Predicting Long Term Outcome in Patients Treated With Continuous Flow Left Ventricular Assist Device: The Penn-Columbia Risk Score.

BACKGROUND: Predicting which patients are unlikely to benefit from continuous flow left ventricular assist device (LVAD) treatment is crucial for the identification of appropriate patients. Previously developed scoring systems are limited to past eras of device or restricted to specific devices. Our objective was to create a risk model for patients treated with continuous flow LVAD based on the preimplant variables. METHODS AND RESULTS: We performed a retrospective analysis of all patients implanted with a continuous flow LVAD between 2006 and 2014 at the University of Pennsylvania and included a total of 210 patients (male 78%; mean age, 56±15; mean follow-up, 465±486 days). From all plausible preoperative covariates, we performed univariate Cox regression analysis for covariates affecting the odds of 1-year survival following implantation (P<0.2). These variables were included in a multivariable model and dropped if significance rose above P=0.2. From this base model, we performed step-wise forward and backward selection for other covariates that improved power by minimizing Akaike Information Criteria while maximizing the Harrell Concordance Index. We then used Kaplan-Meier curves, the log-rank test, and Cox proportional hazard models to assess internal validity of the scoring system and its ability to stratify survival. A final optimized model was identified based on clinical and echocardiographic parameters preceding LVAD implantation. One-year mortality was significantly higher in patients with higher risk scores (hazard ratio, 1.38; P=0.004). This hazard ratio represents the multiplied risk of death for every increase of 1 point in the risk score. The risk score was validated in a separate patient cohort of 260 patients at Columbia University, which confirmed the prognostic utility of this risk score (P=0.0237). CONCLUSION: We present a novel risk score and its validation for prediction of long-term survival in patients with current types of continuous flow LVAD support.

Bridging the generation gap: Intergenerational service-learning benefits young and old.

Intergenerational service-learning is commonly used in aging courses. Although benefits are well documented for college students, fewer studies have examined benefits for older adults. This article discusses the development and implementation of an intergenerational program designed as a brief service-learning experience to reduce age-related stereotypes and increase generativity in older adults. Young adults enrolled in an aging course and older adults from a local assisted-living community met three times to discuss a variety of topics and get to know one another. Results showed a significant reduction in ageism on the Fraboni Scale of Ageism for young adults. Descriptive data suggested an increase in generativity on the Loyola Generativity Scale for older adults. Qualitative data suggested that all participants gained a greater appreciation for one another and recognized how much they had in common. Limitations, challenges, and lessons learned are also discussed. Intergenerational service-learning, even in small doses, shows promise for bridging the generation gap.

A "Repair-All" Strategy for Degenerative Mitral Valve Disease Safely Minimizes Unnecessary Replacement.

BACKGROUND: We examined the feasibility and efficacy of a "repair-all" strategy applied in all patients with degenerative mitral regurgitation, regardless of valve complexity, risk profile, and surgical approach. METHODS: Between 2002 and 2011, 4,241 patients underwent mitral operations at our institution. Analysis was limited to 525 consecutive patients with mitral regurgitation due to leaflet prolapse (posterior, 75%; anterior, 5%; bileaflet, 20%) who underwent isolated mitral operations. A right minithoracotomy was used in 46% of procedures. Propensity scores identified 153 well-matched patient pairs for evaluation of the effect of surgical approach on valve reparability. RESULTS: Mitral repair was successful in 99% (520 of 525) of patients. The location of the leaflet prolapse did not significantly influence the repair rate or the need for intraoperative revision of the initial repair. The repair rate and the need for intraoperative repair revision also did not significantly differ by surgical approach. Intraoperative revision did not confer a greater risk of perioperative morbidity or longer length of stay. At 8 years, freedom from severe mitral regurgitation was 97% ± 2%. Development of residual mitral regurgitation did not differ by location of the leaflet prolapse, need for repair revision, or surgical approach. After discharge, the survival trend did not differ between patients who did and did not require intraoperative repair revision. CONCLUSIONS: In experienced centers, a "repair-all" strategy for degenerative mitral regurgitation can be used with nearly 100% repair rates and excellent outcomes, regardless of valve complexity. When necessary, intraoperative revision of the initial repair may be performed in most patients without a significant incremental risk, thereby further enhancing repair rates.

