Colonoscopic Ultrasound-Guided Fine-Needle Aspiration Using a Curvilinear Array Transducer: A Single-Center Retrospective Cohort Study.

BACKGROUND: Curvilinear array ultrasound transducers enable tissue sampling and have therapeutic capabilities. Nevertheless, colonic intubation and maneuvering with these transducers is technically challenging and is therefore typically limited to the rectosigmoid area. This retrospective cohort study aimed to evaluate the safety, feasibility, and diagnostic yield of colonoscopic ultrasound-guided fine-needle aspiration in deep colonic intubation. IMPACT OF INNOVATION: The impact of this innovation is to enable tissue sampling of colonic and extracolonic lesions guided by endoscopic ultrasound. TECHNOLOGY, MATERIALS, AND METHODS: Curvilinear array ultrasound is used in the evaluation of luminal and extraluminal colonic diseases. Thirteen patients underwent colonoscopic ultrasound with a curvilinear array ultrasound endoscope in a single center for subepithelial lesions, cancer staging, and extracolonic lesions from July 2015 to February 2021. Endosonography was performed using an Olympus EU-ME1 and GF-UCT 180 with a 5-12MHz curvilinear array transducer. The primary outcome was the percentage of patients who were successfully scanned with the endoscopic ultrasound. The secondary outcomes included the success rate of fine-needle aspiration, the diagnostic yield of the tissue samples, and the adverse events related to the procedure. PRELIMINARY RESULTS: A total of 13 female patients underwent colonoscopic ultrasound. All patients (100%, 13/13) were successfully scanned. Fine-needle aspiration was deemed necessary and successfully performed in 100% (5/5) of the patients. Tissue samples collected by fine-needle aspiration resulted in a diagnostic yield of 60%, and no adverse events resulted from this intervention. CONCLUSIONS: This study demonstrates the feasibility of performing colonoscopic ultrasound with a curvilinear array transducer. Fine-needle aspiration for subepithelial, colonic, and extracolonic lesions is feasible and safe in this setting with no adverse events reported in our study. FUTURE DIRECTIONS: Future research should be directed toward validating colonoscopic ultrasound with a curvilinear array transducer technique in prospective randomized trials. Studies evaluating the feasibility and safety of endoscopic ultrasound-guided interventions in the colon, such as abscess drainage and enteral anastomosis, should be considered.

Cardiovascular Events Associated with Chimeric Antigen Receptor T Cell Therapy: Cross-Sectional FDA Adverse Events Reporting System Analysis.

Chimeric antigen receptor (CAR) T cell therapy is approved in the United States for the treatment of acute lymphocytic leukemia and aggressive B cell lymphomas. Multiple cardiovascular adverse events (CVEs) associated with CAR-Ts have been observed in small studies, but no large-scale studies exist. Leveraging the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS), we identified all reported adverse events (AEs) associated with CAR-T therapy (tisagenlecleucel and axicabtagene ciloleucel) from 2017 to 2019. Reports with missing age and sex were excluded. CVEs were classified into arrhythmias, heart failure (HF), myocardial infarction (MI), and other CVEs. Logistic regression and hierarchical clustering were used to identify factors associated with CVEs. A total of 996 reported AEs were observed (39.1% associated with tisagenlecleucel and 60% with axicabtagene ciloleucel). Of all patients experiencing AEs, the median age was 54 (interquartile range, 21 to 65) years; 38.9% were females. In total, 19.7% (196) of all AEs reported to the FDA were CVEs. The most common CVEs were arrhythmia (77.6%), followed by HF (14.3%) and MI (0.5%). In adjusted analysis a positive association was observed between those presenting with CVE with neurotoxicity (odds ratio, 1.76; 95% confidence interval, 1.20 to 2.60; P = .004). Additionally, when both CVE and cytokine release syndrome (CRS) are present, neurotoxicity is the most common noncardiac AE, which clusters with them (Jaccard similarity: 73.1). The mortality rate was 21.1% overall but 30.1% for those reporting CVEs. In FAERS, reported CVEs with CAR-T are associated with high reported mortality. The development of either CRS or neurotoxicity should prompt vigilance for cardiovascular events.

Waitlist Mortality of Patients With Amyloid Cardiomyopathy who Are Listed for Heart Transplantation and Implications for Organ Allocation.

