This study proposed a processing algorithm of dynamic chest radiography (DCR) for diagnosing pulmonary embolism (PE) based on perfusion defect area in the image of lung perfusion (LP) map with optimal perfusion defect criteria (PDC). Seventy-seven patients (16 with acute PE and 16 with chronic PE) who underwent DCR and chest contrast-enhanced computed tomography within 72 h of the interval were retrospectively enrolled. PDC was set as the threshold for determining the presence or absence of perfusion defects based on the imported LP map. Twenty steps of PDCs were set, from − 5 to − 290, with a tolerance of − 15. The perfusion defect area was defined as the number of pixels exceeding the PDC in the right and left lung. The fractional perfusion defect area (FPDA) was calculated as its percentage relative to the total lung area. Sensitivity and specificity of PE diagnosis by FPDA at each PDC were calculated using receiver operating characteristic (ROC) analysis. PE detection by FPDA at the best PDC of − 110 and − 125 in right and left lungs showed cut-off values of 46.0

Background Group 2 pulmonary hypertension (PH), defined as PH caused due to left heart disease, remains a challenging condition. However, its prognostic impact and implications for emerging therapies are unclear. We aimed to evaluate the real‐world relationship between pulmonary vascular resistance (PVR) and prognosis in Group 2 PH and assess the efficacy of emerging therapies. Methods Two prospective registries supported by Japanese PH societies were analyzed: a current (2018–2024; n=563) and a previous (2012–2016; n=425) registry. The composite end points were hospitalization for heart failure, all‐cause death, ventricular assist device implantation, or cardiac transplantation. Results Stratified analyses using propensity score–matched data demonstrated a significant association between PVR >3 Wood units and prognosis in patients with Group 2 PH (6‐year event‐free rates, PVR >3 Wood units versus PVR ≦3 Wood units, previous registry: 72.9% versus 61.4%; current registry: 75.2% versus 55.4%). Consistent patterns were observed in both heart failure with reduced ejection fraction and heart failure with preserved ejection fraction subgroups. The use of SGLT2 (sodium‐glucose cotransporter‐2) inhibitors in the current registry was associated with improved outcomes in patients with elevated PVR, showing event‐free rates of 73.8% versus 35.5% in those without treatment. Among multivariate analyses including major treatment options, SGLT2 inhibitor treatment exhibited significant associations with improvement of composite end points. Conclusions Elevated PVR (>3 Wood units) identified a high‐risk subset of patients with Group 2 PH. The association between the use of SGLT2 inhibitors and better outcomes suggests a potential therapeutic role that warrants further investigation through controlled studies.

IntroductionChronic thromboembolic pulmonary hypertension (CTEPH) is a treatable cause of pulmonary hypertension but remains under-recognized and is often diagnosed with delay. Limited access to lung ventilation-perfusion (V/Q) scintigraphy, especially outside tertiary centers, is one contributor. Dynamic chest radiography (DCR), with a pulmonary circulation analysis program, can provide a rapid, non-invasive, and widely deployable assessment of pulmonary perfusion. We describe the protocol of a multicenter reader study testing whether adding DCR-based analysis to standard initial work-up improves diagnostic accuracy for CTEPH among patients with echocardiographically suspected pulmonary hypertension.Methods and analysisThis investigator-initiated, multicenter, assessor-blinded, case-wise randomized superiority reader study compares standard initial work-up (blood tests, chest X-ray, ECG, pulmonary function tests, and transthoracic echocardiography per guidelines) with standard work-up plus DCR-based pulmonary circulation analysis. The primary endpoint is diagnostic accuracy for discrimination between CTEPH and non-CTEPH in the intention-to-treat set. The final diagnosis of CTEPH versus non-CTEPH will be defined as the reference standard according to the Japanese and European guidelines for pulmonary hypertension. Secondary endpoints include sensitivity, specificity, positive and negative predictive values; agreement with V/Q scintigraphy regarding regional perfusion defects using κ statistics; and STARD-conformant academic performance evaluation of DCR-based pulmonary circulation analysis and lung perfusion scintigraphy in relation to the site-level final diagnosis of CTEPH versus non-CTEPH in a full analysis set. Safety endpoints include adverse events during DCR acquisition and device malfunctions. The target sample size is 108 cases with 1:1 allocation. Recruitment started on 30/07/2025 and is expected to continue until 28/02/2027, with overall study completion planned for 31/05/2027.DiscussionThis multicenter reader study addresses a key limitation of current CTEPH diagnostic pathways-reliance on V/Q scintigraphy, which may be delayed or unavailable outside tertiary centers-by evaluating whether DCR-based pulmonary circulation analysis can improve early discrimination of CTEPH and support timely referral.Trial registration numberJapan Registry of Clinical Trials (jRCT), jRCT2072250027.

