Randomized, controlled trial of ultrasound-assisted catheter-directed thrombolysis for acute intermediate-risk pulmonary embolism.

BACKGROUND: In patients with acute pulmonary embolism, systemic thrombolysis improves right ventricular (RV) dilatation, is associated with major bleeding, and is withheld in many patients at risk. This multicenter randomized, controlled trial investigated whether ultrasound-assisted catheter-directed thrombolysis (USAT) is superior to anticoagulation alone in the reversal of RV dilatation in intermediate-risk patients. METHODS AND RESULTS: Fifty-nine patients (63±14 years) with acute main or lower lobe pulmonary embolism and echocardiographic RV to left ventricular dimension (RV/LV) ratio ≥1.0 were randomized to receive unfractionated heparin and an USAT regimen of 10 to 20 mg recombinant tissue plasminogen activator over 15 hours (n=30; USAT group) or unfractionated heparin alone (n=29; heparin group). Primary outcome was the difference in the RV/LV ratio from baseline to 24 hours. Safety outcomes included death, major and minor bleeding, and recurrent venous thromboembolism at 90 days. In the USAT group, the mean RV/LV ratio was reduced from 1.28±0.19 at baseline to 0.99±0.17 at 24 hours (P<0.001); in the heparin group, mean RV/LV ratios were 1.20±0.14 and 1.17±0.20, respectively (P=0.31). The mean decrease in RV/LV ratio from baseline to 24 hours was 0.30±0.20 versus 0.03±0.16 (P<0.001), respectively. At 90 days, there was 1 death (in the heparin group), no major bleeding, 4 minor bleeding episodes (3 in the USAT group and 1 in the heparin group; P=0.61), and no recurrent venous thromboembolism. CONCLUSIONS: In patients with pulmonary embolism at intermediate risk, a standardized USAT regimen was superior to anticoagulation with heparin alone in reversing RV dilatation at 24 hours, without an increase in bleeding complications. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01166997.

Acute outcomes of MitraClip therapy for mitral regurgitation in high-surgical-risk patients: emphasis on adverse valve morphology and severe left ventricular dysfunction.

AIMS: We sought to assess the feasibility of catheter-based mitral valve repair using the MitraClip system in high-surgical-risk patients with mitral regurgitation (MR) > or =grade 3+. METHODS AND RESULTS: MitraClip therapy was performed in 51 consecutive patients [73 +/- 10 years; 34 (67%) men] with symptomatic functional [n = 35 (69%)] or organic MR [n = 16 (31%)]. Mean logistic EuroSCORE was 29 +/- 22%; Society of Thoracic Surgeons score was 15 +/- 11. Left ventricular (LV) ejection fraction was 36 +/- 17%. In 35 patients (69%), adverse mitral valve morphology and/or severe LV dysfunction were present. MitraClip implantation was successful in 49 patients (96%). Most patients [n = 34/49 (69%)] were treated with a single clip, whereas 14 patients (29%) received two clips and one patient received three clips. Mean device and fluoroscopy times were 105 +/- 65 min and 44 +/- 28 min, respectively. Procedure-related reduction in MR severity was one grade in 16 patients (31%), two grades in 24 patients (47%), and three grades in 9 patients (18%). Forty-four of the 49 successfully treated patients (90%) showed clinical improvement at discharge [NYHA functional class > or =III in 48 patients (98%) before and 16 patients (33%) after the procedure (P < 0.0001)]. There were no procedure-related major adverse events and no in-hospital mortality. CONCLUSION: Mitral valve repair using the MitraClip system was shown to be feasible in patients at high surgical risk primarily determined by an adverse mitral valve morphology and/or severe LV dysfunction.

Interventricular mechanical dyssynchrony: quantification with velocity-encoded MR imaging.

PURPOSE: To evaluate the performance of velocity-encoded (VENC) magnetic resonance (MR) imaging, as compared with pulsed-wave echocardiography (PW-ECHO), in the quantification of interventricular mechanical dyssynchrony (IVMD) as a predictor of response to cardiac resynchronization therapy (CRT). MATERIALS AND METHODS: The study was approved by the local ethics committee, and all patients provided written informed consent. The study involved the examination of 45 patients (nine women, 36 men; median age, 60 years; interquartile age range, 47-69 years) with New York Heart Association class 2.0-3.0 heart failure and a reduced left ventricular ejection fraction (median, 25%; interquartile range, 21%-32%), with (n = 25) or without (n = 20) left bundle branch block. Aortic and pulmonary flow curves were constructed by using VENC MR imaging and PW-ECHO. IVMD was defined as the difference between the onset of aortic flow and the onset of pulmonary flow. Intraclass correlation coefficient, Spearman correlation coefficient, Bland-Altman, and Cohen kappa analyses were used to assess agreement between observers and methods. RESULTS: Inter- and intraobserver agreement regarding VENC MR imaging IVMD measurements was very good (intraclass r = 0.96, P < .001; mean bias, -3 msec +/- 11 [standard deviation] and 0 msec +/- 10, respectively). A strong correlation (Spearman r = 0.92, P < .001) and strong agreement (mean difference, -6 msec +/- 16) were found between VENC MR imaging and PW-ECHO in the quantification of IVMD. Agreement between VENC MR imaging and PW-ECHO in the identification of potential responders to CRT was excellent (Cohen kappa = 0.94). CONCLUSION: VENC MR measurements of IVMD are equivalent to PW-ECHO measurements and can be used to identify potential responders to CRT.

