Acute myocarditis after COVID-19 vaccination with mRNA-1273 in a patient with former SARS-CoV-2 infection.

We describe a case of a 20-year-old healthy man developing chest pain and classical symptoms of vaccine reactogenicity 12 h after receiving the first dose of mRNA-1273 (Moderna). Cardiac troponin T was increased, and subepicardial inflammation and focal contractile dysfunction were detected by cardiac magnetic resonance imaging and echocardiography. We confirmed the diagnosis of acute myocarditis by endomyocardial biopsy demonstrating significant infiltration of monocytes and T lymphocytes. Although we detected IgG against nucleocapsid protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) indicating prior infection, the patient repeatedly tested negative for SARS-CoV-2 and had been asymptomatic for several months. Furthermore, viral genome analysis of endomyocardial biopsy samples was negative for SARS-CoV-2 and other potential cardiotropic viruses. These findings and the strong temporal relation between the vaccination and the symptom onset imply a potential side effect of mRNA-1273.

Longitudinal profiling of circulating miRNA during cardiac allograft rejection: a proof-of-concept study.

AIMS: Allograft rejection following heart transplantation (HTx) is a serious complication even in the era of modern immunosuppressive regimens and causes up to a third of early deaths after HTx. Allograft rejection is mediated by a cascade of immune mechanisms leading to acute cellular rejection (ACR) and/or antibody-mediated rejection (AMR). The gold standard for monitoring allograft rejection is invasive endomyocardial biopsy that exposes patients to complications. Little is known about the potential of circulating miRNAs as biomarkers to detect cardiac allograft rejection. We here present a systematic analysis of circulating miRNAs as biomarkers and predictors for allograft rejection after HTx using next-generation small RNA sequencing. METHODS AND RESULTS: We used next-generation small RNA sequencing to investigate circulating miRNAs among HTx recipients (10 healthy controls, 10 heart failure patients, 13 ACR, and 10 AMR). MiRNA profiling was performed at different time points before, during, and after resolution of the rejection episode. We found three miRNAs with significantly increased serum levels in patients with biopsy-proven cardiac rejection when compared with patients without rejection: hsa-miR-139-5p, hsa-miR-151a-5p, and hsa-miR-186-5p. We identified miRNAs that may serve as potential predictors for the subsequent development of ACR: hsa-miR-29c-3p (ACR) and hsa-miR-486-5p (AMR). Overall, hsa-miR-486-5p was most strongly associated with acute rejection episodes. CONCLUSIONS: Monitoring cardiac allograft rejection using circulating miRNAs might represent an alternative strategy to invasive endomyocardial biopsy.

Meta-analysis for the value of colchicine for the therapy of pericarditis and of postpericardiotomy syndrome.

BACKGROUND: Colchicine has been used as anti-inflammatory agent in pericardial effusion (PE). We sought to perform a meta-analysis of randomized trials assessing the efficacy and safety of colchicine in patients with pericarditis or postpericardiotomy syndrome (PPS). METHODS: In the systematic literature search following the PRISMA statement, 10 prospective randomized controlled studies with 1981 patients with an average follow-up duration of 13.6 months were identified. RESULTS: Colchicine reduced the recurrence rate of pericarditis in patients with acute and recurrent pericarditis and reduced the incidence of PPS (RR: 0.57, 95% CI: 0.44-0.74). Additionally, the rate of rehospitalizations as well as the symptom duration after 72 h was significantly decreased in pericarditis (RR 0.33; 95% CI 0.18-0.60; and RR 0.43; 95% CI 0.34-0.54; respectively), but not in PPS. Treatment with colchicine was associated with significantly higher adverse event (AE) rates (RR 1.42; 95% CI 1.05-1.92), with gastrointestinal intolerance being the leading AE. The reported number needed to treat (NNT) for the prevention of recurrent pericarditis ranged between 3 and 5. The reported NNT for PPS prevention was 10, and the number needed to harm (NNH) was 12, respectively. Late colchicine administration > 7 days after heart surgery did not reduce postoperative PE. CONCLUSIONS: Our meta-analysis confirms that colchicine is efficacious and safe for prevention of recurrent pericarditis and PPS, while it reduces rehospitalizations and symptom duration in pericarditis. The clinical use of colchicine for the setting of PPS and postoperative PE after heart surgery should be investigated in further multicenter RCT.

