Very Elderly Patients With Atrial Fibrillation Treated With Edoxaban: Impact of Frailty on Outcomes.

Background: Age and frailty are associated with underuse of anticoagulation in elderly patients with atrial fibrillation (AF). Objectives: This study aimed at assessing major clinical outcomes in very elderly patients with AF treated with recommended dose edoxaban and look for a possible relation with frailty measured by a validated score. Methods: This prospective multicenter cohort study enrolled consecutive very elderly (age ≥80 years) anticoagulation-naïve patients starting recommended doses of edoxaban. Upon entry into the study, patients were categorized into nonfrail, prefrail and frail with the SHARE-FI (Survey of Health, Ageing, and Retirement in Europe-Frailty Index) score. The primary outcome was a composite incidence of stroke/systemic embolism, major bleeding, clinically relevant nonmajor bleeding, and death between frail and fitter patients over 2 years follow-up. Secondary outcomes were frailty-related incidence of the individual components part of the composite outcome. Results: Of the 180 screened patients, 176 were enrolled in the study. Of these, 58 (32.9%) were frail, 35 (19.8%) prefrail, and 83 (47.2%) nonfrail. The composite outcome occurred in 49 patients (18.9% per patient-year). No difference in the primary endpoint between frail and fitter patients (incidence rate ratio: 1.2; 95% CI: 0.6-2.2) was observed. On multivariable analysis, anemia was significantly related to the primary outcome (HR: 3.6; 95% CI: 1.8-7.3; P < 0.001), while frailty was not (frail vs nonfrail HR: 0.9; 95% CI: 0.5-1.8). No difference across frailty categories of the individual components of composite events was observed, except for death. Conclusions: Anticoagulation with recommended dose edoxaban is feasible in very elderly patients with AF even if frail. (ESCAPE [Edoxaban and Frailty in Senior Individuals]; NCT03524924).

Benefit of dual antithrombotic therapy with direct oral anticoagulants in patients with atrial fibrillation undergoing percutaneous coronary intervention: a systematic review and metaanalysis of randomized clinical trials.

Antithrombotic treatment in patients with atrial fibrillation undergoing percutaneous coronary intervention is still debated. We conducted a meta-analysis of recent randomized controlled trials to evaluate the benefit of different antithrombotic strategies. Data were analyzed between May and September 2019. Efficacy outcomes were trial-defined major adverse cardiovascular events (MACE); its individual components; stent thrombosis. Safety outcomes were trial-defined primary bleeding outcome; TIMI and ISTH major bleeding; clinically relevant non-major bleeding; intracranial hemorrhage. Differences in outcomes among groups were expressed as pooled odds ratio (OR) and corresponding 95% confidence interval (CI). Four randomized studies were included (10,969 patients). The mean age ranged from 69 to 72 years, prevalence of acute coronary syndrome (ACS) varied from 48 to 62%. Comparing dual antithrombotic therapy (DAT) with a direct oral anticoagulant (DOAC) versus triple antithrombotic therapy (TAT) with vitamin K antagonist (VKA), OR for trial-defined MACE and primary bleeding outcome were 1.03 (95% CI, 0.86-1.24) and 0.59 (95% CI, 0.41-0.86), respectively. There was a 68% lower risk of intracranial hemorrhage and a non-statistically significant higher risk of stent thrombosis with DAT. DAT was as effective and safer than TAT in patients with stable coronary artery disease, while a trend towards increased ischemic events was seen in ACS patients. DAT with a DOAC showed similar efficacy and less bleeding than TAT with a VKA. However, increased stent thrombosis with DAT may be present, and TAT should be considered in patients at high ischemic risk, such as ACS patients.

Balloon Pulmonary Angioplasty in Patients With Chronic Thromboembolic Pulmonary Hypertension　- A Systematic Review and Meta-Analysis.

