John Pepper

Difficulties in predicting outcome in cardiac surgery patients

OBJECTIVE To evaluate a novel combination of preoperative, intraoperative, and postoperative variables (including the Parsonnet, and the Acute Physiology and Chronic Health Evaluation II and III [APACHE II and III] scores) in cardiac surgery patients in order to predict hospital outcome, complications, and length of stay. DESIGN Prospective survey. SETTING Adult intensive care unit (ICU) at a tertiary care cardiothoracic surgery center. PATIENTS All cardiac surgery patients admitted to the ICU over a 1-yr period. INTERVENTIONS Medical history, Parsonnet score, intraoperative data (including bypass and ischemic times), APACHE II and III scores, complications, and outcome were collected for each patient. MEASUREMENTS AND MAIN RESULTS One thousand eight patients were entered into the study. The mean Parsonnet score was 7.8 (range 0 to 33), mean APACHE II score 11.8 (range 2 to 33), and mean APACHE III score 42.5 (range 9 to 132). ICU mortality rate was 2.7% and hospital mortality rate was 3.8%. The mean APACHE II predicted risk of dying was 5.31%, which gave a standardized mortality ratio of 0.71. The above scores were all statistically well correlated with hospital mortality. Further, a logistic regression model was developed for the probability of hospital death. This model (which included bypass time, need for inotropes, mean arterial pressure, urea, and Glasgow Coma Scale) had an area under the receiver operating characteristic curve of 0.87, while the Parsonnet score had an area of 0.82 and the APACHE II risk of dying had an area of 0.84. CONCLUSIONS Cardiac surgery remains a difficult area for outcome prediction. A combination of intraoperative and postoperative variables can improve predictive ability.

Thoracic endovascular aortic repair (TEVAR) in proximal (type A) aortic dissection: Ready for a broader application?

Objective: Thoracic endovascular aortic repair (TEVAR) has demonstrated encouraging results and is gaining increasing acceptance as a treatment option for aortic aneurysms and dissections. Yet, its role in managing proximal aortic pathologies is unknown—this is important because in proximal (Stanford type A) aortic dissections, 10% to 30% are not accepted for surgery and 30% to 50% are technically amenable for TEVAR. We describe our case series of type A aortic dissections treated by using TEVAR. Methods: Between year 2009 and 2016, 12 patients with acute, subacute, or chronic type A aortic dissection with the proximal entry tear located between the coronaries and brachiocephalic artery were treated with TEVAR at 3 centers. Various stent‐graft configurations were used to seal the proximal entry tear in the ascending aorta under rapid pacing. Results: A total of 12 patients (9 male, 3 female), mean age 81 ± 7 years, EuroSCORE II 9.1 ± 4.5, underwent TEVAR for the treatment of type A aortic dissection. Procedural success was achieved in 11 of 12 patients (91.7%). There was 1 minor stroke and 1 intraprocedural death. No additional deaths were reported at 30 days. At 36 months, there were 4 further deaths (all from nonaortic causes). The mean survival of these 4 deceased was 23 months (range 15‐36 months). Follow‐up computed tomography demonstrated favorable aortic remodeling. Conclusions: TEVAR is feasible and reveals promising early results in selected patients with type A aortic dissection who are poor candidates for surgical repair. The current iteration of stent‐graft technology, however, needs to be adapted to features specific to the ascending aorta.

Personalized external aortic root support: a review of the current status

Personalized external aortic root support (PEARS) is an emerging technology. It is a pre-emptive operation to halt aortic root expansion and maintain aortic valve function in Marfan syndrome and is also applicable to aortic root aneurysms of other aetiologies. To fully evaluate PEARS, awareness of all those who advise these patients is necessary to ensure that patients are fully informed of the alternative operations, to carefully build experience, to ensure safety and quality and to monitor outcomes. Herein, we present a summary of published methods and outcomes and the arrangements in place for fuller evaluation.

