Faculty Bibliography

AIMS/OBJECTIVE:Type 2 myocardial infarction due to myocardial oxygen supply-demand imbalance is associated with poor outcomes. There are no guidelines to inform care for these patients. The consensus on the assessment and management of type 2 myocardial infarction is gained. METHODS AND RESULTS/RESULTS:An international e-Delphi study including experts in type 2 myocardial infarction identified through systematic review was conducted. Participants were asked to describe their approach to (i) definition and diagnosis, (ii) risk stratification, (iii) assessment of coronary artery disease and cardiac function, (iv) specialty management, (v) treatment and secondary prevention, and (vi) communication and rehabilitation. Statements generated in round one were circulated, with consensus defined a priori as ≥70% agreement on a 5-point Likert scale. Where no consensus was reached, statements were amended and recirculated for a final round. The response rate was 56% (38/68), 54% (37/68), and 72% (49/68) in the first, second, and third rounds, respectively. Following the first round, 67 unique statements were generated across six domains. Overall, consensus was achieved on 64% (43/67) of statements. Consensus was achieved for 42% (5/12) of statements on the diagnosis of type 2 myocardial infarction, 75% (3/4) on risk stratification, 50% (9/18) on the assessment of coronary artery disease and cardiac function, 60% (6/10), on specialty management, 100% (9/9) on treatment and secondary prevention, and 79% (11/15) on communication and rehabilitation. CONCLUSION/CONCLUSIONS:Consensus was obtained across a number of domains for the assessment and management of patients with type 2 myocardial infarction. However, there was limited agreement amongst experts on the diagnostic criteria, which may benefit from refinement.

BACKGROUND/UNASSIGNED:compared with the conventional index of microcirculatory resistance (IMR) in a cohort of individuals with INOCA. METHODS/UNASSIGNED:was calculated retrospectively, blinded to CFT results. CMD was defined by IMR ≥25 or CFR <2.5. RESULTS/UNASSIGNED:and IMR. CONCLUSIONS/UNASSIGNED:appears unreliable for identifying CMD in patients with INOCA.

Coronary endothelial dysfunction plays a key role in the pathogenesis of acute coronary syndromes. During myocardial infarction (MI), activated platelets release prothrombotic and proinflammatory factors, contributing to vascular injury and dysfunction. To investigate platelet-mediated endothelial dysfunction, endothelial cells (ECs) were treated with platelet-released factors from patients with MI and non-MI controls undergoing coronary angiography. RNA sequencing revealed that MI platelets induced EC mitochondrial dysfunction, confirmed by reduced mitochondrial membrane potential and disrupted mitochondrial networks. Integrating platelet transcriptomic data, we identified the C-C motif chemokine ligand 3 (CCL3) as significantly up-regulated in MI platelets and a key mediator of EC mitochondrial dysfunction. Blocking its receptor, CCR5, attenuated CCL3 effects. In an independent cohort of 261 patients with established cardiovascular disease, higher circulating CCL3 levels were associated with incident major adverse cardiovascular events. Together, these findings establish a mechanistic link between platelet activation and coronary endothelial dysfunction in MI.

BACKGROUND/UNASSIGNED:Myeloproliferative neoplasms (MPN) are a group of chronic leukemias that are associated with pulmonary hypertension (PH), which has been associated with increased risk adverse outcomes. The echocardiographic characterization of PH in MPN has not been reported, and the prognostic significance of PH among patients with MPN remains unclear. METHODS/UNASSIGNED:Multicenter, retrospective cohort study of patients with MPN with ≥1 echocardiogram from 2010 to 2023. The echocardiographic probability of PH was determined according to the guidelines. The outcomes were hematologic progression and major adverse cardiovascular events. Exploratory analysis included outcomes among patients with right heart catheterization after the first echocardiogram, with PH defined as mean pulmonary artery pressure of >20 mm Hg. Multivariable Fine-Gray competing risk regression was used to estimate the subhazard ratio of hematologic progression and major adverse cardiovascular events. RESULTS/UNASSIGNED:=0.048). CONCLUSIONS/UNASSIGNED:Among patients with MPN, echocardiographic probability of PH was associated with an increased risk of hematologic progression. Prospective studies are needed to assess the optimal use of echocardiography on MPN-specific prognostication.

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.

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.