ECMO in acute fulminant myocarditis in pediatrics

Objectives: To describe our experience in ECMO for acute myocarditis Methods: Descriptive, retrospective study (2018-2022) of a cohort of 8 patients < 16 years with acute myocarditis who were assisted on ECMO. Result(s): 8 patients were collected, (6 females), with a mean age 7;8 years [range 0;1-13;8]. In 7/8, the reason for cannulation was hemodynamic instability refractory to medical treatment, with a mean inotropic score of 70 [range 10-122]. Sixty-two percent presented cardiorespiratory arrest prior to cannulation and 2 of them needed ECRP. The mean precannulation troponin level was 1498 ng/ml [range 89-6212]. Primary transport was performed in 4 patients. ECMO was peripheral veno-arterial in 100%, jugulo-carotid in 2/8 and femoro-femoral in 6/8. All patients underwent atrioseptostomy. They received treatment with levosimendan, immunoglobulins, corticoids and carnitine. In 4 acute infectious etiology was confirmed (parvovirus, influenza and SARSCoV2), another one was due to PIMS-TS and in 3 no etiology was found. Six patients underwent myocardial biopsy and 5 of them showed inflammatory infiltrates. The mean time on ECMO was 8 days [range 3-14], 2 of them requiring 2 ECMO courses. The mean length of PICU stay was 21 days [range 10-50]. Two were transferred to a heart transplant center. The main complications were arterial hypertension (88%), bleeding (63%), neurological (50%), arrhythmias (38%), coagulopathy (38%) and infectious (38%). One patient required renal replacement therapy. 1 patient died, 2 had moderate neurological sequels. Conclusion(s): ECMO is a therapeutic option in patients with fulminant myocarditis refractory to medical treatment and may help improve their prognosis.

On-Site Whole-Genome Sequencing of Sars-Cov-2 Reveals C3037t Mutation in Patient with Atrioventricular Nodal Reentry Tachycardia (Avnrt)

Intro: The spike protein of the SARS-CoV-2 virus targets the human cell receptor of angiotensin-converting enzyme (ACE2), including the myocardium and heart's conduction system. Patients diagnosed with COVID-19 have also been found to exhibit cardiac arrhythmia. Here, a whole-genome sequencing analysis using long-read sequencing was proposed to evaluate the virus genome in a patient who presented with AVNRT as a main presentation of COVID-19. Method(s): The sample was recovered from nasopharyngeal and oropharyngeal swab specimens of a 46-year-old female with no comorbidities who presented with palpitation, and ECG showed typical AVNRT features. The RT-qPCR of SARS- CoV-2 was confirmed positive with a CT-value of 15.82. The total RNAs were extracted and proceeded for RT-qPCR and proceeded with Oxford Nanopore Flongle sequencing. The genomics data of the virus was deposited in GISAID (EPI_ISL_3241561) and further analysed using online bioinformatics tools such as Nextclade CLI 2.3.0. Ethical approval (IREC 2021-080) for the study was obtained from IIUM Research Ethics Committee. Finding(s): Here, we reported a total of 29,775 bp near-complete whole-genome belonging to clade 21J (Delta) of AY.79 lineage (also known as B.1.617.2.79), which formed a dominant variant in Malaysia during the time of sampling. Discussion(s): While a previous study showed an association between Delta variant infection with fulminant myocarditis, the present study reported the benign AVNRT as the main presentation of SARS-CoV-2 infection. Furthermore, we observed the presence of the C3037T mutation previously described in the endomyocardial biopsy of a patient with persistent arrhythmia. Conclusion(s): Even though SARS-CoV-2 targets the respiratory tract, the present study supports the evidence that the ACE2 receptors are present in the heart. In addition, COVID19 is causing more and more damage to heart tissue, and viral transcription has been confirmed on cardiomyocytes. Further functional studies are needed to explore the associated mutations and their relation to cardiac manifestation.Copyright © 2023

Uncontrolled Acromegaly Resulting in the Need for LVAD as Bridge to Heart Transplant

Introduction: Acromegaly is an uncommon pituitary disorder with an incidence of six per million persons. While hypertension is often encountered in these patients, heart failure rarely is seen with an incidence rate under 10%. We describe a case of an individual who was diagnosed with acromegaly after an acute exacerbation of heart failure with subsequent management requiring an LVAD to perform Transsphenoidal Surgery (TSS). Case Description: 37-year-old male otherwise healthy initially presented to an emergency room and was found to be in acute heart failure exacerbation. Concerning acromegaly features included macrognathia, enlarged hands and feet, swollen phalanges, widened spacing of teeth, and frontal bossing. IGF-1 level was found 455 ng/mL. MRI showed a 10mm macroadenoma. A right heart catheterization showed elevated filling pressures. Cardiac MRI showed no defects or enhancement. Endomyocardial biopsy showed no inflammatory infiltrates or evidence of infiltrative diseases. Patient had an ejection fraction of 15% corroborated by cardiac MRI along with the presence of aortic root dilatation and mitral regurgitation. The patient started on 0.5mg of Cabergoline twice weekly and 120mg weekly Lanreotide injections. Patient stabilized with plans for further close monitoring and outpatient neurosurgical evaluation. The COVID-19 pandemic and insurance gaps led the patient to spend two years off his medicines and he was unable to be seen by his medical team. Patient was seen by our system after recurrent hospitalizations for heart failure at our sister hospital, AICD was unable to be placed due to the patient's anatomy, he was placed on wearable cardiac defibrillator and required milrinone infusion for progression to end-stage heart failure with cardiac cachexia. At our institution, the patient was evaluated for Orthotopic Heart Transplant (OHT) but due to active GH secreting macroadenoma there was concern for OHT failure without TSS. Decision was made to utilize LVAD as Bridge-to-Transplant for OHT so the patient could be stabilized and safely undergo TSS. The patient tolerated surgeries well and is currently on the active transplant list. Discussion(s): Heart failure is an uncommon presentation of severe acromegaly requiring multidisciplinary management. We describe a case of a patient who initially presented with heart failure too unstable for surgery. Due to the COVID-19 pandemic the patient's disease progressed resulting in end-stage heart failure requiring LVAD placement for further treatment. We would like to draw attention to the use of LVAD placement in acromegalic patients who develop severe cardiovascular disease who are not candidates for OHT.Copyright © 2023

