Impact of Mitral Regurgitation Severity and Cause on Effort Tolerance-Integrated Stress Myocardial Perfusion Imaging and Echocardiographic Assessment of Patients With Known or Suspected Coronary Artery Disease Undergoing Exercise Treadmill Testing.

Background Mitral regurgitation ( MR ) has the potential to impede exercise capacity; it is uncertain whether this is because of regurgitation itself or the underlying cause of valvular insufficiency. Methods and Results The population comprised 3267 patients who underwent exercise treadmill myocardial perfusion imaging and transthoracic echocardiography within 6±8 days. MR was present in 28%, including 176 patients (5%) with moderate or greater MR . Left ventricular systolic function significantly decreased and chamber size increased in relation to MR , paralleling increments in stress and rest myocardial perfusion deficits (all P<0.001). Exercise tolerance (metabolic equivalents of task) decreased stepwise in relation to graded MR severity ( P<0.05). Workload was significantly lower with mild versus no MR (mean±SD, 9.8±3.0 versus 10.1±3.0; P=0.02); magnitude of workload reduction significantly increased among patients with advanced versus those with mild MR (mean±SD, 8.6±3.0 versus 9.8±3.0; P<0.001). MR -associated exercise impairment was accompanied by lower heart rate and blood pressure augmentation and greater dyspnea (all P<0.05). Both functional and nonfunctional MR subgroups demonstrated significantly decreased effort tolerance in relation to MR severity ( P≤0.01); impairment was greater with functional MR ( P=0.04) corresponding to more advanced left ventricular dysfunction and dilation (both P<0.001). Functional MR predicted reduced metabolic equivalent of task-based effort (B=-0.39 [95% CI, -0.62 to -0.17]; P=0.001) independent of MR severity. Among the overall cohort, advanced (moderate or greater) MR was associated with reduced effort tolerance (B=-1.36 [95% CI, -1.80 to -0.93]; P<0.001) and remained significant ( P=0.01) after controlling for age, clinical indexes, stress perfusion defects, and left ventricular dysfunction. Conclusions MR impairs exercise tolerance independent of left ventricular ischemia, dysfunction, and clinical indexes. Magnitude of exercise impairment parallels severity of MR .

Right Ventricular Dysfunction Impairs Effort Tolerance Independent of Left Ventricular Function Among Patients Undergoing Exercise Stress Myocardial Perfusion Imaging.

BACKGROUND: Right ventricular (RV) and left ventricular (LV) function are closely linked due to a variety of factors, including common coronary blood supply. Altered LV perfusion holds the potential to affect the RV, but links between LV ischemia and RV performance, and independent impact of RV dysfunction on effort tolerance, are unknown. METHODS AND RESULTS: The population comprised 2051 patients who underwent exercise stress myocardial perfusion imaging and echo (5.5±7.9 days), among whom 6% had echo-evidenced RV dysfunction. Global summed stress scores were ≈3-fold higher among patients with RV dysfunction, attributable to increments in inducible and fixed LV perfusion defects (all P≤0.001). Regional inferior and lateral wall ischemia was greater among patients with RV dysfunction (both P<0.01), without difference in corresponding anterior defects (P=0.13). In multivariable analysis, inducible inferior and lateral wall perfusion defects increased the likelihood of RV dysfunction (both P<0.05) independent of LV function, fixed perfusion defects, and pulmonary artery pressure. Patients with RV dysfunction demonstrated lesser effort tolerance whether measured by exercise duration (6.7±2.8 versus 7.9±2.9 minutes; P<0.001) or peak treadmill stage (2.6±0.9 versus 3.1±1.0; P<0.001), paralleling results among patients with LV dysfunction (7.0±2.9 versus 8.0±2.9; P<0.001|2.7±1.0 versus 3.1±1.0; P<0.001 respectively). Exercise time decreased stepwise in relation to both RV and LV dysfunction (P<0.001) and was associated with each parameter independent of age or medication regimen. CONCLUSIONS: Among patients with known or suspected coronary artery disease, regional LV ischemia involving the inferior and lateral walls confers increased likelihood of RV dysfunction. RV dysfunction impairs exercise tolerance independent of LV dysfunction.

Myocardial perfusion pattern for stratification of ischemic mitral regurgitation response to percutaneous coronary intervention.

