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Biomedical subjects

G Fragasso

Publications and source records attributed to G Fragasso.

At least 19 recordsLinked to original sources

Time course and determinants of left ventricular function recovery after primary angioplasty in patients with acute myocardial infarction.

OBJECTIVES: We sought to evaluate the importance of time in relation to treatment, time course and determinants of recovery of left ventricular (LV) function in patients with acute myocardial infarction (AMI) undergoing primary percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Myocardial salvage has been shown to be dependent on the time elapsed from the onset of AMI to reperfusion. METHODS: Left ventricular function was evaluated at hospital admission, after angioplasty, at 24 h and 6 months by both echocardiography and angiography and at 1, 7, 30, 90 and 180 days by echocardiography in 101 consecutive patients. RESULTS: Patients were allocated to three groups according to interval between symptom onset and angioplasty: <2 h (group A), 2 to 4 h (group B) and >4 h (group C). Patients in groups A and B showed a progressive improvement of LV function between day 7 and day 90, which became statistically significant at day 30 (p < 0.01). No LV function changes were noted in group C patients. Thrombolysis In Myocardial Infarction (TIMI) flow grade <3 at 24 h was not associated with any significant change in LV volume and function during the six-month follow-up period. Restenosis, when associated with TIMI flow grade 3 in the infarct-related vessel, did not influence LV function. Flow grade <3 of the infarct-related artery was not associated with any improvement of cardiac events independently from the time to treatment at the initial procedure. CONCLUSIONS: Patients undergoing primary PTCA for AMI have a good recovery of LV function if TIMI flow grade 3 is restored within 4 h. Coronary angioplasty limits further remodeling of the LV in patients treated after 4 h.

Angioplasty, Balloon, Coronary↗

Influence of treatment delay on long-term left ventricular function in patients with acute myocardial infarction successfully treated with primary angioplasty.

BACKGROUND: Myocardial salvage has been shown to be dependent on the time elapsed from the onset of acute myocardial infarction (AMI) to reperfusion. The aim of this study was to evaluate the importance of time to reperfusion for left ventricular function recovery after primary angioplasty (percutaneous transluminal coronary angioplasty [PTCA]) for AMI. METHODS: Ninety-five patients undergoing long-term successful PTCA for AMI were studied. Echocardiography was performed before and 3, 7, 30, 90, and 180 days after PTCA. End-diastolic volume index (EDVI) and end-systolic volume index (ESVI), ejection fraction, and left ventricular wall motion score index (WMSI) were evaluated. RESULTS: Patients were divided into group A, 23 patients reperfused within 2 hours; group B, 32 patients reperfused between 2 and 4 hours; group C, 22 patients reperfused between 4 and 6 hours; and group D, 18 patients reperfused between 6 and 12 hours. Both EDVI and ESVI were reduced in groups A and B at 90 days. Groups C and D did not show any changes of EDVI and ESVI at any stage throughout the study. Ejection fraction improved only in groups A and B at 30, 90, and 180 days. At study entry, WMSI was similar in all groups. After 7 days, in group A and in group B, WMSI was improved, no changes were observed in group C, and a mild deterioration was observed in group D at 3 and 7 days. Subsequent evaluations showed progressive improvement of WMSI in all groups. CONCLUSIONS: Myocardial salvage is achieved only in patients revascularized within 4 hours from AMI onset. However, revascularization after 6 hours may be worthwhile by preventing ventricular remodeling.

Adult↗

Enoximone echocardiography for predicting recovery of left ventricular dysfunction after revascularization : a novel test for detecting myocardial viability.

