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Systemic and cerebral embolisms are serious complications of associated with cardiac myxoma. Embolism risk reportedly depends on the gross and histological morphology. This study is aimed at analyzing the morphologic pattern of excised cardiac myxoma as a high-risk embolic cause. Between 1978 and April 2022, 116 surgical specimens of cardiac myxomas were recorded at the pathology department of our hospital. The tumors were classified into three types based on their macroscopic shapes and external morphology-round-smooth, irregular, and villous-to investigate the embolic complications. Of the 116 specimens, 106 macroscopic images of cardiac myxoma (89% were located in the left atrium) were prepared. Round-smooth types were found in 36 (34.0%) patients, irregular types in 32 (30.2%) patients, and the villous types in 38 (35.8%) patients. Multivariable analysis revealed that a villous external appearance was an independent predictor of embolic events (odds ratio: 8.7; 95% confidence interval: 2.4-42.1; p 0.001). Villous external appearance of cardiac myxoma was associated with the highest risk of distal embolism.

Immune checkpoint inhibitor (ICI)-induced myocarditis is a potentially life-threatening adverse event. We herein report a rare case of sick sinus syndrome (SSS) co-occurring with ICI-associated myocarditis. A 71-year-old woman with lung cancer undergoing pembrolizumab monotherapy was admitted owing to a fever, worsening kidney function, and sinus bradycardia. She was diagnosed with multi-organ immune-related adverse events, including myocarditis. Pulse steroid therapy was initiated immediately under the support of a temporary pacemaker, which resulted in the resolution of SSS in a few days. Biopsy specimens of the endomyocardium showed active myocarditis. Thus, we should be aware that SSS can co-occur with ICI-induced myocarditis.

BACKGROUND Pregnant women with a Fontan circulation have a high risk of obstetric complications, such as preterm delivery and small for gestational age (SGA), which may be affected by low blood flow to the placenta and hypoxia. This study investigated placental pathology in a Fontan circulation.Methods and Results:Eighteen pregnancies in 11 women with a Fontan circulation were reviewed. Pregnancy outcomes showed 9 miscarriages and 9 live births, with 4 preterm deliveries. Five neonates were SGA (

Numerous basic studies have shown a relationship between interleukin-6 (IL-6) and the development or severity of myocarditis. However, there has been no study in which the effect of IL-6 levels in patients with myocarditis was evaluated.We enrolled control patients (n = 12) and consecutive patients with acute myocarditis (n = 13), including lymphocytic, eosinophilic, and giant cell myocarditis, and investigated the pathological and clinical effects of IL-6 on human myocarditis.The serum IL-6 level in patients with myocarditis (16.7 [9.9, 103.8] pg/mL) was significantly higher than that in the control patients (1.4 [1.0, 1.9] pg/mL) (P0.001). Immunohistochemical analysis showed that IL-6 was expressed in infiltrating inflammatory cells of endomyocardial biopsy samples from all patients with myocarditis. Moreover, the log-transformed value of serum IL-6 level showed significant positive correlations with serum creatine kinase (CK) level, CK-MB level, peak CK level, peak CK-MB level and C-reactive protein level (all P ≤ 0.005) and a negative correlation with the left ventricular (LV) ejection fraction (p = 0.014). We divided the patients with myocarditis into a low IL-6 group (9.9 [4.5, 14.2] pg/dL, n = 7) and a high IL-6 group (108.9 [51.1, 130.9] pg/dL, n = 6). The degree of infiltration of IL-6-expressing inflammatory cells in myocardial samples obtained from patients in the high IL-6 group was significantly more severe than that in samples obtained from patients in the low IL-6 group. Furthermore, patients in the high IL-6 group significantly more frequently received catecholamine therapy (P = 0.005), venoarterial extracorporeal membrane oxygenation (P = 0.029), and artificial respirator support (P = 0.021) in the acute phase of myocarditis.The results suggest that there is a strong impact of IL-6 on cardiac injury and dysfunction in patients with myocarditis.

