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Background and aimCardiotoxicity has become the most common cause of non-cancer death among breast cancer patients. Pyrotinib, a tyrosine kinase inhibitor targeting HER2, has been successfully used to treat breast cancer patients but has also resulted in less well-understood cardiotoxicity. This prospective, controlled, open-label, observational trial was designed to characterize pyrotinib’s cardiac impacts in the neoadjuvant setting for patients with HER2-positive early or locally advanced breast cancer.Patients and methodsThe EARLY-MYO-BC study will prospectively enroll HER2-positive breast cancer patients who are scheduled to receive four cycles of neoadjuvant therapy with pyrotinib or pertuzumab added to trastuzumab before radical breast cancer surgery. Patients will undergo comprehensive cardiac assessment before and after neoadjuvant therapy, including laboratory measures, electrocardiography, transthoracic echocardiography, cardiopulmonary exercise testing (CPET), and cardiac magnetic resonance (CMR). To test the non-inferiority of pyrotinib plus trastuzumab therapy to pertuzumab plus trastuzumab therapy in terms of cardiac safety, the primary endpoint will be assessed by the relative change in global longitudinal strain from baseline to completion of neoadjuvant therapy by echocardiography. The secondary endpoints include myocardial diffuse fibrosis (by T1-derived extracellular volume), myocardial edema (by T2 mapping), cardiac volumetric assessment by CMR, diastolic function (by left ventricular volume, left atrial volume, E/A, and E/E’) by echocardiography, and exercise capacity by CPET.DiscussionThis study will comprehensively assess the impacts of pyrotinib on myocardial structural, function, and tissue characteristics, and, furthermore, will determine whether pyrotinib plus trastuzumab is a reasonable dual HER2 blockade regimen with regard to cardiac safety. Results may provide information in selecting an appropriate anti-HER2 treatment for HER2-positive breast cancer.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT04510532

BackgroundCurrent mouse models still have limitations in studying aortic valve stenosis (AVS). A suitable animal model bearing a close resemblance to the pathophysiological processes of humans needs to be developed. Here, we combined two risk factors to create a mouse model that mimics the pathological features of human AVS.Methods and resultsWe combined WI and hyperlipidemia in ApoE–/– mice to explore the synergistic effect on the stenosis of the aortic valve. Transthoracic echocardiography revealed progressively increased peak velocity with age in ApoE–/– mice to velocities above C57 mice when fed a high-fat diet after wire injury. Moreover, ApoE–/– mice demonstrated lower cusp separation and lower aortic valve area after 8 weeks vs. C57 mice. Gross morphology and MRI showed advanced thickening, sclerosis aortic valve, narrowing of the orifice area, and micro-CT showed obvious calcification in the aortic valves in the hyperlipidemia group after wire injury. Histopathology studies showed thickening and fibrosis of aortic valve leaflets in the hyperlipidemia group after wire injury. Notably, lipid deposition was observed in ApoE–/– mice 8 weeks after wire injury, accompanied by overexpressed apoB and apoA proteins. After wire injury, the hyperlipidemia group exhibited augmented inflammation, ROS production, and apoptosis in the leaflets. Moreover, the combination group exhibited advanced fibro-calcific aortic valves after wire injury.ConclusionOverall, we present the synergistic effect of wire injury and hyperlipidemia on lipoproteins deposition in the development of AVS in ApoE–/– mice, this model bear close resemblance to human AVS pathology.

