Takotsubo Syndrome Occurring after mRNA COVID-19 Vaccination in a Patient with Graves' Disease.

Cardiovascular events such as myocarditis following mRNA COVID-19 vaccination are increasing. We present a 67-year-old postmenopausal woman with Takotsubo Syndrome and Graves' disease after mRNA COVID-19 vaccination. She developed chest pain and shortness of breath one week after vaccination. An electrocardiogram revealed ST elevation in the precordial leads. Coronary angiography revealed the absence of obstructive coronary artery disease, and the left ventriculography showed a typical feature with apical ballooning. Laboratory workup showed the elevation of free T4 and thyrotropin receptor antibodies. It was presumed that Takotsubo Syndrome and Graves' disease were probably related to the COVID-19 mRNA vaccination. The patient was treated with low-dose bisoprolol, diuretics, carbimazole, and steroid and discharged uneventfully. The mRNA COVID-19 vaccination is still safe and effective to defend against COVID-19 pandemic. However, clinicians should be aware of the possible cardiovascular adverse events other than myocarditis following vaccination.

Assessment of thromboembolism risk in COVID-19 patients with cardiovascular disease risk factors: Analysis of a Japanese Nationwide Registry.

INTRODUCTION: Patients with COVID-19 and cardiovascular disease risk factors (CVDRF) have been reported to develop coagulation abnormalities frequently. However, there are limitations in conventional predictive models for the occurrence of thromboembolism in patients with COVID-19 and CVDRF. METHODS: Among data on 1518 hospitalized patients with COVID-19 registered with CLAVIS-COVID, a Japanese nationwide cohort study, 693 patients with CVDRF were subjected to least absolute shrinkage and selection operator (LASSO) analysis; a method of shrinking coefficients for reducing variance and minimizing bias to increase predictive accuracy. LASSO analysis was performed to identify risk factors for systemic thromboembolic events; occurrence of arterial and venous thromboembolism during the index hospitalization as the primary endpoint. RESULTS: LASSO analysis identified a prior systemic thromboembolism, male sex, hypoxygenemia requiring invasive mechanical ventilation support, C-reactive protein levels and D-dimer levels at admission, and congestion on chest X-ray at admission as potential risk factors for the primary endpoint. The developed risk model consisting of these risk factors showed good discriminative performance (AUC-ROC: 0.83, 95 % confidence interval [CI]: 0.77-0.90), which was significantly better than that shown by D-dimer (AUC-ROC: 0.70, 95 % CI: 0.60-0.80) (p < 0.001). Furthermore, systemic embolic events were independently associated with in-hospital mortality (adjusted odds ratio: 3.29; 95 % CI: 1.31-8.00). CONCLUSIONS: Six parameters readily available at the time of admission were identified as risk factors for thromboembolic events, and these may be capable of stratifying the risk of in-hospital thromboembolic events, which are associated with in-hospital mortality, in patients with COVID-19 and CVDRF.

Impact of serum lactate dehydrogenase on the short-term prognosis of COVID-19 with pre-existing cardiovascular diseases.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) and underlying cardiovascular comorbidities have poor prognoses. Our aim was to identify the impact of serum lactate dehydrogenase (LDH), which is associated with mortality in acute respiratory distress syndrome, on the prognoses of patients with COVID-19 and underlying cardiovascular comorbidities. METHODS: Among 1518 patients hospitalized with COVID-19 enrolled in the CLAVIS-COVID (Clinical Outcomes of COVID-19 Infection in Hospitalized Patients with Cardiovascular Diseases and/or Risk Factors study), 515 patients with cardiovascular comorbidities were analyzed. Patients were divided into tertiles based on LDH levels at admission [tertile 1 (T1), <235 U/L; tertile 2 (T2), 235-355 U/L; and tertile 3 (T3); ≥356 U/L]. We investigated the impact of LDH levels on the in-hospital mortality. RESULTS: The mean age was 70.4 ± 30.0 years, and 65.3% were male. There were significantly more in-hospital deaths in T3 than in T1 and T2 [n = 50 (29.2%) vs. n = 15 (8.7%), and n = 24 (14.0%), respectively; p < 0.001]. Multivariable analysis adjusted for age, comorbidities, vital signs, and laboratory data including D-dimer and high-sensitivity troponin showed T3 was associated with an increased risk of in-hospital mortality (adjusted hazard ratio, 3.04; 95% confidence interval, 1.50-6.13; p = 0.002). CONCLUSIONS: High serum LDH levels at the time of admission are associated with an increased risk of in-hospital death in patients with COVID-19 and known cardiovascular disease and may aid in triage of these patients.

