Faculty Bibliography

The role of revascularization and percutaneous coronary intervention (PCI) in patients with acute coronary syndrome is well established. However, the incremental value of revascularization over guideline-directed medical therapy is controversial. Currently available data supports the use of PCI to improve angina and quality of life for chronic coronary disease and heart failure (HF). However, there is insufficient data to support revascularization with PCI to improve mortality, reduce cardiovascular events, or improve ejection fraction over medical therapy alone. Additional trials are necessary to identify HF patients who may benefit from revascularization, and the optimal revascularization strategy for this population.

Therapeutic anticoagulation is the mainstay therapy in acute pulmonary embolism (PE), however, select patients benefit from emergent reperfusion to prevent or rescue acute right ventricular failure and haemodynamic collapse. Compared to other leading causes of cardiovascular mortality such as myocardial infarction and stroke, there is a substantial paucity of literature informing on advanced therapies in PE. Recent years have seen significant evolution in the armamentarium available for PE care with the uptake of several endovascular treatment modalities and increased use of mechanical circulatory support. While several ongoing randomised controlled trials may alter the therapeutic landscape and approach to PE management, at present, we are left with multiple selections with limited guidance. In this review, we discuss the latest therapeutic options available for acute PE and offer an approach to their implementation.

BACKGROUND/UNASSIGNED:The association between cardiovascular disease and advanced liver disease is incompletely understood. To explore this interaction, we compared management, clinical outcomes, readmission rates, and resource utilization in ST-elevation myocardial infarction (STEMI) patients with and without liver disease. METHODS/UNASSIGNED:The Nationwide Readmissions Database (2016-2020) was queried to identify hospitalizations for STEMI. Cohorts were stratified by presence of liver disease. Liver disease was defined as documented diagnosis of liver cirrhosis or liver failure. Multivariable regression model and propensity score matching was used to compare the risk of outcomes. RESULTS/UNASSIGNED:Among 1,029,608 hospitalizations for STEMI; 45,478 (4.4 %) patients had a history of significant liver disease. Patient with liver disease had higher baseline prevalence of diabetes, chronic kidney disease, anemia, and heart failure. After propensity matching (N = 24,067 in each group), patients with liver disease had higher in-hospital mortality (48.8 % vs 17.3 %, aOR: 6.80 [CI: 6.55-7.06], p < 0.001) and adverse events, including cerebrovascular accidents (6.8 % vs 4.4 %, aOR:1.74 [CI: 1.62-1.86], p < 0.001), cardiac arrest (24.4 % vs 10.3 %, aOR:3.34 [CI: 3.21-3.48], p < 0.001), cardiogenic shock (55.9 % vs 21.1 %, aOR: 6.4 [CI: 6.18-6.64], p < 0.001), mechanical circulatory support requirement (36.2 % vs 14.4 %, aOR: 4.2 [CI: 4.01-4.34], p < 0.001), and major adverse cardiovascular and cerebrovascular events (61.1 % vs 25.3 %, aOR:6.5 [CI: 6.28-6.75], p < 0.001). From 2016 to 2020, in-hospital mortality for STEMI did not change significantly for patients with liver disease (47.4 % to 48.6 % p-trend: 0.826), however percutaneous coronary intervention (PCI) use increased from 43.6 % to 52.2 % (p-trend <0.001). CONCLUSION/UNASSIGNED:In STEMI hospitalizations, patients with liver disease have significantly higher mortality, and adverse events as compared with those without liver disease. Despite the increasing use of primary PCI, mortality remains high in STEMI patients with liver disease.

