Nico Merkle

Results of Intracoronary Stem Cell Therapy After Acute Myocardial Infarction

To assess the effect of autologous bone-marrow cell (BMC) therapy in patients with acute myocardial infarction in a rigorous double-blind, randomized, placebo-controlled trial. Patients with reperfusion >6 hours after symptom onset were randomly assigned in a 2:1 ratio to receive intracoronary BMC or placebo therapy 5 to 7 days after symptom onset. The patients were stratified according to age, acute myocardial infarction localization, and left ventricular (LV) function. Rigorous double-blinding was ensured using autologous erythrocytes for the placebo preparation that was visually indistinguishable from the active treatment. Serial cardiac magnetic resonance imaging studies were performed before study therapy and after 1, 3, and 6 months. The primary end point was the difference in the LV ejection fraction from baseline to 6 months. The secondary end points included changes in the LV end-diastolic and end-systolic volume indexes and infarct size. A total of 42 patients were enrolled (29 in the BMC group and 13 in the placebo group) in the integrated pilot phase. A mean of 381 x 10(6) mononuclear BMCs were administered. The baseline clinical and cardiac magnetic resonance imaging parameters did not differ. Compared to baseline, the difference in LV ejection fraction for the placebo group versus BMC group was 1.7 +/- 6.4% versus -0.9 +/- 5.5% at 1 month, 3.1 +/- 6.0% versus 1.9 +/- 4.3% at 3 months, and 5.7 +/- 8.4% versus 1.8 +/- 5.3% at 6 months (primary end point; not significant). No difference was found in the secondary end points between the 2 groups, including changes in infarct size or LV end-diastolic and end-systolic volume indexes. In conclusion, in this rigorous double-blind, randomized, placebo-controlled trial, we did not observe an evidence for a positive effect for intracoronary BMC versus placebo therapy with respect to LV ejection fraction, LV volume indexes, or infarct size.

Electrocardiographic and cardiac magnetic resonance imaging parameters as predictors of a worse outcome in patients with idiopathic dilated cardiomyopathy

Aims Clinical parameters are weak predictors of outcome in patients with idiopathic dilated cardiomyopathy (IDC). We assessed the prognostic value of cardiac magnetic resonance (CMR) parameters in addition to conventional clinical and electrocardiographic characteristics. Methods and results One hundred and forty-one IDC patients were studied. QRS and QTc intervals were measured in 12-lead surface electrocardiogram. Patients were followed for median 1339 days, including 483 patient-years. The primary endpoint—cardiac death or sudden death—occurred in 25 (18%) patients, including 16 patients with cardiac death, 3 patients with sudden cardiac death (SCD), and 6 patients with ICD shock. Late gadolinium enhancement (LGE) was detected in 36 patients (26%). Kaplan–Meier survival analysis displayed QRS >110 ms (P = 0.010), the presence of LGE (P = 0.037), and diabetes mellitus (P < 0.001) as significant parameters for a worse outcome. Multivariable analysis revealed cardiac index (P < 0.001), right ventricular end-diastolic volume index (RVEDVI) (P = 0.006) derived from CMR imaging, the presence of diabetes mellitus (P = 0.006), and QRS >110 ms (P = 0.045) as significant predictors for the primary endpoint. Conclusion Cardiac index and RVEDVI derived from CMR imaging in addition to QRS duration >110 ms from conventional surface ECG and diabetes mellitus provide prognostic impact for cardiac death and SCD in patients with IDC.

Assessment of Left Ventricular Outflow Tract Geometry in Non-Stenotic and Stenotic Aortic Valves by Cardiovascular Magnetic Resonance

