A. Ruzza

Survival and Allograft Rejection Rates after Combined Heart and Kidney Transplantation in Comparison with Heart Transplantation Alone

BACKGROUND The role of solid multiorgan transplantation remains to be determined. We compared our experience with combined heart-kidney transplantation (HKT) and heart transplant alone (HT), and assessed patient survival rates and freedom from allograft rejection in these two patient groups. METHODS We reviewed the clinical outcomes of patients undergoing HKT (n=30) or HT (n=440) between June 1992 and March 2009. Baseline patient characteristics, perioperative factors, incidence of rejection, and survival were examined. RESULTS There were no significant differences between the two groups for age, gender, etiology of heart disease, functional class, preoperative left ventricular ejection fraction, end-diastolic diameter, cardiac output, or transplant waitlist status. Patients with HKT had a higher serum creatinine level (P<.001) and a greater incidence of hypertension (P=.04). No differences were found in cardiac allograft ischemic times, including cardiopulmonary bypass or cross-clamp times. Kidney allograft ischemic time was 14.6±9 hours (mean±SD; range, 4 hours to 49 hours). Kaplan-Meier survival estimates were similar for the HKT and HT groups at 30 days (93%±4.6% versus 98%±0.7%), 1 year (87%±6.2% versus 93%±1.2%), 5 years (68%±9.0% versus 76%±2.1%), and 10 years (51%±11% versus 53%±3.0%; P=.54 for all comparisons). Follow-up serum creatinine levels were similar after HKT and HT at 30 days (1.6±1.8 mg/dL versus 1.1±0.4 mg/dL), 1 year (1.4±0.6 mg/dL versus 1.5±0.6 mg/dL), and 5 years (1.8±1.8 mg/dL versus 1.8±1.2 mg/dL; P>.05 for all comparisons). CONCLUSIONS HKT offers excellent survival and similar renal function when compared with HT alone. Patients with end-stage cardiac and renal failure can be considered for HKT.

Combined Heart and Liver Transplantation: The Cedars-Sinai Experience

PURPOSE Combined heart-liver transplantation is an increasingly accepted treatment for select patients with heart and liver disease. Despite growing optimism, heart-liver transplantation remains an infrequent operation. We report our institutional experience with heart-liver transplantation. METHODS All combined heart-liver transplantations at Cedars-Sinai Medical Center from 1998-2014 were analyzed. Primary outcomes were patient and graft survival and secondary outcomes included rejection, infection, reoperation, length of stay, and readmission. RESULTS There were 7 heart-liver transplants: 6 simultaneous (single donor) and 1 staged (2 donors). Median follow-up was 22.1 (IQR 13.2-48.4) months. Mean recipient age was 50.8 ± 19.5 years. Heart failure etiologies included familial amyloidosis, congenital heart disease, hypertrophic cardiomyopathy, systemic lupus erythematosus, and dilated cardiomyopathy. Preoperative left ventricular ejection fraction averaged 32.3 ± 12.9%. Five (71.4%) patients required preoperative inotropic support; 1 required mechanical circulatory support. The most common indications for liver transplant were amyloidosis and cardiac cirrhosis. Median Model for End-stage Liver Disease score was 10.0 (9.3-13.8). Six-month and 1-year actuarial survivals were 100% and 83.3%, with mean survival exceeding 4 years. No patient experienced cardiac allograft rejection, 1 experienced transient liver allograft rejection, and 1 developed progressive liver dysfunction resulting in death. Five developed postoperative infections and 3 (42.9%) required reoperation. Median ICU and hospital stays were 7.0 (7.0-11.5) and 17.0 (13.8-40.5) days. There were 4 (57.1%) readmissions. CONCLUSIONS For carefully selected patients with coexisting heart and liver disease, combined heart and liver transplantation offers acceptable patient and graft survival.