BACKGROUND: Balloon pulmonary angioplasty (BPA) is a percutaneous treatment option for patients affected by chronic thromboembolic pulmonary hypertension (CTEPH) and either judged inoperable or with persistent symptoms after pulmonary endoarteriectomy. Current data regarding BPA are sparse and results vary according to local center experience. A systematic review of the literature was performed to better understand the effectiveness and safety of BPA in the treatment of CTEPH.Methods and Results:PubMed and EMBASE were searched for studies reporting BPA results in patients with CTEPH. Differences in clinical and hemodynamic parameters before and after the procedure were analyzed. Weighted mean proportion and 95% confidence intervals (CIs) of adverse events were calculated. In total, 14 studies were included (725 patients). BPA was associated with a reduction in mean pulmonary artery pressure (from 43 to 32.5 mmHg), reduction in pulmonary vascular resistance (from 9.94 to 5.06 Woods units), increase in cardiac index (from 2.35 to 2.62 L/min/m2), and improvement of 6-minute walking distance (from 345 to 442 m). Periprocedural mortality occurred in 2.1% of patients (95% CoI 0.8-4.1) while reperfusion and pulmonary vessel injuries occurred in 9.3% (95% CoI 3.1-18.4) and 2.3% (95% CoI 0.9-4.5) of total BPA sessions, respectively. CONCLUSIONS: Our systematic review suggested that BPA for CTEPH patients was an effective and relatively safe treatment option.

Primary thromboembolic prevention in multiple myeloma patients: An exploratory meta-analysis on aspirin use.

BACKGROUND: Multiple myeloma (MM) is a common hematological disorder, often complicated by venous thromboembolism, especially during treatment with immunomodulatory drugs. Acetylsalicylic acid (ASA) has been extensively used as thromboprophylaxis but its rationale is unclear and the efficacy versus low-molecular weight heparins (LMWH) is still matter of debate. European and American guidelines suggest different approaches and the optimal antithrombotic strategy is yet to be established. METHODS: We conducted an exploratory metanalysis and a systematic review on studies comparing ASA versus other interventions for thromboprophylaxis (no intervention or LMWH) in patients with MM. RESULTS: Ten studies were included (2 randomized controlled trials, 6 longitudinal and 2 retrospective studies) with 1,964 participants (1,257 treated with ASA, 640 with LMWH and 67 with no thromboprophylaxis). Patients treated with ASA had a significantly lower risk of VTE compared to no intervention (OR=0.20; 95%CI: 0.07-0.61, p=0.005; I2=41%). The use of ASA was associated with a higher VTE risk compared to LMWH in longitudinal studies (OR=2.60; 95%CI: 1.08-6.25; p=0.03; I2=0%), however no differences have been showed in randomized controlled trials. CONCLUSIONS: ASA demonstrated a good efficacy compared to no intervention; data are insufficient to confirm superiority of LMWH over ASA as thromboprophylaxis in MM patients. Large and well powered trials are warranted.

Risk factors for intracranial hemorrhage during vitamin K antagonist therapy in patients with nonvalvular atrial fibrillation: A case-control study.

BACKGROUND: Intracranial hemorrhage (ICH) is the most fearful side effect of oral anticoagulant therapy. It is still unclear which risk factor is involved in ICH during vitamin K antagonists (VKAs) treatment and if commonly used bleeding risk scores are able to predict ICH. PURPOSE: Search for individual risk factors and bleeding risk scores (HAS-BLED, ATRIA and ORBIT) associated with ICHs in patients with atrial fibrillation treated with VKAs. METHODS: This is a retrospective case-control study in a single Thrombosis Center. During a 7-year period, patients with nonvalvular atrial fibrillation (NVAF) who developed ICH during VKAs were identified as cases. Four control patients matched for gender, age and length of VKAs were assigned to each case. The association between considered risk factors and ICHs was evaluated using a linear logistic regression method and expressed as odds ratio. Receiver operator characteristic (ROC) curves to assess the predictive ability of bleeding risk scores HAS-BLED, ATRIA and ORBIT were also evaluated. RESULTS: Fifty-one cases of ICH, most of whom were 80 years of age or older (72.5%), were retrieved from the Thrombosis Center's database. Compared to 204 controls, no individual risk factors were associated with ICH. Poor ability to predict ICH was also found using ROC curves (C-statistic for HAS-BLED, ATRIA, and ORBIT were 0.55, 0.53 and 0.54, respectively). CONCLUSIONS: ICHs during VKA therapy preferentially occur in very elderly patients. The risk of ICH is not predicted by the commonly used risk scores.

Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome.