BACKGROUND: Outcomes of patients with amyloid cardiomyopathy (ACM) undergoing heart transplantation have been reported, but there are scant data concerning the waitlist mortality (WLM) of these patients. AIM: The aim of this study was to investigate whether patients with ACM have higher waitlist mortality compared to those with other types of cardiomyopathies. METHODS: We queried the United Network for Organ Sharing registry for all patients (age ≥ 18 years) listed for heart transplantation between 2008 and 2015. We compared patients with ACM to those with dilated cardiomyopathy (DCM) or idiopathic restrictive cardiomyopathy (RCM) for WLM and waitlist mortality or delisting for deterioration (WLM/D). We identified 306 patients with ACM, 183 with RCM and 8416 with DCM. Patients with ACM were older (ACM 61 vs RCM 49 vs DCM 51 years, P < .001), were more likely to be male (82% vs 60% vs 73%, P < .001) but less likely to be listed as status 1A (16% vs 18% vs 23%, P< .001). After adjusting for baseline characteristics, ACM was associated with increased risk of mortality and mortality/delisting compared with DCM (HR 2.03 [1.36-3.04], P = .001 for WLM; HR 2.07 [1.55-2.78], P < .001 for WLM/D) but not with other RCMs (HR 1.28 [0.54-3.02], P = .58 for WLM; HR 0.97 [0.56-1.69], P = .91 for WLM/D). RESULTS: Patients with ACM are listed with lower acuity and have higher waitlist mortality compared with those with dilated cardiomyopathies. Further studies are needed to identify whether special prioritization should be considered for patients with ACM listed for heart transplantation.

HeartMate II pump exchange with HeartMate III implantation to the descending aorta.

Removal of the HeartMate II left ventricular assist device (LVAD) usually requires a sternotomy. We report a case of HeartMate III LVAD implantation to the descending aorta via a left thoracotomy while leaving most of the HeartMate II device in place to avoid redo-sternotomy.

The contribution of selected organic substrates to the anaerobic cometabolism of sulfamethazine.

Biodegradation of organic micropollutants is likely to occur due to cometabolism by particular microbial groups. In an effort to identify the stages of anaerobic digestion potentially involved in the biodegradation of the veterinary antimicrobial sulfamethazine (SMZ), the influence of selected carbon sources (sucrose, glucose, fructose, ethanol, meat extract, cellulose, soluble starch, soy oil, acetic acid, propionic acid and butyric acid) on SMZ removal by anaerobic sludge was evaluated in short-term batch experiments. Adsorption to the granular sludge constituted a significant removal mechanism, accounting for 39% of SMZ removal in control experiments. The presence of glucose, fructose, sucrose and meat extract exerted an inducing effect on SMZ degradation, resulting in removal efficiencies of 54, 53, 58 and 61%, respectively, indicating the occurrence of cometabolism. Time courses of sucrose and meat extract degradation revealed markedly distinct organic acid profiles but resulted in similar SMZ removals. Temporal profiles of acetic and propionic acid degradation were not associated with SMZ removal, as changes in SMZ concentration were observed even after the organic acids had been completely removed. The experimental results suggest that SMZ cometabolism is not associated to sucrose hydrolysis, acetoclastic methanogenesis and acetogenesis from propionic acid.

Heart transplant outcomes in patients with Chagas cardiomyopathy in the United States.

BACKGROUND: Chagas cardiomyopathy (CC) is one of the chronic manifestations of Trypanosoma cruzi (T. cruzi) infection and is among the leading reasons for heart transplantation (HT) in Latin America. Chagas disease is also present in areas with large Hispanic communities in the United States. Our objective is to evaluate the outcomes of cardiac allograft recipients with the diagnosis of CC in the United States. METHODS AND RESULTS: We identified 25 adult patients with CC and 15 930 with idiopathic dilated cardiomyopathy (IDCMP) who underwent HT between 1987 and 2015. CC patients were mostly Hispanics, had lower mean pulmonary artery pressure (23 vs 29 mm Hg, P = .035) and lower BMI (24 vs 26, P = .007). Patients with CC were more likely to be supported with a total artificial heart (TAH) as bridge to transplant (P = .009). There were no statistical differences for overall mortality and graft survival between CC and IDCMP cardiac allograft recipients. Induction therapy and mycophenolate mofetil (MMF) use were associated with higher rate of infection in Chagas patients. CONCLUSIONS: Heart transplantation recipients with CC diagnosis appear to have similar outcomes to IDCMP patients. Induction therapy and MMF use may be associated with higher risk of infection in CC patients who underwent transplantation.