BACKGROUND:We investigated associations between the low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) ratio (L/H ratio) and cardiovascular events in high-risk type 2 diabetes (T2D) patients with diabetic retinopathy receiving statins. METHODS AND RESULTS:We conducted a post hoc analysis of the EMPATHY study, a randomized controlled trial comparing intensive vs. standard statin therapy in T2D patients with retinopathy and hypercholesterolemia without cardiovascular disease. Baseline and 12-month (12M) L/H ratios were assessed as single and serial measures. Baseline data were available for 5,006 patients (median L/H ratio 2.016), categorized as having either a high (≥2.0) or low (<2.0) L/H ratio. Over a median 36.8-month follow-up, 184 cardiovascular events occurred. The risk of cardiovascular events was higher in the group with a high than low L/H ratio, even after adjusting for age, sex, and LDL-C (hazard ratio 1.89; 95% confidence interval 1.31-2.73; P<0.001); 12M L/H ratio analysis yielded similar results. In serial categories, both low-high (baseline <2.0; 12M ≥2.0) and high-high (baseline ≥2.0; 12M ≥2.0) groups had higher risk than the low-low group (baseline <2.0; 12M <2.0). No significant interactions were observed by age, sex, LDL-C, HDL-C, or statin intensity. CONCLUSIONS:An L/H ratio ≥2.0 identifies increased cardiovascular risk in statin-treated T2D patients with diabetic retinopathy and hypercholesterolemia without prior cardiovascular disease. Serial L/H ratio assessment may aid risk stratification in this high-risk population.

Sepsis-induced myocardial dysfunction (SIMD) is a prevalent complication among septic patients, significantly worsening patient prognosis and elevating the mortality rate. Connexin 43 (Cx43), a pivotal cardiac gap junction protein, maintains cardiac function, and its disarrangement is closely linked to cardiac diseases. However, the role of Cx43 localization changes in SIMD remains unclear. Amphiregulin (AREG) was recently reported to promote the recovery of Cx43 disarrangements. This research aimed to explore the role of Cx43 in SIMD and the preventive potential of AREG. A mouse model of SIMD was induced using lipopolysaccharide (LPS) and treated with AREG. Cardiac function and electrical conduction were assessed using echocardiography and an electrocardiogram. Inflammatory responses, Cx43 regulation, and related signaling pathways were further investigated in serum and cardiac tissues. Relevant signal pathway analysis was investigated in cultured cardiomyocytes. LPS administration significantly reduced cardiac ejection fraction and left ventricular fractional shortening, which were accompanied by disorganization, fragmentation, and lateralization of Cx43 at 6 h. These pathological alterations were associated with increased phosphorylation of pS368-Cx43, mediated by p38 activation. AREG pretreatment improved cardiac function and QRS interval, and preserved Cx43 localization at intercellular discs, along with pS368-Cx43 phosphorylation with reduction of p38 inhibition. Myocardial cell studies confirmed that AREG inhibited p38 phosphorylation, independent of AKT, in LPS-induced cardiac dysfunction. This study highlights the role of Cx43 phosphorylation in SIMD and demonstrates the preventive potential of AREG in SIMD, which is associated with a reduction in p38 activation and a decrease in the phosphorylation level of pS368-Cx43. These findings may provide a novel therapeutic target for SIMD. Created in BioRender. Chen, M. (2026) https://BioRender.com/ur0tpol

