Matthias Gutberlet

Clinical Characteristics and Cardiovascular Magnetic Resonance Findings in Stress (Takotsubo) Cardiomyopathy.

CONTEXT Stress cardiomyopathy (SC) is a transient form of acute heart failure triggered by stressful events and associated with a distinctive left ventricular (LV) contraction pattern. Various aspects of its clinical profile have been described in small single-center populations, but larger, multicenter data sets have been lacking so far. Furthermore, it remains difficult to quickly establish diagnosis on admission. OBJECTIVES To comprehensively define the clinical spectrum and evolution of SC in a large population, including tissue characterization data from cardiovascular magnetic resonance (CMR) imaging; and to establish a set of CMR criteria suitable for diagnostic decision making in patients acutely presenting with suspected SC. DESIGN, SETTING, AND PATIENTS Prospective study conducted at 7 tertiary care centers in Europe and North America between January 2005 and October 2010 among 256 patients with SC assessed at the time of presentation as well as 1 to 6 months after the acute event. MAIN OUTCOME MEASURES Complete recovery of LV dysfunction. RESULTS Eighty-one percent of patients (n = 207) were postmenopausal women, 8% (n = 20) were younger women (aged ≤50 years), and 11% (n = 29) were men. A stressful trigger could be identified in 182 patients (71%). Cardiovascular magnetic resonance imaging data (available for 239 patients [93%]) revealed 4 distinct patterns of regional ventricular ballooning: apical (n = 197 [82%]), biventricular (n = 81 [34%]), midventricular (n = 40 [17%]), and basal (n = 2 [1%]). Left ventricular ejection fraction was reduced (48% [SD, 11%]; 95% confidence interval [CI], 47%-50%) in all patients. Stress cardiomyopathy was accurately identified by CMR using specific criteria: a typical pattern of LV dysfunction, myocardial edema, absence of significant necrosis/fibrosis, and markers for myocardial inflammation. Follow-up CMR imaging showed complete normalization of LV ejection fraction (66% [SD, 7%]; 95% CI, 64%-68%) and inflammatory markers in the absence of significant fibrosis in all patients. CONCLUSIONS The clinical profile of SC is considerably broader than reported previously. Cardiovascular magnetic resonance imaging at the time of initial clinical presentation may provide relevant functional and tissue information that might aid in the establishment of the diagnosis of SC.

Prognostic Significance and Determinants of Myocardial Salvage Assessed by Cardiovascular Magnetic Resonance in Acute Reperfused Myocardial Infarction

OBJECTIVES The aim of the study was to determine the prognostic significance and determinants of myocardial salvage assessed by cardiovascular magnetic resonance (CMR) in reperfused ST-segment elevation myocardial infarction. BACKGROUND In acute myocardial infarction, CMR can retrospectively detect the myocardium at risk and the irreversible injury. This allows for quantifying the extent of salvaged myocardium after reperfusion as a potential strong end point for clinical trials and outcome. METHODS We analyzed 208 consecutive ST-segment elevation myocardial infarction patients undergoing primary angioplasty <12 h after symptom onset. T2-weighted and contrast-enhanced CMR was used to calculate the myocardial salvage index (MSI). Patients were categorized into 2 groups defined by the median MSI. The primary end point of the study was occurrence of major adverse cardiovascular events defined as death, reinfarction, and occurrence of new congestive heart failure within 6 months after the index event. RESULTS The median MSI was 48 (interquartile range 27 to 73). Major adverse cardiovascular events were significantly lower in the MSI >or= median group (2.9% vs. 22.1%, p < 0.001). The stepwise Cox proportional hazards model revealed that the MSI was the strongest predictor of major adverse cardiovascular events at 6-month follow-up (p < 0.001). All prognostic clinical (symptom onset to reperfusion), angiographic (Thrombolysis In Myocardial Infarction flow grade before angioplasty), and electrocardiographic (ST-segment resolution) parameters showed significant correlations with the MSI (p < 0.001 for all). CONCLUSIONS This study for the first time demonstrates that the MSI assessed by CMR predicts the outcome in acute reperfused ST-segment elevation myocardial infarction. Therefore, MSI assessment has important implications for patient prognosis as well as for the design of future trials intended to test new reperfusion therapy efficacy. (Myocardial Salvage Assessed by Cardiovascular Magnetic Resonance-Impact on Outcome; NCT00952224).

