Long-distance donor heart procurement using an innovative cold static storage system.

The global lack of donor shortage poses a major limitation for heart transplantation. New concepts with expanded donor inclusion criteria comprise extended transport distances and prolonged ischemic times with the aim of reaching a larger number of potential donors. Recent developments in cold storage solutions may allow more donor hearts with prolonged ischemic times to be use for transplantation in the future. We present our experience during a long-distance donor heart procurement with the longest reported transport distance and transport time in the current literature. This was made possible through the use of SherpaPak™, an innovative cold storage system which allows for controlled temperatures during transportation.

The use of serotonin reuptake inhibitors increases the risk of bleeding in patients with assist devices.

BACKGROUND: Bleedings are frequent and dreaded complications in heart failure patients with ventricular assist devices (VAD). Serotonin reuptake inhibitor (SRI) antidepressants are widely used to treat depression in these patients, though they are attributed an increased risk of bleeding due to their modification of hemostasis. Evidence on bleeding risk of VAD patients under SRI medication is scarce and limited. We therefore aimed to assess if SRI use is associated with an elevated bleeding risk in this particularly vulnerable population. METHODS: We analyzed the medical records of 92 VAD patients at the University Heart Center Zurich between September 2004 and April 2018 for the occurrence of bleedings and the concomitant use of an SRI. Bleeding was defined as any type of post-implantation bleeding requiring medical treatment. We performed univariate analyses and linear mixed-effects models, adjusting for baseline clinical characteristics as potential predictors to identify differences in bleeding rates in patients with vs. without SRI intake. RESULTS: The cohort comprised 60.9% of patients with a continuous-flow VAD and 39.1% with a pulsatile-flow VAD. A total of 77.2% of patients experienced at least one bleeding incident. Overall, 28.6% of bleedings occurred under SRI therapy. A generalized linear mixed model showed a predictive effect of SRI medication on bleeding rate, independent of VAD type (z = 2.091, p = 0.037). CONCLUSIONS: Bleeding events in heart failure patients occur frequently after VAD implantation. Patients with SRI medication were at increased risk of bleeding. The indication and use of SRI, therefore, should be considered carefully.

Impact of progressive aortic regurgitation on outcomes after left ventricular assist device implantation.

Aortic regurgitation (AR) following continuous flow left ventricular assist device implantation (cf-LVAD) may adversely impact outcomes. We aimed to assess the incidence and impact of progressive AR after cf-LVAD on prognosis, biomarkers, functional capacity and echocardiographic findings. In an analysis of the PCHF-VAD database encompassing 12 European heart failure centers, patients were dichotomized according to the progression of AR following LVAD implantation. Patients with de-novo AR or AR progression (AR_1) were compared to patients without worsening AR (AR_0). Among 396 patients (mean age 53 ± 12 years, 82% male), 153 (39%) experienced progression of AR over a median of 1.4 years on LVAD support. Before LVAD implantation, AR_1 patients were less frequently diabetic, had lower body mass indices and higher baseline NT-proBNP values. Progressive AR did not adversely impact mortality (26% in both groups, HR 0.91 [95% CI 0.61-1.36]; P = 0.65). No intergroup variability was observed in NT-proBNP values and 6-minute walk test results at index hospitalization discharge and at 6-month follow-up. However, AR_1 patients were more likely to remain in NYHA class III and had worse right ventricular function at 6-month follow-up. Lack of aortic valve opening was related to de-novo or worsening AR (P < 0.001), irrespective of systolic blood pressure (P = 0.67). Patients commonly experience de-novo or worsening AR when exposed to continuous flow of contemporary LVADs. While reducing effective forward flow, worsening AR did not influence survival. However, less complete functional recovery and worse RV performance among AR_1 patients were observed. Lack of aortic valve opening was associated with progressive AR.

Heart Failure After Right Ventricular Myocardial Infarction.

