Kalpa De Silva

High-Resolution Magnetic Resonance Myocardial Perfusion Imaging at 3.0-Tesla to Detect Hemodynamically Significant Coronary Stenoses as Determined by Fractional Flow Reserve

OBJECTIVES The objective of this study was to compare visual and quantitative analysis of high spatial resolution cardiac magnetic resonance (CMR) perfusion at 3.0-T against invasively determined fractional flow reserve (FFR). BACKGROUND High spatial resolution CMR myocardial perfusion imaging for the detection of coronary artery disease (CAD) has recently been proposed but requires further clinical validation. METHODS Forty-two patients (33 men, age 57.4 ± 9.6 years) with known or suspected CAD underwent rest and adenosine-stress k-space and time sensitivity encoding accelerated perfusion CMR at 3.0-T achieving in-plane spatial resolution of 1.2 × 1.2 mm(2). The FFR was measured in all vessels with >50% severity stenosis. Fractional flow reserve <0.75 was considered hemodynamically significant. Two blinded observers visually interpreted the CMR data. Separately, myocardial perfusion reserve (MPR) was estimated using Fermi-constrained deconvolution. RESULTS Of 126 coronary vessels, 52 underwent pressure wire assessment. Of these, 27 lesions had an FFR <0.75. Sensitivity and specificity of visual CMR analysis to detect stenoses at a threshold of FFR <0.75 were 0.82 and 0.94 (p < 0.0001), respectively, with an area under the receiver-operator characteristic curve of 0.92 (p < 0.0001). From quantitative analysis, the optimum MPR to detect such lesions was 1.58, with a sensitivity of 0.80, specificity of 0.89 (p < 0.0001), and area under the curve of 0.89 (p < 0.0001). CONCLUSIONS High-resolution CMR MPR at 3.0-T can be used to detect flow-limiting CAD as defined by FFR, using both visual and quantitative analyses.

Long-Term Mortality Data From the Balloon Pump–Assisted Coronary Intervention Study (BCIS-1) A Randomized, Controlled Trial of Elective Balloon Counterpulsation During High-Risk Percutaneous Coronary Intervention

Background— There is conflicting evidence on the utility of elective intra-aortic balloon pump (IABP) use during high-risk percutaneous coronary intervention (PCI). Observational series have indicated a reduction in major in-hospital adverse events, although randomized trial evidence does not support this. A recent study has suggested a mortality benefit trend early after PCI, but there are currently no long-term outcome data from randomized trials in this setting. Methods and Results— Three hundred one patients with left ventricular impairment (ejection fraction <30%) and severe coronary disease (BCIS-1 jeopardy score ≥8; maximum possible score=12) were randomized to receive PCI with elective IABP support (n=151) or without planned IABP support (n=150). Long-term all-cause mortality was assessed by tracking the databases held at the Office of National Statistics (in England and Wales) and the General Register Office (in Scotland). The groups were balanced in terms of baseline characteristics (left ventricular ejection fraction, 23.6%; BCIS-1 jeopardy score, 10.4) and the amount and type of revascularization performed. Mortality data were available for the entire cohort at a median of 51 months (interquartile range, 41–58) from randomization. All-cause mortality at follow-up was 33% in the overall cohort, with significantly fewer deaths occurring in the elective IABP group (n=42) than in the group that underwent PCI without planned IABP support (n=58) (hazard ratio, 0.66; 95% confidence interval, 0.44–0.98; P=0.039). Conclusions— In patients with severe ischemic cardiomyopathy treated with PCI, all-cause mortality was 33% at a median of 51 months. Elective IABP use during PCI was associated with a 34% relative reduction in all-cause mortality compared with unsupported PCI. Clinical Trial Registration— URL: http://www.isrctn.org. Unique identifier: ISRCTN40553718; and http://www.clinicaltrials.gov. Unique identifier: NCT00910481.

Validation of dynamic 3-dimensional whole heart magnetic resonance myocardial perfusion imaging against fractional flow reserve for the detection of significant coronary artery disease.

