Fatal Systemic Capillary Leak Syndrome in a Patient with a COVID-19 Infection.

A 29-year-old Japanese woman was admitted to our hospital with a fever, cardiogenic shock, and cardiac arrest. Laboratory data indicated multiple organ failure in addition to hemoconcentration, hypoalbuminemia, and myocardial damage. The coronary angiography findings were normal, and fulminant myocarditis was suspected. Venoarterial peripheral extracorporeal membrane oxygenation and an Impella CP left ventricular assist device were initiated, along with the administration of positive inotropic agents. However, hypovolemic shock and hypoalbuminemia progressed along with severe anemia, and the patient died 18 hours after admission. The patient was diagnosed with systemic capillary leak syndrome associated with coronavirus disease 2019.

An Iron-chelating Agent Improved the Cardiac Function in a Patient with Severe Heart Failure Due to Hereditary Hemochromatosis.

A 24-year-old man was admitted to our hospital because of severe heart failure. Although he was treated with diuretics and positive inotropic agents, his heart failure progressed. An endomyocardial biopsy revealed iron deposition in his myocytes. Finally, he was diagnosed with hereditary hemochromatosis. After starting administration of an iron-chelating agent in addition to conventional treatment for heart failure, his condition improved. We should consider hemochromatosis in heart failure patients with severe right ventricular dysfunction in addition to left ventricular dysfunction.

Real-world Safety and Effectiveness of Edoxaban in Patients with Venous Thromboembolism with or without Preceding Parenteral Anticoagulants: A Single-center Retrospective Study.

Objective Edoxaban is an anticoagulant used for venous thromboembolism (VTE) treatment and requires pretreatment with parenteral anticoagulants. However, pretreatment is not always performed in the clinical setting. In this study, we investigated the safety and effectiveness of edoxaban treatment in patients with VTE with or without pretreatment. Methods We retrospectively enrolled 364 patients who received edoxaban for VTE treatment between September 2014 and March 2020 and investigated patient demographics, VTE recurrence, and major bleeding as clinical outcomes in patients with or without pretreatment. Furthermore, the factors contributing to pretreatment decisions were assessed. Results Patients without pretreatment (n=208) had more active cancer cases and fewer pulmonary embolism complications than those with pretreatment (n=156). Lower levels of hemoglobin and higher levels of white blood cell counts, C-reactive protein, and D-dimer at the diagnosis were found in patients who received pretreatment than in those without pretreatment. No symptomatic VTE recurrence was observed. After propensity score matching, the cumulative incidence of major bleeding was not significantly higher in patients with pretreatment than in those without it (log-rank test, p=0.136). The incidence of deteriorated VTE on imaging did not significantly differ between patients with and without pretreatment, even after propensity matching (log-rank test, p=0.414). Conclusion In a real-world clinical setting, where physicians determined the use of parenteral anticoagulant lead-in according to their experience, patient demographics, and VTE characteristics, no significant differences were found regarding safety and effectiveness in edoxaban-treated VTE patients with or without pretreatment with parenteral anticoagulants.

Attitude of Emergency Medical Technicians Toward Electrocardiogram　- Needs of Electrocardiogram Training Courses and Other Learning Opportunities.

BACKGROUND: Early intervention in prehospital settings is important for treating patients with acute coronary syndrome (ACS). Emergency medical technicians (EMTs) are the essential first responders who treat these patients, and their current attitudes towards electrocardiograms (ECGs) have not been identified. This study investigated the awareness of EMTs of ECGs to shorten hospital arrival time, improving patient prognosis.Methods and Results: An anonymous questionnaire survey, with 27 statements about ECG and ACS response, was administered to 395 EMTs. The statements were related to interest, motivation, learning status, confidence, and norms pertaining to ECGs, a sense of perceived behavioral control, and training courses. The primary outcome was the perception of EMTs that their interpretation of an ECG affected patient prognosis (Statement [S] 1). Participants assigned scores for each statement using a scale ranging from 1 (strongly disagree) to 10 (strongly agree). The mean score for S1 was 7.09. Mean scores for statements regarding confidence and learning status were 3.96 and 3.53, respectively. The participants had a positive impression of training courses (score >5.5). CONCLUSIONS: The EMTs experience was that their interpretation of an ECG could affect the prognosis of patients with ACS. Conversely, they lacked confidence reading ECGs, but were willing to attend ECG training courses. Therefore, efficient training programs need to be established to achieve a better prognosis for ACS patients.

Fulminant Myocarditis and Acute Appendicitis after COVID-19 Vaccination.

