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Key Points Approximately 2% of patients who present to hospital with suspected acute coronary syndrome have Takotsubo syndrome, with a predominance in postmenopausal women Mortality is higher than initially thought, and recurrence is seen in 1.2% of patients within 6 months and nearly 5% at 6 years, with no preventive therapy currently available Systemic catecholamine surges can cause acute coronary and peripheral vasospasm followed by peripheral vasodilation; a common complication is cardiogenic shock, due at least in part to left ventricular systolic dysfunction Biopsy samples taken during the acute phase of Takotsubo syndrome show morphological changes similar to those after catecholamine-induced cardiotoxic effects, supporting direct effects as well as vascular influences The apical myocardium of the left ventricle has a high density of β-adrenoceptors and, therefore, is the region most sensitive to circulating catecholamines During extreme stress, excessive epinephrine levels cause a switch from the G s α stimulatory to the cardioprotective G i α cardioinhibitory secondary messenger pathway within cardiomyocytes, thereby acting as a positive inotrope Takotsubo syndrome is an acute cardiac disorder first identified in Japan in 1990. The pathophysiology of Takotsubo syndrome is complex and involves the neuroendocrine system. Cardiovascular responses are often induced by a sudden surge in sympathetic activation and subsequent catecholamine concentration. In this Review, Akashi et al . discuss the epidemiology, diagnosis, and prognosis of the syndrome, as well as some of the proposed pathophysiological mechanisms underlying its development. Takotsubo syndrome is an acute cardiac syndrome first described in 1990 and characterized by transient left ventricular dysfunction affecting more than one coronary artery territory, often in a circumferential apical, mid-ventricular, or basal distribution. Several pathophysiological explanations have been proposed for this syndrome and its intriguing appearance, and awareness is growing that these explanations might not be mutually exclusive. The reversible apical myocardial dysfunction observed might result from more than one pathophysiological phenomenon. The pathophysiology of Takotsubo syndrome is complex and integrates neuroendocrine physiology, potentially involving the cognitive centres of the brain, and including the hypothalamic–pituitary–adrenal axis. Cardiovascular responses are caused by the sudden sympathetic activation and surge in concentrations of circulating catecholamines. The multiple morphological changes seen in the myocardium match those seen after catecholamine-induced cardiotoxicity. The acute prognosis and recurrence rate are now known to be worse than initially thought, and much still needs to be learned about the epidemiology and the underlying pathophysiology of this fascinating condition in order to improve diagnostic and treatment pathways.

Diastolic stress echocardiography is useful in patients with heart failure with preserved ejection fraction (EF); however, its utility in asymptomatic patients with aortic stenosis (AS) remains unexplored. We investigated the value of diastolic stress echocardiography using a 6-minute walk test (6-MWT) in elderly AS patients. This retrospective observational study included 96 consecutive asymptomatic patients (82 years, 39.6% male) with at least moderate AS (mean pressure gradient (MPG) ≥ 20 mm Hg or aortic valve area < 1.5 cm2) and preserved left ventricular EF. All underwent diastolic stress echocardiography using the 6-MWT. Patients were classified into a post-exercise impaired relaxation pattern (pIR) and a post-exercise pseudo-normalised/restrictive pattern (pPN) groups, based on transmitral flow velocity post-6-MWT. The primary endpoint was the time to first occurrence of the composite endpoint (all-cause mortality, aortic valve replacement due to AS-related symptoms, and hospitalization for heart failure).22 patients (23%) changed from baseline IR pattern at rest to the pPN pattern after the 6-MWT.The pPN group demonstrated lower %predicted walking distance than the pIR group. Additionally, the pPN group exhibited greater dyspnea after the 6-MWT. During a median follow-up of 536 days (interquartile range, 106–720 days), 46 patients experienced AS-related events. Multivariable Cox regression analysis indicated that the pPN group was independently associated with increased event risk (hazard ratio: 5.37, p < 0.001). In conclusion, this study suggests that the diastolic stress echocardiography using the 6-MWT is useful for risk stratification in asymptomatic elderly AS patients.

