Viral Cardiomyopathy Research Articles

Machine learning methods for diagnostic disease prediction and treatment decisions in parvovirus B19 positive viral cardiomyopathy

Abstract Background Parvovirus B19 (B19V) is the most common type of virus found in endomyocardial biopsies (EMB) from patients with inflammatory heart disease. However, the detection of genomic B19V-DNA appears to have little clinical significance and is often considered an incidental finding. Recent analyses of a large cohort of B19V-positive patients revealed that the detection of RNA transcripts rather than DNA is of clinical importance, as B19V-RNA-positive patients have a significantly worse cardiovascular outcome. Here, we applied machine learning (ML) methods to assess the impact of B19V transcriptional activity on cardiac inflammation and patient clinical outcome. Methods and results A total of 305 patients with a known clinical course and a positive endomyocardial B19V-DNA test were included in this study. Follow-up measurements of the B19V-specific transcripts VP1/2 and NS1 revealed significantly worse clinical courses than in patients without B19V-RNA detection (P=0.019, hazard ratio (95% CI)=1.62 (1.10-2.57)). LVEF at follow-up was significantly lower in patients with detected B19V-RNA (P=0.007), and adverse events such as worsening LV function (P=0.003) or stable systolic dysfunction (P=0.013) were more frequent in this group. Importantly, analysis of inflammatory markers in EMB showed no difference in patients with and without RNA detection (P=0.432), suggesting that the deterioration in clinical outcome was related to B19V transcriptional activity rather than an increase in inflammation. The analysis of area under the receiver operating characteristic curve (AUROC) of B19V-RNA-negative patients revealed that the macrophage marker MAC-1 (AUROC=0.66, P=0.002) was the single most prognostically relevant parameter, while the T cell marker CD3 (AUROC=0.73, P<0.001) was identified as the most prognostically relevant marker in B19V-RNA-positive patients. The linear combination of several inflammatory markers increased the AUROC value to 0.67 in B19V-RNA-negative patients and to 0.74 in B19V-RNA-positive patients. To further increase prognostic accuracy, we trained ML models on features derived from EMB inflammatory markers. For the prediction of major adverse cardiac events within 60 months, the best ML-models achieved an AUROC of 0.87 in B19V-RNA-positive and of 0.86 in B19V-RNA-negative patients, while models that neglect the differentiation of patients with regard to the presence of B19V RNA transcripts only achieved an AUROC of up to 0.76. Conclusions These results show that B19V transcriptional activity is an independent risk marker for adverse cardiac events in patients with viral cardiomyopathy and thus confirm the clinical-therapeutic importance of myocardial biopsy. Furthermore, we present an ML-based algorithm that accurately indicates disease progression in B19V-positive cardiomyopathy patients and is thus helpful for appropriate therapy recommendation.

Arrhythmias and conduction disorders in patients with viral heart disease.

Viral heart disease comprises of two cardiovascular entities being evoked by viral infection: acute viral myocarditis and viral cardiomyopathy. Viral myocarditis may completely resolve leaving no traceable sign or cause ongoing inflammation with subsequent development of hypokinetic dilated/non-dilated cardiomyopathy. The exact epidemiology of viral myocarditis remains unknown due to its sometimes asymptomatic course, but according to the Global Burden of Disease Study 2019, the prevalence of myocarditis in young adults is estimated to range between 6.1 per 100,000 in men and 4.4 per 100,000 in women, with the most common viral etiology. According to the literature viral genome can be found in considerable percentage (up to 67,4%) of endomyocardial biopsy specimens obtained from patients with idiopathic left ventricular dysfunction- suggesting viral etiology of the cardiomyopathy. In this review we would like to enlighten most common types of arrhythmias and conduction disorders as well as their prevalence in patients with viral heart disease. Moreover, our paper depicts probable pathological mechanisms in which viruses induce arrhythmias and cardiac conduction system disease in both, acute viral infection and chronic viral disease. We would also like to highlight unresolved problem of sudden death protection in the course of acute myocarditis.

