Axillary vs Femoral Arterial Cannulation in Acute Type A Dissection: International Multicenter Data.

BACKGROUND: Cannulation strategy in acute type A dissection (ATAD) varies widely without known gold standards. This study compared ATAD outcomes of axillary vs femoral artery cannulation in a large cohort from the International Registry of Acute Aortic Dissection (IRAD). METHODS: The study retrospectively reviewed 2145 patients from the IRAD Interventional Cohort (1996-2021) who underwent ATAD repair with axillary or femoral cannulation (axillary group: n = 1106 [52%]; femoral group: n = 1039 [48%]). End points included the following: early mortality; neurologic, respiratory, and renal complications; malperfusion; and tamponade. All outcomes are presented as axillary with respect to femoral. RESULTS: The proportion of patients younger than 70 years in both groups was similar (n = 1577 [74%]), as were bicuspid aortic valve, Marfan syndrome, and previous dissection. Patients with femoral cannulation had slightly more aortic insufficiency (408 [55%] vs 429 [60%]; P = .058) and coronary involvement (48 [8%] vs 70 [13%]; P = .022]. Patients with axillary cannulation underwent more total aortic arch (156 [15%] vs 106 [11%]; P = .02) and valve-sparing root replacements (220 [22%] vs 112 [12%]; P < .001). More patients with femoral cannulation underwent commissural resuspension (269 [30.9%] vs 324 [35.3%]; P = .05). Valve replacement rates were not different. The mean duration of cardiopulmonary bypass was longer in the femoral group (190 [149-237] minutes vs 196 [159-247] minutes; P = .037). In-hospital mortality was similar between the axillary (n = 165 [15%]) and femoral (n = 149 [14%]) groups (P = .7). Furthermore, there were no differences in stroke, visceral ischemia, tamponade, respiratory insufficiency, coma, or spinal cord ischemia. CONCLUSIONS: Axillary cannulation is associated with a more stable ATAD presentation, but it is a more extensive intervention compared with femoral cannulation. Both procedures have equivalent early mortality, stroke, tamponade, and malperfusion outcomes after statistical adjustment.

Neurological event rates and associated risk factors in acute type B aortic dissections treated by thoracic aortic endovascular repair.

OBJECTIVES: Thoracic endovascular aortic repair is the method of choice in patients with complicated type B acute aortic dissection. However, thoracic endovascular aortic repair carries a risk of periprocedural neurological events including stroke and spinal cord ischemia. We aimed to look at procedure-related neurological complications within a large cohort of patients with type B acute aortic dissection treated by thoracic endovascular aortic repair. METHODS: Between 1996 and 2021, the International Registry of Acute Aortic Dissection collected data on 3783 patients with type B acute aortic dissection. For this analysis, 648 patients with type B acute aortic dissection treated by thoracic endovascular aortic repair were included (69.4% male, mean age 62.7 ± 13.4 years). Patients were excluded who presented with a preexisting neurologic deficit or received adjunctive procedures. Demographics, clinical symptoms, and outcomes were analyzed. The primary end point was the periprocedural incidence of neurological events (defined as stroke, spinal cord ischemia, transient neurological deficit, or coma). Predictors for perioperative neurological events and follow-up outcomes were considered as secondary end points. RESULTS: Periprocedure neurological events were noted in 72 patients (11.1%) and included strokes (n = 29, 4.6%), spinal cord ischemias (n = 21, 3.3%), transient neurological deficits (n = 16, 2.6%), or coma (n = 6, 1.0%). The group with neurological events had a significantly higher in-hospital mortality (20.8% vs 4.3%, P < .001). Patients with neurological events were more likely to be female (40.3% vs 29.3%, P = .077), and aortic rupture was more often cited as an indication for thoracic endovascular aortic repair (38.8% vs 16.5%, P < .001). In patients with neurological events, more stent grafts were used (2 vs 1 stent graft, P = .002). Multivariable logistic regression analysis showed that aortic rupture (odds ratio, 3.12, 95% confidence interval, 1.44-6.78, P = .004) and female sex (odds ratio, 1.984, 95% confidence interval, 1.031-3.817, P = .040) were significantly associated with perioperative neurological events. CONCLUSIONS: In this highly selected group from dedicated aortic centers, more than 1 in 10 patients with type B acute aortic dissection treated by thoracic endovascular aortic repair had neurological events, in particular women. Further research is needed to identify the causes and presentation of these events after thoracic endovascular aortic repair, especially among women.

