Background Coronavirus disease-2019 (COVID-19) is thought to predispose patients to thrombotic disease. To date there are few reports of ST-segment elevation myocardial infarction (STEMI) caused by type 1 myocardial infarction in patients with COVID-19. Objectives The aim of this study was to describe the demographic, angiographic, and procedural characteristics alongside clinical outcomes of consecutive cases of COVID-19–positive patients with STEMI compared with COVID-19–negative patients. Methods This was a single-center, observational study of 115 consecutive patients admitted with confirmed STEMI treated with primary percutaneous coronary intervention at Barts Heart Centre between March 1, 2020, and May 20, 2020. Results Patients with STEMI presenting with concurrent COVID-19 infection had higher levels of troponin T and lower lymphocyte count, but elevated D-dimer and C-reactive protein. There were significantly higher rates of multivessel thrombosis, stent thrombosis, higher modified thrombus grade post first device with consequently higher use of glycoprotein IIb/IIIa inhibitors and thrombus aspiration. Myocardial blush grade and left ventricular function were significantly lower in patients with COVID-19 with STEMI. Higher doses of heparin to achieve therapeutic activated clotting times were also noted. Importantly, patients with STEMI presenting with COVID-19 infection had a longer in-patient admission and higher rates of intensive care admission. Conclusions In patients presenting with STEMI and concurrent COVID-19 infection, there is a strong signal toward higher thrombus burden and poorer outcomes. This supports the need for establishing COVID-19 status in all STEMI cases. Further work is required to understand the mechanism of increased thrombosis and the benefit of aggressive antithrombotic therapy in selected cases.

Reactivation of varicella zoster virus (VZV) is a common event in patients undergoing allogeneic bone marrow transplantation (BMT) and may lead to life-threatening complications. We retrospectively analyzed the incidence, clinical outcome, and risk factors for VZV infections occurring within the first 5 years of transplantation in 100 consecutive adults undergoing allogeneic BMT between 1992 and 1997. Forty-one patients (41%) developed VZV reactivation a median of 227 days (range 45-346 days) post-transplantation. Twelve percent of VZV reactivation occurred in the first 100 days and 88% within the first 24 months. Among those who survived for 2 or more years after transplantation (n = 47), 59% developed VZV infection. Forty percent of patients with VZV reactivation required admission with a mean hospital stay of 7.2 days. Two patients developed encephalitis, and 1 died despite antiviral therapy. The most frequent complications were post-herpetic neuralgia and peripheral neuropathy (68%). Thoracic dermatomal zoster represented 41% of the infections; disseminated cutaneous involvement was observed in 17% of patients. No clinical or epidemiologic risk factors were associated with recurrence. Administration of ganciclovir for prevention of cytomegalovirus infection delayed the onset of VZV infection beyond 4 months (P = .06). In a further subset analysis, patients with a limited chronic graft-versus-host disease (GVHD) had a lower estimated incidence of VZV reactivation compared with those with extensive chronic GVHD (P = .11). We conclude that complications from reactivation of VZV infection are common and associated with considerable morbidity and mortality in patients undergoing allogeneic BMT.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by pathogenic variants in the-galactosidase A (GLA) gene that leads to reduced or undetectable-galactosidase A enzyme activity and progressive accumulation of globotriaosylceramide and its deacylated form globotriaosylsphingosine in cells throughout the body. FD can be multisystemic with neurological, renal, cutaneous and cardiac involvement or be limited to the heart. Cardiac involvement is characterized by progressive cardiac hypertrophy, fibrosis, arrhythmias, heart failure and sudden cardiac death. The cardiac management of FD requires specific measures including enzyme replacement therapy or small pharmacological chaperones in patients carrying amenable pathogenic GLA gene variants and more general management of cardiac symptoms and complications. In this paper, we summarize current knowledge of FD-related heart disease and expert consensus recommendations for its management.

Aims  Myocardial scar detected by cardiovascular magnetic resonance has been associated with sudden cardiac death in dilated cardiomyopathy (DCM). Certain genetic causes of DCM may cause a malignant arrhythmogenic phenotype. The concepts of arrhythmogenic left ventricular (LV) cardiomyopathy (ALVC) and arrhythmogenic DCM are currently ill-defined. We hypothesized that a distinctive imaging phenotype defines ALVC. Methods and results  Eighty-nine patients with DCM-associated mutations [desmoplakin (DSP) n = 25, filamin C (FLNC) n = 7, titin n = 30, lamin A/C n = 12, bcl2-associated athanogene 3 n = 3, RNA binding motif protein 20 n = 3, cardiac sodium channel NAv1.5 n = 2, and sarcomeric genes n = 7] were comprehensively phenotyped. Clustering analysis resulted in two groups: ‘DSP/FLNC genotypes’ and ‘non-DSP/FLNC’. There were no significant differences in age, sex, symptoms, baseline electrocardiography, arrhythmia burden, or ventricular volumes between the two groups. Subepicardial LV late gadolinium enhancement with ring-like pattern (at least three contiguous segments in the same short-axis slice) was observed in 78.1% of DSP/FLNC genotypes but was absent in the other DCM genotypes (P < 0.001). Left ventricular ejection fraction (LVEF) and global longitudinal strain were lower in other DCM genotypes (P = 0.053 and P = 0.015, respectively), but LV regional wall motion abnormalities were more common in DSP/FLNC genotypes (P < 0.001). DSP/FLNC patients with non-sustained ventricular tachycardia (NSVT) had more LV scar (P = 0.010), whereas other DCM genotypes patients with NSVT had lower LVEF (P = 0.001) than patients without NSVT. Conclusion DSP/FLNC genotypes cause more regionality in LV impairment. The most defining characteristic is a subepicardial ring-like scar pattern in DSP/FLNC, which should be considered in future diagnostic criteria for ALVC.

