Myocarditis following COVID-19 vaccination

The coronavirus disease 2019 (COVID-19) vaccination frequently leads to minor side-effects, that may be more intense after the second dose, but more serious side effects have been reported. We report a case of a 24-year-old man who presented to the hospital with acute substernal chest pain, 4 days after his second COVID-19 Moderna vaccination. Laboratory studies revealed elevated troponins and negative viral serologies. Cardiac magnetic resonance imaging (cMRI) demonstrated edema and delayed gadolinium enhancement of the left ventricle in a midmyocardial and epicardial distribution. The patient was diagnosed with myocarditis following Moderna vaccination. Our case report raises concern that myocarditis is a rare side effect of COVID-19 vaccine. Despite our report, it appears that there is a significantly higher risk of cardiac involvement from COVID-19 infection compared to COVID-19 vaccination

Effect of Left Atrial Function Index on Late Atrial Fibrillation Recurrence after Pulmonary Vein Isolation

Background: Although the rates of catheter ablation (CA) for atrial fibrillation (AF) are rapidly increasing, there are few predictors of outcome to help inform appropriate patient selection for this procedure. Traditional echocardiographic measures of atrial structure do not significantly reclassify risk of AF recurrence over and above the clinical risk factors. Left Atrial Function Index (LAFI) is a rhythm-independent measure of atrial function. We hypothesized that baseline LAFI would relate to AF recurrence after CA. Methods: Pre-procedural echocardiograms from 170 participants, who underwent CA for AF and were enrolled in the UMMC AF Treatment Registry, were analyzed. LAFI was calculated by a previously validated formula. Primary outcome was late or clinically significant AF recurrence 3-12 months after CA. Baseline clinical, laboratory and echocardiographic variables were compared between the recurrence and non-recurrence groups. Results: Study participants were middle aged (60+/10 years) and had a moderate-to-severe burden of cardiovascular comorbidities. 78 participants (46%) experienced late AF recurrence. Mean LAFI was 0.26+/-0.18. In multivariate analysis, lower LAFI was independently associated with the risk of recurrence (0.23 in recurrence group vs 0.29 in non-recurrence group, p \u3c 0.01). Predictive value of LAFI for AF recurrence was similar to CHADS2 score (c-statistic 0.60 vs 0.58, p 0.76). In subgroup of patients with persistent AF, LAFI predicted AF recurrence more strongly than CHADS2 score (c-statistic: 0.79 vs 0.58, p 0.02). Conclusions: In our cohort of 170 participants with AF undergoing index CA ablation, we observed that LAFI related to late AF recurrence after CA, independent of the traditional risk factors. Since LAFI can be calculated from almost any traditional echocardiographic recording, our findings suggest that LAFI may help guide therapeutic decision-making regarding application of CA, particularly among challenging patients with symptomatic persistent AF

Assessment of left ventricular diastolic function in children after successful repair of aortic coarctation

The purpose of the study was an assessment of left ventricular diastolic function in children after the successful repair of aortic coarctation (CoA). The prospective study concerned 32 pediatric patients after the CoA surgery. Tissue Doppler imaging parameters including strain and strain rate and the conventional echocardiographic indexes were analyzed in patients and healthy controls. Analysis of mitral annulus velocities, E–E′ ratio, strain, and strain rate of left ventricular mid-cavity segments and conventional indexes of mitral inflow showed the worsening of left ventricular diastolic mechanics in the study group compared to healthy controls. The E/E′ ratio was significantly higher in the study group compared to the control group (8.30 ± 3.24 vs. 6.95 ± 1.36; p < 0.05). The early diastolic strain rate to late diastolic strain rate ratio as well as early to late diastolic strain ratio of the left ventricular mid-cavity segments were significantly lower in the study group compared to healthy controls (1.81 ± 0.63 vs. 3.74 ± 1.53; p < 0.001 and 1.20 ± 0.49 vs. 3.41 ± 1.26; p < 0.001). No differences of the pulmonary venous flow parameters between those two groups were observed. The left ventricular diastolic mechanics in hypertensive patients after CoA repair did not differ from normotensive subjects. Hypertensive and normotensive children after surgical repair of CoA are found to have worsening of the left ventricular diastolic mechanics suggesting the impairment of the active myocardial relaxation

The PPARGC1A Gly482Ser polymorphism is associated with left ventricular diastolic dysfunction in men

