Research

Zentner D, James P, Bannon P, Jeremy R

Heart Lung Circ 2020 Apr;29(4):607-618

PMID: 32067919

Abstract

Aortopathies are conditions that result in aortic dilatation, aneurysm formation and dissection. Familial aortopathies (perhaps better known as heritable thoracic aortic aneurysm and dissection, h-TAAD, as not all have a positive family history) are recognised to have an underlying genetic cause and affect the aorta, predisposing it to the above pathologies. These conditions can also affect the extra-aortic vasculature, particularly large elastic arteries and other body systems. Mutations in a number of genes have been associated with h-TAAD. However, not all affected families have a pathogenic gene variant identified-highlighting the importance of a three-generational family history and the likely role of both environmental factors and future gene discoveries in furthering knowledge. Survival has improved over the last few decades, essentially due to surgical intervention. The benefit of identifying affected individuals depends upon a regular surveillance program and timely referral for surgery before complications such as dissection. Further research is required to appreciate fully the effects of individual gene variants and improve evidence for prophylactic medical therapy, as well as to understand the effect of h-TAAD on quality of life and life choices, particularly around exercise and pregnancy, for affected individuals. This will be complemented by laboratory-based research that seeks to understand the tissue pathways that underlie development of arterial pathology, ideally providing targets for novel medical therapies and a means of non-invasively identifying individuals at increased vascular risk to reduce dissection, which remains a devastating life-threatening event.

Myles PS, Smith JA, Kasza J, Silbert B, Jayarajah M, Painter T, Cooper DJ, Marasco S, McNeil J, Bussières JS, McGuinness S, Byrne K, Chan MTV, Landoni G, Wallace S, Forbes A,

J. Thorac. Cardiovasc. Surg. 2019 02;157(2):644-652.e9

PMID: 30459103

Abstract

BACKGROUND: Tranexamic acid reduces blood loss and transfusion requirements in cardiac surgery but may increase the risk of coronary graft thrombosis. We previously reported the 30-day results of a trial evaluating tranexamic acid for coronary artery surgery. Here we report the 1-year clinical outcomes.

METHODS: Using a factorial design, we randomly assigned patients undergoing coronary artery surgery to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary 1-year outcome was death or severe disability, the latter defined as living with a modified Katz activities of daily living score of less than 8. Secondary outcomes included a composite of myocardial infarction, stroke, and death from any cause through to 1 year after surgery.

RESULTS: The rate of death or disability at 1 year was 3.8% in the tranexamic acid group and 4.4% in the placebo group (relative risk, 0.85; 95% confidence interval, 0.64-1.13; P = .27), and this did not significantly differ according to aspirin exposure at the time of surgery (interaction P = .073). The composite rate of myocardial infarction, stroke, and death up to 1 year after surgery was 14.3% in the tranexamic acid group and 16.4% in the placebo group (relative risk, 0.87; 95% CI, 0.76-1.00; P = .053).

CONCLUSIONS: In this trial of patients having coronary artery surgery, tranexamic acid did not affect death or severe disability through to 1 year after surgery. Further work should be done to explore possible beneficial effects on late cardiovascular events.

Callaghan FM, Bannon P, Barin E, Celemajer D, Jeremy R, Figtree G, Grieve SM

J Magn Reson Imaging 2019 01;49(1):90-100

PMID: 30102443

Abstract

BACKGROUND: Abnormal flow dynamics play an early and causative role in pathologic changes of the ascending aorta.

PURPOSE: To identify: 1) the changes in flow, shape, and size that occur in the ascending aorta with normal human ageing and 2) the influence of these factors on aortic flow dynamics.

STUDY TYPE: Retrospective.

SUBJECTS: In all, 247 subjects (age range 19-86 years, mean 49 ± 17.7, 169 males) free of aortic or aortic valve pathology were included in this study. Subjects were stratified by youngest (18-33 years; n = 64), highest (>60 years, n = 67), and the middle two quartiles (34-60 years, n = 116).

FIELD STRENGTH/SEQUENCE: Subjects underwent a cardiac MRI (3T) exam including 4D-flow MRI of the aorta.

ASSESSMENT: Aortic curvature, arch shape, ascending aortic angle, ascending aortic diameter, and the stroke volume normalized by the aortic volume (nSV) were measured. Velocity, vorticity, and helicity were quantified across the thoracic aorta.

STATISTICAL TESTS: Univariate and multivariate regressions were used to quantify continuous relationships between variables.

