Publications

BACKGROUND: Shared decision-making is mandated for patients receiving primary prevention implantable cardioverter defibrillators (ICDs). Less attention has been paid to generator exchange decisions, although at the time of generator exchange, patients' risk of sudden cardiac death, risk of procedural complications, quality of life, or prognosis may have changed. This study was designed to explore how patients make ICD generator exchange decisions.

METHODS: Emory Healthcare patients with primary prevention ICDs implanted from 2013 to 2021 were recruited to complete in-depth interviews exploring perspectives regarding generator exchanges. Interviews were conducted in 2021. Transcribed interviews were qualitatively coded using multilevel template analytic methods. To investigate benefit thresholds for pursuing generator exchanges, patients were presented standard-gamble type hypothetical scenarios where their ICD battery was depleted but their 5-year risk of sudden cardiac death at that time varied (10%, 5%, and 1%).

RESULTS: Fifty patients were interviewed; 18 had a prior generator exchange, 16 had received ICD therapy, and 17 had improved left ventricular ejection fraction. As sudden cardiac death risk decreased from 10% to 5% to 1%, the number of participants willing to undergo a generator exchange decreased from 48 to 42 to 33, respectively. Responses suggest that doctor's recommendations are likely to substantially impact patients' decision-making. Other drivers of decision-making included past experiences with ICD therapy and device implantation, as well as risk aversion. Therapeutic inertia and misconceptions about ICD therapy were common and represent substantive barriers to effective shared decision-making in this context.

CONCLUSIONS: Strong defaults may exist to continue therapy and exchange ICD generators. Updated risk stratification may facilitate shared decision-making and reduce generator exchanges in very low-risk patients, especially if these interventions are directed toward clinicians. Interventions targeting phenomena such as therapeutic inertia may be more impactful and warrant exploration in randomized trials.

IMPORTANCE: Trials showing equivalent or better outcomes with initial evaluation using coronary computed tomography angiography (cCTA) compared with stress testing in patients with stable chest pain have informed guidelines but raise questions about overtesting and excess catheterization.

OBJECTIVE: To test a modified initial cCTA strategy designed to improve clinical efficiency vs usual testing (UT).

DESIGN, SETTING, AND PARTICIPANTS: This was a pragmatic randomized clinical trial enrolling participants from December 3, 2018, to May 18, 2021, with a median of 11.8 months of follow-up. Patients from 65 North American and European sites with stable symptoms of suspected coronary artery disease (CAD) and no prior testing were randomly assigned 1:1 to precision strategy (PS) or UT.

INTERVENTIONS: PS incorporated the Prospective Multicenter Imaging Study for the Evaluation of Chest Pain (PROMISE) minimal risk score to quantitatively select minimal-risk participants for deferred testing, assigning all others to cCTA with selective CT-derived fractional flow reserve (FFR-CT). UT included site-selected stress testing or catheterization. Site clinicians determined subsequent care.

MAIN OUTCOMES AND MEASURES: Outcomes were clinical efficiency (invasive catheterization without obstructive CAD) and safety (death or nonfatal myocardial infarction [MI]) combined into a composite primary end point. Secondary end points included safety components of the primary outcome and medication use.

RESULTS: A total of 2103 participants (mean [SD] age, 58.4 [11.5] years; 1056 male [50.2%]) were included in the study, and 422 [20.1%] were classified as minimal risk. The primary end point occurred in 44 of 1057 participants (4.2%) in the PS group and in 118 of 1046 participants (11.3%) in the UT group (hazard ratio [HR], 0.35; 95% CI, 0.25-0.50). Clinical efficiency was higher with PS, with lower rates of catheterization without obstructive disease (27 [2.6%]) vs UT participants (107 [10.2%]; HR, 0.24; 95% CI, 0.16-0.36). The safety composite of death/MI was similar (HR, 1.52; 95% CI, 0.73-3.15). Death occurred in 5 individuals (0.5%) in the PS group vs 7 (0.7%) in the UT group (HR, 0.71; 95% CI, 0.23-2.23), and nonfatal MI occurred in 13 individuals (1.2%) in the PS group vs 5 (0.5%) in the UT group (HR, 2.65; 95% CI, 0.96-7.36). Use of lipid-lowering (450 of 900 [50.0%] vs 365 of 873 [41.8%]) and antiplatelet (321 of 900 [35.7%] vs 237 of 873 [27.1%]) medications at 1 year was higher in the PS group compared with the UT group (both P < .001).

CONCLUSIONS AND RELEVANCE: An initial diagnostic approach to stable chest pain starting with quantitative risk stratification and deferred testing for minimal-risk patients and cCTA with selective FFR-CT in all others increased clinical efficiency relative to UT at 1 year. Additional randomized clinical trials are needed to verify these findings, including safety.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03702244.