Background: Truncating variants in the TTN gene (TTNtv) are the commonest cause of heritable dilated cardiomyopathy. This study aimed to study the phenotypes and outcomes of TTNtv carriers. Methods: Five hundred thirty-seven individuals (61% men; 317 probands) with TTNtv were recruited in 14 centers (372 [69%] with baseline left ventricular systolic dysfunction [LVSD]). Baseline and longitudinal clinical data were obtained. The primary end point was a composite of malignant ventricular arrhythmia and end-stage heart failure. The secondary end point was left ventricular reverse remodeling (left ventricular ejection fraction increase by ≥10% or normalization to ≥50%). Results: Median follow-up was 49 (18–105) months. Men developed LVSD more frequently and earlier than women (45±14 versus 49±16 years, respectively; P =0.04). By final evaluation, 31%, 45%, and 56% had atrial fibrillation, frequent ventricular ectopy, and nonsustained ventricular tachycardia, respectively. Seventy-six (14.2%) individuals reached the primary end point (52 [68%] end-stage heart failure events, 24 [32%] malignant ventricular arrhythmia events). Malignant ventricular arrhythmia end points most commonly occurred in patients with severe LVSD. Male sex (hazard ratio, 1.89 [95%CI, 1.04–3.44]; P =0.04) and left ventricular ejection fraction (per 10% decrement from left ventricular ejection fraction, 50%; hazard ratio, 1.63 [95%CI, 1.30–2.04]; P <0.001) were independent predictors of the primary end point. Two hundred seven of300 (69%) patients with LVSD had evidence of left ventricular reverse remodeling. In a subgroup of 29 of74 (39%) patients with initial left ventricular reverse remodeling, there was a subsequent left ventricular ejection fraction decrement. TTNtv location was not associated with statistically significant differences in baseline clinical characteristics, left ventricular reverse remodeling, or outcomes on multivariable analysis ( P =0.07). Conclusions: TTNtv is characterized by frequent arrhythmia, but malignant ventricular arrhythmias are most commonly associated with severe LVSD. Male sex and LVSD are independent predictors of outcomes. Mutation location does not impact clinical phenotype or outcomes.

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More than a century has passed since the first description of Hashimoto thyroiditis (HT) as a clinicopathologic entity. HT is an autoimmune disease in which a breakdown of immune tolerance is caused by interplay of a variety of immunologic, genetic, and environmental factors. Thyrocyte injury resulting from environmental factors results in expression of new or hidden epitopes that leads to proliferation of autoreactive T and B cells. Infiltration of thyroid by these cells results in HT. In addition to the usual type of HT, several variants such as the fibrous type and Riedal thyroiditis are also recognized. The most recently recognized variant is immunoglobulin G4(+) HT, which may occur as isolated thyroid limited disease or as part of a generalized Ig4-related sclerosing disease. The relationship between HT and Riedel thyroiditis remains unclear; however, recent evidence seems to suggest that it may also be part of the spectrum of Ig4-related sclerosing disease. HT is frequently associated with papillary thyroid carcinoma and may indeed be a risk factor for developing this type of cancer. The relationship between thyroid lymphoma and HT on the other hand appears well established.

Background: Pathogenic variants in the filamin C (FLNC) gene are associated with inherited cardiomyopathies including dilated cardiomyopathy with an arrhythmogenic phenotype. We evaluated FLNC variants in arrhythmogenic cardiomyopathy (ACM) and investigated the disease mechanism at a molecular level. Methods: 120 gene-elusive ACM patients who fulfilled diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC) were screened by whole exome sequencing. Fixed cardiac tissue from FLNC variant carriers who had died suddenly was investigated by histology and immunohistochemistry. Results: Novel or rare FLNC variants, four null and five variants of unknown significance, were identified in nine ACM probands (7.5%). In FLNC null variant carriers (including family members, n = 16) Task Force diagnostic electrocardiogram repolarization/depolarization abnormalities were uncommon (19%), echocardiography was normal in 69%, while 56% had N500 ventricular ectopics/24 h or ventricular tachycardia on Holter and 67% had late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMRI). Ten gene positive individuals (63%) had abnormalities on ECG or CMRI that are not included in the current diagnostic criteria for ARVC. Immunohistochemistry showed altered key protein distribution, distinctive from that observed in ARVC, predominantly in the left ventricle. Conclusions: ACM associated with FLNC variants presents with a distinctive phenotype characterized by Holter arrhythmia and LGE on CMRI with unremarkable ECG and echocardiographic findings. Clinical presentation in asymptomatic mutation carriers at risk of sudden death may include abnormalities which are currently nondiagnostic for ARVC. At the molecular level, the pathogenic mechanism related to FLNC appears different to classic forms of ARVC caused by desmosomal mutations.