Joseph B. Selvanayagam

Troponin elevation after percutaneous coronary intervention directly represents the extent of irreversible myocardial injury: insights from cardiovascular magnetic resonance imaging

Background—Although troponin elevation after percutaneous coronary intervention (PCI) is common, uncertainties remain about the mechanisms of its release and its relationship to the volume of myocardial tissue loss. Delayed-enhancement MRI of the heart has been shown to reliably quantify areas of irreversible myocardial injury. To investigate the quantitative relationship between irreversible injury and cardiac troponin release, we studied the incidence and extent of new irreversible injury in patients undergoing PCI and correlated it to postprocedural changes in cardiac troponin I. Methods and Results—Fifty patients undergoing PCI were studied with preprocedural and postprocedural (24 hours) delayed-enhancement MRI for assessment of new irreversible myocardial injury. Cardiac troponin I measurements were obtained before PCI and 24 hours after PCI. Of these 50 patients, 24 underwent a further third MRI scan at a median of 8 months after the procedure. Mean patient age was 64±12 years. After the procedure, 14 patients (28%) had evidence of new myocardial hyperenhancement, with a mean mass of 6.0±5.8 g, or 5.0±4.8% of total left ventricular mass. All of these patients had raised troponin I levels (range 1.0 to 9.4 &mgr;g/L). Thirty-four patients (68%) had no elevated troponin I and no evidence of new myocardial necrosis on MRI. There was a strong correlation between the rise in troponin I measurements at 24 hours and mean mass of new myocardial hyperenhancement, both early (r=0.84; P<0.001) and late (r=0.71; P<0.001) after PCI, although there was a trend for a reduction in the size of PCI-induced myocardial injury in the late follow-up scan (P=0.07). Conclusions—In the setting of PCI, patients demonstrating postprocedural elevation in troponin I have evidence of new irreversible myocardial injury on delayed-enhancement MRI. The magnitude of this injury correlates directly with the extent of troponin elevation.

Value of Delayed-Enhancement Cardiovascular Magnetic Resonance Imaging in Predicting Myocardial Viability After Surgical Revascularization

Background—Despite the accepted utility of delayed-enhancement MRI in identifying irreversible myocardial injury, no study has yet assessed its role as a viability tool exclusively in the setting of coronary artery bypass surgery (CABG), and no study has repeated delayed-enhancement MRI late after revascularization. In a clinical trial in which patients underwent CABG by either the off-pump or on-pump surgical technique, we hypothesized that (1) preoperative delayed-enhancement MRI would have high diagnostic accuracy in predicting viability and (2) the occurrence of perioperative myocardial necrosis would affect late regional wall motion recovery. Methods and Results—Fifty-two patients undergoing multivessel CABG were studied by preoperative and early (day 6) and late (6 months) postoperative cine MRI for global and regional functional assessment and delayed-enhancement MRI for assessment of irreversible myocardial injury. Preoperatively, 611 segments (21%) had abnormal regional function, whereas 421 segments (14%) showed evidence of hyperenhancement. At 6 months after revascularization, 57% (343 of 611) of dysfunctional segments improved contraction by at least 1 grade. When all preoperative dysfunctional segments were analyzed, there was a strong correlation between the transmural extent of hyperenhancement and the recovery in regional function at 6 months (P<0.001). Of a total of 96 previously dysfunctional but nonenhancing or minimally hyperenhancing myocardial segments that did not improve regional function at 6 months, 35 (36%) demonstrated new perioperative hyperenhancement in the early postoperative MRI scan. Conclusions—Delayed-enhancement MRI is a powerful predictor of myocardial viability after surgery, suggesting an important role for this technique in clinical viability assessment.

The role of cardiovascular magnetic resonance imaging in heart failure.

Noninvasive imaging plays a central role in the diagnosis of heart failure, assessment of prognosis, and monitoring of therapy. Cardiovascular magnetic resonance (CMR) offers a comprehensive assessment of heart failure patients and is now the gold standard imaging technique to assess myocardial anatomy, regional and global function, and viability. Furthermore, it allows assessment of perfusion and acute tissue injury (edema and necrosis), whereas in nonischemic heart failure, fibrosis, infiltration, and iron overload can be detected. The information derived from CMR often reveals the underlying etiology of heart failure, and its high measurement accuracy makes it an ideal technique for monitoring disease progression and the effects of treatment. Evidence on the prognostic value of CMR-derived parameters in heart failure is rapidly emerging. This review summarizes the advantages of CMR for patients with heart failure and its important role in key areas.

