Congenital heart disease (CHD) accounts for nearly one-third of all major congenital anomalies, with atrial septal defect (ASD) and ventricular septal defect (VSD) being the most common forms of simple CHD, which involve a large number of susceptibility genes. However, despite extensive research, the etiology of ASD and VSD remains unclear. Yunnan Province has advantages in exploring CHD pathogenesis due to its unique genetic background. Therefore, we aimed to evaluate the association between single nucleotide polymorphisms (SNPs) of genes and susceptibility to simple CHD in a specific population by means of a case-control study. A total of 337 healthy controls and 767 patients with simple CHD (501 ASD and 266 VSD) from China were recruited. Candidate SNPs were identified through whole-genome sequencing of pooled CHD patients and controls (pool-seq). Genotyping from 1,104 samples was performed, and stratified analysis was conducted to explore the association between positive SNPs and CHD subtypes. χ² tests and logistic regression were used to analyze the relationship between each SNP and simple CHD. Of 11 SNPs identified, SOD2 rs62437333 (P = 0.005) and POU5F1 rs3130504 (P = 0.017) showed differences between the control and ASD cohorts. In the dominant inheritance model hypothesis, rs62437333 allele C carriers had increased ASD (odds ratio (OR) = 2.04, P = 0.005) and combined simple CHD risk (OR = 2.33, P = 0.012) compared to DD genotype, while rs3130504 allele C carriers had increased ASD risk (OR = 1.121, P = 0.045) compared to DD genotype.

Cholesterol crystal (CC) embolism is a disease in which CCs from atherosclerotic lesions embolize peripheral arteries, causing organ dysfunction. In this case, a patient with spontaneously ruptured aortic plaques (SRAPs) identified by non-obstructive general angioscopy (NOGA) may have developed a CC embolism. This is the first report of a CC embolism in a patient with SRAPs identified using NOGA, which further supports the previously speculated pathogenesis of CC embolism due to SRAPs.

Shoshin beriberi is a fulminant form of wet beriberi, but there are no large-scale studies detailing the clinical features of this disease. We investigated the clinical features and outcomes of Shoshin beriberi using data from a nationwide database in Japan.

Using the Diagnosis Procedure Combination database, we identified patients with Shoshin beriberi between July 2010 and March 2021. We retrospectively investigated the characteristics, comorbidities, treatment, and in-hospital mortality of patients with Shoshin beriberi. The chi-square test or Fisher's exact test was used for categorical variables, and the Mann-Whitney U-test was used for continuous variables.

We identified 62 patients with Shoshin beriberi. The median (interquartile range) age was 63 (48-69) years. Furthermore, 54 patients were male (87%). The most common comorbidity was alcohol-related disorder (34%). The median (interquartile range) length of hospital and intensive care unit stays were 17 (range, 10-35) and 5 (range, 1-9) days, respectively. The proportion of patients who received venoarterial extracorporeal membrane oxygenation, intra-aortic balloon pump, continuous renal replacement therapy, and mechanical ventilation was 11, 5, 29, and 63%, respectively. Among the patients with Shoshin beriberi, 53% received 2 or more catecholamines or inotropes. The in-hospital mortality was 23%. Impaired consciousness at admission was significantly related to in-hospital death (P < 0.001).

The present study is the first and largest to describe the clinical features of patients with Shoshin beriberi using a nationwide database. Impaired consciousness at admission was significantly associated with in-hospital death.

This study present a case of a 49-year-old woman who suffered from resistant hypertension, hypokalemia, hypomenorrhea, and infertility. She was hospitalized 6 years earlier for hypomenorrhea and abdominal pain at the Xiamen Maternity and Child Health Hospital, where she was diagnosed with Asherman syndrome. During hospitalization, a computed tomography examination revealed an adrenal mass. She was referred to Xiamen University Affiliated Zhongshan Hospital for pheochromocytoma and underwent surgical resection of the left adrenal gland. The adrenal cortex adenoma was confirmed by pathological biopsy. Six years later, the patient also presented with hypertension and hypokalemia to our emergency department. A diagnosis of 17α-hydroxylase deficiency was established through the analysis of clinical and laboratory characteristics. The genetic analysis of CYP17A1 revealed compound heterozygous mutations, 1 of which was a mutation of c.1226 C>G, and the other c.297+2T>C.