What's new in heart failure therapy 2018?

Even though significant progress has been made over the past 3 decades, heart failure remains one of the leading causes of mortality and morbidity in developed countries and contributes significantly to the economic burden of modern health care systems. Especially in patients with preserved ejection fraction, valid therapeutic options are missing due to a lack of evidence. In face of a very heterogeneous condition with an ongoing debate over aetiology and pathophysiology, clinicians face a challenge in providing optimal care for these patients. Recent data suggest that the optimal treatment of the underlying conditions as well as comorbidities that are associated with heart failure might play an ever increasing role in improving outcomes. This focused review summarizes and reviews current data for the treatment of heart failure with both preserved and reduced ejection fractions based on the latest recommendations covering medical therapy and interventional strategies.

Multibiomarker analysis in patients with acute myocardial infarction.

BACKGROUND: Novel biomarkers representing different pathobiological pathways and their role in patients with acute myocardial infarction (AMI) were studied. METHODS: We retrospectively analysed serum levels of soluble suppression of tumorigenicity (sST2), growth-differentiation factor-15 (GDF-15), soluble urokinase plasminogen activator receptor (suPAR), heart-type fatty acid-binding protein (H-FABP) and plasma fetuin A in blood of patients with AMI (STEMI, n = 61; NSTEMI, n = 57) compared to controls with excluded coronary artery disease (n = 76). Furthermore, detailed correlation analysis was performed. RESULTS: Compared with controls, in patients with STEMI and NSTEMI higher levels expressed as median of sST2 in pg/mL (STEMI: 13210·9, NSTEMI: 11989·1, control: 5248; P < 0·001), GDF-15 in pg/mL (STEMI: 818·8, NSTEMI 677·5, control 548·6; P < 0·001), suPAR in pg/mL (STEMI: 3461·1, NSTEMI: 3466·7, control: 2463·6; P < 0·001), H-FABP in ng/mL (STEMI: 5·8, NSTEMI: 5·4, control: 0·0; P < 0·001) and lower plasma fetuin A levels in µg/mL (STEMI: 95, NSTEMI: 54, control: 116·6; P < 0·001) were detected. Correlation analysis found clinical and biochemical parameters such as ejection fraction, length of hospital stay, creatine kinase, NT-proBNP and hs Troponin T levels as well as inflammatory markers (CRP, leucocytes) to be significantly correlated with novel biomarkers. CONCLUSION: Plasma levels of novel biomarkers were significantly elevated (sST2, GDF-15, H-FABP, suPAR) or inversely downregulated (fetuin A) in patients with AMI compared to a control group with excluded coronary artery disease. Significant correlations with various clinical parameters and standard biochemical markers were found.

Metastatic obliterating mass of right ventricular cavity: A report of case and echocardiographic features.

We present the case of a 63-year-old man with a history of non-small cell lung carcinoma (NSCLC) and systemic chemotherapy who suffered from progressive shortness of breath and peripheral edema. Transthoracic echocardiography showed a huge non-homogenous mass nearly completely filling the dilated right ventricle. The border of mass was not differentiable from the right ventricular myocardium. The findings of echocardiographic study were highly suggestive for cardiac metastasis. Computed tomography and positron emission computed tomography confirmed the presumed diagnosis. Lung cancer is one of the most common primary tumors of cardiac metastasis and NSCLC accounts for about 85% of all lung cancers. Lymphatic spread or direct invasion usually involves the pericardium or epicardium. However, metastasis to the myocardium and endocardium is extremely rare. The huge size, location, direct invasion to myocardium and echocardiographic features of this cardiac mass have made it a unique case for presentation. .

