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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.

Electronic patient records represent a potential data source for the future, as digital free text extraction by artificial intelligence is coming closer to safe options for handling of confidential information. Big data from patient records could in turn be applied to improve risk prediction for several disease groups. In this project, a pilot dataset based on information from patient journals was collected to explore the suitability of free text information in risk prediction for patients with carotid stenosis. 863 patients with the ICD-10 diagnosis carotid stenosis were included, and the risk of stroke was analysed in relation to treatment and variables previously shown to impact disease progression or stroke risk. Variables previously shown to have a strong impact on this risk were included with time dependency, to allow analysis of trends in risk in relation to changes in risk profile over time. Multiple endpoint analysis was performed to explore the excess risk in patients who suffered more than one event. Results from the suggested model were compared to results from traditional cox regression, and concordance analysis was performed to compare these two models. In analysis of the pilot dataset, the expanded model with time dependency and multiple endpoint analysis appears to provide a better model fit then a traditional cox regression analysis performed on the same dataset.

Digitalised patient records represent a large potential source of real-world data. Nevertheless, confidentiality and data protection has made big data extraction from patient records impossible in the past. Future options for artificial intelligence in free text reading might enable data extraction while maintaining confidentiality. In turn this could enable improvement in risk prediction for several disease groups. Still, it is not known if free text record data provides an appropriate data source for this purpose. In this project we have analysed a pilot dataset of patients with carotid stenosis in order to estimate the stroke risk in relation to treatment, and by that to assess the individual risk profile. The pilot dataset is applied to design a statistical model suitable for patient record data analysis. In this article a detailed description of the data set, and the methods behind our model choice will be presented.

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.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.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).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.

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.

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.

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.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.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.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.

Source at https://doi.org/10.1002/ehf2.12433. Aims: The aims of this study were to evaluate health-related quality of life (HRQL) among patients treated with extracorpo-real membrane oxygenation (ECMO) in northern Norway over a period of 27years (1988–2015) and to identify variables related to HRQL. Methods and results: A retrospective inquiry of the ECMO registry at the University Hospital of North Norway identified 74 ECMO-treated patients (mean age 49 years, 65% males). Acute cardiac failure was the dominant indication (58%), and venoarterial ECMO was the dominant mode of treatment (87%). Mortality for discharged patients was recorded on 20 September 2016. Thirty (41%) survivors were identified. Twenty-three survivors were eligible for the survey and received a set of questionnaires at home. The main outcome measure was HRQL as measured with the 36-item Short-Form health survey (SF-36) (RAND Short Form-36 v1.2). Other questionnaires covered demographic information, problems with functioning in usual daily activities (such as hobbies, household chores, family, or work), employment status, and psychological distress. The survey was completed by 20 (87%) survivors (mean age =49 years, 12 men). Indications for ECMO treatment (VA = 90%) had been respiratory failure (25%), cardiac failure (60%), and extracorporeal cardiopulmonary resuscitation (15%). The average time since ECMO treatment was 6.5 years. Seventy-five percent reported mental HRQL (SF-36 Mental Component Summary,mean =43,SD=5) or physical HRQL (SF-36 Physical Component Summary, mean =43,SD=4.5) within the normal range(T=50±10) in comparison with age-matched population data from national norms. Half of the responders reported problems on the SF-36 subscales general health and role physical. Seventy percent reported problems on the SF-36 subscale role emotional. All but one responder lived independently without any organized care, and 90% reported no problems related to basic self-care. Half of those in working age had returned to work after ECMO treatment. Forty percent of the responders reported some degree of restrictions in usual daily activities, problems with mobility (35%), anxiety/depression (35%), or pain/discomfort (55%). Significant univariate associations were observed for poorer HRQL and higher reports of psychological distress, pain, and experiencing restrictions in usual everyday activities. Improved HRQL was significantly related to an extended time since ECMO treatment. Conclusions: Our survey indicates an overall positive long-term HRQL outcome for our ECMO survivors. A subset reported problems with functioning and HRQL. Future research should focus on identification of the survivors at risk for poor recovery who may benefit from rehabilitation interventions.

