Effects of Irradiation During Computed Tomography Scanning on the Function of Implantable Cardioverter-defibrillators.

The effect of irradiation during computed tomography (CT) imaging on implantable cardioverter-defibrillators (ICDs) has not been fully evaluated in various settings. The purposes of this study were to evaluate the occurrence of electromagnetic interference (EMI) during CT irradiation in various clinically available ICDs with phantom experiments and to determine the potential risks related to irradiation during CT imaging. Five types of clinically available ICDs from five manufacturers were tested. An ICD was combined with an electrocardiogram (ECG) simulator, mounted in a chest phantom, and subjected to CT imaging. Each ICD was irradiated at the maximal power level (tube voltage, 135 kVp; tube current, 510 mA; rotation time, 1.5 s). EMI was defined as oversensing, ventricular tachycardia/ventricular fibrillation (VT/VF) detection, noise, or shock delivery during CT imaging. For ICDs in which EMI was observed, EMI was then evaluated under 144 different irradiation conditions (tube voltage [four patterns from 80-135 kVp], tube current [six patterns from 50-550 mA], and rotation time [six patterns from 0.35-1.5 s]). Testing was also performed during irradiation at the typical doses in three clinical settings and in two settings with inappropriate irradiation of ICDs due to incorrect setup. Among the five ICDs, a shock was delivered by one ICD manufactured by Medtronic (Minneapolis, MN, USA) due to oversensing during irradiation, which occurred at the maximal power level. No oversensing was observed in other ICDs. In the malfunctioned ICD, oversensing was observed in 134 of 144 irradiation patterns, even at a low power in the ICD. The VF-detection criterion was fulfilled in 20 of 134 tests and was significantly associated with tube voltage, tube current, ration time, and tube voltage × rotation time interaction. Although oversensing was observed in three clinical settings (typical chest CT, CT coronary angiography after coronary artery bypass graft, and dynamic assessment for pleural tumors) and one situation during an incorrect scan range on the chest for head perfusion CT, they were not recognized as tachycardia beats. Oversensing was observed when scans were incorrectly set over the ICD during bolus tracking of contrast-enhanced CT. Maximal power CT imaging induced VT/VF detection and shock delivery in one model of ICD placed in a chest phantom. VT/VF detection was observed when tube voltages were high and irradiation times were longer. Oversensing can occur during inappropriate CT imaging, particularly when slices are positioned over the ICD.

QT Prolongation and Torsade De Pointes After Catheter Ablation for Persistent Atrial Fibrillation in a Patient With Tachycardia-Induced Cardiomyopathy: A Case Report.

Atrial fibrillation (AF) is the most common cause of tachycardia-induced cardiomyopathy (TIC). A 75-year-old woman was referred to our hospital for catheter ablation for persistent AF. On admission, transthoracic echocardiography (TTE) revealed diffuse left ventricular (LV) hypokinesis, which was suspected to be due to TIC. Catheter ablation was performed on the fifth day of hospitalization, and Torsade de Pointes (TdP) appeared on the sixth day. The serum concentration of bepridil and potassium was below the reference level. An electrocardiogram revealed marked QT prolongation, giant-negative T waves, and T-wave alternans on the seventh day of hospitalization. Cardiac magnetic resonance imaging with no contrast indicated diffuse mild LV hypokinesis, mild prolonged native T1, and no evidence of myocardial edema at T2. Coronary angiography revealed normal coronary arteries, and the ergonovine stress test results were negative. The results for five long QT syndrome susceptibility genes, including the three major genes, were negative. Subsequently, QT prolongation, giant-negative T waves, and LV dysfunction improved without treatment. This case report highlights the importance of risk management for AF patients with TIC scheduled for catheter ablation and carefully evaluating the risks of QT prolongation. Moreover, patients with TIC can experience marked QT prolongation and TdP during the perioperative period of catheter ablation. Therefore, caution should be required.

Cardiac angiosarcoma with pulmonary and adrenal metastases diagnosed by FDG-PET/CT-guided adrenal biopsy.

