Sohah N. Iqbal

Mechanisms of Myocardial Infarction in Women Without Angiographically Obstructive Coronary Artery Disease

Background— There is no angiographically demonstrable obstructive coronary artery disease (CAD) in a significant minority of patients with myocardial infarction, particularly women. We sought to determine the mechanism(s) of myocardial infarction in this setting using multiple imaging techniques. Methods and Results— Women with myocardial infarction were enrolled prospectively, before angiography, if possible. Women with ≥50% angiographic stenosis or use of vasospastic agents were excluded. Intravascular ultrasound was performed during angiography; cardiac magnetic resonance imaging was performed within 1 week. Fifty women (age, 57±13 years) had median peak troponin of 1.60 ng/mL; 11 had ST-segment elevation. Median diameter stenosis of the worst lesion was 20% by angiography; 15 patients (30%) had normal angiograms. Plaque disruption was observed in 16 of 42 patients (38%) undergoing intravascular ultrasound. There were abnormal myocardial cardiac magnetic resonance imaging findings in 26 of 44 patients (59%) undergoing cardiac magnetic resonance imaging, late gadolinium enhancement (LGE) in 17 patients, and T2 signal hyperintensity indicating edema in 9 additional patients. The most common LGE pattern was ischemic (transmural/subendocardial). Nonischemic LGE patterns (midmyocardial/subepicardial) were also observed. Although LGE was infrequent with plaque disruption, T2 signal hyperintensity was common with plaque disruption. Conclusions— Plaque rupture and ulceration are common in women with myocardial infarction without angiographically demonstrable obstructive coronary artery disease. In addition, LGE is common in this cohort of women, with an ischemic pattern of injury most evident. Vasospasm and embolism are possible mechanisms of ischemic LGE without plaque disruption. Intravascular ultrasound and cardiac magnetic resonance imaging provide complementary mechanistic insights into female myocardial infarction patients without obstructive coronary artery disease and may be useful in identifying potential causes and therapies. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00798122.

Sex and Race Are Associated With the Absence of Epicardial Coronary Artery Obstructive Disease at Angiography in Patients With Acute Coronary Syndromes

A substantial minority of patients with acute coronary syndromes (ACS) do not have a diameter stenosis of any major epicardial coronary artery on angiography (“no obstruction at angiography”) of ≥ 50%. We examined the frequency of this finding and its relationship to race and sex.

Characteristics of plaque disruption by intravascular ultrasound in women presenting with myocardial infarction without obstructive coronary artery disease

BACKGROUND In a prospective study, we previously identified plaque disruption (PD: plaque rupture or ulceration) in 38% of women with myocardial infarction (MI) without angiographically obstructive coronary artery disease (CAD), using intravascular ultrasound (IVUS). Underlying plaque morphology has not been described in these patients and may provide insight into the mechanisms of MI without obstructive CAD. METHODS Forty-two women with MI and <50% angiographic stenosis underwent IVUS (n = 114 vessels). Analyses were performed by a blinded core laboratory. Sixteen patients had PD (14 ruptures and 5 ulcerations in 18 vessels). Plaque area, % plaque burden, lumen area stenosis, eccentricity, and remodeling index were calculated for disrupted plaques and largest plaque by area in each vessel. RESULTS Disrupted plaques had lower % plaque burden than the largest plaque in the same vessel (31.9% vs 49.8%, P = .005) and were rarely located at the site of largest plaque (1/19). Disrupted plaques were typically fibrous and were not more eccentric or remodeled than the largest plaque in the same vessel. CONCLUSIONS Plaque disruption was often identifiable on IVUS in women with MI without obstructive CAD. Plaque disruption in this patient population occurred in fibrous or fibrofatty plaques and, contrary to expectations based on prior studies of plaque vulnerability, did not typically occur in eccentric, outwardly remodeled, or soft plaque in these patients. Plaque disruption rarely occurred at the site of the largest plaque in the vessel. These findings suggest that the pathophysiology of PD in women with MI without angiographically obstructive CAD may be different from MI with obstructive disease and requires further investigation.

Impact of Sex and Contact‐to‐Device Time on Clinical Outcomes in Acute ST‐Segment Elevation Myocardial Infarction—Findings From the National Cardiovascular Data Registry

Background Emergent myocardial reperfusion via primary percutaneous coronary intervention is optimal care for patients presenting with ST‐segment elevation myocardial infarction (STEMI). Delays in such interventions are associated with increases in mortality. With the shift in focus to contact‐to‐device (C2D) time as a new perfusion metric, this study was designed to examine how sex affects C2D time and mortality in STEMI patients. Methods and Results Clinical data on male and female STEMI patients were extracted and analyzed from the National Cardiovascular Data Registry from July 1, 2008 to December 31, 2014. A total of 102 515 patients were included in the final analytic cohort. The median C2D time in female patients with STEMI was delayed when compared to male patients (80 [65–97] versus 75 [61–90] minutes; P<0.001). The unadjusted mortality was higher in female patients when compared to male patients with STEMI (4.1% versus 2.0%; P<0.001). For every 5‐minute increase in C2D time, the adjusted odds ratio for mortality was 1.04 (95% CI, 1.03–1.06) for female patients with STEMI and 1.07 (95% CI, 1.06–1.09) for male patients (P for sex by C2D interaction=0.003). Conclusions To date, this is the largest analysis of STEMI patients that measures the impact of the new recommended C2D reperfusion metric on in‐hospital mortality. Female STEMI patients have longer C2D times and increased mortality. The disparity can be improved and survival can increase in this high‐risk patient cohort by decreasing systems issues that cause increased reperfusion times in female STEMI patients.