RESULTS: Aortic diameter, ascending aortic angle, shape, and curvature all increased across age while nSV decreased (all P < 0.0001). Systolic vorticity in the mid arch decreased by 50% across the age range (P < 0.0001), while peak helicity decreased by 80% (P < 0.0001). Curvature tightly governs optimal flow in the youngest quartile, with an effect size 1.5 to 4 times larger than other parameters in the descending aorta, but had a minimal influence with advancing age. In the upper quartile of age, flow dynamics were almost completely determined by nSV, exerting an effect size on velocity and vorticity >10 times that of diameter and other shape factors.

DATA CONCLUSION: Aortic shape influences flow dynamics in younger subjects. Flow conditions become increasingly disturbed with advancing age, and in these conditions nSV has a more dominant effect on flow patterns than shape factors.

LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:90-100.

Kay S, Moore BM, Moore L, Seco M, Barnes C, Marshman D, Grieve SM, Celermajer DS

Heart Lung Circ 2020 Feb;29(2):196-201

PMID: 31494040

Abstract

BACKGROUND: Prompted by a cluster of observations concerning ascending aortic pathology in elite rugby players, we assessed over 150 asymptomatic predominantly retired players with echocardiography, aiming to document the prevalence and severity of ascending aortic dilatation and/or anterior aortic effacement, both ‘risk factors’ for potentially catastrophic aortic complications.

METHODS: Rugby players (at least 5 years of high level competitive rugby) were classified as elite (national, state or first grade representatives) or non-elite. A total of 152 asymptomatic players with a mean age of 45 ± 13 years (range 21-65) underwent transthoracic echocardiography. Z-scores (number of standard deviations from a population mean) were calculated for aortic root and ascending aortic size.

RESULTS: Regarding the aortic root, a Z-score of >2 was seen in 24% (expected prevalence 2.3%, p < 0.001) and a Z-score >3 was seen in 4% (expected prevalence 0..1%, p < 0.001). Sixty-two (62) players (41%) had an aortic root greater than 40 mm diameter. Ascending aortic Z-scores were >2 in 53% of players and >3 in 22% (p < 0.001). Abnormal anterior aortic effacement at the sinotubular junction (STJ) was seen in 88 players (58%). Abnormal aortic dilatation and effacement were associated with a longer duration of competitive rugby participation and elite status, respectively.

CONCLUSIONS: Ascending aortic dilatation with abnormal anterior effacement is exceedingly common in asymptomatic retired elite rugby players. This warrants increased surveillance in retired players until the clinical significance of these findings can be further investigated.

Carelli M, Seco M, Forrest P, Wilson MK, Vallely MP, Ramponi F

Perfusion 2019 11;34(8):717-720

PMID: 31046596

Abstract

In recent years, extracorporeal membrane oxygenation has become increasingly common in the treatment of in-hospital cardiac arrest in non-cardiac surgery patients. This includes cardiac arrest secondary to perioperative anaphylactic shock refractory to standard advanced life support protocols, which is a rare but catastrophic event associated with significant mortality. Neuromuscular blocking drugs are most commonly implicated in perioperative anaphylaxis, with rocuronium playing a major role. In this article, we report two cases of young and otherwise fit and well patients who experienced a perioperative arrest secondary to rocuronium anaphylaxis before elective surgery; both patients did not respond to conventional advanced life support, but survived neurologically intact after institution of urgent veno-arterial extracorporeal membrane oxygenation.

Chakos A, Ferret P, Muston B, Yan TD, Tian DH

Ann Cardiothorac Surg 2020 Jan;9(1):1-9

PMID: 32175234

Abstract

Background: While extended criteria lung donation has helped expand the lung donor pool, utilization of lungs from donors of at least one other solid organ is still limited to around 15-30%. Ex-vivo lung perfusion (EVLP) offers the ability to expand the number of useable lung grafts through assessment and reconditioning of explanted lungs, particularly those not initially meeting criteria for transplantation. This meta-analysis aimed to examine the mid- to long-term survival and other short-term outcomes of patients transplanted with EVLP-treated lungs versus standard/cold-storage protocol lungs.

Methods: Literature search of ten medical databases was conducted for original studies involving “ex-vivo lung perfusion” and “EVLP”. Included articles were assessed by two independent researchers, survival data from Kaplan-Meier curves digitized, and individual patient data imputed to conduct aggregated survival analysis. Meta-analyses of suitably reported outcomes were conducted using a random-effects model.

