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Despite its high prevalence, effective treatment for degenerative mitral regurgitation (MR) remains elusive. Although the mineralocorticoid-receptor antagonist spironolactone, in conjunction with renin-angiotensin system (RAS) inhibitors, has been shown to reduce mortality in patients with heart failure with reduced ejection fraction (HFrEF), its efficacy in managing degenerative MR is uncertain. In this study, we aimed to compare the effectiveness of valsartan (a renin-angiotensin system inhibitor), spironolactone, and combination therapy in mitigating MR-induced myocardial dysfunction. Using a mini-invasive model of degenerative MR, we administered valsartan (31 mg/kg/day), spironolactone (80 mg/kg/day), or a combination of both to rats over a 4-week period. Serial echocardiography and pressure-volume loops were utilized to assess cardiac function and hemodynamics. Rats with degenerative MR treated with valsartan or spironolactone alone did not show significant improvement in myocardial dysfunction. In contrast, combination therapy resulted in significant improvement. Similarly, the pressure-volume relationship was significantly improved in rats treated with the combination therapy compared to that in rats treated with a single therapy. Mechanistically, combination therapy effectively suppressed circulating and cardiac expression of aldosterone- and apoptosis-associated proteins. Overall, combination treatment with valsartan and spironolactone significantly attenuated the degenerative MR-induced myocardial stress and dysfunction, suggesting a potential therapeutic avenue for managing degenerative MR-induced HF.

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Introduction: Although angiotensin receptor-neprilysin inhibitor (ARNI) has shown promise in patients with heart failure and reduced ejection fraction (HFrEF), the treatment effect in HFrEF patients with end-stage renal disease (ESRD) undergoing dialysis is uncertain. This study aimed to examine the real-world effects of ARNI vs. angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in this subpopulation. Methods: This multi-institutional, retrospective study identified 349 HFrEF patients with ESRD on dialysis, who initiated either ARNI or ACEI/ARB therapy. Efficacy outcomes included rates of hospitalization for heart failure (HHF) and mortality, as well as changes in echocardiographic parameters. Safety outcomes encompassed hypotension and hyperkalemia. Treatment effects were assessed using Cox proportional hazards models, with additional sensitivity analyses for robustness. Results: Out of 349 patients screened, 89 were included in the final analysis (42 in the ARNI group and 47 in the ACEI/ARB group). After 1 year of treatment, echocardiographic measures between the two groups were comparable. The primary composite rate of HHF or mortality was 20.6 events per 100 patient-years in the ARNI group and 26.1 in the ACEI/ARB group; the adjusted hazard ratio was 0.98 (95% CI: 0.28-3.43, P = 0.97). Their safety outcomes did not differ significantly. Sensitivity analyses, including repetitive sampling, propensity score matching, and extended follow-up, corroborated these findings. Conclusion: ARNI has proven effective in treating HFrEF patients; however, significant benefits were not observed in these patients with ESRD undergoing dialysis compared with ACEI/ARB in this real-world cohort. Future research employing a more extended follow-up period, larger sample size, or randomized design is warranted to investigate the treatment effects in this subpopulation.

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BACKGROUND: Patients with chronic kidney disease (CKD) experience atrial fibrillation more frequently. The balance of medical management for stroke prevention and bleeding events presents a challenging issue in CKD population. Left atrial appendage occlusion (LAAO) may be an effective solution for stroke prevention in patients who experience frequent bleeding with oral anticoagulants. However, the specific impact of CKD on the procedural success, complications, and outcomes of LAAO implantations remains underexplored. METHODS: We conducted a search of various databases for articles published before October 31, 2023. This search yielded 7 studies, comparing outcomes between CKD and non-CKD cohorts undergoing LAAO implantation. Our analysis focused on CHA2DS2-VASc scores, average eGFR, use of oral anticoagulants, procedural success rates, procedural complications, and associated outcomes. RESULTS: The meta-analysis included data from 2576 patients, with 1131 identified as having CKD. The CKD group also had higher CHA2DS2-VASc scores (4.7 ±â€…1.4 vs 4.0 ±â€…1.5; P < .001) and HAS-BLED scores (3.8 ±â€…1.1 vs 3.1 ±â€…1.0; P < .001) than the non-CKD group. CKD patients showed a nonreduction in procedural success rates and a nonsignificant increase in total complications. The risks of stroke and transient ischemic attack, major bleeding, and cardiovascular mortality were not significantly different between the 2 groups. However, a significantly lower rate of total mortality was observed in the non-CKD group (odds ratio: 0.43; 95% confidence interval, 0.32-0.60). CONCLUSION: While CKD is associated with a nonsignificant decrease in procedural success and a nonsignificant increase in complication risks, the outcomes of LAAO implantation are comparably favorable between CKD and non-CKD groups. Despite similar procedural outcomes, the CKD group exhibited a higher rate of all-cause mortality.