AimsEthanol infusion into the VOM (EIVOM) adjunctive to radiofrequency catheter ablation (RFCA) was a novel approach facilitating mitral isthmus (MIth) block for persistent atrial fibrillation (PeAF); However, there were remarkable disparities in its technical aspects. This study aimed to evaluate the impact of EIVOM technical aspects on acute MIth block.MethodsEighty consecutive patients (63 males, average age 66.4 ± 8.6 years) undergoing de novo PeAF ablation were assigned to different groups. The procedural parameters in “EIVOM first” (n = 13) or “RFCA first” (n = 13) as well as small dose ([SD], ≤4 ml, n = 26) or big dose ([BD], >4 ml, n = 54) approaches were analyzed to identify the predictors for acute MIth block.ResultsCompared with the “EIVOM first” approach, the “RFCA first” approach was associated with longer procedural and MIth ablation time (134 ± 27 min vs. 112 ± 17 min; 14.9 ± 5.5 min vs. 9.3 ± 5.1 min, both P < 0.05, respectively), but with comparable success of MIth block. The ethanol dose was 6.3 ± 1.5 ml in BD group vs. 3.1 ± 1.0 ml in SD group (P < 0.001) and was correlated significantly with the size of Δlow voltage area (r = 0.66, P < 0.001). The success of MIth block was 92.6% in BD group vs. 73.1% in SD group, P = 0.03. The ethanol dose >5.75 ml independently predicted successful MIth block (OR: 0.428, 95% CI: 0.219–0.839, P = 0.01).ConclusionsDespite the comparable effectiveness on MIth block, the “EIVOM first” approach was associated with shorter procedural and MIth ablation time than the “RFCA first” approach. The ethanol dose in EIVOM was an independent predictor for MIth block.

BackgroundThis study aimed to investigate the hypothesis that specific pattern of myocardial work (MW) distribution in patients with acute anterior ST-segment elevation myocardial infarction (STEMI) could provide prognostic value for predicting left ventricular (LV) remodeling.MethodsA total of 98 first anterior wall STEMI patients treated with primary percutaneous coronary intervention [85 men (86.7%), mean age: 58 ± 12 years] were enrolled. Transthoracic echocardiography was performed 24–72 h after angioplasty and during 3-month follow-up. MW was estimated from the left ventricular pressure–strain loop derived from speckle tracking echocardiography and simultaneous noninvasive brachial artery cuff pressure. The primary endpoint was early LV remodeling, defined as an increase in LV end-diastolic volume ≥20% compared with baseline at 3 months after STEMI. Major adverse cardiac events and combined clinical outcomes were recorded.ResultsLV remodeling was present in 32 patients (33%), who exhibited lower global and culprit-regional work index (WI), constructive work (CW), work efficiency (WE), and specifically, greater differences of WE (delta-WE) and CW (delta-CW) between the culprit and non-culprit region than those without LV remodeling both at the acute phase and follow-up (all P < 0.0125). During follow-up, all global and regional WI, CW, and WE were improved (P < 0.0125 compared with baseline), with less improvement in patients with LV remodeling. In multivariate analysis, baseline delta-WE (odds ratio: 2.304; 95% CI: 1.093–4.856, P = 0.028) and peak troponin I level (odds ratio: 1.035; 95%CI: 1.008–1.063, P = 0.010) were independently associated with early LV remodeling. Patients with greater delta-WE at baseline were associated with a higher incidence of heart failure and combined clinical outcomes during follow-up.ConclusionAfter reperfused acute anterior STEMI, patients with LV remodeling presented with more inhomogeneous MW distribution. The absolute difference of WE between culprit and non-culprit territory at the acute phase is an independent predictor for early LV remodeling.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier: NCT05107102.

AimsTo explore the relationship between the severity of coronary artery disease (CAD) and the occurrence of ventricular tachycardia/ventricular fibrillation (VT/VF) in patients with acute myocardial infarction (AMI).MethodsWe retrospectively enrolled 705 patients with AMI, who were hospitalized and underwent percutaneous coronary intervention (PCI), in Nanfang Hospital from July 2017 to July 2020. Logistic regression analysis and backward stepwise approach were taken to select the correlation factors. The left and the receiver operating characteristic curves (ROC) analysis were plotted to observe the discriminative power of the SYNTAX score (SS)/caFFR-guided functional SS (FSScaFFR) on the incident VT/VF.ResultsAbout 58 (8.2%) patients experienced life-threatening VT/VF. The FSScaFFR (OR: 1.155; 95% CI: 1.047 to 1.273; p = 0.004) was an independent predictor of VT/VF after AMI. The ROC analysis showed that the discriminative power of FSScaFFR on the incident VT/VF was significantly better than SS (0.759 vs.0.695, p < 0.0001). Patients with VT/VF were categorized into 2 groups according to the interval between the onset of AMI and the VT/VF. The logistic regression analysis revealed that FSScaFFR was a significant independent correlation of early- and late-VT/VF.ConclusionThe incident VT/VF in patients with AMI is closely associated with the severity of CAD evaluated by SS and FSScaFFR. Compared to SS, FSScaFFR has a higher correlation with VT/VF, and FSScaFFR was demonstrated to be an independent correlation factor of incident VT/VF after AMI.