A 19-year-old Japanese man was hospitalized for cardiogenic shock 28 days after receiving a second dose of the coronavirus disease 2019 (COVID-19) mRNA-1273 vaccine. He had had a high fever for three days with vomiting and abdominal pain before arriving at our hospital. The patient visited a local hospital and was diagnosed with heart failure and acute appendicitis. An endomyocardial biopsy specimen showed myocarditis. Thereafter, Impella CP left ventricular assist device implantation and venoarterial peripheral extracorporeal membranous oxygenation were initiated immediately along with inotropic support and steroid pulse therapy. Given these findings, he was finally diagnosed with multiple inflammatory syndrome and fulminant myocarditis.

Life-threatening Vasospastic Angina Induced by Carteolol Eye Drops.

Vasospastic angina (VSA) can be worsened by oral nonselective beta-blockers. Ophthalmic carteolol eye drops are nonselective beta-blockers and effective against glaucoma and ocular hypertension. Systemic effects of ophthalmic beta-blockers on VSA have not yet been reported. We herein report a case of VSA that developed after a patient started carteolol eye drops for ocular hypertension. Even though benidipine, a calcium channel blocker, was started, a VSA attack with incessant non-sustained ventricular tachycardia occurred. Once the carteolol eyedrops were discontinued, the VSA resolved. This case demonstrates that carteolol eye drops can induce life-threatening VSA.

Comparison of Effectiveness and Safety Among 3 Direct Oral Anticoagulants in Patients With Venous Thromboembolism　- A Single-Center Retrospective Study.

Background: Direct oral anticoagulants (DOACs), including edoxaban, rivaroxaban, and apixaban, are administered for the treatment of venous thromboembolism (VTE) in Japan. However, only a few reports have compared the effectiveness and safety of these DOACs. Methods and Results: We retrospectively enrolled 702 patients who received DOACs for VTE treatment between September 2014 and March 2020. We investigated patient demographics, VTE recurrence, major bleeding, and mortality until March 2021, and compared them among the 3 DOACs. Most patients (~70%; n=496) were prescribed edoxaban, followed by apixaban (n=107) and rivaroxaban (n=99). Age, body mass index, renal function, and the proportion of cancer patients did not differ significantly among the DOACs. Edoxaban was administered relatively more in women with low body weight and anemia. The rate of pulmonary embolism was significantly lower among patients receiving edoxaban than apixaban or rivaroxaban (24.4% vs. 41.1% and 53.5%, respectively). VTE reoccurred in 2 patients administered apixaban and 1 patient administered edoxaban. The cumulative incidence of major bleeding at 1 year was 11.7%, 18.5%, and 9.0% in the edoxaban, apixaban, and rivaroxaban groups, respectively. There were no significant differences in the cumulative incidence of major bleeding and all-cause death, estimated by Kaplan-Meier analysis, among the DOACs (log-rank P=0.316 and 0.722, respectively). Conclusions: The safety of the 3 DOACs did not differ significantly in clinical settings, despite differences in patient demographics.

Successful percutaneous transluminal renal angioplasty with multimodality imaging guidance for a juvenile patient with renovascular hypertension due to fibromuscular dysplasia.

Percutaneous transluminal renal angioplasty (PTRA) is an effective treatment for renovascular hypertension due to fibromuscular dysplasia (FMD). PTRA for renovascular FMD is performed with only balloons based on the consensus that stent kinking and fracture have been reported in cases of PTRA using stents for FMD. Therefore, it is important to avoid procedural complications, such as flow-limiting dissection or arterial rupture, in PTRA for renovascular FMD.We present a case of a juvenile patient who presented with renovascular hypertension due to FMD. Angiography revealed focal stenosis of the right renal artery, and the pressure wire showed a resting distal coronary to aortic pressure ratio (Pd/Pa) of 0.83. Intravascular ultrasound (IVUS) showed an intima-media complex that could not be qualitatively assessed. Optical coherence tomography (OCT) showed intimal fibroplasia and medial hyperplasia with areas of low intensity. Based on the OCT images, balloon angioplasty was performed using a semi-compliant balloon. After balloon angioplasty, IVUS and OCT revealed luminal expansion with mild residual stenosis, and the Pd/Pa ratio was 0.99. We decided not to increase the balloon size to avoid vascular injuries. In conclusion, PTRA with only balloon can be safely performed for FMD under the guidance of multimodal imaging, using IVUS, OCT, and a pressure wire. Learning objectives: This report describes successful percutaneous transluminal renal angioplasty (PTRA) for a juvenile patient with renovascular hypertension due to fibromuscular dysplasia (FMD) under the guidance of multimodal imaging, using intravascular ultrasound (IVUS), optical coherence tomography (OCT), and a pressure wire. When IVUS for FMD cannot assess the culprit lesion qualitatively, OCT could be effective in performing angioplasty with only balloon, without significant vascular injuries. A pressure wire can show the endpoint of PTRA and help avoid increasing the balloon size to prevent significant vascular injuries.

