Ayyaz Ali

Remote Ischemic Preconditioning Reduces Myocardial and Renal Injury After Elective Abdominal Aortic Aneurysm Repair A Randomized Controlled Trial

Background— Myocardial and renal injury commonly contribute to perioperative morbidity and mortality after abdominal aortic aneurysm repair. Remote ischemic preconditioning (RIPC) is a phenomenon whereby brief periods of ischemia followed by reperfusion in one organ provide systemic protection from prolonged ischemia. To investigate whether remote preconditioning reduces the incidence of myocardial and renal injury in patients undergoing elective open abdominal aortic aneurysm repair, we performed a randomized trial. Method and Results— Eighty-two patients were randomized to abdominal aortic aneurysm repair with RIPC or conventional abdominal aortic aneurysm repair (control). Two cycles of intermittent crossclamping of the common iliac artery with 10 minutes ischemia followed by 10 minutes reperfusion served as the RIPC stimulus. Myocardial injury was assessed by cardiac troponin I (>0.40 ng/mL), myocardial infarction by the American College of Cardiology/American Heart Association definition and renal injury by serum creatinine (>177 &mgr;mol/L) according to American Heart Association guidelines for risk stratification in major vascular surgery. The groups were well matched for baseline characteristics. RIPC reduced the incidence of myocardial injury by 27% (39% versus 12% [95% CI: 8.8% to 45%]; P=0.005), myocardial infarction by 22% (27% versus 5% [95% CI: 7.3% to 38%]; P=0.006), and renal impairment by 23% (30% versus 7%; [95% CI: 6.4 to 39]; P=0.009). Multivariable analysis revealed the protective effect of RIPC on myocardial injury (OR: 0.22, 95% CI: 0.07 to 0.67; P=0.008), myocardial infarction (OR: 0.18, 95% CI: 0.04 to 0.75; P=0.006) and renal impairment were independent of other covariables. Conclusions— In patients undergoing elective open abdominal aortic aneurysm repair, RIPC reduces the incidence of postoperative myocardial injury, myocardial infarction, and renal impairment.

Are stentless valves superior to modern stented valves? A prospective randomized trial.

Background— It is presumed that stentless aortic bioprostheses are hemodynamically superior to stented bioprostheses. A prospective randomized controlled trial was undertaken to compare stentless versus modern stented valves. Methods and Results— Patients with severe aortic valve stenosis (n=161) undergoing aortic valve replacement (AVR) were randomized intraoperatively to receive either the C-E Perimount stented bioprosthesis (n=81) or the Prima Plus stentless bioprosthesis (n =80). We assessed left ventricular mass (LVM) regression with transthoracic echocardiography (TTE) and magnetic resonance imaging (MRI). Transvalvular gradients were measured postoperatively by Doppler echocardiography to compare hemodynamic performance. There was no difference between groups with regard to age, symptom status, need for concomitant coronary artery bypass surgery, or baseline LVM. LVM regressed in both groups but with no significant difference between groups at 1 year. In a subset of 50 patients, MRI was also used to assess LVM regression, and again there was no significant difference between groups at 1 year. Hemodynamic performance of the 2 valves was similar with no difference in mean and peak systolic transvalvular gradients 1 year after surgery. In patients with reduced ventricular function (left ventricular ejection fraction [LVEF] <60%), there was a significantly greater improvement in LVEF from baseline to 1 year in stentless valve recipients. Conclusions— Both stented and stentless bioprostheses are associated with excellent clinical and hemodynamic outcomes 1 year after AVR. Comparable hemodynamics and LVM regression can be achieved using a second-generation stented pericardial bioprosthesis. In patients with ventricular impairment, stentless bioprostheses may allow for greater improvement in left ventricular function postoperatively.

Indirect comparison meta-analysis of aspirin therapy after coronary surgery.

Objectives To evaluate the efficacy of low and medium dose aspirin therapy after coronary surgery by using an indirect comparison meta-analysis. Data sources Systematic literature search of Medline, Embase, Cochrane controlled trials register, and trial register sites on the internet. Study selection Outcome was evaluated by angiography and reported as graft occlusion and rate of events in patients. Trials that did not include aspirin as the sole therapy or did not have a placebo control arm were excluded. Articles were assessed for eligibility and quality and grouped according to dosage. The estimated difference in effect of low and medium dose aspirin on graft occlusion was obtained by combining the estimated log relative risks of low dose with placebo and medium dose with placebo. Results For graft occlusion, the medium dose trials yielded a relative risk reduction of 45% compared with 26% for the low dose trials. The greater effect in the medium dose trials is summarised by a relative risk ratio of 0.74 (95% confidence interval 0.52 to 1.06; P = 0.10) for graft occlusion and 0.81 (0.57 to 1.16; P = 0.25) for events in patients. Conclusions Medium dose aspirin may more successfully reduce graft occlusion than low dose regimens within the first year after coronary surgery.

