Research Spotlight

Shah, P. B., F. G. P. Welt, E. Mahmud, A. Phillips, N. S. Kleiman, M. N. Young, M. Sherwood, W. Batchelor, D. D. Wang, L. Davidson, J. Wyman, S. Kadavath, M. Szerlip, J. Hermiller, D. Fullerton and S. Anwaruddin (2020). “Triage Considerations for Patients Referred for Structural Heart Disease Intervention During the Coronavirus Disease 2019 (COVID-19) Pandemic: An ACC /SCAI Consensus Statement.” Catheter Cardiovasc Interv Apr 6. [Epub ahead of print].

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The COVID-19 pandemic has strained health care resources around the world causing many institutions to curtail or stop elective procedures. This has resulted in the inability to care for patients valvular and structural heart disease (SHD) in a timely fashion potentially placing these patients at increased risk for adverse cardiovascular complications including congestive heart failure and death. The effective triage of these patients has become challenging in the current environment as clinicians have had to weigh the risk of bringing susceptible patients into the hospital environment during the COVID-19 pandemic versus the risk of delaying a needed procedure. In this document, we suggest guidelines as to how to triage patients in need of SHD interventions and provide a framework of how to decide when it may be appropriate to proceed with intervention despite the ongoing pandemic. In particular, we address the triage of patients in need of trans-catheter aortic valve replacement and percutaneous mitral valve repair. We also address procedural issues and considerations for the function of structural heart disease teams during the COVID-19 pandemic.

Schinstock, C. A., R. B. Mannon, K. Budde, A. S. Chong, M. Haas, S. Knechtle, C. Lefaucheur, R. A. Montgomery, P. Nickerson, S. G. Tullius, C. Ahn, M. Askar, M. Crespo, S. J. Chadban, S. Feng, S. C. Jordan, K. Man, M. Mengel, R. E. Morris, I. O’Doherty, B. H. Ozdemir, D. Seron, A. R. Tambur, K. Tanabe, J. L. Taupin and P. J. O’Connell (2020). “Recommended Treatment for Antibody-mediated Rejection After Kidney Transplantation: The 2019 Expert Consensus From the Transplantion Society Working Group.” Transplantation 104(5): 911-922.

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With the development of modern solid-phase assays to detect anti-HLA antibodies and a more precise histological classification, the diagnosis of antibody-mediated rejection (AMR) has become more common and is a major cause of kidney graft loss. Currently, there are no approved therapies and treatment guidelines are based on low-level evidence. The number of prospective randomized trials for the treatment of AMR is small, and the lack of an accepted common standard for care has been an impediment to the development of new therapies. To help alleviate this, The Transplantation Society convened a meeting of international experts to develop a consensus as to what is appropriate treatment for active and chronic active AMR. The aim was to reach a consensus for standard of care treatment against which new therapies could be evaluated. At the meeting, the underlying biology of AMR, the criteria for diagnosis, the clinical phenotypes, and outcomes were discussed. The evidence for different treatments was reviewed, and a consensus for what is acceptable standard of care for the treatment of active and chronic active AMR was presented. While it was agreed that the aims of treatment are to preserve renal function, reduce histological injury, and reduce the titer of donor-specific antibody, there was no conclusive evidence to support any specific therapy. As a result, the treatment recommendations are largely based on expert opinion. It is acknowledged that properly conducted and powered clinical trials of biologically plausible agents are urgently needed to improve patient outcomes.

Sapir-Pichhadze, R. and B. Kaplan (2020). “Seeing the Forest for the Trees: Random Forest Models for Predicting Survival in Kidney Transplant Recipients.” Transplantation 104(5): 905-906.

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Most practice guidelines are geared toward the “average patient.” Machine learning tools can capture the complexity of individual patients’ characteristics and aid transplant clinicians with patient-specific care decisions. As these tools become more prevalent, it is important to develop best practice guidelines and ensure there is regulatory oversight on their development and application. (Excerpt from text; no abstract available.)

Rooney, M., T. Bottiglieri, B. Wasek-Patterson, A. McMahon, C. F. Hughes, A. McCann, G. Horigan, J. J. Strain, H. McNulty and M. Ward (2020). “Impact of the MTHFR C677T polymorphism on one-carbon metabolites: Evidence from a randomised trial of riboflavin supplementation.” Biochimie Apr 21. pii: S0300-9084(20)30074-2. [Epub ahead of print].

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Homozygosity for the C677T polymorphism in MTHFR (TT genotype) is associated with a 24-87% increased risk of hypertension. Blood pressure (BP) lowering was previously reported in adults with the TT genotype, in response to supplementation with the MTHFR cofactor, riboflavin. Whether the BP phenotype associated with the polymorphism is related to perturbed one-carbon metabolism is unknown. This study investigated one-carbon metabolites and their responsiveness to riboflavin in adults with the TT genotype. Plasma samples from adults (n 115) screened for the MTHFR genotype, who previously participated in RCTs to lower BP, were analysed for methionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), betaine, choline and cystathionine by liquid chromatography tandem mass spectrometry (LC-MS/MS). The one-carbon metabolite response to riboflavin (1.6 mg/d; n 24) or placebo (n 23) for 16 weeks in adults with the TT genotype was also investigated. Plasma SAM (74.7 +/- 21.0 vs 85.2 +/- 22.6 nmol/L, P = 0.013) and SAM:SAH ratio (1.66 +/- 0.55 vs 1.85 +/- 0.51, P = 0.043) were lower and plasma homocysteine was higher (P = 0.043) in TT, compared to CC individuals. In response to riboflavin, SAM (P = 0.008) and cystathionine (P = 0.045) concentrations increased, with no responses in other one-carbon metabolites observed. These findings confirm perturbed one-carbon metabolism in individuals with the MTHFR 677TT genotype, and for the first time demonstrate that SAM, and cystathionine, increase in response to riboflavin supplementation in this genotype group. The genotype-specific, one-carbon metabolite responses to riboflavin intervention observed could offer some insight into the role of this gene-nutrient interaction in blood pressure.

Roberts, C. S., R. C. Stoler and W. C. Roberts (2020). “The Case for Primary Prevention of Atherosclerotic Events from Study of a Single Patient.” Am J Cardiol 125(9): 1443-1445.

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This report describes a 64-year-old woman who presented with unstable angina pectoris, her first atherosclerotic event, and who underwent coronary bypass including endarterectomy of the entire right coronary artery which was diffusely and severely narrowed by atherosclerotic plaque. Preoperatively, she fulfilled none of the present-day criteria for lipid-lowering drug therapy. The report demonstrates the deficiency of present-day lipid-lowering drug guidelines and emphasizes the need to switch emphasis from decreasing risk of an atherosclerotic event to the prevention of arterial plaques, a goal which will require a much lower threshold of low-density lipoprotein cholesterol to initiate drug therapy.