Igor Klem

Detection of Myocardial Damage in Patients With Sarcoidosis

Background— In patients with sarcoidosis, sudden death is a leading cause of mortality, which may represent unrecognized cardiac involvement. Delayed-enhancement cardiovascular magnetic resonance (DE-CMR) can detect minute amounts of myocardial damage. We sought to compare DE-CMR with standard clinical evaluation for the identification of cardiac involvement. Methods and Results— Eighty-one consecutive patients with biopsy-proven extracardiac sarcoidosis were prospectively recruited for a parallel and masked comparison of cardiac involvement between (1) DE-CMR and (2) standard clinical evaluation with the use of consensus criteria (modified Japanese Ministry of Health [JMH] guidelines). Standard evaluation included 12-lead ECG and at least 1 dedicated non-CMR cardiac study (echocardiography, radionuclide scintigraphy, or cardiac catheterization). Patients were followed for 21±8 months for major adverse events (death, defibrillator shock, or pacemaker requirement). Patients were predominantly middle-aged (46±11 years), female (62%), and black (73%) and had chronic sarcoidosis (median, 7 years) and preserved left ventricular ejection fraction (median, 56%). DE-CMR identified cardiac involvement in 21 patients (26%) and JMH criteria in 10 (12%, 8 overlapping), a >2-fold higher rate for DE-CMR (P=0.005). All patients with myocardial damage on DE-CMR had coronary disease excluded by x-ray angiography. Pathology evaluation in 15 patients (19%) identified 4 with cardiac sarcoidosis; all 4 were positive by DE-CMR, whereas 2 were JMH positive. On follow-up, 8 had adverse events, including 5 cardiac deaths. Patients with myocardial damage on DE-CMR had a 9-fold higher rate of adverse events and an 11.5-fold higher rate of cardiac death than patients without damage. Conclusions— In patients with sarcoidosis, DE-CMR is more than twice as sensitive for cardiac involvement as current consensus criteria. Myocardial damage detected by DE-CMR appears to be associated with future adverse events including cardiac death, but events were few, and this needs confirmation in a larger cohort.

Assessment of Myocardial Scarring Improves Risk Stratification in Patients Evaluated for Cardiac Defibrillator Implantation

OBJECTIVES We tested whether an assessment of myocardial scarring by cardiac magnetic resonance imaging (MRI) would improve risk stratification in patients evaluated for implantable cardioverter-defibrillator (ICD) implantation. BACKGROUND Current sudden cardiac death risk stratification emphasizes left ventricular ejection fraction (LVEF); however, most patients suffering sudden cardiac death have a preserved LVEF, and many with poor LVEF do not benefit from ICD prophylaxis. METHODS One hundred thirty-seven patients undergoing evaluation for possible ICD placement were prospectively enrolled and underwent cardiac MRI assessment of LVEF and scar. The pre-specified primary endpoint was death or appropriate ICD discharge for sustained ventricular tachyarrhythmia. RESULTS During a median follow-up of 24 months the primary endpoint occurred in 39 patients. Whereas the rate of adverse events steadily increased with decreasing LVEF, a sharp step-up was observed for scar size >5% of left ventricular mass (hazard ratio [HR]: 5.2; 95% confidence interval [CI]: 2.0 to 13.3). On multivariable Cox proportional hazards analysis, including LVEF and electrophysiological-study results, scar size (as a continuous variable or dichotomized at 5%) was an independent predictor of adverse outcome. Among patients with LVEF >30%, those with significant scarring (>5%) had higher risk than those with minimal or no (≤5%) scarring (HR: 6.3; 95% CI: 1.4 to 28.0). Those with LVEF >30% and significant scarring had risk similar to patients with LVEF ≤30% (p = 0.56). Among patients with LVEF ≤30%, those with significant scarring again had higher risk than those with minimal or no scarring (HR: 3.9; 95% CI: 1.2 to 13.1). Those with LVEF ≤30% and minimal scarring had risk similar to patients with LVEF >30% (p = 0.71). CONCLUSIONS Myocardial scarring detected by cardiac MRI is an independent predictor of adverse outcome in patients being considered for ICD placement. In patients with LVEF >30%, significant scarring (>5% LV) identifies a high-risk cohort similar in risk to those with LVEF ≤30%. Conversely, in patients with LVEF ≤30%, minimal or no scarring identifies a low-risk cohort similar to those with LVEF >30%.