OBJECTIVE: Ischemic mitral regurgitation (MR) is common, but its response to percutaneous coronary intervention (PCI) is poorly understood. This study tested the utility of myocardial perfusion imaging (MPI) for the stratification of MR response to PCI. METHODS: MPI and transthoracic echocardiography (echo) were performed among patients undergoing PCI. MPI was used to assess stress/rest myocardial perfusion. MR was assessed via echo (performed before and after PCI). RESULTS: A total of 317 patients with abnormal myocardial perfusion on MPI underwent echo 25±39 days before PCI. MR was present in 52%, among whom 24% had advanced (≥moderate) MR. MR was found to be associated with left ventricular (LV) chamber dilation on MPI and echo (both P<0.001). The magnitude of global LV perfusion deficits increased in relation to MR severity (P<0.01). Perfusion differences were greatest for global summed rest scores, which were 1.6-fold higher among patients with advanced MR versus those with mild MR (P=0.004), and 2.4-fold higher versus those without MR (P<0.001). In multivariate analysis, advanced MR was found to be associated with a fixed perfusion defect size on MPI [odds ratio 1.16 per segment (confidence interval 1.002-1.34), P=0.046], independent of LV volume [odds ratio 1.10 per 10 ml (confidence interval 1.04-1.17), P=0.002]. Follow-up via echo (1.0±0.6 years) demonstrated MR to decrease (≥1 grade) in 31% of patients and increase in 12% of patients. Patients with increased MR after PCI had more severe inferior perfusion defects on baseline MPI (P=0.028), whereas defects in other distributions and LV volumes were similar (P=NS). CONCLUSION: The extent and distribution of single-photon emission computed tomography-evidenced myocardial perfusion defects impact MR response to revascularization. An increased magnitude of inferior fixed perfusion defects predicts post-PCI progression of MR.

Effect of myocardial perfusion pattern on frequency and severity of mitral regurgitation in patients with known or suspected coronary artery disease.

Mitral regurgitation (MR) is common with coronary artery disease as altered myocardial substrate can affect valve performance. Single-photon emission computed tomography myocardial perfusion imaging (MPI) enables assessment of myocardial perfusion alterations. This study examined perfusion pattern in relation to MR. A total of 2,377 consecutive patients with known or suspected coronary artery disease underwent stress MPI and echocardiography within 1.6 ± 2.3 days. MR was present on echocardiography in 34% of patients, among whom 13% had advanced (moderate or more) MR. MR prevalence was higher in patients with abnormal MPI (44% vs 29%, p <0.001), corresponding to increased global ischemia (p <0.001). Regional perfusion varied in left ventricular segments adjacent to each papillary muscle: adjacent to the anterolateral papillary muscle, magnitude of baseline and stress-induced anterior/anterolateral perfusion abnormalities was greater in patients with MR (both p <0.001). Adjacent to the posteromedial papillary muscle, baseline inferior/inferolateral perfusion abnormalities were greater with MR (p <0.001), whereas stress inducibility was similar (p = 0.39). In multivariate analysis, stress-induced anterior/anterolateral and rest inferior/inferolateral perfusion abnormalities were independently associated with MR (both p <0.05) even after controlling for perfusion in reference segments not adjacent to the papillary muscles. MR severity increased in relation to magnitude of perfusion abnormalities in each territory adjacent to the papillary muscles, as evidenced by greater prevalence of advanced MR in patients with at least moderate anterior/anterolateral stress perfusion abnormalities (10.7% vs 3.6%), with similar results when MR was stratified based on rest inferior/inferolateral perfusion (10.4% vs 3.0%, both p <0.001). In conclusion, findings demonstrate that myocardial perfusion pattern in left ventricular segments adjacent to the papillary muscles influences presence and severity of MR.

Stress-induced ST-segment deviation in relation to the presence and severity of coronary artery disease in patients with normal myocardial perfusion imaging.

OBJECTIVE: To assess the utility of stress electrocardiography (ECG) for identifying the presence and severity of obstructive coronary artery disease (CAD) defined by coronary computed tomographic angiography (CCTA) among patients with normal nuclear myocardial perfusion imaging (MPI). METHODS: The study population comprised 119 consecutive patients with normal MPI who also underwent CCTA (interval 3.5+/-3.8 months). Stress ECG was performed at the time of MPI. CCTA and MPI were interpreted using established scoring systems, and CCTA was used to define the presence and extent of CAD, which was quantified by a coronary artery jeopardy score. RESULTS: Within this population, 28 patients (24%) had obstructive CAD identified by CCTA. The most common CAD pattern was single-vessel CAD (61%), although proximal vessel involvement was present in 46% of patients. Patients with CAD were nearly three times more likely to have positive standard test responses (1 mm ST-segment deviation) than patients with patent coronary arteries (36 vs. 13%, P=0.007). In multivariate analysis, a positive ST-segment test response was an independent marker for CAD (odds ratio: 2.02, confidence interval: 1.09-3.78, P=0.03) even after adjustment for a composite of clinical cardiac risk factors (odds ratio: 1.85, confidence interval: 1.05-3.23, P=0.03). Despite uniformly normal MPI, mean coronary jeopardy score was three-fold higher among patients with positive compared to those with negative ST-segment response to exercise or dobutamine stress (1.9+/-2.7 vs. 0.5+/-1.4, P=0.03). CONCLUSION: Stress-induced ST-segment deviation is an independent marker for obstructive CAD among patients with normal MPI. A positive stress ECG identifies patients with a greater anatomic extent of CAD as quantified by coronary jeopardy score.

Multidetector computed tomography coronary artery plaque predictors of stress-induced myocardial ischemia by SPECT.

