Effects of sodium-glucose cotransporter 2 inhibitors on cardiovascular and renal outcomes in people with diabetes and advanced chronic kidney disease.

AIMS/HYPOTHESIS: Although the benefits of sodium-glucose cotransporter 2 inhibitor (SGLT2i) use in chronic kidney disease (CKD) are well established, the effects of these therapeutic agents in patients with advanced CKD are less certain. We hypothesised that the continued use of these drugs, even when renal function deteriorates to stage 4 CKD or worse, is safe and associated with improved cardiorenal survival. METHODS: This is a retrospective cohort study utilising data from medical records from two institutions. All patients with type 2 diabetes mellitus who were prescribed an SGLT2i between 1 January 2016 and 31 December 2021, who subsequently had eGFR <30 ml/min per 1.73 m2 recorded on two occasions at least 90 days apart, were identified. The date on which the eGFR first reached any level less than 30 ml/min per 1.73 m2 was defined as the index date. Individuals were then categorised into the SGLT2i continuation group or the discontinuation group according to the use of SGLT2i after the index date. Inverse probability of treatment weighting (IPTW) was performed to minimise confounding. Outcomes of interest included heart failure outcomes, cardiovascular outcomes, renal outcomes and safety outcomes. RESULTS: According to the eligibility criteria, 337 patients in the continuation group and 358 in the discontinuation group were identified. After IPTW, continuation of SGLT2i use was associated with significantly lower risks of the composite of major adverse cardiovascular events compared with discontinuation of SGLT2i use (HR 0.65 [95% CI 0.43, 0.99]), largely driven by reduced risk of myocardial infarction during follow-up (subdistribution HR [SHR] 0.43 [95% CI 0.21, 0.89]). The incidences of an eGFR decline of 50% or more (SHR 0.58 [95% CI 0.42, 0.81]) and all-cause hospital admission (SHR 0.77 [95% CI 0.64, 0.94]) were also significantly lower in the continuation group. None of the studied safety outcomes were significantly different when comparing the two groups. Blood haemoglobin levels were significantly higher in the continuation group at the end of follow-up (114.6 g/l vs 110.4 g/l, with a difference of 4.12 g/l; p=0.047). CONCLUSIONS/INTERPRETATION: In patients with CKD who were treated with an SGLT2i, continuation of SGLT2i use after eGFR declined to 30 ml/min per 1.73 m2 or less was associated with lower risks of cardiovascular and renal events compared with discontinuation of SGLT2i use. Continued use of SGLT2i throughout the course of CKD should be considered to optimise patient outcomes.

Effects of Colchicine on Major Adverse Limb and Cardiovascular Events in Patients With Peripheral Artery Disease.

OBJECTIVE: To assess the effects of colchicine, which has been shown to reduce the risks of coronary artery disease but scarcely studied in peripheral artery disease (PAD), on major adverse limb events (MALE) in patients with PAD. METHODS: This is a retrospective study based on a nationwide database. Patients who were diagnosed with PAD between 2010 and 2020 and prescribed with colchicine after the diagnosis of PAD were identified. Patients were then categorized into the colchicine or the control group according to drug use. Propensity score matching was performed to mitigate selection bias. Risks of MALE (including lower limb revascularization and nontraumatic amputation) and major adverse cardiovascular events were compared between the two groups. RESULTS: After patient selection and propensity score matching, there were 60,219 patients in both colchicine and control groups. After a mean follow-up of 4.5 years, the risk of MALE was significantly lower in the colchicine group compared with control (subdistribution HR, 0.75; 95% CI, 0.71 to 0.80), as were the incidence of both components of MALE, lower limb revascularization and major amputations. Colchicine treatment was also associated with lower risk of cardiovascular death. The lower risk of MALE observed with colchicine therapy was accentuated in the subgroup of patients receiving concomitant urate-lowering medications. CONCLUSION: In patients diagnosed with PAD, the use of colchicine is associated with lower risks of MALE and cardiovascular death. Anti-inflammatory therapy with colchicine may provide benefits in vascular beds beyond the coronary arteries.

