Decision analysis in cardiac surgery:a scoping review and methodological primer

OBJECTIVES: Randomized controlled trials are the gold standard for evidence generation in medicine but are limited by their real-world generalizability, resource needs, shorter follow-up durations and inability to be conducted for all clinical questions. Decision analysis (DA) models may simulate trials and observational studies by using existing data and evidence- and expert-informed assumptions and extend analyses over longer time horizons, different study populations and specific scenarios, helping to translate population outcomes to patient-specific clinical and economic outcomes. Here, we present a scoping review and methodological primer on DA for cardiac surgery research. METHODS: A scoping review was performed using the PubMed/MEDLINE, EMBASE and Web of Science databases for cardiac surgery DA studies published until December 2021. Articles were summarized descriptively to quantify trends and ascertain methodological consistency.RESULTS: A total of 184 articles were identified, among which Markov models (N = 92, 50.0%) were the most commonly used models. The most common outcomes were costs (N = 107, 58.2%), quality-adjusted life-years (N = 96, 52.2%) and incremental cost-effectiveness ratios (N = 89, 48.4%). Most (N = 165, 89.7%) articles applied sensitivity analyses, most frequently in the form of deterministic sensitivity analyses (N = 128, 69.6%). Reporting of guidelines to inform the model development and/or reporting was present in 22.3% of articles. CONCLUSION: DA methods are increasing but remain limited and highly variable in cardiac surgery. A methodological primer is presented and may provide researchers with the foundation to start with or improve DA, as well as provide readers and reviewers with the fundamental concepts to review DA studies.</p

Registry of Aortic Diseases to Model Adverse Events and Progression (ROADMAP) in Uncomplicated Type B Aortic Dissection: Study Design and Rationale

PURPOSE To describe the design and methodological approach of a multicenter, retrospective study to externally validate a clinical and imaging-based model for predicting the risk of late adverse events in patients with initially uncomplicated type B aortic dissection (uTBAD). MATERIALS AND METHODS The Registry of Aortic Diseases to Model Adverse Events and Progression (ROADMAP) is a collaboration between 10 academic aortic centers in North America and Europe. Two centers have previously developed and internally validated a recently developed risk prediction model. Clinical and imaging data from eight ROADMAP centers will be used for external validation. Patients with uTBAD who survived the initial hospitalization between January 1, 2001, and December 31, 2013, with follow-up until 2020, will be retrospectively identified. Clinical and imaging data from the index hospitalization and all follow-up encounters will be collected at each center and transferred to the coordinating center for analysis. Baseline and follow-up CT scans will be evaluated by cardiovascular imaging experts using a standardized technique. RESULTS The primary end point is the occurrence of late adverse events, defined as aneurysm formation (≥6 cm), rapid expansion of the aorta (≥1 cm/y), fatal or nonfatal aortic rupture, new refractory pain, uncontrollable hypertension, and organ or limb malperfusion. The previously derived multivariable model will be externally validated by using Cox proportional hazards regression modeling. CONCLUSION This study will show whether a recent clinical and imaging-based risk prediction model for patients with uTBAD can be generalized to a larger population, which is an important step toward individualized risk stratification and therapy.Keywords: CT Angiography, Vascular, Aorta, Dissection, Outcomes Analysis, Aortic Dissection, MRI, TEVAR© RSNA, 2022See also the commentary by Rajiah in this issue

Self-renewing resident arterial macrophages arise from embryonic CX3CR1+ precursors and circulating monocytes immediately after birth

Resident macrophages densely populate the normal arterial wall, yet their origins and the mechanisms that sustain them are poorly understood. Here we use gene-expression profiling to show that arterial macrophages constitute a distinct population among macrophages. Using multiple fate-mapping approaches, we show that arterial macrophages arise embryonically from CX3CR1+ precursors and postnatally from bone marrow–derived monocytes that colonize the tissue immediately after birth. In adulthood, proliferation (rather than monocyte recruitment) sustains arterial macrophages in the steady state and after severe depletion following sepsis. After infection, arterial macrophages return rapidly to functional homeostasis. Finally, survival of resident arterial macrophages depends on a CX3CR1-CX3CL1 axis within the vascular niche

Gene Expression Changes in Rats with Diastolic Dysfunction Induced by Diabetes and Hypertension, and in Humans with Diastolic Heart Failure

