Sebastian Kelle

Prognostic Value of Cardiac Magnetic Resonance Stress Tests Adenosine Stress Perfusion and Dobutamine Stress Wall Motion Imaging

Background— Adenosine stress magnetic resonance perfusion (MRP) and dobutamine stress magnetic resonance (DSMR) wall motion analyses are highly accurate for the detection of myocardial ischemia. However, knowledge about the prognostic value of stress MR examinations is limited. We sought to determine the value of MRP and DSMR, as assessed during a single-session examination, in predicting the outcome of patients with known or suspected coronary artery disease. Methods and Results— In 513 patients (with known or suspected coronary disease, prior coronary artery bypass graft, or percutaneous coronary intervention), a combined single-session magnetic resonance stress examination (MRP and DSMR) was performed at 1.5 T. For first-pass perfusion imaging, the standard adenosine stress imaging protocol (140 &mgr;g · kg−1 · min−1 for 6 minutes, 3-slice turbo field echo-echo-planar imaging or steady-state free precession sequence, 0.05 mmol/kg Gd-DTPA) was applied, and for DSMR, the standard high-dose dobutamine/atropine protocol (steady-state free-precession cine sequence) was applied. Stress testing was classified as pathological if at MRP ≥1 segment showed an inducible perfusion deficit >25% transmurality or if at DSMR ≥1 segment showed an inducible wall motion abnormality. During a median follow-up of 2.3 years (range, 0.06 to 4.55 years), 19 cardiac events occurred (4.1%; 9 cardiac deaths, 10 nonfatal myocardial infarctions). The 3-year event-free survival was 99.2% for patients with normal MRP and DSMR and 83.5% for those with abnormal MRP and DSMR. Univariate analysis showed ischemia identified by MRP and DSMR to be predictive of cardiac events (hazard ratio, 12.51; 95% confidence interval, 3.64 to 43.03; and hazard ratio, 5.42; 95% confidence interval, 2.18 to 13.50; P<0.001, respectively); other predictors were diabetes mellitus, known coronary artery disease, and the presence of resting wall motion abnormality. By multivariate analysis, ischemia on magnetic resonance stress testing (MRP or DSMR) was an independent predictor of cardiac events. In a stepwise multivariate model (Cox regression), an abnormal magnetic resonance stress test result had significant incremental value over clinical risk factors and resting wall motion abnormality (P<0.001). Conclusions— In patients with known or suspected coronary artery disease, myocardial ischemia detected by MRP and DSMR can be used to identify patients at high risk for subsequent cardiac death or nonfatal myocardial infarction. For patients with normal MRP and DSMR, the 3-year event-free survival was 99.2%. MR stress testing provides important incremental information over clinical risk factors and resting wall motion abnormalities.

Prognostic Value of Myocardial Infarct Size and Contractile Reserve Using Magnetic Resonance Imaging

OBJECTIVES Our aim was to assess the predictive value of myocardial infarct size assessed with late gadolinium-enhanced (LGE) magnetic resonance imaging (MRI) in medically treated patients with chronic myocardial infarction relative to contractile reserve on low-dose dobutamine magnetic resonance (DSMR) for long-term event-free survival. BACKGROUND Information on the relative merits of scar tissue and contractile reserve to predict long-term prognosis in patients with chronic myocardial infarction is lacking. METHODS A total of 177 patients with known coronary artery disease and scar tissue on LGE MRI were enrolled. Left ventricular (LV) functional parameters at rest and during low-dose DSMR were assessed, and the wall motion score index was calculated. RESULTS Eleven patients (6.2%) suffered an event during follow-up (average 20.3 months). Infarct size was a stronger predictor of events than LV ejection fraction and LV volumes at rest and during low-dose DSMR. Myocardial infarct size was used to separate patients at high risk (spatial extent > or =6 segments, n = 98) from those at low risk (spatial extent <6 segments, n = 79) for mortality. In the subgroup of patients at high risk, transmurality of infarct was not a predictor of events. However, the presence of contractile reserve (n = 63) was associated with a significantly higher number of events (12.7%) compared with no change in wall motion score index (6.7%; n = 15; p = 0.008). CONCLUSIONS Myocardial infarct size on LGE MRI is a stronger predictor of clinical outcome than contractile reserve in medically treated patients with myocardial infarction. In patients with large myocardial scar, the presence of contractile reserve is more important for the prediction of events than scar tissue.

