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.

Olanexidine gluconate 1.5% (Olanedine^®) is a colorless and transparent antiseptic agent introduced in 2015. In this study, we examined its usefulness and safety for cardiovascular catheterization and compared them to 10% povidone-iodine (PI). The study included 1,001 and 1,000 consecutively enrolled patients using Olanedine^® and PI, respectively [649 (PI, 687) males; mean age: 72.1 ± 9.6 (70.9 ± 9.6) years] who underwent cardiovascular catheterization [diagnostic cardiac catheterization: 624 (509) cases, percutaneous coronary intervention: 288 (390) cases, and endovascular treatment: 89 (101) cases]. Clinically, there were no significant differences in the backgrounds between the two groups. The amount of Olanedine^® used per case was approximately 20 mL. Blood tests were performed before and after catheterization. The presence or absence of discoloration on clothes containing cotton by Olanedine^® was also examined. One mild rash that disappeared within one day occurred in each of the two groups. Some blood tests before and after cardiac catheterization indicated significant differences, but they did not seem to be clinically relevant. The use of Olanedine^® in hemodialysis patients (117 cases) was uneventful. Its use in 37 patients with contraindications for ethanol disinfection was also uneventful. Although PI is extremely difficult to remove from white coats containing cotton, Olanedine^® did not cause any discoloration on clothes. This is the first report of cardiovascular catheterization using Olanedine^®. The efficacy and safety of Olanedine^® and PI seem to be equivalent. Olanedine^® could be a new useful option as a disinfectant of cardiovascular catheterization.

Obesity is assumed to be one of the robust risk factors for coronary artery disease. However, the effects of obesity on the progression of atherosclerosis in patients in different age groups after percutaneous coronary intervention (PCI) remain unclear. This study aimed to examine the effect of obesity on prognosis in different age groups.

Consecutive patients who underwent urgent or elective PCI were surveyed for this study and were then divided into the elderly group and middle-aged group with a cut-off age of 70 years. All patients underwent coronary angiography or coronary computed tomography angiography 1 year after PCI to examine the progression of atherosclerosis. The primary endpoint was revascularization for a new lesion within 2 years after PCI. In addition, the main effects and correlations between obesity and age were examined. Multivariate logistic regression analysis was conducted to identify independent predictors of non-target lesion revascularization (non-TLR).

Of the 711 patients who met the criteria and were available for follow-up analysis, the incidence of non-TLR within 2 years was 97/711 (13.6%). The higher incidence of non-TLR in patients with obesity was observed only in the middle-aged group. Furthermore, in the multivariate analysis, obesity was independently associated with non-TLR only in the middle-aged group.

The findings of the present study would enable us to construct the hypothesis that obesity in elderly patients may not be an independent predictor of the incidence of non-TLR, indicating that the management to prevent non-TLR may vary depending on the age of the patient.

The intracoronary drug provocation test has been the gold standard for diagnosis of coronary artery spasm (CAS); however, it has been identified with severe complications. In this study, we investigated the sensitivity, specificity, and safety of radial artery provocation test at different doses of ergonovine in the diagnosis of CAS. This study enrolled 57 patients, which were then divided into CAS group (n = 24) and control group (n = 33) after intracoronary ergonovine provocation test. All patients underwent radial artery provocation test at different doses of ergonovine. The predictive values of radial artery provocation test for the diagnosis of CAS were analyzed using receiver operator characteristic curve. In the radial artery provocation test at different doses of ergonovine, radial artery stenosis degree was all found to be significantly higher in the CAS group than in the control group (all P < 0.001). In the control group, significant differences were noted in the radial artery stenosis degree between different doses of ergonovine (all P < 0.05). In the CAS group, the radial artery stenosis degree was significantly higher in 160 μg and 100 μg of ergonovine than in 60 μg of ergonovine (all P < 0.001). The radial artery provocation test at 60 μg and 100 μg of ergonovine did not cause CAS, chest pain, and ECG ischemic changes. In the radial artery provocation test at 160 μg of ergonovine, some patients had CAS, chest pain, and ECG ischemic changes. The specificity and sensitivity of radial artery provocation test were 90.91% and 50.00% at 60 μg of ergonovine, 96.97% and 66.67% at 100 μg of ergonovine, and 90.91% and 95.83% at 160 μg of ergonovine for the diagnosis of CAS. As per our findings, we can conclude that the basic tension of radial artery increases in the CAS group. With the increase of ergonovine doses, its sensitivity and specificity improve, but its safety decreases. We will explore the most optimal dose of ergonovine in future studies.

Previous studies have indicated that low-dose new generation of P2Y12 receptor antagonists may be more suitable compared with clopidogrel at a standard dose for the dual antiplatelet therapy (DAPT) for East Asian patients receiving percutaneous coronary intervention (PCI). However, there remains no consensus in clinical practice. Thus, in this study, we aimed to determine the efficacy and safety of low-dose P2Y12 receptor antagonists, compared to clopidogrel at a standard dose, in DAPT in East Asian patients after PCI. We systematically searched literatures for randomized controlled trials (RCT) comparing low-dose P2Y12 receptor antagonists with standard-dose clopidogrel for the treatment of East Asian patients undergoing PCI. The endpoints of efficacy include major adverse cardiac events (MACEs), all-cause mortality, and the number of target vessel revascularization. The indicators of safety include major and minor bleeding events. Heterogeneity was evaluated by I² statistic test. Begg's and Egger's tests were used to evaluate publication bias. In total, 2,747 subjects from 8 RCT studies were included. Low-dose new P2Y12 receptor antagonists, that is, ticagrelor or prasugrel, showed significantly lower incidence of MACEs, as compared with standard-dose clopidogrel, in the East Asian patients who are in DAPT after undergoing PCI. Further, no difference was noted for the risk of major and minor bleeding events. In East Asian patients undergoing PCI and receiving DAPT, the use of low-dose P2Y12 receptor antagonists, ticagrelor or prasugrel, has been determined to be superior than clopidogrel at standard dose; this has been evidenced by a lower incidence of MACEs without increasing the risk of bleeding.

