In vivo pulsed-field ablation in healthy vs. chronically infarcted ventricular myocardium: biophysical and histologic characterization.

AIMS: Data on ventricular pulsed-field ablation (PFA) are sparse in the setting of chronic myocardial infarction (MI). The objective of this study was to compare the biophysical and histopathologic characteristics of PFA in healthy and MI swine ventricular myocardium. METHODS AND RESULTS: Myocardial infarction swine (n = 8) underwent coronary balloon occlusion and survived for 30 days. We then performed endocardial unipolar, biphasic PFA of the MI border zone and a dense scar with electroanatomic mapping and using an irrigated contact force (CF)-sensing catheter with the CENTAURI System (Galaxy Medical). Lesion and biophysical characteristics were compared with three controls: MI swine undergoing thermal ablation, MI swine undergoing no ablation, and healthy swine undergoing similar PFA applications that included linear lesion sets. Tissues were systematically assessed by gross pathology utilizing 2,3,5-triphenyl-2H-tetrazolium chloride staining and histologically with haematoxylin and eosin and trichrome. Pulsed-field ablation in healthy myocardium generated well-demarcated ellipsoid lesions (7.2 ± 2.1 mm depth) with contraction band necrosis and myocytolysis. Pulsed-field ablation in MI demonstrated slightly smaller lesions (depth 5.3 ± 1.9 mm, P = 0.0002), and lesions infiltrated into the irregular scar border, resulting in contraction band necrosis and myocytolysis of surviving myocytes and extending to the epicardial border of the scar. Coagulative necrosis was present in 75% of thermal ablation controls but only in 16% of PFA lesions. Linear PFA resulted in contiguous linear lesions with no gaps in gross pathology. Neither CF nor local R-wave amplitude reduction correlated with lesion size. CONCLUSION: Pulsed-field ablation of a heterogeneous chronic MI scar effectively ablates surviving myocytes within and beyond the scar, demonstrating promise for the clinical ablation of scar-mediated ventricular arrhythmias.

Hypoxia inducible factor-prolyl hydroxylase inhibitors in anemic patients with non-dialysis dependent chronic kidney disease: a meta-analysis of randomized clinical trials.

PURPOSE: Anemia persists as a challenge in chronic kidney disease (CKD) patients. Current therapies are the injectable erythropoietin stimulating agents (ESA). Concerns have been raised regarding ESA cardiovascular safety, therefore search for an alternative, convenient and safe therapy is underway. Hypoxia inducible factors-prolyl hydroxylase inhibitors (HIF-PHI) are oral agents with promising results. Numerous small studies reported favorable effects with lack of large, powered studies. METHODS: We conducted a meta-analysis of randomized clinical trials to assess the efficacy and safety of HIF-PHI in non-dialysis-dependent CKD patients. Primary outcome was hemoglobin (Hb) concentration post intervention. Secondary outcomes were all-cause mortality, MACE, and changes in iron metabolism (ferritin, hepcidin). We reported total and serious adverse effects. Data were pooled using a random effect model via RevMan 5.4 software. RESULTS: We identified 7 trials comprising of 8228 patients (mean age 66.5 ± 13.2 years, 42% were females, 53% used iron replacement) with a mean follow-up of 52 weeks. Compared with the standard of care (ESA), HIF-PHI were non-inferior for treatment of anemia, with comparable effect on mortality and major adverse cardiovascular events. HIF-PHI showed no major safety concerns. Main side effect of HIF-PHI was diarrhea. CONCLUSION: HIF-PHI might represent a safe, and convenient alternative to ESA in non-dialysis dependent CKD patients with anemia.

Sex-based outcomes of surgical myectomy for hypertrophic cardiomyopathy: An analysis from the National Readmission Database.

BACKGROUND: There is a paucity of data on sex differences in outcomes after surgical myectomy (SM) for hypertrophic cardiomyopathy (HCM). METHODS: Patients who received SM for HCM during October 1, 2015, through December 31, 2018, were identified from the US National Readmission Database. The primary end point of this study was in-hospital mortality. The secondary end points were major bleeding, acute kidney injury, new pacemaker implantation, severe disability surrogates (non-home discharge and need for mechanical ventilation), resources utilization surrogates (length of stay and cost of hospitalization), and 30-day outcomes (readmission rate, mortality, and new pacemaker insertion). RESULTS: A total of 3031 patients were included in the current analysis. Using propensity score matching, 2 well matched cohorts were compared (women = 1170 and men = 1127). Women had a higher requirement for new pacemaker insertion compared with men (10.9% vs 6.8%; P = .029), higher number of non-home discharges (13.8% vs 7.9%; P < .01), and longer length of hospital stay (median = 7 [interquartile range, 5-9] days) versus (median = 6 [interquartile range, 5-8] days). There was no difference in in-hospital mortality, major bleeding, blood transfusion, acute kidney injury, or hospitalization costs for women versus men. At 30 days, women continued to show a higher need for pacemaker insertion (11.3% vs 7.1%; P = .03) and had a higher readmission rate than men (10.9% vs 7.1%; P = .02). There was no difference in 30-day mortality between women and men (3% vs 2.4%; P = .54). CONCLUSIONS: Among the HCM cohort who received SM, significant sex-based differences in the outcomes were observed. Women had higher new pacemaker insertion rate, higher non-home discharge rate, and higher rate of 30-day readmission compared with men.

