Faculty Bibliography

Pulmonary hypertension (PH) is a frequent complication of Philadelphia-negative myeloproliferative neoplasms (MPN), including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). However, its prognostic significance is understudied, thus we aimed to evaluate the effect of PH identified by echocardiography on risk of progression to secondary MF or acute leukemia in MPN patients. We conducted a multicenter, retrospective cohort study of MPN patients with ≥ 1 echocardiogram from 2010-2023. PH was defined as pulmonary artery systolic pressure (PASP) ≥ 40 mmHg. Outcomes were progression to secondary myelofibrosis or leukemia, major adverse cardiovascular event (MACE) and all-cause death. Multivariable Fine-Gray competing-risk regression was used to estimate subhazard ratio (SHR) of hematologic progression and MACE. 555 patients were included (42.7% PV, 41.1% ET, 16.2% MF) or which 195 (35.1%) had PH. Over a median follow-up period of 51.2 months, PH was associated with increased risk of secondary MF progression (aSHR 2.40, 95% CI 1.25-4.59), leukemia progression (aSHR 3.06, 95% CI 1.13 - 8.25), and MACE (aSHR 1.59, 95% CI 1.01- 2.49) but not all-cause death (aHR 1.48, 95% CI 0.96-2.26). Among patients with PH, absence of left heart disease (LHD) was associated with higher risk of secondary MF progression among patients with ET or PV (aSHR 2.76, 95% CI 1.19 - 6.38) and leukemia progression among patients with MF (aSHR 7.18, 95% CI 1.59-32.46). Prospective studies are needed to assess the role of echocardiography on MPNspecific prognostication.

BACKGROUND:Platelets are major players in the pathogenesis of cardiovascular events, and the number of circulating platelets in whole blood is routinely available in clinical testing. The relationship between the preoperative platelet count and major adverse cardiovascular events (MACE) after non-cardiac surgery is uncertain. METHODS:We identified adults age ≥18 years undergoing non-cardiac surgery from 2009 to 2015 from the National Surgical Quality Improvement Program. Pre-operative platelet counts within 90 days of surgery were recorded. Patients were prospectively followed for 30-days. The primary outcome was 30-day MACE (a composite of death, myocardial infarction [MI], or stroke). Multivariable logistic regression models estimated the association between platelet count and odds of postoperative outcomes. RESULTS:/L]). There was a U-shaped relationship between platelet count and MACE. The adjusted odds of MACE were elevated in mild(aOR 1.44, 95% CI 1.39-1.48) and moderate-severe thrombocytopenia (aOR 2.79, 95% CI 2.69-2.90), and in moderate (aOR 1.57, 95% CI 1.52-1.63) and severe (aOR 1.91, 95% CI 1.74-2.09) thrombocytosis. Findings were consistent for the individual endpoints of death, MI, and stroke. CONCLUSION/CONCLUSIONS:In adults undergoing non-cardiac surgery, pre-operative thrombocytopenia and thrombocytosis was identified in nearly 12% of cases and was associated with increased odds of cardiovascular events at 30 days.

BACKGROUND:High-sensitivity cardiac troponin (hs-cTnI) assays can quantify troponin concentrations with low limits of detection, potentially expediting and enhancing myocardial infarction diagnoses. This study investigates the real-world impact of hs-cTnI implementation on operational metrics and downstream cardiac services in patients presenting to the emergency department with chest pain. METHODS AND RESULTS/RESULTS:[lt] 0.001) during the index encounter. CONCLUSION/CONCLUSIONS:Implementation of the hs-cTnI assay was associated with reduced hospital admissions, shorter length of stay, and decreases in most downstream cardiac testing.