Viral myocarditis in combination with genetic cardiomyopathy as a cause of sudden death. An autopsy series

Sudden cardiac death (SCD) is a major public health issue worldwide. In the young (< 40 years of age), genetic cardiomyopathies and viral myocarditis, sometimes in combination, are the most frequent, but underestimated, causes of SCD. Molecular autopsy is essential for prevention. Several studies have shown an association between genetic cardiomyopathies and viral myocarditis, which is probably underestimated due to insufficient post-mortem investigations. We report on four autopsy cases illustrating the pathogenesis of these combined pathologies. In two cases, a genetic hypertrophic cardiomyopathy was diagnosed in combination with Herpes Virus Type 6 (HHV6) and/or Parvovirus-B19 (PVB19) in the heart. In the third case, autopsy revealed a dilated cardiomyopathy and virological analyses revealed acute myocarditis caused by three viruses: PVB19, HHV6 and Epstein-Barr virus. Genetic analyses revealed a mutation in the gene coding for desmin. The fourth case illustrated a channelopathy and a PVB19/HHV6 coinfection. Our four cases illustrate the highly probable deleterious role of cardiotropic viruses in the occurrence of SCD in subjects with genetic cardiomyopathies. We discuss the pathogenetic link between viral myocarditis and genetic cardiomyopathy. Molecular autopsy is essential in prevention of these SCD, and a close collaboration between cardiologists, pathologists, microbiologists and geneticians is mandatory.

Coronavirus disease 2019 and the cardiologist.

There continues to be extensive clinical and epidemiological data to suggest that coronavirus disease 2019 (COVID-19) infection is associated with numerous different types of cardiac involvement. Myocardial injury has been reported in over 25% of patients hospitalized due to COVID-19 infection and is not only associated with a worse prognosis but with higher mortality, approaching 40%. Currently proposed mechanisms of myocardial injury include direct viral infection, cytokine storm, endothelial inflammation, demand ischemia, interferon-mediated response and stress cardiomyopathy. COVID-19 infection is associated with new-onset arrhythmias and heart failure regardless of history of previous cardiovascular disease. Echocardiographic findings can be useful to predict mortality in COVID-19 patients and cardiac MRI is an effective tool to both assess COVID-19 induced myocarditis and to follow-up on cardiac complications of COVID-19 long-term. Although there is an association between COVID-19 vaccination and myocarditis, pericarditis or arrhythmias, the risk appears lower when compared to risk attributable to the natural infection. Patients with cardiovascular disease are not only more likely to suffer from severe COVID-19 infection but are at increased risk for further complications and higher mortality. Further data compilation on current and emerging treatments of COVID-19 will have additional impact on cardiovascular morbidity and mortality of COVID-19 infection.

Abstract 11844: Viral Gene Signatures in Patients With Cardiomyopathy After Chemotherapy

Introduction: Chemotherapy for hematologic malignancies can cause severe cardiomyopathy. Chemotherapeutic agents also induce immune suppression increasing the risk of opportunistic infections. Hypothesis: We have hypothesized that immunosuppression after chemotherapy increases opportunistic viral infections, myocarditis and cardiomyopathy. Methods: Viral gene sequences were identified using an unbiased high-throughput sequencing approach of patient blood samples following chemotherapy treatment for hematological malignancies (N = 28). Detected viral sequences were correlated with cardiac ejection fraction (LVEF) measured before and after treatment. Results: In a blinded analysis undertaken by two investigators viral sequences were identified in blood samples from patients after chemotherapy. Low levels of Influenza A, orthomyxovirus and Avian Paramyxovirus sequences were detected but identified individual virus sequences did not have a significant correlation to reduced LVEF post chemotherapy (r = 0.177-0.293). Detected sequences for all RNA viruses combined did indicate some correlation with LVEF, r = 0.621, suggesting potential for nonspecific RNA virus detection ( p &lt; 0.0078). In a secondary broad screen, data mining was performed including all detectable viral sequences without the filtering of human related sequences. In this broad analysis a significant correlation was detected for Paramyxovirus with reduced cardiac LVEF (r = 0.592 post, compared to r = 0.464 prior to chemotherapy; P &lt; .0096). For detected Orthomyxovirus sequences correlations were similar for LVEF pre- and post- chemotherapy (R = 0.483, P &lt; 0.0451). Retroviruses reads were increased but suspect due to human genome retrovirus sequences (R= 0.512; P &lt; 0.0351). No correlation was seen for Anellovirus, a DNA virus. Reduced LVEF did not correlate with chemotherapy (p = NS). Conclusions: This is the first report of screening for RNA viruses in the circulating blood of patients post chemotherapy using a high-throughput sequencing approach. Influenza Orthomyxovirus and Avian Paramyxovirus sequences were detectable in patients with reduced LVEF after chemotherapy. Further analysis for RNA virus infections in cardiomyopathy after chemotherapy is warranted.

