Sparing the Prod: Providing an Alternative to Endomyocardial Biopsies With Noninvasive Surveillance After Heart Transplantation During COVID-19.

Background: The COVID-19 pandemic has reduced access to endomyocardial biopsy (EMB) rejection surveillance in heart transplant (HT) recipients. This study is the first in Canada to assess the role for noninvasive rejection surveillance in personalizing titration of immunosuppression and patient satisfaction post-HT. Methods: In this mixed-methods prospective cohort study, adult HT recipients more than 6 months from HT had their routine EMBs replaced by noninvasive rejection surveillance with gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) testing. Demographics, outcomes of noninvasive surveillance score, hospital admissions, patient satisfaction, and health status on the medical outcomes study 12-item short-form health survey (SF-12) were collected and analyzed, using t tests and χ2 tests. Thematic qualitative analysis was performed for open-ended responses. Results: Among 90 patients, 31 (33%) were enrolled. A total of 36 combined GEP/dd-cfDNA tests were performed; 22 (61%) had negative results for both, 10 (27%) had positive GEP/negative dd-cfDNA results, 4 (11%) had negative GEP/positive dd-cfDNA results, and 0 were positive on both. All patients with a positive dd-cfDNA result (range: 0.19%-0.81%) underwent EMB with no significant cellular or antibody-mediated rejection. A total of 15 cases (42%) had immunosuppression reduction, and this increased to 55% in patients with negative concordant testing. Overall, patients' reported satisfaction was 90%, and on thematic analysis they were more satisfied, with less anxiety, during the noninvasive testing experience. Conclusions: Noninvasive rejection surveillance was associated with the ability to lower immunosuppression, increase satisfaction, and reduce anxiety in HT recipients, minimizing exposure for patients and providers during a global pandemic.

Contexte: La pandémie de COVID-19 a réduit l'accès à la biopsie endomyocardique pour surveiller le risque de rejet après une greffe du cœur. Cette étude est la première à être menée au Canada pour évaluer le rôle de la surveillance non invasive du risque de rejet en personnalisant le titrage de l'immunosuppression et la satisfaction du patient après la greffe cardiaque. Méthodologie: Dans le cadre de cette étude de cohorte prospective à méthodes mixtes, des adultes ayant reçu une greffe cardiaque depuis plus de six mois ont vu leurs biopsies endomyocardiques régulières remplacées par une surveillance non invasive du risque de rejet qui consiste à établir le profil de l'expression génique et à analyser l'ADN acellulaire dérivé du donneur. Les données démographiques, les résultats du score de surveillance non invasive, les admissions à l'hôpital, la satisfaction des patients et l'état de santé tirés du questionnaire SF-12 (questionnaire abrégé sur la santé comprenant 12 items) de l'étude sur les issues médicales ont été colligés et analysés au moyen des tests T et des tests χ2. Les réponses ouvertes ont fait l'objet d'une analyse qualitative thématique. Résultats: Parmi 90 patients, 31 (33 %) ont été recrutés. Au total, 36 tests combinés de profilages de l'expression génique et d'ADN acellulaire dérivé du donneur ont été réalisés; les résultats ont été négatifs pour les deux tests dans 22 cas (61 %), positifs pour le profilage de l'expression génique et négatifs pour l'ADN acellulaire dans 10 cas (27 %), négatifs pour le profilage de l'expression génique et positifs pour l'ADN acellulaire dans quatre cas (11 %) et aucun cas n'a donné de résultats positifs pour les deux types de tests. Tous les patients qui ont donné des résultats positifs à l'analyse de l'ADN acellulaire dérivé du donneur (fourchette : 0,19 % à 0,81 %) ont subi une biopsie endomyocardique n'ayant révélé aucun rejet cellulaire ou à médiation par anticorps important. Au total, 15 cas (42 %) affichaient une immunosuppression réduite, proportion qui a grimpé à 55 % chez les patients dont les tests de concordance ont donné des résultats négatifs. Dans l'ensemble, le niveau de satisfaction rapporté par les patients était de 90 % et, à l'analyse thématique, ils étaient plus satisfaits et moins anxieux pendant les tests non invasifs. Conclusions: La surveillance non invasive du risque de rejet a été associée à la capacité de diminuer l'immunosuppression, d'augmenter la satisfaction et de réduire l'anxiété chez les patients qui ont reçu une greffe cardiaque, en plus de réduire l'exposition des patients et du personnel médical dans le contexte d'une pandémie.

