Divaka Perera

Intra-aortic balloon counterpulsation and infarct size in patients with acute anterior myocardial infarction without shock: the CRISP AMI randomized trial.

CONTEXT Intra-aortic balloon counterpulsation (IABC) is an adjunct to revascularization in patients with cardiogenic shock and reduces infarct size when placed prior to reperfusion in animal models. OBJECTIVE To determine if routine IABC placement prior to reperfusion in patients with anterior ST-segment elevation myocardial infarction (STEMI) without shock reduces myocardial infarct size. DESIGN, SETTING, AND PATIENTS An open, multicenter, randomized controlled trial, the Counterpulsation to Reduce Infarct Size Pre-PCI Acute Myocardial Infarction (CRISP AMI) included 337 patients with acute anterior STEMI but without cardiogenic shock at 30 sites in 9 countries from June 2009 through February 2011. INTERVENTION Initiation of IABC before primary percutaneous coronary intervention (PCI) and continuation for at least 12 hours (IABC plus PCI) vs primary PCI alone. MAIN OUTCOME MEASURES Infarct size expressed as a percentage of left ventricular (LV) mass and measured by cardiac magnetic resonance imaging performed 3 to 5 days after PCI. Secondary end points included all-cause death at 6 months and vascular complications and major bleeding at 30 days. Multiple imputations were performed for missing infarct size data. RESULTS The median time from first contact to first coronary device was 77 minutes (interquartile range, 53 to 114 minutes) for the IABC plus PCI group vs 68 minutes (interquartile range, 40 to 100 minutes) for the PCI alone group (P = .04). The mean infarct size was not significantly different between the patients in the IABC plus PCI group and in the PCI alone group (42.1% [95% CI, 38.7% to 45.6%] vs 37.5% [95% CI, 34.3% to 40.8%], respectively; difference of 4.6% [95% CI, -0.2% to 9.4%], P = .06; imputed difference of 4.5% [95% CI, -0.3% to 9.3%], P = .07) and in patients with proximal left anterior descending Thrombolysis in Myocardial Infarction flow scores of 0 or 1 (46.7% [95% CI, 42.8% to 50.6%] vs 42.3% [95% CI, 38.6% to 45.9%], respectively; difference of 4.4% [95% CI, -1.0% to 9.7%], P = .11; imputed difference of 4.8% [95% CI, -0.6% to 10.1%], P = .08). At 30 days, there were no significant differences between the IABC plus PCI group and the PCI alone group for major vascular complications (n = 7 [4.3%; 95% CI, 1.8% to 8.8%] vs n = 2 [1.1%; 95% CI, 0.1% to 4.0%], respectively; P = .09) and major bleeding or transfusions (n = 5 [3.1%; 95% CI, 1.0% to 7.1%] vs n = 3 [1.7%; 95% CI, 0.4% to 4.9%]; P = .49). By 6 months, 3 patients (1.9%; 95% CI, 0.6% to 5.7%) in the IABC plus PCI group and 9 patients (5.2%; 95% CI, 2.7% to 9.7%) in the PCI alone group had died (P = .12). CONCLUSION Among patients with acute anterior STEMI without shock, IABC plus primary PCI compared with PCI alone did not result in reduced infarct size. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00833612.

Elective intra-aortic balloon counterpulsation during high-risk percutaneous coronary intervention: a randomized controlled trial.

