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Biomedical subjects

P G Camici

Publications and source records attributed to P G Camici.

At least 55 records · Page 3Linked to original sources
PubMed1999

Cardiomyopathy in duchenne, becker, and sarcoglycanopathies: a role for coronary dysfunction?

Dilated cardiomyopathy is a feature of Duchenne and Becker muscular dystrophies and occasionally of sarcoglycanopathies. Its pathogenesis is unknown. Patients with myotonic dystrophy have an impairment of coronary smooth muscle and this could contribute to their cardiomyopathy. We used positron emission tomography (PET) to study myocardial blood flow and coronary vasodilator reserve at baseline and during hyperemia in 7 Duchenne, 8 Becker, and 5 sarcoglycanopathy patients. The study was normal in all Becker patients. In contrast, baseline myocardial blood flow was increased and coronary vasodilator reserve blunted in Duchenne and sarcoglycanopathy patients despite normal hyperemic myocardial blood flow. The reduction of coronary vasodilator reserve was due to an increased baseline myocardial blood flow. In Duchenne dystrophy, but not in sarcoglycanopathies, correction for cardiac workload normalized the coronary vasodilator reserve. In the latter patients, abnormal baseline myocardial blood flow could be due to vascular smooth muscle dysfunction.

Adolescent↗
PubMed1999

PET measurement of the coronary flow reserve and microcirculatory function.

This review article discusses some of the potentially beneficial effects of calcium antagonists on the coronary microcirculation. These include their vasodilating action on coronary resistance vessels as well as their effects on extravascular resistance (i.e. intramyocardial pressure). Examples are presented of how the non-invasive measurement of myocardial blood flow and flow reserve by means of positron emission tomography (PET) can contribute to the understanding of the effects of drug treatment on the coronary microcirculation. The action of calcium antagonists on the coronary microcirculation can contribute to explain the efficacy of these drugs against ischemia and ischemia-reperfusion damage.

Animals↗
PubMed1999

Transmural myocardial blood flow distribution in hypertrophic cardiomyopathy and effect of treatment.

Verapamil alleviates symptoms in patients with hypertrophic cardiomyopathy (HCM), but the underlying mechanism of improvement remains speculative. Baseline and dipyridamole myocardial blood flow (MBF) were measured in 15 HCM patients (14 men, 42 +/- 10 years), before and after 4 weeks of verapamil SR 480 mg daily, using 15O labelled water the positron emission tomography (PET). Subendocardial (endo) and subepicardial (epi) MBF was measured in the septum (thickness 25.4 +/- 5.8 mm). Pre-treatment baseline whole heart MBF was 1.02 +/- 0.28 ml/min/g and 1.01 +/- 0.30 ml/min/g on treatment (p = ns). Dipyridamole MBF was 1.39 +/- 0.31 ml/min/g off treatment and 1.23 +/- 0.34 ml/min/g on treatment (p = ns). Coronary flow reserve (dipyridamole/resting MBF) was 1.45 +/- 0.52 and 1.30 +/- 0.51, respectively (p = ns). At baseline, the septal endo/epi MBF ratio was uniform off and on treatment (1.13 +/- 0.18 vs 1.18 +/- 0.21, p = ns). Before treatment, the endo/epi ratio following dipyridamole decreased to 0.93 +/- 0.24 (p < 0.01 vs baseline) and 5/15 (33%) patients had a ratio < 0.8 which would suggest subendocardial underperfusion. During treatment, the endo/epi ratio following dipyridamole was no more different from baseline (1.06 +/- 0.24, p = ns vs baseline) and 2/14 (14%) patients had an endo/epi < 0.8. PET can be successfully used to determine transmural MBF in vivo in patients with hypertrophied ventricles. Despite symptomatic improvement, high dose verapamil therapy does not increase total MBF in patients with HCM but may improve septal transmural MBF distribution during dipyridamole in some patients.

Adult↗
PubMed1999

Insulin resistance in patients with cardiac hypertrophy.