This study aimed to evaluate the concentration of plasma elabela (ELA) in patients with coronary heart disease (CHD) and its correlation with the disease classification.

We enrolled 238 patients diagnosed by coronary angiography as CHD and 86 controls. The CHD group was divided into three subgroups: stable angina (SA), unstable angina (UAP), and acute myocardial infarction (AMI). The plasma levels of ELA were measured in all participants and compared among different groups. The relationship between ELA and CHD classification was analyzed.

ELA levels were markedly higher by 10.71% in patients with CHD than in controls (P < 0.05). The concentration of ELA in UAP and AMI subgroups were higher than in controls and SA subgroup. The former difference was significant (P < 0.05), but the latter was not. In addition, the ELA concentration was not correlated with SYNTAX score, left ventricular ejection fraction, and other biochemical variables.

The newfound hormone, ELA, significantly increased in patients with UAP and AMI. There is a tendency that ELA levels might be correlated with CHD classification, but not with lesion severity. ELA may play a role in acute coronary syndrome.

The clinical outcomes in acute myocardial infarction (AMI) patients with Killip class 3 are often inconsistent with those in the literature, and the factors associated with poor outcomes have not been sufficiently investigated. The purpose of this study was to identify factors associated with in-hospital death in AMI patients with Killip class 3. We included 205 AMI patients with Killip class 3, and divided them into a survived group (n = 189) and in-hospital death group (n = 16). The primary objective was to identify factors associated with in-hospital death using multivariate analysis. Age was significantly younger in the survived group than in the in-hospital death group (73.1 ± 11.2 versus 83.2 ± 6.2 years, P < 0.001). Systolic blood pressure (SBP) was significantly higher in the survived group than in the in-hospital death group (150.0 ± 31.2 versus 124.8 ± 25.3 mmHg, P = 0.002). The prevalence of TIMI thrombus grade ≥ 2 was significantly greater in the in-hospital death group than in the survived group (56.3 versus 22.2%, P = 0.005). In multivariate logistic regression analysis, in-hospital death was significantly associated with age [odds ratio (OR) 1.168, 95% confidence interval (CI) 1.061-1.287, P = 0.002] and TIMI thrombus grade ≥ 2 (versus ≤ 1: OR 5.743, 95% CI 1.717-19.214, P = 0.005), and inversely associated with SBP on admission (per 10 mmHg increase: OR 0.764, 95% CI 0.613-0.953, P = 0.017). In conclusion, in-hospital death was associated with age and coronary thrombus burden, and was inversely associated with SBP on admission in patients with Killip class 3. It may be important to recognize these high risk features to improve the clinical outcomes of patients with Killip class 3.

Left atrial appendage (LAA) has been found to be associated with the occurrence of thromboembolism in patients with nonvalvular atrial fibrillation (NVAF). Stapling exclusion of LAA during surgical ablation could be an alternative to oral anticoagulation for NVAF patients. However, its safety and efficacy have rarely been examined. Thus, in this study, we aimed to evaluate the safety and efficacy of a powered surgical stapler for LAA resection during ablation for patients with NVAF.

Adult patients with NVAF undergoing stapler surgery were included in this study. LAAs of patients were cut off using a powered surgical stapler. Intraoperative transesophageal echocardiogram (TEE) was applied before and after the operation. Each patient received anticoagulant therapy for 2 months after surgery and was regularly followed up by appointment or via telephone call. Patients would undergo physical examinations, echocardiography, and 24-hour dynamic electrocardiogram in a local or in our hospital to determine whether there was a recurrence of atrial fibrillation (AF) or thromboembolism caused by AF.

In total, 124 patients were included in this study (male: 88 (71.0%); mean age: 62.3 years). Blood loss was less than 100 mL in all patients with no operative complications or hospital deaths. Moreover, 119 (96.0%) follow-up data were collected, with a mean period of 27.4 months. All patients discontinued oral anticoagulants 2 months after their operation. As per our findings, AF recurred in 23 patients (18.5%), with an average of 9.1 months after surgery. No patients were diagnosed with thromboembolism related to AF.

Stapling exclusion of LAA during surgical ablation could safely and completely resect the LAA. The effect of thrombus prevention was deemed satisfactory.

Radiofrequency catheter ablation (RFCA) for pulmonary artery ventricular arrhythmia (PAVA) can be difficult because of the occasional existence of PAVA with preferential conduction.

This study described the characteristics of PAVA that demonstrate preferential conduction.

We analyzed electrocardiographic and electrophysiological data from 8 patients found to have PAVAs with preferential conduction out of 183 patients (4.4%) with right ventricular outflow tract (RVOT) arrhythmias who underwent RFCA at our hospitals. The PAVA with preferential conduction were classified into two types. In type 1 PAVA, successful ablation sites (success-sites) exhibited discrete prepotentials with an isoelectric line, in which the activation time (AT) was ≥ 50 milliseconds. In type 2 PAVA, excellent pace mapping was achieved at two sites separated by ≥ 20 mm: one in the RVOT free wall and the other at the success-site in the pulmonary artery. Type 1 and 2 PAVA features were considered signs of a short and long preferential conduction pathway, respectively.

