Research Spotlight

Rizkalla, J. M., B. P. Gladnick, A. A. Bhimani, D. S. Wood, K. J. Kitziger and P. C. Peters, Jr. (2020). “Triaging Total Hip Arthroplasty During the COVID-19 Pandemic.” Curr Rev Musculoskelet Med May 22;1-9. [Epub ahead of print].

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PURPOSE OF REVIEW: The purpose of this review was to evaluate the available literature to determine what may be considered urgent indications for total hip arthroplasty, in the unprecedented setting of the worldwide COVID-19 pandemic. RECENT FINDINGS: SARS-CoV-2 is a novel coronavirus currently presenting in the form of a global pandemic, referred to as COVID-19. In this setting, multiple states have issued executive orders prohibiting “elective” surgery, including arthroplasty, in order to preserve healthcare resources. However, during this unprecedented reduction in elective surgery, there is likely to be some controversy as to what constitutes a purely “elective” procedure, versus an “urgent” procedure, particularly regarding hip arthroplasty. We reviewed the available literature for articles discussing the most commonly encountered indications for primary, conversion, and revision hip arthroplasty. Based upon the indications discussed in these articles, we further stratified these indications into “elective” versus “urgent” categories. In patients presenting with hip arthroplasty indications, the decision to proceed urgently with surgery should be based upon (a) the potential harm incurred by the patient if the surgery was delayed and (b) the potential risk incurred by the patient in the context of COVID-19 if surgery was performed. The authors present a decision-making algorithm for determining surgical urgency in three patients who underwent surgery in this context. Urgent total hip arthroplasty in the setting of the COVID-19 pandemic is a complex decision-making process, involving clinical and epidemiological factors. These decisions are best made in coordination with a multidisciplinary committee of one’s peers. Region-specific issues such as hospital resources and availability of PPE may also inform the decision-making process.

Pfeffer, G. B., T. Gonzalez, J. Brodsky, J. Campbell, C. Coetzee, S. Conti, G. Guyton, D. N. Herrmann, K. Hunt, J. Johnson, W. McGarvey, M. Pinzur, S. Raikin, B. Sangeorzan, A. Younger, M. Michalski, T. An and N. Noori (2020). “A Consensus Statement on the Surgical Treatment of Charcot-Marie-Tooth Disease.” Foot Ankle Int Jun 1;1071100720922220. [Epub ahead of print]. 1071100720922220.

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BACKGROUND: Charcot-Marie-Tooth (CMT) disease is a hereditary motor-sensory neuropathy that is often associated with a cavovarus foot deformity. Limited evidence exists for the orthopedic management of these patients. Our goal was to develop consensus guidelines based upon the clinical experiences and practices of an expert group of foot and ankle surgeons. METHODS: Thirteen experienced, board-certified orthopedic foot and ankle surgeons and a neurologist specializing in CMT disease convened at a 1-day meeting. The group discussed clinical and surgical considerations based upon existing literature and individual experience. After extensive debate, conclusion statements were deemed “consensus” if 85% of the group were in agreement and “unanimous” if 100% were in support. CONCLUSIONS: The group defined consensus terminology, agreed upon standardized templates for history and physical examination, and recommended a comprehensive approach to surgery. Early in the course of the disease, an orthopedic foot and ankle surgeon should be part of the care team. This consensus statement by a team of experienced orthopedic foot and ankle surgeons provides a comprehensive approach to the management of CMT cavovarus deformity. LEVEL OF EVIDENCE: Level V, expert opinion.

Packer, M. and M. Metra (2020). “Guideline-directed medical therapy for heart failure does not exist: a non-judgmental framework for describing the level of adherence to evidence-based drug treatments for patients with a reduced ejection fraction.” Eur J Heart Fail May 20. [Epub ahead of print].

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Numerous guideline documents have issued recommendations to clinicians concerning the treatment of chronic heart failure and a reduced ejection fraction. However, guidelines do not describe what constitutes an acceptable standard of care, and thus, practitioners who adhere to only a small fraction of the recommendations might claim that they are treating patients ‘in accordance with the guidelines’. As a result, <1% of patients with heart failure are receiving all life-prolonging treatments at trial-proven doses. A major impediment to the widespread adoption of trial-based treatments is a lack of any existing framework that would allow physicians to describe the adequacy of care. To address this deficiency, we propose a novel simple approach that would ask practitioners if a patient had been treated using the dosing algorithm that had been shown to be effective for each drug class. The proposed framework recognizes that all landmark survival trials in heart failure were 'strategy trials', i.e. the studies mandated a standardized forced-titration treatment plan that required timely uptitration to specified target dose unless patients experienced clinically meaningful, intolerable or serious adverse events, which persisted or recurred despite adjustment of other medications. Adherence to trial-proven regimens might be improved if physicians were asked to describe the degree to which a patient's treatment adhered to or deviated from the strategies that had been used to demonstrate the survival benefits of neurohormonal antagonists. The proposed framework should also promote practitioner self-awareness about the lack of evidence supporting the current widespread use of subtarget doses that are non-adherent with trial-proven forced-titration strategies.

