Nishant D. Patel

Angiotensin II Blockade and Aortic-Root Dilation in Marfan's Syndrome

BACKGROUND Progressive enlargement of the aortic root, leading to dissection, is the main cause of premature death in patients with Marfans syndrome. Recent data from mouse models of Marfans syndrome suggest that aortic-root enlargement is caused by excessive signaling by transforming growth factor beta (TGF-beta) that can be mitigated by treatment with TGF-beta antagonists, including angiotensin II-receptor blockers (ARBs). We evaluated the clinical response to ARBs in pediatric patients with Marfans syndrome who had severe aortic-root enlargement. METHODS We identified 18 pediatric patients with Marfans syndrome who had been followed during 12 to 47 months of therapy with ARBs after other medical therapy had failed to prevent progressive aortic-root enlargement. The ARB was losartan in 17 patients and irbesartan in 1 patient. We evaluated the efficacy of ARB therapy by comparing the rates of change in aortic-root diameter before and after the initiation of treatment with ARBs. RESULTS The mean (+/-SD) rate of change in aortic-root diameter decreased significantly from 3.54+/-2.87 mm per year during previous medical therapy to 0.46+/-0.62 mm per year during ARB therapy (P<0.001). The deviation of aortic-root enlargement from normal, as expressed by the rate of change in z scores, was reduced by a mean difference of 1.47 z scores per year (95% confidence interval, 0.70 to 2.24; P<0.001) after the initiation of ARB therapy. The sinotubular junction, which is prone to dilation in Marfans syndrome as well, also showed a reduced rate of change in diameter during ARB therapy (P<0.05), whereas the distal ascending aorta, which does not normally become dilated in Marfans syndrome, was not affected by ARB therapy. CONCLUSIONS In a small cohort study, the use of ARB therapy in patients with Marfans syndrome significantly slowed the rate of progressive aortic-root dilation. These findings require confirmation in a randomized trial.

Aortic Root Replacement in 372 Marfan Patients: Evolution of Operative Repair Over 30 Years

BACKGROUND We reviewed the evolution of practice and late results of aortic root replacement (ARR) in Marfan syndrome patients at our institution. METHODS A retrospective clinical review of Marfan patients undergoing ARR at our institution was performed. Follow-up data were obtained from hospital and office records and from telephone contact with patients or their physicians. RESULTS Between September 1976 and September 2006, 372 Marfan syndrome patients underwent ARR: 269 had a Bentall composite graft, 85 had valve-sparing ARR, 16 had ARR with homografts, and 2 had ARR with porcine xenografts. In the first 24 years of the study, 85% received a Bentall graft; during the last 8 years, 61% had a valve-sparing procedure. There was no operative or hospital mortality among the 327 patients who underwent elective repair; there were 2 deaths among the 45 patients (4.4%) who underwent emergent or urgent operative repair. There were 74 late deaths (70 Bentalls, 2 homograft, and 2 valve-sparing ARRs). The most frequent causes of late death were dissection or rupture of the residual aorta (10 of 74) and arrhythmia (9 of 74). Of the 85 patients who had a valve-sparing procedure, 40 had a David II remodeling operation; there was 1 late death in this group, and 5 patients required late aortic valve replacement for aortic insufficiency. A David I reimplantation procedure using the De Paulis Valsalva graft has been used exclusively since May 2002. All 44 patients in this last group have 0 to 1+ aortic insufficiency. CONCLUSIONS Prophylactic surgical replacement of the ascending aorta in patients with Marfan syndrome has low operative risk and can prevent aortic catastrophe in most patients. Valve-sparing procedures, particularly using the reimplantation technique with the Valsalva graft, show promise but have not yet proven as durable as the Bentall.