Aortic root surgery in Marfan syndrome

Elective root replacement of the ascending aorta in people with Marfan syndrome has been established practice for more than 25 years; it greatly reduces the risk they face from fatal aortic dissection.1 Now that low perioperative risk is assured and long-term survival is expected, long-term consequences and the durability of the surgery have become important considerations. The question for people with Marfan syndrome, their families and their surgeons is whether to choose the valve-sparing or valve-replacement forms of surgery. This question is at the core of the systematic review and meta-analysis published in Heart ( in press ).2 The decision as to which option to prefer is dominated by a trade-off between these competing risks; the analysis presented informs the choice but does not make it any easier. How would an individual patient weigh the risk of stroke versus a given possibility of the need for reoperation? The calculated estimates of the thromboembolic hazards associated with a mechanical valve at 0.7% per year, and the risk of native valve failure mandating reoperation at 1.3% a year, are the central conclusions of this report. The review incorporates 12 publications from 1995 to 2009, comprising reports of 35–675 patients, with a total of 1434. The average age of the patients at the time of surgery was 34 years. The systematic reviewers could not find data on the degree of aortic regurgitation, or the aortic root dimensions before surgery, which are two of the important criteria used in decision-making1 and would have informed readers of the severity of disease in patients in whom surgery was undertaken. But the large majority of patients with Marfan syndrome develop aortic root dilatation and we know that if this is allowed to continue unchecked then about two-thirds of …

Quality of life after intervention on the thoracic aorta

Surgery on the thoracic aorta is challenging and historically associated with significant mortality and morbidity. In recent times, there has been increased emphasis on the importance of health-related quality of life (HRQOL) measures. It is seen as a development beyond isolated markers of outcome such as operative mortality and is particularly applicable to aortic surgery given the number of asymptomatic patients operated on (for prognostic grounds), and rapidly advancing endovascular technologies which require proper assessment. This systematic review provides an outline of all available literature detailing HRQOL in patients receiving intervention (both open and endovascular) on the thoracic aorta. In total, 30 studies were identified encompassing 4746 patients undergoing a variety of procedures from aortic root replacement to thoracoabdominal aortic aneurysm repair. While there were deficiencies in the underlying literature such as lack of baseline HRQOL assessment, the majority of the studies confirm that HRQOL after major aortic surgery (including on the elderly and in emergency situations) is acceptable and compares well to matched general populations. Strategies for improving the HRQOL in aortic surgery are summarized and include the need for surgeons to plan cerebral protection methods more carefully and to develop operative strategies to avoid reoperation or reintervention, as this is associated with deterioration of long-term HRQOL. Randomized studies measuring baseline and follow-up HRQOL at specific set points are needed. Innovative research methods could be employed in future studies with the aim of correlating HRQOL with imaging or physiological/inflammation biomarkers, or other end points such as aortic stiffness or wall shear stress to characterize disease progression and prognosis.

On the choice of outlet boundary conditions for patient-specific analysis of aortic flow using computational fluid dynamics

Boundary conditions (BCs) are an essential part in computational fluid dynamics (CFD) simulations of blood flow in large arteries. Although several studies have investigated the influence of BCs on predicted flow patterns and hemodynamic wall parameters in various arterial models, there is a lack of comprehensive assessment of outlet BCs for patient-specific analysis of aortic flow. In this study, five different sets of outlet BCs were tested and compared using a subject-specific model of a normal aorta. Phase-contrast magnetic resonance imaging (PC-MRI) was performed on the same subject and velocity profiles extracted from the in vivo measurements were used as the inlet boundary condition. Computational results obtained with different outlet BCs were assessed in terms of their agreement with the PC-MRI velocity data and key hemodynamic parameters, such as pressure and flow waveforms and wall shear stress related indices. Our results showed that the best overall performance was achieved by using a well-tuned three-element Windkessel model at all model outlets, which not only gave a good agreement with in vivo flow data, but also produced physiological pressure waveforms and values. On the other hand, opening outlet BCs with zero pressure at multiple outlets failed to reproduce any physiologically relevant flow and pressure features.

Inhibition of factor IXa by the pegnivacogin system during cardiopulmonary bypass: a potential substitute for heparin. A study in baboons

