Immune checkpoint inhibitors (ICIs) deliver prominent anti-tumor efficacy across multiple malignancies, yet ICI-associated myocarditis represents a life-threatening adverse event requiring standardized management. Updated from the 2022 version, these recommendations integrate up-to-date domestic and international real-world data and emerging evidence concerning bispecific antibody-related cardiac injury, thymic imaging grading, artificial intelligence-assisted early screening, and optimized second-line immunosuppressive regimens. These recommendations provide standardized practical guidance for prevention, early recognition and individualized intervention to improve patient outcomes.

Peripheral artery disease (PAD) is a prominent contributor to the global prevalence and mortality of cardiovascular diseases, yet the therapeutic strategies remain limited and urgently to explore the new methods of promoting vascular regeneration. Metabolism involves numerous aspects of angiogenesis, including the energetics, proliferation, signal transduction and gene expression of endothelial cells (ECs). Sirtuin (SIRT) family play an important role in regulating numerous metabolic processes due to its protein modification activity. Herein, the effect of SIRTs on regulating muscle vascular regeneration of PAD patients was demonstrated. We reanalyzed the SIRTs family by using the reported data of single-nuclei atlas of human PAD limb muscle and found that SIRT5 expression in ECs was significantly downregulated. Then the dynamic changes of SIRTs in ischemic hindlimb of mice and hypoxia-induced HUVECs were observed, among which, SIRT5 showed the most sensitive and significant change in responding to ischemia. Deletion of SIRT5 inhibited the blood flow perfusion recovery and consequently aggravated ischemic hindlimb injury in mice. SIRT5 knock down in vitro inhibited the proliferation, migration and angiogenesis of HUVECs both under normoxia and hypoxia. The mechanism was involved in significantly decreased expression of glycolytic enzymes and increased malonylation of proteins, especially GAPDH, in HUVECs with SIRT5 knock down. In conclusion, SIRT5 controlled the vascular regeneration capacity of lower limb muscles by regulating glycolysis and malonylation modification. Regulating SIRT5 activity might be novel therapeutic target for PAD patients.

Transcatheter tricuspid valve replacement has demonstrated efficacy in reducing the severity of tricuspid regurgitation and improving functional capacity. However, postoperative complications require further investigation. We present 2 cases of patients who developed acute left heart failure following transcatheter tricuspid valve replacement. Both patients presented with clinical manifestations including dyspnea, pulmonary crackles, hypoxemia, bilateral pulmonary edema on chest radiography, and elevated N-terminal pro-B-type natriuretic peptide levels. Notably, diuretic therapy combined with inotropic agents and noninvasive ventilatory support was effective in improving symptoms. The underlying mechanism of this complication is related to an abrupt increase in right ventricular output that exceeds the left ventricle's capacity to accommodate. Potential risk factors include left ventricular diastolic dysfunction and small left ventricular dimensions. Importantly, acute left heart failure has also been observed following other right-sided heart procedures with similar mechanisms. To prevent and manage this complication, comprehensive perioperative management is crucial, including identifying high-risk factors preoperatively and actively treating heart failure postoperatively.

Background Cavotricuspid isthmus (CTI) ablation performed using thermal ablation or pentaspline pulsed field ablation (PFA) catheters has demonstrated favorable efficacy and safety. Objective To evaluate the safety, effectiveness, and mid-term outcomes of focal PFA for CTI-dependent atrial flutter. Methods We performed a retrospective analysis of consecutive patients who underwent focal PFA for CTI-dependent AFL between August 2025 and December 2025. The primary endpoints were acute procedural success, periprocedural complications, and recurrence of any documented atrial arrhythmia lasting >30 seconds during follow-up. Results A total of 61 patients underwent CTI ablation with focal PFA. The mean age was 60.4 years, and 36.1% were female. Acute bidirectional conduction block was achieved in all patients (100%), with no cases requiring supplemental radiofrequency ablation to complete the linear lesion. Periprocedural complications included transient ST-segment elevation in 2 patients (3.3%), and PR interval prolongation in 2 patients (3.3%). Over a median 113-day follow-up, 58 (95.1%) of patients remained free from any atrial arrhythmias, with an estimated 180-day event-free survival of 91.9%. Sixty patients (98.4%) did not have typical atrial flutter recurrence, with an estimated 180-day event-free rate of 96.9%. Conclusion Focal pulsed field ablation appears to be a feasible and effective approach for treating CTI-dependent atrial flutter with a satisfactory mid-term outcome. The selection of optimized catheter ablation parameters (bipolar, biphasic, voltage 1800 V, pulse width 10 μs) may help to minimize procedural complication risks. However, larger prospective randomized trials with extended follow-up and systematic monitoring are required to confirm its durable efficacy.

