A 27-year-old Japanese woman with a history of depression and an eating disorder presented to our emergency department with a chief complaint of generalized weakness. Electrocardiography showed prominent QT prolongation with multiple ventricular contractions. Chest X-ray plain computed tomography revealed pulmonary edema. Echocardiography showed decreased left ventricular systolic function. Suspecting acute myocarditis, we performed a myocardial biopsy from the right ventricular septum. The biopsy histology revealed extensive myocardial fibrosis and a very mild inflammatory cell infiltrate. In an additional detailed medical interview, the patient admitted that she had consumed three bottles of a first-aid liquid containing naphazoline approximately ~12 h before her presentation, in a suicide attempt. Her QTc and left ventricular ejection fraction improved during hospitalization.
UNASSIGNED: Acute drug intoxication can cause QT prolongation and ventricular arrhythmias, cardiomyopathy, and pulmonary edema. When acute QT prolongation, myocardial damage, and pulmonary edema are seen (suggesting acute myocarditis), naphazoline intoxication should be investigated in the differential diagnosis.

Cardiac cysticercosis is rare in clinical practice and is usually accidentally identified during cardiac surgery or autopsies. Although mostly asymptomatic, cardiac cysticercosis could present with severe clinical conditions such as myocarditis, acute myocardial infarction, and arrhythmia. We present a 51-year-old female patient who accidentally discovered a solitary mass in the myocardium. The cardiac magnetic resonance imaging revealed a nonenhanced cyst in the interventricular septum protruding into the right ventricular chamber. Because of cardiac tamponade presenting during a right ventricular endomyocardial biopsy, an emergency open-heart surgery was performed to suture the ventricular wall perforation and remove the tumor. The histopathologic report demonstrated typical cysticercosis. Cardiac cysticercosis is an uncommon lesion and may present with atypical clinical and laboratory features. Therefore, this diagnosis should be considered single or multiple cardiac cystic lesions.

Desminopathy is a cardiac and skeletal myopathy caused by disease-causing variants in the desmin (DES) gene and represents a subgroup of myofibrillar myopathies, where cytoplasmic desmin-postive immunoreactivity is the pathological hallmark. We herein report a 28-year-old Japanese man who was initially diagnosed with sporadic hypertrophic cardiomyopathy with atrioventricular block at 9 years old and developed weakness in the soft palate and extremities. The myocardial tissue dissected during implantation of the ventricular-assisted device showed a dilated phase of hypertrophic cardiomyopathy and intracellular accumulation of proteinase K-resistant desmin aggregates. Genetic testing confirmed a de novo mutation of DES, which has already been linked to desminopathy. As the molecular diagnosis of desminopathy is challenging, particularly if patients show predominantly cardiac signs and a routine skeletal muscle biopsy is unavailable, these characteristic pathological findings of endomyocardial proteinase K-resistant desmin aggregates might aid in clinical practice.

Scleredema is a rare cutaneous mucinosis characterized by diffuse swelling and non-pitting induration. A 63-year-old man reported a 5-year history of skin thickening of the trunk and a 3-week history of dyspnea. Echocardiography revealed diffuse hypokinesis. Skin biopsies obtained from the waist showed thickened dermis with mucin. Myocardial biopsies showed alcian blue-stained tissue between the muscle fibers. The patient was referred to a dermatologist for phototherapy. Cardiomyopathy should be considered in patients with scleredema. Scleredema usually has a good prognosis; however, the mortality risk could be high when accompanied by cardiomyopathy.