The Efficacy and Safety of Direct Oral Anticoagulants versus Standard of Care in Patients without an Indication of Anti-Coagulants after Transcatheter Aortic Valve Replacement: A Meta-Analysis of Randomized Controlled Trials.

Transcatheter aortic valve replacement (TAVR) is now considered the mainstay of aortic stenosis management; however, the optimal antithrombotic therapy in patent without indications for an oral anticoagulant (OAC) is yet to be identified. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of direct oral anticoagulant (DOAC) treatment versus the standard of care in patients without indications of OACs after TAVR. We synthesized randomized controlled trials (RCTs) from Web of Science, SCOPUS, EMBASE, PubMed, and Cochrane until 18 August 2022. We used the risk ratio (RR) for dichotomous outcomes with the corresponding 95% confidence interval (CI). We registered our protocol in PROSPERO with ID: CRD42022357027. Three RCTs with 2922 patients were identified. DOACs were significantly associated with higher incidence of all-cause mortality (RR: 1.68 with 95% CI [1.22, 2.30], p = 0.001), mortality due to non-cardiovascular causes (RR: 2.34 with 95% CI [1.36, 4.02], p = 0.002), and the composite outcome of death, myocardial infarction, or stroke (RR: 1.41 with 95% CI [1.13, 1.76], p = 0.002). However, DOACs were associated with decreased incidence of reduced leaflet motion (RLM) (RR: 0.19 with 95% CI [0.09, 0.41], p = 0.0001) and hypoattenuated leaflet thickening (HALT) (RR: 0.50 with 95% CI [0.36, 0.70], p = 0.0001). DOACs were effective to reduce RLM and HALT; however, the clinical effect of this is still controversial. DOACs were associated with worse efficacy and safety outcomes, including all-cause mortality. Further RCTs investigating the optimal antithrombotic regimen after TAVR.

Effect of TAVR Approach and Other Baseline Factors on the Incidence of Acute Kidney Injury: A Systematic Review and Meta-Analysis.

Background: Acute kidney injury (AKI) is a well-known complication following a transcatheter aortic valve replacement (TAVR) and is associated with higher morbidity and mortality. Objective: We aim to compare the risk of developing AKI after transfemoral (TF), transapical (TA), and transaortic (TAo) approaches following TAVR. Methods: We searched Medline and EMBASE databases from January 2009 to January 2021. We included studies that evaluated the risk of AKI based on different TAVR approaches. After extracting each study's data, we calculated the risk ratio and 95% confidence intervals using RevMan software 5.4. Publication bias was assessed by the forest plot. Results: Thirty-six (36) studies, consisting of 70,406 patients undergoing TAVR were included. Thirty-five studies compared TF to TA, and only seven investigations compared TF to TAo. AKI was documented in 4,857 out of 50,395 (9.6%) patients that underwent TF TAVR compared to 3,155 out of 19,721 (16%) patients who underwent TA-TAVR, with a risk ratio of 0.49 (95% CI, 0.36-0.66; p < 0.00001). Likewise, 273 patients developed AKI out of the 1,840 patients (14.8%) that underwent TF-TAVR in contrast to 67 patients out of the 421 patients (15.9%) that underwent TAo-TAVR, with a risk ratio of 0.51 (95% CI, 0.27-0.98; p = 0.04). There was no significant risk when we compared TA to TAo approaches, with a risk ratio of 0.89 (95% CI, 0.29-2.75; p = 0.84). Conclusion: The risk of post-TAVR AKI is significantly lower in patients who underwent TF-TAVR than those who underwent TA-TAVR or TAo-TAVR.

Incidence and outcomes of cardiogenic shock among women with spontaneous coronary artery dissection.