BACKGROUND/UNASSIGNED:Myocardial injury detected after percutaneous coronary intervention (PCI) is associated with increased mortality. Predictors of post-PCI myocardial injury are not well established. The long-term prognostic relevance of post-PCI myocardial injury remains uncertain. METHODS/UNASSIGNED:Consecutive adults aged ≥18 years with stable ischemic heart disease who underwent elective PCI at NYU Langone Health between 2011 and 2020 were included in a retrospective, observational study. Patients with acute myocardial infarction or creatinine kinase myocardial band (CKMB) or troponin concentrations >99% of the upper reference limit before PCI were excluded. All patients had routine measurement of CKMB concentrations at 1 and 3 hours post-PCI. Post-PCI myocardial injury was defined as a peak CKMB concentration >99% upper reference limit. Linear regression models were used to identify clinical factors associated with post-PCI myocardial injury. Cox proportional hazard models were generated to evaluate relationships between post-PCI myocardial injury and all-cause mortality at long-term follow-up. RESULTS/UNASSIGNED:<0.001). After adjustment for demographics and clinical covariates, post-PCI myocardial injury was associated with an excess hazard for long-term mortality (hazard ratio, 1.46 [95% CI, 1.20-1.78]). CONCLUSIONS/UNASSIGNED:Myocardial injury defined by elevated CKMB early after PCI is common and associated with all-cause, long-term mortality. More complex coronary anatomy is predictive of post-PCI myocardial injury.

BACKGROUND:Chronic coronary syndromes (CCS) occur commonly in the absence of flow-limiting epicardial coronary stenoses. Ischemia or angina with no obstructive coronary arteries (INOCA/ANOCA) may be caused by coronary microvascular disease, coronary artery spasm, myocardial bridging, diffuse atherosclerosis, or a combination of disorders. METHODS & RESULTS/RESULTS:We highlight the new recommendations in the 2024 European Society of Cardiology (ESC) guidelines on CCS relevant to the diagnosis and management of INOCA/ANOCA. The guidelines place a new emphasis on consideration of INOCA/ANOCA early during cardiovascular risk stratification and the initial diagnostic workup for chest pain. There is a new class I recommendation for the availability of invasive coronary function testing (CFT) at the time of initial coronary angiography, when mechanisms of chest pain are uncertain after non-invasive testing, and in patients with established INOCA/ANOCA who have persistent symptoms and poor quality of life despite medical therapy. Once underlying disorders have been identified based on the results of invasive CFT, the ESC guidelines emphasize a patient-centered, mechanism-based approach to medical treatment of INOCA/ANOCA to improve symptoms and quality of life. CONCLUSIONS:The 2024 ESC CCS guidelines provide a new vision for the diagnosis and management of ANOCA/INOCA, with an expanded role for invasive CFT and targeted medical therapy to improve symptoms and quality of life in patients with angina.

BACKGROUND:Limited data exist on noncardiac surgery patients with prior percutaneous coronary intervention (PCI) in the contemporary era. The objective was to examine rate, characteristics, and outcomes of patients who underwent noncardiac surgery within 2 years of PCI and develop a risk model of factors that predict long-term postoperative outcomes among patients with recent PCI. METHODS AND RESULTS/RESULTS:Patients in the Veterans Affairs Surgical Quality Improvement Program database who underwent noncardiac surgery between October 1, 2017 and September 30, 2021 were included. Patients with versus without PCI within 2 years were propensity matched to examine major adverse cardiovascular events (MACE), defined as a 1-year composite of mortality, revascularization, and rehospitalization for myocardial infarction or stroke. Among patients with recent PCI, multivariable logistic regression was used to develop a risk model to predict 1-year postoperative MACE. Among 334 828 patients undergoing surgery, 2297 (0.68%) had PCI within 2 years. Among 9160 propensity-matched veterans, there was no difference in MACE between patients with and without preceding PCI (hazard ratio [HR], 1.04 [95% CI, 0.96-1.17]). Patients with versus without preceding PCI within 2 years had lower risk of all-cause death (HR, 0.83 [95% CI, 0.72-0.96]) but higher risk of revascularization (HR, 1.88 [95% CI, 1.50-2.36]) at 1 year. A 13-component MACE prediction model among patients with recent PCI had moderate discrimination (area under the receiver operating characteristic curve 0.73 derivation, 0.72 validation). CONCLUSIONS:Among patients who underwent surgery, risk of MACE did not differ, but the risk of revascularization was higher and all-cause death was lower in patients with versus without recent PCI. A risk model can be used to stratify risk of surgery among patients with preceding PCI.

