Male-female differences following concomitant coronary artery bypass grafting and aortic valve replacement surgery.

AIMS: Combined coronary artery bypass grafting (CABG) and aortic valve replacement (AVR), and female sex are associated with increased perioperative mortality in clinical risk scores. This study investigated male-female differences in short-term outcome stratified by age groups. METHODS AND RESULTS: All patients undergoing AVR and CABG between January 2001 and June 2021 at our institution were included. 1963 patients were grouped by decades into: 59 years and younger (n = 127), 60-69 (n = 471), 70-79 (n = 1070), and 80 years and older (n = 295). The primary end points of this study were 30 and 180 days mortality. Secondary end points were influence of preoperative risk factors and impact of sex on survival and postoperative major adverse events. Female patients showed higher 30 and 180 days mortality after combined CABG and AVR surgery (8.3% vs. 4.2%, P < 0.01; 15.8% vs. 9.4%, P < 0.01). Stratified by age groups, 30 and 180 days mortality remained significantly higher in septuagenarians (9.6% vs. 2.5%, P < 0.01; 16.3% vs. 7.7%, P < 0.01). Females were significantly older, had better preserved left ventricular function, and higher incidence of diabetes mellitus compared with male patients in this subgroup (P < 0.01; P = 0.01; P < 0.01). Additionally, females received significantly less internal mammary artery (IMA) conduits (P < 0.01). Female sex (OR: 3.33, 95% CI: [1.76-6.31]; 1.93, [1.22-3.06]), higher age (1.28, [1.13-1.45]; 1.16, [1.06-1.26]), diabetes mellitus (1.93, [1.03-3.60]; 1.70, [1.08-2.67]) and LVEF <30% (3.26, [1.48-7.17]; 2.23, [1.24-4.02]) were correlated with 30 and 180 days mortality, respectively. Upon multivariable testing, sex (1.77, [1.21-2.58]) and LVEF <30% (3.71, [2.39-5.76]) remained independent predictors for major adverse postoperative events. Infrequent use of IMA grafts was associated with increased 30 and 180 days mortality as well as adverse events (0.47, [0.25-0.87]; 0.46, [0.29-0.72]; 0.61, [0.42-0.88]). CONCLUSIONS: Sex disparities in baseline characteristics may delay operative intervention in female patients. The inherent risk profiles might be responsible for outcome differences in septuagenarians.

Risk factors for long-term mortality after acute aortic dissection-results of the German registry for acute aortic dissection type a long-term follow-up.

OBJECTIVES: Several short-term analyses from German Registry for Acute Aortic Dissection Type A (GERAADA) have been published. This study investigated whether short-term risk factors are transferable to the long-term prognosis of patients. METHODS: Thirty-three centres with 2686 patients participated in the long-term follow-up. A total of 1164 patients died, 1063 survived and 459 were lost to follow-up during the follow-up timeframe (mean duration: 10.2 years). Long-term mortality of the cohort was compared with an age-stratified, German population. RESULTS: One, 5 and 10 years after initial surgery, the survival of the GERAADA patient cohort was 71.4%, 63.4% and 51%, respectively. Without the early deaths (90-day mortality 25.4%), survival was calculated after 1, 5 and 10 years: 95.6%, 83.5% and 68.3%. Higher age, longer extracorporeal circulation time, shorter perioperative ventilation time and postoperative neurologic deficits were predictive of long-term prognosis. In an age-divided landmark analysis, the mortality of aortic dissection surgery survivors was found to be similar to that of the general German population. If patients are sorted in risk groups according to the GERAADA score, long-term survival differs between the risk groups. CONCLUSIONS: If patients have survived an acute postoperative period of 90 days, life expectancy comparable to that of the general German population can be assumed in lower- and medium-risk patients. Whether the GERAADA score can provide valuable insights into the long-term prognosis of patients undergoing surgery for acute aortic dissection type A is still unclear.

Acute antiarrhythmic effects of SGLT2 inhibitors-dapagliflozin lowers the excitability of atrial cardiomyocytes.