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Previous studies have suggested a possible association between carbon monoxide poisoning (COP) and hypothyroidism, but the evidence is limited. Therefore, the aim of this study was to further investigate this relationship. Using data from the Taiwan National Health Research Database, we identified 32,162 COP patients and matched with 96,486 non-COP patients by age and index date for an epidemiological study. The risk of hypothyroidism was compared between the two cohorts until 2018. Independent predictors of hypothyroidism were analyzed using competing risk analysis. An animal study was also conducted to support the findings. COP patients had an increased risk of hypothyroidism compared to non-COP patients in the overall analysis (adjusted hazard ratio [AHR]= 3.88; 95 % confidence interval [CI]: 3.27-4.60) and in stratified analyses by age, sex, and comorbidities. The increase in the overall risk persisted even after more than six years of follow-up (AHR= 4.19; 95 % CI: 3.18-5.53). Independent predictors of hypothyroidism, in addition to COP, included age ≥65 years, female sex, hyperlipidemia, and mental disorder. The animal study showed damages in the hypothalamus, pituitary gland, and thyroid, as well as altered hormone levels 28 days after COP exposure. The epidemiological results showed an increased risk of hypothyroidism in COP patients, which was further supported by the animal study. These findings suggest the need for close monitoring of thyroid function in COP patients, especially in those who are age ≥65 years, female, and have hyperlipidemia or mental disorder.

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High-frequency ultrasound (HFUS; >30 MHz) Doppler imaging has been widely used in the imaging of small animals and humans because of its high resolution. Vector Doppler imaging (VDI) has certain advantages for visualizing complex flow patterns independent of the Doppler angle. However, no commercial HFUS VDI system is currently available; therefore, several studies have connected an ultrasound research platform (Verasonics Vantage 256) with an HFUS array transducer for HFUS VDI. Unfortunately, the maximum frame rate of this system is only 10 kHz at an operational frequency of 40 MHz because of limitations related to data transmission hardware, thereby restricting the maximum detectable velocity of Doppler measurements. To address this drawback, in the present study, an electrocardiography (ECG)-gating-based HFUS VDI system was developed to avoid Doppler flow aliasing in data acquisition by ultrasound research platform at its maximum frame rate of 10 kHz. The developed method aligns all tilted plane waves with the ECG R-wave, which avoids the trade-off between frame rate and tilted angles number in conventional VDI. The performance of the proposed data acquisition method in HFUS VDI was verified using a steady-flow phantom, for which estimation errors were less than 10% under different flow settings. In animal studies, peak flow velocities in the carotid artery, left ventricle, and aortic arch of wild-type mice were measured (approximately 55, 655, and 765 mm/s, respectively). Also, the HFUS VDI from the mitral regurgitation mice model was obtained to present the complex flow patterns through the proposed method. In contrast to the conventional method, no Doppler aliasing occurs in the proposed method because the frame rate is sufficient. The experimental results indicate the developed HFUS VDI has the potential to become a useful tool for vector flow visualization in small animals, even under a high flow velocity.

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BACKGROUND Long-term right ventricular (RV) pacing has been linked to left atrial enlargement (LAE). The incidence and risk factors associated with significant LAE after RV pacing remain unknown. This retrospective study included 461 patients requiring RV pacing at 2 centers between 2012 and 2020 and aimed to evaluate the incidence, risk factors, outcomes, and complications of LAE. MATERIAL AND METHODS A total of 461 patients with normal-sized pre-implant left atrial dimension and dual-chamber pacing pacemaker implantation for complete atrioventricular block were enrolled. Patients were grouped based on a ≥20% increase from their baseline left atrial dimension by echocardiography, indicating significant LAE, and initial characteristics, echocardiographic data, and outcomes were compared. RESULTS During a mean 7.0±4.9 years follow-up period, 96 patients (20.8%) developed significant LAE, whereas 365 patients did not. In multivariate logistic regression analysis, smaller pre-implant left atrial dimension (OR, 0.776; 95% CI, 0.728-0.828; P<0.001), lower post-implant left ventricular ejection fraction (OR, 0.976; 95% CI, 0.957-0.995; P=0.014), post-implant development of moderate to severe mitral regurgitation (OR, 2.357; 95% CI, 1.172-4.740; P=0.016), and RV pacing duration ≥3.3 years (OR, 1.576; 95% CI, 1.039-2.646; P=0.045) were independent predictors of significant LAE after RV-dependent pacing. There was a significant difference in the incident stroke events between patients without and with significant LAE (9.9% vs 17.7%; log-rank P=0.047). CONCLUSIONS Long-term RV pacing was linked to significant LAE in 20.8% of patients with complete atrioventricular block, with those affected experiencing a higher stroke rate during follow-up.

