Amit Korach

IRAD experience on surgical type A acute dissection patients: Results and predictors of mortality

Type A acute aortic dissection (TAAD) is a disease that has a catastrophic impact on a patients 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.

Changes in operative strategy for patients enrolled in the International Registry of Acute Aortic Dissection interventional cohort program

Objective: Advancements in cardiothoracic surgery prompted investigation into changes in operative management for acute type A aortic dissections over time. Methods: One thousand seven hundred thirty‐two patients undergoing surgery for type A aortic dissection were identified from the International Registry of Acute Aortic Dissection Interventional Cohort Database. Patients were divided into time tertiles (T) (T1: 1996–2003, T2: 2004–2010, and T3: 2011–2016). Results: Frequency of valve sparing procures increased (T1: 3.9%, T2: 18.6%, and T3: 26.7%; trend P < .001). Biologic valves were increasingly utilized (T1: 35.6%, T2; 40.6%, and T3: 52.0%; trend P = .009), whereas mechanical valve use decreased (T1: 57.6%, T2: 58.0%, and T3: 45.4%; trend P = .027) for aortic valve replacement. Adjunctive cerebral perfusion use increased (T1: 67.1%, T2: 89.5%, and T3: 84.8%; trend P < .001), with increase in antegrade cerebral techniques (T1: 55.9%, T2: 58.8%, and T3: 66.1%; trend P = .005) and hypothermic circulatory arrest (T1: 80.1%, T2: 85.9%, and T3: 86.8%; trend P = .030). Arterial perfusion through axillary cannulation increased (T1: 18.0%, T2: 33.2%, and T3: 55.7%), whereas perfusion via a femoral approach diminished (T1: 76.0%, T2: 53.3%, and T3: 30.1%) (both P values < .001). Hemiarch replacement was utilized more frequently (T1: 27.0%, T2: 63.3%, and T3: 51.7%; trend P = .001) and partial arch was utilized less frequently (T1: 20.7%, T2: 12.0%, and T3: 8.4%; trend P < .001), whereas complete arch replacement was used similarly (P = .131). In‐hospital mortality significantly decreased (T1: 17.5%, T2: 15.8%, and T3: 12.2%; trend P = .017). Conclusions: There have been significant changes in operative strategy over time in the management of type A aortic dissection, with more frequent use of valve‐sparing procedures, bioprosthetic aortic valve substitutes, antegrade cerebral perfusion strategies, and hypothermic circulatory arrest. Most importantly, a significant decrease of in‐hospital mortality was observed during the 20‐year timespan.

Successful restoration of function of frozen and thawed isolated rat hearts

OBJECTIVE Long-term organ preservation for transplantation may allow optimal donor-recipient matching with potential reduction in the incidence and severity of rejection. Complete cessation of metabolism may be obtained by freezing. Previous attempts to freeze intact mammalian hearts were limited to -3.6 degrees C, restricting tissue ice content to 34%. We hypothesized that our method will allow recovery of function of the intact rat heart after freezing to -8 degrees C, a temperature at which most of the tissue water is frozen. METHODS Isolated rat hearts were attached to a Langendorff apparatus. After normothermic perfusion, cold cardioplegia was induced followed by perfusion with a cryoprotecting agent. Hearts were than frozen to -8 degrees C (45 +/- 8 minutes), thawed, and reperfused (60 minutes). RESULTS All frozen and thawed hearts regained normal electric activity. At -8 degrees C, ice content was 64.36% +/- 13%. The use of 10% ethylene glycol for cryoprotection (n = 13) resulted in recovery (mean +/- standard deviation) of 49.7% +/- 21.8% of +dP/dt, 48.0% +/- 23.5% of -dP/dt, 65.2% +/- 30.8% of coronary flow, and 50.4% +/- 23.9% of left ventricular developed pressure. Hearts in this group (n = 4) maintained 81.3% +/- 10% viability compared with 69.3% +/- 14% (not significant) in control hearts kept at 0 degrees C for the same duration. Energy stores, represented by adenosine triphosphate and phosphocreatine, were depleted to 12.2 +/- 6.1 micromol/g dry weight and 22.5 +/- 6.4 micromol/g dry weight, respectively, compared with 19.0 +/- 2.5 micromol/g dry weight and 36.6 +/- 3.0 micromol/g dry weight, respectively (P < .05) in the control hearts. The integrity of muscle fibers and intracellular organelles after thawing and reperfusion was demonstrated by electron microscopy. CONCLUSION We demonstrate for the first time the feasibility of functional recovery after freezing and thawing of the isolated rat heart while maintaining structural integrity and viability.

Chronicle of a death foretold: a case of catastrophic vascular Behcet's disease

A 20-year-old man with Behcets disease characterized by recurrent arterial aneurysms presented with a new aortic root aneurysm. This patient previously had aneurysms of the coronary arteries and vein, as well as ruptured renal artery aneurysm. Chronic maintenance immunosuppressive therapy was recommended due to the catastrophic nature of the disease, which the patient refused to take. The patient died shortly after admission. This case demonstrates the unique catastrophic natural history of vascular Behcets disease with recurrent life-threatening arterial events, and this case stresses the therapeutic dilemma of maintenance immunosuppressive therapy in selected patients.