Evidence for Microvascular Dysfunction in Hypertrophic Cardiomyopathy: New Insights From Multiparametric Magnetic Resonance Imaging

Background— Microvascular dysfunction in hypertrophic cardiomyopathy (HCM) may create an ischemic substrate conducive to sudden death, but it remains unknown whether the extent of hypertrophy is associated with proportionally poorer perfusion reserve. Comparisons between magnitude of hypertrophy, impairment of perfusion reserve, and extent of fibrosis may offer new insights for future clinical risk stratification in HCM but require multiparametric imaging with high spatial and temporal resolution. Methods and Results— Degree of hypertrophy, myocardial blood flow at rest and during hyperemia (hMBF), and myocardial fibrosis were assessed with magnetic resonance imaging in 35 HCM patients (9 [26%] male/26 female) and 14 healthy controls (4 [29%] male/10 female), aged 18 to 78 years (mean±SD, 42±14 years) with the use of the American Heart Association left ventricular 16-segment model. Resting MBF was similar in HCM patients and controls. hMBF was lower in HCM patients (1.84±0.89 mL/min per gram) than in healthy controls (3.42±1.76 mL/min per gram, with a difference of −0.95±0.30 [SE] mL/min per gram; P<0.001) after adjustment for multiple variables, including end-diastolic segmental wall thickness (P<0.001). In HCM patients, hMBF decreased with increasing end-diastolic wall thickness (P<0.005) and preferentially in the endocardial layer. The frequency of endocardial hMBF falling below epicardial hMBF rose with wall thickness (P=0.045), as did the incidence of fibrosis (P<0.001). Conclusions— In HCM the vasodilator response is reduced, particularly in the endocardium, and in proportion to the magnitude of hypertrophy. Microvascular dysfunction and subsequent ischemia may be important components of the risk attributable to HCM.

Plaque Volume and Occurrence and Location of Periprocedural Myocardial Necrosis After Percutaneous Coronary Intervention Insights From Delayed-Enhancement Magnetic Resonance Imaging, Thrombolysis in Myocardial Infarction Myocardial Perfusion Grade Analysis, and Intravascular Ultrasound

Background— Myocardial necrosis can occur during percutaneous coronary intervention (PCI) despite optimal adjunctive pharmacology and careful technique. We investigated the mechanisms of procedural infarction using angiographic analysis, intravascular ultrasound, and delayed-enhancement magnetic resonance imaging. Methods and Results— Fifty-two patients (64 vessels) who underwent complex PCI were studied. All patients were preloaded with clopidogrel and received glycoprotein IIb/IIIa inhibitors. “Adjacent” myonecrosis was defined as the presence of an area of new gadolinium hyperenhancement close to the stent. “Distal” myonecrosis was defined as situated at least 10 mm downstream from the stent. Fifteen vessels (23%) had evidence of new hyperenhancement after PCI. Of these, 8 (12%) had the distal type, and 7 (11%) had the adjacent type. Intravascular ultrasound showed a significantly greater reduction in plaque volume (91.6±51.5 versus 8±14 versus 20±35 mm3; P<0.001) in the group with distal hyperenhancement compared with patients without new hyperenhancement or adjacent hyperenhancement. In the entire sample, a significant correlation was seen between changes in plaque volume (&rgr;=0.58, P<0.001) after PCI and the mass of new necrosis measured by magnetic resonance imaging. Thrombolysis in Myocardial Infarction perfusion grade assessment of a closed microvasculature after PCI carried an odds ratio of 8.0 (95% confidence interval, 1.4 to 46.1; P=0.02) for the occurrence of hyperenhancement, whereas side-branch occlusion was associated with an odds ratio of 16.2 (95% confidence interval, 2.6 to 102.5; P=0.03). However, a closed microvasculature was associated with distal hyperenhancement (P=0.02), and side-branch occlusion was associated with adjacent hyperenhancement (P<0.001). Conclusions— These data suggest that distal embolization of plaque material occurs in contemporary PCI of native coronary arteries. Efforts to minimize procedural necrosis may require careful review of side branch anatomy and/or use of distal protection during extensive coronary stenting.

Effects of Off-Pump Versus On-Pump Coronary Surgery on Reversible and Irreversible Myocardial Injury A Randomized Trial Using Cardiovascular Magnetic Resonance Imaging and Biochemical Markers

