Daly, Richard C.

AbstractSirolimus is used in heart transplant patients with CAV and CNI‐induced nephropathy. However, little is known regarding the tolerability, rejection rate, and effect on renal function when used empirically in children. We describe our experience with the empiric use of a sirolimus‐based immunosuppressive regimen in pediatric heart transplantation recipients. We reviewed records of patients in whom conversion was attempted to a CNI‐free sirolimus‐based regimen. Rejection episodes and measures of renal function were recorded. We attempted to convert 20 patients, of which 16 were successful. In total, six of 20 patients (30%) experienced adverse effects. Of the 16 converted, four patients converted to sirolimus due to CNI‐induced disease (three nephropathy, one CAV), while 12 patients (mean age 5.5 yr, range 0.1–21 yr; 33% female; 33% with a history of congenital heart disease) were empirically switched to sirolimus at a mean of 2.3 yr after transplant. Follow‐up was available for a mean of 2.5 yr after conversion (range 0.5–8.3 yr). The rate of rejection while taking CNIs was 0.18 rejection episodes per patient‐year (total of five episodes), compared with 0.03 rejection episodes per patient‐year (total of one episode) while on sirolimus. Renal function, in terms of GFR, significantly improved after sirolimus conversion at latest follow‐up (from 86 ± 37 mL/min to 130 ± 49 mL/min, p = 0.02). Here, we demonstrate the potential benefit of empiric use of sirolimus in pediatric heart transplant patients in a CNI‐free regimen. Larger and longer studies are needed to further clarify risks of rejection and adverse effect profiles.

This study is a retrospective analysis of the influence of previous cardiac surgery on the outcome of heart transplantation in 118 consecutive recipients from January 1988 to December 1996. Group 1 consisted of 67 patients who had no previous sternotomy, group 2 was 33 patients who had one previous sternotomy, and group 3 was 18 patients who had two or more previous sternotomies. The three groups were demographically similar apart from the indication for transplantation and the sex distribution. Preoperative hemodynamic data, except systolic pulmonary artery pressure, were similar among the three groups. There was no significant difference in hospital mortality, 1-year and 5-year actuarial survival rates, incidence of renal dysfunction requiring dialysis, prolonged respiratory support, elevated total bilirubin, re-exploration for bleeding, incidence of mediastinitis, or postoperative hospital stay between the groups. The rejection-free and infection-free survival rates were similar in the three groups. However, previous sternotomy resulted in significantly longer cardiopulmonary bypass times and increased requirement for blood and blood products. The use of a cell saver limited the need for stored red blood cells. This study demonstrated no survival disadvantage of previous sternotomy in patients undergoing heart transplantation.

BackgroundEndocardial ablation approaches targeting the retroatrial cardiac ganglia to treat atrial fibrillation (AF) have been proposed. However, the potential value using this approach is unknown. Disruption of the autonomic inputs with orthotropic heart transplant (OHT) provides a unique opportunity to study the effects of autonomic innervation on AF genesis and maintenance. We hypothesized that due to denervation, the risk of postoperative AF would be lower following OHT compared to surgical maze even though both groups get isolation of the pulmonary veins.Methods and ResultsWe reviewed 155 OHTs (mean age 52 ± 11 years, 72% males) and used 1:1 age‐, sex‐, and date‐of‐surgery‐matched two control groups from patients undergoing surgical maze or only coronary artery bypass grafting (CABG). Using conditional logistic regression we compared the odds of AF within 2 weeks following OHT versus controls. Postoperative AF occurred in 10/155 (6.5%) OHT patients. The conditional odds of postoperative AF were lower for OHT as compared to controls (vs maze: odds ratio [OR] 0.27 [95% confidence interval (CI) 0.13–0.57], vs CABG: OR 0.38 [0.17–0.81], P = 0.003; and on additional adjustment for left atrial enlargement, vs maze: OR 0.28 [0.13–0.60], vs CABG: OR 0.14 [0.04–0.47], P = 0.0009).ConclusionsRisk of postoperative AF is significantly lower with OHT as in comparison to surgical maze. As both surgeries entail isolation of the pulmonary veins but only OHT causes disruption of autonomic innervation, this observation supports a mechanistic role of autonomic nervous system in AF. The benefit of targeting the cardiac autonomic system to treat AF needs further investigation.