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AIMS: Heart failure with reduced ejection fraction (HFrEF) significantly impacts health-related quality of life (HR-QoL). Existing HR-QoL questionnaires can show inconsistencies, potentially misrepresenting patient self-reports. This study examines the variation in HR-QoL measurement tools for HFrEF patients, identifying related determinants. METHODS AND RESULTS: We retrospectively analysed 134 hospitalized patients with acute decompensated HFrEF at a Taiwanese tertiary centre's Heart Failure Post-Acute-Care (HF-PAC) programme. Participants completed the EuroQol-5 dimension (EQ-5D) questionnaire, the EQ-5D visual analogue scale (VAS), and the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Utility values were obtained from the EQ-5D questionnaire. Demographic features were depicted using descriptive statistics, while multivariate regression was used to ascertain relationships between HR-QoL measurements and determinants. Average scores for EQ-5D, MLHFQ, EQ-5D utility, and VAS were 6.1 ± 1.6, 21.8 ± 21.3, 81.7 ± 27.0, and 59.5 ± 14.6, respectively. Significant correlations were observed among the three tools. The New York Heart Association functional class showed a notable association with all tool scores. Other associations encompassed EQ-5D with coronary artery disease, mineralocorticoid receptor antagonists, and the 6 min walk test; EQ-5D VAS with chronic kidney disease; and MLHFQ with age. CONCLUSIONS: This study illuminates the variance in HR-QoL measurement tools for Taiwanese HFrEF patients. Using a range of these tools is beneficial in unveiling diverse determinants and approaching comprehensive patient-centred care. However, for a more precise HR-QoL assessment in Taiwanese HFrEF patients, recalibrating the EQ-5D-derived utility scores might be necessary, emphasizing the importance of patient-specific considerations within the HF-PAC programme.

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Background: The door-to-balloon (D2B) time is a critical quality measure in managing ST-segment elevation myocardial infarction (STEMI) patients receiving primary percutaneous coronary intervention (PCI). We developed an integrated STEMI activation system, named Acute Myocardial Infarction Software Aids (AMISTAD), to optimize care for STEMI patients. This study aimed to evaluate the impact of the AMISTAD system on D2B times and clinical outcomes. Methods: We retrospectively collected data of consecutive STEMI patients receiving primary PCI between July 2017 and December 2018 at a single center. The patients were categorized into AMISTAD and non-AMISTAD groups. Outcomes included D2B time, length of hospital stay, and 12-month cardiovascular outcomes. Data were analyzed using multiple regression models; subgroup and sensitivity analyses were applied to examine the robustness of the results. Results: A total of 114 STEMI patients were enrolled (38 AMISTAD, 76 non-AMISTAD). The AMISTAD group had a significantly shorter mean D2B time (66.7 ± 13.2 vs. 76.6 ± 24.9 minutes, p = 0.02) and non-significantly shorter length of hospital stay (4.7 vs. 7.2 days, p = 0.09). The 12-month cardiovascular outcomes between the two groups were not significantly different (adjusted hazard ratio 0.79, 95% confidence interval 0.30-2.09, p = 0.64). Subgroup and sensitivity analyses had consistent outcomes. Conclusions: Integrating the AMISTAD system into the STEMI workflow was associated with a reduced D2B time and shorter hospital stay. Further research involving larger cohorts and extended follow-up periods is needed to assess the generalizability and impact on cardiovascular outcomes. The AMISTAD system has the potential to improve the quality of care for STEMI patients.

