OBJECTIVES:

The aim of this meta-analysis was to assess the diagnostic performance of various CMR imaging parameters for evaluating acute cardiac transplant rejection.

BACKGROUND:

Endomyocardial biopsy is the current gold standard for detection of acute cardiac transplant rejection. Cardiac magnetic resonance (CMR) is uniquely capable of myocardial tissue characterization and may be useful as a noninvasive alternative for the diagnosis of graft rejection.

METHODS:

PubMed and Web of Science were searched for relevant publications reporting on the use of CMR myocardial tissue characterization for detection of acute cardiac transplant rejection with endomyocardial biopsy as the reference standard. Pooled sensitivity, specificity, and hierarchical modeling-based summary receiver-operating characteristic curves were calculated.

RESULTS:

Of 478 papers, 10 studies comprising 564 patients were included. The sensitivity and specificity for the detection of acute cardiac transplant rejection were 84.6 (95% CI: 65.6-94.0) and 70.1 (95% CI: 54.2-82.2) for T1, 86.5 (95% CI: 72.1-94.1) and 85.9 (95% CI: 65.2-94.6) for T2, 91.3 (95% CI: 63.9-98.4) and 67.6 (95% CI: 56.1-77.4) for extracellular volume fraction (ECV), and 50.1 (95% CI: 31.2-68.9) and 60.2 (95% CI: 36.7-79.7) for late gadolinium enhancement (LGE). The areas under the hierarchical modeling-based summary receiver-operating characteristic curve were 0.84 (95% CI: 0.81-0.87) for T1, 0.92 (95% CI: 0.89-94) for T2, 0.78 (95% CI: 0.74-0.81) for ECV, and 0.56 (95% CI: 0.51-0.60) for LGE. T2 values demonstrated the highest diagnostic accuracy, followed by native T1, ECV, and LGE (all P values <0.001 for T1, ECV, and LGE vs T2).

CONCLUSIONS:

T2 mapping demonstrated higher diagnostic accuracy than other CMR techniques. Native T1 and ECV provide high diagnostic use but lower diagnostic accuracy compared with T2, which was related primarily to lower specificity. LGE showed poor diagnostic performance for detection of rejection.

Simultaneous heart-kidney transplant (sHK) has enabled the successful transplantation of patients with end-stage heart disease and concomitant kidney disease, with non-inferior outcomes to heart transplant (HT) alone. The decision for sHK is challenged by difficulties in differentiating those patients with a significant component of reversible kidney injury due to cardiorenal syndrome who may recover kidney function after HT, from those with intrinsic advanced kidney disease who would benefit most from sHK. A consensus conference on sHK took place on June 1, 2019 in Boston, Massachusetts. The conference represented a collaborative effort by experts in cardiothoracic and kidney transplantation from centers across the United States to explore the development of guidelines for the interdisciplinary criteria for kidney transplantation in the sHK candidate, to evaluate the current allocation of kidneys to follow the heart for sHK, and to recommend standardized care for the management of sHK recipients. The conference served as a forum to unify criteria between the different specialties and to forge a pathway for patients who may need dual organ transplantation. Due to the continuing shortage of available donor organs, ethical problems related to multi-organ transplantation were also debated. The findings and consensus statements are presented.

A consensus conference on frailty in solid organ transplantation took place on February 11, 2018, to discuss the latest developments in frailty, adopt a standardized approach to assessment, and generate ideas for future research. The findings and consensus of the Frailty Heart Workgroup (American Society of Transplantation's Thoracic and Critical Care Community of Practice) are presented here. Frailty is defined as a clinically recognizable state of increased vulnerability resulting from aging-associated decline in reserve and function across multiple physiologic systems such that the ability to cope with every day or acute stressors is compromised. Frailty is increasingly recognized as a distinct biologic entity that can adversely affect outcomes before and after heart transplantation. A greater proportion of patients referred for heart transplantation are older and have more complex comorbidities. However, outcomes data in the pretransplant setting, particularly for younger patients, are limited. Therefore, there is a need to develop objective frailty assessment tools for risk stratification in patients with advanced heart disease. These tools will help to determine appropriate recipient selection for advanced heart disease therapies including heart transplantation and mechanical circulatory support, improve overall outcomes, and help distinguish frailty phenotypes amenable to intervention.

BACKGROUND:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by an overwhelming cytokine response. Various treatment strategies have been attempted.