Detection of Left Ventricular Thrombus by Delayed-Enhancement Cardiovascular Magnetic Resonance : Prevalence and Markers in Patients With Systolic Dysfunction

OBJECTIVES This study sought to assess the prevalence and markers of left ventricular (LV) thrombus among patients with systolic dysfunction. BACKGROUND Prior studies have yielded discordant findings regarding prevalence and markers of LV thrombus. Delayed-enhancement cardiovascular magnetic resonance (DE-CMR) identifies thrombus on the basis of tissue characteristics rather than just anatomical appearance and is potentially highly accurate. METHODS Prevalence of thrombus by DE-CMR was determined in 784 consecutive patients with systolic dysfunction (left ventricular ejection fraction [LVEF] <50%) imaged between July 2002 and July 2004. Patients were recruited from 2 separate institutions: a tertiary-care referral center and an outpatient clinic. Comparison to cine-cardiovascular magnetic resonance (CMR) was performed. Follow-up was undertaken for thrombus verification via pathology evaluation or documented embolic event within 6 months after CMR. Clinical and imaging parameters were assessed to determine risk factors for thrombus. RESULTS Among this at-risk population (age 60 +/- 14 years; LVEF 32 +/- 11%), DE-CMR detected thrombus in 7% (55 patients) and cine-CMR in 4.7% (37 patients, p < 0.005). Follow-up was consistent with DE-CMR as a better reference standard than cine-CMR, including 100% detection among 5 patients with thrombus verified by pathology (cine-CMR, 40% detection), and logistic regression analysis testing the contributions of DE-CMR and cine-CMR simultaneously, which showed that only the presence of thrombus by DE-CMR was associated with follow-up end points (p < 0.005). Cine-CMR generally missed small intracavitary and small or large mural thrombus. In addition to traditional indices such as low LVEF and ischemic cardiomyopathy, multivariable analysis showed that increased myocardial scarring, an additional parameter available from DE-CMR, was an independent risk factor for thrombus. CONCLUSIONS In a broad cross section of patients with systolic dysfunction, thrombus prevalence was 7% by DE-CMR and included small intracavitary and small or large mural thrombus missed by cine-CMR. Prevalence increased with worse LVEF, ischemic etiology, and increased myocardial scarring.

Rapid Detection of Myocardial Infarction by Subsecond, Free-Breathing Delayed Contrast-Enhancement Cardiovascular Magnetic Resonance

Background— An ultrafast, delayed contrast-enhancement cardiovascular magnetic resonance technique that can acquire subsecond, “snapshot” images during free breathing (subsecond) is becoming widely available. This technique provides myocardial infarction (MI) imaging with complete left ventricular coverage in <30 seconds. However, the accuracy of this technique is unknown. Methods and Results— We prospectively compared subsecond imaging with routine breath-hold delayed contrast-enhancement cardiovascular magnetic resonance (standard) in consecutive patients. Two cohorts with unambiguous standards of truth were prespecified: (1) patients with documented prior MI (n=135) and (2) patients without MI and with low likelihood of coronary disease (lowest Framingham risk category; n=103). Scans were scored masked to identity and clinical information. Sensitivity, specificity, and accuracy of subsecond imaging for MI diagnosis were 87%, 96%, and 91%, respectively. Compared with the standard technique (98%, 100%, 99%), the subsecond technique had modestly reduced sensitivity (P=0.0001), but specificity was excellent. Missed infarcts were generally small or subendocardial (87%). Overall, regional transmural extent of infarction scores were highly concordant (2083/2294; 91%); however, 51 of 337 regions (15%) considered predominantly infarcted (>50% transmural extent of infarction) by the standard technique were considered viable (≤25% transmural extent of infarction) by the subsecond technique. Quantitative analysis demonstrated moderately reduced contrast-to-noise ratios for subsecond imaging between infarct and remote myocardium (12.0±7.2 versus 20.1±6.6; P<0.0001) and infarct and left ventricular cavity (−2.5±2.7 versus 3.6±3.7; P<0.0001). Conclusions— MI can be rapidly detected by subsecond delayed contrast-enhancement cardiovascular magnetic resonance during free breathing with high accuracy. This technique could be considered the preferred approach in patients who are more acutely ill or unable to hold their breath. However, compared with standard imaging, sensitivity is mildly reduced, and the transmural extent of infarction may be underestimated.

Unrecognized Non-Q-Wave Myocardial Infarction: Prevalence and Prognostic Significance in Patients with Suspected Coronary Disease

Using delayed-enhancement cardiovascular magnetic resonance, Han Kim and colleagues show that in patients with suspected coronary disease the prevalence of unrecognized myocardial infarction without Q-waves is more than 3-fold higher than that with Q-waves and predicts subsequent mortality.

