A challenging case of eosinophilic myocarditis leading to heart failure and transplantation.

The large spectrum of etiologies, severities, and histologic appearances of eosinophilic myocarditis (EoM) poses challenges to its diagnosis and management. Endomyocardial biopsy is the current gold standard for diagnosis. However, cardiovascular magnetic resonance imaging is becoming more frequently used to diagnose acute myocarditis because of enhanced sensitivity when compared to histopathologic examination, and its less invasive nature. We report a complicated case of EoM in a male in his mid-thirties that led to fulminant cardiogenic shock that required immunosuppressive therapy on day 5 of admission and implantation of a left ventricular assist device (LVAD) on day 30. EoM was diagnosed on histopathologic examination of the resected fragment of the left ventricular myocardium. Nine months after the initial presentation, the patient ultimately required heart transplantation. The explanted heart showed minimal residual interstitial inflammation with evidence of mildly active intimal arteritis and patchy areas of interstitial fibrosis. In this report, we describe our patient's clinical features and correlate them with imaging and histopathologic findings to illustrate the difficulty in diagnosing EoM, particularly in this complicated patient that ultimately required heart transplantation. The diagnosis can be challenging due to the variable histopathologic features, clinical presentation, and utilization of therapeutic medications and devices.

Crash Landing of Thyroid Storm: A Case Report and Review of the Role of Extra-Corporeal Systems.

Thyroid storm is a rare but life-threatening endocrinological emergency with significant mortality ranging from 10-30% with multi-organ involvement and failure. In view of the rarity of this condition and efficacy of established first line medical treatment, use of extra-corporeal treatments are uncommon, not well-studied, and its available evidence exists only from case reports and case series. We describe a 28-year-old man who presented with an out-of-hospital cardiac arrest secondary to thyroid storm. Despite conventional first-line pharmacotherapy, he developed cardiogenic shock and circulatory collapse with intravenous esmolol infusion, as well as multi-organ failure. He required therapeutic plasma exchange, concurrent renal replacement therapy, and veno-arterial extra-corporeal membrane oxygenation, one of the few reported cases in the literature. While there was clinical stabilization and improvement in tri-iodothyronine levels on three extra-corporeal systems, he suffered irreversible hypoxic-ischemic brain injury. We reviewed the use of early therapeutic plasma exchange and extra-corporeal membrane oxygenation, as well as the development of other novel extra-corporeal modalities when conventional pharmacotherapy is unsuccessful or contraindicated. This case also highlights the complexities in the management of thyroid storm, calling for caution with beta-blockade use in thyrocardiac disease, with close monitoring and prompt organ support.

Safety of Endomyocardial Biopsy in New-Onset Acute Heart Failure Requiring Veno-Arterial Extracorporeal Membrane Oxygenation.

BACKGROUND: Endomyocardial biopsy (EMB) has an important role in determining the pathogenesis of new-onset acute heart failure (new-AHF) when noninvasive testing is impossible. However, data on safety and histopathologic outcomes in patients requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is lacking. METHODS: A retrospective, multicenter cohort of patients undergoing EMB while requiring VA-ECMO for new-AHF between 1990 and 2020 was compared with a cohort of nontransplant related biopsies not requiring VA-ECMO. Primary end point of the study was to determine the safety of EMB. Additionally, we describe the underlying pathogenesis causing new-AHF based on histopathologic examination of the samples obtained. RESULTS: A total of 23 patients underwent EMB while requiring VA-ECMO (10.0%), 125 (54.3%) during an unplanned admission, and 82 (35.7%) in elective setting. Major complications occurred in 8.3% of all procedures with a significantly higher rate in patients requiring VA-ECMO (26.1% versus 8.0% versus 3.7%, P=0.003) predominately due to the occurrence of sustained ventricular tachycardia or need of resuscitation (13.0% versus 3.2% versus 1.2%, P=0.02). EMB led to a histopathologic diagnosis in 78.3% of the patients requiring VA-ECMO which consisted primarily of patients with myocarditis (73.9%). CONCLUSIONS: EMB in patients requiring VA-ECMO can be performed albeit with a substantial risk of major complications. The risk of the procedure was offset by a histopathologic diagnosis in 78.3% of the patients, which for the majority consisted of patients with myocarditis. The important therapeutic and prognostic implications of establishing an underlying pathogenesis causing new-AHF in this population warrant further refinement to improve procedural safety.

One-year outcome and survival analysis of deferred ventricular septal repair in cardiogenic shock supported with mechanical circulatory support.