Effects of Sacubitril/Valsartan on Survival in Patients with Heart Failure and Significant Valvular Heart Disease.

Although the benefits of sacubitril/valsartan in heart failure with reduced ejection fraction (HFrEF) are well established, patients with hemodynamically significant mitral regurgitation (MR) were excluded from pivotal trials. We aimed to assess the effects of sacubitril/valsartan on survival in patients with HFrEF and concomitant significant MR. All patients from a single center who underwent echocardiography between June 2008 and December 2020, with a left ventricular ejection fraction (LVEF) of less than 40% and hemodynamically significant MR were recruited. Patients were categorized according to drug use and year of the index echocardiogram into the angiotensin receptor/neprilysin inhibitor (ARNI), non-ARNI before 2017, and non-ARNI after 2017 groups. Patients in the ARNI and non-ARNI after 2017 groups were compared directly, whereas patients in the non-ARNI before 2017 group were matched to the ARNI group in a 3:1 ratio. The outcome of interest was all-cause mortality. Death was compared between the groups using univariate and multivariate Cox proportional hazard models. After exclusion by criteria and matching, there remained 610 patients in the ARNI group, 434 in the non-ARNI after 2017 group, and 1,722 in the non-ARNI before 2017 group. During follow-up, all-cause mortality was significantly lower in the ARNI group compared with both non-ARNI after 2017 and non-ARNI before 2017 groups. Multivariate analysis of both pairs of comparison between groups found the use of ARNI to be significantly associated with increased survival. In patients with HFrEF and concomitant significant MR, treatment with sacubitril/valsartan was associated with lower risks of all-cause death.

Genetic and clinical characteristics of catecholaminergic polymorphic ventricular tachycardia in a Taiwanese nationwide cohort.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare and lethal arrhythmia. Ryanodine receptor 2 (RYR2) mutation accounts for ∼60% of CPVT patients which is inherited in an autosomal dominant pattern. OBJECTIVE: This study aimed to identify CPVT-related mutations and clinical characteristics among Taiwanese CPVT patients and compare to other cohorts worldwide. METHODS: Clinical and genetic data were obtained from the Sudden Arrhythmia Death Syndrome Registry in Taiwan (SADS-TW). Forty clinically diagnosed Taiwanese CPVT patients were included. RESULTS: This is the first nationwide CPVT cohort in Taiwan. Among the 29 Taiwanese patients with CPVT-related gene mutations, 55% had RYR2 mutations, a rate similar to other ethnicities. Three out of 12 RYR2 variants were unreported. Exercise-induced symptoms including syncope and cardiac arrest were more frequent in East Asian cohorts (Taiwanese 79%, Japanese 91%), compared to Caucasian cohorts (59%) (p = 0.002). CONCLUSION: The discovery of diverse RYR2 mutations in the Taiwanese CVPT population demonstrates the importance of genetic testing in different ethnicities.

Long-term exposure to air pollution and the risks of venous thromboembolism: a nationwide population-based retrospective cohort study.

OBJECTIVES: To delineate the effects of exposure to air pollution on the risk of venous thromboembolism (VTE). BACKGROUND: The association between air pollution and arterial occlusive diseases has been well reported in the literature. VTE is the third most common acute cardiovascular syndrome; however, its relationship with exposure to air pollution has been controversial. METHODS: This study linked data from the Taiwan National Health Insurance Research Database with that from the Taiwan Environmental Protection Administration. Patients who were first admitted for VTE between January 1, 2001, and December 31, 2013, were analyzed. A time-stratified, case-crossover design was employed. Three different exposure periods were defined: exposure for 1 month, one quarter, and 1 year. Four control periods were designated for each exposure period. The association between exposure to air pollutants and the risk of VTE was tested using logistic regression analysis. Subgroup analyses were also performed, stratified by age, sex, type of VTE, the use of hormone therapy, and level of urbanization at the site of residence. RESULTS: Exposures to particulate matter (PM) smaller than 2.5 µm (PM2.5) and those smaller than 10 µm (PM10) were associated with higher risks of VTE, with longer exposures associated with higher risk. The concentration of PM2.5 exposure for 1 month was linearly associated with a greater risk of VTE up to 28.0 µg/m3, beyond which there was no association. PM2.5 exposure for one quarter or 1 year remained significantly associated with higher risks of VTE at higher concentrations. The increased risk in VTE associated with exposure to PM2.5 was more prominent in older patients and in patients not under hormone therapy. Similar results were observed for PM10 exposures. CONCLUSIONS: Exposure to PM, particularly PM2.5, leads to an increased risk of VTE, with possible accumulative effects. With increased PM production in industrializing countries, the effects of PM on VTE occurrence warrant further attention.