Background—There is biochemical evidence that off-pump coronary artery bypass grafting (OPCABG) reduces myocardial injury compared with the use of cardiopulmonary bypass (ONCABG), but the functional significance of this is uncertain. We hypothesized that OPCABG surgery would result in reduced postoperative reversible (stunning) and irreversible myocardial injury, as assessed by cardiovascular MRI (CMRI). Methods and Results—In a single-center randomized trial, 60 patients undergoing multivessel total arterial revascularization were randomly assigned: 30 to OPCABG and 30 to ONCABG. Patients underwent preoperative and early postoperative cine MRI for assessment of global left ventricular function, and contrast-enhanced CMRI for assessment of irreversible myocardial injury. Serial troponin I measurements were obtained perioperatively and correlated with the CMRI findings. The mean preoperative cardiac index was similar in the 2 surgical groups (2.9±0.7 ONCABG; 2.9±0.8 OPCABG; P =0.9). After surgery, the cardiac index was significantly higher in the OPCABG group (2.7±0.6 ONCABG; 3.2±0.8 OPCABG; P =0.04). New irreversible myocardial injury was similar in incidence (36% ONCABG; 44% OPCABG; P =0.8) and magnitude (6.3±3.6 g ONCABG; 6.8±4.0 g OPCABG; P =0.9) across the 2 groups. The median area-under-the-curve (AUC) troponin I values were significantly larger in the ONCABG group (182 versus 135 &mgr;g/L; P =0.02). There was a moderate correlation between the troponin I AUC values and mean mass of new myocardial hyperenhancement (r2=0.4; P =0.008). Conclusions—OPCABG results in significantly better left ventricular function early after surgery but does not reduce the incidence or extent of irreversible myocardial injury.

Resting Myocardial Blood Flow Is Impaired in Hibernating Myocardium. A Magnetic Resonance Study of Quantitative Perfusion Assessment

Background— Although impairment in perfusion reserve is well recognized in hibernating myocardium, there is substantial controversy as to whether resting myocardial blood flow (MBF) is reduced in such circumstances. Quantitative first-pass cardiovascular magnetic resonance (CMR) perfusion imaging allows absolute quantification of MBF. We hypothesized that MBF assessed at rest by quantitative CMR perfusion imaging is reduced in hibernating myocardium. Methods and Results— Twenty-seven patients with 1 or 2-vessel coronary disease and at least 1 dysfunctional myocardial segment undergoing PCI were studied with preprocedure, early (24 hours), and late (9 months) postprocedure CMR imaging. First-pass perfusion images at rest were acquired in 3 short-axis planes by use of a T1-weighted turboFLASH sequence. In each slice, MBF was determined for 8 myocardial segments in mL · min−1 · g−1 by deconvolution of signal intensity curves with an arterial input function measured in the left ventricular blood pool. Cine MRI for assessment of global and segmental function and delayed enhancement MRI for detection of viability were also obtained. All coronary lesions were 80% to 95% stenosis in severity. Over all segments, mean MBF normalized by rate-pressure product (“corrected MBF”) was 1.2±0.3 mL · min−1 · g−1 · (mm Hg · bpm/104)−1 in segments without significant coronary stenosis and 0.7±0.2 mL · min−1 · g−1 · (mm Hg · bpm/104)−1 in segments with coronary stenosis before PCI (mixed model controlling for slice and segment z=−23.9, P<0.001). Early after the procedure, the MBF was 1.2±0.2 mL · min−1 · g−1 · (mm Hg · bpm/104)−1 in revascularized segments and 1.3±0.2 mL · min−1 · g−1 · (mm Hg · bpm/104)−1 in nondiseased segments (z=−6.1, P<0.001). Late after PCI, the systolic wall thickening and end-diastolic wall thickness both increased significantly more (both P<0.001) in the myocardial segments subtended by severe coronary stenosis (8±17% to 40±19% and 6.5±1.1 to 9.3±2 mm, respectively) than in the myocardial segments supplied by nondiseased vessels. Mean MBF in dysfunctional segments with significantly improved contraction after revascularization was 0.8±0.2 mL · min−1 · g−1 · (mm Hg · bpm/104)−1 before PCI and 1.2±0.2 mL · min−1 · g−1 · (mm Hg · bpm/104)−1 after PCI (z=2.0, P=0.04). Conclusions— CMR perfusion imaging detects impaired resting MBF in hibernating myocardial segments.

The Syntax score predicts peri-procedural myocardial necrosis during percutaneous coronary intervention.