High-resolution visualization and assessment of basal and OXPHOS-induced mitophagy in H9c2 cardiomyoblasts.

Mitochondria are susceptible to damage resulting from their activity as energy providers. Damaged mitochondria can cause harm to the cell and thus mitochondria are subjected to elaborate quality-control mechanisms including elimination via lysosomal degradation in a process termed mitophagy. Basal mitophagy is a house-keeping mechanism fine-tuning the number of mitochondria according to the metabolic state of the cell. However, the molecular mechanisms underlying basal mitophagy remain largely elusive. In this study, we visualized and assessed the level of mitophagy in H9c2 cardiomyoblasts at basal conditions and after OXPHOS induction by galactose adaptation. We used cells with a stable expression of a pH-sensitive fluorescent mitochondrial reporter and applied state-of-the-art imaging techniques and image analysis. Our data showed a significant increase in acidic mitochondria after galactose adaptation. Using a machine-learning approach we also demonstrated increased mitochondrial fragmentation by OXPHOS induction. Furthermore, super-resolution microscopy of live cells enabled capturing of mitochondrial fragments within lysosomes as well as dynamic transfer of mitochondrial contents to lysosomes. Applying correlative light and electron microscopy we revealed the ultrastructure of the acidic mitochondria confirming their proximity to the mitochondrial network, ER and lysosomes. Finally, exploiting siRNA knockdown strategy combined with flux perturbation with lysosomal inhibitors, we demonstrated the importance of both canonical as well as non-canonical autophagy mediators in lysosomal degradation of mitochondria after OXPHOS induction. Taken together, our high-resolution imaging approaches applied on H9c2 cells provide novel insights on mitophagy during physiologically relevant conditions. The implication of redundant underlying mechanisms highlights the fundamental importance of mitophagy.Abbreviations: ATG: autophagy related; ATG7: autophagy related 7; ATP: adenosine triphosphate; BafA1: bafilomycin A1; CLEM: correlative light and electron microscopy; EGFP: enhanced green fluorescent protein; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; OXPHOS: oxidative phosphorylation; PepA: pepstatin A; PLA: proximity ligation assay; PRKN: parkin RBR E3 ubiquitin protein ligase; RAB5A: RAB5A, member RAS oncogene family; RAB7A: RAB7A, member RAS oncogene family; RAB9A: RAB9A, member RAS oncogene family; ROS: reactive oxygen species; SIM: structured illumination microscopy; siRNA: short interfering RNA; SYNJ2BP: synaptojanin 2 binding protein; TEM: transmission electron microscopy; TOMM20: translocase of outer mitochondrial membrane 20; ULK1: unc-51 like kinase 1.

Venoarterial extracorporeal membrane oxygenation or standard care in patients with cardiogenic shock complicating acute myocardial infarction: the multicentre, randomised EURO SHOCK trial.

BACKGROUND: Cardiogenic shock (CGS) occurs in 10% of patients presenting with acute myocardial infarction (MI), with in-hospital mortality rates of 40-50% despite revascularisation. AIMS: The EURO SHOCK trial aimed to determine if early use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) could improve outcomes in patients with persistent CGS following primary percutaneous coronary intervention (PPCI). METHODS: This multicentre, pan-European trial randomised patients with persistent CGS 30 minutes after PPCI of the culprit lesion to receive either VA-ECMO or continue with standard therapy. The primary outcome measure was 30-day all-cause mortality in an intention-to-treat analysis. Secondary endpoints included 12-month all-cause mortality and 12-month composite of all-cause mortality or rehospitalisation due to heart failure. RESULTS: Due to the impact of the COVID-19 pandemic, the trial was stopped before completion of recruitment, after randomisation of 35 patients (standard therapy n=18, VA-ECMO n=17). Thirty-day all-cause mortality occurred in 43.8% of patients randomised to VA-ECMO and in 61.1% of patients randomised to standard therapy (hazard ratio [HR] 0.56, 95% confidence interval [CI]: 0.21-1.45; p=0.22). One-year all-cause mortality was 51.8% in the VA-ECMO group and 81.5% in the standard therapy arm (HR 0.52, 95% CI: 0.21-1.26; p=0.14). Vascular and bleeding complications occurred more often in the VA-ECMO arm (21.4% vs 0% and 35.7% vs 5.6%, respectively). CONCLUSIONS: Due to the limited number of patients recruited to the trial, no definite conclusions could be drawn from the available data. Our study demonstrates the feasibility of randomising patients with CGS complicating acute MI but also illustrates the challenges. We hope these data will inspire and inform the design of future large-scale trials.