Complications Of A Severe Case Of Multisystem Inflammatory Syndrome In Children

Case Presentation: A 10 year old male with prior COVID-19 exposure presented with 7 days of fever, rash, cough, vomiting, and hypotension. Laboratory evaluation was notable for SARS-CoV2 antibodies, elevated cardiac enzymes, BNP, and inflammatory markers. Initial echocardiogram showed normal cardiac function and a small LAD coronary aneurysm. He was diagnosed with Multisystemic Inflammatory Syndrome in Children (MIS-C) and given methylprednisolone and IVIG. Within 24 hours, he developed severe LV dysfunction and progressive cardiorespiratory failure requiring VA-ECMO cannulation and anticoagulation with bivalirudin. Cardiac biopsy demonstrated lymphocytic infiltration consistent with myocarditis. On VA-ECMO, he had transient periods of complete AV block. With immunomodulator treatment (anakinra, infliximab) and 5 days of plasmapheresis, inflammatory symptoms and cardiac function improved. He weaned off ECMO, and anticoagulation was transitioned to enoxaparin. He had left sided weakness 5 days later, and brain MRI revealed an MCA infarct. Ten days later, he had focal right sided weakness and repeat MRI showed multiple hemorrhagic cortical lesions, thought to be thromboembolic with hemorrhagic conversion secondary to an exaggerated inflammatory response to an MSSA bacteremia in the setting of MIS-C. Enoxaparin was discontinued. After continued recovery and a slow anakinra and steroid wean, he has normal coronary arteries, cardiac function, and baseline ECG but requires ongoing neurorehabilitation. Discussion(s): COVID-19 infection in children is often mild, but MIS-C is an evolving entity that can present with a wide range of features and severity. This case highlights two concepts. While first degree AV block is often reported in MIS-C, there is potential for progression to advanced AV block. Close telemetry monitoring is critical, especially if there is evidence of myocarditis. MIS-C shares features with Kawasaki disease, with a notable difference being a higher likelihood of shock and cardiac dysfunction in MIS-C. In MIS-C patients with cardiovascular collapse requiring ECMO, there is a risk for stroke. There should be a low threshold for neuroimaging and multidisciplinary effort to guide anticoagulation in these complex cases.

Frequency of Pathological MRI Findings in Suspected Myocarditis during the COVID-19Pandemic

Background: COVID-associated and vaccine-triggered myocarditis in young people have received much attention over the course of the pandemic due to early results of vaccination associated myocarditis. This may have led to an increase in myocarditis suspicions. In this study we wanted to examine the actual amount of COVID-associated myocarditis in ourtertiary center. Method(s): We included all cardiac MRIs performed in our institution for the indication of suspected myocarditis between 2020and 2022. We excluded patients with primary cardiomyopathy. We divided the patients into three groups: Group 1 had noCOVID infection or COVID-vaccine associated with their suspected myocarditis, group 2 had received a COVID vaccination prior to developing symptoms, group 3 had had an acute COVID infection and group 4 had a clinical diagnosis of Pediatric inflammatory multisystem syndrome (PIMS). Result(s): Overall, 28 patients had MRIs for suspected myocarditis performed at our center in the investigated time frame. They were 10 to 18 years of age (mean: 15.1 years). Symptoms included chest pain, fatigue, palpitations and reduction in exercise tolerance. Nineteen patients were in group one, 4 patients had symptoms associated with COVID vaccination, three had acute infection and two had a clinical diagnosis of PIMS. Late gadolinium enhancement (LGE) was found in 7 patients. None of these were in groups 2 or 3. Both patients with PIMS(n = 2) had myocarditis on biopsy but only one on MRI. Myocardial biopsy was performed in 8 patients. They showed myocarditis in 6 patients. Apart from the PIMS cases, none of them were associated with Corona infection or COVID vaccine. Three patients had parvovirus B19 on biopsy and one also had EBV. One of the PIMS patients also had HHV6. Theother four biopsies did not yield any viral DNA on PCR. Conclusion(s): Myocarditis associated with acute COVID infection or vaccination was not found in our cohort. Exercise intolerance or chest pain was not reliable indicators of cardiac causes. Even in the pandemic, coronavirus and COVID-19vaccines are unlikely causes of myocarditis. Most cases were associated with classic cardiotropic viruses. However, in cases of PIMS, cardiac involvement is likely and should be investigated accordingly.

