Ejection fraction (EF) and end-systolic volume index (ESVI) are established predictors of outcomes following ST-segment elevation myocardial infarction (STEMI). We sought to assess the relative ...impact of infarct size, EF and ESVI on clinical outcomes and left ventricular (LV) remodelling.
Prospective cohort study.
Academic hospital in Chicago, USA.
122 patients with STEMI following acute percutaneous reperfusion.
Death, recurrent myocardial infarction (MI) and heart failure.
Cardiac magnetic resonance imaging was obtained within 1 week following STEMI in 122 subjects. ESVI, EF and infarct size were tested for the association with outcomes over 2 years in 113 subjects, and a repeat study was obtained 4 months later to assess LV remodelling in 91 subjects.
Acute infarct size correlated linearly with the initial ESVI (r = 0.69, p<0.001), end-diastolic volume index (EDVI) (r = 0.42, p<0.001) and EF (r = -0.75, p<0.001). All were independently associated with outcomes (one death, one recurrent MI and 16 heart failure admissions). However, infarct size was the only significant predictor of adverse outcomes (p<0.05) by multivariate analysis. The smallest infarct size tertile had an increased EF (49% (SD 8%) to 53% (6%); p = 0.002) and unchanged EDVI (p = 0.7). In contrast, subjects with the largest infarct tertile also had improved EF (32% (9%) to 36% (11%); p = 0.002) at the expense of a dramatic increase in EDVI (86 (19) to 95 (21) ml/m(2); p = 0.005).
Infarct size, EF and ESVI can predict the development of future cardiac events. Acute infarct size, which is independent of LV stunning and loading, directly relates to LV remodelling and is a stronger predictor of future events than measures of LV systolic performance.
Contrast MRI enhancement patterns in several pathophysiologies resulting from ischemic myocardial injury are controversial or have not been investigated. We compared contrast enhancement in acute ...infarction (AI), after severe but reversible ischemic injury (RII), and in chronic infarction.
In dogs, a large coronary artery was occluded to study AI and/or chronic infarction (n = 18), and a second coronary artery was chronically instrumented with a reversible hydraulic occluder and Doppler flowmeter to study RII (n = 8). At 3 days after surgery, cine MRI revealed reduced wall thickening in AI (5+/-6% versus 33+/-6% in normal, P<0.001). In RII, wall thickening before, during, and after inflation of the occluder for 15 minutes was 35+/-5%, 1+/-8%, and 21+/-10% and Doppler flow was 19.8+/-5.3, 0.2+/-0.5, and 56.3+/-17.7 (peak hyperemia) cm/s, respectively, confirming occlusion, transient ischemia, and reperfusion. Gd-DTPA-enhanced MR images acquired 30 minutes after contrast revealed hyperenhancement of AI (294+/-96% of normal, P<0.001) but not of RII (98+/-6% of normal, P = NS). Eight weeks later, the chronically infarcted region again hyperenhanced (253+/-54% of normal, n = 8, P<0.001). High-resolution (0.5 x 0.5 x 0.5 mm) ex vivo MRI demonstrated that the spatial extent of hyperenhancement was the same as the spatial extent of myocyte necrosis with and without reperfusion at 1 day (R = 0.99, P<0.001) and 3 days (R = 0.99, P<0.001) and collagenous scar at 8 weeks (R = 0.97, P<0.001).
In the pathophysiologies investigated, contrast MRI distinguishes between reversible and irreversible ischemic injury independent of wall motion and infarct age.
In patients with coronary artery disease and left ventricular dysfunction, the distinction between reversible and irreversible myocardial injury is important. The identification of viable myocardium ...is useful in predicting which patients will have increased left ventricular ejection fractions
1
–
7
and improved survival
8
–
11
after revascularization. Noninvasive methods for assessing myocardial viability include positron-emission tomography, single-photon-emission computed tomography, and dobutamine echocardiography. These techniques have proven clinical utility, but each has limitations that may reduce its diagnostic accuracy. For example, they interpret myocardial viability as an all-or-none phenomenon within a myocardial region, since none can assess the transmural extent of viability of . . .
Aims
Global angiographic scores have been developed to determine the extent of myocardium jeopardized by significant coronary stenosis. We adapted these scores to quantify the anatomic area at risk ...during acute myocardial infarction. We used contrast-enhanced magnetic resonance (CMR) infarct imaging to measure the portion of myocardium that developed necrosis within the so defined angiographic area at risk.
Methods and results
In 83 subjects presenting for primary percutaneous intervention, the myocardium at risk was estimated angiographically using the Myocardial Jeopardy Index (BARI) and a modified version of the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) scores. CMR was performed within a week to measure infarct size, infarct endocardial surface area (infarct-ESA), and infarct transmurality. As infarct transmurality increased, the infarct size closely approximated the myocardium at risk by angiography. In 35 subjects with transmural infarcts, the area at risk by BARI and APPROACH scores matched the infarct size (r = 0.90 and r = 0.92, P < 0.001). Additionally, BARI and APPROACH scores matched the infarct-ESA in all subjects independently of collateral flow and time to reperfusion (r = 0.90 and r = 0.87, P < 0.001). The presence of early reperfusion, collaterals, or both was associated with a progressive decrease in infarct transmurality (P < 0.001 for trend) with no difference in the infarct-ESA.