PURPOSE OF REVIEW: Heart failure (HF) after right ventricular myocardial infarction (RVMI) is common and complicates its clinical course. This review aims to provide a current overview on the characteristic features of RV failure with focus on acute management. RECENT FINDINGS: While HF after RVMI is classically seen after acute proximal right coronary artery occlusion, RV dysfunction may also occur after larger infarctions in the left coronary artery. Because of its different anatomy and physiology, the RV appears to be more resistant to permanent infarction compared to the LV with greater potential for recovery of ischemic myocardium. Hypotension and elevated jugular pressure in the presence of clear lung fields are hallmark signs of RV failure and should prompt confirmation by echocardiography. Management decisions are still mainly based on small studies and extrapolation of findings from LV failure. Early revascularization improves short- and long-term outcomes. Acute management should further focus on optimization of preload and afterload, maintenance of sufficient perfusion pressures, and prompt management of arrhythmias and concomitant LV failure, if present. In case of cardiogenic shock, use of vasopressors and/or inotropes should be considered along with timely use of mechanical circulatory support (MCS) in eligible patients. HF after RVMI is still a marker of worse outcome in acute coronary syndrome. Prompt revascularization, careful medical therapy with attention to the special physiology of the RV, and selected use of MCS provide the RV the time it needs to recover from the ischemic insult.

Treatment of Advanced Heart Failure-Focus on Transplantation and Durable Mechanical Circulatory Support: What Does the Future Hold?

Heart transplantation (HTx) is the treatment of choice in patients with late-stage advanced heart failure (Advanced HF). Survival rates 1, 5, and 10 years after transplantation are 87%, 77%, and 57%, respectively, and the average life expectancy is 9.16 years. However, because of the donor organ shortage, waiting times often exceed life expectancy, resulting in a waiting list mortality of around 20%. This review aims to provide an overview of current standard, recent advances, and future developments in the treatment of Advanced HF with a focus on long-term mechanical circulatory support and HTx.

Effects of hemodialysis on blood volume, macro- and microvascular function.

BACKGROUND: Vascular dysfunction is considered to spur the progression of cardiovascular disease in hemodialysis (HD) patients. Whether the HD procedure itself contributes to vascular dysfunction remains incompletely investigated. The present study sought to comprehensively assess the effects of HD on arterial and venous function along with concomitant changes in blood volume (BV). METHODS AND RESULTS: We determined BV with high-precision, automated carbon monoxide-rebreathing, arterial stiffness using applanation tonometry and intrinsic microvascular function via retinal vessel analysis prior to and after conventional 4-hour HD in fasting-controlled conditions in 10 patients. All HD patients were non-smokers and non-obese (body mass index = 22.8 ±â€¯2.8 m·kg-2). Hypertension (70%), coronary artery disease (40%) and diabetes mellitus (20%) were the most prevalent comorbidities. Prior to HD, all patients presented with hypervolemia (+2208 ±â€¯1213 ml). HD decreased body weight (-1.72 ±â€¯1.25 kg, P = 0.002) and plasma volume (-689 ±â€¯566 ml, P = 0.004), while hematocrit (Hct) was concomitantly increased (+4.8 ±â€¯4.5%, P = 0.009). HD did not affect large elastic artery stiffness, as determined by carotid-femoral pulse wave velocity (P = 0.448) and carotid distensibility (P = 0.562). In contrast, flicker light-induced retinal venular dilation was reduced by three-fourths after HD (-2.4 ±â€¯1.7%, P = 0.039), in parallel to increased retinal venular diameter (+11.2 ±â€¯4.9 µm, P = 0.002). In regression analyses, a negative association was observed between HD-induced changes in Hct and retinal venular dilation (r ≥ -0.89, P ≤ 0.045). CONCLUSION: Conventional HD resulting in substantial plasma volume removal do not alter large artery elastic properties, whereas intrinsic microvascular venular dilator function is markedly impaired, an effect directly associated with the increase in hemoconcentration.

Authorship: from credit to accountability. Reflections from the Editors' Network.

The Editors' Network of the European Society of Cardiology provides a dynamic forum for editorial discussions and endorses the recommendations of the International Committee of Medical Journal Editors (ICMJE) to improve the scientific quality of biomedical journals. Authorship confers credit and important academic rewards. Recently, however, the ICMJE emphasized that authorship also requires responsibility and accountability. These issues are now covered by the new (fourth) criterion for authorship. Authors should agree to be accountable and ensure that questions regarding the accuracy and integrity of the entire work will be appropriately addressed. This review discusses the implications of this paradigm shift on authorship requirements with the aim of increasing awareness on good scientific and editorial practices.

Daratumumab for relapsed or refractory AL amyloidosis with high plasma cell burden.

