S. Winowich

Incidence and Patterns of Adverse Event Onset During the First 60 Days After Ventricular Assist Device Implantation

BACKGROUND Although ventricular assist devices (VADs) provide effective treatment for end-stage heart failure, VAD support remains associated with significant risk for adverse events (AEs). To date there has been no detailed assessment of the incidence of a full range of AEs using standardized event definitions. We sought to characterize the frequency and timing of AE onset during the first 60 days of VAD support, a period during which clinical observation suggests the risk of incident AEs is high. METHODS A retrospective analysis was performed utilizing prospectively collected data from a single-site clinical database including 195 patients aged 18 or greater receiving VADs between 1996 and 2006. Adverse events were coded using standardized criteria. Cumulative incidence rates were determined, controlling for competing risks (death, transplantation, recovery-wean). RESULTS During the first 60 days after implantation, the most common AEs were bleeding, infection, and arrhythmias (cumulative incidence rates, 36% to 48%), followed by tamponade, respiratory events, reoperations, and neurologic events (24% to 31%). Other events (eg, hemolysis, renal, hepatic events) were less common (rates <15%). Some events (eg, bleeding, arrhythmias) showed steep onset rates early after implantation. Others (eg, infections, neurologic events) had gradual onsets during the 60-day period. Incidence of most events did not vary by implant era (1996 to 2000 vs 2001 to 2006) or by left ventricular versus biventricular support. CONCLUSIONS Understanding differential temporal patterns of AE onset will allow preventive strategies to be targeted to the time periods when specific AE risks are greatest. The AE incidence rates provide benchmarks against which future studies of VAD-related risks may be compared.

Early adverse events as predictors of 1-year mortality during mechanical circulatory support

BACKGROUND Ventricular assist devices (VADs) provide effective treatment for end-stage heart failure; however, most patients experience > or =1 major adverse events (AEs) while on VAD support. Although early, non-fatal AEs may increase the risk of later death during VAD support, this relationship has not been established. Therefore, we sought to determine the impact on 1-year mortality of AEs occurring during the first 60 days of VAD support. METHODS A retrospective analysis was performed using prospectively collected data from a single-site database for patients aged > or =18 years receiving left ventricular or biventricular support during 1996 to 2008 and who survived >60 days on VAD support. Fourteen major classes of AEs occurring during this 60-day period were examined. One-year survival rates of patients with and without each major AE were compared. RESULTS The study included 163 patients (80% men; mean age, 49.5 years), of whom 87% were European American, 72% had left ventricular support, and 83% were bridge to transplant. The occurrence of renal failure, respiratory failure, bleeding events, and reoperations during the first 60 days after implantation significantly increased the risk of 1-year mortality. After controlling for gender, age, VAD type, and intention to treat, renal failure was the only major AE significantly associated with later mortality (hazard ratio, 2.96; p = .023). CONCLUSIONS Specific AEs, including renal failure, respiratory and bleeding events, and reoperations, significantly decrease longer-term survival. Renal failure conferred a 3-fold increased risk of 1-year mortality. Peri-operative management should focus on strategies to mitigate risk for renal failure in order to maximize later outcomes.

DOES A ROTARY PUMP PROVIDE FULL CARDIAC DECOMPRESSION AND CIRCULATORY SUPPORT? -FROM CLINICAL EXPERIENCES OF HEARTMATE II WITH SEVERE CONGESTIVE HEART FAILURE PATIENTS-

AND CIRCULATORY SUPPORT? -FROM CLINICAL EXPERIENCES OF HEARTMATE II WITH SEVERE CONGESTIVE HEART FAILURE PATIENTSHiroyuki Tsukui, Steve Winowich, Eileen Stanford, Jeffrey J Teuteberg, Robert L Kormos. Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA; Cardiology, University of Pittsburgh, Pittsburgh, PA. Purpose: Rotary pumps such as the Heartmate II left ventricular assist device (LVAD) (Thoratec Corporation, Pleasanton, CA) are small, nonpulsatile pumps designed for long-term use. However, its capability for providing full cardiac decompression and circulatory support has been questioned and indeed some have felt that the only safe way rotary pumps can be used is in an assistive mode. Methods: Three patients (Ischemic cardiomyopathy: 2, Post-partum cardiomyopathy: 1, ejection fraction: 10–20%) implanted the HeartMate II LVAD were followed using regular transthoracic echocardiography (TTE). Pump rpm, aortic valve opening (AVO), and left ventricular end-diastolic diameter (LVDd) were measured while changing pump rpm. Results: Full cardiac decompression and circulatory support were observed in all three patients. With the increasing of pump rpm, LVDd and the frequency of AVO decreased in inverse proportion. At an appropriate pump rpm setting, the aortic valve closed completely and LVDd decreased to 60–70% of preoperative LVDd without causing suction by the apical cannula. Longterm renal and circulatory function was normal without heart failure symptoms. Considerations: The Heartmate II provides sufficient circulatory support at an appropriate pump rpm setting in patients with severe congestive heart failure. Long-term full circulatory support can be achieved which is a requirement for destination therapy. INITIAL RESULTS WITH THE PEDIATRIC JARVIK 2000 HEART Robert Jarvik, Bartley Griffith, Greg Burgreen, Michael Morrow, Andrew Lewis. Research, Jarvik Heart, Inc., New York, NY; U of Maryland, Baltimore, MD; Mississippi State U, Starkville, MS. Under the NIH program to develop pediatric mechanical circulatory support systems, we have completed design, fabrication, and initial bench testing of the child model pump, an intraventricular axial flow pump connected from apex to aorta like the adult model Jarvik 2000. The device is one third the size and weight of the adult pump. Parameters include: Adult Jarvik 2000: 26 mm diameter x 7.5 cm long, 30cc, 90g, 16 mm diameter aortic graft, 8–12,000 RPM, 1–6 L/min. Pediatric Jarvik 2000: 17.8 mm diameter x 5.5 cm long, 10cc, 35g, 10mm diameter aortic graft, 10–14,000 RPM, 0.5–5 L/min. Computational fluid dynamics run on the initial prototype blade design predicted excellent flow pressure performance and very good pressure recovery by the stators which has been confirmed In Vitro, as shown below. Negligible losses were predicted by CFD at the pump outflow and graft. Modification of the leading edge of the impeller based on the CFD results was made to avoid local cavitation. Other blade design iterations are planned based on the In Vivo findings. Implants in small sheep will begin in February 2005. The system initially utilizes the same controller as the adult model while a smaller controller and battery system are developed.