BACKGROUND: The possibility that enoximone, a nonglycoside, noncatechol, positive inotropic agent, in combination with 2-dimensional echocardiography may predict recovery of myocardial dysfunction after revascularization has not been yet evaluated. METHODS AND RESULTS: Forty-five patients with chronic coronary artery disease and left ventricular dysfunction underwent dobutamine (DE, 5 to 10 microg. kg(-1). min(-1)) and enoximone (EE, 1.5 mg/kg, over 10 minutes) echocardiography. Myocardial wall motion was scored from 1 (normal) to 4 (dyskinesia): an asynergic segment was considered to have contractile enhancement when the score decreased by >/=1 grade. Of 478 asynergic segments, 216 (45%) exhibited functional recovery after revascularization. Dobutamine- and enoximone-induced contractile enhancement was observed in 41% and 46% of segments, respectively. Compared with DE, EE had higher sensitivity (88% versus 79%, P<0.01) and negative predictive value (90% versus 84%, P<0.05) in predicting functional recovery. The specificity (89% versus 90%) and positive predictive value (87% for both EE and DE) were similar. Concordant interpretation of EE and DE findings was found in 85% (406 of 478) of affected segments. Prerevascularization coronary angiography showed that stenosis severity of vessels supplying areas which only improved with enoximone was significantly greater (89.9%) than that of vessels (77.7%) supplying areas that responded to both agents (P<0.02). Both dobutamine and enoximone increased heart rate (16% and 10%, respectively), whereas enoximone did not cause changes in systolic blood pressure that increased by 14% with dobutamine. CONCLUSIONS: Enoximone echocardiography provides a novel and reliable approach for the prediction of functional recovery after revascularization. Compared with dobutamine echocardiography, the test yields higher sensitivity and induces lesser hemodynamic alterations.

Adult↗

Relationship between endothelin-1 concentration and metabolic alterations typical of the insulin resistance syndrome.

The purpose of the study was to examine the relationship between the endothelin-1 (ET-1) concentration and the metabolic variables characteristic of the insulin resistance syndrome ([IRS] hyperinsulinemia, insulin resistance, hypertriglyceridemia, low high-density lipoprotein [HDL] cholesterol, visceral obesity, and glycemic abnormalities). The measurement of circulating ET-1 is a well-recognized marker of endothelial atherosclerotic and cardiovascular disease. Two hundred subjects were divided into 3 groups. Group 1 included 50 subjects with impaired glucose tolerance (IGT) or non-insulin-dependent diabetes mellitus (NIDDM) with IRS. Group 2 included 50 subjects with IGT or NIDDM without IRS. Group 3 included 100 normal subjects as controls. ET-1 levels were higher in group 1 versus groups 2 and 3 in women (11.2 +/- 0.7 v 7.9 +/- 0.5 and 6.6 +/- 0.4 pg/mL, P < .01) and men (10.1 +/- 0.6 v 6.5 +/- 0.8 and 7.2 +/- 0.3 pg/mL, P < .01). No differences were found between groups 2 and 3. With simple regression analysis, ET-1 levels significantly correlated with insulin, glycosylated hemoglobin, body weight, waist to hip ratio, and triglyceride values. However, with multiple regression analysis, only triglycerides (P < .009) and glycosylated hemoglobin (P < .001) remained independently correlated with ET-1. In conclusion, this cross-sectional study indicates that glycosylated hemoglobin and triglycerides are independently correlated with ET-1 levels in patients with IRS.

Blood Glucose↗

[The primary and secondary prevention of ischemic cardiopathy].

The aim of this paper was to summarize the most important clinical issues on coronary artery disease prevention, in order to provide the best advice to cardiologists, and facilitate their work on primary and secondary prevention. Although in recent years the knowledge of the beneficial effects of major risk factor modification has been increasing, most physicians still concentrate only on patients with overt coronary artery disease. Many high-risk individuals are not adequately advised and treated, whilst a great effort should be made by national institutions and individual doctors to implement primary prevention schemes. Indeed, the potential for preventive measures is greatest in high-risk groups. Specific international task forces have issued official recommendations on the prevention of coronary heart disease in clinical practice, which have been intended to encourage the development and revision of national guidelines on coronary prevention. The challenge for cardiologists in the year 2000 is to realize the potential for coronary prevention in all patients, and to contribute to reduce the enormous socio-economic burden of cardiovascular disease.

Fibrinolytic Agents↗

Detrimental effects of acute heparin administration on ischemic threshold in patients with coronary artery disease.

