Background: The optimal device for mechanical circulatory support (MCS) in patients with acute myocardial infarction (AMI) complicated with cardiogenic shock (CS) remains unknown. Therefore, in this study we aimed to analyze which MCS (intra-aortic balloon pumping (IABP) or IMPELLA) is associated with better outcomes in patients with AMI-related CS.

Methods and Results: This systematic review and meta-analysis used a random-effects model to account for potential heterogeneity. Risk ratios (RRs) and 95% confidence intervals (CIs) were used for the dichotomous outcomes. The PubMed, Web of Science, and CENTRAL databases were searched up to April 30, 2023. The risk of bias was evaluated using the Revised Cochrane risk-of-bias tool for randomized trials (RoB2) tool, and the certainty of evidence was evaluated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. Two randomized controlled trials were included in the meta-analysis. For the primary outcome of 30-day survival, IMPELLA probably improves the outcome by a small amount compared with IABP (RR0.94 [95% CI 0.5–1.53], 29 fewer per 1,000 [95% CI from 204 fewer to 258 more], low certainty of evidence).

Conclusions: We could not show a survival benefit of IMPELLA compared with IABP in patients with AMI complicated by CS. Further investigation is required to resolve this issue.

Background: Point-of-care (POC) cardiac troponin testing, although less sensitive than high-sensitivity cardiac troponin assays, allows for rapid bedside evaluation. This study assessed the diagnostic performance of POC troponin tests for both ruling in and ruling out acute myocardial infarction (AMI) at the time of patient presentation.

Methods and Results: In accordance with PRISMA-DTA guidelines, we conducted a systematic review and meta-analysis using PubMed, Web of Science, and the Cochrane Library from inception through June 17, 2023. We included all studies evaluating the diagnostic accuracy of POC troponin assays for identifying AMI among adult patients. Among the 551 studies initially screened, 6 met the eligibility criteria for inclusion. A meta-analysis of diagnostic accuracy based on these 6 observational datasets demonstrated pooled sensitivity and specificity values of 47% (95% confidence interval (CI) 45–49%) and 90% (95% CI 89–90%), respectively, for AMI detection. In a subgroup meta-analysis of non-ST-segment elevation MI using 4 observational datasets, the pooled sensitivity and specificity were 48% (95% CI 45–50%) and 89% (95% CI 89–90%), respectively.

Conclusions: These findings emphasize that the clinical application of POC troponin assays in AMI diagnosis must consider the test’s robust specificity (≈90%) alongside its limited sensitivity (<50%).

Background: The Navitor valve shows excellent valve function and high deliverability. However, valve pop-up during valve implantation remains a concern.

Methods and Results: We defined pop-up as an upward valve dislocation ≥3 mm after implantation. Pop-up occurred in 13 (19%) of 67 patients, with 2 (3.0%) patients requiring a second valve. The depth ratio between non- and left-coronary cusp side at the 80% release and aortic valve calcification score were identified as predictors of valve pop-up.

Conclusions: Pop-up of the Navitor valve occurred in 19% of patients. Inconsistent valve depth and severe leaflet calcification were predictors of valve pop-up.

Background: This study aimed to assess the accuracy and intra-operator reproducibility of ischemia assessments from coronary angiography, as performed by interventional cardiologists, and its influence on treatment strategies.

Methods and Results: Twenty-two interventionalists predicted fractional flow reserve (predFFR) from 194 angiograms obtained from patients with single-vessel disease in the Objective Randomized Blinded Investigation with Optimal Medical Therapy of Angioplasty in Stable Angina (ORBITA) study. For each case, respondents selected either angio-guided percutaneous coronary intervention (PCI), medication, or a physiology-guided approach. Respondents were divided into high- and low-physiology-use groups based on the frequency of selecting physiology-guided treatment. Physiological strategies were chosen for 60.3% and 23.9% of the cases in the high and low groups, respectively. Correlations between predFFR and measured FFR values were weak (r=0.451; P<0.001), with 84.7% agreement for fractional flow reserve ≤0.80 and 75.0% for severity classification. Intra-operator agreement for treatment strategy in duplicate cases was 76.9%. Bland–Altman analysis showed considerable variability in repeated predFFR estimations (limits of agreement −0.16 to +0.15), exceeding thresholds considered acceptable in clinical practice. Although the diagnostic concordance was similar, the low group made more inappropriate treatment decisions, notably selecting PCIs for non-ischemic lesions, and more often opted for medication in truly ischemic patients compared with the high group (P<0.001).

Conclusions: Visual prediction of ischemia from angiography is limited in accuracy and reproducibility. Physiological assessment remains essential for determining the appropriate treatment.

Background: Risk scores have been developed to determine the treatment strategies and predict the prognosis of acute coronary syndromes (ACS). It remains unclear whether risk score-guided management improves prognosis. Therefore, this systematic review aimed to evaluate whether the use of risk scores to assess the acute severity of illness affects the prognosis of adult patients with ACS.

Methods and Results: We conducted a systematic review and meta-analysis to evaluate whether risk score-guided management improves clinical outcomes in patients with ACS. We searched MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science up to November 30, 2024, and included randomized controlled trials comparing risk score-based care with standard care. Two cluster randomized trials, using the Global Registry of Acute Coronary Events risk score (GRS), were identified, with a total of 5,368 patients. A systematic review adjusted for clustering revealed no significant differences in clinical outcomes, including in-hospital and 1-year mortality, in-hospital cardiac arrest, in-hospital recurrent ischemia, in-hospital and 1-year heart failure, and early invasive angiography.

