Allen Cheng

Survival on the Heart Transplant Waiting List: Impact of Continuous Flow Left Ventricular Assist Device as Bridge to Transplant

BACKGROUND Continued donor organ shortage and improved outcomes with current left ventricular assist device (LVAD) technology have increased the number of patients supported with bridge-to-transplantation (BTT) therapy. Using the United Network of Organ Sharing (UNOS) database, we assessed the impact on survival in patients supported with BTT while on the heart transplant waiting list. METHODS The UNOS database was queried from January 2005 to June 2012 to identify patients listed for heart transplantation as UNOS status 1A or 1B. Patients implanted with a pulsatile-flow device or an LVAD other than the HeartMate II (HM II; Thoratec Inc, Pleasanton, CA) were excluded. Patients were divided into LVAD and non-LVAD groups based on status at the time of listing. Patients were propensity matched (LVAD -non-LVAD = 1:2) for age, sex, weight, presence of diabetes, creatinine levels, mean pulmonary artery pressure, and UNOS status. Kaplan-Meier curves were analyzed for survival. RESULTS A total of 8,688 patients were analyzed, with 1,504 (17%) in the LVAD group. Average age (52.6 ± 11.8 versus 51.3 ± 12.9 years; p = 0.0002) and weight (86.6 ± 18.6 versus 80.8 ± 18.2 kg; p < 0.0001) at time of listing were higher in the LVAD group. There were more men (79% versus 74%; p < 0.0001) and more patients with diabetes (30% versus 27%; p = 0.03) in the LVAD group. Of all patients, 6,943 patients (80%) underwent transplantation, 862 (10%) died, and 883 (10%) remained on the waiting list. After propensity matching, survival to transplantation was significantly better in the LVAD group than in the non-LVAD group at both 1 year (91% versus 77%) and 2 years (85% versus 68%). CONCLUSIONS Patients supported with an HM II LVAD as BTT therapy were older with increased comorbidities; they demonstrated an improved survival while listed for heart transplantation. The use of LVADs as a BTT strategy can potentially improve patient survival while waiting for transplantation and allow better allocation of donor hearts.

Comparison of continuous-flow and pulsatile-flow left ventricular assist devices: is there an advantage to pulsatility?

BACKGROUND Continuous-flow left ventricular assist devices (CFVAD) are currently the most widely used type of mechanical circulatory support as bridge-to-transplant and destination therapy for end-stage congestive heart failure (HF). Compared to the first generation pulsatile-flow left ventricular assist devices (PFVADs), CFVADs have demonstrated improved reliability and durability. However, CFVADs have also been associated with certain complications thought to be linked with decreased arterial pulsatility. Previous studies comparing CFVADs and PFVADs have presented conflicting results. It is important to understand the outcome differences between CFVAD and PFVAD in order to further advance the current VAD technology. METHODS In this review, we compared the outcomes of CFVADs and PFVADs and examined the need for arterial pulsatility for the future generation of mechanical circulatory support. RESULTS CVADs offer advantages of smaller size, increased reliability and durability, and subsequent improvements in survival. However, with the increasing duration of long-term support, it appears that CFVADs may have specific complications and a lower rate of left ventricular recovery associated with diminished pulsatility, increased pressure gradients on the aortic valve and decreased compliance in smaller arterial vessels. PFVAD support or pulsatility control algorithms in CFVADs could be beneficial and potentially necessary for long term support. CONCLUSIONS Given the relative advantages and disadvantages of CFVADs and PFVADs, the ultimate solution may lie in incorporating pulsatility into current and emerging CFVADs whilst retaining their existing benefits. Future studies examining physiologic responses, end-organ function and LV remodeling at varying degrees of pulsatility and device support levels are needed.

