Medium-term outcome of recipients of marginal donor hearts selected with new stress-echocardiographic techniques over standard criteria

The ethics committee of the Emilia-Romagna and Tuscany regions of Italy approved the Aged Donor Heart Rescue by Stress Echo Project in 2004 (number 142/2004/U/Oss, October 19, 2004). Partial funding for the Stress Echo project was provided by the Italian Health Ministry (CCM project #48, 2010). On May 11, 2011 the Italian National Transplant Center/Italian National Institute of Health (CNT/ISS 2011) approved the Guidelines: Increase available organs for heart transplant with heart assessed by stress echocardiography in older donors or in donors with several risk factors, with a second-opinion telemedicine system from the core echo lab, IFC-Pisa.

Donors enrolled in the stress echo protocols were enrolled in neurological intensive care units, without direct access to coronary angiography facilities. Standard coronary angiography with IVUS was performed 1 month after heart TX [18]. Donors enrolled in the HT protocol underwent coronary angiography before heart harvesting. Once transplanted, all patients underwent usual surveillance and immunosuppression protocol and infection prophylaxis, with serial endomyocardial biopsies according to guidelines [19].

SPSS version 21 for Windows (SPSS, Inc., Chicago, IL, USA) was used for statistical analyses. The statistical analyses included descriptive statistics (frequencies and percentages for categorical variables and mean ± SD for continuous variables). Patient’s survival curves were estimated using the Kaplan–Meier method and compared between groups using the log-rank test. The survival was censored at the time of death. For patients who were still alive, survival was censored at date of last known follow-up. Two-tailed p < 0.05 was considered statistically significant.

Supply of donor hearts is a critical rate-limiting step in heart transplantation. An effective way to solve the current shortage would be to accept an upward shift of the age cut-off limit and to accept for transplant normal but temporarily stunned donor hearts [4, 5, 13, 22]. Pharmacological stress echo (with stress being classical pharmacological stress or HT extended for several hours) can identify aged good hearts with normal resting function (and normal response during stress) and even with abnormal resting function (and functional recovery during stress or following HT) [23, 24].

The suggested first choice was dipyridamole, with dobutamine as the alternative, acceptable second choice. There were two reasons for the choice: dipyridamole is equally as accurate but technically simpler than dobutamine because of a lesser increase in heart rate, and the image quality is therefore less degraded during stress [3, 4] (this aspect is especially important in the technically challenging theater of testing potential donors who have high resting heart rates), and further catecholamine stress with dobutamine is in principle undesirable for these patients, because they already have high, and potentially toxic, levels of circulating catecholamines, which may damage the heart [19, 22, 25].

Although appealingly simple, a stress-echo driven approach depends on the qualitative, operator-dependent assessment of regional wall motion, requiring strict criteria in the process of execution, acquisition, analysis and interpretation. The Italian National Transplant Center recently approved the stress echo methodology for selection of older donor hearts (CNT/ISS; 2011) for all Italian regions [25, 26]. The Core Echo Lab, Pisa (IFC, National Research Council) is responsible for accreditation of cardiologists to carry out stress echo in each center involved in the project, certification of a “second opinion” in near real time, and final acceptance of the donation [12]. For this, an Italian network of stress echo laboratories has been organized by IFC (CNR, Pisa). All network laboratories have agreed to pass a quality control examination on stress echo reading before entering the study, to code the LV segments similarly, and to adopt a common scoring system for wall motion analysis. The Transplantation Network involves the cardiac-transplant program throughout Italy. There are no specific requirements for instruments and there are no additional costs for local health agencies. In this way, at nearly no extra cost, the research infrastructure allows access to donation to feed an activity such as heart transplantation with high running fixed costs and obvious beneficial impact on the sustainability of the health system. With standard Italian health care costs in the public system, a stress echo is priced at around € 100, and a heart transplant (made possible by stress echo-driven selection) around € 80,000.

In theory, it may seem more convenient to perform stress echocardiography at the bedside rather than transport the donor to the cardiac catheterization laboratory [25‐29]. The concept of replacing an invasive test requiring transportation to the cardiac catheterization laboratory with one that could potentially be performed at the bedside is appealing; however, the practicality of bedside stress echocardiography requires further evaluation [25]. The decision to screen more marginal donors noninvasively will increase the risk for hearts with CAD being accepted for transplantation. The implications of this are unclear. It has been demonstrated that the presence of donor-transmitted coronary atherosclerosis does not accelerate the progression of intimal hyperplasia or affect the 3-year prognosis of transplant recipients. Recent studies indicate that deleterious transplant vasculopathy (TVP) as a result of chronic rejection is multifactorial and that atherosclerotic plaque in the donor heart may not necessarily progress to TVP [30‐32]. Instead, using serial Intravascular Ultrasound (IVUS) measurements, Li et al. [33] demonstrated that pre-existing donor atherosclerotic lesions do not accelerate the development of TVP either at the site of pre-existing donor atherosclerosis or elsewhere within the same artery. However, donor-transmitted coronary atherosclerosis increases the incidence of cardiac allograft vasculopathy. Recently, Grauhan et al. [18] described an overall prevalence of donor-transmitted coronary atherosclerosis of 7.0%, and he stated that donor screening without coronary angiogram overlooks a significant proportion of coronary lesions. In that study, the prevalence of donor transmitted CAD in recipients who underwent coronary angiography within 6 months post-transplantation was 5.2%, whereas it was 15.1% on autopsy in those recipients who died within 6 months without coronary angiogram. Among all patients with early graft failure, prevalence was as high as 22.8% indicating that donor CAD represents a significant risk factor for early graft failure [34].