Right Heart Dysfunction After Left Ventricular Assist Device Implantation: A Comparison of the Pulsatile HeartMate I and Axial-Flow HeartMate II Devices

BACKGROUND Right heart dysfunction confers significant morbidity and mortality after left ventricular assist device implantation and historically occurs in as many as a third of patients. It is unknown whether newer axial flow pumps have a different impact on postimplant right heart dysfunction. We compared the incidence of right heart dysfunction after implantation of the pulsatile HeartMate I (XVE) and the continuous flow HeartMate II left ventricular assist device. METHODS We retrospectively reviewed patients who underwent HeartMate I or HeartMate II implantation between June 2000 and March 2007. Right heart dysfunction was defined as inotropic/vasodilator support for 14 or more consecutive days or the need for a right ventricular assist device, or both. RESULTS Seventy-seven patients underwent HeartMate implantation; 43 received a HeartMate I and 34 received a HeartMate II, for a mean left ventricular assist device support time of 202 and 160 days, respectively. Operative mortality was lower for HeartMate II patients (28% versus 15%; p = 0.26). The HeartMate II patients had lower preoperative right ventricular stroke work index. Pulmonary vascular resistance index, right ventricular stroke work index, and pulmonary and right atrial pressures improved and were similar between groups postoperatively. Overall, right heart dysfunction developed in 35% of HeartMate I patients (15 of 43) and 41% of HeartMate II patients (14 of 34; p = 0.63). Fewer HeartMate II patients (2) than HeartMate I patients (5) required 7 or more days of epinephrine, whereas more HeartMate II patients (7) than HeartMate I patients (5) required 7 or more days of milrinone. Six HeartMate I and 3 HeartMate II patients required right ventricular assist device implantation for right heart failure. Survival was similar (p = 0.7) between groups at, respectively, 3 (63% versus 62%), 6 (58% versus 58%), and 12 months (49% versus 48%). CONCLUSIONS Right heart dysfunction is a persistent clinical problem after left ventricular assist device placement. We report the first study comparing the incidence of right heart dysfunction after HeartMate I versus HeartMate II implantation. Although the incidence of right heart dysfunction was similar, fewer HeartMate II patients required right ventricular assist device placement and fewer required pure inotropic support for right heart failure.

Quality of life and functional status in patients surviving 12 months after left ventricular assist device implantation.

BACKGROUND As left ventricular assist device (LVAD) support duration increases, quality of life (QoL) becomes a concern. We reviewed the QoL in patients on LVAD support for >or=1 year. METHODS We retrospectively reviewed our prospective database for patients supported >or=1 year by HeartMate pulsatile- (HM1) or continuous-flow (HM2) LVADs from 2000 to 2009. Transplant or death before 1 year merited exclusion. Metabolic equivalents of tasks (METs), the Minnesota Living with Heart Failure Questionnaire (MLHFQ), the 6-minute walk distance (6MWD), and New York Heart Association (NYHA) class were reviewed. Complications and re-admissions were assessed. RESULTS Thirty patients were supported for >or=1 year (7 HM1s, 23 HM2s). Mean support duration was 594 +/- 173 days. Mean QoL metrics/functional status indicators at 12 months were: 6MWD, 393 +/- 290 m; MET tolerance, 3.3 +/- 1; MLHFQ, 35 +/- 31; and NYHA, 1.4 +/- 0.6. Mean re-admissions/year was 2.9 +/- 2, with a duration of 13.8 +/- 21 days. Three patients were never re-admitted. Mean out-of-hospital time was 471 +/- 172 days (87.3% of days). Infectious complications led to 43% of re-admissions and occurred in the: drive-line (47%) at 442 +/- 236 days; blood (37%) at 472 +/- 257 days; and LVAD pocket (20%) at 550 +/- 202 days. Twenty-three patients (77%) required additional operations (1.7 +/- 1.8/year). The most common indication was drive-line infection, but ranged from ischemic bowel to defibrillator exchange. Eight required LVAD exchanges for mechanical (n = 4), electrical (n = 3), and thrombotic (n = 1) issues. CONCLUSIONS Although LVAD support is not without complications, patients spend the majority of time outside the hospital enjoying a good quality of life.

