Postoperative Myocardial Infarction Due to Coronary Embolization of Valve Tissue After Surgical Mitral Valve Replacement.

We present the case of a 61-year-old man with known Morbus Barlow disease, who presented with postoperative myocardial infarction and cardiac arrest within 1 hour after minimally invasive mitral valve surgery owing to coronary artery occlusion by native mitral valve tissue.

Heart team approach in treatment of mitral regurgitation: patient selection and outcome.

OBJECTIVE: A multidisciplinary heart valve team is recommended for the evaluation of treatment in patients with valvular heart disease, but evidence supporting this concept is lacking. In patients with severe mitral regurgitation, we thought to analyse the patient selection process by the heart team for different treatment options and the outcome after treatment. METHODS: In this single-centre cohort study, all patients treated for mitral regurgitation between July 2013 and September 2018 were included. Primary end points during follow-up were all-cause mortality and a combined end point, consisting of all-cause mortality, cardiovascular rehospitalisation and mitral valve reintervention. RESULTS: 179 patients (44.8%) were treated using Mitraclip, 185 (46.2%) by surgical repair and 36 (9.0%) by surgical replacement. The mortality risk according to EuroScore II differed significantly between treatment groups (6.6%±5.6%, 1.7%±1.5% and 3.6%±2.7% for Mitraclip, surgical repair and replacement, respectively, p<0.001). In-hospital mortality for the 3 groups were 3.4%, 1.6% and 8.3%, respectively (p=0.091). Overall, surgical repair patients had higher 4-year survival (HR 0.40 (95% CI 0.26 to 0.63), p<0.001) and fewer combined end points (HR 0.51 (95% CI 0.32 to 0.80), p<0.001) compared with surgical replacement and Mitraclip patients. However, patients undergoing Mitraclip for isolated, primary mitral regurgitation achieved very good long-term survival. CONCLUSION: The multidisciplinary heart team assigned only low-risk patients with favourable anatomy to surgical repair, while high-risk patients underwent Mitraclip or surgical replacement. This strategy was associated with lower than expected in-hospital mortality for Mitraclip patients and high 4-year survival rates for patients undergoing surgical or percutaneous repair of isolated primary mitral regurgitation.

"AF HeartTeam" Guided Indication for Stand-alone Thoracoscopic Left Atrial Ablation and Left Atrial Appendage Closure.

BACKGROUND: Traditional surgical treatment for patients with atrial fibrillation (AF) is performed via sternotomy and on cardiopulmonary bypass. It is very effective in regard to rhythm control, but remains unpopular due to its invasiveness. Truly endoscopic AF treatments have decreased the threshold for electrophysiologists (and cardiologists) to refer, and the reluctance of patients to accept a standalone surgical approach. Practice guidelines from around the world have recognized this as an acceptable therapeutic approach. Current guidelines recommend the HeartTeam approach in treating these complex AF cases. In this study we report our experience with AF HeartTeam approach for surgical stand-alone AF ablation. METHODS: The AF HeartTeam Program began in 2013, patients qualified for inclusion if either of the following was present: failed catheter ablation and/or medication, not suitable for catheter ablation, contraindication to anticoagulation, or patients preferring such an approach. All patients with a complex AF history were assessed by the AF HeartTeam, from which 42 patients were deemed suitable for a totally endoscopic AF procedure (epicardial ablation and LAA closure). Endpoints were intraoperative bidirectional block of the pulmonary veins and closure of left atrial appendage confirmed by transesophageal echocardiography (TEE). Post discharge rhythm follow-up was performed after 3 and 12, 24 and 36 months. Anticoagulation was discontinued 6 weeks after the procedure in patients after documented LAA closure. RESULTS: In total 42 patients underwent the endoscopic procedure (Median CHA2DS2-VASC=3 (1-6), HAS-BLED=2 (1-6)) for paroxysmal (15/42) and non-paroxysmal AF (27/42) respectively. Bidirectional block was obtained in all patients and complete LAA closure was obtained in all but one Patient on TEE (41/42). In one patient the LAA was not addressed due to extensive adhesions. Two patients underwent median sternotomy because of bleeding during the endoscopic surgery early in the series. There were no deaths. Procedure duration was a median of 124min (Range 83-211) and duration of hospitalization was median of 5 days (Range 3-12). During 36 months follow-up survival free of mortality, thromboembolic events or strokes was 100%. Twelve month freedom from atrial arrhythmia off anti-arrhythmic medication was 93% and 89% for paroxysmal and non-paroxysmal patients respectively. 6/42 patients who had an AF recurrence during the follow-up underwent touch-up catheter ablation. CONCLUSIONS: Atrial fibrillation heart team approach provides excellent outcomes for patients with AF. This approach is beneficial for patients after failed catheter ablation or not candidates for such and offers a very effective mid-term outcome data. In addition to effective rhythm control the protective effect of epicardial LAA closure may play an important role in effectively reducing stroke. The creation of an AF HeartTeam as recommended by the guidelines insures unbiased therapies and provides access to this minimally invasive but effective therapeutic option for AF patients.