A Rare Case Of Eosinophilic Myocarditis Due To Subacute Sars-cov-2 Illness

Background: Eosinophilic myocarditis is a rare inflammatory cardiomyopathy with a poor prognosis. SARS-CoV-2 (COVID-19) illness has been associated with myocarditis, particularly of lymphocytic etiology. Although there have been cases of eosinophilic myocarditis associated with COVID-19 vaccination, there have been few reported cases secondary to COVID-19 illness, with the majority being diagnosed via post-mortem autopsy. Case: A 44-year-old woman with no significant medical history other than recent COVID-19 illness 6 weeks prior presented with progressive dyspnea. Patient developed acute dyspnea and diffuse pruritic rash after taking hydroxyzine. Labs were significant for mild eosinophilia. Echocardiography showed biventricular systolic dysfunction with left ventricular ejection fraction of 40%, and a moderate pericardial effusion that was drained percutaneously. She underwent left heart and right heart catheterization showing elevated biventricular filling pressures, Fick cardiac index of 1.6 L/min/m2, and no coronary disease. She was started on intravenous diuretics and transferred to our facility for further management. Her course was complicated by cardiogenic shock requiring intra-aortic balloon pump (IABP) support. Mixed venous saturations continued to decline and the patient was placed on veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. The patient underwent endomyocardial biopsy (EMB) showing marked interstitial infiltration of eosinophils and macrophages with myocyte injury (see image). She was intubated with mechanical ventilation as well due to worsening pulmonary edema and hypoxemia. She was started on intravenous steroids with improvement of hemodynamics and myocardial function and eventually VA- ECMO was decannulated to low-dose inotropic support which in turn was ultimately weaned after 3 days of mechanical support. Conclusion(s): Eosinophilic myocarditis is a rare and under-recognized sequela of acute COVID-19 infection associated with high mortality rates. It requires prompt diagnosis and aggressive supportive care, including temporary mechanical circulatory support. There are few literature-reported cases of COVID-19 myocarditis requiring use of both IABP and VA-ECMO, none of which were used in biopsy-proven eosinophilic myocarditis, with most of these cases resulting in either fatal or unreported outcomes. Most cases of covid myocarditis required IV glucocorticoids therapy in conjunction with IVIG or interferon therapy. Here, we present a rare case of cardiogenic shock secondary to biopsy-proven eosinophilic myocarditis associated with recent COVID-19 illness with a survival outcome after temporary use of IABP and VA-ECMO support, as well as aggressive immunosuppressive therapy.Copyright © 2022

Analysis of fatal cardiac adverse events caused by chloroquine: a study based on the related data from the WHO global database of individual case safety reports. TT -:Who.

Objective: To analyze the clinical characteristics of fatal cardiac adverse events associated with chloroquine, which was recommended for the antiviral treatment of novel coronavirus pneumonia, and provide reference for clinical safe drug use. Method(s): The fatal cardiac adverse events associated with chloroquine were searched from the World Health Organization global database of individual case safety reports (VigiBase). The clinical characteristics of the individual cases with well-documented reports (VigiGrade completeness score >=0.80 or with detailed original reports) were analyzed. The adverse events were coded using the systematic organ classification (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities (MedDRA) version 22.1 of International Conference on Harmonization (ICH). Result(s): Up to 23 February 2020, a total of 45 reports of fatal heart injuries related to chloroquine were reported in VigiBase, which were from 16 countries. Of them, 30 reports were fully informative. Among the 30 reports,20 cases developed fatal cardiac adverse events after a single large dose of chloroquine. Of them, 17 cases' fatal cardiac adverse events were caused by overdose of chloroquine (15 cases were suicide or suspected suicide, and 2 children took chloroquine by mistake);3 cases' fatal cardiac adverse events were caused in clinical treatment;18 cases showed arrhythmia and cardiac arrest;6 cases showed prolonged QRS wave or QT interval;6 cases were with hypokalemia, including 4 severe ones. Among the 30 reports, 10 cases developed fatal cardiac adverse events after multiple administration of chloroquine, of which 4 cases were treated with chloroquine for 23 days to 2 months and died of heart failure, cardiac arrest or myocardial infarction;6 cases were treated with chloroquine for 20 months to 29 years and all of them had cardiomyopathy, which were confirmed by endomyocardial biopsy to be caused by chloroquine in 3 cases. Conclusion(s): Cardiac toxicity was the primary cause of fatal adverse events caused by chloroquine;the main manifestation of single large dose of chloroquine was arrhythmia and the manifestation of multiple administration was cardiomyopathy.Copyright © 2020 by the Chinese Medical Association.

