Cost-effectiveness of percutaneous coronary intervention with drug-eluting stents in patients with multivessel coronary artery disease compared to coronary artery bypass surgery five-years after intervention.

OBJECTIVES: Cost-effectiveness of percutaneous coronary intervention (PCI) using drug-eluting stents (DES), and coronary artery bypass surgery (CABG) was analyzed in patients with multivessel coronary artery disease over a 5-year follow-up. BACKGROUND: DES implantation reducing revascularization rate and associated costs might be attractive for health economics as compared to CABG. METHODS: Consecutive patients with multivessel DES-PCI (n = 114, 3.3 ± 1.2 DES/patient) or CABG (n = 85, 2.7 ± 0.9 grafts/patient) were included prospectively. Primary endpoint was cost-benefit of multivessel DES-PCI over CABG, and the incremental cost-effectiveness ratio (ICER) was calculated. Secondary endpoint was the incidence of major adverse cardiac and cerebrovascular events (MACCE), including acute myocardial infarction (AMI), all-cause death, revascularization, and stroke. RESULTS: Despite multiple uses for DES, in-hospital costs were significantly less for PCI than CABG, with 4551 €/patient difference between the groups. At 5-years, the overall costs remained higher for CABG patients (mean difference 5400 € between groups). Cost-effectiveness planes including all patients or subgroups of elderly patients, diabetic patients, or Syntax score >32 indicated that CABG is a more effective, more costly treatment mode for multivessel disease. At the 5-year follow-up, a higher incidence of MACCE (37.7% vs. 25.8%; log rank P = 0.048) and a trend towards more AMI/death/stroke (25.4% vs. 21.2%, log rank P = 0.359) was observed in PCI as compared to CABG. ICER indicated 45615 € or 126683 € to prevent one MACCE or AMI/death/stroke if CABG is performed. CONCLUSIONS: Cost-effectiveness analysis of DES-PCI vs. CABG demonstrated that CABG is the most effective, but most costly, treatment for preventing MACCE in patients with multivessel disease.

The effect of device-based cardiac contractility modulation therapy on myocardial efficiency and oxidative metabolism in patients with heart failure.

PURPOSE: Cardiac contractility modulation (CCM) is a device-based therapy that involves delivery of nonexcitatory electrical signals resulting in improved ventricular function and a reversal of maladaptive cardiac fetal gene programmes. Our aim was to evaluate whether acute application of CCM leads to an increase in myocardial oxygen consumption (MVO(2)) in patients with chronic heart failure using (11)C-acetate positron emission tomography (PET). METHODS: We prospectively enrolled 21 patients with severe heart failure. (11)C-acetate PET was performed before and after activation of the CCM device. In 12 patients an additional stress study with dobutamine was performed. RESULTS: Under resting conditions, the values of myocardial blood flow (MBF), MVO(2) and work metabolic index (WMI, reflecting myocardial efficiency) with the CCM device activated did not differ significantly from the values with the device deactivated. MBF was 0.81 ± 0.18 ml min(-1) g(-1) with the device off and 0.80 ± 0.15 ml min(-1) g(-1) with the device on (p = 0.818), MVO(2) was 6.81 ± 1.69 ml/min/100 g with the device off and 7.15 ± 1.62 ml/min/100 g with the device on (p = 0.241) and WMI was 4.94 ± 1.14 mmHg ml/m(2) with the device off and 5.21 ± 1.36 mmHg ml/m(2) with the device on (p = 0.344). Under dobutamine stress, the values of MBF, MVO(2) and WMI with the CCM device activated did not differ from the values with the device deactivated, but were significantly increased compared with the values obtained under resting conditions. CONCLUSION: These results indicate that CCM does not induce increased MVO(2), even under stress conditions.

Assessment of left ventricular volume and ejection fraction: comparison of QGS and MBGS analyses of ECG-gated myocardial perfusion SPECT imaging.

OBJECTIVES: The purpose of this study was to compare quantitative ECG-gated single-photon emission computed tomography (SPECT) (QGS) and model-based ECG-gated single-photon emission computed tomography (MBGS) for determination of end-diastolic cardiac volume (EDV), end-systolic cardiac volume (ESV), and left ventricular ejection fraction (LVEF). The accuracy of both methods was evaluated by measurements obtained from contrast left ventriculography (LVG). METHODS: Forty-five patients (40 male, age: 55+/-11 years) with coronary artery disease were studied by angiography and ECG-gated SPECT using technetium-99m-sestamibi for the evaluation of myocardial perfusion and LVEF. Short axis SPECT images were analyzed by QGS and MBGS to estimate endocardial and epicardial surfaces and to derive EDV, ESV, and LVEF. RESULTS: EDV by gated SPECT (QGS: 187+/-71 ml; MBGS: 191+/-76 ml) were lower than corresponding values by LVG (203+/-59 ml), whereas ESV by gated SPECT (QGS: 121+/-62 ml; MBGS: 108+/-54 ml) were higher than by LVG (105+/-49 ml). Thus, LVEFs by gated SPECT (QGS: 39+/-12%; MBGS: 45+/-9%) were significantly lower than by LVG (50+/-15%). LVEF by MBGS was significantly higher than by QGS (P<0.05). A significant correlation was observed among QGS, MBGS, and LVG for the calculation of EDV, ESV, and LVEF. CONCLUSION: Measurements of LV volumes and LVEF by QGS and MBGS showed close agreement with each other and with results from LVG. However, both methods measure lower values for EDV and higher values for ESV and thus underestimate LVEF compared with LVG.