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BACKGROUND: Sodium-glucose cotransporter 2-inhibitors (SGLT2i) improve cardiovascular outcomes including reduction in risk of first hospitalisation for heart failure (HF), worsening HF and cardiovascular death regardless of HF or diabetes mellitus (DM) status. It is not known whether SGLT2i can prevent the development of incident HF or reduce the risk of HF in patients receiving trastuzumab with or without other concurrent anti-HER2 agent or sequential anthracycline for treatment of HER2 positive breast cancer. Patients with active malignancy or recent history of malignancy were excluded from participating in the main cardiovascular outcome trials involving SGLT2i. AIM: A systematic review was performed to objectively assess published literature on the cardioprotective effects of SGLT2i in breast cancer treatment-related cardiotoxicity. METHODS: Systematic searches of Embase, Medline, The Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases were performed. Titles and abstracts were screened separately by two cardio-oncologists (JHC, WTC). Full texts of potentially eligible records were then assessed separately by JHC and WTC before inclusion into review upon joint agreement. RESULTS: 479 records were identified from 3 databases (MEDLINE=51, EMBASE=408, CENTRAL=13) and 1 registry (Clinicaltrials.gov=7). 460 records were excluded based on title and abstract (including duplicates). 19 full text reports were assessed for eligibility and included in review (basic science/animal study paper 2, Clinicaltrials.gov randomised controlled trial submission 1 (currently recruiting), basic science/animal study conference abstract 5, case report 2, review 3, editorial comment 2, clinical guidelines 1, retrospective/registry-based conference abstract 3). CONCLUSION: Cardiotoxicity is the most common dose-limiting toxicity associated with trastuzumab. Discontinuation of trastuzumab however, can lead to worse cancer outcomes. There have been case reports, registry-based, retrospective cohort-based and mechanistic studies suggesting the cardioprotective potential of SGLT2i in cancer therapy-related cardiac dysfunction (CTRCD). Based on these, there is now a call for randomised controlled trials to be performed in this patient cohort to advise guideline-directed therapy for CTRCD, which will in turn also provide detailed safety information and improve cancer and cardiovascular outcomes.

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BACKGROUND: Ivabradine, a medical treatment for heart failure (HF), reduces heart rate (HR) and prolongs diastolic perfusion time. It is frequently prescribed to patients with HF who have a suboptimal response or intolerance to beta-blockers. Degenerative mitral regurgitation (MR) is a valvular heart disease often associated with the development of HF and atrial fibrillation (AF). However, studies comparing the effects of ivabradine and beta-blockers on MR are lacking. Therefore, this study aimed to explore the potential therapeutic effects of ivabradine and carvedilol on MR using a rat model. METHODS AND RESULTS: Using a novel echo-guided mini-invasive surgery, MR was created in 12-weeks-old Sprague-Dawley rats. After 2 weeks, the rats were randomized to receive either ivabradine or carvedilol for 4 weeks. Echocardiography was performed at baseline and at two-week intervals. Following haemodynamic studies, postmortem tissues were analysed. Notably, the MR-induced myocardial dysfunction did not improve considerably after treatment with ivabradine or carvedilol. However, in haemodynamic studies, pharmacological therapies, particularly carvedilol, mitigated MR-induced chamber dilatation (end-systolic volume and end-diastolic volume; MR vs. MR + Carvedilol; P < 0.05) and decreased compliance (end-systolic pressure-volume relationship; MR vs. MR + Carvedilol; P < 0.05). Compared with ivabradine, a shorter duration (MR vs. MR + Carvedilol; P < 0.05) and reduced inducibility (MR vs. MR + Carvedilol and MR vs. MR + Ivabradine; P < 0.05) of AF were observed in MR rats treated with carvedilol. Similarly, reduced cardiac fibrosis and apoptosis were observed in the MR rat model in the treatment groups, especially in those treated with carvedilol (MR vs. MR + Carvedilol; P < 0.01). CONCLUSIONS: Although both ivabradine and carvedilol, at least in part, mitigated MR-induced chamber dilatation and decreased compliance, carvedilol had a better effect on reversing MR-induced cardiac fibrosis, apoptosis, and arrhythmogenesis than ivabradine. When compared with Ivabradine, MR rats treated with carvedilol exhibited a shorter duration and reduced inducibility of AF, thus providing more effective suppression of HCN4. Further investigations are required to validate our findings.

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Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.