There were four patients each with type 1 and 2 PAVA. Type 1 PAVA was distinguished by the isoelectric line at success-sites with the mean AT of 78 ± 25.1 milliseconds. In type 2 PAVAs, although the AT at RVOT sites was very short (18.5 ± 10.1 milliseconds), the AT at success-sites was longer than that at the RVOT by 42.3 ± 36.2 milliseconds. Type 2 PAVAs displayed distinct electrocardiogram (ECG) features (R wave in lead I, RR′ in inferior leads, and transitional zone in V4) not found in typical PAVA ECGs.

PAVA with preferential conduction can manifest in distinct ways on the ECG and intracardiac mapping. Knowledge of these features may facilitate successful RFCA of such PAVA cases.

Whether deep sedation with intravenous anesthesia will affect the recurrence after cryoballoon ablation (CBA) of paroxysmal atrial fibrillation (AF) is yet to be examined. Thus, in this study, we hypothesize that there is difference in terms of the recurrence between local anesthesia and deep sedation with intravenous anesthesia after an index ablation procedure.

In total, 109 patients were enrolled and received CBA, of which 68 (58.2 years) patients underwent pulmonary vein (PV) isolation with a local anesthesia (group 1) and 41 patients (63.2 years) underwent PV isolation with deep sedation using intravenous anesthesia (group 2).

During the index procedure, isolation of all major PVs was achieved in 66 patients in group 1 and in 41 patients in group 2. There was no difference in non-PV triggers between the two groups. The periprocedural complication was found to be similar between the two groups (2.9% in group 1 and 4.9% in group 2). Further, 17 patients in group 1 and 4 patients in group 2 experienced recurrences after a follow-up of 19.3 months (P = 0.019). Repeat procedures revealed similar PV reconnection rates between the two groups. It has also been noted that the number of reconnected PV and incidence of atypical flutter seem to increase in group 1.

Deep sedation with intravenous anesthesia during CBA for paroxysmal AF is safe and had a better long-term outcome than those with local anesthesia.

Asymptomatic recurrences of atrial fibrillation (AF) have been found to be common after ablation.

A randomized controlled trial of AF screening using a handheld single-lead ECG monitor (BigThumb^®) or a traditional follow-up strategy was conducted in patients with non-valvular AF after catheter ablation. Consecutive patients were randomized to either BigThumb Group (BT Group) or Traditional Follow-up Group (TF Group). The ECGs collected via BigThumb were compared using the automated AF detection algorithm, artificial intelligence (AI) algorithm, and cardiologists' manual review. Subsequent changes in adherence to oral anticoagulation of patients were also recorded. In this study, we examined 218 patients (109 in each group). After a follow-up of 345.4 ± 60.2 days, AF-free survival rate was 64.2% in BT Group and 78.9% in TF Group (P = 0.0163), with more adherence to oral anticoagulation in BT Group (P = 0.0052). The participants in the BT Group recorded 26133 ECGs, among which 3299 (12.6%) were diagnosed as AF by cardiologists' manual review. The sensitivity and specificity of the AI algorithm were 94.4% and 98.5% respectively, which are significantly higher than the automated AF detection algorithm (90.7% and 96.2%).

As per our findings, it was determined that follow-up after AF ablation using BigThumb leads to a more frequent detection of AF recurrence and more adherence to oral anticoagulation. AI algorithm improves the accuracy of ECG diagnosis and has the potential to reduce the manual review.

Myocardial contrast echocardiography (MCE) and two-dimensional speckle tracking echocardiography (2D-STE) were used to detect left ventricular myocardial microcirculation perfusion and myocardial systolic function in dilated cardiomyopathy (DCM) and to explore the relationship between the two.

Conventional ultrasound, MCE, and 2D-STE examinations were performed on 30 patients and 30 controls. Left ventricular microcirculation perfusion, left ventricular longitudinal strain (GLS), and circumferential strain (GCS) were analyzed to further compare the correlation between left ventricular perfusion and myocardial strain parameters.

Regional myocardial perfusion was reduced in patients with DCM, manifesting as a decrease in the rising slope (A) of the mid-segment of the posterior septum, the peak intensity (PI) of the mid-segment of the anterior septum and the posterior septum, the apical segment of the lateral wall, the area under the curve (AUC) of the posterior septum, the basal segment of the posterior wall, the anterior septum, posterior septum, posterior wall, mid-segment of the lateral wall, and apical segment of the lateral wall and the overall average PI and AUC of the mid-segment, compared with that in the controls (P < 0.05). The left ventricular systolic function and the strain parameters GLS and GCS of DCM patients were lower than those of the controls (P < 0.001). Correlation analysis revealed a positive correlation between the A of the mitral valve and GCS (r = 0.372, P = 0.043), and MV-E/e' had a positive correlation with the AUC of the basal and intermediate segments (r = 0.379, P = 0.039; r = 0.404, P = 0.027).

In patients with DCM, regional myocardial microcirculation perfusion is reduced, and myocardial strain is impaired. Myocardial perfusion has a good positive correlation with myocardial mechanics.

Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) have been shown to prevent left ventricular remodeling and improve outcomes of patients with heart failure (HF). This study aimed to investigate whether the use of ACEi/ARB could be associated with HF with recovered ejection fraction (HFrecEF) in patients with dilated cardiomyopathy (DCM).

We collected individual patient data regarding demographics, echocardiogram, and treatment in DCM between 2003 and 2014 from the clinical personal record, a national database of the Japanese Ministry of Health, Labour and Welfare. Patients with left ventricular ejection fraction (LVEF) < 40% were included. Eligible patients were divided into two groups according to the use of ACEi/ARB. A propensity score matching analysis was employed. The primary outcome was defined as LVEF ≥ 40% at 3 years of follow-up.