CONTEXT Observational studies have previously reported that elective intra-aortic balloon pump (IABP) insertion may improve outcomes following high-risk percutaneous coronary intervention (PCI). To date, this assertion has not been tested in a randomized trial. OBJECTIVE To determine whether routine intra-aortic balloon counterpulsation before PCI reduces major adverse cardiac and cardiovascular events (MACCE) in patients with severe left ventricular dysfunction and extensive coronary disease. DESIGN, SETTING, AND PATIENTS The Balloon Pump-Assisted Coronary Intervention Study, a prospective, open, multicenter, randomized controlled trial conducted in 17 tertiary referral cardiac centers in the United Kingdom between December 2005 and January 2009. Patients (n = 301) had severe left ventricular dysfunction (ejection fraction < or = 30%) and extensive coronary disease (Jeopardy Score > or = 8/12); those with contraindications to or class I indications for IABP therapy were excluded. INTERVENTION Elective insertion of IABP before PCI. MAIN OUTCOME MEASURES Primary end point was MACCE, defined as death, acute myocardial infarction, cerebrovascular event, or further revascularization at hospital discharge (capped at 28 days). Secondary end points included all-cause mortality at 6 months, major procedural complications, bleeding, and access-site complications. RESULTS MACCE at hospital discharge occurred in 15.2% (23/151) of the elective IABP and 16.0% (24/150) of the no planned IABP groups (P = .85; odds ratio [OR], 0.94 [95% confidence interval {CI}, 0.51-1.76]). All-cause mortality at 6 months was 4.6% and 7.4% in the respective groups (P = .32; OR, 0.61 [95% CI, 0.24-1.62]). Fewer major procedural complications occurred with elective IABP insertion compared with no planned IABP use (1.3% vs 10.7%, P < .001; OR, 0.11 [95% CI, 0.01-0.49]). Major or minor bleeding occurred in 19.2% and 11.3% (P = .06; OR, 1.86 [95% CI, 0.93-3.79]) and access-site complications in 3.3% and 0% (P = .06) of the elective and no planned IABP groups, respectively. CONCLUSIONS Elective IABP insertion did not reduce the incidence of MACCE following PCI. These results do not support a strategy of routine IABP placement before PCI in all patients with severe left ventricular dysfunction and extensive coronary disease. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN40553718; clinicaltrials.gov Identifier: NCT00910481.

Quantification of absolute myocardial perfusion in patients with coronary artery disease: comparison between cardiovascular magnetic resonance and positron emission tomography

OBJECTIVES The aim of this study was to compare fully quantitative cardiovascular magnetic resonance (CMR) and positron emission tomography (PET) myocardial perfusion and myocardial perfusion reserve (MPR) measurements in patients with coronary artery disease (CAD). BACKGROUND Absolute quantification of myocardial perfusion and MPR with PET have proven diagnostic and prognostic roles in patients with CAD. Quantitative CMR perfusion imaging has been established more recently and has been validated against PET in normal hearts. However, there are no studies comparing fully quantitative CMR against PET perfusion imaging in patients with CAD. METHODS Forty-one patients with known or suspected CAD prospectively underwent quantitative (13)N-ammonia PET and CMR perfusion imaging before coronary angiography. RESULTS The CMR-derived MPR (MPR(CMR)) correlated well with PET-derived measurements (MPR(PET)) (r = 0.75, p < 0.0001). MPR(CMR) and MPR(PET) for the 2 lowest scoring segments in each coronary territory also correlated strongly (r = 0.79, p < 0.0001). Absolute CMR perfusion values correlated significantly, but weakly, with PET values both at rest (r = 0.32; p = 0.002) and during stress (r = 0.37; p < 0.0001). Area under the receiver-operating characteristic curve for MPR(PET) to detect significant CAD was 0.83 (95% confidence interval: 0.73 to 0.94) and for MPR(CMR) was 0.83 (95% confidence interval: 0.74 to 0.92). An MPR(PET) ≤1.44 predicted significant CAD with 82% sensitivity and 87% specificity, and MPR(CMR) ≤1.45 predicted significant CAD with 82% sensitivity and 81% specificity. CONCLUSIONS There is good correlation between MPR(CMR) and MPR(PET.) For the detection of significant CAD, MPR(PET) and MPR(CMR) seem comparable and very accurate. However, absolute perfusion values from PET and CMR are only weakly correlated; therefore, although quantitative CMR is clinically useful, further refinements are still required.

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.