Conclusion
The myocardium at risk of infarction can be determined angiographically as validated in subjects with transmural myocardial infarcts. Salvage provided by early reperfusion or collaterals occurs by limiting infarct transmurality, thereby the extent of endocardial infarct involved also allows estimation of the myocardium at risk in patients presenting with STEMI.
Mild elevations in creatine kinase-MB (CK-MB) are common after successful percutaneous coronary interventions and are associated with future adverse cardiac events. The mechanism for CK-MB release ...remains unclear. A new contrast-enhanced MRI technique allows direct visualization of myonecrosis.
Fourteen patients without prior infarction underwent cine and contrast-enhanced MRI after successful coronary stenting; 9 patients had procedure-related CK-MB elevation, and 5 did not (negative controls). The mean age of all patients was 61 years, 36% had diabetes, 43% had multivessel coronary artery disease, and all had a normal ejection fraction. Twelve patients (86%) received an intravenous glycoprotein IIb/IIIa inhibitor; none underwent atherectomy, and all had final TIMI 3 flow. Of the 9 patients with CK-MB elevation, 5 had a minor side branch occlusion during stenting, 2 had transient ECG changes, and none developed Q-waves. The median CK-MB was 21 ng/mL (range, 12 to 93 ng/mL), which is 2.3x the upper limit of normal. Contrast-enhanced MRI demonstrated discrete regions of hyperenhancement within the target vessel perfusion territory in all 9 patients. Only one developed a new wall motion abnormality. The median estimated mass of myonecrosis was 2.0 g (range, 0.7 to 12.2 g), or 1.5% of left ventricular mass (range, 0.4% to 6.0%). Hyperenhancement persisted in 5 of the 6 who underwent a repeat MRI at 3 to 12 months. No control patient had hyperenhancement.
Contrast-enhanced MRI provides an anatomical correlate to biochemical evidence of procedure-related myocardial injury, despite the lack of ECG changes or wall motion abnormalities. Mild elevation of CK-MB after percutaneous coronary intervention is the result of discrete microinfarction.
We sought to determine the relationship of delayed hyperenhancement by contrast magnetic resonance imaging (MRI) to viable and nonviable myocardium within the region at risk throughout infarct ...healing.
The relationship of delayed MRI contrast enhancement patterns to injured but viable myocardium within the ischemic bed at risk has not been established.
We compared in vivo and ex vivo MRI contrast enhancement to histopathologic tissue sections encompassing the entire left ventricle in dogs (n = 24) subjected to infarction with (n = 12) and without (n = 12) reperfusion at 4 h, 1 day, 3 days, 10 days, 4 weeks and 8 weeks. In vivo MR imaging was performed 30 min after contrast injection.
The sizes and shapes of in vivo myocardial regions of elevated image intensity (828+/-132% of remote) were the same as those observed ex vivo (241 slices, r = 0.99, bias = 0.05+/-1.6% of left ventricle LV). Comparison of ex vivo MRI to triphenyltetrazolim chloride-stained sections demonstrated that the spatial extent of hyperenhancement was the same as the spatial extent ofinfarction at every stage of healing (510 slices, lowest r = 0.95, largest bias = 1.7+/-2.9% of LV). Conversely, hyperenhanced regions were smaller than the ischemic bed at risk defined by fluorescent microparticles at every stage of healing (239 slices, 35+/-24% of risk region, p<0.001). Image intensities of viable myocardium within the risk region were the same as those of remote, normal myocardium (102+/-9% of remote, p = NS).
Delayed contrast enhancement by MRI distinguishes between viable and nonviable regions within the myocardium at risk throughout infarct healing.
In some patients with heart failure, beta-blockers can improve left ventricular (LV) function and reduce morbidity and mortality. We hypothesized that gadolinium-enhanced cardiovascular magnetic ...resonance imaging (CMR) can predict reversible myocardial dysfunction and remodeling in heart failure patients treated with beta-blockers.
Forty-five patients with chronic heart failure underwent CMR. Contrast imaging using gadolinium was performed to obtain high-resolution spatial maps of myocardial scarring and viability. Cine imaging was performed to assess LV function and morphology and was repeated in 35 patients after 6 months of beta-blockade. Gadolinium CMR demonstrated scarring in 30 of 45 patients (67%). Scarring was found in 100% of patients with ischemic cardiomyopathy (28 of 28) but in only 12% with nonischemic cardiomyopathy (2 of 17). In the 35 patients who were maintained on beta-blockers and had a second study, there was an inverse relation between the extent of scarring at baseline and the likelihood of contractile improvement 6 months later (P<0.001). For instance, contractility improved in 56% (674 of 1207) of regions with no scarring but in only 3% with >75% scarring (8 of 232). Multivariate analysis showed that the amount of dysfunctional but viable myocardium by CMR was an independent predictor of the change in ejection fraction (P=0.01), mean wall motion score (P=0.0007), LV end-diastolic volume index (P=0.007), and LV end-systolic volume index (P< or =0.0001).