Circulatory power (CP) and ventilatory power (VP), obtained by cardiopulmonary exercise testing (CPX), have been suggested to be excellent prognostic markers for heart failure. However, the normal values of these parameters in healthy Japanese populations remain unknown; thus, we aimed to investigate these values in such a population. A total of 391 healthy Japanese participants, 20–78 years of age, underwent CPX with a cycle ergometer with ramp protocols. Systolic blood pressure (SBP), heart rate, oxygen uptake ( V ˙ O 2 ) at peak exercise, and the slope of minute ventilation ( V ˙ E) versus carbon dioxide ( V ˙ CO 2 ) ( V ˙ E vs. V ˙ CO 2 slope) were measured. CP was calculated by multiplying the peak V ˙ O 2 and SBP values, and VP was calculated by dividing the peak SBP value by the V ˙ E versus V ˙ CO 2 slope. For males and females, the average CP values were 6119 ± 1280 (mean ± standard deviation) and 4775 ± 914 mmHg·mL/min/kg, respectively ( p  < 0.001). The average VP values for males and females were 8.0 ± 1.3 and 6.9 ± 1.3 mmHg ( p  < 0.001). CP decreased with age in both sexes. VP increased with age in females, with no significant change in males. We calculated the normal values for CP and VP in a healthy Japanese population. The results can contribute to the evaluation of patients’ CPX results as a reference.

Fulminant myocarditis (FM) is an acute fatal inflammation disease, but its chronic phase is unclear. A Japanese nationwide registry evaluated the long-term mortality in FM patients using a prognostic nutritional index (PNI). The retrospective cohort study included patients with clinically suspected or histologically proven FM available for PNI. PNI was assessed on admission and at discharge. We divided patients into two groups based on PNI at discharge (PNI ≤ 40 or PNI > 40) and analyzed the change in PNI and mortality between the groups. Of 323 patients (the median [first-third quartiles] age of this cohort was 50 [37–64] years, and 143 [44%] were female), PNI ≤ 40 at discharge was in 99 (31%) patients. The median PNI in all patients increased from 41 (36– 46) on admission to 43 (39–48) at discharge (P < 0.0001). Patients with PNI ≤ 40 had a lower event-free rate of death or rehospitalization with cardiovascular causes than those with PNI > 40 (log-rank P = 0.0001). When the PNI at discharge, age, sex, left ventricular ejection fraction, and Barthel index were evaluated in a multivariable Cox regression analysis, PNI ≤ 40 had an independent association with the death or rehospitalization with cardiovascular causes (hazard ratio, 2.14 [95% confidence interval, 1.14–4.01]; P = 0.0191). One-third of FM patients with low PNI at discharge had a higher risk of mortality than those with high PNI in the chronic phase. This study provokes clinical insight into the phenotype of chronic inflammation in FM and optimal follow-up management with low PNI.

Aortic stenosis is a prevalent valvular heart disease, especially in the older people. They often coexist with other co-morbidities, and noncardiac surgery carries a higher risk because of the underlying valve condition. Despite the growing concern about the safety and optimal management of noncardiac surgery post-transcatheter aortic valve replacement (TAVR), there is limited evidence on this matter. This study aims to assess the clinical outcomes of noncardiac surgeries after TAVR. This retrospective study included 718 patients who underwent TAVR. Of these, 36 patients underwent noncardiac surgery after TAVR. The primary end point was the incidence of cardiovascular adverse events post-TAVR and the secondary end point was the incidence of structural valve deterioration. Composite end points included disabling stroke, heart failure requiring hospitalization, and cardiac death as defined by Valve Academic Research Consortium 3. Most of these surgeries were orthopedic and classified as intermediate risk. All noncardiac surgeries were performed without perioperative adverse events. There was no observed structural valve deterioration, and the incidence of composite end points did not significantly differ between the surgical and nonsurgical groups during the follow-up period. Noncardiac surgery after TAVR can be performed safely and does not have a negative impact on prognosis. Further studies are warranted to determine the optimal strategy for noncardiac surgery after TAVR.

Weather conditions influence the incidence of cardiovascular disease. However, few studies have investigated the association between weather temperature and humidity and cerebrovascular disease hospitalizations in a super-aging society. We included 606,807 consecutive patients with cerebrovascular disease admitted to Japanese acute-care hospitals between 2015 and 2019. The primary outcome was the number of cerebrovascular disease hospitalizations per day. Multilevel mixed-effects linear regression models were used to estimate the association of mean temperature and humidity, 1 day before hospital admission, with cerebrovascular disease hospitalizations, after adjusting for air pollution, hospital, and patient demographics. Lower mean temperatures and humidity < 70% or humidity ≧ 70% are associated with an increased incidence of cerebrovascular disease hospitalization (coefficient, − 1.442 [− 1.473 to − 1.411] per °C, p  < 0.001, coefficient, − 0.084 [− 0.112 to − 0.056] per%, p  < 0.001, and coefficient, 0.136 [0.103 to 0.168] per %, p  < 0.001, respectively). Lower mean temperatures and extremely lower or higher humidity are associated with an increased incidence of cerebrovascular disease hospitalization in a super-aging society.

