Digitally enabled cardiac rehabilitation following coronary revascularization: results from a single centre feasibility study.

Wearable activity monitors, together with smartphone-based health and fitness applications (apps), are becoming more accessible and their widespread use provides an additional opportunity for the recording of cardiovascular metrics in patients with cardiovascular disease. The use of selected metrics by cardiac rehabilitation (CR) programmes allows the facilitation of individualized and tailored positive lifestyle changes to patients and places the patient at the centre of their recovery programme. To investigate the role of such devices on outcomes with patients on a CR programme, a cohort/case-control study was conducted. Patients post-myocardial infarction who were treated with either percutaneous coronary intervention or surgical coronary revascularisation at a single centre were invited to use a physical activity monitor linked to a customized app at their initial assessment for the rehabilitation programme. Those who accepted were allocated to the treatment group. The control group was selected from a larger pool of 400 historical and concurrent patients. Propensity matching was used to associate each case with their closest control. The changes in self-reported physical activity were similar for both groups at the end of the CR programme (EOP). The digitally monitored group tended to achieve greater METS (metabolic equivalent of task - a measure of exercise intensity) at 12 weeks (P < 0.059); however, no difference was observed in the overall change in METS at EOP (P < 0.333). Although no difference was noted in diastolic blood pressure, a statistically significant drop in the systolic blood pressure in the digitally monitored group (P < 0.004) was detected. In this study, the innovative combination of technology and face-to-face CR showed promising results and assisted the individualization of delivered content. This intervention could easily be replicated and expanded. Challenges are the recruitment of the elderly population, those who may be less engaged with or have less access to technology, and the underrepresentation of women in the study sample.

Percutaneous Device Closure of Paravalvular Leak: Combined Experience From the United Kingdom and Ireland.

BACKGROUND: Paravalvular leak (PVL) occurs in 5% to 17% of patients following surgical valve replacement. Percutaneous device closure represents an alternative to repeat surgery. METHODS: All UK and Ireland centers undertaking percutaneous PVL closure submitted data to the UK PVL Registry. Data were analyzed for association with death and major adverse cardiovascular events (MACE) at follow-up. RESULTS: Three hundred eight PVL closure procedures were attempted in 259 patients in 20 centers (2004-2015). Patient age was 67±13 years; 28% were female. The main indications for closure were heart failure (80%) and hemolysis (16%). Devices were successfully implanted in 91% of patients, via radial (7%), femoral arterial (52%), femoral venous (33%), and apical (7%) approaches. Nineteen percent of patients required repeat procedures. The target valve was mitral (44%), aortic (48%), both (2%), pulmonic (0.4%), or transcatheter aortic valve replacement (5%). Preprocedural leak was severe (61%), moderate (34%), or mild (5.7%) and was multiple in 37%. PVL improved postprocedure (P<0.001) and was none (33.3%), mild (41.4%), moderate (18.6%), or severe (6.7%) at last follow-up. Mean New York Heart Association class improved from 2.7±0.8 preprocedure to 1.6±0.8 (P<0.001) after a median follow-up of 110 (7-452) days. Hospital mortality was 2.9% (elective), 6.8% (in-hospital urgent), and 50% (emergency) (P<0.001). MACE during follow-up included death (16%), valve surgery (6%), late device embolization (0.4%), and new hemolysis requiring transfusion (1.6%). Mitral PVL was associated with higher MACE (hazard ratio [HR], 1.83; P=0.011). Factors independently associated with death were the degree of persisting leak (HR, 2.87; P=0.037), New York Heart Association class (HR, 2.00; P=0.015) at follow-up and baseline creatinine (HR, 8.19; P=0.001). The only factor independently associated with MACE was the degree of persisting leak at follow-up (HR, 3.01; P=0.002). CONCLUSION: Percutaneous closure of PVL is an effective procedure that improves PVL severity and symptoms. Severity of persisting leak at follow-up is independently associated with both MACE and death. Percutaneous closure should be considered as an alternative to repeat surgery.

A fatal case of infective endocarditis complicated by acute COVID-19 pneumonia.

