Transcatheter or Surgical Treatment of Aortic-Valve Stenosis.

BACKGROUND: Among low-risk patients with severe, symptomatic aortic stenosis who are eligible for both transcatheter aortic-valve implantation (TAVI) and surgical aortic-valve replacement (SAVR), data are lacking on the appropriate treatment strategy in routine clinical practice. METHODS: In this randomized noninferiority trial conducted at 38 sites in Germany, we assigned patients with severe aortic stenosis who were at low or intermediate surgical risk to undergo either TAVI or SAVR. Percutaneous- and surgical-valve prostheses were selected according to operator discretion. The primary outcome was a composite of death from any cause or fatal or nonfatal stroke at 1 year. RESULTS: A total of 1414 patients underwent randomization (701 to the TAVI group and 713 to the SAVR group). The mean (±SD) age of the patients was 74±4 years; 57% were men, and the median Society of Thoracic Surgeons risk score was 1.8% (low surgical risk). The Kaplan-Meier estimate of the primary outcome at 1 year was 5.4% in the TAVI group and 10.0% in the SAVR group (hazard ratio for death or stroke, 0.53; 95% confidence interval [CI], 0.35 to 0.79; P<0.001 for noninferiority). The incidence of death from any cause was 2.6% in the TAVI group and 6.2% in the SAVR group (hazard ratio, 0.43; 95% CI, 0.24 to 0.73); the incidence of stroke was 2.9% and 4.7%, respectively (hazard ratio, 0.61; 95% CI, 0.35 to 1.06). Procedural complications occurred in 1.5% and 1.0% of patients in the TAVI and SAVR groups, respectively. CONCLUSIONS: Among patients with severe aortic stenosis at low or intermediate surgical risk, TAVI was noninferior to SAVR with respect to death from any cause or stroke at 1 year. (Funded by the German Center for Cardiovascular Research and the German Heart Foundation; DEDICATE-DZHK6 ClinicalTrials.gov number, NCT03112980.).

Age-Related Quality of Life in Cardiac Surgical Patients with Extracorporeal Life Support.

BACKGROUND: The rationale of the study was to analyze the impact of age on quality of life (QoL) in patients who had undergone cardiac surgery with consecutive extracorporeal life support (ECLS) treatment. METHODS: The study population consisted of 200 patients, operated upon between August 2006 and December 2018. The patient cohort was divided into two groups following an arbitrary cutoff age of 70 years. Comparative outcome analysis was calculated utilizing the European Quality of Life-5-Dimensions-5-Level Version (EQ-5D-5L). RESULTS: A total of 113 patients were 70 years or less old (group young), whereas 87 patients were older than 70 years (group old). In 45.7% of cases, the ECLS system was established during cardiogenic shock and external cardiac massage. The overall survival-to-discharge was 31.5% (n = 63), with a significantly better survival in the younger patient group (young = 38.9%; old = 21.8%, p = 0.01). Forty-two patients (66%) responded to the QoL survey after a median follow-up of 4.3 years. Older patients reported more problems with mobility (y = 52%; o = 88%, p = 0.02) and self-care (y = 24%; o = 76%, p = 0.01). However, the patients' self-rated health status utilizing the Visual Analogue Scale revealed no differences (y = 70% [50-80%]; o = 70% [60-80%], p = 0.38). Likewise, the comparison with an age-adjusted German reference population revealed similar QoL indices. There were no statistically significant differences in the EQ-5D-5L index values related to sex, number of comorbidities, and emergency procedures. CONCLUSION: Despite the limited sample size due to the high mortality rate especially in elderly, the present study suggests that QoL of elderly patients surviving ECLS treatment is almost comparable to younger patients.

Sleep-Disordered Breathing, Advanced Age, and Diabetes Mellitus Are Associated with De Novo Atrial Fibrillation after Cardiac Surgery.