Primary cardiac angiosarcoma is a high-grade aggressive tumor with a poor prognosis and low incidence. We describe a case of cardiac angiosarcoma, with pulmonary and adrenal metastases, diagnosed via fluorodeoxyglucose-positron emission tomography/computed tomography-guided adrenal biopsy. Learning objective: Cardiac angiosarcoma should be considered in a patient with a cardiac mass with no tumor cells in the pericardial fluid. Fluorodeoxyglucose-positron emission tomography/computed tomography could be useful in determining the biopsy site.

The Protective Role of KANK1 in Podocyte Injury.

Approximately 30% of steroid-resistant nephrotic syndromes are attributed to monogenic disorders that involve 27 genes. Mutations in KANK family members have also been linked to nephrotic syndrome; however, the precise mechanism remains elusive. To investigate this, podocyte-specific Kank1 knockout mice were generated to examine phenotypic changes. In the initial assessment under normal conditions, Kank1 knockout mice showed no significant differences in the urinary albumin-creatinine ratio, blood urea nitrogen, serum creatinine levels, or histological features compared to controls. However, following kidney injury with adriamycin, podocyte-specific Kank1 knockout mice exhibited a significantly higher albumin-creatinine ratio and a significantly greater sclerotic index than control mice. Electron microscopy revealed more extensive foot process effacement in the knockout mice than in control mice. In addition, KANK1-deficient human podocytes showed increased detachment and apoptosis following adriamycin exposure. These findings suggest that KANK1 may play a protective role in mitigating podocyte damage under pathological conditions.

A case of acute kidney injury and Fanconi syndrome while taking multiple supplements, including Red Yeast Rice Cholesterol Help®.

A 62-year-old man visited his primary care physician with the complaints of loss of appetite and fatigue. He was admitted to our hospital based on a diagnosis of acute kidney injury, Fanconi syndrome as indicated by hypokalemia, hypouricemia, hypophosphatemia, elevated glucose levels in urine, and aminoaciduria. He had been taking multiple supplements, including Red Yeast Rice Cholesterol Help®, for one and a half years. After admission, all the supplements were stopped. Blood samples were collected; however, the samples were negative for diseases that could cause Fanconi syndrome. Renal biopsy revealed renal proximal tubular damage, mainly characterized by simplification of the proximal tubular epithelium. The mycotoxin, citrinin, which is reported to be produced by the mold used for producing red yeast rice, but not the mold Monascus pilosus used for Red Yeast Rice Cholesterol Help®, reportedly causes proximal tubular damage. However, although the causative agent has not been identified, it was thought that a substance similar to citrinin, produced by the mold used for Red Yeast Rice Cholesterol Help®, caused proximal tubular damage, leading to acute kidney injury and Fanconi syndrome. Hence, all supplements were stopped, and the patient was treated with oral potassium and phosphorus preparations, leading to gradual recovery of his kidney function. We herein report the first case of acute kidney injury and Fanconi syndrome in a patient taking multiple health supplements, including Red Yeast Rice Cholesterol Help®. Early discontinuation of the oral supplements was probably useful in improving the patient's kidney function.

Cardiovascular Magnetic Resonance Radiomics to Identify Components of the Extracellular Matrix in Dilated Cardiomyopathy.