Out of 5,955 patients with DCM and LVEF < 40%, propensity score matching yielded 830 pairs. The mean age was 58.8 years, and 1,184 (71.3%) of the patients were male. The primary outcome was observed more frequently in the ACEi/ARB group than in the no ACEi/ARB group (57.0% versus 49.3%; odds ratio 1.36; 95% confidence interval (CI) 1.12-1.65; P = 0.002). Subgroup analysis revealed that the use of ACEi and ARB was associated with recovery of LVEF regardless of atrial fibrillation. The change in LVEF from baseline to 3 years of follow-up was greater in the ACEi-ARB group (14.9% ± 0.6% versus 12.3% ± 0.5%; P = 0.001).

The use of ACEi/ARB is associated with HFrecEF in patients with DCM and reduced LVEF.

Management of constrictive pericarditis is often clinically challenging. Heart rate (HR) modulation using ivabradine is associated with improved clinical outcomes in patients with systolic heart failure, although it remains uninvestigated for other clinical purposes. We aimed to assess the impact of HR control in patients with constrictive pericarditis. In this retrospective study, consecutive patients who were diagnosed with constrictive pericarditis were included. Transthoracic echocardiography was performed at index discharge (day 0). The impact of HR difference between actual HR and ideal HR, which was calculated using a formula consisting of deceleration time, on heart failure readmission rates was investigated. A total of 15 patients (73 years old on median, 11 men) with constrictive pericarditis were included. On median, actual HR was 71 bpm and ideal HR was 81 bpm. Heart failure readmission rates were stratified into three groups by the HR difference: (1) optimal HR group satisfying "−10 bpm ≤ HR difference ≤ 10 bpm" (n = 4, 0.067 events per year); (2) lower HR group satisfying "HR difference < −10 bpm" (n = 7, 0.118 events per year, incidence rate ratio 1.98, 95% confidence interval 0.06-61.6); (3) higher HR group satisfying "HR difference > 10 bpm" (n = 4, 0.231 events per year, incidence rate ratio 9.22, 95% confidence interval 0.36-237.8). In conclusion, non-optimized HR was associated with an increased risk of heart failure recurrence in patients with constrictive pericarditis. Prospective assessment of deceleration time-guided HR optimization in patients with constrictive pericarditis is needed.

Ideal heart rate (HR), particularly for those with heart failure with preserved ejection fraction (HFpEF), remains unknown. We hypothesized that cardiac output would be maximum when the overlap between E-wave and A-wave at the trans-mitral flow is "zero" in the Doppler echocardiography. We retrospectively investigated the association among the overlap length between two waves, actual HR, and other echocardiographic parameters to construct a formula for estimating theoretically ideal HR among those with HFpEF. In total, 48 HFpEF patients were included (70-year-olds, 18 males). Given the results of multivariate linear regression analyses, the overlap length was estimated as follows: -1,050 + 8.4 × (HR [bpm]) + 0.6 × (deceleration time [millisecond]) + 1.7 × (A-width [millisecond]), which had a strong agreement with the actually measured overlap length (r = 0.86, P < 0.001). Theoretically ideal HR was calculated by substituting zero into the estimated overlap length as follows: 125 − 0.07 × (deceleration time [millisecond]) − 0.20 × (A-width [millisecond]). In the validation cohort including another 143 HFpEF patients, the estimated overlap using the formula again had a strong agreement with the actually measured overlap (r = 0.72, P < 0.001). In this study, we proposed a novel formula for calculating theoretically ideal HR, consisting of deceleration time and A-width, in the HFpEF cohort. Clinical implication to optimize the HR targeting the theoretically ideal HR should be investigated in prospective studies.

Liver stiffness (LS) assessed by ultrasound elastography reflects right-sided filling pressure and offers additional prognostic information in patients with acute decompensated heart failure (ADHF). However, the prognostic value of LS in heart failure (HF) with preserved ejection fraction (HFpEF) remains unclear. This study aimed to investigate the prognostic value of LS measured by two-dimensional shear wave elastography (2D-SWE) in patients with HFpEF.

We prospectively enrolled 80 patients hospitalized for decompensated HFpEF between September 2019 and June 2020. Patients were categorized into three groups based on the tertile values of LS at discharge.

The third tertile LS group had an older age; more advanced New York Heart Association functional class; higher total bilirubin, γ-glutamyl transferase (GGT), N-terminal pro-B type natriuretic peptide (NT pro-BNP), and Fibrosis-4 index; a larger right ventricle diastolic diameter, higher tricuspid regurgitation pressure gradient, and a larger maximal inferior vena cava diameter. During a median [interquartile range] follow-up period of 212 (82-275) days, 25 (31.2%) patients suffered composite end points (all-cause mortality and rehospitalization for worsening HF). The third tertile LS group had a significantly higher rate of composite end points (log-rank P = 0.002). A higher LS and the third tertile LS were significantly associated with the composite end points, even after adjusting for a conventional validated HF risk score and other previously reported prognostic risk factors.

Increased LS measured by 2D-SWE reflects the severity of liver impairment by liver congestion and fibrosis, underlying right HF, and provides additional information for the prediction of poor outcomes in HFpEF.

Liver dysfunction is one of the most recognized complications in patients with acute heart failure (HF) and therefore a liver function score may be useful for risk-stratification in those patients. Recently, the albumin-bilirubin (ALBI) score was developed as a new model to assess liver function in liver disease. We explored the association between the ALBI score at admission and in-hospital mortality in patients with acute HF.