BACKGROUND: Recent studies have indicated that heparin administration might decrease endothelial nitric oxide production. The aim of this study was to investigate the effect of heparin on ischemic threshold. METHODS: Eighteen patients with a positive exercise test and proven coronary artery disease were submitted to a randomized, placebo-controlled trial using i.v. 0.9% NaCl as placebo and i.v. heparin (5,000 IU bolus + 1,000 IU/h). After both saline and heparin bolus, the infusion was started and, after 10 min, the exercise test was performed. Blood samples for nitric oxide metabolites and free fatty acid determinations were taken before, at peak exercise, and at ECG recovery. RESULTS: As compared to placebo, heparin significantly decreased time to 1 mm ST segment depression (241 +/- 160 vs 303 +/- 175 s, p = 0.003) and prolonged recovery (573 +/- 177 vs 441 +/- 195 s, p = 0.003), while exercise duration was similar. Accordingly, rate-pressure product at 1 mm ST segment depression was lower after heparin, while it was similar at peak exercise. No significant differences were found for plasma nitric oxide metabolite levels. Conversely, free fatty acid levels were higher after heparin throughout the study in all patients. The increase in free fatty acids was not correlated with the difference in rate-pressure product at 1 mm ST segment depression between placebo and heparin (r = 0.34, p = NS). CONCLUSIONS: In patients with stable coronary artery disease, heparin significantly decreased exercise ischemic threshold. The lower rate-pressure product at 1 mm ST segment depression during heparin, compared to placebo, suggests an impairment of coronary blood flow, which does not seem to be mediated by decreased nitric oxide production/release. The increased free fatty acid release, on the other hand, might contribute to the detrimental effect of heparin on exercise-induced ischemia, but the lack of a correlation with changes in ischemic threshold suggests that other, still unknown, factors are involved.

Aged↗

Diagnosing coronary artery disease in patients with hypertension: a resolved dilemma?

Patients with hypertension frequently complain of chest pain and exhibit ischemic-like ST segment changes on exercise electrocardiogram. However, the specificity of such changes for predicting significant coronary artery disease is very low, since these patients often exhibit a normal coronary angiogram. Several alternative non-invasive tests have been proposed and, recently, the relative performance of the available techniques has been systematically assessed. The purpose of this article is to review the relevant literature on the diagnostic tests employed in the clinical setting. Recent evidence suggests that stress echocardiography yields a better diagnostic accuracy than perfusion scintigraphy in identifying significant epicardial coronary artery disease in patients with hypertension. The low specificity of myocardial scintigraphy probably relates to the fact that this method traces perfusion abnormalities, not necessarily caused by epicardial coronary artery disease, possibly due to microvascular disease, and not axiomatically causing obvious wall motion abnormalities.

Cardiotonic Agents↗

Endothelial and metabolic characteristics of patients with angina and angiographically normal coronary arteries: comparison with subjects with insulin resistance syndrome and normal controls.

OBJECTIVES: This study was performed to characterize the endothelial and metabolic alterations of patients with angina and angiographically normal coronary arteries ("cardiac" syndrome X [CSX]) compared with subjects with insulin resistance syndrome ("metabolic" syndrome X [MSX]) and normal controls. BACKGROUND: Previous studies have found high endothelin-1 levels, impaired endothelium-dependent vasodilation and insulin resistance in patients with angina pectoris and angiographically normal coronary arteries. On the other hand, subjects with insulin resistance syndrome have shown high endothelin-1 levels. METHODS: Thirty-five subjects were studied: 13 patients with angina pectoris and angiographically normal coronary arteries (CSX group); 9 subjects with insulin resistance syndrome (MSX group) and 13 normal controls. All subjects received an acute intravenous bolus of insulin (0.1 U/kg) combined with a euglycemic clamp and forearm indirect calorimetry. Endothelin-1 levels, nitrite/nitrate (NOx) levels, end products of nitric oxide metabolism, glucose infusion rates (index of insulin sensitivity) and their incremental areas (deltaAUCs [area under curves]) were measured during this period. RESULTS: Basal endothelin-1 levels were higher in CSX and MSX groups than in normal controls (8.19 +/- 0.46 and 6.97 +/- 0.88 vs. 3.67 +/- 0.99 pg/ml; p < 0.01), while basal NOx levels were significantly higher in MSX group than in CSX and normal controls (36.5 +/- 4.0 vs. 24.2 +/- 3.3 and 26.8 +/- 3.2 mol/liter, p < 0.05). After insulin administration, the deltaAUCs of NOx (p < 0.05) were lower in CSX group than in MSX and normal controls, and the deltaAUCs of endothelin-1 were lower in group CSX than in normal controls. Glucose infusion rate was significantly lower in CSX and MSx groups than in normal controls (p < 0.01), suggesting that in both CSX and MSX groups insulin resistance is present. A positive correlation was found between the deltaAUCs of nitric oxide and the AUCs of glucose infusion rate. CONCLUSIONS: Blunted nitric oxide and endothelin responsiveness to intravenously infused insulin is a typical feature of patients with angina pectoris and angiographically normal coronary arteries and may contribute to the microvascular dysfunction observed in these subjects.

