Low-Dose Unfractionated Heparin Administration During Intravascular Ultrasound Studies is Safe Even Shortly After Endomyocardial Biopsy in Cardiac Transplant Patients


Reza Arsanjani, MD, Avinash Khitri, MD, Mehrnoosh Hashemzadeh, PhD, Mohammad Reza Movahed, MD

Abstract: Background. Full therapeutic heparin doses ranging from 5000-10,000 units or weight based (70-100 units/kg) have been recommended during percutaneous coronary interventions. However, there are currently no data available in regards to the appropriate dosing of unfractionated heparin during intravascular ultrasound (IVUS) studies without therapeutic coronary interventions. The goal of this study was to evaluate the safety of low dose unfractionated heparin during IVUS studies, shortly after endomyocardial biopsy in cardiac transplant patients. Methods. At the University of Arizona Medical Center, transplant patients routinely undergo diagnostic IVUS studies for the detection of early cardiac allograft vasculopathy (CAV) shortly after endomyocardial biopsy. A low-dose heparin (2000 to 3000 Units) is given before coronary wire and IVUS catheter advancement without checking activated clotting time. We evaluated the occurrence of any thromboembolic event or any other adverse outcomes in this population. Results. A total of 108 cardiac transplant patients, who had underwent routine IVUS studies between 2004-2008 were identified retrospectively. The average heparin dose used was 2528 ± 501 units. The left anterior descending artery was studied in 93% of cases. There was no thromboembolic event. Only one catheter-induced coronary dissection occurred treated with percutaneous coronary intervention.  An endomyocardial biopsy was performed 10-15 minutes before the administration of low-dose heparin. There were no other major adverse cardiac events in this population during the procedure. Conclusion. This is the first study showing the safety of low-dose heparin use during diagnostic IVUS studies in cardiac transplant patients, even shortly after endomyocardial biopsy.

J INVASIVE CARDIOL 2012;24(4):154-156

Key words: heparin, anticoagulation, transplant, transplantation, myocardial biopsy, cardiac transplant, rejection, IVUS


The prevalence and incidence of heart failure continues to grow leading to cardiac transplantation as the last resort in many patients with end-stage heart failure.1-2 Significant advances have been made over the last 30 years in heart transplant management, with marked improvement in overall prognosis.3 Despite the overall improvement in survival, patients often face many complications during the post-transplant period. The post-transplant period can be broken up into two distinct stages, specifically, early and late. The early post-transplant stage is defined as the period within 1 year of transplantation, while the late stage is defined as 1 year after transplantation and beyond. Mortality in the early stage is associated with such entities as infection, multi-organ failure, and acute rejection.4 On the other hand, the leading cause of mortality after the first year of transplantation is cardiac allograft vasculopathy (CAV) and cancers.4,5 Endomyocardial biopsy has traditionally been utilized during the post-transplant period to provide morphological index of acute rejection.6-9 CAV is an accelerated form of intimal hyperplasia that affects the transplanted heart. CAV consists of a diffuse endothelial thickening that is secondary to the accumulation of smooth muscle cells.10 While the exact etiology of CAV is unknown, it has been postulated that both immune and non-immune mechanisms may play a role. The diagnosis of CAV is often difficult to establish based upon clinical evaluation. Despite continued advances in noninvasive techniques, the gold standard remains yearly angiography. Yet, the concept of intravascular ultrasound (IVUS) as a screening tool is gaining popularity. It allows for quantification of intimal wall thickness and has been shown to have prognostic value in predicting overall mortality, cardiac mortality, and need for re-transplantation.11-13

Full therapeutic heparin doses ranging from 5000-10,000 U or weight-based (70-100 U/kg) have been recommended during percutaneous coronary interventions.14,15 However, there are currently no data available about the appropriate dosing of heparin during IVUS studies only without therapeutic coronary interventions. The goal of this study is to retrospectively evaluate the safety of low-dose heparin (2000-3000 U) used during IVUS studies in this population shortly after endomyocardial biopsy. 


At the University of Arizona Medical Center, routine annual surveillance endomyocardial biopsy and IVUS studies are performed to evaluate for acute rejection and CAV. In addition, symptom-based biopsy and IVUS studies are performed on more frequent intervals if clinically indicated. At our center, transplant patients undergo annual right heart catheterization, endomyocardial biopsy, coronary angiography, and IVUS via femoral approach. Following hemodynamic measurements using 7 Fr thermodilution Swan-Ganz catheter, the 7 Fr venous sheath is exchanged for an 8 Fr Mullins sheath. The Mullins sheath is advanced into the right ventricle over a 0.032˝ J-wire, under fluoroscopic guidance. Using a 6 Fr bioptome forceps, multiple endomyocardial biopsies are obtained and sent to the laboratory for evaluation. Following serial biopsies, the Mullins sheath is pulled back into the inferior vena cava. Next, routine coronary angiography is performed in multiple projections. Following angiography, 2000-3000 U of unfractionated heparin is administered. Patients who weigh less than 100 kg routinely receive 2000 U of heparin and those who weigh greater than 100 kg receive 3000 U of heparin. Subsequently, IVUS is performed in the vessel of choice using standard techniques (Volcano IVUS catheter and Boston Scientific 40 mHz rotational IVUS catheter) using manual pullback. The cardiac vessel chosen for IVUS examination was determined on a case-to-case basis by the interventional cardiologist performing the study. Intracoronary nitroglycerin was routinely administered prior to IVUS examination. The left anterior descending artery was the primary target in the majority of cases. If wiring of the LAD was difficult, the circumflex artery was used for IVUS studies initially and thereafter. Upon completion of IVUS, final angiographic images are obtained and all catheters are removed.  Protamine was administered in all cases prior to sheath removal. Following the procedure, the patients are observed for 4 hours for any evidence of bleeding, arrhythmias, electrocardiographic changes, or significant hemodynamic changes. 

In our study, we retrospectively evaluated cardiac transplant patients who underwent endomyocardial biopsy followed by routine IVUS examination using low-dose heparin (2000-3000 U) at our institution between the years 2004-2008. Patients under the age of 18 at the time of transplantation were excluded from the study. The outcome data for all patients were abstracted from medical records to evaluate for occurrence of major adverse cardiac events (MACE), including myocardial infarction, need for percutaneous intervention, coronary artery bypass grafting, re-transplantation, and death, up to 30 days post procedure. In addition, we examined the incidence of major complications associated with administration of anticoagulation following endomyocardial biopsy, including pericardial tamponade requiring pericardiocentesis, hemothorax, urgent cardiac surgery, or death.


A cohort of 108 patients had an endomyocardial biopsy and IVUS study performed for diagnosis of acute rejection and CAV between 2004 and 2008 at our institution. A total of 179 IVUS studies were performed during that time period. The patient’s baseline characteristics are listed in Table 1. The average age was 51 years old. The left anterior descending artery was the vessel studied in 93% of cases. Based on angiographic findings, 10% of patients had mild luminal irregularities and  3% had moderate stenosis. The average heparin dose used during the procedure was 2522 ± 497 U. No thromboembolic events occurred during the procedure. There was one catheter-induced coronary dissection requiring percutaneous coronary intervention. There were no deaths in our cohort. In addition, there were no other procedure-related MACE following low-dose heparin administration shortly after performance of endomyocardial biopsy.

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