BACKGROUND: Current cardiovascular magnetic resonance sequences cannot discriminate between different myocardial extracellular space (ECSs), including collagen, noncollagen, and inflammation. We sought to investigate whether cardiovascular magnetic resonance radiomics analysis can distinguish between noncollagen and inflammation from collagen in dilated cardiomyopathy. METHODS: We identified data from 132 patients with dilated cardiomyopathy scheduled for an invasive septal biopsy who underwent cardiovascular magnetic resonance at 3 T. Cardiovascular magnetic resonance imaging protocol included native and postcontrast T1 mapping and late gadolinium enhancement (LGE). Radiomic features were computed from the midseptal myocardium, near the biopsy region, on native T1, extracellular volume (ECV) map, and LGE images. Principal component analysis was used to reduce the number of radiomic features to 5 principal radiomics. Moreover, a correlation analysis was conducted to identify radiomic features exhibiting a strong correlation (r>0.9) with the 5 principal radiomics. Biopsy samples were used to quantify ECS, myocardial fibrosis, and inflammation. RESULTS: Four histopathological phenotypes were identified: low collagen (n=20), noncollagenous ECS expansion (n=49), mild to moderate collagenous ECS expansion (n=42), and severe collagenous ECS expansion (n=21). Noncollagenous expansion was associated with the highest risk of myocardial inflammation (65%). Although native T1 and ECV provided high diagnostic performance in differentiating severe fibrosis (C statistic, 0.90 and 0.90, respectively), their performance in differentiating between noncollagen and mild to moderate collagenous expansion decreased (C statistic: 0.59 and 0.55, respectively). Integration of ECV principal radiomics provided better discrimination and reclassification between noncollagen and mild to moderate collagen (C statistic, 0.79; net reclassification index, 0.83 [95% CI, 0.45-1.22]; P<0.001). There was a similar trend in the addition of native T1 principal radiomics (C statistic, 0.75; net reclassification index, 0.93 [95% CI, 0.56-1.29]; P<0.001) and LGE principal radiomics (C statistic, 0.74; net reclassification index, 0.59 [95% CI, 0.19-0.98]; P=0.004). Five radiomic features per sequence were identified with correlation analysis. They showed a similar improvement in performance for differentiating between noncollagen and mild to moderate collagen (native T1, ECV, LGE C statistic, 0.75, 0.77, and 0.71, respectively). These improvements remained significant when confined to a single radiomic feature (native T1, ECV, LGE C statistic, 0.71, 0.70, and 0.64, respectively). CONCLUSIONS: Radiomic features extracted from native T1, ECV, and LGE provide incremental information that improves our capability to discriminate noncollagenous expansion from mild to moderate collagen and could be useful for detecting subtle chronic inflammation in patients with dilated cardiomyopathy.

Diagnostic performance of fluoroscopic video analysis for pulmonary embolism: a prospective observational study.

PURPOSE: Dynamic chest radiography using X-ray fluoroscopic video analysis has shown potential for the diagnosis of pulmonary embolism (PE), but its diagnostic performance remains uncertain. We aimed to evaluate the diagnostic performance of fluoroscopic video analysis for diagnosing PE. METHODS: A prospective single-center observational study was conducted between October 2020 and January 2022. Fifty consecutive adult patients, comprising definitive PE, pulmonary hypertension (PH), or suspected PH, were enrolled. The study population was classified into 23 PE and 27 non-PE cases by contrast-enhanced computed tomography, lung scintigraphy, right heart catheterization, and pulmonary angiography. Cineradiographic images of 10-second breath-holds were obtained and analyzed using a fluoroscopic video analysis workstation to generate pulmonary circulation images. Two blinded cardiologists qualitatively assessed the presence or absence of perfusion defects on the pulmonary circulation images. The diagnosis obtained from the fluoroscopic analysis was compared with the definitive diagnosis. The primary outcomes included sensitivity, specificity, positive and negative predictive values, and overall accuracy for diagnosing PE. RESULTS: Perfusion defects were observed in 21 of 23 PE patients and 13 of 27 non-PE patients. The diagnostic performance of fluoroscopic video analysis for diagnosing PE showed a sensitivity of 91%, specificity of 52%, positive predictive value of 62%, negative predictive value of 88%, and overall accuracy of 70%. CONCLUSIONS: The high sensitivity of the fluoroscopic video analysis suggests its potential usefulness in ruling out PE without the need for contrast media or radionuclide; however, its specificity and overall accuracy remain limited.

Clinical Value of Troponin Levels to Cardiac Function and Prognosis in Patients with Fulminant Myocarditis.