Calorimetry, Indirect↗

Comparison of stress/rest myocardial perfusion tomography, dipyridamole and dobutamine stress echocardiography for the detection of coronary disease in hypertensive patients with chest pain and positive exercise test.

OBJECTIVES: Although different noninvasive tests have been proposed for detecting coronary artery disease (CAD) in patients with hypertension and chest pain symptoms, the relative performance of the available techniques has not been systematically assessed. BACKGROUND: Patients with hypertension frequently complain of chest pain and exhibit ischemic-like ST segment changes on the exercise electrocardiogram (ECG). However, the specificity of such changes for predicting significant CAD is very low, because these patients often exhibit a normal coronary angiogram. METHODS: In 101 patients with hypertension, chest pain and positive exercise ECG, we performed stress/rest myocardial single photon emission computed tomography with 99mTc-MIBI, dipyridamole and dobutamine stress echocardiography and coronary angiography. All patients had normal global ventricular function and 57 had left ventricular hypertrophy. All were kept on ACE inhibitors during the study period. RESULTS: No patients had significant side effects during perfusion scintigraphy. Dose-limiting side effects were observed in five patients with dipyridamole and in seven patients with dobutamine. Only 56% of study patients exhibited significant CAD. Sensitivity, specificity, accuracy, positive and negative predictive values were, respectively, 98%, 36%, 71%, 67% and 94% for perfusion scintigraphy, 61%, 91%, 74%, 90% and 64% for dipyridamole and 88%, 80%, 84%, 85% and 83% for dobutamine stress echocardiography. CONCLUSIONS: This study shows that stress echo in patients with hypertension yields a satisfactory diagnostic accuracy for identifying significant epicardial CAD. Our results indicate that dobutamine might be superior to dipyridamole. The low specificity of myocardial scintigraphy probably relates to the fact that this method traces perfusion abnormalities, not necessarily caused by epicardial CAD, possibly due to microvascular disease and not causing obvious wall motion abnormalities.

Aged↗

Left ventricular dysfunction during dobutamine stress echocardiography in patients with syndrome X and positive myocardial perfusion scintigraphy.

AIMS: A sizeable proportion of patients with angina, angiographically smooth coronary arteries and positive exercise test (syndrome X) have stress/rest myocardial perfusion defects. The aim of the study was to assess whether perfusion defects are dependent upon a reduction in coronary flow reserve causing regional left ventricular dysfunction in syndrome X patients. METHODS AND RESULTS: Twenty-two syndrome X patients underwent dobutamine stress echocardiography (DSE). All had stress-induced perfusion defects documented by 99m-Tc-MIBI scintigraphy. Resting and peak DSE wall motion score index (WMSI) were evaluated. Six patients exhibited resting wall motion abnormalities in 10 segments (WMSI 1.05 +/- 0.11). DSE was positive in 12 patients (53%), in whom 16 myocardial segments were involved: of these, 12 were normokinetic and 4 hypokinetic at rest. Peak WMSI was 1.17 +/- 0.17 (p < 0.05 vs rest). Of the 12 patients with a positive DSE, 9 also showed diagnostic ECG changes and 6 complained of angina. Of the 10 patients with negative DSE, 5 had angina and 5 (one with angina) showed ECG changes. In 7 patients (7 segments) (32%), the location of dobutamine-induced wall motion abnormalities coincided with the area where exercise-induced hypoperfusion was observed with MIBI. CONCLUSIONS: More than a half of syndrome X patients with myocardial perfusion abnormalities also develop regional LV dysfunction during DSE. However, the site of perfusion defects and wall motion abnormalities can be different. Reversible ischemia, defined as a parallel limitation of flow reserve and inducible dysfunction, could be identified as the cause of chest pain in almost one-third of patients.