Rotary pump speed modulation for generating pulsatile flow and phasic left ventricular volume unloading in a bovine model of chronic ischemic heart failure

BACKGROUND Rotary blood pumps operate at a constant speed (rpm) that diminishes vascular pulsatility and variation in ventricular end-systolic and end-diastolic volumes, which may contribute to adverse events, including aortic insufficiency and gastrointestinal bleeding. In this study, pump speed modulation algorithms for generating pulsatility and variation in ventricular end-systolic and end-diastolic volumes were investigated in an ischemic heart failure (IHF) bovine model (n = 10) using a clinically implanted centrifugal-flow left ventricular assist device (LVAD). METHODS Hemodynamic and hematologic measurements were recorded during IHF baseline, constant pumps speeds, and asynchronous (19-60 cycles/min) and synchronous (copulse and counterpulse) pump speed modulation profiles using low relative pulse speed (±25%) of 3,200 ± 800 rpm and high relative pulse speed (±38%) of 2,900 ± 1,100 rpm. End-organ perfusion, hemodynamics, and pump parameters were measured to characterize pulsatility, myocardial workload, and LVAD performance for each speed modulation profile. RESULTS Speed modulation profiles augmented aortic pulse pressure, surplus hemodynamic energy, and end-organ perfusion (p < 0.01) compared with operation at constant speed. Left ventricular external work and myocardial oxygen consumption were significantly reduced compared with IHF baseline (p < 0.01) but at the expense of higher LVAD power consumption. CONCLUSIONS Pump speed modulation increases pulsatility and improves cardiac function and end-organ perfusion, but the asynchronous mode provides the technologic advantage of sensorless control. Investigation of asynchronous pump speed modulation during long-term support is warranted to test the hypothesis that operating an LVAD with speed modulation will minimize adverse events in patients supported by an LVAD that may be associated with long-term operation at a constant pump speed.

Hemodynamic Support With a Microaxial Percutaneous Left Ventricular Assist Device (Impella) Protects Against Acute Kidney Injury in Patients Undergoing High-Risk Percutaneous Coronary InterventionNovelty and Significance

Rationale: Acute kidney injury (AKI) is common during high-risk percutaneous coronary intervention (PCI), particularly in those with severely reduced left ventricular ejection fraction. The impact of partial hemodynamic support with a microaxial percutaneous left ventricular assist device (pLVAD) on renal function after high-risk PCI remains unknown. Objective: We tested the hypothesis that partial hemodynamic support with the Impella 2.5 microaxial pLVAD during high-risk PCI protected against AKI. Methods and Results: In this retrospective, single-center study, we analyzed data from 230 patients (115 consecutive pLVAD-supported and 115 unsupported matched-controls) undergoing high-risk PCI with ejection fraction ⩽35%. The primary outcome was incidence of in-hospital AKI according to AKI network criteria. Logistic regression analysis determined the predictors of AKI. Overall, 5.2% (6) of pLVAD-supported patients versus 27.8% (32) of unsupported control patients developed AKI (P<0.001). Similarly, 0.9% (1) versus 6.1% (7) required postprocedural hemodialysis (P<0.05). Microaxial pLVAD support during high-risk PCI was independently associated with a significant reduction in AKI (adjusted odds ratio, 0.13; 95% confidence intervals, 0.09–0.31; P<0.001). Despite preexisting CKD or a lower ejection fraction, pLVAD support protection against AKI persisted (adjusted odds ratio, 0.63; 95% confidence intervals, 0.25–0.83; P=0.04 and adjusted odds ratio, 0.16; 95% confidence intervals, 0.12–0.28; P<0.001, respectively). Conclusions: Impella 2.5 (pLVAD) support protected against AKI during high-risk PCI. This renal protective effect persisted despite the presence of underlying CKD and decreasing ejection fraction.

Left ventricular volume unloading with axial and centrifugal rotary blood pumps.