T1-Mapping and Outcome in Nonischemic Cardiomyopathy: All-Cause Mortality and Heart Failure

OBJECTIVES The study sought to examine prognostic relevance of T1 mapping parameters (based on a T1 mapping method) in nonischemic dilated cardiomyopathy (NIDCM) and compare them with conventional markers of adverse outcome. BACKGROUND NIDCM is a recognized cause of poor clinical outcome. NIDCM is characterized by intrinsic myocardial remodeling due to complex pathophysiological processes affecting myocardium diffusely. Lack of accurate and noninvasive characterization of diffuse myocardial disease limits recognition of early cardiomyopathy and effective clinical management in NIDCM. Cardiac magnetic resonance (CMR) supports detection of diffuse myocardial disease by T1 mapping. METHODS This is a prospective observational multicenter longitudinal study in 637 consecutive patients with dilated NIDCM (mean age 50 years [interquartile range: 37 to 76 years]; 395 males [62%]) undergoing CMR with T1 mapping and late gadolinium enhancement (LGE) at 1.5-T and 3.0-T. The primary endpoint was all-cause mortality. A composite of heart failure (HF) mortality and hospitalization was a secondary endpoint. RESULTS During a median follow-up period of 22 months (interquartile range: 19 to 25 months), we observed a total of 28 deaths (22 cardiac) and 68 composite HF events. T1 mapping indices (native T1 and extracellular volume fraction), as well as the presence and extent of LGE, were predictive of all-cause mortality and HF endpoint (p < 0.001 for all). In multivariable analyses, native T1 was the sole independent predictor of all-cause and HF composite endpoints (hazard ratio: 1.1; 95% confidence interval: 1.06 to 1.15; hazard ratio: 1.1; 95% confidence interval: 1.05 to 1.1; p < 0.001 for both), followed by the models including the extent of LGE and right ventricular ejection fraction, respectively. CONCLUSIONS Noninvasive measures of diffuse myocardial disease by T1 mapping are significantly predictive of all-cause mortality and HF events in NIDCM. We provide a basis for a novel algorithm of risk stratification in NIDCM using a complementary assessment of diffuse and regional disease by T1 mapping and LGE, respectively.

Noninvasive visualization of coronary artery endothelial function in healthy subjects and in patients with coronary artery disease.

OBJECTIVES The goal was to test 2 hypotheses: first, that coronary endothelial function can be measured noninvasively and abnormal function detected using clinical 3.0-T magnetic resonance imaging (MRI); and second, that the extent of local coronary artery disease (CAD), in a given patient, is related to the degree of local abnormal coronary endothelial function. BACKGROUND Abnormal endothelial function mediates the initiation and progression of atherosclerosis and predicts cardiovascular events. However, direct measures of coronary endothelial function have required invasive assessment. METHODS The MRI was performed in 20 healthy adults and 17 patients with CAD. Cross-sectional coronary area and blood flow were quantified before and during isometric handgrip exercise, an endothelial-dependent stressor. In 10 severe, single-vessel CAD patients, paired endothelial function was measured in the artery with severe stenosis and the contralateral artery with minimal disease. RESULTS In healthy adults, coronary arteries dilated and flow increased with stress. In CAD patients, coronary artery area and blood flow decreased with stress (both p ≤ 0.02). In the paired study, coronary artery area and blood flow failed to increase during exercise in the mildly diseased vessel, but both area (p = 0.01) and blood flow (p = 0.02) decreased significantly in the severely diseased, contralateral artery. CONCLUSIONS Endothelial-dependent coronary artery dilation and increased blood flow in healthy subjects, and their absence in CAD patients, can now be directly visualized and quantified noninvasively. Local coronary endothelial function differs between severely and mildly diseased arteries in a given CAD patient. This novel, safe method may offer new insights regarding the importance of local coronary endothelial function and improved risk stratification in patients at risk for and with known CAD.