Typical chest pain and normal coronary angiogram: cardiac risk factor analysis versus PET for detection of microvascular disease.

UNLABELLED: Angiography of patients with typical chest pain reveals normal epicardial coronary arteries in about 20%. Coronary flow reserve (CFR) determination is an elaborate, but helpful, task, as only the evidence of microvascular disease enables appropriate therapy. We prospectively evaluated the incidence of a dysfunctional microcirculation and searched for predictive parameters of a reduced CFR. METHODS: In 79 consecutive patients (52 females, 27 males) with typical angina and a normal angiogram and 10 control subjects (6 females, 4 males), CFR was measured by 13N-ammonia rest/dipyridamole PET and correlated with clinical parameters individually and summarized as the number of risk factors (NRF) using an elaborated cardiac risk factor score. RESULTS: Sixty-five percent of patients had a reduced CFR (CFR < 2.5). CFR correlated with NRF (r = 0.55, P < 0.001), systolic blood pressure (r = 0.46, P < 0.001), interventricular septal thickness (r = 0.33, P < 0.01), and age (r = 0.25, P = 0.02). Eighty-five percent of patients with a high risk factor score (NRF > or = 5) had a reduced CFR. In contrast, 100% of our patients with a low risk factor score (NRF < 2) presented a normal CFR. In total, 55% of our patients could be allocated to either one of these groups. CONCLUSION: In about two thirds of patients, anginal pain can be explained by a reduced CFR. Risk factors have a cumulative negative effect on CFR. A clinical cardiac risk factor analysis enables estimation of individual probability of microvascular dysfunction in a significant proportion of these patients. However, CFR measurements are recommended for those with an intermediate NRF.

Automated assessment of myocardial SPECT perfusion scintigraphy: a comparison of different approaches of case-based reasoning.

OBJECTIVE: This study compared the diagnostic accuracy of different approaches of case-based reasoning (CBR) for the assessment of coronary artery disease (CAD) using thallium-201 myocardial perfusion scintigraphy in comparison with coronary angiography. METHODS AND MATERIAL: For each scintigraphic image set, regional myocardial tracer uptake was obtained by polar map analysis. CBR algorithms based on a similarity measure were employed to identify similar scintigraphic images within the case library, where each case contained the scintigraphic data together with results of coronary angiography. The angiographic data of retrieved cases were then used to determine whether significant CAD was present in one of the major coronary arteries. Three different approaches of CBR were compared: (1) case retrieval based on a global comparison of polar map data (GLOB), (2) case retrieval based on a territorial comparison of polar map data (TER), and (3) case retrieval based on a comparison of a given case with eight sub-libraries classified according to the involvement of the three major coronary vessels using a group similarity measure (GROUP). Two matching algorithms the best-match approach and an adapted retrieving approach were combined with all three case retrieval methods and their influence on the diagnostic accuracy were investigated. RESULTS: For overall detection of significant CAD, the best-match approach of both TER and GROUP retrieval methods showed a higher diagnostic accuracy than the GLOB retrieval method (75% and 77% versus 70%, respectively). ROC analysis for the adapted retrieving approach showed a similar diagnostic accuracy for all three methods with an area under the curve of 0.79, 0.8, and 0.8 for GLOB, TER, and GROUP, respectively. CONCLUSION: The observed improvement in the diagnostic accuracy by the new approaches may lead to further improvements of CBR systems, which have the potential to offer valuable decision support for human readers, especially for less experienced investigators.

NOGA-guided analysis of regional myocardial perfusion abnormalities treated with intramyocardial injections of plasmid encoding vascular endothelial growth factor A-165 in patients with chronic myocardial ischemia: subanalysis of the EUROINJECT-ONE multicenter double-blind randomized study.