<p>Abstract</p> <p>Background</p> <p>The Gly482Ser polymorphism in peroxisome proliferator-activated receptor gamma coactivator-1 alpha (<it>PPARGC1A</it>) has been demonstrated to be associated with diabetes, obesity and hypertension, all of which are important risk factors for left ventricular diastolic dysfunction.</p> <p>Methods</p> <p>The <it>PPARGC1A </it>Gly482Ser polymorphism was genotyped in a community-based cohort of 499 men and 533 women, who also underwent an echocardiographic examination to determine their left ventricular diastolic function. The association between the polymorphism and the presence of diastolic dysfunction was evaluated using logistic regression models.</p> <p>Results</p> <p>The Ser allele of the <it>PPARGC1A </it>Gly482Ser polymorphism was significantly associated with a lower risk of diastolic dysfunction in men, but not in women. In a model adjusting for potential confounders (age, body mass index, leisure time physical activity, hypertension and diabetes) the results were still significant and substantial (odds ratio 0.13, 95% confidence interval 0.03–0.54, p for trend = 0.004). The results were consistent in a series of models, and they imply a multiplicative, protective effect of the Ser allele, with lower risk of diastolic dysfunction for each copy of the allele.</p> <p>Conclusion</p> <p>The Ser allele of the <it>PPARGC1A </it>Gly482Ser polymorphism was associated with decreased risk of diastolic left ventricular dysfunction in men, but not in women, in our large community-based sample. It was associated with a substantially decreased risk, even after adjustment for potential confounders. The clinical importance of the findings has to be established in further studies.</p

Androgens Contribute to Sex Differences in Myocardial Remodeling under Pressure Overload by a Mechanism Involving TGF-β

Background: In clinical studies, myocardial remodeling in aortic valve stenosis appears to be more favorable in women than in men, even after menopause. In the present study, we assessed whether circulating androgens contribute to a less favorable myocardial remodeling under pressure overload in males. We examined sex-related differences in one-year-old male and female mice. Whereas male mice at this age exhibited circulating androgen levels within the normal range for young adults, the circulating estrogens in females were reduced. The contribution of gonadal androgens to cardiac remodeling was analyzed in a group of same-age castrated mice. Methodology/Principal Findings: Animals were subjected to transverse aortic constriction (TAC). Echocardiography was performed 2 weeks after TAC and myocardial mRNA levels of TGF-bs, Smads 2 and 3, collagens, fibronectin, b-myosin heavy chain and a-myosin heavy chain were determined by q-PCR. Protein detection of p-SMAD2/3 was performed by Western Blot. Histological staining of fibrosis was performed with picrosirius red and Masson’s trichrome. Compared with females, males developed more severe tissue fibrosis, LV dilation and hemodynamic dysfunction. TAC-males showed higher myocardial expression levels of TGF-bs and the treatment with a neutralizing antibody to TGF-b prevented myocardial fibrosis development. Orchiectomy diminished TAC-induced up-regulation of TGF-bs and TGF-b target genes, and it also reduced fibrosis and hemodynamic dysfunction. The capability of androgens to induce TGF-b expression was confirmed i

Sex-specific pathways in early cardiac response to pressure overload in mice

Pressure overload (PO) first causes cardiac hypertrophy and then heart failure (HF), which are associated with sex differences in cardiac morphology and function. We aimed to identify genes that may cause HF-related sex differences. We used a transverse aortic constriction (TAC) mouse model leading to hypertrophy without sex differences in cardiac function after 2 weeks, but with sex differences in hypertrophy 6 and 9 weeks after TAC. Cardiac gene expression was analyzed 2 weeks after surgery. Deregulated genes were classified into functional gene ontology (GO) categories and used for pathway analysis. Classical marker genes of hypertrophy were similarly upregulated in both sexes (α-actin, ANP, BNP, CTGF). Thirty-five genes controlling mitochondrial function (PGC-1, cytochrome oxidase, carnitine palmitoyl transferase, acyl-CoA dehydrogenase, pyruvate dehydrogenase kinase) had lower expression in males compared to females after TAC. Genes encoding ribosomal proteins and genes associated with extracellular matrix remodeling exhibited relative higher expression in males (collagen 3, matrix metalloproteinase 2, TIMP2, and TGFβ2, all about twofold) after TAC. We confirmed 87% of the gene expression by real-time polymerase chain reaction. By GO classification, female-specific genes were related to mitochondria and metabolism and males to matrix and biosynthesis. Promoter studies confirmed the upregulation of PGC-1 by E2. Less downregulation of metabolic genes in female hearts and increased protein synthesis capacity and deregulation of matrix remodeling in male hearts characterize the sex-specific early response to PO. These differences could contribute to subsequent sex differences in cardiac function and HF

Prevalence of Symptomatic Heart Failure with Reduced and with Normal Ejection Fraction in an Elderly General Population-The CARLA Study

