The Time-Varying Cardiovascular Benefits of Glucagon-Like Peptide-1 Receptor Agonist Therapy in Patients with Type 2 Diabetes Mellitus: Evidence from Large Multinational Trials

Aims: To evaluate the time-varying cardio-protective effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) using pooled data from eight contemporary cardiovascular outcome trials using the difference in the restricted mean survival time (ΔRMST) as the effect estimate. Material and Methods: Data from eight multinational cardiovascular outcome randomized controlled trials of GLP-1RAs for type 2 diabetes mellitus were pooled. Flexible parametric survival models were fit from published Kaplan-Meier plots. The differences between arms in RMST (ΔRMST) were calculated at 12, 24, 36 and 48 months. ΔRMST values were pooled using an inverse variance-weighted random-effects model; heterogeneity was tested with Cochran\u27s Q statistic. The endpoints studied were: three-point major adverse cardiovascular events (MACE), all-cause mortality, stroke, cardiovascular mortality and myocardial infarction. Results: We included eight large (3183-14 752 participants, total = 60 080; median follow-up range: 1.5 to 5.4 years) GLP-1RA trials. Among GLP-1RA recipients, we observed an average delay in three-point MACE of 0.03, 0.15, 0.37 and 0.63 months at 12, 24, 36 and 48 months, respectively. At 48 months, while cardiovascular mortality was comparable in both arms (pooled ΔRMST 0.163 [−0.112, 0.437]; P = 0.24), overall survival was higher (ΔRMST = 0.261 [0.08-0.43] months) and stroke was delayed (ΔRMST 0.22 [0.15-0.33]) in patients receiving GLP-1RAs. Conclusions: Glucagon-like peptide-1 receptor agonists may delay the occurrence of MACE by an average of 0.6 months at 48 months, with meaningfully larger gains in patients with cardiovascular disease. This metric may be easier for clinicians and patients to interpret than hazard ratios, which assume a knowledge of absolute risk in the absence of treatment

Aortic Root Reconstruction

Aortic root reconstruction represents one of the most complex areas of cardiac surgery as well as one of the most dynamic-major developments in understanding of the aortic root anatomy and physiology, improvements in imaging and surgical technique allowed for development and acceptance into clinical practice of several novel procedures over last couple of decades. From first aortic root replacement reported by Bentall and De Bono in 1968 to aortic root reimplantation (David procedure) and remodeling (Yacoub operation) with multiple contemporary modifications, aortic root reconstruction now is widely used in treatment of chronic aortic aneurysmal disease and acute aortic dissections alike. Basic principles of aortic root structure and function and critical operative strategies for aortic root surgery are reviewed in this chapter

Trends in prescriptions of cardioprotective diabetic agents after coronary artery bypass grafting among U.S. veterans

OBJECTIVE: Patients with type 2 diabetes undergoing coronary artery bypass grafting (CABG) are at risk for cardiovascular events. Sodium–glucose cotransporter 2 receptor inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) are effective cardioprotective agents; however, their prescription among CABG patients is uncertain. The aims of this study were 1) to evaluate the overall use of SGLT2i/GLP-1RA after CABG and explore longitudinal trends and 2) to examine patient-related factors associated with the use of SGLT2i or GLP-1RA. RESEARCH DESIGN AND METHODS: We analyzed the nationwide Veterans Affairs (VA) database (2016–2019) to report trends and factors associated with SGLT2i or GLP-1RA prescription after CABG. RESULTS: Among 5,109 patients operated on at 40 different VA medical centers, 525 of 5,109 (10.4%), 352 of 5,109 (6.8%), and 91 of 5,109 (1.8%) were prescribed SGLT2i, GLP-1RA, and both, respectively. A substantial increase in the quarterly SGLT2i prescription rates (1.6% [first quarter of 2016 (2016Q1)], 33% [2019Q4]) was present but was lower for GLP-1RA (0.8% [2016Q1], 11.2% [2019Q4]). SGLT2i use was less likely with preexisting vascular disease (odd ratio [OR] 0.75, 95% CI 0.75, 0.94) or kidney disease (OR 0.72, 95% CI 0.58, 0.88), while GLP-1RA use was associated with obesity (OR 1.91, 95% CI 1.50, 2.46). CONCLUSIONS: The overall utilization of SGLT2i or GLP-1RA drugs in U.S. veterans with type 2 diabetes undergoing CABG is low, with SGLT2i preferred over GLP-1RA

Off‐pump coronary artery bypass grafting: department of veteran affairs’ use and outcomes

