Faculty Bibliography

BACKGROUND/UNASSIGNED:The appropriate use criteria for revascularization of stable ischemic heart disease have not been evaluated using randomized data. Using data from the randomized ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches; July 2012 to January 2018, 37 countries), the health status benefits of an invasive strategy over a conservative one were examined within appropriate use criteria scenarios. METHODS/UNASSIGNED:Among 1833 participants mapped to 36 appropriate use criteria scenarios, symptom status was assessed using the Seattle Angina Questionnaire-7 at 1 year for each scenario and for each of the 6 patient characteristics used to define the scenarios. Coronary anatomy and SYNTAX(Synergy between percutaneous coronary intervention with Taxus and cardiac surgery) scores were measured using coronary computed tomography angiography. Treatment effects are expressed as an odds ratio for a better health status outcome with an invasive versus conservative treatment strategy using Bayesian hierarchical proportional odds models. Differences in the primary clinical outcome were similarly examined. RESULTS/UNASSIGNED:The mean age was 63 years, 81% were male, and 71% were White. Diabetes was present in 28% and multivessel disease in 51%. Most clinical scenarios favored invasive for better 1-year health status. The benefit of an invasive strategy on Seattle Angina Questionnaire angina frequency scores was reduced for asymptomatic patients (odds ratio [95% credible interval], 1.16 [0.66-1.71] versus 2.26 [1.75-2.80]), as well as for those on no antianginal medications. Diabetes, number of diseased vessels, proximal left anterior descending coronary artery location, and SYNTAX score did not effectively identify patients with better health status after invasive treatment, and minimal differences in clinical events were observed. CONCLUSIONS/UNASSIGNED:Applying the randomization scheme from the ISCHEMIA trial to appropriate clinical scenarios revealed baseline symptoms and antianginal therapy to be the primary drivers of health status benefits from invasive management. Consideration should be given to reducing the patient characteristics collected to generate appropriateness ratings to improve the feasibility of future data collection. REGISTRATION/UNASSIGNED:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

Blood pressure variability (BPV) predicts cardiovascular events independent of mean blood pressure. BPV is defined as short-term (24-h), medium or long- term (weeks, months or years). Standard deviation, coefficient of variation and variation independent of the mean have been used to quantify BPV. High BPV is associated with increasing age, diabetes, smoking and vascular disease and is a consequence of premature ageing of the vasculature. Long-term BPV has been incorporated into cardiovascular risk models (QRISK) and elevated BPV confers an increased risk of cardiovascular outcomes even in subjects with controlled blood pressure. Long-acting dihydropyridine calcium channel blockers and thiazide diuretics are the only drugs that reduce BPV and for the former explains their beneficial effects on cardiovascular outcomes. We believe that BPV should be incorporated into blood pressure management guidelines and based on current evidence, long-acting dihydropyridines should be preferred drugs in subjects with elevated BPV.

BACKGROUND:The relationship between syncope and invasive hemodynamics in patients with pulmonary embolism (PE) remains unknown. The objective of this study was to assess the ability of syncope, as a single clinical variable, to predict a low cardiac index in patients with acute PE. METHODS:) in patients with acute intermediate- high risk PE. Secondary outcomes included 30-day mortality, hemodynamic instability, 90-day readmission rates, other invasive hemodynamic parameters, intensive care unit (ICU) length of stay (LOS), and hospital LOS. Regression analyses were used to evaluate the association between cardiac index and syncope. RESULTS:A total of 132 patients (86% intermediate- and 14% high-risk) were included in the study, with 27 (20%) presenting with syncope. Among the 114 intermediate-risk patients, 24 (21%) presented with syncope. In all-comers, there was no significant difference between groups at baseline. Within the intermediate-only subgroup, there were no significant differences between groups at baseline, except that the syncope group was older (62.6 ± 14.9 vs. 56.1 ± 13.9, p=0.048, Table 2) and had significantly higher troponin elevation at presentation (684.3 ± 1361.8ng/L vs. 195.6 ± 278.1ng/L, p=0.003, Table 2). In all-comers, there was no difference in rates of low cardiac index (63% vs. 59%, p=0.71) or mPAP (33.9 ± 8.6 vs. 32.7 ± 9.6 mm Hg, p=0.57) between patients who presented with and without syncope. Similarly, among intermediate-risk patients, there was also no difference in the rates of low cardiac index (67% vs. 57%, p=0.38) or mPAP (34.0 ± 9.2 vs. 33.1 ± 9.8 mmHg, p=0.69) between patients with and without syncope. There was no difference in clinical outcomes between those who presented with and without syncope. CONCLUSION/CONCLUSIONS:In conclusion, in patients with acute PE, syncope was not associated with a low cardiac index or higher mPAP.