A 74-year-old man with no co-morbidities presented to hospital with a 3-day history of diarrhoea and vomiting. He met the modified Duke's criteria for definite infective endocarditis and was immediately started on an intravenous antibiotic. Over Days 1-9, he developed renal failure. On Day 10, he was transferred to a tertiary hospital for mitral valve replacement. However, he tested positive for SARS-CoV-2 on arrival at the tertiary hospital, which delayed his surgery. He underwent bi-weekly nasopharyngeal swabs for SARS-CoV-2 with a plan to operate as soon as he tested negative, or as soon as his incubation period for COVID-19 pneumonia had elapsed. Unfortunately, he died on Day 31 from acute respiratory distress syndrome secondary to COVID-19 pneumonia. We describe the challenges in deciding on the optimal timing for valve replacement. We conclude by suggesting that earlier valve replacement may result in better outcomes.

Usefulness of the NULL-PLEASE Score to Predict Survival in Out-of-Hospital Cardiac Arrest.

PURPOSE: Out-of-hospital cardiac arrest (OHCA) carries a very high mortality rate even after successful cardiopulmonary resuscitation. Currently, information given to relatives about prognosis following resuscitation is often emotive and subjective, and varies with clinician experience. We aimed to validate the NULL-PLEASE score to predict survival following OHCA. METHODS: A multicenter cohort study was conducted, with retrospective and prospective validation in consecutive unselected patients presenting with OHCA. The NULL-PLEASE score was calculated by attributing points to the following variables: Nonshockable initial rhythm, Unwitnessed arrest, Long low-flow period, Long no-flow period, pH <7.2, Lactate >7.0 mmol/L, End-stage renal failure, Age ≥85 years, Still resuscitation, and Extracardiac cause. The primary outcome was in-hospital death. RESULTS: We assessed 700 patients admitted with OHCA, of whom 47% survived to discharge. In 300 patients we performed a retrospective validation, followed by prospective validation in 400 patients. The NULL-PLEASE score was lower in patients who survived compared with those who died (0 [interquartile range 0-1] vs 4 [interquartile range 2-4], P < .0005) and strongly predictive of in-hospital death (C-statistic 0.874; 95% confidence interval, 0.848-0.899). Patients with a score ≥3 had a 24-fold increased risk of death (odds ratio 23.6; 95% confidence interval, 14.840-37.5; P < .0005) compared with those with lower scores. A score ≥3 has a 91% positive predictive value for in-hospital death, while a score <3 predicts a 71% chance of survival. CONCLUSION: The easy-to-use NULL-PLEASE score predicts in-hospital mortality with high specificity and can help clinicians explain the prognosis to relatives in an easy-to-understand, objective fashion, to realistically prepare them for the future.

Proteomic identification of non-Gal antibody targets after pig-to-primate cardiac xenotransplantation.

BACKGROUND: Experience with non-antigenic galactose alpha1,3 galactose (alphaGal) polymers and development of alphaGal deficient pigs has reduced or eliminated the significance of this antigen in xenograft rejection. Despite these advances, delayed xenograft rejection (DXR) continues to occur most likely due to antibody responses to non-Gal endothelial cell (EC) antigens. METHODS: To gauge the diversity of the non-Gal antibody response we used antibody derived from CD46 transgenic heterotopic cardiac xenografts performed without T-cell immunosuppression, Group A (n = 4) and Gal knockout (GT-KO) heart transplants under tacrolimus and sirolimus immunosuppression, Group B (n = 8). Non-Gal antibody was measured by flow cytometry and by western blots using GT-KO EC membrane antigens. A nanoLC/MS/MS analysis of proteins recovered from 2D gels was used to identify target antigens. RESULTS: Group A recipients exhibited a mixed cellular and humoral rejection. Group B recipients mainly exhibited classical DXR. Western blot analysis showed a non-Gal antibody response induced by GT+ and GT-KO hearts to an overlapping set of pig aortic EC membrane antigens. Proteomic analysis identified 14 potential target antigens but failed to define several immunodominant targets. CONCLUSIONS: These experiments indicate that the non-Gal antibody response is directed to a number of stress response and inflammation related pig EC antigens and a few undefined targets. Further analysis of these antibody specificities using alternative methods is required to more fully define the repertoire of non-Gal antibody responses.

Effects of Patent Foramen Ovale Closure on Obstructive Sleep Apnea Syndrome: PCOSA Study.