METHODS AND RESULTS:

A 61-year-old man with heart transplantation in 2017 presented with fever, cough, and dyspnea, and was confirmed positive for coronavirus disease 2019 (COVID-19). Laboratory tests showed significant elevations in C-reactive protein and interleukin-6 (IL-6). Echocardiogram showed left ventricular ejection fraction 58% (with ejection fraction 57% 6 months prior). Given the lack of clear management guidelines, the patient was initially managed symptomatically. However, the patient subsequently had a rapid respiratory deterioration with worsening inflammatory markers on day 5 of admission. Tocilizumab (anti-IL-6R) was in low supply in the hospital. The patient was offered clazakizumab (anti-IL-6) for compassionate use. Patient received 25 mg intravenously × 1 dose. Within 24 hours, he showed significant improvement in symptoms, oxygen requirements, radiological findings, and inflammatory markers. There was a transient leukopenia that improved in 4 days. He was discharged home on day 11, with negative nasopharyngeal SARS-CoV-2 PCR as an outpatient on day 35, development of positive serum COVID-19 IgG antibody, and he continued to do well on day 60, with no heart-related symptoms.

CONCLUSION:

Clazakizumab is a monoclonal antibody against human IL-6, which may be helpful in inhibiting the cytokine response to SARS-CoV-2 in COVID-19. Although not yet FDA approved, it is being investigated for treatment of renal antibody-mediated rejection. Clinical trials of clazakizumab for treatment of COVID-19 are underway worldwide.

Although primary graft dysfunction (PGD) is fairly common early after cardiac transplant, standardized schemes for diagnosis and treatment remain contentious. Most major cardiac transplant centers use different definitions and parameters of cardiac function. Thus, there is difficulty comparing published reports and no agreed protocol for management. A consensus conference was organized to better define, diagnose, and manage PGD. There were 71 participants (transplant cardiologists, surgeons, immunologists and pathologists), with vast clinical and published experience in PGD, representing 42 heart transplant centers worldwide. State-of-the-art PGD presentations occurred with subsequent breakout sessions planned in an attempt to reach consensus on various issues. Graft dysfunction will be classified into primary graft dysfunction (PGD) or secondary graft dysfunction where there is a discernible cause such as hyperacute rejection, pulmonary hypertension, or surgical complications. PGD must be diagnosed within 24 hours of completion of surgery. PGD is divided into PGD-left ventricle and PGD-right ventricle. PGD-left ventricle is categorized into mild, moderate, or severe grades depending on the level of cardiac function and the extent of inotrope and mechanical support required. Agreed risk factors for PGD include donor, recipient, and surgical procedural factors. Recommended management involves minimization of risk factors, gradual increase of inotropes, and use of mechanical circulatory support as needed. Retransplantation may be indicated if risk factors are minimal. With a standardized definition of PGD, there will be more consistent recognition of this phenomenon and treatment modalities will be more comparable. This should lead to better understanding of PGD and prevention/minimization of its adverse outcomes. © 2014 International Society for Heart and Lung Transplantation.

BACKGROUND:

The Organ Care System (OCS), an ex vivo heart perfusion platform, represents an alternative to the current standard of cold organ storage that sustains the donor heart in a near-physiologic state. Previous reports showed that this system had significantly shortened the cold ischemic time from standard cold storage (CS). However, the effect of reduced ischemic injury against the coronary vascular bed has not been examined by intravascular ultrasound (IVUS).

METHODS:

Between August 2011 and February 2013, heart transplant (HTx) candidates enrolled in the PROCEED 2 trial were randomized to either CS or OCS. IVUS was performed at 4-6 weeks (baseline) and repeated 1 year after transplantation. The change in maximal intimal thickness (MIT) and other clinical outcomes were examined.

RESULTS:

Thirty-nine patients were randomized and underwent HTx by OCS (n=16) or CS (n=18). Of these, 18 patients (OCS: n=5, CS: n=13) with paired IVUS were examined. There were no significant differences in the change of MIT and other clinical outcomes between the groups.

CONCLUSION:

The incidence of cardiac allograft vasculopathy in donor hearts preserved with the OCS versus CS was similar. These results suggest that this ex vivo allograft perfusion system is a promising and valid platform for donor heart transportation.

A consensus conference on frailty in kidney, liver, heart, and lung transplantation sponsored by the American Society of Transplantation (AST) and endorsed by the American Society of Nephrology (ASN), the American Society of Transplant Surgeons (ASTS), and the Canadian Society of Transplantation (CST) took place on February 11, 2018 in Phoenix, Arizona. Input from the transplant community through scheduled conference calls enabled wide discussion of current concepts in frailty, exploration of best practices for frailty risk assessment of transplant candidates and for management after transplant, and development of ideas for future research. A current understanding of frailty was compiled by each of the solid organ groups and is presented in this paper. Frailty is a common entity in patients with end-stage organ disease who are awaiting organ transplantation, and affects mortality on the waitlist and in the posttransplant period. The optimal methods by which frailty should be measured in each organ group are yet to be determined, but studies are underway. Interventions to reverse frailty vary among organ groups and appear promising. This conference achieved its intent to highlight the importance of frailty in organ transplantation and to plant the seeds for further discussion and research in this field.