OBJECTIVE: Animal studies suggest that left ventricular hypertrophy might be associated with insulin resistance and alterations in glucose transporters. We have previously demonstrated myocardial insulin resistance in patients with post-ischemic heart failure. The aim was to investigate whether myocardial insulin resistance could be demonstrated in human cardiac hypertrophy in the absence of hypertension, diabetes and coronary artery disease. METHODS: Eleven normotensive nondiabetic patients with cardiac hypertrophy due to aortic stenosis and angiographically normal coronary arteries were compared to 11 normal volunteers. Myocardial glucose uptake (MGU) was measured with positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose during fasting (low insulinemia) or during euglycemic-hyperinsulinemic clamp (physiologic hyperinsulinemia). Myocardial biopsies were obtained in order to investigate changes in insulin-independent (GLUT-1) and insulin-dependent (GLUT-4) glucose transporters. RESULTS: During fasting, plasma insulin (7 +/- 1 vs. 6 +/- 1 mU/l) and MGU (0.12 +/- 0.05 vs. 0.11 +/- 0.04 mumol/min/g) were comparable in patients and controls. By contrast, during clamp, MGU was markedly reduced in patients (0.48 +/- 0.02 vs. 0.70 +/- 0.03 mumol/min/g, p < 0.01) despite similar plasma insulin levels (95 +/- 6 vs. 79 +/- 6 mU/l). A decreased GLUT-4/GLUT-1 ratio was shown by Western blot analysis in patients. CONCLUSIONS: Insulin resistance seems to be a feature of the hypertrophied heart even in the absence of hypertension, coronary artery disease and diabetes and may be explained, at least in part, by abnormalities in glucose transporters.

Aortic Valve Stenosis↗
PubMed1999

Myocardial revascularization for the treatment of post-ischemic heart failure.

Heart failure due to coronary artery disease is a major public health problem. Medical treatment ameliorates symptoms and prognosis, although mortality remains high. Heart failure occurs when a sizeable number of myocytes do not contract. This may be due to irreversible myocyte loss (infarct) and/or dysfunctional but viable myocytes (hibernating), which can resume function following coronary artery bypass surgery. The presence of hibernating myocardium can be predicted by noninvasive nuclear imaging using both single photon (SPECT) and positron emission tomography, and also by stress echocardiography. A number of uncontrolled studies have demonstrated a promising role for coronary artery bypass surgery in patients with heart failure in whom a substantial amount of hibernating myocardium is present. These findings, particularly the magnitude of the benefits reported, justify the need for a randomized trial in this patient population.

Angina, Unstable↗
PubMed1999

Effect of alpha1-adrenoceptor blockade on coronary vasodilator reserve in cardiac syndrome X.

We sought to test the response of the coronary microcirculation to alpha-adrenoceptor blockade in patients with syndrome X (angina, ischemia-like stress electrocardiogram, and a normal coronary arteriogram). The response of the microcirculation was assessed by quantification of coronary vasodilator reserve (the ratio of hyperemic to resting myocardial blood flow). We investigated 28 patients with syndrome X [18 women, age 54.4 (7.6) years]. Myocardial blood flow was measured at rest and after dipyridamole by using positron emission tomography with H(2)15O. The measurements were made before and after treatment for 10 days with doxazosin (1 mg o.d. for 3 days, followed by 2 mg o.d. for 7 days) or a matched placebo, similarly administered. Patients were randomized to alpha1-blockade or to placebo in double-blind fashion. No significant differences were demonstrable between syndrome X patients treated with doxazosin and those receiving placebo, with respect to resting myocardial blood flow, myocardial blood flow after dipyridamole, or coronary vasodilator reserve (the ratio of the latter two). In addition, no relations were demonstrable among myocardial blood flow, coronary vasodilator reserve, development of chest pain after dipyridamole, or development of ischemia-like ECG changes. Doxazosin had no effect on the perception of chest pain after dipyridamole. No differences were found between the effects of alpha1-blockade with doxazosin or those of placebo with respect to myocardial blood flow in syndrome X. The values obtained for myocardial blood flow and coronary vasodilator reserve for the patients were within the normal range. The data do not support the case for alpha1-mediated vasoconstriction having an etiologic role in the chest pain of syndrome X.

Adrenergic alpha-Antagonists↗
PubMed1999

A report system for PET assessment of myocardial viability.

Coronary bypass surgery can improve the prognosis of patients with heart failure due to coronary artery disease. However, these patients have a high operative risk and should be operated on only if they have a sizeable amount of viable tissue (i.e. asynergic myocardium) that can recover contractile function following coronary revascularization. In the clinical setting, regional wall motion is usually evaluated by two-dimensional echocardiography, whereas retained metabolic activity assessed by positron emission tomography (PET) and 18F-fluorodeoxyglucose is a well-established means for the evaluation of myocardial viability. Unfortunately, the two-dimensional echocardiography and PET reports are often different, and this renders the matching of information difficult and the estimation of the risk-benefit ratio of the operation unreliable. In this paper, we present a report system for the evaluation of myocardial viability with PET. We divided the left ventricle into 16 segments following the proposal of the American Society of Echocardiography for wall motion analysis by two-dimensional echocardiography. Following this partition, three portions of the left ventricle are identified along the long axis: basal, mid and apical. Each plane of the basal and mid portions is automatically divided into six segments with the super-imposition of a radial divider over the short-axis images. Similarly, each plane of the apical portion is automatically divided, but into four segments. This partition of the left ventricle permits a precise match between the information on wall motion obtained with two-dimensional echocardiography and that on viability obtained with PET.