Dilated cardiomyopathy (DCM) associated with inflammation is diagnosed by endomyocardial biopsy; patients with this have a poorer prognosis than patients without inflammation. To date, standard diagnostic criteria have not been established.Methods and Results: This study analyzed clinical records and endomyocardial biopsy samples of 261 patients with DCM (201 males, median left ventricular ejection fraction; 28%) from 8 institutions in a multicenter retrospective study. Based on the European Society of Cardiology criteria and CD3 (T-lymphocytes) and CD68 (macrophages) immunohistochemistry, 48% of patients were categorized as having inflammatory DCM. For risk-stratification, we divided patients into 3 groups using Akaike Information Criterion/log-rank tests, which can determine multiple cut-off points: CD3Myocardial CD3

BACKGROUND The clinical characteristics and prognostic outcomes of dilated cardiomyopathy (DCM) with a familial history (FHx) via pedigree analysis are unclear.Methods and Results:We conducted a prospective observational study of 514 consecutive Japanese patients with DCM. FHx was defined as the presence of DCM in ≥1 family member within 2-degrees relative based on pedigree analysis. The primary endpoint was a composite of major cardiac events (sudden cardiac death and pump failure death). The prevalence of FHx was 7.4% (n=38). During a median follow-up of 3.6 years, 77 (15%) patients experienced a major cardiac event. Multivariable Cox regression analysis identified FHx as independently associated with major cardiac events (hazard ratio [HR] 4.32; 95% confidence interval [CI], 2.04-9.19; P

Pulmonary capillary hemangiomatosis is a rare form of pulmonary artery hypertension; to date, only few descriptions of myocardial pathology in pulmonary capillary hemangiomatosis have been reported in the literature. We report the case of a Japanese female patient who was diagnosed with pulmonary capillary hemangiomatosis combined with acute myocardial inflammation on performing autopsy. She was admitted to our hospital because of acute pneumonia and subsequently suddenly developed severe hypoxemia with breathing difficulty and died 13 days after admission. At autopsy, the histology of the lung was consistent with pulmonary capillary hemangiomatosis. Additionally, a diffuse severe infiltration of inflammatory cells was associated with edema in the myocardium. Myocytolysis was limited and fibrosis was absent. To the best of our knowledge, pulmonary capillary hemangiomatosis with acute myocarditis-like histological findings has been described for the first time through our case.

Pulmonary hypertension (PH) is associated with high morbidity in children undergoing hematopoietic stem cell transplantation (HSCT). However, owing to the lack of sequential echocardiography, the nature of the condition is not fully understood. This study was conducted to investigate whether routine echocardiography performed after HSCT could detect patients with PH at an earlier stage and elucidate the role of intervention using tadalafil. The study population comprised 93 consecutive children age18 years who underwent a total of 109 HSCTs. All patients underwent routine transthoracic echocardiography during HSCT. Four children (4%) with a median age of 4 years (range, 0.7 to 6 years) were found to have PH, and their median tricuspid regurgitation peak velocity (TRV) was 4.1 m/s (range, 3.5 to 4.2 m/s). PH was diagnosed at a median of 52 days (range, 21 to 118 days) after HSCT. Three of them were diagnosed with neuroblastoma, and 1 was diagnosed with infantile leukemia. One patient developed PH after autologous HSCT, and 3 received killer immunoglobulin-like receptor ligand-mismatched cord blood. Busulfan was used for conditioning in all patients, and the proportion of patients receiving this medication was significantly higher in the PH group compared with the non-PH group (100% versus 30%; P = .011). Three of the 4 patients had a durable response (TRV ≤2.8 m/s) at a median of 46 days (range, 14 to 79 days) after starting treatment with tadalafil. No patient experienced exacerbation of PH, and treatment was completed at median of 96 days (range, 46 to 212 days). Our data suggest that routine echocardiography monitoring after HSCT should be considered in children receiving busulfan, although the precise follow-up timing needs further study. In addition, safe and effective administration of tadalafil must be ensured by close monitoring.