Troponin (Tn) is a biomarker related to myocardial necrosis and is elevated in patients with myocarditis. This study aimed to investigate the association between cardiac Tn levels and the course of cardiac function, and prognosis in patients with fulminant myocarditis (FM) receiving percutaneous mechanical circulatory support (MCS).We used data from a multicenter retrospective registry, CHANGE PUMP 2, which included 216 patients with FM who required MCS. Among them, 141 patients whose Tn levels were available were analyzed. The patients were divided into low and high Tn groups according to the median values of TnT and TnI.The median age was 54 years, and 59.6% were male. The TnT and TnI on day 1 (at MCS initiation) were 3.8 (1.4-10.0) and 21.4 (8.4-68.8) ng/mL. While the left ventricular ejection fraction (LVEF) was similar on day 1 (25.0% versus 24.5%), the low Tn group showed better LVEF improvement on day 7 than the high Tn group (45.0% versus 25.3%, P < 0.001). LVEF at 1 year after admission was higher in the low Tn group (65.0% versus 59.7%, P = 0.039). The low Tn group had a better 90-day composite endpoint in death, durable left ventricular assist device implantation, and heart transplantation compared to the high Tn group (hazard ratio 0.47, 95% CI 0.23-0.95).Tn levels were associated with short- and long-term cardiac recovery and adverse outcomes in patients with FM receiving MCS due to cardiogenic shock.

Fragility and long-term clinical outcomes in patients with venous thromboembolism receiving direct oral anticoagulants: From the COMMAND VTE REGISTRY-2.

INTRODUCTION: There is limited data on the safety of direct oral anticoagulants (DOACs) in fragile patients with venous thromboembolism (VTE). MATERIALS AND METHODS: We used the COMMAND VTE Registry-2 enrolling patients with acute symptomatic VTE. The study population consisted of 3928 patients receiving DOACs, who were divided into fragile (2136 patients) and non-fragile groups (1792 patients). Fragility was defined as patients of age ≥ 75 years, creatinine clearance level ≤ 50 ml/min, and/or body weight ≤ 50 kg. RESULTS: The fragile group significantly more often received reduced doses of DOACs compared to the non-fragile group (51 % and 19 %, P < 0.001). The cumulative 5-year incidence of major bleeding was numerically higher in the fragile group than the non-fragile group (15.0 % and 11.1 %, P = 0.052), even with no significant excess risk after adjusting for confounders (HR 1.03, 95%CI 0.81-1.31, P = 0.78). The cumulative 5-year incidence of clinically relevant bleeding was significantly higher in the fragile group than the non-fragile group (28.6 % and 19.6 %, P < 0.001), even after adjusting for confounders (HR 1.28, 95%CI 1.08-1.53, P = 0.005). There was no significant difference in cumulative 5-year incidence of recurrent VTE between the groups (9.6 % and 8.9 %, P = 0.68), which was consistent after adjusting for confounders (HR 1.13, 95%CI 0.84-1.51, P = 0.41). CONCLUSIONS: Among VTE patients receiving DOACs, fragile patients were associated with a numerically higher rate of major bleeding and a significantly increased risk of clinically relevant bleeding, but not an increased risk of recurrent VTE.

Myosin Light Chain Phosphatase Plays an Important Role in Cardiac Fibrosis in a Model of Mineralocorticoid Receptor-Associated Hypertension.

BACKGROUND: Myosin phosphatase targeting subunit 2 (MYPT2) is an important subunit of cardiac MLC (myosin light chain) phosphatase, which plays a crucial role in regulating the phosphorylation of MLC to phospho-MLC (p-MLC). A recent study demonstrated mineralocorticoid receptor-related hypertension is associated with RhoA/Rho-associated kinase/MYPT1 signaling upregulation in smooth muscle cells. Our purpose is to investigate the effect of MYPT2 on cardiac function and fibrosis in mineralocorticoid receptor-related hypertension. METHODS AND RESULTS: HL-1 murine cardiomyocytes were incubated with different concentrations or durations of aldosterone. After 24-hour stimulation, aldosterone increased CTGF (connective tissue growth factor) and MYPT2 and decreased p-MLC in a dose-dependent manner. MYPT2 knockdown decreased CTGF. Cardiac-specific MYPT2-knockout (c-MYPT2-/-) mice exhibited decreased type 1 phosphatase catalytic subunit ß and increased p-MLC. A disease model of mouse was induced by subcutaneous aldosterone and 8% NaCl food for 4 weeks after uninephrectomy. Blood pressure elevation and left ventricular hypertrophy were observed in both c-MYPT2-/- and MYPT2+/+ mice, with no difference in heart weights or nuclear localization of mineralocorticoid receptor in cardiomyocytes. However, c-MYPT2-/- mice had higher ejection fraction and fractional shortening on echocardiography after aldosterone treatment. Histopathology revealed less fibrosis, reduced CTGF, and increased p-MLC in c-MYPT2-/- mice. Basal global radial strain and global longitudinal strain were higher in c-MYPT2-/- than in MYPT2+/+ mice. After aldosterone treatment, both global radial strain and global longitudinal strain remained higher in c-MYPT2-/- mice compared with MYPT2+/+ mice. CONCLUSIONS: Cardiac-specific MYPT2 knockout leads to decreased myosin light chain phosphatase and increased p-MLC. MYPT2 deletion prevented cardiac fibrosis and dysfunction in a model of mineralocorticoid receptor-associated hypertension.