In recent years, SGLT2 inhibitors have become an integral part of heart failure therapy, and several mechanisms contributing to cardiorenal protection have been identified. In this study, we place special emphasis on the atria and investigate acute electrophysiological effects of dapagliflozin to assess the antiarrhythmic potential of SGLT2 inhibitors. Direct electrophysiological effects of dapagliflozin were investigated in patch clamp experiments on isolated atrial cardiomyocytes. Acute treatment with elevated-dose dapagliflozin caused a significant reduction of the action potential inducibility, the amplitude and maximum upstroke velocity. The inhibitory effects were reproduced in human induced pluripotent stem cell-derived cardiomyocytes, and were more pronounced in atrial compared to ventricular cells. Hypothesizing that dapagliflozin directly affects the depolarization phase of atrial action potentials, we examined fast inward sodium currents in human atrial cardiomyocytes and found a significant decrease of peak sodium current densities by dapagliflozin, accompanied by a moderate inhibition of the transient outward potassium current. Translating these findings into a porcine large animal model, acute elevated-dose dapagliflozin treatment caused an atrial-dominant reduction of myocardial conduction velocity in vivo. This could be utilized for both, acute cardioversion of paroxysmal atrial fibrillation episodes and rhythm control of persistent atrial fibrillation. In this study, we show that dapagliflozin alters the excitability of atrial cardiomyocytes by direct inhibition of peak sodium currents. In vivo, dapagliflozin exerts antiarrhythmic effects, revealing a potential new additional role of SGLT2 inhibitors in the treatment of atrial arrhythmias.

Regnase-1 overexpression as a therapeutic approach of Marfan syndrome.

Rupture or dissection of thoracic aortic aneurysms is still the leading cause of death for patients diagnosed with Marfan syndrome. Inflammation and matrix digestion regulated by matrix metalloproteases (MMPs) play a major role in the pathological remodeling of the aortic media. Regnase-1 is an endoribonuclease shown to cleave the mRNA of proinflammatory cytokines, such as interleukin-6. Considering the major anti-inflammatory effects of regnase-1, here, we aimed to determine whether adeno-associated virus (AAV)-mediated vascular overexpression of the protein could provide protection from the development and progression of aortic aneurysms in Marfan syndrome. The overexpression of regnase-1 resulted in a marked decrease in inflammatory parameters and elastin degradation in aortic smooth muscle cells in vitro. Intravenous injection of a vascular-targeted AAV vector resulted in the efficient transduction of the aortic wall and overexpression of regnase-1 in a murine model of Marfan syndrome, associated with lower circulating levels of proinflammatory cytokines and decreased MMP expression and activity. Regnase-1 overexpression strongly improved elastin architecture in the media and reduced aortic diameter at distinct locations. Therefore, AAV-mediated regnase-1 overexpression may represent a novel gene therapy approach for inhibiting aortic aneurysms in Marfan syndrome.

Octogenarian patients and laser-assisted lead extraction: Should we put a limit?

BACKGROUND: Transvenous laser lead extraction (TLE) for cardiac implantable electric devices (CIED) is a challenging procedure especially if performed in octogenarians. In this study we evaluated the safety and efficacy of transvenous laser lead extraction in elderly patients. METHODS: This is a retrospective study of octogenarian patients who underwent laser-assisted lead extraction (LLE) (GlideLight laser sheath, Philips, San Diego, USA). 270 Consecutive patients were included. Patients were divided into two groups. Octogenarian group and non-octogenarian group. The Data was gathered from patients treated between September 2013 and January 2020 and is retrospectively analyzed. RESULTS: Of 270 consecutive patients, 38 (14.0%) were 80 years old or more. The total number of the extracted leads was 556 among which 84(15.0%) from the Octogenarian group. From these leads were 155 single coil leads, 82 dual coil leads, 129 right ventricular pacing leads, 155 right atrial leads, and 35 left ventricular leads. In the Octogenarian group the number of removed leads was as follows: 13 single coil leads, 10 dual coil leads, 28 right ventricular pacing leads, 28 right atrial leads and 5 left ventricular leads. No mortality was recorded in the Octogenarian group. One patient in the YG suffered from a superior vena cava tear and one patient suffered from pulmonary embolism. CONCLUSION: In octogenarian laser assisted lead extraction patients is a safe and effective procedure. No increase in morbidity, mortality or perioperative complication could be recorded in this group. Age should not be a limiting factor to perform this procedure.