Editor's Choice - Trends in Management and Outcomes of Type B Aortic Dissection: A Report From the International Registry of Aortic Dissection.

OBJECTIVE: To describe the trends in management and outcomes of patients with acute type B aortic dissection in the International Registry of Acute Aortic Dissection. METHODS: From 1996 - 2022, 3 908 patients were divided into similar sized quartiles (T1, T2, T3, and T4). In hospital outcomes were analysed for each quartile. Survival rates following admission were compared using Kaplan-Meier analyses with Mantel-Cox Log rank tests. RESULTS: Endovascular treatment increased from 19.1% in T1 to 37.2% in T4 (ptrend < .001). Correspondingly, medical therapy decreased from 65.7% in T1 to 54.0% in T4 (ptrend < .001), and open surgery from 14.8% in T1 to 7.0% in T4 (ptrend < .001). In hospital mortality decreased in the overall cohort from 10.7% in T1 to 6.1% in T4 (ptrend < .001), as well as in medically, endovascularly and surgically treated patients (ptrend = .017, .033, and .011, respectively). Overall post-admission survival at three years increased (T1: 74.8% vs. T4: 77.3%; p = .006). CONCLUSION: Considerable changes in the management of acute type B aortic dissection were observed over time, with a significant increase in the use of endovascular treatment and a corresponding reduction in open surgery and medical management. These changes were associated with a decreased overall in hospital and three year post-admission mortality rate among quartiles.

Survival after PCI or CABG for left main stem coronary stenosis. A single institution registry from the NOBLE study period.

Objective. To analyze 10 years mortality in an all-comers registry of patients with left main coronary artery stenoses treated with either PCI or CABG. Design. Patients with left main coronary stenoses treated with either PCI or CABG in the period of the NOBLE trial (2010-2015) were all included in an institutional database and registry (University Hospital North Norway). Fifty-six of totally 429 patients were included in the randomized, multicenter and international NOBLE trail; 426 eligible patients from the trial and registry were analyzed for mortality on 20 October 2020. The longest observation time on this date was 3611 days (9.9 years); 205 patients were treated with PCI and 221 with CABG. The patients treated with PCI were 74 ± 10 years vs 68 ± 10 years (CABG). Also, on average the PCI patients had more comorbidities (lower ejection fraction, more peripheral artery disease, more often acute presentation). Results. Survival at the last observation date was 80% for CABG patients vs 48% for PCI. A Cox proportional hazards analysis found PCI to be the strongest independent predictor for mortality (HR = 2.5, 95% CI 1.7-3.7). Also, COPD, chronic kidney disease, age, peripheral vascular disease, cerebrovascular incidents and acute presentation were factor predicting increased 10 years mortality. Conclusion. These data indicate that life expectancy in the overall patient population is shorter for patient treated for left main disease with PCI than with CABG.

Survival after operative repair of acute type A aortic dissection varies according to the presence and type of preoperative malperfusion.