Objectives: Fulminant myocarditis (FM) is a rapidly progressive and frequently fatal form of myocarditis that has been difficult to classify. This study aims to compare the clinical characteristics, treatments and outcomes in patients with fulminant giant cell myocarditis (FGCM) and fulminant lymphocytic myocarditis (FLM). Methods and Results: In our retrospective study, nine patients with FGCM (mean age 47.9 ± 7.5 years, six female) and 7 FLM (mean age 42.1 ± 12.3 years, four female) patients confirmed by histology in the last 11 years were included. Most patients with FGCM and FLM were NYHA functional class IV (56 vs. 100%, p = 0.132). Patients with FGCM had significantly lower levels of high-sensitivity C-reactive protein [hs-CRP, 4.4 (2.0-10.2) mg/L vs. 13.6 (12.6-14.6) mg/L, P = 0.004, data shown as the median with IQR], creatine kinase-myoglobin [CK-MB, 1.4 (1.0-3.2) ng/ml vs. 14.6 (3.0-64.9) ng/ml, P = 0.025, median with IQR], and alanine aminotransferase [ALT, 38.0 (25.0-61.5) IU/L vs. 997.0 (50.0-3,080.0) IU/L, P = 0.030, median with IQR] and greater right ventricular end-diastolic diameter (RVEDD) [2.9 ± 0.3 cm vs. 2.4 ± 0.6 cm, P = 0.034, mean ± SD] than those with FLM. No differences were observed in the use of intra-aortic balloon pump (44 vs. 43%, p = 1.000) and extracorporeal membrane oxygenation (11 vs. 43%, p = 0.262) between the two groups. The long-term survival rate was significantly lower in FGCM group compared with FLM group (0 vs. 71.4%, p = 0.022). A multivariate cox regression analysis showed the level of hs-CRP (hazard ratio = 0.871, 95% confidence interval: 0.761-0.996, P = 0.043) was an independent prognostic factor for FM patients. Furthermore, the level of hs-CRP had a good ability to discriminate between patients with FGCM and FLM (AUC = 0.94, 95% confidence interval: 0.4213-0.9964). Conclusions: The inflammatory response and myocardial damage in the patients with FGCM were milder than those with FLM. Patients with FGCM had distinctly poorer prognoses compared with those with FLM. Our results suggest that hs-CRP could be a promising prognostic biomarker and a hs-CRP level of 11.71 mg/L is an appropriate cutoff point for the differentiating diagnosis between patients with FGCM and FLM.

Among non-ischemic cardiomyopathies, cardiac amyloidosis is one of the most common, being caused by extracellular depositions of amyloid fibrils in the myocardium. Two main forms of cardiac amyloidosis are known so far, including 1) light-chain (AL) amyloidosis caused by monoclonal production of light-chains, and 2) transthyretin (ATTR) amyloidosis, caused by dissociation of the transthyretin tetramer into monomers. Both AL and ATTR amyloidosis are progressive diseases with median survival from diagnosis of less than 6 months and 3 to 5 years, respectively, if untreated. In this regard, death occurs in most patients due to cardiac causes, mainly congestive heart failure, which can be prevented due to the presence of effective, life-saving treatment regimens. Therefore, early diagnosis of cardiac amyloidosis is crucial more than ever. However, diagnosis of cardiac amyloidosis may be challenging due to variable clinical manifestations and the perceived rarity of the disease. In this regard, clinical and laboratory reg flags are available, which may help clinicians to raise suspicion of cardiac amyloidosis. In addition, advances in cardiovascular imaging have already revealed a higher prevalence of cardiac amyloidosis in specific populations, so that the diagnosis especially of ATTR amyloidosis has experienced a >30-fold increase during the past ten years. The goal of our review article is to summarize these findings and provide a practical approach for clinicians on how to use cardiovascular imaging techniques, such as echocardiography, cardiac magnetic resonance, bone scintigraphy and, if required, organ biopsy within predefined diagnostic algorithms for the diagnostic work-up of patients with suspected cardiac amyloidosis. In addition, two clinical cases and practical tips are provided in this context.

Multisystem Inflammatory Syndrome (MIS) is a novel hyperinflammatory syndrome associated with SARS-CoV-2 infection. It predominantly affects children (MIS-C) a few weeks after a usually asymptomatic SARS-CoV-2 infection and is only rarely seen in adults above 21 years (MIS-A). Only scarce data on histological findings in both pediatric and adult patients has been published so far. An 18-year-old male patient was admitted to hospital in a febrile state, which progressed to severe cardiogenic shock and multi-organ failure requiring extracorporeal life support. Myocardial biopsy revealed small vessel-associated immune cell infiltrates. Diagnosis of MIS-C was made after ruling out all potential differential diagnosis. Use of immunosuppressive treatment with steroids, interleukin-1 blockade and high-dose intravenous immunoglobulins resulted in the patient\'s full recovery. Multisystem Inflammatory Syndrome (MIS) is a new differential diagnosis of cardiac dysfunction in pediatric and adult patients. The lack of myocardial necrosis differentiates the disease from other viral myocarditis and offers an explanation for the fast response to immunomodulatory therapy and the favorable prognosis. The preceding SARS-CoV-2 infection might only have been mildly symptomatic or even asymptomatic.