ImportanceEarly 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.ObjectiveTo examine early mortality rates for patients with TAAAD in the contemporary era.Design, Setting, and ParticipantsThis 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.ExposureSurgical treatment.Main Outcomes and MeasuresMortality was assessed in the initial 48 hours after hospital arrival using Kaplan-Meier curves. In-hospital complications were also evaluated.ResultsA 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 RelevanceIn 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%.

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.

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 to cells under normal growth conditions. Furthermore, the results reveal a large untapped potential of 3DSIM in MDV research. This article is protected by copyright. All rights reserved.

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).

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.

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.

This is an Accepted Manuscript of an article published by Taylor & Francis in Scandinavian Cardiovascular Journal on 30. june 2020, available online: https://doi.org/10.1080/14017431.2020.1784454. Objectives: The benefits of coronary artery bypass surgery depend on lasting graft patency. To aid rational graft selection, the relative long-term merits of radial artery and saphenous vein grafts need to be determined by a gold standard method and with minimal clinically driven selection bias. Methods: The patency rates of various conduits were determined by direct angiography in 76 patients from a cohort of 119 undergoing coronary artery bypass grafting 7.6–12.1 (mean 8.9) years before. Results: 14 out of 76 radial artery and 10 out of 61 saphenous vein grafts were occluded (rates 0.18 and 0.16, respectively). Conclusion: The high long-term patency rate of saphenous vein grafts does not support a preferential use of the radial artery as a coronary artery bypass conduit.

To analyze presentation, management, and outcomes of acute aortic dissections with proximal entry tear in the arch.Patients enrolled in the International Registry of Acute Aortic Dissection and entry tear in the arch were classified into 2 groups: arch A (retrograde extension into the ascending aorta with or without antegrade extension) and arch B (only antegrade extension into the descending aorta or further distally). Presentation, management, and in-hospital outcomes of the 2 groups were compared.The arch A (n = 228) and arch B (n = 140) groups were similar concerning the presence of any preoperative complication (68.4% vs 60.0%; P = .115), but the types of complication were different. Arch A presented more commonly with shock, neurologic complications, cardiac tamponade, and grade 3 or 4 aortic valve insufficiency and less frequently with refractory hypertension, visceral ischemia, extension of dissection, and aortic rupture. Management for both groups were open surgery (77.6% vs 18.6%; P .001), endovascular treatment (3.5% vs 25.0%; P .001), and medical management (16.2% vs 51.4%; P .001). Overall in-hospital mortality was similar (16.7% vs 19.3%; P = .574), but mortality tended to be lower in the arch A group after open surgery (15.3% vs 30.8%; P = .090), and higher after endovascular (25.0% vs 14.3%; P = .597) or medical treatment (24.3% vs 13.9%; P = .191), although the differences were not significant.Acute aortic dissection patients with primary entry tear in the arch are currently managed by a patient-specific approach. In choosing the management type of these patients, it may be advisable to stratify them based on retrograde or only antegrade extension of the dissection.

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.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.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.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.

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.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.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.A surgical strategy of MHCA + antegrade cerebral perfusion is at least as safe as DHCA during repair of acute type A aortic dissection.

Acute aortic dissection (AAD) is a life-threatening disorder that is challenging to diagnose and with defined optimal therapies and outcomes. It is associated with high morbidity and mortality rates, in spite of new management approaches developed over the past few decades. In this article we review lessons learned from the 20-year IRADRegistry experience and its nearly 100 publications. The International Registry of Acute Aortic Dissection (IRAD) is an ongoing registry, which was established in 1996 with the aim to collect data and provide information on this rare disease in order to provide better decision making on clinical practice and surgical management. Acute aortic dissection, including intramural hematoma, is defined as onset of symptoms within 14 days to hospital admission. After 20 years of enrollment, more than 8000 patients with AAD have been collected worldwide, roughly two-thirds with type Aand one-third with type B. Data shows trend for a reduced overall in hospital mortality over the years, in particular for those operated on for type AAAD, due to the improvement in operative technologies, organ perfusion and surgeons taking on even high-risk patients. In contrast, for type B AADendovascular repair has been more frequently adopted in recent years but without a significant demonstrable reduction of in hospital mortality, although an increased survival rate at 5 years was observed. Data suggest an increase in surgical intervention treatment for both type Aand B AAD, particularly in B due to expansion of endovascular treatment. While expanded surgical repair for type Ahas shown a trend for a better outcome, this was not observed for type B patients. In addition, debate continues about endovascular treatment of uncomplicated type B and IMH.