BACKGROUND: Previous studies have shown a higher prevalence of patent foramen ovale (PFO) in patients with obstructive sleep apnea syndrome (OSAS). Right to left shunting through a PFO may be encouraged by the respiratory physiology of OSAS, contributing to the disease pathophysiology. We assessed whether PFO closure would improve respiratory polygraphy parameters compared with baseline measurements in patients with OSAS. METHODS: Twenty-six patients with newly diagnosed OSAS and a moderate-large PFO (prevalence, 18% of 143 patients screened) were referred for PFO closure. The oxygen desaturation index (ODI), apnea-hypopnea index (AHI), Epworth Sleepiness Scale (ESS), 6-minute walk test (6MWT), and Sleep Apnea Quality of Life Index (SAQLI) results were compared in these patients at baseline (before continuous positive pressure ventilation [CPAP]) and at 6-month follow-up (after interrupting CPAP for 1 week). RESULTS: All PFOs were safely sealed at 6 months, as confirmed by repeated transthoracic echocardiography. The ODI (44.8 [interquartile range (IQR), 31.2-63.5) vs 42.3 [IQR, 34.0-60.8]; P = 0.89) and AHI (47.9 [IQR, 31.5-65.2] vs 42.3 [IQR, 32.1-63]; P = 0.99) did not change after PFO closure nor did the 6MWT, although the ESS (13.0 [IQR, 12.0-16.8] vs 6.0 [IQR, 4.0-8.8]; P < 0.001) and the SAQLI (3.4 [IQR, 2.8-4.3] vs 4.4 [IQR, 3.9-5.3]; P < 0.001) did improve. CONCLUSIONS: The prevalence of PFO in OSAS appears to be no higher than that in the general population. Although PFO closure is safe and effective, it did not improve respiratory polygraphy measures of OSAS severity. The improvement in the ESS and SAQLI likely reflect residual benefits from CPAP.

Stunning and Right Ventricular Dysfunction Is Induced by Coronary Balloon Occlusion and Rapid Pacing in Humans: Insights From Right Ventricular Conductance Catheter Studies.

BACKGROUND: We sought to determine whether right ventricular stunning could be detected after supply (during coronary balloon occlusion [BO]) and supply/demand ischemia (induced by rapid pacing [RP] during transcatheter aortic valve replacement) in humans. METHODS AND RESULTS: Ten subjects with single-vessel right coronary artery disease undergoing percutaneous coronary intervention with normal ventricular function were studied in the BO group. Ten subjects undergoing transfemoral transcatheter aortic valve replacement were studied in the RP group. In both, a conductance catheter was placed into the right ventricle, and pressure volume loops were recorded at baseline and for intervals over 15 minutes after a low-pressure BO for 1 minute or a cumulative duration of RP for up to 1 minute. Ischemia-induced diastolic dysfunction was seen 1 minute after RP (end-diastolic pressure [mm Hg]: 8.1±4.2 versus 12.1±4.1, P<0.001) and BO (end-diastolic pressure [mm Hg]: 8.1±4.0 versus 8.7±4.0, P=0.03). Impairment of systolic and diastolic function after BO remained at 15-minutes recovery (ejection fraction [%]: 55.7±9.0 versus 47.8±6.3, P<0.01; end-diastolic pressure [mm Hg]: 8.1±4.0 versus 9.2±3.9, P<0.01). Persistent diastolic dysfunction was also evident in the RP group at 15-minutes recovery (end-diastolic pressure [mm Hg]: 8.1±4.1 versus 9.9±4.4, P=0.03) and there was also sustained impairment of load-independent indices of systolic function at 15 minutes after RP (end-systolic elastance and ventriculo-arterial coupling [mm Hg/mL]: 1.25±0.31 versus 0.85±0.43, P<0.01). CONCLUSIONS: RP and right coronary artery balloon occlusion both cause ischemic right ventricular dysfunction with stunning observed later during the procedure. This may have intraoperative implications in patients without right ventricular functional reserve.

Increased immunosuppression, not anticoagulation, extends cardiac xenograft survival.