Mid-term clinical evidence for the VitaFlow LibertyTM transcatheter aortic valve system in anatomically complex populations is limited. This was a prospective, multicenter, single-arm Objective Performance Criteria study performed at 22 Chinese sites, with follow-up at 30 days, 6 months, 1 year, and annually through 5 years. The prespecified primary endpoint of the parent study was 1-year all-cause mortality. Other clinical events were adjudicated according to Valve Academic Research Consortium-2 definitions. A total of 163 patients underwent transcatheter aortic valve replacement (TAVR) with the VitaFlow LibertyTM system. The mean age was 76.8 ± 5.0 years, 65.0

BACKGROUND:Despite treatment, many hypertensive patients with coronary heart disease (CHD) have blood pressure (BP) that remains above guideline targets. However, less is known about patients in whom on-treatment BP is below target and major European guidelines differ substantially in their recommendations for such patients. Specifically, 2023 European Society of Hypertension (ESH) guidelines provide a Class 3 recommendation to proactively avoid BP below target whereas 2024 European Society of Cardiology (ESC) guidelines do not. METHODS:Between 2020 and 2023, adults hospitalised in the previous 6-24 months with incident or recurrent CHD were sampled in 14 countries from all six WHO regions and invited for a standardised interview and examination as part of the International Action on Secondary and Primary Prevention by Intervention to Reduce Events (INTERASPIRE) study. We measured seated BP twice using an automated oscillometric device after 5 min of rest. We defined participants as having BP above target (BP ≥130/80 mm Hg), at target (BP 120-129/70-79 mm Hg) or below target (<120/70 mm Hg); according to both 2023 ESH and 2024 ESC guidelines. RESULTS:Among 4548 participants (21.1% female), the mean age (±SD) was 60.0 (±10.3) years. At a median (IQR) of 1.05 (0.76-1.45) years after index CHD hospitalisation, 10.3% of patients had BP readings within the target range of 120-129/70-79 mm Hg, with 53.9% above target and 35.7% below target. Patients with below-target BP were more likely to have heart failure (13.6% vs 10.0%, p=0.041) and estimated glomerular filtration rate <60 mL/min/1.73 m² (18.9% vs 10.7%, p<0.001), when compared with those at target. They were also statistically more likely to be severely frail (p=0.030). The median number of BP-lowering medications did not differ significantly between the 3 BP target groups. Cumulative dosing of BP-lowering medications in the below-target group was also not more intensive than that in the at-target group. CONCLUSIONS:More than one-third of INTERASPIRE patients with CHD presented with BP <120/70 mm Hg, which is below target per current European hypertension guidelines. Further research is needed in this population to resolve discordant guideline recommendations and determine whether de-escalation of BP-lowering therapies is beneficial or even harmful in this setting.

BACKGROUND:Chronic kidney disease (CKD) is an important risk factor for the progression of coronary artery disease (CAD). OBJECTIVES:The purposes of this study were to quantify the prevalence of CKD in CAD patients from 14 countries from all World Health Organization regions and to evaluate the prognostic value of estimated glomerular filtration rate (eGFR) and urinary albumin/creatinine ratio (UACR). METHODS:A total of 4,548 patients with CAD were included (79.6% were males; age range: 18-80 years). They were assessed for eGFR and UACR 6 to 24 months after the CAD diagnosis. Complete information on kidney function and cardio-renal protective therapy was available for 3,865 patients and follow-up data after a median of 1 year were available for 3,577 (92.5%). RESULTS:CKD according to the Kidney Disease Improving Global Outcomes classification was present in 32% of whom 19.7% were classified as low-moderate, 6.9% as high, and 5.6% as very high risk. Without UACR, 51.3% of them would have been undetected. The primary event, first of cardiovascular death, myocardial infarction, stroke, and hospitalization for heart failure, was observed in 7.9%, with the highest incidence in the Kidney Disease Improving Global Outcomes high-risk group (men: 13.0%; women: 11.8%). This relationship was independent of other risk factors and evident soon after the index examination. Only a minority of the patients received adequate cardio-renal protective therapy. CONCLUSIONS:Early screening for CKD in patients with CAD is important and should preferably include both eGFR and UACR to provide a complete diagnosis. Without UACR, half of those with CKD would remain undetected. Treatment with cardio-renal protective therapy was low, providing great potential for improvement.