Sacubitril/valsartan improves outcomes in patients with heart failure (HF) with reduced ejection fraction. However, the relationship between longitudinal changes in natriuretic peptides and echocardiographic parameters in patients with HF treated with sacubitril/valsartan across the left ventricular ejection fraction (LVEF) range is not fully understood.

In patients with HF treated with sacubitril/valsartan, comprehensive data on natriuretic peptides, including atrial natriuretic peptide (ANP), N-terminal pro-brain-type natriuretic peptide (NT-proBNP), BNP, and echocardiography, were measured after 6 months of treatment. We assessed the change in natriuretic peptides and echocardiographic parameters in LVEF classification subgroups.

Among 49 patients, the median ANP concentration increased from 55 pg/mL at baseline to 78 pg/mL (P < 0.001). The NT-proBNP concentration decreased from 250 pg/mL to 146 pg/mL (P < 0.001). No significant change was observed in the BNP concentration (P = 0.640). The trajectories of each natriuretic peptide in patients with LVEF > 40% (n = 22) were similar to those in individuals with LVEF ≤ 40% (n = 27). Regardless of LVEF classification, echocardiography at 6 months showed a significant improvement in LVEF, left ventricular end-diastolic volume, and the ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e'). The reduction in natriuretic peptide concentration was related to LV reverse remodeling and decreased left and right atrial pressures assessed by E/e' and inferior vena cava diameter.

Sacubitril/valsartan induced an increase in ANP, a reduction in NT-proBNP, and no change in plasma BNP, regardless of LVEF. It caused LV reverse remodeling, and the natriuretic peptide concentration changes were associated with structural and functional echocardiographic parameters.

Whether a nodular calcification (NC), which is the precursor to intracoronary thrombosis, is focally or diffusely distributed in the coronary tree has major implications for ongoing efforts to identify. This study aimed to investigate the frequency and spatial distribution patterns of sheet calcification (SC) and NC in a 3-vessel examination of autopsied human hearts.

A total of 323 coronary artery specimens from 110 cadavers were obtained from autopsy cases. After fixation and decalcification, the coronary artery trees were cut every 5 mm into 4-μm transverse cross-sections for histological assessment. An SC was defined as a plate-like calcification of > 1 quadrant of the vessel or > 3 mm in diameter, and NC as nodular calcium deposits separated by fibrin, and a deposit size > 1 mm in diameter.

Of the 6,306 histological cross-sections, SCs and NCs were identified in 1,627 (26%) and 233 (4%) cross-sections, respectively. SCs and NCs had a similar distribution pattern in all 3 coronary arteries. In the left anterior descending artery (LAD), NCs were predominantly located in the proximal segment: the first 45 mm from the LAD ostium (72%) and the first 60 mm from the LAD ostium (84%), respectively. However, NCs were evenly distributed throughout the length of the coronary artery in the right coronary artery (RCA) and left circumflex artery (LCX).

NCs coexisted with SCs, and tended to cluster in predictable parts within the proximal segments of the LAD, but were evenly distributed throughout the RCA and LCX in coronary arteries from cadavers.

Takayasu arteritis (TA or TAK) is a chronic large vessel vasculitis with predilection to affect the aorta and its branches. The new 2022 ACR/EULAR classification criteria for Takayasu arteritis incorporated imaging characteristics as an absolute requirement. ESR and CRP fails in accuracy as disease activity markers. Pentraxin 3 appears to be a relatively superior biomarker, which correlates with ITAS 2010 as per several studies. PET-CT is also increasingly being studied for assessing disease activity with variable results. The management of TAK involves use of steroids with upfront steroid sparing immunosuppressive agents. MMF is one such conventional DMARD/immunosuppressant with good efficacy and better safety profile, as reported in various cohort studies. Tocilizumab is proved to be a rapid remission inducing agent in refractory Takayasu arteritis in observational studies. TNF inhibitors in many uncontrolled studies showed good responses, and there is a need for good RCTs for confirmation. JAK inhibitors have also been used with success in a few reports.

