Michael L. Steigner

Prognostic Value of Nonobstructive and Obstructive Coronary Artery Disease Detected by Coronary Computed Tomography Angiography to Identify Cardiovascular Events

Background—The contribution of plaque extent to predict cardiovascular events among patients with nonobstructive and obstructive coronary artery disease (CAD) is not well defined. Our objective was to evaluate the prognostic value of plaque extent detected by coronary computed tomography angiography. Methods and Results—All consecutive patients without prior CAD referred for coronary computed tomography angiography to evaluate for CAD were included. Examination findings were classified as normal, nonobstructive (<50% stenosis), or obstructive (≥50%). Based on the number of segments with disease, extent of CAD was classified as nonextensive (⩽4 segments) or extensive (>4 segments). The cohort included 3242 patients followed for the primary outcome of cardiovascular death or myocardial infarction for a median of 3.6 (2.1–5.0) years. In a multivariable analysis, the presence of extensive nonobstructive CAD (hazard ratio, 3.1; 95% confidence interval, 1.5–6.4), nonextensive obstructive (hazard ratio, 3.0; 95% confidence interval, 1.3–6.9), and extensive obstructive CAD (hazard ratio, 3.9; 95% confidence interval, 2.2–7.2) were associated with an increased rate of events, whereas nonextensive, nonobstructive CAD was not. The addition of plaque extent to a model that included clinical probability as well as the presence and severity of CAD improved risk prediction. Conclusions—Among patients with nonobstructive CAD, those with extensive plaque experienced a higher rate of cardiovascular death or myocardial infarction, comparable with those who have nonextensive disease. Even among patients with obstructive CAD, greater extent of nonobstructive plaque was associated with higher event rate. Our findings suggest that regardless of whether obstructive or nonobstructive disease is present, the extent of plaque detected by coronary computed tomography angiography enhances risk assessment.

Iodinated Contrast Opacification Gradients in Normal Coronary Arteries Imaged with Prospectively ECG-Gated Single Heart Beat 320-Detector Row Computed Tomography

Background—To define and evaluate coronary contrast opacification gradients using prospectively ECG-gated single heart beat 320-detector row coronary angiography (CTA). Methods and Results—Thirty-six patients with normal coronary arteries determined by 320×0.5-mm detector row coronary CTA were retrospectively evaluated with customized image postprocessing software to measure Hounsfield Units at 1-mm intervals orthogonal to the artery center line. Linear regression determined correlation between mean Hounsfield Units and distance from the coronary ostium (regression slope defined as the distance gradient Gd), lumen cross-sectional area (Ga), and lumen short-axis diameter (Gs). For each gradient, differences between the 3 coronary arteries were analyzed with ANOVA. Linear regression determined correlations between measured gradients, heart rate, body mass index, and cardiac phase. To determine feasibility in lesions, all 3 gradients were evaluated in 22 consecutive patients with left anterior descending artery lesions ≥50% stenosis. For all 3 coronary arteries in all patients, the gradients Ga and Gs were significantly different from zero (P<0.0001), highly linear (Pearson r values, 0.77 to 0.84), and had no significant difference between the left anterior descending, left circumflex, and right coronary arteries (P>0.503). The distance gradient Gd demonstrated nonlinearities in a small number of vessels and was significantly smaller in the right coronary artery when compared with the left coronary system (P<0.001). Gradient variations between cardiac phases, heart rates, body mass index, and readers were low. Gradients in patients with lesions were significantly different (P<0.021) than in patients considered normal by CTA. Conclusions—Measurement of contrast opacification gradients from temporally uniform coronary CTA demonstrates feasibility and reproducibility in patients with normal coronary arteries. For all patients, the gradients defined with respect to the coronary lumen cross-sectional area and short-axis diameters are highly linear, not significantly influenced by the coronary artery (left anterior descending artery versus left circumflex versus right coronary artery), and have only small variation with respect to patient parameters. Preliminary evaluation of gradients across coronary artery lesions is promising but requires additional study.