Background Balloon pulmonary angioplasty (BPA) has shown beneficial effects for chronic thromboembolic pulmonary hypertension (CTEPH). However, previous studies have shown less cardiac output improvement and symptoms remaining after BPA, implying poor right ventricular (RV) function recovery. Therefore, we investigated the residual RV dysfunction after BPA to reveal risk factors, clinical effects, and possible underlying histopathological mechanisms. Methods and results We investigated 61 consecutive CTEPH patients who underwent cardiovascular magnetic resonance before and 3 and 12 months after BPA series. Residual dysfunction (RD) of RV was defined as RV end-diastolic volume index >100 ml/m2 or RV ejection fraction (EF) Compared with the ND group, the RD group had significantly worse World Health Organization (WHO) functional class at follow-up. No significant hemodynamic differences were observed between the groups. On multivariable logistic regression analysis, male sex (odds ratio [OR] 12.5, p = 0.004) and prolonged QRS duration (OR 1.08, p = 0.029) were independently associated with residual RV dysfunction. Additionally, RV histopathology in 11 CTEPH autopsy cases showed that QRS duration was correlated with RV fibrosis area. Conclusions Relatively high percentage (44%) of residual RV dysfunction with worse WHO functional class was observed in CTEPH patients even after BPA. Prolonged QRS duration may predict poor recovery in RV function after BPA.

A 44-year-old woman with previous myocarditis underwent several syncopal events due to self-terminated ventricular fibrillation (VF) with hypokalemia. Electrocardiogram showed a normal QT duration and premature ventricular contraction with a short coupling interval (280 ms), and the R-on-T phenomenon induced Torsade de pointes (TdP) that deteriorated into VF, a condition known as short coupled TdP (ScTdP). Cardiac magnetic resonance imaging showed left ventricular dilatation and diffuse high T2 signal intensity, and endomyocardial biopsy exhibited a failing myocardium. This is a rare case of ScTdP accompanied by a failing myocardium. Some instances of ScTdP may be associated not only with an electrical disorder but also with a structural myocardial disorder.

Tafamidis meglumine, a transthyretin (TTR) stabilizer, is effective in delaying the progression of neuropathy in TTR amyloidosis with Val30Met mutations. However, its efficacy in TTR amyloid cardiomyopathy is not fully elucidated. Herein, we report a 73-year-old Japanese man with a diagnosis of TTR amyloid cardiomyopathy with Val30Met mutation treated with tafamidis. To evaluate treatment response, cardiac magnetic resonance imaging was performed before and after 12 months of tafamidis treatment. Native T1, extracellular volume, and left ventricular mass showed no obvious worsening, and findings of other diagnostic studies also supported the efficacy of tafamidis to delay the progression of amyloid cardiomyopathy. Our case suggests that serial native T1 and extracellular volume may be novel non-invasive imaging methods to monitor the treatment response to TTR stabilizers in cardiac amyloidosis and also that tafamidis may be effective in suppressing cardiac progression in TTR amyloid cardiomyopathy with Val30Met mutation.

A 35-year-old woman was referred to our hospital for the management of acutely decompensated heart failure due to peripartum cardiomyopathy (PPCM). Generally, cardiac examinations are performed after the manifestation of heart failure in patients with PPCM. Thus, reports of serial cardiac examinations before the onset of PPCM are scarce. In this case, we were able to document the serial echocardiographic findings before the onset of life-threatening PPCM. We found that the left ventricular systolic function was preserved at 35 weeks of gestation but declined acutely after delivery at 38 weeks. Although speculative, these findings suggest that left ventricular dilation might precede the onset of PPCM.

Background Thyroid storm (TS) is a rare but potentially life-threatening sequelae of untreated or undertreated hyperthyroidism. While TS frequently causes high-output heart failure, low-output heart failure related to dilated cardiomyopathy (DCM) is extremely rare. Tachycardia is a common clinical presentation of TS, and β1-selective blockers are the first-line agents for treating TS-associated tachycardia. However, given that β-blockers have negative chronotropic and negative inotropic effects, amiodarone may be safe and effective for the treatment of TS-induced tachyarrhythmia in patients with moderate to severe heart failure. While long-term amiodarone administration causes hypothyroidism, or less frequently, hyperthyroidism, little is known about the effects of short-term amiodarone administration on thyroid function. Case presentation A 31-year-old healthy woman presented with worsening dyspnoea. She was tachycardic with multifocal atrial tachycardia (MAT) of 184 beats/min, confirmed by electrocardiogram. Echocardiographic findings were consistent with DCM, with an ejection fraction of 20%. Thus, she was initially diagnosed with acute heart failure due to DCM with coexistent MAT. Tachycardia persisted despite cardioversion attempts and treatment with multiple anti-arrhythmic drugs. Consequently, she rapidly progressed to cardiogenic shock and respiratory decompensation, which required intubation and an intra-aortic balloon pump support. Moreover, the undiagnosed Graves' disease, lack of suspicion, and postponed analysis of thyroid function tests led to a delayed diagnosis of TS. Amiodarone, which was initiated for MAT, unexpectedly ameliorated thyrotoxicosis, resulting in a euthyroid state and the patient’s significantly improved condition and cardiac function. She was discharged on day 40. Finally, she underwent total thyroidectomy; thyroid pathology was consisting with Graves' disease. Her postoperative course was uneventful. Conclusions Herein, we describe a case of delayed diagnosis of dilated thyrotoxic cardiomyopathy with coexistent MAT. The patient required intensive care due to the catastrophic sequelae and was successfully treated with amiodarone. This is the first case report of TS-associated MAT and highlights the clinical importance of high suspicion of TS in de novo heart failure with any tachyarrhythmia or DCM of unknown etiology and the potential effects of short-term amiodarone administration in the treatment of TS.