Suspected Chronic Myocarditis at Cardiac MR: Diagnostic Accuracy and Association with Immunohistologically Detected Inflammation and Viral Persistence

PURPOSE To retrospectively compare the diagnostic accuracy of three cardiac magnetic resonance (MR) imaging approaches for the detection of histologic and immunohistologic criteria (reference standard) proved myocardial inflammation in patients clinically suspected of having chronic myocarditis (CMC). MATERIALS AND METHODS Cardiac MR imaging was performed in 83 consecutive patients (55 male, 28 female; mean age, 44.8 years +/- 17.7 [standard deviation]) clinically suspected of having CMC, after written informed consent was obtained according to guidelines of the local ethics committee, which approved the study. T2-weighted triple-inversion-recovery imaging to calculate the edema ratio (ER), T1-weighted imaging before and after contrast agent administration to calculate the myocardial global relative enhancement (gRE), and inversion-recovery gradient-echo imaging to evaluate areas of late gadolinium enhancement (LE) were performed. The MR results were correlated with the endomyocardial biopsy (EMB) findings to detect intramyocardial inflammation and cardiotropic viral genomes analyzed at polymerase chain reaction assay. For statistical analyses, receiver operating characteristic analysis and the Wilcoxon test for unpaired data were used because the Kolomogorov-Smirnov test revealed a distribution of data that was different from normality. RESULTS Intramyocardial inflammation and cardiotropic viral persistence were confirmed at immunohistologic analysis in 48 and 49 of the 83 patients, respectively. The sensitivity, specificity, and diagnostic accuracy of the MR parameters, as compared with the immunohistologic detection of inflammation, were, respectively, 62%, 86%, and 72% for gRE; 67%, 69%, and 68% for ER; and 27%, 80%, and 49% for LE. Cardiac MR-derived gRE, ER, and LE were not associated with polymerase chain reaction proof of viral genomes. CONCLUSION In patients clinically suspected of having CMC, increased gRE and ER indicating inflammation were common findings that could be confirmed at immunohistologic analysis, whereas LE had low sensitivity and accuracy. Cardiac MR imaging may be helpful in detecting intramyocardial inflammation noninvasively, but it fails to depict viral persistence.

Clinical outcomes of fractional flow reserve by computed tomographic angiography-guided diagnostic strategies vs. usual care in patients with suspected coronary artery disease: the prospective longitudinal trial of FFRCT: outcome and resource impacts study

Aims In symptomatic patients with suspected coronary artery disease (CAD), computed tomographic angiography (CTA) improves patient selection for invasive coronary angiography (ICA) compared with functional testing. The impact of measuring fractional flow reserve by CTA (FFRCT) is unknown. Methods and results At 11 sites, 584 patients with new onset chest pain were prospectively assigned to receive either usual testing (n = 287) or CTA/FFRCT (n = 297). Test interpretation and care decisions were made by the clinical care team. The primary endpoint was the percentage of those with planned ICA in whom no significant obstructive CAD (no stenosis ≥50% by core laboratory quantitative analysis or invasive FFR < 0.80) was found at ICA within 90 days. Secondary endpoints including death, myocardial infarction, and unplanned revascularization were independently and blindly adjudicated. Subjects averaged 61 ± 11 years of age, 40% were female, and the mean pre-test probability of obstructive CAD was 49 ± 17%. Among those with intended ICA (FFRCT-guided = 193; usual care = 187), no obstructive CAD was found at ICA in 24 (12%) in the CTA/FFRCT arm and 137 (73%) in the usual care arm (risk difference 61%, 95% confidence interval 53–69, P< 0.0001), with similar mean cumulative radiation exposure (9.9 vs. 9.4 mSv, P = 0.20). Invasive coronary angiography was cancelled in 61% after receiving CTA/FFRCT results. Among those with intended non-invasive testing, the rates of finding no obstructive CAD at ICA were 13% (CTA/FFRCT) and 6% (usual care; P = 0.95). Clinical event rates within 90 days were low in usual care and CTA/FFRCT arms. Conclusions Computed tomographic angiography/fractional flow reserve by CTA was a feasible and safe alternative to ICA and was associated with a significantly lower rate of invasive angiography showing no obstructive CAD.