Background: Sotatercept is a first-in-class activin signaling inhibitor, developed for the treatment of pulmonary arterial hypertension (PAH). Objectives: This open-label single-arm, multicenter, phase 3 study was initiated to evaluate the efficacy and safety of sotatercept in Japanese participants with PAH. Methods: Forty-six adult Japanese participants with PAH on stable background therapy were enrolled and received subcutaneous sotatercept starting at 0.3 mg/kg with a target dose of 0.7 mg/kg administered every 3 weeks. The primary efficacy endpoint was the change from baseline in pulmonary vascular resistance at 24 weeks. Results: Of 46 participants, 29 (63%) were WHO functional class II and 17 (37%) were class III. At 24 weeks, pulmonary vascular resistance decreased 99.2 (95% CI: –129.6 to –68.4) dynes·s/cm5 and, 6-minute walk distance (key secondary endpoint) increased 41.8 (95% CI: 27.8-55.5) meters. There were 6 (13%) serious adverse events (AEs) and no discontinuations due to AEs in the primary period. Safety was consistent with the known safety profile for sotatercept with AEs that were clinically manageable. Conclusions: In this study of Japanese participants with PAH, improvements in pulmonary vascular resistance and 6-minute walk distance were observed, consistent with the pivotal phase 3 STELLAR (A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension [MK-7692-003/A011-11]) trial. These data suggest that sotatercept may be an important treatment option for Japanese patients with PAH. (A Study of Sotatercept in Japanese Pulmonary Arterial Hypertension [PAH] Participants [MK-7962-020], NCT05818137; Japan Registry of Clinical Trials, jRCT2031230046)

A 55-year-old woman developed Stanford type A acute aortic dissection complicated by occlusion of the left main coronary artery. The patient underwent an emergency ascending aortic replacement with concomitant coronary artery bypass grafting to the left anterior descending artery. Owing to extensive myocardial ischemia and the resultant severe cardiopulmonary impairment, the patient could not be weaned from the cardiopulmonary bypass. Therefore, central veno-arterial extracorporeal membrane oxygenation was initiated, with aortic perfusion via a branch of the ascending aortic graft and right atrial drainage. The central veno-arterial extracorporeal membrane oxygenation system was subsequently converted to a paracorporeal left ventricular assist device with an oxygenator, following which respiratory support was no longer required. The patient was listed for heart transplantation and underwent an elective conversion to a durable left ventricular assist device as a bridge-to-bridge strategy. During this operation, relocation of the outflow graft was necessary, and aortic valvuloplasty was performed simultaneously to address the mild residual post-dissection aortic insufficiency. Ultimately, the patient underwent heart transplantation more than 4 years after the bridge-to-bridge operation. An effective sequential mechanical circulatory support strategy, combined with meticulous technical management during bridge-to-bridge surgery, can successfully facilitate bridging to heart transplantation.