Validation of transpulmonary thermodilution variables in hemodynamically stable patients with heart diseases.

BACKGROUND: Transpulmonary thermodilution is recommended in the treatment of critically ill patients presenting with complex shock. However, so far it has not been validated in hemodynamically stable patients with heart disease. METHODS: We assessed the validity of cardiac output, global end-diastolic volume index (GEDVI), an established marker of preload thought to reflect the volume of all four heart chambers, global ejection fraction (GEF) and cardiac function index (CFI) as variables of cardiac function, and extravascular lung water index (EVLWI) as indicator of pulmonary edema in 29 patients undergoing elective left and right heart catheterization including left ventricular angiography with stable coronary heart disease and normal cardiac function (controls, n = 11), moderate-to-severe aortic valve stenosis (AS, n = 10), or dilated cardiomyopathy (DCM, n = 8). RESULTS: Cardiac output was similar in controls, AS, and DCM, with good correlation between transpulmonary thermodilution and pulmonary artery catheter using the Fick method (r = 0.69, p < 0.0001). Left ventricular end-diastolic volume was normal in controls and AS, but significantly higher in DCM (104 ± 37 vs 135 ± 63 vs 234 ± 24 ml, p < 0.01). GEDVI did not differentiate between patients with normal and patients with enlarged left ventricular end-diastolic volume (848 ± 128 vs 882 ± 213 ml m-2, p = 0.60). No difference in GEF and CFI was found between patients with normal and patients with reduced left ventricular ejection fraction. Patients with AS but not DCM had higher EVLWI than controls (9 ± 2 vs 12 ± 4 vs 11 ± 3 ml kg-1, p = 0.04), while there was only a trend in pulmonary artery occlusion pressure (8 ± 3 vs 10 ± 5 vs 14 ± 7 mmHg, p = 0.05). CONCLUSIONS: Cardiac output measurement by transpulmonary thermodilution is unaffected by differences in ventricular size and outflow obstruction. However, GEDVI did not identify markedly enlarged left ventricular end-diastolic volumes, and neither GEF nor CFI reflected the increased heart chamber volumes and markedly impaired left ventricular function in patients with DCM. In contrast, EVLWI is probably a sensitive marker of subclinical pulmonary edema particularly in patients with elevated left-ventricular-filling pressure irrespective of differences in left ventricular function.

Intracoronary injection of bone marrow-derived mononuclear cells early or late after acute myocardial infarction: effects on global left ventricular function.

BACKGROUND: Intracoronary administration of autologous bone marrow-derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction. The optimal time point of administration of BM-MNC is still uncertain and has rarely been addressed prospectively in randomized clinical trials. METHODS AND RESULTS: In a multicenter study, we randomized 200 patients with large, successfully reperfused ST-segment elevation myocardial infarction in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were administered either early (i.e., 5 to 7 days) or late (i.e., 3 to 4 weeks) after acute myocardial infarction. Cardiac magnetic resonance imaging was performed at baseline and after 4 months. The primary end point was the change from baseline to 4 months in global LV ejection fraction between the 2 treatment groups and the control group. The absolute change in LV ejection fraction from baseline to 4 months was -0.4±8.8% (mean±SD; P=0.74 versus baseline) in the control group, 1.8±8.4% (P=0.12 versus baseline) in the early group, and 0.8±7.6% (P=0.45 versus baseline) in the late group. The treatment effect of BM-MNC as estimated by ANCOVA was 1.25 (95% confidence interval, -1.83 to 4.32; P=0.42) for the early therapy group and 0.55 (95% confidence interval, -2.61 to 3.71; P=0.73) for the late therapy group. CONCLUSIONS: Among patients with ST-segment elevation myocardial infarction and LV dysfunction after successful reperfusion, intracoronary infusion of BM-MNC at either 5 to 7 days or 3 to 4 weeks after acute myocardial infarction did not improve LV function at 4-month follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00355186.