Heart Transplantation in Giant Cell Myocarditis: Analysis of the United Network for Organ Sharing Registry.

BACKGROUND: Giant cell myocarditis (GCM) is a lethal, rapidly progressive disease, for which heart transplantation is the treatment of choice. We sought to describe the characteristics and outcomes of patients with GCM who undergo heart transplantation. METHODS AND RESULTS: We used the United Network for Organ Sharing thoracic organ transplantation registry to identify adults with GCM as the primary diagnosis and compared their characteristics and outcomes with patients who underwent transplantation for other types of myocarditis and for idiopathic dilated cardiomyopathy (IDCMP). A total of 32 patients with GCM were compared with 219 patients with myocarditis and 14,221 patients with IDCMP. Median age at listing for GCM was 52 years (interquartile range 40-55 y), and the majority were white (94%), male (63%), and listed as 1A (44%). Biventricular assist devices were used more frequently in GCM compared with IDCMP (31% vs 2%; P < .001). After transplantation, there were no statistically significant differences among GCM, myocarditis, and IDCMP patients regarding pacemaker implantation, dialysis initiation, or stroke rate. GCM patients had increased risk of acute rejection compared with IDCMP patients (16% vs 5.0%; P = .021) but no difference in rehospitalization for rejection among the 3 etiologies (P = .88). The cumulative survivals for GCM patients at 1, 5, and 10 years were 94%, 82%, and 68%, respectively, which was similar to the other etiologies (P = .11). CONCLUSIONS: Compared with patients with IDCMP, those with GCM present more acutely and have significantly higher utilization of biventricular mechanical circulatory support. Despite higher rates of early rejection, post-transplantation survival of patients with GCM was similar to that of other myocarditides and IDCMP.

Left Ventricular Assist Devices or Inotropes for Decreasing Pulmonary Vascular Resistance in Patients with Pulmonary Hypertension Listed for Heart Transplantation.

BACKGROUND: Fixed pulmonary hypertension is common in patients with advanced heart failure and is a contraindication for heart transplantation. Left ventricular assist devices (LVAD) and inotropes have been used to reduce pulmonary vascular resistance (PVR) and allow transplantation. However, little is known about the efficacy of this strategy. METHODS: We queried the United Network for Organ Sharing registry for all adult patients (age ≥18 years) listed for primary heart transplantation (2008-2014) with PVR of >5 wood units (WU) or transpulmonary gradient >16 mmHg who were treated with LVAD or IV inotropes as status 1a, 1b, or 7. We compared waitlist mortality/delisting and absolute changes in hemodynamics between listing and transplantation. RESULTS: Of 18,009 patients listed during the study period, 1016 were included in the analysis (393 LVAD, 623 inotropes), with a mean age of 52.9 ± 11.6 years, 74% male, and 38% had ischemic etiology. Mean PVR was 5.7 ± 2.4 WU and transpulmonary pressure gradient 19.3 ± 5.3 mmHg. Compared with the inotrope group, LVAD patients were more likely listed as status 1A (32.8% vs 18.1%, P < .001), had lower PVR (5.3 WU vs 5.9 WU, P = .001), and higher cardiac output (4.1 vs 3.6 L/min, P < .001). After a mean of 239 days, PVR decreased by 1.71 WU in the LVAD group vs 1.85 WU in the inotrope group (P = .52). PVR normalization (<2.5 WU) occurred at similar rates among those treated with inotropes and LVAD (30.7% vs 35.6%, P = .228). Waitlist mortality was similar between LVAD and inotropes (adjusted P = .837). Absolute PVR and transpulmonary pressure gradient reductions correlated with time on the waitlist (P < .001 for both comparisons). CONCLUSION: Only about one-third of patients with fixed pulmonary hypertension achieve normalization of PVR before transplant with either LVAD or inotropes. Similar waitlist mortality was observed among patients bridged with either strategy.

Percutaneous Ventricular Restoration with a Partitioning Device for Ischemic Heart Failure Treatment.

PURPOSE OF THE REVIEW: Percutaneous ventricular restoration with a ventricular partitioning device (VPD) is a novel minimally invasive procedure designed to restore the left ventricular (LV) shape by isolating the infarcted and aneurysmal LV apex from remainder of the cavity in heart failure patients with severely reduced LV ejection fraction. In this review, we perform an in-depth analysis of the design and purpose of the VPD and review the available clinical data, with special attention to hemodynamics, outcomes, and complications. RECENT FINDINGS: PARACHUTE trials have shown >90% procedural success rate of VPD implant. Heart failure patients had improvement in hemodynamics (reduction in LV volumes and increase in LV ejection fraction) and functional status (6-min walking distance and quality of life scores) after the VPD implant. Optimal implant position is necessary to obtain a good clinical outcome. Percutaneous VPD implantation has thus far been a safe intervention capable of improving surrogate markers of heart failure but there is still a need to develop more durable devices with a long-lasting hemodynamics effect.

