Risk Prediction Models for Management of Patients following Acute Aortic Dissection.

Risk prediction of adverse outcomes post aortic dissection is dependet not only on the postdissection-associated clinical factors but on the very foundation of the risk factors that lead up to the dissection itself. There are various such risk factors existing prior to the dissection which impact the postdissection outcomes. In this paper, we review the literature to critically analyze various risk models, burdened by their significant limitations, that attempt to stratify risk prediction based on postdissection patient characteristics. We further review several studies across the literature that investigate the diverse set of predissection risk factors impacting postdissection outcomes. We have discussed and appraised numerous studies which attempt to develop a tool to stratify risk prediction by incorporating the impacts of different factors: malperfusion, blood biochemistry, and perioperative outcomes. The well-validated Penn classification has clearly demonstrated in the literature the significant impact that malperfusion has on adverse outcomes postdissection. Other risk models, already severely hindered by their limitations, lack such validation. We further discuss additional alluded risk factors, including the impact of predissection aortic size, the syndromic and nonsyndromic natures of dissection, and the effects of family history and genetics, which collectively contribute to the risk of adverse outcomes postdissection and prognosis. To achieve the goal of a true risk model, there remains the vital need for appreciation and appropriate consideration for all such aforementioned factors, from before and after the dissection, as discussed in this paper. By being able to incorporate the value of true risk prediction for a patient into the decision-making framework, it will allow a new page of precision medical decision-making to be written.

The Association of ANRIL With Coronary Artery Disease And Aortic Aneurysms, How Far Does The Gene Desert Go?

BACKGROUND: Coronary artery disease (CAD) and aortic aneurysms (AA) are 2 cardiovascular diseases that share a multifactorial aetiology. The influence of family history and genetics on the 2 diseases separately and in association is well known, but poorly elucidated. This comprehensive review aims to examine the current literature on the gene ANRIL (antisense non-coding RNA in the INK4 locus) and its associations with CAD and AA. METHODS: A database search on OVID, PubMed and Cochrane to identify articles concerning single nucleotide polymorphisms (SNPs) associated with ANRIL and their respective incidences of, and impact on, CAD and AA across populations. RESULTS: Cohort studies across various ethnicities reveal that various ANRIL SNPs are significantly associated separately with CAD (rs1333040, rs1333049 and rs2383207) and AA (rs564398, rs10757278 and rs1333049), and that these SNPs are present in significant proportions of the population. SNP rs1333049 is significantly associated with both diseases, but is positively correlated with AAA and negatively correlated with CAD. This review further outlines several pathophysiological links via endothelial and adventitial cells, vascular smooth muscle cells and sense gene interaction, which may explain these genetic associations identified. CONCLUSION: Given the associations uncovered between ANRIL polymorphisms and CAD and AA, as well as the molecular mechanisms which may explain the underlying pathophysiology, ANRIL appears to be strongly linked with both diseases. ANRIL may hence have a future application in screening normal patients and risk stratifying patients with both diseases. Its role in linking the 2 diseases is yet unclear, warranting further studies.

Exploring the Correlation and Protective Role of Diabetes Mellitus in Aortic Aneurysm Disease.

Introduction: Diabetes mellitus is recognised as a significant risk factor for cardiovascular and peripheral vascular disease, as the abnormal metabolic state increases the risk for atherosclerosis, occlusive arterial disease and vascular dysfunction. There have been reports of potential association across the literature that illustrates a link between diabetes mellitus and aortic aneurysm, with the former having a protective role on the development of the latter. Methods: A thorough literature search was performed through electronic databases, to provide a comprehensive review of the study's reporting on the association of diabetes mellitus and aortic aneurysm, discussing the mechanisms that have been reported; furthemore, we reviewed the reports of the impact of oral hypoglycameic agents on aortic aneurysms. Results: Various proposed mechanisms are involved in this protective process including endothelial dysfunction, chronic hyperglycemia and insulin resistance. The evidence suggests a negative association between these disease process, with prevelance of diabetes mellitus resulting in lower rates of aortic aneurysm, via its protective mechanistic action. The increase in advanced glycation end products, increased arterial stiffness and vascular remodelling seen in diabetes, was found to have a profound impact on aneurysm development, its slow progression and lower rupture rate in these individuals. This review has also highlighted the role of oral hypoglycaemic agents having a protective effect against AA disease. Conclusion: A decrease in development, progression and mortality from aortic aneurysms as well as reduced rates of dissection, have been observed in those with diabetes. This review has provided a comprehensive insight on the effect of diabetes and its physiological processes, and elements of its con-committant treatment, having a protective role against these aortic diseases.