BACKGROUND: There is a paucity of data on cardiogenic shock (CS) incidence and outcomes among patients with spontaneous coronary artery dissection (SCAD). METHODS: Women admitted to the hospital for acute myocardial infarction (AMI) with and without SCAD were identified from the United States National Readmission Database from October 1, 2015 to December 31, 2018. We calculated the incidence of CS among women with AMI with and without SCAD and odds for developing CS after adjusting for baseline characteristics. In addition, we report the utilization of percutaneous coronary intervention, mechanical circulatory support, severe disability surrogates, and 30-day readmission rates. RESULTS: A total of 664,292 patients admitted for AMI were eligible for analysis, including 6643 patients with SCAD and 657,649 without SCAD. Patients with SCAD were younger (57 years [interquartile range, IQR 48-68] vs. 71 years [IQR 60-81], p < 0.01) and had fewer comorbidities yet had a higher incidence of CS as compared to patients without SCAD (9% vs. 5%, p < 0.01) and remained at elevated risk after adjusting for baseline comorbidities (adjusted odds ratio 1.5 [95% confidence interval, CI 1.2-1.7]). Among patients who developed CS, those with SCAD had lower in-hospital mortality than non-SCAD (31% vs. 39%, p < 0.01), and were more likely to receive mechanical circulatory support. CONCLUSIONS: In a nationally representative sample of women admitted for AMI, we found that patients with SCAD had a higher risk of developing CS and required more frequent use of mechanical circulatory support but were more likely to survive to discharge than women suffering AMI from causes other than SCAD.

Polypill for cardiovascular disease prevention: Systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Cardiovascular disease is the leading cause of death worldwide. Although many pharmacological agents exist, drug compliance and therapeutic goal achievement continue to be suboptimal. This meta-analysis aims to study the effectiveness of polypills in controlling blood pressure, dyslipidemia and in reducing future cardiovascular events. METHODS: We conducted a systematic search of electronic databases using pre-specified terms. Randomized clinical trials (RCT) comparing polypills (statin, antihypertensive agents, with or without aspirin) with the standard of care were included. Outcomes of interest were changes in [systolic blood pressure (SBP), diastolic blood pressure (DBP)] mmHg, [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C)] mg/dl, cardiovascular (CVD) mortality, and major adverse cardiovascular events (MACE). RESULTS: A total of 18 RCTs with 26,483 participants were included. The population had 55% males, with a mean age of 61.8 ± 7 years, and a mean BMI of 26.7 ± 4.2 kg/m2. The mean follow-up was 15.0 ± 20 months. Compared with standard of care, polypill use was associated with a significant reduction of SBP (Mean Difference [MD] -6.39; [95%CI -9.21, -3.56] p < 0.001), DBP (MD -4.19, [95%CI -5.48, -2.89; p < 0.001], TC (MD -24.95, [95%CI -33.86, -16.04]; p < 0.001), and LDL-C (MD -27.92, [95%CI -35.39, -20.44]; p < 0.001). Polypill use was also associated with a significant reduction of CVD mortality (RR = 0.78; 95% CI (0.61, 0.99); P = 0.04) and MACE [RR = 0.76;95% CI (0.64, 0.91); P = 0.002]. CONCLUSION: This meta-analysis showed that compared to standard of care, polypill use was associated with a significant reduction of SBP, DBP, TC, LDL-C, and a significant reduction in fatal and non-fatal cardiovascular events.

Age stratified sex-related differences in incidence, management, and outcomes of cardiogenic shock.

BACKGROUND: There is a lack of data on age-stratified sex differences in the incidence, treatment, and outcomes of cardiogenic shock (CS). We sought to study these differences from a contemporary database. METHODS: Patients admitted with CS (2004-2018) were identified from the United States National Inpatient Sample. We compared CS (acute myocardial infarction-related cardiogenic shock [AMI-CS] and non-acute myocardial infarction-related cardiogenic shock [Non-AMI-CS]) incidence, management, and outcomes in males and females, stratified into four age groups (20-44, 45-64, 65-84, and ≥85 years of age). Propensity score matching (PSM) was used for adjustment. RESULTS: A total of 1,506,281 weighted hospitalizations for CS were included (AMI-CS, 39%; Non-AMI-CS, 61%). Across all age groups, females had a lower incidence of CS compared with males. After PSM and among the AMI-CS cohort, higher mortality among females compared with males was observed in the age groups 45-64 (28.5% vs. 26.3%) and 65-84 years (39.3% vs. 37.9%) (p < 0.01, for all). Among the Non-AMI-CS cohort, higher mortality among females compared with males was observed in the age groups 20-44 (33.5% vs. 30.5%), 45-64 (35.1% vs. 31.9%), and 65-84 years (41.7% vs. 40.3%) (p < 0.01, for all). Similar age-dependent differences in the management of CS were also observed between females and males. CONCLUSIONS: Females have a lower incidence of CS regardless of age. Significant disparities in the management and outcomes of CS were observed based on sex. However, these disparities varied by age and etiology of CS (AMI-CS vs. Non-AMI-CS) with pronounced disparity among females in the age range of 45-84 years.