OBJECTIVES The goal of this study was to determine the diagnostic accuracy of dynamic 3-dimensional (3D) whole heart myocardial perfusion cardiovascular magnetic resonance (CMR) against invasively determined fractional flow reserve (FFR) and to establish the correlation between myocardium at risk defined by using the invasive Duke Jeopardy Score (DJS) and noninvasive 3D whole heart myocardial perfusion CMR. BACKGROUND 3D whole heart myocardial perfusion CMR overcomes the limited spatial coverage of conventional two-dimensional perfusion CMR methods and allows estimation of the extent of ischemia. The method has shown good diagnostic accuracy for the detection of coronary artery disease (CAD) as defined by using quantitative coronary angiography. However, quantitative coronary angiography does not provide a functional assessment of CAD as available from pressure wire-derived FFR. In the catheter laboratory, the DJS can complement FFR to estimate the myocardium at risk. METHODS Fifty-three patients referred for angiography underwent rest and adenosine stress 3D whole heart myocardial perfusion CMR at 3-T. Perfusion was scored visually on a patient and coronary territory basis, and ischemic burden was calculated by quantitative segmentation of the volume of hypoenhancement. FFR was measured in vessels with ≥50% severity stenosis and an FFR <0.75 considered as hemodynamically significant. The DJS was calculated from the coronary angiograms to quantify the myocardium at risk. RESULTS FFR was measured in 64 of 159 coronary vessels, and 39 had an FFR <0.75. Sensitivity, specificity, and diagnostic accuracy of CMR for the detection of significant CAD were 91%, 90%, and 91%, on a patient basis and 79%, 92%, and 88%, respectively, by coronary territory. There was a strong correlation between the DJS and ischemic burden on CMR (p < 0.0001; Pearsons r = 0.82). CONCLUSIONS 3D whole heart myocardial perfusion CMR accurately detects functionally significant CAD as defined by using FFR and provides an assessment of ischemic burden in agreement with the invasive DJS. The accurate detection of significant CAD combined with an estimation of ischemic burden by using 3D myocardial perfusion CMR holds promise for noninvasive guidance of therapy and risk stratification of patients with CAD.

Synergistic Adaptations to Exercise in the Systemic and Coronary Circulations That Underlie the Warm-Up Angina Phenomenon

Background— The mechanisms of reduced angina on second exertion in patients with coronary arterial disease, also known as the warm-up angina phenomenon, are poorly understood. Adaptations within the coronary and systemic circulations have been suggested but never demonstrated in vivo. In this study we measured central and coronary hemodynamics during serial exercise. Methods and Results— Sixteen patients (15 male, 61±4.3 years) with a positive exercise ECG and exertional angina completed the protocol. During cardiac catheterization via radial access, they performed 2 consecutive exertions (Ex1, Ex2) using a supine cycle ergometer. Throughout exertions, distal coronary pressure and flow velocity were recorded in the culprit vessel using a dual sensor wire while central aortic pressure was recorded using a second wire. Patients achieved a similar workload in Ex2 but with less ischemia than in Ex1 (P<0.01). A 33% decline in aortic pressure augmentation in Ex2 (P<0.0001) coincided with a reduction in tension time index, a major determinant of left ventricular afterload (P<0.001). Coronary stenosis resistance was unchanged. A sustained reduction in coronary microvascular resistance resulted in augmented coronary flow velocity on second exertion (both P<0.001). These changes were accompanied by a 21% increase in the energy of the early diastolic coronary backward-traveling expansion, or suction, wave on second exercise (P<0.05), indicating improved microvascular conductance and enhanced left ventricular relaxation. Conclusions— On repeat exercise in patients with effort angina, synergistic changes in the systemic and coronary circulations combine to improve vascular–ventricular coupling and enhance myocardial perfusion, thereby potentially contributing to the warm-up angina phenomenon.

Coronary and Microvascular Physiology During Intra-Aortic Balloon Counterpulsation

OBJECTIVES This study sought to identify the effect of coronary autoregulation on myocardial perfusion during intra-aortic balloon pump (IABP) therapy. BACKGROUND IABP is the most commonly used circulatory support device, although its efficacy in certain scenarios has been questioned. The impact of alterations in microvascular function on IABP efficacy has not previously been evaluated in humans. METHODS Thirteen patients with ischemic cardiomyopathy (left ventricular ejection fraction: 34 ± 8%) undergoing percutaneous coronary intervention were recruited. Simultaneous intracoronary pressure and Doppler-flow measurements were undertaken in the target vessel following percutaneous coronary intervention, during unassisted and IABP-assisted conditions. Coronary autoregulation was modulated by the use of intracoronary adenosine, inducing maximal hyperemia. Wave intensity analysis characterized the coronary wave energies associated with balloon counterpulsation. RESULTS Two unique diastolic coronary waves were temporally associated with IABP device use; a forward compression wave and a forward expansion wave caused by inflation and deflation, respectively. During basal conditions, IABP therapy increased distal coronary pressure (82.4 ± 16.1 vs. 88.7 ± 17.8 mm Hg, p = 0.03), as well as microvascular resistance (2.32 ± 0.52 vs. 3.27 ± 0.41 mm Hg cm s(-1), p = 0.001), with no change in average peak velocity (30.6 ± 12.0 vs. 26.6 ± 11.3 cm s(-1), p = 0.59). When autoregulation was disabled, counterpulsation caused an increase in average peak velocity (39.4 ± 10.5 vs. 44.7 ± 17.5 cm s(-1), p = 0.002) that was linearly related with IABP-forward compression wave energy (R(2) = 0.71, p = 0.001). CONCLUSIONS Autoregulation ameliorates the effect of IABP on coronary flow. However, during hyperemia, IABP augments myocardial perfusion, principally due to a diastolic forward compression wave caused by balloon inflation, suggesting IABP would be of greatest benefit when microcirculatory reserve is exhausted.