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Introduction: Contrast-induced nephropathy (CIN) is a common complication of percutaneous coronary intervention (PCI). Identifying patients at high CIN risk remains challenging. The triglyceride-glucose (TyG) index may help predict CIN but evidence is limited. We conducted a meta-analysis to evaluate the diagnostic value of TyG index for CIN after PCI. Methods: A systematic literature search was performed in MEDLINE, Cochrane, and EMBASE until August 2023 (PROSPERO registration: CRD42023452257). Observational studies examining TyG index for predicting CIN risk in PCI patients were included. This diagnostic meta-analysis aimed to evaluate the accuracy of the TyG index in predicting the likelihood of CIN. Secondary outcomes aimed to assess the pooled incidence of CIN and the association between an elevated TyG index and the risk of CIN. Results: Five studies (Turkey, n=2; China, n=3) with 3518 patients (age range: 57.6 to 68.22 years) were included. The pooled incidence of CIN was 15.3% [95% confidence interval (CI) 11-20.8%]. A high TyG index associated with increased CIN risk (odds ratio: 2.25, 95% CI 1.82-2.77). Pooled sensitivity and specificity were 0.77 (95% CI 0.59-0.88) and 0.55 (95% CI 0.43-0.68) respectively. Analysis of the summary receiver operating characteristic (sROC) curve revealed an area under the curve of 0.69 (95% CI 0.65-0.73). There was a low risk of publication bias (p = 0.81). Conclusion: The TyG index displayed a noteworthy correlation with the risk of CIN subsequent to PCI. However, its overall diagnostic accuracy was found to be moderate in nature. While promising, the TyG index should not be used in isolation for CIN screening given the heterogeneity between studies. In addition, the findings cannot be considered conclusive given the scarcity of data. Further large-scale studies are warranted to validate TyG cutoffs and determine how to optimally incorporate it into current risk prediction models. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023452257, identifier CRD42023452257.

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AIMS: Critical limb ischemia (CLI) is an emerging public health threat and lacks a reliable score for predicting the outcomes. The Age, Body Mass Index, Chronic Kidney Disease, Diabetes, and Genotyping (ABCD-GENE) risk score helps identify patients with coronary artery disease who have cytochrome P450 2C19 (CYP2C19) polymorphism-related drug resistance and are at risk for cardiovascular adverse events. However, its application to CLI remains unknown. In this study, we aim to validate a modified ACD-GENE-CLI score to improve the prediction of major adverse limb events (MALEs) in patients with CLI receiving clopidogrel. METHODS: Patients with CLI receiving clopidogrel post-endovascular intervention were enrolled prospectively in two medical centers. Amputation and revascularization as MALEs were regarded as the outcomes. RESULTS: A total of 473 patients were recruited, with a mean follow-up duration of 25 months. Except for obesity, old age, diabetes, chronic kidney disease (CKD), and CYP2C19 polymorphisms were significantly associated with MALEs. Using bootstrap regression analysis, we established a modified risk score (ACD-GENE-CLI) that included old age (≥ 65 years), diabetes, CKD, and CYP2C19 polymorphisms. At a cutoff value of 8, the ACD-GENE-CLI score was superior to the CYP2C19 deficiency only, and the conventional ABCD-GENE score in predicting MALEs (area under the curve: 0.69 vs. 0.59 vs. 0.67, p=0.01). The diagnostic ability of the ACD-GENE-CLI score was consistent in the external validation. Also, Kaplan-Meier curves showed that in CYP2C19 deficiency, the ABCD-GENE and ACD-GENE-CLI scores could all differentiate patients with CLI who are free from MALEs. CONCLUSIONS: The modified ACD-GENE-CLI score could differentiate patients with CLI receiving clopidogrel who are at risk of MALEs. Further studies are required to generalize the utility of the score.