CT Coronary Angiography: 256-Slice and 320-Detector Row Scanners

Multidetector computed tomography (MDCT) has rapidly evolved from 4-detector row systems in 1998 to 256-slice and 320-detector row CT systems. With smaller detector element size and faster gantry rotation speed, spatial and temporal resolution of the 64-detector MDCT scanners have made coronary artery imaging a reliable clinical test. Wide-area coverage MDCT, such as the 256-slice and 320-detector row MDCT scanners, has enabled volumetric imaging of the entire heart free of stair-step artifacts at a single time point within one cardiac cycle. It is hoped that these improvements will be realized with greater diagnostic accuracy of CT coronary angiography. Such scanners hold promise in performing a rapid high quality “triple rule-out” test without high contrast load, improved myocardial perfusion imaging, and even four-dimensional CT subtraction angiography. These emerging technical advances and novel applications will continue to change the way we study coronary artery disease beyond detecting luminal stenosis.

The “Post-64” Era of Coronary CT Angiography: Understanding New Technology from Physical Principles

Multidetector CT now provides noninvasive coronary imaging, and patients with a low or intermediate probability of coronary artery disease can be imaged with radiation levels comparable to catheterization. Cardiac imaging drives rapid progress in CT hardware. To best apply evolving technology, imagers and referring clinicians need a solid understanding of spatial resolution, temporal resolution, volume coverage, and radiation dose. This article defines and discusses interactions between these parameters for state-of-the-art CT.

Coronary Artery Disease Detected by Coronary Computed Tomographic Angiography Is Associated With Intensification of Preventive Medical Therapy and Lower Low-Density Lipoprotein Cholesterol

Background—Coronary computed tomographic angiography (CCTA) is an accurate test for the identification of coronary artery disease (CAD), yet the impact of CCTA results on subsequent medical therapy and risk factors has not been widely reported. Methods and Results—We identified consecutive patients aged >18 years without prior CAD who underwent CCTA from 2004 to 2011 and had complete data on medications before and after CCTA. CCTA results were categorized as no CAD, <50% stenosis, and ≥50% stenosis. Based on the number of involved segments, extent of disease was categorized as nonextensive (⩽4 segments) or extensive CAD (>4 segments). Electronic medical records and patient interviews were reviewed blinded to CCTA findings to assess initiation of aspirin and intensification of lipid-lowering therapies. Survival analysis was performed to evaluate intensification of lipid therapy as a predictor of cardiovascular death or nonfatal myocardial infarction. Among 2839 patients with mean follow-up of 3.6 years, the odds of physician intensification of lipid-lowering therapy significantly increased for those with nonobstructive CAD (odds ratio, 3.6; 95% confidence interval, 2.9–4.9; P<0.001) and obstructive CAD (odds ratio, 5.6; 95% confidence interval, 4.3–7.3; P<0.001). Low-density lipoprotein cholesterol levels declined significantly in association with intensification of lipid-lowering therapy after CCTA in all patient subgroups. In a hypothesis-generating analysis, among patients with nonobstructive but extensive CAD, statin use after CCTA was associated with a reduction in cardiovascular death or myocardial infarction (hazards ratio, 0.18; 95% confidence interval, 0.05–0.66; P=0.01). Conclusions—Abnormal CCTA findings are associated with downstream intensification in statin and aspirin therapy. In particular, CCTA may lead to increased use of prognostically beneficial therapies in patients identified as having extensive, nonobstructive CAD.

Effect of Sleep Apnea and Continuous Positive Airway Pressure on Cardiac Structure and Recurrence of Atrial Fibrillation

Background Sleep apnea (SA) is associated with an increased risk of atrial fibrillation (AF). We sought to determine the effect of SA on cardiac structure in patients with AF, whether therapy for SA was associated with beneficial cardiac structural remodelling, and whether beneficial cardiac structural remodelling translated into a reduced risk of recurrence of AF after pulmonary venous isolation (PVI). Methods and Results A consecutive group of 720 patients underwent a cardiac magnetic resonance study before PVI. Patients with SA (n=142, 20%) were more likely to be male, diabetic, and hypertensive and have an increased pulmonary artery pressure, right ventricular volume, atrial dimensions, and left ventricular mass. Treated SA was defined as duration of continuous positive airway pressure therapy of >4 hours per night. Treated SA patients (n=71, 50%) were more likely to have paroxysmal AF, a lower blood pressure, lower ventricular mass, and smaller left atrium. During a follow‐up of 42 months, AF recurred in 245 patients. The cumulative incidence of AF recurrence was 51% in patients with SA, 30% in patients without SA, 68% in patients with untreated SA, and 35% in patients with treated SA. In a multivariable model, the presence of SA (hazard ratio 2.79, CI 1.97 to 3.94, P<0.0001) and untreated SA (hazard ratio 1.61, CI 1.35 to 1.92, P<0.0001) were highly associated with AF recurrence. Conclusions Patients with SA have an increased blood pressure, pulmonary artery pressure, right ventricular volume, left atrial size, and left ventricular mass. Therapy with continuous positive airway pressure is associated with lower blood pressure, atrial size, and ventricular mass, and a lower risk of AF recurrence after PVI.