Aortic Root Operations for Marfan Syndrome: A Comparison of the Bentall and Valve-Sparing Procedures

BACKGROUND We compared results of the Bentall procedure with valve-sparing aortic root replacement (VSRR) for aortic root aneurysm in Marfan syndrome. METHODS Marfan syndrome patients who had the Bentall procedure or VSRR at our institution between April 1997 and September 2006 were identified. Follow-up information was obtained from hospital charts and contact with patients or their physicians. Kaplan-Meier survival and propensity score analyses were performed. RESULTS One hundred forty Marfan syndrome patients had either the Bentall procedure (n = 56) or VSRR (n = 84; 40 remodeling and 44 reimplantation). Bentall patients were older than VSRR patients (38 versus 29 years; p = 0.0001) and had more aortic dissections (16% versus 1%; p = 0.0012); more urgent/emergent surgery (20% versus 2%; p = 0.0008); larger preoperative sinus diameter (5.7 versus 5.1 cm; p = 0.0004); and more preoperative 3+/4+ aortic insufficiency (59% versus 10%; p < 0.0001). There were no operative deaths. Postoperatively, 9% Bentall patients (5 of 56) and 1% of VSRR patients (1 of 84) suffered thromboembolic events (p = 0.03). Two percent (1 of 56) of Bentall patients required reoperation on the aortic root versus 6% of VSRR patients (5 of 84; p = 0.40). Eight-year freedom from aortic valve replacement was 90% for VSRR patients. Eight-year survival was 90% for Bentall and 100% for VSRR patients (p = 0.01). Propensity-adjusted regression showed that the Bentall procedure did not predict mortality (p = 1.00) and did not protect from reoperation (odds ratio = 0.28; 95% confidence interval: 0.01 to 4.33; p = 0.36). CONCLUSIONS The Bentall procedure and VSRR have similar operative results in Marfan syndrome. The procedures are distinguished by higher rates of thromboembolism among Bentall patients and higher rates of reoperation among VSRR patients. Lower late survival among Bentall patients probably reflects the preferential use of the Bentall procedure for higher risk patients.

Aortic Valve Replacement and Concomitant Mitral Valve Regurgitation in the Elderly Impact on Survival and Functional Outcome

Background—The impact of mitral regurgitation (MR) on elderly patients (≥70 years) undergoing isolated aortic valve replacement (AVR) is not clearly defined. This study investigates the long-term effects of preoperative, moderate MR on survival and functional outcome in elderly AVR patients. Methods and Results—A retrospective review identified 408 consecutive elderly patients who underwent isolated AVR from January 1983 to February 2004. The pathologic etiology of MR was determined on preoperative echocardiogram, and patients were stratified into no/mild MR (Group I; n =338) versus moderate MR (Group II; n =70). Follow-up was 95.1% complete. Functional outcome was evaluated using the Short Form-12 questionnaire. On univariate analysis, Groups I and II differed in incidence of previous myocardial infarction (13.9% versus 28.6%; P=0.004), hyperlipidemia (18.7% versus 33.3%; P=0.009), and congestive heart failure (50.0% versus 70.0%; P=0.002). On multivariate analysis, moderate MR was an independent risk factor impacting long-term survival (P=0.04). Actuarial survival at 1, 5, and 10 years for Group I was 93.8%, 73.3%, and 40.1% versus 92.3%, 58.2%, and 14.6% for Group II (P=0.04). Available postoperative echocardiograms for Group II (n =37) demonstrated improvement in MR in 81.8% of functional MR patients. However, MR persisted or worsened in 65.4% of patients with intrinsic mitral valve disease (myxomatous, calcific, or ischemic MR). Functional outcomes showed 77% of Group I versus 78.6% of Group II rated their health as good to excellent post-AVR. Conclusions—Moderate MR is an independent risk factor impacting long-term survival in elderly patients undergoing AVR. Therefore, patients with intrinsic mitral valve disease should be considered for concomitant MV surgery.