Arrhythmia-induced cardiomyopathy (AIC) occurring in patients with atrial fibrillation (AF) is a reversible form of cardiomyopathy characterized by LV systolic dysfunction. However, it is difficult to predict the reversibility before rhythm control therapy. We performed this study to develop a parameter for the identification of AIC in routine transthoracic echocardiography (TTE) in patients with presumptive AIC due to AF.

We retrospectively studied 72 patients treated with catheter ablation therapy for persistent AF, and LV ejection fraction (LVEF) ≤ 45%. The patients were divided into 2 groups by follow-up TTE performed within 12 ± 6 months postoperatively. Patients with ≥ 15% improvement in LVEF or ≥ 10% improvement and ≥ 50% in LVEF were classified as the AIC group, and the others were classified as the non-AIC group.

A total of 57 (79%) patients were classified as the AIC group. In the stepwise multivariate logistic regression model, LV end-diastolic dimension (LVDd) and e' (septal) were independent predictors of AIC. The sensitivities of LVDd ≤ 53 mm and e' (septal) ≥ 6.3 cm/second were 60% and 75%, respectively. Their specificities were 80% and 67%, respectively. The presence of either LVDd ≤ 53 mm or e' (septal) ≥ 6.3 cm/second had a higher sensitivity (90%); their co-occurrence had a higher specificity (93%) in predicting AIC.

The functional recovery in patients with AIC can occur in LV systolic dysfunction without remodeling and impairment of relaxation. The combination of LVDd and e' (septal) is useful in predicting AIC due to AF with routine TTE.

In heart failure with preserved ejection fraction (HFpEF), left atrial enlargement is a surrogate marker reflecting chronic left ventricular diastolic dysfunction. As a result, the left atrial volume is often evaluated in daily clinical practice to determine the presence of left ventricular diastolic dysfunction. However, recent studies have shown that left atrial dysfunction is an important factor contributing to the pathogenesis of HFpEF, and it is expected to become one of the therapeutic targets of HFpEF, rather than just a surrogate marker. Echocardiography plays a central role in the identification of left atrial dysfunction and remodeling in HFpEF. In this review, we describe an approach to the evaluation of left atrial function in HFpEF using echocardiography.

Immunosuppressive therapy with prednisolone (PSL) is the first-line treatment for cardiac sarcoidosis (CS), and ¹⁸F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) is used to evaluate its efficacy to guide treatment. However, the appropriate timing of FDG-PET in CS remains unknown. This single-center, retrospective, observational study included 15 consecutive CS patients who underwent 3 serial FDG-PET scans (at baseline, in the early phase [1-2 months after PSL introduction], and in the late phase [≥ 5 months after PSL introduction with a maintenance dose of PSL]). We adhered to the PSL tapering protocol by the Japanese Circulation Society even when early FDG-PET showed positive results (SUVmax ≥ 4.0). No patient died during the 908 (644-1600) days of observation. Negative results in the late phase were observed in 3 of 6 early-positive patients, and 3 of 9 early-negative patients showed positive results in the late phase. Changes in echocardiographic parameters from baseline to the late phase were significantly better in late-negative patients than in late-positive patients (left ventricular end-diastolic diameter: -0.7 (-9.3-[-0.5]) mm versus +3.5 (0.8-7.5) mm, P = 0.039; left ventricular end-systolic diameter: -4.2 (-6.9-[-0.1]) mm versus +5.1 (0.5-7.0) mm, P = 0.015; left ventricular ejection fraction: +4.7% (-1.0-9.0%) versus -1.5% (-11.3-1.5%), P = 0.045) ), although early FDG-PET did not predict those consequent changes. An interval of ≥ 5 months after introducing the PSL with a maintenance dose of PSL is long enough for FDG-PET to reflect consequent left ventricular functions, while an interval of 1-2 months can be too short.