BackgroundCatheter ablation for parahisian ventricular arrhythmias (PHVA) is technically challenging and associated with increased risks of atrioventricular block (AVB). We developed a systemic mapping approach to improve the efficacy and safety of PHVA ablation.MethodsForty-three patients (29 males; average age 65.8 ± 10.5 years) with PHVAs were enrolled. A systemic mapping approach comprising differential electrocardiogram, sequential mapping, and ablation beneath/above the septal leaflet of the tricuspid valve (SLTV) and at the neighboring/contralateral regions (the aortic root and sub-aortic valve region) was applied for PHVA. The effectiveness and safety of this approach was evaluated at 1 year's follow-up.ResultsSequential ablation beneath the SLTV (B-SLTV) succeeded in 24 (66.7 %) of 36 with right PHVA and ablation above the SLTV succeeded in 6 of the remaining 12 with failed B-SLTV ablation. Target-His bundle (HB) distance > 4.5 mm significantly predicted successful right PHVA ablation (OR 1.703; 95% CI 1.084–2.676, P = 0.02). “Seeming” right PHVA by electrocardiogram in 4 and apparent left PHVA in 3 was successfully ablated at the sub-aortic parahisian region. At 1 year's follow-up, 27 (75%) of 36 patients with right PHVA and 6 (85.7%) of 7 patients with left PHVA were free of PHVA recurrence off anti-arrhythmic drugs. The total success rate was 76.7% by using the systemic mapping approach for PHVA. One patient with A-SLTV ablation underwent pacemaker implantation due to complete AVB.ConclusionsThe systemic mapping approach was effective and safe for treating PHVA. The target-HB distance was a significant predictor for right PHVA ablation.

Background: Walking, as the most common campaign in older people, is recommended to improve their cardiovascular health. However, the direct association between weekly walking activity and asymptomatic hypertensive mediated organ damage (HMOD) remains unclear.Methods: 2,830 community-dwelling elderly subjects (over 65 years) in northern Shanghai were recruited from 2014 to 2018. Weekly walking activity was assessed by International Physical Activity Questionnaires (IPAQ). Within the framework of comprehensive cardiovascular examinations, HMOD, including left ventricular mass index, peak transmitral pulsed Doppler velocity/early diastolic tissue Doppler velocity, creatinine clearance rate, urinary albumin–creatinine ratio, carotid-femoral pulse wave velocity (cf-PWV), carotid intima–media thickness (CIMT), arterial plaque, and ankle-brachial index (ABI), were all evaluated.Results: 1,862 (65.8%) participants with weekly walking activity showed lower CIMT, lower cf-PWV, fewer abnormal ABI, and lower prevalence of hypertension and coronary heart disease (p < 0.05). Walking activity was negatively correlated with age and smokers (correlation coefficient: −0.066, −0.042; both p < 0.05). After adjusting for cardiovascular risk factors and concomitant diseases, walking activity was significantly associated with better indicator of most vascular HMOD in multivariate logistic regressions, including arterial stiffness [odds ratio (OR) = 0.75, p = 0.01], increased CIMT (OR = 0.70, p = 0.03), and peripheral artery disease (OR = 0.72, p = 0.005), but not cardiac or renal HMOD. Subgroup analysis further showed that walking duration ≥1 h/day was significantly associated with decreased risk of most vascular HMOD after adjustment for confounders and moderate-to-vigorous physical activity based on IPAQ (all p < 0.05).Conclusions: In the community-dwelling elderly Chinese, there was a significant negative association of weekly walking activity with vascular HMOD, but not cardiac or renal HMOD. Increased daily walking duration, but not walking frequency, was significantly associated with improved vascular HMOD. Hence, increasing daily walking duration seems to encourage a healthy lifestyle in terms of vascular protection.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT02368938.