Conclusions: Risk score-guided management of patients with ACS using risk scores, particularly the GRS, did not consistently lead to improved clinical outcomes. Further research is needed to assess whether risk score-guided management can improve patient outcomes.

Background: Inotropes play a significant role in the treatment of cardiogenic shock (CS). Phosphodiesterase 3 inhibitors (PDE3i) are being used with increasing frequency, despite limited supporting evidence.

Methods and Results: We performed a systematic review to assess the clinical importance of PDE3i in CS. The search included studies that compared the effect of ‘PDE3i with or without inotropes’ with ‘No PDE3i with or without inotropes’ in patients with cardiogenic shock. Early death, cardiac arrest, and initiation of renal replacement therapy were assessed as outcomes. We identified 2 randomized controlled trials (RCT) with a total of 224 patients who met the eligibility requirements from the PubMed, Web of Science, and CENTRAL databases, up until October 31, 2024. One RCT compared milrinone with dobutamine (DOB), and another compared enoximone with levosimendan. Meta-analysis revealed that PDE3i were neither superior nor inferior for the outcomes in the total cohort (odds ratio [OR] 1.47, 95% confidence interval [CI] 0.35–6.26 for early deaths; OR 1.14, 95% CI 0.42–3.14 for cardiac arrest; OR 1.53, 95% CI 0.80–2.92 for the initiation of renal replacement therapy).

Conclusions: The present systematic review revealed no difference in outcomes, early deaths, cardiac arrest and initiation of renal replacement therapy when using PDE3i in patients with CS treated with or without other inotropes.

Background: Patients with endstage kidney disease undergoing hemodialysis (HD) have higher risks of ischemic and bleeding events after percutaneous coronary intervention (PCI). However, the association between high platelet reactivity (HPR) and clinical events in dialysis patients remains unclear. This post hoc analysis of the PENDULUM registry examined the relationships of HPR with major adverse cardiac and cerebrovascular events (MACCE) and major bleeding in dialysis patients.

Methods and Results: Based on P2Y₁₂reaction unit (PRU) levels, patients were stratified into HPR (PRU >208) and non-HPR (PRU ≤208) groups. Clinical events were assessed up to 30 months after the index PCI. A total of 6,266 patients were enrolled. Of the 5,907 patients with available PRU data, 357 were dialysis patients (HPR, n=199; Non-HPR, n=158), and 5,550 were non-dialysis patients (HPR, n=2,030; Non-HPR, n=3,520). Dialysis patients had significantly more frequent MACCE and major bleeding than non-dialysis patients. In non-dialysis patients, MACCE, but not bleeding events, were significantly more common in the HPR subgroup. However, in dialysis patients, no significant association was found between HPR and both MACCE and major bleeding.

Conclusions: HPR was not associated with increased risks of MACCE and major bleeding in dialysis patients.

Background: The number of adult congenital heart disease (ACHD) patients is rising due to advancements in surgery and medical treatment for congenital heart disease (CHD) during childhood. However, acute treatment and stroke prevention measures in ACHD patients have been insufficiently assessed. To address this insufficiency, we conducted a retrospective single-center investigation of the clinical characteristics of ACHD patients who experienced stroke.

Methods and Results: We studied adult patients with acute stroke hospitalized within 7 days of onset between January 2011 and March 2017. Among 4,837 adults with stroke, 22 (0.5%) had CHD, including 19 with ischemic stroke and 3 with intracerebral hemorrhage. Compared with the non-CHD group, the ACHD group was younger (median age 56 vs. 75 years; P<0.01), had a higher incidence of large vessel occlusion (LVO; 53 vs. 24%; P=0.01), and exhibited more favorable functional outcomes at discharge (median modified Rankin scale 2 vs. 3; P=0.03). Atrial septal defect (ASD) was the most common underlying CHD, accounting for 55% of cases.

Conclusions: ACHD patients with acute stroke were significantly younger and more frequently developed LVO compared with the general stroke population, with ASD being the most common type of CHD. Despite their favorable short-term prognosis, these characteristics must be considered to implement effective acute treatment and prevention strategies.

Background: Chronic obstructive pulmonary disease (COPD) is a known risk factor for aortic aneurysm (AA) enlargement and rupture. This study investigated the effects of clarithromycin (CAM) and montelukast (Mont), which are medications used to treat COPD, on AA progression in a murine model of COPD.

Methods and Results: Apolipoprotein E-deficient mice, aged 28–40 weeks, were infused with angiotensin II by osmotic pumps to induce AA formation. Some of them received COPD induction through a single dose of porcine pancreatic elastase via the trachea. Mice were divided into 3 groups: AA (n=16; AA only, treated with saline); AA-C (n=10; AA and COPD, treated with saline); and AA-Cm (n=10; AA and COPD, treated with CAM and Mont). CAM and Mont were administered orally on a daily basis. After 28 days, aortic diameter, elastin content, matrix metalloproteinase (MMP) activity, and inflammatory markers were evaluated. The AA-C group exhibited significantly larger aneurysm diameter than the AA group (2.41 vs. 1.97 mm; P<0.05). Compared with the AA-C group, the AA-Cm group had higher elastin content (46.8 vs. 32.3%; P<0.01), decreased TNF-α level (115.5 vs. 141.0 pg/mL; P<0.05), reduced MMP-9 activity (54.8 vs. 75.4 pg/mL; P<0.01), and lower M1/M2 macrophage ratio.