Adult↗

Long-term preservation of left ventricular function in medically treated patients with coronary artery disease and persistent exercise-induced ischemia.

Little information is available on the long-term evolution of left ventricular function of medically treated patients with coronary artery disease and gross limitation of coronary flow reserve. The aim of this study was to assess the long-term evolution of effort tolerance and left ventricular function and their relation to the control of ischemic events in patients with coronary artery disease and prolonged inducible exercise-induced myocardial dysfunction who either declined or were ineligible for cardiac revascularization.

Aged↗

Magnetic resonance contrast enhancement with gadolinium-DTPA in patients with angina and angiographically normal coronary arteries: effect of chronic beta-blockade.

BACKGROUND: The syndrome of angina and normal coronary arteries (syndrome X) comprises a heterogeneous group of patients with typical chest pain, a positive exercise test, angiographically smooth coronary arteries and no evidence of spasm. Magnetic resonance imaging (MRI) has been used to detect areas of myocardial ischemia and/or recent necrosis both in animal and human studies. Most of these studies have been conducted after intravenous administration of the paramagnetic contrast medium gadolinium-DTPA (Gd-DTPA), that is considered a sensitive marker of extracellular, probably ischemic in origin, edema. On the basis of these data, we used MRI to evaluate the possibility of myocardial Gd-DTPA deposition at rest in patients with syndrome X, and to assess the effects of oral treatment with atenolol. METHODS: We have studied 24 patients with syndrome X, 10 patients with coronary artery disease and 10 age-matched control subjects. The protocol was similar in all study subjects. Exercise testing and MRI were undertaken off therapy after coronary arteriography. Following MRI, patients underwent a 10 day treatment period with atenolol and repeated exercise stress test and MRI while on therapy. RESULTS: In all patients with syndrome X and coronary artery disease were observed effort diagnostic ST-segment changes that were associated with angina in 9 (37%) and 7 (70%) patients, respectively. Of 24 patients with syndrome X, 16 (66.6%) showed areas of myocardial enhancement after Gd-DTPA in comparison to the precontrast imaging. In 4 out of 10 patients with coronary artery disease (40%), Gd-DTPA accumulation was documented. Finally, focal Gd-DTPA myocardial enhancement was not observed in any normal control subject. After beta-blockade, 22 (92%) patients with syndrome X and 2 (20%) with coronary artery disease did not show any ischemic ST-segment changes on effort; 14 syndrome X patients (88%) and 2 coronary artery disease patients (50%) showed complete disappearance of the previously Gd-DTPA enhanced areas on MRI. CONCLUSIONS: Patients with syndrome X often exhibit regional accumulation of Gd-DTPA on MRI. The agent is believed to trace interstitial water accumulation as occurs during ischemia and its accumulation is reduced or abolished by treatment with atenolol, probably by different mechanisms. It is likely that an overactivation of the sympathetic outflow to the cardiovascular system can induce most of the abnormalities observed in syndrome X patients. In this context, beta-blockers probably represent the mainstay of the medical treatment of this condition.

Adrenergic beta-Antagonists↗

Comparison of trimetazidine with atenolol in patients with syndrome X: effects on diastolic function and exercise tolerance.