Acute Myocardial Injury and Rhabdomyolysis in COVID-19 Patients: Incidence and Mortality.

BackgroundMyocardial injury has been defined as an elevated troponin level. The frequency of acute myocardial injury of hospitalized coronavirus disease 2019 (COVID-19) patients ranges from 7% to 36%. COVID-19 patients with cardiovascular disease (CVD) have a four-fold higher risk of mortality (odds ratio, 4.33; CI 95%, 3.16-5.94). In COVID-19 hospitalized patients’ study showed mortality rate was 18.5%. Rhabdomyolysis is considered as muscle necrosis and the release of intracellular muscles elements and enzymes into blood. In one of retrospective cohort study of COVID-19 hospitalized patients, incidence of rhabdomyolysis was 16.7%.Materials and methodsThis retrospective observational study consisted of 413 COVID-19 hospitalized patients. Patients with rhabdomyolysis was defined as creatine kinase level greater than 1,000 U/L and acute myocardial injury was defined as serum high-sensitivity troponin-T for males greater than 30 ng/l and for female greater than 20 ng/l. The primary outcome was in-hospital mortality of COVID-19 patients with acute myocardial injury and rhabdomyolysis. ResultsThe incidence of acute myocardial injury and rhabdomyolysis in hospitalized COVID-19 patients was 23.9% (99) and 15.7% (65), respectively. The mortality rate of in hospitalized COVID-19 patients who developed acute myocardial injury (28.3%) was significantly higher in comparison to patients who developed rhabdomyolysis (13.8%).DiscussionThe binding of SARS-CoV-2 virus to the angiotensin-converting enzyme 2 (ACE2) is a critical step in the pathophysiology in patients with COVID-19. There may be diverse direct and indirect mechanisms of acute myocardial injury in COVID-19 including ischemic injury, hypoxic injury (MI type 2), direct viral myocarditis, stress cardiomyopathy and systemic cytokine storm. Musculoskeletal injury may be caused by direct viral myositis or indirectly by host immune hyperinflammatory cytokine storm response that leads to skeletal muscle fiber proteolysis and fibrosis.ConclusionsAcute myocardial injury and rhabdomyolysis were underreported in COVID-19 patients. The incidence and mortality of acute myocardial injury are higher than that of rhabdomyolysis in COVID-19 hospitalized patients. The outcome was worse in COVID-19 patients with severe acute myocardial injury. Patients with acute myocardial injury and rhabdomyolysis may get benefits from rehabilitation programs.

Ofatumumab and Tocilizumab Desensitization in a Highly Sensitized Recipient: A Case Report