Background: Coronary artery bypass can be performed off pump (OPCAB) without cardiopulmonary bypass. However, trends over time for OPCAB versus on‐pump (ONCAB) use and long‐term outcome has not been reported, nor has their long‐term outcome been compared. Methods and Results: We queried the national Veterans Affairs database (2005–2019) to identify isolated coronary artery bypass procedures. Procedures were classified as OPCAB on ONCAB using the as‐treated basis. Trend analyses were performed to evaluate longitudinal changes in the preference for OPCAB. The median follow‐up period was 6.6 (3.5–10) years. An inverse probability weighted Cox model was used to compare all‐cause mortality between OPCAB and ONCAB. From 47 685 patients, 6759 (age 64±8 years) received OPCAB (14%). OPCAB usage declined from 16% (2005–2009) to 8% (2015–2019). Patients with triple vessel disease who received OPCAB received a lower mean number of grafts (2.8±0.8 versus 3.2±0.8; P<0.01). The ONCAB 5‐, 10‐, and 15‐year survival rates were 82.9% (82.5–83.3), 60.4% (59.8–61.1), and 37.2% (36.1–38.4); correspondingly, OPCAB rates were 80.7% (79.7–81.7), 57.4% (56–58.7), and 34.1% (31.7–36.6) (P<0.01). OPCAB was associated with increased risk‐adjusted all‐cause mortality (hazard ratio, 1.15 [1.13–1.18]; P<0.01) and myocardial infarction (incident rate ratio, 1.16 [1.05–1.28]; P<0.01). Conclusions: Over 15 years, OPCAB use declined considerably in Veterans Affairs medical centers. In Veterans Affairs hospitals, late all‐cause mortality and myocardial infarction rates were higher in the OPCAB cohort

Association between the AHA Life's Essential 8 score and incident all-cause dementia: a prospective cohort study from UK Biobank

Aim: This study aimed to investigate the association between the LE8 score and incident all-cause dementia (including Alzheimer's disease [AD] and vascular dementia) in UK Biobank. Methods: 259,718 participants were included in this prospective study. Smoking, non-HDL cholesterol, blood pressure, body mass index, HbA1c, physical activity, diet, and sleep were used to create the LE8 score. Associations between the score (both continuous and as quartiles) and outcomes were investigated using adjusted linear and nonlinear Cox proportional hazard models. The potential impact fractions of two scenarios and the rate advancement periods were also calculated. Results: Over a median follow-up of 10.6 years, 4,958 participants were diagnosed with any dementia. Higher LE8 scores were associated with lower risk of all-cause and vascular dementia in an exponential decay pattern. Compared with individuals in the healthiest quartile, those in the least healthy quartile had a higher risk of all-cause dementia (HR: 1.50 [95% CI: 1.37 to 1.65] and vascular dementia (HR: 1.86 [1.44 to 2.42]). A targeted intervention that increased, by 10-points, the score among individuals in the lowest quartile could have prevented 6.8% of all-cause dementia cases. Individuals in the least healthy LE8 quartile might develop all-cause dementia 2.45 years earlier than their counterparts. Conclusions: Individuals with higher LE8 scores had lower risk of all-cause and vascular dementia. Because of nonlinear associations, interventions targeted at the least healthy individuals might produce greater population-level benefits

Outcomes of surgical mitral and aortic valve replacements among kidney transplant candidates: implications for valve selection

Background: Limited literature exists that evaluated outcomes of kidney transplant–eligible patients who are having dialysis and who are undergoing valve replacement. Our main objective in this study was to compare mortality, reoperation, and bleeding episodes between bioprosthetic and mechanical valve procedures among kidney transplant–eligible patients who are having dialysis. Methods and Results: We studied 887 and 1925 dialysis patients from the United States Renal Data System, who underwent mitral valve replacement and aortic valve replacement (AVR) after being waitlisted for a kidney transplant (2000–2015), respectively. Time to death, time to reoperation, and time to bleeding requiring hospitalizations were compared separately for AVR and mitral valve replacement. Kaplan–Meier survival curves, Cox proportional hazards model for time to death, accelerated time to event model for time to reoperation, and counting process model for time to recurrent bleeding were used. There were no differences in mortality (hazard ratio [HR], 0.92; 95% CI, 0.77–1.09) or risk of reoperation or risk of significant bleeding events between bioprosthetic and mechanical mitral valve replacement. However, mechanical AVR was associated with a modestly significant less hazard of death (HR, 0.83; 95% CI, 0.74–0.94) compared with bioprosthetic AVR. There were no differences in time to reoperation, or time to significant bleeding events between bioprosthetic and mechanical AVR. Conclusions: For kidney transplant waitlisted patients who are on dialysis and who are undergoing surgical valve replacement, bioprosthetic and mechanical valves have comparable survival, reoperation rates, and bleeding episodes requiring hospitalizations at both mitral and aortic locations. These findings emphasize that an individualized informed decision is recommended when choosing the type of valve for this special group of patients having dialysis

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK

Systematic review and meta-analysis: a brief introduction

Learning objectives: 1. Understand the basic structure and parts of a systematic review 2. Be able to read and critically appraise a published systematic revie

Model-free estimates that complement information obtained from the hazard ratio

Learning objectives 1. Understand the limitations of the modeling of survival data, especially as pertains to the Cox proportional hazards model. 2. An introduction to model-free estimates of survival, namely, the restricted mean survival time/restricted mean lost time. 3. Use R (The R Foundation for Statistical Computing, Austria) or STATA® (The STATACorp, College Station, TX, USA) to perform analyses and obtain these parameters from a dataset

Reply to the editor: Mīlle viae dūcunt hominēs per saecula Rōmam

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