Rivaroxaban is an effective and safe alternative to warfarin in patients with atrial fibrillation and venous thromboembolism. We tested the efficacy and safety of rivaroxaban compared with warfarin in high-risk patients with thrombotic antiphospholipid syndrome. This is a randomized open-label multicenter noninferiority study with blinded end point adjudication. Rivaroxaban, 20 mg once daily (15 mg once daily based on kidney function) was compared with warfarin (international normalized ratio target 2.5) for the prevention of thromboembolic events, major bleeding, and vascular death in patients with antiphospholipid syndrome. Only high-risk patients triple positive for lupus anticoagulant, anti-cardiolipin, and anti-ß2-glycoprotein I antibodies of the same isotype (triple positivity) were included in the study. The trial was terminated prematurely after the enrollment of 120 patients (59 randomized to rivaroxaban and 61 to warfarin) because of an excess of events among patients in the rivaroxaban arm. Mean follow-up was 569 days. There were 11 (19%) events in the rivaroxaban group, and 2 (3%) events in the warfarin group. Thromboembolic events occurred in 7 (12%) patients randomized to rivaroxaban (4 ischemic stroke and 3 myocardial infarction), whereas no event was recorded in those randomized to warfarin. Major bleeding occurred in 6 patients: 4 (7%) in the rivaroxaban group and 2 (3%) in the warfarin group. No death was reported. The use of rivaroxaban in high-risk patients with antiphospholipid syndrome was associated with an increased rate of events compared with warfarin, thus showing no benefit and excess risk. This trial was registered at www.clinicaltrials.gov as #NCT02157272.

RANKL Expression Is Increased in Circulating Mononuclear Cells of Patients with Calcific Aortic Stenosis.

We aimed to investigate whether the expression of the OPG/RANK/RANKL triad in peripheral blood mononuclear cells (PBMC) and circulating levels of markers of ectopic mineralization (OPG, FGF-23, PPi) are modified in patients with calcific aortic valve disease (CAVD). We found that patients affected by CAVD (n = 50) had significantly higher circulating levels of OPG as compared to control individuals (p = 0.003). No differences between the two groups were found in FGF-23 and PPi levels. RANKL expression was higher in the PBMC from CAVD patients (p = 0.018) and was directly correlated with the amount of valve calcification (p = 0.032). In vitro studies showed that treatment of valve interstitial cells (VIC) with RANKL plus phosphate was followed by increase in matrix mineralization (p = 0.001). In conclusion, RANKL expression is increased in PBMC of patients with CAVD, is directly correlated with the degree of valve calcification, and promotes pro-calcific differentiation of VIC.

Cardio-oncology: the role of advanced echocardiography in cancer patients.

INTRODUCTION: Cardio-oncology is a rapidly growing field aimed at improving the quality of care of cancer patients by preventing and monitoring cardiovascular complications resulting from cancer treatment. Cardiac imaging, and in particular, transthoracic echocardiography, plays an essentialrole in the baseline assessment and serial follow-up of cardio-oncology patients. Areas covered: This review article discusses the role of cardiac imaging with a focus on advanced echocardiography for the detection and management of cancer therapy related cardiovascular complications, in particular, left ventricular dysfunction and heart failure. Expert commentary: While traditional imaging based assessment of left ventricular ejection fraction still has its place in cardiac monitoring, more advanced echocardiographic modalities, in particular, myocardial deformation imaging with speckle tracking strain analysis, show great potential for detecting early signs of cardiotoxicity. Larger studies are needed to determine both the clinical role of strain measurement in influencing initiation of cardioprotective agents and its prognostic value in long term outcome.

Laboratory Diagnostics of Antiphospholipid Syndrome.

Diagnosis of antiphospholipid syndrome (APS) lies in the recognition of antiphospholipid antibodies (aPL). As standardization of tests for the detection of aPL is far from being optimal and reference material is not available, inappropriate diagnoses of APS are not unusual. In the last few years, the concept of triple test positivity has emerged as a useful tool to identify patients with APS. Clinical studies on patients and carriers of triple positivity clearly show that these individuals are at high risk of thromboembolic events and pregnancy loss. Moreover, triple positivity arises from a single (probably pathogenic) antibody directed to domain 1 of ß2-glycoprotein I, a protein whose function is still unknown. Studies on homogenous group of patients with single or double positivity are scant, and uncertainties arise on their association with clinical events. Promising but undetermined results come also from the determination of antibodies directed to phosphatidylserine/prothrombin complex. Interpretation of laboratory profile in APS is challenging, and the collaboration between clinical pathologists and clinicians is highly desirable.

Warfarin prescription in patients with nonvalvular atrial fibrillation and one non-gender-related risk factor (CHA2 DS2 VASc 1 or 2): A treatment dilemma.