Introduction Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of pulmonary hypertension. Its effect on cardiometabolic efficiency is unknown. A potential cardiac energy sparing effect of this drug could imply a positive prognostic effect, particularly in patients with right heart failure from pulmonary hypertension. Method We infused Riociguat in six healthy juvenile pigs and measured the integrated cardiovascular effect and myocardial oxygen consumption. To assess the interplay with NO‐blockade on cardiac function and efficiency we also administered the NO‐blocker L‐ NAME to the animals after Riociguat. Results and Discussion Infusion of 100 µg/kg Riociguat gave modest systemic vasodilatation seen as a drop in coronary and systemic vascular resistance of 36% and 26%, respectively. Right and left ventriculoarterial coupling index (Ees/Ea), stroke work efficiency (SWeff), and the relationship between left ventricular myocardial oxygen consumption (MVO2) and total mechanical work (pressure–volume area; PVA) were unaffected by Riociguat. In contrast, systemic and pulmonary vasoconstriction induced by L‐NAME (15 mg/kg) shifted the Ees/Ea ratio toward reduced SWeff in both systemic and pulmonary circulation. However, there was no surplus oxygen consumption, that was measured by the MVO2/PVA relationship after L‐NAME in Riociguat‐treated pigs. This suggests that Riociguat can reduce the NO‐related cardiometabolic inefficiency previously observed by blocking the NO pathway., The sGC stimulator Riociguat hamper the energy wasting effect of NO‐blocade in Health juvenile pig hearts

Background Acute Respiratory Failure (ARF) has been noted in up to 20% of patients undergoing cardiac surgery and is associated with increased mortality. Cardiopulmonary bypass (CPB) is often followed by pulmonary dysfunction, although literature on the subject in the setting of Type A acute aortic dissection (TAAAD) is limited. Methods This study identified the incidence of ARF after TAAAD, associated risk factors, and the impact of ARF on early and late outcomes. All data have been derived from the International Registry of Acute Aortic Dissection (IRAD). Results Postoperative ARF (defined as ventilator support for ≥3 days, tracheostomy, and/or pneumonia) occurred in 434 (24.6%) of 1764 surgically managed TAAAD patients (mean age 60.1±14.2 years) from November 2001 until November 2017. Peripheral vessel procedures (6.4% v 2.8%, p=0.002), cerebral perfusion (89.2% v 82.3%, p On multivariable logistic regression analysis, age ≥70 years (OR 1.019, 95% CI 1.005–1.034, p=0.008), current smoking (OR 1.744, 95% CI 1.184–2.570, p=0.005), peripheral vessel procedures (OR 2.457, 95% CI 1.132–5.334, p=0.023), presenting hypotension/shock (OR 2.036, 95% CI 1.336–3.102, p=0.001), lower extremity ischemia at surgery (OR 2.77, 95% CI 1.574–4.875, p Post-operative complications were more common in ARF patients. In-hospital mortality was higher in the ARF cohort (16.4% v 4.7%, p Conclusions Post-operative ARF is common after TAAAD repair; in-hospital complications and death are higher in this cohort. Acknowledgement/Funding W.L. Gore & Associates, Inc.; Medtronic; Varbedian Aortic Fund; Hewlett Foundation; Mardigian Foundation; UM Faculty Group Practice; Ann & Bob Aikens