BACKGROUND AND OBJECTIVE: The effectiveness of deferred surgical repair of ventricular septal rupture (VSR) post-myocardial infarction (MI) with cardiogenic shock remains limited to case reports. Our study aimed to investigate the outcomes and survival analysis following mechanical circulatory support (MCS) in patients after VSR who develop cardiogenic shock. METHODS: We analyzed 27 patients with post-MI VSR and cardiogenic shock who received deferred surgical repair while stabilized on MCS between January 2018 and March 2020. After normality test adjustments, continuous variables were expressed as mean ± standard deviation (SD). These were compared using the Mann-Whitney U test and Student's t-test. Categorical variables were compared using chi-square or Fisher's exact test. To identify predictors of operative mortality, univariate analysis of clinical characteristics and interventions followed by logistic regression was carried out. P-value of < 0.05 was considered significant. RESULTS: All patients had preoperative MCS. Emergency repair was avoided in all the patients. The mean age of the participants was 64.96 with the majority being males (74.1%). On average, the mean time from MI to VSR repair was 18.85 days. Delayed revascularization was associated with increased mortality (OR 17.500, 95% CI 2.365-129.506, P = 0.005). Other factors associated with increased mortality were ejection fraction (EF), three-vessel disease, Killip class, early surgery, and prolonged use of inotropes. The operative mortality was 11% with an overall mortality of 33.3%. The one-year survival rate was 66.7%. CONCLUSION: The use of MCS in adjunct to a deferred surgical approach shows an improved survival outcome of patients with VSR complicated by cardiogenic shock. Further investigations are required regarding the optimal time for MCS and surgical repair.

Endothelial Dysfunction as a Component of Severe Acute Respiratory Syndrome Coronavirus 2-Related Multisystem Inflammatory Syndrome in Children With Shock.

TRIAL REGISTRATION: NCT04420468. OBJECTIVES: Severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children is frequently associated with shock; endothelial involvement may be one of the underlying mechanisms. We sought to describe endothelial dysfunction during multisystem inflammatory syndrome in children with shock and then assess the relationship between the degree of endothelial involvement and the severity of shock. DESIGN: Observational study. SETTING: A PICU in a tertiary hospital. PATIENTS: Patients aged under 18 (n = 28) with severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children and shock, according to the Centers for Disease Control and Prevention criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Correlations between endothelial marker levels and shock severity were assessed using Spearman coefficient. The median (interquartile range) age was 9 years (7.5-11.2 yr). Sixteen children presented with cardiogenic and distributive shock, 10 presented with cardiogenic shock only, and two presented with distributive shock only. The median left ventricular ejection fraction, troponin level, and lactate level were, respectively, 40% (35-45%), 261 ng/mL (131-390 ng/mL), and 3.2 mmol/L (2-4.2 mmol/L). Twenty-five children received inotropes and/or vasopressors; the median Vasoactive and Inotropic Score was 8 (5-28). Plasma levels of angiopoietin-2 (6,426 pg/mL [2,814-11,836 pg/mL]), sE-selectin (130,405 pg/mL [92,987-192,499 pg/mL]), von Willebrand factor antigen (344% [288-378%]), and the angiopoietin-2/angiopoietin-1 ratio (1.111 [0.472-1.524]) were elevated and significantly correlated with the Vasoactive and Inotropic Score (r = 0.45, p = 0.016; r = 0.53, p = 0.04; r = 0.46, p = 0.013; and r = 0.46, p = 0.012, respectively). CONCLUSIONS: Endothelial dysfunction is associated with severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children with shock and may constitute one of the underlying mechanisms.

Electron Microscopy Revealed Massive Lipid Droplets in Cardiomyocytes in a Patient with Cardiogenic Shock Following a Fulminant Type 1 Diabetes Mellitus.

A 52-year-old man with consciousness disorder following a 2-day history of general fatigue, diarrhea, vomiting and excessive thirst was admitted to our hospital. Severe hyperglycemia (1,739 mg/dL) with a slightly elevated HbA1c level (6.9%), ketonuria and low C-peptide level (0.07 ng/mL) confirmed the diagnosis of fulminant type 1 diabetes mellitus (FT1DM). Following sudden unexplained cardiogenic shock shortly after the initiation of insulin therapy with no evidence of myocardial ischemia assessed by coronary angiography, the patient was supported with percutaneous venoarterial extracorporeal membrane oxygenation. Electron microscopic analysis of the myocardium revealed massive lipid droplets without the infiltration of inflammatory cells. His left ventricular function began to recover during the following days and returned to a normal level on day 14. Currently, the impact of FT1DM on intramyocardial lipid deposition is poorly understood. However, this case suggests that even short-term exposure to high concentrations of glucose can be responsible for lipotoxicity followed by severe cardiac dysfunction.

Coronavirus disease-19 and cardiovascular disease: A risk factor or a risk marker?

