Short-term outcome and attainment of secondary prevention goals in patients with acute coronary syndrome--results from the countrywide TARGET study.

BACKGROUND/OBJECTIVES: Acute coronary syndromes (ACS) continue to pose a significant medical and socioeconomic burden worldwide. Optimal management strategy aims to improve short and long-term outcome. The present study aims to assess short-term outcome of real-world ACS patients and evaluate the achievement rate of secondary prevention goals. METHODS: The TARGET study is an observational study enrolling 418 consecutive ACS patients from 17 centers countrywide (78.0% males, 63.9 ± 12.9 years). After the in-hospital phase, patients were followed for 6 months. In total, 366 patients were included in the prospective phase of the study. At the end of the follow-up, mortality, major adverse cardiovascular events (MACE), prescription pattern of cardiovascular medications, lipid levels, adherence rate to treatment and behavioral recommendations were measured. RESULTS: The overall mortality was 4.8% and the rate of MACE was 17.5%. At 6 months, a significantly lower proportion of patients received antiplatelet agents and statins as compared to hospital discharge. At the end of the follow-up, 87.7% of patients remained on statin treatment, yet only 18.2% of patients had LDL cholesterol levels less than 70 mg/dL. The adherence pattern to lifestyle and dietary recommendations remained low (66.2% quit smoking, 55.8% and 81.3% followed physical activity and dietary recommendations respectively). CONCLUSION: Despite the low rate of mortality and MACE occurrence rate in this countrywide observational study, the attainment rate of secondary prevention goals is relatively poor. Improvement interventions focusing in these gaps of optimal care provision are expected to have a favorable impact on the prognosis of real world ACS patients.

Myocardial blood flow at rest and contractile reserve in patients with chronic coronary artery disease and left ventricular dysfunction.

BACKGROUND: The mechanisms that determine chronic left ventricular dysfunction in coronary artery disease (in particular, critical reductions in coronary artery blood flow leading to hibernating myocardium) may affect the ability of the myocardium to respond to inotropic stimulation with dobutamine. This study was designed to investigate the relationship between resting myocardial blood flow and contractile reserve in patients with coronary artery disease and chronic left ventricular dysfunction. METHODS AND RESULTS: Twenty-three patients (21 men and 2 women; age 61 +/- 9 years) underwent transesophageal echocardiography during infusion of dobutamine (2.5 microg/kg to 40 microg/kg per minute) and positron emission tomography (PET) with 150-water (9 patients) or 13N-ammonia (14 patients). Systolic wall thickening at each dose of dobutamine and resting myocardial blood flow were quantitatively analyzed in 8 anatomically matched regions at mid-ventricular level. Myocardial regions with preserved contraction had higher blood flow compared with regions with basal dyssynergy (0.99 +/- 0.3 vs 0.65 +/- 0.3 mL/min/gm; P < .0001). Among myocardial regions with preserved resting contraction, no relation was observed between blood flow and the response to dobutamine (r = 0.06). In contrast, among myocardial regions with diminished resting contraction, a significant correlation was observed between resting blood flow and contractile reserve (r = 0.53; P < .0001). The maximum increase in percent systolic wall thickening with dobutamine was 32.8% +/- 14% in regions with normal blood flow, 21.5% +/- 17% in regions with mildly to moderately reduced blood flow, and 10.7% +/- 10% in regions with severely reduced blood flow (P < .0001). CONCLUSIONS: These findings emphasize the importance of resting myocardial blood flow for the preservation of contractile reserve in patients with coronary artery disease and left ventricular dysfunction. Because a positive inotropic response to dobutamine is more likely to occur in dyssynergic regions with preserved rather than reduced myocardial blood flow, regional perfusion may determine in which circumstances dobutamine echocardiography contributes to the assessment of myocardial viability.

13N-ammonia myocardial blood flow and uptake: relation to functional outcome of asynergic regions after revascularization.