OBJECTIVE: Approximately one-quarter of patients with acute type A aortic dissection (TAAD) present with concomitant malperfusion of coronary arteries, mesenteric circulation, lower extremities, kidneys, brain, and/or coma. It is generally accepted that TAAD patients who present with malperfusion experience higher mortality rates than patients without, although how specific malperfusion syndromes, alone or in combination, affect mortality is not well described. METHODS: The International Registry of Acute Aortic Dissection database was queried for patients who underwent surgical repair of TAAD. Patients were stratified according to the presence/absence of malperfusion at presentation. Multivariable logistic regression was used to evaluate in-hospital mortality according to malperfusion type. Kaplan-Meier estimates were used to estimate 30-day postoperative survival. RESULTS: Six thousand four hundred thirty-seven patients underwent surgical repair of acute TAAD, of whom 2642 (41%) had 1 or more preoperative malperfusion syndromes. Mesenteric malperfusion (adjusted odds ratio [AOR], 4.84; P < .001) was associated with the highest odds of in-hospital mortality, followed by coma (AOR, 1.88; P = .007), limb ischemia (AOR, 1.73; P = .008), and coronary malperfusion (AOR, 1.51; P = .02). Renal malperfusion (AOR, 1.37; P = .24) and neurologic deficit (AOR, 1.35; P = .28) were not associated with increased in-hospital mortality. In patients who survived to discharge, there was no difference in 1-year postdischarge survival in the malperfusion and no malperfusion cohorts (P = .36). CONCLUSIONS: Survival during the index admission after TAAD repair varies according to the presence and type of malperfusion syndromes, with mesenteric malperfusion being associated with the highest odds of in-hospital death. Not only the presence of malperfusion but rather specific malperfusion syndromes should be considered when assessing a patient's risk of undergoing TAAD repair.

Virtual labeling of mitochondria in living cells using correlative imaging and physics-guided deep learning.

Mitochondria play a crucial role in cellular metabolism. This paper presents a novel method to visualize mitochondria in living cells without the use of fluorescent markers. We propose a physics-guided deep learning approach for obtaining virtually labeled micrographs of mitochondria from bright-field images. We integrate a microscope's point spread function in the learning of an adversarial neural network for improving virtual labeling. We show results (average Pearson correlation 0.86) significantly better than what was achieved by state-of-the-art (0.71) for virtual labeling of mitochondria. We also provide new insights into the virtual labeling problem and suggest additional metrics for quality assessment. The results show that our virtual labeling approach is a powerful way of segmenting and tracking individual mitochondria in bright-field images, results previously achievable only for fluorescently labeled mitochondria.

Early Mortality in Type A Acute Aortic Dissection: Insights From the International Registry of Acute Aortic Dissection.

Importance: Early data revealed a mortality rate of 1% to 2% per hour for type A acute aortic dissection (TAAAD) during the initial 48 hours. Despite advances in diagnostic testing and treatment, this mortality rate continues to be cited because of a lack of contemporary data characterizing early mortality and the effect of timely surgery. Objective: To examine early mortality rates for patients with TAAAD in the contemporary era. Design, Setting, and Participants: This cohort study examined data for patients with TAAAD in the International Registry of Acute Aortic Dissection between 1996 and 2018. Patients were grouped according to the mode of their intended treatment, surgical or medical. Exposure: Surgical treatment. Main Outcomes and Measures: Mortality was assessed in the initial 48 hours after hospital arrival using Kaplan-Meier curves. In-hospital complications were also evaluated. Results: A total of 5611 patients with TAAAD were identified based on intended treatment: 5131 (91.4%) in the surgical group (3442 [67.1%] male; mean [SD] age, 60.4 [14.1] years) and 480 (8.6%) in the medical group (480 [52.5%] male; mean [SD] age, 70.9 [14.7] years). Reasons for medical management included advanced age (n = 141), comorbidities (n = 281), and patient preference (n = 81). Over the first 48 hours, the mortality for all patients in the study was 5.8%. Among patients who were medically managed, mortality was 0.5% per hour (23.7% at 48 hours). For those whose intended treatment was surgical, 48-hour mortality was 4.4%. In the surgical group, 51 patients (1%) died before the operation. Conclusions and Relevance: In this study, the overall mortality rate for TAAAD was 5.8% at 48 hours. For patients in the medical group, TAAAD had a mortality rate of 0.5% per hour (23.7% at 48 hours). However, among those in the surgical group, 48-hour mortality decreased to 4.4%.