Myocardial contractile response to increasing doses of dobutamine in patients with reperfused acute myocardial infarction by cardiac magnetic resonance imaging.

BACKGROUND: Cardiac magnetic resonance imaging uses contractile response to dobutamine (DCMR) and delayed contrast enhancement (DE) to assess myocardial viability. However, early after acute myocardial infarction (AMI) the optimal dose of dobutamine is unclear. METHODS: In patients early after reperfused AMI, DCMR at 5, 10 and 20 microg*kg(-1)*min(-1) and measurement of DE was performed. On three short-axis slices 18 segments were graded as no DE, DE <50% and DE >or=50%. Thickening (systolic-diastolic wall thickness) and contractile reserve (max. thickening - rest) were determined. Segments were classified dysfunctional if thickening was >2 SD below normal or <2 mm. RESULTS: Forty-nine patients participated. In segments with no DE, thickening increased continuously but contractile reserve was low (0.9 +/- 3.2 mm) and dysfunctional segments were unchanged (rest: 13.1% vs. 20 microg: 14.8%). In segments with DE, contractile reserve was high (1.4 +/- 3.0 mm and 1.5 +/- 3.0 mm) and dysfunctional segments decreased from rest to 20 microg (50 vs. 24.8% and 79.9 vs. 43.2%). Between 5 and 10 microg no change of thickening and of dysfunctional segments occurred. CONCLUSION: Early after AMI, DCMR demonstrated no diagnostic benefit in segments with no DE. In segments with DE, higher dose of dobutamine can provide additional information on contractile reserve and dysfunctional segments.

Coronary angiography and intervention during hypothermia can be performed safely without cardiac arrhythmia or vasospasm.

PURPOSE: Mild therapeutic hypothermia is a neuroprotective procedure after cardiac arrest. Therefore, it is increasingly used. Likewise, there is a growing demand for coronary angiography and percutaneous coronary interventions under hypothermia. Case studies suggested that hypothermia may be associated with coronary vasospasm, heart rhythm events and platelet dysfunction. In this study, it was evaluated whether vasospasm, arrhythmia or bleeding occur to a relevant degree during cardiac catheterization under concomitant hypothermia. METHODS: In this prospective, single-center, open-label, non-interventional study, 29 patients after resuscitation for cardiac arrest were treated with mild hypothermia and underwent cardiac catheterization (coronary angiography n = 11, coronary angiography plus percutaneous intervention n = 18). The incidence of vasospasm, cardiac arrhythmia and relevant bleeding at the puncture site were evaluated. RESULTS: Mean temperature at cardiac catheterization was 33.9 ± 0.76°C. The mean heart rate was 82 ± 26 bpm at hospital admission and 67 ± 17 bpm under hypothermia (p < 0.05). There was no patient with relevant bradycardia beyond the expected hypothermia-induced rate reduction during the procedure. There were no unexpected ventricular tachycardias or episodes of ventricular fibrillation which might have been attributed to hypothermia. Twenty-nine of 29 patients (100%) were free from coronary vasospasm. There was no patient with a relevant bleeding at the puncture site. Potassium levels were low in 52% of the patients, even after resuscitation, which was partially attributed to hypothermia. CONCLUSION: Coronary angiography and percutaneous coronary interventions under mild therapeutic hypothermia were safe in this small cohort and were performed without hypothermia-induced vasospasm, relevant rhythm events or bleeding complications. This result has to be confirmed in a large series of patients.

Comparison of antero-lateral versus antero-posterior electrode position for biphasic external cardioversion of atrial flutter.