Quantitative Perfusion Analysis of First-Pass Contrast Enhancement Kinetics: Application to MRI of Myocardial Perfusion in Coronary Artery Disease.

Purpose Perfusion analysis from first-pass contrast enhancement kinetics requires modeling tissue contrast exchange. This study presents a new approach for numerical implementation of the tissue homogeneity model, incorporating flexible distance steps along the capillary (NTHf). Methods The proposed NTHf model considers contrast exchange in fluid packets flowing along the capillary, incorporating flexible distance steps, thus allowing more efficient and stable calculations of the transit of tracer through the tissue. We prospectively studied 8 patients (62 ± 13 years old) with suspected CAD, who underwent first-pass perfusion CMR imaging at rest and stress prior to angiography. Myocardial blood flow (MBF) and myocardial perfusion reserve index (MPRI) were estimated using both the NTHf and the conventional adiabatic approximation of the TH models. Coronary artery lesions detected at angiography were clinically assigned to one of three categories of stenosis severity (‘insignificant’, ‘mild to moderate’ and ‘severe’) and related to corresponding myocardial territories. Results The mean MBF (ml/g/min) at rest/stress and MPRI were 0.80 ± 0.33/1.25 ± 0.45 and 1.68 ± 0.54 in the insignificant regions, 0.74 ± 0.21/1.09 ± 0.28 and 1.54 ± 0.46 in the mild to moderate regions, and 0.79 ± 0.28/0.63 ± 0.34 and 0.85 ± 0.48 in the severe regions, respectively. The correlation coefficients of MBFs at rest/stress and MPRI between the NTHf and AATH models were r = 0.97/0.93 and r = 0.91, respectively. Conclusions The proposed NTHf model allows efficient quantitative analysis of the transit of tracer through tissue, particularly at higher flow. Results of initial application to MRI of myocardial perfusion in CAD are encouraging.

Ascending Aortic Stenting for Acute Supra-aortic Stenosis from Graft Collapse

A 78-year-old man with remote type-A dissection presented with acute-onset dyspnea. Twenty-two years prior, treatment for his aortic disease required replacement of ascending and arch aneurysms with a polyester graft (Dacron) using the graft inclusion technique. He presented currently in cardiogenic shock. Echocardiography demonstrated new severe hypokinesis of all apical segments. Left-heart catheterization revealed a 120 mm Hg intragraft gradient. Computed tomography arteriography was unrevealing, but intraaortic ultrasound demonstrated critical intragraft stenosis. A balloon expandable stent (Palmaz stent, Cordis, Milpitas, CA) was deployed in the stenotic region with gradient resolution. The patient later underwent aortic root replacement and ascending aneurysm repair (Bio-Bentall technique) and is doing well at 24 months.

MR myocardial perfusion analysis of first-pass enhancement kinetics with a lagrangian approach.

Background Observation of the kinetics of tissue enhancement after the injection of a bolus of tracer has been used for the analysis of perfusion and related variables. In general, a gradient of concentration in the exchanging vascular compartment between the ar terial and venous ends is represented in models via focus on maintaining the detailed balance between the advective and diffusive exchange processes. Conventionally, this is by considering the exchange in an Eulerian framework, based on considering the exchange within each compartment as a separate unit (e.g., tissue homogeneity (TH) model [1]). Herein, we present a Lagrangian approach to the exchange modeling, such that the blood flowing between compartments is considered as the primary unit, and, thereby, allowing for coarser discretization and more efficient calculations (Figure 1a). Methods

Response to Letters Regarding Article, “Mechanisms of Myocardial Infarction in Women Without Angiographically Obstructive Coronary Artery Disease”

Dr Ward suggests that plaque ruptures identified by the core laboratory in our study1 were not responsible for troponin elevation and instead had a nonischemic cause, and that these plaque ruptures may have been caused by intravascular ultrasound. We respectfully disagree. We believe that the observed ruptured plaques were responsible for troponin elevation in patients in this study for several reasons. First, all patients presented with acute onset of ischemic symptoms, and we find it very unlikely that plaque rupture is incidental in this setting. We acknowledge that it is impossible to exclude plaque rupture caused by the intravascular ultrasound procedure in this or any study using intravascular ultrasound. Though we did not include stable control patients, …