Pomerantsev Ev

Visualization of Coronary Atherosclerotic Plaques in Patients Using Optical Coherence Tomography: Comparison With Intravascular Ultrasound

OBJECTIVES The aim of this study was to evaluate the feasibility and the ability of intravascular optical coherence tomography (OCT) to visualize the components of coronary plaques in living patients. BACKGROUND Disruption of a vulnerable coronary plaque with subsequent thrombosis is currently recognized as the primary mechanism for acute myocardial infarction. Although such plaques are considered to have a thin fibrous cap overlying a lipid pool, imaging modalities in current clinical practice do not have sufficient resolution to identify thin (< 65 microm) fibrous caps. Optical coherence tomography is a new imaging modality capable of obtaining cross-sectional images of coronary vessels at a resolution of approximately 10 microm. METHODS The OCT images and corresponding histology of 42 coronary plaques were compared to establish OCT criteria for different types of plaques. Atherosclerotic lesions with mild to moderate stenosis were identified on angiograms in 10 patients undergoing cardiac catheterization. Optical coherence tomography and intravascular ultrasound (IVUS) images of these sites were obtained in all patients without complication. RESULTS Comparison between OCT and histology demonstrated that lipid-rich plaques and fibrous plaques have distinct OCT characteristics. A total of 17 IVUS and OCT image pairs obtained from patients were compared. Axial resolution measured 13 +/- 3 microm with OCT and 98 +/- 19 microm with IVUS. All fibrous plaques, macrocalcifications and echolucent regions identified by IVUS were visualized in corresponding OCT images. Intimal hyperplasia and echolucent regions, which may correspond to lipid pools, were identified more frequently by OCT than by IVUS. CONCLUSIONS Intracoronary OCT appears to be feasible and safe. Optical coherence tomography identified most architectural features detected by IVUS and may provide additional detailed structural information.

In vivo association between positive coronary artery remodelling and coronary plaque characteristics assessed by intravascular optical coherence tomography

AIMS Positive coronary arterial remodelling has been shown to be associated with unstable coronary syndromes and ex vivo histological characteristics of plaque vulnerability such as a large lipid core and high macrophage content. The aim of this study is to evaluate the in vivo association between coronary artery remodelling and underlying plaque characteristics identified by optical coherence tomography (OCT). OCT is a unique imaging modality capable of characterizing these important morphological features of vulnerable plaque. METHODS AND RESULTS OCT and intravascular ultrasound imaging was performed at corresponding sites in patients undergoing catheterization. OCT plaque characteristics for lipid content, fibrous cap thickness, and macrophage density were derived using previously validated criteria. Thin-cap fibroatheroma (TCFA) was defined as lipid-rich plaque (two or more quadrants) with fibrous cap thickness <65 microm. Remodelling index (RI) was calculated as the ratio of the lesion to the reference external elastic membrane area. A total of 54 lesions from 48 patients were imaged. Positive remodelling compared with absent or negative remodelling was more commonly associated with lipid-rich plaque (100 vs. 60 vs. 47.4%, P = 0.01), a thin fibrous cap (median 40.2 vs. 51.6 vs. 87 microm, P = 0.003) and the presence of TCFA (80 vs. 38.5 vs. 5.6%, P < 0.001). Fibrous cap macrophage density was also higher in plaques with positive remodelling showing a positive linear correlation with the RI (r = 0.60, P < 0.001). CONCLUSION Coronary plaques with positive remodelling exhibit characteristic features of vulnerable plaque. This may explain the link between positive remodelling and unstable clinical presentations.

Assessment of nonstenotic coronary lesions by 64-slice multidetector computed tomography in comparison to intravascular ultrasound: Evaluation of nonculprit coronary lesions

BACKGROUND Multidetector computed tomography (MDCT) has recently emerged as a potential noninvasive alternative for high-resolution imaging of coronary arteries. OBJECTIVE In this study, we evaluated 64-slice MDCT for detection, quantification, and characterization of atherosclerotic plaque burden in nonculprit lesions. METHODS Data from 11 patients who underwent both MDCT and intravascular ultrasound (IVUS) for suspected coronary artery disease were collected, and a total of 17 coronary segments and 122 cross-sectional slices were analyzed by MDCT and IVUS. Coronary segments on MDCT were coregistered to IVUS, and each obtained slice was scored by 2 blinded observers for presence and type of plaque. Quantitative measurements included cross-sectional vessel area, lumen area, wall area, plaque volume, and plaque burden. Mean and standard deviation of Hounsfield units (HUs) were recorded for plaque when present. RESULTS Overall sensitivity for plaque detection was 95.0%, and specificity, positive predictive value, negative predictive value were 88.7%, 89.1%, and 94.8%, respectively. Spearmans correlation coefficients were 0.85, 0.75, 0.70, 0.89, and 0.54 for cross-sectional vessel area, lumen area, wall area, plaque volume, and plaque burden, respectively. The interobserver variability for plaque burden and plaque volume measurements between readers on 64-MDCT was high at 32.7% and 30.4%, respectively. Combined noncalcified plaque had a mean MDCT density significantly different from that of calcified plaque. Soft and fibrous plaques were not able to be distinguished based on their HU values. CONCLUSION Sixty-four-slice MDCT had good correlation with IVUS but with high interobserver variability. Plaque characterization remains a challenge with present MDCT technology.