BACKGROUND AND AIMS/OBJECTIVE:Multiple randomized trials have shown that renal denervation (RDN) reduces blood pressure (BP) when compared with sham control but the antihypertensive efficacy of radiofrequency vs. ultrasound-based RDN is uncertain. We aimed to compare the outcomes of radiofrequency RDN (rRDN) and ultrasound RDN (uRDN), when compared with sham in patients with hypertension. METHODS:PubMed, EMBASE, and clinicaltrials.gov databases were searched for randomized sham-controlled trials (RCTs) of rRDN or uRDN or for trials of rRDN vs. uRDN. Primary efficacy outcome was 24-h ambulatory SBP. A mixed treatment comparison meta-analysis was performed comparing the efficacy and safety against sham and against each other. RESULTS:Among 13 RCTs that enrolled 2285 hypertensive patients, rRDN reduced 24-h ambulatory SBP [(MD = 2.34 mmHg; 95% confidence interval (95% CI): 0.72-3.95], office SBP (MD = 5.04 mmHg; 95% CI: 2.68-7.40)], and office DBP (MD = 2.95 mmHg; 95% CI: 1.68-4.22) when compared with sham. Similarly, uRDN reduced 24-h ambulatory SBP (MD = 4.74 mmHg; 95% CI: 2.80-6.67), day-time ambulatory SBP (MD = 5.40 mmHg; 95% CI: 3.68-7.13), night-time ambulatory SBP (MD = 3.84 mmHg; 95% CI: 0.02-7.67), and office SBP (3.98 mmHg; 95% CI: 0.78-7.19) when compared with sham. There was significantly greater reduction in 24-h ambulatory SBP (MD = 2.40 mmHg; 95% CI: 0.09-4.71), day-time ambulatory SBP (MD = 4.09 mmHg; 95% CI: 1.61-6.56), and night-time ambulatory SBP (MD = 5.76 mmHg; 95% CI: 0.48-11.0) with uRDN when compared with rRDN. For primary efficacy outcome, uRDN ranked #1, followed by rRDN (#2), and sham (#3). CONCLUSION/CONCLUSIONS:In hypertensive patients, rRDN and uRDN significantly reduced 24-h ambulatory and office SBP when compared with sham control with significantly greater reduction in ambulatory BP with uRDN than with rRDN at 4 months (mean) of follow-up. A large-scale randomized head-to-head trial of rRDN or uRDN is warranted to evaluate if there are differences in efficacy.

BACKGROUND/UNASSIGNED:Elevated perceived stress is associated with adverse outcomes following myocardial infarction (MI) and may account for poorer recovery among women vs men. OBJECTIVES/UNASSIGNED:This randomized controlled trial tested effects of a mindfulness-based intervention on stress levels among women with MI. METHODS/UNASSIGNED:Women with elevated stress (Perceived Stress Scale [PSS-4]≥6) at least 2 months after MI were enrolled from 12 hospitals in the United States and Canada and via community advertising. Participants were randomized to a remotely delivered mindfulness intervention (MBCT-Brief) or heart disease education, both 8 weeks long. Follow-up was 6 months. Changes in stress (PSS-10; primary outcome) and secondary outcomes (depressive symptoms, anxiety, quality of life, disease-specific health status, actigraphy-assessed sleep) were compared between groups. RESULTS/UNASSIGNED: = 0.036). CONCLUSIONS/UNASSIGNED:MBCT-Brief was associated with greater 6-month reductions in stress than an active control among adherent participants. More frequent mindfulness practice was associated with greater improvements in psychological outcomes. Strategies to engage women with MI in mindfulness training and support regular home practice may enhance these effects.