We describe our use of intracardiac echocardiography (ICE) to guide endomyocardial biopsy of the left ventricle in a patient with chronic heart failure secondary to endocardial fibroelastosis. Under ICE guidance, we advanced the bioptome through the middle of the mitral annulus, within a trans-septal sheath, and guided the bioptome to the correct location on the mid-posterior wall of the left ventricle. This was performed without adverse events, such as injury to the chordae tendineae or mitral valve regurgitation. Therefore, ICE-guidance is possible for left-sided heart procedures and could lower the risk of complications and improve the biopsy rate for diagnosis.

Background Pulmonary arterial hypertension (PAH), particularly connective tissue disease-associated PAH (CTD-PAH), is a progressive disease and novel therapeutic agents based on the specific molecular pathogenesis are desired. In the pathogenesis of CTD-PAH, inflammation, immune cell abnormality, and fibrosis play important roles. However, the existing mouse pulmonary hypertension (PH) models do not reflect these features enough. The relationship between inflammation and hypoxia is still unclear.Methods and Results:Intraperitoneal administration of pristane, a kind of mineral oil, and exposure to chronic hypoxia were combined, and this model is referred to as pristane/hypoxia (PriHx) mice. Hemodynamic and histological analyses showed that the PriHx mice showed a more severe phenotype of PH than pristane or hypoxia alone. Immunohistological and flow cytometric analyses revealed infiltration of immune cells, including hemosiderin-laden macrophages and activated CD4+helper T lymphocytes in the lungs of PriHx mice. Pristane administration exacerbated lung fibrosis and elevated the expression of fibrosis-related genes. Inflammation-related genes such asIl6andCxcl2were also upregulated in the lungs of PriHx mice, and interleukin (IL)-6 blockade by monoclonal anti-IL-6 receptor antibody MR16-1 ameliorated PH of PriHx mice. Conclusions A PriHx model, a novel mouse model of PH reflecting the pathological features of CTD-PAH, was developed through a combination of pristane administration and exposure to chronic hypoxia.

Connective tissue disorders sometimes involve cardiovascular systems. This report describes the case of a middle-aged man with mitral regurgitation and heart failure. He had distinctive features of mucopolysaccharidosis type (MPS) III, but no gene mutations that were known to be associated with MPS. Meanwhile, he had a COL1A2 gene mutation that is associated with osteogenesis imperfecta (OI), and had some features that were compatible with OI. The patient might have had a rare connective tissue disorder with the characteristics of MPS III and OI, which was initially detected as a result of the cardiovascular manifestations.

We present the unexpected death of an elderly man who died from saddle thromboemboli in the pulmonary artery trunk and organized thrombi in the distal arteries in every lobe. The inferior vena cava was compressed between the horseshoe kidney and ossified spinal ligament, thereby generating fresh thrombi (aged within three days) composed of numerous erythrocytes, platelets, neutrophils, and fibrin fibers. Cardiac hypertrophy with a myocardial lesion reduces the cardiac reserve. The lobar and segmental arteries contained not only fresh emboli but also mural and luminal thrombi at various stages of organization. Organized thrombi with recanalized neo-vessels were further connected with collateral bronchial artery circulation. These remodeling reactions maintained pulmonary blood flow until the last embolization. A year prior to his death, the patient became aware of his illness. Four months before death, he was hospitalized and pulmonary emboli were found, but neither their cause nor origin was detected. The clinical course, histological, and computed tomography findings imply that repeated inferior vena cava compression generated thrombi, resulting in pulmonary embolization and remodeling.