The IMPACT-CABG trial: A multicenter, randomized clinical trial of CD133+ stem cell therapy during coronary artery bypass grafting for ischemic cardiomyopathy.

OBJECTIVES: The IMPACT-CABG trial is the first North American multicenter phase II randomized study of intramyocardial delivery of autologous CD133+ stem cells in patients with chronic ischemic cardiomyopathy undergoing coronary artery bypass grafting. The primary objective was to demonstrate safety, including freedom from major adverse cardiac events. The secondary objective was to evaluate feasibility of same-day autologous cell preparation. Although the trial was not powered to evaluate LV function, exploratory data were collected. METHODS: After 7 open-label patients who received cells, patients randomly received stem cells or placebo (N = 40 total, 20 per center). After completion of coronary anastomoses, up to 10 million CD133+, CD34+, CD45+ triple-positive cells or placebo were injected into the infarct and border zones. Patients were followed up clinically and underwent magnetic resonance imaging preoperatively and after 6 months. RESULTS: There were no procedural complications from bone marrow isolation and cell injection, no in-hospital mortality, and no protocol-related complications. Four patients had transient renal insufficiency, with 1 death during 6-month follow-up. Magnetic resonance imaging revealed that left ventricular volumes and ejection fractions improved in all patients (no difference between groups). CONCLUSIONS: The trial successfully met both primary and secondary objectives, demonstrating that same-day isolation and autologous CD133+ cell delivery with coronary artery bypass grafting is safe and feasible. The positive findings support a larger randomized, multicenter trial, with higher numbers of transplanted cells to demonstrate beneficial effects. The upcoming IMPACT-CABG II trial will evaluate higher cell doses and pharmacologic enhancement to determine whether these cells improve perfusion and myocardial function.

Microplegia during coronary artery bypass grafting was associated with less low cardiac output syndrome: a propensity-matched comparison.

BACKGROUND: Microplegia delivers blood and additives for cardioplegia with minimal crystalloid. We retrospectively compared microplegia with standard 8:1 blood cardioplegia with a propensity-matched analysis in patients undergoing isolated coronary artery bypass graft (CABG) surgery. METHODS: Prospectively collected data for 2,630 consecutive patients who underwent isolated CABG surgery (2004 to 2006) with the exclusive use of microplegia was compared with an equivalent 3-year cohort (1998 to 2000) of 5,058 consecutive isolated CABG patients with the exclusive use of 8:1 diluted blood cardioplegia. Propensity score matching identified 1,980 matched pairs (in each group) for analysis. RESULTS: In the matched groups, the hospital mortality was identical (1.2%). The prevalence of low cardiac output syndrome was significantly (p< 0.001) lower in the later period when microplegia was employed (2.7%) compared with the standard cardioplegia group (5.0%). Although these results may also reflect improvements in care with time, a multivariable logistic regression analysis of the entire cohort (not matched) also demonstrated a twofold independent reduction in low cardiac output syndrome in microplegia patients (odds ratio, 1.9; 95% confidence interval 1.4 to 2.5). CONCLUSIONS: Compared with 8:1 blood cardioplegia, microplegia during isolated CABG surgery was associated with a lower incidence of postoperative low cardiac output syndrome. Microplegia may reduce postoperative cardiac edema, increase buffering, and permit more rapid recovery of ventricular function. Randomized trials are required to determine whether the relationship between microplegia and reduced low output syndrome is causal or is merely an association.