Multivessel Epicardial Coronary Artery Thrombosis after Heart Transplantation

Introduction: Although cardiac allograft vasculopathy (CAV) remains one of the leading causes of graft failure after heart transplantation (HTx), simultaneous thrombosis of multiple epicardial coronary arteries (CA) is an uncommon finding. Case Report: A 43-year-old male patient with non-ischemic dilated cardiomyopathy underwent successful HTx in 2019. The first two years after HTx were uneventful, surveillance endomyocardial biopsies (EMB) did not reveal any rejection episodes, coronary CTA revealed only minimal non-calcified CA plaques. The patient was admitted to hospital due to fever and chest pain in 2021. Immunosuppressive therapy consisted of tacrolimus, mycophenolate-mofetil and methylprednisolone. ECG verified sinus rhythm. Laboratory test revealed elevated hsTroponin T, NT-proBNP and CRP levels. Cytomegalovirus, SARS-CoV-2-virus and hemoculture testing was negative. Several high-titre donor-specific HLA class I and II antibodies (DSAs;including complement-binding DQ7) could have been detected since 2020. Echocardiography confirmed mildly decreased left ventricular systolic function and apical hypokinesis. EMB verified mild cellular and antibody-mediated rejection (ABMR) according to ISHLT grading criteria. Cardiac MRI revealed inferobasal and apical myocardial infarction (MI);thus, an urgent coronary angiography was performed. This confirmed thrombotic occlusions in all three main epicardial CAs and in first diagonal CA. As revascularization was not feasible, antithrombotic therapy with acetylsalicylic acid, clopidogrel and enoxaparin was started for secondary prevention. Tests for immune system disorders, thrombophilia and cancer were negative. Patient suddenly died ten days after admission. Necropsy revealed intimal proliferation in all three main epicardial CAs, endothelitis, thrombosis, chronic pericoronary fat inflammation, fat necrosis, and subacute MI. CA vasculitis owing to persistent high-titre DSAs, chronic ABMR and acute cellular and antibody-mediated rejection led to multivessel CA thrombosis and acute multiple MI. ABMR after HTx may be underdiagnosed with traditional pathological methods. Pathologies affecting coronary vasculature of HTx patients with DSAs, unique manifestations of CAV lesions and occlusive thrombosis of non-stenotic, non-atherosclerotic lesions should be emphasized.Copyright © 2023

Dilated Cardiomyopathy: Unmasking Contributing Etiologies

Background: The role of genetic conditions in the development of cardiomyopathy is well established;however, recognition and referral for genetic testing remains underutilized. Systematic review of complex cases can increase general awareness in this area of practice. Here we describe the case of a patient with resolved severe stress induced cardiomyopathy (SIC), who was ultimately found to have heterozygous transthyretin-mediated amyloidosis (TTRA). Case: A 27-year-old man (family history positive for a brother status post heart transplant) presented with ataxia and cough due to legionella pneumonia. TTE showed left ventricular (LV) diastolic diameter of 6.2cm, LV ejection fraction 20-25%. He suffered rapid decompensation with mixed cardiogenic/septic shock requiring peripheral VA ECMO and Impella-CP placement. Course notable for brief cardiac arrest on hospital day (HD) 2, incidental diagnosis of COVID 19 on HD 14, conversion to VV ECMO on HD 15, and ECMO decannulation on HD 23. Repeat TTE prior to discharge showed normalization of biventricular function. Discussion(s): Despite resolution of refractory shock and normalization of biventricular function prior to discharge, the TTE finding of mild LV dilation and strong family history prompted outpatient pursuit of genetic testing which revealed a heterozygous TTRA mutation (val142ile). Work-up to assess cardiac involvement included: a 99m-technetium pyrophosphate scintigraphy found to be indeterminate, an aborted endomyocardial biopsy due to inability to smoothly advance a bioptome (presumably related to ECMO cannulation), and a cardiac MRI (pending at the time of this submission). If a cardiac phenotype is discovered, the patient will be started on targeted treatment of cardiac amyloid. Screening of first-degree family members has been initiated. Conclusion(s): Given the current state of under-diagnosis of genetic cardiomyopathies and its association with significant morbidity and mortality, it is prudent to consider genetic testing in young patients based on clinical history. Examples of clinical scenarios to prompt further testing include: anatomical findings (i.e. cardiac chamber enlargement, left ventricular hypertrophy), family history of cardiomyopathy, or clinical markers suggestive of alternative diagnoses (i.e. neuropathy, renal insufficiency, mediastinal lymphadenopathy). This thoughtful and algorithmic use of genetic testing may help improve long-term patient outcomes given improvements in both detection, family screening, and treatment for disease-specific cardiomyopathies.Copyright © 2022

Myocarditis Following Covid-19 Vaccination In Adolescents And Adults In 2021

Background: Clinical course and outcomes of myocarditis after COVID-19 vaccination remain variable. Method(s): We retrospectively collected data on patients >12 years old from 01/01/2021 to 12/30/2021 who received COVID-19 vaccination and were diagnosed with myocarditis within 60 days of vaccination. Myocarditis cases were based on case definitions by authors. Result(s): We report on 238 patients of whom most were male (n=208;87.1%). The mean age was 27.4 +/- 16 (Range 12-80) years. Females presented at older ages (41.3 +/- 21.5 years) than men 25.7 +/- 14 years (p=0.001). In patients >20 years of age, the mean duration from vaccination to symptoms was 4.8 days +/-5.5 days but in <20, it was 3.0 +/- 3.3 days (p=0.04). Myocarditis occurred most commonly after the Pfizer-BioNTech vaccine;(n=183;76.45) and after the second dose (n=182;80%). Symptoms started 3.95 +/-4.5 days after vaccination. The commonest symptom was chest pain (n=221;93%). Patients were treated with non-steroidal anti-inflammatory drugs (n=105;58.3%), colchicine (n=38;21.1%), or glucocorticoids (n=23;12.7%). About 30% of the patients had left ventricular ejection fraction but more than half recovered on repeat imaging. Abnormal cardiac MRI was common;168 patients (96% of 175 patients that had MRI) had late gadolinium enhancement, while 120 patients (68.5%) had myocardial edema. Heart failure guideline-directed medical therapy use was common (n=27;15%). Eleven patients had a cardiogenic shock, and 4 patients required mechanical circulatory support. Five patients (1.7%) died, of these, 3 patients had endomyocardial biopsy/autopsy-confirmed myocarditis. Conclusion(s): Most cases of COVID-19 vaccine myocarditis are mild. Females presented at older ages than men and the duration from vaccination to symptoms was longer in patients >20 years. Cardiogenic shock requiring mechanical circulatory support was seen and mortality was low. Future studies are needed to better evaluate risk factors and long-term outcomes of COVID-19 vaccine myocarditis.Copyright © 2022