Results: Thirteen studies met inclusion criteria, with a total of 407 EVLP lung transplants and 1,765 as per standard/cold storage protocol. One study was a randomized controlled trial while the remainder were single-institution cohort series of varying design. The majority of donor lungs were from brain death donors, with EVLP lungs having significantly worse PaO/FiO ratio and significantly greater rate of abnormal chest X-ray. Aggregated survival analysis of all included studies revealed no significant survival difference for EVLP or standard protocol lungs (hazard ratio 1.00; 95% confidence interval: 0.79-1.27, P=0.981). Survival at 12, 24, and 36 months for the EVLP cohort was 84%, 79%, and 74%, respectively. Survival at 12, 24, and 36 months for the standard protocol cohort was 85%, 79%, and 73%, respectively. Meta-analysis did not find a significant difference in risk of 30-day mortality or primary graft dysfunction grade 3 at 72 hours between cohorts.

Conclusions: There was no significant difference in mid- to long-term survival of EVLP lung transplant patients when compared to standard protocol donor lungs. The incidence of 30-day mortality and primary graft dysfunction grade 3 at 72 hours did not differ significantly between groups. EVLP offers the potential to increase lung donor utilization while providing similar short-term outcomes and mid- to long-term survival.

Wilson-Smith AR, Kim YS, Evans GE, Yan TD

Ann Cardiothorac Surg 2020 Jan;9(1):10-19

PMID: 32175235

Abstract

Background: Lung transplantation has long been the accepted therapy for end-stage pulmonary fibrotic disease. Presently, there is an ongoing debate over whether single or bilateral transplantation is the most appropriate treatment for end-stage disease, with a paucity of high-quality evidence comparing the two approaches head-to-head.

Methods: This review was performed in accordance with PRISMA recommendations and guidance. Searches were performed on PubMed Central, Scopus and Medline from dates of database inception to September 2019. For the assessed papers, data was extracted from the reviewed text, tables and figures, by two independent authors. Estimated survival was analyzed using the Kaplan-Meier method for studies where time-to-event data was provided.

Results: Overall, 4,212 unique records were identified from the literature search. Following initial screening and the addition of reference list findings, 83 full-text articles were assessed for eligibility, of which 17 were included in the final analysis, with a total of 5,601 patients. Kaplan-Meier survival analysis illustrated improved survival in patients receiving bilateral lung transplantation (BLTx) than in those receiving unilateral transplantation for idiopathic pulmonary fibrosis at all time intervals, with aggregated survival for BLTx at 57%, 35.3% and 24% at 5-, 10- and 15-year follow-up, respectively. Survival rates for SLTx were 50%, 27.8% and 13.9%, respectively.

Conclusions: Whilst a number of studies present conflicting results with respect to short-term transplantation outcomes, BLTx confers improved long-term survival over SLTx, with large-scale registries supporting findings from single- and multi-center studies. Through an aggregation of published survival data, this meta-analysis identified improved survival in patients receiving BLTx versus SLTx at all time intervals.

Tian DH, Wilson-Smith A, Koo SK, Forrest P, Kiat H, Yan TD

Heart Lung Circ 2019 Jun;28(6):844-849

PMID: 30773323

Abstract

BACKGROUND: Antegrade cerebral perfusion (ACP) is an essential adjunct for prolonged hypothermic circulatory arrest (HCA) during aortic arch surgery. However, it has yet to be established whether ACP should be delivered unilaterally or bilaterally. The aim of the present meta-analysis is to investigate outcomes of unilateral ACP (uACP) compared to bilateral ACP (bACP) in comparative studies.

METHODS: Electronic searches were performed using four databases from their inception to February 2017. Relevant comparative studies with adult patients who underwent aortic arch surgery using unilateral or bilateral ACP were included. Data was extracted by two independent researchers and analysed according to predefined endpoints using a random-effects model. Meta-regression was used to identify predictors of primary outcomes.

RESULTS: Nine comparative studies were identified, comprising 967 uACP patients and 879 bACP patients. No significant differences in age, sex, or proportion of total arch replacements were identified. The uACP cohort had a greater proportion of acute dissections (86% vs 75%, p = 0.04). Hypothermic circulatory arrest and cerebral perfusion times were similar between both groups. No significant differences were seen between unilateral and bilateral groups in terms of mortality (odds ratio [OR] 0.97; 95% confidence interval [CI] 0.64-1.48; p = 0.90; I = 0%), permanent neurological deficit (PND) (OR 1.04; 95% CI 0.74-1.45; p = 0.85; I = 0%), temporary neurological deficit (p = 0.74), acute kidney injury (p = 0.36) or reoperation for bleeding (p = 0.65). No factors affecting mortality or PND were identified on meta-regression.

CONCLUSION: For patients undergoing aortic arch surgery, the available evidence supports either uACP or bACP as an adjunct to HCA. However, there is insufficient comparative evidence available to determine the benefit of either modalities in patients with longer durations of circulatory arrest.