OBJECTIVES: In this study we determined whether 13N-ammonia uptake measured late after injection provides additional insight into myocardial viability beyond its value as a myocardial blood flow tracer. BACKGROUND: Myocardial accumulation of 13N-ammonia is dependent on both regional blood flow and metabolic trapping. METHODS: Twenty-six patients with chronic coronary artery disease and left ventricular dysfunction underwent prerevascularization 13N-ammonia and 18F-deoxyglucose (FDG) positron emission tomography, and thallium single-photon emission computed tomography. Pre- and postrevascularization wall-motion abnormalities were assessed using gated cardiac magnetic resonance imaging or gated radionuclide angiography. RESULTS: Wall motion improved in 61 of 107 (57%) initially asynergic regions and remained abnormal in 46 after revascularization. Mean absolute myocardial blood flow was significantly higher in regions that improved compared to regions that did not improve after revascularization (0.63+/-0.27 vs. 0.52+/-0.25 ml/min/g, p < 0.04). Similarly, the magnitude of late 13N-ammonia uptake and FDG uptake was significantly higher in regions that improved (90+/-20% and 94+/-25%, respectively) compared to regions that did not improve after revascularization (67+/-24% and 71+/-25%, p < 0.001 for both, respectively). However, late 13N-ammonia uptake was a significantly better predictor of functional improvement after revascularization (area under the receiver operating characteristic [ROC] curve = 0.79) when compared to absolute blood flow (area under the ROC curve = 0.63, p < 0.05). In addition, there was a linear relationship between late 13N-ammonia uptake and FDG uptake (r = 0.68, p < 0.001) as well as thallium uptake (r = 0.76, p < 0.001) in all asynergic regions. CONCLUSIONS: These data suggest that beyond its value as a perfusion tracer, late 13N-ammonia uptake provides useful information regarding functional recovery after revascularization. The parallel relationship among 13N-ammonia, FDG, and thallium uptake supports the concept that uptake of 13N-ammonia as measured from the late images may provide important insight regarding cell membrane integrity and myocardial viability.

Stress-induced reversible and mild-to-moderate irreversible thallium defects: are they equally accurate for predicting recovery of regional left ventricular function after revascularization?

BACKGROUND: In patients with coronary artery disease, stress-redistribution-reinjection thallium scintigraphy provides important information regarding myocardial ischemia and viability. Although both reversible and mild-to-moderate irreversible thallium defects retain metabolically active, viable myocardium, we hypothesized that stress-induced reversible thallium defects may better differentiate reversible from irreversible regional left ventricular dysfunction after revascularization. METHODS AND RESULTS: Twenty-four patients with chronic coronary artery disease underwent prerevascularization and postrevascularization exercise-redistribution-reinjection thallium single photon emission CT, gated MRI, and radionuclide angiography. After revascularization, mean left ventricular ejection fraction increased from 30+/-9% to 37+/-13% at rest (P<0.001). Before revascularization, abnormal contraction at rest was observed in 56 of 110 reversible and 20 of 37 mild-to-moderate irreversible thallium defects (51% and 54%, respectively). After revascularization, regional contraction improved in 44 of 56 reversible compared with 6 of 20 mild-to-moderate irreversible thallium defects (79% and 30%, respectively; P<0.001). The final thallium content (maximum tracer uptake on redistribution-reinjection images) was significantly higher in regions with reversible defects that improved than in those that did not improve after revascularization (86+/-16% versus 66+/-9%, P<0.001). In contrast, final thallium content was similar in regions with mild-to-moderate irreversible defects that improved and in those that did not improve after revascularization (69+/-9% versus 65+/-10%, P=NS). Furthermore, when asynergic regions were grouped according to the final thallium content, at 60% threshold value, functional recovery was observed in 83% of regions with reversible defects compared with 33% of regions with mild-to-moderate irreversible defects (P<0.001). CONCLUSIONS: These findings suggest that although both reversible and mild-to-moderate irreversible thallium defects after stress retain viable myocardium, the identification of reversible thallium defect on stress in an asynergic region more accurately predicts recovery of function after revascularization. Even at a similar mass of viable myocardial tissue (as reflected by the final thallium content), the presence of inducible ischemia is associated with an increased likelihood of functional recovery.

[18F]fluorodeoxyglucose single photon emission computed tomography: can it replace PET and thallium SPECT for the assessment of myocardial viability?

BACKGROUND: New high-energy collimators for single photon emission computed tomography (SPECT) cameras have made imaging of positron-emitting tracers, such as [18F]fluorodeoxyglucose (18FDG), possible. We examined differences between SPECT and PET technologies and between 18FDG and thallium tracers to determine whether 18FDG SPECT could be adopted for assessment of myocardial viability. METHODS AND RESULTS: Twenty-eight patients with chronic coronary artery disease (mean left ventricular ejection fraction [LVEF]=33+/-15% at rest) underwent 18FDG SPECT, 18FDG PET, and thallium SPECT studies. Receiver operating characteristic curves showed overall good concordance between SPECT and PET technologies and thallium and 18FDG tracers for assessing viability regardless of the level of 18FDG PET cutoff used (40% to 60%). However, in the subgroup of patients with LVEF< or =25%, at 60% 18FDG PET threshold value, thallium tended to underestimate myocardial viability. In a subgroup of regions with severe asynergy, there were considerably more thallium/18FDG discordances in the inferior wall than elsewhere (73% versus 27%, P<.001), supporting attenuation of thallium as a potential explanation for the discordant observations. When uptake of 18FDG by SPECT and PET was compared in 137 segments exhibiting severely irreversible thallium defects (scarred by thallium), 59 (43%) were viable by 18FDG PET, of which 52 (88%) were also viable by 18FDG SPECT. However, of the 78 segments confirmed to be nonviable by 18FDG PET, 57 (73%) were nonviable by 18FDG SPECT (P<.001). CONCLUSIONS: Although 18FDG SPECT significantly increases the sensitivity for detection of viable myocardium in tissue declared nonviable by thallium (to 88% of the sensitivity achievable by PET), it will occasionally (27% of the time) result in falsely identifying as viable tissue that has been identified as nonviable by both PET and thallium.

