Faculty Bibliography

OBJECTIVES:Acute kidney injury (AKI) remains a leading source of morbidity and mortality after cardiothoracic surgery. Insulin-like growth factor-binding protein 7 (IGFBP7), and tissue inhibitor of metalloproteinases-2 (TIMP-2), are novel early-phase renal biomarkers that have been validated as sensitive predictors of AKI. Here the authors studied the efficacy of these biomarkers for predicting AKI after left ventricular assist device (LVAD) implantation and cardiac transplantation. DESIGN/SETTING/PARTICIPANTS/INTERVENTIONS:This was a prospective study of 73 patients undergoing LVAD implantation (n = 37) or heart transplant (n = 36) from 2016 to 2017 at the authors' center. TIMP-2 and IGFBP7 were measured with the NephroCheck Test on urine samples before surgery and one-to-six hours after surgery. NephroCheck scores were assessed as predictors of moderate/severe AKI (Kidney Disease International Global Outcomes 2/3 creatinine criteria) within 48 hours of surgery, and the association with survival to one year was investigated. MEASUREMENTS AND MAIN RESULTS:The LVAD and transplant cohorts overall were similar in demographics and baseline creatinine (p > 0.05), with the exception of having more African-American patients in the LVAD arm (p = 0.003). Eleven (30%) LVAD and 16 (44%) transplant patients developed moderate/severe AKI. Overall, AKI was associated with postsurgery NephroCheck (odds ratio [95% confidence interval] for 0.1 mg/dL increase: 1.36 [1.04-1.79]; p = 0.03), but not with baseline NephroCheck (p = 0.92). When analyzed by cohort, this effect remained for LVAD (1.68 [1.05-2.71]; p = 0.03) but not for transplant (p = 0.15). Receiver operating characteristic analysis showed postoperative NephroCheck to be superior to baseline creatinine in LVAD (p = 0.046). Furthermore, an increase of 0.1 mg/dL in postoperative NephroCheck was associated with a 10% increase in the risk of mortality (adjusted hazard ratio: 1.11 [1.01-1.21]; p = 0.04) independent of age and body mass index. CONCLUSION:Assessment of TIMP-2 and IGFBP7 within six hours after surgery appeared effective at predicting AKI in patients with LVADs. Larger studies are warranted to validate these findings.

Up to one-third of all patients admitted to intensive care units carry a diagnosis of shock. The use of angiotensin II is becoming widespread in all forms of shock, including cardiogenic, after the U.S. Food and Drug Administration's (FDA's) initial approval for vasoplegic shock in 2017. Here, the authors review the literature on angiotensin II's mechanism of action, benefits, and future therapeutic opportunities.

Donor-derived cell free DNA (dd-cfDNA) has rapidly become part of rejection surveillance following orthotopic heart transplantation. However, some patients show elevated dd-cfDNA without clinical evidence of rejection. With the aim to provide a clinical description of this subpopulation, we retrospectively analyzed 35 cardiac transplant recipients at our center who experienced elevated (≥.20%) dd-cfDNA in the absence of clinical rejection, out of a total 106 recipients who had dd-cfDNA results available during the first year. The median time to first elevated dd-cfDNA level was 46 days, and the highest dd-cfDNA recorded within 1 year was .31% [inter-quartile range, .23-.45]. Twenty-two (63%) patients experienced infections (cytomegalovirus (CMV) or other), and 16 (46%) presented with de novo donor-specific antibodies. Cluster analysis revealed four distinct groups characterized by (a) subclinical rejection with 50% CMV (n = 16), (b) non-CMV infections and the longest time to first elevated dd-cfDNA (187 days) (n = 8), (c) right ventricular dysfunction (n = 6), and (d) women who showed the youngest median age (45 years) and highest median dd-cfDNA (.50%) (n = 5). Continued prospective analysis is needed to determine if these observations warrant changes in patient management to optimize the utilization of this vital non-invasive graft surveillance tool.

Patients with chronic congestive heart failure belong to a population with reduced quality of life, poor functional class, and increased risk of mortality and morbidity. In these patients, assessment of invasive hemodynamics both serves therapeutic purposes and is useful for stratification roles. The right heart catheterization has become a cornerstone diagnostic tool for patients in refractory heart failure or cardiogenic shock, as well as for the assessment of candidacy for heart replacement therapies, and the management of patients following mechanical circulatory assist device implantation and heart transplantation.

Right heart failure is a major cause of morbidity and mortality following left ventricular assist device implantation. Over the past few decades, the definition proposed by the Interagency Registry of Mechanical Circulatory Support and Society of Thoracic Surgeons has continually evolved to better identify this complex pathology. We propose that the latest definition proposed by the Mechanical Circulatory Support Academic Research Consortium in 2020 will increase our recognition and understanding of this complex disease phenomenon.

An association has been reported between factor VIII and arterial thrombosis such as ischemic stroke and myocardial infarction. We report a 36-year-old man who had a myocardial infarction despite lacking traditional cardiac risk factors. He developed end-stage heart failure and renal insufficiency necessitating a HeartMate II left ventricular assist device (LVAD). While on the transplant list, he experienced two episodes of LVAD thrombosis 6 months apart, prompting device exchange and escalation of anticoagulation therapy. He eventually underwent a successful heart-kidney transplant before suffering an extensive left lower extremity deep vein thrombosis 6 weeks later. A thrombophilia workup revealed elevated factor VIII activity of 319% (normal range, 50%-150%). He was placed on indefinite anticoagulation with apixaban with no further thrombotic episode in 18 months of follow-up to date.