Preclinical Models for Translational Investigations of Left Ventricular Assist Device-Associated von Willebrand Factor Degradation.

Evidence suggests a major role for von Willebrand factor (vWF) in left ventricular assist device (LVAD)-associated bleeding. However, the mechanisms of vWF degradation during LVAD support are not well understood. We developed: (i) a simple and inexpensive vortexer model; and (ii) a translational LVAD mock circulatory loop to perform preclinical investigations of LVAD-associated vWF degradation. Whole blood was obtained from LVAD patients (n = 8) and normal humans (n = 15). Experimental groups included: (i) blood from continuous-flow LVAD patients (baseline vs. post-LVAD, n = 8); (ii) blood from normal humans (baseline vs. 4 h in vitro laboratory vortexer, ∼ 2400 rpm, shear stress ∼175 dyne/cm(2) , n = 8); and (iii) blood from normal humans (baseline vs. 12 h HeartMate II mock circulatory loop, 10 000 rpm, n = 7). vWF multimers and degradation fragments were characterized with electrophoresis and immunoblotting. Blood from LVAD patients, blood exposed to in vitro supraphysiologic shear stress, and blood circulated through an LVAD mock circulatory loop demonstrated a similar profile of decreased large vWF multimers and increased vWF degradation fragments. A laboratory vortexer and an LVAD mock circulatory loop reproduced the pathologic degradation of vWF that occurs during LVAD support. Both models are appropriate for preclinical studies of LVAD-associated vWF degradation.

Evaluation of late aortic insufficiency with continuous flow left ventricular assist device†.

OBJECTIVES: The aim of this study was to evaluate late development of aortic insufficiency (AI) with continuous flow left ventricular assist device (CLVAD). Development of AI is an increasingly recognized important complication in CLVAD therapy, but there are still few reports about this topic. METHODS: We analysed data from 99 patients who underwent CLVAD implantation. De novo AI was defined as the development of mild or greater AI in patients with none or trace preoperative AI. Anatomic and functional correlates of de novo AI were investigated. RESULTS: Among the 17 patients with preoperative mild AI, no improvements were observed in mitral regurgitation or LV end-systolic dimension. Of the remaining 82 patients, de novo AI was identified in 43 patients (52%), on the most recent follow-up echocardiography, and did not influence survival nor improvement of LV geometry. Rate of freedom from de novo AI at 1 year after CLVAD implantation was 35.9%. Development of significantly greater AI was observed in patients without valve opening (AI grade 1.3 ± 1.0 vs 0.7 ± 0.9; P = 0.005). By multivariate Cox hazard model, smaller body surface area (BSA) [hazard ratio: 0.83 [95% confidence interval (CI): 0.72-0.97], P = 0.018], larger aortic root diameter (AOD) [hazard ratio: 1.11 (95% CI: 1.02-1.22), P = 0.012] and higher pulmonary artery systolic pressure (PASP) [hazard ratio: 1.24 (95% CI: 1.10-1.41), P < 0.001] were identified as the independent preoperative risk factors for de novo AI. In a subset of patients with speed adjustments, increase of CLVAD speed worsened AI and led to insufficient LV unloading in patients with aortic dilatation (AOD ≥ 3.5 cm). CONCLUSION: Any significant mortality difference related to preoperative or development of postimplant AI was not found. AI was associated with changes in LV size, and there appears to be an interaction between BSA, preoperative PASP, time since implant, aortic valve opening, aortic size and development of AI. Longitudinal clinical management in CLVAD patients, particularly in terms of CLVAD speed optimization, should include careful assessment.

Natural history of coexistent tricuspid regurgitation in patients with degenerative mitral valve disease: implications for future guidelines.