Antibody phage display assisted identification of junction plakoglobin as a potential biomarker for atherosclerosis.

To date, no plaque-derived blood biomarker is available to allow diagnosis, prognosis or monitoring of atherosclerotic vascular diseases. In this study, specimens of thrombendarterectomy material from carotid and iliac arteries were incubated in protein-free medium to obtain plaque and control secretomes for subsequent subtractive phage display. The selection of nine plaque secretome-specific antibodies and the analysis of their immunopurified antigens by mass spectrometry led to the identification of 22 proteins. One of them, junction plakoglobin (JUP-81) and its smaller isoforms (referred to as JUP-63, JUP-55 and JUP-30 by molecular weight) were confirmed by immunohistochemistry and immunoblotting with independent antibodies to be present in atherosclerotic plaques and their secretomes, coronary thrombi of patients with acute coronary syndrome (ACS) and macrophages differentiated from peripheral blood monocytes as well as macrophage-like cells differentiated from THP1 cells. Plasma of patients with stable coronary artery disease (CAD) (n = 15) and ACS (n = 11) contained JUP-81 at more than 2- and 14-fold higher median concentrations, respectively, than plasma of CAD-free individuals (n = 13). In conclusion, this proof of principle study identified and verified JUP isoforms as potential plasma biomarkers for atherosclerosis. Clinical validation studies are needed to determine its diagnostic efficacy and clinical utility as a biomarker for diagnosis, prognosis or monitoring of atherosclerotic vascular diseases.

Diagnostic value of 13N-ammonia myocardial perfusion PET: added value of myocardial flow reserve.

UNLABELLED: The ability to obtain quantitative values of flow and myocardial flow reserve (MFR) has been perceived as an important advantage of PET over conventional nuclear myocardial perfusion imaging (MPI). We evaluated the added diagnostic value of MFR over MPI alone as assessed with (13)N-ammonia and PET/CT to predict angiographic coronary artery disease (CAD). METHODS: Seventy-three patients underwent 1-d adenosine stress-rest (13)N-ammonia PET/CT MPI, and MFR was calculated. The added value of MFR as an adjunct to MPI for predicting CAD (luminal narrowing ≥ 50%) was evaluated using invasive coronary angiography as a standard of reference. RESULTS: Per patient, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MPI for detecting significant CAD were 79%, 80%, 91%, 59%, and 79%, respectively. Adding a cutoff of less than 2.0 for global MFR to MPI findings improved the values to 96% (P < 0.005), 80%, 93%, 89% (P < 0.005), and 92% (P < 0.005), respectively. CONCLUSION: The quantification of MFR in (13)N-ammonia PET/CT MPI provides a substantial added diagnostic value for detection of CAD. Particularly in patients with normal MPI results, quantification of MFR helps to unmask clinically significant CAD.

Whole-heart dynamic three-dimensional magnetic resonance perfusion imaging for the detection of coronary artery disease defined by fractional flow reserve: determination of volumetric myocardial ischaemic burden and coronary lesion location.