Coronary Wave Energy A Novel Predictor of Functional Recovery After Myocardial Infarction

Background—Revascularization after acute coronary syndromes provides prognostic benefit, provided that the subtended myocardium is viable. The microcirculation and contractility of the subtended myocardium affect propagation of coronary flow, which can be characterized by wave intensity analysis. The study objective was to determine in acute coronary syndromes whether early wave intensity analysis-derived microcirculatory (backward) expansion wave energy predicts late viability, defined by functional recovery. Methods and Results—Thirty-one patients (58±11 years) were enrolled after non-ST elevation myocardial infarction. Regional left ventricular function and late-gadolinium enhancement were assessed by cardiac magnetic resonance imaging, before and 3 months after revascularization. The backward-traveling (microcirculatory) expansion wave was derived from wave intensity analysis of phasic coronary pressure and velocity in the infarct-related artery, whereas mean values were used to calculate hyperemic microvascular resistance. Twelve-hour troponin T, left ventricular ejection fraction, and percentage late-gadolinium enhancement mass were 1.35±1.21 µg/L, 56±11%, and 8.4±6.0%, respectively. The infarct-related artery backward-traveling (microcirculatory) expansion wave was inversely correlated with late-gadolinium enhancement infarct mass (r=–0.81; P<0.0001) and strongly predicted regional left ventricular recovery (r=0.68; P=0.001). By receiver operating characteristic analysis, a backward-traveling (microcirculatory) expansion wave threshold of 2.8 W m–2 s–2×105 predicted functional recovery with sensitivity and specificity of 0.91 and 0.82 (AUC 0.88). Hyperemic microvascular resistance correlated with late-gadolinium enhancement mass (r=0.48; P=0.03) but not left ventricular recovery (r=–0.34; P=0.07). Conclusions—The microcirculation-derived backward expansion wave is a new index that correlates with the magnitude and location of infarction, which may allow for the prediction of functional myocardial recovery. Coronary wave intensity analysis may facilitate myocardial viability assessment during cardiac catheterization.

Does left ventricular function continue to influence mortality following contemporary percutaneous coronary intervention

BackgroundLeft ventricular (LV) dysfunction was associated with adverse outcome after percutaneous coronary intervention (PCI) in the balloon-angioplasty and bare-metal stent era. Technological advances have reduced complications after PCI. The impact of left ventricular ejection fraction (LVEF) on outcomes in current clinical practice is unknown, with commonly used risk stratification models not consistently incorporating preprocedural LVEF. MethodsA total of 2328 consecutive patients undergoing PCI in a single centre between April 2005 and July 2009 were analysed. Patients were eligible if LVEF had been categorized before PCI as good (LVEF ≥50%), moderate (LVEF 30–49%) or poor (LVEF <30%). Those in cardiogenic shock were excluded. Mortality data were tracked using the UK Office of National statistics database. Logistic regression analysis was used to predict the risk of mortality at 30-day and long-term follow-up. ResultsOverall all-cause mortality was 1.0% at 30 days and 5% at long-term follow-up. Kaplan–Meier analysis revealed an early divergence in survival curves according to LVEF. Mortality rates stratified by LVEF category were 0.4, 1.3 and 6.3% at 30 days and 3.3, 5.7 and 12.0% in the long term (2.2±1.1 years) (P<0.0001). Multiple regression analysis confirmed that impaired LVEF (⩽50%) independently predicts 30-day [hazard ratio 4.20 (confidence interval 2.50–7.04), P=0.001] and long-term all-cause mortality [hazard ratio 1.67 (1.28–2.19), P=0.001]. ConclusionLV impairment remains a strong predictor of early and late mortality after PCI. LV function assessment is integral in risk stratification and patient optimization and should be recommended, wherever feasible, before PCI.