Conclusions: CAM and Mont attenuate AA progression in COPD by reducing inflammation, preserving elastin, and increasing infiltrated M2 macrophages, suggesting they have a therapeutic potential.

Background: Prolonged exposure to high low-density lipoprotein cholesterol (LDL-C) levels may be associated with arteriosclerosis progression. This study investigated whether the running average of LDL-C (Ra-LDL-C) measured after percutaneous coronary intervention (PCI) was associated with the occurrence of subsequent cardiovascular events.

Methods and Results: The clinical records of 1,761 patients who underwent successful PCI were examined retrospectively. Ra-LDL-C values were calculated by adding consecutive LDL-C values and averaging them. Based on the Ra-LDL-C over an observation period of up to 10 years after PCI, patients were divided into 3 groups: Ra-LDL-C <70, 70–100, and ≥100 mg/dL. The incidence of major adverse cardiovascular events (MACE; defined as coronary-related death, myocardial infarction, and new coronary stenosis of non-culprit lesions) was investigated in these groups. Kaplan-Meier analysis demonstrated that the incidence of MACE was significantly lower in the Ra-LDL-C <70 mg/dL group than in the other 2 groups. Multivariate analysis indicated that the Ra-LDL-C was significantly correlated with the incidence of MACE. Furthermore, the incidence of MACE was significantly lower among patients with Ra-LDL-C values lower than LDL-C values 3 months after PCI.

Conclusions: High Ra-LDL-C values are a predictor of increased recurrence of MACE after PCI, and long-term management of LDL-C using Ra-LDL-C values may be useful for preventing cardiovascular disease.

Background: Elevated pulmonary arterial pressure (PAP) is associated with poor prognosis in patients with functional mitral regurgitation (MR) undergoing transcatheter mitral valve repair (TMVr). Nitric oxide (NO) inhalation therapy reduces PAP and pulmonary vascular resistance (PVR) after open-heart surgery, but its efficacy in patients with pulmonary hypertension (PH) undergoing catheter intervention remains unclear.

Methods and Results: This open-label, interventional, randomized controlled trial will investigate the efficacy of NO inhalation therapy after TMVr for MR complicated by PH. A total of 40 patients aged ≥18 years diagnosed with PH (mean PAP >20 mmHg) during preoperative right heart catheterization and scheduled for TMVr for MR are included in this study. Patients receiving pulmonary vasodilators, with NO contraindications, and with unstable conditions requiring intravenous catecholamines or mechanical circulatory support devices are excluded. Eligible patients are randomly allocated to the NO inhalation or control group in a 1 : 1 ratio. NO (20 ppm) is administered post-TMVr (D0) until the day after TMVr (D1). The control group is administered oxygen as necessary. The primary endpoint is the change in PVR (baseline to D1). The secondary endpoints include changes in cardiac index and mean PAP (baseline to D1), changes in PVR immediately before NO administration post-TMVr to D1, and postoperative complication rates.

Conclusions: This study will assess the efficacy of NO inhalation in patients with PH undergoing TMVr for MR.

Background: Several antiarrhythmic agents, including amiodarone (AMD) and nifekalant (NIF), are used in the management of life-threatening arrhythmias such as ventricular fibrillation (VF) and ventricular tachycardia (VT). Although a few studies have compared the antiarrhythmic effect of NIF and AMD, most have focused on termination or defibrillation of VF/VT. In this meta-analysis, we aimed to assess the current evidence on the preventive effects of NIF and AMD on recurrent VF and electrical storm (ES).

Methods and Results: The protocol was registered in PROSPERO (CRD42024578486). PubMed (MEDLINE and PMC), Cochrane Central Register of Controlled Trials (CENTRAL), Science Citation Index Expanded, and Igaku Chuo Zasshi were searched for observational studies and randomized controlled trials evaluating patients with cardiac arrest due to recurrent VF and ES treated with AMD or NIF, published before 28 August 2024. The primary endpoint was the recurrence of VF/VT. Secondary outcomes included short-term death and incidence of torsades de pointes (TdP). 5 eligible studies comprising 222 participants were included. Evidence regarding differences between NIF and AMD in the recurrence of VF/VT, short-term death, and incidence of TdP was of very low certainty and remains highly uncertain.

Conclusions: NIF and AMD may have little to no difference in preventing the recurrence of VF/VT, short-term death, or incidence of TdP; however, the certainty of the evidence is very low.

Background: Immune checkpoint inhibitors (ICIs) enhance T-cell activity against cancer, but can cause immune-related adverse events, including myocarditis, a rare yet potentially fatal complication. Cardiac troponin I (cTnI) is widely used for screening the development of myocarditis, but its efficacy remains uncertain.

Methods and Results: From January 2016 to June 2024, we conducted a single-center retrospective study of 468 cancer patients receiving ICI therapy. Serum cTnI levels were assessed at baseline, at 1, 3, 6, 9, 12 months, and every 4 months. During the follow-up period, 26 patients (5.6%) exhibited cTnI elevation. This group had a higher prevalence of breast cancer, higher baseline cTnI levels, lower estimated glomerular filtration rates, and a greater proportion of concomitant ipilimumab and nivolumab use. Multivariate analysis revealed that high baseline cTnI levels and concomitant ipilimumab and nivolumab use were independent predictors of cTnI elevation. Of the 26 patients with elevated cTnI, 4 developed myocarditis, requiring steroid therapy, and exhibited a progressive increase in cTnI levels, whereas the remaining 22 patients without myocarditis did not show such an increase.