The intra-observer reproducibility of cardiovascular magnetic resonance myocardial feature tracking strain assessment is independent of field strength

BACKGROUND Cardiovascular magnetic resonance myocardial feature tracking (CMR-FT) is a promising novel method for quantification of myocardial wall mechanics from standard steady-state free precession (SSFP) images. We sought to determine whether magnetic field strength affects the intra-observer reproducibility of CMR-FT strain analysis. METHODS We studied 2 groups, each consisting of 10 healthy subjects, at 1.5 T or 3T Analysis was performed at baseline and after 4 weeks using dedicated CMR-FT prototype software (Tomtec, Germany) to analyze standard SSFP cine images. Right ventricular (RV) and left ventricular (LV) longitudinal strain (Ell(RV) and Ell(LV)) and LV long-axis radial strain (Err(LAX)) were derived from the 4-chamber cine, and LV short-axis circumferential and radial strains (Ecc(SAX), Err(SAX)) from the short-axis orientation. Strain parameters were assessed together with LV ejection fraction (EF) and volumes. Intra-observer reproducibility was determined by comparing the first and the second analysis in both groups. RESULTS In all volunteers resting strain parameters were successfully derived from the SSFP images. There was no difference in strain parameters, volumes and EF between field strengths (p>0.05). In general Ecc(SAX) was the most reproducible strain parameter as determined by the coefficient of variation (CV) at 1.5 T (CV 13.3% and 46% global and segmental respectively) and 3T (CV 17.2% and 31.1% global and segmental respectively). The least reproducible parameter was Ell(RV) (CV 1.5 T 28.7% and 53.2%; 3T 43.5% and 63.3% global and segmental respectively). CONCLUSIONS CMR-FT results are similar with reasonable intra-observer reproducibility in different groups of volunteers at 1.5 T and 3T. CMR-FT is a promising novel technique and our data indicate that results might be transferable between field strengths. However there is a considerable amount of segmental variability indicating that further refinements are needed before CMR-FT can be fully established in clinical routine for quantitative assessment of wall mechanics and strain.

Detection of intracoronary thrombus by magnetic resonance imaging in patients with acute myocardial infarction.

Background— Persistent intracoronary thrombus after plaque rupture is associated with an increased risk of subsequent myocardial infarction and mortality. Coronary thrombus is usually visualized invasively by x-ray coronary angiography. Non–contrast-enhanced T1-weighted magnetic resonance (MR) imaging has been useful for direct imaging of carotid thrombus and intraplaque hemorrhage by taking advantage of the short T1 of methemoglobin present in acute thrombus and intraplaque hemorrhage. The aim of this study was to investigate the use of non–contrast–enhanced MR for direct thrombus imaging (MRDTI) in patients with acute myocardial infarction. Methods and Results— Eighteen patients (14 men; age, 61±9 years) underwent MRDTI within 24 to 72 hours of presenting with an acute coronary syndrome before invasive x-ray coronary angiography; MRDTI was performed with a T1-weighted, 3-dimensional, inversion-recovery black-blood gradient-echo sequence without contrast administration. Ten patients were found to have intracoronary thrombus on x-ray coronary angiography (left anterior descending, 4; left circumflex, 2; right coronary artery, 4; and right coronary artery–posterior descending artery, 1), and 8 had no visible thrombus. We found that MRDTI correctly identified thrombus in 9 of 10 patients (sensitivity, 91%; posterior descending artery thrombus not detected) and correctly classified the control group in 7 of 8 patients without thrombus formation (specificity, 88%). The contrast-to-noise ratio was significantly greater in coronary segments containing thrombus (n=10) compared with those without visible thrombus (n=131; mean contrast-to-noise ratio, 15.9 versus 2.6; P<0.001). Conclusion— Use of MRDTI allows selective visualization of coronary thrombus in a patient population with a high probability of intracoronary thrombosis.