BACKGROUND: Cardiac xenograft function is lost due to delayed xenograft rejection (DXR) characterized by microvascular thrombosis and myocardial necrosis. The cause of DXR is unknown but may result from thrombosis induced by antibody-mediated activation of endothelial cells and/or by incompatibilities in thromboregulatory interactions. METHODS: To examine these issues, a series (Groups 1-6) of previous transgenic CD46 pig-to-baboon heterotopic cardiac transplants were reanalyzed for baseline immunosuppressive levels, graft survival and infectious complications with and without systemic anticoagulation. Groups 1-4 received low dose tacrolimus and sirolimus maintenance therapy, with splenectomy, anti-CD20 and daily alpha-Gal polymer. Group 1 recipients received no anticoagulation. Groups 2-4 were anticoagulated with aspirin and Plavix, Lovenox, or Coumadin, respectively. Group 5 was treated with Lovenox and high dose tacrolimus and sirolimus maintenance therapy. Group 6 recipients received no postoperative anticoagulation but the same immunosuppression as group 5. RESULTS: Median survival (15-22 days) within groups 1-4 was not significantly different. At rejection all tissues exhibited microvascular thrombosis, coagulative necrosis and similar levels of platelet and fibrin deposition. Groups 5 and 6 median survival (76 days) was significantly increased compared to groups 1-4. There was no significant difference in median survival between Lovenox treated recipients (68 days) and anticoagulant free recipients (96 days). Rejected tissues showed vascular antibody deposition, microvascular thrombosis, and myocyte necrosis. CONCLUSION: Significant prolongation in xenograft survival is achieved by improved immunosuppression. These results suggest that ongoing immune responses remain the major stimulus for DXR.

Cardiac xenotransplantation: recent preclinical progress with 3-month median survival.

OBJECTIVES: Transplantation is limited by a lack of human organ donors. Organs derived from animals, most likely the pig, represent a potential solution to this problem. For the heart, 90-day median graft survival of life-supporting pig hearts transplanted to nonhuman primates has been considered a reasonable standard for entry into the clinical arena. Overcoming the immune barrier to successful cardiac xenotransplantation is most appropriately first explored with the non-life-supporting heterotopic model. METHODS: We performed a series of 7 heterotopic heart transplantations from CD46 transgenic pigs to baboons using a combination of therapeutic agents largely targeted at controlling the synthesis of anti-pig antibodies. Rituximab (anti-CD20) and Thymoglobulin (rabbit antithymocyte globulin [ATG]; SangStat Medical Corp, Fremont, Calif) were used as induction therapy. Baseline immunosuppression consisted of splenectomy, tacrolimus, sirolimus, steroids, and TPC (an anti-Gal antibody therapeutic). Rejection events were not treated. RESULTS: By using Kaplan-Meier analysis, median graft survival was 96 days (range, 15-137 days; 95% confidence interval, 38-99 days). Only 2 grafts were lost as a result of rejection, as defined by cessation of graft palpation. There was no evidence of a consumptive coagulopathy, infectious complications were treatable, and no posttransplantation lymphoproliferative disorders occurred. No cellular infiltration was observed. CONCLUSIONS: This study reports the longest median survival to date (96 days) of pig hearts transplanted heterotopically into baboons. Duplication of these results in the orthotopic life-supporting position could bring cardiac xenotransplantation to the threshold of clinical application.

European experience and perspectives on transcatheter aortic valve replacement.

It could be argued that the European experience with transcatheter aortic valve replacement (TAVR) has been central to the success of this novel technology. After all, Europe provided the birthplace for the first clinical TAVR and allowed commercial approval of the early devices long before they were widely available elsewhere. Many of the largest registries are also European, helping to formulate contemporaneous guidelines with the backing of the influential cardiology and cardiothoracic societies. Despite the significant economic downturn that coincided with the availability of transcatheter technology, funding has been largely forthcoming and is increasing year on year. As we await the results of the randomised controlled trials examining TAVR in a lower risk cohort, the European adoption of the TAVR technology appears set to continue.

Direct TAVI using a balloon-expandable system: a novel technique to eliminate pre-deployment balloon aortic valvuloplasty.

AIMS: Transcatheter aortic valve implantation (TAVI) is now the therapy of choice for those patients with severe symptomatic aortic stenosis who are considered to be at too high risk for conventional surgery. Balloon aortic valvuloplasty (BAV) is routinely performed to allow placement of the balloon-expandable valve during the procedure. Instrumentation of the valve has been linked to procedural stroke risk, with the associated runs of rapid pacing risking haemodynamic compromise. We outline a novel technique to eliminate BAV prior to transcatheter valve placement. METHODS AND RESULTS: We illustrate a clinical case that outlines the problems encountered in transcatheter valve placement despite a prior BAV. The solution used in this case involved the partial inflation of the distal section of the balloon allowing easy passage of the SAPIEN XT valve from the transaortic route. After bench testing, we report a series of patients who have undergone this "direct TAVI" procedure from both the transaortic and the transfemoral routes. CONCLUSIONS: In a limited series within a single centre, "direct TAVI" has been shown to be effective in allowing accurate placement of a balloon-expandable device without the need for prior BAV.