Role of WNT/ß-catenin signaling in rejuvenating myogenic differentiation of aged mesenchymal stem cells from cardiac patients.

Autologous stem cell therapy has not been as effective as forecasted from preclinical studies. Patient age was reported as an important contributing factor. The goal of this study was to uncover age-dependent mechanisms of stem cell dysfunction and to investigate possible means to restore the cellular function. Bone marrow mesenchymal stem cells (MSCs) were isolated from cardiovascular patients. Cell proliferation and number of colonies were inversely correlated with patient age. Myogenic differentiation of MSCs in culture was induced with 5-azacytidine. Differentiation correlated with age, with less differentiation in MSCs from aged patients. We performed real-time PCR to identify genes in the WNT/ß-catenin signaling network and found that transcript levels of CTNNB1, LEF1, FZD8, WNT3A, and SFRP4 were negatively correlated with age, whereas FOSL1, LRP6, and FZD6 were positively correlated with age. Protein evaluation showed that ß-catenin nuclear translocation correlated with age and was lower in aged MSCs. Aged MSCs treated with lithium chloride-to increase the bioavailability of ß-catenin-recovered their capacity for myogenic differentiation through myocyte enhancer factor 2C but not with the knockdown of ß-catenin using small-interfering RNA. This study may be the first to relate reduced nuclear ß-catenin bioavailability in MSCs from aged patients. Most important, this abnormality was potentially recoverable, providing a target for improving the function of bone marrow stem cells and their clinical utility in aged patients.

A multicenter prospective randomized trial of a second-generation anastomotic device in coronary artery bypass surgery.

OBJECTIVE: Our objective was to perform a prospective randomized trial to evaluate the clinical and angiographic outcomes of a second-generation anastomotic device used for saphenous vein grafts. METHODS: Patients undergoing nonemergency isolated coronary artery bypass grafting at 3 centers from August 2003 to December 2004 with at least 2 saphenous vein grafts were included. The proximal anastomoses were randomized, within each patient, to be constructed by the connector or by suture. One-year graft patency was evaluated by coronary angiography, magnetic resonance imaging, or computed tomography and analyzed on an intent-to-treat basis. RESULTS: A total of 151 patients (65 +/- 9 years, 87% male) who met inclusion/exclusion criteria were enrolled in the study and were analyzed. A total of 489 grafts were constructed (3.2 +/- 0.5 grafts per patient), including 327 vein grafts randomized to the connector (n = 162) or suture (n = 165). In 162 connector grafts, 151 devices were successfully implanted. Technical issues required explantation of 11 devices intraoperatively. Patency was evaluated in 120 (81%) patients with 260 study grafts. Seventy-four patients with 161 grafts were evaluated by coronary angiography, 31 patients with 69 grafts by magnetic resonance imaging, and 15 patients with 30 grafts by computed tomography. The 1-year patency rate for study grafts constructed with the anastomotic connector was 92.2% (118/128) and for hand-sutured grafts, 91.7% (121/132). CONCLUSIONS: This prospective multicenter randomized controlled trial demonstrated good in-hospital and late clinical outcomes and excellent 1-year patency for vein grafts anastomosed both by the St Jude Medical second-generation aortic connector system and by hand. The patency of the connector grafts did not differ from that of the hand-sutured grafts.

Autologous cell transplantation and a discussion of the implications for nursing practice.

Heart failure is a progressive disorder. An estimated 400,000 Canadians are diagnosed annually with heart failure, and a quarter experience severe heart failure that is unresponsive to medical therapy. Autologous cell transplantation (ACT) has been proposed as a new approach for cardiac repair, and holds enormous potential for the regeneration of injured myocardium cells. This paper explores the nursing implications of ACT. Specifically, the need for ongoing education, the delivery of psychosocial counseling interventions, and ongoing health assessments of the individual will be addressed.