Postoperative myocardial infarction remains a serious complication in cardiac surgery. The incidence and impact of this condition in acute type A aortic dissection are poorly understood.A total of 1445 patients with acute type A aortic dissection who underwent surgery were enrolled in the International Registry of Acute Aortic Dissection from 1996 to 2013. Individuals with preoperative myocardial infarction at hospital presentation and a history of myocardial infarction were excluded. Patients with postoperative myocardial infarction (n = 38, 2.6%) were compared with those without postoperative myocardial infarction (n = 1407, 97.4%).The postoperative myocardial infarction group was more often of white race (100% vs 90%, P = .043) with bicuspid aortic valve (15.6% vs 4.5%, P = .015). Imaging demonstrated more aortic root involvement (75.8% vs 49.5%, P = .003), pericardial effusion (65.5% vs 44.1%, P = .022), and coronary artery compromise (27.3% vs 10.2%, P = .022). Patients with postoperative myocardial infarction were more frequently hypotensive or in shock during surgery (42.9% vs 25.5%, P = .021). Patients with postoperative myocardial infarction were more likely to have undergone root replacement (54.5% vs 33.3%, P = .011), coronary artery bypass grafting (28.6% vs 7.4%, P .001), or aortic valve replacement (40.0% vs 23.8%, P = .027), and less likely to have had complete arch replacement (2.8% vs 14.0%, P = .050). Median circulatory arrest time was higher in postoperative myocardial infarction (60 vs 38 minutes, P = .024). In-hospital mortality (57.9% vs 16.3%, P .001) and Kaplan-Meier estimates of 5-year mortality (P = .007) were distinctly higher in postoperative myocardial infarction.Postoperative myocardial infarction is a devastating complication of type A aortic dissection repair. It is associated with bicuspid aortic valve, root involvement, pericardial effusion, and extent of surgical repair. Patients with postoperative myocardial infarction have higher serious postoperative complications, in-hospital mortality, and 5-year mortality rates than those without postoperative myocardial infarction.

Type A acute aortic dissection (TAAD) is a disease that has a catastrophic impact on a patient’s life and emergent surgery represents a key goal of early treatment. Despite continuous improvements in imaging techniques, medical therapy and surgical management, early mortality in patients undergoing TAAD repair still remains high, ranging from 17% to 26%. In this setting, the International Registry of Acute Aortic Dissection (IRAD), the largest worldwide registry for acute aortic dissection, was established to assess clinical characteristics, management and outcomes of TAAD patients. The present review aimed to evaluate and comment on outcomes of TAAD surgery as reported from IRAD series.

AIM Compensatory tachycardia can potentially be deleterious in acute heart failure. In this study, we tested a therapeutic strategy of combined inotropic support (dobutamine) and selective heart rate (HR) reduction through administration of ivabradine. METHODS In an open-chest pig model (n = 12) with left ventricular (LV) post-ischaemia dysfunction, cardiac function was assessed by LV pressure catheter and sonometric crystals. Coronary flow and blood samples from the coronary sinus were used to measure myocardial oxygen consumption (MVO2 ). LV energetics was assessed by comparing MVO2 with cardiac work at a wide range of workloads. RESULTS In the post-ischaemia heart, dobutamine (5 μg kg(-1) min(-1) ) increased cardiac output (CO) by increasing HR from 102 ± 21 to 131 ± 16 bpm (beats per min; P

Inotropic support in ischemic acute heart failure (AHF) is controversial. We tested a therapeutic principle for AHF by combining a low dose of omecamtiv mecarbil (OM; 0.25 mg/kg bolus plus 0.25 mg/kg/h) with a low dose of dobutamine (Dobut; 1.25 µg/kg/min). In 10 pigs subjected to myocardial ischemia by left coronary microembolization, this cotreatment increased cardiac power (CP) from 0.48 ± 0.14 to 0.81 ± 0.22 W ( P < .05). When the drugs were given as a monotherapy, CP increased from 0.57 ± 0.11 to 0.65 ± 0.15 W (OM; n = 5; not significant) and from 0.40 ± 0.07 to 0.70 ± 0.10 W (Dobut; n = 5; P < .05). Dobut counteracted OM-mediated impairments in early relaxation and diastolic shortening. In a second protocol using the same doses, we assessed cardiac efficiency in 5 healthy pigs by relating myocardial oxygen consumption (MVO2) to the pressure–volume area. Here, the increases in cardiac work and MVO2 were matched, leaving cardiac efficiency unaltered by this drug combination. Low-dose cotreatment with OM + Dobut produces an appropriate hemodynamic effect with improved CP at doses that do not affect cardiac efficiency. This outcome is mainly attributed to the inotropic effect of Dobut.