Heart Failure With Severely Reduced Ejection Fraction Following Covid-19 Vaccine: A Case Series

Introduction: With the rise of the pandemic, the development of the COVID-19 vaccine has helped alleviate the burden on the healthcare system. However, rare cardiac side effects have been reported, especially within the young healthy population. Herein, we present a case series of four patients who received the Pfizer mRNA COVID-19 vaccine and were noted to have heart failure with severely reduced ejection fraction (<= 25%) a few weeks following the 2nd dose of the Pfizer vaccine. Method(s): This is a retrospective study from January 2021 to August 2021. Patient cases were identified from hospitalizations or clinic visits. Each case was evaluated for underlying predisposing conditions, vaccination type, symptoms onset, diagnostic studies, and outcomes. Result(s): A total of four patients were identified (table). Patients' ages ranged from 22-43 years old. Seventy-five percent of the patient population were male. All patients commonly reported clinical symptoms of heart failure including fatigue, orthopnea, paroxysmal nocturnal dyspnea, and peripheral edema starting within three weeks from receiving the second dose of the Pfizer COVID-19 Vaccine. Patients had no prior known cardiac history or predisposing conditions. Diagnostic workup including a left heart catheterization showed normal coronaries. Echocardiograms showed significantly reduced left ventricular ejection fraction (LVEF) <= 25%. Three patients were confirmed to have non-inflammatory cardiomyopathy via endomyocardial biopsy or cardiac MRI. One patient was unable to get a cardiac MRI due to a concomitant acute renal injury. Patients were started on Guideline-directed medical therapy (GDMT). Two patients were noted to have an improvement in their ejection fraction with one patient achieving full recovery to LVEF of 62%. One patient is currently undergoing evaluation for advanced heart failure therapy while the last patient has relocated. Conclusion(s): s The relationship between the novel mRNA COVID-19 vaccine and cardiomyopathy remains to be an area in need of further investigation. Despite the unclear mechanism, management remains to be with GDMT and advanced therapies as indicated. EF recovery and improved clinical outcomes can be achieved in some.Copyright © 2022

Subclinical Myocardial Leukocyte Infiltration after COVID-19 Vaccination in HeartTransplant Recipients

Background: mRNA-based COVID-19 vaccines have been reported to rarely cause myocarditis. Although myocardial biopsy is considered gold standard in the diagnosis of myocarditis, no standardized study following COVID-19 vaccination in humans was performed so far. Since heart transplant (HTX) recipients frequently undergo routine myocardial biopsy, we here aimed to investigate effects of COVID-19 vaccination by analyzing myocardial inflammation by state-of-the-art quantitative immunohistochemistry. Method(s): Consecutive patients after HTX who underwent routine endomyocardial biopsies at a median of 167 days before and 136 days after their first COVID-19 vaccination with a mRNA vaccine were included and divided into groups with and without inflammatory response following vaccination, defined as increased number of CD3+ lymphocytes >14/mm2. Patients with histological signs of rejection (ISHLT Grade >1) or >14 CD3+ lymphocytes/mm2 at baseline were excluded. Afterward clinical characteristics of patients with inflammatory response were screened for signs of myocarditis. Result(s): The final analysis included 46 patients with a median age of 63 years and a time post-HTX of 2.4 years. Immunosuppressive therapy remained unchanged between biopsies. 36 (78%) patients remained below the cut-off of 14 CD3+ lymphocytes/mm2. However, in 10 (22%) recipients, we detected significant leucocyte infiltration by quantitative analysis of endomyocardial biopsies following vaccination (4 vs. 33.7 leucocytes/mm2, p = 0.001). Groups did not differ in age (63 vs. 57 years, p = 0.21), body mass index (25 vs. 24 kg/m2, p = 0.24), NYHA-class (>=2 in 19 vs. 10%, p = 0.4), NTProBNP levels (592 vs. 514 ng/L, p = 0.55) or myocardial CD3+ cell count (4.9 vs. 2.6 cells/mm2, p = 0.07) before vaccination. Patients with leucocyte infiltration remained clinical inapparent with stable NYHA class (>=2 in 10 vs. 20%, p = 0.99) and depicted no increased NT-ProBNP levels (514 vs. 478 ng/L, p = 0.03). No hospitalizations due to suspected myocarditis were reported. Conclusion(s): For the first time, we report subclinical myocardial leucocyte infiltration following COVID-19 mRNA vaccination in every fifth patients without clinical consequences during the short observation period.