Packer, M., C. S. P. Lam, L. H. Lund, M. S. Maurer and B. A. Borlaug (2020). “Characterization of the Inflammatory-Metabolic Phenotype of Heart Failure and a Preserved Ejection Fraction: a Hypothesis to Explain Influence of Sex on the Evolution and Potential Treatment of the Disease.” Eur J Heart Fail May 22. [Epub ahead of print].

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Accumulating evidence points to the existence of an inflammatory-metabolic phenotype of heart failure with a preserved ejection fraction (HFpEF), which is characterized by biomarkers of inflammation, an expanded epicardial adipose tissue mass, microvascular endothelial dysfunction, normal-to-mildly increased left ventricular volumes and systolic blood pressures, and possibly, altered activity of adipocyte-associated inflammatory mediators. A broad range of adipogenic metabolic and systemic inflammatory disorders – e.g., obesity, diabetes and metabolic syndrome as well as rheumatoid arthritis and psoriasis – can cause this phenotype, independent of the presence of large vessel coronary artery disease. Interestingly, when compared with men, women are both at greater risk of and may suffer greater cardiac consequences from these systemic inflammatory and metabolic disorders. Women show disproportionate increases in left ventricular filling pressures following increases in central blood volume and have greater arterial stiffness than men. Additionally, they are particularly predisposed to epicardial and intramyocardial fat expansion and imbalances in adipocyte-associated proinflammatory mediators. The hormonal interrelationships seen in inflammatory-metabolic phenotype may explain why mineralocorticoid receptor antagonists and neprilysin inhibitors may be more effective in women than in men with HFpEF. Recognition of the inflammatory-metabolic phenotype may improve an understanding of the pathogenesis of HFpEF and enhance the ability to design clinical trials of interventions in this heterogenous syndrome.

Packer, M. (2020). “What causes sudden death in patients with chronic heart failure and a reduced ejection fraction?” Eur Heart J 41(18): 1757-1763.

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Sudden death characterizes the mode of demise in 30-50% of patients with chronic heart failure and a reduced ejection fraction. Occasionally, these events have an identifiable pathophysiological trigger, e.g. myocardial infarction, catecholamine surges, or electrolyte imbalances, but in most circumstances, there is no acute precipitating mechanism. Instead, adverse left ventricular remodelling and fibrosis creates an exceptionally fragile and highly vulnerable substrate, which can be characterized using the model developed in theoretical physics of ‘self-organizing criticality’. This framework has been applied to describe the genesis of avalanches, nodes of traffic congestion unrelated to an accident, the abrupt system-wide failure of electrical grids, and the initiation of cancer and neurodegenerative diseases. Self-organizing criticality within the ventricular myocardium relies on complex adaptations to progressive stress and stretch, which evolve inevitably to an abrupt end (termed ‘cascading failure’), even though the rate of deterioration of the underlying disease process has not changed. The result is acute circulatory collapse (i.e. sudden death) in the absence of an identifiable triggering event. Cascading failure in a severely remodelled or fibrotic heart can become manifest electrically as a first-time ventricular tachyarrhythmia that is responsive to the shock delivered by an implantable cardioverter-defibrillator (ICD). Alternatively, it may present as an acute mechanical failure, which is manifest as (i) asystole, bradyarrhythmia, or electromechanical dissociation; or (ii) incessant ventricular fibrillation that persists despite repetitive ICD discharges; in both instances, the sudden deaths cannot be prevented by an ICD. This conceptual framework explains why anti-remodelling and antifibrotic interventions (i.e. neurohormonal antagonists and cardiac resynchronization) reduce the risk of sudden death in patients with heart failure in the absence of an ICD and provide incremental benefits in those with an ICD. The adoption of anti-remodelling and antifibrotic treatments may explain why the incidence of sudden death in clinical trials of heart failure has declined dramatically over the past 10-15 years, independent of the use of ICDs.