Serial echocardiography using tissue Doppler and speckle tracking imaging to monitor right ventricular failure before and after left ventricular assist device surgery.

OBJECTIVES: This study aimed to investigate the utility of serial tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) for monitoring right ventricular failure (RVF) after left ventricular assist device (LVAD) surgery. BACKGROUND: RVF post-LVAD is a devastating adverse event. METHODS: The authors prospectively studied 68 patients undergoing elective LVAD surgery. Echocardiograms were performed within 72 h before and 72 h after surgery. RVF was pre-specified as: 1) the need for salvage right ventricular assist device (RVAD); or 2) persistent need for inotrope and/or pulmonary vasodilator therapy 14 days after surgery. Patients were classified as Group RVF or Group Non-RVF. RESULTS: A total of 24 patients (35.3%) met criteria for RVF. Preoperative TDI-derived S' was lower and RV E/E' ratio was higher (3.7 ± 0.6 cm/s vs. 4.7 ± 0.9 cm/s, 12.0 ± 2.3 vs. 10.0 ± 2.5, both p < 0.001, respectively), and the absolute value of RV longitudinal strain (RV-strain) obtained from STE was lower (-12.6 ± 3.3% vs. -16.2 ± 4.3%, p < 0.001) in Group RVF vs. Group Non-RVF. Echo parameters within 72 h after surgery showed higher RV-E/E', (13.9 ± 4.6 vs. 10.1 ± 3.0, p < 0.001) and lower RV-strain (-11.8 ± 3.5% vs. -16.7 ± 4.4%, p < 0.001) in Group RVF vs. Group Non-RVF. Preoperative S'<4.4 cm/s, RV-E/E'>10 and RV-strain < -14% discriminated patients who developed RVF at day 14 with a predictive accuracy of 76.5%. When we included postoperative RV-E/E' and RV-strain, the predictive accuracy increased to 80.9%, with a sensitivity of 66.7% and a specificity of 88.7%. CONCLUSIONS: Serial echocardiograms using TDI and STE before and soon after LVAD surgery may aid in identifying need to initiate targeted RVF specific therapy in this population.

Usefulness of two-dimensional echocardiographic parameters of the left side of the heart to predict right ventricular failure after left ventricular assist device implantation.

Right ventricular failure (RVF) after left ventricular assist device (LVAD) placement is associated with increased morbidity and mortality. Echocardiography is a primary imaging method in the assessment of cardiac function; however, visualization of the right-sided heart is often technically difficult in patients with heart failure. We aimed to create a simple and generally applicable scoring system based on "left-sided echocardiographic parameters" to provide complementary information for predicting RVF after LVAD surgery. We reviewed 111 consecutive patients undergoing LVAD surgery from 2007 through 2010. Echocardiograms within 5 days before surgery were analyzed. RVF was defined as an unexpected RV assist devices requirement, nitric oxide inhalation >48 hours, and/or inotropic support >14 days. Thirty-five patients (32%) developed RVF. LV end-diastolic dimension (LVEDD) was smaller, LV ejection fraction was greater, and the left atrial diameter/LVEDD ratio was greater (p < 0.05 for all comparisons) in patients with RVF than in those without RVF. An RVF score (LV echocardiographic RVF score) was determined as a sum of points based on receiver operator characteristics analysis: LVEDD >78, 79 to 70, and <70 mm; LV ejection fraction ≤19%, 19% to 33%, and >33%; and left atrial diameter/LVEDD <0.63, 0.63 to 0.68, and >0.68; each variable was associated with 0 and 1 point and 2 points, respectively. LV echocardiographic RVF score ≥3 was associated with RVF with a sensitivity of 88.6% and score ≥5 with a specificity of 80.3%. In conclusion, patients with relatively small LV size, preserved LV contraction, and dilated left atrium were at higher risk for RVF after LVAD surgery. In conclusion, LV echocardiographic RVF score provides a novel tool to predict RVF after LVAD surgery, which does not involve invasive or technically complicated procedures.