INTRODUCTION: The issue of anticoagulation in individuals with nonvalvular atrial fibrillation (NVAF) and 1 non-gender-related (NGR) risk factor is subject to debate. The reported risk of stroke in untreated individuals is not uniform, and the rate of hemorrhage associated with anticoagulation in this group of individuals is not well defined. To this end, we assessed the rate of stroke and major hemorrhage in individuals treated with warfarin. MATERIALS AND METHODS: individuals were extracted from the START register, an observational, multicenter, dynamic inception cohort study that collects data on NVAF individuals starting anticoagulation therapy. Risk of stroke is stratified using the CHA2 DS2 VASc score upon entry into the registry. RESULTS: Overall, 431 individuals with 1 NGR risk factor were followed up for 604 person-years. One nonfatal ischemic stroke was recorded (0.17 per 100 person-years) during follow-up. On the other hand, there were 9 major bleeding events (1.49 per 100 person-years), with 4 being intracranial hemorrhage (0.66 per 100 person-years), 1 of which was fatal. No difference in patient characteristics, bleeding risk factors, and quality of treatment were found between individuals who bled versus those who did not. However, a trend toward more bleeding events was observed in individuals <65 years old. CONCLUSION: We found an elevated risk of major bleeding and intracranial hemorrhage in NVAF individuals treated with warfarin with 1 NGR risk factor for stroke. These data call for caution when treating with warfarin these individuals.

Effectiveness and safety of oral anticoagulation with non-vitamin K antagonists compared to well-managed vitamin K antagonists in naïve patients with non-valvular atrial fibrillation: Propensity score matched cohort study.

BACKGROUND: The global real-life impact of non-vitamin K antagonist oral anticoagulants (NOACs) introduction in the healthcare system in a setting of well-managed vitamin K antagonist (VKA) therapy has not been specifically addressed. METHODS: We did a population-based retrospective cohort study in naïve patients initiating oral anticoagulants for stroke prevention in atrial fibrillation in a region with a well-managed VKA therapy. NOAC and VKA cohorts were identified using Anatomical Therapeutic Chemical (ATC) codes, while excluding other indications for anticoagulation therapy using ICD-9CM codes. Propensity score was conducted using two different approaches: stratification and 1:1 matching. Event-rates were assessed using both an intention to treat (ITT) and as treated analyses. RESULTS: Of the 137,800 selected patients, 40,411 (6923 treated with NOACs and 33,488 with VKAs) were identified (June 2013-December 2015). Overall ischaemic stroke and major bleeding risk did not significantly differ between the groups both in the ITT and as treated analyses. Noteworthy, intracranial bleeding risk was lower with NOACs (stratified model HR=0.69; 95%CI 0.48-0.99; 1:1 matched model HR=0.73; 95%CI 0.47-1.13) reaching statistical significance in the as treated analysis in both stratified and 1:1 matched models (HR=0.51; 95%CI 0.32-0.80 and HR=0.52; 95%CI 0.30-0.90, respectively). CONCLUSION: Despite well-managed anticoagulation with VKAs, NOACs' introduction has a positive global impact in the public healthcare system in terms of effectiveness and safety especially by lowering intracranial bleeding.

Lupus Anticoagulant Testing: Diluted Russell Viper Venom Time (dRVVT).

Diluted Russell Viper Venom Time (dRVVT) has become the most popular test to detect Lupus Anticoagulant (LA). dRVVT is more sensitive than other global tests employed to detect LA and is not affected by inhibitors of factor VIII or IX. The test is most successfully implemented if you observe three steps in its execution: screening, mixing, and confirmatory studies. Interference due to the presence of heparin in tested plasma must be excluded by means of thrombin time (TT). The prior use of Vitamin K Antagonists (VKAs) or Non-vitamin K Oral Anticoagulants (NOACs) must also be evaluated by means of International Normalized Ratio, or specific tests, respectively.

The Novel Oral Anticoagulants for Acute Venous Thromboembolism: Is Warfarin Dead?

The direct oral anticoagulants (DOACs) have been compared with parenteral anticoagulants and vitamin K antagonists (VKAs) for the treatment of venous thromboembolism (VTE) in several robust studies. DOACs have shown similar efficacy in preventing recurrent VTE and significant reductions in critical site (intracranial) bleeding, fatal bleeding, major and nonmajor bleeding. Warfarin and other VKAs are not dead as treatment modalities for VTE. A better way to describe the current situation is to use a boxing expression, "down but not out." VKAs and parenteral anticoagulants still have a role to play in the management of VTE in several clinical settings. In indications where DOACs can be used, VKAs should not, as the safety profile of VKAs is considerably worse than DOACs. Hence, guidelines are now recommending DOACs in preference to VKAs. In this article, we consider where DOACs are indicated, where there is growing evidence for use, where we have little evidence for use, and finally where there is no evidence for use and where they, thus, should not be used. We have included recommendations and examples of our own practice which may not be applicable to all settings.