BACKGROUND: The aim of this substudy of the EUROINJECT-ONE double-blind randomized trial was to analyze changes in myocardial perfusion in NOGA-defined regions with intramyocardial injections of plasmid encoding plasmid human (ph)VEGF-A(165) using an elaborated transformation algorithm. METHODS AND RESULTS: After randomization, 80 no-option patients received either active, phVEGF-A165 (n=40), or placebo plasmid (n=40) percutaneously via NOGA-Myostar injections. The injected area (region of interest, ROI) was delineated as a best polygon by connecting of the injection points marked on NOGA polar maps. The ROI was projected onto the baseline and follow-up rest and stress polar maps of the 99m-Tc-sestamibi/tetrofosmin single-photon emission computed tomography scintigraphy calculating the extent and severity (expressed as the mean normalized tracer uptake) of the ROI automatically. The extents of the ROI were similar in the VEGF and placebo groups (19.4+/-4.2% versus 21.5+/-5.4% of entire myocardium). No differences were found between VEGF and placebo groups at baseline with regard to the perfusion defect severity (rest: 69+/-11.7% versus 68.7+/-13.3%; stress: 63+/-13.3% versus 62.6+/-13.6%; and reversibility: 6.0+/-7.7% versus 6.7+/-9.0%). At follow-up, a trend toward improvement in perfusion defect severity at stress was observed in VEGF group as compared with placebo (68.5+/-11.9% versus 62.5+/-13.5%, P=0.072) without reaching normal values. The reversibility of the ROI decreased significantly at follow-up in VEGF group as compared with the placebo group (1.2+/-9.0% versus 7.1+/-9.0%, P=0.016). Twenty-one patients in VEGF and 8 patients in placebo group (P<0.01) exhibited an improvement in tracer uptake during stress, defined as a >or =5% increase in the normalized tracer uptake of the ROI. CONCLUSIONS: Projection of the NOGA-guided injection area onto the single-photon emission computed tomography polar maps permits quantitative evaluation of myocardial perfusion in regions treated with angiogenic substances. Injections of phVEGF A165 plasmid improve, but do not normalize, the stress-induced perfusion abnormalities.

Gated cardiac 13N-NH3 PET for assessment of left ventricular volumes, mass, and ejection fraction: comparison with electrocardiography-gated 18F-FDG PET.

UNLABELLED: The purpose of this study was to evaluate myocardial electrocardiography (ECG)-gated 13N-ammonia (13N-NH3) PET for the assessment of cardiac end-diastolic volume (EDV), cardiac end-systolic volume (ESV), left ventricular (LV) myocardial mass (LVMM), and LV ejection fraction (LVEF) with gated 18F-FDG PET as a reference method. METHODS: ECG-gated 13N-NH3 and 18F-FDG scans were performed for 27 patients (23 men and 4 women; mean+/-SD age, 55+/-15 y) for the evaluation of myocardial perfusion and viability. For both 13N-NH3 and 18F-FDG studies, a model-based image analysis tool was used to estimate endocardial and epicardial borders of the left ventricle on a set of short-axis images and to calculate values for EDV, ESV, LVEF, and LVMM. RESULTS: The LV volumes determined by 13N-NH3 and 18F-FDG were 108+/-60 mL and 106+/-63 mL for ESV and 175+/-71 mL and 169+/-73 mL for EDV, respectively. The LVEFs determined by 13N-NH3 and 18F-FDG were 42%+/-13% and 41%+/-13%, respectively. The LVMMs determined by 13N-NH3 and 18F-FDG were 179+/-40 g and 183+/-43 g, respectively. All P values were not significant, as determined by paired t tests. A significant correlation was observed between 13N-NH3 imaging and 18F-FDG imaging for the calculation of ESV (r=0.97, SEE=14.1, P<0.0001), EDV (r=0.98, SEE=15.4, P<0.0001), LVEF (r=0.9, SEE=5.6, P<0.0001), and LVMM (r=0.93, SEE=15.5, P<0.0001). CONCLUSION: Model-based analysis of ECG-gated 13N-NH3 PET images is accurate in determining LV volumes, LVMM, and LVEF. Therefore, ECG-gated 13N-NH3 can be used for the simultaneous assessment of myocardial perfusion, LV geometry, and contractile function.

Characterization of hibernating myocardium with NOGA electroanatomic endocardial mapping.

Because the terms "hibernation" and "viability" are not interchangeable, the recognition of hibernating myocardium within viable segments remained elusive for NOGA electroanatomic endocardial mapping. The aim of the present study was to determine the characteristics of hibernating myocardium in NOGA mapping. Baseline and follow-up endocardial mapping, thallium-201 myocardial perfusion scintigraphy at rest, and contrast ventriculography were performed in 28 patients who had proved viable myocardium before and 7.3 +/- 2.5 months after percutaneous coronary intervention. Significantly improved regional wall motion in the revascularized territory (region of interest) was confirmed in 9 patients (group 1) at follow-up (from -2.11 +/- 0.87 to -1.48 +/- 0.43 SD/chord, p <0.05), whereas no change in regional wall motion was observed in 19 patients (group 2; from -2.56 +/- 0.88 to -2.79 +/- 0.91 SD/chord). Average normalized thallium uptake at rest increased significantly in groups 1 and 2 after revascularization. A trend toward increased unipolar voltages in the region of interest was observed in group 1 at follow-up (from 10.6 +/- 3.5 to 11.7 +/- 4.0 mV, p = 0.073), whereas no change was observed in group 2 (from 8.7 +/- 4.4 to 8.9 +/- 3.8 mV). A significant increase in local linear shortening was measured only in group 1 (from 7.5 +/- 5.2% to 10.3 +/- 3.9%, p <0.05). Hibernating myocardial segments exhibited significantly higher unipolar voltages and late thallium uptake at rest at baseline. Receiver-operator characteristic analysis showed a mean unipolar voltage of 9.0 mV (predictive accuracy 0.708, common sensitivity and specificity 72%) in the region of interest for prediction of functional recovery. In conclusion, for characterizing the hibernating myocardium within viable segments, NOGA endocardial mapping offers on-line guidance for percutaneous coronary and noncoronary myocardial revascularization.