Severe acute respiratory syndrome coronavirus-2 causes the clinical syndrome of coronavirus disease of 2019 (COVID-19) which has become a global pandemic resulting in significant morbidity and mortality. While the virus primarily affects the respiratory system, it also causes a wide variety of complex cardiac manifestations such as acute myopericarditis, acute coronary syndrome, congested heart failure, cardiogenic shock and cardiac arrhythmias. There are numerous proposed mechanisms of cardiac injury, including direct cellular injury, pro-inflammatory cytokine storm, myocardial oxygen-demand mismatch, and systemic inflammation causing multi-organ failure. Additionally, medications commonly used to treat COVID-19 patients have various cardiovascular side effects. We aim to provide a succinct review about the pathophysiology and cardiac manifestations of COVID-19, as well as treatment considerations and the various adaptations made to the current healthcare structure as a result of the pandemic.

Biventricular assistance with 2 hm3 in a small chest patient: extra-pericardial implant.

We describe the clinical course and treatment of a 53-year-old female, with small chest dimensions, referred to our institution for a primary cardiogenic shock. The patient underwent an on-pump left ventricular assist-device (VAD) implantation with the aid of immediate post-operative paracorporeal right-VAD assistance for an acute right ventricular failure. After two unsuccessful weaning attempts, she underwent extrapericardial HM 3 RVAD implantation.

Total percutaneous biventricular assist device implantation for fulminant myocarditis.

We report an effective therapeutic approach of mechanical circulatory support for a patient with cardiogenic shock and respiratory insufficiency due to fulminant myocarditis. An Impella® 5.0 was utilized as a left ventricular assist device (VAD) and percutaneous veno-pulmonary extracorporeal membrane oxygenation (ECMO) as a right VAD. These devices were implanted without sternotomy or thoracotomy. Although a combination of Impella and veno-arterial ECMO has been reported as percutaneous biventricular support, there are concerns that this combination is not beneficial for myocardial recovery in patients with respiratory insufficiency, because Impella expels insufficiently oxygenated blood from the left ventricle to the coronary arteries. Our approach took advantage of percutaneous implantation of ECMO and temporary VAD, eliminating the drawbacks of both devices, thus providing a more effective and less invasive form of temporary biventricular support.

Sudden cardiogenic shock mimicking fulminant myocarditis in a surviving teenager affected by severe acute respiratory syndrome coronavirus 2 infection.

In the context of the coronavirus disease 2019 pandemic, myocardial injury is a relatively frequent finding. Progression to cardiogenic shock has been rarely described, especially in healthy young patients. The underlying mechanisms are to date controversial. A previously healthy 18-year-old female teenager affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) developed fulminant cardiogenic shock requiring a prompt extracorporeal membrane oxygenation support. Cardiac involvement was predominant compared with the pulmonary one. Myocardial biopsies were performed; and in order to clarify the pathophysiology of the acute heart failure, optical and transmission electron microscopy study was realized. Two additional immunohistology techniques were developed in order to (i) detect a SARS-CoV-2 recombinant fusion nucleoprotein by using a specific antibody and (ii) study fractalkine expression induced by activated endothelium because this molecule is well known to be elevated in patients with severe cytokine release syndrome. SARS-CoV-2 genome was not detected in the myocardium. Even if the clinical presentation, laboratory markers, and cardiac imaging techniques strongly suggested fulminant myocarditis, histology and immunohistology were not fully consistent with this diagnosis according to the Dallas criteria. Although rare suspected coronavirus particles were found by transmission electron microscopy in the cardiac endothelium, neither significant immunoreactivity for the viral nucleocapsid protein nor image suggestive of endotheliitis was detected. Intense endothelial immunoreactivity pattern for fractalkine expression was observed. From a clinical point of view, the left ventricular systolic function gradually improved, and the patient survived after a long stay in the intensive care unit. Our observations suggest that a massive cytokine storm induced by SARS-CoV-2 infection was the main cause of the cardiogenic shock, making a direct viral injury pathway very unlikely.

Mortality in cardiogenic shock is stronger associated to clinical factors than contemporary biomarkers reflecting neurohormonal stress and inflammatory activation.

PURPOSE: To validate the IABP-SHOCK II risk score in a Danish cohort and assess the association between the IABP-SHOCK II risk score and admission concentration of biomarkers reflecting neurohormonal - (Copeptin, Pro-atrial natriuretic peptide (proANP), Mid-regional pro-adrenomedullin (MRproADM)) and inflammatory (ST2) activation in patients with CS complicating ST segment elevation myocardial infarction (STEMI). METHODS: A total of 137 consecutive patients admitted with STEMI and CS at two tertiary heart centres were stratified according to the IABP-SHOCK II risk score (0-2; 3/4; 5-9), and had blood sampled upon admission. RESULTS: Plasma concentrations of Copeptin (median (pmol/L) score 0-2: 313; score 3/4: 682; score 5-9: 632 p < 0.0001), proANP (pmol/L) (1459; 2225; 2876 p = 0.0009) and MRproADM (nmol/L) (0.86; 1.2; 1.4 p = 0.04) were significantly associated with the risk score, whereas ST2 (ng/mL) was not (44; 60; 45 p = 0.23). The IABP-SHOCK II risk score predicted 30-day mortality (score 0-2: 22%; score 4/3: 51%; score 5-9: 72%, area under the curve (AUC): 0.73, plogrank < 0.0001), while the tested biomarkers did not (AUC: 0.51