Incidence and progression of diabetic retinopathy in patients treated with glucagon-like peptide-1 receptor agonists versus sodium-glucose cotransporter 2 inhibitors: A population-based cohort study.

AIM: Glucagon-like peptide 1 receptor agonists (GLP1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) are both recommended for patients with diabetes, yet their effects on the development or progression of diabetic retinopathy (DR) are largely unknown. METHODS: In this retrospective cohort study, data were collected from a nationwide database. Patients with diabetes who initiated treatment with a GLP1RA or SGLT2i between 1 May 2016 and 31 December 2017, were identified. Patients were divided into those with or without a previous diagnosis of DR and then categorized into the GLP1RA and the SGLT2i groups according to drug use. The primary outcome of interest in the DR group was the composite of new-onset proliferative DR, vitreous haemorrhage and tractional retinal detachment (RD). In the non-DR group, the primary outcome was the composite of newly diagnosed DR of any severity, vitreous haemorrhage and RD. RESULTS: In total, 97 413 patients were identified. After matching, 1517 patients were treated with a GLP1RA and 3034 with an SGLT2i in the DR cohort. In the non-DR cohort, 9549 initiated a GLP1RA and 19 098 initiated an SGLT2i. In patients with pre-existing DR, the incidence of any DR progression event was significantly higher in the GLP1RA group than the SGLT2i group (subdistribution hazard ratio 1.50, 95% confidence interval 1.01-2.23), primarily because of the increased risk of tractional RD. In patients without DR at baseline, the risks of all ocular outcomes were similar between the GLP1RA and SGLT2i groups. CONCLUSIONS: In patients with diabetes mellitus and established DR, GLP1RA treatment was associated with increased risks of DR progression compared with SGLT2i use.

Effect of body mass index on mortality for diabetic patients with aortic stenosis.

BACKGROUND: Several studies suggest an "obesity paradox," associating obesity with better cardiovascular outcomes in patients with type 2 diabetes mellitus (DM) or aortic stenosis (AS) compared to normal or underweight individuals. This study explores the impact of body mass index (BMI) on diabetic patients with AS. METHODS: Between 2014 and 2019, patients with DM who underwent echocardiography were analyzed. Outcomes included all-cause mortality, cardiovascular, and non-cardiovascular death. Patients were categorized as underweight, normal weight, or obese based on BMI (<18.5, 18.5 to 27, and >27 kg/m2, respectively). RESULTS: Among 74,835 DM patients, 734 had AS. Normal weight comprised 65.5% (n=481), underweight 4.1% (N=30), and 30.4% were obese. Over a 6-year follow-up, underweight patients had significantly higher all-cause mortality (HR 1.96, 95% CI 1.22 - 3.14, p = 0.005), while obese patients had significantly lower mortality (HR 0.79, 95% CI 0.68 - 0.91, p=0.001) compared to the normal group. Regarding etiologies, underweight patients had a higher risk of non-cardiovascular death (HR 2.47, 95% CI 1.44-4.25, p = 0.001), while obese patients had a lower risk of cardiovascular death (HR 0.66, 95% CI 0.50-0.86, p=0.003). Subgroup analysis showed a consistent trend without significant interaction. CONCLUSIONS: BMI significantly impacts mortality in DM patients with AS. Being underweight is associated with worse non-cardiovascular death, while obesity is linked to improved cardiovascular death outcomes.

