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Vascular Abnormalities of the Nasal Mucosa Are Associated with Gastrointestinal Bleeding During Continuous Flow LVAD Support
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The Journal of Heart and Lung Transplantation, Vol 35, No 4S, April 2016
2( 05)
patients may be predisposed to higher incidence of bleeding and clotting events due to difficulty in management of anticoagulation. Methods: CF-LVAD patients with warfarin genotype data at a single institution were included in this study. Genotyping was performed for *1, *2 and *3 variants in CYP2C9 gene, and 1639G> A variant in VKORC1 gene. Patients were categorized as wild-type (not carrying any rare variants) or rare-variant for each gene. Time-to-event analysis was performed to investigate effect of rare variants of bleeding and thrombotic complications. Results: 148 CF-LVAD patients had warfarin genotype data at the time of analysis. 41 patients carried a rare variant in CYP2C9 gene and 53 patients (37.3%) carried a rare variant in VKORC1 gene. CYP2C9 rare variant group had significantly increased risk of device thrombosis (25.7% vs. 9.4% at 1 year, p= 0.029) and a trend towards increased risk of gastrointestinal bleeding (GIB: 41.4% vs. 24.0% at 1 year, p= 0.054) compared to wild-type group. Interestingly, the majority of GIB events occurred early after CF-LVAD implantation, when INR levels tend to fluctuate most (Figure). VKORC1 rare variant group had a trend towards increase in device thrombosis (21.5% vs. 10.2%, p= 0.123) and risk of GI Bleeding (32.9% vs. 26.9%, p= 0.097). Conclusion: Our findings suggest that warfarin sensitive patients are at higher risk for both bleeding and thrombosis complications following CF-LVAD support. Genotype-guided dosing and frequent INR monitoring may improve outcomes in this group.
Vascular Abnormalities of the Nasal Mucosa Are Associated with Gastrointestinal Bleeding During Continuous Flow LVAD Support S.R. Patel , O. Saeed, S. Madan, M. Algodi, A. Luke, M. Gibber, D.J. Goldstein, U.P. Jorde. Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY. Purpose: Bleeding from mucosal surfaces of the nasopharynx and gastrointestinal (GI) tract is the most common complication of CF-LVAD support and facilitated by nearly uniform Von Willebrand factor deficiency combined with a high incidence of arteriovenous malformations (AVM). The etiology of AVM formation during CF-LVAD support remains uncertain, largely due to difficult access of GI AVMs by enteroscopy. In contrast, nasal endoscopy is a minimally invasive bedside test giving ready access to a mucosal surface. To explore the possible contribution of CF-LVAD support induced systemic mucosal vascular abnormalities to clinical bleeding, we examined nasal mucosal abnormalities in patients with and without gastrointestinal bleeding. Methods: Subjects at least 60 days post implantation of CF-LVAD were prospectively recruited from Montefiore Medical Center. Systematic evaluation of the intranasal mucosa and vasculature was performed with nasal endoscopy. The sites of all vascular abnormalities were recorded with particular attention to the presence of hypervascularity. Patient records were reviewed for episodes and etiology of GI bleeding. Results: Thirty-five subjects, with a median age of 55 years (25-76), 17% female, and 37% ischemic etiology, underwent nasal endoscopy. Overall, 10 (29%) subjects had experienced a GIB episode during LVAD support, 7 (70%) of which were due to AVMs. Hypervascularity (HV) was seen in the nasal mucosa of 22 (63%) subjects. There were no significant differences in baseline characteristics between patients with and without HV. Patients with hypervascularity demonstrated a higher incidence of GIB (41% vs 8%, p= 0.0356) and of confirmed GIB from AVM (32% vs 0%, p= 0.0230). Figure 1. Conclusion: Hypervascularity in the nasal mucosa is strongly associated with AVM bleeding in CF-LVAD patients. Study of the nasal mucosa may allow to identify CF-LVAD patients at high risk for GI bleeding and provide insights into the pathophysiology of AVM formation.
2( 07) Predictors of Out-of-Therapeutic-Range INR during Support with Continuous-Flow Left Ventricular Assist Device M. Yin , W. Schultz, Y. Ko, R.T. Cole, D. Gupta, S. Laskar, A. Smith, D. Vega, D. Nguyen, A. Pekarek, K. Wittersheim, A. Morris. Emory University School of Medicine, Atlanta, GA.