<h3>Introduction</h3> Sensitization is a challenge in heart transplant recipients, often increasing wait time and decreasing access to acceptable organs. We present a case of a highly sensitized 47-year-old female listed for re-do heart and kidney transplant who was desensitized utilizing ofatumumab and tocilizumab. <h3>Case Report</h3> The patient received her first heart transplant in 1992 (induction muromonab-CD3) for viral cardiomyopathy at an outside hospital; in 2015 she was treated for antibody mediated rejection with plasma exchange (PLEX), intravenous immunoglobulin (IVIG), and bortezomib. She later developed cardiac allograft vasculopathy. In 2018 she was brought to our center with cardiogenic shock and worsening renal function, required dual inotropic support, and evaluated and listed for a re-do heart and kidney transplant. Her peak PRA was 90% with several class I and II antibodies. She underwent desensitization therapy with PLEX, IVIG (2 g/kg), ofatumumab (1 dose), and monthly tocilizumab (3 doses). No adverse drug events were reported during therapy. Her PRA remained persistently ∼90%; MFI trends of her antibodies are presented in Figure 1. After her 3^rd tocilizumab dose she received an offer which was crossmatch negative and no pre-existing antibodies. She received basiliximab induction and maintenance immunosuppression of tacrolimus, mycophenolate, and prednisone. During the 1 year follow-up post-transplant, she had excellent graft function with ejection fraction >60%, serum creatinine <1.2 mg/dL and no episodes of rejection. Tacrolimus levels remained between 5-13 mcg/ml. Post-transplant infections included BK viremia with persistent PCR levels between 600-1500 copies/mL. <h3>Summary</h3> Desensitization with ofatumumab and tocilizumab resulted in successful heart and kidney transplantation. Although PRA and MFI of pre-existing antibodies were not significantly altered, this regimen may have been helpful in reducing de novo donor specific antibodies and preventing acute rejection post-transplant.

CORONAVIRUS-INDUCED MYOCARDITIS REQUIRING BI-VENTRICULAR ASSIST DEVICE

SESSION TITLE: Medical Students/Residents' COVID-19 SESSION TYPE: Med Student/Res Case Report PRESENTED ON: October 18-21, 2020 INTRODUCTION: Myocarditis describes an inflammatory disorder of the myocardium. Typical presentation occurs with new-onset heart failure and can occur secondary to infection, autoimmune, drug reaction, or other etiology. Literature review describes only two previous cases of coronavirus induced myocarditis in humans. CASE PRESENTATION: A 72-year-old male presented with chest pressure, progressive dyspnea, and cough over one week. Labs demonstrated no leukocytosis but an elevated troponin of 313ng/L, BNP of 696pg/m, and an RNA PCR was positive for Coronavirus-COVID19. CT-scan of the chest revealed bilateral ground-glass opacities with bilateral pleural effusion. Due to acute hypoxic respiratory failure, the patient was intubated and subsequently developed wide-complex tachycardia and was cardioverted to sinus rhythm. The patient was found to be in cardiogenic-shock and placed on vasopressors. Solumedrol and hydroxychloroquine were initiated for five days. The patient was also given tocilizumab and IVIG for 2 days. Echocardiogram revealed biventricular cardiomyopathy, severely depressed LV systolic function, and an ejection fraction of <10%. Cardiac catheterization revealed no significant signs of epicardial CAD. Given the acute nature of his heart failure, an LVAD and RVAD were placed for hemodynamic support. The patient developed hemolysis secondary to these devices and they were removed in the following days. The non-ischemic cardiomyopathy resolved as repeat echocardiography revealed an ejection fraction of 55% and the patient was successfully extubated. The patient was discharged to subacute rehabilitation on hospital day-18. DISCUSSION: We present an exceptional case of viral myocarditis caused by Coronavirus-COVID19. Previously, limited cases have claimed Coronavirus as the culprit of myocarditis; the novel middle east respiratory syndrome Coronavirus seemed to be the only documented subtype causing severe myocarditis leading to viral dilated cardiomyopathy. CONCLUSIONS: Documenting this case is important to raise awareness of the potential life-threatening COVID19 as a cause of acute congestive heart failure and allow for possible diagnosis and prompt treatment of the future of cases especially since coronavirus seems to carry a high mortality rate in patients with cardiac risk factors. Reference #1: Postgrad Med J. 2001 Jan; 77(903): 4–10. doi: 10.1136/pmj.77.903.4 Reference #2: Postgrad Med J. 2006 Feb; 82(964): 140–144. doi: 10.1136/pgmj.2005.037515 Reference #3: European Heart Journal, ehaa190, https://doi.org/10.1093/eurheartj/ehaa190 Published: 16 March 2020 DISCLOSURES: No relevant relationships by Marianna Avagyan, source=Web Response No relevant relationships by Gurinder Pal Gakhal, source=Web Response no disclosure on file for Samer Kazziha; No relevant relationships by Connor Kerndt, source=Web Response No relevant relationships by Hayk Papukhyan, source=Web Response