Tirzepatide, a dual agonist for glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has shown robust efficacy in treating diabetes and obesity, and in obese patients with heart failure with preserved ejection fraction (HFpEF), it reduced weight, lowered blood pressure, and improved outcomes. However, its cardiovascular effects in non-obese, non-diabetic hypertension remain unclear. We investigated the impact of tirzepatide on blood pressure, cardiac function, and sympathetic nervous system activity in stroke-prone spontaneously hypertensive rats. Starting at 8 weeks of age, rats received tirzepatide (TZP, 25 nmol/kg, every two days), vehicle (VEH), or pair-fed vehicle (VEH-PF) to control for differences in food intake for 4 weeks. Tirzepatide significantly reduced food intake and body weight. Contrary to prior clinical observations, tirzepatide elevated mean blood pressure (197.4 ± 16.6 vs. 153.7 ± 5.4 mmHg at Day 28; TZP vs. VEH-PF, n = 9 vs. 8; p < 0.05) and increased heart rate, accompanied by left ventricular hypertrophy, myocardial fibrosis, and impaired diastolic function. Sympathetic activation was evident, with higher plasma norepinephrine levels and increased ΔFosB expression-a marker of sustained neuronal excitation-in the parvocellular paraventricular nucleus and the rostral ventrolateral medulla. Moreover, ΔFosB expression was increased in anorexigenic proopiomelanocortin neurons within the hypothalamic arcuate nucleus, which reduce feeding and have been implicated in promoting sympathetic excitation. These findings point to a central mechanism underlying increased sympathetic outflow. In conclusion, tirzepatide increased blood pressure and sympathetic activity in hypertensive rats without cardiac protection, highlighting context-dependent cardiovascular actions. Tirzepatide increased blood pressure, impaired LV diastolic function, and induced cardiac hypertrophy and fibrosis, as well as sympathetic overactivation in SHRSP.

BACKGROUND:In treatment of pulmonary arterial hypertension (PAH), the prostacyclin (PGI2) pathway is targeted by oral selexipag and parenteral PGI2 analogs. Although guidelines recommend therapeutic strategies based on disease severity and etiology, there are limited data on real-world use of selexipag and parenteral PGI2 analogs in Japan. This study aimed to characterize the use of these drugs in treatment of PAH in Japan, with a focus on differences related to patient characteristics and PAH etiology. METHODS:Patients with PAH registered in the Japan PH Registry (JAPHR) from November 2016 to March 2023 were evaluated. Patients who met the inclusion criteria were further stratified by PAH etiologies, drug used, severity of disease, treatment strategies, time from diagnosis to drug initiation, and pulmonary hemodynamics. RESULTS:A total of 235 patients were treated with selexipag and 121 patients with parenteral PGI2. Selexipag and parenteral PGI2 analogs were most frequently used for idiopathic PAH (IPAH) or heritable PAH (HPAH), at 56.2 % (132/235) and 82.6 % (100/121), respectively. Selexipag was also used more frequently than parenteral PGI2 analogs for PAH associated with connective tissue disease and congenital heart disease. Most patients received triple therapy, with 76.2 % (179/235) and 59.5 % (72/121) receiving selexipag and parenteral PGI2 analogs, respectively. Regarding New York Heart Association functional class (NYHA-FC), selexipag was primarily administered to Class II-III patients and parenteral PGI2 analogs to Class III patients. Both mean pulmonary artery pressure and pulmonary vascular resistance values were lower in the selexipag group than in the parenteral PGI2 group. CONCLUSION:Parenteral PGI2 analogs tend to be used mainly in patients with severe IPAH/HPAH, while selexipag is used in patients with a broader range of etiologies around NYHA-FC II-III. Choice of selexipag and parenteral PGI2 analogs for treatment of PAH is influenced by disease severity and etiology.

Background Intercoronary communication (ICC) is an extremely rare congenital coronary anomaly that is generally considered benign. We herein report a novel case in which an ICC itself caused coronary vasospasm, leading to myocardial ischemia. Case Summary A 79-year-old woman presented with rest angina. Transthoracic echocardiography revealed hypokinesia of the posterolateral left ventricular wall. Coronary angiography demonstrated an ICC between the left circumflex artery and right coronary artery, and acetylcholine-induced focal coronary vasospasm was provoked exclusively in the ICC and was relieved with intracoronary isosorbide dinitrate. The patient was treated with oral vasodilators, after which she remained symptom-free. Follow-up echocardiography showed complete recovery of wall motion. Discussion This case illustrates a paradoxical scenario in which an ICC, typically considered as a “safety valve,” instead caused localized vasospastic myocardial ischemia. Take-Home Messages ICC itself may cause coronary vasospasm, resulting in myocardial ischemia.