Delayed Acute Perimyocarditis and Bilateral Facial Nerve Palsy in a Patient with COVID-19.

A 41-year-old Japanese man was admitted to our hospital with acute perimyocarditis 4 weeks after coronavirus disease 2019 (COVID-19) infection. Ten days after admission, the patient showed bilateral facial nerve palsy in the course of improvement of perimyocarditis under treatment with aspirin and colchicine. After prednisolone therapy, perimyocarditis completely improved, and the facial nerve palsy gradually improved. Acute perimyocarditis and facial nerve palsy can occur even 4 weeks after contracting COVID-19.

Fulminant Myocarditis 24 Days after Coronavirus Disease Messenger Ribonucleic Acid Vaccination.

A 60-year-old Japanese woman was hospitalized for cardiogenic shock 24 days after receiving the second dose of the coronavirus disease 2019 BNT162b2 vaccine. Impella CP left ventricular assist device implantation and venoarterial peripheral extracorporeal membranous oxygenation were immediately initiated along with inotropic support and steroid pulse therapy, as an endomyocardial biopsy specimen showed myocarditis. Three weeks later, her cardiac function had recovered, and she was discharged. An immune response associated with the presence of spike protein in cardiac myocytes may be related to myocarditis in the present case because of positive immunostaining for severe acute respiratory syndrome coronavirus 2 spike protein and C4d in the myocardium.

Vasospastic Angina: An Immune-related Adverse Event.

A 54-year-old Japanese woman was admitted to our ward because of recurrent chest pain at rest for 2 months. She had been treated with nivolumab, an immune checkpoint inhibitor for inoperable advanced hypopharyngeal cancer for 21 months. She had no chest pain after cessation of nivolumab treatment. Cardiac catheterization confirmed the presence of vasospastic angina. Benidipine 8 mg was started, and she had no chest pain even after resuming therapy with nivolumab. Vasospastic angina is an adverse effect of nivolumab.

Cardio-ankle vascular index is associated with coronary plaque composition assessed with iMAP-intravascular ultrasound in patients with coronary artery disease.

BACKGROUND: The cardio-ankle vascular index (CAVI) is an indicator of arterial stiffness and has been reported to be associated with the severity of coronary artery disease and cardiovascular events. However, whether CAVI can predict the composition of coronary plaques remains unclear. METHODS: We enrolled 208 patients who underwent percutaneous coronary intervention (PCI) for culprit lesions evaluated with iMAP-intravascular ultrasound (IVUS), a radiofrequency imaging system for characterizing tissues. iMAP-IVUS classified the culprit plaque composition as fibrotic, lipidic, necrotic, or calcified, and the respective absolute volumes [fibrotic volume (FV), lipidic volume (LV), necrotic volume NV, and calcified volume] and their ratios (%) within the total plaque volume were calculated. A plaque with a median %NV of ≥ 33.2% was defined as a larger NV (LNV) plaque. We measured CAVI and divided the patients into two groups according to CAVI ≥8 (high CAVI, n = 164) or <8 (low CAVI, n = 44). RESULTS: Culprit plaques had significantly greater absolute NV (p = 0.016), %NV (p = 0.01), and smaller %FV (p = 0.02) in patients with high CAVI than in those with low CAVI. Patients with high CAVI had a higher prevalence of LNV plaques in culprit lesions than those with low CAVI (54% vs. 34%, p = 0.026). CAVI correlated significantly and positively with absolute NV, LV, and negatively with %FV. In logistic regression analysis after adjustment for the classic coronary risk factors and possible variables associated with vulnerable plaques, high CAVI had an independent and significant association with the presence of LNV plaques (OR, 3.37; 95% CI, 1.45-7.79; p = 0.0032). CONCLUSIONS: A high CAVI is associated with the composition of coronary culprit plaques, particularly increased amount of necrotic tissue, in patients with coronary artery disease undergoing PCI .

Serum soluble Klotho is inversely related to coronary artery calcification assessed by intravascular ultrasound in patients with stable coronary artery disease.