AIM: The "2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease" provides an update to and consolidates new evidence since the "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease" and the corresponding "2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease."

METHODS: A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.

STRUCTURE: This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

AIM: The "2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease" provides an update to and consolidates new evidence since the "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease" and the corresponding "2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease."

METHODS: A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.

STRUCTURE: This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost-value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

AIMS: Heart failure with reduced ejection fraction (HFrEF) is treatable but guideline-directed medical therapy (GDMT) may not be affordable or accessible to people living with the disease.

METHODS AND RESULTS: In this cross-sectional survey, we investigated the price, affordability, and accessibility of four pivotal classes of HFrEF GDMT: angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB) or angiotensin-neprilysin inhibitors (ARNI); beta-blockers; mineralocorticoid receptor antagonists (MRA); and sodium glucose co-transporter 2 inhibitors (SGLT2i). We sampled online or community pharmacies in 10 countries across a range of World Bank income groups, assessing mean 30 day retail prescription prices, affordability relative to gross national income per capita per month, and accessibility. We reported median price ratios relative to the International Reference Standard. We performed a literature review to evaluate accessibility to GDMT classes through publicly funded drug programmes in each country. HFrEF GDMT prices, both absolute and relative to the international reference, were highest in the United States and lowest in Pakistan and Bangladesh. The most expensive drug was the ARNI, sacubitril/valsartan, with a mean (standard deviation, SD) 30 day price ranging from $11.06 (0.81) in Pakistan to $611.50 (3.54) in United States. The least expensive drug was the MRA, spironolactone, with a mean (SD) 30 day price ranging from $0.18 (0.00) in Pakistan to $12.32 (0.00) in England. Affordability (SD) of quadruple therapy-ARNI, beta-blockers, MRA, and SGLT2i-was best in high-income and worst in low-income countries, ranging from 1.49 (0.00)% of gross national income per capita per month in England to 232.47 (31.47)% in Uganda. Publicly funded drug programmes offset costs for eligible patients, but ARNI and SGLT2i were inaccessible through these programmes in low- and middle-income countries. Price, affordability, and access were substantially improved in all countries by substituting ARNI for ACEi/ARB.

CONCLUSIONS: There was marked variation between countries in the retail price of HFrEF GDMT. Despite higher prices in high-income countries, GDMT was more accessible and affordable than in low- and middle-income countries. Publicly funded drug programmes in lower income countries increased affordability but limited access to newer HFrEF GDMT classes. Pharmaco-disparities must be addressed to improve HFrEF outcomes globally.

BACKGROUND: The recommendation for transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) in patients 65 to 80 years of age is equivocal, leaving patients with a difficult decision. We evaluated whether TAVR compared to SAVR is associated with reduced odds for loss of independent living in patients ≤65, 66 to 79, and ≥80 years of age. Further, we explored mechanisms of the association of TAVR and adverse discharge.

METHODS: Adult patients undergoing TAVR or SAVR within a large academic medical system who lived independently before the procedure were included. A multivariable logistic regression model, adjusting for a priori defined confounders including patient demographics, preoperative comorbidities, and a risk score for adverse discharge after cardiac surgery, was used to assess the primary association. We tested the interaction of patient age with the association between aortic valve replacement (AVR) procedure and loss of independent living. We further assessed whether the primary association was mediated (ie, percentage of the association that can be attributed to the mediator) by the procedural duration as prespecified mediator.

RESULTS: A total of 1751 patients (age median [quartiles; min-max], 76 [67, 84; 23-100]; sex, 56% female) were included. A total of 27% (222/812) of these patients undergoing SAVR and 20% (188/939) undergoing TAVR lost the ability to live independently. In our cohort, TAVR was associated with reduced odds for loss of independent living compared to SAVR (adjusted odds ratio [OR adj ] 0.19 [95% confidence interval {CI}, 0.14-0.26]; P < .001). This association was attenuated in patients ≤65 years of age (OR adj 0.63 [0.26-1.56]; P = .32) and between 66 and 79 years of age (OR adj 0.23 [0.15-0.35]; P < .001), and magnified in patients ≥80 years of age (OR adj 0.16 [0.10-0.25]; P < .001; P -for-interaction = .004). Among those >65 years of age, a shorter procedural duration mediated 50% (95% CI, 28-76; P < .001) of the beneficial association of TAVR and independent living.

CONCLUSIONS: Patients >65 years of age undergoing TAVR compared to SAVR had reduced odds for loss of independent living. This association was partly mediated by shorter procedural duration. No association between AVR approach and the primary end point was found in patients ≤65 years of age.