Daratumumab, an anti-CD38 antibody, is effective in AL amyloidosis with low tumor burden. Data of daratumumab treatment in patients with AL amyloidosis but high tumor burden (≥10% bone marrow plasma cells) are limited. We report retrospective data of 10 consecutive patients with high tumor burden treated with daratumumab for relapsed/refractory AL amyloidosis. The median age at diagnosis was 62.3 years; all patients had cardiac involvement, and six (60%) patients had renal involvement. Median bone marrow plasma cell infiltration was 15% (range 10%-40%), and the median difference between involved and noninvolved free light-chains (dFLC) was 446 mg/L (range 102-1392 mg/L). Patients had a median of three prior lines of therapy, including bortezomib in all patients and lenalidomide in seven (70%) patients. The median time to first hematological response was 14 days (range 7-28 days), and the median time to best hematological response was 64 days (range 7-301 days). The hematological overall response was 90%, with high-quality response (≥ very good partial remission [VGPR]) in 70% of the patients. Fifty percent of the patients had a cardiac response after a median of 3.8 months (range 0.7-9.1). Infusion-related adverse events ≤ grade 2 occurred in seven (70%) patients and grade 3 adverse events in one patient. After a median follow-up time of 10 months, eight (80%) patients continued to receive daratumumab. We conclude that daratumumab is a very effective and safe treatment option in AL patients with relapsed/refractory disease and high disease burden at diagnosis. Daratumumab leads to rapid disease control and improvement of organ function.

Characterizing cardiac involvement in amyloidosis using cardiovascular magnetic resonance diffusion tensor imaging.

BACKGROUND: In-vivo cardiovascular magnetic resonance (CMR) diffusion tensor imaging (DTI) allows imaging of alterations of cardiac fiber architecture in diseased hearts. Cardiac amyloidosis (CA) causes myocardial infiltration of misfolded proteins with unknown consequences for myocardial microstructure. This study applied CMR DTI in CA to assess microstructural alterations and their consequences for myocardial function compared to healthy controls. METHODS: Ten patients with CA (8 AL, 2 ATTR) and ten healthy controls were studied using a diffusion-weighed second-order motion-compensated spin-echo sequence at 1.5 T. Additionally, left ventricular morphology, ejection fraction, strain and native T1 values were obtained in all subjects. In CA patients, T1 mapping was repeated after the administration of gadolinium for extracellular volume fraction (ECV) calculation. CMR DTI analysis was performed to yield the scalar diffusion metrics mean diffusivity (MD) and fractional anisotropy (FA) as well as the characteristics of myofiber orientation including helix, transverse and E2A sheet angle (HA, TA, E2A). RESULTS: MD and FA were found to be significantly different between CA patients and healthy controls (MD 1.77 ± 0.17 10- 3 vs 1.41 ± 0.07 10- 3 mm2/s, p <  0.001; FA 0.25 ± 0.04 vs 0.35 ± 0.03, p <  0.001). MD demonstrated an excellent correlation with native T1 (r = 0.908, p <  0.001) while FA showed a significant correlation with ECV in the CA population (r = - 0.851, p <  0.002). HA exhibited a more circumferential orientation of myofibers in CA patients, in conjunction with a higher TA standard deviation and a higher absolute E2A sheet angle. The transmural HA slope was found to be strongly correlated with the global longitudinal strain (r = 0.921, p < 0.001). CONCLUSION: CMR DTI reveals significant alterations of scalar diffusion metrics in CA patients versus healthy controls. Elevated MD and lower FA values indicate myocardial disarray with higher diffusion in CA that correlates well with native T1 and ECV measures. In CA patients, CMR DTI showed pronounced circumferential orientation of the myofibers, which may provide the rationale for the reduction of global longitudinal strain that occurs in amyloidosis patients. Accordingly, CMR DTI captures specific features of amyloid infiltration, which provides a deeper understanding of the microstructural consequences of CA.

Myocardial triglycerides in cardiac amyloidosis assessed by proton cardiovascular magnetic resonance spectroscopy.