Copyright 2019 Society of Photo‑Optical Instrumentation Engineers (SPIE). One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this publication for a fee or for commercial purposes, and modification of the contents of the publication are prohibited. In this work we have explored the live-cell friendly nanoscopy method Multiple Signal Classification Algorithm (MUSICAL) for multi-colour imaging of various organelles and sub-cellular structures in the cardiomyoblast cell line H2c9. We have tested MUSICAL for fast (up to 230Hz), multi-colour time-lapse sequences of various sub-cellular structures (mitochondria, endoplasmic reticulum, microtubules, endosomes and nuclei) in living cells using low excitation-light dose. Challenges and opportunities with applying MUSICAL for studying rapid sub-cellular dynamics are discussed.

Acute aortic dissection (AAD) is a life-threatening condition associated with high morbidity and mortality rates, and it remains a challenge to diagnose and treat. The International Registry of Acute Aortic Dissection was established in 1996 with the mission to raise awareness of this condition and provide insights to guide diagnosis and treatment. Since then, >7300 cases have been included from >51 sites in 12 countries. Although presenting symptoms and physical findings have not changed significantly over this period, the use of computed tomography in the diagnosis has increased, and more patients are managed with interventional procedures: surgery in type A AAD and endovascular therapy in type B AAD; with these changes in care, there has been a significant decrease in overall in-hospital mortality in type A AAD but not in type B AAD. Herein, we summarized the key lessons learned from this international registry of patients with AAD over the past 20 years.

Background— Omecamtiv mecarbil (OM) is a novel inotropic agent that prolongs systolic ejection time and increases ejection fraction through myosin ATPase activation. We hypothesized that a potentially favorable energetic effect of unloading the left ventricle, and thus reduction of wall stress, could be counteracted by the prolonged contraction time and ATP-consumption. Methods and Results— Postischemic left ventricular dysfunction was created by repetitive left coronary occlusions in 7 pigs (7 healthy pigs also included). In both groups, systolic ejection time and ejection fraction increased after OM (0.75 mg/kg loading for 10 minutes, followed by 0.5 mg/kg/min continuous infusion). Cardiac efficiency was assessed by relating myocardial oxygen consumption to the cardiac work indices, stroke work, and pressure–volume area. To circumvent potential neurohumoral reflexes, cardiac efficiency was additionally assessed in ex vivo mouse hearts and isolated myocardial mitochondria. OM impaired cardiac efficiency; there was a 31% and 23% increase in unloaded myocardial oxygen consumption in healthy and postischemic pigs, respectively. Also, the oxygen cost of the contractile function was increased by 63% and 46% in healthy and postischemic pigs, respectively. The increased unloaded myocardial oxygen consumption was confirmed in OM-treated mouse hearts and explained by an increased basal metabolic rate. Adding the myosin ATPase inhibitor, 2,3-butanedione monoxide abolished all surplus myocardial oxygen consumption in the OM-treated hearts. Conclusions— Omecamtiv mecarbil, in a clinically relevant model, led to a significant myocardial oxygen wastage related to both the contractile and noncontractile function. This was mediated by that OM induces a continuous activation in resting myosin ATPase.