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Background: Postoperative infectious complications (PICs) are major concerns. Early and accurate diagnosis is critical for timely treatment and improved outcomes. Presepsin is an emerging biomarker for bacterial infections. However, its diagnostic efficacy for PICs across surgical specialties remains unclear. Methods: In this study, a systematic search on MEDLINE, Embase, Google Scholar, and Cochrane Library was performed on September 30, 2023, to identify studies that evaluated presepsin for diagnosing PICs. PIC is defined as the development of surgical site infection or remote infection. Pooled sensitivity, specificity, and hierarchical summary receiver operating characteristic (HSROC) curves were calculated. The primary outcome was the assessment of the efficacy of presepsin for PIC diagnosis, and the secondary outcome was the investigation of the reliability of procalcitonin or C-reactive protein (CRP) in the diagnosis of PICs. Results: This meta-analysis included eight studies (n = 984) and revealed that the pooled sensitivity and specificity of presepsin for PIC diagnosis were 76% (95% confidence interval [CI] 68%-82%) and 83% (95% CI 75%-89%), respectively. The HSROC curve yielded an area under the curve (AUC) of 0.77 (95% CI 0.73-0.81). Analysis of six studies on procalcitonin showed a combined sensitivity of 78% and specificity of 77%, with an AUC of 0.83 derived from the HSROC. Meanwhile, data from five studies on CRP indicated pooled sensitivity of 84% and specificity of 79%, with the HSROC curve yielding an AUC of 0.89. Conclusion: Presepsin exhibits moderate diagnostic accuracy for PIC across surgical disciplines. Based on the HSROC-derived AUC, CRP has the highest diagnostic efficacy for PICs, followed by procalcitonin and presepsin. Nonetheless, presepsin demonstrated greater specificity than the other biomarkers. Further study is warranted to validate the utility of and optimize the cutoff values for presepsin. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023468358.

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BACKGROUND: Pulmonary artery hypertension (PAH) is a fatal disease characterized by a complex pathogenesis. Exosomes containing microRNAs (miRs) have emerged as a novel biomarker. Transpulmonary exosomal miRs offer valuable insights into pulmonary circulation microenvironments. Hereby, we aimed to explore the potentials of transpulmonary exosomal miRs as differentiating factors between idiopathic PAH and congenital heart disease (CHD)-related PAH. METHODS AND RESULTS: During right heart catheterization, we collected exosomes at pulmonary arteries in 25 patients diagnosed with idiopathic PAH and 20 patients with CHD-related PAH. Next-generation sequencing identified several candidate exosomal miRs. Using quantitative polymerase chain reaction, we validated the expressions of these miRs and revealed significantly elevated expressions of miR-21, miR-139-5p, miR-155-5p, let-7f-5p, miR-328-3p, miR-330-3p, and miR-103a-3p in patients with CHD-related PAH, in contrast to patients with idiopathic PAH. Among these miRs, miR-21 exhibited the highest expression in patients with CHD-related PAH. These findings were further corroborated in an external cohort comprising 10 patients with idiopathic PAH and 8 patients with CHD-related PAH. Using an in vitro flow model simulating the shear stress experienced by pulmonary endothelial cells, we observed a significant upregulation of miR-21. Suppressing miR-21 rescued the shear stress-induced downregulation of the RAS/phosphatidylinositol 3-kinase/protein kinase B pathway, leading to a mitigation of apoptosis. CONCLUSIONS: Our study identified a pronounced expression of transpulmonary exosomal miR-21, particularly in patients with CHD-related PAH, through next-generation sequencing analysis. Further investigation is warranted to elucidate the regulatory mechanisms involving miR-21 in the pathophysiology of PAH.

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The predictive value of the prognostic nutritional index (PNI) for the long-term prognosis of patients with acute coronary syndrome (ACS) remains uncertain. Medline, Embase, Cochrane Library, and Google Scholar were searched from inception until January 2023 to study the relationship between all-cause mortality risk and PNI in patients receiving percutaneous coronary intervention for ACS (i.e., primary outcome). Thirteen observational studies were included in this meta-analysis. Analysis of seven studies using PNI as a categorical variable showed a pooled hazard ratio (HR) of all-cause mortality of 2.97 (95% CI 1.65 to 5.34, p = 0.0003, I2 = 89%, n = 11,245) for patients with a low PNI. The meta-analysis also showed a higher risk of major adverse cardiovascular events (MACEs) in patients with a low PNI (HR 2.04; 95% CI 1.59 to 2.61; p < 0.00001; I2 = 21%; n = 8534). Moreover, advanced age, diabetes mellitus, and high Global Registry of Acute Coronary Events risk scores were associated with a high risk of all-cause mortality, whereas a high body mass index was associated with a low risk of all-cause mortality. The results showed an association between a low PNI and an increased risk of long-term mortality in patients undergoing coronary interventions for ACS. Further randomized controlled trials are necessary to confirm these findings.

