Heart transplantation from donation after circulatory death: Impact on waitlist time and transplant rate.

The effect of using donation after circulatory death (DCD) hearts on waitlist outcomes has not been substantiated. We retrospectively analyzed 184 heart transplant (HT) candidates at our institution from 2019 to 2021. Patients were stratified into 2 observation periods centered on September 12, 2020, when the adult DCD HT program officially began. The primary outcome was a comparison of transplant rate between period 1 (pre-DCD) and period 2 (post-DCD). Secondary outcomes included waitlist time-to-transplant, waitlist mortality rate, independent predictors of incidence of HT, and posttransplant outcomes. A total of 165 HTs (n = 92 in period 1 and n = 73 in period 2) were performed. The median waitlist time-to-transplant decreased from 47.5 to 19 days in periods 1 and 2, respectively (P = .004). The transplant rate increased from 181 per 100 patient-years in period 1 to 579 per 100 patient-years in period 2 (incidence rate ratio, 1.87; 95% CI, 1.04-3.38; P = .038). There were no statistical differences in waitlist mortality rate (P = .566) and 1-year survival (P = .699) between the 2 periods. DCD HTs (n = 36) contributed to 49.3% of overall HT activity in period 2. We concluded that utilization of DCD hearts significantly reduced waitlist time and increased transplant rate. Short-term posttransplant outcomes were comparable between the pre-DCD and post-DCD periods.

Oligonucleotide-based Preconditioning of DCD Cardiac Donors and Its Impact on Cardiac Viability.

BACKGROUND: While clinical donation after circulatory death (DCD) cardiac transplantation is being implemented with increasing frequency to address the supply/demand mismatch of donor grafts, no research to date has examined a strategy of donor preconditioning to optimize the viability of DCD hearts for transplantation. In our rat model of the DCD protocol, we investigate the impact of pretreating donors with phosphorothioate-linked cytosine and guanine rich oligodeoxynucleotides (CpG ODN) and their effects on cardiac function, injury, and a novel left ventricular (LV) mRNA biomarker panel. METHODS: DCD rats were subjected to a withdrawal protocol, followed by 20 minutes of warm acirculatory standoff, representing a group of severely injured hearts as previously demonstrated. Beating heart controls and DCD rats were pretreated with vehicle or stimulatory CpG ODN (beating heart control and DCD stimulated with CpG ODN, BST and DST). Hearts were harvested for ex situ heart perfusion (ESHP), where LV function, histochemical injury, and differences in gene expression were characterized between groups. RESULTS: Donor pretreatment with CpG ODN doubled the number of functional DCD hearts at ESHP. Pretreatment was associated with improved systolic and diastolic LV function, a reduction in histological injury, and markedly reduced elaboration of cardiac troponin-I in coronary effluent during ESHP. Pretreatment was also associated with a reduction in mRNA biomarkers associated with myocardial injury. CONCLUSIONS: A single dose of CpG ODN was associated with reduced biomarkers of cardiac injury and a 100% increase in cardiac viability in this rodent model of marginal DCD cardiac donation.

Tamponade: Hemodynamic and Echocardiographic Diagnosis.

Cardiac tamponade is a medical emergency that can be readily reversed with timely recognition and appropriate intervention. The clinical diagnosis of cardiac tamponade requires synthesis of a constellation of otherwise nonspecific features based on an understanding of the underlying pathophysiological characteristics. Although echocardiographic examination is a central component of diagnosis, alone it is insufficient to establish the physiological diagnosis of hemodynamically significant cardiac tamponade. The hemodynamic diagnosis of cardiac tamponade requires clinical evidence of low cardiac output and stroke volume in the setting of elevated cardiac filling pressures, with evidence of increased sympathetic tone (eg, tachycardia, peripheral vasoconstriction), and exclusion of other causes of shock as the primary problem (particularly cardiogenic shock). The hemodynamic features of tamponade are revealed by considering the effects of pericardial constraint. Pulsus paradoxus and loss of the normal "y" descent of a jugular venous pressure waveform may be appreciated on clinical examination. When a pulmonary artery catheter is placed, equalization of diastolic pressures across all chambers is observed. Echocardiographic examination confirms the size, location, and other characteristics of the causal pericardial collection. Several echocardiographic features support the hemodynamic diagnosis of tamponade, including early diastolic collapse of the right ventricle, late diastolic collapse of the right atrium, respiratory variation in mitral valve inflow (akin to pulsus paradoxus), and decreased early filling (E wave) of mitral valve inflow (related to loss of the y descent). Echocardiographic examination then supports decisions about the early treatment and drainage of the tamponading effusion.

A Rodent Model of Cardiac Donation After Circulatory Death and Novel Biomarkers of Cardiac Viability During Ex Vivo Heart Perfusion.