Case Report: Lacosamide unmasking SCN5A-associated Brugada syndrome in a young female with epilepsy.

Background: Lacosamide is frequently used as a mono- or adjunctive therapy for the treatment of adults with epilepsy. Although lacosamide is known to act on both neuronal and cardiac sodium channels, potentially leading to cardiac arrhythmias, including Brugada syndrome (BrS), its adverse effects in individuals with genetic susceptibility are less understood. Case: We report a 33-year-old female with underlying epilepsy who presented to the emergency department with a four-day history of seizure clusters, and was initially treated with lacosamide therapy. During the intravenous lacosamide infusion, the patient developed sudden cardiac arrest caused by ventricular arrhythmias necessitating resuscitation. Of note, the patient had a family history of sudden cardiac death. Workup including routine laboratory results, 12-lead electrocardiogram (ECG), echocardiogram, and coronary angiogram was non-specific. However, a characteristic type 1 Brugada ECG pattern was identified by ajmaline provocation testing; thus, confirming the diagnosis of BrS. Subsequently, the genotypic diagnosis was confirmed by Sanger sequencing, which revealed a heterozygous mutation (c.2893C>T, p.Arg965Cys) in the SCN5A gene. Eventually, the patient underwent implantable cardioverter-defibrillator implantation and was discharged with full neurological recovery. Conclusion: This case highlights a rare but lethal adverse event associated with lacosamide treatment in patients with genetic susceptibility. Further research is warranted to investigate the interactions between lacosamide and SCN5A variants.

Epicardial Adipose Tissue is Associated with Geometry Alteration and Diastolic Dysfunction in Prediabetic Cardiomyopathy.

BACKGROUND: Diastolic dysfunction and alterations in cardiac geometry are early indicators of diabetic cardiomyopathy. However, the association between cardiac changes across the glucose continuum and the contribution of epicardial adipose tissue (EAT) to these changes has not yet been investigated. PURPOSE: In this study, we aim to investigated the EAT on cardiac diastolic function and structural alterations along the diabetic continuum using cardiac magnetic resonance imaging (CMRI). METHODS: We enrolled individuals who were categorized into groups based on glucose tolerance status. Left ventricular structure and diastolic function were assessed using echocardiography and CMRI to determine the EAT, intramyocardial fat, and associated parameters. Multivariable logistic regression models were also used. RESULTS: In a study of 370 patients (209 normal glucose tolerance, 82 prediabetes, 79 diabetes), those with prediabetes and diabetes showed increased heart dimensions and diastolic dysfunction, including E/E' (the ratio of early mitral inflow velocity to mitral annular early diastolic velocity) (7.9±0.51 vs. 8.5±0.64 vs. 10.0±0.93, p=0.010), left atrial volume index (28.21±14.7 vs. 33.2±12.8 vs. 37.4±8.2 mL/m2, p<0.001), and left ventricular peak filling rate (4.46±1.75 vs. 3.61±1.55 vs. 3.20±1.30 mL/s, p<0.001). EAT significantly increased in prediabetes and diabetes (26.3±1.16 vs. 31.3±1.83 vs. 33.9±1.9 gm, p=0.001), while intramyocardial fat did not differ significantly. Prediabetes altered heart geometry, but not diastolic function (OR 1.22 [1.02-1.83], p=0.012; and 1.70 [0.79-3.68], p=0.135). Diabetes significantly affected both heart structure and diastolic function (OR 1.42 [1.11-1.97], p=0.032; and 2.56 [1.03-5.40], p=0.034) after adjusting for covariates. CONCLUSIONS: Elevated EAT was observed in patients with prediabetes and is associated with adverse alterations in cardiac structure and diastolic function, potentially serving as an underlying mechanism for the early onset of diabetic cardiomyopathy.

The effect of antiarrhythmic medications on the risk of cardiovascular outcomes in patients with atrial fibrillation and coronary artery disease.