A "hybrid" method for measuring myocardial wall thickening from gated PET/SPECT images.

UNLABELLED: We introduce a hybrid index, HYB, which combines counts with geometric information to measure wall thickening from PET/SPECT gated images. Its accuracy is compared with that of a count-based index (MAX) and a geometric index (FWHM). METHODS: For each index, the index values versus thickness and the estimated thickening values versus true thickening were investigated using theoretical analyses, realistic simulated data obtained from clinical gated MR scans, phantom measurements and preliminary gated MRI and PET patient studies. Each index was studied for different spatial resolutions and noise and background conditions. The performance of each index was quantified using a parameter "Q" reflecting bias and variability of thickening estimates. RESULTS: HYB varied more linearly with thickness than MAX and FWHM, resulting in a better Q value than with MAX and FWHM for all noise, background and spatial resolutions. ROC analysis confirmed that HYB significantly increases the sensitivity and specificity for detection of wall thickening abnormalities (sensitivity = 100%; specificity = 85% for HYB, 95% and 50% for MAX and 100% and 0% for FWHM, respectively). CONCLUSION: Use of the hybrid index instead of conventional count-based or geometric indices should improve the classification of normal/abnormal wall thickening values in gated SPECT and PET.

Left ventricular ejection fraction: comparison of results from planar and SPECT gated blood-pool studies.

UNLABELLED: Global ejection fraction (EF) from planar gated blood-pool (GBP) imaging is a widely accepted measure of cardiac function. It has been suggested that planar GBP could be replaced by SPECT. In this article, we compare counts-based global EF measured from SPECT and planar images and investigate reasons for discrepancies between the two. METHODS: Twenty-three subjects were imaged with both planar and SPECT GBP. SPECT short-axis slices were projected to create reprojected images. Reprojected SPECT (rSPECT) images were created in both the true long-axis view and also in a view typical of planar studies (found to be 60 degrees from the true long-axis). Thus, angle of view effects on global EF could be investigated. In addition, we studied the effects of background and attenuation. RESULTS: Long-axis rSPECT EF correlated well with planar EF (r = 0.89) but EF values were significantly higher for rSPECT than for planar (slope = 1.4, intercept = -8 EF units; p < 0.001). We found that background correction may not be necessary with rSPECT, but neither background nor attenuation explained the observed discrepancy between rSPECT and planar EFs. This discrepancy was found to be caused by atrial overlap in the planar image and disappeared when the SPECT slices were reprojected at the same angle of view as the planar images. CONCLUSION: Global EF can be easily measured from rSPECT GBP images. Long-axis rSPECT EFs are, however, greater than planar EFs by a factor of 1.4 because atrial overlap causes a significant drop in planar EF in planar images. These results suggest that (long-axis) rSPECT EFs may be more accurate than planar EFs.

Comparative effects of basic fibroblast growth factor and vascular endothelial growth factor on coronary collateral development and the arterial response to injury.

BACKGROUND: We have shown that the angiogenic peptides basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) enhance canine coronary collateral development when administered for > or = 4 weeks. bFGF, a pluripotent mitogen of mesodermally derived cells, could theoretically exacerbate neointimal smooth muscle cell hyperplasia, a fundamental component of atherosclerosis. VEGF, an endothelial cell-specific mitogen and vascular permeability factor, could have deleterious effects related to vascular hyperpermeability. The present investigation had two aims: (1) to ascertain whether brief (7-day) systemic arterial treatment with bFGF or VEGF would improve myocardial collateral perfusion and (2) to determine whether these peptides induce neointimal accumulation in vivo. METHODS AND RESULTS: Dogs were subjected to ameroid-induced occlusion of the left circumflex coronary artery and randomized to bFGF 1.74 mg (n = 9), VEGF 0.72 mg (n = 9), or saline (n = 10) as a daily left atrial bolus (days 10 to 16). Additional dogs were randomized to VEGF 0.72 mg (n = 6) or saline (n = 5); however, treatment was delayed by 1 week. Coincident with the institution of treatment, all dogs underwent balloon denudation injury of the iliofemoral artery. bFGF markedly increased maximal collateral flow but did not exacerbate neointimal accumulation. VEGF had no discernible effect on maximal collateral flow, but it exacerbated neointimal thickening after vascular injury. CONCLUSIONS: Short-term treatment with bFGF enhanced collateral development without increasing neointimal accumulation at sites of vascular injury. Although VEGF did not increase collateral development as administered in this study, it significantly exacerbated neointimal accumulation. These data provide support for the clinical investigation of bFGF in selected patients with ischemic heart disease.