Axial (AX) and centrifugal (CFG) rotary blood pumps have gained clinical acceptance for the treatment of advanced heart failure. Differences between AX and CFG designs and mechanism of blood flow delivery may offer clinical advantages. In this study, pump characteristics, and acute physiologic responses during support with AX (HeartMate II) and CFG (HVAD) left ventricular assist devices (LVAD) were investigated in mock loop and chronic ischemic heart failure bovine models. In the mock loop model, pump performance was characterized over a range of pump speeds (HeartMate II: 7,000–11,000 rpm, HVAD: 2,000–3,600 rpm) and fluid viscosities (2.7 cP, 3.2 cP, 3.7 cP). In the ischemic heart failure bovine model, hemodynamics, echocardiography, and end-organ perfusion were investigated. CFG LVAD had a flatter HQ curve, required less power, and had a more linear flow estimation relation than AX LVAD. The flow estimation error for the AX LVAD (±0.9 L/min at 2.7 cP, ±0.7 L/min at 3.2 cP, ±0.8 L/min at 3.7 cP) was higher than the CFG LVAD (±0.5 L/min at 2.7 cP, ±0.2 L/min at 3.2 cP, ±0.5 L/min at 3.7 cP). No differences in acute hemodynamics, echocardiography, or end-organ perfusion between AX and CFG LVAD over a wide range of support were statistically discernible. These findings suggest no pronounced acute differences in LV volume unloading between AX and CFG LVAD.

The association of pretransplant HeartMate II left ventricular assist device placement and heart transplantation mortality.

Previous United Network for Organ Sharing (UNOS) analysis has shown an increase in posttransplant mortality with pretransplant pulsatile-flow left ventricular assist device (LVAD). Recent studies evaluating continuous-flow LVAD demonstrated improved durability, excellent survival, and improved quality of life. This study investigates the association of preheart transplant continuous-flow LVAD placement and posttransplant mortality using the UNOS database. Heart transplant patients listed after April 2004 (N = 48,090) during the era of HeartMate (HM) II LVAD usage were investigated. Patients with UNOS 1A and 1B status with (n = 1,435) and without HMII (n = 16,379) placement before the heart transplantation were evaluated. Preliminary descriptive statistics suggested an extensive heterogeneity in patient characteristics between HMII LVAD recipients and nonrecipients. Propensity scores (1:2) were used to match HMII LVAD recipients and nonrecipients characteristics and donor characteristics. This resulted in a final sample of 2,265 patients (758 with HMII pretransplant placement and 1,507 without HMII pretransplant placement). The Kaplan–Meier curves were evaluated for the differences in postheart transplant mortality in patients with and without HMII pretransplant placement. A time-dependent Cox regression model was used to study the hazard ratios (HRs) for the association between HMII pretransplant placement and posttransplant survival. The mean age of the study group was 51.9 years old (standard deviation: 12.3). HeartMate II pretransplant placement was associated with no statistically significant difference in the risk of 30 days (HR = 1.23, 95% confidence interval [CI]: 0.79–1.95, p = 0.36) and 1 year posttransplant mortality (HR = 1.31, 95% CI: 0.85–2.01, p = 0.22) compared with non-HMII recipients. The use of HMII LVAD before heart transplantation, however, was associated with a statistically significant 64% lower risk (HR = 0.36, 95% CI: 0.16–0.77, p = 0.01) of mortality among heart transplant patients who survived beyond the first year of transplantation. Continuous-flow LVAD pretransplant placement is associated with improved long-term (>1 year) survival after heart transplantation.

How I choose conduits and configure grafts for my patients-rationales and practices.

Coronary artery bypass grafting (CABG) continues to be an effective therapy for many patients with lasting long-term durability and consistent outcomes, despite the development of percutaneous revascularization. The long-term outcome for surgical revascularization depends on multiple variables, including the choice of conduits. However, the choice of coronary conduits has been studied and debated for decades now. In this review article, we examined the current evidences and described our choice on coronary conduits and grafting strategies at our medical center.

Hemodynamic changes and retrograde flow in LVAD failure.

