Cardiology

van Zyl, J. S., T. Sam, D. M. Clark, J. Felius, A. K. Doss, K. R. Kerlee, Z. O. Cheung, K. Martits-Chalangari, A. K. Jamil, S. A. Carey, R. L. Gottlieb, C. Y. Guerrero-Miranda, P. Kale and S. A. Hall (2021). “De novo tacrolimus extended-release tablets (LCPT) versus twice-daily tacrolimus in adult heart transplantation: Results of a single-center non-inferiority matched control trial.” Clin Transplant: e14487.

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Extended-release tacrolimus for prophylaxis of allograft rejection in orthotopic heart transplant (OHT) recipients is currently not FDA-approved. One such extended-release formulation of tacrolimus known as LCPT allows once-daily dosing and improves bioavailability compared to immediate-release tacrolimus (IR-tacrolimus). We compared the efficacy and safety of LCPT to IR-tacrolimus applied de novo in adult OHT recipients. Twenty-five prospective recipients on LCPT at our center from 2017 to 2019 were matched 1:2 with historical control recipients treated with IR-tacrolimus based on age, gender, and baseline creatinine. The primary composite outcome of death, acute cellular rejection, and/or new graft dysfunction within 1 year was compared using non-inferiority analysis. LCPT demonstrated non-inferiority to IR-tacrolimus, with a primary outcome risk reduction of 20% (90% CI: -40%, -.5%; non-inferiority P = .001). Tacrolimus trough levels peaked at 2-3 months and were higher in LCPT (median 14.5 vs. 12.7 ng/ml; P = .03) with similar dose levels (LCPT vs. IR-tacrolimus: .08 vs. .09 mg/kg/day; P = .33). Cardiovascular-related readmissions were reduced by 62% (P = .046) in LCPT patients. The complication rate per transplant admission and all-cause readmission rate did not differ significantly. These results suggest that LCPT is non-inferior in efficacy to IR-tacrolimus with a similar safety profile and improved bioavailability in OHT.

Cox, M., J. Thatcher, D. Graybeal and J. Hise (2021). “Intrasinus tPA for Successful Treatment of Extensive Dural Sinus Thrombosis in a Young Patient With COVID-19: Rationale and Protocol.” Neurohospitalist 11(4): 382-384.

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A 34-year-old with a recent diagnosis of COVID-19 with mild symptoms (fever, cough, mild dyspnea on exertion), presented to an outside hospital with severe headaches and nausea. Other than COVID-19, her only other notable history was the use of oral contraceptives. Her initial non-contrast CT scan was reportedly normal. She was discharged home with anti-emetics and medications for pain control. Her symptoms persisted, and she presented to our emergency department for repeat evaluation. [No abstract; excerpt from article].

Cox, M., J. Thatcher, R. Mayer, I. Thacker, R. Pearson and K. Layton (2021). “Spontaneous Intracranial Artery Dissection causing Subarachnoid Hemorrhage: Importance of Short-Term Surveillance.” Neurohospitalist 11(4): 379-381.

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Hemorrhagic intracranial artery dissections are unstable lesions, with a high propensity for rebleeding (up to 40%) in the acute period. Imaging plays an important role in the diagnosis and management of intracranial artery dissections. In this paper, we describe 2 cases in which the dissected intracranial artery underwent rapid morphological change within 3 days or less, highlighting the importance of short-term follow-up imaging in patients with these hemorrhagic lesions.

Ismaeel, A., D. Miserlis, E. Papoutsi, G. Haynatzki, W. T. Bohannon, R. S. Smith, J. L. Eidson, G. P. Casale, Pipinos, II and P. Koutakis (2021). “Endothelial Cell-Derived Pro-fibrotic Factors Increase TGF-β1 Expression by Smooth Muscle Cells in Response to Cycles of Hypoxia-Hyperoxia.” Biochim Biophys Acta Mol Basis Dis: 166278. Oct 1. [Epub ahead of print].

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BACKGROUND: The vascular pathology of peripheral artery disease (PAD) encompasses abnormal microvascular architecture and fibrosis in response to ischemia-reperfusion (I/R) cycles. We aimed to investigate the mechanisms by which pathological changes in the microvasculature direct fibrosis in the context of I/R. METHODS: Primary human aortic endothelial cells (ECs) were cultured under cycles of normoxia-hypoxia (NH) or normoxia-hypoxia-hyperoxia (NHH) to mimic I/R. Primary human aortic smooth muscle cells (SMCs) were cultured and treated with media from the ECs. FINDINGS: The mRNA and protein expression of the pro-fibrotic factors platelet derived growth factor (PDGF)-BB and connective tissue growth factor (CTGF) were significantly upregulated in ECs undergoing NH or NHH cycles. Treatment of SMCs with media from ECs undergoing NH or NHH cycles led to significant increases in TGF-β1, TGF-β pathway signaling intermediates, and collagen expression. Addition of neutralizing antibodies against PDGF-BB and CTGF to the media blunted the increases in TGF-β1 and collagen expression. Treatment of SMCs with PAD patient-derived serum also led to increased TGF-β1 levels. INTERPRETATION: In an in-vitro model of I/R, which recapitulates the pathophysiology of PAD, increased secretion of PDGF-BB and CTGF by ECs was shown to be predominantly driving TGF-β1-mediated expression by SMCs. These cell culture experiments help elucidate the mechanism and interaction between ECs and SMCs in microvascular fibrosis associated with I/R. Thus, targeting these pro-fibrotic factors may be an effective strategy to combat fibrosis in response to cycles of I/R. FUNDING: National Institute on Aging at the National Institutes of Health grant number R01AG064420.

Alam, A., G. P. Milligan and T. Gong (2021). “The dominant left ventricular assist device: lessons from an era.” ESC Heart Fail. [Epub ahead of print].

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The production and distribution of the HeartWare ventricular assist device has come to an abrupt end, but with this end comes the opportunity to reflect upon lessons learned from its lifespan. Running counter to the standard of evidence-based practice, the era of the HeartWare ventricular assist device was marred with fragmented data in relation to its primary counterpart, the HeartMate III. This created an incomplete understanding of devices, limited individualized patient care, and effectively positioned providers to make inferences regarding device superiority. We briefly review pertinent literature on this topic among the most commonly implanted durable devices from the era, detail the inherent limitations of this data, and argue the necessity of randomized clinical trials among novel devices towards the optimization of patient care.