Relationship between Plasma Neuregulin-1 and MDA Levels with Severity of CAD

BACKGROUND: Neuregulins (NRGs) are one of the epidermal growth factors (EGF) superfamily, which released in cellular injuries, such as neurons and myocardial cells. Neuregulin-1β (NRG-1β) could be activated when stress happens to myocardial cells, acting as a survival factor to repair the injury. Malondialdehyde (MDA) is also produced during oxidative stress in cardiac injury. In vivo study of myocardial cells in rats and dogs that got ischemic, dilated, and viral cardiomyopathy showed that NRG-1 could improve the injured cardiac performance, attenuated pathological changes, and prolonged survival of the cells.&#x0D; AIM: We aimed to observe NRG-1 levels in CAD patients in Indonesia, mainly focused in Minang ethnicity. This study also analyzes the relationship between NRG-1 and MDA with CAD’s severity.&#x0D; METHODS: We measured plasma NRG-1 in 61 nondiabetic patients within 38–82 years old range with STEMI, NSTEMI, and UAP.&#x0D; RESULTS: We found their plasma NRG1, respectively, was 10.3 (1.9–38.2) ng/ml, 14.3 ± 7.2 ng/ml, and 7.05 (4.5–0.4) ng/mL. Plasma NRG 1 increased in AMI patients.&#x0D; CONCLUSION: This study concludes that NRG1’s activated during cardiac cells injury, in any AMI.

MANAGEMENT OF COVID-19 IN PERSPECTIVE OF CARDIOLOGISTS

MANAGEMENT OF COVID-19 IN PERSPECTIVE OF CARDIOLOGISTS

Two cases of coronavirus 2019–related cardiomyopathy in pregnancy

At our institution, 2 of the initial 7 pregnant patients with confirmed coronavirus disease 2019 severe infection (28.6%; 95% CI, 8.2%–64.1%) developed cardiac dysfunction with moderately reduced left ventricular ejection fractions of 40%–45% and hypokinesis. Viral myocarditis and cardiomyopathy have also been reported in nonpregnant coronavirus disease 2019 patients. A case series of nonpregnant patients with coronavirus disease 2019 found that 33% of those in intensive care developed cardiomyopathy. More data are needed to ascertain the incidence of cardiomyopathy from coronavirus disease 2019 in pregnancy, in all pregnant women with coronavirus disease 2019, and those with severe disease (eg, pneumonia). We suggest an echocardiogram in pregnant women with coronavirus disease 2019 pneumonia, in particular those necessitating oxygen, or those who are critically ill, and we recommend the use of handheld, point-of-care devices where possible to minimize contamination of staff and traditional large echocardiogram machines.

Inflammatory dilated cardiomyopathy : Etiology and clinical management.

Inflammatory dilated cardiomyopathy (DCMi) is a syndrome, not an etiological disease entity. The infective etiology and the immunopathology can be best determined through endomyocardial biopsy with a complete work-up by light microscopy, immunohistology, and polymerase chain reaction for microbial agents. This review focuses on the methodological advances in diagnosis in the past few years and exemplifies the importance of an etiology-orientated treatment in different case scenarios. In fulminant nonviral myocarditis, immunosuppressive treatment together with hemodynamic stabilization of the patient via mechanical circulatory support (e.g., microaxial pumps, extracorporeal membrane oxygenation, left ventricular assist device) can be life-saving. For viral inflammatory cardiomyopathy, intravenous immunoglobulin treatment can resolve inflammation and often eradicate the virus.