Background/Objectives: Chronic heart failure (CHF) is one of the most important public health concerns in the industrialized world having increasing incidence and prevalence. Although there are several studies describing the prevalence of heart failure with reduced ejection fraction (HFREF) and heart failure with normal ejection fraction (HFNEF) in selected populations, there are few data regarding the prevalence and the determinants of symptomatic heart failure in the general population. Methods: Cross-sectional data of a population-based German sample (1,779 subjects aged 45-83 years) were analyzed to determine the prevalence and determinants of chronic SHF and HFNEF defined according to the European Society of Cardiology using symptoms, echocardiography and serum NT-proBNP. Prevalence was age-standardized to the German population as of December 31st, 2005. Results: The overall age-standardized prevalence of symptomatic CHF was 7.7% (95%CI 6.0-9.8) for men and 9.0% (95%CI 7.0-11.5) for women. The prevalence of CHF strongly increased with age from 3.0% among 45-54- year-old subjects to 22.0% among 75-83- year-old subjects. Symptomatic HFREF could be shown in 48% (n = 78), symptomatic HFNEF in 52% (n = 85) of subjects with CHF. The age-standardized prevalence of HFREF was 3.8 % (95%CI 2.4-5.8) for women and 4.6 % (95%CI 3.6-6.3) for men. The age-standardized prevalence of HFNEF for women and men was 5.1 % (95%CI 3.8-7.0) and 3.0 % (95%CI 2.1-4.5), respectively. Persons with CHF were more likely to have hypertension (PR = 3.4; 95%CI 1.6-7.3) or to have had a previous myocardial infarction (PR = 2.5, 95%CI 1.8-3.5). Conclusion: The prevalence of symptomatic CHF appears high in this population compared with other studies. While more women were affected by HFNEF than men, more male subjects suffered from HFREF. The high prevalence of symptomatic CHF seems likely to be mainly due to the high prevalence of cardiovascular risk factors in this population

Regulation of early steps of GPVI signal transduction by phosphatases: a systems biology approach

We present a data-driven mathematical model of a key initiating step in platelet activation, a central process in the prevention of bleeding following Injury. In vascular disease, this process is activated inappropriately and causes thrombosis, heart attacks and stroke. The collagen receptor GPVI is the primary trigger for platelet activation at sites of injury. Understanding the complex molecular mechanisms initiated by this receptor is important for development of more effective antithrombotic medicines. In this work we developed a series of nonlinear ordinary differential equation models that are direct representations of biological hypotheses surrounding the initial steps in GPVI-stimulated signal transduction. At each stage model simulations were compared to our own quantitative, high-temporal experimental data that guides further experimental design, data collection and model refinement. Much is known about the linear forward reactions within platelet signalling pathways but knowledge of the roles of putative reverse reactions are poorly understood. An initial model, that includes a simple constitutively active phosphatase, was unable to explain experimental data. Model revisions, incorporating a complex pathway of interactions (and specifically the phosphatase TULA-2), provided a good description of the experimental data both based on observations of phosphorylation in samples from one donor and in those of a wider population. Our model was used to investigate the levels of proteins involved in regulating the pathway and the effect of low GPVI levels that have been associated with disease. Results indicate a clear separation in healthy and GPVI deficient states in respect of the signalling cascade dynamics associated with Syk tyrosine phosphorylation and activation. Our approach reveals the central importance of this negative feedback pathway that results in the temporal regulation of a specific class of protein tyrosine phosphatases in controlling the rate, and therefore extent, of GPVI-stimulated platelet activation

Diastolic dysfunction in diabetes and the metabolic syndrome: promising potential for diagnosis and prognosis

Cardiac disease in diabetes mellitus and in the metabolic syndrome consists of both vascular and myocardial abnormalities. The latter are characterised predominantly by diastolic dysfunction, which has been difficult to evaluate in spite of its prevalence. While traditional Doppler echocardiographic parameters enable only semiquantitative assessment of diastolic function and cannot reliably distinguish perturbations in loading conditions from altered diastolic functions, new technologies enable detailed quantification of global and regional diastolic function. The most readily available technique for the quantification of subclinical diastolic dysfunction is tissue Doppler imaging, which has been integrated into routine contemporary clinical practice, whereas cine magnetic resonance imaging (CMR) remains a promising complementary research tool for investigating the molecular mechanisms of the disease. Diastolic function is reported to vary linearly with age in normal persons, decreasing by 0.16 cm/s each year. Diastolic function in diabetes and the metabolic syndrome is determined by cardiovascular risk factors that alter myocardial stiffness and myocardial energy availability/bioenergetics. The latter is corroborated by the improvement in diastolic function with improvement in metabolic control of diabetes by specific medical therapy or lifestyle modification. Accordingly, diastolic dysfunction reflects the structural and metabolic milieu in the myocardium, and may allow targeted therapeutic interventions to modulate cardiac metabolism to prevent heart failure in insulin resistance and diabetes