Objective Emerging off-pump beating heart valve repair techniques offer patients less invasive alternatives for mitral valve (MV) repair. However, most of these techniques rely on the limited spatial and temporal resolution of transesophageal echocardiography (TEE) alone, which can make tool visualization and guidance challenging. Methods Using a magnetic tracking system and integrated sensors, we created an augmented reality (AR) environment displaying virtual representations of important intracardiac landmarks registered to biplane TEE imaging. In a porcine model, we evaluated the AR guidance system versus TEE alone using the transapically delivered NeoChord DS1000 system to perform MV repair with chordal reconstruction. Results Successful tool navigation from left ventricular apex to MV leaflet was achieved in 12 of 12 and 9 of 12 (P = 0.2) attempts with AR imaging and TEE alone, respectively. The distance errors of the tracked tool tip from the intended midline trajectory (5.2 ± 2.4 mm vs 16.8 ± 10.9 mm, P = 0.003), navigation times (16.7 ± 8.0 seconds vs 92.0 ± 84.5 seconds, P = 0.004), and total path lengths (225.2 ± 120.3 mm vs 1128.9 ± 931.1 mm, P = 0.003) were significantly shorter in the AR-guided trials compared with navigation with TEE alone. Furthermore, the potential for injury to other intracardiac structures was nearly 40-fold lower when using the AR imaging for tool navigation. The AR guidance also seemed to shorten the learning curve for novice surgeons. Conclusions Augmented reality–enhanced TEE facilitates more direct and safe intracardiac navigation of the NeoChord DS tool from left ventricular apex to MV leaflet. Tracked tool path results demonstrate fourfold improved accuracy, fivefold shorter navigation times, and overall improved safety with AR imaging guidance.

Background— Use of the left internal mammary artery (LIMA) in multivessel coronary artery disease improves survival after coronary artery bypass graft surgery; however, the survival benefit of multiple arterial (MultArt) grafts is debated. Methods and Results— We reviewed 8622 Mayo Clinic patients who had isolated primary coronary artery bypass graft surgery for multivessel coronary artery disease from 1993 to 2009. Patients were stratified by number of arterial grafts into the LIMA plus saphenous veins (LIMA/SV) group (n=7435) or the MultArt group (n=1187). Propensity score analysis matched 1153 patients. Operative mortality was 0.8% (n=10) in the MultArt and 2.1% (n=154) in the LIMA/SV ( P =0.005) group, which was not statistically different ( P =0.996) in multivariate analysis or the propensity-matched analysis ( P =0.818). Late survival was greater for MultArt versus LIMA/SV (10- and 15-year survival rates were 84% and 71% versus 61% and 36%, respectively [ P <0.001], in unmatched groups and 83% and 70% versus 80% and 60%, respectively [ P =0.0025], in matched groups). MultArt subgroups with bilateral internal mammary artery/SV (n=589) and bilateral internal mammary artery only (n=271) had improved 15-year survival (86% and 76%; 82% and 75% at 10 and 15 years [ P <0.001]), and patients with bilateral internal mammary artery/radial artery (n=147) and LIMA/radial artery (n=169) had greater 10-year survival (84% and 78%; P <0.001) versus LIMA/SV. In multivariate analysis, MultArt grafts remained a strong independent predictor of survival (hazard ratio, 0.79; 95% confidence interval, 0.66–0.94; P =0.007). Conclusions— In patients undergoing isolated coronary artery bypass graft surgery with LIMA to left anterior descending artery, arterial grafting of the non–left anterior descending vessels conferred a survival advantage at 15 years compared with SV grafting. It is still unproven whether these results apply to higher-risk subgroups of patients.