The effects of cigarette smoking on C-reactive protein concentrations in men and women and its modification by exogenous oral hormones in women.

BACKGROUND: Previous studies have shown dose-dependent and time-dependent effects of cigarette smoking and smoking cessation on C-reactive protein (CRP) concentrations in men, but results were inconsistent for women. The aim of this study was to evaluate the dose-dependent and time-dependent association of smoking and smoking cessation with CRP concentrations in men and women using a novel comprehensive smoking index (CSI). DESIGN: Cross-sectional study of representative US survey data (National Health and Nutrition Examination Survey 1999-2002). METHODS: The CSI simultaneously accounts for intensity, duration and time since cessation of smoking. We analyzed data of 3505 men and 3896 women using sex-specific multiple linear regression models adjusting for other determinants of CRP concentrations, including age, race/ethnicity, body mass index, alcohol intake, diabetes, physical activity, oral hormone use among women, and history of coronary heart disease, stroke, chronic obstructive pulmonary disease and arthritis. RESULTS: A positive association of similar strength was found between smoking and CRP concentrations in both men and women who did not use exogenous oral hormones. Among women who used exogenous oral hormones, no association with smoking was found. In older men and women it took several years after smoking cessation for CRP concentrations to return to that of individuals who never smoked. CONCLUSION: Smoking is associated with dose-dependent and time-dependent increases in CRP concentrations in both men and women. Furthermore, the effect of exogenous oral hormones on CRP concentrations in women is affected by smoking in a dose-dependent fashion.

Effects of exercise training on insulin-like growth factor-I expression in the skeletal muscle of non-cachectic patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is associated with progressive muscle atrophy and reduced local expression of insulin-like growth factor I (IGF-I). DESIGN: The present study was designed to test the hypothesis that the local deficiency of IGF-I in the skeletal muscle of patients with CHF would respond to a 6-months aerobic training intervention. Therefore, 18 patients [mean age 52.4 (SD 4.8) years, left ventricular ejection function (LVEF) 27 (SD 6)%] were prospectively randomized to either 6 months of training or sedentary lifestyle. METHODS: Serum levels of growth hormone (GH) were measured by immunofluorometric assay, IGF-I by competitive solid phase immunoassay. IGF-I expression was assessed in vastus lateralis biopsies by real-time PCR. RESULTS: Exercise training led to a significant increase in peak oxygen uptake by 26% [from 20.3 (SD 3.3) ml/kg per min to 25.5 (SD 5.7) ml/kg per min, P=0.003 versus control]. Local expression of IGF-I increased significantly after exercise training by 81% [from 6.3 (SE 0.8) to 11.4 (SE 1.4) relative units, P=0.007 versus control] while IGF-I receptor expression was reduced by 33% [from 20.0 (SE 2.1) to 13.8 (SE 1.7) relative units, P=0.008 versus control]. Serum growth hormone (GH) rose modestly from 0.12 (SE 0.07) to 0.65 (SE 0.37) ng/ml in the training group (P=0.043 versus baseline), however, this change was not significant compared to the control group (P=0.848). IGF-I serum levels remained virtually unchanged. CONCLUSIONS: Exercise training improves local IGF-I expression without significant changes of systemic parameters of the GH/IGF-I axis. These findings indicate that exercise training has the therapeutic potential to attenuate peripheral skeletal muscle alterations in particular with respect to local IGF-I expression in patients with moderate CHF.

Chronic heart failure and skeletal muscle catabolism: effects of exercise training.