Temporary circulatory support with surgically implanted microaxial pumps in postcardiotomy cardiogenic shock following coronary artery bypass surgery.

Objectives: Patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting (CABG) surgery may develop postcardiotomy cardiogenic shock. In these cases, implantation of an Impella 5.0 or 5.5 microaxial pump offers full hemodynamic support while simultaneously unloading of the left ventricle. Methods: Preoperative, perioperative, and postoperative data of all patients receiving postoperative support with an Impella 5.0 or 5.5 after CABG surgery between September 2017 and October 2022 were retrospectively collected. Cohort built-up was performed according to the timing of Impella implantation, either simultaneous during CABG surgery or delayed. Results: A total of n = 42 patients received postoperative Impella support, of whom 27 patients underwent simultaneous Impella implantation during CABG surgery and 15 patients underwent delayed Impella therapy. Preoperative left ventricular ejection fraction was similarly low in both groups (26.7 ± 0.7% vs 24.8 ± 11.3%; P = .32). In the delayed cohort, Impella implantation was performed after a median of 1 (1; 2) days after CABG surgery. Survival after 30 days (75.6% vs 47.6%, P = .04) and 1 year (69.4% vs 29.8%, P = .03) was better in the cohort receiving simultaneous Impella implantation. Conclusions: The combined advantages of hemodynamic support and LV unloading with microaxial pumps may lead to a favorable survival in patients with left ventricular failure following CABG surgery. Early implantation during the initial surgery shows a trend toward a more favorable survival as compared with patients receiving delayed support.

The correlation of age and extension length in DeBakey type I aortic dissection: are older patients over 70 years at a lower risk?

OBJECTIVES: Age-related atherosclerosis has been shown to cause aortic stiffness and wall rigidification. This analysis aimed to correlate age and dissection extension length in a large contemporary multicentre study. We hypothesize that younger patients suffer more extensive DeBakey type I dissection due to aortic wall integrity, allowing unhindered extension within the layers. METHODS: The perioperative data of 3385 patients from the German Registry for Acute Aortic Dissection Type A were retrospectively analyzed with regard to postoperative outcomes and dissection extension. Patients with DeBakey type I aortic dissection (n = 2510) were retrospectively identified and divided into 2 age groups for comparison: ≤69 years (n = 1741) and ≥70 years (n = 769). Patients with DeBakey type II dissection or connective tissue disease were excluded from the analysis. RESULTS: In younger patients (≤69 years), aortic dissection involved the supra-aortic vessels significantly more often (52.0% vs 40.1%; P < 0.001) and extended significantly further downstream the aorta: descending aorta (68.4% vs 57.1%; P < 0.001), abdominal aorta (54.6% vs 42.1%; P < 0.001) and iliac bifurcation (36.6% vs 26.0%; P < 0.001). Consequently, younger patients also presented with significantly higher incidences of preoperative cerebral (P < 0.001), spinal (P < 0.001), visceral (P < 0.001), renal (P = 0.013) and peripheral (P < 0.001) malperfusion. In older patients (≥70 years), dissection extent was significantly more often limited to the level of the aortic arch (40.9% vs 29.2%; P < 0.001). No significant difference was found with regard to 30-day mortality (20.7% vs 23.6%; P = 0.114). CONCLUSIONS: Extensive DeBakey type I aortic dissection is less frequent in older patients ≥70 years than in younger patients. In contrast, younger patients suffer more often from preoperative organ malperfusion and associated complications. Postoperative mortality remains high irrespective of age groups.