BACKGROUND: Cardiac involvement of amyloidosis leads to left-ventricular (LV) wall thickening with progressive heart failure requiring rehospitalization. Cardiovascular magnetic resonance (CMR) is a valuable tool to non-invasively assess myocardial thickening as well as structural changes. Proton CMR spectroscopy (1H-CMRS) additionally allows assessing metabolites including triglycerides (TG) and total creatine (CR). However, opposing results exist regarding utilization of these metabolites in LV hypertrophy or thickening. Therefore, the aim of this study was to measure metabolic alterations using 1H-CMRS in a group of patients with thickened myocardium caused by cardiac amyloidosis. METHODS: 1H-CMRS was performed on a 1.5 T system (Achieva, Philips Healthcare, Best, The Netherlands) using a 5-channel receive coil in 11 patients with cardiac amyloidosis (60.5 ± 11.4 years, 8 males) and 11 age- and gender-matched controls (63.2 ± 8.9 years, 8 males). After cardiac morphology and function assessment, proton spectra from the interventricular septum (IVS) were acquired using a double-triggered PRESS sequence. Post-processing was performed using a customized reconstruction pipeline based on ReconFrame (GyroTools LLC, Zurich, Switzerland). Spectra were fitted in jMRUI/AMARES and the ratios of triglyceride-to-water (TG/W) and total creatine-to-water (CR/W) were calculated. RESULTS: Besides an increased LV mass and a thickened IVS concomitant to the disease characteristics, patients with cardiac amyloidosis presented with decreased global longitudinal (GLS) and circumferential (GCS) strain. LV ejection fraction was preserved relative to controls (60.0 ± 13.2 vs. 66.1 ± 4.3%, p = 0.17). Myocardial TG/W ratios were significantly decreased compared to controls (0.53 ± 0.23 vs. 0.80 ± 0.26%, p = 0.015). CR/W ratios did not show a difference between both groups, but a higher standard deviation in patients with cardiac amyloidosis was observed. Pearson correlation revealed a negative association between elevated LV mass and TG/W (R = - 0.59, p = 0.004) as well as GCS (R = - 0.48, p = 0.025). CONCLUSIONS: A decrease in myocardial TG/W can be detected in patients with cardiac amyloidosis alongside impaired cardiac function with an association to the degree of myocardial thickening. Accordingly, 1H-CMRS may provide an additional diagnostic tool to gauge progression of cardiac amyloidosis along with standard imaging sequences. TRIAL REGISTRATION: EK 2013-0132.

Retinal microvascular dysfunction in heart failure.

Aims: Retinal vessel analysis (RVA) represents a novel, non-invasive, and reliable method to study the microcirculation in the eye. The goal of this study was to assess the extent of retinal microvascular dysfunction in patients with chronic heart failure (CHF) compared to controls and established measures of vascular function. Methods and results: In this prospective, single-centre, observational study, 74 patients with compensated CHF (mean age 63.5 ± 11.2 years, 32% female, mean left-ventricular ejection fraction 37 ± 12.8%), 74 patients with cardiovascular risk factors (CVRF; 64.1 ± 12.7 years, 34% female), and 74 healthy controls (HC; 57.8 ± 14.2 years, 35% female) were included. The primary endpoint, flicker-induced dilatation of retinal arterioles (FIDart), was significantly reduced in patients with CHF compared to CVRF and HC (mean FIDart 0.9 ± 0.2 vs. 2.3 ± 0.3 and vs. 3.6 ± 0.3%, respectively, both P < 0.001 before and after propensity score-weighted analysis). Similar differences were seen for venular FID. FIDart was less impaired in patients with dilated compared to ischaemic cardiomyopathy. No significant differences were observed for arteriovenous ratio and flow-mediated dilatation. Impaired FIDven was associated with echocardiographically estimated systolic pulmonary artery pressure and left atrial volume index. Conclusion: Retinal microvascular dilatation in response to flicker light is impaired in CHF. RVA may represent a new and useful method to non-invasively monitor microvascular abnormalities in heart failure in an easy and standardized way without the use of radiation.

Differential blood pressure effects of ibuprofen, naproxen, and celecoxib in patients with arthritis: the PRECISION-ABPM (Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen Ambulatory Blood Pressure Measurement) Trial.

AIMS: Non-steroidal anti-inflammatory drugs (NSAIDs), both non-selective and selective cyclooxygenase-2 (COX-2) inhibitors, are among the most widely prescribed drugs worldwide, but associate with increased blood pressure (BP) and adverse cardiovascular (CV) events. PRECISION-ABPM, a substudy of PRECISION was conducted at 60 sites, to determine BP effects of the selective COX-2 inhibitor celecoxib vs. the non-selective NSAIDs naproxen and ibuprofen. METHODS AND RESULTS: In this double-blind, randomized, multicentre non-inferiority CV-safety trial, 444 patients (mean age 62 ± 10 years, 54% female) with osteoarthritis (92%) or rheumatoid arthritis (8%) and evidence of or at increased risk for coronary artery disease received celecoxib (100-200 mg bid), ibuprofen (600-800 mg tid), or naproxen (375-500 mg bid) with matching placebos in a 1: 1: 1 allocation, to assess the effect on 24-h ambulatory BP after 4 months. The change in mean 24-h systolic BP (SBP) in celecoxib, ibuprofen and naproxen-treated patients was -0.3 mmHg [95% confidence interval (CI), -2.25, 1.74], 3.7 (95% CI, 1.72, 5.58) and 1.6 mmHg (95% CI, -0.40, 3.57), respectively. These changes resulted in a difference of - 3.9 mmHg (P = 0.0009) between celecoxib and ibuprofen, of - 1.8 mmHg (P = 0.12) between celecoxib and naproxen, and of - 2.1 mmHg (P = 0.08) between naproxen and ibuprofen. The percentage of patients with normal baseline BP who developed hypertension (mean 24-h SBP ≥ 130 and/or diastolic BP ≥ 80 mmHg) was 23.2% for ibuprofen, 19.0% for naproxen, and 10.3% for celecoxib (odds ratio 0.39, P = 0.004 and odds ratio 0.49, P = 0.03 vs. ibuprofen and naproxen, respectively). CONCLUSIONS: In PRECISION-ABPM, allocation to the non-selective NSAID ibuprofen, compared with the COX-2 selective inhibitor celecoxib was associated with a significant increase of SBP, and a higher incidence of new-onset hypertension. CLINICALTRIALS: gov number NCT00346216.