Background Dilated cardiomyopathy (DCM) is the most common cardiomyopathy and causes left ventricular enlargement and contractile dysfunction, with a poor prognosis. The mechanisms underlying the disease process have not been precisely identified, but recent evidence has suggested that the activation of myocardial inflammation is involved in the deterioration associated with the condition. Methods and results Biopsy samples from 182 consecutive DCM patients were immunohistochemically stained with antibodies specific to CD3 (T lymphocytes), CD68 (whole macrophages), and CD163 (M2 macrophages), and each type of infiltrating cell was counted. Masson's trichrome staining was used to determine the collagen area fraction (CAF) in each sample. Patients were followed up for 6.9 ± 2.4 years, and their clinical data were obtained for analysis. Median (interquartile range) numbers of myocardial CD3, CD68, and CD163-cell infiltrates were 8.1 (4.0–14.2)/mm2, 22.3 (12.1–36.0)/mm2, and 6.5 (2.0–14.0)/mm2, respectively. Patients with higher counts of infiltrating CD3-, CD68-, and CD163-positive cells had significantly poorer outcomes (P = 0.007, P = 0.011, and P = 0.022, respectively). A high CD163-positive infiltrate count was independently associated with worse outcome in multivariate Cox regression analysis (hazard ratio 1.77, P = 0.004), and multivariate linear regression analysis revealed that the CD163 cell count was an independent determinant of CAF (P

Background The diagnosis of cardiac sarcoidosis ( CS ) is challenging because endomyocardial biopsy has only a 20% to 30% sensitivity rate for diagnosis and it presents with similar clinical features of idiopathic dilated cardiomyopathy ( DCM ). Lymphatic vessel proliferation in pulmonary sarcoidosis has been previously demonstrated. In this study, we compared endomyocardial biopsy samples obtained from patients with CS and DCM to determine whether lymph vessel counts using D2‐40 immunostaining can be utilized as a complementary tool to distinguish CS from DCM . Methods and Results Endomyocardial biopsy tissues were obtained from 62 patients with CS (30 patients with a diagnosis made histologically, 32 patients with a diagnosis made clinically), and hematoxylin/eosin, Masson trichrome, and D2‐40 immunostaining were performed. Their results were compared with those from 53 patients with DCM. The histological CS group showed significantly increased lymphatic vessels (12.0 [4.0–40.0] versus 2.6 [1.9–3.4], P P DCM group. The optimal threshold was 7.5 lymphatic vessels, and this resulted in a sensitivity of 0.67 and specificity of 0.96. The clinical CS group diagnosed according to Japanese Circulation Society 2016 criteria showed increased lymphatic vessels (4.0 [3.3–9.0] versus 2.6 [1.9–3.4], P P P P =0.0012) compared with the DCM group. The optimal threshold of lymphatic vessels was 3.5, which resulted in a sensitivity of 0.75 and specificity of 0.68. Conclusions Lymphatic vessel counts using D2‐40 immunostaining may help to distinguish clinical CS without granuloma from DCM .

Vaccine-associated myocarditis is an extremely rare, yet potentially lethal disease, which requires early diagnosis and prompt treatment. However, its pathogenesis remains elusive. We report the first case of biopsy-proven eosinophilic myocarditis related to tetanus toxoid immunization, with unique histopathologic findings, characterized by perivascular eosinophilic infiltrates with myocyte necrosis and abundant interstitial lymphocytic infiltrates with myocyte necrosis, separately. A systemic high-dose corticosteroid treatment had a dramatic beneficial effect on hemodynamic instability and resulted in complete recovery. This case highlights the value of endomyocardial biopsy in establishing a definite diagnosis and understanding the pathogenesis of vaccine-associated myocarditis.