Fulminant Myocarditis (Fm) Requiring Heart Transplantation: A Rare Sequela of Sars-Cov-2 Infection

Background SARS-CoV-2 infection, the cause of COVID-19, has been associated with myocarditis. Fulminant myocarditis (FM) is rare. Case A 30-year-old male with a past medical history of SARS-CoV-2 infection 7 months prior, presented with a 2-week history of malaise, cough, dyspnea, and signs of cardiogenic shock. He was fully vaccinated 9 months prior. Respiratory viral PCR testing, including SARSCoV-2, was negative. HS-troponin was >20,000 ng/L (NR: 0-53 ng/L). An echocardiogram revealed a dilated cardiomyopathy with an EF of 15-20%. Cardiac catheterization revealed no CAD. Workup for an autoimmune etiology was unrevealing. His condition worsened and he required inotropic support, eventual placement of an LVAD, and initiation of ECMO. He was not able to tolerate cardiac MRI or endomyocardial biopsy. Ultimately, he underwent orthotopic heart transplantation. Pathologic examination of the explanted heart confirmed lymphocytic myocarditis. Decision-making Myocardial injury due to the cardiotropic nature of SARS CoV-2 has been increasingly reported. There has been a 42% increase in viral myocarditis, and the risk is 16 times greater with a history of COVID-19. Symptomatic myocarditis typically manifests within weeks of infection. Such a delayed presentation has not been described. Data from autopsies of deceased COVID-19 patients revealed a 25% to 50% detection rate of SARS-CoV-2 mRNA in the myocardium. One case report described a deceased FM patient with multiple negative SARS-CoV-2 PCR tests, including bronchial lavage samples, having confirmed SARS-CoV-2 within the myocardium postmortem. Hence SARS-Cov-2 can persist in the heart after the resolution of respiratory infection, possibly leading to ongoing inflammation and myocardial damage. This may explain why our patient presented 7 months after a resolved infection. Conclusion SARS-CoV-2 is cardiotropic and can cause fulminant myocarditis even in the absence of a detectable respiratory infection. Hence closer monitoring of post-COVID-19 patients, including screening for subclinical myocarditis, may be prudent. Further research on monitoring and an evaluation of the clinical utility of medical therapy, is also warranted.Copyright © 2023 American College of Cardiology Foundation

Czech Cardiovascular Research and Innovation Day 2022

The proceedings contain 67 papers. The topics discussed include: role of endomyocardial biopsy in differential diagnosis of non- -ischemic cardiomyopathy;metformin treatment is associated with improved quality of life and outcome in patients with diabetes and advanced heart failure (HFREF);translational research in the field of inherited arrhythmias;same day discharge via a dedicated radial lounge - results of 1-year experience during the COVID-19 pandemic;functional assessment of microcirculation in takotsubo cardiomyopathy - a pilot study;an interplay of genetics and inflammation affecting left ventricular reverse remodeling in dilated cardiomyopathy;sildenafil inhibits pulmonary hypertension induced by left heart pressure overload in rats;predicting long-term survival after an ischemic stroke;and longitudinal trends in blood pressure, prevalence, awareness, treatment, and control of hypertension in the Czech population. are there any sex differences?.

Viralvector Covid19 Vaccine Related Constrictive Pericarditis a Case Report

Background COVID19 has emerged in the last 3 years thus different types of vaccines are massively administered globally which exhibit systemic and cardiac side effects mostly myocarditis and pericarditis. We present a case of a 29 YO completely healthy male, non-smoker with negative FHX of cardiac diseases, who developed acute pericarditis after the first dose of the "viral-vector" vaccine and evolved rapidly into constrictive pericarditis in 3 weeks duration. The patient started to complain of dyspnea III-IV and central chest pain relieved by bending forward day 3 post-vaccine, labeled at EMD with acute pericarditis. NSAID and colchicine were started & by 3rd-week outpatient follow-up. Despite a full adequate medx course, we found him to have persistent Dyspnea NYHA II with evidence of constrictive pericarditis on echocardiography, cCT and cMRI after 1 month. He refused myocardial biopsy. Methods we used the serial TTE studies showed small pericardial effusion <1cm and then signs of septal bounce, tran MV/TV respiratory variation and thickned pericardium, same features seen on cCT scan. In addition to a positive LGE on cMRI with 18 months follow-up. Results post vaccine constrictive pericarditis is not uncommon, early detection and appropriate management is the mainstay to avoid unwanted consequences. Conclusion Although there are many reports and registries of post-vaccine myo/pericarditis, the exact association is still unclear and requires further investigation. [Formula presented]Copyright © 2023 American College of Cardiology Foundation