BACKGROUND: Trimetazidine has been shown to improve anginal symptoms without altering hemodynamic variables in patients with coronary artery disease. The aim of this study was to compare the effect of trimetazidine and atenolol upon symptoms, resting left ventricular filling dynamics and exercise tolerance. METHODS: Sixteen patients (3 males, 13 females, mean age 62 +/- 7 years) were randomized to receive trimetazidine for 2 weeks (20 mg 3 times daily) or atenolol (100 mg daily), according to a double-blind, randomized, cross-over, placebo-controlled design. At the end of each treatment period patients underwent symptom-limited exercise testing, an echocardiogram and a Doppler assessment of transmitral flow pattern. Daily life anginal symptoms were annotated on a diary throughout the study. Two patients discontinued trimetazidine because of severe palpitations and only 14 patients completed the study. RESULTS: Atenolol significantly reduced the number of anginal episodes as compared to placebo or trimetazidine (0.44 +/- 0.53, 4.8 +/- 4, 2.9 +/- 4.9, p < 0.01). On atenolol, the exercise test was negative in 8 patients, but none of the patients had a negative test while on trimetazidine. Atenolol increased both time to 1 mm ST segment depression (668 +/- 213 vs 838 +/- 81 s, p < 0.05) and Doppler-derived indices of ventricular filling (E/A ratio 0.87 +/- 0.20 vs 1.21 +/- 0.26, p < 0.05). CONCLUSIONS: These results confirm the beneficial effects of atenolol in improving symptoms, exercise performance and diastolic function in syndrome X patients. Trimetazidine did not exert any significant effect on any of the analyzed variables. Since trimetazidine has been previously shown to improve myocardial ischemia in patients with overt coronary artery disease to a similar extent of beta-blockers, it is likely that other mechanisms are responsible for angina in patients with syndrome X.

Adrenergic beta-Antagonists↗

Effects of trimetazidine on ischemic left ventricular dysfunction in patients with coronary artery disease.

We studied 15 patients with chronic coronary artery disease (13 men aged 62 +/- 8 years) undergoing dobutamine (5 to 40 microg/kg/min) echocardiography at the end of two 15-day treatment periods with placebo and trimetazidine (20 mg 3 times daily) given in random order, according to a double-blind, crossover design. Results show that trimetazidine improves resting left ventricular function and reduces the severity of dobutamine-induced ischemic myocardial dysfunction.

Administration, Oral↗

Regional glucose utilization in infarcted and remote myocardium: its relation to coronary anatomy and perfusion.

We studied the relationship between coronary anatomy, perfusion and metabolism in myocardial segments exhibiting transient and persistent perfusion defects on stress/rest 99Tcm-MIBI single photon emission tomography in 35 patients (31 males, 4 females, mean age 56 +/- 7 years) with a previous myocardial infarction. Quantitative coronary angiography and assessment of myocardial perfusion reserve and glucose metabolism were performed within 1 week of one another. Perfusion was assessed by SPET after the intravenous injection of 740 MBq of 99Tcm-MIBI at rest and after exercise. Regional myocardial glucose metabolism was assessed by position emission tomography at rest (200 MBq of 18F-2-deoxyglucose, FDG) after an overnight fast with no glucose loading. All 35 patients exhibited persistent perfusion defects consistent with the clinically identified infarct site, and 27 (77%) also showed various degrees of within-infarct FDG uptake; 11 patients developed exercise-induced transient perfusion defects within, or in the vicinity of, 15 infarct segments and resting FDG uptake was present in 10 of these segments (67%). Five patients also showed exercise-induced transient perfusion defects in nine segments remote from the site of infarct: resting FDG uptake was present in six of these regions (67%). Finally, nine patients had increased glucose uptake in non-infarcted regions not showing transient perfusion defects upon exercise testing and perfused by coronary arteries with only minor irregularities. Our results confirm the presence of viable tissue in a large proportion of infarct sites. Moreover, FDG uptake can be seen in regions perfused by coronary arteries showing minor irregularities, not necessarily resulting in detectable transient perfusion defects on a MIBI stress scan. Since the clinical significance of such findings is not clear, further studies should be conducted to assess the long-term evolution of perfusion, function and metabolism in non-revascularized patients of those remote areas which are apparently normally perfused, but show abnormal fasting FDG uptake after myocardial infarction. Such studies may have important implications for the management of post-infarct patients, as the preservation of coronary vasodilator reserve and myocardial metabolism in remote myocardium may be seen as an additional goal in the treatment of such patients.

Blood Glucose↗