The retroperitoneal approach for contemporary open abdominal aortic aneurysm surgery: The anatomical reasoning.

In current practice, the place of open surgery in managing abdominal aortic aneurysm is a contentious issue. The principal reason being greater applications of endovascular techniques treating increasingly complicated aortic disease. Development of branched and fenestrated devices enabled this, with numbers increasing annually. This meant a good risk patient with a long infrarenal aortic neck and normal diameter non-tortuous iliac arteries may be suitable for both endovascular and open techniques. However, indications for open surgery are becoming increasingly unclear nowadays due to short-term gains in morbidity and mortality. Exact aortic anatomical morphologies optimum for open or endovascular techniques remains unclear. As graft technology evolves, possibilities for endovascular options are expanding. Currently, establishing optimum treatment plans for complicated abdominal aortic aneurysm (little or no infrarenal neck) is difficult without considering general fitness of the patient. Hence, two sets of possible postoperative complications and follow-up protocols must be explained to patients before either approach. Complicating matters is the optimum surgical approach used for any open repair. The standard approach for open abdominal aortic aneurysm surgery has been transperitoneal as this provides excellent access to the infrarenal aorta and iliac arteries. However, although less commonly used, the retroperitoneal approach has advantages particularly when location of proximal aortic disease indicates suprarenal clamp might be optimum. This paper scrutinises benefits of the retroperitoneal approach performed purely for anatomical reasons where stent graft may be considered complicated. Also, long-term outcomes are examined in terms of endo-leak and subsequent development of true and false aneurysm following both endovascular and open repair.

Management of the penetrating atherosclerotic ulcer in the descending thoracic aorta.

Penetrating atherosclerotic ulcers present with an insidious onset with a reported mortality of 9%, varying across populations. With vast arrays of risk factors and potentially ominous complications, it is vital to efficiently provide optimum strategies for management. There exists controversy in the literature regarding management, especially for Type B penetrating atherosclerotic ulcers; the decision-making framework encompasses numerous factors in considerations for medical management versus invasive intervention and choice of endovascular versus open repair in the latter. The concomitant presence of intramural haematoma adds further complexity to the already intricate decision-making for management. We performed searches through PubMed and SCOPUS analysing studies reporting outcomes for management strategies for penetrating atherosclerotic ulcers treatment, focusing on Type B, further seeking to analyse studies reporting their experiences of PAU patients with concomitant intramural haematoma. Our review highlights the ambiguity and controversy existing in the literature, comprising studies burdened by their inherent hindering limitations of their single-centre retrospective experiences. Endovascular therapy has come to the forefront of penetrating atherosclerotic ulcers management, often considered first line therapy. In the case of penetrating atherosclerotic ulcers alongside intramural haematoma, there have been reports of potential hybrid surgical approaches to management. Studies further show misdiagnosis of penetrating atherosclerotic ulcers in earlier data sets further complicates management. However, it is clear we must progress on the journey towards precision medicine, allowing delivery of optimum care to our patients.

TEVAR for complicated and uncomplicated type B aortic dissection-Systematic review and meta-analysis.

BACKGROUND: Type B aortic dissection (TBAD), is defined as a dissection involving the aorta distal to left subclavian artery with the ascending aorta and the aortic arch not affected. TBAD is classified due to the time frame and presence of complications. Complicated TBAD (co-TBAD) patients have a greater mortality rate than uncomplicated TBAD (un-TBAD) and thoracic endovascular aortic repair (TEVAR) is considered the gold-standard intervention for these clinical challenges. METHODS: We undertook a systematic review of the literature regarding TEVAR intervention in co-TBAD and un-TBAD. A comprehensive search was undertaken across four major databases and was evaluated and assessed until June 2020. RESULTS: A total of 16,104 patients were included in the study (7772 patients co-TBAD and 8352 un-TBAD). A significantly higher proportion of comorbidities were seen in co-TBAD patients compared with un-TBAD. Acute dissection was more frequent in the co-TBAD group (73.55% vs. 66.91%), while chronic dissection was more common in un-TBAD patients (33.8% vs. 70.73%). Postprocedure stroke was higher in co-TBAD (5.85% vs. 3.92%; p < .01), while postprocedural renal failure was higher in un-TBAD patients (7.23 vs. 11.38%; p < .01). No difference was observed in in-hospital mortality however the 30 days mortality was higher in the co-TBAD group. One-year survival was higher in the uncomplicated group but this difference was not observed in the 5-year survival. CONCLUSION: In our analysis we can appreciate that despite significantly higher comorbidities in the co-TBAD cohort, there was no difference in in-hospital mortality between the two groups and the 5-year survival did not have any difference.

