Steffen E. Petersen

Normal Human Left and Right Ventricular and Left Atrial Dimensions Using Steady State Free Precession Magnetic Resonance Imaging

PURPOSE The aim of this project was to establish a database of left and right ventricular and left atrial dimensions in healthy volunteers using steady-state free precession cardiac magnetic resonance imaging, the clinical technique of choice, across a wide age range. METHODS 108 healthy volunteers (63 male, 45 female) underwent cardiac magnetic resonance imaging using steady-state free precession sequences. Manual analysis was performed by 2 experienced observers. RESULTS Left and right ventricular volumes and left ventricular mass were larger in males than females: LV end-diastolic volume 160 +/- 29 mL vs. 135 +/- 26 mL, LV end-systolic volume 50 +/- 16 mL vs. 42 +/- 12 mL; RV end-diastolic volume 190 +/- 33 mL vs. 148 +/- 35 mL, RV end-systolic volume 78 +/- 20 mL vs. 56 +/- 18 mL (p < .05 for all). Normalization of values to body surface area removed the statistical differences for LV volumes, but not for LV mass or RV volumes. With increased age, males showed a significant decrease in volume and mass indices for both ventricles, while female values remained unchanged. Compared to females, males had significantly larger maximal left atrial volumes (103 +/- 30 mL vs. 89 +/- 21 mL, p = .01) and left atrial stroke volumes (58 +/- 23 mL vs. 48 +/- 15 mL, p = .01). There was no difference in left atrial ejection fraction between the sexes. CONCLUSION We have produced a large database of age-related normal ranges for left and right ventricular function and left atrial function in males and females. This will allow accurate interpretation of clinical and research datasets.

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.

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.

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.

Beneficial Cardiovascular Effects of Bariatric Surgical and Dietary Weight Loss in Obesity

OBJECTIVES We hypothesized that, in obese persons without comorbidities, cardiovascular responses to excess weight are reversible during weight loss by either bariatric surgery or diet. BACKGROUND Obesity is associated with cardiac hypertrophy, diastolic dysfunction, and increased aortic stiffness, which are independent predictors of cardiovascular risk. METHODS Thirty-seven obese (body mass index 40 +/- 8 kg/m(2)) and 20 normal-weight subjects (body mass index 21 +/- 2 kg/m(2)) without identifiable cardiac risk factors underwent cardiac magnetic resonance imaging for the assessment of the left and right ventricles and of indexes of aortic function. Thirty of the obese subjects underwent repeat imaging after 1 year of significant weight loss, achieved in 17 subjects by diet and in 13 subjects by bariatric surgery. Seven obese subjects underwent repeat imaging after 1 year of continued obesity. RESULTS Left and right ventricular masses were significantly increased, left ventricular diastolic function impaired, and aortic distensibility reduced in the obese. Both diet and bariatric surgery led to comparable, significant decreases in left and right ventricular masses, end-diastolic volume, and diastolic dysfunction, and an increase in aortic distensibility at all levels of the aorta, most pronounced distally (e.g., distal descending aorta 5.1 +/- 1.8 mm Hg(-1) x 10(-3) before weight loss and 6.8 +/- 2.5 mm Hg(-1) x 10(-3) after weight loss; p < 0.001). No improvements were observed in continued obesity. CONCLUSIONS Irrespective of method, 1 year of weight loss leads to partial regression of cardiac hypertrophy and to reversal of both diastolic dysfunction and aortic distensibility impairment. These findings provide a potential mechanism for the reduction in mortality seen with weight loss.

European cardiovascular magnetic resonance (EuroCMR) registry – multi national results from 57 centers in 15 countries

BackgroundThe EuroCMR registry sought to evaluate indications, image quality, safety and impact on patient management of clinical routine CMR in a multi-national European setting. Furthermore, interim analysis of the specific protocols should underscore the prognostic potential of CMR.MethodsMulti-center registry with consecutive enrolment of patients in 57 centers in 15 countries. More than 27000 consecutive patients were enrolled.ResultsThe most important indications were risk stratification in suspected CAD/Ischemia (34.2%), workup of myocarditis/cardiomyopathies (32.2%), as well as assessment of viability (14.6%). Image quality was diagnostic in more than 98% of cases. Severe complications occurred in 0.026%, always associated with stress testing. No patient died during or due to CMR. In 61.8% CMR findings impacted on patient management. Importantly, in nearly 8.7% the final diagnosis based on CMR was different to the diagnosis before CMR, leading to a complete change in management. Interim analysis of suspected CAD and risk stratification in HCM specific protocols revealed a low rate of adverse events for suspected CAD patients with normal stress CMR (1.0% per year), and for HCM patients without LGE (2.7% per year).ConclusionThe most important indications in Europe are risk stratification in suspected CAD/Ischemia, work-up of myocarditis and cardiomyopathies, as well as assessment of viability. CMR imaging is a safe procedure, has diagnostic image quality in more than 98% of cases, and its results have strong impact on patient management. Interim analyses of the specific protocols underscore the prognostic value of clinical routine CMR in CAD and HCM.Condensed abstractThe EuroCMR registry sought to evaluate indications, image quality, safety and impact on patient management of clinical routine CMR in a multi-national European setting in a large number of cases (n > 27000). Based on our data CMR is frequently performed in European daily clinical routine. The most important indications in Europe are risk stratification in suspected CAD/Ischemia, work-up of myocarditis and cardiomyopathies, as well as assessment of viability. CMR imaging is a safe procedure, has diagnostic image quality in more than 98% of cases, and its results have strong impact on patient management. Interim analyses of the specific protocols underscore the prognostic value of clinical routine CMR in CAD and HCM.

Prediction model to estimate presence of coronary artery disease: Retrospective pooled analysis of existing cohorts

Objectives To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations. Design Retrospective pooled analysis of individual patient data. Setting 18 hospitals in Europe and the United States. Participants Patients with stable chest pain without evidence for previous coronary artery disease, if they were referred for computed tomography (CT) based coronary angiography or catheter based coronary angiography (indicated as low and high prevalence settings, respectively). Main outcome measures Obstructive coronary artery disease (≥50% diameter stenosis in at least one vessel found on catheter based coronary angiography). Multiple imputation accounted for missing predictors and outcomes, exploiting strong correlation between the two angiography procedures. Predictive models included a basic model (age, sex, symptoms, and setting), clinical model (basic model factors and diabetes, hypertension, dyslipidaemia, and smoking), and extended model (clinical model factors and use of the CT based coronary calcium score). We assessed discrimination (c statistic), calibration, and continuous net reclassification improvement by cross validation for the four largest low prevalence datasets separately and the smaller remaining low prevalence datasets combined. Results We included 5677 patients (3283 men, 2394 women), of whom 1634 had obstructive coronary artery disease found on catheter based coronary angiography. All potential predictors were significantly associated with the presence of disease in univariable and multivariable analyses. The clinical model improved the prediction, compared with the basic model (cross validated c statistic improvement from 0.77 to 0.79, net reclassification improvement 35%); the coronary calcium score in the extended model was a major predictor (0.79 to 0.88, 102%). Calibration for low prevalence datasets was satisfactory. Conclusions Updated prediction models including age, sex, symptoms, and cardiovascular risk factors allow for accurate estimation of the pretest probability of coronary artery disease in low prevalence populations. Addition of coronary calcium scores to the prediction models improves the estimates.

Detailed analysis of myocardial motion in volunteers and patients using high-temporal-resolution MR tissue phase mapping

To detect and investigate details in left ventricular (LV) motion patterns with a temporal resolution comparable to that of echocardiography.