PURPOSE To assess the geometry and area of the left ventricular outflow tract (LVOT) in non-stenotic and stenotic aortic valves and to determine the aortic valve area (AVA) in non-stenotic valves by magnetic resonance imaging (MRI) using a modified continuity equation. METHODS Twenty patients (10 male, mean age 54.8 +/- 15 years) without known aortic valve disease and 10 patients (7 male, mean age 65.1 +/- 14 years) with moderate to severe aortic stenosis were included in this study. MRI was performed using a 1.5 T scanner (Philips Intera CV). AVA was assessed by planimetry on high quality SSFP cine sequences and used as reference standard. LVOT area was defined by calculating a circular area using the LVOT diameter from the 3 chamber view (3CV) and by planimetry. Peak flow velocity was assessed in the LVOT and the proximal aorta. AVA was calculated by a modified Gorlin equation, the continuity equation and a modified continuity equation using the planimetric LVOT area. RESULTS Planimetric AVA ranged from 2.9 to 6.4 cm2 in patients with non-stenotic and from 0.3 to 1.3 cm2 with stenotic valves, LVOT area from 3.4 to 6.1 cm2 and from 2.6 to 6.5 cm2, respectively. The LVOT area based on the LVOT diameter derived from the 3CV was significantly underestimated in comparison to planimetry in non-stenotic and stenotic aortic valves (3.3 +/- 0.7 vs. 4.7 +/- 1.0 cm2, p < 0.0001; mean difference 1.1 +/- 0.12 cm2, CI 0.86-1.36 and 3.7 +/- 1.2 vs. 4.7 +/- 1.5 cm2, p < 0.05; mean difference 1.0 +/- 1.0 cm2, CI 0.24-1.71). The Gorlin formula showed a poor agreement with planimetry, whereas continuity equation and the modified continuity equation revealed a very good agreement. Planimetry of the LVOT displayed an elliptic shape of the LVOT in all patients with the minimum diameter perpendicular to the 3CV, which was the reason for the above mentioned underestimation. CONCLUSION The LVOT area calculated from the 3CV-LVOT diameter underestimates the LVOT area compared to planimetry due to an elliptic shape of the LVOT in patients with non-stenotic as well as with stenotic aortic valves. The modified Gorlin equation proved to be less useful to assess AVA in non-stenotic valves, whereas the continuity equation and a modified continuity equation displayed a very good agreement with planimetric area measurements.

Myocardial biopsy findings and gadolinium enhanced cardiovascular magnetic resonance in dilated cardiomyopathy

In some patients suffering from dilated cardiomyopathy (DCM) magnetic resonance imaging (MRI) shows late gadolinium enhancement with variable distribution. Myocardial biopsies in DCM reveal a chronic myocardial inflammatory process in almost 50% and myocardial persistence of adenoviral or enteroviral genome in about 15% of the patients.

Assessment of myocardial perfusion for detection of coronary artery stenoses by steady-state, free-precession magnetic resonance first-pass imaging.

Objective: To evaluate the diagnostic impact of magnetic resonance imaging (MRI) first-pass perfusion using steady-state, free-precession (SSFP) sequences with parallel imaging (SENSE) for detection of coronary stenoses. Design: Prospective observational study. Setting: University hospital, cardiac MRI and catheterisation laboratories. Patients and methods: 228 patients were examined with coronary angiography and MRI (1.5 T Intera CV). A three-slice, short-axis SSFP perfusion scan with a saturation prepulse was performed during infusion of adenosine and at rest followed by myocardial scar (late enhancement) imaging. Gadolinium-DTPA was given at 0.1 mmol/kg body weight. Perfusion images were visually assessed. Analysis for myocardial hypoperfusion was done according to patient group and according to vessel. Results: Sensitivity, specificity and accuracy of MRI first-pass perfusion for detection of a coronary artery stenosis (>50% luminal narrowing) in the total patient group were 93.0%, 85.7%, 91.2% and for a significant lesion (>70% luminal narrowing) 96.1%, 72.0%, 88.2%, respectively. Based on 536 coronary artery territories without myocardial scar, the sensitivity of MRI perfusion analysis for detection of a significant lesion was for the left anterior descending artery 91.4%, for the circumflex artery 81.6% and for the right coronary artery 65.1% (p<0.001). Conclusions: MRI first-pass perfusion analysis using an SSFP sequence with three myocardial slices was a highly accurate diagnostic method for detection of coronary artery stenoses. This MRI technique can be included in daily practice and has the potential to guide the indication for invasive coronary angiography.

Whole-heart coronary vein imaging: a comparison between non-contrast-agent- and contrast-agent-enhanced visualization of the coronary venous system.

The feasibility of three‐dimensional (3D) whole‐heart imaging of the coronary venous (CV) system was investigated. The hypothesis that coronary magnetic resonance venography (CMRV) can be improved by using an intravascular contrast agent (CA) was tested. A simplified model of the contrast in T2‐prepared steady‐state free precession (SSFP) imaging was applied to calculate optimal T2‐preparation durations for the various deoxygenation levels expected in venous blood. Non‐contrast‐agent (nCA)‐ and CA‐enhanced images were compared for the delineation of the coronary sinus (CS) and its main tributaries. A quantitative analysis of the resulting contrast‐to‐noise ratio (CNR) and signal‐to‐noise ratio (SNR) in both approaches was performed. Precontrast visualization of the CV system was limited by the poor CNR between large portions of the venous blood and the surrounding tissue. Postcontrast, a significant increase in CNR between the venous blood and the myocardium (Myo) resulted in a clear delineation of the target vessels. The CNR improvement was 347% (P < 0.05) for the CS, 260% (P < 0.01) for the mid cardiac vein (MCV), and 430% (P < 0.05) for the great cardiac vein (GCV). The improvement in SNR was on average 155%, but was not statistically significant for the CS and the MCV. The signal of the Myo could be significantly reduced to about 25% (P < 0.001). Magn Reson Med 57:1019–1026, 2007.