BACKGROUND:Patients with intermediate-risk pulmonary embolism (PE) have outcomes worse than uncomplicated ST elevation myocardial infarction. Yet, no large-scale study has compared the outcomes of large-bore mechanical thrombectomy (LBMT) with anticoagulation alone (AC). The aim of this study was to compare the clinical outcomes among patients receiving LBMT vs AC alone. METHODS:This was a two-center retrospective study that included patients with intermediate-risk PE from October 2016 - October 2023 from the institution's Pulmonary Embolism Response Team (PERT) database. The primary outcome was a composite of 30-day mortality, resuscitated cardiac arrest or hemodynamic decompensation. Inverse probability of treatment weighting (IPTW) was used to balance covariates; Kaplan Meir curves and IPTW multivariable Cox regression were used to assess the relationship between treatment groups and outcomes. RESULTS:Of the 273 patients included in the analysis, 192 (70 %) patients received AC alone and 81 (30 %) patients received LBMT and AC. A total of 30 (10.9 %) patients experienced the primary composite outcome over a median follow-up of 30 days. The primary composite outcome was significantly lower in the group that received LBMT compared to those on AC alone (1.2 % vs 15.1 %, log-rank p < 0.001; adjusted HR: 0.02; 95 % CI: 0.002-0.17, p < 0.001) driven by a lower rate of 30-day all-cause mortality (0 % vs 7.3 %, log-rank p = 0.01), resuscitated cardiac arrest (0 % vs 6.8 %, log-rank p = 0.016) and new or worsening hemodynamic instability (4 % vs 11.1 %, log-rank p = 0.007). CONCLUSION/CONCLUSIONS:In this largest cohort to date comparing LBMT versus AC alone in acute intermediate-risk PE, LBMT had a significantly lower rate of the primary composite outcome including a lower rate of all-cause mortality when compared to AC alone. Ongoing randomized trials will test these associations.

BACKGROUND:Evidence is limited regarding the comparative effectiveness and safety of mechanical thrombectomy (MT) vs catheter-directed thrombolysis (CDT) for high-risk pulmonary embolism (PE). OBJECTIVES/OBJECTIVE:This observational study aimed to compare the outcomes of older adults with high-risk PE treated with MT vs CDT using a target trial emulation framework. METHODS:We included Medicare fee-for-service beneficiaries aged 65 to 99 years admitted with high-risk PE (defined by cardiac arrest, shock, and vasopressor use) who underwent MT/CDT from 2017 to 2020. We evaluated 1-year mortality using an inverse probability of treatment weighting approach, controlling for 62 baseline covariates. We also evaluated readmissions and in-hospital outcomes, including intracranial hemorrhage. Patients were followed from the date of the index procedure to the outcomes of interest, 1 year, or December 2020. RESULTS:We included 235 and 484 patients in the MT and CDT groups, respectively. The absolute risk of 1-year mortality was 48.4% (95% CI: 34.1%-63.3%) in the MT group and 45.4% (95% CI: 37.8%-55.8%) in the CDT group, with an adjusted HR of 1.16 (95% CI: 0.84-1.59). We found no evidence that all-cause readmission (MT vs CDT; subdistribution HR: 0.89; 95% CI: 0.56-1.40), intracranial hemorrhage (adjusted OR: 0.36; 95% CI: 0.07-1.77), or transfusions (adjusted OR: 0.96; 95% CI: 0.52-1.76) differed significantly between the 2 groups. CONCLUSIONS:Among older adults with high-risk PE treated with catheter-based therapies, the clinical outcomes were similar between the patients treated with MT vs CDT. Randomized trials are needed to confirm our findings.

BACKGROUND:This study examined stress echocardiography (SE) in relation to coronary artery anatomy, and outcome in subjects randomized in the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) Trial. METHODS:Of 5,179 patients randomized to initial invasive or conservative strategy, SE was performed in 1,079. Coronary computed tomographic angiogram (CCTA) excluded left main disease and quantified coronary lesions. Degree of ischemia was defined by number of segments with stress-induced wall motion abnormalities (WMA) (mild < 3, moderate = 3 and severe > 3). Transient ischemic dilation (TID) was defined as a 10% increase in stress left ventricular (LV) end systolic volume. Primary end point was a composite of cardiovascular death (CVD), nonfatal myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS:On CCTA, 607/715 (84%) with CCTA evaluable for ≥70% lesion had one such lesion. Features associated with coronary lesions ≥ 70% were number of ischemic/infarcted segments, 3 or more ischemic segments in the anterior territory and inability to augment LV ejection fraction 10 percentage points . TID, present in 28.5%, was significantly associated with severity of ischemia. For every 0.10 increase in peak wall motion score index (WMSI), there was 12% increased risk of CVD or MI (adjusted HR=1.12 (95% CI: 1.04, 1.21), p=0.003. CONCLUSION/CONCLUSIONS:In patients with chronic coronary disease and moderate or severe myocardial ischemia receiving contemporary therapies, stress echocardiography identified subjects with significant CAD and WMSI provided prognostic value.

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.