Advanced Heart Failure Therapies for Cancer Therapeutics-Related Cardiac Dysfunction.

End-stage heart failure in cancer survivors may result from cardiotoxic chemotherapy and/or chest radiation and require advanced therapies, including left ventricular assist devices (LVADs) and transplantation. Traditionally, such therapies have been underutilized in cancer survivors owing to lack of experience and perceived risk of cancer recurrence. Recent data from large registries, however, have shown excellent outcomes of LVADs and transplantation in cancer survivors, albeit subject to careful selection and special considerations. This article summarizes all aspects of advanced heart failure therapies in patients with cancer therapy-related cardiac dysfunction and underscores the need for careful selection of these candidates.

Characteristics and Survival of Malignant Cardiac Tumors: A 40-Year Analysis of >500 Patients.

BACKGROUND: The aim of this study was to investigate the incidence, histopathology, demographics, and survival associated with primary malignant cardiac tumors (PMCTs). METHODS AND RESULTS: We queried the Surveillance, Epidemiology and End Results (SEER) 18 registry from the National Cancer Institute for all PMCTs diagnosed from 1973 to 2011. We describe PMCT histopathology and incidence, comparing characteristics and survival of these patients with those of patients with extracardiac malignancies of similar histopathology. From a total of 7 384 580 cases of cancer registered in SEER, we identified 551 PMCTs (0.008%). The incidence of PMCT diagnosis is 34 cases per 100 million persons and has increased over time (25.1 in 1973-1989, 30.2 in 1990-1999, and 46.6 in 2000-2011). Most patients are female (54.1%) and white (78.6%) with median age at diagnosis of 50 years. The most common PMCTs are sarcomas (n=357, 64.8%), followed by lymphomas (n=150, 27%) and mesotheliomas (n=44, 8%). Most patients are diagnosed with tissue sample (96.8%). Although use of chemotherapy is not documented in SEER, 19% of patients received radiation and 44% had surgery. After a median follow-up of 80 months, 413 patients had died. The 1-, 3-, and 5-year survival rates were 46%, 22%, and 17% and have improved over the eras, with 1-, 3-, and 5-year survival rates of 32%, 17%, and 14% for 1973 to 1989 and 50%, 24%, and 19% for 2000 to 2011 (P=0.009). Cardiac sarcomas and mesotheliomas are the most lethal PMCTs, with 1-, 3-, 5-year survival rates of 47%, 16%, and 11% and of 51%, 26%, and 23% compared with 59%, 41%, and 34% for lymphomas, respectively (log rank test P<0.001). Patients with cardiac lymphomas and sarcomas are younger and have worse survival than patients with extracardiac disease of similar histopathology (P<0.001). CONCLUSIONS: PMCTs are extremely rare and continue to be associated with poor prognosis. Over the past 5 decades, the incidence and survival of patients diagnosed with PMCT appear to have increased. Compared with those with extracardiac cancers of similar histopathology, patients with PMCTs are often younger and have worse survival.

Heart Transplantation Outcomes in Radiation-Induced Restrictive Cardiomyopathy.

BACKGROUND: Some cancer therapies can cause advanced heart failure requiring heart transplantation. Although dilated cardiomyopathy is the most common phenotype, those who receive radiation may develop restrictive cardiomyopathy. The characteristics and transplantation outcomes patients with radiation-induced restrictive cardiomyopathy are not established. METHODS AND RESULTS: We used United Network for Organ Sharing registry to identify adults who were listed for heart transplantation between 2000 and 2015 for radiation-induced restrictive cardiomyopathy (RT-RCM) and compared their characteristics and transplant outcomes to restrictive cardiomyopathies of other etiologies (RCM) and all other patients listed for heart transplantation (others). Of 45,041 adults, 87 (0.2%) of transplantations were due to RT-RCM, 1049 (2.3%) were due to RCM, and there were 44,805 others. Compared with patients with RCM and other etiologies, those with RT-RCM were younger, less likely male, more likely to be white, listed as status 2, and were also more likely to have had previous cardiac surgeries. Posttransplant, patients with RT-RCM had longer lengths of stay and higher early mortality; 1-, 3-, and 5-year cumulative survival were as follows for RT-RCM (76%, 66%, 58%), RCM (88%, 79%, 73%; P = .025 compared with RT-RCM), and other etiologies (88%, 82%, 76%; P = .012 compared with RT-RCM). CONCLUSIONS: Patients with end-stage RT-RCM are predominantly younger females with previous cardiac surgeries. Posttransplantation survival in these patients appears to be lower than in those with other forms of restrictive cardiomyopathies and heart failure etiologies, mainly because of higher early postoperative mortality. Further studies are needed to confirm these findings.