Effect of renal denervation on left ventricular mass and function in patients with resistant hypertension: data from a multi-centre cardiovascular magnetic resonance imaging trial

AIMS Sympathetic stimulation induces left ventricular hypertrophy and is associated with increased cardiovascular risk. Catheter-based renal denervation (RDN) has been shown to reduce sympathetic outflow and blood pressure (BP). The present multi-centre study aimed to investigate the effect of RDN on anatomic and functional myocardial parameters, assessed by cardiac magnetic resonance (CMR), in patients with resistant hypertension. METHODS AND RESULTS Cardiac magnetic resonance was performed in 72 patients (mean age 66 ± 10 years) with resistant hypertension (55 patients underwent RDN, 17 served as controls) at baseline and after 6 months. Clinical data and CMR results were analysed blindly. Renal denervation significantly reduced systolic and diastolic BP by 22/8 mm Hg and left ventricular mass index (LVMI) by 7.1% (46.3 ± 13.6 g/m(1.7) vs. 43.0 ± 12.6 g/m(1.7), P < 0.001) without changes in the control group (41.9 ± 10.8 g/m(1.7) vs. 42.0 ± 9.7 g/m(1.7), P = 0.653). Ejection fraction (LVEF) in patients with impaired LVEF at baseline (<50%) significantly increased after RDN (43% vs. 50%, P < 0.001). Left ventricular circumferential strain as a surrogate of diastolic function in the subgroup of patients with reduced strain at baseline increased by 21% only in the RDN group (-14.8 vs. -17.9; P = 0.001) and not in control patients (-15.5 vs. -16.4, P = 0.508). CONCLUSIONS Catheter-based RDN significantly reduced BP and LVMI and improved EF and circumferential strain in patients with resistant hypertension, occurring partly BP independently.

A Prospective Study for Comparison of MR and CT Imaging for Detection of Coronary Artery Stenosis

OBJECTIVES the purpose of the present study was to directly compare the diagnostic accuracy of magnetic resonance imaging (MRI) and multislice computed tomography (CT) for the detection of coronary artery stenosis. BACKGROUND both imaging modalities have emerged as potential noninvasive coronary imaging modalities; however, CT-unlike MRI-exposes patients to radiation and iodinated contrast agent. METHODS one hundred twenty consecutive patients with suspected or known coronary artery disease prospectively underwent 32-channel 3.0-T MRI and 64-slice CT before elective X-ray angiography. The diagnostic accuracy of the 2 modalities for detecting significant coronary stenosis (≥ 50% luminal diameter stenosis) in segments ≥ 1.5 mm diameter was compared with quantitative invasive coronary angiography as the reference standard. RESULTS in the patient-based analysis MRI and CT angiography showed similar diagnostic accuracy of 83% (95% confidence interval [CI]: 75 to 87) versus 87% (95% CI: 80 to 92), p = 0.38; sensitivity of 87% (95% CI: 76 to 93) versus 90% (95% CI: 80 to 95), p = 0.16; and specificity of 77% (95% CI: 63 to 87) versus 83% (95% CI: 70 to 91), p = 0.06, respectively. All cases of left main or 3-vessel disease were correctly diagnosed by MRI and CT angiography. In the patient-based analysis MRI and CT angiography were similar in their ability to identify patients who subsequently underwent revascularization: the area under the receiver-operator characteristic curve was 0.78 (95% CI: 0.69 to 0.87) for MRI and 0.82 (95% CI: 0.74 to 0.90) for CT angiography. CONCLUSIONS thirty-two channel 3.0-T MRI and 64-slice CT angiography similarly identify significant coronary stenosis in patients with suspected or known coronary artery disease scheduled for elective coronary angiography. However, CT angiography showed a favorable trend toward higher diagnostic performance.