Use of Ventricular Assist Device as Bridge to Simultaneous Heart and Kidney Transplantation in Patients with Cardiac and Renal Failure

BACKGROUND Ventricular assist device (VAD) implantation as a bridge to cardiac transplantation is an effective treatment option for end-stage heart failure. Renal dysfunction is not uncommon but is considered to be a poor prognostic factor. We present our experience with 6 patients who had combined heart and kidney transplantation (HKT) after VAD implantation for advanced cardiac and renal failure. METHODS Of 74 patients who underwent VAD implantation as a bridge to transplant from May 2001 to September 2009, 28 patients developed renal failure, and of these, 6 (5 male, 1 female, ages 40-64 years) had HKT. All required hemodialysis because of renal failure before HKT. Immunosuppression consisted of anti-thymocyte globulin followed by triple drug therapy consisting of calcineurin inhibitors, mycophenolate, and corticosteroids. RESULTS Of the 6 HKT patients, 5 (83%) were alive without hemodialysis at 1 and 2 years; of the 22 patients with renal failure after VAD implantation without subsequent transplant, 1- and 2-year survivals were zero. Interval from VAD implantation to HKT ranged from 36 to 366 days (133 ± 127 days). At 6 months after HKT (100% alive), left ventricular ejection fraction was 60.2 ± 5.8% and serum creatinine 1.1 ± 0.2 mg/dL. Three HKT patients required temporary hemodialysis after surgery. Endomyocardial biopsy showed absence of ISHLT grade 2R-3A or greater cellular rejection, and none showed evidence of definite antibody-mediated rejection. CONCLUSIONS Based on our initial experience, simultaneous HKT is a safe treatment option with excellent outcomes for patients with advanced heart failure and persistent renal dysfunction after VAD implantation.

Heterotopic Heart Transplantation in Rats: Improved Anesthetic and Surgical Technique

OBJECTIVE An updated anesthetic and surgical technique in a rat model of heterotopic heart transplantation is described. MATERIALS AND METHODS A microsurgical technique via a suprarenal approach was performed, and is described in stepwise fashion, and several technical improvements are compared with previous descriptions. Lewis rats were used as donors and recipients (syngeneic model). RESULTS Factors that affected early surgical outcome included type of anesthetic used; surgeon skill, experience in handling blood vessels, and knowledge of small-animal anatomy; gentle manipulation during the operation; and duration of surgery (<1 hour). Use of isoflurane inhalation anesthesia (10 rats) vs intraperitoneal injection of ketamine, 75 mg/kg, and dexmedetomidine, 0.25 mg/kg (20 rats), was associated with improved early survival (90%) and no occurrence of paralysis, paraparesis, bleeding, or intestinal ischemia. Long-term survival (>11 months) with a functioning graft was achieved in all 9 surviving animals. CONCLUSIONS Survival was substantially improved with administration of isoflurane anesthesia; surgeon microvascular surgical skills and knowledge of small-animal anatomy, and duration of surgery less than 1 hour. These factors collectively contributed to successful early outcomes after heterotopic heart transplantation in rats, with 90% freedom from morbidity and mortality, and resulted in long-term survival (>11 months) with a functioning graft in a syngeneic model. This heterotopic model in rats is suitable for short- and long-term studies of heart transplantation.

Adult Heart Transplantation Following Ventricular Assist Device Implantation: Early and Late Outcomes

PURPOSE The impact of prior implantation of a ventricular assist device (VAD) on short- and long-term postoperative outcomes of adult heart transplantation (HTx) was investigated. METHODS Of the 359 adults with prior cardiac surgery who underwent HTx from December 1988 to June 2012 at our institution, 90 had prior VAD and 269 had other (non-VAD) prior cardiac surgery. RESULTS The VAD group had a lower 60-day survival when compared with the Non-VAD group (91.1% ± 3.0% vs 96.6% ± 1.1%; P = .03). However, the VAD and Non-VAD groups had similar survivals at 1 year (87.4% ± 3.6% vs 90.5% ± 1.8%; P = .33), 2 years (83.2% ± 4.2% vs 88.1% ± 2.0%; P = .21), 5 years (75.7% ± 5.6% vs 74.6% ± 2.9%; P = .63), 10 years (38.5% ± 10.8% vs 47.6% ± 3.9%; P = .33), and 12 years (28.9% ± 11.6% vs 39.0% ± 4.0%; P = .36). The VAD group had longer pump time and more intraoperative blood use when compared with the Non-VAD group (P < .0001 for both). Postoperatively, VAD patients had higher frequencies of >48-hour ventilation and in-hospital infections (P = .0007 and .002, respectively). In addition, more VAD patients had sternal wound infections when compared with Non-VAD patients (8/90 [8.9%] vs 5/269 [1.9%]; P = .005). Both groups had similar lengths of intensive care unit (ICU) and hospital stays and no differences in the frequencies of reoperation for chest bleeding, dialysis, and postdischarge infections (P = .19, .70, .34, .67, and .21, respectively). Postoperative creatinine levels at peak and at discharge did not differ between the 2 groups (P = .51 and P = .098, respectively). In a Cox model, only preoperative creatinine ≥1.5 mg/dL (P = .006) and intraoperative pump time ≥210 minutes (P = .022) were individually considered as significant predictors of mortality within 12 years post-HTx. Adjusting for both, pre-HTx VAD implantation was not a predictor of mortality within 12 years post-HTx (hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.77-1.97; P = .38). However, pre-HTx VAD implantation was a risk factor for 60-day mortality (HR, 2.86; 95% CI, 1.07-7.62; P = .036) along with preoperative creatinine level ≥2 mg/dL (P = .0006). CONCLUSIONS HTx patients with prior VAD had lower 60-day survival, higher intraoperative blood use, and greater frequency of postoperative in-hospital infections when compared with HTx patients with prior Non-VAD cardiac surgery. VAD implantation prior to HTx did not have an additional negative impact on long-term morbidity and survival following HTx. Long-term (1-, 2-, 5-, 10-, and 12-year) survival did not differ significantly in HTx patients with prior VAD or non-VAD cardiac surgery.