AIMS: Dynamic three-dimensional-cardiac magnetic resonance (3D-CMR) perfusion proved highly diagnostic for the detection of angiographically defined coronary artery disease (CAD) and has been used to assess the efficacy of coronary stenting procedures. The present study aimed to relate significant coronary lesions as assessed by fractional flow reserve (FFR) to the volume of myocardial hypoenhancement on 3D-CMR adenosine stress perfusion imaging and to define the inter-study reproducibility of stress inducible 3D-CMR hypoperfusion. METHODS AND RESULTS: A total of 120 patients with known or suspected CAD were examined in two CMR centres using 1.5 T systems. The protocol included cine imaging, 3D-CMR perfusion during adenosine infusion, and at rest followed by delayed enhancement (DE) imaging. Fractional flow reserve was recorded in epicardial coronary arteries and side branches with ≥2 mm luminal diameter and >40% severity stenosis (pathologic FFR < 0.75). Twenty-five patients underwent an identical repeat CMR examination for the determination of inter-study reproducibility of 3D-CMR perfusion deficits induced by adenosine. Three-dimensional CMR perfusion scans were visually classified as pathologic if one or more segments showed an inducible perfusion deficit in the absence of DE. Myocardial ischaemic burden (MIB) was measured by segmentation of the area of inducible hypoenhancement and normalized to left ventricular myocardial volume (MIB, %). Three-dimensional CMR perfusion resulted in a sensitivity, specificity, and diagnostic accuracy of 90, 82, and 87%, respectively. Substantial concordance was found for inter-study reproducibility [Lin's correlation coefficient: 0.98 (95% confidence interval: 0.96-0.99)]. CONCLUSION: Three-dimensional CMR stress perfusion provided high diagnostic accuracy for the detection of functionally significant CAD. Myocardial ischaemic burden measurements were highly reproducible and allowed the assessment of CAD severity.

Associated vascular lesions in patients with spontaneous coronary artery dissection.

AIM: To identify vascular abnormalities in patients presenting with spontaneous coronary artery dissection (SCAD). METHODS: We performed a whole-body MR angiography and a duplex sonography of the renal and carotid arteries in 12 patients (9 women, 3 men) with SCAD to identify vascular abnormalities. RESULTS: MR angiography revealed abnormalities of the renal arteries in 3/12 patients (25%). All 3 patients were women, 2 presented with changes suggesting fibromuscular dysplasia (FMD), 1 had a spontaneous renal artery dissection. No other vascular abnormalities were identified in any of the patients. Duplex sonography confirmed MR findings and showed non-significant renal artery stenoses in both patients with FMD. CONCLUSIONS: Abnormalities of the renal arteries were found in 3/12 (25%) of the patients with SCAD. No other vascular abnormalities were identified. Additional diagnostic tests of the renal arteries such as renal artery angiography or duplex sonography may be considered in patients presenting with SCAD.

Radiation doses from phantom measurements at high-pitch dual-source computed tomography coronary angiography.

OBJECTIVE: To compare radiation doses delivered at prospectively ECG-triggered sequential- (SEQ), retrospectively ECG-gated spiral- (RETRO) and prospectively ECG-triggered high-pitch spiral- (HP) computed tomography coronary angiography (CTCA) protocols, as well as catheter coronary angiography (CCA) using an anthropomorphic phantom. MATERIALS AND METHODS: An anthropomorphic Alderson phantom equipped with 50 thermoluminescent dosimeters (TLDs) was scanned using different CTCA protocols and an uncomplicated diagnostic CCA examination was simulated. Absorbed doses were experimentally determined and effective doses calculated using the dose-length product (DLP) for CTCA and the dose-area product (DAP) for CCA, as well as according to International Commission on Radiation Protection (ICRP) publications 60 and 103. RESULTS: Effective organ doses were significantly lower for HP protocols (100kV: 0.17±0.26mSv; 120kV: 0.26±0.39mSv) compared to SEQ protocols (100kV: 0.50±0.79mSv; 120kV: 0.90±1.41mSv; each p<0.05) and compared to RETRO protocols (100kV: 1.59±2.12mSv; 120kV: 2.75±3.50mSv; each p<0.05). Effective organ doses at HP-CTCA tended to be lower than at CCA (0.37±0.40mSv), however this was not statistically significant (p=0.13). Effective doses calculated according to ICRP guidelines could be estimated using the DLP and a conversion coefficient of k=0.034mSv/[mGycm] (ICRP103) or k=0.028mSv/[mGycm] (ICRP60), respectively. HP-CTCA led to a dose reduction of 89% compared to RETRO-CTCA, regardless of the calculation method used. CONCLUSIONS: Radiation doses as determined by phantom measurements are significantly lower at HP-CTCA compared to SEQ-CTCA and RETRO-CTCA and comparable to uncomplicated diagnostic CCA.

Adenosine stress high-pitch 128-slice dual-source myocardial computed tomography perfusion for imaging of reversible myocardial ischemia: comparison with magnetic resonance imaging.