Visualization of the Cardiac Venous System Using Cardiac Magnetic Resonance

We sought to investigate the value of cardiac magnetic resonance to depict cardiac venous anatomy. For cardiac resynchronization therapy the lead for the left ventricle is usually placed by transvenous approach into a tributary of the coronary sinus (CS). Knowledge of the anatomy and variations of the cardiac venous system may facilitate the positioning of the left ventricle lead. The cardiac magnetic resonance examinations of 23 subjects (16 volunteers and 7 patients) were retrospectively analyzed. All examinations were performed using navigator-gated whole-heart steady-state free precession coronary artery imaging after administration of intravascular contrast agents (gadofosveset in volunteers; Gadomer-17 in patients). The cardiac venous system was visualized in all subjects. The most frequent anatomical variant observed (in 12 subjects [52%]) was a connection of the small cardiac vein to the CS at the crux cordis. In 10 subjects (44%) the small veins entered the right atrium independently from the CS, and the posterior interventricular vein was connected to the CS at the crux cordis. Only one subject had a disconnection between the CS and posterior interventricular vein, which entered into the right atrium independently. The mean distance of the posterior vein of the left ventricle and the left marginal vein to the ostium of the CS was 15.2+/-4.7 mm and 49.7+/-14.1 mm, respectively. In conclusion, the anatomy of the cardiac venous system and its anatomical variability can be described using cardiac magnetic resonance. Its preimplantation visualization may help to facilitate the implant procedure and to reduce fluoroscopy time.

Diagnostic Performance of Myocardial Perfusion MR at 3 T in Patients with Coronary Artery Disease

PURPOSE To prospectively determine the diagnostic performance of myocardial perfusion magnetic resonance (MR) imaging at 3 T for helping depict clinically relevant coronary artery stenosis (> or =50% diameter) in patients with suspected or known coronary artery disease (CAD), with coronary angiography as the reference standard. MATERIALS AND METHODS The study was approved by the local ethics committee; written informed consent was obtained. Vasodilator stress perfusion imaging by using a turbo field-echo sequence was obtained in 101 patients (71 men, 30 women; mean age, 62 years +/- 7.7 [standard deviation]) scheduled for coronary angiography. Myocardial ischemia was defined as stress-inducible perfusion deficit in arterial territories without delayed enhancement (DE) or additional stress-inducible perfusion deficit in territories with nontransmural DE. Images were evaluated in consensus by two blinded readers. Diagnostic performance was determined on per-patient and per-coronary artery territory bases. The number of dark rim artifacts in patients without DE was determined in a second read. Interobserver variability was assessed in 40 randomly selected patients. RESULTS One hundred one patients underwent MR examinations. Coronary angiography depicted relevant stenosis in 70 (69%) patients. Patient-based sensitivity and specificity were 90% and 71%, respectively. Sensitivity, specificity, and diagnostic accuracy for the detection of coronary stenosis in a specific territory were 76%, 89%, and 86%, respectively. In 24% of patients without DE, dark rim artifacts were detected, mostly in the left anterior descending artery territory (56%). In 40 randomly selected patients, there was agreement in the determination of myocardial perfusion deficits in 37 (93%, kappa = 0.79) patients. CONCLUSION Myocardial perfusion MR imaging by using saturation-recovery spoiled gradient-echo imaging at 3 T has an accuracy of 84% for depicting hemodynamically relevant coronary artery stenosis in patients with suspected and known CAD.

T1 Mapping in Discrimination of Hypertrophic Phenotypes: Hypertensive Heart Disease and Hypertrophic Cardiomyopathy Findings From the International T1 Multicenter Cardiovascular Magnetic Resonance Study