Preservation of the mitral valve apparatus: evidence synthesis and critical reappraisal of surgical techniques

Sub-valvular apparatus preservation after mitral valve replacement is not a new concept, yet to date there has been no quantification of its clinical effectiveness as a procedure and no consensus as to which surgical preservation technique should be adopted to achieve the best immediate and midterm clinical outcomes. This systematic review of current available literature aims to use an evidence synthesis and meta-analytic approach to compare outcomes following replacement of the mitral valve with (MVR-P) or without preservation (MVR-NP) of its apparatus. It considers all the relevant anatomical, experimental, echocardiographic, and clinical studies published in the literature and appraises all reported mitral valve sub-valvular apparatus preservation techniques. The results of this review strongly suggest that MVR-P is superior to MVR-NP with regards to the incidence of early postoperative low-cardiac output requiring inotropic support, and early or mid-term survival. They also suggest that the operative decision should be individualised based on patients anatomy, pathology and ventricular function and therefore surgeons should be familiar with more than one surgical preservation technique. Finally, this paper highlights the need for further high quality research focusing particularly on the long-term assessment of quality of life and health utility following MVR-P.

Cardiac recovery in a human non-heart-beating donor after extracorporeal perfusion: source for human heart donation?

Successful renal, liver and more recently lung transplantation using organs from non-heart-beating donors (NHBDs) has been reported. Regarding the heart, it has generally been assumed that warm ischemic insult would result in overwhelming and irreversible myocardial damage. We report recovery of cardiac function in a human NHBD by using extracorporeal perfusion 23 minutes after cardiorespiratory arrest. Successful cardiac resuscitation in the NHBD represents a potential source of increased donor organ supply for clinical heart transplantation.

Functional assessment and transplantation of the donor heart after circulatory death

BACKGROUND After a severe shortage of brain-dead donors, the demand for heart transplantation has never been greater. In an attempt to increase organ supply, abdominal and lung transplant programs have turned to the donation after circulatory-determined death (DCD) donor. However, because heart function cannot be assessed after circulatory death, DCD heart transplantation was deemed high risk and never adopted routinely. We report a novel method of functional assessment of the DCD heart resulting in a successful clinical program. METHODS Normothermic regional perfusion (NRP) was used to restore function to the arrested DCD heart within the donor after exclusion of the cerebral circulation. After weaning from support, DCD hearts underwent functional assessment with cardiac-output studies, echocardiography, and pressure-volume loops. In the feasibility phase, hearts were transported perfused before evaluation of function in modified working mode extracorporeally. After the establishment of a reliable assessment technique, hearts with demonstrable good function were then selected for clinical transplantation. RESULTS NRP was instituted in 13 adult DCD donors, median age of 33 years (interquartile range [IQR], 28-38 years), after a median ischemic time from withdrawal to perfusion of 24 minutes (IQR, 21-29; range, 17-146 minutes). Two of 4 hearts in the feasibility phase were unsuitable for transplantation after functional assessment. Nine DCD hearts were transplanted in the clinical phase, with 100% survival. The median intensive care duration was 5 days (IQR, 4-5 days), with 2 patients requiring mechanical support. There were no episodes of rejection (total, 1,436 patient-days; range, 48-297). During the same period, we performed 20 standard heart transplants using brain-dead donors. CONCLUSIONS NRP allows rapid reperfusion and functional assessment of the DCD donor heart, ensuring only viable hearts are selected for transplantation. This technique minimizes the risk of primary graft dysfunction and maximizes confidence in DCD heart transplantation, realizing a 45% increase in our heart transplant activity.

A cardioprotective preservation strategy employing ex vivo heart perfusion facilitates successful transplant of donor hearts after cardiocirculatory death

BACKGROUND Ex vivo heart perfusion (EVHP) has been proposed as a means to facilitate the resuscitation of donor hearts after cardiocirculatory death (DCD) and increase the donor pool. However, the current approach to clinical EVHP may exacerbate myocardial injury and impair function after transplant. Therefore, we sought to determine if a cardioprotective EVHP strategy that eliminates myocardial exposure to hypothermic hyperkalemia cardioplegia and minimizes cold ischemia could facilitate successful DCD heart transplantation. METHODS Anesthetized pigs sustained a hypoxic cardiac arrest and a 15-minute warm ischemic standoff period. Strategy 1 hearts (S1, n = 9) underwent initial reperfusion with a cold hyperkalemic cardioplegia, normothermic EVHP, and transplantation after a cold hyperkalemic cardioplegic arrest (current EVHP strategy). Strategy 2 hearts (S2, n = 8) underwent initial reperfusion with a tepid adenosine-lidocaine cardioplegia, normothermic EVHP, and transplantation with continuous myocardial perfusion (cardioprotective EVHP strategy). RESULTS At completion of EVHP, S2 hearts exhibited less weight gain (9.7 ± 6.7 [S2] vs 21.2 ± 6.7 [S1] g/hour, p = 0.008) and less troponin-I release into the coronary sinus effluent (4.2 ± 1.3 [S2] vs 6.3 ± 1.5 [S1] ng/ml; p = 0.014). Mass spectrometry analysis of oxidized pleural in post-transplant myocardium revealed less oxidative stress in S2 hearts. At 30 minutes after wean from cardiopulmonary bypass, post-transplant systolic (pre-load recruitable stroke work: 33.5 ± 1.3 [S2] vs 19.7 ± 10.9 [S1], p = 0.043) and diastolic (isovolumic relaxation constant: 42.9 ± 6.7 [S2] vs 65.2 ± 21.1 [S1], p = 0.020) function were superior in S2 hearts. CONCLUSION In this experimental model of DCD, an EVHP strategy using initial reperfusion with a tepid adenosine-lidocaine cardioplegia and continuous myocardial perfusion minimizes myocardial injury and improves short-term post-transplant function compared with the current EVHP strategy using cold hyperkalemic cardioplegia before organ procurement and transplantation.