Myocardial Perfusion Reserve in Cardiovascular Magnetic Resonance: Correlation to Coronary Microvascular Dysfunction

The present study examined the association of myocardial perfusion reserve index (MPRI) in cardiovascular magnetic resonance (CMR) with coronary microvascular dysfunction (CMD) and serum levels of markers of inflammation or endothelial activation. Twelve patients with typical angina pectoris without coronary artery disease were enrolled in this study, and CMR perfusion was analyzed using a steady-state-free-precession sequence with 3 short axis slices per heartbeat during first pass of 0.025 mmol Gadolinium-DTPA/kg body weight. The upslope of myocardial signal intensity curves was used to calculate MPRI. CMD was assessed by intracoronary Doppler flow measurement and biplane angiography. Both MPRI and CMD were assessed during endothelium-independent stimulation with intravenous adenosine and during endothelium-dependent stimulation with intracoronary infusion of acetylcholine. Serum values of soluble CD40 ligand (sCD40L), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble intercellular adhesion molecule-1 (sICAM-1), and C-reactive protein (CRP) were measured. Impaired MPRI correlated significantly with a decrease in coronary blood flow reserve after both endothelium-dependent (p = 0.033) and endothelium-independent (p = 0.022) stimulation. Serum levels above the median of all normal ranged biomarkers sCD40L, TNF-alpha, IL-6, sICAM-1 and CRP were associated with an impaired MPRI for stimulation with adenosine as well as acetylcholine. In multivariable analyses, sCD40L (p < 0.001) and TNF-alpha (p = 0.011) were significantly associated with a decrease in MPRI on adenosine, as were TNF-alpha (p = 0.016) and sICAM-1 (p = 0.022) for a decrease in MPRI on acetylcholine. MPRI on adenosine significantly correlated with MPRI on acetylcholine (p < 0.001). Therefore, the present study demonstrates safety and feasibility of an intracoronary infusion of acetylcholine during CMR perfusion analysis, thus allowing direct assessment of endothelial dependent vasomotor function at the myocardial level by CMR. Furthermore, we show that an impaired myocardial perfusion reserved in CMR is associated with established biomarkers of early atherosclerosis and significantly correlated with CMD. CMR combined with adenosine could be proposed as a non-invasive tool to evaluate CMD.

Magnetic resonance imaging to assess acute changes in atrial and ventricular parameters after transcatheter closure of atrial septal defects

To evaluate acute changes in atrial and ventricular parameters by the use of cardiac magnetic resonance imaging (MRI) in patients with percutaneous transcatheter atrial septal defects (ASD) closure.

Prevalence of Myocardial Scar in Patients With Cryptogenic Cerebral Ischemic Events and Patent Foramen Ovale

OBJECTIVES This study sought to evaluate the prevalence of subclinical myocardial infarctions with cardiovascular magnetic resonance imaging (CMRI) in patients with patent foramen ovale (PFO) after cryptogenic cerebral ischemic events. BACKGROUND A thrombotic mass passing a PFO may embolize in cerebral but also in coronary arteries, resulting in both cerebral and myocardial ischemic events. CMRI with late gadolinium enhancement (LGE) analysis is the most sensitive imaging technique to detect small myocardial infarctions. METHODS PFO patients (n = 74) with a first cryptogenic cerebral ischemic event without a clinical history for myocardial infarction underwent CMRI and coronary angiography. Right and left ventricular volumes and ejection fractions were measured by CMRI. LGE imaging was performed after administration of gadolinium-diethylenetriaminepentaacetic acid. The presence of atrial septal aneurysm (ASA) was evaluated by transesophageal echocardiography. RESULTS LGE was detected in 8 of 74 (10.8%) patients. LGE pattern was transmural or subendocardial. Patients with LGE and those without did not differ in cardiovascular risk factors, type of ischemic event, presence of ASA, right and left ventricular volumes, and ejection fractions. LGE volume was small and comprised only 7.9 +/- 2.4% of left ventricular muscle mass. Coronary artery disease was ruled out in 7 of 8 patients with LGE. There was a trend towards a larger PFO size in patients with LGE compared with patients without LGE (13.2 +/- 4.1 mm vs. 16.0 +/- 2.8 mm, p = 0.06). CONCLUSIONS Subclinical myocardial infarctions determined in CMRI were observed in 10.8% of patients with PFO after a first cryptogenic cerebral ischemic event. Our results strengthen the pathophysiologic role of a PFO with paradoxical embolism in patients with cryptogenic cerebral ischemic events.

Volume‐targeted and whole‐heart coronary magnetic resonance angiography using an intravascular contrast agent

To compare volume‐targeted and whole‐heart coronary magnetic resonance angiography (MRA) after the administration of an intravascular contrast agent.