Clinical and Functional Correlates of Early Microvascular Dysfunction After Heart Transplantation

Haddad, François; Khazanie, Prateeti; Deuse, T.; Weisshaar, Dana; Zhou, Jessica; Nam, Chang Wook; Vu, Tai Anh; Gomari, Fatemeh A.; Skhiri, Mehdi; Simos, A.M.; Schnittger, Ingela; Vrotvec, Bojan; Hunt, Sharon A.; Fearon, William F.

doi:10.1161/circheartfailure.111.962787

Cited by 58 publications

(46 citation statements)

References 34 publications

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“…In addition, the IMR measurement at 1 year was an independent predictor of death or retransplantation, while IVUS parameters were not, suggesting that microvascular function may be a more important indicator of long-term outcome as compared to epicardial plaque. Moreover, in another study IMR was found to predict development of CAV and graft dysfunction (13). In non-transplant recipients IMR has also been found to be useful in identifying the cause of chest pain in patients with non-obstructive epicardial coronary disease and in predicting poor recovery of left ventricular function and mortality when measured after primary percutaneous coronary intervention in patients with ST segment elevation myocardial infarction (14,15).…”

Section: Discussionmentioning

confidence: 99%

Angiotensin-Converting Enzyme Inhibition Early After Heart Transplantation

Fearon

Okada

Kobashigawa

et al. 2017

Journal of the American College of Cardiology

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BACKGROUND Cardiac allograft vasculopathy (CAV) remains a leading cause of mortality after heart transplantation (HT). Angiotensin converting enzyme inhibitors (ACEIs) may retard the development of CAV, but have not been well studied after HT. OBJECTIVES We tested the safety and efficacy of the ACEI ramipril on the development of CAV early after HT. METHODS In this prospective, multicenter, randomized, double-blind, placebo-controlled trial, 96 HT recipients were randomized to ramipril or placebo. They underwent coronary angiography, endothelial function testing, measurement of fractional flow reserve (FFR), coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR), and intravascular ultrasound (IVUS) of the left anterior descending coronary artery within 8 weeks of HT. At 1 year, the invasive assessment was repeated. Circulating endothelial progenitor cells (EPCs) were quantified at baseline and 1 year. RESULTS Plaque volume at 1 year was similar between the ramipril and placebo groups (162.1 ± 70.5 vs. 177.3 ± 94.3 mm3, p =0.73). Patients receiving ramipril had improvement in microvascular function as evidenced by a significant decrease in IMR (21.4 ± 14.7 to 14.4 ± 6.3, p =0.001) and increase in CFR (3.8 ± 1.7 to 4.8 ± 1.5, p =0.017) from baseline to 1 year. This did not occur with IMR (17.4 ± 8.4 to 21.5 ± 20.0, p =0.72) or CFR (4.1 ± 1.8 to 4.1 ± 2.2, p =0.60) in the placebo-treated patients. EPCs decreased significantly at 1 year in the placebo group but not in the ramipril group. CONCLUSION Ramipril does not slow development of epicardial plaque volume but does stabilize EPC levels and improve microvascular function, which have been associated with improved long-term survival after HT.

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Section: Discussionmentioning

confidence: 99%

Angiotensin-Converting Enzyme Inhibition Early After Heart Transplantation

Fearon

Okada

Kobashigawa

et al. 2017

Journal of the American College of Cardiology

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“…Cutoff values of 20 for baseline and 1-year IMR, 2.5 for baseline and 1-year CFR, 0.90 for baseline FFR, and 0.85 for 1-year FFR were obtained from the literature. 10,14 Time-to-event data were analyzed with the Kaplan-Meier method and compared by use of the log-rank test. Cox regression analysis was performed to determine predictors of death/retransplantation.…”

Section: Discussionmentioning

confidence: 99%

“…This finding may be explained by the facts that microvascular dysfunction at 1 year is associated with impaired ventricular function and that an increase in IMR correlates with a decrease in cardiac index and stroke volume index and more hemodynamically compromising rejection. 10 The lack of correlation between an elevated IMR at baseline and outcomes implies that whatever factors contribute to an abnormal IMR at baseline (eg, inflammation and edema resulting from the transplantation process) are likely not important mediators of long-term outcome. Others have reported that in the absence of significant epicardial CAV, episodes of rejection are associated with microvascular dysfunction, 24 which also was found in this study.…”