2( 06) Warfarin Sensitive Patients Have Higher Risk of Gastrointestinal Bleeding and Device Thrombosis on Continuous-Flow Left Ventricular Assist Device (CF-LVAD) Support V.K. Topkara ,1 A.B. Eisenberger,1 R. Knotts,1 D. Jennings,1 A.R. Garan,1 M. Yuzefpolskaya,1 K. Takeda,2 H. Takayama,2 R.C. Li,1 J.A. Fried,1 F. Castagna,1 B. Cagliostro,1 M. Tiburcio,2 D.M. Mancini,1 Y. Naka,2 P.C. Colombo,1 U.P. Jorde.3 1Medicine, Columbia University, New York, NY; 2Surgery, Columbia University, New York, NY; 3Medicine, Montefiore Medical Center, New York, NY. Purpose: A significant portion of inter-individual variability of warfarin response appears to have a genetic basis. We have previously reported that patients carrying rare variants in CYP2C9 or VKORC1 genes require lower doses of warfarin following continuous-flow left ventricular assist device (CF-LVAD) implantation. We hypothesized that warfarin sensitive CF-LVAD
Purpose: Our prior data has confirmed that patients with INR out of therapeutic range are at higher risk of stroke after left ventricular assist device (LVAD) implantation. We performed a retrospective cohort analysis to determine the effect of INR on the onset of stroke after LVAD, and to identify which clinical risk factors put patients at high risk for out-of-therapeuticrange INR. Methods: Advanced heart failure patients (N= 110) discharged from Emory University Hospital after implantation with a HeartMate II (N= 74) or HeartWare (N= 36) LVAD were retrospectively evaluated. Time to first stroke was evaluated as a function of whether INR was in-therapeuticrange (ITR) or out-of-therapeutic range (OTR) at the time of stroke. INR was treated as a categorical variable (ITR vs. OTR) and as a continuous variable (overall time-in-therapeutic-range [TTR] derived via the Rosendaal method) to determine which clinical characteristics were associated with OTR INR. Results: Our cohort included 35 (32%) females, 63 (57%) Blacks with mean age 49.6 ± 13.6 years and median follow up time of 417 days (interquartile range 226-765). During the follow-up period, 20 (43%) patients with OTR INR developed stroke compared to 6 (10%) patients with ITR INR (Figure 1). Risk of OTR INR was higher for females (odds ratio [OR] 1.99, 95% confidence interval [CI] 0.88-4.50, p = 0.1) and for patients with higher creatinine (OR 1.57, 95% CI 0.92-2.71, p = 0.1). Overall TTR was 49.9% for the cohort. Predictors of lower TTR were black race (p = 0.09), higher BMI (p = 0.06), lower albumin (p = 0.02), and lower hematocrit (p= 0.06). Conclusion: OTR INR is associated with increased risk of stroke in patients after LVAD implantation. Female sex, black race, elevated creatinine, high BMI and low albumin and hematocrit are clinical predictors of
The Journal of Heart and Lung Transplantation, Vol 35, No 4S, April 2016
2( 05)
patients may be predisposed to higher incidence of bleeding and clotting events due to difficulty in management of anticoagulation. Methods: CF-LVAD patients with warfarin genotype data at a single institution were included in this study. Genotyping was performed for *1, *2 and *3 variants in CYP2C9 gene, and 1639G> A variant in VKORC1 gene. Patients were categorized as wild-type (not carrying any rare variants) or rare-variant for each gene. Time-to-event analysis was performed to investigate effect of rare variants of bleeding and thrombotic complications. Results: 148 CF-LVAD patients had warfarin genotype data at the time of analysis. 41 patients carried a rare variant in CYP2C9 gene and 53 patients (37.3%) carried a rare variant in VKORC1 gene. CYP2C9 rare variant group had significantly increased risk of device thrombosis (25.7% vs. 9.4% at 1 year, p= 0.029) and a trend towards increased risk of gastrointestinal bleeding (GIB: 41.4% vs. 24.0% at 1 year, p= 0.054) compared to wild-type group. Interestingly, the majority of GIB events occurred early after CF-LVAD implantation, when INR levels tend to fluctuate most (Figure). VKORC1 rare variant group had a trend towards increase in device thrombosis (21.5% vs. 10.2%, p= 0.123) and risk of GI Bleeding (32.9% vs. 26.9%, p= 0.097). Conclusion: Our findings suggest that warfarin sensitive patients are at higher risk for both bleeding and thrombosis complications following CF-LVAD support. Genotype-guided dosing and frequent INR monitoring may improve outcomes in this group.