Estimating the likelihood of urgent mechanical circulatory support (MCS) can facilitate procedural planning and clinical decision-making in chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We analyzed 2,784 CTO PCIs performed between 2012 and 2021 at 12 centers. The variable importance was estimated by a bootstrap applying a random forest algorithm to a propensity-matched sample (a ratio of 1:5 matching cases with controls on center). The identified variables were used to predict the risk of urgent MCS. The performance of the risk model was assessed in-sample and on 2,411 out-of-sample procedures that did not require urgent MCS. Urgent MCS was used in 62 (2.2%) of cases. Patients who required urgent MCS were older (70 [63 to 77] vs 66 [58 to 73] years, p = 0.003) compared with those who did not require urgent MCS. Technical (68% vs 87%, p <0.001) and procedural success (40% vs 85%, p <0.001) was lower in the urgent MCS group compared with cases that did not require urgent MCS. The risk model for urgent MCS use included retrograde crossing strategy, left ventricular ejection fraction, and lesion length. The resulting model demonstrated good calibration and discriminatory capacity with the area under the curve (95% confidence interval) of 0.79 (0.73 to 0.86) and specificity and sensitivity of 86% and 52%, respectively. In the out-of-sample set, the specificity of the model was 87%. The Prospective Global Registry for the Study of Chronic Total Occlusion Intervention CTO MCS score can help estimate the risk of urgent MCS use during CTO PCI.

IMPORTANCE: Observational (nonexperimental) studies that aim to emulate a randomized trial (ie, the target trial) are increasingly informing medical and policy decision-making, but it is unclear how these studies are reported in the literature. Consistent reporting is essential for quality appraisal, evidence synthesis, and translation of evidence to policy and practice.

OBJECTIVE: To assess the reporting of observational studies that explicitly aimed to emulate a target trial.

EVIDENCE REVIEW: We searched Medline, Embase, PsycINFO, and Web of Science for observational studies published between March 2012 and October 2022 that explicitly aimed to emulate a target trial of a health or medical intervention. Two reviewers double-screened and -extracted data on study characteristics, key predefined components of the target trial protocol and its emulation (eligibility criteria, treatment strategies, treatment assignment, outcome[s], follow-up, causal contrast[s], and analysis plan), and other items related to the target trial emulation.

FINDINGS: A total of 200 studies that explicitly aimed to emulate a target trial were included. These studies included 26 subfields of medicine, and 168 (84%) were published from January 2020 to October 2022. The aim to emulate a target trial was explicit in 70 study titles (35%). Forty-three studies (22%) reported use of a published reporting guideline (eg, Strengthening the Reporting of Observational Studies in Epidemiology). Eighty-five studies (43%) did not describe all key items of how the target trial was emulated and 113 (57%) did not describe the protocol of the target trial and its emulation.

CONCLUSION AND RELEVANCE: In this systematic review of 200 studies that explicitly aimed to emulate a target trial, reporting of how the target trial was emulated was inconsistent. A reporting guideline for studies explicitly aiming to emulate a target trial may improve the reporting of the target trial protocols and other aspects of these emulation attempts.

BACKGROUND: Indications and outcomes for percutaneous ventricular assist device (pVAD) use in surgically ineligible patients undergoing percutaneous coronary intervention (PCI) remain poorly characterized.

AIMS: We sought to describe the use and timing of pVAD and outcome in surgically ineligible patients.

METHODS: Among 726 patients enrolled in the prospective OPTIMUM study, clinical and health status outcomes were assessed in patients who underwent pVAD-assisted PCI and those without pVAD.

RESULTS: Compared with patients not receiving pVAD (N = 579), those treated with pVAD (N = 142) more likely had heart failure, lower left ventricular ejection fraction (30.7 ± 13.6 vs. 45.9 ± 15.5, p < 0.01), and higher STS 30-day predicted mortality (4.2 [2.1-8.0] vs. 3.3 [1.7-6.6], p = 0.01) and SYNTAX scores (36.1 ± 12.2, vs. 31.5 ± 12.1, p < 0.01). While the pVAD group had higher in-hospital (5.6% vs. 2.2%, p = 0.046), 30-day (9.0% vs. 4.0%, p = 0.01) and 6-month (20.4% vs. 11.7%, p < 0.01) mortality compared to patients without pVAD, this difference appeared to be largely driven by significantly higher mortality among the 20 (14%) patients with unplanned pVAD use (30% in-hospital mortality with unplanned PVAD vs. 1.6% with planned, p < 0.01; 30-day mortality, 38.1% vs. 4.5%, p < 0.01). The degree of 6-month health status improvement among survivors was similar between groups.

CONCLUSION: Surgically ineligible patients with pVAD-assisted PCI had more complex baseline characteristics compared with those without pVAD. Higher mortality in the pVAD group appeared to be driven by very poor outcomes by patients with unplanned, rescue pVAD.