Microcirculatory tissue oxygenation correlates with kidney function after transcatheter aortic valve implantation-Results from a prospective observational study.

Introduction: Kidney dysfunction is common in patients with aortic stenosis (AS) and correction of the aortic valve by transcatheter aortic valve implantation (TAVI) often affects kidney function. This may be due to microcirculatory changes. Methods: We evaluated skin microcirculation with a hyperspectral imaging (HSI) system, and compared tissue oxygenation (StO2), near-infrared perfusion index (NIR), tissue hemoglobin index (THI) and tissue water index (TWI) in 40 patients undergoing TAVI versus 20 control patients. HSI parameters were measured before TAVI (t1), directly after TAVI (t2), and on postinterventional day 3 (t3). The primary outcome was the correlation of tissue oxygenation (StO2) to the creatinine level after TAVI. Results: We performed 116 HSI image recordings in patients undergoing TAVI for the treatment of severe aortic stenosis and 20 HSI image recordings in control patients. Patients with AS had a lower THI at the palm (p = 0.034) and a higher TWI at the fingertips (p = 0.003) in comparison to control patients. TAVI led to an increase of TWI, but had no uniform enduring effect on StO2 and THI. Tissue oxygenation StO2 at both measurement sites correlated negatively with creatinine levels after TAVI at t2 (palm: ρ = -0.415; p = 0.009; fingertip: ρ = -0.519; p < 0.001) and t3 (palm: ρ = -0.427; p = 0.008; fingertip: ρ = -0.398; p = 0.013). Patients with higher THI at t3 reported higher physical capacity and general health scores 120 days after TAVI. Conclusion: HSI is a promising technique for periinterventional monitoring of tissue oxygenation and microcirculatory perfusion quality, which are related to kidney function, physical capacity, and clinical outcomes after TAVI. Clinical trial registration: https://drks.de/search/de/trial, identifier DRKS00024765.

Influence of Tricuspid Regurgitation After Heart Transplantation: A Single-center Experience.

Tricuspid valve regurgitation (TVR) is often observed after orthotopic heart transplantation. However, there is a scarcity of data regarding long-term outcomes of patients with TVR. Methods: Between January 2008 and December 2015, 169 patients underwent orthotopic heart transplantation at our center and were included in this study. TVR trends and associated clinical parameters were retrospectively analyzed. TVR was assessed after 30 d, 1 y, 3 y, and 5 y, and groups were defined according to changes in TVR grade: constant (group 1; n = 100), improvement (group 2; n = 26), and deterioration (group 3; n = 43). Survival, outcome with regard to operative technique, and long-term kidney and liver function during follow-up were assessed. Results: Mean follow-up time was 7.67 ± 4.17 y (median 8.62, Q1 5.06, Q3 11.16). Overall mortality was 42.0%, with differences between the groups (P < 0.01). Cox regression analysis revealed improvement of TVR as a significant predictor for survival (hazard ratio 0.23; 95% confidence interval, 0.08-0.63, P < 0.01). After 1 y 2.7%, after 3 y 3.7%, and after 5 y 3.9% of the patients showed persistent severe TVR. Creatinine levels after 30 d and 1, 3, and 5 y showed significant differences between the groups (P = 0.02, P < 0.01, P < 0.01, and P = 0.01), deterioration of TVR being associated with higher creatinine levels during follow-up. Conclusions: Deterioration of TVR is associated with higher mortality and renal dysfunction. Improvement of TVR may function as a positive predictor for long-term survival after heart transplantation. Improvement of TVR should be a therapeutic goal offering a prognostic value for long-term survival.

Early outcomes of patients with Marfan syndrome and acute aortic type A dissection.