In the event of left ventricular assist device (LVAD) failure, we hypothesized that rotary blood pumps will experience significant retrograde flow and induce adverse physiologic responses. Catastrophic LVAD failure was investigated in computer simulation with pulsatile, axial, and centrifugal LVAD, mock flow loop with pulsatile (PVAD) and centrifugal (ROTAFLOW), and healthy and chronic ischemic heart failure bovine models with pulsatile (PVAD), axial (HeartMate II), and centrifugal (HVAD) pumps. Simulated conditions were LVAD “off” with outflow graft clamped (baseline), LVAD “off” with outflow graft unclamped (LVAD failure), and LVAD “on” (5 L/min). Hemodynamics (aortic and ventricular blood pressures, LVAD flow, and left ventricular volume), echocardiography (cardiac volumes), and end-organ perfusion (regional blood flow microspheres) were measured and analyzed. Retrograde flow was observed with axial and centrifugal rotary pumps during LVAD failure in computer simulation (axial = -3.4 L/min, centrifugal = -2.8 L/min), mock circulation (pulsatile = -0.1 L/min, centrifugal = -2.7 L/min), healthy (pulsatile = -1.2 ± 0.3 L/min, axial = -2.2 ± 0.2 L/min, centrifugal = -1.9 ± 0.3 L/min), and ischemic heart failure (centrifugal = 2.2 ± 0.7 L/min) bovine models for all test conditions (p < 0.05). Differences between axial and centrifugal LVAD were statistically indiscernible. Retrograde flow increased ventricular end-systolic and end-diastolic volumes and workload, and decreased myocardial and end-organ perfusion during LVAD failure compared with baseline, LVAD support, and pulsatile LVAD failure.

Heart Transplant Survival Based on Recipient and Donor Risk Scoring: A UNOS Database Analysis.

Unlike the lung allocation score, currently, there is no quantitative scoring system available for patients on heart transplant waiting list. By using United Network for Organ Sharing (UNOS) data, we aim to generate a scoring system based on the recipient and donor risk factors to predict posttransplant survival. Available UNOS data were queried between 2005 and 2013 for heart transplant recipients aged ≥18 years to create separate cox-proportional hazard models for recipient and donor risk scoring. On the basis of risk scores, recipients were divided into five groups and donors into three groups. Kaplan–Meier curves were used for survival. Total 17,131 patients had heart transplant within specified time period. Major factors within high-risk groups were body mass index > 30 kg/m2 (46%), mean pulmonary artery pressure >30 mmHg (65%), creatinine > 1.5 mg% (63%), bilirubin > 1.5 mg% (54%), noncontinuous-flow left ventricular assist devices (45%) for recipients and gender mismatch (81%) and ischemia time >4 hours (88%) for donors. Survival in recipient groups 1, 2, 3, 4, and 5 at 5 years was 81, 80, 77, 74, and 62%, respectively, and in donor groups 1, 2, and 3 at 5 years was 79, 77, and 70%, respectively (p < 0.001). Combining donor and recipient groups based on scoring showed acceptable survival in low-risk recipients with high-risk donor (75% at 5 years). A higher recipient and donor risk score are associated with worse long-term survival. A low-risk recipient transplanted with high-risk donor has acceptable survival at 5 years, but high-risk recipient combined with a high-risk donor has marginal results. Using an objective scoring system could help get the best results when utilizing high-risk donors.

Predictors of Donor Heart Utilization for Transplantation in United States

BACKGROUND Optimum use of donor organs can increase the reach of the transplantation therapy to more patients on waiting list. The heart transplantation (HTx) has remained stagnant in United States over the past decade at approximately 2,500 HTx annually. With the use of the United Network of Organ Sharing (UNOS) deceased donor database (DCD) we aimed to evaluate donor factors predicting donor heart utilization. METHODS UNOS DCD was queried from 2005 to 2014 to identify total number of donors who had at least one of their organs donated. We then generated a multivariate logistic regression model using various demographic and clinical donor factors to predict donor heart use for HTx. Donor hearts not recovered due to consent or family issues or recovered for nontransplantation reasons were excluded from the analysis. RESULTS During the study period there were 80,782 donors of which 23,606 (29%) were used for HTx, and 38,877 transplants (48%) were not used after obtaining consent because of poor organ function (37%), donor medical history (13%), and organ refused by all programs (5%). Of all, 22,791 donors with complete data were used for logistic regression (13,389 HTx, 9,402 no-HTx) which showed significant predictors of donor heart use for HTx. From this model we assigned probability of donor heart use and identified 3,070 donors with HTx-eligible unused hearts for reasons of poor organ function (28%), organ refused by all programs (15%), and recipient not located (9%). CONCLUSIONS An objective system based on donor factors can predict donor heart use for HTx and may help increase availability of hearts for transplantation from existing donor pool.