BACKGROUND: While current guidelines recommend amiodarone and dronedarone for rhythm control in patients with atrial fibrillation (AF) and coronary artery disease (CAD), there was no comparative study of antiarrhythmic drugs (AADs) on the cardiovascular outcomes in general practice. METHODS: This study included patients with AF and CAD who received their first prescription of amiodarone, class Ic AADs (flecainide, propafenone), dronedarone or sotalol between January 2016 and December 2020. The primary outcome was a composite of hospitalization for heart failure (HHF), stroke, acute myocardial infarction (AMI), and cardiovascular death. We used Cox proportional regression models, including with inverse probability of treatment weighting (IPTW), to estimate the relationship between AADs and cardiovascular outcomes. RESULTS: Among the AF cohort consisting of 8752 patients, 1996 individuals had CAD, including 477 who took dronedarone and 1519 who took other AADs. After a median follow-up of 38 months, 46.3% of patients who took dronedarone and 54.4% of patients who took other AADs experienced cardiovascular events. Compared to dronedarone, the use of other AADs was associated with increased cardiovascular events after adjusting for covariates (hazard ratio [HR] 1.531, 95% confidence interval [CI] 1.112-2.141, p = 0.023) and IPTW (HR 1.491, 95% CI 1.174-1.992, p = 0.012). The secondary analysis showed that amiodarone and class Ic drugs were associated with an increased risk of HHF. The low number of subjects in the sotalol group limits data interpretation. CONCLUSION: For patients with AF and CAD, dronedarone was associated with better cardiovascular outcomes than other AADs. Amiodarone and class Ic AADs were associated with a higher risk of cardiovascular events, particularly HHF.

Left Ventricular Segmentation, Warping, and Myocardial Registration for Automated Strain Measurement.

The left ventricular global longitudinal strain (LVGLS) is a crucial prognostic indicator. However, inconsistencies in measurements due to the speckle tracking algorithm and manual adjustments have hindered its standardization and democratization. To solve this issue, we proposed a fully automated strain measurement by artificial intelligence-assisted LV segmentation contours. The LV segmentation model was trained from echocardiograms of 368 adults (11,125 frames). We compared the registration-like effects of dynamic time warping (DTW) with speckle tracking on a synthetic echocardiographic dataset in experiment-1. In experiment-2, we enrolled 80 patients to compare the DTW method with commercially available software. In experiment-3, we combined the segmentation model and DTW method to create the artificial intelligence (AI)-DTW method, which was then tested on 40 patients with general LV morphology, 20 with dilated cardiomyopathy (DCMP), and 20 with transthyretin-associated cardiac amyloidosis (ATTR-CA), 20 with severe aortic stenosis (AS), and 20 with severe mitral regurgitation (MR). Experiments-1 and -2 revealed that the DTW method is consistent with dedicated software. In experiment-3, the AI-DTW strain method showed comparable results for general LV morphology (bias - 0.137 ± 0.398%), DCMP (- 0.397 ± 0.607%), ATTR-CA (0.095 ± 0.581%), AS (0.334 ± 0.358%), and MR (0.237 ± 0.490%). Moreover, the strain curves showed a high correlation in their characteristics, with R-squared values of 0.8879-0.9452 for those LV morphology in experiment-3. Measuring LVGLS through dynamic warping of segmentation contour is a feasible method compared to traditional tracking techniques. This approach has the potential to decrease the need for manual demarcation and make LVGLS measurements more efficient and user-friendly for daily practice.

Long-term Effect of Thyrotropin-binding Inhibitor Immunoglobulin on Atrial Fibrillation in Euthyroid Patients.