Sinus of Valsalva aneurysm (SVA) is a rare cardiovascular disease with male predominance. Recently, an association with aortic aneurysm and SVA has been revealed in periventricular nodular heterotopia patients with loss-of-function Filamin A (FLNA) mutations, which were located on chromosome X and almost exclusively affect females.

Among patients hospitalized for aortic surgery with aortic root diameter over 4.0 cm, next-generation sequencing was performed to investigate 30 candidate genes related to inherited aortic aneurysm syndromes and familial thoracic aortic aneurysm and dissection. The present report reviewed an electronic case database and identified two female cases of unruptured SVA with heterozygous FLNA truncating mutations.

Case 1 displaying a rare SVA phenotype involving left and noncoronary sinus harbored a nonsense variant p.Tyr1720Ter/c.5160C > G. Case 2 displayed right and noncoronary SVA with predominantly enlarged right coronary sinus, posterior mitral valve prolapse, and harbored a frameshift variant p.Val1724fs*68/c.5171_5172delTG. Both novel mutations resulted in the premature termination of filamin A with the loss of functional Rod 2 and dimerization region.

The present report raised the possibility of the presence of a cardiovascular onset form in the spectrum of FLNA hereditary diseases. The association between SVA and loss-of-function FLNA mutations indicates a unique etiology and pathogenesis among female patients, which requires further investigation to establish the linkage between FLNA variants and a wide spectrum of phenotypes.

Nonalcoholic fatty liver disease (NAFLD) is an emerging driver of cardiac arrhythmias. However, the relationship between NAFLD and malignant arrhythmia in non-ST-segment elevation myocardial infarction (NSTEMI) patients is still unclear.

In this study, 358 NSTEMI inpatients were enrolled. They all received 24-hour Holter monitoring after percutaneous coronary intervention. All inpatients were divided into two groups: the non-NAFLD group (236 cases, 65.9%) and the NAFLD group (122 cases, 34.1%). Compared with the non-NAFLD group, the NAFLD group had a significantly higher incidence of PVCs/hour > 5 (premature ventricular complexes, 32.0% versus 9.3%, P < 0.001), ventricular tachycardia (VT, 22.1% versus 5.9%, P < 0.001), and sinus arrest (SA, 7.4% versus 1.3%, P = 0.002). We found that NAFLD was closely associated with the occurrence of VT [unadjusted odds ratio (OR) 4.507, 95% confidence interval (CI) 2.263-8.974, P < 0.001] and SA (OR 6.186, 95%CI 1.643-23.291, P = 0.007). After adjusting for age, sex, body mass index, and other confounding factors, the above differences were still statistically significant (VT: OR 4.808, 95%CI 2.254-10.253, P < 0.001; SA: OR 9.589, 95%CI 2.027-45.367, P = 0.004).

NAFLD is associated with the occurrence of VT and SA in NSTEMI patients. It indicates that NAFLD might be a risk factor for malignant arrhythmias in post-NSTEMI patients.