The risk factors for radial artery and saphenous vein graft occlusion are different.

Objectives. To determine risk factors for radial artery and saphenous vein graft occlusion during long-term follow-up after coronary artery bypass grafting (CABG). Methods: From a cohort of 119 patients who had received a radial artery graft, 76 - of whom 55 also had at least one saphenous vein graft - underwent a preplanned direct angiography and anthropometric, biochemical, and endothelial function assessment 7.6-12.1 (mean 8.9) years after CABG. Comorbidity, medication, and smoking habits were also recorded. The association between these parameters and conduit longevity was analyzed in univariable and multivariable logistic regression models. Results: Radial artery graft occlusions were associated with higher plasma levels of high-sensitive C-reactive protein and patency was best among patients with pharmacologically treated hypertension. The sole independent risk factor identified for saphenous vein graft occlusion was tobacco smoking 8-12 years postoperatively. Conclusion: Our data support the contention that the pathogenesis of radial artery graft failure is distinct from vein graft disease and is related to hypertension status and systemic inflammation. These risk factors are potential targets for preventive measures. Accordingly, the study supports the eventual design of personalized secondary prevention regimens.Clinical registration number: ISRCTN23118170.

Clinically induced hypothermia with cardiopulmonary support in a high-risk patient undergoing carotid endarterectomy.

Contralateral carotid occlusion increases the risk of stroke by hypoperfusion in patients undergoing carotid surgery. We present the case of a high-risk patient with crescendo cerebral ischemic events, for whom clinically induced hypothermia controlled by cardiopulmonary bypass was applied as a protective measure during carotid endarterectomy.

Three-dimensional structured illumination microscopy data of mitochondria and lysosomes in cardiomyoblasts under normal and galactose-adapted conditions.

This three-dimensional structured illumination microscopy (3DSIM) dataset was generated to highlight the suitability of 3DSIM to investigate mitochondria-derived vesicles (MDVs) in H9c2 cardiomyoblasts in living or fixed cells. MDVs act as a mitochondria quality control mechanism. The cells were stably expressing the tandem-tag eGFP-mCherry-OMP25-TM (outer mitochondrial membrane) which can be used as a sensor for acidity. A part of the dataset is showing correlative imaging of lysosomes labeled using LysoTracker in fixed and living cells. The cells were cultivated in either normal or glucose-deprived medium containing galactose. The resulting 3DSIM data were of high quality and can be used to undertake a variety of studies. Interestingly, many dynamic tubules derived from mitochondria are visible in the 3DSIM videos under both glucose and galactose-adapted growth conditions. As the raw 3DSIM data, optical parameters, and reconstructed 3DSIM images are provided, the data is especially suitable for use in the development of SIM reconstruction algorithms, bioimage analysis methods, and for biological studies of mitochondria.

Mitochondrial dynamics and quantification of mitochondria-derived vesicles in cardiomyoblasts using structured illumination microscopy.

Mitochondria are essential energy-providing organelles of particular importance in energy-demanding tissue such as the heart. The production of mitochondria-derived vesicles (MDVs) is a cellular mechanism by which cells ensure a healthy pool of mitochondria. These vesicles are small and fast-moving objects not easily captured by imaging. In this work, we have tested the ability of the optical super-resolution technique 3DSIM to capture high-resolution images of MDVs. We optimized the imaging conditions both for high-speed video microscopy and fixed-cell imaging and analysis. From the 3DSIM videos, we observed an abundance of MDVs and many dynamic mitochondrial tubules. The density of MDVs in cells was compared for cells under normal growth conditions and cells during metabolic perturbation. Our results indicate a higher abundance of MDVs in H9c2 cells during glucose deprivation compared with cells under normal growth conditions. Furthermore, the results reveal a large untapped potential of 3DSIM in MDV research.

Sex-Based Aortic Dissection Outcomes From the International Registry of Acute Aortic Dissection.