Psychiatric and psychosocial issues and intervention among ventricular assist device patients

Candidates for heart transplantation face increasingly lengthy waits for donor hearts. In the United States, candidates may wait for well over 12 months (United Network of Organ Sharing statistics for 1994), and during this period, life-threatening deteriorations in their condition often occur. When death is imminent or when survival to transplant is unlikely given declining clinical condition, mechanical circulatory support can often be successfully utilized to bridge patients to cardiac transplantation. By mid-1992, a total of 380 persons had received one of the four most-used types of ventricular assist devices approved as bridges in the United States (38). These devices include the Pierce-Donachy Assist Device (Thoratec, Berkeley, CA) (n = 172 bridged patients by August, 1992); the Abiomed BVS-5000 (Abiomed Cardiovascular Inc., Danvers, MA) (n = 58 patients); the Novacor Left Ventricular Assist System (Novacor Division, Baxter Health Care Corporation, Oakland, CA) (n = 124 patients), and the CardioWest device (CardioWest, Inc., Tempe, AZ) (n = 26 patients). Clinical reports of patients supported by these and similar devices approved more recently show not only remarkable physical rehabilitation in many cases after device insertion, but excellent post-transplant survival rates that meet and sometimes exceed survival rates in nonbridged patients (21,38).

Early atrial and ventricular arrhythmias following ventricular assist device implantation predict a poor prognosis

predict development of C REJ, CRB or allograft vasculopathy. VAD was not associated with sudden death post HT (VAD 3/48 vs. no VAD 2/50, p 0.6) In the entire group of 98, neither H REJ nor CRB predicted development of allograft vasculopathy. Longer ischemic time was correlated with C REJ (p 0.01). Conclusions: Patients bridged with ventricular assist device have increased PRA prior to heart transplantation, but this does not appear to translate into increased risk of either humoral or cellular rejection post-transplant or development of allograft vasculopathy as seen by coronary angiography.

Using non-invasive quantitative echocardiography during weaning trials to assess left ventricular recovery on mechanical assist devices

compare pulsatile and nonpulsatile flow generated by LVADs with outflow to the ascending aorta and descending aorta. Methods: An in vitro mock circulatory loop, driven by either a pulsatile or a nonpulsatile LVAD was anastomosed to transparent aortic models at either ascending or descending aortic position. The aortic valve was kept closed modeling no native cardiac output. Normal saline was used as a blood substitute. Methylene blue dye was injected to illustrate flow patterns in the ascending aorta and aortic arch. Dye washout time was used as a marker of flow stagnation and potential thrombogenicity. Cardiac output, afterload and coronary flow were measured. Results: Dye washout times for 5 L/min flow rate were 2.0 0.8, 2.0 0.7, 5.0 0.8, and 8.0 4.4 sec for pulsatile ascending (PA), continuous ascending (CA), pulsatile descending (PD), and continuous descending (CD), respectively. Coronary flow was 265, 312, 310, and 286 ml/min for PA, CA, PD, and CD, respectively. Dye washout times for 4 L/min flow rate were 3.0 1.0, 3.0 0.8, 14.0 3.8, and 25.0 9.1 sec for PA, CA, PD, and CD, respectively. Coronary flow was 210, 240, 225, and 233 ml/min for PA, CA, PD, and CD, respectively. Conclusion: LVAD descending aortic anastomosis and retrograde aortic flow is associated with significantly increased (P 0.001) flow stagnation in the ascending aorta. This may increase the risk for thromboembolism in patients solely relying on retrograde aortic flow. There were no differences in coronary flow across the study groups.

RIGHT VENTRICULAR PERFORMANCE AND LEFT VENTRICULAR ASSIST DEVICE FILLING

BACKGROUND Right ventricular (RV) function is believed to be an important determinant of left ventricular assist device (LVAD) filling. This study was designed to demonstrate this relation in patients. METHODS To demonstrate the interaction between RV ejection and LVAD filling, 10 patients (mean age, 49 +/- 13 years) supported with an LVAD were studied. Right ventricular pressure-area loops from cross-sectional area using transesophageal echocardiographic automated border detection and high-fidelity RV pressure were recorded simultaneously with LVAD volume during intraoperative inferior vena cava occlusion. Beat-by-beat RV ejection phase indices were calculated: stroke area, peak ejection rate, and stroke work. The LVAD filling rate was calculated as the first derivative of the volume, and the peak filling rate and the mean filling rate during RV systole were determined for each cardiac cycle. RESULTS Right ventricular stroke area, peak ejection rate, and stroke work were closely correlated with LVAD peak filling rate (r = 0.87 +/- 0.09, r = 0.83 +/- 0.09, and r = 0.85 +/- 0.10, respectively). Also, baseline LVAD mean filling rate correlated with RV stroke work (r = 0.77) and LVAD peak filling rate with RV peak ejection rate for the group (r = 0.75). CONCLUSIONS These correlations demonstrate predictable associations of RV ejection with LVAD filling.