BACKGROUND: Acute aortic Stanford type A dissection remains a frequent and life-limiting event for patients with Marfan syndrome. Outcome results in this high-risk group are limited. METHODS: The German Registry for Acute Aortic Dissection Type A collected the data of 56 centers between July 2006 and June 2015. Of 3385 patients undergoing operations for acute aortic Stanford type A dissection, 117 (3.5%) were diagnosed with Marfan syndrome. We performed a propensity score match comparing patients with Marfan syndrome with patients without Marfan syndrome in a 1:2 fashion. RESULTS: Patients with Marfan syndrome were significantly younger (42.9 vs 62.2 years; P < .001), predominantly male (76.9% vs 62.9%; P = .002), and less catecholamine dependent (9.4% vs 20.3%; P = .002) compared with the unmatched cohort. They presented with aortic regurgitation (41.6% vs 23.0%; P < .001) and involvement of the supra-aortic vessels (50.4% vs 39.5%; P = .017) more often. Propensity matching revealed 82 patients with Marfan syndrome (21 female) with no significant differences in baseline characteristics compared with patients without Marfan syndrome (n = 159, 36 female; P = .607). Although root preservation was more frequent in patients with Marfan syndrome, procedure types did not differ significantly (18.3% vs 10.7%; P = .256). Aortic arch surgery was performed more frequently in matched patients (87.5% vs 97.8%; P = .014). Thirty-day mortality did not differ between patients with and without Marfan syndrome (19.5% vs 20.1%; P = .910). Multivariate regression showed no influence of Marfan syndrome on 30-day mortality (odds ratio, 0.928; 95% confidence interval, 0.346-2.332; P = .876). CONCLUSIONS: Marfan syndrome does not adversely affect 30-day outcomes after surgical repair for acute aortic Stanford type A dissection compared with a matched cohort. Long-term outcome analysis is needed to account for the influence of further downstream interventions.

Prospective clinical study testing the efficacy and safety of a new formula to increase the precision of oxygen therapy in the initiation phase of cardiopulmonary bypass.

INTRODUCTION: During cardiopulmonary bypass (CPB), supranormal concentrations of oxygen are routinely administered with the intention to prevent cellular hypoxia. However, hyperoxemia may have adverse effects on patient outcome. Oxygen settings are based on the perfusionist's individual work experience rather than profound recommendations and studies analyzing the effect of oxygen levels are in need of methodological improvement. We aimed to advance perfusion technique by developing and clinically applying a formula for tailored oxygen therapy in CPB. METHODS: A formula to precalculate the oxygenator setting before CPB was developed. The newly-derived formula was then evaluated in a prospective, single-center pilot study to test whether a predefined arterial partial oxygen pressure (PaO2) of 150-250 mmHg could be reached. 80 patients were enrolled in the study between April and September 2021. RESULTS: The mean oxygen fraction calculated for the setting of the gas blender was 52% ±0,12. The mean PaO2 after initiation of the CPB was 193 ± 99 mmHg (min-max: 61-484, median 163 mmHg). 38.75% of the values were in the desired PaO2 corridor of 150 to 250 mmHg. 8.75% of all PaO2 values were below <79.9 mmHg, 31.25% between 80 and 149.9 mmHg, 38.75% between 150 and 249.9 mmHg and 21.25%>250 mmHg. CONCLUSIONS: Conceptually, perfusion technique should be goal-directed, guided by objective parameters and formulas. Although the optimal CPB oxygenation target remains unknown, it is nevertheless important to develop strategies to tailor oxygen therapy to aid in creating evidence as to what level of oxygen is best for patients during CPB. The formula we derived needs further adjustments to increase results in the target range.

Redo aortic arch replacement through a second transcostal approach for closure of type 1A endoleak after endovascular treatment of type B aortic dissection in Marfan syndrome.

A 41-year-old woman with Marfan syndrome suffering from chronic expanding type A dissection of the distal aortic arch and pectus excavatum underwent aortic arch replacement through a left parasternal approach. We demonstrate that this approach is also feasible in complex redo surgery on the aortic arch in selected patients.

Long-Term Patency of Venous Conduits Targeting the Right Coronary Artery System-Single Is Superior to Sequential bypass Grafting.