Spotting the Needle Amongst the Haystack - When Asthma Isn't Asthma

Introduction/Background: Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss Syndrome, is a rare, small to medium vessel ANCA associated vasculitis. Hallmarks of EGPA include asthma, chronic rhinosinusitis, and peripheral neuropathy. EGPA is characterized by a prodrome of asthma and allergic rhinitis, followed by peripheral blood hyper-eosinophilia and accumulation of extravascular eosinophils, and finally systemic vasculitis. Extrapulmonary involvement is common, sometimes with fatal outcomes. The onset of EPGA is typically between 25-50 years;however, EGPA also occurs during childhood and has a significant morbidity and mortality. Description/Method: Our patient presented to the emergency department with a 2-week history of lethargy, wheeze and left sided neck swelling. After testing COVID-19 positive eight months prior to this, she developed wheezy episodes and was subsequently diagnosed with asthma which was managed with bronchodilators as required. She was reviewed by an allergist who confirmed a dust mite allergy and prescribed Montelukast. She remained well during the summer months however during winter she had 3 distinctive episodes of wheeze and cough which were managed by antibiotics and prednisolone. In the emergency department, an echocardiogram was performed which showed a cardiac tamponade. She was transferred to CICU where she had a pericardial drain inserted. The fluid was abundant with inflammatory cells. Multiple investigations were performed as follows: Hb: 135g/L, wbc: 20.30 x 10 9/L, Eosinophils: 12.77 x 10 9/L, CRP: 51 mg/L, ESR: 75 mm/hr, LDH: 1188 IU/L, IgE: 8000 UI/ml, ANA, ANCA: negative. CT chest showed mediastinal lymphadenopathy and patchy bilateral infiltrate and cardiac MRI showed myopericarditis and LV fibrosis. BMA showed no malignant cells and sinusitis was confirmed by CT. On examination, she was underweight. Her nasal mucosa looked inflamed. Otherwise systemic examination was unremarkable. In the context of poor ejection fraction (20%) with LV fibrosis, urgent MDT was arranged and concluded that our working diagnosis was EGPA. The decision was made to start IV methylprednisolone 10mg/kg/day for 3 days and Ivermectin. That night our patient had a VF arrest which required a single shock conversion 4J/kg. There was 7-minute downtime. Treatment was escalated to include cyclophosphamide, rituximab and plasmapheresis. The patient made a remarkable recovery, extubated and transferred to a normal ward. Her eosinophils count and inflammatory markers improved dramatically following treatment. However, she developed severe neuropathic left leg pain and NCS confirmed peripheral neuropathy Discussion/Results: EGPA is a very rare disease and diagnosis can be challenging especially with the absence of histopathology diagnosis. Early empirical treatment especially in a very ill child in intensive care unit can save lives and divert the progress of the disease. This patient has fulfilled the American College of Rheumatology criteria to diagnose EGPA including asthma, eosinophil count > 10% of upper normal, peripheral neuropathy, pulmonary infiltrates on CT thorax and paranasal sinuses abnormalities. Cardiac biopsy of the fibrotic mass may be a useful tool for diagnosis;however, this invasive procedure may expose this patient with high risk of fatal arrhythmias. Since other causes of eosinophilia were ruled out including parasitic infections, lymphoproliferative disorders, and rare primary immunodeficiency syndromes (hyper-IgE syndrome due to STAT3 or DOCK8 deficiency and Omenn syndrome) and the patient responded well to treatment, the diagnosis of EGPA was supported. Key learning points/Conclusion: Asthma not responding to bronchodilator could be another diagnosis Eosinophilia should be interpreted with caution. Defer the need for histopathology diagnosis in critically ill children Cardiac involvement is a life-threatening marker Early diagnosis prevents life threatening complications.

COVID-19 and Cardiac Complication: what is new?

Coronavirus disease 2019 (COVID-19) has been reported to cause cardiovascular complications such as myocardial injury, thromboembolic events, arrhythmia, and heart failure. Multiple mechanisms-some overlapping, notably the role of inflammation and IL-6-potentially underlie these complications. The reported cardiac injury may be a result of direct viral invasion of cardiomyocytes with consequent unopposed effects of angiotensin II, increased metabolic demand, immune activation, or microvascular dysfunction. Thromboembolic events have been widely reported in both the venous and arterial systems that have attracted intense interest in the underlying mechanisms. These could potentially be due to endothelial dysfunction secondary to direct viral invasion or inflammation. Additionally, thromboembolic events may also be a consequence of an attempt by the immune system to contain the infection through immunothrombosis and neutrophil extracellular traps. Cardiac arrhythmias have also been reported with a wide range of implicated contributory factors, ranging from direct viral myocardial injury, as well as other factors, including at-risk individuals with underlying inherited arrhythmia syndromes. Heart failure may also occur as a progression from cardiac injury, precipitation secondary to the initiation or withdrawal of certain drugs, or the accumulation of des-Arg9-bradykinin (DABK) with excessive induction of pro-inflammatory G protein coupled receptor B1 (BK1). The presenting cardiovascular symptoms include chest pain, dyspnoea, and palpitations. There is currently intense interest in vaccine-induced thrombosis and in the treatment of Long COVID since many patients who have survived COVID-19 describe persisting health problems. This review will summarise the proposed physiological mechanisms of COVID-19-associated cardiovascular complications. Copyright © 2022, Anka Publishers. All rights reserved.

Outcome and Morpho-Functional Changes on Cardiac Magnetic Resonance in Patient with Acute Myocarditis Following Mrna Covid 19 Vaccination