Cardio-Oncology Training: A Proposal From the International Cardioncology Society and Canadian Cardiac Oncology Network for a New Multidisciplinary Specialty.

There is an increasing awareness and clinical interest in cardiac safety during cancer therapy as well as in optimally addressing cardiac issues in cancer survivors. Although there is an emerging expertise in this area, known as cardio-oncology, there is a lack of organization in the essential components of contemporary training. This proposal, an international consensus statement organized by the International Cardioncology Society and the Canadian Cardiac Oncology Network, attempts to marshal the important ongoing efforts for training the next generation of cardio-oncologists. The necessary elements are outlined, including the expectations for exposure necessary to develop adequate training. There should also be a commitment to local, regional, and international education and research in cardio-oncology as a requirement for advancement in the field.

Contemporary clinical trial updates in heart failure.

PURPOSE OF REVIEW: Heart failure is a major source of cardiovascular morbidity and mortality worldwide. The field has benefited from steady progress, and there are now multiple strategies - medical and surgical - to improve cardiovascular outcomes. The quest continues for enhanced pathophysiologic insights and therapies. RECENT FINDINGS: The chosen studies highlight new ways of treating heart failure with reduced ejection fraction (HFrEF) with pharmacotherapy such as sacubitril/valsartan and explore the role of antimicrobial therapy for chronic Chagas' cardiomyopathy. The role of iron supplementation, spinal cord stimulation and gene therapy are evaluated. The treatment of heart failure with preserved ejection fraction (HFpEF) is scrutinized, and the role of nitrates is discussed. The use of left ventricular assist devices in wider populations of HFrEF patients is considered. SUMMARY: These pivotal contemporary trials will impact bedside management. Sacubitril/valsartan's mortality benefit in HFrEF and the negative effect of nitrates in HFpEF provide novel insights. Progress with durable mechanical circulatory support and nonpharmacological approaches to heart failure management expand therapeutic options.

Ivabradine in Management of Heart Failure: a Critical Appraisal.

Elevated resting heart rate has been linked to poor outcomes in patients with chronic systolic heart failure. Blockade of funny current channel with ivabradine reduces heart rate without inotropic effects. Ivabradine was recently approved by US Food and Drug Administration for patients with stable, symptomatic chronic heart failure (HF) with left ventricular ejection fraction (LVEF) ≤35 %, who are in sinus rhythm with resting heart rate (HR) ≥ 70 bpm and either are on maximally tolerated doses of beta-blockers, or have a contraindication to beta-blockers. This article will review and evaluate the data supporting the use of ivabradine in patients with HF and explore its mechanisms and physiologic effects.

Effects of Liraglutide on Clinical Stability Among Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.