OBJECTIVE: Individuals with hyperthyroidism are at an increased risk of atrial fibrillation (AF), but the association between autoantibodies and AF or cardiovascular mortality in individuals who have returned to normal thyroid function remains unclear. METHODS: The study utilized electronic medical records from National Taiwan University Hospital between 2000 and 2022. Each hyperthyroidism patient had at least 1 thyrotropin-binding inhibiting immunoglobulin (TBII) measurement. The relationship between TBII levels and the risk of AF and cardiovascular mortality was assessed using multivariable Cox regression models and Kaplan-Meier survival analysis. RESULTS: Among the 14 618 enrolled patients over a 20-year timeframe, 173 individuals developed AF, while 46 experienced cardiovascular mortality. TBII values exceeding 35% were significantly associated with an elevated risk of AF for both the first TBII (hazard ratio {HR} 1.48 [1.05-2.08], P = .027) and mean TBII (HR 1.91 [1.37-2.65], P < .001). Furthermore, after free T4 levels had normalized, a borderline association between first TBII and AF (HR 1.59 [0.99-2.56], P = .056) was observed, while higher mean TBII increased AF (HR 1.78 [1.11-2.85], P = .017). Higher first and mean TBII burden continued to significantly impact the incidence of cardiovascular mortality (HR 6.73 [1.42-31.82], P = .016; 7.87 [1.66-37.20], P = .009). Kaplan-Meier analysis demonstrated that elevated TBII levels increased the risk of AF and cardiac mortality (log-rank P = .035 and .027, respectively). CONCLUSION: In euthyroid individuals following antithyroid treatment, elevated circulating TBII levels and burden are associated with an elevated risk of long-term incident AF and cardiovascular mortality. Further reduction of TBII level below 35% will benefit to clinical outcomes.

Novel scoring system derived from meta-analysis and validated in cohort population for predicting 1-year atrial fibrillation recurrence after cryoballoon catheter ablation: The HeLPS-Cryo score.

BACKGROUND: Atrial fibrillation (AF) recurrence rates in 1 year after cryoballoon ablation catheter (CBCA) are still high. We purposed to identify strong predictors for AF recurrence after the successful CBCA procedure and develop a new scoring system based only on pre-procedural parameters. METHODS: In the derivation phase, a systematic review and meta-analysis identified the strong predictors of AF recurrence after the CBCA. The pooled hazard ratio (HR) was used to create the new scoring system. The second phase validated the new scoring system in the cohort population. RESULTS: A meta-analysis including 29 cohort studies with 16196 participants confirmed that persistent AF, stroke, heart failure, and left atrial diameter (LAD) >40 mm were powerful predictors for AF recurrence after the CBCA procedure. The HeLPS-Cryo (heart failure [1], left atrial dilatation [1], persistent AF [2], and stroke [2]) was developed based on those pre-procedural predictors. It was validated in 140 patients receiving CBCA procedures and revealed excellent predictive performance for 1-year AF recurrence (AUC = 0.8877; 95% CI = 0.8208 to 0.9546). The HeLPS-Cryo score of ≥3 could predict 1-year AF recurrence with sensitivity and specificity of 78.9% and 87.9%, respectively. The positive predictive value was 66.7%, and the negative predictive value was 93.1%. CONCLUSION: The HeLPS-Cryo score can help the physician estimate the probability of 1-year AF recurrence after the successful CBCA procedure. Patients with HeLPS-Cryo score <3 are good candidates for the CBCA procedure.

Long-term outcomes of left atrial appendage occlusion in patients with atrial fibrillation and end stage renal disease.

OBJECTIVE: In patients with atrial fibrillation (AF) and end-stage renal disease (ESRD), oral anticoagulants are contraindicated, and left atrial appendage occlusion (LAAO) is an alternative treatment. However, the efficacy of thromboembolic prevention using LAAO in these patients has rarely been reported in Asian populations. To our knowledge, this is the first long-term LAAO study in patients with AF undergoing dialysis in Asia. METHODS: In this study, 310 patients (179 men) with a mean age of 71.3 ± 9.6 years and mean CHA2DS2-VASc 4.2 ± 1.8 were consecutively enrolled at multiple centers in Taiwan. The outcomes of 29 patients with AF and ESRD undergoing dialysis who underwent LAAO were compared to those without ESRD. The primary composite outcomes were stroke, systemic embolization, or death. RESULTS: No difference in mean CHADS-VASc score was noted between patients with versus without ESRD (4.1 ± 1.8 vs. 4.6 ± 1.9, p = 0.453). After a mean follow-up of 38 ± 16 months, the composite endpoint was significantly higher in patients with ESRD (hazard ratio, 5.12 [1.4-18.6]; p = 0.013) than in those without ESRD after LAAO therapy. Mortality was also higher in patients with ESRD (hazard ratio, 6.6 [1.1-39.7]; p = 0.038). The stroke rate was numerically higher in patients with versus without ESRD, but the difference was not statistically significant (hazard ratio, 3.2 [0.6-17.7]; p = 0.183). Additionally, ESRD was associated with device-related thrombosis (odds ratio, 6.15; p = 0.047). CONCLUSION: Long-term outcomes of LAAO therapy may be less favorable in patients with AF undergoing dialysis, possibly because of the poor condition of patients with ESRD.