BACKGROUND: Although the Klotho gene is recognized as an aging-suppressor gene, the clinical significance of its soluble product, soluble Klotho, in coronary artery disease (CAD) has not been completely determined. The relationship between soluble Klotho and coronary artery calcification (CAC) was investigated in patients with stable CAD. METHODS: CAC in culprit lesions was analyzed in 75 non-dialysis patients with stable CAD who were scheduled for percutaneous coronary intervention (PCI) following intravascular ultrasound (IVUS). The main outcome measure was the calcium index (CalcIndex), a volumetric IVUS-derived measure of total calcification per culprit lesion. A low CalcIndex was defined as a first-quartile calcium index (<0.042). Patients were divided into two groups according to the median serum Klotho value: low Klotho (n = 37, ≤460 pg/mL) and high Klotho (n = 38, >460 pg/mL). RESULTS: The CalcIndex was significantly lower in patients with high than with low Klotho. Patients with high Klotho had a significantly higher prevalence of a low CalcIndex than those with low Klotho. The number of angiographic moderate-severe CACs in whole coronary arteries was significantly decreased in patients with high Klotho compared to low Klotho. Serum Klotho levels correlated significantly and inversely with the CalcIndex. This relationship was pronounced in patients with estimated glomerular filtration rate <60 mL/min/1.73 m2. Logistic regression analysis showed that high Klotho was associated with a low CalcIndex independent of classical coronary risk factors and markers of mineral metabolism. CONCLUSIONS: High serum soluble Klotho levels are associated with a low degree of CAC in non-dialysis, stable CAD patients treated by PCI.

Effects of Vonoprazan on the Antiplatelet Function of Prasugrel Assessed by the VerifyNow P2Y12 Assay in Patients With Coronary Artery Disease.

Background: Vonoprazan is a potassium-competitive acid blocker increasingly used in Japan to prevent upper gastrointestinal bleeding in patients undergoing dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). Cytochrome P450 (CYP) 3A4 is involved in the primary metabolism of both vonoprazan and prasugrel. This raises concern about the possibility of a CYP3A4-mediated drug-drug interaction between vonoprazan and prasugrel that may lead to attenuation of prasugrel's antiplatelet effect. Methods and Results: We evaluated 88 PCI patients who were taking either vonoprazan (n=45) or proton pump inhibitors (PPIs; n=43) in combination with DAPT (aspirin and prasugrel). Platelet reactivity on prasugrel was assessed using the VerifyNow P2Y12 assay. The primary endpoint was comparison of P2Y12 reaction units (PRU) between patients on vonoprazan and PPIs. PRU >208 and <85 were defined as high (HPR) and low (LPR) on-treatment platelet reactivity for prasugrel. PRU was comparable between patients receiving vonoprazan and PPIs (169±52 vs. 179±61, respectively; P=0.75). There were no significant differences between the vonoprazan and PPI groups in the prevalence of HPR (22% vs. 37%, respectively; P=0.16) and LPR (4 vs. 7%, respectively; P=0.48). The results were consistent regardless of the type of clinical presentation and DAPT duration. Conclusions: PRU under DAPT with aspirin plus prasugrel in patients receiving vonoprazan was not significantly different from that in patients receiving PPIs after PCI in routine clinical practice.

The Relationship between Circulating Polyunsaturated Fatty Acid Levels and Exercise Responses of Patients with Non-ischemic Heart Failure.

Objective Polyunsaturated fatty acids (PUFAs) are associated with heart failure (HF) as well as coronary artery disease. However, little is known about the relationships between PUFAs and the exercise responses of patients with HF. We evaluated the relationships between PUFAs and the parameters of cardiopulmonary exercise tests (CPETs) in patients with non-ischemic HF. Methods Fifty patients with stable non-ischemic HF underwent CPETs at our hospital. Data were analyzed to evaluate the relationships between PUFAs and echocardiographic findings as well as CPET and other test parameters. Results Correlations were significant and negative between dihomo-γ-linolenic acid (DGLA) + arachidonic acid (AA) and minute ventilation versus carbon dioxide production (VE/VCO2) slope, and positive between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and VE/VCO2 slope. A multivariate regression analysis selected DGLA+AA and AA as independent predictors of VE/VCO2 slope. However, eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) were not significantly correlated with the CPET parameters. Conclusion Low levels of circulating DGLA+AA and AA among PUFAs were associated with decreased exercise responses in patients with stable non-ischemic HF. These findings suggest that high levels of omega-6 PUFAs may improve the clinical outcomes of patients with non-ischemic HF via their effects on exercise responses.

Seizures and syncope due to complete atrioventricular block in a patient with acute myocarditis with a normal left ventricular systolic function.

A 43-year-old man was admitted to our hospital presenting with seizures and syncope. He had a history of a cold with a fever of 39°C occurring three days earlier. Electrocardiography (ECG) showed complete atrioventricular block (AV block) with a maximum pause of 32 seconds, for which temporary pacing was performed. Echocardiography showed mild hypertrophy of the left ventricle (LV) with a normal ejection fraction of 61%. Coronary angiography showed normal coronary arteries. Then, an endomyocardial biopsy was performed, the results of which indicated a diagnosis of acute myocarditis. After admission, the complete atrioventricular block disappeared together with normalization of the LV wall thickness.