Non-invasive detection of human cardiomyocyte death using methylation patterns of circulating DNA

Detection of cardiomyocyte death is crucial for the diagnosis and treatment of heart disease. Here we use comparative methylome analysis to identify genomic loci that are unmethylated specifically in cardiomyocytes, and develop these as biomarkers to quantify cardiomyocyte DNA in circulating cell-free DNA (cfDNA) derived from dying cells. Plasma of healthy individuals contains essentially no cardiomyocyte cfDNA, consistent with minimal cardiac turnover. Patients with acute ST-elevation myocardial infarction show a robust cardiac cfDNA signal that correlates with levels of troponin and creatine phosphokinase (CPK), including the expected elevation-decay dynamics following coronary angioplasty. Patients with sepsis have high cardiac cfDNA concentrations that strongly predict mortality, suggesting a major role of cardiomyocyte death in mortality from sepsis. A cfDNA biomarker for cardiomyocyte death may find utility in diagnosis and monitoring of cardiac pathologies and in the study of normal human cardiac physiology and development.The detection of cardiomyocyte death is a critical aspect in the diagnosis and monitoring of heart diseases. Here the authors show that cardiomyocyte-specific methylation patterns of circulating cell-free DNA may serve as a biomarker of cardiac cell death in infarcted and septic patients.

Aortic dissection in patients with Marfan syndrome based on the IRAD data

Between January 1996 and May 2017, the International Registry on Acute Aortic Dissections has collected information on a total of 6,424 consecutive patients with acute aortic dissection, including 258 individuals with a diagnosis of Marfan syndrome. Patients with Marfan syndrome presented at a significantly younger age compared to patients without Marfan syndrome (38.2±13.2 vs. 63.0±14.0 years; P<0.001) and in general had fewer comorbidities, although they more frequently had a known aortic aneurysm and history of prior cardiac surgery. We noted significantly larger diameters of the aortic annulus and root in the Marfan syndrome cohort, but no larger diameters more distally. The in-hospital mortality in type A dissection was not significantly different in patients with or without Marfan syndrome, despite the differences in age and comorbidities and the lower incidence of aortic rupture in the Marfan syndrome cohort. In contrast, the in-hospital mortality of Marfan syndrome patients with type B dissection appears to be lower than that of patients without Marfan syndrome. The Marfan syndrome cohort that was treated with open surgery for type B dissection seemed to do especially well, with a 0% mortality rate (n=27). Follow-up data for type A and B dissections combined show an estimated five-year survival rate of 80.1% and an estimated reintervention rate of 55.3% in patients with Marfan syndrome. Such a high rate of reinterventions highlights the need for careful surveillance and treatment for patients with Marfan syndrome surviving the acute phase of aortic dissection.

Comprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease

Methylation patterns of circulating cell-free DNA (cfDNA) contain rich information about recent cell death events in the body. Here, we present an approach for unbiased determination of the tissue origins of cfDNA, using a reference methylation atlas of 25 human tissues and cell types. The method is validated using in silico simulations as well as in vitro mixes of DNA from different tissue sources at known proportions. We show that plasma cfDNA of healthy donors originates from white blood cells (55%), erythrocyte progenitors (30%), vascular endothelial cells (10%) and hepatocytes (1%). Deconvolution of cfDNA from patients reveals tissue contributions that agree with clinical findings in sepsis, islet transplantation, cancer of the colon, lung, breast and prostate, and cancer of unknown primary. We propose a procedure which can be easily adapted to study the cellular contributors to cfDNA in many settings, opening a broad window into healthy and pathologic human tissue dynamics.

Ischemic Mitral Regurgitation: The Value of Flexibility in the Quest for a Perfect Repair

The Fattouch paper in this issue adds valuable data to suggest that semirigid rings may be better in repairing ischemic MR. The Road goes ever on and on, Down from the door where it began. Now far ahead the Road has gone, And I must follow, if I can, Pursuing it with eager feet, Until it joins some larger way Where many paths and errands meet. And whither then? I cannot say! —JRR Tolkien. The Lord of the Rings.

Acute Type B Aortic Pathology Mimicking Acute Type A Intramural Hematoma with Organ Malperfusion.

The management of acute Stanford Type A intramural hematoma (IMH) of the aorta remains controversial. Most surgeons advocate emergency surgery in a manner similar to frank acute Type A dissection. Others recommend a conservative approach to this distinct clinicopathological entity. We describe a case of acute aortic pathology initially diagnosed as Type A IMH with organ malperfusion, subsequently identified as acute Type B pathology with retrograde and antegrade extension. An endovascular approach was successfully used to exclude the site of origin.