Background: Recent studies have suggested that soluble suppression of tumorigenicity-2 (sST2), an inflammation-related protein receptor, is associated with atherosclerotic diseases. This study aimed to investigate the potential predictive value of sST2 on plaque vulnerability by assessing whether elevated serum levels of sST2 are associated with vulnerable plaque features in patients with non-ST-elevation acute coronary syndrome (ACS).Methods: A total of 120 patients with non-ST-elevation ACS (167 lesions) were prospectively enrolled and evaluated by standard coronary computed tomography angiography (CCTA) and coronary angiography in this study. Serum sST2 levels were measured by ELISA (Presage® ST2 Assay Kit, Critical Diagnostics), and semiautomated software (QAngioCT, Medis) was used to quantify coronary plaques.Results: The included patients were divided into 4 groups by serum sST2 level quartiles. Volumetric analysis of the whole lesion revealed that patients with higher sST2 levels had a larger absolute necrotic core (NC) volume (Quartile 4 vs. Quartile 1, 86.16 ± 59.71 vs. 45.10 ± 45.80 mm3, P = 0.001; Quartile 4 vs. Quartile 2, 86.16 ± 59.71 vs. 50.22 ± 42.56 mm3, P = 0.002) and a higher NC percentage (Quartile 4 vs. Quartile 1, 35.16 ± 9.82 vs. 23.21 ± 16.18%, P < 0.001; Quartile 4 vs. Quartile 2, 35.16 ± 9.82% vs. 22.50 ± 14.03%, P < 0.001; Quartile 4 vs. Quartile 3, 35.16 ± 9.82% vs. 25.04 ± 14.48%, P < 0.001). Correlation analysis revealed that serum sST2 levels were positively correlated with the NC (r = 0.323, P < 0.001) but negatively correlated with dense calcium (r = −0.208, P = 0.007). Furthermore, among those with plaque calcification, patients with spotty calcification exhibited higher serum sST2 levels than those with large calcification (26.06 ± 16.54 vs. 17.55 ± 7.65 ng/mL, P = 0.002). No significant differences in plaque components at the level of the minimal lumen area (MLA) were found among the groups.Conclusions: Serum sST2 levels were correlated with different coronary plaque components in patients with non-ST-elevation ACS. A higher serum level of sST2 was correlated with plaque vulnerability.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04797819.

Background: Emerging studies have described and analyzed epidemiological, clinical, laboratory, and radiological features of COVID-19 patients. Yet, scarce information is available regarding the association of lipid profile features and disease severity and mortality.Methods: We conducted a prospective observational cohort study to investigate lipid profile features in patients with COVID-19. From 9 February to 4 April 2020, a total of 99 patients (31 critically ill and 20 severely ill) with confirmed COVID-19 were included in the study. Dynamic alterations in lipid profiles were recorded and tracked. Outcomes were followed up until 4 April 2020.Results: We found that high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A-1 (apoA-1) levels were significantly lower in the severe disease group, with mortality cases showing the lowest levels (p < 0.0001). Furthermore, HDL-C and apoA-1 levels were independently associated with disease severity (apoA-1: odds ratio (OR): 0.651, 95% confidence interval (CI): 0.456–0.929, p = 0.018; HDL-C: OR: 0.643, 95% CI: 0.456–0.906, p = 0.012). For predicting disease severity, the areas under the receiver operating characteristic curves (AUCs) of HDL-C and apoA-1 levels at admission were 0.78 (95% CI, 0.70–0.85) and 0.85 (95% CI, 0.76–0.91), respectively. For in-hospital deaths, HDL-C and apoA-1 levels demonstrated similar discrimination ability, with AUCs of 0.75 (95% CI, 0.61–0.88) and 0.74 (95% CI, 0.61–0.88), respectively. Moreover, patients with lower serum concentrations of apoA-1 (