BACKGROUND Peri-procedural myocardial injury (PPI) during percutaneous coronary intervention (PCI) is common and associated with a poor outcome. No reliable angiographic or clinical predictors of PPI exist. We evaluated the ability of the SYNTAX score (SXscore), Gensini score, American Heart Association/American College of Cardiology (AHA/ACC) and Society for Cardiovascular Angiography and Intervention (SCAI) classifications to predict PPI. METHODS Consecutive patients were included from two existing databases of PCI. Patients with coronary bypass grafts or instent restenosis were excluded. PPI was defined as troponin I elevation (>1.0 microg/L) at 6-24 h post-PCI. Delayed enhancement magnetic resonance imaging distinguished PPI territory in patients undergoing multi-vessel PCI. Quantitative coronary angiography was performed blinded to PPI. In total, 100 patients underwent PCI to 122 vessels. PPI occurred in 20/100 (20.0%) patients. RESULTS Mean patient SXscore was higher in patients with PPI (20.6 vs. 12.4, p = 0.0001), however Gensini score was not significantly different (34.2 vs. 27.3, p = 0.15). Mean vessel SXscore was higher in vessels associated with PPI (12.1 vs. 7.6, p = 0.002), but not different for vessel Gensini score (16.2 vs. 13.6, p = 0.42). No vessels with AHA type A or B1 lesions were associated with PPI. Higher AHA scores (B2 and C) were associated with PPI (chi2 for trend 11.6, p = 0.0007). SCAI scores were not predictive of PPI (chi2 for trend 3.6, p = 0.06). By ROC analysis, a patient SXscore of > or = 17 predicted PPI with a sensitivity of 75.0% and specificity of 70.0%. CONCLUSION Higher SXscores are predictive of myocardial injury, whilst AHA type A and B1 lesions have a high negative predictive value for PPI.

Operator Induced Variability in Left Ventricular Measurements with Cardiovascular Magnetic Resonance is Improved After Training

BACKGROUND Accurate and reproducible measurement of left ventricular (LV) mass and function is a significant strength of Cardiovascular Magnetic Resonance (CMR). Reproducibility and accuracy of these measurements is usually reported between experienced operators. However, an increasing number of inexperienced operators are now training in CMR and are involved in post-processing analysis. The aim of the study was to assess the interobserver variability of the manual planimetry of LV contours amongst two experienced and six inexperienced operators before and after a two months training period. METHODS Ten healthy normal volunteers (5 men, mean age 34+/-14 years) comprised the study population. LV volumes, mass, and ejection fraction were manually evaluated using Argus software (Siemens Medical Solutions, Erlangen, Germany) for each subject, once by the two experienced and twice by the six inexperienced operators. The mean values of experienced operators were considered the reference values. The agreement between operators was evaluated by means of Bland-Altman analysis. Training involved standardized data acquisition, simulated off-line analysis and mentoring. RESULTS The trainee operators demonstrated improvement in the measurement of all the parameters compared to the experienced operators. The mean ejection fraction variability improved from 7.2% before training to 3.7% after training (p=0.03). The parameter in which the trainees showed the least improvement was LV mass (from 7.7% to 6.7% after training). The basal slice selection and contour definition were the main sources of errors. CONCLUSIONS An intensive two month training period significantly improved the accuracy of LV functional measurements. Adequate training of new CMR operators is of paramount importance in our aim to maintain the accuracy and high reproducibility of CMR in LV function analysis.

Percutaneous Treatment of Chronic Total Coronary Occlusions Improves Regional Hyperemic Myocardial Blood Flow and Contractility: Insights From Quantitative Cardiovascular Magnetic Resonance Imaging

OBJECTIVES We sought to investigate temporal changes in contractility and hyperemic and resting myocardial blood flow (MBF) in dependent and remote myocardium after percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs) by using cardiovascular magnetic resonance (CMR) imaging. BACKGROUND Data about the physiological consequences of revascularization of CTOs are limited. The use of CMR allows investigation of the regional effects of revascularization on MBF and left ventricular contractility. METHODS We prospectively recruited 3 patient groups: 17 patients scheduled for CTO PCI, 17 scheduled for PCI of a stenosed but nonoccluded coronary artery (non-CTO), and 6 patients with CTO who were not scheduled for revascularization. All patients undergoing PCI underwent CMR imaging <24 h before PCI, with repeat CMR imaging 24 h and 6 months after PCI. Each CMR scan consisted of cine, perfusion, and delayed enhancement imaging. Regional hyperemic and resting MBF, wall thickening, and transmural extent of infarction were calculated. RESULTS In both intervention groups, hyperemic MBF in treated segments increased 24 h after PCI compared with baseline: CTO group, 2.1 +/- 0.2 ml/min/g versus 1.4 +/- 0.2 ml/min/g (p < 0.01); non-CTO group, 2.5 +/- 0.2 ml/min/g versus 1.6 +/- 0.2 ml/min/g (p < 0.01). This improvement persisted 6 months after PCI (p < 0.01 for both groups). Contractility in treated segments was improved at 24 h and 6 months after CTO PCI but only at 6 months after non-CTO PCI. In both intervention groups, treated segments no longer had reduced MBF or contractility compared with remote segments. In patients with untreated CTO segments, MBF and wall thickening did not improve at follow-up. CONCLUSIONS Successful CTO PCI increases hyperemic MBF as early as 24 h after the procedure, with a greater and earlier improvement in regional contractility than after non-CTO PCI, despite a greater likelihood of irreversible injury in CTO segments.