BACKGROUND: Coronary computed tomography angiography (CTA) enables accurate anatomic evaluation of coronary artery stenosis but lacks information about hemodynamic significance. The aim of this study was to evaluate 128-slice myocardial CT perfusion (CTP) imaging with adenosine stress using a high-pitch mode, in comparison with cardiac MRI (CMR). METHODS AND RESULTS: Thirty-nine patients with intermediate to high coronary risk profile underwent adenosine stress 128-slice dual source CTP (128×0.6 mm, 0.28 seconds). Among those, 30 patients (64 ± 10 years, 6% women) also underwent adenosine stress CMR (1.5T). The 2-step CTP protocol consisted of (1) adenosine stress-CTP using a high-pitch factor (3.4) ECG-synchronized spiral mode and (2) rest-CTP/coronary-CTA using either high-pitch (heart rate <63 bpm) or prospective ECG-triggering (heart rate >63 bpm). Results were compared with CMR and with invasive angiography in 25 patients. The performance of stress-CTP for detection of myocardial perfusion defects compared with CMR was sensitivity, 96%; specificity, 88%; positive predictive value (PPV), 93%; negative predictive value (NPV), 94% (per vessel); and sensitivity, 78%; specificity, 87%; PPV, 83%; NPV, 84% (per segment). The accuracy of stress-CTP for imaging of reversible ischemia compared with CMR was sensitivity, 95%; specificity, 96%; PPV, 95%; and NPV, 96% (per vessel). In 25 patients who underwent invasive angiography, the accuracy of CTA for detection of stenosis >70% was (per segment): sensitivity, 96%; specificity, 88%; PPV, 67%; and NPV, 98.9%. The accuracy improved from 84% to 95% after adding stress CTP to CTA. Radiation exposure of the entire stress/rest CT protocol was only 2.5 mSv. CONCLUSIONS: Adenosine-induced stress 128-slice dual-source high-pitch myocardial CTP allows for simultaneously assessment of reversible myocardial ischemia and coronary stenosis, with good diagnostic accuracy as compared with CMR and invasive angiography, at a very low radiation exposure.

Myeloid related proteins activate Toll-like receptor 4 in human acute coronary syndromes.

INTRODUCTION: We previously reported increased expression of TLR4 on monocytes in thrombi from patients with acute coronary syndromes (ACS). In mice, myeloid related protein (MRP) 8 and MRP14, cytoplasmic proteins of neutrophils and monocytes, activate Toll-like receptor (TLR) 4 during sepsis. In human ACS, we investigated now whether the pro-inflammatory action of MRPs occurs through TLR4 in monocytes derived from thrombi. METHODS: Coronary thrombi and peripheral blood of 27 ACS patients were analyzed. CD14(+) monocytes were isolated and incubated with TLR2 ligand PM3SKA, TLR4 ligand lipopolysaccharide (LPS), MRP8, MRP14, or MRP8/14 heterocomplex. Anti-TLR4 antibodies (HTA125) were used to block TLR4 and polymyxin B (PMB) was employed to inhibit endotoxins. Before and after stimulation, the release of TNFα was measured by ELISA and the expression of TLR4 on CD14(+) monocytes was determined by flow cytometry. Further, selected pathways of downstream signaling were analyzed. RESULTS: MRP8 and MRP8/14 increased release of TNFα in cultures of CD14(+) monocytes, more in cells derived from thrombi compared with matched peripheral blood cells (p<0.001). LPS, MRP8, and MRP8/14, but much less PM3SKA and MRP14 alone, stimulated TNFα release, which can be inhibited by HTA125. MRP8/14 enhanced TLR4 expression on monocytes from thrombi (p<0.001), but not on monocytes from peripheral blood of the same patients. CONCLUSION: In ACS, MRP8 and MRP8/14 complex are specific ligands of TLR4, which induce the release of TNFα and probably other pro-inflammatory agents from monocytes. This specific MRP8/14-dependent pathway with striking similarities to sepsis increasing expression of TLR4 in thrombi appears to be involved in the pathogenesis of coronary occlusion and may represent a novel therapeutic target in ACS.

Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease.