Coronary Artery Bypass↗
PubMed1999

Efficacy of coronary angioplasty for the treatment of hibernating myocardium.

OBJECTIVES: To determine the efficacy of coronary angioplasty as the sole method of revascularisation in patients with coronary artery disease and chronically dysfunctional but viable myocardium (hibernating myocardium), and to assess the effect of restenosis on functional outcome. DESIGN AND PATIENTS: 24 consecutive patients with hibernating myocardium were studied. Positron emission tomography was used to assess myocardial viability, blood flow, and flow reserve. One patient refused angioplasty, one had bypass surgery, and one died while waiting for an elective procedure. The procedure failed in three patients. The remaining 18 patients had repeat echocardiography, 15 had repeat coronary angiography, and nine had repeat assessments of blood flow and flow reserve at mean (SD) 17 (2) weeks after angioplasty. In three patients restenosis was documented. RESULTS: The wall motion score index in the revascularised territories improved from 1.71 (0.37) to 1.34 (0.47) (p = 0.008). Thirty of 51 dysfunctional segments improved in territories without restenosis compared with three of 14 in restenosed territories (p = 0.001). Hibernating and normal segments had comparable flows (0.82 (0.26) v 0.89 (0.24) ml/min/g; NS) while flow reserve was lower in hibernating segments (1.55 (0.68) v 2.07 (1.08); p = 0.03). In segments without restenosis flow reserve improved from 2.03 (1.25) to 2.33 (1.4) (p = 0.03). Sensitivity, specificity, and positive and negative predictive accuracy of the viability study were 97%, 77%, 82%, and 96%, respectively. After excluding patients with restenosis, specificity and positive predictive accuracy improved to 90% and 93%. CONCLUSIONS: Angioplasty improves function in hibernating myocardium, and restenosis prevents recovery; hibernating myocardium is characterised by an impairment of flow reserve; restenosis affects the diagnostic accuracy of viability studies.

Adult↗
PubMed1999

Coronary revascularisation for postischaemic heart failure: how myocardial viability affects survival.

OBJECTIVE: To assess the impact of revascularisation of viable myocardium on survival in patients with postischaemic heart failure. METHODS: 35 patients (mean (SD) age 58 (7) years) with severe heart failure (New York Heart Association (NYHA) functional class > or = III), mean left ventricular ejection fraction (LVEF) 24 (7)% (range 10-35%), and limited exercise capacity (peak oxygen consumption (VO(2)) 15 (4) ml/kg/min) were studied. 21/35 patients had no angina. Myocardial viability was assessed with quantitative positron emission tomography and the glucose analogue (18)F-fluorodeoxyglucose (FDG) (viable segment = FDG uptake > or = 0.25 micromol/min/g) in all patients before coronary artery bypass grafting. Patients were divided into two groups: group 1, > or = 8 viable dysfunctional segments (mean 12 (2), range 8-15); and group 2, < 8 viable dysfunctional segments (mean 3.5 (3), range 0-7). The two groups were comparable for age, sex, NYHA class, LVEF, and peak VO(2). RESULTS: Two patients died perioperatively and seven patients died during follow up (mean 33 (14) months). All deaths were from cardiac causes. Kaplan-Meyer survival analysis showed 86% survival for group 1 patients versus 57% for group 2 (p = 0.03). Analysis by Cox proportional hazard model revealed three independent factors for cardiac event free survival: presence of > or = 8 viable segments (p = 0.006); preoperative LVEF (p = 0.002); and patient age (p = 0.01). CONCLUSION: Revascularisation for postischaemic heart failure can be associated with good survival, which is critically dependent upon the amount of viable myocardium.

Adult↗
PubMed1999

Parametric polar maps of regional myocardial beta-adrenoceptor density.