External cardioversion is an established and very important tool to terminate symptomatic atrial flutter. The superiority of the biphasic waveform has been demonstrated for atrial flutter, but whether electrode position affects the efficacy of cardioversion in this population is not known. The aim of this trial was to evaluate whether anterior-lateral (A-L) compared with anterior-posterior (A-P) electrode position improves cardioversion results. Of 130 screened patients, 96 (72 men, mean age 62 +/- 12 years) were included and randomly assigned to a cardioversion protocol with either A-L or A-P electrode position. In each group, 48 patients received sequential biphasic waveform shocks using a step-up protocol consisting of 50, 75, 100, 150, or 200 J. The mean energy (65 +/- 13 J for A-L vs 77 +/- 13 J for A-P, p = 0.001) and mean number of shocks (1.48 +/- 1.01 for A-L vs 1.96 +/- 1.00 for A-P, p = 0.001) required for successful cardioversion were significantly lower in the A-L group. The efficacy of the first shock with 50 J in the A-L electrode position (35 of 48 patients [73%]) was also highly significantly greater than the first shock with 50 J in the A-P electrode position (18 of 48 patients [36%]) (p = 0.001). In conclusion, the A-L electrode position increases efficacy and requires fewer energy and shocks in external electrical cardioversion of common atrial flutter. Therefore, A-L electrode positioning should be recommended for the external cardioversion of common atrial flutter.

Detection of mechanical ventricular asynchrony by high temporal resolution cine MRI.

The purpose was to assess the feasibility of high temporal resolution cine MRI (HTRC-MRI) to detect and to quantify mechanical ventricular asynchrony in patients with left bundle branch block (LBBB). Inter- and intraventricular delays were quantified by HTRC-MRI in 32 patients with (n=17) and without (n=15) LBBB. In patients with LBBB, delays by HTRC-MRI were correlated with echocardiographic parameters using pulsed wave Doppler echocardiography (PW-Echo) and tissue Doppler imaging (TDI-Echo). The interventricular delay by HTRC-MRI was 110+/-50 ms in patients with and -1+/-18 ms in patients without LBBB (P<0.0001). The intraventricular delay was 336+/-86 ms in patients with compared to 40+/-49 ms in patients without LBBB (P<0.0001). A strong correlation (r=0.78, P=0.0002) and good agreement (mean difference: 39+/-36 ms) was found for the interventricular delay between HTRC-MRI and PW-Echo. A good correlation (r=0.66, P=0.0042), but a large discrepancy (mean difference: 257+/-64 ms) was found for the intraventricular delay between HTRC-MRI and TDI-Echo. Detection and quantification of mechanical ventricular asynchrony using HTRC-MRI is feasible. However, further comparison with other imaging modalities is required.

Comparison of quantitative coronary angiography and first-pass perfusion magnetic resonance imaging for the detection of an impaired coronary perfusion in nonsevere coronary stenosis.

PURPOSE: To compare quantitative coronary angiography (QCA) and first-pass perfusion magnetic resonance imaging (FPP-MRI) in symptomatic patients with nonsevere coronary stenosis to detect a reduced coronary flow velocity reserve (CFVR). MATERIALS AND METHODS: In 35 patients, FPP-MRI and CFVR measurements were performed in 40 coronary arteries with a diameter stenosis (DS) <70% by QCA. From FPP-MRI a myocardial perfusion reserve index (MPRI) was calculated. CFVR was calculated as the ratio of the average peak flow velocity during infusion of adenosine and at rest and was considered reduced if <2. Diagnostic performance of MPRI and DS to detect a reduced CFVR was compared by receiver operating characteristic (ROC) curve analysis. RESULTS: CFVR was reduced in 16 coronary arteries (40%). Mean DS did not differ in coronary arteries with a reduced CFVR (41.0% +/- 13.3) and a normal CFVR (36.5% +/- 12.3; P = 0.281). Mean MPRI was lower in coronary arteries with a reduced CFVR (1.12 +/- 0.12) compared to a normal CFVR (1.33 +/- 0.2; P < 0.001). Sensitivity, specificity, and area under the ROC curve (AUC) were higher for MPRI (81%, 79%, 0.84) than for DS (56%, 58%, 0.60). CONCLUSION: FPP-MRI detects impaired CFVR in symptomatic patients with nonsevere coronary stenosis more accurately than QCA and can identify patients with symptomatic ischemia.

Prediction of myocardial recovery by dobutamine magnetic resonance imaging and delayed enhancement early after reperfused acute myocardial infarction.

The purpose was to study dobutamine magnetic resonance cine imaging (DOB-MRI) and delayed myocardial contrast enhancement (DE) early after reperfused acute myocardial infarction (AMI) for the predicion of segmental myocardial recovery and to find the optimal dose of dobutamine. Fifty patients (56+/-12 years, 42 males) with reperfused AMI underwent DOB-MRI and DE studies 3.5 (1-19) days after reperfusion. In DOB-MRI systolic wall thickening (SWT) was measured in 18 segments at rest and during dobutamine at 5, 10 and 20 microg*kg(-1)*min(-1). Dysfunctional segments were identified and the extent of DE was measured for each segment. Segmental recovery was examined after 8 (5-15) months. Two hundred-forty-eight segments were dysfunctional with presence of DE in 193. DOB-MRI showed the best prediction of recovery at 10 microg*kg(-1)*min(-1) of dobutamine with sensitivity of 67%, specificity of 63% and accuracy of 66% using a cut-off value for SWT of 2.0 mm. DE revealed a sensitivity of 68%, specificity of 65% and accuracy of 67% using a cut-off value of 46%. Combined analysis of DOB-MRI and DE did not improve diagnostic performance. Early prediction of segmental myocardial recovery after AMI is possible with DOB-MRI and DE. No improvement is achieved by dobutamine >10 microg*kg(-1)*min(-1) or a combination of DOB-MRI and DE.