New cut-off values of cardiac markers for risk stratification of angina pectoris.

BACKGROUND: The aim of this present prospective study was to investigate the accuracy of cardiac markers for the prediction of subsequent cardiac events (cardiac death, acute myocardial infarction and recurrent ischemia requiring coronary revascularization). METHODS: Fibrinogen, cardiac troponin T, troponin I, creatine phosphokinase myocardial fraction, C-reactive protein and myoglobin at baseline and after 6 h were measured on 154 patients (109 male, 63+/-11 years) with chest pain. Receiver operator characteristic analyses were performed to determine cut-off points of cardiac markers in prediction of adverse events. RESULTS: The following cut-off values for prediction of cardiac events were calculated: troponin I at baseline 0.3 ng/ml (predictive accuracy=0.870), troponin I at 6 h 0.50 ng/ml (p.a.=0.909); troponin T at baseline 0.05 ng/ml (p.a.=0.643), troponin T at 6 h 0.05 ng/ml (p.a.=0.612), creatine phosphokinase myocardial fraction at baseline 2.0 ng/ml (p.a.=0.721), creatine phosphokinase myocardial fraction at 6 h 2.5 ng/ml (p.a.=0.734), myoglobin at baseline 23 ng/ml (p.a.=0.623), myoglobin at 6 h 26 ng/ml (p.a.=0.617), C-reactive protein at baseline 0.31 mg/dl (p.a.=0.662), C-reactive protein at 6 h 0.55 mg/dl (p.a.=0.682), and fibrinogen at baseline 360 mg/dl (p.a.=0.701). The combination of baseline troponin I with different parameters resulted in a higher sensitivity of up to 98%, with a similar predictive accuracy, but a lower specificity. Additive measurements of cardiac troponin I at 6 h to baseline cardiac troponin T and I proved to be the best combination for prediction of subsequent cardiac events. CONCLUSIONS: Changes in cut-off levels of cardiac markers and inflammatory parameters results in a high accuracy of risk stratification in patients with chest pains. Combination of these measurements might further help in the identification of patients who would benefit from early coronary revascularization.

Electromechanical properties of perfusion/metabolism mismatch: comparison of nonfluoroscopic electroanatomic mapping with 18F-FDG PET.

UNLABELLED: The aim of this study was to compare nonfluoroscopic electroanatomic mapping (NOGA), SPECT perfusion imaging, and PET metabolic imaging for assessment of myocardial viability. In particular, we sought to elucidate differences of electromechanical properties between the perfusion/metabolism mismatch as an indicator of a potentially reversible ischemic injury and the perfusion/metabolism match indicating irreversibly damaged myocardial tissue. METHODS: Twenty-one patients with coronary artery disease underwent NOGA mapping of endocardial unipolar voltage, cardiac 18F-FDG PET of glucose utilization, and resting 201Tl SPECT of myocardial perfusion. RESULTS: Electrical activity was 10.8 +/- 4.6 mV (mean +/- SD) in normal myocardium and was unchanged in hypoperfused segments with maintained glucose metabolism (perfusion/metabolism mismatch), 9.3 +/- 3.4 mV (P = not significant). In contrast, hypoperfused segments with a perfusion/metabolism match and nonviable segments showed significantly lower voltage (6.9 +/- 3.1 mV, P < 0.0001 and 4.1 +/- 1.1 mV, P < 0.0001 vs. normal). In hypoperfused segments, metabolic activity was more closely related to endocardial voltage than was myocardial perfusion (201Tl vs. voltage: r = 0.38, SEE = 3.2, P < 0.001; 18F-FDG PET vs. voltage: r = 0.6, SEE = 2.8, P < 0.0001). CONCLUSION: In hypoperfused myocardium, electrical activity by NOGA mapping is more closely related to PET metabolic activity than to SPECT myocardial perfusion. As NOGA mapping does not differentiate hypoperfused myocardium with enhanced glucose utilization from normal myocardium, results from NOGA mapping need to be correlated with results from perfusion imaging to identify hypoperfused, yet viable, myocardium and to stratify patients for revascularization procedures.