OBJECTIVE: The management of coexistent tricuspid regurgitation in patients with mitral regurgitation remains controversial. We sought to define the incidence and natural history of coexistent tricuspid regurgitation in patients undergoing isolated mitral surgery for degenerative mitral regurgitation, as well as the effect of late secondary tricuspid regurgitation on cardiovascular symptom burden and survival. METHODS: To minimize confounding, analysis was limited to 495 consecutive patients who underwent isolated mitral surgery for degenerative mitral valve disease between 2002 and 2011. Patients with coexistent severe tricuspid regurgitation were excluded because such patients typically undergo concomitant tricuspid intervention. RESULTS: Grade 1 to 3 coexistent tricuspid regurgitation was present in 215 patients (43%) preoperatively. Actuarial freedom from grade 3 to 4 tricuspid regurgitation 1, 5, and 9 years after surgery was 100% ± 0%, 90% ± 2%, and 64% ± 7%, respectively. Older age (P < .001) and grade of preoperative tricuspid regurgitation (P = .006) independently predicted postoperative progression of tricuspid regurgitation on multivariable analysis. However, when limited to patients with mild or absent tricuspid regurgitation, indexed tricuspid annular diameter was the only significant risk factor for late tricuspid regurgitation (P = .04). New York Heart Association functional class and long-term survival did not worsen with development of late secondary tricuspid regurgitation (P = .4 and P = .6, respectively). However, right ventricular dysfunction was significantly more common in patients with more severe late tricuspid regurgitation (P = .007). CONCLUSIONS: Despite durable correction of degenerative mitral regurgitation, less than severe tricuspid regurgitation is likely to progress after surgery if uncorrected. Given the low incremental risk of tricuspid annuloplasty, a more aggressive strategy of concomitant tricuspid repair may be warranted.

Continuous flow left ventricular assist device implant significantly improves pulmonary hypertension, right ventricular contractility, and tricuspid valve competence.

BACKGROUND: Continuous flow left ventricular assist devices (CF LVAD) are being implanted with increasing frequency for end-stage heart failure. At the time of LVAD implant, a large proportion of patients have pulmonary hypertension, right ventricular (RV) dysfunction, and tricuspid regurgitation (TR). RV dysfunction and TR can exacerbate renal dysfunction, hepatic dysfunction, coagulopathy, edema, and even prohibit isolated LVAD implant. Repairing TR mandates increased cardiopulmonary bypass time and bicaval cannulation, which should be reserved for the time of orthotopic heart transplantation. We hypothesized that CF LVAD implant would improve pulmonary artery pressures, enhance RV function, and minimize TR, obviating need for surgical tricuspid repair. METHODS: One hundred fourteen continuous flow LVADs implanted from 2005 through 2011 at a single center, with medical management of functional TR, were retrospectively analyzed. Pulmonary artery pressures were measured immediately prior to and following LVAD implant. RV function and TR were graded according to standard echocardiographic criteria, prior to, immediately following, and long-term following LVAD. RESULTS: There was a significant improvement in post-VAD mean pulmonary arterial pressures (26.6 ± 4.9 vs. 30.2 ± 7.4 mmHg, p = 0.008) with equivalent loading pressures (CVP = 12.0 ± 4.0 vs. 12.1 ± 5.1 p = NS). RV function significantly improved, as noted by right ventricular stroke work index (7.04 ± 2.60 vs. 6.05 ± 2.54, p = 0.02). There was an immediate improvement in TR grade and RV function following LVAD implant, which was sustained long term. CONCLUSION: Continuous flow LVAD implant improves pulmonary hypertension, RV function, and tricuspid regurgitation. TR may be managed nonoperatively during CF LVAD implant.

Ventricular assist device implant in the elderly is associated with increased, but respectable risk: a multi-institutional study.