Prediction of coronary artery plaque progression and potential rupture from 320-detector row prospectively ECG-gated single heart beat CT angiography: Lattice Boltzmann evaluation of endothelial shear stress

Advances in MDCT will extend coronary CTA beyond the morphology data provided by systems that use 64 or fewer detector rows. Newer coronary CTA technology such as prospective ECG-gating will also enable lower dose examinations. Since the current standard of care for coronary diagnoses is catheterization, CT will continue to be benchmarked against catheterization reference points, in particular temporal resolution, spatial resolution, radiation dose, and volume coverage. This article focuses on single heart beat cardiac acquisitions enabled by 320-detector row CT. Imaging with this system can now be performed with patient radiation doses comparable to catheterization. The high image quality, excellent contrast opacification, and absence of stair-step artifact provide the potential to evaluate endothelial shear stress (ESS) noninvasively with CT. Low ESS is known to lead to the development and progression of atherosclerotic plaque culminating in high-risk vulnerable plaque likely to rupture and cause an acute coronary event. The magnitude of local low ESS, in combination with the local remodeling response and the severity of systemic risk factors, determines the natural history of each plaque. This paper describes the steps required to derive an ESS map from 320-detector row CT data using the Lattice Boltzmann method to include the complex geometry of the coronary arterial tree. This approach diminishes the limitations of other computational fluid dynamics methods to properly evaluate multiple coronary arteries, including the complex geometry of coronary bifurcations where lesions tend to develop.

Effect of Omega-3 Acid Ethyl Esters on Left Ventricular Remodeling After Acute Myocardial Infarction: The OMEGA-REMODEL Randomized Clinical Trial.

Background: Omega-3 fatty acids from fish oil have been associated with beneficial cardiovascular effects, but their role in modifying cardiac structures and tissue characteristics in patients who have had an acute myocardial infarction while receiving current guideline-based therapy remains unknown. Methods: In a multicenter, double-blind, placebo-controlled trial, participants presenting with an acute myocardial infarction were randomly assigned 1:1 to 6 months of high-dose omega-3 fatty acids (n=180) or placebo (n=178). Cardiac magnetic resonance imaging was used to assess cardiac structure and tissue characteristics at baseline and after study therapy. The primary study endpoint was change in left ventricular systolic volume index. Secondary endpoints included change in noninfarct myocardial fibrosis, left ventricular ejection fraction, and infarct size. Results: By intention-to-treat analysis, patients randomly assigned to omega-3 fatty acids experienced a significant reduction of left ventricular systolic volume index (–5.8%, P=0.017), and noninfarct myocardial fibrosis (–5.6%, P=0.026) in comparison with placebo. Per-protocol analysis revealed that those patients who achieved the highest quartile increase in red blood cell omega-3 index experienced a 13% reduction in left ventricular systolic volume index in comparison with the lowest quartile. In addition, patients in the omega-3 fatty acid arm underwent significant reductions in serum biomarkers of systemic and vascular inflammation and myocardial fibrosis. There were no adverse events associated with high-dose omega-3 fatty acid therapy. Conclusions: Treatment of patients with acute myocardial infarction with high-dose omega-3 fatty acids was associated with reduction of adverse left ventricular remodeling, noninfarct myocardial fibrosis, and serum biomarkers of systemic inflammation beyond current guideline-based standard of care. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00729430.