We enrolled 262 patients (median age, 86 years, 137 males) who were admitted to our hospital for treatment of acute HF. The following data were recorded: vital signs, laboratory data including B-type natriuretic peptide (BNP) level, echocardiographic data at admission, demographic and clinical characteristics, and treatment and prognostic information. The Get With the Guidelines-Heart Failure (GWTG-HF) risk score was calculated as an established risk model for each patient. The primary outcome was all-cause in-hospital mortality.

During hospitalization, 37 patients (14.1%) died. The in-hospital mortality rate was significantly higher in patients with ALBI scores > -2.25 compared with patients with ALBI scores ≤ -2.25 (21.1% versus 4.5%, respectively; P = 0.0001). Multivariate analysis revealed that the GWTG-HF score (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.08-1.25, P < 0.0001), BNP level (OR 1.0007, 95% CI 1.0003-1.001, P = 0.0003) and ALBI score (OR 6.0, 95% CI 1.8-19.6, P = 0.0017) were independently associated with in-hospital mortality.

Our results indicated that the ALBI score was independently associated with in-hospital mortality in patients hospitalized for acute HF.

Chronic inflammation due to abdominal obesity plays a major role in the development of cardiovascular disease (CVD). Gender differences are well characterized in the development of CVD; however, in the association among abdominal obesity, chronic inflammation, and preclinical atherosclerosis, gender differences in the general population remain to be clarified. We retrospectively analyzed 1,163 subjects who underwent voluntary health checkups at our institute. We defined carotid artery plaque formation as carotid intima-media thickness ≥ 1.1 mm. Multiple regression analysis showed that waist circumference was a major independent predictor of increase in serum C-reactive protein (CRP) level in both men and women. Serum CRP level was significantly increased in men with carotid artery plaque formation, but not in women. Multivariable logistic regression analysis demonstrated that serum CRP level, as well as age and hypertension, was independently associated with carotid artery plaque formation only in men. This result may suggest a potential of gender-specific difference in the association between serum CRP level and the prevalence of carotid artery plaque formation. Further investigations are required to confirm our results and to clarify the underlying mechanism.

The DAPA-HF trial demonstrated that sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduced worsening heart failure (HF) events in chronic HF patients with or without type 2 diabetic mellitus (T2DM). However, it remains unclear whether the effectiveness of SGLT2i is also observed in patients with decompensated HF irrespective of HbA1c level. Eighty-one T2DM patients hospitalized due to decompensated HF were enrolled and divided into 2 groups according to their HbA1c levels (group H, HbA1c 6.9-13.0%, n = 41; group L, HbA1c < 6.9%, n = 40). After the initial management of HF, one of the SGLT2i (canagliflozin 100 mg/day or dapagliflozin 5 mg/day or empagliflozin 10 mg/day) was non-randomly administered, and clinical parameters associating with HF and T2DM were followed for 7 days. No symptomatic hypoglycemia was observed in any patient. In both groups, urine glucose excretion was increased significantly after the administration of SGLT2i. However, its amount was greater in group H than group L. Urine volume was increased significantly at day 1 in both groups. Urine volume returned to the baseline after one week in group L. In contrast, the increase in urine volume persisted at least for one week in group H. Of note, a decrease in B-type natriuretic peptide levels after the initiation of SGLT2i was observed in both groups similarly despite differences in urine output and excretion of urine glucose. In conclusion, SGLT2i can improve decompensated HF in patients with T2DM irrespective of the HbA1c level.

Cardiorenal syndrome (CRS) frequently occurs in end-stage heart failure patients waiting for heart transplantation (HT). Decision-making regarding simultaneous heart and kidney transplantation is an unresolved issue in these patients. We investigated clinical factors associated with renal outcome after HT. A total of 180 patients who received HT from 1996 to 2015 were included. Factors associated with early post-HT chronic kidney disease (CKD, estimated glomerular filtration rate [eGFR] < 60 mL/minute/1.73 m² within 1 year post-HT), post-HT end-stage kidney disease (ESKD), and significant renal function improvement (%ΔeGFR > 15%) at 1 year post-HT were analyzed. Early post-HT CKD and post-HT ESKD developed in 61 (33.9%) and 8 (4.4%) of 180 patients, respectively. Old age was only independently associated with early post-HT CKD and preexisting CKD tended to be associated with early post-HT CKD. Old age and preexisting CKD were independently associated with post-HT ESKD. Low pre-HT eGFR and preoperative renal replacement therapy were not associated with early post-HT CKD or post-HT ESKD. Young age, low pre-HT eGFR, and high %ΔeGFR 1 month post-HT were independently associated with significant renal function improvement. Preoperative renal function, including preoperative RRT, was not associated with post-HT mortality. In conclusion, preexisting CKD may impact renal outcomes after HT, but preoperative severe renal dysfunction, even that severe enough to require RRT, may not be a contraindication for HT alone. Our data suggest the necessity of early HT in end-stage heart failure patients with CRS and the importance of careful management during the early postoperative period.

The Fibrosis-4 (FIB4) index could indicate the liver fibrosis in patients with chronic hepatic diseases. It was calculated using the following formula: (age × aspartate aminotransferase [U/L]) / (platelet count [10³/μL] × √alanine aminotransferase [U/L]). However, the clinical impact of the FIB4 index in the acute phase of acute heart failure (AHF) has not been sufficiently investigated.