Infectious complications after pulsatile-flow and continuous-flow left ventricular assist device implantation.

BACKGROUND Infection is a significant source of morbidity and mortality after left ventricular assist device (LVAD) implantation. Newer generation continuous-flow (CF) LVADs are smaller, requiring smaller pump pockets and drive-line exit sites as compared with pulsatile-flow (PF) devices. With their recent adoption, CF device patients benefit from improved provider experience in the detection and treatment of infectious complications. Given these advances in design and experience, we examined the incidence of infectious complications in patients receiving CF and PF devices. METHODS We reviewed patients who received CF or PF LVADs (June 2000 to May 2009) at our institution. Incidences and timing of systemic infections (bacteremia, sepsis, severe sepsis, septic shock), device-associated infections (drive-line, LVAD pocket, sternal wound) and non-device-associated infections (catheter-related bloodstream, pneumonia, urinary tract) were compared between devices. Primary outcomes were sepsis, severe sepsis, a composite of drive-line and LVAD pocket infection, and catheter-related bloodstream infection. RESULTS Of 133 LVADs, 86 were CF. CF patients had lower pre-operative risk, more recent device implantation, and longer LVAD support time. Device type was highly correlated with reduced infections; however, on multivariate analysis, implantation date appeared to drive this association. Kaplan-Meier estimates of freedom from all primary outcomes were improved with more recent implantation (p < 0.05). On multivariate analysis, implantation date was predictive of all primary outcomes except severe sepsis, for which advanced age and worse Seattle Heart Failure Model score were predictive. CONCLUSION In this institutional review of post-LVAD infections, a decrease in infectious complications in CF patients was likely related to increased provider experience associated with a more recent date of implantation.

Outcomes in Patients Older Than 60 Years of Age Undergoing Orthotopic Heart Transplantation: An Analysis of the UNOS Database

BACKGROUND Patients 60 years and older have traditionally not been considered candidates for orthotopic heart transplantation (OHT). Recent studies have shown equivalent survival between older and younger patients, leading many to question this traditional ethos. As these studies may lack significant power to draw meaningful conclusions, the United Network for Organ Sharing (UNOS) database provides a unique opportunity to examine the effects of age on OHT. METHODS We retrospectively reviewed the UNOS dataset to identify 14,401 first-time OHT recipients between the years 1999 and 2006. Stratification was by age into those >or=60 years and younger patients aged 18 to 59 years. Baseline demographic and clinical factors were recorded. The primary end-point was all-cause mortality during the study period. Secondary outcomes included length of hospital stay (LOS), post-operative stroke, post-operative infections, acute renal failure (ARF) and rejection within 1 year of transplant. Post-transplant survival was modeled using the Kaplan-Meier method and compared between groups using Cox proportional hazard regression. RESULTS Of the 14,401 patients who met the inclusion criteria, 30% (n = 4,273) were >or=60 years of age. The elderly group had higher serum creatinine levels (1.5 vs 1.3, p < 0.001), longer waitlist times (255 vs 212 days, p < 0.001), and were more likely to have hypertension (HTN; 46% vs 37%, p < 0.001) or diabetes mellitus (DM; 25% vs 20%, p < 0.001). Survival at 30 days, 1 year and 5 years was 94%, 87% and 75% for the young group, and 93%, 84% and 69% for the older group (p < 0.001). Multivariate analysis revealed age >or=60 years, donor age, ischemic time, creatinine, HTN and DM to be independent predictors of mortality. Older patients had more infections (26% vs 23%, p < 0.001), ARF (9% vs 7%, p < 0.001) and longer LOS (21 vs 19 days, p < 0.001), but had lower rates of rejection (34% vs 43%, p < 0.001) as compared with younger recipients. CONCLUSIONS The UNOS database has provided a large multi-institutional sample examining OHT in the elderly. Although our analysis shows lower survival in patients >or=60 years of age, the cumulative 5-year survival in these patients of close to 70% is acceptable. OHT should not be restricted based on age, as encouraging long-term results exist.