The incidence of cardiovascular disease and mortality rates are high among patients with left ventricular hypertrophy (LVH). Obstructive sleep apnea (OSA) has been reported to increase left ventricular mass (LVM) and cause LVH. The prevalence of hypertension, a major cause of increased LVM, is high in OSA; however, it is still unknown whether OSA is an independent factor that increases LVM in addition to triggering LVH. This study investigated out-of-office blood pressure (BP) via ambulatory BP monitoring (ABPM) in patients with OSA diagnosed by polysomnography (PSG) and sought to determine the effects of OSA and hypertension on LVM. A total of 432 patients with OSA underwent ABPM and echocardiography. These patients were stratified into four groups according to their left ventricular mass index (LVMI) quartiles, and the component factors influencing LVMI, such as patient background, sleep data and all-day BP data, were analyzed. This study included 356 men and 76 women. The mean age was 54.6±13.2 years, the mean body mass index was 26.7±4.6 kg m and the mean apnea-hypopnea index (AHI) was 37.9±22.5. Multivariate analysis indicated that antihypertensive agent use (β=0.143, P=0.002), an AHI ⩾15/h (β=0.100, P=0.045) and 24-h systolic BP (β=0.252, P<0.001) were significant independent factors for increased LVM. The significant LVMI component factors in OSA patients were an AHI ⩾15/h and 24-h systolic BP. The results of this study demonstrated that both elevated BP and OSA were independently associated with increased LVM.

Weather conditions affect the incidence of acute myocardial infarction (AMI). However, little is known on the association of weather temperature and humidity with AMI hospitalizations in a super-aging society. This study sought to examine this association. We included 87,911 consecutive patients with AMI admitted to Japanese acute-care hospitals between April 1, 2012 and March 31, 2015. The primary outcome was the number of AMI hospitalizations per day. Multilevel mixed-effects linear regression models were used to estimate the association of the average temperature and humidity, 1 day before hospital admission, with AMI hospitalizations, after adjusting for weather, hospital, and patient demographics.Lower temperature and humidity were associated with an increased number of AMI hospitalizations (coefficient − 0.500 [− 0.524 to − 0.474] per °C change, p  < 0.001 and coefficient − 0.012 [− 0.023 to − 0.001] per % change, p  = 0.039, respectively). The effects of temperature and humidity on AMI hospitalization did not differ by age and sex (all interaction p > 0.05), but differed by season. However, higher temperatures in spring (coefficient 0.089 [0.025 to 0.152] per °C change, p  = 0.010) and higher humidity in autumn (coefficient 0.144 [0.121 to 0.166] per % change, p  < 0.001) were risk factors for AMI hospitalization. Increased average temperatures and humidity, 1 day before hospitalization, are associated with a decreased number of AMI hospitalizations.

Immune checkpoint inhibitor (ICI)-induced myocarditis is rare but fatal. Because of the rapid course of ICI-induced myocarditis, understanding of clinical course is only possible through information from case reports. We report a case of pembrolizumab-induced myocarditis in which we were able to document the course of electrocardiographic changes from onset to death. A 58-year-old woman with stage IV lung adenocarcinoma, who had completed her first cycle of pembrolizumab, carboplatin, and pemetrexed, was admitted with pericardial effusion. She underwent pericardiocentesis after admission. A second cycle of chemotherapy was administered 3 weeks after the first cycle. Twenty-two days after admission, she developed a mild sore throat and tested positive for SARS-CoV-2 antigen. She was diagnosed with mild coronavirus disease 2019 (COVID-19), isolated, and treated with sotrovimab. Thirty-two days after admission, an electrocardiogram showed monomorphic ventricular tachycardia (VT). Suspecting myocarditis caused by pembrolizumab, the patient was started on daily methylprednisolone after coronary angiography and endocardial biopsy. Eight days after the start of methylprednisolone administration, she was considered to have passed the acute stage. However, four days later, R-on-T phenomenon triggered polymorphic VT and she died. The impact of viral infections such as COVID-19 on patients be treated with immune checkpoint inhibitors is still unknown and we need to be careful with systemic management after viral infections.