There are several causes of heart failure during pregnancy and the peripartum period, which include peripartum cardiomyopathy, Takotsubo cardiomyopathy or stress cardiomyopathy, exacerbation of a preexisting cardiomyopathy, and acute myocarditis. It is important to determine the cause of the heart failure as the medical treatment may be different based on the diagnosis. However, it has been sometimes challenging to diagnose the cause because of the limited diagnostic tools, especially in pregnant women. Cardiac MRI can characterize myocardial injury and can be used to track the changes in myocardial tissue. We herein report a 35-year-old woman diagnosed with peripartum mid-ventricular-type Takotsubo cardiomyopathy, who was referred to our hospital due to worsening dyspnea the day after cesarean delivery. On admission, electrocardiography showed sinus tachycardia and poor progression of R waves in the precordial leads. Bedside echocardiography revealed severe hypokinesis in the mid- and apical left ventricle (LV) with a LV ejection fraction of 20%. Cardiac catheterization showed normal coronary arteries, and myocardial biopsy revealed contraction band necrosis. On acute phase (Day 4), cardiac MRI showed prolonged native T1 and T2, and severe hypokinesis and decreased regional longitudinal peak strain in the mid-anterior LV wall. During the 1^st week, precordial ST fluctuation was observed, and LV wall motion had gradually recovered. Repeat cardiac MRI revealed normalized LV wall motion and shortened values for global native T1 and T2. Thus, she was diagnosed with peripartum Takotsubo cardiomyopathy. Serial cardiac MRI may be able to differentiate Takotsubo cardiomyopathy during pregnancy and the peripartum period from other preexisting cardiomyopathies.

This study aims to explore the associations between uric acid (UA) and long-term outcomes among patients with acute coronary syndrome (ACS). A total of 1068 consecutive patients with ACS who underwent percutaneous coronary intervention (PCI) were analyzed retrospectively. The patients were divided into 3 groups based on the levels of serum UA upon admission (bottom quintile, middle 3 quintiles, and top quintile). The primary endpoint was all-cause mortality. The patients in the higher UA groups were associated with younger age (71 ± 11 versus 68 ± 12 versus 67 ± 14 years; P < 0.05) and were more likely to be male (57.6 versus 76.9 versus 84.7%; P < 0.001). Furthermore, these patients had lower estimated glomerular filtration rates (83 ± 27 versus 74 ± 23 versus 59 ± 24 mL/minute/1.73 m²; P < 0.001) and lower left ventricular ejection fractions (58 ± 14 versus 57 ± 14 versus 53 ± 15%; P < 0.001). During the median 4-year follow-up, there were 158 incidents of all-cause death. Patients in the top quintile, followed by patients in the bottom quintile, had greater all-cause mortality compared with patients in the middle quintile (16.5 versus 11.4 versus 23.8%; P < 0.001). When the middle of the 3 quintiles was assigned as the reference group, the adjusted hazard ratios for all-cause mortality for the top and bottom quintiles were 1.72 (95% confidence interval [CI] 1.16-2.53, P < 0.05) and 1.57 (95% CI 1.03-2.36, P < 0.05), respectively. These results demonstrate that UA levels upon admission in patients with ACS who underwent PCI exhibited a 'J-shaped' association with all-cause mortality.

Mutant cardiac ryanodine receptor channels (RyR2) are "leaky," and spontaneous Ca²⁺ release through these channels causes delayed afterdepolarizations that can deteriorate into ventricular fibrillation. Some patients carrying RYR2 mutations in type 1 catecholaminergic polymorphic ventricular tachycardia exhibit QT prolongation and are initially diagnosed with long QT syndrome. However, none have been reported to cause drug-induced ventricular fibrillation in patients with RYR2 variants. We describe the first case of an elderly woman with drug-induced QT prolongation and ventricular fibrillation who carried a novel RYR2 variant but no other mutations related to long QT syndrome. Oral adrenergic agents might induce QT prolongation and subsequent ventricular fibrillation in patients carrying an RYR2 variant. Screening for RYR2 could be valuable in patients with suspected drug-induced long QT syndrome.

Heart failure and frailty share aging as a strong risk factor. The prevalence of frailty has been shown to be particularly high in elderly patients with heart failure. Moreover, it is important not to confine frailty to physical aspects. Rather, it should be considered to consist of multiple domains, including physical disability, psychiatric disorders, cognitive impairment, depression, and social disconnection. Development of interventions that can improve frailty domains are not well established, although observational studies have evaluated the association of various frailty domains and their prognostic impact. Some interventions, including resistance exercise, functional exercise, and respiratory muscle training have been demonstrated to hold potential for improving physical frailty. In terms of cognitive dysfunction, previous studies have demonstrated that exercise therapy is also effective for cognitive dysfunction. The social domain of frailty is one of the least investigated domains, particularly in patients with heart failure. However, heart failure is also strongly associated with physical frailty and cognitive impairment and has a poor prognosis in old patients. The prevalence of social frailty in elderly patients who need hospitalization due to heart failure is higher than previously thought. Very few studies have tested interventions targeting social frailty. Frailty and heart failure affect each other, and both are becoming increasingly important in society. In this article, we review the physical, cognitive, and social domains of frailty and the possible interventions to improve them in patients with heart failure.