A total 1,468 AHF patients were analyzed. The median FIB4 index was 2.71 [1.85-4.22]. The patients were divided into three groups according to the quartiles of their FIB4 index (low-FIB4 [Q1, ≤ 1.847], middle-FIB4 [Q2/Q3, 1.848-4.216], and high-FIB4 [Q4, ≥ 4.216] groups). A Kaplan-Meier curve analysis showed that the prognosis, such as all-cause mortality and HF events within 365 days, was significantly poorer in the high-FIB4 group than in the middle-FIB4 and low-FIB4 groups. A multivariate Cox regression model identified high FIB4 index as an independent predictor of 365-day all-cause death (hazard ratio (HR): 1.660, 95% CI: 1.136-2.427) and HF events (HR: 1.505, 95% CI: 1.145-1.978). The multivariate logistic regression analysis showed that the high plasma volume status (PVS) (Q4, odds ratio [OR]: 2.099, 95% CI: 1.429-3.082), low systolic blood pressure (SBP) (< 100 mmHg, OR: 3.825, 95% CI: 2.504-5.840), and low left ventricular ejection fraction (< 40%, OR: 1.321, 95% CI: 1.002-1.741) were associated with a high FIB4 index.

A high FIB4 index can predict adverse outcomes in AHF patients, which indicate that congestive liver and liver hypoperfusion occur due to low cardiac output in the acute phase of AHF.

The monocyte to high-density lipoprotein cholesterol (HDL-C) ratio has been considered to be a prognostic marker. Whether this ratio is associated with left ventricular (LV) diastolic function remains undetermined. We tested the hypothesis that the monocyte to HDL-C ratio is associated with LV diastolic parameters derived from gated myocardial perfusion single-photon emission computed tomography (SPECT) in patients with no significant perfusion abnormality.

The study population included 196 patients with no significant perfusion abnormalities and preserved ejection fraction. The peak filling rate (PFR) and one-third mean filling rate (1/3 MFR) were obtained as LV diastolic parameters using gated SPECT. Monocyte counts and plasma HDL-C levels were also examined.

Significant associations were observed between the monocyte to HDL-C ratio and PFR (r = −0.20; P = 0.005) and 1/3 MFR (r = −0.19; P = 0.009). Multivariate linear regression analysis was performed to determine factors associated with LV diastolic parameters. Age (β = −0.27; P < 0.001), LV end-diastolic volume (β = −0.19; P = 0.034), and monocyte to HDL-C ratio (β = −0.15; P = 0.027) were determined to be significantly associated with PFR. Moreover, age (β = −0.13; P = 0.007), LV mass index (β = −0.18; P = 0.037), and the monocyte to HDL-C ratio (β = −0.13; P = 0.045) were significantly associated with 1/3 MFR.

These results demonstrated that the monocyte to HDL-C ratio is associated with LV diastolic function, as derived from gated SPECT in patients with no significant perfusion abnormality.

Little is known about the association between limb prognosis in peripheral artery disease and apolipoprotein E (apoE). We evaluated the long-term impact of apoE on adverse limb events in patients with intermittent claudication receiving statin treatment.

A total of 218 consecutive patients (mean age, 73 ± 8 years; 81% men) with intermittent claudication who underwent their first intervention between 2009 and 2020 were included in this study. All patients had achieved LDL-C < 100 mg/dL on statin treatment and were divided into two groups based on the apoE value (≥ 4.7 or < 4.7 mg/dL). We evaluated the incidence of major adverse limb events (MALEs), including vessel revascularization and limb ischemia development.

A total of 39 and 179 patients were allocated to the higher and lower apoE groups, respectively. Compared to the lower apoE group, the higher apoE group had a significantly higher total cholesterol level, triglyceride level, and non-high-density lipoprotein cholesterol level. During the median follow-up period of 3.6 years, 30 patients (13.8%) developed MALEs. Kaplan-Meier analysis revealed that the cumulative incidence of MALEs in the higher apoE group was significantly higher than that in the lower apoE group (44.0% versus 21.6%, log-rank test, P = 0.002). During multivariable Cox hazard analysis, higher apoE level (≥ 4.7 mg/dL) (hazard ratio, 2.61; 95% confidence interval, 1.18-5.70, P = 0.019) was the only strong independent predictor of MALEs.

ApoE levels could be a strong predictor and residual risk for long-term limb prognosis in patients with intermittent claudication and achieving LDL-C < 100 mg/dL with statin treatment.

The frequencies of autonomous bystander-initiated cardiopulmonary resuscitation (CPR) and public access defibrillation have not yet been clarified. We aimed to evaluate the frequency of autonomous actions by citizens not having a duty to act.

This retrospective observational study included patients who suffered an out-of-hospital cardiac arrest (OHCA) in Tokyo between January 1, 2013 and December 31, 2017. The Delphi method with a panel of 11 experts classified the locations of OHCA resuscitations into 3 categories as follows; autonomous, non autonomous, and undetermined. The locations determined as autonomous were further divided into 2 groups; home and other locations. Bystander-initiated CPR and application of an automated external defibrillator (AED) pad were evaluated in 43,460 patients with OHCA.

Group A (non autonomous), group B (autonomous, not home), and group C (home), consisted of 7,352, 3,193, and 32,915 patients, respectively. Compared with group A, group B and group C had significantly lower rates of bystander-initiated CPR (group A, B, C; 68.3% versus 38.6% versus 23.9%) and AED pad application (groups A, B, C; 26.8% versus 15.1% versus 0.6%). In addition, multivariate analysis demonstrated that an autonomous location of resuscitation was independently associated with the frequencies of bystander-initiated CPR and AED pad application, even after adjusting for age, sex, and witness status.

Autonomous actions by citizens were unacceptably infrequent. Therefore, the education and training of citizens is necessary to further enhance autonomous CPR.