Cardiovascular magnetic resonance myocardial feature tracking for quantitative viability assessment in ischemic cardiomyopathy

BACKGROUND Low dose dobutamine stress magnetic resonance imaging is valuable to assess viability in patients with ischemic cardiomyopathy. Analysis is usually qualitative with considerable operator dependency. The aim of the current study was to investigate the feasibility of cine images derived quantitative cardiac magnetic resonance (CMR) myocardial feature tracking (FT) strain parameters to assess viability in patients with ischemic cardiomyopathy. METHODS 15 consecutive patients with ischemic cardiomyopathy referred for viability assessment were studied at 3T at rest and during low dose dobutamine stress (5 and 10μg/kg/min of dobutamine). Subendocardial and subepicardial circumferential (Eccendo and Eccepi) and radial (Err) strains were assessed using steady state free precession (SSFP) cine images orientated in 3 short axis slices covering 16 myocardial segments. RESULTS Dysfunctional segments without scar (n=75) improved in all three strain parameters: Eccendo (Rest: -10.5±6.9; 5μg: -12.1±6.9; 10μg: -14.1±9.2; p<0.05), Eccepi (Rest: -7±4.8; 5μg: -8.2±5.5; 10μg: -9.1±5.9; p<0.05) and Err (Rest: 11.7±8.3; 5μg: 16±10.9; 10μg: 16.5±12.8; p<0.05). There was no response to dobutamine in dysfunctional segments with scar transmurality above 75% (n=6): Eccendo (Rest: -4.7±3.0; 5μg: -2.9±2.5; 10μg: -6.6±3.3; p=ns), Eccepi (Rest: -2.9±2.9; 5μg: -5.4±3.9; 10μg: -4.5±4.2; p=ns) and Err (Rest:9.5±5; 5μg:5.4±6.2; 10μg:4.9±3.3; p=ns). Circumferential strain (Eccendo, Eccepi) improved in all segments up to a transmurality of 75% (n=60; p<0.05). Err improved in segments <50% transmurality (n=45; p<0.05) and remained unchanged above 50% transmurality (n=21; p=ns). CONCLUSIONS CMR-FT is a novel technique, which detects quantitative wall motion derived from SSFP cine imaging at rest and with low dose dobutamine stress. CMR-FT holds promise of quantitative assessment of viability in patients with ischemic cardiomyopathy.

Appearance of microvascular obstruction on high resolution first-pass perfusion, early and late gadolinium enhancement CMR in patients with acute myocardial infarction

BackgroundThe presence and extent of microvascular obstruction (MO) after acute myocardial infarction can be measured by first-pass gadolinium-enhanced perfusion cardiovascular magnetic resonance (CMR) or after gadolinium injection with early or late enhancement (EGE/LGE) imaging. The volume of MO measured by these three methods may differ because contrast agent diffusion into the MO reduces its apparent extent over time. Theoretically, first-pass perfusion CMR should be the most accurate method to measure MO, but this technique has been limited by lower spatial resolution than EGE and LGE as well as incomplete cardiac coverage. These limitations of perfusion CMR can be overcome using spatio-temporal undersampling methods. The purpose of this study was to compare the extent of MO by high resolution first-pass k-t SENSE accelerated perfusion, EGE and LGE.Methods34 patients with acute ST elevation myocardial infarction, treated successfully with primary percutaneous coronary intervention (PPCI), underwent CMR within 72 hours of admission. k-t SENSE accelerated first-pass perfusion MR (7 fold acceleration, spatial resolution 1.5 mm × 1.5 mm × 10 mm, 8 slices acquired over 2 RR intervals, 0.1 mmol/kg Gd-DTPA), EGE (1-4 minutes after injection with a fixed TI of 440 ms) and LGE images (10-12 minutes after injection, TI determined by a Look-Locker scout) were acquired. MO volume was determined for each technique by manual planimetry and summation of discs methodology.Resultsk-t SENSE first-pass perfusion detected more cases of MO than EGE and LGE (22 vs. 20 vs. 14, respectively). The extent of MO imaged by first-pass perfusion (median mass 4.7 g, IQR 6.7) was greater than by EGE (median mass 2.3 g, IQR 7.1, p = 0.002) and LGE (median mass 0.2 g, IQR 2.4, p = 0.0003). The correlation coefficient between MO mass measured by first-pass perfusion and EGE was 0.91 (p < 0.001).ConclusionThe extent of MO following acute myocardial infarction appears larger on high-resolution first-pass perfusion CMR than on EGE and LGE. Given the inevitable time delay between gadolinium administration and acquisition of either EGE or LGE images, high resolution first-pass perfusion imaging may be the most accurate method to quantify MO.