Section: Importance Of Microvascular Dysfunctionmentioning

confidence: 99%

Invasive Assessment of Coronary Physiology Predicts Late Mortality After Heart Transplantation

et al. 2016

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This study included patients from 2 consecutive prospective trials at Stanford University Medical Center between 2002 and 2014. The aim of the first study was to evaluate the role of cytomegalovirus in the development of CAV (1 PO1-AI50153). The second study evaluated the role of the angiotensin-converting enzyme inhibitor ramipril in the development of CAV (5 R01 HL093475-02; ClinicalTrials.gov number NCT01078363). Patients were included if they were >18 years old, received their first cardiac transplantation, survived >1 year, and were willing and able to provide informed written consent. All patients underwent a baseline coronary angiogram with measurement of FFR, coronary flow reserve (CFR), and IMR and performance of IVUS of the left anterior descending artery (LAD) within 8 weeks and 1 year after transplantation. The study protocols were approved by the Stanford University Institutional Review Board on Human Subjects Research, and informed consent was obtained from all patients before enrollment. Immunosuppressive RegimenAll patients received standard immunosuppressive therapy, including induction therapy with daclizumab, an anti-interleukin-2 monoclonal antibody, OKT3, or antithymocyte globulin. Corticosteroid therapy Background-The aim of this study is to determine the prognostic value of invasively assessing coronary physiology early after heart transplantation. Methods and Results-Seventy-four cardiac transplant recipients had fractional flow reserve, coronary flow reserve, index of microcirculatory resistance (IMR), and intravascular ultrasound performed down the left anterior descending coronary artery soon after (baseline) and 1 year after heart transplantation. The primary end point was the cumulative survival free of death or retransplantation at a mean follow-up of 4.5±3.5 years. The cumulative event-free survival was significantly lower in patients with a fractional flow reserve <0.90 at baseline (42% versus 79%; P=0.01) or an IMR ≥20 measured 1 year after heart transplantation (39% versus 69%; P=0.03). Patients in whom IMR decreased or did not change from baseline to 1 year had higher event-free survival compared with patients with an increase in IMR (66% versus 36%; P=0.03). Fractional flow reserve <0.90 at baseline (hazard ratio, 0.13; 95% confidence interval, 0.02-0.81; P=0.03), IMR ≥20 at 1 year (hazard ratio, 3.93; 95% confidence interval, 1.08-14.27; P=0.04), and rejection during the first year (hazard ratio, 6.00; 95% confidence interval, 1.56-23.09; P=0.009) were independent predictors of death/retransplantation, whereas intravascular ultrasound parameters were not. Conclusions-Invasive measures of coronary physiology (fractional flow reserve and IMR) determined early after heart transplantation are significant predictors of late death or retransplantation.

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“…While a variety of post-transplant complications may explain this later attrition, common predictors of late survival including perioperative renal function and rejection episodes are similar between the two groups. Possible reasons include a higher incidence of microvascular dysfunction associated with undersized donor hearts,[16] which may be more likely with greater gender mismatch seen in the IABP group. It is important to re-emphasize; however, that upon risk-adjusted analysis the post-transplant survival between groups was equivalent.…”

Section: Discussionmentioning

confidence: 99%

Assessing Consequences of Intraaortic Balloon Counterpulsation Versus Left Ventricular Assist Devices at the Time of Heart Transplantation

Castleberry¹,

DeVore

Southerland

et al. 2016

ASAIO Journal

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The proportion of heart transplant recipients bridged with durable left ventricular assist devices (dLVADs) has dramatically increased; however, concern exists regarding obligate repeat sternotomy, increase bleeding risk due to anticoagulation and acquired von Willebrand disease, and increased rates of allosensitization. Whether dLVAD patients have impaired post-transplant outcomes compared to equivalent patients with less invasive intraaortic balloon counterpulsation (IABP) at the time of transplant is unknown. We therefore analyzed adult, first time, heart-only transplant procedures with dLVAD (n=2,636) compared to IABP (n=571) at the time of transplant based on data from the United Network for Organ Sharing (UNOS) 07/2004 – 12/2011. There was clear geographic variation in IABP and dLVAD at transplant. Multivariable analysis demonstrated equivalent cumulative risk of death (adjusted Cox proportional hazard ratio: 1.08, 95% confidence interval: 0.87 – 1.33, p=0.51). There was no significant difference in adjusted comparison of perioperative morality, length of stay, postoperative renal failure requiring dialysis, or early acute rejection (p≥0.14 for all). Data from UNOS therefore suggests that the presence of dLVAD at the time of heart transplantation does not have a detrimental effect on postoperative outcomes compared to IABP, which must be considered in the context of pre-transplant mortality and locoregional organ availability.

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Clinical and Functional Correlates of Early Microvascular Dysfunction After Heart Transplantation

Cited by 58 publications

References 34 publications

Angiotensin-Converting Enzyme Inhibition Early After Heart Transplantation

Angiotensin-Converting Enzyme Inhibition Early After Heart Transplantation

Invasive Assessment of Coronary Physiology Predicts Late Mortality After Heart Transplantation

Assessing Consequences of Intraaortic Balloon Counterpulsation Versus Left Ventricular Assist Devices at the Time of Heart Transplantation

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