IMPORTANCE: Abnormal cardiac metabolism contributes to the pathophysiology of advanced heart failure with reduced left ventricular ejection fraction (LVEF). Glucagon-like peptide 1 (GLP-1) agonists have shown cardioprotective effects in early clinical studies of patients with advanced heart failure, irrespective of type 2 diabetes status. OBJECTIVE: To test whether therapy with a GLP-1 agonist improves clinical stability following hospitalization for acute heart failure. DESIGN, SETTING, AND PARTICIPANTS: Phase 2, double-blind, placebo-controlled randomized clinical trial of patients with established heart failure and reduced LVEF who were recently hospitalized. Patients were enrolled between August 2013 and March 2015 at 24 US sites. INTERVENTIONS: The GLP-1 agonist liraglutide (n = 154) or placebo (n = 146) via a daily subcutaneous injection; study drug was advanced to a dosage of 1.8 mg/d during the first 30 days as tolerated and continued for 180 days. MAIN OUTCOMES AND MEASURES: The primary end point was a global rank score in which all patients, regardless of treatment assignment, were ranked across 3 hierarchical tiers: time to death, time to rehospitalization for heart failure, and time-averaged proportional change in N-terminal pro-B-type natriuretic peptide level from baseline to 180 days. Higher values indicate better health (stability). Exploratory secondary outcomes included primary end point components, cardiac structure and function, 6-minute walk distance, quality of life, and combined events. RESULTS: Among the 300 patients who were randomized (median age, 61 years [interquartile range {IQR}, 52-68 years]; 64 [21%] women; 178 [59%] with type 2 diabetes; median LVEF of 25% [IQR, 19%-33%]; median N-terminal pro-B-type natriuretic peptide level of 2049 pg/mL [IQR, 1054-4235 pg/mL]), 271 completed the study. Compared with placebo, liraglutide had no significant effect on the primary end point (mean rank of 146 for the liraglutide group vs 156 for the placebo group, P = .31). There were no significant between-group differences in the number of deaths (19 [12%] in the liraglutide group vs 16 [11%] in the placebo group; hazard ratio, 1.10 [95% CI, 0.57-2.14]; P = .78) or rehospitalizations for heart failure (63 [41%] vs 50 [34%], respectively; hazard ratio, 1.30 [95% CI, 0.89-1.88]; P = .17) or for the exploratory secondary end points. Prespecified subgroup analyses in patients with diabetes did not reveal any significant between-group differences. The number of investigator-reported hyperglycemic events was 16 (10%) in the liraglutide group vs 27 (18%) in the placebo group and hypoglycemic events were infrequent (2 [1%] vs 4 [3%], respectively). CONCLUSIONS AND RELEVANCE: Among patients recently hospitalized with heart failure and reduced LVEF, the use of liraglutide did not lead to greater posthospitalization clinical stability. These findings do not support the use of liraglutide in this clinical situation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01800968.

Percutaneous left ventricular restoration.

The ventricular partitioning device known as Parachute is the first and only percutaneously implantable device aimed at restoration of normal left ventricular geometry in humans. Since its conception, this technology has undergone extensive animal and human testing, with proved feasibility and safety, and is currently being studied in a pivotal randomized clinical trial. This article discusses ventricular remodeling and therapies attempted in the past, details the components of the ventricular partitioning device, describes the implanting technique, and reviews the most current experience of this device in humans.

Relationship between blood and tissue-based rejection-related transcripts in heart transplantation.

BACKGROUND: The purpose of the study is to investigate the relationship between blood and tissue-derived rejection-related transcripts from blood gene expression profiling (GEP) and molecular microscope in the setting of allograft rejection in heart transplant. METHODS: All heart transplant patients from August 2021 to May 2022 with both circulating blood GEP (AlloMap) and endomyocardial biopsy with molecular microscope diagnostic system (MMDx) within 4 weeks were included (N = 173 samples). We obtained individual blood GEP-based messenger RNA transcript expression levels of the 11 target genes from CareDx. Student's t-test was performed to compare blood GEP transcript expression levels between no rejection and rejection as assessed by MMDx. A Scatter plot with Spearman correlation analysis was performed to compare the relationship between transcript expression levels from AlloMap and MMDx, with and without allograft rejection. RESULTS: There were 52 samples (30.1%) with antibody-mediated rejection (ABMR) and 15 samples (8.7%) with T-cell-mediated rejection (TCMR), as assessed by MMDx. Expression of one of the blood ITGA4 (Integrin alpha 4) expression level was elevated in ABMR, compared to no ABMR (4,607.5 vs 4,217.5; p = 0.019). Most tissue rejection-associated transcript expression levels were elevated in ABMR, and tissue ROBO4 expression correlated with the blood ITGA4 expression with moderate or greater effect size in all samples (Spearman's R = 0.31; p < 0.001). There was also a positive correlation between blood ITGA4 and tissue ROBO4 expression in samples without ABMR (Spearman's R = 0.33; p < 0.001), but no correlation between blood ITGA4 and tissue ROBO4 expression in samples with ABMR (Spearman's R = 0.009; p = 0.513). CONCLUSIONS: Circulating blood ITGA4 expression is elevated in antibody-mediated rejection (AMR) and correlates with myocardial expression of ROBO4. The knowledge of individual transcript expression levels in blood and in tissue may provide insights into various disease processes in heart transplant patients. Taken together, the results of our study reveal an overlap between 2 objective post-heart transplant rejection surveillance methods, identify potential novel markers for ABMR, and reveal the need for a deeper understanding of molecular mechanisms underlying allograft rejection.