Heart Transplantation for Adults With Congenital Heart Disease: Analysis of the United Network for Organ Sharing Database

BACKGROUND Congenital heart disease (CHD) in the adult is an uncommon indication for heart transplantation but has been increasing. We assessed survival and predictors of death after heart transplantation for adults with CHD. METHODS Adult primary heart transplant recipients (aged > 17 years) reported to the United Network for Organ Sharing (1987 to 2006) were reviewed and categorized by diagnosis of CHD vs other diagnoses. Kaplan-Meier survival analysis and Cox regression modeling were performed. RESULTS During the study period, 35,334 adults underwent primary heart transplantation, and 689 (2%) had CHD. Adult CHD recipients had longer mean waiting list time (218 vs 195 days; p = 0.004), longer ischemic time (3.5 vs 2.9 hours, p < 0.0001), and were more likely to have pretransplant pulmonary vascular resistance exceeding 4 Woods Units (62% vs 51%, p < 0.0001) vs other recipients. Thirty-day mortality was 16% vs 6% (p < 0.0001), although Kaplan-Meier survival did not differ between groups (p = 0.92) out to 10 years. Ischemic time (hazard ratio [HR], 1.2; 95% confidence interval [CI], 1.02 to 1.35; p = 0.02), African American race (HR, 1.9; 95% CI, 1.04 to 3.58; p = 0.03), and pulmonary vascular resistance exceeding 4 Woods Units (HR, 1.5; 95% CI, 1.01 to 2.19; p = 0.04) were predictors of death for adult CHD recipients. CONCLUSIONS Heart transplantation for adults with CHD is effective and has good long-term prognosis. The 30-day mortality rate is high, but 5- and 10-year survival is not statistically different from patients without CHD.

Impact of Donor-to-Recipient Weight Ratio on Survival After Heart Transplantation : Analysis of the United Network for Organ Sharing Database

Background— Generally accepted donor criteria for heart transplantation limit allografts from donors within approximately 20% to 30% of the recipient’s weight. We analyzed the impact of donor-to-recipient weight ratio on survival after heart transplantation. Methods and Results— Adult heart transplant recipients reported to the United Network for Organ Sharing from 1999 to 2007 were divided into 3 groups based on donor-to-recipient weight ratio: <0.8, 0.8 to 1.2, and >1.2. Kaplan–Meier methodology was used to estimate survival. Propensity-adjusted Cox regression modeling was used to analyze predictors of mortality. A total of 15 284 heart transplant recipients were analyzed; 2078 had weight ratio of <0.8, 9684 had 0.8 to 1.2, and 3522 had >1.2. Kaplan–Meier survival was not statistically different between groups at 5 years (P=0.26). Among patients with weight ratio <0.8, 5-year survival was lower for recipients with high pulmonary vascular resistance (>4 Woods units; P=0.02). Among recipients with high pulmonary vascular resistance, 5-year survival was similar for those with weight ratio 0.8 to 1.2 and >1.2 (P=0.44). Furthermore, male recipients with elevated pulmonary vascular resistance who received hearts from female donors had a significantly worse survival than males who received hearts from male donors (P=0.01). Propensity-adjusted multivariable analysis demonstrated that weight ratio <0.8 did not predict mortality (hazard ratio, 1.09; 95% CI, 0.94 to 1.27; P=0.21). Five-year survival after propensity matching was not statistically different between those with weight ratio <0.8 versus ≥0.8 (P=0.37). Conclusions— Weight ratio did not predict mortality after heart transplantation. However, recipients with elevated pulmonary vascular resistance who received undersized hearts had poor survival. Furthermore, in the setting of high pulmonary vascular resistance, male recipients who received hearts from female donors had worse survival than those who received hearts from male donors. Extending donor criteria to include undersized hearts in select recipients should be considered.