BACKGROUND: There are an increasing number of elderly patients with end-stage heart failure. Destination mechanical circulatory support is often the only therapy available for these patients who are not transplant candidates. The outcomes after continuous flow left ventricular assist device (CF LVAD) implant in older patients remains unclear. We undertook this multi-institutional study to quantify short-term and midterm outcomes after CF LVAD implant in the elderly. METHODS: We retrospectively analyzed all patients in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) national registry that underwent implant of a CF LVAD (June 2006 to April 2012). Patients were divided into 2 cohorts based upon age (<70 years [n = 4,439] and ≥ 70 years (n = 590]). Preoperative, intraoperative, and postoperative variables were analyzed. The primary endpoint, survival, was compared between cohorts. RESULTS: Patients age 70 and older were more hemodynamically stable pre-VAD implant as evidenced by INTERMACS profile and inotrope dependence. Perioperative outcomes, including median bypass time (89 vs 89 minutes) and length of stay (0.657 vs 0.657 months) were similar between cohorts (p = not significant). Kaplan-Meier analysis revealed a significant difference in 2-year survival between patients aged 70 years or greater (63%) and less than 70 (71%, p < 0.001). Multivariable Cox proportional hazard analysis revealed age as an independent predictor of mortality during follow-up (p < 0.001). Nonetheless, midterm cumulative survival in the older cohort was still reasonable (63% at 2 years). CONCLUSIONS: Multi-institutional analysis revealed advanced age as a predictor of increased mortality after CF LVAD implantation. Careful patient selection is critical in the elderly to optimize long-term outcomes after CF LVAD implantation.

Predicting right ventricular failure in the modern, continuous flow left ventricular assist device era.

BACKGROUND: In the era of destination continuous flow left ventricular assist devices (LVAD), the decision of whether a patient will tolerate isolated LVAD support or will need biventricular support (BIVAD) can be challenging. Incorrect decision making with delayed right ventricular (RV) assist device implantation results in increased morbidity and mortality. Continuous flow LVADs have been shown to decrease pulmonary hypertension and improve RV function. We undertook this study to determine predictors in the continuous flow LVAD era that identify patients who are candidates for isolated LVAD therapy as opposed to biventricular support. METHODS: We reviewed demographic, hemodynamic, laboratory, and echocardiographic variables for 218 patients who underwent VAD implant from 2003 through 2011 (LVAD=167, BIVAD=51), during the era of continuous flow LVADs. RESULTS: Fifty preoperative risk factors were compared between patients who were successfully managed with an LVAD and those who required a BIVAD. Seventeen variables demonstrated statistical significance by univariate analysis. Multivariable logistic regression analysis identified central venous pressure>15 mmHg (OR 2.0, "C"), severe RV dysfunction (OR 3.7, "R"), preoperative intubation (OR 4.3, "I"), severe tricuspid regurgitation (OR 4.1, "T"), heart rate>100 (OR 2.0, Tachycardia-"T")-CRITT as the major criteria predictive of the need for biventricular support. Utilizing these data, a highly sensitive and easy to use risk score for determining RV failure was generated that outperformed other established risk stratification tools. CONCLUSIONS: We present a preoperative risk calculator to determine suitability of a patient for isolated LVAD support in the current continuous flow ventricular assist device era.

Minimally invasive approach provides at least equivalent results for surgical correction of mitral regurgitation: a propensity-matched comparison.

OBJECTIVE: Minimally invasive approaches to mitral valve surgery are increasingly used, but the surgical approach must not compromise the clinical outcome for improved cosmesis. We examined the outcomes of mitral repair performed through right minithoracotomy or median sternotomy. METHODS: Between January 2002 and October 2011, 1011 isolated mitral valve repairs were performed in the University of Pennsylvania health system (455 sternotomies, 556 right minithoracotomies). To account for key differences in preoperative risk profiles, propensity scores identified 201 well-matched patient pairs with mitral regurgitation of any cause and 153 pairs with myxomatous disease. RESULTS: In-hospital mortality was similar between propensity-matched groups (0% vs 0% for the degenerative cohort; 0% vs 0.5%, P = .5 for the overall cohort; in minimally invasive and sternotomy groups, respectively). Incidence of stroke, infection, myocardial infarction, exploration for postoperative hemorrhage, renal failure, and atrial fibrillation also were comparable. Transfusion was less frequent in the minimally invasive groups (11.8% vs 20.3%, P = .04 for the degenerative cohort; 14.0% vs 22.9%, P = .03 for the overall cohort), but time to extubation and discharge was similar. A 99% repair rate was achieved in patients with myxomatous disease, and a minimally invasive approach did not significantly increase the likelihood of a failed repair resulting in mitral valve replacement. Patients undergoing minimally invasive mitral repair were more likely to have no residual post-repair mitral regurgitation (97.4% vs 92.1%, P = .04 for the degenerative cohort; 95.5% vs 89.6%, P = .02 for the overall cohort). In the overall matched cohort, early readmission rates were higher in patients undergoing sternotomies (12.6% vs 4.4%, P = .01). Over 9 years of follow-up, there was no significant difference in long-term survival between groups (P = .8). CONCLUSIONS: In appropriate patients with isolated mitral valve disease of any cause, a right minithoracotomy approach may be used without compromising clinical outcome.