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) reduces mortality and morbidity in patients with chronic heart failure (HF). However, the clinical implication of SGLT2i therapy in patients with acute decompensated HF remains uncertain. We prospectively studied 86 type 2 diabetic mellitus (T2DM) patients (71.8 ± 12.1 years, 55 men) who were hospitalized for acute decompensated HF and received SGLT2i during the index hospitalization. Among the patients, 56 continued SGLT2i at discharge and 30 did not. The continued group experienced fewer HF re-hospitalizations than the discontinued group (24% versus 39%, P = 0.008) with a hazard ratio of 0.29 (95% confidence interval 0.10-0.85) adjusted for other significant potential confounders. In conclusion, long-term SGLT2i therapy might prevent unplanned HF re-hospitalization in patients with T2DM and acute decompensated HF.

Long-chain noncoding RNA (lncRNA) is a new class of molecular regulators in heart development and disease. However, the role of specific lncRNA in cardiac fibrosis remains to be fully explored. This study aimed to investigate the role and potential mechanism of lncRNA MHRT in myocardial fibrosis after myocardial infarction (MI).

Cardiac fibroblasts (CFs) were isolated from a mouse model of MI. The expression levels of MHRT and miR-3185 in the hearts of MI and CFs mice treated with transforming growth factor beta 1 (TGF-β1) were analyzed by qRT-PCR. The collagen expression was assessed using qRT-PCR and Western blot. Cell proliferation was assessed by performing MTT and EdU assays. The direct interaction between lncRNA and miRNA was analyzed by luciferase assay, RNA-binding protein immunoprecipitation (RIP) assay, and RNA pull-down assay.

The expression levels of MHRT were raised in MI and CFs mice treated with TGF-β1. Overexpression of MHRT promoted collagen production and CF proliferation, while silencing of MHRT showed the opposite effect. MiR-3185 was a target gene of MHRT. In addition, overexpression of MHRT reduced the expression levels of miR-3185, and siMHRT reversed the inhibitory effect of TGF-β1 on the expression of miR-3185. Overexpression of miR-3185 inhibited the upregulation of Col I and Col III induced by TGF-β1.

MHRT promoted cardiac fibrosis after MI through miR-3185 and increased myocardial collagen deposition and promoted myocardial fibrosis.

Virus myocarditis (VMC) is a common cardiovascular disease and a major cause of sudden death in young adults. However, there is still a lack of effective treatments. Our previous studies found that calpain activation was involved in VMC pathogenesis. This study aims to explore the underlying mechanisms further. Neonatal rat cardiomyocytes (NRCMs) and transgenic mice overexpressing calpastatin (Tg-CAST), the endogenous calpain inhibitor, were used to establish VMC model. Hematoxylin and eosin and Masson staining revealed inflammatory cell infiltration and fibrosis. An ELISA array detected myocardial injury. Cardiac function was measured using echocardiography. CVB3 replication was assessed by capsid protein VP1. Apoptosis was measured by TUNEL staining, flow cytometry, and western blot. The endoplasmic reticulum (ER) stress-related proteins were detected by western blot. Our data showed that CVB3 infection resulted in cardiac injury, as evidenced by increased inflammatory responses and fibrosis, which induced myocardial apoptosis. Inhibiting calpain, both by PD150606 and calpastatin overexpression, could attenuate these effects. Furthermore, ER stress was activated during CVB3 infection. However, calpain inhibition could downregulate some ER stress-associated protein levels such as GRP78, pancreatic ER kinase-like ER kinase (PERK), and inositol-requiring enzyme-1α (IRE-1α), and ER stress-related apoptotic factors, during CVB3 infection. In conclusion, calpain inhibition attenuated CVB3-induced myocarditis by suppressing ER stress, thereby inhibiting cardiomyocyte apoptosis.

Calcium antagonists are used for coronary spastic angina (CSA) treatment. We previously identified a phospholipase C (PLC) -δ1 gene variant that results in enhanced PLC activity in patients with CSA and developed a CSA animal model by generating vascular smooth muscle cell-specific human variant PLC-δ1 overexpression (PLC-TG) mice. In this study, we investigated the molecular mechanism of CSA using the PLC-TG mice and the inhibitory effect of a calcium antagonist, diltiazem hydrochloride (DL).

We treated the PLC-TG and wild-type (WT) mice with oral DL or trichlormethiazide (TM) (control) for 2 weeks. Ergometrine injection-induced coronary spasm was observed on the electrocardiogram in all 5 PLC-TG mice treated with TM, but only in 1 of 5 PLC-TG mice treated with DL. Voltage-dependent calcium channel (Cav1.2) phosphorylation and protein kinase C (PKC) activity were enhanced in the aortas of PLC-TG mice treated with TM. DL treatment significantly inhibited Cav1.2 phosphorylation and PKC activity. Although total Cav1.2 expression was similar between WT and PLC-TG mice treated with TM, DL treatment significantly increased its expression in PLC-TG mice. Furthermore, its expression remained high after DL discontinuation. DL and PKC inhibitor suppressed intracellular calcium response to acetylcholine in cultured rat aortic smooth muscle cells transfected with variant PLC-δ1.

These results indicate that enhanced PLC activity causes coronary spasm, presumably via enhanced Cav1.2 phosphorylation and PKC activity, both of which were inhibited by DL. Enhanced total Cav1.2 expression after DL discontinuation and high PKC activity may be an important mechanism underlying the calcium antagonist withdrawal syndrome.

An early repolarization (ER) pattern or J waves are considered to be a benign finding observed in the healthy population, however, it has been pointed out that the ER pattern seen in the inferolateral leads could be an independent risk factor for fatal arrhythmias. We present a pediatric case in which early repolarization syndrome (ERS) was suspected due to the presence of ER or J waves in the inferior leads, which eventually disappeared after the administration of pilsicainide. During the follow-up period, several fatal ventricular arrhythmias were recorded after implantation of a subcutaneous implantable cardiac defibrillator (S-ICD). This report describes the efficacy of S-ICDs in a child with an ER pattern after aborted sudden cardiac death.