Therapies that raise levels of HDL, which is thought to exert atheroprotective effects via effects on endothelium, are being examined for the treatment or prevention of coronary artery disease (CAD). However, the endothelial effects of HDL are highly heterogeneous, and the impact of HDL of patients with CAD on the activation of endothelial eNOS and eNOS-dependent pathways is unknown. Here we have demonstrated that, in contrast to HDL from healthy subjects, HDL from patients with stable CAD or an acute coronary syndrome (HDLCAD) does not have endothelial antiinflammatory effects and does not stimulate endothelial repair because it fails to induce endothelial NO production. Mechanistically, this was because HDLCAD activated endothelial lectin-like oxidized LDL receptor 1 (LOX-1), triggering endothelial PKCßII activation, which in turn inhibited eNOS-activating pathways and eNOS-dependent NO production. We then identified reduced HDL-associated paraoxonase 1 (PON1) activity as one molecular mechanism leading to the generation of HDL with endothelial PKCßII-activating properties, at least in part due to increased formation of malondialdehyde in HDL. Taken together, our data indicate that in patients with CAD, HDL gains endothelial LOX-1- and thereby PKCßII-activating properties due to reduced HDL-associated PON1 activity, and that this leads to inhibition of eNOS-activation and the subsequent loss of the endothelial antiinflammatory and endothelial repair-stimulating effects of HDL.

Very high coronary calcium score unmasks obstructive coronary artery disease in patients with normal SPECT MPI.

OBJECTIVES: To study the clinical impact of a very high coronary artery calcium score (CAC >1000) in patients with no known coronary artery disease (CAD) and normal single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). The secondary aim was to evaluate whether triple vessel disease would support the notion of balanced ischaemia as an underlying mechanism of false negative SPECT MPI in patients with very high CAC. BACKGROUND: No data exist on the clinical value of high CAC in patients with normal SPECT MPI. METHODS: 50 patients with suspected CAD and normal stress/rest SPECT MPI and CAC >1000 prospectively underwent invasive coronary angiography as the standard of reference. Coronary lesions with ≥50% luminal diameter narrowing on invasive coronary angiography were considered to represent significant stenosis. RESULTS: The median total CAC was 1975 (range 1018-8046). In 37/50 (74%) patients, coronary angiography revealed one-vessel disease (1-VD) (n=15), 2-VD (n=10) or 3-VD (n=12). Twenty-six revascularisations (percutaneous coronary intervention/coronary artery bypass grafting) were performed in seven (6/1), seven (6/1) and 12 (7/5) patients with 1-VD, 2-VD and 3-VD, respectively. CONCLUSIONS: In patients with normal SPECT MPI, a CAC >1000 confers a high diagnostic added value for detecting CAD. This is not solely based on unmasking balanced ischaemia due to epicardial 3-VD, as it occurred predominantly in patients with 1-VD and 2-VD.

3D fusion of functional cardiac magnetic resonance imaging and computed tomography coronary angiography: accuracy and added clinical value.

PURPOSE: To evaluate the accuracy and added diagnostic value of 3-dimensional (3D) image fusion of computed tomography coronary angiography (CTCA) and functional cardiac magnetic resonance (CMR) for assessing hemodynamically relevant coronary artery disease (CAD). METHODS: Twenty-seven patients with significant coronary stenoses on prospectively electrocardiography-gated dual-source CTCA, confirmed by catheter angiography and perfusion defects on CMR at 1.5 T were included. Surface representations and volume-rendered images from 3D-fused CTCA/CMR data were generated using a software prototype. Fusion accuracy was evaluated by calculating surface distances of blood pools and Dice similarity coefficients. Two independent, blinded readers assigned myocardial defects to culprit coronary arteries with side-by side analysis of CTCA and CMR and using fused CTCA/CMR. Added value of fused CTCA/CMR was defined as change in assignment of culprit coronary artery to myocardial defect compared with side-by-side analysis. RESULTS: 3D fusion of CTCA/CMR was feasible and accurate (surface distance of blood pools: 4.1 ± 1.3 mm, range: 2.4-7.1 mm; Dice similarity coefficients: 0.78 ± 0.08, range: 0.51-0.86) in all patients. Side-by-side analysis of CTCA and CMR allowed no assignment of a single culprit artery to a myocardial defect in 6 of 27 (22%) patients. Fused CTCA/CMR allowed further confinement of culprit coronary arteries in 3 of these 6 patients (11%). Myocardial defects were reassigned in 2 of 27 (7%) patients using fused CTCA/CMR, whereas the results remained unchanged in 22 of 27 (81%) patients. Interobserver agreement for assignment of culprit arteries to myocardial defects increased with fused CTCA/CMR (k = 0.66-0.89). CONCLUSION: 3D fusion of low-dose CTCA and functional CMR is feasible and accurate, and adds, at a low radiation dose, diagnostic value for the assessment of hemodynamically relevant CAD as compared with side-by-side analysis alone. This technique can be clinically useful for the following: planning of surgical or interventional procedures in patients having a high prevalence of CAD and for improved topographic assignment of coronary stenoses to corresponding myocardial perfusion defects.