Conclusions: Occasional cTnI elevation occurs during ICI therapy. However, a marked and sustained increase in cTnI levels may be a sign of the development of myocarditis.

Background: Difficulties opening plastic bottles may be associated with muscle weakness. We investigated association between the ability to open plastic bottles and muscle weakness, and determined cut-off values for and sex-related differences in handgrip strength and pinch strength associated with opening plastic bottles in patients with coronary artery disease (CAD).

Methods and Results: This cross-sectional study enrolled 224 consecutive patients with CAD who underwent in-hospital cardiac rehabilitation. Multiple linear regression analyses was used to determine the association between the ability to open plastic bottles and muscle weakness, with cut-off values for handgrip strength, lateral pinch strength, and 3-fingered pinch strength required to open plastic bottles determined by receiver operating characteristic curve analyses. Multiple linear regression showed that the ability to open plastic bottles was independently associated with handgrip, lateral pinch, and 3-fingered pinch strength after adjusting for confounders. Areas under the curves for all patients were 0.96 (95% confidence interval [CI] 0.93–0.99), 0.91 (95% CI 0.83–0.99), and 0.93 (95% CI 0.88–0.99) for handgrip, lateral pinch, and 3-fingered pinch strength, respectively, with corresponding cut-off values of 20.0, 7.1, and 6.1 kgf.

Conclusions: The ability to open plastic bottles was independently associated with handgrip strength and pinch strength in patients with CAD. Evaluating the ability to open plastic bottles may be a simple and practical tool for assessing muscle weakness in patients with CAD.

Heart failure with preserved ejection fraction (HFpEF) is becoming increasingly prevalent in aging societies. A recent multicenter cohort study in Japan demonstrated that cardiac rehabilitation (CR) significantly improves the prognosis of patients with HFpEF and frailty. The 2025 Japanese Heart Failure Guidelines recommend pharmacologic therapies for HFpEF. Recent international trials have led to the adoption of sodium-glucose transporter 2 inhibitors and angiotensin-receptor-neprilysin inhibitors in Japan, supported by evidence showing reduced rates of heart failure readmission. However, it should be noted that the majority of patients enrolled in those trials were in their early 70s. In real-world clinical practice, the number of patients in their 80s and 90s receiving treatment is increasing. This older population is more susceptible to adverse effects such as orthostatic hypotension, hyperkalemia, and urinary tract infections. Polypharmacy further complicates medication management. In such cases, CR plays a vital role in maintaining quality of life and supporting long-term prognosis. Furthermore, HFpEF is frequently accompanied by comorbidities such as atrial fibrillation, hypertension, and ischemic heart disease. It is important to note that elderly patients are also susceptible to additional conditions, including cerebrovascular disease, musculoskeletal disorders and malignancies. A multidisciplinary approach to CR, tailored to these complex health profiles, is essential to prevent the progression of functional decline and frailty.

Background: Although tafamidis is used in patients with wild-type transthyretin cardiac amyloidosis (ATTRwt-CM), the effects of β-blockers, one of the conventional heart failure medications, are unclear. Therefore, this study aimed to investigate the effect of β-blockers on left ventricular function using speckle-tracking echocardiography after 1 year of treatment in patients with ATTRwt-CM.

Methods and Results: We included 46 patients (median age, 78 years) with ATTRwt-CM confirmed via biopsy. We analyzed laboratory and echocardiographic data, including global longitudinal strain (GLS) to determine left ventricular strain, using 2D speckle-tracking echocardiography and compared the changes in these parameters before and 1 year after treatment with tafamidis between 24 patients who did not receive β-blockers and 22 patients who received β-blockers. The absolute GLS deterioration was higher in patients taking β-blockers by a mean of 0.48±1.55% compared with −0.68±1.65% in patients not taking β-blockers (P=0.0181). However, other conventional heart failure medications showed no change in the GLS.

Conclusions: Left ventricular function may deteriorate with the use of β-blockers in patients with ATTRwt-CM treated with tafamidis for 1 year.

Background: Systemic and cardiac metabolic disorders play a key role in patients with heart failure (HF). Fibroblast growth factor 21 (FGF21) is mainly secreted from the liver and has various effects on cardiomyocytes, including protection against oxidative stress, cardiac hypertrophy, and inflammation. However, the pathophysiologic and prognostic impact of FGF21 remains unknown.

Methods and Results: Serum levels of FGF21 and echocardiography were performed in patients with compensated HF (n=162) and control patients without HF (n=20). Compared with the control patients, those with HF displayed higher FGF21 levels (100 [76–213] vs. 237 [135–575] pg/mL; P=0.0006). There were no or modest correlations of FGF21 levels with clinical variables and echocardiographic parameters. During a median follow up of 12.0 months, there were 56 primary composite endpoints of all-cause death or HF hospitalization in the HF cohort. The highest FGF21 tertile was associated with a 3-fold increased risk of the composite outcome compared with the lowest tertile. After adjusting for age, sex, and the presence of atrial fibrillation, serum FGF21 remained independently associated with the outcome. Adding FGF21 levels to the model based on N-terminal pro B-type natriuretic peptide levels significantly improved the prognostic value (global chi-square 13.07 vs. 8.65; P=0.04).

Conclusions: Data from the present study demonstrated the importance of FGF21 as a potential biomarker that may reflect a different pathophysiologic implication from natriuretic peptides.