Background— The differential diagnosis of left ventricular (LV) hypertrophy remains challenging in clinical practice, in particular, between hypertrophic cardiomyopathy (HCM) and increased LV wall thickness because of systemic hypertension. Diffuse myocardial disease is a characteristic feature in HCM, and an early manifestation of sarcomere–gene mutations in subexpressed family members (G+P− subjects). This study aimed to investigate whether detecting diffuse myocardial disease by T1 mapping can discriminate between HCM versus hypertensive heart disease as well as to detect genetically driven interstitial changes in the G+P− subjects. Methods and Results— Patients with diagnoses of HCM or hypertension (HCM, n=95; hypertension, n=69) and G+P− subjects (n=23) underwent a clinical cardiovascular magnetic resonance protocol (3 tesla) for cardiac volumes, function, and scar imaging. T1 mapping was performed before and >20 minutes after administration of 0.2 mmol/kg of gadobutrol. Native T1 and extracellular volume fraction were significantly higher in HCM compared with patients with hypertension ( P 15 mm ( P 2 SD above the mean of the normal range. Native T1 was an independent discriminator between HCM and hypertension, over and above extracellular volume fraction, LV wall thickness and indexed LV mass. Native T1 was also useful in separating G+P− subjects from controls. Conclusions— Native T1 may be applied to discriminate between HCM and hypertensive heart disease and detect early changes in G+P− subjects.Background—The differential diagnosis of left ventricular (LV) hypertrophy remains challenging in clinical practice, in particular, between hypertrophic cardiomyopathy (HCM) and increased LV wall thickness because of systemic hypertension. Diffuse myocardial disease is a characteristic feature in HCM, and an early manifestation of sarcomere–gene mutations in subexpressed family members (G+P− subjects). This study aimed to investigate whether detecting diffuse myocardial disease by T1 mapping can discriminate between HCM versus hypertensive heart disease as well as to detect genetically driven interstitial changes in the G+P− subjects. Methods and Results—Patients with diagnoses of HCM or hypertension (HCM, n=95; hypertension, n=69) and G+P− subjects (n=23) underwent a clinical cardiovascular magnetic resonance protocol (3 tesla) for cardiac volumes, function, and scar imaging. T1 mapping was performed before and >20 minutes after administration of 0.2 mmol/kg of gadobutrol. Native T1 and extracellular volume fraction were significantly higher in HCM compared with patients with hypertension (P<0.0001), including in subgroup comparisons of HCM subjects without evidence of late gadolinium enhancement, as well as of hypertensive patients LV wall thickness of >15 mm (P<0.0001). Compared with controls, native T1 was significantly higher in G+P− subjects (P<0.0001) and 65% of G+P− subjects had a native T1 value >2 SD above the mean of the normal range. Native T1 was an independent discriminator between HCM and hypertension, over and above extracellular volume fraction, LV wall thickness and indexed LV mass. Native T1 was also useful in separating G+P− subjects from controls. Conclusions—Native T1 may be applied to discriminate between HCM and hypertensive heart disease and detect early changes in G+P− subjects.

Long-Term Prognostic Value of Dobutamine Stress CMR

OBJECTIVES The aim of this study was to assess the long-term value of high-dose dobutamine cardiac magnetic resonance (DCMR) for the prediction of cardiac events in a large cohort of patients with known or suspected coronary artery disease. BACKGROUND High-dose DCMR has been shown to be a useful technique for diagnosis and intermediate-term prognostic stratification. METHODS Clinical data and DCMR results were analyzed in 1,463 consecutive patients undergoing DCMR between 2000 and 2004. Ninety-four patients were lost to follow-up. The remaining 1,369 patients were followed up for a mean of 44 ± 24 months. Cardiac events, defined as cardiac death and nonfatal myocardial infarction, were related to clinical and DCMR results. RESULTS Three-hundred fifty-two patients underwent early revascularization (≤ 3 months of DCMR) and were excluded from analysis. Of the remaining 1,017 patients, 301 patients (29.6%) experienced inducible wall motion abnormalities (WMA). Forty-six cardiac events were reported. In those with and without inducible WMA, the proportion of patients with cardiac events was 8.0% versus 3.1%, respectively, p = 0.001 (hazard ratio: 3.3; 95% confidence interval: 1.8 to 5.9 for the presence of inducible WMA; p < 0.001). A DCMR without inducible WMA carried an excellent prognosis, with a 6-year cardiac event-free survival of 96.8%. In all 1,369 patients in the patient group with stress-inducible WMA, those patients with medical therapy demonstrated a trend to a higher cardiac event rate (8.0%) than those with early revascularization (5.4%) (p = 0.234). Patients with normal DCMR and medical therapy or early revascularization demonstrated similar cumulative cardiac event rates (3.1% vs. 3.2%, p = 0.964). CONCLUSIONS In a large cohort of patients, DCMR has an added value for predicting cardiac events during long-term follow-up, improving the differentiation between high-risk and low-risk patients. Patients with inducible WMA and following early revascularization, demonstrate lower cardiac event rates than patients with medical therapy alone.