A case of J wave syndrome with ventricular fibrillation (VF) storm and severe hypercalcemia due to primary hyperparathyroidism is presented. VF storm subsided with an isoproterenol infusion. Prominent J waves and a Brugada-like electrocardiogram pattern disappeared after parathyroidectomy. Ventricular tachyarrhythmia was not induced during an electrophysiological study. The patient remained asymptomatic up to the 12-month follow-up.

A 70-year-old female with dextrocardia with situs inversus (DSI) totalis and inferior vena cava occlusion underwent radiofrequency catheter ablation because she had symptomatic paroxysmal atrial fibrillation (AF). Careful preoperative examination made successful pulmonary vein isolation through the left jugular vein approach. One-year later, however, AF recurred, and symptomatic sinus bradycardia or junctional bradycardia often occurred. Then, the pacemaker was implanted. We here reported a rare case of congenital abnormality, DSI with inferior vena cava occlusion who had undergone successful pulmonary vein isolation and pacemaker implantation without any complications.

Sacubitril/valsartan improves mortality and morbidity in patients with heart failure with reduced ejection fraction. However, its impact on right heart failure remains unknown. We experienced a 70-year-old man who was started on sacubitril/valsartan to treat his right heart failure with moderate tricuspid regurgitation. Following the 3-month sacubitril/valsartan treatment, a functional and geological improvement was observed in the right heart as well as amelioration of his congestive symptoms. Sacubitril/valsartan might improve right heart failure in addition to conventionally-proven left heart failure. Further large-scale studies are warranted to validate our findings.

Spontaneous spinal epidural hematoma (SSEH) is considered to be a relatively rare disease that can result in serious neurological sequelae. The pathogenesis and risk factors of SSEH are still unknown, and its differential diagnosis varies widely. Misdiagnosis with more common conditions such as stroke or aortic syndromes can occur. We report the case of a 27-year-old man who developed sudden upper back pain with no specific precipitant. Five days later, he visited our emergency department complaining of weakness in both lower limbs and dysuria. He had a history of intracardiac repair and a Blalock-Park procedure for an interrupted aortic arch and ventricular septal defect in infancy. Additionally, he had undergone an aortic root dilatation and aortic valve replacement at the age of 10 because of progression of aortic and supra-aortic stenosis and had received chronic anticoagulation and antiplatelet therapy with warfarin and aspirin, respectively. An emergency spine magnetic resonance imaging scan indicated a mass at the Th3-Th5 level with severe compression of the dural sac and the spinal cord. Emergency excision showed a spinal epidural hematoma. Mild postoperative gait disturbance and dysuria persisted, requiring rehabilitation and intermittent self-urethral catheterization. As patients with adult congenital heart disease have an increased risk of bleeding, they may be at risk of developing SSEH. However, this is the first report to describe such an association.

A pulmonary artery (PA) aneurysm is an extremely rare condition that can be idiopathic or secondary. Only a few reports on giant PA aneurysms associated with chronic thromboembolic pulmonary hypertension (CTEPH) are available in the literature. Here, we present a case of CTEPH associated with a secondary giant PA aneurysm detected by autopsy. A 68-year-old woman was diagnosed with pulmonary hypertension (PH) and a PA aneurysm with a diameter of 7.5 cm 7 years before admission. CTEPH was suspected as the cause of PH; however, she refused to undergo surgical treatment. Although her condition improved temporarily with pulmonary vasodilators, she had recurrence of heart failure and died because of the deterioration of her general condition. An autopsy revealed a giant PA aneurysm without medial degeneration, suggesting a secondary PA aneurysm associated with PH. Histological findings indicated multiple organized thrombi with recanalization in the PA bilaterally, and CTEPH was diagnosed as the cause of PH. Although rare, when a PA aneurysm is detected, it is important to consider that CTEPH might be associated with a giant PA aneurysm. A better understanding of this condition is necessary to improve the therapeutic strategy.

Extrinsic compression of the left atrium (LA) due to esophageal achalasia has been considered a rare occurrence. Patients might present with dysphagia, dyspnea, and even hemodynamic compromise simultaneously. Prompt detection with a thorough differential diagnosis is crucial for subsequent management. In this case report, we present a patient with LA compression by esophageal achalasia and performed a literature review to gather information as regards the clinical manifestation, diagnosis, and treatment strategy of this rare disease.

A 59-year-old man with intermittent palpitation, heartburn sensation, and difficulty swallowing came to our emergency department due to acute onset of chest compression and breathlessness after a large meal. As per his chest X-ray, dilated mediastinum and small gastric bubble were noted. Electrocardiogram implied left atrial enlargement, and the Holter monitor reported one episode of paroxysmal atrial fibrillation attack during his meal. Transthoracic echocardiogram showed a round-shaped, well-bordered, hyperechogenic, and heterogeneous mass compressing the LA irrespective of the systolic or diastolic phase. A chest contrast-enhanced computed tomography scan was then performed, wherein it showed diffuse esophageal dilatation with a smoothly thickening wall aligned compressing the LA. Meanwhile, the barium swallow esophagogram revealed contrast pooling at the esophagogastric junction with a bird beak shape. Accordingly, extrinsic compression of LA by esophageal achalasia was diagnosed.

Esophageal achalasia compressing LA has been considered rare. Remarkably, given that a patient is presenting with dysphagia and concurrent chest tightness, palpitation, and dyspnea after swallowing food, the clinicians should keep this diagnosis in mind. Careful history review to clarify the causal relationship between the symptoms, specific findings on electrocardiogram and chest X-ray, and utilization of echocardiography and esophagography are beneficial for a prompt and accurate diagnosis.