Faculty Bibliography

BACKGROUND:Microvascular density and endothelial glycocalyx function may provide insights into early atherosclerosis and cardiovascular disease (CVD) risk. Sublingual sidestream darkfield (SDF) microscopy permits imaging of red blood cells (RBC) to assess the microcirculation. We sought to define reference ranges for SDF microscopy parameters in healthy populations and individuals with coronary artery disease (CAD) and to assess factors correlated with microcirculatory abnormalities. METHODS:Adults with and without CVD risk factors and epicardial CAD underwent SDF microscopy using a CapiScope Handheld Video Capillaroscopy System and Glycocheck analytic software to measure the perfused boundary region (a measure of RBC glycocalyx penetration), percent RBC filling (%RBC, a measure of microvascular perfusion) and microvascular density. RESULTS:<0.0001), though values overlapped substantially; after adjustment for demographics and CVD risk factors, obstructive CAD was not independently associated with sublingual microvascular parameters. CONCLUSIONS:Obstructive CAD was not associated with sublingual microvascular parameters after accounting for demographics and CVD risk factors. The overlap of microvascular parameters in patients with and without CAD limits the clinical utility of SDF microscopy to identify traditional CVD.

BACKGROUND/UNASSIGNED:ST-segment-elevation myocardial infarction (STEMI) is uncommon among inpatients already admitted to the hospital for other indications. Prior studies reported significant differences in clinical characteristics and outcomes of patients who develop STEMI while hospitalized versus those who present with out-of-hospital STEMI. However, prior studies were small or not contemporary. METHODS/UNASSIGNED:We compared the characteristics and outcomes of patients presenting with STEMI at the time of hospital admission (preadmission STEMI) versus in-hospital STEMI (occurring during the hospitalization) using data from the National Cardiovascular Data Registry Chest Pain-MI Registry from 2019 to 2022. RESULTS/UNASSIGNED:<0.001). CONCLUSIONS/UNASSIGNED:Patients who experience in-hospital STEMI represent a high-risk group, with significantly longer times from the diagnostic ECG to primary percutaneous coronary intervention, more complications, and higher mortality.

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:The Universal Definition classifies myocardial infarction (MI) by etiology, but its prognostic implications are uncertain. OBJECTIVES/OBJECTIVE:The goal was to compare the rate and risk of recurrent MI or cardiovascular death among patients with myocardial injury and infarction classified according to the Universal Definition. METHODS:A systematic search of MEDLINE, EMBASE, Central, and Web of Science from January 1, 2007 to July 1, 2025 was performed to identify prospective studies where cardiac troponin was measured for suspected acute coronary syndrome, diagnoses were adjudicated using the Universal Definition, and both MI and cause-specific mortality were reported at a minimum of 1 year. Subdistribution HRs were derived to account for the competing risk of noncardiovascular death. Meta-analysis was performed with random-effects models. The primary outcome was major adverse cardiovascular events (MACE), defined as MI or cardiovascular death. The secondary outcome was noncardiovascular death. RESULTS:= 20%), respectively. CONCLUSIONS:All patients with myocardial injury and infarction are at increased risk of future cardiovascular events. However, in type 2 MI, this apparent risk is reduced by a substantially greater competing risk of noncardiovascular death. (PROSPERO Registration: CRD42023464836).

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:Coronary microvascular dysfunction (CMD) is present in approximately 40% of patients with ischemia with no obstructive coronary arteries (INOCA) and has been associated with inflammation. We investigated associations between measures of inflammation of the coronary perivascular adipose tissue assessed by coronary computed tomography angiography (CCTA) and results of invasive coronary function testing (CFT) to diagnose CMD. METHODS:Adults referred for clinically indicated invasive coronary angiography who had less than 50% stenosis in all epicardial arteries were prospectively enrolled. CMD was defined as a coronary flow reserve (CFR) less than 2.5 or index of microvascular resistance (IMR) greater than or equal to 25 using bolus thermodilution in the left anterior descending (LAD) coronary artery. Coronary perivascular fat attenuation index was assessed by CCTA in the right coronary artery (RCA) and LAD. T tests were used to evaluate differences in perivascular FAI by CMD status. RESULTS:A total of 31 participants underwent CFT and CCTA. The mean age was 58 ± 11.7 years, 77% were female, and 61% were white. CMD was present in 15 participants (48%). No differences in perivascular FAI were observed in patients with and without CMD, either in the RCA [-74.2 ± 9.8 vs. -69.9 ± 10.3 Hounsfield units (HU), P = 0.24] or LAD (-76.4 ± 10.2 vs. -74.8 ± 12.7 HU, P = 0.69). Perivascular FAI was not correlated with CFR or IMR measurements in the RCA or LAD. CONCLUSION/CONCLUSIONS:There were no associations between CMD diagnosed by invasive CFT and perivascular FAI by CCTA in patients with INOCA. Further research is needed to understand the relationship between vascular inflammation and CMD in INOCA.

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.

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.