The therapeutic dilemma of immunosuppressive drugs for refractory cardiac sarcoidosis in COVID-19 infection.

Patients with refractory cardiac sarcoidosis (CS) take a high dose of corticosteroid and immunosuppressive agents. During the pandemic outbreak of severe acute respiratory syndrome coronavirus 2, appropriate treatment of corticosteroids or immunosuppressive agents in CS patients with coronavirus disease 2019 (COVID-19) is unknown. Here, the woman with refractory CS receiving maintenance therapy with 15 mg of prednisolone daily and 10 mg of methotrexate weekly was emergently admitted to our hospital because of COVID-19. This case was successfully treated by the intravenous administration of dexamethasone 6 mg/day instead of prednisolone and interruption of methotrexate without resulting in recurrent life-threatening ventricular lethal arrhythmias or obvious sarcoidosis flare-ups. She started taking prednisolone and methotrexate at the maintenance dose immediately and at 2 weeks after discharge, respectively. Although the optimal regimen of immunosuppressive agents during COVID-19 is under intense debate, this report might provide an effective treatment strategy for CS patients with COVID-19.

External validation of the 4C Mortality Score for patients with COVID-19 and pre-existing cardiovascular diseases/risk factors.

OBJECTIVES: Predictive algorithms to inform risk management decisions are needed for patients with COVID-19, although the traditional risk scores have not been adequately assessed in Asian patients. We aimed to evaluate the performance of a COVID-19-specific prediction model, the 4C (Coronavirus Clinical Characterisation Consortium) Mortality Score, along with other conventional critical care risk models in Japanese nationwide registry data. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Hospitalised patients with COVID-19 and cardiovascular disease or coronary risk factors from January to May 2020 in 49 hospitals in Japan. MAIN OUTCOME MEASURES: Two different types of outcomes, in-hospital mortality and a composite outcome, defined as the need for invasive mechanical ventilation and mortality. RESULTS: The risk scores for 693 patients were tested by predicting in-hospital mortality for all patients and composite endpoint among those not intubated at baseline (n=659). The number of events was 108 (15.6%) for mortality and 178 (27.0%) for composite endpoints. After missing values were multiply imputed, the performance of the 4C Mortality Score was assessed and compared with three prediction models that have shown good discriminatory ability (RISE UP score, A-DROP score and the Rapid Emergency Medicine Score (REMS)). The area under the receiver operating characteristic curve (AUC) for the 4C Mortality Score was 0.84 (95% CI 0.80 to 0.88) for in-hospital mortality and 0.78 (95% CI 0.74 to 0.81) for the composite endpoint. It showed greater discriminatory ability compared with other scores, except for the RISE UP score, for predicting in-hospital mortality (AUC: 0.82, 95% CI 0.78 to 0.86). Similarly, the 4C Mortality Score showed a positive net reclassification improvement index over the A-DROP and REMS for mortality and over all three scores for the composite endpoint. The 4C Mortality Score model showed good calibration, regardless of outcome. CONCLUSIONS: The 4C Mortality Score performed well in an independent external COVID-19 cohort and may enable appropriate disposition of patients and allocation of medical resources.Trial registration number UMIN000040598.

Clinical and Biomarker Profiles and Prognosis of Elderly Patients With Coronavirus Disease 2019 (COVID-19) With Cardiovascular Diseases and/or Risk Factors.