Coronary artery bypass graft surgery using the radial artery as a secondary conduit improves patient survival.

Background The clinical benefits of the left internal thoracic artery–to–left anterior descending coronary artery graft are well established in coronary artery bypass graft surgery (CABG). However, limited data are available regarding the long‐term outcome of the radial artery (RA) as a secondary conduit over the established standard of the saphenous venous graft. Methods and Results We compared the 12‐year survival outcome in a set of propensity‐matched CABG patients who received either the RA or the saphenous vein as a secondary conduit. A multivariable logistic regression that included 18 baseline characteristics was used to define the propensity of receiving an RA graft. The propensity model resulted in 260 matched pairs who underwent first‐time isolated CABG from 1996 to 2001 with similar preoperative characteristics (C statistic=0.86). The cumulative 12‐year survival estimated by use of the Kaplan–Meier method was higher for the RA graft patients (hazard ratio 0.76; P=0.03). This survival advantage was especially significant in diabetics (P=0.005), in women (P=0.02), and in the elderly (P=0.04.) The protective effect appeared beginning at year 5 post surgical intervention. Conclusion The RA as a secondary conduit provided superior long‐term survival after CABG, especially in diabetic patients, women, and the elderly. This effect was most pronounced >5 years after surgery.

Prevalence of hypertension in the Gambia and Sierra Leone, western Africa : a cross-sectional study : cardiovascular topic

Summary Background Hypertension (HTN) is one of the causes of cardiovascular disease (CVD) in Africa, and may be associated with lower socio-economic status (SES). The prevalence of HTN is not well established in the Gambia or in Sierra Leone. Methods A cross-sectional, population-based study of adults was conducted in the Gambia in 2000 and in Sierra Leone from 2001 to 2003 and in 2009. The study was conducted as part of the annual visit to countries in western Africa sponsored by a medical delegation from California. People from the Gambia and Sierra Leone were examined by the medical delegation and blood pressures were measured. Results A total of 2 615 adults were examined: 1 400 females and 1 215 males. The mean systolic blood pressure (SBP) of the females was 134.3 ± 29.7 mmHg, mean diastolic blood pressure (DBP) was 84.5 ± 17.5 mmHg, and 46.2% were hypertensive. The mean SBP of the males was 132.8 ± 28.5 mmHg, mean DBP was 82.8 ± 16.2 mmHg, and 43.2% were hypertensive. Overall prevalence of HTN in the subjects was 44.8%. Mean SBP, mean DBP and HTN prevalence increased with age decade, both in males and females. In addition, after age adjustment (known age), females had higher mean SBP (p = 0.042), mean DBP (p = 0.001) and rate of occurrence of HTN (p = 0.016) when compared with males. Conclusions Prevalence rates of HTN in the Gambia and Sierra Leone were higher than 40% in males and females, and may be a major contributor to CVD in both countries. Due to the association of HTN with low SES, improvements in educational, public health, economic, non-governmental and governmental efforts in the Gambia and Sierra Leone may lead to a lower prevalence of HTN. The cause of the higher prevalence in women may be due to post-menopausal hormonal changes.

Prior sternotomy increases the mortality and morbidity of adult heart transplantation.