Background— Whether mitral valve repair during coronary artery bypass grafting (CABG) improves survival in patients with ischemic mitral regurgitation (MR) remains unknown. Methods and Results— Patients with ejection fraction ≤35% and coronary artery disease amenable to CABG were randomized at 99 sites worldwide to medical therapy with or without CABG. The decision to treat the mitral valve during CABG was left to the surgeon. The primary end point was mortality. Of 1212 randomized patients, 435 (36%) had none/trace MR, 554 (46%) had mild MR, 181 (15%) had moderate MR, and 39 (3%) had severe MR. In the medical arm, 70 deaths (32%) occurred in patients with none/trace MR, 114 (44%) in those with mild MR, and 58 (50%) in those with moderate to severe MR. In patients with moderate to severe MR, there were 29 deaths (53%) among 55 patients randomized to CABG who did not receive mitral surgery (hazard ratio versus medical therapy, 1.20; 95% confidence interval, 0.77–1.87) and 21 deaths (43%) among 49 patients who received mitral surgery (hazard ratio versus medical therapy, 0.62; 95% confidence interval, 0.35–1.08). After adjustment for baseline prognostic variables, the hazard ratio for CABG with mitral surgery versus CABG alone was 0.41 (95% confidence interval, 0.22–0.77; P =0.006). Conclusion— Although these observational data suggest that adding mitral valve repair to CABG in patients with left ventricular dysfunction and moderate to severe MR may improve survival compared with CABG alone or medical therapy alone, a prospective randomized trial is necessary to confirm the validity of these observations. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00023595.

Context— Posttransplant quality of life can be significantly affected by personality characteristics identified before transplant. Objective— Although overall quality of life in heart transplant patients improves after transplant, many studies reveal poorer mental health outcomes after transplant. We aimed to determine whether transplant recipients with an optimistic explanatory style had improved quality of life, fewer depressive symptoms, and increased survival. Design— We reviewed 68 patients who had completed a Minnesota Multiphasic Personality Inventory a mean of 2 years before transplant and examined associations between scores on the Optimism-Pessimism scale, survival rates, and results from the Health Status Questionnaire nearly 4 years after transplant. Results— Optimism was significantly associated with higher quality of life even after age (at the time of transplant), sex, depression score before transplant, time from the personality inventory to transplant, and time from transplant to the Health Status Questionnaire were controlled for. Furthermore, a pessimistic explanatory style was significantly associated with self-reported depressive symptoms, even after depression before transplant was adjusted for. Neither optimism nor pessimism was associated with length of survival. Conclusions— Pretransplant patients with a pessimistic explanatory style reported depressive symptoms nearly 5 years later. Furthermore, over the same time span, patients with an optimistic explanatory style described a significantly higher quality of life than the pessimists described.

Background— We retrospectively analyzed the potential of sirolimus as a primary immunosuppressant in the long-term attenuation of cardiac allograft vasculopathy progression and the effects on cardiac-related morbidity and mortality. Methods and Results— Forty-five cardiac transplant recipients were converted to sirolimus 1.2 years (0.2, 4.0) after transplantation with complete calcineurin inhibitor withdrawal. Fifty-eight control subjects 2.0 years (0.2, 6.5 years) from transplantation were maintained on calcineurin inhibitors. Age, sex, ejection fraction, and time from transplantation to baseline intravascular ultrasound study were not different ( P >0.2 for all) between the groups; neither were secondary immunosuppressants and use of steroids. Three-dimensional intravascular ultrasound studies were performed at baseline and 3.1 years (1.3, 4.6 years) later. Plaque index progression (plaque volume/vessel volume) was attenuated in the sirolimus group (0.7±10.5% versus 9.3±10.8%; P =0.0003) owing to reduced plaque volume in patients converted to sirolimus early (<2 years) after transplantation ( P =0.05) and improved positive vascular remodeling ( P =0.01) in patients analyzed late (>2 years) after transplantation. Outcome analysis in 160 consecutive patients maintained on 1 therapy was performed regardless of performance of intravascular ultrasound examinations. Five-year survival was improved with sirolimus (97.4±1.8% versus 81.8±4.9%; P =0.006), as was freedom from cardiac-related events (93.6±3.2% versus 76.9±5.5%; P =0.002). Conclusions— Substituting calcineurin inhibitor with sirolimus as primary immunosuppressant attenuates long-term cardiac allograft vasculopathy progression and may improve long-term allograft survival owing to favorable coronary remodeling. Because of the lack of randomization and retrospective nature of our analysis, the differences in outcome should be interpreted cautiously, and prospective clinical trials are required.