This study was designed to assess whether altered RV geometry and deformation parameters persisted well into the recovery period after presumably uncomplicated coronary artery bypass grafting (CABG). It was our hypothesis that the altered geometry of and load in the RV following pericardial opening would change both regional and global deformation indices for an extensive period postoperatively.Fifty-seven patients scheduled for CABG underwent preoperative and 8-10 months postoperative magnetic resonance imaging (MRI) for RV volume measurements, and resting echocardiography with assessment of geometry and RV mechanical function determined by tissue Doppler imaging (TDI) based longitudinal strain. Both MRI and echocardiography revealed postoperative dilatation of the RV apex, shortened longitudinal RV length but unchanged RV ejection fraction. Echocardiography parameters associated with filling of the right atrium showed signs of constraint with a reduced systolic filling fraction and increased right atrial size. Right ventricular segmental strain (-20 ± 13% vs. -29 ± 20% preoperatively; mean ±SD, P0.0001) was reduced postoperatively in parallel with TAPSE (1.3 ± 0.3 cm vs. 2.2 ± 0.4 cm; P0.0001).Post-CABG longitudinal motion of the RV lateral wall is reduced after uneventful CABG despite preserved RV ejection fraction and stroke volume. The discrepancy in various RV systolic performance indicators results from increased sphericity of the RV following opening the pericardium during surgery. Therefore, longitudinal functional parameters may underestimate RV systolic function for at least 8-10 months post-CABG. Changes in deformation parameters should thus always be interpreted in relation to changes in geometry.

Source at https://doi.org/10.14814/phy2.13879 . Acute ischemic cardiogenic shock is associated with poor prognosis, and the impact of inotropic support on diastolic function in this context is unclear. We assessed two suggested new inotropic strategies in a clinically relevant pig model of ischemic acute heart failure (AHF): treatment with the myosin activator omecamtiv mecarbil (OM) or dobutamine and ivabradine (D+I). Left ventricular (LV) ischemia was induced in anesthetized pigs by coronary microembolization (n = 12). The animals then received OM (bolus 0.75 mg/kg, followed by 0.5 mg/kg per h) (n = 6) or D+I (5 μg/kg per min + 0.29 ± 0.16 mg/kg) (n = 6), respectively. Ischemia reduced the stroke volume (SV), despite the increased left atrial pressure associated with impaired LV early relaxation, systolic dilatation, and LV late diastolic stiffness. Both treatments improved systolic ejection, but only D+I increased the SV from 26 ± 5 to 33 ± 5 mL. D+I enhanced LV early relaxation (Tau; from 45 ± 11 to 29 ± 4 msec) and prolonged the diastolic time (DT) from 338 ± 60 to 352 ± 40 msec. In contrast, OM prolonged Tau (42 ± 5 to 62 ± 10 msec) and shortened the DT (from 326 ± 68 to 248 ± 84 msec). Our data suggest that enhanced early relaxation by D+I improves LV pump function in postischemic acute heart failure. In contrast, OM worsened lusitropy in this model.

Venous return, the right heart function and the pulmonary circulation is an integrated functional unit. The right ventricle is particularly load sensitive, and will be influenced directly by the venous and pulmonary physiology. In this paper we present important physiological principles that govern the diagnosis and treatment of dysfunctions affecting the return of blood to the heart and the transfer of the cardiac output from the right to the left side. We do evaluate both basic science and the clinical literature pointing to practical aspects of physiological knowledge.

Acute aortic dissection (AoD) during pregnancy or postpartum is rare and is related to aortic wall, hormonal and hemodynamic changes in pregnancy. Women with underlying aortopathy are at increased risk. All women with pregnancy-related AoD enrolled in IRAD from 1998 to 2019 were included. Clinical

While a genetic basis for thoracic aortic aneurysm and dissection is well established, little is known about endovascular stent graft therapy (TEVAR) outcomes in patients with family history of aortic disease following Type B acute aortic dissection (TBAD). Patients enrolled in the International