Prognostic value of routine cardiac magnetic resonance assessment of left ventricular ejection fraction and myocardial damage: An international, multicenter study

Background— Cardiac magnetic resonance (CMR) is considered the reference standard for assessment of left ventricular ejection fraction (LVEF) and myocardial damage. However, few studies have evaluated the relationship between CMR findings and patient outcome, and of these, most are small and none multicenter. We performed an international, multicenter study to assess the prognostic importance of routine CMR in patients with known or suspected heart disease. Methods and Results— From 10 centers in 6 countries, consecutive patients undergoing routine CMR assessment of LVEF and myocardial damage by cine and delayed-enhancement imaging (DE-CMR), respectively, were screened for enrollment. Clinical data, CMR protocol information, and findings were collected at all sites and submitted to the data coordinating center for verification of completeness and analysis. The primary end point was all-cause mortality. A total of 1560 patients (age, 59±14 years; 70% men) were enrolled. Mean LVEF was 45±18%, and 1049 (67%) patients had hyperenhanced tissue (HE) on DE-CMR indicative of damage. During a median follow-up time of 2.4 years (interquartile range, 1.2, 2.9 years), 176 (11.3%) patients died. Patients who died were more likely to be older (P<0.0001), have coronary disease (P=0.004), have lower LVEF (P<0.0001), and have more segments with HE (P<0.0001). In multivariable analysis, age, LVEF, and number of segments with HE were independent predictors of mortality. Among patients with near-normal LVEF (≥50%), those with above-median HE (>4 segments) had reduced survival compared to patients with below- or at-median HE (P=0.02). Conclusions— Both LVEF and amount of myocardial damage as assessed by routine CMR are independent predictors of all-cause mortality. Even in patients with near-normal LVEF, significant damage identifies a cohort with a high risk for early mortality.

LV Thrombus Detection by Routine Echocardiography : Insights Into Performance Characteristics Using Delayed Enhancement CMR

OBJECTIVES This study sought to evaluate performance characteristics of routine echo for left ventricular thrombus (LVT). BACKGROUND Although the utility of dedicated echocardiography (echo) for LVT is established, echo is widely used as a general test for which LVT is rarely the primary indication. We used delayed-enhancement cardiac magnetic resonance (DE-CMR) as a reference to evaluate LVT detection by routine echo. METHODS Dedicated LVT assessment using DE-CMR was prospectively performed in patients with left ventricular systolic dysfunction. Echoes were done as part of routine clinical care. Echo and CMR were independently read for LVT and related indexes of LVT size, shape, and image quality/diagnostic confidence. Follow-up was done for embolic events and pathology validation of LVT. RESULTS In this study, 243 patients had routine clinical echo and dedicated CMR within 1 week without intervening events. Follow-up supported DE-CMR as a reference standard, with >5-fold difference in endpoints between patients with versus without LVT by DE-CMR (p = 0.02). LVT prevalence was 10% by DE-CMR. Echo contrast was used in 4% of patients. Echo sensitivity and specificity were 33% and 91%, with positive and negative predictive values of 29% and 93%. Among patients with possible LVT as the clinical indication for echo, sensitivity and positive predictive value were markedly higher (60%, 75%). Regarding sensitivity, echo performance related to LVT morphology and mirrored cine-CMR, with protuberant thrombus typically missed when small (p ≤ 0.02). There was also a strong trend to miss mural thrombus irrespective of size (p = 0.06). Concerning positive predictive value, echo performance related to image quality, with lower diagnostic confidence scores for echoes read positive for LVT in discordance with DE-CMR compared with echoes concordant with DE-CMR (p < 0.02). CONCLUSIONS Routine echo with rare contrast use can yield misleading results concerning LVT. Echo performance is improved when large protuberant thrombus is present and when the clinical indication is specifically for LVT assessment.

Value of Cardiovascular Magnetic Resonance Stress Perfusion Testing for the Detection of Coronary Artery Disease in Women

