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Unexpected Contribution of Pulsatility to Pump Thrombosis
S232
The Journal of Heart and Lung Transplantation, Vol 38, No 4S, April 2019 D.M. McNamara,2 and M.A. Simon.2 1Emory University, Atlanta, GA; 2 University of Pittsburgh Medical Center, Pittsburgh, PA; 3University of Pittsburgh School of Medicine, Pittsburgh, PA; and the 4University of Pittsburgh Vascular Medicine Institute, Pittsburgh, PA.
561 Unexpected Contribution of Pulsatility to Pump Thrombosis J. Engelman, K. Muthiah, P. Jain, D. Robson, P. Jansz and C. Hayward. Heart Failure and Transplant Unit, St Vincent's Hospital, Sydney, Australia. Purpose: Diminished pulsatility during continuous flow left ventricular assist device (CF-LVAD) support has been hypothesized to be a causative factor for adverse events, such as neurological events (NE), pump thrombus (PT) and gastrointestinal bleeding (GIB). We assessed outcomes between CF-LVAD patients according to measured pulsatility. Methods: Log-files from 61 HVAD (HeartWare) patients with pulsatility data were analyzed. Mean, peak, trough flow and pulsatility (peak - trough flow) were extracted. Flow pulsatility index (PI), defined as pulsatility/ mean flow, was calculated for each patient at 1, 3, 6, 9 and 12 months. Patients were categorized into low, intermediate and high PI tertiles (table 1). Baseline demographic factors and outcomes (NE, GIB, PT) were compared. NE included both cerebrovascular accidents and transient ischemic attacks. One way ANOVAs and chi-square analyses were performed to analyze continuous and categorical variables respectively. Results: There were no significant differences in demographics between the 3 groups according to pulsatility. Surprisingly, there was a significantly higher rate of PT in the high PI group compared to the low and intermediate groups (p=0.013). Factors that contribute to the PI demonstrated that low trough flow was an independent predictor of PT according to logistic regression (OR 0.205, p=0.028). Marginally higher rates of NE were found in the high PI group compared to the low and intermediate groups, however this was not statistically significant (p=0.30). There were no differences in rates of GIB between groups. Conclusion: High PI, particularly driven by low trough flow, was associated with an increased risk of PT highlighting an important therapeutic target for potential prevention or intervention for PT.
Table 1
Demographics and Outcomes according to PI Group
Variables median (range) Age at Implant (yrs) Male n(%) Duration of Support (days) Outcomes n(%) Alive Transplanted Dead Gastrointestinal Bleeding Neurological Event Pump Thrombus
Low PI (<0.85) n=19
Intermediate PI High PI (0.85-1) n=21 (>1) n=21
56 (36-70) 52 (39-68) 16 (84.2) 18 (85.7) 312 (119-1032) 284 (36-985) 12 (63.2) 5 (26.3) 2 (10.5) 2 (11) 3 (17) 0 (0)
10 (47.6) 9 (42.9) 2 (9.5) 2 (10) 4 (19) 1 (5)
p-value
60 (33-76) 0.354 15 (71.4) 0.445 305 (59-811) 0.913 0.613 11 (52.4) 8 (38.1) 2 (9.5) 2 (10) 1.000 8 (36) 0.298 6 (29) 0.013
562 CCR5 Expression is Lower in Women, and Mediates Sex-Based Differences in Post-LVAD Right Ventricular Failure A. Nayak,1 A.A. Morris,1 C.M. Sciortino,2 C. Neill,3 R.L. Kormos,2 C. McTiernan,4 J. Larsen,3 T.N. Bachman,4 K. Hanley-Yanez,4
Purpose: Women have increased risk of right ventricular failure (RVF) after LVAD implant, however the underlying pathophysiology is unknown. Chemokines are inflammatory signaling molecules, and fundamental to cardiac homeostasis and stress adaptation. Prior studies have demonstrated a cardioprotective role for chemokine receptor-5 (CCR5) in viral myocarditis and severe Chagas cardiomyopathy, and that sex hormones modulate CCR5 gene expression. We have previously shown that CCR 3-8 down-regulation is predictive of RVF and 1-year survival after implant. We hypothesized that CCR5 expression mediates sex-based differences in post-LVAD RVF. Methods: CCR expression was examined in patient’s peripheral blood 24 hours pre-LVAD. RNA was isolated using PAXgene protocol. Gene expression was assessed using a targeted microarray (RT2 Profiler PCR array, Qiagen). Results were expressed as PCR cycles to threshold (CT). DCT was calculated as (CCR gene CT) - (HPRT1 control gene CT), and log2 transformed for analysis. Log-fold differences in expression were reported using 2¡DDCT method. RVF was defined as both planned and unplanned RVAD requirement. Multivariable logistic regression was used to determine the association of sex with RVF, adjusting for significantly different covariates (p<0.05) from Table 1. Results: We analyzed 111 LVAD patients (mean age: 53.57 § 13 years, 18% female, 17.1% black). The criteria for RVF was met in 35 (31.5%) patients. Women had increased incidence of RVF (50% vs. 27.5%, p=0.047), and under-expressed CCR5 (1.41 fold decrease, p=0.012) compared to men. After controlling for age, heart failure etiology, albumin, BUN, creatinine and cardiac output, women had a higher risk of RVF (HR: 3.18, 95% CI: 1.04-9.8, p=0.043). Addition of CCR5 as a covariate to the model attenuated the association of female sex with RVF (HR: 2.86, 95% CI: 0.91-8.97, p=0.071). Conclusion: Pre-implant CCR5 expression is lower in women than in men and may mediate sex disparities in post-LVAD RVF.