Management of pulmonary hemodynamics prior to delivery in a pregnant woman with development of decompensated pulmonary arterial hypertension.

Prompt termination of pregnancy in patients with decompensated pulmonary arterial hypertension (PAH) is imperative for improvement of maternal hemodynamics, but such termination may also result in maternal death due to further deterioration of PAH immediately after delivery. However, there have been limited reports on whether implementation of PAH therapy with continuation of pregnancy improves the maternal outcome, especially in treatment-naïve patients with PAH. A 24-year-old woman was admitted to our hospital with a chief complaint of dyspnea (WHO functional class IV) at 22 weeks and 3 days of gestation. She was diagnosed with PAH accompanied by right heart failure and low cardiac output. Intensive treatment was initiated with inotropic agents, oxygen therapy, and PAH therapy, resulting in improvement of her hemodynamics. A caesarean section was performed at 23 weeks and 3 days. Although her pulmonary arterial pressure transiently increased with oxygenation deteriorating immediately after delivery, worsening PAH improved without mechanical circulatory support. She continued receiving pulmonary vasodilators without relapse of pulmonary hypertension for three years. The improvement of pulmonary hemodynamics prior to delivery with PAH therapy led to a favorable outcome after delivery. Learning objective: Pulmonary hemodynamics in pregnant patients with pulmonary arterial hypertension (PAH) can deteriorate with the continuation of pregnancy, while termination can also cause PAH surge immediately after delivery. In treatment-naïve patients with PAH, who are most likely to benefit from PAH therapy, implementation of PAH therapy with continuation, even with a decompensated status, may improve the hemodynamics prior to delivery, resulting in a favorable outcome after delivery.

Nephrotic syndrome with acute kidney injury due to combination therapy of immune checkpoint inhibitors: a case report and review of the literature.

BACKGROUND: Recent studies have focused on immune checkpoint inhibitors. Renal complications associated with the use of immune checkpoint inhibitors are uncommon compared with other immune-related adverse events. Acute interstitial nephritis accounts for most of these renal complications, with nephrotic syndrome quite rare. We herein report a case of nephrotic syndrome associated with immune checkpoint inhibitors that was more severe than that in previous cases. By comparing this case with previous reports, the possible reasons for the particular severity of this case are discussed. CASE PRESENTATION: A 75-year-old man developed nephrotic syndrome with acute kidney injury after the first combination therapy of nivolumab and ipilimumab for malignant pleural mesothelioma. The results of a kidney biopsy indicated minimal change disease with mild atherosclerosis, acute interstitial nephritis, and fusion of nearly all podocyte foot processes. Nivolumab and ipilimumab therapy were stopped, and treatment with corticosteroids was initiated. We investigated previously reported cases of nephrotic syndrome using immune checkpoint inhibitors. Seventeen cases of immune checkpoint inhibitor-related nephrotic syndrome, including ours, have been reported. Two of the 17 patients with immune checkpoint inhibitor-related nephrotic syndrome required hemodialysis treatment for acute kidney injury. Unlike many previously reported cases, the present patient was administered two different immune checkpoint inhibitors, which may be one of the reasons for the development of severe nephrotic syndrome. CONCLUSIONS: In addition to previously reported risk factors, immune checkpoint inhibitor combination therapy can exacerbate nephrotic syndrome compared to immune checkpoint inhibitor monotherapy.