Objective: Little is known about the fate of bypass grafts to the right coronary system. To investigate the long-term patency of venous bypass grafts directed to the right coronary artery (RCA) based on postoperative angiograms and to identify predictors of graft occlusion. Methods: In this single-center study, all patients who underwent coronary angiography from 2005 to 2021 after previously undergoing isolated coronary artery bypass grafting (CABG) were included. The primary endpoint was graft occlusion over a median follow-up of 9.1 years. Results: Among a total of 1106 patients (17.0% women, 64 (57−71) years median age), 289 (26.1%) received a sequential vein graft and 798 (72.2%) a single graft. Multivariate regression revealed age (HR 1.019, CI 95% 1.007−1.032), the urgency of CABG (HR 1.355, CI 95% 1.108−1.656), and severely impaired left ventricular function (HR 1.883, CI 95% 1.290−2.748), but not gender and chronic total occlusion (CTO) as predictive factors for graft occlusion. Single conduits were found to be a predictor of graft patency (HR 0.575 CI 95% 0.449−0.737). The angiographic outcome showed an overall 10-year freedom from graft occlusion of 73.4% ± 1.6%. The 5-year (10-year) freedom from graft occlusion was 76.9% ± 2.8% (57.8% ± 4.0%) for sequential grafts and 90.4% ± 1.1% (77.8% ± 1.7%) for single grafts (log-rank p < 0.001). Conclusions: In symptomatic patients with renewed angiography, venous bypass grafting of the RCA showed acceptable long-term patency rates. Single bypass grafting of the RCA was superior to sequential grafting, which needs to be further investigated.

Monocyte Metabolism and Function in Patients Undergoing Cardiac Surgery.

Objective: Cardiopulmonary bypass (CPB) can lead to systemic inflammation, which is associated with higher morbidity. Therefore, we investigated the metabolism of isolated blood monocytes before and after CPB compared to healthy controls. Methods: In this prospective, monocentric, observational study, we included 30 patients undergoing CPB and 20 controls. We isolated monocytes from heparinized blood and investigated their metabolism by using Seahorse technology before (t0), 4 h (t4), and 24 h (t24) after the start of the CPB. We also examined programmed cell death 1 ligand (PD-L1), PD-L2, V-domain Ig suppressor of T cell activation (VISTA), and human leukocyte antigen-DR isotype (HLA-DR) using fluorescence-activated cell sorting analysis. Additionally, we investigated plasma cytokine levels in patients without and after ex vivo stimulation. Results: CPB-induced inflammatory responses are shown by significantly elevated plasma interleukin-6 levels in the CPB group compared to baseline and controls [t0: 0 ng/ml (95%CI 0-0 ng/ml); t4: 0.16 ng/ml (95%CI 0.1-0.197 ng/ml), p < 0.0001; t24: 0.11 ng/ml (95% CI 0.1-0.16 ng/ml), p < 0.0001, and controls: 0 ng/ml (95% CI 0-0 ng/ml)]. The cytokine release in the ex vivo stimulation is reduced for lipopolysaccharide stimulation at t4 [t0: 35.68 ng/ml (95% CI 22.17-46.57 ng/ml) vs. t4: 15.02 (95% CI 10.25-24.78 ng/ml), p < 0.0001]. Intracellular metabolism of monocytes after CPB showed a protracted shift to aerobic glycolysis [t0: 179.2 pmol/min (95% CI 138.0-205.1 pmol/min) vs. t24: 250.1 pmol/min (95% CI 94.8-300.2 pmol/min), p < 0.0001]. Additionally, we observed an altered metabolism in monocytes in patients undergoing cardiac surgery compared to controls even before any surgical procedure [t0: 179.2 pmol/min (95% CI 138.0-205.1) vs. controls 97.4 (95% CI 59.13-144.6 pmol/min), p = 0.0031]. Conclusion: After CPB, patients' monocytes show a shift in metabolism from oxidative phosphorylation to aerobic glycolysis, which is associated with energy-demanding and proinflammatory processes. This is the first study to show changes in monocyte immunometabolism in cardiac surgery. Monocytes of patients undergoing cardiac surgery were leaning toward aerobic glycolysis even before any surgical procedure was conducted. Leaving the question of the pathophysiological mechanisms for future studies to be investigated and paving the way for potential therapy approaches preventing inflammatory effects of CPB.