Rapid cardiac hybrid imaging with minimized radiation dose for accurate non-invasive assessment of ischemic coronary artery disease.

BACKGROUND: Ischemic coronary artery disease (CAD) is a major cause for morbidity and mortality resulting in a continuously increasing number of diagnostic interventions. We have validated a new hybrid imaging method using minimized radiation dose for rapid non-invasive prediction of invasive coronary angiography (CA) findings with regard to coronary lesion detection and revascularization. METHODS: Forty patients referred for elective invasive coronary angiography (CA) due to suspected CAD were prospectively enrolled to undergo a low-dose CTCA with prospective ECG-triggering and a stress-only SPECT-MPI scan administering half of the standard low-dose stress (99m)Tc-tetrofosmin activity. The latter was acquired immediately after adenosine stress (omitting the standard 30-60 min waiting time). After fusing CTCA and SPECT-MPI decisions towards conservative management versus revascularization strategy based on hybrid images were compared to the decisions taken by the interventional operator in the catheterization laboratory based on CA. The latter served as standard of reference. RESULTS: Hybrid images yielded sensitivity, specificity, positive and negative predictive values and accuracy of 100%, 96.0%, 100%, 93.8% and 97.5% for predicting coronary revascularization. The estimated mean effective radiation doses were significantly lower for hybrid imaging (4.7 ± 1.0 mSv) than for invasive CA (8.7 ± 4.2 mSv; P<0.001 vs. hybrid). Total non-invasive protocol time was below 60 min, comparing favourably to standard SPECT protocols. CONCLUSIONS: Rapid cardiac hybrid imaging allows accurate prediction of invasive CA findings and of treatment decision despite minimized radiation dose and protocol time.

Cell-based therapy for myocardial repair in patients with acute myocardial infarction: rationale and study design of the SWiss multicenter Intracoronary Stem cells Study in Acute Myocardial Infarction (SWISS-AMI).

BACKGROUND: Recent studies report that intracoronary administration of autologous bone marrow mononucleated cells (BM-MNCs) may improve remodeling of the left ventricle after acute myocardial infarction (AMI). Subgroup analysis suggest that early treatment between days 4 and 7 after AMI is probably most effective; however, the optimal time point of intracoronary cell administration has never been addressed in clinical trials. Furthermore, reliable clinical predictors are lacking for identifying patients who are thought to have most benefit from cellular therapy. STUDY DESIGN: In a multicenter trial, 192 patients with AMI successfully treated by percutaneous coronary intervention (PCI) of the infarct-related artery will be randomized in a 1:1:1 pattern to 1 control and 2 BM-MNC treatment groups. The control group will be treated with state-of-the-art medical management. The treatment groups will receive intracoronary administration of autologous BM-MNC at 5 to 7 days or 3 to 4 weeks after the initial event, respectively. Left ventricular function as well as scar size, transmural extension, and regional wall motion score will be assessed by cardiac magnetic resonance (CMR) studies at baseline and after 4 and 12 months. METHODS: Fifty milliliters of bone marrow will be harvested by aspiration from the iliac crest and then carried by courier to a centralized cell processing facility. The mononucleated cell fraction will be isolated by density gradient centrifugation, washed, and resuspended in 10 mL of injection medium. The cells will be characterized by fluorescence-activated cell sorting analysis and tested for sterility and potency both "in vitro" and "in vivo." Bone marrow MNC will then be reinfused directly in the infarct-related coronary artery. END POINTS: The primary end point is the change in global left ventricular (LV) ejection fraction by CMR at 4 months as compared to baseline. Comparisons will then be made between each of the prespecified therapy subgroups (early and late after AMI) and the control group. Secondary end points include change in infarct size, change in regional myocardial thickness, and wall motion at 4 and 12 months compared to baseline. Infarct extension (size and transmural extension), time delay to PCI, and coronary flow characteristics after PCI will be assessed as potential predictors of LV remodeling and change after cell therapy. Major adverse cardiac events (MACE) (death, myocardial infarction, coronary revascularization, rehospitalization for heart failure) will be assessed at 4, 12, and 24 months and time to MACE will be estimated. DISCUSSION: With the present study, we aim to determine the optimal time point of intracoronary administration of autologous BM-MNC after AMI on LV remodeling.

