Publications

BACKGROUND: Patients with both peripheral artery disease (PAD) and coronary artery disease are at heightened risk for adverse cardiovascular outcomes. Although long-term risk has been well documented, contemporary in-hospital outcomes for patients with PAD presenting with acute myocardial infarction (AMI) are less well characterized.

METHODS: We analyzed 493 740 AMI hospitalizations from 670 US sites in the NCDR (National Cardiovascular Data Registry) Chest Pain-MI Registry between January 2019 and March 2023. Primary outcomes were in-hospital mortality and major bleeding; secondary end points included cardiac arrest, cardiogenic shock, heart failure, stroke, and new dialysis initiation. Subgroup analyses were conducted by age, sex, race, AMI type, revascularization status, and extent of coronary disease. We used the NCDR validated risk model for multivariable adjustment.

RESULTS: PAD was present in 36 274 patients with AMI (7.4%). In-hospital mortality was significantly higher in patients with PAD compared with those without (8.23% versus 4.87%; adjusted odds ratio [aOR], 1.25 [95% CI, 1.19-1.31]). Increased mortality persisted across age groups (<65 years: aOR, 1.42; ≥65 years: aOR, 1.18) and AMI type (non-ST-segment-elevation MI: aOR, 1.14; ST-segment-elevation MI: aOR, 1.46), with significant interactions by both age and AMI type. Among revascularized patients, mortality was elevated in those with PAD (aOR, 1.49). PAD was associated with increased rates of major bleeding (aOR, 1.23), particularly among revascularized patients (aOR, 1.31), as well as cardiac arrest, shock, heart failure, stroke, and new dialysis.

CONCLUSIONS: PAD was independently associated with markedly worse in-hospital outcomes in AMI, highlighting the need for risk mitigation strategies in this high-risk population.

BACKGROUND: Symptomatic peripheral artery disease (PAD) is prevalent and guideline-recommended therapies include optimal medical therapy (OMT), supervised exercise therapy (SET), and revascularization (stenting). The Claudication: Exercise Versus Endoluminal Revascularization (CLEVER) trial examined longitudinal patient-reported outcomes to assess response to OMT, SET, and stenting. The predictors of symptomatic improvement have not been fully assessed.

METHODS: This is a secondary analysis of the CLEVER trial, which randomized patients with claudication to OMT alone, OMT plus SET, or OMT plus stenting. The primary outcome was a change in the Peripheral Artery Questionnaire (PAQ) summary score by 10 points or more from baseline to 6 and 18 months. Multivariate logistic regression was used to identify predictors of response.

RESULTS: Of the 103 participants (66 men, median age 63 years), 65 (63%) had a response to therapy at 6 months. Of 98 participants who completed the 18-month PAQ, 52 (53%) had a symptomatic response. On binary logistic regression, when compared to OMT, SET (6 months: odds ratio [OR] 4.25, 95% CI: 1.33-13.58; 18 months: OR 3.92, 95% CI: 1.04-14.70) and ST (6 months: OR 5.19, 95% CI: 1.58-17.03; 18 months: OR 11.50, 95% CI: 2.89-45.72) were associated with an increase in PAQ at 6 and 18 months.

CONCLUSION: Among randomized patients in the CLEVER trial, treatment with either SET or stenting was predictive of clinically meaningful change in the PAQ summary score from baseline to 6 and 18 months. These interventions, with a prioritization of SET, should be more widely available to patients with PAD. This study adds to the findings of the CLEVER trial by denoting that SET and stenting are beneficial in patients with PAD, independent of comorbidities.