Background: Plaque morphology evaluation using optical coherence tomography (OCT) is vital for planning an optimized strategy for percutaneous coronary intervention (PCI), and an assessment of thrombotic risk (TR) and bleeding risk (BR) is crucial in managing patients who have undergone PCI. We examined the association of TR and BR with plaque morphology in patients with coronary artery disease (CAD).

Methods and Results: We conducted a multicenter prospective observational study and enrolled 325 patients with CAD who underwent PCI with OCT (median age 70 years, 19% women). The calcium index, which is equivalent to the calcium plaque volume, was assessed using OCT. Nondeformable calcified plaque was defined as a calcium score ≥3, the threshold for necessitating aggressive lesion modification. The TR and BR were evaluated using CREDO-Kyoto risk scores. The calcium index and prevalence of nondeformable calcified plaque increased significantly with increasing TR and BR scores. The TR and BR scores were significantly associated with higher calcium index after adjustment for confounders (TR score: β, 0.757; 95% confidence interval [CI], 0.568–0.946; P<0.001 and BR score: β, 0.623; 95% CI, 0.374–0.871; P<0.001). Both the calcium index and prevalence of nondeformable calcified plaque were highest in patients with both high TR and BR.

Conclusions: The TR and BR scores were associated with significant calcification and nondeformable calcified plaques in patients with CAD.

Background: Flow-mediated dilation (FMD) is the established parameter of endothelial function but requires skill and specialized equipment. This study aimed to investigate whether changes in carotid artery ultrasound parameters during passive leg raising (PLR) could reflect FMD values.

Methods and Results: Thirty-six adult males underwent standard FMD measurement. After 15 min of rest, a carotid artery ultrasound was performed to measure the maximal common carotid artery (CCA) diameter and stiffness parameter β. The PLR maneuver was then performed, and the change in these parameters (∆CCA_PLRand ∆β_PLR) was calculated. There were 6 participants with decreased FMD value (<4%). While the maximal CCA diameter remained unchanged during PLR (P=0.54), the stiffness parameter β significantly decreased during PLR compared with baseline (P=0.014). Among several carotid artery ultrasound parameters, ∆β_PLRcorrelated most strongly with FMD (r=−0.70; P<0.001). Receiver operating characteristic analysis showed that ∆β_PLRpredicted decreased FMD with an area under the curve of 0.89, sensitivity of 87%, and specificity of 83% at an optimal cut-off of 4.7%.

Conclusions: Change in carotid arterial stiffness parameter β during the PLR maneuver correlated with FMD, suggesting it may serve as an alternative indicator for endothelial function.

Background: The use of temporary mechanical circulatory support (tMCS) has revolutionized the management of cardiogenic shock (CS). However, standardized readiness-to-explant criteria for venoarterial extracorporeal membrane oxygenation (VA-ECMO) have not been established.

Methods and Results: We performed a retrospective analysis of 37 patients with CS who were explanted from VA-ECMO at Okayama University Hospital from December 2018 to May 2024 to evaluate the diagnostic performance of each readiness-to-explant criterion for explant success or failure. Explant success was defined as 30-day survival without re-insertion of MCS. Hemodynamic parameters were assessed at explant, weaning (1.0 to 1.5 L/min), and the off test (5 min). We assessed the predictive performance among parameters in successful or unsuccessful explantation of VA-ECMO using receiver operative characteristic curve analysis. The pulmonary artery catheter (PAC) criteria (pulmonary artery wedge pressure ≤18 mmHg, central venous pressure ≤12 mmHg, and cardiac index ≥2.2 L/min/m²) at the off test showed the highest predictability for successful explantation of VA-ECMO (area under the receiver operating characteristics curve 0.83; 95% confidence interval 0.71–0.96). The sensitivity, specificity, positive predictive value, and negative predictive value of the PAC criteria were 67%, 100%, 100%, and 38%, respectively.

Conclusions: Our results suggest that the PAC criteria at the off test may be the most appropriate algorithm for predicting successful explantation of VA-ECMO. Further prospective studies are needed to validate the present findings and to establish standardized VA-ECMO explantation practices.

Background: Acute pulmonary embolism (PE) is a life-threatening condition, and the diagnosis of acute PE remains difficult.

Methods and Results: In all, 133 consecutive patients with acute PE (mean [±SD] age 72±17 years, 53 men) were classified into 4 groups based on the severity of PE: high risk (n=12); intermediate–high risk (n=86); intermediate–low risk (n=1); and low risk (n=34). After excluding the 1 patient with intermediate–low-risk PE, clinical characteristics, the high-, intermediate–high-, and low-risk groups were compared: T wave inversion (V1–V3) was seen in 83%, 56%, and 18% of patients, respectively (P<0.001); an S1Q3T3 pattern was seen in 75%, 35%, and 0% of patients, respectively (P<0.001); echocardiographic evidence of right ventricular (RV) dysfunction was seen in 100%, 86%, and 0% of patients, respectively (P<0.001); the median (interquartile range) door-to-treatment time (n=11, 44, and 15, respectively) was 65 (43–116), 116 (78–213), and 183 (104–222) min, respectively (P<0.01); and the in-hospital death rate was 50%, 1%, and 0%, respectively (P<0.001). Multivariate analysis revealed that T wave inversion and an S1Q3T3 pattern were independently associated with intermediate–high- and high-risk acute PE, with adjusted odds ratios (95% confidence intervals) of 5.85 (2.14–15.96; P=0.0006) and 4.31 (1.65–11.27; P=0.0029), respectively.

