.8; 95% CI: 1.4-5.5; P = 0.003; and HR: 3.9; 95% CI: 1.9-7.5; P < 0.001, respectively), whereas immunosuppressive therapy showed a reverse association with MACE at 60 months (HR: 0.10; 95% CI: 0.05-0.40; P < 0.001). CONCLUSIONS:Presentation with malignant VA or AM associates with MACE in ULVACM patients.

BACKGROUND:mRNA COVID-19 vaccines have been associated with myocarditis in the general population. However, application of gold standard techniques is often missing, and data about patients with history of myocarditis have not been reported yet.METHODS:We evaluated 21 patients (median age 27, 86% males) for suspected myocarditis after receiving mRNA COVID-19 vaccine. We divided cases with previous diagnosis of myocarditis (PM, N.=7), from naïve controls (NM, N.=14). All patients were investigated thoroughly by cardiac magnetic resonance (100%) with or without endomyocardial biopsy (14%).RESULTS:Overall, 57% of patients met updated Lake Louise criteria and none fulfilled Dallas criteria, with no remarkable differences between groups. Acute coronary syndrome-like presentation was more frequent in NM with earlier normalization of troponin than PM. NM and PM already healed from myocarditis were clinically comparable, whereas PM with active inflammation had subtle presentation and were evaluated for immunosuppressive therapy modulation. None had fulminant myocarditis and/or malignant ventricular arrhythmia at presentation. No major cardiac events occurred by 3 months.CONCLUSIONS:In this study, the suspicion of mRNA COVID-19 vaccine-associated myocarditis was inconstantly confirmed by gold standard diagnostics. Myocarditis was uncomplicated in both PM and NM patients. Larger studies with longer follow-up are needed to validate COVID-19 vaccination in this population.

Peretto, Giovanni; Maranta, Francesco; Cianfanelli, Lorenzo; Sala, Simone; Cianflone, Domenico Author Information