BACKGROUND: This study investigated the effects of age on the outcomes of coronavirus disease 2019 (COVID-19) and on cardiac biomarker profiles, especially in patients with cardiovascular diseases and/or risk factors (CVDRF).Methods and Results:A nationwide multicenter retrospective study included 1,518 patients with COVID-19. Of these patients, 693 with underlying CVDRF were analyzed; patients were divided into age groups (<55, 55-64, 65-79, and ≥80 years) and in-hospital mortality and age-specific clinical and cardiac biomarker profiles on admission evaluated. Overall, the mean age of patients was 68 years, 449 (64.8%) were male, and 693 (45.7%) had underlying CVDRF. Elderly (≥80 years) patients had a significantly higher risk of in-hospital mortality regardless of concomitant CVDRF than younger patients (P<0.001). Typical characteristics related to COVID-19, including symptoms and abnormal findings on baseline chest X-ray and computed tomography scans, were significantly less prevalent in the elderly group than in the younger groups. However, a significantly (P<0.001) higher proportion of elderly patients were positive for cardiac troponin (cTn), and B-type natriuretic peptide (BNP) and N-terminal pro BNP (NT-proBNP) levels on admission were significantly higher among elderly than younger patients (P<0.001 and P=0.001, respectively). CONCLUSIONS: Elderly patients with COVID-19 had a higher risk of mortality during the hospital course, regardless of their history of CVDRF, were more likely to be cTn positive, and had significantly higher BNP/NT-proBNP levels than younger patients.

Association Between Statin Use Prior to Admission and Lower Coronavirus Disease 2019 (COVID-19) Severity in Patients With Cardiovascular Disease or Risk Factors.

BACKGROUND: Cardiovascular diseases and/or risk factors (CVDRF) have been reported as risk factors for severe coronavirus disease 2019 (COVID-19).Methods and Results:In total, we selected 693 patients with CVDRF from the CLAVIS-COVID database of 1,518 cases in Japan. The mean age was 68 years (35% females). Statin use was reported by 31% patients at admission. Statin users exhibited lower incidence of extracorporeal membrane oxygenation (ECMO) insertion (1.4% vs. 4.6%, odds ratio [OR]: 0.295, P=0.037) and septic shock (1.4% vs. 6.5%, OR: 0.205, P=0.004) despite having more comorbidities such as diabetes mellitus. CONCLUSIONS: This study suggests the potential benefits of statins use against COVID-19.

SARS-CoV-2 surreptitiously injures the heart of Japanese: echocardiography is useful in evaluating cardiac damage.

Coronavirus disease 2019 (COVID-19) remains a threat worldwide over a year after the outbreak. Recently, several studies have reported that elevated serum troponin, which reflects myocardial injury, has a significant impact on worsening cardiovascular disease and the death of patients with COVID-19. In addition, magnetic resonance imaging (MRI) and echocardiography revealed abnormal myocardial findings in patients with COVID-19 who have recovered, as exemplified by a slight elevation of high-sensitivity troponin T (hsTnT). This editorial will discuss the impacts of SARS-CoV-2 on the heart of Japanese patients during infection and recovery and future perspectives.

Cardiology Department Practices in the First Wave of the Coronavirus Disease Pandemic　- A Nationwide Survey in Japan by the Japanese Circulation Society.

Background: From the early phase of the Coronavirus disease-2019 (COVID-19) pandemic, cardiologists have paid attention not only to COVID-19-associated cardiovascular sequelae, but also to treatment strategies for rescheduling non-urgent procedures. The chief objective of this study was to explore confirmed COVID-19 cardiology case experiences and departmental policies, and their regional heterogeneity in Japan. Methods and Results: We performed a retrospective analysis of a nationwide survey performed by the Japanese Circulation Society on April 13, 2020. The questionnaire included cardiology department experience with confirmed COVID-19 cases and restriction policies, and was sent to 1,360 certified cardiology training hospitals. Descriptive analysis and spatial autocorrelation analysis of each response were performed to reveal the heterogeneity of departmental policies. The response rate was 56.8% (773 replies). Only 16% of all responding hospitals experienced a COVID-19 cardiology case. High-risk procedures were restricted in more than one-fifth of hospitals, including transesophageal echocardiography (34.9%) and scheduled catheterization (39.5%). The presence of a cardiologist in the COVID-19 team, the number of board-certified cardiologists, any medical resource shortage and a state of emergency were positively correlated with any type of restriction. Conclusions: We found both low clinical case experiences with COVID-19 and restrictions of cardiovascular procedures during the first COVID-19 wave in Japan. Restrictions arising as a result of COVID-19 were affected by hospital- and country-level variables, such as a state of emergency.