Acute coronary syndrome is a common clinical presentation of in-stent restenosis ☆

Coronary stents have been the major advancement in percutaneous coronary intervention in the last decade and are used in 60% to 80% of patients. However, in-stent restenosis continues to be a problem, occurring in 20% to 30% of cases. The clinical presentation of patients who develop restenosis after stenting has not been well characterized. In this study we compared the clinical presentation of in-stent restenosis with that of restenosis without stenting. Of 739 patients who underwent percutaneous coronary intervention and had repeat catheterization between October 1, 1997, and June 30, 2000, 262 consecutive patients with recurrent ischemia and restenosis were identified: 191 patients with (group A) and 71 without (Group B) stenting. Patients who underwent interventions in bypass grafts and those who developed early acute stent thrombosis were excluded from the study. Recurrent clinical ischemia occurred at a mean of 5.5 months in group A and 6.5 months in group B (p = 0.24). Rest angina (Braunwald class II and III) was more frequent in group A (48% vs 32%, p = 0.032). Acute coronary syndromes, the combination of rest angina, and acute myocardial infarction were also more frequent in group A (68% vs 46%, p = 0.03). Patients in group A were more likely to have angiographically visible thrombus than those in group B (9% vs 0%, p = 0.02). Thus, acute coronary syndromes are a common clinical presentation of restenosis among patients whose follow-up angiogram is obtained for clinical reasons, and occur more frequently in patients with in-stent restenosis than in those with restenosis without stenting.

Hemodynamic monitoring in obese patients: the impact of body mass index on cardiac output and stroke volume.

Objective:Interpreting hemodynamic parameters in critically ill obese patients can be difficult as the effects of body mass index (BMI) on cardiac output (CO) and stroke volume (SV) at the extremes of body size remains unknown. We examined the relationship between BMI and both CO and SV for patients with varying body sizes. Design:Retrospective cohort analysis. Setting:A large tertiary care academic medical center. Patients:A total of 700 consecutive adults who were found to have disease-free coronary arteries and a cardiac output measurement (thermodilution or Fick method) during coronary angiography between July 1, 2000, and July 31, 2004. Measurements and Results:We examined the relationship between BMI (mean, 28 kg/m2; range, 10.6–91.6 kg/m2) and cardiac hemodynamics after adjusting for demographic (age, sex) and clinical (diabetes, smoking status, valvular heart disease, medications, indications for catheterization) characteristics using multivariable regression. Body mass index was positively correlated with CO and SV. Each 1 kg/m2 increase in BMI was associated with a 0.08 L/min (95% confidence interval [CI], 0.06–0.10; p < .001) increase in CO and 1.35 mL (95% CI, 0.96–1.74; p < .001) increase in SV. There was no significant association between BMI and both cardiac index (0.003 L/min/m2; 95% CI, −0.008–0.014; p = .571) and stroke volume index (0.17 mL/m2; 95% CI, −0.03–0.37; p = .094). Conclusion:Variations in BMI translate into predictable but only modest differences in CO and SV, even at the extremes of body size. Indexing hemodynamic measurements to body surface area attenuates the effects of BMI. Body habitus should not appreciably complicate the interpretation of hemodynamic measurements.

Impact of rapid ventricular pacing during percutaneous balloon aortic valvuloplasty in patients with critical aortic stenosis: Should we be using it?