Remote ischemic preconditioning improves outcome at 6 years after elective percutaneous coronary intervention: the CRISP stent trial long-term follow-up.

BACKGROUND: Postprocedural myocardial infarction (type 4a) has been shown to be an adverse prognostic indicator after elective percutaneous coronary intervention (PCI). The Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) study demonstrated that remote ischemic preconditioning reduced procedural symptoms, ECG ST-segment deviation, and cardiac troponin I release after elective PCI and reduced the major adverse cardiac and cerebral event (MACCE) rate at 6 months. We were interested to confirm if this early benefit in MACCE rate in the remote ischemic preconditioning group was sustained long-term. METHODS AND RESULTS: Patients were telephoned by researchers blinded to the randomization details. MACCE, defined as all-cause mortality, nonfatal myocardial infarction, transient ischemic attack or stroke, and heart failure requiring hospital admission, were adjudicated by case note and national database review. One hundred ninety-two (89.3%) of the 225 patients with elective PCI randomized in the original study were available for long-term follow-up (mean time to event or last follow-up: 1579.7±603.6 days). There were a total of 59 (30.7%) MACCEs. Patients with an MACCE had a higher mean cardiac troponin I after PCI (±SD): 2.07±6.99 versus 0.91±2.07 ng/mL (P=0.05). The MACCE rate at 6 years remained lower in the remote ischemic preconditioning group (hazard ratio, 0.58; 95% confidence interval, 0.35-0.97; P=0.039; absolute risk reduction=0.13 and number needed to treat=8 to prevent the MACCE at 6 years). CONCLUSIONS: Remote ischemic preconditioning reduces the incidence of postprocedural cardiac troponin I after elective PCI and confers an MACCE-free survival benefit at both short- and long-term follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.ukcrn.org.uk. Unique identifier: UKCRN 4074.

Relative radio-opacity of commonly consumed fish species in South East Queensland on lateral neck x-ray: an ovine model.

OBJECTIVE: To determine the relative radio-opacity on plain x-ray of bones of fish species commonly consumed in South East Queensland. DESIGN: A cadaveric sheep model was used to mimic the soft tissues of a human neck. Bones of 10 fish species were placed in the paratracheal tissues and adjacent to the larynx. X-rays were taken and the images (including four control images with no bones) were incorporated into a Microsoft PowerPoint presentation to be interpreted by emergency specialists and registrars. Observers were blinded to which specimens contained fishbones and which did not. MAIN OUTCOME MEASURES: Sensitivity and specificity of plain x-rays for detecting impacted fishbones. RESULTS: Significant interobserver variability was identified. Despite this, the overall specificity of plain x-rays was 90%. The sensitivity of the technique was 79% overall, but varied significantly between fish species. CONCLUSION: Lateral soft tissue neck x-ray is an appropriate screening tool in cases of a suspected impacted fishbone. If a fishbone is identified on x-ray, the patient should be referred for endoscopy without further imaging. X-ray may be of limited value in cases of Dory or Spanish mackerel bone ingestion. In such cases, a computed tomography scan should be the first-line investigation.

Ex vivo hypothermic recirculatory adenoviral gene transfer to the transplanted pig heart.

BACKGROUND: To facilitate the application of adenoviral gene therapy in clinical heart transplantation, we developed an ex vivo hypothermic recirculatory adenoviral gene transfer method to the transplanted pig heart. METHODS: Experimental animals were assigned into three groups; controls, 1x10(8) plaque-forming units (pfu)/ml group and 1x10(9) pfu/ml group. During the 30 min gene transfer perfusion, 200 ml of University of Wisconsin solution containing the adenoviral vector was recirculated through the coronary vessels. The myocardial temperature was maintained below 4 degrees C and the perfusion pressure was adjusted at 50 mmHg. RESULTS: Cardiac myocyte transduction efficiencies in the 1x10(8) pfu/ml group were 0.04% and 0.07%, whereas transduction efficiencies in the 1x10(9) pfu/ml group were widely distributed from 0.45% to 22.62%. The gene transduction efficiency increased with the virus titer. Additionally, no difference in the transduction efficiency was observed between different segments of the left ventricle. The current gene transfer method at 1x10(9) pfu/ml of adenovirus titer enabled homogeneous gene transduction into the transplanted pig heart up to a maximum of 22.62%. CONCLUSIONS: This model can be applied to a large isolated heart and will greatly facilitate the investigation of gene therapy in large animal models of heart transplantation.