Conclusions: Electrocardiographic evidence of right precordial T wave inversion and an S1Q3T3 pattern, followed by echocardiographic confirmation of RV dysfunction, may help with the early diagnosis of intermediate–high- and high-risk acute PE and thus contribute to improved door-to-treatment times and the prevention of adverse outcomes.

Background: Patients with left ventricular (LV) dysfunction have a higher risk of ventricular arrhythmia (VA) compared with those without, and are candidates for implantable cardioverter defibrillator (ICD). Response to cardiac resynchronization therapy (CRT) decreases the risk of VA; however, selection of a suitable CRT device remains challenging.

Methods and Results: In 678 patients with a CRT/ICD device and LV dysfunction, we investigated 325 CRT and 142 ICD patients for primary prevention. VA was defined as lasting ≥30 s or being treated with an ICD. CRT non-responders were defined as patients without reduced LV end-systolic volume ≥15%. During the follow-up period, 98 (21%) patients had a VA event (CRT 71 [22%] vs. ICD 27 [19%]; P=0.49). The VA risk score was calculated by summing values for non-left bundle branch block, left atrial diameter >45 mm, persistent atrial fibrillation, male sex, LV ejection fraction <25%, and ischemic cardiomyopathy. Our results showed that the VA risk score stratified the risk of VA among CRT patients (P<0.01), but was not significant for ICD patients (P=0.24). Patients with a VA risk score ≥4 (divided by receiver operating characteristic analysis) had a higher risk of VA among CRT patients (log rank P<0.01); however, it was not significant for ICD patients (log rank P=0.71).

Conclusions: The VA risk score could be a useful indicator for VA among CRT candidates.

Background: Left ventricular ejection fraction (LVEF) is widely used to assess systolic function and to predict cardiovascular outcomes, but its prognostic role in patients undergoing transcatheter aortic valve implantation (TAVI) remains uncertain.

Methods and Results: We performed a systematic review and meta-analysis of studies published from 2001 to 2024 that evaluated the association between preprocedural LVEF and post-TAVI outcomes. Eligible studies were identified via PubMed and Scopus, and included those reporting hazard ratios for preprocedural LVEF. A total of 92 studies comprising 98 patient cohorts and 75,085 individuals were included. Random-effects models were used for univariable and multivariable analyses. Subgroup and meta-regression analyses assessed effect modifiers, including ethnicity, LVEF classification, endpoints, and study design. Each 1% decrease in LVEF was associated with an increased risk of adverse events (hazard ratio 1.02, 95% confidence interval: 1.01–1.03), and this association remained significant after adjusting for confounders. Subgroup analyses confirmed the robustness of this association in various settings. In the multivariable meta-regression, studies with lower mean LVEF demonstrated a stronger association between reduced LVEF and adverse outcomes, but this association was attenuated or nonsignificant in cohorts with preserved systolic function. This suggests that the prognostic value of LVEF may depend on the baseline level of ventricular function and is subject to effect modification.

Conclusions: Reduced preprocedural LVEF is independently associated with worse prognosis after TAVI. These results highlight the continued importance of LVEF in risk stratification and clinical decision-making in TAVI candidates.

Background: Because the sustained effects of physical activity (PA) and the positive psychological and social aspects during the chronic phase of cardiac rehabilitation (CR) have not been clarified, we examined the sustained post-intervention effects of small community walking (SCW) on PA, well-being, and individual-level social capital in older patients with cardiovascular disease (CVD) in the chronic phase and the influence of increased well-being and social capital on increased PA.

Methods and Results: The subjects were 48 older patients with CVD who were randomly divided into SCW and walking-alone groups and were available for a 6-month follow-up survey after a 3 months’ intervention by healthcare workers. We measured PA, well-being (subjective happiness scale), and social capital before, 3 months after the intervention, and 6 months after the intervention ended. At 6 months post-intervention, only the SCW group maintained significant increases from the pre-intervention values in PA and well-being (P<0.01). Furthermore, increased well-being was a predictor of increased PA in the SCW group (P<0.01).

Conclusions: Our results suggest that SCW effectively maintains PA and well-being, even after the intervention ends, in older patients with CVD during the chronic phase. In addition, the effects of SCW are associated with PA and well-being. The relationship between PA and individual-level social capital should be further investigated.

Background: Many patients with cardiovascular disease show no obvious physical disability after hospital discharge, making it difficult to recognize functional decline and adapt appropriate accommodations. Therefore, this study examined return-to-work (RTW) outcomes and barriers after hospital discharge.

Methods and Results: We conducted a questionnaire among patients aged 18–64 years who underwent inpatient cardiac rehabilitation and were discharged between January 2018 and March 2023. Of 133 eligible patients, 54 responded (response rate 41%). Respondents were classified as: (1) returned to their original job; (2) returned to a different job; and (3) did not return to any job. The overall RTW rate was 96%, with 92% returning to their original job within 3 months. However, 81% of the respondents reported anxiety, mainly about physical strain and limited workplace understanding. Physicians were the most frequently consulted professionals, while other healthcare providers were rarely sought for advice.

Conclusions: Although most patients successfully returned to work, substantial anxiety persisted regarding workplace reintegration. A structured vocational support system is required, wherein healthcare providers proactively identify at-risk patients and deliver comprehensive guidance to support sustainable RTW outcomes.

Background: The microbial landscape of infective endocarditis (IE) has evolved over time, with Staphylococcus species recognized as the predominant pathogens. This shift has complicated IE management, and its impact on clinical outcomes remains unclear. We investigated recent microbial trends and their relationship with clinical outcomes in patients with IE.