The Incidence, Pattern, and Prognostic value of Left Ventricular Myocardial Scar by Late Gadolinium Enhancement in Patients with Atrial Fibrillation

OBJECTIVES This study sought to identify the frequency, pattern, and prognostic significance of left ventricular (LV) late gadolinium enhancement (LGE) in patients with atrial fibrillation (AF). BACKGROUND There are limited data on the presence, pattern, and prognostic significance of LV myocardial fibrosis in patients with AF. LGE during cardiac magnetic resonance imaging is a marker for myocardial fibrosis. METHODS A group of 664 consecutive patients without known prior myocardial infarction who were referred for radiofrequency ablation of AF were studied. Cardiac magnetic resonance imaging was requested to assess pulmonary venous anatomy. RESULTS Overall, 73% were men, with a mean age of 56 years and a mean LV ejection fraction of 56 ± 10%. LV LGE was found in 88 patients (13%). The endpoint was all-cause mortality, and in this cohort, 68 deaths were observed over a median follow-up period of 42 months. On univariate analysis, age (hazard ratio [HR]: 1.05; 95% confidence interval [CI]: 1.03 to 1.08; chi-square likelihood ratio [LRχ(2)]: 15.2; p = 0.0001), diabetes (HR: 2.39; 95% CI: 1.41 to 4.09; LRχ(2): 10.3; p = 0.001), a history of heart failure (HR: 1.78; 95% CI: 1.09 to 2.91; LRχ(2): 5.37; p = 0.02), left atrial dimension (HR: 1.04; 95% CI: 1.01 to 1.08; LRχ(2): 6.47; p = 0.01), presence of LGE (HR: 5.08; 95% CI: 3.08 to 8.36; LRχ(2): 28.8; p < 0.0001), and LGE extent (HR: 1.15; 95% CI: 1.10 to 1.21; LRχ(2): 35.6; p < 0.0001) provided the strongest associations with mortality. The mortality rate was 8.1% per patient-year in patients with LGE compared with 2.3% patients without LGE. In the best overall multivariate model for mortality, age and the extent of LGE were independent predictors of mortality. Indeed, each 1% increase in the extent of LGE was associated with a 15% increased risk for death. CONCLUSIONS In patients with AF, LV LGE is a frequent finding and is a powerful predictor of mortality.

Stress Cardiac Magnetic Resonance Imaging Provides Effective Cardiac Risk Reclassification in Patients With Known or Suspected Stable Coronary Artery Disease

Background— A recent large-scale clinical trial found that an initial invasive strategy does not improve cardiac outcomes beyond optimized medical therapy in patients with stable coronary artery disease. Novel methods to stratify at-risk patients may refine therapeutic decisions to improve outcomes. Methods and Results— In a cohort of 815 consecutive patients referred for evaluation of myocardial ischemia, we determined the net reclassification improvement of the risk of cardiac death or nonfatal myocardial infarction (major adverse cardiac events) incremental to clinical risk models, using guideline-based low (<1%), moderate (1% to 3%), and high (>3%) annual risk categories. In the whole cohort, inducible ischemia demonstrated a strong association with major adverse cardiac events (hazard ratio=14.66; P<0.0001) with low negative event rates of major adverse cardiac events and cardiac death (0.6% and 0.4%, respectively). This prognostic robustness was maintained in patients with previous coronary artery disease (hazard ratio=8.17; P<0.0001; 1.3% and 0.6%, respectively). Adding inducible ischemia to the multivariable clinical risk model (adjusted for age and previous coronary artery disease) improved discrimination of major adverse cardiac events (C statistic, 0.81–0.86; P=0.04; adjusted hazard ratio=7.37; P<0.0001) and reclassified 91.5% of patients at moderate pretest risk (65.7% to low risk; 25.8% to high risk) with corresponding changes in the observed event rates (0.3%/y and 4.9%/y for low and high risk posttest, respectively). Categorical net reclassification index was 0.229 (95% confidence interval, 0.063–0.391). Continuous net reclassification improvement was 1.11 (95% confidence interval, 0.81–1.39). Conclusions— Stress cardiac magnetic resonance imaging effectively reclassifies patient risk beyond standard clinical variables, specifically in patients at moderate to high pretest clinical risk and in patients with previous coronary artery disease. Clinical Trial Registration:— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01821924.