Early planned institution of biventricular mechanical circulatory support results in improved outcomes compared with delayed conversion of a left ventricular assist device to a biventricular assist device.

OBJECTIVE: It is generally accepted that patients who require biventricular assist device support have poorer outcomes than those requiring isolated left ventricular assist device support. However, it is unknown how the timing of biventricular assist device insertion affects outcomes. We hypothesized that planned biventricular assist device insertion improves survival compared with delayed conversion of left ventricular assist device support to biventricular assist device support. METHODS: We reviewed and compared outcomes of 266 patients undergoing left ventricular assist device or biventricular assist device placement at the University of Pennsylvania from April 1995 to June 2007. We subdivided patients receiving biventricular assist devices into planned biventricular assist device (P-BiVAD) and delayed biventricular assist device (D-BiVAD) groups based on the timing of right ventricular assist device insertion. We defined the D-BiVAD group as any failure of isolated left ventricular assist device support. RESULTS: Of 266 patients who received left ventricular assist devices, 99 (37%) required biventricular assist device support. We compared preoperative characteristics, successful bridging to transplantation, survival to hospital discharge, and Kaplan-Meier 1-year survival between the P-BiVAD (n = 71) and D-BiVAD (n = 28) groups. Preoperative comparison showed that patients who ultimately require biventricular support have similar preoperative status. Left ventricular assist device (n = 167) outcomes in all categories exceeded both P-BiVAD and D-BiVAD group outcomes. Furthermore, patients in the P-BiVAD group had superior survival to discharge than patients in the D-BiVAD group (51% vs 29%, P < .05). One-year and long-term Kaplan-Meier survival distribution confirmed this finding. There was also a trend toward improved bridging to transplantation in the P-BiVAD (n = 55) versus D-BiVAD (n = 22) groups (65% vs 45%, P = .10). CONCLUSION: When patients at high risk for failure of isolated left ventricular assist device support are identified, proceeding directly to biventricular assist device implantation is advised because early institution of biventricular support results in dramatic improvement in survival.

Risk score derived from pre-operative data analysis predicts the need for biventricular mechanical circulatory support.

BACKGROUND: Right ventricular (RV) failure after left ventricular assist device (LVAD) placement is a serious complication and is difficult to predict. In the era of destination therapy and the total artificial heart, predicting post-LVAD RV failure requiring mechanical support is extremely important. METHODS: We reviewed patient characteristics, laboratory values and hemodynamic data from 266 patients who underwent LVAD placement at the University of Pennsylvania from April 1995 to June 2007. RESULTS: Of 266 LVAD recipients, 99 required RV assist device (BiVAD) placement (37%). We compared 36 parameters between LVAD (n = 167) and BiVAD patients (n = 99) to determine pre-operative risk factors for RV assist device (RVAD) need. By univariate analysis, 23 variables showed statistically significant differences between the two groups (p < or = 0.05). By multivariate logistic regression, cardiac index < or =2.2 liters/min/m(2) (odds ratio [OR] 5.7), RV stroke work index < or =0.25 mm Hg . liter/m(2) (OR 5.1), severe pre-operative RV dysfunction (OR 5.0), pre-operative creatinine > or =1.9 mg/dl (OR 4.8), previous cardiac surgery (OR 4.5) and systolic blood pressure < or =96 mm Hg (OR 2.9) were the best predictors of RVAD need. CONCLUSIONS: The most significant predictors for RVAD need were cardiac index, RV stroke work index, severe pre-operative RV dysfunction, creatinine, previous cardiac surgery and systolic blood pressure. Using these data, we constructed an algorithm that can predict which LVAD patients will require RVAD with >80% sensitivity and specificity.