The left atrial appendage: from embryology to prevention of thromboembolism.

The left atrial appendage (LAA) is the main source of thromboembolism in patients with non-valvular atrial fibrillation (AF). As such, the LAA can be the target of specific occluding device therapies. Optimal management of patients with AF includes a comprehensive knowledge of the many aspects related to LAA structure and thrombosis. Here we provide baseline notions on the anatomy and function of the LAA, and then focus on current imaging tools for the identification of anatomical varieties. We also describe pathogenetic mechanisms of LAA thrombosis in AF patients, and examine the available evidence on treatment strategies for LAA thrombosis, including the use of non-vitamin K antagonist oral anticoagulants and interventional approaches.

Simultaneous Assessment of Myocardial Perfusion, Wall Motion, and Deformation during Myocardial Contrast Echocardiography: A Feasibility Study.

AIMS: Ultrasound contrast agents may be used for the assessment of regional wall motion and myocardial perfusion, but are generally considered not suitable for deformation analysis. The aim of our study was to assess the feasibility of deformation imaging on contrast-enhanced images using a novel methodology. METHODS AND RESULTS: We prospectively enrolled 40 patients who underwent stress echocardiography with continuous intravenous infusion of SonoVue for the assessment of myocardial perfusion imaging with flash replenishment technique. We compared longitudinal strain (Lε) values, assessed with a vendor-independent software (2D CPA), on 68 resting contrast-enhanced and 68 resting noncontrast recordings. Strain analysis on contrast recordings was evaluated in the first cardiac cycles after the flash. Tracking of contrast images was deemed feasible in all subjects and in all views. Contrast administration improved image quality and increased the number of segments used for deformation analysis. Lε of noncontrast and contrast-enhanced images were statistically different (-18.8 ± 4.5% and -22.8 ± 5.4%, respectively; P < 0.001), but their correlation was good (ICC 0.65, 95%CI 0.42-0.78). Patients with resting wall-motion abnormalities showed lower Lε values on contrast recordings (-18.6 ± 6.0% vs. -24.2 ± 5.5%, respectively; P < 0.01). Intra-operator and inter-operator reproducibility was good for both noncontrast and contrast images with no statistical differences. CONCLUSIONS: Our study shows that deformation analysis on postflash contrast-enhanced images is feasible and reproducible. Therefore, it would be possible to perform a simultaneous evaluation of wall-motion abnormalities, volumes, ejection fraction, perfusion defects, and cardiac deformation on the same contrast recording.

Diagnosis and therapy of antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a clinical condition that has not been well defined yet. Although the clinical component is well established, the laboratory part is a mood issue. According to current guidelines, 3 tests (lupus anticoagulant, anticardiolipin, and anti ß2-glycoprotein I antibodies) are officially recommended to assess the presence of antiphospholipid antibodies. According to test positivity, patients are classified into categories in clinical studies. However, it is now clear that classification categories have a different impact on the clinical course of APS. Indeed, patients and healthy carriers with a full positive antibody profile (triple positivity) are those at the highest risk of events. Patients with a single test positivity are those at a lower risk. In this review, on the basis of a laboratory profile, we grade the diagnosis of APS into definite, probable/possible, and uncertain. We also discuss secondary prevention of thrombotic APS, prevention of pregnancy morbidity, and treatment of catastrophic APS. Finally, new tools in laboratory diagnosis and treatment are highlighted.

European Association of Cardiovascular Imaging/Cardiovascular Imaging Department of the Brazilian Society of Cardiology recommendations for the use of cardiac imaging to assess and follow patients after heart transplantation.