BACKGROUND This study investigated the effect of prior sternotomy (PS) on the postoperative mortality and morbidity after orthotopic heart transplantation (HTx). METHODS Of 704 adults who underwent HTx from December 1988 to June 2012 at a single institution, 345 had no PS (NPS group) and 359 had ≥ 1 PS (PS group). Survival, intraoperative use of blood products, intensive care unit (ICU) and hospital stays, frequency of reoperation for bleeding, dialysis, and >48-hour ventilation were examined. RESULTS The NPS and PS groups had similar 60-day survival rates (97.1 ± 0.9% vs 95.3 ± 1.1%; P = .20). However, the 1-year survival was higher in the NPS group (94.7 ± 1.2% vs 89.7 ± 1.6%; hazard ratio [HR], 1.98; 95% CI, 1.12-3.49; P = .016). The PS group had longer pump time and more intraoperative blood use (P < .0001 for both). Postoperatively, the PS group had longer ICU and hospital stays, and higher frequencies of reoperation for bleeding and >48-hour ventilation (P < .05 for all comparisons). Patients with 1 PS (1PS group) had a higher 60-day survival rate than those with ≥ 2 PS (2+PS group; 96.7 ± 1.1% vs 91.1 ± 3.0%; HR, 2.70; 95% CI, 1.04-7.01; P = .033). The 2+PS group had longer pump time and higher frequency of postoperative dialysis (P < .05 for both). Patients with prior VAD had lower 60-day (91.1 ± 3.0% vs 97.1 ± 0.9%; P = .010) and 1-year (87.4 ± 3.6% vs 94.7 ± 1.2%; P = .012) survival rates than NPS group patients. Patients with prior CABG had a lower 1-year survival than NPS group patients (89.0 ± 2.3% vs 94.7 ± 1.2%; P = .018). CONCLUSION The PS group had lower 1-year survival and higher intraoperative blood use, postoperative length of ICU and hospital stays, and frequency of reoperation for bleeding than the NPS group. Prior sternotomy increases morbidity and mortality after HTx.

Combined heart and kidney transplantation: what is the appropriate surgical sequence?

Combined heart and kidney transplantation is increasing in frequency but there are no guidelines to establish the indications, contraindications and sequence for this surgical procedure. We report our single-centre experience on 30 consecutive patients who underwent combined heart and kidney transplant in comparison with heart transplant alone. Patients had similar preoperative characteristics in both groups. Combined heart and kidney transplant is associated with the same long-term survival rate, low cellular rejection and antibody-mediated rejection rates when compared with heart transplant alone. We did not observe any difference in the outcomes related to preoperative patient characteristics. We suggest the staged surgical approach as the preferred method for transplant.

Prophylaxis of Cytomegalovirus Disease in Mismatched Patients after Heart Transplantation Using Combined Antiviral and Immunoglobulin Therapy

BACKGROUND Cytomegalovirus (CMV) is a common cause of infection and morbidity after heart transplantation. Seronegative recipients (R-) of seropositive donor hearts (D+) are at high risk for CMV disease. We compared three different CMV prophylaxis regimens using combined antiviral and immunoglobulin therapy. METHODS In 99 patients who survived more than 30 days after heart transplant, all received induction with antilymphocytic therapy and triple-drug therapy. In group A, D+R- patients received one dose of intravenous immunoglobulin (IVIG) followed by one dose of CMV-specific immunoglobulin (CMV-IVIG), and intravenous ganciclovir (GCV) for 4 weeks followed by 11 months of oral acyclovir (ACV). In group B, D+R- patients received one dose IVIG followed by five doses of CMV-IVIG and intravenous GCV for 14 weeks followed by 9 months of oral ACV. In group C, D+R- patients were treated with the same regimen as for group B, except oral ACV was replaced with oral GCV. RESULTS The actuarial freedom from CMV disease for D+R- patients at 1 month, 1 year, and 2 years after transplantation in group A was 100%, 25% ± 15%, and 25% ± 15%, respectively; group B was 100%, 67% ± 27%, and 67% ± 27%; group C was 100%, 83% ± 15%, and 83% ± 15% (P < .01, groups B and C vs group A). By comparison, the actuarial freedom from CMV disease for seropositive recipients (D-R+ or D+R+) at 1 month, 1 year, and 2 years in group A was 100%, 87% ± 7%, and 82% ± 8%, respectively; group B was 100%, 88% ± 8%, and 75% ± 11%; group C was 100%, 72% ± 9%, and 72% ± 9% (P = NS among groups). Rejection rates did not differ among the three groups. CONCLUSIONS A longer course of intravenous GCV with multiple doses of CMV-IVIG was a more effective prophylaxis regimen against CMV disease for the high-risk group of seronegative recipients of seropositive donor hearts.