Methods and Results: This study retrospectively examined 222 consecutive patients with suspected IE who underwent transesophageal echocardiography. Fifty-six met the modified Duke criteria for definite IE and were included in the final analysis. Microbiological trends indicated a significant increase and decrease in Staphylococcus spp. (P=0.040) and Streptococcus spp. (P<0.001) abundance, respectively. Patients infected with Staphylococcus spp. were more frequently treated surgically (75%) than those with other pathogens. Despite being associated with more extensive intracardiac lesions, Staphylococcus correlated with better functional status at discharge, with the highest proportion of patients achieving modified Rankin Scale (mRS) scores of 0–3 (P=0.049). Multivariate logistic regression analysis identified surgical intervention (odds ratio [OR] 5.40; 95% confidence interval [CI] 1.25–23.27; P=0.024) and younger age (OR 0.94; 95% CI 0.90–0.99; P=0.031) as independent predictors of favorable outcomes (mRS score 0–3).

Conclusions: Staphylococcus spp. are predominant pathogens in IE and are frequently associated with intense intracardiac involvement. Age and appropriately timed surgical intervention correlated with improved functional outcomes, indicating that early recognition and individualized treatment strategies may enhance prognosis. Timely and pathogen-directed management are important in IE.

Background: Hypercholesterolemia is a major risk factor for cardiovascular disorders. Evolocumab is efficacious and safe for the management of low-density lipoprotein cholesterol (LDL-C); however, evidence supporting the utility of evolocumab in Japanese patients is lacking. To fill this evidence gap, we conducted this systematic review and meta-analysis.

Methods and Results: PubMed, EMBASE, Web of Science, and the Cochrane Library from inception to October 2023 were searched for relevant publications. The primary outcomes were LDL-C levels and coronary artery plaque regression or stabilization. The secondary outcome was the incidence of adverse events. Nine studies were included: 6 randomized control trials (RCTs) and 3 cohort studies. The meta-analysis showed that evolocumab significantly reduced LDL-C levels in RCTs in the short (≤1 month), medium (≤3 months), and long (1 year) term, with a mean difference (MD) relative to placebo/standard of care (SOC) of −52.06% (95% confidence interval [CI] −59.32%, −44.79%), −69.12% (95% CI −71.45%, −66.79%), and −78.08% (95% CI −82.98%, −73.18%), respectively, and in the mid- to long (≤6 months) term in a cohort study, with an MD of −57.81% (95% CI −74.37%, −41.25%). Evolocumab also increased fibrous cap thickness and reduced macrophage grade. Adverse events were rare across included studies.

Conclusions: Evolocumab seems to be effective and safe in reducing the LDL-C levels and leading to plaque regression/stabilization in Japanese patients.

Background: Many patients with non-valvular atrial fibrillation (NVAF) on direct oral anticoagulants (DOACs) in real-world practice were ineligible for DOAC phase III trials. We aimed to determine the proportion of Japanese patients with NVAF eligible for these trials and compare the characteristics and outcomes of ineligible and eligible patients to determine the generalizability of the trial results.

Methods and Results: This retrospective cohort study included 7,826 Japanese NVAF patients on warfarin from 71 hospitals. We assessed trial eligibility and analyzed outcomes (major bleeding, stroke/systemic embolism, all-cause mortality) using Cox proportional hazards models. Nearly half (48.2%; n=3,772) of the patients were ineligible for DOAC phase III trials. Ineligible patients were older with more comorbidities and exhibited significantly higher risks of death (unadjusted hazard ratio [HR] 2.84; 95% confidence interval [CI] 2.36–3.43; P<0.0001), stroke/systemic embolism (unadjusted HR 1.53; 95% CI 1.17–1.98; P=0.0016), and major bleeding (unadjusted HR 2.00; 95% CI 1.63–2.44; P<0.0001) compared with eligible patients.

Conclusions: Half of the NVAF patients receiving anticoagulant therapy in real-world practice were ineligible for phase III DOAC trials, primarily due to safety concerns. This population differs substantially from eligible patients in characteristics and outcomes. The generalizability of phase III results to real-world patients remains uncertain, warranting additional assessment.

Background: There is significant circadian variation in the frequency of myocardial infarction onset, with a notable increase during the early morning. However, it remains unclear whether this circadian rhythm influences post-acute myocardial infarction (AMI) clinical outcomes and infarct size.

Methods and Results: This study included 2,251 patients enrolled in the Japan AMI Registry (JAMIR) who had ST-elevation myocardial infarction (STEMI) with a documented time of onset, stratified into 4 time periods: 00:00–06:00, 06:00–12:00, 12:00–18:00, and 18:00–00:00 h. The primary outcome measure, used as an indicator of infarct size, was peak creatine kinase (CK) level. The median peak CK level among patients was 1,978 IU/L. No significant differences in peak CK levels were observed among the 4 time period groups (P=0.117). Similarly, the relationship between onset time and peak CK levels was not significant (P=0.215). There were no significant differences among the 4 time period groups in secondary endpoints of in-hospital mortality (P=0.788) and 1-year clinical outcomes, including all-cause mortality (P=0.544), myocardial infarction (P=0.636), stroke (P=0.943), stent thrombosis (P=0.344), and a composite endpoint (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke; P=0.430).

Conclusions: Circadian variation had no effect on infarct size or clinical outcomes in patients with STEMI.