Background Infections remain a major complication in patients with left ventricular assist devices (LVADs). Case Summary A 51-year-old male with a history of LVAD implantation presented with vertigo and was found to have an occipital cerebral hemorrhage. Further evaluation revealed a ruptured infectious intracranial aneurysm. Blood cultures confirmed Candida parapsilosis, and 18F-fluorodeoxyglucose-position emission tomography/computed tomography demonstrated abnormal uptake at the outflow graft and driveline, providing adjunctive evidence suggestive of LVAD-related infection. He was successfully treated with micafungin and liposomal amphotericin B without LVAD exchange. Discussion This case emphasizes the importance of considering systemic fungal infection in LVAD patients even in the absence of fever or elevated inflammatory markers. Early recognition with blood cultures and advanced imaging is essential to guide management. Take-Home Messages Systemic fungal infection should be suspected in LVAD patients with unexplained weight loss or a ruptured intracranial aneurysm, even without fever. Early blood cultures and advanced imaging are essential for timely diagnosis.

BACKGROUND:Paradoxical embolism is a clinically important complication of secundum atrial septal defect (ASD), yet anatomical characteristics predisposing to embolic events remain incompletely defined. We investigated clinical and morphological factors associated with paradoxical embolism among adults undergoing transcatheter ASD closure, with particular focus on ASD size. METHODS:We retrospectively analyzed 270 adults who underwent transcatheter closure of secundum ASD between 2013 and 2024. Patients were classified according to history of paradoxical embolism. ASD morphology, including maximum diameter, was assessed by intra-operative transesophageal echocardiography (TEE). Logistic regression evaluated ASD size continuously (per 1-mm increase) and as a categorical threshold (<10 mm vs. ≥10 mm). RESULTS:Paradoxical embolism occurred in 14/270 patients. Patients with paradoxical embolism had a significantly smaller maximum ASD diameter on TEE (12.92 ± 5.79 vs 16.94 ± 5.96 mm, p=0.02). In univariable logistic regression, maximum ASD size (per 1-mm increase) was inversely associated with paradoxical embolism (odds ratio [OR] 0.88, 95% confidence interval [CI] 0.80-0.98; p=0.02). In multivariable analysis adjusted for age, sex and hypertension, ASD size <10 mm remained independently associated with paradoxical embolism (Firth penalized likelihood, Model 1: OR 7.75, 95% CI 2.51-24.50; p<0.001). CONCLUSION:Smaller maximum ASD diameter, particularly <10 mm, was consistently associated with paradoxical embolism, suggesting that even small ASDs may carry clinically meaningful embolic risk in this closure cohort.

Background: Although early right ventricular failure (eRVF) following durable left ventricular assist device (dLVAD) implantation is associated with a poor prognosis, reliable predictive parameters have not yet been established. In this study we evaluated the predictive value of right ventricular (RV) to pulmonary artery (PA) uncoupling, measured by the ratio of tricuspid annular plane systolic excursion (TAPSE) to PA systolic pressure (PASP), in patients undergoing dLVAD implantation. Methods and Results: We conducted a single-center retrospective study of adult patients who underwent dLVAD implantation between January 2008 and December 2024. eRVF was defined as receiving short- or long-term right-sided circulatory support, or continuous inotropic support for more than 14 days within 30 days after dLVAD implantation. Preoperative echocardiographic variables, including the TAPSE/PASP ratio and right-sided heart catheter parameters, were analyzed using univariate and multivariate logistic regression models to identify eRVF predictors. We analyzed data for 111 patients who underwent dLVAD implantation and 46.8% developed eRVF postoperatively. The TAPSE/PASP ratio was an independent predictor of eRVF, even after adjustments for other echocardiographic variables (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.004-0.67, P=0.024) and right-sided heart catheter variables (OR, 0.04; 95% CI, 0.002-0.69, P=0.027). Conclusions: Preoperative RV-PA uncoupling, assessed using the TAPSE/PASP ratio, may predict eRVF following dLVAD implantation. This parameter is clinically accessible and valuable for preoperative risk stratification and may facilitate improved perioperative management.