Cardiology Department Policy in Japan After Coronavirus Disease-2019 (COVID-19)　- Descriptive Summary of 2nd Nationwide Survey by the Japanese Circulation Society.

Background: Cardiovascular department restriction policies on procedures resulting from the COVID-19 pandemic have not been fully evaluated. Methods and Results: We performed a retrospective analysis of a nationwide survey performed by the Japanese Circulation Society in August 2020. The total response rate was 48.9% (651/1,331). The rate of restriction of cardiovascular procedures peaked in April. Exacerbations of heart failure due to hospital restrictions were noted in 43.8% of departments. Conclusions: Many departments restricted their cardiological procedures, and this rate changed according to the pandemic situation. The exacerbation of cardiovascular disease resulting from pandemic restrictions should not be ignored.

Recommendations for Maintaining the Cardiovascular Care System Under the Conditions of the COVID-19 Pandemic　- 1st Edition, April 2020.

BACKGROUND: The Japanese Circulation Society proposes recommendations for all healthcare professionals involved in cardiovascular medicine to protect them from infection and ensure that seriously ill patients requiring urgent care receive proper treatment.Methods and Results:Patients are divided into "Positive or suspected coronavirus disease 2019 (COVID-19)" and "All others". Furthermore, tests and treatments are divided into emergency or standby. For each category, we propose recommendations. CONCLUSIONS: To maintain the cardiovascular care system, The Japanese Circulation Society recommends completely preventing nosocomial COVID-19 infections, ensuring adequate PPE necessary for healthcare personnel, and learning and implementing standard precautions.

Remote cardiac rehabilitation is a good alternative of outpatient cardiac rehabilitation in the COVID-19 era.

BACKGROUND: In the wake of the coronavirus disease 2019 (COVID-19) pandemic, people need to practice social distancing in order to protect themselves from SARS-CoV-2 infection. In such stressful situations, remote cardiac rehabilitation (CR) might be a viable alternative to the outpatient CR program. METHODS: We prospectively investigated patients hospitalized for heart failure (HF) with a left ventricular ejection fraction of < 50%. As for patients who participated in the remote CR program, telephone support was provided by cardiologists and nurses who specialized in HF every 2 weeks after discharge. The emergency readmission rate within 30 days of discharge was compared among the outpatient CR, remote CR, and non-CR groups, and the EQ-5D score was compared between the outpatient CR and remote CR groups. RESULTS: The participation rate of HF patients in our remote CR program elevated during the COVID-19 pandemic. As observed in the outpatient CR group (n = 69), the emergency readmission rate within 30 days of discharge was lower in the remote CR group (n = 30) than in the non-CR group (n = 137) (P = 0.02). The EQ-5D score was higher in the remote CR group than in the outpatient CR group (P = 0.03) 30 days after discharge. CONCLUSIONS: Remote CR is as effective as outpatient CR for improving the short-term prognosis of patients hospitalized for heart failure post-discharge. This suggests that the remote CR program can be provided as a good alternative to the outpatient CR program.

Coronavirus Disease 2019 (COVID-19) Information for Cardiologists　- Systematic Literature Review and Additional Analysis.

BACKGROUND: Despite the rapidly increasing attention being given to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, more commonly known as coronavirus disease 2019 (COVID-19), the relationship between cardiovascular disease and COVID-19 has not been fully described.Methods and Results:A systematic review was undertaken to summarize the important aspects of COVID-19 for cardiologists. Protection both for patients and healthcare providers, indication for treatments, collaboration with other departments and hospitals, and regular update of information are essentials to front COVID-19 patients. CONCLUSIONS: Because the chief manifestations of COVID-19 infection are respiratory and acute respiratory distress syndrome, cardiologists do not see infected patients directly. Cardiologists need to be better prepared regarding standard disinfection procedures, and be aware of the indications for extracorporeal membrane oxygenation and its use in the critical care setting.