For heart failure patients treated with beta-blockers, gadolinium-enhanced CMR predicts the response in LV function and remodeling.
Myocardial infarcts are routinely detected by nuclear imaging techniques such as single photon emission computed tomography (SPECT) myocardial perfusion imaging. A newly developed technique for ...infarct detection based on contrast-enhanced cardiovascular magnetic resonance (CMR) has higher spatial resolution than SPECT. We postulated that this technique would detect infarcts missed by SPECT.
We did contrast-enhanced CMR and SPECT examinations in 91 patients with suspected or known coronary artery disease. All CMR and SPECT images were scored, using a 14-segment model, for the presence, location, and spatial extent of infarction. To compare each imaging modality to a gold standard, we also acquired contrast-enhanced CMR and SPECT images in 12 dogs with, and three dogs without, myocardial infarction as defined by histochemical staining.
In animals, contrast-enhanced CMR and SPECT detected all segments with nearly transmural infarction (>75% transmural extent of the left-ventricular wall). CMR also identified 100 of the 109 segments (92%) with subendocardial infarction (<50% transmural extent of the left-ventricular wall), whereas SPECT identified only 31 (28%). SPECT and CMR showed high specificity for the detection of infarction (97% and 98%, respectively). In patients, all segments with nearly transmural infarction, as defined by contrast-enhanced CMR, were detected by SPECT. However, of the 181 segments with subendocardial infarction, 85 (47%) were not detected by SPECT. On a per patient basis, six (13%) individuals with subendocardial infarcts visible by CMR had no evidence of infarction by SPECT.
SPECT and CMR detect transmural myocardial infarcts at similar rates. However, CMR systematically detects subendocardial infarcts that are missed by SPECT.
Myocardial ischemia and reperfusion lead to myocyte cell death, at least in part, by an apoptotic mechanism. Caspases are a conserved family of proteases that play an essential role in the execution ...of apoptosis; however, their potential contribution to ischemic myocardial cell death is largely unknown. To examine their role in this process, we subjected rabbits to 30 min of coronary artery occlusion followed by 3 h of reperfusion. Immunoblot analyses revealed that caspases-2, -3 and -7 were proteolytically activated during myocardial ischemia and reperfusion in vivo. In addition, the well-characterized caspase substrate poly(ADP-ribose) polymerase (PARP) was selectively cleaved into its signature apoptotic fragment in ischemic/reperfused myocardium. Systemic administration of the broad-spectrum caspase inhibitor acetyl-Tyr-Val-Ala-Asp chloromethylketone (YVAD-cmk, 4.8 mg/kg) partially blocked caspase activation and dramatically reduced the percentage of terminal dUTP deoyxynucleotidyl-transferase nick end-labeling (TUNEL)-positive myocyte nuclei in the infarct region (3.9±0.8%v 13.0±2.2% in control animals, P=0.012). Moreover, YVAD-cmk reduced myocardial infarct size by approximately 31% (31.1±3.3%v 45.3±4.9% in control animals,P =0.032). These results indicate that caspases are critical mediators of myocardial injury induced by ischemia and reperfusion in vivo, and they suggest that caspase inhibition may be therapeutically beneficial in myocardial infarction.
We sought to ascertain whether myocardial scarring occurs in living unselected patients with hypertrophic cardiomyopathy (HCM).
Myocardial scarring is known to occur in select HCM patients, who were ...highly symptomatic prior to death or who died suddenly. The majority of HCM patients, however, are minimally symptomatic and have not suffered sudden death.
Cine and gadolinium-enhanced magnetic resonance imaging was performed in 21 HCM patients who were predominantly asymptomatic. Gadolinium hyperenhancement was assumed to represent myocardial scar, and the extent of scar was compared to left ventricular (LV) morphology and function.
Scarring was present in 17 patients (81%). Scarring occurred only in hypertrophied regions (≥10 mm), was patchy with multiple foci, and predominantly involved the middle third of the ventricular wall. All 17 patients had scarring at the junction of the interventricular septum and the right ventricular (RV) free wall. On a regional basis, the extent of scarring correlated positively with wall thickness (r = 0.36, p < 0.0001), and inversely with wall thickening (r = −0.21, p < 0.0001). On a per patient basis, the extent of scarring (mean, 8 ± 9% of LV mass) was minimally related to maximum wall thickness (r = 0.40, p = 0.07) and LV mass (r = 0.33, p = 0.15), and correlated inversely with ejection fraction (r = −0.46, p = 0.04).
Myocardial scarring is common in asymptomatic or mildly symptomatic HCM patients who have not suffered sudden death. When present, scarring occurs in hypertrophied regions, is consistently localized to the junctions of the septum and RV free wall, and correlates positively with regional hypertrophy and inversely with regional contraction.
PDF