The Journal of Heart and Lung Transplantation, Vol 38, No 4S, April 2019 D.M. McNamara,2 and M.A. Simon.2 1Emory University, Atlanta, GA; 2 University of Pittsburgh Medical Center, Pittsburgh, PA; 3University of Pittsburgh School of Medicine, Pittsburgh, PA; and the 4University of Pittsburgh Vascular Medicine Institute, Pittsburgh, PA.
561 Unexpected Contribution of Pulsatility to Pump Thrombosis J. Engelman, K. Muthiah, P. Jain, D. Robson, P. Jansz and C. Hayward. Heart Failure and Transplant Unit, St Vincent's Hospital, Sydney, Australia. Purpose: Diminished pulsatility during continuous flow left ventricular assist device (CF-LVAD) support has been hypothesized to be a causative factor for adverse events, such as neurological events (NE), pump thrombus (PT) and gastrointestinal bleeding (GIB). We assessed outcomes between CF-LVAD patients according to measured pulsatility. Methods: Log-files from 61 HVAD (HeartWare) patients with pulsatility data were analyzed. Mean, peak, trough flow and pulsatility (peak - trough flow) were extracted. Flow pulsatility index (PI), defined as pulsatility/ mean flow, was calculated for each patient at 1, 3, 6, 9 and 12 months. Patients were categorized into low, intermediate and high PI tertiles (table 1). Baseline demographic factors and outcomes (NE, GIB, PT) were compared. NE included both cerebrovascular accidents and transient ischemic attacks. One way ANOVAs and chi-square analyses were performed to analyze continuous and categorical variables respectively. Results: There were no significant differences in demographics between the 3 groups according to pulsatility. Surprisingly, there was a significantly higher rate of PT in the high PI group compared to the low and intermediate groups (p=0.013). Factors that contribute to the PI demonstrated that low trough flow was an independent predictor of PT according to logistic regression (OR 0.205, p=0.028). Marginally higher rates of NE were found in the high PI group compared to the low and intermediate groups, however this was not statistically significant (p=0.30). There were no differences in rates of GIB between groups. Conclusion: High PI, particularly driven by low trough flow, was associated with an increased risk of PT highlighting an important therapeutic target for potential prevention or intervention for PT.
Table 1
Demographics and Outcomes according to PI Group
Variables median (range) Age at Implant (yrs) Male n(%) Duration of Support (days) Outcomes n(%) Alive Transplanted Dead Gastrointestinal Bleeding Neurological Event Pump Thrombus
Low PI (<0.85) n=19
Intermediate PI High PI (0.85-1) n=21 (>1) n=21
56 (36-70) 52 (39-68) 16 (84.2) 18 (85.7) 312 (119-1032) 284 (36-985) 12 (63.2) 5 (26.3) 2 (10.5) 2 (11) 3 (17) 0 (0)
10 (47.6) 9 (42.9) 2 (9.5) 2 (10) 4 (19) 1 (5)
p-value
60 (33-76) 0.354 15 (71.4) 0.445 305 (59-811) 0.913 0.613 11 (52.4) 8 (38.1) 2 (9.5) 2 (10) 1.000 8 (36) 0.298 6 (29) 0.013
562 CCR5 Expression is Lower in Women, and Mediates Sex-Based Differences in Post-LVAD Right Ventricular Failure A. Nayak,1 A.A. Morris,1 C.M. Sciortino,2 C. Neill,3 R.L. Kormos,2 C. McTiernan,4 J. Larsen,3 T.N. Bachman,4 K. Hanley-Yanez,4
Purpose: Women have increased risk of right ventricular failure (RVF) after LVAD implant, however the underlying pathophysiology is unknown. Chemokines are inflammatory signaling molecules, and fundamental to cardiac homeostasis and stress adaptation. Prior studies have demonstrated a cardioprotective role for chemokine receptor-5 (CCR5) in viral myocarditis and severe Chagas cardiomyopathy, and that sex hormones modulate CCR5 gene expression. We have previously shown that CCR 3-8 down-regulation is predictive of RVF and 1-year survival after implant. We hypothesized that CCR5 expression mediates sex-based differences in post-LVAD RVF. Methods: CCR expression was examined in patient’s peripheral blood 24 hours pre-LVAD. RNA was isolated using PAXgene protocol. Gene expression was assessed using a targeted microarray (RT2 Profiler PCR array, Qiagen). Results were expressed as PCR cycles to threshold (CT). DCT was calculated as (CCR gene CT) - (HPRT1 control gene CT), and log2 transformed for analysis. Log-fold differences in expression were reported using 2¡DDCT method. RVF was defined as both planned and unplanned RVAD requirement. Multivariable logistic regression was used to determine the association of sex with RVF, adjusting for significantly different covariates (p<0.05) from Table 1. Results: We analyzed 111 LVAD patients (mean age: 53.57 § 13 years, 18% female, 17.1% black). The criteria for RVF was met in 35 (31.5%) patients. Women had increased incidence of RVF (50% vs. 27.5%, p=0.047), and under-expressed CCR5 (1.41 fold decrease, p=0.012) compared to men. After controlling for age, heart failure etiology, albumin, BUN, creatinine and cardiac output, women had a higher risk of RVF (HR: 3.18, 95% CI: 1.04-9.8, p=0.043). Addition of CCR5 as a covariate to the model attenuated the association of female sex with RVF (HR: 2.86, 95% CI: 0.91-8.97, p=0.071). Conclusion: Pre-implant CCR5 expression is lower in women than in men and may mediate sex disparities in post-LVAD RVF.