AIMS:Despite intensive lipid-lowering therapy, residual cardiovascular risk remains prevalent among patients with coronary artery disease. Although triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) metabolism are closely interrelated, their combined prognostic significance in secondary prevention remains unclear. METHODS:This study analyzed the Clinical Deep Data Accumulation System- Percutaneous Coronary Intervention (CLIDAS-PCI) database, a multicenter Japanese registry of patients with acute coronary syndrome undergoing PCI. Patients were stratified into four combined TG-HDL phenotypic groups using guideline-consistent cutoff values for high TG (≥ 175 mg/dL) and low HDL-C (≤ 40 mg/dL) levels. The primary outcome was a composite of major adverse cardiac and cerebrovascular events plus hospitalization for heart failure and its components. RESULTS:Among 3,352 patients, high TG levels were not associated with the composite outcome but were consistently associated with an increased risk of recurrent myocardial infarction. Although low HDL-C levels were associated with increased cardiovascular risk, this association was attenuated after adjustment for renal function and nutritional status. Combined TG-HDL phenotyping revealed distinct risk profiles: patients with high TG and low HDL-C levels had the highest risk of recurrent myocardial infarction, while those with low TG and low HDL-C levels exhibited a markedly higher risk of cardiovascular death. CONCLUSIONS:In a Japanese secondary prevention cohort undergoing PCI, TG and HDLC demonstrated complementary and outcome-specific prognostic associations. Thus, combined TG-HDL phenotyping using guideline-based cutoffs may provide a simple and clinically relevant approach to stratifying residual cardiovascular risk beyond low-density lipoprotein cholesterol lowering.

Reduced diffusing capacity of the lungs for carbon monoxide (DLco) reflects microvasculopathy in chronic thromboembolic pulmonary hypertension, yet its clinical value is uncertain. In a Japanese nationwide registry (2018-2023) we studied 1270 patients: 486 formed an event cohort and 299 a treatment cohort who underwent pulmonary endarterectomy or balloon pulmonary angioplasty. Lower baseline DLco was indicative of smaller postprocedural improvements in mean pulmonary artery pressure, pulmonary vascular resistance and cardiac index (all p≤0.023) and a higher risk of clinical events (HR 0.971, p=0.005). Outcomes deteriorated below 59.6%, indicating DLco may help stratify prognosis and treatment benefit.

Background Mechanical valve thrombosis is a serious complication in adults with congenital heart disease (ACHD). Although low-dose thrombolytic therapy has emerged as a potential alternative to surgery, evidence in ACHD patients with right-sided mechanical valve thrombosis remains limited. We evaluated the feasibility and safety of a standardized low-dose thrombolytic protocol in this population. Methods We retrospectively reviewed consecutive ACHD patients with right-sided mechanical valve thrombosis treated at our institution between 2022 and 2025. Diagnosis was based on fluoroscopic, echocardiographic, and computed tomography findings. All patients received a standardized low-dose alteplase regimen (25 mg over 6 hours). Treatment efficacy was assessed primarily by restoration of prosthetic leaflet mobility on fluoroscopy. Results Five patients were included, including four with mechanical pulmonary valves and one with a mechanical tricuspid valve. Thrombosis occurred a median of 2.3 years after valve replacement, and all patients had subtherapeutic anticoagulation (international normalized ratio <2.0) during the preceding month. At presentation, four patients were in New York Heart Association functional class II and one in class III. Following a median of 5 days of thrombolytic therapy, complete restoration of prosthetic leaflet mobility was achieved in all patients. No major bleeding or thromboembolic complications occurred. During a median follow-up of 0.7 years, no recurrent valve thrombosis was observed. Conclusions Standardized low-dose thrombolytic therapy was safe and feasible in this case series and may provide a non-surgical treatment option for ACHD patients with right-sided mechanical valve thrombosis.