Objective To determine the hemodynamic effect of an off-pump Apicoaortic valved graft (AAVG) implantation, we performed a quantitative coronary flow analysis in a swine model of severe aortic stenosis. Methods In 10 swine, cardiac output, coronary flow, right common carotid artery flow, and internal mammary artery flow were measured along with left and right ventricular pressures and aortic and pulmonary artery pressures. A novel AAVG was implanted off-pump on the left ventricular (LV) apex using a specially designed implantation tool and anastomosed to the descending thoracic aorta. Aortic flow was measured proximally and distally of the AAVG-to-descending thoracic aorta anastomosis. After AAVG implantation, epicardial echo confirmed occlusion of the LV outflow tract by a valvuloplasty balloon. Baseline simultaneous measurements of all parameters were repeated after AAVG implantation and intravenous Dobutamine administration. Results The AAVG was implanted without any blood loss. After AAVG implantation and LV outflow tract occlusion, the aortic flow proximal to the AAVG-to-descending thoracic aorta anastomosis changed from antegrade (1508 ± 435 mL/min) to retrograde (–529 ± 241 mL/min, P < 0.001). All other measured parameters remained unchanged compared with baseline. After intravenous Dobutamine administration, LV pressure increased from 88 ± 20 to 184 ± 36 mm Hg (+209%, P < 0.0001) and coronary flow increased from 75 ± 34 to 193 ± 90 mL/min (+257%, P = 0.001). Conclusions The off-pump implantation of an AAVG is bloodless, safe, reproducible and has no negative impact on coronary flow and hemodynamics. In addition, to the best of our knowledge, this is the first study where blood flow in all coronary arteries was measured simultaneously during an AAVG implantation.

Background— Few data exist on long-term outcomes of elderly patients after aortic valve replacement. We evaluated latest follow-up information for patients ≥70 years of age after aortic valve replacement. Methods and Results— Late overall survival of 2890 consecutive patients ≥70 years of age who underwent aortic valve replacement between January 1993 and December 2007 was reviewed retrospectively, analyzed, and stratified by preoperative and intraoperative variables. Observed 5-, 10-, and 15-year late postoperative survival was lower than generally expected (68%, 34%, and 8% versus 70%, 42%, and 20%, respectively; P <0.001). Independent predictors of late death included older age, renal failure, diabetes mellitus, stroke, myocardial infarction, immunosuppression, prior coronary artery bypass grafting, implanted pacemaker, lower ejection fraction, hypertension, and New York Heart Association class III or IV. After stratification by age–comorbidity risk score, 10-year survival for the lowest-risk group (n=946 [33%]) was similar to expected survival (55% versus 55%; P =0.50), but for the highest-risk group (n=564 [20%]), survival was significantly lower than expected (9% versus 26%; P <0.001). For 229 pairs of propensity-matched patients with mechanical or biological prostheses, survival was not significantly different (67%, 40%, and 19% versus 71%, 45%, and 7% at 5, 10, and 15 years, respectively; P =0.81). Structural deterioration of bioprostheses occurred in 64 patients (2.4%). Conclusions— Survival of elderly patients after aortic valve replacement is influenced by age and preoperative comorbidities; 33% at lowest risk had overall survival similar to that of an age- and sex-matched general population. There was no sufficient evidence that valve type affected survival. Structural deterioration of aortic bioprostheses was rare.