Differential diagnosis of suspected apical ballooning syndrome using contrast-enhanced magnetic resonance imaging

AIMS The apical ballooning syndrome (ABS) is a new diagnostic entity which is increasingly recognized. Precise magnetic resonance imaging (MRI) data are not yet available and there is little evidence for the differential diagnosis of ABS assessed by MRI. METHODS AND RESULTS Between January 2005 and January 2008, 6100 consecutive patients with diagnosis of acute coronary syndrome underwent left heart catheterization. In 59 patients (1.0%), coronary angiography revealed normal coronary arteries, but left ventriculography showed left ventricular dysfunction with apical ballooning. These 59 patients underwent cardiac MRI using a 1.5 T MRI scanner. In 13 patients (22.0%), MRI revealed diagnosis of myocardial infarction, in eight patients (13.6%) diagnosis of myocarditis. In all other 38 (64.4%) patients (36 female, age 73 +/- 10 years) with suspected ABS, no delayed enhancement or signs of inflammation were detected. Follow-up MRI after 3 months showed a completely normalized left ventricular ejection in all patients with suspected ABS. Similarly, the end-diastolic volume and end-systolic volume improved at follow-up. CONCLUSION Cardiac MRI allows differentiating ABS from other rare causes with unobstructed coronary vessels such as myocarditis and coronary emboli with spontaneous lysis. Therefore, cardiac MRI can add valuable information in all patients with suspected ABS for further differential diagnosis.

Comparison of transthoracic three dimensional echocardiography with magnetic resonance imaging in the assessment of right ventricular volume and mass.

OBJECTIVE: Assessment of right ventricular volume and mass with three dimensional echocardiography and comparison with magnetic resonance imaging. METHODS: Measurements of right ventricular volumes performed on three dimensional datasets acquired by transthoracic echocardiography were compared to those obtained from magnetic resonance imaging performed on the same day. Volumes were measured in end systole and end diastole and ejection fraction calculated. Right ventricular mass was assessed in end systole. With both methods, the areas of a 2 mm thick slice of the ventricle were manually outlined and multiplied by the slice thickness to obtain slice volume. Slice volumes were multiplied by the number of measured slices to obtain the ventricular volume. PATIENTS: 16 patients were studied: three with normal hearts, three after surgical repair of coarctation of the aorta, nine following repair of tetralogy of Fallot, and one with Mustard atrial repair of complete transposition of the great arteries. RESULTS: Correlation between end diastolic volumes measured by both methods was r = 0.95 with limits of agreement ranging from -3.5 to 12.5 ml; correlation for end systolic volumes was r = 0.87 with limits of agreement between -4.0 and 16.4 ml; correlation for end systolic right ventricular mass was r = 0.81 with limits of agreement between -7.0 and 20.6 g. Interobserver variability ranged from 4.3% (range 0.2% to 9.3%) for end diastolic volume to 7.6% (1.8% to 15.4%) for mass measurements. CONCLUSIONS: With transthoracic three dimensional echocardiography, end diastolic right ventricular volumes can be assessed with acceptable accuracy in normal hearts and those with enlarged right ventricles, whereas the current method of three dimensional echocardiography is less good for end systolic volumes and not satisfactory for right ventricular mass measurements.