[Acute heart failure]. / Akute Herzinsuffizienz.

Acute heart failure Abstract. Acute heart failure (AHF) is a life-threatening condition requiring immediate treatment. The initial therapy should take into account the clinical presentation, the pathophysiology at play, the precipitating factors, and the underlying cardiac pathology. Particular attention should be given to polymorbidity and the avoidance of potential iatrogenic harms. Patient preferences and ethical issues should be integrated into the treatment plan at an early stage. The average survival of AHF patients is two years and the most vulnerable period is the three-month time window directly after discharge. Therefore, reducing both persistent subclinical congestion and underutilization of disease-modifying heart failure therapies as well as ensuring optimal transitions of care after hospital discharge are essentials in improving outcomes of AHF patients.

SAVE-AMD: Safety of VEGF Inhibitors in Age-Related Macular Degeneration.

OBJECTIVE: To determine whether intraocular treatment with vascular endothelial growth factor (VEGF) inhibitors change systemic endothelial function (EF) in patients with neovascular age-related macular degeneration (AMD). METHODS: In this prospective, randomized, 2-center, double-masked controlled interventional trial, patients with neovascular and dry AMD were enrolled. Eligible neovascular AMD patients received 2 intravitreal loading doses of either ranibizumab 0.5 mg or bevacizumab 1.25 mg at 4-week intervals and were subsequently followed every 4 weeks and treated according to a pro re nata regime for up to 1 year. Patients with dry AMD served as controls. The primary endpoint was the change in EF assessed by flow-mediated dilatation (FMD) after 2 months of treatment with VEGF inhibitors in patients with AMD compared to patients with dry AMD. FMD was assessed with B-mode high-resolution ultrasonography of the left brachial artery. RESULTS: 24 patients with neovascular AMD and 26 patients with dry ADM were included in the trial. Treatment with VEGF inhibitors did not significantly change FMD (from 4.7 ± 2.4 to 3.9 ± 1.9% after 8 weeks, p = 0.07, and to 5.1 ± 2.0% after 1 year; p = 0.93 vs. baseline, respectively). CONCLUSIONS: EF did not significantly differ between patients with neovascular AMD treated with intravitreal VEGF inhibition and patients with dry AMD.

The eye and the heart.

The vasculature of the eye and the heart share several common characteristics. The easily accessible vessels of the eye are therefore-to some extent-a window to the heart. There is interplay between cardiovascular functions and risk factors and the occurrence and progression of many eye diseases. In particular, arteriovenous nipping, narrowing of retinal arteries, and the dilatation of retinal veins are important signs of increased cardiovascular risk. The pressure in the dilated veins is often markedly increased due to a dysregulation of venous outflow from the eye. Besides such morphological criteria, functional alterations might be even more relevant and may play an important role in future diagnostics. Via neurovascular coupling, flickering light dilates capillaries and small arterioles, thus inducing endothelium-dependent, flow-mediated dilation of larger retinal vessels. Risk factors for arteriosclerosis, such as dyslipidaemia, diabetes, or systemic hypertension, are also risk factors for eye diseases such as retinal arterial or retinal vein occlusions, cataracts, age-related macular degeneration, and increases in intraocular pressure (IOP). Functional alterations of blood flow are particularly relevant to the eye. The primary vascular dysregulation syndrome (PVD), which often includes systemic hypotension, is associated with disturbed autoregulation of ocular blood flow (OBF). Fluctuation of IOP on a high level or blood pressure on a low level leads to instable OBF and oxygen supply and therefore to oxidative stress, which is particularly involved in the pathogenesis of glaucomatous neuropathy. Vascular dysregulation also leads to a barrier dysfunction and thereby to small retinal haemorrhages.