Renal denervation (RDN) is an innovative procedure with regulatory approval for treating patients whose blood pressure remains uncontrolled despite lifestyle changes and the prescription of antihypertensive medications. It is important to consider how to create accessible patient referral pathways for this complementary therapy in the context of differing healthcare systems and the availability of appropriate resources. Today, most hypertensive patients are managed by primary care practitioners in the community. This paper considers various program models that integrate RDN into clinical practice, from decentralized systems where community physicians refer patients to an RDN facility, to centralized hypertension or academic centers that provide comprehensive care. Providing community practices with checklists that guide patient selection for possible referral for RDN is an important start to the process. Key to the success of an RDN program at an interventional facility is the careful selection of patients. Ideally, this is managed by a team that includes interventional physicians skilled in the RDN procedure, clinicians knowledgeable about hypertension management who can confirm the suitability of patients referred for the procedure, and supporting nursing staff to guide patients through the process. By adopting the practices outlined in this paper, the availability of RDN can be appropriately applied to improving hypertension control in patients at need, in turn reducing their risk of adverse cardiovascular outcomes.

BACKGROUND: Risk-benefit tradeoffs between restrictive versus liberal red blood cell transfusion strategies may vary across individuals. This exploratory analysis aimed to derive and evaluate individualized treatment effects of defined transfusion strategies in patients with acute MI and anemia with the goal of minimizing adverse cardiovascular outcomes.

METHODS: This study analyzed 3,447 (98.4%) patients randomized in the MINT (Myocardial Ischemia and Transfusion) trial between April 2017 to April 2023. Outcomes for this analysis included 30-day death or recurrent MI, death, and major adverse cardiovascular events (MACE, a composite of death, MI, stroke, and ischemia-driven unscheduled revascularization). Machine learning methods were used to identify baseline patient characteristics that informed the individualized treatment effect of a restrictive versus liberal transfusion strategy for each patient. The expected population risk of an outcome under a scenario in which patients received their optimal treatment, as indicated by the individualized treatment effect, was contrasted with expected risks for universally applying a restrictive strategy or a liberal strategy to all patients.

RESULTS: Baseline characteristics did not inform individualized treatment effects on 30-day death and death or MI, suggesting minimal heterogeneity in treatment effect on these outcomes. An algorithm for estimating the individualized treatment effect on 30-day MACE included 12 baseline factors. If all patients received the optimal treatment as indicated by their estimated individualized treatment effect, the predicted risk of 30-day MACE in the sample population was 15.2% (95% CI 14.2%-16.2%). This corresponded to 4.0 (difference: -4.0%, 95% CI -5.8, -2.1) and 2.3 (difference: -2.3%, 95% CI -3.7, -0.9) percentage point risk reductions compared to applying a restrictive or liberal strategy to everyone respectively.

CONCLUSIONS: The MINT trial average treatment effect, favoring a liberal strategy, may be optimal to minimize risk of 30-day death and death or MI for acute MI patients with anemia represented in the MINT sample as no individualized treatment effects were estimated on these outcomes. However, individualized transfusion strategy decisions have potential to reduce risk of 30-day MACE. External validation of the MACE algorithm is required before clinical use.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT02981407, https://clinicaltrials.gov/study/NCT02981407.

BACKGROUND: Blood transfusion may precipitate adverse outcomes, including heart failure (HF), among patients with acute myocardial infarction (MI). This study characterizes the effects of a restrictive or liberal transfusion strategy on outcomes in patients with MI and anemia with and without baseline HF.

METHODS: In the MINT trial (Myocardial Ischemia and Transfusion), 3504 patients with MI and anemia (hemoglobin <10 g/dL) were randomized to a restrictive (hemoglobin <8 g/dL) or liberal (hemoglobin <10 g/dL) transfusion strategy. We compared the effects of transfusion strategy on outcomes among patients with and without baseline HF. The primary outcome was death or HF at 30 days.

RESULTS: Compared with patients without baseline HF (n=1633), those with baseline HF (n=1871) had higher rates of death or HF (18.0% versus 10.0%) at 30 days. Restrictive transfusion resulted in numerically higher rates of death or HF (rate ratio, 1.20 [95% CI, 0.99-1.45] versus 0.94 [95% CI, 0.70-1.26]; Pinteraction=0.18) in patients with than in those without baseline HF. Among secondary outcomes, death or recurrent MI and death were more frequent among those with baseline HF. Restrictive transfusion resulted in numerically higher rates of death or MI and death in patients with than in those without baseline HF. Rates of HF were similar between restrictive and liberal transfusion in patients with baseline HF but lower with restrictive transfusion (rate ratio, 0.51 [95% CI, 0.29-0.92]; Pinteraction=0.02) in patients without baseline HF.