Longitudinal study of the profile and predictors of left ventricular mass regression after stentless aortic valve replacement.

BACKGROUND The aim of this study was to evaluate the long-term profile and determine the factors that would influence the effect and rate of ventricular mass regression with time after aortic valve replacement with a stentless or a homograft valve. METHODS We studied 300 patients during a 10-year period with at least a year of follow-up with a total of 1,273 serial echocardiographic measurements. Left ventricular mass was calculated from M-mode recordings and indexed to body surface area. Longitudinal data analysis was performed using a linear mixed effects model. RESULTS The mean age (+/- standard deviation) was 65 (+/-14) years, consisting of 216 (72%) males. A stentless valve was implanted in 156 (52%), and a homograft in 144 (48%). The median time (interquartile range) to follow-up was 4.7 (2.8 to 6.6) years. The greatest rate of left ventricular mass regression occurred in the first year after surgery. On multivariable modeling, independent predictors of left ventricular mass were valve size (p = 0.011), left ventricular function (moderate impairment, p = 0.418; severe impairment, p = 0.011), and baseline left ventricular mass (middle tercile, p < 0.001; highest tercile, p < 0.001). Only baseline ventricular mass influenced the rate of subsequent left ventricular mass regression; the greatest rate of regression occurred in patients with the highest baseline values of ventricular mass (p < 0.001). CONCLUSIONS The greatest rate of left ventricular mass regression occurs in the first year with baseline left ventricular mass as the strongest predictor and the only identified variable that influenced the rate of left ventricular mass regression.

Hearts From DCD Donors Display Acceptable Biventricular Function After Heart Transplantation in Pigs

Cardiac transplantation is in decline, in contrast to other solid organs where the number of solid organ transplants from donors after circulatory death (DCD) is increasing. Hearts from DCD donors are not currently utilized due to concerns that they may suffer irreversible cardiac injury with resultant poor graft function. Using a large animal model, we tested the hypothesis that hearts from DCD donors would be suitable for transplantation. Donor pigs were subjected to hypoxic cardiac arrest (DCD) followed by 15 min of warm ischemia and resuscitation on cardiopulmonary bypass, or brainstem death (BSD) via intracerebral balloon inflation. Cardiac function was assessed through load‐independent measures and magnetic resonance imaging and spectroscopy. After resuscitation, DCD hearts had near normal contractility, although stroke volume was reduced, comparable to BSD hearts. DCD hearts had a significant decline in phosphocreatine and increase in inorganic phosphate during the hypoxic period, with a return to baseline levels after reperfusion. After transplantation, cardiac function was comparable between BSD and DCD groups. Therefore, in a large animal model, the DCD heart maintains viability and recovers function similar to that of the BSD heart and may be suitable for clinical transplantation. Further study is warranted on optimal reperfusion strategies.

Impact of donor cardiac arrest on heart transplantation

BACKGROUND Cardiac transplantation is an effective therapy for patients with end-stage heart failure, but it is still hindered by the lack of donor organs. A history of donor cardiac arrest raises trepidation regarding the possibility of poor post-transplant outcomes. The impact of donor cardiac arrest following successful cardiopulmonary resuscitation on heart transplant outcomes is unknown. Therefore, we sought to evaluate the impact of donor cardiac arrest on orthotropic heart transplantation using the United Network for Organ Sharing database. METHODS We performed a secondary longitudinal analysis of all cardiac transplants performed between April 1994 and December 2011 through the United Network for Organ Sharing registry. Multiorgan transplants, repeat transplants, and pediatric recipients were excluded. Survival analyses were performed using Kaplan-Meier methods as well as multivariate adjusted logistic regression and Cox proportional hazard models. RESULTS A total of 19,980 patients were analyzed. In 856 cases, the donors had histories of cardiac arrest, and in the remaining 19,124 cases, there was no history of donor cardiac arrest. The unadjusted 1-, 5-, and 10-year actuarial survival rates between the arrest and the nonarrest groups were not significantly different. Multivariate logistic regression demonstrated no difference in survival in the donor arrest group at 30 days, 1 year, or 3 years. Furthermore, the adjusted Cox proportional hazard model for cumulative survival also showed no survival difference between the 2 groups. CONCLUSION If standard recipient and donor transplantation criteria are met, a history of donor cardiac arrest should not prohibit the potential consideration of an organ for transplantation.