Endothelial dysfunction over the course of coronary artery disease.

The vascular endothelium regulates blood flow in response to physiological needs. Endothelial dysfunction is closely related to atherosclerosis and its risk factors, and it constitutes an intermediate step on the progression to adverse events throughout the natural history of coronary artery disease (CAD), often affecting clinical outcomes. Understanding the relation of endothelial function with CAD provides an important pathophysiological insight, which can be useful both in clinical and research management. In this review, we summarize the current knowledge on endothelial dysfunction and its prognostic influence throughout the natural history of CAD, from early atherosclerosis to post-transplant management.

Long-term outcomes of fractional flow reserve-guided vs. angiography-guided percutaneous coronary intervention in contemporary practice.

AIMS: Fractional flow reserve (FFR) is the reference standard for the assessment of the functional significance of coronary artery stenoses, but is underutilized in daily clinical practice. We aimed to study long-term outcomes of FFR-guided percutaneous coronary intervention (PCI) in the general clinical practice. METHODS AND RESULTS: In this retrospective study, consecutive patients (n = 7358), referred for PCI at the Mayo Clinic between October 2002 and December 2009, were divided in two groups: those undergoing PCI without (PCI-only, n = 6268) or with FFR measurements (FFR-guided, n = 1090). The latter group was further classified as the FFR-Perform group (n = 369) if followed by PCI, and the FFR-Defer group (n = 721) if PCI was deferred. Clinical events were compared during a median follow-up of 50.9 months. The Kaplan-Meier fraction of major adverse cardiac events at 7 years was 57.0% in the PCI-only vs. 50.0% in the FFR-guided group (P = 0.016). Patients with FFR-guided interventions had a non-significantly lower rate of death or myocardial infarction compared with those with angiography-guided interventions [hazard ratio (HR): 0.85, 95% CI: 0.71-1.01, P = 0.06]; the FFR-guided deferred-PCI strategy was independently associated with reduced rate of myocardial infarction (HR: 0.46, 95% CI: 0.26-0.82, P = 0.008). After excluding patients with FFR of 0.75-0.80 and deferring PCI, the use of FFR was significantly associated with reduced rate of death or myocardial infarction (HR: 0.80, 95% CI: 0.66-0.96, P = 0.02). CONCLUSION: In the contemporary practice, an FFR-guided treatment strategy is associated with a favourable long-term outcome. The current study supports the use of the FFR for decision-making in patients undergoing cardiac catheterization.

Repeated episodes of thrombosis as a potential mechanism of plaque progression in cardiac allograft vasculopathy.

AIMS: The pathogenesis of cardiac allograft vasculopathy (CAV) remains complex and may involve multiple mechanisms. We tested the hypothesis that the multilayer (ML) appearance, an intravascular ultrasound (IVUS) finding suggestive of repetitive thrombosis, is associated with plaque progression in heart transplant (HTx) recipients. METHODS AND RESULTS: Our study population consisted of 132 HTx recipients undergoing at least two grayscale and virtual histology (VH)-IVUS examinations. A retrospective serial analysis was performed between the first (baseline) and the last (follow-up) IVUS data during a median follow-up of 3.0 years. The subjects were divided into two groups based on the presence of the ML appearance on the baseline IVUS. At baseline, subjects with ML appearance (n = 38) had a longer time elapsed since transplant, larger vessel volume, and larger plaque volume than those without (n = 94) (all P < 0.01). Intraluminal thrombi and plaque ruptures were identified only in subjects with ML appearance (P < 0.01 vs. those without). More subjects with ML appearance at baseline developed subsequent ML formation compared with those without [21 (55%) vs. 22 (23%), P < 0.01] during follow-up. There was an increase in plaque volume, necrotic core volume, and dense calcium volume in subjects with ML appearance (all P < 0.01 vs. those without). Multivariable linear regression analysis showed that ML appearance was a potential predictor of plaque progression (regression coefficient 0.28, 95% CI 0.10-0.45, P < 0.01). CONCLUSIONS: The current study demonstrates that a finding of ML appearance, indicative of repeated episodes of mural thrombosis, is not infrequent in asymptomatic HTx recipients and possibly contributes to progression of CAV.