CONCLUSIONS: A liberal transfusion strategy is safe for patients with MI and anemia, including those with baseline HF. Restrictive transfusion tended to result in worse outcomes, particularly in patients with baseline HF.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02981407.

BACKGROUND: Orthostatic hypotension (OH) is associated with cardiovascular disease, particularly among older adults. While a standing transthoracic echocardiogram (TTE) could theoretically identify changes in cardiac output to diagnose cardiogenic OH, there are no established protocols for orthostatic TTEs and their feasibility is unknown.

METHODS AND RESULTS: We recruited 115 patients scheduled for elective outpatient TTE. Consenting participants, who were able to stand safely, underwent their scheduled recumbent TTE, followed by a standing TTE, performed within 1-2 minutes of standing. The focused TTE used the apical window to measure velocity time integral across the aortic valve to assess cardiac output. Blood pressure (BP) was measured in the supine and standing positions and patients were asked about symptoms of dizziness and lightheadedness. OH was defined as a change in standing minus supine systolic BP ≤-20 mm Hg or in diastolic BP of ≤-10 mm Hg. Of the 115 enrolled participants, 102 (89%) completed the standing echocardiogram protocol. Among those completing, mean age was 63.4 (SD, 14.8) years (38% were ≥ 70 years), 48% women, and 34% had a BMI ≥ 30 kg/m2. There were 21% with OH. Upon standing, systolic BP changed by -5.9 mm Hg (95% CI: -9.5, -2.2), diastolic BP by 2.4 mm Hg (-0.1, 4.8), and cardiac output by -0.4 L/min (95% CI: -0.7, -0.1). Change in cardiac output (per 1 L/min) was associated with a higher odds of systolic OH (OR: 1.60; 95% CI: 1.05, 2.42), but not diastolic OH (OR: 1.21; 95% CI: 0.63, 2.32).

CONCLUSIONS: Standing TTE is safe, well-tolerated, and feasible in the ambulatory setting. Moreover, TTE changes in cardiac output are associated with systolic OH. This clinical assessment shows promise for distinguishing OH etiologies and could inform further research on treatments to prevent OH.

BACKGROUND: Ultrasound enhancing agents (UEAs) are an important diagnostic tool for transthoracic or stress echocardiography (TTE/SE) but recent concerns have been raised about their safety in reports from individual health systems. As such, we aimed to identify if UEAs for TTE/SE are associated with serious adverse events within 2 days of administration.

METHODS AND RESULTS: All-payor nationwide claims from 11.4 million insured individuals across the United States, 2018 to 2022 were used to evaluate rates of death, anaphylaxis, myocardial infarction, ventricular tachycardia, or cardiac arrest within 2 days of TTE/SE among adults receiving and not receiving UEAs. Of the 11 421 463 individuals included (mean age 57.5±16.2, 54.0% female, 46.2% White), a total of 500 073 (4.4%) received TTE/SE with UEAs. After propensity score matching, the odds of death were lower in those receiving UEAs (receipt versus nonreceipt, 0.02% versus 0.14%, odds ratio [OR], 0.23 [95% CI, 0.19-0.28], P<0.001) and were not different across agents (Definity: 0.02%, OR, 0.22 [95% CI, 0.18-0.28]; Lumason: 0.03%, OR, 0.33 [95% CI, 0.20-0.57]; Optison: 0.01%, OR, 0.17 [95% CI, 0.08-0.38]; all P < 0.001). Rates of nondeath outcomes were similar to those observed in individuals not receiving UEAs, overall, and across specific agents. Rates of all outcomes were stable across years, including considering pre- and post-COVID periods.

CONCLUSIONS: In this large nationwide claims analysis from 2018 to 2022, serious adverse events associated with UEAs for TTE/SE were uncommon and overall consistent across agents and years of study. Compared with nonreceipt, receipt of UEAs was associated with a lower odds of death within 2 days of TTE/SE.