Aortic proximalization-Zone 0 versus Zone 2: A concept or true challenge?

BACKGROUND: The use of the Frozen Elephant Trunk (FET) device to manage complex surgical pathologies of the aorta (such as acute type A aortic dissection) has gained popularity since its introduction in the early 2000s. Though the distal anastomosis was traditionally performed at aortic Zone 3 (Z-3-FET), preference gradually shifted towards Zone 2 (Z-2-FET) in favor of improved surgical access and clinical outcomes. This review seeks to elucidate whether proximalization of arch repair to Zone 0 (Z-0-FET) would further improve postoperative outcomes. METHODS: We performed a review of available literature to evaluate the comparative efficacies of Z-2-FET versus Z-0-FET, in terms of surgical technique, clinical outcomes, and incidence of adverse events. RESULTS: Z-0-FET seems to be associated with a more accessible surgical approach, and shorter cardiopulmonary bypass, antegrade cerebral perfusion, and cardioplegia durations than Z-2-FET. Further, Z-0-FET is could potentially be associated with a lower incidence of neurological, renal, and recurrent laryngeal nerve injury, as well as mortality and reintervention rates than Z-2-FET. This said, Z-0-FET is itself associated with significant challenges, and efficacy in terms of postoperative true lumen integrity and false lumen thrombosis is mixed. CONCLUSION: Current literature seems to suggest that Z-0-FET procedures are more straightforward and associated with lower rates of certain adverse events, however, the majority of data reviewed is retrospective. This review, therefore, recommends prospective research into the comparative strengths and limitations of Z-0-FET and Z-2-FET to better substantiate whether proximalization of arch repair represents a concept, or a true challenge to advance surgical intervention for arch pathologies.

Short- and long-term outcomes of aortic root-sparing repair and replacement in acute type A aortic dissection repair.

Acute type A aortic dissection is a surgical emergency with a high mortality rate if left untreated. Management of the aortic root in this setting constitutes an intricate decision-making framework, further complicated by the emergent nature of the dissection. There exists much controversy regarding pursuit of the aggressive aortic root replacement versus a conservative root-sparing repair, alongside considerations for valve-sparing root replacement. In this review, we critically appraise the current controversy in the literature considering the fate of the aortic root, discussing the aforementioned root interventions for which provides better outcomes for mortality and risk of re-intervention. Literature search was performed using electronic database through PubMed, Google scholar, and Embase focussing on studies reporting outcomes and re-intervention rates for these approaches. Limited by the heterogeneity in surgical strategy, with most studies being single-centred retrospective experiences, further fuel this ongoing debate. The literature reveals rather contrasting results whilst comparing root-sparing repair, versus the extensive root replacement; whilst some studies report no statistically significant difference, others show one superior over the other. There is greater consensus when considering risk of re-operation, with studies showing higher rates of re-operation in root-sparing group compared to replacement; however, many others show no statistically significant difference. In conclusion, the conflicting outcomes reported in the literature, with their inherent limitations, results in the current inability to reach a definitive answer. There remains support in the current literature for both approaches with much of the decision-making being surgeon-bound with many significant influencing factors on a case-by-case basis.

Aortic aneurysm disease-Make room for chronobiology.

BACKGROUND: Aortic aneurysm (AA) is a common atherosclerotic condition, accounting for nearly 6000 deaths in England and up to 175,000 deaths globally each year. The pathological outward bulging of the aorta typically results from atherosclerosis or hereditary connective tissue disorders. AAs are usually asymptomatic until spontaneous rupture or detected on incidental screening. Eight in 10 patients do not survive the rupture and die either before reaching hospital or from complications following surgery. Similar to other cardiovascular pathologies, AA is thought to be subject to chronobiological patterns of varying incidence. METHODS: We performed a literature review of the current literature to evaluate the association between circadian rhythms, seasonal variations, and genetic factors and the pathogenesis of AA, reviewing the impact of chronobiology. RESULTS: The incidence of AA is found to peak in the early morning (6-11 a.m.) and colder months, and conversely troughs towards the evening and warmer months, exhibiting a similar pattern of chronobiological rhythm as other cerebrovascular pathologies, such as myocardial infarcts, or cerebrovascular strokes. CONCLUSION: Literature suggests there exists a clear relationship between chronobiology and the incidence and pathogenesis of ruptured AA; incidence increases in the morning (6-11 a.m.), and during colder months (December-January). This is more pronounced in patients with Marfan syndrome, or vitamin D deficiency. The underlying pathophysiology and implications this has for chronotherapeutics, are also discussed. Our review shows a clear need for further research into the chronotherapeutic approach to preventing ruptured AA in the journey towards precision medicine.