Background: Malnutrition and impaired physical function are common comorbidities of heart failure (HF). We investigated the relationship between malnutrition and physical function, factors associated with these values, and their prognostic impact on clinical outcomes.

Methods and Results: We retrospectively analyzed 151 patients with HF to determine the correlation between the nutritional index, assessed using the controlling nutritional status (CONUT) score, and physical function, assessed using the short physical performance battery (SPPB). We analyzed the prognostic role of nutrition and physical function for the composite endpoints of death or HF hospitalization. The median CONUT and SPPB scores were 3 (1, 4) and 11 (8, 12), respectively. These scores showed a significant but weak correlation (r=−0.214; P=0.008). While the CONUT and SPPB scores were a significant predictor of the composite endpoint in univariable Cox analysis, only the CONUT score remained significant after adjustment for confounders. Factors associated with the CONUT score were hemoglobin and B-type natriuretic peptide levels, and those associated with the SPPB score were age, sex, and CONUT score. Using established cutoffs (i.e., CONUT ≥5, SPPB ≤9), malnutrition remained independently associated with the composite endpoint (adjusted hazard ratio 2.56; 95% confidence interval 1.46–4.48; P<0.001).

Conclusions: Malnutrition and poor physical function had a weak correlation and factors associated while these values were different. Both predicted a poor prognosis and need to be assessed in patients with HF.

Background: Heart failure (HF) and frailty are increasing among aging populations, but because data on the association between potential cardiac overload or asymptomatic HF, measured by the serum level of N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and frailty among community-dwelling old-old older adults (≥75 years) are limited, we examined this association.

Methods and Results: A cross-sectional analysis was conducted using data from a longitudinal cohort study. Frailty was assessed using the Japanese version of the Cardiovascular Health Study (J-CHS) criteria. Association between log-transformed NT-proBNP levels and frailty were examined using multinomial logistic regression. The discriminative ability of NT-proBNP for frailty was assessed using receiver operating characteristic (ROC) curve analysis. A total of 588 participants (46.9% female, median age: 77 (76–86) years) were included. Log-transformed NT-proBNP was significantly associated with frailty compared to robust (OR 1.69; 95% CI 1.23–2.32; P=0.001), even after adjusting for potential confounding factors. NT-proBNP had modest discriminative ability for frailty (AUC 0.64; 95% CI 0.59–0.70; P<0.001), with an optimal cutoff of 94.5 pg/mL.

Conclusions: Elevated serum NT-proBNP levels are independently associated with frailty onset in community-dwelling old-old older adults, driven by the interaction between potential cardiac overload or asymptomatic HF and frailty. Serum NT-proBNP may be a useful tool for identifying frailty associated with cardiac overload.

Background: The correlation between pulmonary-to-systemic flow ratio (Qp/Qs) and right heart enlargement in children with atrial septal defect (ASD) remains unclear. This study aimed to (1) assess echocardiographic Z-scores of the right heart, and (2) determine whether they predict Qp/Qs.

Methods and Results: This retrospective study included 175 children (median age 6.8 years; 68 males) with isolated ASD who underwent cardiac catheterization between 2013 and 2020 at 2 centers in Japan. Patients with genetic anomalies or other conditions affecting right heart size were excluded. Echocardiographic parameters were measured, converted to a Z-score, and compared with the catheterization data. In all patients, the Qp/Qs on cardiac catheterization (cQp/Qs) significantly correlated with the Z-scores of the right ventricular end-diastolic diameter of the basal (RVB), mid-cavity (RVM), and longitudinal length (RVL; r=0.54, 0.57, and 0.52, respectively). The average of these 3 parameters (ARV) showed the strongest correlation (r=0.63). Z-scores of the right atrium, tricuspid valve, and pulmonary artery showed weaker correlations. An ARV cut-off of +2.0 best predicted cQp/Qs ≥1.5 (area under the curve 0.85; 95% confidence interval 0.79–0.92; sensitivity 76.8%; specificity 82.4%). Regression-predicted cQp/Qs also significantly correlated with measured cQp/Qs (r=0.63).

Conclusions: ARV may be a useful, non-invasive marker for assessing cQp/Qs and determining the indication for closure in children with ASD.

Background: The pathophysiological condition between heart failure (HF) with preserved left ventricular ejection fraction (LVEF; HFpEF) and non-HFpEF is different. To elucidate the prognostic value of monocytes, as representatives of the innate immune system, we examined the association between peripheral monocyte counts and future HF-related events in patients with HF.

Methods and Results: A total of 678 patients with HF referred for hospitalization was enrolled. These patients were categorized into 2 groups according to LVEF: HFpEF, and non-HFpEF. Based on the median monocyte values, we then defined the high monocyte group as having peripheral monocyte counts ≥363/mm³in patients with non-HFpEF, and as peripheral monocyte counts ≥322/mm³in patients with HFpEF. There were 200 patients with non-HFpEF and 478 with HFpEF. Based on receiver operating characteristic analysis, patients with non-HFpEF who were in the high peripheral monocyte group had a significantly higher risk of HF-related events compared with those in the low peripheral monocyte group. In contrast, the high and low peripheral monocyte groups for patients with HFpEF had no significant difference in HF-related events. Multivariate Cox hazard analysis identified high peripheral monocyte counts as an independent and significant predictor of future HF-related events only in patients with non-HFpEF.

Conclusions: High peripheral monocyte count was an independent and incremental predictor of HF-related events in non-HFpEF, rather than in patients with HFpEF.