Background: Rapid ventricular pacing (RP) during percutaneous balloon aortic valvuloplasty (BAV) facilitates balloon positioning by preventing the “watermelon seeding” effect during balloon inflation. The clinical consequences of RP BAV have never been compared with standard BAV in which rapid pacing in not used. We evaluated the immediate results and in‐hospital adverse events of patients with severe aortic stenosis (AS) undergoing BAV with and without RP. Methods: This is a retrospective study of patients with severe AS undergoing retrograde BAV. Patients who underwent BAV with RP were compared to those who did not receive RP during BAV. Procedural outcomes, complications, and in‐hospital adverse events were compared between both groups. Stratified analyses were performed to evaluate RP in pre‐specified subsets for confounding and effect modification. Results: Between January 2005 and December 2008, 111 consecutive patients underwent retrograde BAV at Massachusetts General Hospital. Sixty‐seven patients underwent BAV with RP. Nearly 90% of patients were NYHA class III or IV and the mean AVA was 0.64 cm2. Baseline characteristics and balloon sizes were similar in the two groups. The average post‐BAV AVA was smaller in the RP group compared to the no‐RP group (0.87 v. 1.02 cm2, p = 0.02). Pre and post‐cardiac output, in‐hospital mortality, myocardial infarction, stroke, frequency of cardiopulmonary arrest, vasopressor use, and major complications were similar in the two groups. Conclusions: 1) RP allows precise balloon placement during BAV. 2) RP BAV is associated with lower post‐BAV AVA. 3) RP BAV may be safely performed in patients with high‐risk cardiac features.

Coronary artery compliance and adaptive vessel remodelling in patients with stable and unstable coronary artery disease

OBJECTIVE To test the hypothesis that patients with unstable coronary syndromes show accentuated compensatory vessel enlargement compared with patients with stable angina, and that this may in part be related to increased coronary artery distensibility. DESIGN AND PATIENTS In 23 patients with unstable coronary syndromes (10 with non-Q wave myocardial infarction and 13 with unstable angina), the culprit lesion was investigated by intravascular ultrasound before intervention. The vessel cross sectional area (VA), lumen area (LA), and plaque area (VA minus LA) were measured at end diastole and end systole at the lesion site and at the proximal and distal reference segments. Similar measurements were made in 23 patients with stable angina admitted during the same period and matched for age, sex, and target vessel. Calculations were made of remodelling index (VA at lesion site ÷ VA at reference site), distensibility index ([(ΔA/A)/ΔP] × 103, where ΔA is the luminal area change in systole and diastole and ΔP the difference in systolic and diastolic blood pressure measured at the tip of the guiding catheter during a cardiac cycle), and stiffness index β ([ln(Psys/Pdias)]/(ΔD/D), where Psys is systolic pressure, Pdias is diastolic pressure, and ΔD is the difference between systolic and diastolic lumen diameters). Positive remodelling was defined as when the VA at the lesion was > 1.05 times larger than at the proximal reference site, and negative remodelling when the VA at the lesion was < 0.95 of the reference site. RESULTS Mean (SD) LA at the lesion site was similar in both groups (4.03 (1.8) v4.01 (1.93) mm2), while plaque area was larger in the unstable group (13.29 (4.04) v 8.34 (3.6) mm2, p < 0.001). Remodelling index was greater in the unstable group (1.14 (0.18) v 0.83 (0.15), p < 0.001). Positive remodelling was observed in 15 patients in the unstable group (65%) but in only two (9%) in the stable group (p < 0.001). Negative remodelling occurred only in two patients with unstable symptoms (9%) but in 17 (74%) with stable symptoms. At the proximal reference segment, the difference in LA between systole and diastole was 0.99 (0.66) mm2 in the unstable group and 0.39 (0.3) mm2 in the stable group (p < 0.001), and the calculated coronary artery distensibility was 3.09 (2.69) and 0.94 (0.83) per mm Hg in unstable and stable patients, respectively (p < 0.001). The stiffness index β was lower in patients with unstable angina (1.95 (0.94) v 3.1 (0.96), p < 0.001). CONCLUSIONS Compensatory vessel enlargement occurs to a greater degree in patients with unstable than with stable coronary syndromes, and is associated with increased coronary artery distensibility.

High-resolution cardiovascular function confirms functional orthology of myocardial contractility pathways in zebrafish

Phenotype-driven screens in larval zebrafish have transformed our understanding of the molecular basis of cardiovascular development. Screens to define the genetic determinants of physiological phenotypes have been slow to materialize as a result of the limited number of validated in vivo assays with relevant dynamic range. To enable rigorous assessment of cardiovascular physiology in living zebrafish embryos, we developed a suite of software tools for the analysis of high-speed video microscopic images and validated these, using established cardiomyopathy models in zebrafish as well as modulation of the nitric oxide (NO) pathway. Quantitative analysis in wild-type fish exposed to NO or in a zebrafish model of dilated cardiomyopathy demonstrated that these tools detect significant differences in ventricular chamber size, ventricular performance, and aortic flow velocity in zebrafish embryos across a large dynamic range. These methods also were able to establish the effects of the classic pharmacological agents isoproterenol, ouabain, and verapamil on cardiovascular physiology in zebrafish embryos. Sequence conservation between zebrafish and mammals of key amino acids in the pharmacological targets of these agents correlated with the functional orthology of the physiological response. These data provide evidence that the quantitative evaluation of subtle physiological differences in zebrafish can be accomplished at a resolution and with a dynamic range comparable to those achieved in mammals and provides a mechanism for genetic and small-molecule dissection of functional pathways in this model organism.