OBJECTIVE: The purpose of this study was to assess osimertinib-associated cardiac adverse events (AEs) in a real-world setting, using a retrospective single-center cohort study in Japan.
BACKGROUND: Cases of osimertinib-associated cardiac AEs have been reported but remain poorly understood.
METHODS: A total of 123 cases of advanced non-small cell lung cancer (NSCLC) with confirmed EGFR mutations who received osimertinib monotherapy from 2014 to 2019 at the Osaka International Cancer Institute (Osaka, Japan) were evaluated. Cardiac AEs were defined according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Changes in left ventricular ejection fraction (LVEF) and rates of cancer therapeutics-related cardiac dysfunction (CTRCD), defined as a ≥10 % absolute decline in LVEF from baseline to a value of <53%, were further assessed in 36 patients in whom serial measurements of LVEF were obtained before and during osimertinib treatment.
RESULTS: Severe cardiac AEs (CTCAE grade 3 or higher) occurred in 6 patients (4.9%) after osimertinib administration. These AEs included acute myocardial infarction (n = 1), heart failure with reduced LVEF (n = 3), and valvular heart disease (n = 2). Five of the 6 patients had a history of cardiovascular risk factors or disease. Myocardial biopsies in 2 of the patients showed cardiomyocyte hypertrophy and lipofuscin deposition. In 36 patients assessed with serial LVEF, LVEF declined from 69.4 ± 4.2% to 63.4 ± 10.5% with osimertinib therapy (p < 0.001). CTRCD occurred in 4 patients with a nadir LVEF of 40.3 ± 9.1% with osimertinib.
CONCLUSIONS: In this retrospective cohort analysis, the incidence of cardiac AEs in patients treated with osimertinib was 4.9%. Additional prospective data collected from patients with NSCLC treated with osimertinib will be important in understanding the incidence, pathophysiology, and management of cardiac AEs with osimertinib.

BACKGROUND: We aim to evaluate the value of Cardiac magnetic resonance (CMR) feature tracking (CMR-FT) in addition to Task Force Criteria(TFC) in patients with (arrhythmogenic cardiomyopathy) AC biopsy-proved.
METHODS: Thirty-five patients with AC histologically proven who performed CMR with late gadolinium enhancement (LGE) acquisition were enrolled. The study population was divided in Group1 (negative CMR TFC and LV ejection fraction≥55%) and Group2 (positive CMR TFC and/or LVEF<55%) and compared to an age and gender-matched control group. CMR datasets of all patients were analyzed to calculate LV indexed end-diastolic (LVEDi) and end-systolic (LVESi) volumes and RV indexed end-diastolic (RVEDi) and end-systolic (RVESi) volumes, both LV ejection fraction (LVEF) and RV ejection fraction (RVEF). Moreover, LV and RV global longitudinal (GLS), circumferential (GCS) and radial (GRS) strain were measured.
RESULTS: The AC patients showed both higher LVEDi (p:0.002) and RVEDi (p:0.017) and lower LVEF (p: 0.016) as compared to control patients. Moreover, AC patients showed impaired LV-GLS (p < 0.001), LV-GRS (p < 0.001), LV-GCS (p < 0.001) and RV-GRS (p:0.026) as compared to control subjects. Group1 patients showed a significant reduction of LV-GRS (p < 0.05) and LV-GCS p < 0.01) as compared to control subjects. At univariate analysis LV-GCS was the most discriminatory parameter between Group1 vs heathy subjects with an optimal cut-off of -15.8 (Sensitivity: 74%; Specificity: 10%).
CONCLUSIONS: In patients with AC biopsy-proven, CMR-FT could improve the diagnostic yield in the subset of patients who results negative for imaging TFC criteria resulting as useful gatekeeper for indication of myocardial biopsy in case of equivocal clinical and imaging presentation.

A 73-year-old woman with a history of diarrhea for one year and other various symptoms was admitted to our hospital. Gastrointestinal endoscopy that included enteroscopy with multiple biopsies was performed. However, no significant findings were observed. Electrocardiography showed low voltage in all limb leads, and an echocardiogram showed thickened cardiac walls with granular sparkling pattern. A myocardial biopsy revealed amyloidosis, and a bone marrow biopsy showed multiple myeloma. This case suggests that we should suspect the possibility of amyloidosis in a patient with diarrhea and various symptoms involving multiple organ systems. Additionally, electrocardiograms and echocardiograms should be performed even when gastrointestinal biopsies reveal negative results.