Current therapies for heart failure are administered across a heterogeneous spectrum of disease etiology and phenotype. Standard treatments for systolic heart failure are not efficacious for patients with diastolic heart failure, raising the possibility that as of yet unidentified mechanisms are responsible for disease pathogenesis. We observed that diabetic rats treated with Angiotensin II infusion developed cardiac hypertrophy, fibrosis, and impaired diastolic function. Using a systems biology approach, we identified (a) changes in the cardiac transcriptome of rats in response to diabetes and hypertension; (b) the subset of genes that were simultaneously regulated in both the heart and whole blood of rats exposed to diabetes and hypertension; and (c) differentially expressed genes in whole blood of patients with diastolic heart failure compared to those with systolic heart failure and controls. In each experiment, we identified differential expression of functionally related groups of genes, suggesting coordinated regulation of multiple genes. Protein processing, extracellular matrix remodeling and inflammation were three of the dominant processes in cardiac tissue of diabetic hypertensive rats that were simultaneously regulated in whole blood. Extracellular matrix protein 1, transforming growth factor beta family members, and angiopoietin-like four were identified as part of a panel of extracellular matrix mediators that were coordinately regulated in both tissues. Gene expression profiles in blood of patients with diastolic heart failure allowed us to study networks and relationships of interactions that may not have been available from the study of single targets. A panel of eleven candidate markers was identified, including several that participate in cytoskeletal rearrangement or cell adhesion (plexin C1, transgelin 2, ninein, villin 2, and dock 2), and others involved in protein processing (ubiquitination factor E4B, myotubularin related protein 3, presenilin 1). These sets of experiments contribute to the literature regarding the myocardial effects of diabetes and hypertension and provide novel insight into the coordinated regulation of genes in the heart and blood in response to cardiovascular stress. The list of top candidate genes identified from the blood of patients with diastolic heart failure may have clinical utility as disease biomarkers.Ph

Hyperbaric oxygen therapy for spinal cord ischaemia after complex aortic repair — a retrospective review

Background: Complex aortic repair (CAR) carries high rates of debilitating postoperative complications, including spinal cord injury. The rate of spinal cord deficits post-CAR is approximately 10%, with permanent paraplegia in 2.9% and paraparesis in 2.4% of patients. Treatment options are limited. Rescue therapies include optimization of spinal cord perfusion and oxygen delivery by mean arterial pressure augmentation (&gt; 90 mm Hg), cerebrospinal fluid drainage, and preservation of adequate haemoglobin concentration (&gt; 100 g L-1). Hyperbaric oxygen therapy (HBOT) has been described in several case reports as part of the multimodal treatment for spinal cord ischemia. HBOT has been used in our centre as adjunct rescue treatment for patients with spinal cord injury post-CAR that were refractory to traditional medical management, and we aimed to retrospectively review these cases. Methods: After Research Ethics Board approval, we performed a retrospective review of all post-CAR patients who developed spinal cord injury with severe motor deficit and were treated with HBOT at our institution since 2013. Results: Seven patients with spinal cord injury after CAR were treated with HBOT in addition to traditional rescue therapies. Five patients showed varying degrees of recovery, with two displaying full recovery. One developed oxygen-induced seizure, medically treated. No other HBOT-related complications were noted. Conclusions: Our retrospective study shows a potential benefit of hyperbaric oxygen therapy on neurological outcome in patients who developed spinal cord injury after CAR. Prospective research is needed to understand the role, efficacy, benefits and risks of HBOT in this setting

Decision analysis in cardiac surgery:a scoping review and methodological primer

OBJECTIVES: Randomized controlled trials are the gold standard for evidence generation in medicine but are limited by their real-world generalizability, resource needs, shorter follow-up durations and inability to be conducted for all clinical questions. Decision analysis (DA) models may simulate trials and observational studies by using existing data and evidence- and expert-informed assumptions and extend analyses over longer time horizons, different study populations and specific scenarios, helping to translate population outcomes to patient-specific clinical and economic outcomes. Here, we present a scoping review and methodological primer on DA for cardiac surgery research. METHODS: A scoping review was performed using the PubMed/MEDLINE, EMBASE and Web of Science databases for cardiac surgery DA studies published until December 2021. Articles were summarized descriptively to quantify trends and ascertain methodological consistency.RESULTS: A total of 184 articles were identified, among which Markov models (N = 92, 50.0%) were the most commonly used models. The most common outcomes were costs (N = 107, 58.2%), quality-adjusted life-years (N = 96, 52.2%) and incremental cost-effectiveness ratios (N = 89, 48.4%). Most (N = 165, 89.7%) articles applied sensitivity analyses, most frequently in the form of deterministic sensitivity analyses (N = 128, 69.6%). Reporting of guidelines to inform the model development and/or reporting was present in 22.3% of articles. CONCLUSION: DA methods are increasing but remain limited and highly variable in cardiac surgery. A methodological primer is presented and may provide researchers with the foundation to start with or improve DA, as well as provide readers and reviewers with the fundamental concepts to review DA studies.</p