Surgical Ineligibility and Mortality Among Patients With Unprotected Left Main or Multivessel Coronary Artery Disease Undergoing Percutaneous Coronary Intervention

Background— Decisions to proceed with surgical versus percutaneous revascularization for multivessel coronary artery disease are often based on subtle clinical information that may not be captured in contemporary registries. The present study sought to evaluate the association between surgical ineligibility documented in the medical record and long-term mortality among patients with unprotected left main or multivessel coronary artery disease undergoing percutaneous coronary intervention. Methods and Results— All subjects undergoing nonemergent percutaneous coronary intervention for unprotected left main or multivessel coronary artery disease were identified at 2 academic medical centers from 2009 to 2012. Documentation of surgical ineligibility was assessed through review of electronic medical records. Cox proportional hazard models adjusted for known mortality risk factors were created to assess long-term mortality in patients with and without documentation of surgical ineligibility. Among 1013 subjects with multivessel coronary artery disease, 218 (22%) were deemed ineligible for coronary artery bypass graft surgery. The most common explicitly cited reasons for surgical ineligibility in the medical record were poor surgical targets (24%), advanced age (16%), and renal insufficiency (16%). After adjustment for known risk factors, documentation of surgical ineligibility remained independently associated with an increased risk of in-hospital (odds ratio, 6.26; 95% confidence interval, 2.16–18.15; P<0.001) and long-term mortality (hazard ratio, 2.98; 95% confidence interval, 1.88–4.72, P<0.001) after percutaneous coronary intervention. Conclusions— Documented surgical ineligibility is common and associated with significantly increased long-term mortality among patients undergoing percutaneous coronary intervention with unprotected left main or multivessel coronary disease, even after adjustment for known risk factors for adverse events during percutaneous revascularization.

Exercise-induced ST-segment elevation in ECG lead aVR is a useful indicator of significant left main or ostial LAD coronary artery stenosis.

OBJECTIVES The authors tested the hypothesis that exercise treadmill testing (ETT)-induced ST-segment elevation (STE) in electrocardiographic lead aVR is an important indicator of significant left main coronary artery (LMCA) or ostial left anterior descending coronary artery (LAD) stenosis. BACKGROUND Although STE in lead aVR is an indicator of LMCA or very proximal LAD occlusion in acute coronary syndromes, its predictive power in the setting of ETT is uncertain. METHODS Rest and stress electrocardiograms, clinical and stress test parameters, and single photon-emission computed tomographic myocardial perfusion imaging (MPI) data, when available, were obtained in 454 subjects (378 with MPI) who underwent cardiac catheterization and standard Bruce ETT ≤ 6 months before catheterization. Patients were selected for LMCA or ostial LAD disease (≥ 50% stenosis) with or without other coronary artery disease (CAD), CAD (≥ 70% stenosis) without significant LMCA or ostial LAD, or no significant CAD. Univariate followed by multivariate logistic regression analyses of clinical, electrocardiographic, stress test, and single photon-emission computed tomographic MPI variables were used to identify significant correlates of LMCA or ostial LAD stenosis. Bayesian analysis of the data also was performed. RESULTS LMCA (n = 38) or ostial LAD (n = 42) stenosis occurred in 75 patients (5 patients had both). The remainder had CAD without LMCA or ostial LAD stenosis (n = 276) or no CAD (n = 103). In multivariate analysis, the strongest predictor was stress-induced STE in lead aVR (p < 0.0001, area under the curve 0.82). Both left ventricular ejection fraction (after stress) and percent reversible LAD ischemia on single photon-emission computed tomographic MPI also contributed significantly in multivariate analysis (p < 0.005 and p < 0.05, respectively, areas under the curve 0.60 and 0.64, respectively). Although additional electrocardiographic, stress test, and MPI variables were significant univariate predictors, none was statistically significant in multivariate analysis. At 1-mm STE in lead aVR, sensitivity for LMCA or ostial LAD stenosis was 75%, specificity was 81%, overall predictive accuracy was 80%, and post-test probability increased nearly 3 times from 17% to 45%. CONCLUSIONS Stress (ETT)-induced STE in lead aVR is an important indicator of significant LMCA or ostial LAD stenosis and should not be ignored.