Vascular Abnormalities of the Nasal Mucosa Are Associated with Gastrointestinal Bleeding During Continuous Flow LVAD Support S.R. Patel , O. Saeed, S. Madan, M. Algodi, A. Luke, M. Gibber, D.J. Goldstein, U.P. Jorde. Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY. Purpose: Bleeding from mucosal surfaces of the nasopharynx and gastrointestinal (GI) tract is the most common complication of CF-LVAD support and facilitated by nearly uniform Von Willebrand factor deficiency combined with a high incidence of arteriovenous malformations (AVM). The etiology of AVM formation during CF-LVAD support remains uncertain, largely due to difficult access of GI AVMs by enteroscopy. In contrast, nasal endoscopy is a minimally invasive bedside test giving ready access to a mucosal surface. To explore the possible contribution of CF-LVAD support induced systemic mucosal vascular abnormalities to clinical bleeding, we examined nasal mucosal abnormalities in patients with and without gastrointestinal bleeding. Methods: Subjects at least 60 days post implantation of CF-LVAD were prospectively recruited from Montefiore Medical Center. Systematic evaluation of the intranasal mucosa and vasculature was performed with nasal endoscopy. The sites of all vascular abnormalities were recorded with particular attention to the presence of hypervascularity. Patient records were reviewed for episodes and etiology of GI bleeding. Results: Thirty-five subjects, with a median age of 55 years (25-76), 17% female, and 37% ischemic etiology, underwent nasal endoscopy. Overall, 10 (29%) subjects had experienced a GIB episode during LVAD support, 7 (70%) of which were due to AVMs. Hypervascularity (HV) was seen in the nasal mucosa of 22 (63%) subjects. There were no significant differences in baseline characteristics between patients with and without HV. Patients with hypervascularity demonstrated a higher incidence of GIB (41% vs 8%, p= 0.0356) and of confirmed GIB from AVM (32% vs 0%, p= 0.0230). Figure 1. Conclusion: Hypervascularity in the nasal mucosa is strongly associated with AVM bleeding in CF-LVAD patients. Study of the nasal mucosa may allow to identify CF-LVAD patients at high risk for GI bleeding and provide insights into the pathophysiology of AVM formation.
2( 07) Predictors of Out-of-Therapeutic-Range INR during Support with Continuous-Flow Left Ventricular Assist Device M. Yin , W. Schultz, Y. Ko, R.T. Cole, D. Gupta, S. Laskar, A. Smith, D. Vega, D. Nguyen, A. Pekarek, K. Wittersheim, A. Morris. Emory University School of Medicine, Atlanta, GA.
2( 06) Warfarin Sensitive Patients Have Higher Risk of Gastrointestinal Bleeding and Device Thrombosis on Continuous-Flow Left Ventricular Assist Device (CF-LVAD) Support V.K. Topkara ,1 A.B. Eisenberger,1 R. Knotts,1 D. Jennings,1 A.R. Garan,1 M. Yuzefpolskaya,1 K. Takeda,2 H. Takayama,2 R.C. Li,1 J.A. Fried,1 F. Castagna,1 B. Cagliostro,1 M. Tiburcio,2 D.M. Mancini,1 Y. Naka,2 P.C. Colombo,1 U.P. Jorde.3 1Medicine, Columbia University, New York, NY; 2Surgery, Columbia University, New York, NY; 3Medicine, Montefiore Medical Center, New York, NY. Purpose: A significant portion of inter-individual variability of warfarin response appears to have a genetic basis. We have previously reported that patients carrying rare variants in CYP2C9 or VKORC1 genes require lower doses of warfarin following continuous-flow left ventricular assist device (CF-LVAD) implantation. We hypothesized that warfarin sensitive CF-LVAD
Purpose: Our prior data has confirmed that patients with INR out of therapeutic range are at higher risk of stroke after left ventricular assist device (LVAD) implantation. We performed a retrospective cohort analysis to determine the effect of INR on the onset of stroke after LVAD, and to identify which clinical risk factors put patients at high risk for out-of-therapeuticrange INR. Methods: Advanced heart failure patients (N= 110) discharged from Emory University Hospital after implantation with a HeartMate II (N= 74) or HeartWare (N= 36) LVAD were retrospectively evaluated. Time to first stroke was evaluated as a function of whether INR was in-therapeuticrange (ITR) or out-of-therapeutic range (OTR) at the time of stroke. INR was treated as a categorical variable (ITR vs. OTR) and as a continuous variable (overall time-in-therapeutic-range [TTR] derived via the Rosendaal method) to determine which clinical characteristics were associated with OTR INR. Results: Our cohort included 35 (32%) females, 63 (57%) Blacks with mean age 49.6 ± 13.6 years and median follow up time of 417 days (interquartile range 226-765). During the follow-up period, 20 (43%) patients with OTR INR developed stroke compared to 6 (10%) patients with ITR INR (Figure 1). Risk of OTR INR was higher for females (odds ratio [OR] 1.99, 95% confidence interval [CI] 0.88-4.50, p = 0.1) and for patients with higher creatinine (OR 1.57, 95% CI 0.92-2.71, p = 0.1). Overall TTR was 49.9% for the cohort. Predictors of lower TTR were black race (p = 0.09), higher BMI (p = 0.06), lower albumin (p = 0.02), and lower hematocrit (p= 0.06). Conclusion: OTR INR is associated with increased risk of stroke in patients after LVAD implantation. Female sex, black race, elevated creatinine, high BMI and low albumin and hematocrit are clinical predictors of