An 85-year-old man was hospitalized because of ST-segment–elevation myocardial infarction 145 months after the implantation of sirolimus-eluting Cypher stent. Emergent coronary angiography identified in-stent restenosis at the body of sirolimus-eluting Cypher stent in the proximal right coronary artery (Figure [A]). Optical coherence tomography visualized rupture of lipidic neointima potentially containing cholesterol crystals (Figure [B]). Near-infrared spectroscopy (NIRS) combined with intravascular ultrasound showed extensive yellow signals indicating lipid accumulation, potentially both within and outside the stent, with a high, maximum 4-mm lipid core burden index with 880 (Figure [C] and [D]). After an implantation of cobalt–chromium everolimus-eluting stent, no-reflow phenomenon with thrombolysis in …

Endomyocardial biopsy (EMB) has been established in parallel with the development of percutaneous catheter technology for the diagnosis of cardiac diseases. It was developed in the early 1960 s in Japan by Drs. Konno, Sakakibara and Sekiguchi of Tokyo Women's Medical University. EMB is a valuable and useful, but invasive, modality for making a definite diagnosis in diseases such as myocarditis and secondary cardiomyopathies, which are often difficult to diagnose by imaging modality alone. In the field of heart transplantation, the histology of EMB helps monitor rejection to allografts. In cases of chronic heart failure, fibrosis and degeneration of cardiomyocytes are very important findings of heart remodeling. Recently, molecular biology technology has been applied to EMB specimens to get more detailed information. However, we must also recognize that EMB is an invasive examination that should not be performed without skillful cardiac catheterization experience to avoid complications. In this review as a message from pathologists, we present key cardiac histopathology using EMB, in a way that allows one to imagine whole cardiac pathological conditions. We also describe the current role of EMB and its significance in order to encourage young cardiologists to perform EMB to see another world of pathology.

Heart transplantation started in Japan in 1999. Since then, 50 transplants have been performed at our center. We performed histopathological analyses of the 50 explanted hearts and the post-transplant biopsy specimens. The median age of recipients was 39 years. The primary diseases before transplant were idiopathic dilated cardiomyopathy in 33 patients (66%), hypertrophic cardiomyopathy in seven (14%), restrictive cardiomyopathy in one, arrhythmogenic right ventricular cardiomyopathy in one, and secondary cardiomyopathy in eight (16%). Before transplantation, 47 patients (94%) had left ventricular assist devices. No severe cardiovascular failure due to allograft rejection occurred. The post-transplant survival rate was 97.6% at 1 year and 93.1% at 10 years. One recipient was lost to sepsis from myelodysplastic syndrome in the fourth year, one died of multiple organ failure and peritonitis 8 months after transplant. Another patient died of recurrent post-transplant lymphoproliferative disorders (PTLD). Mild cardiac dysfunction occurred in seven recipients in the early postoperative period. Moderate acute cellular rejection occurred in six patients (12%), and antibody-mediated rejection occurred in three (6%). The number of heart transplants performed in Japan is very small. However, the outstanding 10-year survival rate is due to donor evaluation and post-transplant care resulting in low grade rejection. Pathological evaluation has also greatly contributed to the results.

Background The histological diagnosis of cardiac sarcoidosis ( CS ) is based on the presence of myocardial granulomas; however, the sensitivity of endomyocardial biopsy is relatively low. We investigated whether immunocompetent cells including dendritic cells ( DC ) and macrophages in nongranuloma sections of endomyocardial biopsy samples could be histopathological surrogates for CS diagnosis. Methods and Results The numbers of DC and macrophages were investigated in 95 consecutive CS patients and 50 patients with nonischemic cardiomyopathy as controls. All patients underwent endomyocardial biopsy, and immunohistochemical staining was performed on all samples. We examined these immunocompetent cells in nongranuloma sections in CS patients diagnosed by the presence of myocardial granulomas (n=26) and in CS patients without myocardial granulomas diagnosed by the Japanese Ministry of Health Welfare 2007 criteria (n=65) or the Heart Rhythm Society 2014 criteria (n=26). In CS patients with and without myocardial granulomas, CD 209 + DC and CD 68 + macrophages were more frequently observed ( P CD 163 + M2 macrophages were less frequently observed ( P CD 163 + M2/ CD 68 + macrophage ratio and increased number of CD 209 + DC in nongranuloma sections of CS patients demonstrated high specificity (100%, 95% CI 92.7–100) for CS diagnosis with each diagnostic criteria and the presence of myocardial granulomas. Conclusions Increased number of DC and decreased M2 among all macrophages in nongranuloma sections of myocardium showed high specificity for CS diagnosis, suggesting DC and macrophage phenotypes as histopathological surrogates for the diagnosis of CS .