Background: MessengerRNA (mRNA) COVID-19 vaccination has been associated with a higher-than-expected occurrence of acute myocarditis. Scarce information is available on mid-term prognosis and changes in cardiac function, volumes, and tissue characterization on cardiac magnetic resonance (CMR). Method(s): Retrospective, multicenter study including patients with a definite diagnosis of acute myocarditis within 30 days from mRNA COVID-19 vaccination, with a confirmed myocarditis diagnosis based on endomyocardial biopsy (EMB) or autopsy or by the coexistence of positive biomarkers (troponin >99th upper reference limit or elevated creatine kinase myocardial band [CK-MB]) and cardiac MRI findings consistent with AM according to the 2018 updated Lake Louise Criteria. Result(s): 77 patients (median age 25 years [IQR 20-35], 15% female) were included and followed-up for 147 days [IQR 74-215]. Follow-up CMR was available in n=49 patients and showed no changes in biventricular ejection fraction (EF) as compared to CMR at diagnosis (left ventricular EF: 59%[55-65]vs. 60%[57-64], p=0.507, right ventricular EF: 56%[52-62]vs. 57%[52-61], p=0.563, respectively). Late gadolinium enhancement was present in all patients at diagnosis and persisted in only n=39 (79.6%) at follow-up (p=0.001), generally sparing the anterior wall and the septum. N=10 (20.4%) had a persistent edema based on T2-weighted short tau inversion recovery (STIR) sequences, with predominant involvement of inferior or inferiorlateral walls. The proportion of patients with increased T1 and T2 mapping signals significantly decreased at follow-up (n=13 (68%) vs. n=4 (13%),p<0.001, and n=21 (84%) vs. n=3 (10%),p<0.001, respectively), as well as the presence of pericardial effusion (n=16 (33%) vs. n=3 (6%),p=0.004). No differences in morpho-functional CMR parameters based on the type of vaccine administered were found (BNT162b2 Pfizer/BioNTech, n=36, 73.5%, m-RNA-1273 Moderna, n=13, 26.5%). Among patients with available follow-up (N=75, 97.4%), no major adverse cardiovascular events nor myocarditis recurrence or death were reported. Conclusion(s): At mid-term follow-up, patients who experienced an acute myocarditis after a mRNA COVID-19 vaccine had preserved biventricular EF. The rate and localization of residual scar or edema on CMR is in line with classic viral myocarditis with a good prognosis. This new piece of information should further reassure patients who experience acute myocarditis after mRNA COVID-19 vaccination.

Effect of Covid-19 Vaccination on Markers of Rejection in Heart Transplant Recipients

Purpose: Heart transplant recipients have worse survival with COVID-19 than the general population, highlighting the importance of vaccination in these patients. The impact of vaccination on rejection in transplant recipients is not well studied. This study examines the association of vaccination for COVID-19 with changes in markers for and evidence of transplant rejection. Method(s): A retrospective analysis of heart transplant recipients vaccinated for COVID-19 was conducted at a major tertiary care center in the American Midwest. Serial antibody responses were drawn after vaccination to assess vaccine response. Data from routine transplant surveillance was extracted from the electronic medical record. Markers of rejection included Allomap, Allosure, donor specific antibodies (DSA), and endomyocardial biopsies. Only patients with comparative data within 365 days of their first COVID-19 vaccination were included for analysis. Numerical data was assessed using descriptive statistics. Categorical variables were analyzed using Fisher's exact tests. Result(s): Between January 1, 2021 and September 30, 2021, 51 heart transplant recipients had COVID-19 antibody levels checked post-vaccination. There was an increase in the mean Allomap (31.19 +/- 5.27 vs 32.14 +/- 4.30), Allosure (0.04 +/- 0.08 vs 0.11 +/- 0.12%), and biopsy C4d% (3.33 +/- 8.16 vs 10.00 +/- 12.65%) levels post-vaccination compared to those pre-vaccination. Both positive and negative responders to vaccination showed this numerical increase in markers of rejection. There was no change in biopsy grades for acute cellular rejection, nor any changes in class I DSA positivity. One patient who had a positive antibody response to the vaccine had a de novo class II DSA post vaccination. No patients in this cohort had an episode of treated rejection post vaccination. Conclusion(s): Heart transplant recipients receiving COVID-19 vaccination have numerical increases in markers of rejection like Allomap, Allosure, and biopsy C4d%. These subtle changes may suggest a difference in the immunologic environment but are of unclear significance. There was no change in biopsy proven ACR or treated episodes of rejection. Further studies are warranted to investigate the effect of COVID-19 vaccination on transplant rejection. (Table Presented).

SARS-CoV-2 infection causes cardiomyocyte swelling, cardiac pericyte loss, increased permeability, and diastolic dysfunction in a hamster model

Background/Introduction: Recovered COVID-19 patients often display cardiac dysfunction, even after a relatively mild infection. Purpose: We present an in-depth physiological and histological timeline of the cardiac consequences of SARS-CoV-2 infection using a hamster model. Methods: We used several methods, including transthoracic echocardiography, RNA sequencing on in vitro cultures, and in-situ hybridization techniques, complemented with histological analysis. Results: We analysed cardiac function by echocardiography over a period of 35 dpi. Already by 14 dpi and continuing at 35 dpi, infected hamsters presented with an increased E/E', decreased MV deceleration time, and an increased isovolumetric contraction time as compared to control, indicating the presence of diastolic dysfunction. Histologically, cardiomyocytes were enlarged already by 4 dpi and remained enlarged over 5 weeks. We observed the presence of fibrin-rich microthrombi at 4 dpi, which were resolved by 14 dpi. SARS-CoV-2 RNA was present in cardiac pericytes, accompanied by reduced pericyte coverage of capillaries at 4 dpi and 14 dpi, which mostly recovered by 35 dpi. At 14 dpi, the reduced pericyte coverage coincided with increased vascular permeability, suggesting that SARS-CoV-2 infection of pericytes affects microvascular integrity. SARS-CoV-2 infection of pericytes in vitro induced the expression of genes involved in viral defence, and affected genes involved in pericyte contractility and extracellular matrix proteins. Loss of cardiac pericytes was observed in cardiac biopsies from patients recovered from SARSCoV- 2 infection. Conclusion(s): Overall, our results demonstrate that SARS-CoV-2 infection causes a phenotype similar to ischemia-reperfusion, without overt ischemia. We propose that partial occlusion by microthrombi and microvascular dilation caused by pericyte loss induces regional variations in blood flow, and results in a stiffer ;swollen' heart that shows diastolic dysfunction.