BACKGROUND: Organ donation after circulatory death (DCD) is increasingly being used as a means of addressing the organ supply/demand mismatch in solid organ transplantation. There is reluctance to use DCD hearts, due to an inability to precisely identify hearts that have suffered irreversible injury. We investigated novel biomarkers and clinically relevant endpoints across a spectrum of warm ischemic times, before and during ex vivo heart perfusion (EVHP), to identify features associated with a nonviable cardiac phenotype. METHODS: Donor rats sustained a hypoxic cardiac arrest, followed by variable acirculatory standoff periods (DCD groups). Left ventricular function, histochemical injury, and differences in left ventricular gene expression were studied before, and during, EVHP. RESULTS: As warm ischemic time exposure increased in DCD groups, fewer hearts were functional during EVHP, and ventricular function was increasingly impaired. Histochemical assessment identified severely injured hearts during EVHP. A novel gene expression signature identified severely injured hearts during EVHP (upregulation of c-Jun, 3.19 (2.84-3.60); P = 0.0014; HMOX-1, 3.87 (2.72-5.50); P = 0.0037; and Hsp90, 7.66 (6.32-9.27); P < 0.0001 in DCD20), and may be useful in identifying high-risk hearts at the point of harvest (Hsp90). CONCLUSIONS: We demonstrate that our preclinical model recapitulates the cardio-respiratory decompensation observed in humans, and that EVHP appears necessary to unmask distinguishing features of severely injured DCD hearts. Furthermore, we outline a clinically relevant multimodal approach to assessing candidate DCD hearts. Novel mRNA signatures correlated with elevations in cardiac Troponin-I in severely injured hearts during EVHP, and may also detect injury at the point of harvest.

Rat Heterotopic Abdominal Heart/Single-lung Transplantation in a Volume-loaded Configuration.

Herein, we describe a novel technique for heterotopic abdominal heart-lung transplantation (HAHLT) in rats. The configuration of the transplant graft involves anastomosis of donor inferior vena cava (IVC) to recipient IVC, and donor ascending aorta (Ao) to recipient abdominal Ao. The right upper and middle lung lobes are preserved and function as conduits for blood flow from right heart to left heart. There are several advantages to using this technique, and it lends itself to a broad range of applications. Because the graft is transplanted in a configuration that allows for dyamic volume-loading, cardiac function may be directly assessed in vivo. The use of pressure-volume conductance catheters permits characterization of load-dependent and load-independent hemodynamic parameters. The graft may be converted to a loaded configuration by applying a clamp to the recipient's infra-hepatic IVC. We describe modified surgical techniques for both donor and recipient operations, and an ideal myocardial protection strategy. Depending on the experimental aim, this model may be adapted for use in both acute and chronic studies of graft function, immunologic status, and variable ventricular loading conditions. The conducting airways to the transplanted lung are preserved, and allow for acute lung re-ventilation. This facilitates analysis of the effects of the mixed venous and arterial blood providing coronary perfusion to the graft. A limitation of this model is its technical complexity. There is a significant learning curve for new operators, who should ideally be mentored in the technique. A surgical training background is advantageous for those wishing to apply this model. Despite its complexity, we aim to present the model in a clear and easily applicable format. Because of the physiologic similarity of this model to orthotopic transplantation, and its broad range of study applications, the effort invested in learning the technique is likely to be worthwhile.

Rubella immunity among pregnant women in a Canadian provincial screening program.

BACKGROUND: There are limited recent data on rubella immunity in women of childbearing age in Canada. In the present paper, the proportion of rubella seroreactivity and redundant testing (testing of women previously seropositive when tested by the same physician) in the Alberta prenatal rubella screening program were studied. METHODS: In the present retrospective observational study, data on all specimens submitted for prenatal screening in Alberta between August 2002 and December 2005 were extracted from the Provincial Laboratory for Public Health database. The proportion of rubella screening and immunoglobulin G (IgG) seroreactivity were determined. Demographic variables were compared between rubella seroreactors and nonseroreactors. The proportion of redundant testing was determined. RESULTS: Of 159,046 prenatal specimens, 88.3% (n=140,473) were screened for rubella immunity. In total, 8.8% of specimens tested negative for rubella IgG. Younger women (23.2% of women younger than 20 years of age versus 4.7% of women between 35 and 39 years of age; P<0.001) and women from northern Alberta (11.9% versus 8.1% [overall]; P<0.001) were significantly more likely to have seronegative specimens. Of the 20,044 women who had multiple rubella immunity screenings, 88.1% (n=17,651) had multiple positive test results. In total, 20.7% of the 42,274 specimens submitted from women with multiple screenings were deemed redundant. DISCUSSION: Younger women were most likely to be seronegative for rubella. The public health significance of women entering their childbearing years with low or undetectable rubella IgG levels remains to be determined. A large number of women with documented rubella immunity were unnecessarily retested.