T-cell responses during pig-to-primate xenotransplantation.

UNLABELLED: Xenotransplantation using porcine organs may resolve a chronic shortage of donor organs for clinical transplantation if significant immunological barriers can be overcome. To determine the potential role of T lymphocytes in Xenograft (Xg) rejection, we transplanted transgenic hCD46 porcine hearts heterotopically into baboon recipients. METHODS: Recipients were treated to deplete anti-Gal antibody with a non-antigenic alpha-Gal polyethylene glycol polymer (TPC) (n = 2), TPC plus rituximab (anti-CD20) (n = 1) or were untreated (n = 1). None of the recipients received T-cell immunosuppression. RESULTS: All Xgs failed within 7 days and showed evidence of a mixed humoral and cellular rejection process. Cellular infiltration consisting primarily of CD4+ T cells and few CD8+ T cells. Proliferation and cytotoxicity assays showed sensitization of CD4+ and CD8+ T cells that reacted with porcine IFN-gamma (pIFN-gamma)-stimulated porcine aortic endothelial cells (PAEC). The CD4+ lymphocytes displayed greater cytotoxicity than CD8+ cells. An increased frequency of PAEC-specific interleukin (IL) 2 and IFN-gamma-secreting T cells was observed, suggesting a Th1 cytokine bias. An increase in the percentage of circulating CD4+CD28- cells was observed at the time of rejection and over 50% of the CD4+ cells recovered from residual pig tissue at necropsy lacked CD28 expression. CONCLUSIONS: These findings show that lymphocytes are efficiently stimulated by PAEC antigens and can mediate direct tissue destruction. These studies (1) provide an insight into the potential of cellular-mediated cardiac Xg rejection, (2) show for the first time the induction of cytotoxic pig-specific CD4+CD28- lymphocytes and (3) provide a rational basis for determining different modes of immunosuppression to treat Xg rejection.

Cyclosporine decreases vascular progenitor cell numbers after cardiac transplantation and attenuates progenitor cell growth in vitro.

OBJECTIVE: Recent experimental evidence suggests that the neointimal proliferation seen in cardiac allograft vasculopathy may in part derive from recipient progenitor cells. The effect of cyclosporine on these circulating progenitors in the setting of cardiac transplantation is currently unknown. METHODS: Three surgical series were performed: sham operation alone, sham operation with immunosuppression, and heterotopic porcine cardiac transplantation with immunosuppression. The sham operation involved laparotomy and consecutive clamping of the abdominal aorta and inferior vena cava. Post-operative immunosuppression consisted of cyclosporine at therapeutic levels (100-300 ng/ml) and 0.5 mg/kg methylprednisolone. Endothelial outgrowth colony numbers (EOC(CFU)) and smooth muscle outgrowth colony numbers (SOC(CFU)) were quantified weekly for 4 weeks post-operatively. A series of in vitro experiments were performed to determine the effect of cyclosporine on the differentiation, migration, and proliferation of EOCs and SOCs. RESULTS: In the sham alone series there were no changes to either EOC(CFU) or SOC(CFU). In the sham with immunosuppression and the transplant series, both EOC(CFU) and SOC(CFU) fell in the first 2 weeks (p < 0.05) compared with baseline (EOC(CFU), 3.4 +/- 0.6; SOC(CFU), 11.1 +/- 2.8). EOC(CFU) recovered at 4 weeks to above baseline levels in the sham immunosuppression group only (15.2 +/- 3.9; p = 0.01). SOC(CFU) showed no recovery in the immunosuppression groups. Cyclosporine, even at a low dose, prevented differentiation, inhibited proliferation, and attenuated migration of both EOCs and SOCs. CONCLUSION: Immunosuppression in the setting of cardiac transplantation causes a profound reduction in circulating progenitor cells capable of differentiating into endothelial and smooth muscle cells. This effect can in part be explained by the inhibitory effects of cyclosporine on progenitor growth and differentiation seen in this study.