BACKGROUND: Worse outcomes have been reported for women with type A acute aortic dissection (TAAD). We sought to determine sex-specific operative approaches and outcomes for TAAD in the current era. METHODS: The Interventional Cohort (IVC) of the International Registry of Acute Aortic Dissection (IRAD) database was queried to explore sex differences in presentation, operative approach, and outcomes. Multivariable logistic regression was performed to identify adjusted outcomes in relation to sex. RESULTS: Women constituted approximately one-third (34.3%) of the 2823 patients and were significantly older than men (65.4 vs 58.6 years, P < .001). Women were more likely to present with intramural hematoma, periaortic hematoma, or complete or partial false lumen thrombosis (all P < .05) and more commonly had hypotension or coma (P = .001). Men underwent a greater proportion of Bentall, complete arch, and elephant trunk procedures (all P < .01). In-hospital mortality during the study period was higher in women (16.7% vs 13.8%, P = .039). After adjustment, female sex trended towards higher in-hospital mortality overall (odds ratio, 1.40; P = .053) but not in the last decade of enrollment (odds ratio, 0.93; P = .807). Five-year mortality and reintervention rates were not significantly different between the sexes. CONCLUSIONS: In-hospital mortality remains higher among women with TAAD but demonstrates improvement in the last decade. Significant differences in presentation were noted in women, including older age, distinct imaging findings, and greater evidence of malperfusion. Although no distinctions in 5-year mortality or reintervention were observed, a tailored surgical approach should be considered to reduce sex disparities in early mortality rates for TAAD.

Effect of Aortic Valve Type on Patients Who Undergo Type A Aortic Dissection Repair.

Aortic valve replacement (AVR) is common in the setting of type A aortic dissection (TAAD) repair. Here, we evaluated the association between prosthesis choice and patient outcomes in an international patient cohort. We reviewed data from the International Registry of Acute Aortic Dissection (IRAD) interventional cohort to examine the relationship between valve choice and short- and mid-term patient outcomes. Between January 1996 and March 2016, 1290 surgically treated patients with TAAD were entered into the IRAD interventional cohort. Of those, 364 patients undergoing TAAD repair underwent aortic valve replacement (AVR; mean age, 57 years). The mechanical valve cohort consisted of 189 patients, of which 151 (79.9%) had a root replacement. The nonmechanical valve cohort consisted of 5 patients who received homografts and 160 patients who received a biologic AVR, with a total of 118 (71.5%) patients who underwent root replacements. The mean follow-up time was 2.92 ± 1.75 years overall (2.46 ± 1.69 years for the mechanical valve cohort and 3.48 ± 1.8 years for the nonmechanical valve cohort). After propensity matching, Kaplan-Meier estimates of 4-year survival rates after surgery were 64.8% in the mechanical valve group compared with 74.7% in the nonmechanical valve group (p = 0.921). A stratified Cox model for 4-year mortality showed no difference in hazard between valve types after adjusting for the propensity score (p = 0.854). A biologic valve is a reasonable option in patients with TAAD who require AVR. Although this option avoids the potential risks of anticoagulation, long-term follow up is necessary to assess the effect of reoperations or transcatheter interventions for structural valve degeneration.

Age-Stratified Outcome in Treatment of Left Main Coronary Artery Stenosis: A NOBLE Trial Substudy.

BACKGROUND: In the treatment of left main coronary artery (LMCA) disease, patients' age may affect the clinical outcome after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). This study stratified the clinical outcome according to the age of patients treated for LMCA stenosis with PCI or CABG in the Nordic-Baltic-British Left Main Revascularization (NOBLE) study. METHODS: Patients with LMCA disease were enrolled in 36 centers in northern Europe and randomized 1:1 to treatment by PCI or CABG. Eligible patients had stable angina pectoris, unstable angina pectoris, or non-ST elevation myocardial infarction. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCEs), a composite of all-cause mortality, nonprocedural myocardial infarction, any repeat coronary revascularization, and stroke. Age-stratified analysis was performed for the groups younger and older than 67 years and for patients older than 80 years. RESULTS: For patients ≥67 years, the 5-year MACCEs were 35.7 versus 22.3% (hazard ratio [HR] 1.72 [95% confidence interval [CI] 1.27-2.33], p = 0.0004) for PCI versus CABG. The difference in MACCEs was driven by more myocardial infarctions (10.8 vs. 3.8% HR 3.01 [95% CI 1.52-5.96], p = 0.0009) and more repeat revascularizations (19.5 vs. 10.0% HR 2.01 [95% CI 1.29-3.12], p = 0.002). In patients younger than 67 years, MACCE was 20.5 versus 15.3% (HR 1.38 [95% CI 0.93-2.06], p = 0.11 for PCI versus CABG. All-cause mortality was similar after PCI and CABG in both age-groups. On multivariate analysis, age was a predictor of MACCE, along with PCI, diabetes, and SYNTAX score. CONCLUSIONS: As the overall NOBLE results show revascularization of LMCA disease, age of 67 years or older was associated with lower 5-year MACCE after CABG compared to PCI. Clinical outcomes were not significantly different in the subgroup younger than 67 years, although no significant interaction was present between age and treatment. Mortality was similar for all subgroups (ClinicalTrials.gov identifier: NCT01496651).