Model-based analysis of electrocardiography-gated cardiac (18)F-FDG PET images to assess left ventricular geometry and contractile function.

UNLABELLED: This study presents and evaluates a model-based image analysis method to calculate from gated cardiac (18)F-FDG PET images diastolic and systolic volumes, ejection fraction, and myocardial mass of the left ventricle. The accuracy of these estimates was delineated using measurements obtained by MRI, which was considered the reference standard because of its high spatial resolution. METHODS: Twenty patients (18 men, 2 women; mean age +/- SD, 59 +/- 12 y) underwent electrocardiography-gated cardiac PET and MRI to acquire a set of systolic and diastolic short-axis images covering the heart from apex to base. For PET images, left ventricular radius and wall thickness were estimated by model-based nonlinear regression analysis applied to the observed tracer concentration along radial rays. Endocardial and epicardial contours were derived from these estimates, and left ventricular volumes, ejection fraction, and myocardial mass were calculated. For MR images, an expert manually drew contours. RESULTS: Left ventricular volumes by PET and MRI were 101 +/- 60 mL and 112 +/- 93 mL, respectively, for end-systolic volume and 170 +/- 68 mL and 189 +/- 99 mL, respectively, for end-diastolic volume. Ejection fraction was 44% +/- 13% by PET and 46% +/- 18% by MRI. The left ventricular mass by PET and MRI was 196 +/- 44 g and 200 +/- 46 g, respectively. PET and MRI measurements were not statistically significant. A significant correlation was observed between PET and MRI for calculation of end-systolic volumes (r = 0.93, SEE = 23.4, P < 0.0001), end-diastolic volumes (r = 0.92, SEE = 26.7, P < 0.0001), ejection fraction (r = 0.85, SEE = 7.4, P < 0.0001), and left ventricular mass (r = 0.75, SEE = 29.6, P < 0.001). CONCLUSION: Model-based analysis of gated cardiac PET images permits an accurate assessment of left ventricular volumes, ejection fraction, and myocardial mass. Cardiac PET may thus offer a near-simultaneous assessment of myocardial perfusion, metabolism, and contractile function.

Arterial compliance: a diagnostic marker for atherosclerotic plaque burden?

BACKGROUND: Previous studies have shown atherogenesis to be related with increased vessel stiffness. Measures of the arterial compliance can be performed noninvasively from pressure pulse contour analysis of arterial waveforms. In this prospective study we aimed to analyze to what extent vessel compliance can reflect the angiographic coronary artery status. METHODS: Large and small arterial elasticity indices (LAEI in milliliters per mm Hg x 10 and SAEI in milliliters per mm Hg x 100) were measured in 151 patients on the radial artery with the PulseWave Sensor HDI device. All patients were classified into diffuse-coronary artery disease (CAD) (defined as stenosis length >15 mm), focal-CAD (defined as stenosis length between 1 and 15 mm), or no-CAD. RESULTS: We found both LAEI and SAEI to be reduced in the diabetic group (LAEI: 11.2 +/- 2.9 v 13.4 +/- 4.5, P =.006; SAEI: 3.7 +/- 1.6 v 4.7 +/- 2.4, P =.01). Inverse association was seen between age and LAEI (r = -0.41; P <.001) and SAEI (r = -0.38; P <.001). No-CAD was found in 31 patients, focal-CAD in 64 patients, and diffuse-CAD in 56 patients. Mean LAEI were 13.8 +/- 3.5, 13.7 +/- 4.7, and 11.3 +/- 3.5 in the groups no-CAD, focal-CAD, and diffuse-CAD, respectively (P =.004), (no-CAD versus diffuse-CAD: P =.04; focal-CAD versus diffuse-CAD: P =.009). Respective SAEI values were 5.6 +/- 2.5, 5.0 +/- 2.1, and 3.1 +/- 1.6 (P <.001), (no-CAD versus diffuse-CAD: P <.001; focal-CAD versus diffuse-CAD: P <.001). Multivariate analysis revealed SAEI (P <.001), hypercholesterolemia (P =.005), systolic blood pressure (BP) (P <.001), mean arterial BP (P <.001), pulse pressure (P =.003), and male gender (P =.001) to be diagnostic markers of the type of vessel disease. CONCLUSIONS: Compliance measurements may be used for identification of patients with diffuse atherosclerotic processes of the coronary arteries.

Agitated saline versus polygelatine for the echocardiographic assessment of patent foramen ovale.