The circadian profile of extrasystolic arrhythmia: its relationship to heart rate and blood pressure.

This paper aims at examining whether there is an association between the circadian patterns of systolic blood pressure, heart rate and the incidence of ventricular ectopic beats, as well as to confirm that reducing the blood pressure by a diuretic may also reduce the ectopic frequency. Thirty-four ambulatory patients with ventricular ectopic beats and a systolic blood pressure of 131.33 +/- 17.46 mmHg had a 24-hour Holter electrocardiographic and blood pressure monitoring following 1 week off any antiarrhythmic and antihypertensive treatment. Then they received for one week a standard diuretic combination (amiloride 5 mg + hydrochlorothiazide 50 mg) at a dose depending on their systolic pressure value and their monitoring was repeated. The mean hourly values of systolic blood pressure, heart rate and ventricular ectopic beats were "normalized", i.e. expressed as (x-x)/SD, taking each patient's 24-hour average as zero and his own standard deviation as the unit of measurement. As a group, there was an independent positive correlation between blood pressure and ectopic beats, while the heart rate was a nonsignificant negative factor for ectopic beats. On an individual level, however, an independent positive significant correlation between blood pressure and ectopic beats was found in only 8 cases, with a negative one in 4 cases. While the blood pressure of the group ranged symmetrically around its daily average value, the corresponding ectopic beat curve was highly asymmetric, with a very high incidence (up to 2.56 +/- 0.52 SD) for a rather short time (only 9.41 +/- 3.56 hours above average) and a low incidence (up to 1.26 +/- 0.49 SD) for the remaining 14.59 hours below average. Sudden rises in ectopic beat (greater than 1 SD/hour) occurred 1 to 6 times per day in each individual, significantly (P less than 0.01) more often (20.31%) with a high (greater than 1 SD) blood pressure than with a low (less than -1 SD) one (8.99%) with intermediate frequencies at intermediate pressures. After treatment with the diuretic, the systolic blood pressure was reduced, the heart rate increased and the ventricular ectopic beat incidence reduced (significant changes). The mean change in systolic pressure in 25 patients with a reduction in ectopy was a significant (P less than 0.01) decrease (-5.21 +/- 8.70 mmHg) while in the remaining 9 cases there was a non significant increase (+1.68 +/- 7.63 mmHg). The heart rate was higher in both subgroups.(ABSTRACT TRUNCATED AT 400 WORDS)

Induced electrophysiological isolation of the myocardium prevents ventricular fibrillation.

STUDY OBJECTIVE: to investigate whether an encircling procedure without ventriculotomy, not involving the endocardium, may have a protective effect against ventricular fibrillation (VF), by achieving a physiological rather than anatomic entrenchment. DESIGN: the occurrence of VF was tested by DC application within an area entrenched by a circular "dotted" line formed by LASER (Nd-Yag) point by point applications. The result was compared with that from similar DC applications before the successful LASER entrenchment or beyond the restricted area. SUBJECTS: 16 anaesthetized mongrel dogs, weights 14-20 kg were used. MEASUREMENTS AND RESULTS: VF occurred 13/118 times by applying DC within the entrenched area and 86/114 times by applying the current outside this area or before the intervention (P less than 0.0005). The pacing threshold was significantly (P less than 0.001) increased within the circumscribed area (4.625 +/- 5.335 vs 0.859 +/- 0.947 mA). The maximal rate at which the ventricles could be driven by pacing at double threshold intensity was not significantly altered by the encircling procedure. Histological examination showed crater-like epicardial destruction with necrosis, loss of myocardial striation, haemorrhage, and polymorphonuclear infiltration, extending about 0.5 cm from the necrotic tissue. The subendocardial area was spared showing only hyperaemia, while the endocardium was intact. CONCLUSIONS: Encircling a small area by LASER point by point applications prevents the occurrence of VF when DC is applied within the restricted area, while permitting the conduction of paced beats. The size of the encircled area necessary to this effect is of importance, possibly reflecting the critical mass needed for the occurrence and maintenance of VF.