Cardiomyopathy in Pregnancy with COVID-19: An Enigma

ABSTRACT Background The coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health emergency. Physiological and mechanical changes in pregnancy increase susceptibility to infections in general, particularly when the cardiorespiratory system is affected, and encourage rapid progression to respiratory and heart failure in the gravida. Case description We present a case report of 30-year-old primigravidae with 36.5 weeks by date and 37 week by scan with diagnosed preeclampsia 2 weeks back on medication with 11 × 10.4 × 10.9 cm single intramural anterior wall fibroid with breech presentation. COVID nasopharyngeal sample reported as SARS-CoV-2 real-time PCR positive. The patient was started on medication defining the Stage 1 Group A Asymptomatic Category. Chest X-ray showed mild bilateral pulmonary infiltrates. On Day 6 of admission, the patient went in labor, and hence was taken for emergency LSCS in view of primigravidae with breech with preeclampsia with fibroid with PROM under spinal anesthesia with all precautions. Intraoperatively, the LSCS was uneventful. Postoperatively 6 hours postpartum, the patient developed sudden onset breathlessness NYHA Grade 4, with saturation of 56%, and patient was intubated and shifted to ICU. Chest X-ray revealed viral pneumonia, and further 2D ECHO was suggestive of cardiomyopathy. Conclusion We suggest an echocardiogram in pregnant women with coronavirus disease 2019 pneumonia, in particular those necessitating oxygen or those who are critically ill. Clinical significance Viral myocarditis and cardiomyopathy have been reported in nonpregnant COVID-19 patients. Information on COVID-19 in pregnancy is currently limited. No specific literature is available of viral cardiomyopathy reported in pregnant women with COVID-19 infection. How to cite this article Mevada SA, Mehendale MA, Nayak AH, et al. Cardiomyopathy in Pregnancy with COVID-19: An Enigma. J South Asian Feder Obst Gynae 2020;12(4):243–244.

Descripción clínico-epidemiologica de los pacientes con falla cardiaca aguda que consultan al servicio de urgencias

Introducción: la falla cardiaca aguda es un motivo de consulta frecuente al servicio de urgencias, se desconoce el perfil clínico de los pacientes con falla cardiaca aguda en nuestro medio &#x0D; Objetivo: describir las características epidemiológicas de los pacientes que ingresan al servicio de urgencias con diagnóstico de falla cardiaca aguda. &#x0D; Metodología: estudio prospectivo, descriptivo. &#x0D; Resultados: se incluyeron 106 pacientes con edad promedio de 62.4 años (16-94), el 52.8% eran hombres, las causas más frecuente de la falla cardiaca fueron: cardiopatía hipertensiva 45.2%, idiopática 31.1%, isquémica 14.1%, valvular 8.4%, viral y periparto 0.9%; 11.2% tenían un síndrome coronario agudo. La medicación que utilizaban al momento del ingreso incluyó digoxina en 26.4%, diuréticos 73%, inhibidores de la enzima convertidora de angiotensina 73.58%, betabloqueadores 32%, espironolactona 34.9% . La clase funcional según la clasificación de Nueva York previa al ingreso fue I en 1.8%, clase II 26.4,% clase III 57.5%, clase IV 14.3%. Se presentaron con edema pulmonar 10.37% (11), el valor promedio del péptido natriurético cerebral fue 2356 pg/ml. El 67.2% tenían fracción de expulsión menor a 40%. La duración promedio de la hospitalización fue de 11.42 (1-69). &#x0D; Conclusiones: en comparación con los registros internacionales nuestra población tiene una edad promedio menor y con menor frecuencia son de etiología isquémica. Respecto al tratamiento existe un uso frecuente de inhibidores de la enzima convertidora de angiotensina y una subutilización de los betabloqueadores&#x0D;

Novel Use of Mitral Clip for Transcatheter Repair of Tricuspid Valve Post Orthotopic Heart Transplant