Moderate Versus Deep Hypothermia in Type A Acute Aortic Dissection Repair: Insights from the International Registry of Acute Aortic Dissection.

BACKGROUND: The optimal strategy for cerebral protection during repair of type A acute aortic dissection has yet to be determined. We sought to determine the impact of differing degrees of hypothermia in patients undergoing acute dissection repair. METHODS: All patients in the International Registry of Acute Aortic Dissection Interventional Cohort database who underwent type A acute aortic dissection repair between 2010 and 2018 were identified. Data for operative temperature were available for 1962 patients subsequently divided into 2 groups according to lowest temperature: moderate hypothermic circulatory arrest (MHCA) (20-28°C) versus deep hypothermic circulatory arrest (DHCA) (<20°C). We then propensity matched 362 pairs of patients and analyzed operative data and short-term outcomes. RESULTS: The median lowest temperature was 25.0°C in the matched MHCA group as compared with 18.0°C in the DHCA group. For the entire cohort of 1962 patients, in-hospital mortality was 14.2% (278 deaths) but was not significantly different between DHCA and MHCA. The perioperative stroke rate was comparable between groups, before and after propensity matching. Circulatory arrest times were significantly longer in the MHCA cohort, regardless of matching. Use of antegrade or retrograde cerebral perfusion was similar in matched groups. There were no differences in 30-day survival or in other major postoperative morbidity between the 2 matched cohorts. CONCLUSIONS: A surgical strategy of MHCA + antegrade cerebral perfusion is at least as safe as DHCA during repair of acute type A aortic dissection.

Clinical Features and Outcomes of Pregnancy-Related Acute Aortic Dissection.

Importance: Women with aortopathy conditions are at risk for pregnancy-related aortic dissection, and these conditions may not be recognized until after the aortic dissection occurs. Objective: To examine the clinical characteristics, imaging features, and outcomes in women with pregnancy-related acute aortic dissection. Design, Setting, and Participants: A cohort study, comprising data from the International Registry of Acute Aortic Dissection (IRAD) (February 1, 1998, to February 28, 2018). The multicenter referral center study included 29 women with aortic dissection during pregnancy or less than 12 weeks post partum in IRAD from 1998 to 2018. Main Outcomes and Measures: Clinical features of pregnancy-related aortic dissection to be studied included underlying aortopathy, aortic size, type of aortic dissection, timing of dissection, hypertension, and previous aortic surgery. Results: A total of 29 women (mean [SD] age, 32 [6] years) had pregnancy-related aortic dissection, representing 0.3% of all aortic dissections and 1% of aortic dissection in women in the IRAD. Among women younger than 35 years, aortic dissection was related to pregnancy in 20 of 105 women (19%). Thirteen women (45%) had type A aortic dissection, and 16 women (55%) had type B. Aortic dissection onset was known in 27 women (93%): 15 during pregnancy, 4 in the first trimester, and 11 in the third trimester; 12 were post partum, occurring a mean (SD) of 12.5 (14) days post partum. At type A aortic dissection diagnosis, the mean (SD) aortic diameters were sinus of Valsalva, 54.5 (5) mm and ascending aorta, 54.7 (6) mm. At type B aortic dissection diagnosis, the mean (SD) descending aortic diameter was 32.5 (5) mm. Twenty women (69%) had an aortopathy condition or a positive family history: 13 women (65%) with Marfan syndrome, 2 women (10%) with Loeys-Dietz syndrome, 2 women (10%) with bicuspid aortic valves, 2 women (10%) with a family history of aortic disease, and 1 woman (5%) with familial thoracic aortic aneurysm. Aortopathy was not recognized until after aortic dissection in 47% of the women. Twenty-eight women (97%) survived aortic dissection hospitalization. Conclusions and Relevance: Aortic dissection complicating pregnancy is rare. Most pregnancy-related aortic dissection is due to an aortopathy often not diagnosed until after aortic dissection. In this study, type A aortic dissections were associated with a dilated aorta, and type B aortic dissections often were not. Recognition of underlying conditions and risks for aortic dissection may improve management of pregnancy in women with aortopathy.

