The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has posed a serious threat to global public health. A novel vaccine made from messenger RNA (mRNA) has been developed and approved for use at an unprecedented pace. However, an increased risk of myocarditis has been reported after BNT162b2 mRNA vaccination due to unknown causes. In this study, we used single-cell RNA sequencing and single-cell T cell receptor sequencing analyses of peripheral blood mononuclear cells (PBMCs) to describe, for the first time, changes in the peripheral immune landscape of a patient who underwent myocarditis after BNT162b2 vaccination. The greatest changes were observed in the transcriptomic profile of monocytes in terms of the number of differentially expressed genes. When compared to the transcriptome of PBMCs from vaccinated individuals without complications, increased expression levels of IL7R were detected in multiple cell clusters. Overall, results from this study can help advance research into the pathogenesis of BNT162b2-induced myocarditis.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been the most dangerous threat to public health worldwide for the last few years, which led to the development of the novel mRNA vaccine (BNT162b2). However, BNT162b2 vaccination is known to be associated with myocarditis. Here, as an attempt to determine the pathogenesis of the disease and to develop biomarkers to determine whether subjects likely proceed to myocarditis after vaccination, we conducted a time series analysis of peripheral blood mononuclear cells of a patient with BNT162b2-induced myocarditis. Single-cell RNA sequence analysis identified monocytes as the cell clusters with the most dynamic changes. To identify distinct gene expression signatures, we compared monocytes of BNT162b2-induced myocarditis with monocytes under various conditions, including SARS-CoV-2 infection, BNT162b2 vaccination, and Kawasaki disease, a disease similar to myocarditis. Representative changes in the transcriptomic profile of classical monocytes include the upregulation of genes related to fatty acid metabolism and downregulation of transcription factor AP-1 activity. This study provides, for the first time, the importance of classical monocytes in the pathogenesis of myocarditis following BNT162b2 vaccination and presents the possibility that vaccination affects monocytes, further inducing their differentiation and infiltration into the heart.

After the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, a novel mRNA vaccine (BNT162b2) was developed at an unprecedented speed. Although most countries have achieved widespread immunity from vaccines and infections, yet people, even who have recovered from SARS-CoV-2 infection, are recommended to receive vaccination due to their effectiveness in lowering the risk of recurrent infection. However, the BNT162b2 vaccine has been reported to increase the risk of myocarditis. To our knowledge, for the first time in this study, we tracked changes in the chromatin dynamics of peripheral blood mononuclear cells (PBMCs) in the patient who underwent myocarditis after BNT162b2 vaccination. A longitudinal study of chromatin accessibility using concurrent analysis of single-cell assays for transposase-accessible chromatin with sequencing and single-cell RNA sequencing showed downregulation of interferon signaling and upregulated RUNX2/3 activity in PBMCs. Considering BNT162b2 vaccination increases the level of interferon-α/γ in serum, our data highlight the immune responses different from the conventional responses to the vaccination, which is possibly the key to understanding the side effects of BNT162b2 vaccination.

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We report a case of excessive QT prolongation and subsequent torsades de pointes (TdP) following the administration of ticagrelor in a 58-year-old male patient. The patient had no suspected cause of QT prolongation. After cessation of ticagrelor, QT interval was normalized and no further TdP was observed.

index (LAVI). Conclusions: By utilizing 2016 versus 2009 diastolic function criteria to a Hispanic population with T2D, the prevalence of PDD decreased from 37% to 7%, consistent with the new guidelines being more specific and less sensitive for diagnosing PDD.

10-15%. Left heart catheterization demonstrated normal coronary arteries and endomyocardial biopsy revealed mild acute cellular rejection (1R). He was treated with intravenous diuretics, steroids and induction with thymoglobulin. Repeat endomyocardial biopsy was negative for cellular rejection and interval transthoracic echocardiography (TTE) showed only minimal improvement in LVEF to 20%. Guidelinedirected medical therapy for heart failure was titrated to maximally tolerated doses with no improvement in LVEF. He subsequently underwent His-bundle pacing (HBP) with defibrillator placement. ECG after showed non-selective His bundle pacing with a QRS duration of 142 ms ( Figure 1B). TTE at one month post-HBP revealed an LVEF of 42% and by four months his LVEF had normalized to 60%. Left ventricular end diastolic diameter decreased from 5.5 cm to 4.7 cm and left ventricular end systolic diameter decreased from 4.8 cm to 3.2 cm after HBP. Our patient developed persistent LBBB 8 years after cardiac transplantation with the development of LVSD 6 months after. To our knowledge, this is the first reported case of LVSD with LBBB in a post heart transplant patient treated successfully with HBP with normalization of LVEF. We believe that this temporal relationship in the onset of LBBB concurrent with the development of LVSD, followed by hyper-response to CRT with HBP, is demonstrative of LBBB-induced cardiomyopathy.

Introduction: Potent antiplatelet therapy has a high bleeding risk after acute myocardial infarction, so de-escalation from ticagrelor to clopidogrel has recently been introduced. But, optimal de-escalation strategy according to BMI is unclear. Method In TALOS-AMI trial, patients with acute myocardial infarction receiving aspirin and ticagrelor after index percutaneous coronary intervention (PCI) were investigated. This post hoc study determined the efficacy and safety of de-escalation (clopidogrel plus aspirin) compared with active control (ticagrelor plus aspirin) across a range of patient BMIs. Results Among 2,686 randomized patients, 1,558 (58.0%) had 18.5 ≤BMI <25 kg/m2, 935 (34.8%) had 25 ≤ BMI < 30 kg/m2, and 154 (5.7%) had BMI ≥ 30 kg/m2. The combination of clopidogrel plus aspirin compared with ticagrelor plus aspirin reduced in the primary outcome led by bleeding events reduction, in 18.5 ≤BMI <25 kg/m2. For 18.5 ≤BMI <25 kg/m2: 4.3% vs. 7.9%; hazard ratio (HR): 0.516 (95% confidential interval [CI]: 0.334 to 0.797); 25 ≤ BMI <30 kg/m2: 4.9% vs. 7.1%; HR: 0.674 (95% CI: 0.389 to 1.166); BMI ≥30 kg/m2: 1.2% vs. 4.2%; HR: 0.284 (95% CI: 0.029 to 2.792). Conclusion In conclusion, our results suggest that in the patients of 18.5 kg/m2 ≤BMI <25 kg/m2, with acute myocardial infarction after index PCI, de-escalation strategy is better net clinical outcome, mainly by reducing the bleeding events. But, there are no differences between two groups BMI ≥25 kg/m2.