Impact of high-dose N-acetylcysteine versus placebo on contrast-induced nephropathy and myocardial reperfusion injury in unselected patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. The LIPSIA-N-ACC (Prospective, Single-Blind, Placebo-Controlled, Randomized Leipzig Immediate PercutaneouS Coronary Intervention Acute Myocardial Infarction N-ACC) Trial.

OBJECTIVES The aim of this randomized, single-blind, controlled trial was to assess N-acetylcysteine effects on contrast-induced nephropathy and reperfusion injury in ST-segment elevation myocardial infarction patients undergoing primary angioplasty with moderate contrast volumes. BACKGROUND High-dose N-acetylcysteine reduced the incidence of contrast-induced nephropathy in patients with high contrast volumes and reduced reperfusion injury in animal trials. METHODS Patients undergoing primary angioplasty were randomized to either high-dose N-acetylcysteine (2 x 1,200 mg/day for 48 h; n = 126) or placebo plus optimal hydration (n = 125). The 2 primary end points were: 1) the occurrence of >25% increase in serum creatinine level <72 h after randomization; and 2) a reduction in reperfusion injury measured as myocardial salvage index by magnetic resonance imaging. RESULTS The median volume of an iso-osmolar contrast agent during angiography was 180 ml (interquartile range [IQR] 140 to 230 ml) in the N-acetylcysteine and 160 ml (IQR 120 to 220 ml) in the placebo group (p = 0.20). The primary end point contrast-induced nephropathy occurred in 14% of the N-acetylcysteine group and in 20% of the placebo group (p = 0.28). The myocardial salvage index was also not different between both treatment groups (43.5; IQR 25.4 to 71.9 vs. 51.5; IQR 29.5 to 75.3; p = 0.36). Activated oxygen protein products and oxidized low-density lipoprotein as markers for oxidative stress were reduced by as much as 20% in the N-acetylcysteine group (p < 0.05), whereas no change was evident in the placebo group. CONCLUSIONS High-dose intravenous N-acetylcysteine reduces oxidative stress. However, it does not provide an additional clinical benefit to placebo with respect to CIN and myocardial reperfusion injury in nonselected patients undergoing angioplasty with moderate doses of contrast medium and optimal hydration. (Myocardial Salvage and Contrast Dye Induced Nephropathy Reduction by N-Acetylcysteine [LIPSIA-N-ACC]; NCT00463749).

Diagnostic Performance of CMR Imaging Compared With EMB in Patients With Suspected Myocarditis

OBJECTIVES The goal of this study was to assess the diagnostic performance of cardiac magnetic resonance (CMR) compared with endomyocardial biopsy in patients with suspected acute myocarditis (AMC) and chronic myocarditis (CMC). BACKGROUND Several studies have reported an encouraging diagnostic performance of CMR in myocarditis. However, the comparison of CMR with clinical data only and the use of preselected patient populations are important limitations of the majority of these reports. METHODS One hundred thirty-two consecutive patients with suspected AMC (defined by symptoms ≤ 14 days; n = 70) and CMC (defined by symptoms >14 days; n = 62) were included. Patients underwent cardiac catheterization with left ventricular endomyocardial biopsy and CMR, including T(2)-weighted imaging for assessment of edema, T(1)-weighted imaging before and after contrast administration for evaluation of hyperemia, and assessment of late gadolinium enhancement. CMR results were considered to be consistent with the diagnosis of myocarditis if 2 of 3 CMR techniques were positive. RESULTS Within the total population, myocarditis was the most common diagnosis on endomyocardial biopsy analysis (62.9%). Viral genomes were detected in 30.3% (40 of 132) of patients within the total patient population and significantly more often in patients with AMC than CMC (40.0% vs. 19.4%; p = 0.013). For the overall cohort of patients with either suspected AMC or CMC, the diagnostic sensitivity, specificity, and accuracy of CMR were 76%, 54%, and 68%, respectively. The best diagnostic performance was observed in patients with suspected AMC (sensitivity, 81%; specificity, 71%; and accuracy, 79%). In contrast, diagnostic performance of CMR in suspected CMC was found to be unsatisfactory (sensitivity, 63%; specificity, 40%; and accuracy, 52%). CONCLUSIONS The results of this study underline the usefulness of CMR in patients with suspected AMC. In contrast, the diagnostic performance of CMR in patients with suspected CMC might not be sufficient to guide clinical management.