BACKGROUND: Atherosclerosis imaging by multidetector computed tomography (MDCT) detects coronary artery plaque extent, distribution, location and composition. In contrast, functional imaging by single-photon emission computed tomography (SPECT) identifies perfusion defects known to predict prognosis of coronary heart disease (CHD). We sought to determine whether anatomic measures of plaque by MDCT predict functional measures of CHD by SPECT and thus, serve as measures of adverse cardiovascular prognosis. METHODS AND RESULTS: Consecutive low-to-intermediate risk symptomatic patients without known CHD (n=163) underwent both stress SPECT and MDCT. MDCT plaque extent and distribution were graded by a segment stenosis score (summation of luminal obstruction in all coronary segments) and segment involvement score (summation of segments exhibiting any plaque), respectively. Plaque location was assessed with a segments-at-risk score (plaque extent weighted by proximity) and a modified Duke CAD index. Plaque composition was graded as non-calcified, calcified and mixed. SPECT findings--summed stress (SSS), rest (SRS) and difference (SDS) scores--were compared to MDCT plaque scores. In univariate analyses, segment stenosis score (p=0.006), segments-at-risk score (p=0.002), Duke CAD index (p=0.02), and mixed plaque score (p=0.01) predicted severely abnormal SPECT. Highest compared to lowest quartile mixed plaque scores were predictive of higher SSS (8.1+/-10.3 versus 3.5+/-5.7, p<0.001), SRS (3.2+/-7.7 versus 0.9+/-3.1, p=0.008), and SDS (4.9+/-6.4 versus 2.6+/-3.9, p=0.012). In contrast, higher segment involvement scores, calcified and non-calcified plaque scores did not predict higher SPECT measures of ischemia. In multivariable analyses, comparing highest to lowest quartiles, individuals with high segment stenosis scores [odds ratio (OR) 1.97 (1.22-3.39), p=0.008], segments-at-risk scores [OR 1.71 (1.24-2.58), p=0.005], highest risk Duke CAD index category [OR 2.25 (1.12-4.41), p=0.02], and mixed plaque scores [OR 1.64 (1.10-2.43), p=0.01] had more severely abnormal SPECT scans. CONCLUSIONS: In low-to-intermediate risk patients without known CHD, MDCT coronary artery plaque assessment successfully identify patients at higher risk of increased extent, severity and reversibility of myocardial perfusion defects by SPECT. Anatomic MDCT findings, including plaque extent, location and composition, are independent predictors of functional ischemia and severe CHD by SPECT and thus, represent markers of adverse cardiovascular prognosis prior to the occurrence of clinical cardiovascular events.

Diagnostic impact of SPECT image display on assessment of obstructive coronary artery disease.

BACKGROUND: Diagnostic assessment of myocardial perfusion impacts the management of patients with suspected coronary artery disease (CAD). Although various image displays are available for single photon emission computed tomography (SPECT) interpretation, the effects of display differences on SPECT interpretation remain undetermined. METHODS AND RESULTS: We studied 183 patients undergoing SPECT, including 131 consecutive patients referred for angiography and 52 at low CAD risk. Studies were visually interpreted by use of color and gray images, with readers blinded to the results of the other display. In accordance with established criteria, a summed stress score (SSS) of 4 or greater was considered abnormal. The prevalence of abnormal SPECT findings was higher with gray images than with color images (54% vs 48%, P < .001) based on a uniform criterion (SSS > or =4). However, color images yielded equivalent sensitivity (79% vs 82%, P = .7) and improved specificity for global (50% vs 33%, P = .02) and vessel-specific CAD involving the right coronary artery (P < .01) and left anterior descending artery (P < .05). When the criterion for gray images was adjusted upward (SSS > or =5) to reflect increased mean defect severity (SSS of 5.1 vs 4.4, P = .01), gray and color images provided equivalent sensitivity and specificity for global and vessel-specific CAD. CONCLUSIONS: SPECT interpretation can vary according to image display as a result of differences in perfusion defect severity. Adjustment of abnormality criteria for gray images to reflect minor increases in defect severity provides equivalent diagnostic performance of gray and color displays for CAD assessment.

Anatomic distribution of myocardial ischemia as a determinant of exercise-induced ST-segment depression.

Cardiac single-photon emission computed tomographic correlates of ST depression were examined in 129 subjects who had inducible ST depression of > or =0.1 mV and reversible perfusion defects. Patients were separated on the basis of single-photon emission computed tomographic defect distribution into a group with anatomically contiguous ischemia (anterior or posterior/inferior defects, n = 68) and a group with anatomically opposed ischemia (anterior and posterior/inferior defects, n = 61). ST depression in the contiguous ischemia group correlated with defect size (r = 0.40, p = 0.001) and severity (r = 0.38, p = 0.002); multivariate regression demonstrated each to be independent determinants of ST-depression magnitude (r = 0.51, p <0.001). In the opposed ischemia group, ST depression did not significantly correlate with defect extent or severity. After adjusting for differences in perfusion indexes, ST depression was paradoxically greater in the contiguous than in the opposed group (2.82 +/- 1.15 vs 2.44 +/- 1.15 mm, p <0.001). In conclusion, these findings demonstrate that the anatomic distribution of ischemia can alter the relation between ST depression and functional indexes of ischemia and may confound the accuracy of assessments of coronary artery disease based on ST-depression magnitude alone.