Kai Nassenstein

Myocardial scar visualized by cardiovascular magnetic resonance imaging predicts major adverse events in patients with hypertrophic cardiomyopathy.

OBJECTIVES We sought to establish the prognostic value of a comprehensive cardiovascular magnetic resonance (CMR) examination in risk stratification of hypertrophic cardiomyopathy (HCM) patients. BACKGROUND With annual mortality rates ranging between 1% and 5%, depending on patient selection, a small but significant number of HCM patients are at risk for an adverse event. Therefore, the identification of and prophylactic therapy (i.e., defibrillator placement) in patients with HCM who are at risk of dying are imperative. METHODS Two-hundred forty-three consecutive patients with HCM were prospectively enrolled. All patients underwent initial CMR, and 220 were available for clinical follow-up. The mean follow-up time was 1,090 days after CMR. End points were all-cause and cardiac mortality. RESULTS During follow-up 20 of the 220 patients died, and 2 patients survived sudden cardiac death due to adequate implantable cardioverter-defibrillator discharge. Most events (n = 16) occurred for cardiac reasons; the remaining 6 events were related to cancer and accidents. Our data indicate that the presence of scar visualized by CMR yields an odds ratio of 5.47 for all-cause mortality and of 8.01 for cardiac mortality. This might be superior to classic clinical risk factors, because in our dataset the presence of 2 risk factors yields an odds ratio of 3.86 for all-cause and of 2.20 for cardiac mortality, respectively. Multivariable analysis also revealed the presence of late gadolinium enhancement as a good independent predictor of death in HCM patients. CONCLUSIONS Among our population of largely low or asymptomatic HCM patients, the presence of scar indicated by CMR is a good independent predictor of all-cause and cardiac mortality.

Running: the risk of coronary events Prevalence and prognostic relevance of coronary atherosclerosis in marathon runners

AIMS To quantify the prevalence of coronary artery calcification (CAC) in relation to cardiovascular risk factors in marathon runners, and to study its role for myocardial damage and coronary events. METHODS AND RESULTS In 108 apparently healthy male marathon runners aged >or=50 years, with >or=5 marathon competitions during the previous three years, the running history, Framingham risk score (FRS), CAC, and presence of myocardial late gadolinium enhancement (LGE) were measured. Control groups were matched by age (8:1) and FRS (2:1) from the Heinz Nixdorf Recall Study. The FRS in marathon runners was lower than in age-matched controls (7 vs. 11%, P < 0.0001). However, the CAC distribution was similar in marathon runners and age-matched controls (median CAC: 36 vs. 38, P = 0.36) and higher in marathon runners than in FRS-matched controls (median CAC: 36 vs. 12, P = 0.02). CAC percentile values and number of marathons independently predicted the presence of LGE (prevalence = 12%) (P = 0.02 for both). During follow-up after 21.3 +/- 2.8 months, four runners with CAC >or= 100 experienced coronary events. Event-free survival was inversely related to CAC burden (P = 0.018). CONCLUSION Conventional cardiovascular risk stratification underestimates the CAC burden in presumably healthy marathon runners. As CAC burden and frequent marathon running seem to correlate with subclinical myocardial damage, an increased awareness of a potentially higher than anticipated coronary risk is warranted.

CMR imaging predicts death and other adverse events in suspected cardiac sarcoidosis.

OBJECTIVES This study aimed to demonstrate that the presence of late gadolinium enhancement (LGE) is a predictor of death and other adverse events in patients with suspected cardiac sarcoidosis. BACKGROUND Cardiac sarcoidosis is the most important cause of patient mortality in systemic sarcoidosis, yielding a 5-year mortality rate between 25% and 66% despite immunosuppressive treatment. Other groups have shown that LGE may hold promise in predicting future adverse events in this patient group. METHODS We included 155 consecutive patients with systemic sarcoidosis who underwent cardiac magnetic resonance (CMR) for workup of suspected cardiac sarcoid involvement. The median follow-up time was 2.6 years. Primary endpoints were death, aborted sudden cardiac death, and appropriate implantable cardioverter-defibrillator (ICD) discharge. Secondary endpoints were ventricular tachycardia (VT) and nonsustained VT. RESULTS LGE was present in 39 patients (25.5%). The presence of LGE yields a Cox hazard ratio (HR) of 31.6 for death, aborted sudden cardiac death, or appropriate ICD discharge, and of 33.9 for any event. This is superior to functional or clinical parameters such as left ventricular (LV) ejection fraction (EF), LV end-diastolic volume, or presentation as heart failure, yielding HRs between 0.99 (per % increase LVEF) and 1.004 (presentation as heart failure), and between 0.94 and 1.2 for potentially lethal or other adverse events, respectively. Except for 1 patient dying from pulmonary infection, no patient without LGE died or experienced any event during follow-up, even if the LV was enlarged and the LVEF severely impaired. CONCLUSIONS Among our population of sarcoid patients with nonspecific symptoms, the presence of myocardial scar indicated by LGE was the best independent predictor of potentially lethal events, as well as other adverse events, yielding a Cox HR of 31.6 and of 33.9, respectively. These data support the necessity for future large, longitudinal follow-up studies to definitely establish LGE as an independent predictor of cardiac death in sarcoidosis, as well as to evaluate the incremental prognostic value of additional parameters.