OBJECTIVES We wanted to assess the value of cardiovascular magnetic resonance (CMR) stress testing for evaluation of women with suspected coronary artery disease (CAD). BACKGROUND A combined perfusion and infarction CMR examination can accurately diagnose CAD in the clinical setting in a mixed gender population. METHODS We prospectively enrolled 147 consecutive women with chest pain or other symptoms suggestive of CAD at 2 centers (Duke University Medical Center, Robert-Bosch-Krankenhaus). Each patient underwent a comprehensive clinical evaluation, a CMR stress test consisting of cine rest function, adenosine-stress and rest perfusion, and delayed-enhancement CMR infarction imaging, and X-ray coronary angiography within 24 h. The components of the CMR test were analyzed visually both in isolation and combined using a pre-specified algorithm. Coronary artery disease was defined as stenosis > or =70% on quantitative analysis of coronary angiography. RESULTS Cardiovascular magnetic resonance imaging was completed in 136 females (63.0 +/- 11.1 years), 37 (27%) women had CAD on coronary angiography. The combined CMR stress test had a sensitivity, specificity, and accuracy of 84%, 88%, and 87%, respectively, for the diagnosis of CAD. Diagnostic accuracy was high at both sites (Duke University Medical Center 82%, Robert-Bosch-Krankenhaus 90%; p = 0.18). The accuracy for the detection of CAD was reduced when intermediate grade stenoses were included (82% vs. 87%; p = 0.01 compared the cutoff of stenosis > or =50% vs. > or =70%). The sensitivity was lower in women with single-vessel disease (71% vs. 100%; p = 0.06 compared with multivessel disease) and small left ventricular mass (69% vs. 95%; p = 0.04 for left ventricular mass < or =97 g vs. >97 g). The latter difference was even more significant after accounting for end-diastolic volumes (70% vs. 100%; p = 0.02 for left ventricular mass indexed to end-diastolic volume < or =1.15 g/ml vs. >1.15 g/ml). CONCLUSIONS A multicomponent CMR stress test can accurately diagnose CAD in women. Detection of CAD in women with intermediate grade stenosis, single-vessel disease, and with small hearts is challenging.

Relationship of T2-Weighted MRI Myocardial Hyperintensity and the Ischemic Area-At-Risk

RATIONALE After acute myocardial infarction (MI), delineating the area-at-risk (AAR) is crucial for measuring how much, if any, ischemic myocardium has been salvaged. T2-weighted MRI is promoted as an excellent method to delineate the AAR. However, the evidence supporting the validity of this method to measure the AAR is indirect, and it has never been validated with direct anatomic measurements. OBJECTIVE To determine whether T2-weighted MRI delineates the AAR. METHODS AND RESULTS Twenty-one canines and 24 patients with acute MI were studied. We compared bright-blood and black-blood T2-weighted MRI with images of the AAR and MI by histopathology in canines and with MI by in vivo delayed-enhancement MRI in canines and patients. Abnormal regions on MRI and pathology were compared by (a) quantitative measurement of the transmural-extent of the abnormality and (b) picture matching of contours. We found no relationship between the transmural-extent of T2-hyperintense regions and that of the AAR (bright-blood-T2: r=0.06, P=0.69; black-blood-T2: r=0.01, P=0.97). Instead, there was a strong correlation with that of infarction (bright-blood-T2: r=0.94, P<0.0001; black-blood-T2: r=0.95, P<0.0001). Additionally, contour analysis demonstrated a fingerprint match of T2-hyperintense regions with the intricate contour of infarcted regions by delayed-enhancement MRI. Similarly, in patients there was a close correspondence between contours of T2-hyperintense and infarcted regions, and the transmural-extent of these regions were highly correlated (bright-blood-T2: r=0.82, P<0.0001; black-blood-T2: r=0.83, P<0.0001). CONCLUSION T2-weighted MRI does not depict the AAR. Accordingly, T2-weighted MRI should not be used to measure myocardial salvage, either to inform patient management decisions or to evaluate novel therapies for acute MI.

Cardiovascular MRI for detection of myocardial viability and ischaemia

Coronary artery disease (CAD) remains the leading cause of death in the United States and Europe. Although there has been a decline in the number of deaths from myocardial infarction throughout the western world, the mortality for congestive heart failure has more than doubled. Importantly, CAD accounts for the majority (almost 70%) of congestive heart failure cases. In the clinical management of patients with congestive heart failure caused by CAD, the accurate assessment of myocardial viability is crucial to guide treatment; this is because revascularisation of dysfunctional but viable myocardium can improve ventricular function and long-term survival. Another everyday clinical scenario is the risk stratification of patients suspected to have CAD presenting for work up of chest pain syndromes. If left ventricular function is normal, stress testing remains the primary approach for detecting myocardial ischaemia. Traditionally nuclear imaging, stress echocardiography and (stress) electrocardiography have been the clinical mainstays for assessing myocardial viability as well as to detect myocardial ischaemia. However, cardiovascular MR (CMR) is a rapidly emerging non-invasive imaging technique, providing high-resolution images of the heart in any desired plane and without radiation. Rather than a single technique, CMR consists of several techniques that can be performed separately or in various combinations during a patient examination. For example, cine-CMR can provide assessment of cardiac morphology, function and contractile reserve; perfusion CMR with and without vasodilators can provide assessment of myocardial perfusion reserve, and contrast enhanced CMR (ceCMR) can be used for infarct detection as well as non-invasive tissue characterisation. This article will review the potential of CMR for managing patients with known or suspected CAD by discussing different CMR techniques for assessment of myocardial viability and myocardial ischaemia. The most precise definition of infarction, and therefore the loss of viability, is that myocyte death must have occurred. All ischaemic events …