Prognostic Value of Neutrophil-Lymphocyte Ratio in Cardiogenic Shock: A Cohort Study.

BACKGROUND Inflammation plays an important part in the pathogenesis of cardiogenic shock (CGS). Whether the neutrophil-lymphocyte ratio (NLR), an integrated biomarker of inflammation, is associated with the outcome of CGS patients remains unknown. This retrospective cohort study was performed to identify the utility of using NLR among patients with CGS. MATERIAL AND METHODS Data were extracted from the MIMIC database. We applied smooth curve fitting to define the NLR cutoff values. The primary outcome was 30-day mortality. Cox proportional hazards models, subgroup analysis, and receiver operator characteristic (ROC) curve analysis were performed. RESULTS A total of 1470 CGS patients were extracted, among which 801 (54.5%) were men. The mean age of the population was 70.37 years. An inverse U-shaped relationship was observed between NLR and mortality in CGS patients, with the highest risk being at values ranging from 9.4 to 15. For the primary outcome of 30-day mortality, the adjusted HR (95% CI) values of the middle tertile (NLR 9.4-15) and the upper tertile (NLR >15) were 1.47 (1.14, 1.88) and 1.22 (0.94, 1.57) compared with the reference of lower tertile (NLR <9.4). ROC curve analysis showed that NLR had a more sensitive prognostic value in predicting 30-day mortality of CGS than the neutrophil or lymphocyte percentage alone (0.660 vs. 0.540, 0.549). CONCLUSIONS An inverse U-shaped curve was presented between NLR and the mortality of CGS. NLR seemed to be a readily available and independent prognostic biomarker for patients with CGS. The prognostic value of NLR was more sensitive than the neutrophil or lymphocyte percentage alone, but not as good as SOFA or SAPSII score.

Myocardial localization of coronavirus in COVID-19 cardiogenic shock.

We describe the first case of acute cardiac injury directly linked to myocardial localization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a 69-year-old patient with flu-like symptoms rapidly degenerating into respiratory distress, hypotension, and cardiogenic shock. The patient was successfully treated with venous-arterial extracorporeal membrane oxygenation (ECMO) and mechanical ventilation. Cardiac function fully recovered in 5 days and ECMO was removed. Endomyocardial biopsy demonstrated low-grade myocardial inflammation and viral particles in the myocardium suggesting either a viraemic phase or, alternatively, infected macrophage migration from the lung.

Current Understanding of Leukocyte Phenotypic and Functional Modulation During Extracorporeal Membrane Oxygenation: A Narrative Review.

A plethora of leukocyte modulations have been reported in critically ill patients. Critical illnesses such as acute respiratory distress syndrome and cardiogenic shock, which potentially require extracorporeal membrane oxygenation (ECMO) support, are associated with changes in leukocyte numbers, phenotype, and functions. The changes observed in these illnesses could be compounded by exposure of blood to the non-endothelialized surfaces and non-physiological conditions of ECMO. This can result in further leukocyte activation, increased platelet-leukocyte interplay, pro-inflammatory and pro-coagulant state, alongside features of immunosuppression. However, the effects of ECMO on leukocytes, in particular their phenotypic and functional signatures, remain largely overlooked, including whether these changes have attributable mortality and morbidity. The aim of our narrative review is to highlight the importance of studying leukocyte signatures to better understand the development of complications associated with ECMO. Increased knowledge and appreciation of their probable role in ECMO-related adverse events may assist in guiding the design and establishment of targeted preventative actions.

Lymphocytic Myocarditis and Cardiogenic Shock in Hawai'i: A Case Series.

Lymphocytic myocarditis is an inflammatory disease of the heart that may present in a myriad of fashions ranging from mild febrile illness to florid myocarditis and cardiogenic shock. Given its nonspecific clinical presentation, the diagnosis of lymphocytic myocarditis is often challenging. The authors describe four cases of lymphocytic myocarditis in young women who presented with cardiogenic shock. Two patients survived and two died. This presentation has not been seen previously in Hawai'i and the public awareness of this condition is critical. Early diagnosis and the prompt initiation of biventricular mechanical circulatory support appear to have been critical in improving patient survival.