Tricuspid regurgitation (TR) is common in orthotopic transplanted hearts secondary to endomyocardial biopsies and right heart catheterizations performed for rejection surveillance. The majority of patients develop mild to moderate TR while 7-10% develop severe TR and right heart failure. While there are no established protocols for managing severe TR in transplant recipients, surgical tricuspid valve repair or replacement can be performed if medical therapy fails but are generally limited to low risk patients. We describe the successful use of a Mitral clip device in the tricuspid location to reduce severe TR in a post-transplant patient deemed high risk for surgical replacement and discuss echocardiographic and clinical improvements. The patient is a 70-year-old male with viral cardiomyopathy status post orthotopic heart transplant 18 years ago, who developed severe TR, right heart failure and NYHA IV symptoms refractory to optimal medical therapy. Co-morbidities that made him a high-risk surgical candidate included chronic kidney disease stage IV, hypertension, prostate cancer, diabetes mellitus, chronic obstructive pulmonary disease and paroxysmal atrial fibrillation. In addition to dyspnea at rest and with exertion, his quality of life was severely limited by severe lower extremity edema and ascites requiring weekly paracentesis. 2D echocardiogram showed preserved left ventricular function, moderate to severely reduced right ventricular function, right ventricular dilatation and severe TR. Due to failure of medical therapy to manage his symptoms and high surgical risk for surgical intervention, he was referred for transcatheter tricuspid valve repair. Two Mitral clips (MitraClip, Abbott Cardiovascular, USA) were positioned between anterior and septal and posterior and septal leaflets of the tricuspid valve respectively. This resulted in successful reduction of TR from severe to mild as seen on his intra operative 3D echocardiogram shown below (Figure). There were no intra operative or post-operative complications. The patient showed dramatic improvement in clinical symptoms to NYHA class II and did not require further paracentesis to manage ascites. His Kansas City Cardiomyopathy questionnaire 12 score improved from 26 to 37. Echocardiography at 30 days showed significant improvement in right ventricular function and mild TR only. This case shows the feasibility of managing severe TR in post cardiac transplant recipients through transcatheter techniques when surgical interventions are limited by high operative risk.

Cardio-Immunology of Myocarditis: Focus on Immune Mechanisms and Treatment Options.

Myocarditis and inflammatory cardiomyopathy are syndromes, not aetiological disease entities. From animal models of cardiac inflammation we have detailed insight of the strain specific immune reactions based on the genetic background of the animal and the infectiosity of the virus. Innate and adaptive immunity also react in man. An aetiological diagnosis of a viral vs. a non-viral cause is possible by endomyocardial biopsy with histology, immunohistology and PCR for microbial agents. This review deals with the different etiologies of myocarditis and inflammatory cardiomyopathy on the basis of the genetic background and the predisposition for inflammation. It analyses the epidemiologic shift in cardiotropic viral agents in the last 30 years. Based on the understanding of the interaction between infection and the players of the innate and adaptive immune system it summarizes pathogenetic phases and clinical faces of myocarditis. It gives an up-to-date information on specific treatment options beyond symptomatic heart failure and antiarrhythmic therapy. Although inflammation can resolve spontaneously, specific treatment directed to the causative etiology is often required. For fulminant, acute, and chronic autoreactive myocarditis without viral persistence immunosuppressive treatment can be life-saving, for viral inflammatory cardiomyopathy ivIg treatment can resolve inflammation and often eradicate the virus.

CCR5 Expression is Lower in Women, and Mediates Sex-Based Differences in Post-LVAD Right Ventricular Failure