Efficacy and Safety of Direct Oral Anticoagulants for Stroke Prevention in Older Patients With Atrial Fibrillation: A Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Although older patients with atrial fibrillation are at heightened risk of thromboembolic and bleeding events, their optimal treatment choice remains uncertain. METHODS AND RESULTS: This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, EMBASE, and Cochrane databases for randomized controlled trials that compared thromboembolic or bleeding outcomes between a direct oral anticoagulant (DOAC) and a vitamin K antagonist (VKA) and reported outcomes for patients aged ≥75 years with atrial fibrillation. The efficacy outcome was the composite of stroke and systemic embolism. Safety outcomes included major bleeding, any clinically relevant bleeding, and intracranial hemorrhage. Each DOAC and VKA was compared pairwise in a network meta-analysis. High- and low-dose regimens and factor IIa and Xa inhibitors were also compared. Seven randomized controlled trials were included in the analysis. Stroke and systemic embolism risks did not differ significantly among DOACs. There were no significant differences in major bleeding between each DOAC and VKA. Intracranial hemorrhage risk was significantly lower with dabigatran, apixaban, and edoxaban than with VKA and rivaroxaban, which had similar risks. High-dose regimens led to lower risks of stroke or systemic embolism compared with VKA and low-dose regimens, with both doses having similar bleeding risks. CONCLUSIONS: In patients aged ≥75 years with atrial fibrillation, DOACs were associated with fewer thromboembolic events compared with VKA, whereas dabigatran, apixaban, and edoxaban were associated with lower risks of intracranial hemorrhage compared with VKA and rivaroxaban. REGISTRATION: URL: www.crd.york.ac.uk/prospero/. Unique identifier: CRD42022329557.

Renal Impact of Culprit-Only versus Multi-Vessel Revascularization for Cardiogenic Shock Complicating Acute Myocardial Infarction: Systematic Review and Meta-Analysis.

Background: The optimal strategy of percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) complicated with cardiogenic shock (CS) remains controversial. We aimed to elucidate the renal and cardiovascular impact of culprit-only (C) revascularization versus additional interventions on non-infarct-related arteries. Methods: PubMed, Embase, MEDLINE, and Cochrane Library were searched for relevant literature. A total of 96,812 subjects [C-PCI: 69,986; multi-vessel (MV)-PCI: 26,826] in nine studies (one randomized control trial; eight observational cohort studies) were enrolled. Results: MV-PCI was associated with a higher kidney event rate [relative risk (RR): 1.29, 95% confidence interval (CI): 1.12-1.49; p < 0.001]. However, the all-cause mortality rate was comparable both during admission (RR: 1.07, 95% CI: 0.94-1.22; p = 0.30) and at one year (RR: 0.96, 95% CI: 0.79-1.16; p = 0.65). MV-PCI was associated with a greater risk of stroke (RR: 1.19, 95% CI: 1.08-1.32; p < 0.001) and bleeding events (RR: 1.27, 95% CI: 1.07-1.51; p = 0.006), but reduced risk of recurrent MI (RR: 0.89, 95% CI: 0.82-0.97; p = 0.009) and repeat revascularization (RR: 0.34, 95% CI: 0.16-0.71; p = 0.004). No increased risk of coronary artery bypass grafting was present (RR: 1.09, 95% CI: 0.38-3.17; p = 0.87). Conclusions: C-PCI was associated with a lower rate of renal dysfunction but not all-cause mortality in patients with CS complicating acute MI.