Sildenafil Is Associated With Reduced Device Thrombosis and Ischemic Stroke Despite Low-Level Hemolysis on Heart Mate II Support

Omar Saeed, Sabarivinoth Rangasamy, Ibrahim Selevany, Shivank Madan, Jeremy Fertel, Ruth E. Eisenberg, Mohammad Aljoudi, Snehal R. Patel, Jooyoung (Julia) Shin, Daniel B. Sims, Morayma Reyes Gil, Daniel J. Goldstein, Marvin J. Slepian, Henny H. Billett, Ulrich P. Jorde

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Abstract

BACKGROUND: Persistent low-level hemolysis (LLH) during continuous-flow mechanical circulatory support is associated with subsequent thrombosis. Free hemoglobin from ongoing hemolysis scavenges nitric oxide (NO) to create an NO deficiency which can augment platelet function leading to a prothrombotic state. The phosphodiesterase-5 inhibitor, sildenafil, potentiates NO signaling to inhibit platelet function. Accordingly, we investigated the association of sildenafil administration and thrombotic events in patients with LLH during Heart Mate II support.

METHODS AND RESULTS: A single-center review of all patients implanted with a Heart Mate II who survived to discharge (n=144). LLH was defined by a discharge lactate dehydrogenase level of 400 to 700 U/L. Patients were categorized as (1) LLH not on sildenafil, (2) LLH on sildenafil, (3) no LLH not on sildenafil, and (4) no LLH on sildenafil. Age, sex, platelet count, and mean platelet volume were similar between groups. Seventeen patients had either device thrombosis or ischemic stroke. Presence of LLH was associated with a greater risk of thrombosis (adjusted hazard ratio, 15; 95% confidence interval, 4.5-50; P<0.001 versus no LLH, not on sildenafil). This risk was reduced in patients with LLH on sildenafil (adjusted hazard ratio, 1.7; 95% confidence interval, 0.2-16.1; P=0.61). Device thrombosis and ischemic stroke were associated with an increase in mean platelet volume (9.6±0.5 to 10.9±0.8 fL, P<0.001). Patients with LLH not on sildenafil had a greater increase in mean platelet volume in comparison to those with LLH on sildenafil (P<0.001).

CONCLUSIONS: Sildenafil is associated with reduced device thrombosis and ischemic stroke during ongoing LLH on Heart Mate II support.

Original languageEnglish (US)
JournalCirculation. Heart failure
Volume10
Issue number11
DOIs
StatePublished - Nov 1 2017

Fingerprint

Hemolysis
Thrombosis
Stroke
Equipment and Supplies
Mean Platelet Volume
Nitric Oxide
Sildenafil Citrate
Blood Platelets
Confidence Intervals
Phosphodiesterase 5 Inhibitors
Platelet Count
L-Lactate Dehydrogenase
Hemoglobins

Keywords

  • hemoglobin
  • hemolysis
  • nitric oxide
  • platelet count
  • thrombosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

@article{2a7c66b3cb3c40ae9fe73cd2732292c0,
title = "Sildenafil Is Associated With Reduced Device Thrombosis and Ischemic Stroke Despite Low-Level Hemolysis on Heart Mate II Support",
abstract = "BACKGROUND: Persistent low-level hemolysis (LLH) during continuous-flow mechanical circulatory support is associated with subsequent thrombosis. Free hemoglobin from ongoing hemolysis scavenges nitric oxide (NO) to create an NO deficiency which can augment platelet function leading to a prothrombotic state. The phosphodiesterase-5 inhibitor, sildenafil, potentiates NO signaling to inhibit platelet function. Accordingly, we investigated the association of sildenafil administration and thrombotic events in patients with LLH during Heart Mate II support.METHODS AND RESULTS: A single-center review of all patients implanted with a Heart Mate II who survived to discharge (n=144). LLH was defined by a discharge lactate dehydrogenase level of 400 to 700 U/L. Patients were categorized as (1) LLH not on sildenafil, (2) LLH on sildenafil, (3) no LLH not on sildenafil, and (4) no LLH on sildenafil. Age, sex, platelet count, and mean platelet volume were similar between groups. Seventeen patients had either device thrombosis or ischemic stroke. Presence of LLH was associated with a greater risk of thrombosis (adjusted hazard ratio, 15; 95{\%} confidence interval, 4.5-50; P<0.001 versus no LLH, not on sildenafil). This risk was reduced in patients with LLH on sildenafil (adjusted hazard ratio, 1.7; 95{\%} confidence interval, 0.2-16.1; P=0.61). Device thrombosis and ischemic stroke were associated with an increase in mean platelet volume (9.6±0.5 to 10.9±0.8 fL, P<0.001). Patients with LLH not on sildenafil had a greater increase in mean platelet volume in comparison to those with LLH on sildenafil (P<0.001).CONCLUSIONS: Sildenafil is associated with reduced device thrombosis and ischemic stroke during ongoing LLH on Heart Mate II support.",
keywords = "hemoglobin, hemolysis, nitric oxide, platelet count, thrombosis",
author = "Omar Saeed and Sabarivinoth Rangasamy and Ibrahim Selevany and Shivank Madan and Jeremy Fertel and Eisenberg, {Ruth E.} and Mohammad Aljoudi and Patel, {Snehal R.} and Shin, {Jooyoung (Julia)} and Sims, {Daniel B.} and {Reyes Gil}, Morayma and Goldstein, {Daniel J.} and Slepian, {Marvin J.} and Billett, {Henny H.} and Jorde, {Ulrich P.}",
year = "2017",
month = "11",
day = "1",
doi = "10.1161/CIRCHEARTFAILURE.117.004222",
language = "English (US)",
volume = "10",
journal = "Circulation: Heart Failure",
issn = "1941-3297",
publisher = "Lippincott Williams and Wilkins",
number = "11",