Background: Postoperative de novo atrial fibrillation (POAF) is one of the most frequently encountered complications following cardiac surgery. Despite the identification of several risk factors, the link between sleep-disordered breathing (SDB) and POAF has barely been examined. The objective of this prospective observational study was to determine whether severe SDB is associated with POAF in patients after elective coronary artery bypass grafting (CABG) surgery. Study design and methods: The incidence and preoperative predictors of in-hospital POAF were assessed in 272 patients undergoing CABG surgery at the University Medical Center Regensburg (Germany). In-hospital POAF was detected by continuous telemetry-ECG monitoring and 12-lead resting ECGs within the first seven postoperative days. POAF that occurred after hospital discharge within 60 days post CABG surgery was classified as post-hospital POAF and was ascertained by standardized phone interviews together with the patients' medical files, including routinely performed Holter-ECG monitoring at 60 days post CABG surgery. The night before surgery, portable SDB monitoring was used to assess the presence and type of severe SDB, defined by an apnea-hypopnea index ≥ 30/h. Results: The incidence of in-hospital POAF was significantly higher in patients with severe SDB compared to those without severe SDB (30% vs. 15%, p = 0.009). Patients with severe SDB suffered significantly more often from POAF at 60 days post CABG surgery compared to patients without severe SDB (14% vs. 5%, p = 0.042). Multivariable logistic regression analysis showed that severe SDB (odds ratio, OR [95% confidence interval, CI]: 2.23 [1.08; 4.61], p = 0.030), age ≥ 65 years (2.17 [1.04; 4.53], p = 0.038), and diabetes mellitus (2.27 [1.15; 4.48], p = 0.018) were significantly associated with in-hospital POAF. After additional adjustment for heart failure, the association between sleep apnea and postoperative atrial fibrillation was attenuated (1.99 [0.92; 4.31], p = 0.081). Conclusions: Amongst established risk factors, severe SDB was significantly associated with in-hospital POAF in patients undergoing CABG surgery. Whether SDB contributes to POAF independently of heart failure and whether risk for POAF may be alleviated by proper treatment of SDB merits further investigation.

Empagliflozin inhibits increased Na influx in atrial cardiomyocytes of patients with HFpEF.

AIMS: Heart failure with preserved ejection fraction (HFpEF) causes substantial morbidity and mortality. Importantly, atrial remodelling and atrial fibrillation are frequently observed in HFpEF. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have recently been shown to improve clinical outcomes in HFpEF, and post-hoc analyses suggest atrial anti-arrhythmic effects. We tested if isolated human atrial cardiomyocytes from patients with HFpEF exhibit an increased Na influx, which is known to cause atrial arrhythmias, and if that is responsive to treatment with the SGTL2i empagliflozin. METHODS AND RESULTS: Cardiomyocytes were isolated from atrial biopsies of 124 patients (82 with HFpEF) undergoing elective cardiac surgery. Na influx was measured with the Na-dye Asante Natrium Green-2 AM (ANG-2). Compared to patients without heart failure (NF), Na influx was doubled in HFpEF patients (NF vs. HFpEF: 0.21 ± 0.02 vs. 0.38 ± 0.04 mmol/L/min (N = 7 vs. 18); P = 0.0078). Moreover, late INa (measured via whole-cell patch clamp) was significantly increased in HFpEF compared to NF. Western blot and HDAC4 pulldown assay indicated a significant increase in CaMKII expression, CaMKII autophosphorylation, CaMKII activity, and CaMKII-dependent NaV1.5 phosphorylation in HFpEF compared to NF, whereas NaV1.5 protein and mRNA abundance remained unchanged. Consistently, increased Na influx was significantly reduced by treatment not only with the CaMKII inhibitor autocamtide-2-related inhibitory peptide (AIP), late INa inhibitor tetrodotoxin (TTX) but also with sodium/hydrogen exchanger 1 (NHE1) inhibitor cariporide. Importantly, empagliflozin abolished both increased Na influx and late INa in HFpEF. Multivariate linear regression analysis, adjusting for important clinical confounders, revealed HFpEF to be an independent predictor for changes in Na handling in atrial cardiomyocytes. CONCLUSION: We show for the first time increased Na influx in human atrial cardiomyocytes from HFpEF patients, partly due to increased late INa and enhanced NHE1-mediated Na influx. Empagliflozin inhibits Na influx and late INa, which could contribute to anti-arrhythmic effects in patients with HFpEF.