Ischemic Burden by 3-Dimensional Myocardial Perfusion Cardiovascular Magnetic Resonance Comparison With Myocardial Perfusion Scintigraphy

Background—The extent and severity of ischemia on myocardial perfusion scintigraphy (MPS) is commonly used to risk-stratify patients with coronary artery disease. Estimation of ischemic burden by cardiovascular magnetic resonance (CMR) with conventional 2-dimensional myocardial perfusion methods is limited by incomplete cardiac coverage. More recently developed 3-dimensional (3D) myocardial perfusion CMR, however, provides whole-heart coverage. The aim of this study was to compare ischemic burden on 3D myocardial perfusion CMR with 99mTc-tetrofosmin MPS. Methods and Results—Forty-five patients who had undergone clinically indicated MPS underwent rest and adenosine stress 3D myocardial perfusion and late gadolinium enhancement CMR. Summed stress and rest scores were calculated for MPS and CMR using a 17-segment model and expressed as a percentage of the maximal possible score. Ischemic burden was defined as the difference between stress and rest scores. 3D myocardial perfusion CMR and MPS agreed in 38 of the 45 patients for the detection of any inducible ischemia. The mean ischemic burden for MPS and CMR was similar (7.5±8.9% versus 6.8±9.5%, respectively, P=0.82) with a strong correlation between techniques (rs=0.70, P<0.001). In a subset of 33 patients who underwent clinically indicated invasive coronary angiography, sensitivities and specificities of the 2 techniques to detect angiographic coronary artery disease were similar (McNemar P=0.45). Conclusions—3D myocardial perfusion CMR is an alternative to MPS for detecting the presence and rating the severity of ischemia.

Physiology of Angina and its Alleviation with Nitroglycerine- Insights from Invasive Catheter Laboratory Measurements During Exercise

Background: The mechanisms governing exercise-induced angina and its alleviation by the most commonly used antianginal drug, nitroglycerin, are incompletely understood. The purpose of this study was to develop a method by which the effects of antianginal drugs could be evaluated invasively during physiological exercise to gain further understanding of the clinical impact of angina and nitroglycerin. Methods: Forty patients (mean age, 65.2±7.6 years) with exertional angina and coronary artery disease underwent cardiac catheterization via radial access and performed incremental exercise using a supine cycle ergometer. As they developed limiting angina, sublingual nitroglycerin was administered to half the patients, and all patients continued to exercise for 2 minutes at the same workload. Throughout exercise, distal coronary pressure and flow velocity and central aortic pressure were recorded with sensor wires. Results: Patients continued to exercise after nitroglycerin administration with less ST-segment depression (P=0.003) and therefore myocardial ischemia. Significant reductions in afterload (aortic pressure, P=0.030) and myocardial oxygen demand were seen (tension-time index, P=0.024; rate-pressure product, P=0.046), as well as an increase in myocardial oxygen supply (Buckberg index, P=0.017). Exercise reduced peripheral arterial wave reflection (P<0.05), which was not further augmented by the administration of nitroglycerin (P=0.648). The observed increases in coronary pressure gradient, stenosis resistance, and flow velocity did not reach statistical significance; however, the diastolic velocity–pressure gradient relation was consistent with a significant increase in relative stenosis severity (k coefficient, P<0.0001), in keeping with exercise-induced vasoconstriction of stenosed epicardial segments and dilatation of normal segments, with trends toward reversal with nitroglycerin. Conclusions: The catheterization laboratory protocol provides a model to study myocardial ischemia and the actions of novel and established antianginal drugs. Administration of nitroglycerin causes changes in the systemic and coronary circulation that combine to reduce myocardial oxygen demand and to increase supply, thereby attenuating exercise-induced ischemia. Designing antianginal therapies that exploit these mechanisms may provide new therapeutic strategies.

Multimodality imaging of the ace of spades.

A 53-year-old man was admitted to our institute with chest pain and palpitation. Using contrast echocardiography, left ventriculography and cardiac MRI, a subsequent diagnosis of mid-ventricular hypertrophic obstructive cardiomyopathy with an apical aneurysm was made. The current case highlights the benefits of multimodality imaging in not only achieving a diagnosis but also in comprehending the pathophysiological origins of this unusual phenomenon.