Myocardial late gadolinium enhancement: prevalence, pattern, and prognostic relevance in marathon runners.

PURPOSE To prospectively analyze the myocardial distribution of late gadolinium enhancement (LGE) with delayed-enhancement cardiac magnetic resonance (MR) imaging, to compare the prevalence of this distribution in nonprofessional male marathon runners with that in asymptomatic control subjects, and to examine the prognostic role of LGE. MATERIALS AND METHODS Institutional review board and ethics committee approval were obtained for this study, and all subjects provided written informed consent. Two-dimensional inversion-recovery segmented k-space gradient-echo MR sequences were performed after administration of a gadolinium-containing contrast agent in 102 ostensibly healthy male runners aged 50-72 years who had completed at least five marathons during the past 3 years and in 102 age-matched control subjects. Predominantly subendocardial regions of LGE typical of myocardial infarction (hereafter, coronary artery disease [CAD] pattern) were distinguished from a predominantly midmyocardial patchy pattern of LGE (hereafter, non-CAD pattern). Marathon runners with LGE underwent repeat cardiac MR imaging and additional adenosine perfusion imaging. Runners were followed up for a mean of 21 months +/- 3 (standard deviation) after initial presentation. The chi(2), Fisher exact, and McNemar exact tests were used for comparisons. Event-free survival rates were estimated with the Kaplan-Meier method, and overall group differences were evaluated with log-rank statistics. RESULTS Of the 102 runners, five had a CAD pattern of LGE, and seven had a non-CAD pattern of LGE. The CAD pattern of LGE was located in the territory of the left anterior descending coronary artery more frequently than was the non-CAD pattern (P = .0027, Fisher exact test). The prevalence of LGE in runners was higher than that in age-matched control subjects (12% vs 4%; P = .077, McNemar exact test). The event-free survival rate was lower in runners with myocardial LGE than in those without myocardial LGE (P < .0001, log-rank test). CONCLUSION Ostensibly healthy marathon runners have an unexpectedly high rate of myocardial LGE, and this may have diagnostic and prognostic relevance.

Hybrid PET/MR Imaging of the Heart: Feasibility and Initial Results

PURPOSE To assess the feasibility of hybrid imaging of the heart with fluorine 18 fluorodeoxyglucose (FDG) on an integrated 3-T positron emission tomography (PET)/magnetic resonance (MR) imaging system. MATERIALS AND METHODS The present study was approved by the local institutional review board. Written informed consent was obtained from all patients before imaging. Twenty consecutive patients with myocardial infarction (n = 20) underwent cardiac PET/MR imaging examination. Ten patients underwent additional cardiac PET/computed tomography (CT) before PET/MR. Two-dimensional half-Fourier acquisition single-shot turbo spin-echo sequences, balanced steady-state free precession cine sequences, two-dimensional turbo inversion-recovery magnitude T2-weighted sequences, and late gadolinium-enhanced (LGE) segmented two-dimensional inversion-recovery turbo fast low-angle shot sequences were performed. According to the 17-segment model, PET tracer uptake, wall motion, and late gadolinium enhancement were visually assessed for each segment on a binary scale, and categorical intermethod agreement was calculated by using the Cohen κ. The maximum standardized uptake value was measured in corresponding myocardial locations on PET/CT and PET/MR images. RESULTS Agreement was substantial over all patients and segments between PET and LGE images (κ = 0.76) and between PET and cine images (κ = 0.78). In 306 segments, 97 (32%) were rated as infarcted on PET images, compared with 93 (30%) rated as infarcted on LGE images and with 90 (29%) rated as infarcted on cine images. In a subgroup of patients (n = 10) with an additional PET/CT scan, no significant difference in myocardial tracer uptake between PET/CT and PET/MR images was found (paired t test, P = .95). CONCLUSION Cardiac PET/MR imaging with FDG is feasible and may add complementary information in patients with ischemic heart disease.