Translational Medicine: Towards Gene Therapy of Marfan Syndrome.

Marfan syndrome (MFS) is one of the most common inherited disorders of connective tissue caused by mutations of the fibrillin-1 gene (FBN1). Vascular abnormalities, such as the enlargement of the aorta with the risk of life-threatening rupture are frequently observed. However, current treatment is limited and therapeutic options focus solely on symptomatic therapy. Gene therapy focuses on genetically modifying cells to produce a therapeutic effect and may be a promising treatment option for MFS. Here, we first provide an overview of the historical background and characterization of MFS. Subsequently, we summarise current gene therapy options and possible translational concepts for this inherited disorder that affects connective tissue.

Treatment of the aortic root in acute aortic dissection type A: insights from the German Registry for Acute Aortic Dissection Type A.

OBJECTIVES: Surgery of the aortic root in acute aortic dissection type A (AADA) remains a topic of vague evidence since the extend of dissection and surgeons' capability and interpretation of the disease vary remarkably. We aimed to interpret root operation strategies in the German Registry for Acute Aortic Dissection cohort. METHODS: German Registry for Acute Aortic Dissection collected the data of 56 centres between July 2006 and June 2015. A total of 3382 patients undergoing operations for AADA were included and divided into 3 groups according to aortic root procedure types: supracommissural replacement (SCR), conduit replacement (CR) and valve sparing root replacement (VSRR). RESULTS: Patients in SCR (2425, 71.7%) were significantly older than CR (681, 20.1%) and VSRR (276, 8.2%) (63.4 vs 57.5 vs 54.2 years; P < 0.001), more female (38.9% vs 32.0% vs 26.1%; P < 0.001) and presented with less aortic regurgitation (26.3% vs 57.1% vs 56.5%; P < 0.001). VSRR presented with slightly less multiple organ malperfusion (11.6% vs 12.0% vs 10.9%; P = 0.045) and were more often diagnosed for Marfan syndrome (2.4% vs 5.1% vs 9.1%; P < 0.001). Thirty-day mortality was lower for VSRR (11.6%) compared to SCR (16.1%) and CR (19.8%; P = 0.010). Despite longer procedural times, multivariable regression showed no influence of total arch replacement for VSRR on mortality compared to CR (odds ratio 0.264; 95% confidence interval, 0.033-2.117; P = 0.21). CONCLUSIONS: SCR remains the procedure of choice in elderly and compromised patients. Extended root preservation techniques may be applied even in combination with extended aortic arch surgery for selected patients for AADA with promising early outcomes.

Treatment of the Aortic Root in Acute Aortic Dissection Type A: Insights from the German Registry for Acute Aortic Dissection Type A (GERAADA) Registry.

OBJECTIVES: Surgery of the aortic root in acute aortic dissection type A (AADA) remains a topic of vague evidence since the extend of dissection and surgeons' capability and interpretation of the disease vary remarkably. We aimed to interpret root operation strategies in the German Registry for Acute Aortic Dissection (GERAADA) cohort. PATIENTS AND METHODS: GERAADA collected the data of 56 centers between July 2006 and June 2015. A total of 3382 patients undergoing operations for AADA were included and divided into three groups according to aortic root procedure types: supracommissural replacement (SCR), conduit replacement (CR) and valve sparing root replacement (VSRR). RESULTS: Patients in SCR (2425, 71.7%) were significantly older than CR (681, 20.1%) and VSRR (276, 8.2%) (63.4 vs 57.5 vs 54.2 yrs; p < 0.001), more female (38.9 vs 32.0 vs 26.1%; p < 0.001) and presented with less aortic regurgitation (26.3 vs 57.1 vs 56.5%; p < 0.001). VSRR presented with slightly less multiple organ malperfusion (11.6 vs 12.0 vs 10.9%; p = 0.045) and were more often diagnosed for Marfan syndrome (2.4 vs 5.1 vs 9.1%; p < 0.001). Thirty-day mortality was lower for VSRR (11.6%) compared to SCR (16.1%) and CR (19.8%; p = 0.010). Despite longer procedural times multivariable regression showed no influence of total arch replacement for VSRR on mortality compared to CR (OR 0.264; 95% CI, 0.033-2.117; p = 0.21). CONCLUSIONS: SCR remains the procedure of choice in elderly and compromised patients. Extended root preservation techniques may be applied even in combination with extended aortic arch surgery for selected patients for AADA with promising early outcomes.