Tian DH, Weller J, Hasmat S, Preventza O, Forrest P, Kiat H, Yan TD

Ann. Thorac. Surg. 2019 07;108(1):283-291

PMID: 30682350

Abstract

BACKGROUND: The increasing use of antegrade cerebral perfusion (ACP) during aortic arch surgery has corresponded with a trend toward warmer target temperatures for hypothermic circulatory arrest. This meta-analysis examined the clinical outcomes using colder or warmer circulatory arrest targets with ACP.

METHODS: Electronic searches were performed using four databases from their inception to February 2017. Comparative studies of adult patients who underwent aortic arch operations using ACP at different circulatory arrest temperatures were included. Data were extracted by 2 independent researchers and analyzed according to predefined end points using a random-effects model.

RESULTS: The literature search identified 18 comparative studies, with 1,215 patients in the “cold” cohort and 1,417 in the “warm” cohort. Mean hypothermic circulatory arrest temperatures were 20.3°C and 26.5°C in the cold and warm groups, respectively. A trend existed for increased permanent neurologic deficit overall when colder targets were used (odds ratio, 1.45; 95% confidence interval, 0.98 to 2.13; p = 0.06); this became significant when adjusted estimates were aggregated (odds ratio, 1.65; 95% confidence interval, 1.06 to 2.55; p = 0.03). No difference in the mortality rate was seen when adjusted effects were aggregated. Temporary neurologic deficit, postoperative dialysis, ventilator time, and intensive care unit stay were significantly reduced in the warm cohort overall. No significant differences in reexploration for bleeding were found.

CONCLUSIONS: ACP with warmer circulatory arrest temperatures may reduce the incidence of permanent neurologic deficit as well as potentially other clinical outcomes. Further studies are required to determine the safe circulatory arrest durations for visceral organs at warmer temperatures.

Chakos A, Twindyawardhani T, Evangelista A, Maldonado G, Piffaretti G, Yan TD, Tian DH

Ann Cardiothorac Surg 2019 Jul;8(4):447-455

PMID: 31463207

Abstract

Background: Aortic intramural hematoma constitutes one of the three classifications of acute aortic syndrome (AAS). Type B intramural hematoma (IMH-B) is localized to the descending thoracic aorta and can be managed through medical, endovascular or surgical means. Data comparing contemporary management with thoracic endovascular aortic repair (TEVAR) versus traditional medical management (MM) is sparse and only moderate strength recommendations for TEVAR are provided in guidelines. This meta-analysis aimed to pool available data from comparative studies between TEVAR and MM and examine differences in outcomes.

Methods: Literature search of electronic medical databases was conducted to identify studies comparing TEVAR and MM for management of IMH-B. Data extraction from studies fulfilling the inclusion criteria was performed by two authors and meta-analysis using a random-effects model applied to pool baseline data and examine risk ratios (RR) for management outcomes.

Results: Of the initial 2,349 studies, nine studies were identified for analysis. There were 161 TEVAR patients and 166 who were medically managed. The mean age of the cohort was 62.2 years [95% confidence interval (CI): 55.8-68.7 years]. Patients with complicating features of IMH-B at presentation were more likely to appear in the TEVAR group, with more penetrating atheromatous ulcer (PAU) [risk difference (RD), 0.565, 95% CI: 0.240-0.889, P=0.001], ulcer-like projection (ULP) (RD 0.240, 95% CI: 0.965-0.384, P=0.001), and greater IMH size (mean difference, MD 5.47 mm, 95% CI: 0.320-10.6, P=0.037). There was no statistical difference between TEVAR and MM for the primary endpoints of aortic-related death (RR 0.535, 95% CI: 0.191-1.5, P=0.234) or IMH-B regression (RR 1.25, 95% CI: 0.859-1.81, P=0.246). Of the secondary endpoints, TEVAR had both significantly less dissection during follow-up (RR 0.295, 95% CI: 0.0881-0.989, P=0.048) and less rupture during follow-up (RR 0.206, 95% CI: 0.0462-0.921, P=0.039).

Conclusions: A small number of series comparing TEVAR and MM for management of IMH-B are available and random-effects meta-analysis did not reveal any statistically significant difference between treatments for aortic related death or IMH-B regression at a mean follow-up of 37 months. TEVAR was found to be associated with lower risk of dissection and lower risk of rupture during follow-up. Baseline data meta-analysis showed patients with complicating features of PAU, ULP, and larger IMH size were more likely to be managed with TEVAR.