Electrical storm (ES), defined by 3 or more occurrences of ventricular arrhythmias within 24 hours, has been shown to be associated with an increased risk of mortality; however, detailed information remains lacking. We aimed to examine the incidence and determinants of ES and its impact on mortality in patients enrolled in the nationwide implantable cardioverter-defibrillator (ICD) registry.

We studied 1,256 patients (age 65 ± 12 years) who had structural heart disease with an ICD. The patients were classified into reduced ejection fraction (EF < 35%; 657 (52%) patients) and preserved or moderately reduced EF (EF ≥ 35%; 599 (48%) patients).

ES occurred in 49 (7%) and 36 (6%) patients in the EF < 35% and EF ≥ 35% groups (log-rank P = 0.297) during the median follow-up of 2.3 years. ICD with resynchronization therapy was associated with a lower incidence of ES in patients with EF < 35%. Non-ischemic heart disease and diuretics were associated with ES in patients with EF ≥ 35%. During the follow-up, 10/49 (20%) patients with ES and 80/608 patients (13%) without ES died in patients with EF < 35%, while 7/36 (19%) patients with ES and 38/563 patients (7%) without ES died in those with EF ≥ 35%. We have created 4 Cox multivariate models. All models showed approximately 2-fold higher hazard ratios in patients with EF ≥ 35% compared to EF < 35%.

Our study showed that the determinants of ES differed between EF < 35% and EF ≥ 35%. The impact of ES for mortality was numerically higher in EF ≥ 35% than in EF < 35%, although a significant interaction was not detected.

Erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, is a targeted drug used for the treatment of non-small cell lung cancer (NSCLC). Erlotinib is considered relatively safe and generally well-tolerated, with rarely reported cardiac side effects. Herein, we report a case of cardiomyopathy that developed during erlotinib treatment for NSCLC. Two months after erlotinib initiation, our 70 year-old female patient complained of progressive dyspnea, and a diagnostic endomyocardial biopsy confirmed non-specific cardiomyopathy, indicating erlotinib-induced cardiomyopathy. We believed that continued administration of erlotinib would exacerbate her heart failure, while treatment of the heart failure with intensive monitoring would allow the administration of erlotinib to be continued. This case report highlights the potential cardiotoxic effects of erlotinib and suggests the need for close clinical and echocardiographic follow-up of patients receiving erlotinib.

Heart rate modulation therapy using ivabradine improves mortality and morbidity in patients with systolic dysfunction. However, a target heart rate remains uncertain. Echocardiography-guided ivabradine therapy, in which we attempt to approach zero overlap between two diastolic filling inflow waves, has recently been proposed to maximize cardiac output, facilitate reverse remodeling, and reduce mortality and morbidity, instead of using an absolute value for the target heart rate. Prospective studies are needed to validate the clinical implication of these therapeutic strategies. Also, this concept should be expanded to other clinical scenarios.

The coronavirus disease 2019 (COVID-19) pandemic has changed the lives of healthcare professionals, especially vulnerable physicians such as young or female cardiologists. In Japan, they are facing the fear of not only infection but also weak and unstable employment, difficulties in medical practice and training anxiety, implications for research and studying abroad, as well as worsened mental health issues due to social isolation. Conversely, some positive aspects are seen through the holding of remote meetings and conferences. Here, we suggest a new working style for cardiologists, as well as offer solutions to the medical employment problems that have been taken place in Japan.