MicroRNAs Regulate TASK-1 and Are Linked to Myocardial Dilatation in Atrial Fibrillation.

Background Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. However, underlying molecular mechanisms are insufficiently understood. Previous studies suggested that microRNA (miRNA) dependent gene regulation plays an important role in the initiation and maintenance of AF. The 2-pore-domain potassium channel TASK-1 (tandem of P domains in a weak inward rectifying K+ channel-related acid sensitive K+ channel 1) is an atrial-specific ion channel that is upregulated in AF. Inhibition of TASK-1 current prolongs the atrial action potential duration to similar levels as in patients with sinus rhythm. Here, we hypothesize that miRNAs might be responsible for the regulation of KCNK3 that encodes for TASK-1. Methods and Results We selected miRNAs potentially regulating KCNK3 and studied their expression in atrial tissue samples obtained from patients with sinus rhythm, paroxysmal AF, or permanent/chronic AF. MiRNAs differentially expressed in AF were further investigated for their ability to regulate KCNK3 mRNA and TASK-1 protein expression in human induced pluripotent stem cells, transfected with miRNA mimics or inhibitors. Thereby, we observed that miR-34a increases TASK-1 expression and current and further decreases the resting membrane potential of Xenopus laevis oocytes, heterologously expressing hTASK-1. Finally, we investigated associations between miRNA expression in atrial tissues and clinical parameters of our patient cohort. A cluster containing AF stage, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left atrial diameter, atrial COL1A2 (collagen alpha-2(I) chain), and TASK-1 protein level was associated with increased expression of miR-25, miR-21, miR-34a, miR-23a, miR-124, miR-1, and miR-29b as well as decreased expression of miR-9 and miR-485. Conclusions These results suggest an important pathophysiological involvement of miRNAs in the regulation of atrial expression of the TASK-1 potassium channel in patients with atrial cardiomyopathy.

Treatment of atrial fibrillation with doxapram: TASK-1 potassium channel inhibition as a novel pharmacological strategy.

AIMS: TASK-1 (K2P3.1) two-pore-domain potassium channels are atrial-specific and significantly up-regulated in atrial fibrillation (AF) patients, contributing to AF-related electrical remodelling. Inhibition of TASK-1 in cardiomyocytes of AF patients was shown to counteract AF-related action potential duration shortening. Doxapram was identified as a potent inhibitor of the TASK-1 channel. In this study, we investigated the antiarrhythmic efficacy of doxapram in a porcine model of AF. METHODS AND RESULTS: Doxapram successfully cardioverted pigs with artificially induced episodes of AF. We established a porcine model of persistent AF in domestic pigs via intermittent atrial burst stimulation using implanted pacemakers. All pigs underwent catheter-based electrophysiological investigations prior to and after 14 days of doxapram treatment. Pigs in the treatment group received intravenous administration of doxapram once per day. In doxapram-treated AF pigs, the AF burden was significantly reduced. After 14 days of treatment with doxapram, TASK-1 currents were still similar to values of sinus rhythm animals. Doxapram significantly suppressed AF episodes and normalized cellular electrophysiology by inhibition of the TASK-1 channel. Patch-clamp experiments on human atrial cardiomyocytes, isolated from patients with and without AF could reproduce the TASK-1 inhibitory effect of doxapram. CONCLUSION: Repurposing doxapram might yield a promising new antiarrhythmic drug to treat AF in patients.