Relation between right ventricular enlargement, QRS duration, and right ventricular function in patients with tetralogy of Fallot and pulmonary regurgitation after surgical repair

OBJECTIVE In patients with repaired tetralogy of Fallot, to examine (1) a possible relation between right ventricular enlargement and QRS prolongation, and (2) the effect of right ventricular enlargement caused by pulmonary regurgitation on the right ventricular ejection fraction, evaluated by three dimensional echocardiography, and global function, evaluated by the myocardial performance index. DESIGN AND PATIENTS 40 patients with repaired tetralogy were studied. Right ventricular volumes were derived from three dimensional echocardiographic data after this method had been validated by comparison with magnetic resonance imaging in 21 patients. Ejection fraction was calculated from end diastolic and end systolic volumes. The Doppler derived myocardial performance index was measured in all patients. Measured data were correlated with QRS duration. SETTING Tertiary cardiac centre for congenital heart disease. RESULTS There was good agreement between three dimensional echocardiographic and magnetic resonance assessment of right ventricular volumes and ejection fraction. The z score of the right ventricular end diastolic volume and ejection fraction of all patients was 1.35 and −4.15, respectively. Patients with severe pulmonary regurgitation had a lower right ventricular ejection fraction (p < 0.01) and an increased myocardial performance index (p < 0.01) compared with patients with mild to moderate pulmonary regurgitation. The correlation between ejection fraction and right ventricular end diastolic volume wasr = −0.35 (p < 0.05). The mean (SD) QRS duration was 131.89 (25.69) ms, range 80–180 ms. The correlation between QRS duration and right ventricular end diastolic volume wasr = 0.6 (p < 0.01). CONCLUSIONS There is a correlation between the right ventricular size obtained by three dimensional echocardiography and QRS duration on the surface ECG, indicating mechanoelectrical interaction. The severity of pulmonary regurgitation has a negative influence on right ventricular ejection fraction and combined systolic and diastolic global function, as assessed by myocardial performance.

Prognostic Value and Determinants of a Hypointense Infarct Core in T2-Weighted Cardiac Magnetic Resonance in Acute Reperfused ST-Elevation Myocardial Infarction

Background—A hypointense core of infarcted myocardium in T2-weighted cardiovascular MRI (CMR) has been used as a noninvasive marker for intramyocardial hemorrhage. However, the clinical significance of such findings not yet been established. The aim of this study was to evaluate determinants and prognostic impact of a hypointense infarct core in T2-weighted CMR images, studied in patients after acute, reperfused ST-elevation–myocardial infarction. Methods and Results—We analyzed 346 patients with ST-elevation–myocardial infarction undergoing primary angioplasty <12 hours after symptoms onset. T2-weighted, contrast-enhanced CMR was used for assessment of the area at risk, myocardial salvage, infarct size, hypointense core in T2-weighted images, and late microvascular obstruction. Patients were categorized into 2 groups defined by the presence or absence of a hypointense core. The primary end point of the study was occurrence of major adverse cardiovascular events defined as death, reinfarction, and congestive heart failure within 6 months after infarction. A hypointense core was present in 122 (35%) patients and was associated with larger infarcts, greater amount of microvascular obstruction, less myocardial salvage, and impaired left ventricular function (P<0.001, respectively). The presence of a hypointense core was a strong univariable predictor of major adverse cardiovascular events (hazard ratio, 2.59; confidence interval, 1.27 to 5.27) and was significantly associated with an increased major adverse cardiovascular events rate (16.4% versus 7.0%, P=0.006) 6 months after infarction. Conclusions—A hypointense infarct core within the area at risk of reperfused infarcted myocardium in T2-weighted CMR is closely related to infarct size, microvascular obstruction, and impaired left ventricular function, with subsequent adverse clinical outcome.