Real-time breath-hold triggering of myocardial perfusion imaging with a novel cadmium-zinc-telluride detector gamma camera.

PURPOSE: The aim of this study was to assess the ability of real-time breath-hold-triggered myocardial perfusion imaging (MPI) using a novel cadmium-zinc-telluride (CZT) gamma camera to discriminate artefacts from true perfusion defects. METHODS: A group of 40 patients underwent a 1-day (99m)Tc-tetrofosmin pharmacological stress/rest imaging protocol on a conventional dual detector SPECT gamma camera with and without attenuation correction (AC), immediately followed by scanning on an ultrafast CZT camera with and without real-time breath-hold triggering (instead of AC) by intermittent scanning confined to breath-hold at deep inspiration (using list mode acquisition). We studied the use of breath-hold triggering on the CZT camera and its ability to discriminate artefacts from true perfusion defects using AC SPECT MPI as the reference standard. Myocardial tracer uptake (percent of maximum) from CZT was compared to AC SPECT MPI by intraclass correlation and by calculating Bland-Altman limits of agreement. RESULTS: AC of SPECT MPI identified 19 apparent perfusion defects as artefacts. Of these, 13 were correctly identified and 4 were partially unmasked (decrease in extent and/or severity) by breath-hold triggering of the CZT scan. All perfusion defects verified by SPECT MPI with AC were appropriately documented by CZT with and without breath-hold triggering. This was supported by the quantitative analysis, as the correlation (r) of myocardial tracer uptake between CZT and AC SPECT improved significantly from 0.81 to 0.90 (p<0.001) when applying breath-hold triggering. Similarly, Bland-Altman limits of agreement were narrower for CZT scans with breath-hold triggering. CONCLUSION: This novel CZT camera allows real-time breath-hold triggering as a potential alternative to AC to assist in the discrimination of artefacts from true perfusion defects.

Low-dose CT and cardiac MR for the diagnosis of coronary artery disease: accuracy of single and combined approaches.

To prospectively compare the diagnostic performance of low-dose computed tomography coronary angiography (CTCA) and cardiac magnetic resonance imaging (CMR) and combinations thereof for the diagnosis of significant coronary stenoses. Forty-three consecutive patients with known or suspected coronary artery disease underwent catheter coronary angiography (CA), dual-source CTCA with prospective electrocardiography-gating, and cardiac CMR (1.5 Tesla). The following tests were analyzed: (1) low-dose CTCA, (2) adenosine stress-rest perfusion-CMR, (3) late gadolinium enhancement (LGE), (4) perfusion-CMR and LGE, (5) low-dose CTCA combined with perfusion-CMR, (5) low-dose CTCA combined with late gadolinium-enhancement, (6) low-dose CTCA combined with perfusion-CMR and LGE. CA served as the standard of reference. CA revealed >50% diameter stenoses in 68/129 (57.7%) coronary arteries in 29/43 (70%) patients. In the patient-based analysis, sensitivity, specificity, NPV and PPV of low-dose CTCA for the detection of significant stenoses were 100, 92.9, 100 and 96.7%, respectively. For perfusion-CMR and LGE, sensitivity, specificity, NPV, PPV, and accuracy were 89.7, 100, 82.4, and 100%, respectively. In the artery-based analysis, sensitivity and NPV of low-dose CTCA was significantly (P < 0.05) higher than that of perfusion-CMR and LGE. All combinations of low-dose CTCA and perfusion-CMR and/or LGE did not improve the diagnostic performance when compared to low-dose CTCA alone. Taking CA as standard of reference, low-dose CTCA outperforms CMR with regard to sensitivity and NPV, whereas CMR is more specific and has a higher PPV than low-dose CTCA.