STUDY OBJECTIVE/OBJECTIVE:To determine whether preoperative LDL-C concentration affects the risk of perioperative major adverse cardiovascular or cerebrovascular events (MACCE) after noncardiac surgery. DESIGN/METHODS:Single center retrospective cohort study. SETTING/METHODS:Hospital (including medical and surgical floor, intensive care unit) and patient disposition location (including the patient's home or any other receiving facility). PATIENTS/METHODS:43,348 non-cardiac surgeries at NYU Langone Health between January 2016 and September 2020. INTERVENTIONS/METHODS:Patients were grouped based on preoperative LDL-C. MEASUREMENTS/METHODS:Complete serum lipid panel obtained within one year prior to the date of noncardiac surgery and rate of perioperative MACCE, defined as a composite of in-hospital non-fatal myocardial infarction, in-hospital acute ischemic stroke, myocardial injury after noncardiac surgery, and death from any cause within 30 days of surgery. MAIN RESULTS/RESULTS:Perioperative MACCE occurred in 1093 patients (2.5 %) overall. After multivariable adjustment, odds of MACCE were significantly lower in patients with higher (≥100 mg/dL) versus lower (<100 mg/dL) LDL-C (adjusted odds ratio [aOR] 0.783, 95 % CI, 0.660-0.926]). CONCLUSIONS:In a large cohort of patients undergoing non-cardiac surgery at a major academic health system in New York City, lower LDL-C concentrations were not associated with a lower incidence of perioperative MACCE. Further investigation into modifiable perioperative cardiovascular risk factors is needed to improve perioperative outcomes.

Although platelets play a critical pathogenic role in myocardial infarction (MI), few studies have characterized the MI platelet transcriptome in the acute or chronic setting in women. We report that transcripts associated with the actin cytoskeleton, Rho family GTPases, mitochondrial dysfunction, and inflammatory signaling are enriched in platelets from MI patients in the acute setting (n = 40, MI; n = 38, control) and do not significantly change over time. Furthermore, 79 platelet genes chronically elevated or suppressed after MI are associated with future cardiovascular events in an independent high-risk cohort (n = 135). Compared with women with MI with nonobstructive coronary arteries, platelets from women with MI and obstructive coronary artery disease were enriched in neutrophil activation and proinflammatory signaling pathways driven by increased tumor necrosis factor (TNF)-α signaling. Hierarchic clustering of the MI transcriptomic profile identified 3 subgroups with distinctive biological pathways and MI correlates. Our data demonstrate that platelets from MI patients are phenotypically different from MI-naïve patients in the acute and chronic settings and reveal a platelet transcriptomic signature with distinct clinical features.

OBJECTIVE:Patients with peripheral artery disease (PAD) undergo lower extremity revascularization (LER) for symptomatic relief or limb salvage. Despite LER, patients remain at increased risk of platelet-mediated complications, such as major adverse cardiac and limb events (MACLEs). Platelet activity is associated with cardiovascular events, yet little is known about the dynamic nature of platelet activity over time. We, therefore, investigated the change in platelet activity over time and its association with long-term cardiovascular risk. METHODS:Patients with PAD undergoing LER were enrolled into the multicenter, prospective Platelet Activity and Cardiovascular Events study. Platelet aggregation was assessed by light transmission aggregometry to submaximal epinephrine (0.4 μmol/L) immediately before LER, and on postoperative day 1 or 2 (POD1 or POD2) and 30 (POD30). A hyperreactive platelet phenotype was defined as >60% aggregation. Patients were followed longitudinally for MACLEs, defined as the composite of death, myocardial infarction, stroke, major lower extremity amputation, or acute limb ischemia leading to reintervention. RESULTS:Among 287 patients undergoing LER, the mean age was 70 ± 11 years, 33% were female, 61% were White, and 89% were on baseline antiplatelet therapy. Platelet aggregation to submaximal epinephrine induced a bimodal response; 15.5%, 16.8%, and 16.4% of patients demonstrated a hyperreactive platelet phenotype at baseline, POD1, and POD30, respectively. Platelet aggregation increased by 18.5% (P = .001) from baseline to POD1, which subsequently returned to baseline at POD30. After a median follow-up of 19 months, MACLEs occurred in 165 patients (57%). After adjustment for demographics, clinical risk factors, procedure type, and antiplatelet therapy, platelet hyperreactivity at POD1 was associated with a significant hazard of long-term MACLE (adjusted hazard ratio, 4.61; 95% confidence interval, 2.08-10.20; P < .001). CONCLUSIONS:Among patients with severe PAD, platelet activity increases after LER. Platelet hyperreactivity to submaximal epinephrine on POD1 is associated with long-term MACLE. Platelet activity after LER may represent a modifiable biomarker associated with excess cardiovascular risk.