Background: Aortic aneurysm/dissection (AAD) is a catastrophic vascular emergency with limited therapeutic options and poorly understood molecular underpinnings. Ferroptosis, an iron-dependent form of regulated cell death, emerged as a crucial driver of vascular degeneration although its pathological mechanisms in AAD remain largely undefined. Methods: We integrated transcriptomic datasets to identify key dysregulated genes in AAD. PHB2 expression was examined by immunohistochemistry, immunofluorescence, and Western blotting in human tissues, murine models, and isolated vascular smooth muscle cells. Functional involvement of PHB2 was evaluated using VSMC-specific conditional knockout mice and AAV9-PHB2 overexpression in β-aminopropionitrile-evoked AAD model. Results: Transcriptomic analysis revealed PHB2 as one of the most significantly downregulated genes in AAD, with selective suppression in VSMCs. Loss of PHB2 aggravated BAPN-induced aortic dilation, medial destruction, and elastic fiber fragmentation, whereas PHB2 overexpression preserved aortic wall integrity. RNAseq profiling implicated ferroptosis as the dominant pathway activated by PHB2 deficiency. Functionally, PHB2 overexpression mitigated Ang II-induced lipid ROS accumulation and Fe2+ overload, while PHB2 silencing aggravated ferroptosis. Mechanistically, rearranged subcellular localization of PHB2 promoted NCOA4 proteasomal degradation by interacting with NCOA4. PHB2 exhibited evident correlation with enhanced NEDD4L dimerization, enabling NEDD4L-mediated K48-linked ubiquitination of NCOA4 at Lys42, thus limiting ferritinophagy and suppressing ferroptosis. In vivo, PHB2 deficiency decreased NCOA4 ubiquitination and promoted ferroptosis, confirming the functional relevance of this pathway. Conclusion: We identify a previously unrecognized PHB2-NEDD4L-NCOA4 regulatory axis that restrains ferroptosis in VSMCs and protects against AAD progression. Targeting this pathway may represent a promising therapeutic strategy for the prevention and treatment of AAD.

AIMS:Pan-vascular diseases pose a significant and growing global public health burden. However, the burden of pan-vascular diseases remains unknown, especially regarding its trends through 2050. METHODS AND RESULTS:The global burden of ischemic heart disease (IHD), ischemic stroke (IS), and lower extremity peripheral arterial disease (LEPAD) was analyzed in this study. We investigated the prevalence trends of these pan-vascular diseases from 1990 to 2021 across 204 countries and territories, assesses the impact of population aging, lifestyle changes, and epidemiological shifts on the prevalence of pan-vascular diseases, examines health inequalities between countries, and forecasts trends through 2050.In 2021, the estimated global cases of IHD, IS, and LEPAD reached 254.3 million, 69.9 million, and 113.7 million, respectively. The age-standardized prevalence rates (ASPR) were 3031, 1018, and 1337 per 100,000 population, with estimated annual percentage changes (EAPC) of 0.61%, 0.95%, and 0.1%, respectively. Over recent years, population growth contributed most to the increasing burden of IHD, IS, and LEPAD, with a slightly higher impact in females for IS and LEPAD. Notably, epidemiological factors (-18.9%) partially mitigated the burden of LEPAD despite demographic pressures. Trend projections indicate a slow increase in IHD ASPR, particularly among females, while males exhibit a relatively stable trend through 2050. A similar pattern was observed for IS, whereas ASPR for LEPAD is expected to remain stable. Significant absolute and relative inequalities in disease burden were observed across countries with varying sociodemographic index (SDI) levels. CONCLUSIONS:The burden of pan-vascular diseases continues to rise globally, driven primarily by demographic changes (population growth and aging). Despite improvements in healthcare, significant cross-country health inequalities persist, particularly in high-SDI countries, where the disease burden has intensified. As prevalence trends are projected to increase further, targeted public health interventions and policies are urgently needed to mitigate the growing impact of pan-vascular diseases and reduce global health disparities.