OBJECTIVES Heparin and protamine are standard for anticoagulation and reversal for cardiopulmonary bypass (CPB). The REGADO biosciences protocol 1 (REG1) anticoagulant system, consisting of the Factor IXa (FIXa)-inhibitor pegnivacogin and its reversal agent (anivamersen), has been studied in patients undergoing coronary catheterization and in CPB in sheep and pigs. Prior to first human use in CPB, we wanted to test the safety and efficacy of REG1 in a primate model. METHODS Fourteen baboons undergoing 2 h of CPB followed by 1 h of reperfusion were studied. Three received heparin/protamine and 11 received 1 of 2 doses of pegnivacogin followed by anivamersen. Thrombin-generating capacity was tested in additional in vitro experiments. RESULTS Targeted drug levels and near-complete FIXa inhibition were achieved. Bypass was run uneventfully in all animals without any clotting in the circuit and bleeding was minimal in the two groups. However, in contrast to heparin-treated baboons, those receiving pegnivacogin/anivamersen displayed thrombi in the bypass cannulae upon cannulation and kidney cortical infarcts. Inter-species comparisons revealed that in the presence of high levels of FIXa inhibition, tissue factor-mediated thrombin generation in baboons was much higher than that in other species. CONCLUSIONS These data highlight the limitations of the baboon model for assessing factor-specific coagulation inhibitors during CPB. The justification for Phase 1 human studies using REG1 for CPB is unclear.

Measurements of Intra-Aortic Balloon Wall Movement During Inflation and Deflation: Effects of Angulation

Abstract The intra‐aortic balloon pump (IABP) is a ventricular assist device that is used with a broad range of pre‐, intra‐, and postoperative patients undergoing cardiac surgery. Although the clinical efficacy of the IABP is well documented, the question of reduced efficacy when patients are nursed in the semi‐recumbent position remains outstanding. The aim of the present work is therefore to investigate the underlying mechanics responsible for the loss of IABP performance when operated at an angle to the horizontal. Simultaneous recordings of balloon wall movement, providing an estimate of its diameter (D), and fluid pressure were taken at three sites along the intra‐aortic balloon (IAB) at 0 and 45°. Flow rate, used for the calculation of displaced volume, was also recorded distal to the tip of the balloon. An in vitro experimental setup was used, featuring physiological impedances on either side of the IAB ends. IAB inflation at an angle of 45° showed that D increases at the tip of the IAB first, presenting a resistance to the flow displaced away from the tip of the balloon. The duration of inflation decreased by 15.5%, the inflation pressure pulse decreased by 9.6%, and volume decreased by 2.5%. Similarly, changing the position of the balloon from 0 to 45°, the balloon deflation became slower by 35%, deflation pressure pulse decreased by 14.7%, and volume suctioned was decreased by 15.2%. IAB wall movement showed that operating at 45° results in slower deflation compared with 0°. Slow wall movement, and changes in inflation and deflation onsets, result in a decreased volume displacement and pressure pulse generation. Operating the balloon at an angle to the horizontal, which is the preferred nursing position in intensive care units, results in reduced IAB inflation and deflation performance, possibly compromising its clinical benefits.

Personalised external aortic root support

Dear Editor , Valve replacing and valve-sparing root replacement were devised on the operating table and evolved by trial and error. Different times set different standards. By contrast, after 4 years of research collaboration between surgeons, anatomists and engineers (2000–2004), personalised external aortic root support (PEARS) has followed a standard protocol in 42 patients with over 170 patient-years of intention-to-treat analysis, and has been systematically and rigorously evaluated. Cameron’s ‘two technical points’1 do not accurately reflect how this operation is in fact performed.2 The proximal …

Developing a shared decision support framework for aortic root surgery in Marfan syndrome

Objective The study is an early phase of development of a decision support framework for people with Marfan syndrome who are anticipating prophylactic aortic root surgery. Implications of the timing and the nature of the operation chosen were previously elicited in focus groups. In this step, we explored the range of relative values placed by individuals on the implications of decisions made about surgery. Methods Following the principles of the Ottawa Decision Support Framework, eight questions in the general form ‘How important is it to you …’ were framed by a panel. Marfan people, families and specialist doctors answered online. Quantitative and qualitative analyses were performed. Results Worldwide, 142 responses were received including 25 specialist doctors. Respondents were 55% female and 46% had previous aortic root surgery. Overall, active lifestyle was more important to males (p=0.03). Patients placed more importance than doctors on not deferring surgery (p=0.04) and on avoidance of anticoagulation in the interests of childbearing (p=0.009). Qualitative analysis showed differing but cogently reasoned values that were sometimes polarised, and mainly driven by the wish to maintain a good quality of life and active lifestyle. Conclusions Given the cogency of these viewpoints, people anticipating root replacement surgery should have ample opportunity to express them and to have them acknowledged ahead of a consultation when they can then be fully explored in a mutually informed forum. If they differ from local medical practice, they can then be discussed in the process of reaching shared and individualised decisions.