BACKGROUND: The choice of the optimal echo contrast agent could be of relevance for the detection of a patent foramen ovale (PFO). This study compares agitated saline solution and oxypolygelatine (OXY) with respect to their ability to detect a PFO. METHODS: A total of 34 patients (13 women, age 45 +/- 16 years) underwent both transthoracic and transesophageal echocardiography. The appearance of contrast and the presence of a PFO was assessed visually and by acoustic densitometry for both agents. RESULTS: The sensitivity of the detection of a PFO (22 patent, 65%) was 71% with saline versus 84.6% for OXY. Maximum, mean acoustic densitometry grayscale intensity values and the duration of opacification was significantly higher for OXY versus saline for all chambers. CONCLUSIONS: OXY has superior echo properties that translate into a higher sensitivity for the detection of a PFO. The choice of the optimal agent must be considered for clinical routine and research studies.

[Long-term results of percutaneous transmyocardial laser revascularization therapy at the University of Vienna Medical Center]. / Langzeitergebnisse der "Perkutanen transmyokardialen Laser-Revaskularisations-Therapie" am AKH Wien.

INTRODUCTION: Percutaneous transmyocardial laser revascularization (PTMR) was used for treating patients with therapy refractory angina pectoris who are not amenable for angioplasty or bypass surgery ("no-option patients"). The aim of this study was to evaluate the short- and long-term results of PTMR-interventions performed at the University of Vienna between February 1999 and May 2000. PATIENTS AND METHODS: Twenty-four "no-option" patients underwent PTMR. The chronically ischemic myocardial areas were determined by perfusion scintigraphy; after coronary angiography and contrast ventriculography 10 patients were treated with the Biosense laser using 3D-NOGA-mapping guidance and 14 patients with the Eclipse laser using biplane fluoroscopic guidance. After an average follow-up period (FUP) of 7.7 +/- 4.2 months, all patients underwent perfusion scintigraphy, coronary angiography and contrast ventriculography. Global and regional left ventricular (LV) function were calculated by the area-length method. RESULTS: The ischemic myocardial areas of the patients were treated with an average of 16 laser points. In one patient, an intramural hematoma caused by the Biosense laser catheter was observed, in another patient the ventricular wall was perforated by the Eclipse laser (both events were resolved conservatively); during the in-hospital stay 2 patients suffered from severe angina pectoris and in one patient a pacemaker was implanted. During the 7-month-FUP one patient had a myocardial infarction; in one patient a stent implantation, in another one coronary bypass surgery had to be performed (in not-lasered areas), 2 patients died. Thus, the composite MACE rate was 33.3%. Angina class improved significantly during the FUP, but a trend to deterioration of global ejection fraction was observed. The rest and late rest myocardial perfusion remained unchanged. CONCLUSION: While the angina class of the patients improved significantly, no significant change of myocardial perfusion but a trend to deterioration of LV function after the FUP were observed.

Two-dimensional strain for the assessment of left ventricular function in low flow-low gradient aortic stenosis, relationship to hemodynamics, and outcome: a substudy of the multicenter TOPAS study.

BACKGROUND: Decision making in patients with low flow-low gradient aortic stenosis mainly depends on the actual stenosis severity and left ventricular function, which is of prognostic importance. We used 2-dimensional strain parameters measured by speckle tracking at rest and during dobutamine stress echocardiography to document the extent of myocardial impairment, its relationship with hemodynamic variables, and its prognostic value. METHODS AND RESULTS: In 47 patients with low flow-low gradient aortic stenosis, global peak systolic longitudinal strain (PLS) and peak systolic longitudinal strain rate (PLSR) were analyzed. PLS and PLSR at rest and peak stress were -7.56±2.34% and -7.41±2.89% (P=NS) and -0.38±0.12 s(-1) and -0.53±0.18 s(-1) (P<0.001), respectively. PLS and PLSR inversely correlated with left ventricular ejection fraction at rest (rs=-0.52; P<0.0001 and -0.38; P=0.008) and peak stress (rs=-0.39; P=0.007 and -0.45; P=0.002). The overall 2-year survival rate was 60%. Univariate predictors of survival were peak stress left ventricular ejection fraction (P=0.0026), peak stress PLS (P=0.0002), peak stress PLSR (P<0.0001), and N-terminal pro-B-type natriuretic peptide (P<0.0001). Three hierarchically nested multivariable Cox regression models were constructed-model 1: The Society of Thoracic Surgeons score as an indicator of clinical risk (area under the receiver operating characteristic=0.59); model 2: model 1+N-terminal pro-B-type natriuretic peptide and peak stress left ventricular ejection fraction (area under the receiver operating characteristic=0.83; incremental P<0.0001); model 3: model 2+peak stress PLSR (area under the receiver operating characteristic=0.89; incremental P=0.035). CONCLUSIONS: In patients with low flow-low gradient aortic stenosis, 2-dimensional strain parameters are strong predictors of outcome. Peak stress PLSR may add incremental prognostic value beyond what is obtained from N-terminal pro-B-type natriuretic peptide and peak stress left ventricular ejection fraction. A larger study is needed to confirm these findings.