BACKGROUND:Management of cardiac implantable electronic device-related tricuspid regurgitation remains challenging, particularly when lead interference coexists with annular dilation. CASE SUMMARY:A 69-year-old woman with a single-chamber pacemaker presented with symptomatic severe lead-related tricuspid regurgitation. Echocardiography demonstrated septal leaflet impingement by the pacing lead and marked annular dilation. Because isolated lead extraction was unlikely to restore valve competence, transvenous lead extraction, leadless pacemaker implantation, and transcatheter tricuspid annuloplasty were performed. At 3-month follow-up, tricuspid regurgitation had decreased to a mild-to-moderate level, with improvement in heart failure symptoms. DISCUSSION:This case illustrates a feasible multimodality strategy for selected patients with cardiac implantable electronic device-related tricuspid regurgitation. Combining lead extraction, leadless pacing, and transcatheter annuloplasty may relieve mechanical leaflet interference, avoid renewed transvalvular lead disruption, and reduce annular dilation. TAKE-HOME MESSAGES:Compared with conventional transvalvular leads, leadless pacing causes less interference with tricuspid valve motion and may therefore reduce lead-related regurgitation. A combined approach involving lead extraction, leadless pacing, and transcatheter tricuspid annuloplasty can provide a practical therapeutic pathway for cardiac implantable electronic device-related tricuspid regurgitation.

BACKGROUND:Transcatheter aortic valve replacement (TAVR) for pure aortic regurgitation (PAR) with an enlarged left ventricular outflow tract (LVOT) remains challenging due to inadequate anchoring. CASE SUMMARY:A 74-year-old woman with severe PAR and an enlarged LVOT (perimeter 93.7 mm), deemed high risk for surgery, underwent TAVR using a 30-mm self-expanding valve. A modified noncoronary sinus pivot implantation (NCPI-plus) technique was performed, deploying the valve above the virtual annular plane on the noncoronary sinus side to create a supra-annular pivot point. Postprocedural imaging and 12-month follow-up confirmed stable anchoring and excellent valve function without regurgitation. DISCUSSION:The NCPI-plus technique provides stable anchoring for TAVR in PAR patients with dilated LVOT, by using the supra-annular pivot point on the noncoronary sinus side as its core design to prevent downward valve displacement during deployment. TAKE-HOME MESSAGE:The NCPI-plus technique offers a feasible anchoring strategy for TAVR in PAR patients with enlarged LVOT.

BACKGROUND:Although drug-coated balloons (DCBs) demonstrate efficacy in de novo coronary artery disease, patients with non-small vessel lesions (NSVLs, ≥2.75 mm) face elevated risks of rescue stenting due to procedure-related coronary dissection. Radial wall stress maximum (RWSmax), an angiography-derived parameter reflecting plaque vulnerability, may predict dissection severity and optimize patient selection for DCB strategies. OBJECTIVES:This study aimed to evaluate the predictive value of RWSmax for severe coronary dissection following DCB treatment in de novo NSVL. METHODS:This study retrospectively analyzed 194 patients with de novo NSVL who were evaluated for DCB angioplasty. Dissections were classified via National Heart, Lung, and Blood Institute criteria: nonsevere (no dissection or Type A/B) vs severe (Type C-F). RWSmax was quantified using electrocardiography-gated angiographic analysis (AngioPlus Core software). Multivariable regression and receiver operating characteristic analyses identified predictors of severe dissection. RESULTS:Severe dissections occurred in 32.0% (62 of 194), predominantly Type C (83.9%, 52 of 62). RWSmax increased progressively with dissection severity (Jonckheere-Terpstra P < 0.001) and was higher compared with patients with nonsevere dissections (14.70% [12.80-16.65] vs 12.20% [11.00-13.30], P < 0.001). RWSmax independently predicted severe dissection (adjusted OR per 1%: 1.55; 95% CI: 1.31-1.90; P < 0.001), with an optimal cutoff of 13.7% (area under the curve = 0.752 [0.673-0.831], sensitivity = 61.3% [56.5% to 66.1%], specificity = 81.1%[74.4% to 87.8%]). Incorporating RWSmax into clinical prediction models significantly improved discrimination (Δarea under the curve = +0.093 [0.035-0.151]; P = 0.008). Subgroup analyses confirmed consistency across lesion types, calcification severity, and operator experience levels. CONCLUSIONS:RWSmax is a robust, angiography-based predictor of severe coronary dissection after DCB in NSVL. A 13.7% cutoff helps identify high-risk patients, supporting precision selection for DCB strategy.