Veno-arterial extracorporeal membrane oxygenation (ECMO) in patients with cardiogenic shock: rationale and design of the randomised, multicentre, open-label EURO SHOCK trial.

AIMS: Cardiogenic shock (CGS) occurs in 6-10% of patients with acute coronary syndromes (ACS). Mortality has fallen over time from 80% to approximately 50% consequent on acute revascularisation but has plateaued since the 1990s. Once established, patients with CGS develop adverse compensatory mechanisms that contribute to the downward spiral towards death, which becomes difficult to reverse. We aimed to test in a robust, prospective, randomised controlled trial whether early support with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides clinical benefit by improving mortality and morbidity. METHODS AND RESULTS: The EURO SHOCK trial will test the benefit or otherwise of mechanical cardiac support using VA-ECMO, initiated early after acute percutaneous coronary intervention (PCI) for CGS. The trial sets out to randomise 428 patients with CGS complicating ACS, following primary PCI (P-PCI), to either very early ECMO plus standard pharmacotherapy, or standard pharmacotherapy alone. It will be conducted in 39 European centres. The primary endpoint is 30-day all-cause mortality with key secondary endpoints: 1) 12-month all-cause mortality or admission for heart failure, 2) 12-month all-cause mortality, 3) 12-month admission for heart failure. Cost-effectiveness analysis (including quality of life measures) will be embedded. Mechanistic and hypothesis-generating substudies will be undertaken. CONCLUSIONS: The EURO SHOCK trial will determine whether early initiation of VA-ECMO in patients presenting with ACS-CGS persisting after PCI improves mortality and morbidity.

Hemodynamic Effects of a Soluble Guanylate Cyclase Stimulator, Riociguat, and an Activator, Cinaciguat, During NO-Modulation in Healthy Pigs.

Cardiovascular diseases are often characterized by dysfunctional endothelium. To compensate for the related lack of nitric oxide (NO), a class of soluble guanylate cyclase (sGC) stimulators and activators have been developed with the purpose of acting downstream of NO in the NO-sGC-cGMP cascade. These drugs have been discovered using photoaffinity labeling of sGC and high-throughput screening of a vast number of chemical compounds. Therefore, an understanding of the integrated physiological effects of these drugs in vivo is necessary on the path to clinical application. We have characterized the integrated hemodynamic impact of the sGC stimulator riociguat and the activator cinaciguat in different NO-states in healthy juvenile pigs (n = 30). We assessed the vascular effects in both systemic and pulmonary circulation, the contractile effects in the right and left ventricles, and the effects on diastolic cardiac functions. Nitric oxide-tone in these pigs were set by using the NO-blocker l-NAME and by infusion of nitroglycerine. The studies show a more pronounced vasodilatory effect in the systemic than pulmonary circulation for both drugs. Riociguat acts integrated with NO in an additive manner, while cinaciguat, in principle, completely blocks the endogenous NO effect on vascular control. Neither compound demonstrated pronounced cardiac effects but had unloading effect on both systolic and diastolic function. Thus, riociguat can potentially act in various disease states as a mean to increase NO-tone if systemic vasodilation can be balanced. Cinaciguat is a complicated drug to apply clinically due to its almost complete lack of integration in the NO-tone and balance.