Systematic analysis of functional and structural changes after coronary microembolization: a cardiac magnetic resonance imaging study.

OBJECTIVES Our study aimed to detect the morphological und functional effects of coronary microembolization (ME) in vivo by cardiac magnetic resonance (CMR) imaging in an established experimental animal model. BACKGROUND Post-mortem morphological alterations of coronary ME include perifocal inflammatory edema and focal microinfarcts. Clinically, the detection of ME after successful coronary interventions identifies a population with a worse long-term prognosis. METHODS In 18 minipigs, ME was performed by intracoronary infusion of microspheres followed by repetitive in vivo imaging on a 1.5-T MR system from 30 min to 8 h after ME. Additionally, corresponding ex vivo CMR imaging and histomorphology were performed. RESULTS Cine CMR imaging demonstrated a time-dependent increase of wall motion abnormalities from 9 of 18 animals after 30 min to all animals after 8 h (0.5 h, 50%; 2 h, 78%; 4 h, 75%; 8 h, 100%). Whereas T2 images were negative 30 min after ME, 4 of 18 animals showed myocardial edema at follow-up (0.5 h, 0%; 2 h, 6%; 4 h, 25%; 8 h, 17%). In vivo late gadolinium enhancement (LGE) was observed in none of the animals after 30 min, but in 33%, 50%, and 83% of animals at 2 h, 4 h, and 8 h, respectively, after ME. Ex vivo CMR imaging showed patchy areas of LGE in all but 1 animal (2 h, 83%; 4 h, 100%; 8 h, 100%). A significant correlation was seen between the maximum troponin I level and LGE in vivo (r = 0.63) and the spatial extent of ex vivo LGE (r = 0.76). CONCLUSIONS Our results show that in vivo contrast-enhanced CMR imaging allows us to detect functional and structural myocardial changes after ME with a high sensitivity. Ex vivo, the pattern of LGE of high-resolution, contrast-enhanced CMR imaging is different from the well-known pattern of LGE in compact myocardial damage. Thus, improvements in spatial resolution are thought to be necessary to improve its ability to visualize ME-induced structural alterations even in vivo.

Integrated 18F-FDG PET/MR Imaging in the Assessment of Cardiac Masses: A Pilot Study

The objective of the present study was to evaluate whether integrated 18F-FDG PET/MR imaging could improve the diagnostic workup in patients with cardiac masses. Methods: Twenty patients were prospectively assessed using integrated cardiac 18F-FDG PET/MR imaging: 16 patients with cardiac masses of unknown identity and 4 patients with cardiac sarcoma after surgical therapy. All scans were obtained on an integrated 3-T PET/MR device. The MR protocol consisted of half Fourier acquisition single-shot turbo spin-echo sequence, cine, and T2-weighted images as well as T1-weighted images before and after injection of gadobutrol. PET data were acquired simultaneously with the MR scan after injection of 199 ± 58 MBq of 18F-FDG. Patients were prepared with a high-fat, low-carbohydrate diet in a period of 24 h before the examination, and 50 IU/kg of unfractionated heparin were administered intravenously 15 min before 18F-FDG injection. Results: Cardiac masses were diagnosed as follows: metastases, 3; direct tumor infiltration via pulmonary vein, 1; local relapse of primary sarcoma after surgery, 2; Burkitt lymphoma, 1; scar/patch tissue after surgery of primary sarcoma, 2; myxoma, 4; fibroelastoma, 1; caseous calcification of mitral annulus, 3; and thrombus, 3. The maximum standardized uptake value (SUVmax) in malignant lesions was significantly higher than in nonmalignant cases (13.2 ± 6.2 vs. 2.3 ± 1.2, P = 0.0004). When a threshold of 5.2 or greater was used, SUVmax was found to yield 100% sensitivity and 92% specificity for the differentiation between malignant and nonmalignant cases. T2-weighted hyperintensity and contrast enhancement both yielded 100% sensitivity but a weak specificity of 54% and 46%, respectively. Morphologic tumor features as assessed by cine MR imaging yielded 86% sensitivity and 92% specificity. Consent interpretation using all available MR features yielded 100% sensitivity and 92% specificity. A Boolean ‘AND’ combination of an SUVmax of 5.2 or greater with consent MR image interpretation improved sensitivity and specificity to 100%. Conclusion: In selected patients, 18F-FDG PET/MR imaging can improve the noninvasive diagnosis and follow-up of cardiac masses.