Thoracic and abdominal aortic aneurysms: exploring their contrast and genetic associations.

Until recently thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) were correlated with atherosclerosis but following a range of cohort studies, a linkage proved unlikely. Instead, data from the Genome wide association study detected two common significantly correlated lncRNA loci: miRNA and the antisense non-coding RNA in the INK4 locus (ANRIL). lncRNAs are sometimes utilized by the body as transcription regulators and signaling molecules. This is crucial in cell transformation and embryology, including that of the mammalian heart. ANRIL, a 19 exon RNA sequence found in the chromosome 9p21 region, will be one of the main focuses of this paper. TAA and AAA have many differences due to their vessel walls but similarities in their gross anatomic structure prove a genetic correlated disease likely. ANRIL has a convincing potential to be used as an additive therapeutic tool in TAA and AAA. This is because Chr9p21 is independent of typical risk factors. However, it remains that further research and clinical studies are required before clinical translation. It is best to consider TAA and AAA separately as the underlying pathophysiology has some distinct differences. They are both commonly diagnosed late, and the hope is that genetic mutations (ANRIL) can act as a biomarker for a faster diagnosis, management and possible treatment alternative.

Type A aortic dissection: involvement of carotid artery and impact on cerebral malperfusion.

Acute type A aortic dissection is a surgical emergency and management of such pathology can be complex with poor outcomes when there is organ malperfusion. Carotid artery involvement is present in 30% of patients diagnosed with acute type A aortic dissection, and given its emergency and complex nature, there is much controversy regarding the approach, extent of treatment, and timing of the intervention. It is clear that the occurrence of cerebral malperfusion adds an extra layer of complexity to the decision-making framework for treatment. Standardization and validation of the optimal management approach is required, and this should ideally be addressed with large-scale studies. Nonetheless, current literature supports the need for rapid recognition and diagnosis of acute type A aortic dissection with cerebral malperfusion, immediate and extensive surgical repair, and the appropriate use of cerebral perfusion techniques. This paper aims to discuss the current evidence regarding the impact of carotid artery involvement in both the management and outcomes of acute type A aortic dissection.

Update on graft infections in thoracoabdominal aortic aneurysm surgery.

The incidence of an aortic graft infection following the repair of thoracoabdominal aortic aneurysm, is a rare yet insidious complication which requires prompt recognition and management. The decision-making framework for management encompasses the choice or antimicrobial therapy alone versus pursuing surgical intervention, which can then also lead to considering the potential for allografts. The current literature on the matter is heavily burdened by limitations of the reported retrospective experiences consisting of small patient cohorts. Studies have reported the favored approach of surgical intervention, although statistical significance is not reached. There is a clear recognized impact that the event surrounding the initial repair has on the occurrence of graft infection itself; with emergency repairs, and incidence of nosocomial infection being associated with higher rates of graft infection. We must consider the influencers of this ominous complications, which go back to the perioperative events itself, whether the initial intervention was elective or an emergency, the impact of nosocomial infections, the choice of open versus endovascular for initial repair. Only with the appropriate management strategy that encompasses all these factors, will allow the best treatment to be provided for patients. A sound understanding and appreciation for the aforementioned can allow the stratification of the risk associated with the occurrence of an aortic graft infection, leading to surveillance opportunities to provide the crucial ability to rapidly recognize this complication.

Does adding a root replacement in type A aortic dissection repair provide better outcomes?

BACKGROUND: Acute type A aortic dissection (ATAAD), is a surgical emergency often requiring intervention on the aortic root. There is much controversy regarding root management; aggressively pursuing a root replacement, versus more conservative approaches to preserve native structures. METHODS: Electronic database search we performed through PubMed, Embase, SCOPUS, google scholar, and Cochrane identifying studies that reported on outcomes of surgical repair of ATAAD through either root preservation or replacement. The identified articles focused on short- and long-term mortalities, and rates of reoperation on the aortic root. RESULTS: There remains controversy on replacing or preserving aortic root in ATAAD. Current evidence supports practice of both trends following an extensive decision-making framework, with conflicting series suggesting favorable results with both procedures as the approach that best defines higher survival rates and lower perioperative complications. Yet, the decision to perform either approach remains surgeon decision and bound to the extent of the dissection and tear entries in strong correlation with status of the aortic valve and involvement of coronaries in the dissection. CONCLUSIONS: There exists much controversy regarding fate of the aortic root in ATAAD. There are conflicting studies for impact of root replacement on mortality, whilst some study's report no significant results at all. There is strong evidence regarding risk of reoperation being greater when root is not replaced. Majority of these studies are limited by the single centered, retrospective nature of these small sample sized cohorts, further hindered by potential of treatment bias.