Transcatheter valve replacement has become the established standard therapy for inoperable, high- and intermediate-risk patients with severe symptomatic aortic stenosis. Leaflet damage due to mechanical loading of the transcatheter valve during crimping process is a significant cause of premature structural valve degeneration. In this study, a novel stagger-folding transcatheter heart valve (THV) was designed to reduce the stress concentration caused by crimping process. The spatial distribution of the leaflets during the crimping process was optimized through axial stagger-folding, effectively mitigating inter-leaflet compression, reducing the risk of leaflet damage, which may enhance the long-term durability of the leaflets. Numerical simulation and multi-objective optimization were employed to optimize the axial displacements of stagger-folding leaflets, and a stagger-folding valve stent was designed based on the optimized design. Compared to conventional normal-folding valve, the novel stagger-folding valve demonstrated significant reductions in damage volume (23.64%), effectively reducing the stress caused by the folding of the valve leaflets. Consequently, the novel THV proposed in this study demonstrated significant potential to mitigate leaflet stress caused by crimping and may enhance valve durability, providing technical support for extending THV service life.

Rationale: Extensive leukocyte diapedesis is a defining step in inflammation and contributes critically to myocardial ischemia/reperfusion injury (MI/RI). Infiltrating leukocytes amplify local inflammation and exacerbate myocardial damage. However, the upstream control of the trans-endothelial migration step remains incompletely understood. Methods: Peripheral blood myeloid cells were isolated from MI/RI patients and healthy donors to examine MAP3K3 expression and its correlation with cardiac markers. Mouse MI/RI models were established to investigate MAP3K3 expression of myeloid cells in the heart. Myeloid-specific Map3k3 deficiency mice were used to evaluate the impact of MAP3K3 depletion on MI/RI severity and on myeloid cell diapedesis from the bone marrow. RNA sequencing and various manipulations of the MAP3K3/TAL1/JAM-A axis were used to elucidate its role in diapedesis. Finally, the therapeutic potential of pazopanib, a MAP3K3 inhibitor, was evaluated in the mouse MI/RI model. Results: MAP3K3 expression was upregulated in both monocytes and neutrophils from MI/RI patients and was positively correlated with the severity of MI/RI. In mice, MAP3K3 in cardiac myeloid cells peaked at day 3 post-MI/RI. Myeloid cell-specific depletion of MAP3K3 alleviated MI/RI by reducing the infiltration of myeloid cells into cardiac tissue. Functionally, MAP3K3 facilitated myeloid cell de-adhesion and transmigration across endothelial barriers. Further mechanistic studies identified the MAP3K3/TAL1/JAM-A signaling pathway as a key regulator of myeloid cell diapedesis. MAP3K3 phosphorylates TAL1 at Ser-122, leading to its ubiquitination and attenuating its transcriptional repression of F11r (encoding JAM-A). Through JAM-A, MAP3K3 promotes integrin internalization, thereby enhancing de-adhesion and myeloid cell transmigration. Treatment with pazopanib, a MAP3K3 inhibitor, ameliorated MI/RI injury and reduced myeloid cell diapedesis into the heart by blocking MAP3K3 phosphorylation activity. Conclusions: MAP3K3 orchestrates myeloid cell diapedesis via a TAL1/JAM-A dependent program during MI/RI. Targeting MAP3K3, exemplified by pazopanib, may offer a therapeutic strategy for MI/RI and related inflammatory conditions.