How Much Myocardial Damage Is Necessary to Enable Detection of Focal Late Gadolinium Enhancement at Cardiac MR Imaging

PURPOSE To assess the visibility of small myocardial lesions at magnetic resonance (MR) imaging and to estimate how much myocardial damage is necessary to enable detection of late gadolinium enhancement (LGE) in vivo. MATERIALS AND METHODS The study was approved by the local bioethics committee. Coronary microembolization was performed by injecting 300,000 microspheres into the distal portion of the left anterior descending artery in 18 anesthetized minipigs to create multifocal areas of myocardial damage. In vivo MR imaging was performed a mean of 6 hours after microembolization by using an inversion-recovery spoiled gradient-echo sequence (repetition time msec/echo time msec, 8/4; inversion time, 240-320 msec; flip angle, 20 degrees; spatial resolution, 1.3 x 1.7 x 5.0 mm(3)) after injection of 0.2 mmol gadopentetate dimeglumine per kilogram of body weight. High-spatial-resolution imaging of the explanted heart was performed by using the same sequence with a higher spatial resolution (0.5 x 0.5 x 2.0 mm(3)). Imaging results were verified with histologic examination. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of in vivo and ex vivo images were calculated, and a t test was used to analyze observed differences. RESULTS Multifocal myocardial damage was successfully induced in all animals. Areas of LGE with low SNR (mean, 36.3 +/- 29.4 [standard deviation]) and CNR (23.7 +/- 19.8) were observed in vivo in 12 (67%) of 18 animals, whereas ex vivo imaging revealed spotted to streaky areas of LGE with higher SNR (91.4 +/- 27.8, P < .0001) and CNR (72.1 +/- 25.4, P < .0001) among normal-appearing myocardium in all cases (100%). Focal myocardial lesions exceeding 5% of myocardium per slice at histologic examination were detected in vivo with a sensitivity of 83%. CONCLUSION Focal myocardial damage exceeding 5% of myocardium within the region of interest seems to be necessary for detection of LGE in vivo in an experimental model of coronary microembolization.

Integrated FDG PET/MR Imaging for the Assessment of Myocardial Salvage in Reperfused Acute Myocardial Infarction

PURPOSE To compare the size of the area with reduced myocardial fluorodeoxygluose (FDG) uptake with the endocardial surface area (ESA) method as a marker for the area at risk in patients with reperfused acute myocardial infarction. MATERIALS AND METHODS The study was approved by the local institutional review board. All patients gave written informed consent prior to their examination. Twenty-five patients (mean age ± standard deviation, 54 years ± 14) underwent prospective cardiac positron emission tomography/magnetic resonance imaging after acute coronary occlusion and interventional reperfusion. On late gadolinium contrast enhancement images, the size of infarction and the area at risk, as determined with ESA, were assessed and compared with the area of reduced FDG uptake. Statistical analysis comprised paired t tests and Mann-Whitney U tests, as well as Pearson r and Spearman ρ for correlations. RESULTS In patients with infarcted myocardium and reduced FDG uptake (n = 18), a good correlation between the area of reduced FDG uptake and the area at risk according to ESA was observed (r = .70, P = .001). The area of reduced FDG uptake (31% ± 11 of left ventricular myocardial mass) was larger than the size of the infarct (10% ± 10, P < .0001) and the area at risk according to ESA (17% ± 13, P < .0001). In six patients, no late contrast enhancement was seen, whereas all patients had an area of reduced FDG uptake (29% ± 8) in the perfusion territory of the culprit artery. CONCLUSION In patients with reperfused acute myocardial infarction, the area of reduced FDG uptake correlates with the area at risk as determined with the ESA method and is localized in the perfusion territory of the culprit artery in the absence of necrosis, although the area of reduced FDG uptake largely overestimates the size of the infarct and the ESA-based area at risk.

Diagnosis and treatment response evaluation of cardiac sarcoidosis using positron emission tomography/magnetic resonance imaging

A 32-year-old man presented with general malaise, acute retrosternal chest pain (CCS III), repeated episodes of fever, dizziness, and palpitations. The ECG demonstrated an incomplete right bundle branch block, persistent precordial S-waves, and a flattened T-wave in lead III. A positron emission tomography/magnetic resonance imaging (PET/MRI) examination of the heart …