Coronary vasoreactivity in subjects with thyroid autoimmunity and subclinical hypothyroidism before and after supplementation with thyroxine.

BACKGROUND: The association of subclinical hypothyroidism (SCH) with increased risk for cardiovascular disease is still controversial. This study aimed to examine coronary vascular reactivity by positron emission tomography (PET) in asymptomatic patients with SCH before and after levothyroxine (LT4) supplementation. METHODS: Ten patients (7 women and 3 men; mean age 43±15 years) with untreated autoimmune SCH, defined by elevated levels of thyroid-stimulating hormone (mean TSH: 16.9±11.3 µU/mL), normal levels of free thyroxine (0.9±0.1 µg/mL), free triiodothyronine (3.2±0.4 pg/mL), and positive thyroid peroxidase antibodies were studied. Eight euthyroid subjects with similar low-risk cardiovascular risk profile served as controls. Myocardial blood flow (MBF) and coronary flow reserve (CFR) were quantitatively assessed with rest/stress N-13 ammonia PET at baseline and after 6 months of LT4 replacement therapy (given only to patients). RESULTS: At baseline, stress MBF and CFR corrected (c) for rate pressure product (RPP) and myocardial vascular resistance (MVR) during stress were significantly reduced in SCH compared with controls (stress MBF: 2.87±0.93 vs. 4.79±1.16 mL/g/min, p=0.003; CFR: 2.6±0.73 vs. 4.66±1.38, p=0.004; MVR: 40.14±18.76 vs. 20.47±6.24 mmHg/mL/min, p=0.02). Supplementation therapy with LT4 normalized TSH in all subjects and was associated with an increase in CFR (2.6±0.73 vs. 3.81±1.19, p=0.003) and with a tendency toward a decrease in MVR. Differences in CFR between SCH and controls were also seen after correction of resting MBF for RPP. CONCLUSIONS: In asymptomatic subjects with SCH due to thyroid autoimmunity, coronary microvascular function is impaired and improves after supplementation with LT4. This may partially explain the increased cardiovascular risk attributed to SCH.

Effect of intramyocardial delivery of autologous bone marrow mononuclear stem cells on the regional myocardial perfusion. NOGA-guided subanalysis of the MYSTAR prospective randomised study.

The aim of the sub-study of the MYSTAR randomised trial was to analyse the changes in myocardial perfusion in NOGA-defined regions of interest (ROI) with intramyocardial injections of autologous bone marrow mononuclear cells (BM-MNC) using an elaborated transformation algorithm. Patients with recent first acute myocardial infarction (AMI) and left ventricular (LV) ejection fraction (EF) between 30-45% received BM-MNC by intramyocardial followed by intracoronary injection 68 +/- 34 days post-AMI (pooled data of MYSTAR). NOGA-guided endocardial mapping and 99m-Sestamibi-SPECT (single photon emission computer tomography) were performed at baseline and at three months follow-up (FUP). ROI was delineated as a best polygon by connecting of injection points of NOGA polar maps. ROIs were projected onto baseline and FUP polar maps of SPECT calculating the perfusion severity of ROI. Infarct size was decreased (from 27.2 +/- 10.7% to 24.1 +/- 11.5%, p<0.001), and global EF increased (from 38 +/- 6.1% to 41.5 +/- 8.4%, p<0.001) three months after BM-MNC delivery. Analysis of ROI resulted in a significant increase in unipolar voltage (index of myocardial viability) (from 7.9 +/- 3.0 mV to 9.9 +/- 2.7 mV at FUP, p<0.001) and local linear shortening (index of local wall motion disturbances) (from 11.0 +/- 3.9% to 12.7 +/- 3.4%, p=0.01). NOGA-guided analysis of the intramyocardially treated area revealed a significantly increased tracer uptake both at rest (from 56.7 +/- 16.1% to 62.9 +/- 14.2%, p=0.003) and at stress (from 59.3 +/- 14.2% to 62.3 +/- 14.9%, p=0.01). Patients exhibiting >or=5% improvement in perfusion defect severity received a significantly higher number of intramyocardial BM-MNC. In conclusion, combined cardiac BM-MNC delivery induces significant improvement in myocardial viability and perfusion in the intramyocardially injected area.

Implantation of paclitaxel-eluting stent impairs the vascular compliance of arteries in porcine coronary stenting model.