Purpose Women have increased risk of right ventricular failure (RVF) after LVAD implant, however the underlying pathophysiology is unknown. Chemokines are inflammatory signaling molecules, and fundamental to cardiac homeostasis and stress adaptation. Prior studies have demonstrated a cardio-protective role for chemokine receptor-5 (CCR5) in viral myocarditis and severe Chagas cardiomyopathy, and that sex hormones modulate CCR5 gene expression. We have previously shown that CCR 3-8 down-regulation is predictive of RVF and 1-year survival after implant. We hypothesized that CCR5 expression mediates sex-based differences in post-LVAD RVF. Methods CCR expression was examined in patient's peripheral blood 24 hours pre-LVAD. RNA was isolated using PAXgene protocol. Gene expression was assessed using a targeted microarray (RT2 Profiler PCR array, Qiagen). Results were expressed as PCR cycles to threshold (CT). ΔCT was calculated as (CCR gene CT) - (HPRT1 control gene CT), and log2 transformed for analysis. Log-fold differences in expression were reported using 2−ΔΔCT method. RVF was defined as both planned and unplanned RVAD requirement. Multivariable logistic regression was used to determine the association of sex with RVF, adjusting for significantly different covariates (p Results We analyzed 111 LVAD patients (mean age: 53.57 ± 13 years, 18% female, 17.1% black). The criteria for RVF was met in 35 (31.5%) patients. Women had increased incidence of RVF (50% vs. 27.5%, p=0.047), and under-expressed CCR5 (1.41 fold decrease, p=0.012) compared to men. After controlling for age, heart failure etiology, albumin, BUN, creatinine and cardiac output, women had a higher risk of RVF (HR: 3.18, 95% CI: 1.04-9.8, p=0.043). Addition of CCR5 as a covariate to the model attenuated the association of female sex with RVF (HR: 2.86, 95% CI: 0.91-8.97, p=0.071). Conclusion Pre-implant CCR5 expression is lower in women than in men and may mediate sex disparities in post-LVAD RVF.

Viral Cardiomyopathy: A Review of Clinical Status and Meta-Analysis of Diagnosis and Clinical Management

Viral Cardiomyopathy: A Review of Clinical Status and Meta-Analysis of Diagnosis and Clinical Management

Forensic Analysis on 52 Medical Malpractice Cases of Cardiac Death.

To synthetically analyse the medical malpractice cases of cardiac death in forensic identification, and to explore the generality and characteristic of cause of death, medical malpractice and assessment of participation degree. Totally 52 medical malpractice cases of cardiac death examined in the Xiaoshan Branch Office, Hangzhou Minghao Forensic Judical Appraisal Institute, from January 2015 to April 2018 were collected. The general information of cases, medical institutions and situations of hospital stay, cause of death, medical malpractice and assessment of participation degree were retrospectively analysed. In 52 cases, the male to female ratio was 2.25:1, and most subjects aged >50-60. Cardiac death caused by hypertensive heart disease or coronary heart disease was most common （67.3%）, followed by viral myocarditis and cardiomyopathy （13.5%）. There were 24 cases involved surgery, and the survival time after surgery was from 1 h to 118 d with a 7 d medium value. There were 63 medical institutes involved in these medical malpractices. Medical malpractice presented in most hospitals more or less, and the participation degree was >20%-30%. Forensic appraisal contributes to determine causes of death, which not only provides scientific evidence for medical malpractice identification, but also improves diagnosis and treatment levels of medical institutions.

Treatment options in myocarditis and inflammatory cardiomyopathy

For myocarditis and inflammatory cardiomyopathy, an etiologically driven treatment is today the best option beyond heart failure therapy. Prerequisites for this are noninvasive and invasive biomarkers including endomyocardial biopsy and polymerase chain reaction on cardiotropic agents. Imaging by Doppler echocardiography and cardiac magnetic resonance imaging as well as cardiac biomarkers such as C‑reactive protein, N‑terminal pro-B-type natriuretic peptide , and troponins can contribute to the clinical work-up of the syndrome but not toward elucidating the underlying cause or pathogenetic process. This review summarizes the phases and clinical features of myocarditis and gives an up-to-date short overview of the current treatment options starting with heart failure and antiarrhythmic therapy. Although inflammation in myocardial disease can resolve spontaneously, often specific treatment directed against the causative agent is required. For fulminant, acute, and chronic autoreactive myocarditis, immunosuppressive treatment has proven to be beneficial in the TIMIC and ESETCID trials; for viral cardiomyopathy and myocarditis, intravenous immunoglobulin IgG subtype and polyvalent intravenous immunoglobulins IgG, IgA, and IgM can frequently resolve inflammation. However, despite the elimination of inflammation, the eradication of parvovirus B19 and human herpesvirus-6 is still a challenge, for which ivIg treatment can become a future key player.