Contrast-enhanced cardiac MR imaging in the detection of reduced coronary flow velocity reserve.

PURPOSE: To prospectively evaluate the accuracy of contrast material-enhanced cardiac magnetic resonance (MR) imaging for determining impaired coronary flow velocity reserve (CFR) by using Doppler flow measurement as the reference standard. MATERIALS AND METHODS: The study was approved by the institutional ethics committee, and all patients gave written informed consent. Eligible patients underwent contrast-enhanced cardiac MR imaging and invasive measurement of CFR. For contrast-enhanced MR imaging, a three-section single-shot saturation recovery gradient-recalled echo sequence with steady-state free precession was used. Sections were divided into six segments. For each segment, a transmural and subendocardial myocardial perfusion reserve index (MPRI) was calculated by using the upslope of the signal intensity-time curve during the first pass of contrast material at rest and during adenosine infusion (140 microg per kilogram body weight per minute). MPRIs of vascular regions were compared with the corresponding CFR. Receiver operating characteristic (ROC) analysis was performed to find the number of segments needed for best diagnostic accuracy of MPRI and to find a cutoff value for MPRI in the detection of a reduced CFR. RESULTS: Thirty-five patients were evaluated (male-to-female ratio, 27:8; mean age +/- standard deviation, 63.5 years +/- 8.2; mean body mass index, 28.8 kg/m(2) +/- 3.8), and 43 vascular regions were analyzed. A linear correlation was found between the MPRI and CFR (r = 0.44, P < .05). The MPRI was significantly lower in vascular regions with a CFR of less than 2.00 than in regions with a CFR of 2.00 or greater (P < .05). Detection of a CFR of less than 2.00 was more accurate with subendocardial MPRI measurements than with transmural measurements. The mean subendocardial MPRI of the segments with the three lowest MPRIs of a vascular region showed the best diagnostic performance in the detection of a CFR of less than 2.00 (area under the ROC curve, 0.85; sensitivity, 84%; specificity, 75%) by using a cutoff value of 1.21. CONCLUSION: The diagnostic accuracy of subendocardial perfusion analysis in contrast-enhanced cardiac MR imaging is higher than that of transmural analysis.

Prediction of left ventricular remodeling and analysis of infarct resorption in patients with reperfused myocardial infarcts by using contrast-enhanced MR imaging.

PURPOSE: To prospectively evaluate the accuracy of clinical and cardiac magnetic resonance (MR) imaging parameters for predicting left ventricular (LV) remodeling by using follow-up imaging as reference standard, and to prospectively evaluate infarct resorption in patients with reperfused first myocardial infarcts. MATERIALS AND METHODS: The study was approved by the institutional ethics committee and all patients gave written informed consent. In 55 patients (48 men, seven women; mean age+/-standard deviation, 56 years+/-13), contrast material-enhanced and cine MR imaging were performed 5 days+/-3 and 8 months+/-3 after myocardial infarction (MI). Microvascular obstruction (MO) and infarct size were estimated at first-pass enhancement (FPE) and delayed enhancement (DE) MR, respectively. Remodeling was defined as an increase in LV end-diastolic volume index of 20% or higher at follow-up. Differences in continuous and categorical data were analyzed by using Student t test and Fischer exact test as appropriate. RESULTS: Patients with remodeling (n=13, 24%) had higher creatine kinase MB (P<.05), more anterior infarcts (P<.05), more often a reduced Thrombolysis in Myocardial Infarction flow (P<.05), larger infarct size at DE MR (P<.001), a greater extent of MO at FPE MR (P<.01), lower ejection fraction (P<.001) and higher LV end-systolic volume index (P<.01). Infarct size at DE MR was a powerful predictor for remodeling (odds ratio: 1.18, P<.001), demonstrating that the risk for remodeling increased 2.8-fold with each 10% increase in infarct size. Infarct size of 24% or more of LV area predicted remodeling with high sensitivity (92%), specificity (93%), and accuracy (93%). Infarct resorption was larger in patients with remodeling (P<.01). CONCLUSION: Infarct size 24% or more of the LV area constitutes an important threshold to predict remodeling. Patients with remodeling develop disproportionate infarct resorption.