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Doxorubicin (Dox) is a potent anticancer agent, but its associated organ toxicity, including nephrotoxicity, restricts clinical applications. Dapagliflozin (DAPA), a sodium-glucose cotransporter-2 inhibitor, has been shown to slow the progression of kidney disease in patients with and without diabetes. However, the effect of DAPA to counteract Dox-induced nephrotoxicity remains uncertain. Therefore, in this study, we aimed to elucidate the effects of DAPA in mitigating Dox-induced nephrotoxicity. We analyzed the Taiwan National Health Insurance Database to evaluate the incidence of renal failure among breast cancer patients receiving Dox treatment compared to those without. After adjusting for age and comorbidities, we found that the risk of renal failure was significantly higher in Dox-treated patients (incidence rate ratio, 2.45; confidence interval, 1.41-4.26; p = 0.0014). In a parallel study, we orally administered DAPA to Sprague-Dawley rats for 6 weeks, followed by Dox for 4 weeks. DAPA ameliorated Dox-induced glomerular atrophy, renal fibrosis, and dysfunction. Furthermore, DAPA effectively suppressed Dox-induced apoptosis and reactive oxygen species production. On a cellular level, DAPA in HK-2 cells mitigated Dox-mediated suppression of the endothelial NOS pathway and reduced Dox-induced activities of reactive oxygen species and apoptosis-associated proteins. DAPA improved Dox-induced apoptosis and renal dysfunction, suggesting its potential utility in preventing nephrotoxicity in patients with cancer undergoing Dox treatment.

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Cardiac amyloidosis is one form of systemic amyloidosis caused by abnormal amyloid fibrils deposited in the extracellular space of the myocardium causing heart failure because of restrictive cardiomyopathy and conduction disturbances. The incidence and prevalence of cardiac amyloidosis are higher than previously noted, particularly among special populations. The most common forms of cardiac amyloidosis are light chain and transthyretin amyloid cardiomyopathy. Even though more than 70% of patients with systemic amyloidosis have cardiac amyloidosis, the diagnosis is often delayed, suggesting significant gaps in the knowledge of cardiac amyloidosis and a lack of multidisciplinary teamwork in our daily practice. The Taiwan Society of Cardiology Heart Failure Committee organized experts to draft the "Expert Consensus on the diagnosis and treatment of cardiac amyloidosis." This statement aims to help clinicians and healthcare professionals improve early diagnosis and management of cardiac amyloidosis in Taiwan. The expert panel met virtually to review the data and discuss the consensus statements. Our review provided practical information about diagnostic methods and algorithms, clinical clues and red-flag signs, cardiac amyloidosis per se and its comorbidities treatment modalities, and follow-up plans for asymptomatic transthyretin gene carriers. We especially innovate two acronyms, "HFpEF MUTED CALL" and "HFmrEF MUST COUNT", to help in the early diagnosis and screening of transthyretin amyloid cardiomyopathy as shown in the Central Illustration.

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Background: People living with HIV (PLWH) have an increased risk of developing cardiovascular diseases (CVD). As speckle-tracking echocardiography (STE) has been used to detect subclinical myocardial abnormalities, this study aims to detect early cardiac impairment among Asian PLWH using STE and to investigate the associated risk factors. Methods: We consecutively recruited asymptomatic PLWH without previous CVD from a medical center of Taiwan, and their cardiac function was evaluated by conventional echocardiogram and STE. Enrolled PLWH were classified as antiretroviral therapy (ART)-experienced and ART-naive, and multivariable regressions were used to assess the association between myocardial strain and risk factors including traditional CVD and HIV-associated factors. Results: A total of 181 PLWH (mean age: 36.4 ± 11.4 years, 173 males) were recruited and conventional echocardiogram parameters were within normal ranges. Decreased myocardial strain across the myocardium was found, with a mean left ventricular (LV) global longitudinal strain of -18.7 ± 2.9%. The LV strain in the ART-experienced group (-19.0 ± 2.9%) was significantly better than the ART-naive group (-17.9 ± 2.8%), despite a younger age and lesser CVD risk factors in the ART-naive group. Hypertension [B = 1.92, 95% confidence interval (95% CI) 0.19-3.62, p = 0.029] and ART-naive with both low and high viral loads (VL) (B = 1.09, 95% CI 0.03-2.16, p = 0.047; and B = 2.00, 95% CI, 0.22-3.79, p = 0.029) were significantly associated with reduced myocardial strain. Conclusion: This is the first and largest cohort using STE to investigate myocardial strain in Asian PLWH. Our results suggest that hypertension and detectable VL are associated with impaired myocardial strain. Thus, timely ART administration with VL suppression and hypertension control are crucial in preventing CVD when making the management parallel with the improved life expectancy of PLWH on ART.