The combination of valsartan and spironolactone mitigated mitral regurgitation induced cardiac dysfunction in a novel rat model.

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.

Incidence, Risk Factors, and Outcomes of Left Atrial Enlargement in Patients Requiring Right Ventricular Pacing: A Retrospective Study of 461 Cases from 2012 to 2020.

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.

Hypothyroidism following carbon monoxide poisoning: An epidemiological study supported by animal experiments.

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.

Impact of the Integrated Activation System on Door-to-Balloon Times and Clinical Outcomes in STEMI Patients Receiving Primary PCI.

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.

Increasing the Maximum Detectable Flow Velocity in High-Frequency Ultrasound Vector Doppler Imaging.

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.

Impact of chronic kidney disease on left atrial appendage occlusion: A meta-analysis of procedural outcomes and complications.

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.

The cardioprotective potential of sodium-glucose cotransporter 2-inhibitors in breast cancer therapy-related cardiac dysfunction - A systematic review.

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.

Real-world experience of angiotensin receptor-neprilysin inhibitors in patients with heart failure and dialysis.

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.

Assessing the diversity and determinants of health-related quality of life measures in patients with acute heart failure.

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.

Diagnostic efficacy of serum presepsin for postoperative infectious complications: a meta-analysis.

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.