OBJECTIVES: Grafted, non-occluded coronary arteries might contribute substantially to the myocardial blood supply and serve as a basis for vascular collateralization which preserves the myocardium in the event of graft occlusion. Early studies indicated that grafting with saphenous vein, but not internal mammary arteries, accelerates coronary atherosclerosis. This has not been extensively studied for the radial artery, which like the internal mammary artery (IMA) is largely resistant to atherosclerosis. A differential effect of various grafts might facilitate identification of disease-modifying principles. Our surgical cohort represented an opportunity to analyse new native coronary occlusions by comparison with preoperative angiograms. METHODS: One hundred and two patients underwent angiography 1.3–3.9 years after coronary artery bypass surgery, primarily in order to compare the patency of radial artery, IMA and saphenous vein grafts. RESULTS: Out of 290 stenotic, grafted vessels, 67 (23%) occluded during follow-up. Native occlusion occurred in 47% of the patients and correlated with serum-cholesterol. In a per target analysis, independent predictors of postoperative native occlusion were the right coronary artery territory, patent corresponding graft, the corresponding graft being an IMA and end-to-side anastomosis. CONCLUSIONS: Target vessel occlusion is similar with radial artery and saphenous vein grafts and proceeds rapidly even in the current era of secondary prophylaxis against atherosclerosis. Competitive graft flow appears to promote occlusion. Contrary to previous studies, we do not find vein grafts to be inferior to IMA grafts with respect to preservation of native vessel patency.

OBJECTIVES The recommended extent of surgical resection and reconstruction of the arch in acute DeBakey Type I aortic dissection is an ongoing controversy. However, several recent reports indicate a trend towards a more extensive arch operation in several institutions. We have analysed the recent data from the International Registry of Acute Aortic Dissection to assess the choice of procedure over time and to evaluate the surgical outcome in a 'real-world' database. Our aim was to compare short- and mid-term outcomes of limited repairs versus complete arch surgery. METHODS Of the 1241 patients included in the 'Interventional Cohort' of the International Registry of Acute Aortic Dissection from March 1996 to March 2015, 907 underwent ascending aortic or hemiarch replacement (Group A) and 334 had extended arch replacement (Group B). An extended resection was a surgeon's 'judgement call'. Logistic regression analysis, propensity-adjusted multivariable comparisons and Kaplan-Meier curves were used for analyses. RESULTS Overall in-hospital mortality was 14.2% with no difference between groups (Group A 13.1%, Group B 17.1%). Coma/altered consciousness (odds ratio 3.16, 95% confidence interval 1.60-6.25, P = 0.001), hypotension, tamponade or shock (2.03, 1.11-3.73, P = 0.022) and any pulse deficit (1.92, 1.04-3.54, P = 0.038) were predictors of in-hospital mortality in a propensity score-adjusted multivariable analysis. Overall 5-year survival was 69.4% in the ascending group and 73.1% in the total arch group (P = 0.83 by Kaplan-Meier analysis). For survivors of the index hospitalization, the 5-year freedom from death, aortic rupture and reintervention were 71.1% in Group A and 76.4% in Group B (P = 0.54 by Kaplan-Meier analysis). CONCLUSIONS Selective, or 'surgeon's choice', extended arch replacement had no discernible acute downside compared with less extensive surgery. Whether extended arch replacement improves the prognosis beyond 5 years remains to be settled.

Adrenomedullin (AM) is a vasodilatory and chronotropic peptide that has cardioprotective properties in settings of ischemia-reperfusion. Specifically, the 52-amino acid peptide hormone has been shown to reduce infarct size and potentially be protective against malignant arrhythmias. AM reduces L-type calcium currents in rabbit ventricular myocytes, and can possibly be utilized as an antiarrhythmic drug. However, at present it is unclear whether AM has cardiac electrophysiological effects in vivo. In the present study, we investigated whether AM affects sinus and atrioventricular nodal functions, cardiac pacing thresholds, refractory properties and intracardiac conduction intervals in an intact porcine model (Norwegian landrace and Yorkshire hybrids; n=12). Hemodynamic and electrophysiological parameters were recorded at baseline and following 60 min of AM-infusion (100 ng/kg/min). The hemodynamic effects of AM were characterized by a reduced mean arterial pressure (76 ± 9 vs. 57 ± 6; p