The cohort of long-term survivors of heart transplant is expanding, and the assessment of these patients requires specific knowledge of the surgical techniques employed to implant the donor heart, the physiology of the transplanted heart, complications of invasive tests routinely performed to detect graft rejection (GR), and the specific pathologies that may affect the transplanted heart. A joint EACVI/Brazilian cardiovascular imaging writing group committee has prepared these recommendations to provide a practical guide to echocardiographers involved in the follow-up of heart transplant patients and a framework for standardized and efficient use of cardiovascular imaging after heart transplant. Since the transplanted heart is smaller than the recipient's dilated heart, the former is usually located more medially in the mediastinum and tends to be rotated clockwise. Therefore, standard views with conventional two-dimensional (2D) echocardiography are often difficult to obtain generating a large variability from patient to patient. Therefore, in echocardiography laboratories equipped with three-dimensional echocardiography (3DE) scanners and specific expertise with the technique, 3DE may be a suitable alternative to conventional 2D echocardiography to assess the size and the function of cardiac chambers. 3DE measurement of left (LV) and right ventricular (RV) size and function are more accurate and reproducible than conventional 2D calculations. However, clinicians should be aware that cardiac chamber volumes obtained with 3DE cannot be compared with those obtained with 2D echocardiography. To assess cardiac chamber morphology and function during follow-up studies, it is recommended to obtain a comprehensive echocardiographic study at 6 months from the cardiac transplantation as a baseline and make a careful quantitation of cardiac chamber size, RV systolic function, both systolic and diastolic parameters of LV function, and pulmonary artery pressure. Subsequent echocardiographic studies should be interpreted in comparison with the data obtained from the 6-month study. An echocardiographic study, which shows no change from the baseline study, has a high negative predictive value for GR. There is no single systolic or diastolic parameter that can be reliably used to diagnose GR. However, in case several parameters are abnormal, the likelihood of GR increases. When an abnormality is detected, careful revision of images of the present and baseline study (side-by-side) is highly recommended. Global longitudinal strain (GLS) is a suitable parameter to diagnose subclinical allograft dysfunction, regardless of aetiology, by comparing the changes occurring during serial evaluations. Evaluation of GLS could be used in association with endomyocardial biopsy (EMB) to characterize and monitor an acute GR or global dysfunction episode. RV size and function at baseline should be assessed using several parameters, which do not exclusively evaluate longitudinal function. At follow-up echocardiogram, all these parameters should be compared with the baseline values. 3DE may provide a more accurate and comprehensive assessment of RV size and function. Moreover, due to the unpredictable shape of the atria in transplanted patients, atrial volume should be measured using the discs' summation algorithm (biplane algorithm for the left atrium) or 3DE. Tricuspid regurgitation should be looked for and properly assessed in all echocardiographic studies. In case of significant changes in severity of tricuspid regurgitation during follow-up, a 2D/3D and colour Doppler assessment of its severity and mechanisms should be performed. Aortic and mitral valves should be evaluated according to current recommendations. Pericardial effusion should be serially evaluated regarding extent, location, and haemodynamic impact. In case of newly detected pericardial effusion, GR should be considered taking into account the overall echocardiographic assessment and patient evaluation. Dobutamine stress echocardiography might be a suitable alternative to routine coronary angiography to assess cardiac allograft vasculopathy (CAV) at centres with adequate experience with the methodology. Coronary flow reserve and/or contrast infusion to assess myocardial perfusion might be combined with stress echocardiography to improve the accuracy of the test. In addition to its role in monitoring cardiac chamber function and in diagnosis the occurrence of GR and/or CAV, in experienced centres, echocardiography might be an alternative to fluoroscopy to guide EMB, particularly in children and young women, since echocardiography avoids repeated X-ray exposure, permits visualization of soft tissues and safer performance of biopsies of different RV regions. Finally, in addition to the indications about when and how to use echocardiography, the document also addresses the role of the other cardiovascular imaging modalities during follow-up of heart transplant patients. In patients with inadequate acoustic window and contraindication to contrast agents, pharmacological SPECT is an alternative imaging modality to detect CAV in heart transplant patients. However, in centres with adequate expertise, intravascular ultrasound (IVUS) in conjunction with coronary angiography with a baseline study at 4-6 weeks and at 1 year after heart transplant should be performed to exclude donor coronary artery disease, to detect rapidly progressive CAV, and to provide prognostic information. Despite the fact that coronary angiography is the current gold-standard method for the detection of CAV, the use of IVUS should also be considered when there is a discrepancy between non-invasive imaging tests and coronary angiography concerning the presence of CAV. In experienced centres, computerized tomography coronary angiography is a good alternative to coronary angiography to detect CAV. In patients with a persistently high heart rate, scanners that provide high temporal resolution, such as dual-source systems, provide better image quality. Finally, in patients with insufficient acoustic window, cardiac magnetic resonance is an alternative to echocardiography to assess cardiac chamber volumes and function and to exclude acute GR and CAV in a surveillance protocol.