Although the clinical picture of cardiac cachexia is well-known in patients with advanced chronic heart failure (CHF) the factors that determine who is at risk for this progressive catabolic syndrome and who is not remain unclear. Different endocrine systems have been accused of being involved in this process: an imbalance between catabolic and anabolic steroids with an elevated cortisol/dihydroepiandrosterone ratio, an increased resting metabolic rate due to high levels of circulating catecholamines, various cytokines are activated in CHF (i.e. TNF-alpha, IL-6, IL-1beta and others), and elevated levels of growth hormone (GH) with inappropriately normal or low serum levels of insulin-like growth factor-I (IGF-I) have been described in cardiac cachexia. These catabolic factors contribute to peripheral muscle atrophy, augment the expression of the inducible nitric oxide synthase (iNOS), which in turn inhibits the aerobic cellular metabolism. The present review examines whether the catabolic factors can be influenced by a classical anabolic intervention: regular physical exercise training. Long-term training programs increase skeletal muscle cytochrome c oxidase activity and are associated with reduced local expression of pro-inflammatory cytokines as well as iNOS, and augment local IGF-I production. In concert, these beneficial effects of exercise training may help to retard the catabolic process in CHF finally leading to cardiac cachexia and death.

Effects of laser-induced thermotherapy (LITT) on proliferation and apoptosis of glioma cells in rat brain transplantation tumors.

BACKGROUND AND OBJECTIVES: Laser-induced thermotherapy (LITT) is an approach to the treatment of brain tumors especially in poorly accessible regions. Its clinical applicability with tumor cell destruction has been shown in several studies. However, no data are known about specific effects on tumors cells due to LITT in the time course of the lesion. STUDY DESIGN/MATERIALS AND METHODS: LITT was performed in adult Lewis rats with implanted glioma cells in the brain using a standard exposure of 3 W for 30 seconds. Before and following LITT, neoplastic lesions were monitored by MRI. Proliferation of implanted cells and gliosis were assessed by several histological techniques and immunohistochemistry. Apoptosis was detected by TUNEL staining. RESULTS: Our experiments show a destruction of neoplastic cells by LITT but surviving tumor cells at the margin of the lesion. Apoptosis was detected following LITT restricted to residual neoplastic cells. Marginal survival of tumor cells lead to a secondary outgrowth into the necrotic lesion adjacent to sprouting capillaries. CONCLUSIONS: LITT is a suitable technique for the treatment of brain neoplasms. However, further investigations are necessary to prevent tumor recurrences after LITT.

Reduction of insulin-like growth factor-I expression in the skeletal muscle of noncachectic patients with chronic heart failure.

OBJECTIVES: We sought to assess the role of insulin-like growth factor-I (IGF-I) in muscle wasting in chronic heart failure (CHF), serum concentrations and local muscular IGF-I expression were determined in patients with severe CHF. BACKGROUND: Chronic heart failure is associated with progressive muscle atrophy, leading to cardiac cachexia. Skeletal muscle disuse and inflammatory activation with elevated cytokine levels have been implicated; however, the pathomechanism involved remains largely unknown. METHODS: Serum levels of IGF-I were measured by competitive solid phase immunoassay in 47 patients with severe CHF (left ventricular ejection fraction < or =30%) and 15 age-matched healthy subjects (HS). Insulin-like growth factor-I and IGF-I receptor expression were assessed in vastus lateralis biopsies by real-time PCR and Western blot analysis. RESULTS: Although serum IGF-I was not significantly different (175 +/- 10 ng/ml in CHF vs. 170 +/- 12 ng/ml in HS, p = NS), local muscle IGF-I mRNA expression was reduced by 52% in CHF (6.7 +/- 0.4 vs. 14.0 +/- 0.9 arbitrary units in HS, p < 0.001). This was accompanied by an increase in IGF-I receptor mRNA expression (86.8 +/- 5.4 in CHF vs. 23.1 +/- 1.8 arbitrary units in HS, p < 0.001). Local IGF-I expression was significantly correlated with muscle cross-sectional area (R = 0.75, p = 0.01). Chronic heart failure patients with a body mass index of < 25 kg/m(2) showed signs of peripheral growth hormone (GH) resistance, as indicated by elevated serum GH, and reduced IGF-I levels. CONCLUSIONS: In CHF patients, muscle IGF-I expression is considerably reduced in the presence of normal serum IGF-I levels, possibly contributing to early loss of muscle mass. These findings are consistent with a potential role of IGF-I for skeletal muscle atrophy in CHF.