BACKGROUND:In patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease, most but not all randomized trials have reported that complete revascularization (CR) offers advantages over culprit vessel-only revascularization. In addition, the optimal timing and assessment methods for CR remain undetermined. OBJECTIVES/OBJECTIVE:The purpose of this study was to identify the optimal revascularization strategy in patients with STEMI and multivessel disease, using a network meta-analysis of randomized controlled trials. METHODS:We searched PUBMED and EMBASE for randomized trials evaluating revascularization strategies in patients with STEMI and multivessel disease through July 2024. A network meta-analysis was performed analyzing CR vs culprit vessel-only revascularization as well as the timing of CR (immediate CR vs staged CR). Outcomes were also assessed with 4 CR strategies based on whether revascularization was immediate or staged and whether it was angiographically guided or functionally guided. The primary outcome was major adverse cardiovascular events (MACE). RESULTS:A total of 26 randomized trials that enrolled 15,902 patients were included. The mean weighted duration of follow-up was 25.2 ± 15.7 months. MACE was reduced with both immediate CR and staged CR compared with culprit-vessel-only treatment (RR: 0.48; 95% CI: 0.36-0.64 and RR: 0.65; 95% CI: 0.52-0.82, respectively), whether with angiographic or functional guidance. Immediate CR was associated with reduced MACE compared with staged CR (RR: 0.74; 95% CI: 0.56-0.97), whether CR was guided angiographically or functionally (RR: 0.77; 95% CI: 0.61-0.99 and RR: 0.49; 95% CI: 0.27-0.89, respectively) caused by reductions in MI. However, when the analysis was restricted to studies that reported both all MI and nonprocedural MI, the benefit of immediate CR in reducing MI compared with staged CR was diminished after excluding procedural MI (RR: 0.44; 95% CI: 0.27-0.71 with procedural MI vs RR: 0.65; 95% CI: 0.36-1.16 without procedural MI). CONCLUSIONS:Among patients with STEMI and multivessel disease, outcomes were better with immediate or staged CR compared with culprit vessel-only treatment, whether with angiographic or functional guidance.

BACKGROUND/UNASSIGNED:The aim of this study was to examine the impact of early versus delayed catheter-based therapies (CBTs) on clinical outcomes in patients with acute intermediate-risk pulmonary embolism (PE). METHODS/UNASSIGNED:This retrospective cohort study analyzed data from 2 academic centers involving patients with intermediate-risk PE from January 2020 to January 2024. Patients were divided into early (<12 hours) and delayed CBT (≥12 hours) groups. The primary outcome was a composite of 30-day mortality, resuscitated cardiac arrest, hemodynamic instability, and 90-day readmission. Secondary outcomes included a composite of 30-day mortality, resuscitated cardiac arrest, and hemodynamic instability. Inverse probability of treatment weighting was used to balance covariates. RESULTS/UNASSIGNED:=0.046). When patients were stratified by timing of CBT (early/late) and the composite PE shock score (high ≥3; low <3), all 16 patients who experienced the primary composite outcome had a high composite PE shock score, with 14/16 (87.5%) having a high composite PE shock score and delayed intervention. CONCLUSIONS/UNASSIGNED:Early CBT was associated with improved clinical outcomes in patients with acute intermediate-risk PE. The composite PE shock score may help identify patients who will benefit from early CBT. Further prospective studies are needed to validate these findings.

BACKGROUND:Randomized trials of bivalirudin in patients with ST elevation myocardial infarction (STEMI) have yielded heterogeneous results. AIMS/OBJECTIVE:Our aim was to evaluate the efficacy and safety of four antithrombin regimens-unfractionated heparin (UFH), bivalirudin (stopped soon after percutaneous coronary intervention [PCI]), extended bivalirudin (continued for a few hours after PCI), and combined UFH and a Gp2b3a inhibitors (GPI) in patients who present with STEMI. METHODS:A PubMed, EMBASE, and clinicaltrials.gov databases were searched for randomized clinical trials (RCTs) of the above antithrombin in patients with STEMI. The primary outcome was net adverse cardiovascular events (NACE). The primary ischemic endpoint was major adverse cardiovascular events (MACE), and the primary safety endpoint was major bleeding, and other endpoints included all-cause mortality and stent thrombosis. The primary analysis compared the effect of these antithrombin regimens in reference to UFH using a mixed treatment comparison meta-analysis. RESULTS:In the 14 RCTs evaluating 25,415 patients with STEMI, when compared to UFH monotherapy, extended bivalirudin lowered NACE (OR = 0.71 with 95% CI: 0.53-0.96; moderate level of confidence) driven by a significant decrease in major bleeding (OR = 0.42 with 95% CI: 0.26-0.68; high level of confidence) without any significant difference in MACE or all-cause mortality. When compared with UFH monotherapy, UFH+GPI reduced risk of MACE (OR = 0.76 with 95% CI: 0.60-0.97; high level of confidence) but at the expense of an increase in major bleeding (OR = 1.48 with 95% CI: 1.11-1.98; high level of confidence) with no difference in NACE or all-cause mortality. For major bleeding, extended bivalirudin infusion ranked #1, bivalirudin ranked #2, UFH monotherapy ranked #3, and combined UFH and GPI ranked #4. For NACE, extended bivalirudin infusion ranked #1, bivalirudin ranked #2, combined UFH and GPI ranked #3, and UFH monotherapy ranked #4. Cluster plots for MACE and major bleeding demonstrated that extended bivalirudin had the best balance for efficacy and safety. CONCLUSIONS:In patients undergoing PCI for STEMI, extended bivalirudin offers the best balance for primary ischemic (MACE) and safety (major bleeding) outcomes.