BACKGROUND: The impaired compliance of large and medium-sized muscular arteries has been shown to correlate with the risk of adverse cardiovascular events. We assessed coronary artery distensibility using simultaneous intracoronary ultrasound and pressure wire measurements in porcine coronary arteries after implantation of paclitaxel-eluting (PES) and bare metal stents (BMS) and compared this with the histopathology of the arterial wall injury. METHODS: PES and BMS were implanted into porcine left coronary arteries under general anesthesia. At 1-month follow-up (FUP) the endothelium-dependent and endothelium-independent vascular compliances were measured after intracoronary infusion of 10(-6)M acetylcholine for 2.5min, and intracoronary bolus of 100microg nitroglycerine, respectively. The arterial stiffness index, distensibility and reflexion index were calculated in stented arteries (n=25 PES and n=25 BMS), and correlated with histopathologic and histomorphometric changes of the vessel wall. RESULTS: In spite of smaller neointimal area, the fibrin deposition, medial thickening, vascular wall inflammation scores and arterial remodeling index were elevated and endothelialization was impaired in arteries with PES. Arteries with PES exhibited significantly worse endothelium-dependent vascular compliance: the stiffness (p<0.001) and reflexion index (p<0.001) were significantly higher and the distensibility index (p<0.001) lower as compared with the arteries with BMS. The endothelium-independent vascular reaction was similarly impaired in arteries with PES, as the stiffness index (p<0.001) and the distensibility index (p<0.001) differed significantly between the PES and BMS groups. Incomplete endothelialization (r=0.617, p<0.001) was significantly associated with the endothelium-dependent increased vascular stiffness. The increased fibrin score (r=0.646, p<0.001), vessel wall inflammation (r=0.657, p<0.001) and medial thickening (r=0.672, p<0.001) correlated significantly with the endothelium-independent stiffness index. CONCLUSIONS: Implantation of PES impairs the coronary artery wall structure and the endothelium-dependent and independent vessel wall dynamics more than does the implantation of BMS.

Combined delivery approach of bone marrow mononuclear stem cells early and late after myocardial infarction: the MYSTAR prospective, randomized study.

BACKGROUND: Combined intracoronary and intramyocardial administration might improve outcomes for bone-marrow-derived stem cell therapy for acute myocardial infarction (AMI). We compared the safety and feasibility of early and late delivery of stem cells with combined therapy approaches. METHODS: Patients with left ventricular ejection fraction less than 45% after AMI were randomly assigned stem cell delivery via intramyocardial injection and intracoronary infusion 3-6 weeks or 3-4 months after AMI. Primary end points were changes in infarct size and left ventricular ejection fraction 3 months after therapy. RESULTS: A total of 60 patients were treated. The mean changes in infarct size at 3 months were -3.5 +/- 5.1% (95% CI -5.5% to -1.5%, P = 0.001) in the early group and -3.9 +/- 5.6% (95% CI -6.1% to -1.6%, P = 0.002) in the late group, and changes in ejection fraction were 3.5 +/- 5.6% (95% CI 1.3-5.6%, P = 0.003) and 3.4 +/- 7.0% (95% CI 0.7-6.1%, P = 0.017), respectively. At 9-12 months after AMI, ejection fraction remained significantly higher than at baseline in both groups. In the early and late groups, a mean of 200.3 +/- 68.7 x 10(6) and 194.8 +/- 60.4 x 10(6) stem cells, respectively, were delivered to the myocardium, and 1.30 +/- 0.68 x 10(9) and 1.29 +/- 0.41 x 10(9) cells, respectively, were delivered into the artery. A high number of cells was required for significant improvements in the primary end points. CONCLUSIONS: Combined cardiac stem cell delivery induces a moderate but significant improvement in myocardial infarct size and left ventricular function.

Assessment of myocardial perfusion by dynamic N-13 ammonia PET imaging: comparison of 2 tracer kinetic models.

BACKGROUND: Measurement of myocardial blood flow (MBF) by dynamic nitrogen 13 ammonia (NH(3)) positron emission tomography (PET) uses tracer kinetic modeling to analyze time-activity curves. We compared 2 commonly used models with 2 compartments (2C) and 3 compartments (3C) for quantification of MBF and coronary flow reserve (CFR). METHODS AND RESULTS: Seventy-seven patients underwent NH(3) PET at rest and during hyperemia. Time-activity curves for blood pool and myocardial segments were obtained from short-axis images of dynamic sequences. Model fitting of the 2C and 3C models was performed to estimate regional MBF. MBF values calculated by 2C and 3C models were 0.98 +/- 0.31 mL.min(-1).g(-1) and 1.11 +/- 0.37 mL.min(-1).g(-1), respectively, at rest (P < .0001) and 2.79 +/- 1.18 mL.min(-1).g(-1) and 2.46 +/- 1.02 mL.min(-1).g(-1), respectively, during hyperemia (P < .01), resulting in a CFR of 3.02 +/- 1.31 and 2.39 +/- 1.15 (P < .0001), respectively. Significant correlation was observed between the 2 models for calculation of resting MBF (r = 0.78), hyperemic MBF (r = 0.68), and CFR (r = 0.68). CONCLUSION: Measurements of MBF and CFR by 2C and 3C models are significantly related. However, quantification of MBF and CFR significantly differs between the methods. This difference needs to be considered when normal values are established or when measurements obtained with different methods need to be compared.