Meta-analysis comparing dexmedetomidine versus standard of care for sedation in patients with sepsis.

We aimed to evaluate the clinical benefits of dexmedetomidine (DEX) in comparison with the standard of care (SOC) sedation in critically ill, septic patients. Electronic databases (PubMed, EMBASE, Cochrane Central, Scopus, and Google Scholar) were systematically searched to identify only randomized clinical trials performed up until February 12, 2021. The primary outcomes were 28-day mortality, 90-day mortality, and intensive care unit (ICU) length of stay (LOS). We calculated risk ratios (RRs), 95% confidence intervals (CIs) for dichotomous data, and weighted mean differences (WMDs) for continuous data using a random-effects model. Seven randomized clinical trials were included, with a total of 529 patients in the DEX group and 520 patients in the SOC group. Compared with SOC, DEX was associated with a nonstatistically significant reduced 28-day mortality (RR = 0.76; 95% CI [0.51, 1.14]; P = 0.19), 90-day mortality (RR = 0.94; 95% CI [0.75, 1.18]; P = 0.60), and ICU LOS (WMD = -0.85; 95% CI [-2.60, 0.90]; P = 0.34). We conclude that among septic patients on sedation, the use of DEX in the ICU demonstrated no significant difference from SOC sedation protocols with respect to 28-day mortality, 90-day mortality, and total ICU LOS. Our findings suggest that DEX does not confer clinical benefit over SOC sedation in critically ill patients with sepsis.

The cardiovascular outcomes of finerenone in patients with chronic kidney disease and type 2 diabetes: A meta-analysis of randomized clinical trials.

Recently, a few randomized control trials (RCTs) suggested that finerenone has been shown to reduce cardiovascular events in patients with CKD and DM-2. We aimed to analyze the cardiovascular benefits of using finerenone in patients with CKD and DM-2. Electronic databases were systematically searched to identify only RCTs comparing finerenone versus placebo. Pooled risk ratios (RR) and their 95% confidence intervals (CI) were calculated using random-effects models. Three RCTs were included, with a total of 13,847 patients. Compared with the placebo group, the use of finerenone was associated with significantly lower rates of cardiovascular events (RR: 0.88; 95% CI: 0.80, 0.96; p < 0.01), which was mainly driven by lower hospitalizations for heart failure (RR: 0.79; 95% CI: 0.66, 0.94; p = 0.01). However, there were no significant differences between groups in terms of cardiovascular death (RR: 0.88; 95% CI: 0.76, 1.02; p = 0.09), non-fatal myocardial infarction (RR: 0.91; 95% CI: 0.74, 1.12; p = 0.38), non-fatal stroke (RR: 0.99; 95% CI: 0.80, 1.22; p = 0.90).

TAVR operator volumes, trends, and geographic variations amongst Medicare beneficiaries in the United States.

OBJECTIVES: To evaluate transcatheter aortic valve replacement (TAVR) operator procedural volumes, and describe temporal and geographic trends. BACKGROUND: TAVR is the standard of care for most patients with severe symptomatic aortic stenosis. Despite an association between operator procedural volume and outcomes, nationwide TAVR operator volumes have been incompletely described. METHODS: We queried the National Medicare Provider Utilization and Payment Database for transfemoral TAVRs from 2014 to 2018. Annual operator volume, state and regional volumes, and longitudinal trends were extracted and analyzed using descriptive statistics. RESULTS: In 2018, the mean annual operator volume was 23.6 TAVRs. The highest 1% of operators by volume performed 7.6% of total TAVR procedures in the United States, while 35.7% of operators performed 10 or fewer TAVRs per year. From 2014 to 2018, there was a 53.9% annualized increase in TAVRs, and the mean annual volume per operator grew from 12.5 to 23.6. There was more than five-fold variability in the density of operators (range 0.35-1.79 operators per 100,000 population) and mean operator volume by state (range 14.2-52.4 TAVRs per operator). CONCLUSIONS: In this nationally representative study of operators performing transfemoral TAVRs among Medicare patients, we found the mean annual volume of TAVR in 2018 to be 23.6 and has increased since 2014. There was considerable variability in operator density and procedural volumes, with a significant proportion of operators performing 10 or fewer TAVRs per year. Ambiguity remains in regard to the optimal balance of procedural requirements to sustain high efficacy outcomes and ensure critical access to TAVR therapies.