}

TY - JOUR

T1 - Sildenafil Is Associated With Reduced Device Thrombosis and Ischemic Stroke Despite Low-Level Hemolysis on Heart Mate II Support

AU - Saeed, Omar

AU - Rangasamy, Sabarivinoth

AU - Selevany, Ibrahim

AU - Madan, Shivank

AU - Fertel, Jeremy

AU - Eisenberg, Ruth E.

AU - Aljoudi, Mohammad

AU - Patel, Snehal R.

AU - Shin, Jooyoung (Julia)

AU - Sims, Daniel B.

AU - Reyes Gil, Morayma

AU - Goldstein, Daniel J.

AU - Slepian, Marvin J.

AU - Billett, Henny H.

AU - Jorde, Ulrich P.

PY - 2017/11/1

Y1 - 2017/11/1

N2 - BACKGROUND: Persistent low-level hemolysis (LLH) during continuous-flow mechanical circulatory support is associated with subsequent thrombosis. Free hemoglobin from ongoing hemolysis scavenges nitric oxide (NO) to create an NO deficiency which can augment platelet function leading to a prothrombotic state. The phosphodiesterase-5 inhibitor, sildenafil, potentiates NO signaling to inhibit platelet function. Accordingly, we investigated the association of sildenafil administration and thrombotic events in patients with LLH during Heart Mate II support.METHODS AND RESULTS: A single-center review of all patients implanted with a Heart Mate II who survived to discharge (n=144). LLH was defined by a discharge lactate dehydrogenase level of 400 to 700 U/L. Patients were categorized as (1) LLH not on sildenafil, (2) LLH on sildenafil, (3) no LLH not on sildenafil, and (4) no LLH on sildenafil. Age, sex, platelet count, and mean platelet volume were similar between groups. Seventeen patients had either device thrombosis or ischemic stroke. Presence of LLH was associated with a greater risk of thrombosis (adjusted hazard ratio, 15; 95% confidence interval, 4.5-50; P<0.001 versus no LLH, not on sildenafil). This risk was reduced in patients with LLH on sildenafil (adjusted hazard ratio, 1.7; 95% confidence interval, 0.2-16.1; P=0.61). Device thrombosis and ischemic stroke were associated with an increase in mean platelet volume (9.6±0.5 to 10.9±0.8 fL, P<0.001). Patients with LLH not on sildenafil had a greater increase in mean platelet volume in comparison to those with LLH on sildenafil (P<0.001).CONCLUSIONS: Sildenafil is associated with reduced device thrombosis and ischemic stroke during ongoing LLH on Heart Mate II support.

AB - BACKGROUND: Persistent low-level hemolysis (LLH) during continuous-flow mechanical circulatory support is associated with subsequent thrombosis. Free hemoglobin from ongoing hemolysis scavenges nitric oxide (NO) to create an NO deficiency which can augment platelet function leading to a prothrombotic state. The phosphodiesterase-5 inhibitor, sildenafil, potentiates NO signaling to inhibit platelet function. Accordingly, we investigated the association of sildenafil administration and thrombotic events in patients with LLH during Heart Mate II support.METHODS AND RESULTS: A single-center review of all patients implanted with a Heart Mate II who survived to discharge (n=144). LLH was defined by a discharge lactate dehydrogenase level of 400 to 700 U/L. Patients were categorized as (1) LLH not on sildenafil, (2) LLH on sildenafil, (3) no LLH not on sildenafil, and (4) no LLH on sildenafil. Age, sex, platelet count, and mean platelet volume were similar between groups. Seventeen patients had either device thrombosis or ischemic stroke. Presence of LLH was associated with a greater risk of thrombosis (adjusted hazard ratio, 15; 95% confidence interval, 4.5-50; P<0.001 versus no LLH, not on sildenafil). This risk was reduced in patients with LLH on sildenafil (adjusted hazard ratio, 1.7; 95% confidence interval, 0.2-16.1; P=0.61). Device thrombosis and ischemic stroke were associated with an increase in mean platelet volume (9.6±0.5 to 10.9±0.8 fL, P<0.001). Patients with LLH not on sildenafil had a greater increase in mean platelet volume in comparison to those with LLH on sildenafil (P<0.001).CONCLUSIONS: Sildenafil is associated with reduced device thrombosis and ischemic stroke during ongoing LLH on Heart Mate II support.

KW - hemoglobin

KW - hemolysis

KW - nitric oxide

KW - platelet count

KW - thrombosis

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U2 - 10.1161/CIRCHEARTFAILURE.117.004222

DO - 10.1161/CIRCHEARTFAILURE.117.004222

M3 - Article

VL - 10

JO - Circulation: Heart Failure

JF - Circulation: Heart Failure

SN - 1941-3297

IS - 11

ER -