UNLABELLED: Quantification of myocardial beta-adrenoceptor density (Bmax) is of interest in cardiac diseases in which altered function of the sympathetic nervous system is thought to play a pathophysiological role. PET provides an unrivaled means of taking regional measurements of cardiac microcirculatory function, tissue metabolism and autonomic nervous system activity. Measurements in small regional areas may be biased because of increased noise levels. This study examined the parametric polar map approach for the regional quantification of Bmax. METHODS: Dynamic PET with parametric polar map imaging was performed in 10 healthy volunteers and 4 patients with hypertrophic cardiomyopathy using (S)-[11C]-(4-(3-tertiarybutylamino-2-hydroxypropoxy)-benzidimaz ole-2)-on hydrochloride (CGP)-12177 and a double-injection protocol. Time-activity curves were corrected for partial volume, spill-over and wall motion effects. The mean Bmax of the left ventricle was calculated in two ways. First, the average time-activity curve of all segments, having the highest achievable signal-to-noise ratio, was used to calculate Bmax(mTAC) (the myocardial beta-adrenoceptor density of the left ventricle calculated using the average time-activity curve). The bias in Bmax(mTAC) introduced by noise is minimal. Second, an estimate of whole-heart receptor density was calculated using the polar map method by averaging the values of Bmax obtained for 576 individual segments. In these calculations, three different filters (3 x 5, 3 x 9 and 3 x 13 segments) were used to smooth the time-activity curves before calculating Bmax. Mean values of whole-left-ventricular receptor density obtained by averaging regional values using the different filters (Bmax(PMF1/2/3)) were compared with Bmax(mTAC) to assess bias introduced by the polar map approach. Segments with a calculated Bmax outside the range 0.1-50 pmol/g were considered unreliable and were excluded from the analysis. RESULTS: The differences between the two methods of calculating Bmax were small (7.8%, 4.8% and 3.2%, with the three filters, respectively). Reliable results were obtained in >95% of the segments and in 9 volunteers and all 4 patients. CONCLUSION: When using PET for the quantification of beta-adrenoceptor density, the regional variation in Bmax can be reliably assessed using the parametric polar map approach.

Adrenergic beta-Antagonists↗
PubMed1999

Assessment of the reproducibility of baseline and hyperemic myocardial blood flow measurements with 15O-labeled water and PET.

UNLABELLED: PET with 15O-labeled water allows noninvasive quantification of myocardial blood flow (MBF) at baseline and during pharmacologically induced hyperemia to assess the coronary vasodilator reserve (CVR = hyperemic/baseline MBF). Despite widespread use of PET, its reproducibility during one study session has not been tested. Intravenous adenosine (Ado), a powerful coronary vasodilator with a very short decay time, is commonly used for the induction of hyperemia. However, it is not known whether Ado can induce tachyphylaxis after short-term repetitive administration. In this study, we aimed to test the reproducibility of PET assessment of CVR during Ado-induced hyperemia. METHODS: In 21 healthy volunteer men, baseline and Ado MBF were measured twice using PET with 15O-labeled water to obtain two CVR assessments within 1 h. RESULTS: There was no significant difference between the two baselines (0.89 +/- 0.14 versus 0.99 +/- 0.15 mL/min/g, mean difference 13% +/- 11%) or between the two hyperemic MBFs (3.51 +/- 0.45 versus 3.83 +/- 0.49 mL/min/g, mean difference 10% +/- 14%), resulting in comparable values of CVR (4.05 +/- 0.75 versus 3.93 +/- 0.72, mean difference 2% +/- 15%). The repeatability coefficient for MBF was 0.17 mL/min/g at baseline and 0.94 mL/min/g during hyperemia. The repeatability coefficient of the rate pressure product (RPP) was lower at baseline (1,304 mm Hg x beat/min) than during hyperemia (3,448 mm Hg x beat/min). CONCLUSION: Repeated measurements of MBF and CVR during the same study session were not significantly different, demonstrating the validity of the technique. The larger variability of hyperemic flow, as indicated by the larger repeatability coefficient, was paralleled by a greater variability of the RPP. This could mean that the greater variability of MBF during stress is more likely due to a variable response to Ado rather than to a measurement error.

Adenosine↗
PubMed1998

Coronary revascularization in the treatment of moderate and severe postischemic left ventricular dysfunction.

Chronic postischemic left ventricular (LV) dysfunction can improve following coronary revascularization (hibernating myocardium). However, it is not clear whether the severity of LV dysfunction determines functional outcome after revascularization and the accuracy of tests to predict myocardial viability. We studied 47 patients with coronary artery disease and chronic LV dysfunction. Before coronary bypass, patients underwent (18F)2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) during euglycemic hyperinsulinemic clamp to assess viability. Global and regional LV function were assessed before and 4 to 6 months after surgery. Patients were arbitrarily divided into 2 groups with moderate and severe LV dysfunction. Group 1 (n = 26) had an ejection fraction (EF) of < or = 30% and group 2 (n = 21) > 30%. After bypass, the EF (22+/-6% vs 31+/-10%; p <0.0001) and global wall motion score (WMS) (2.05+/-0.39 vs 1.56+/-0.34; p <0.001) improved in group 1, whereas the EF (43+/-9% vs 43+/-12%; p = NS) was unchanged in group 2, although WMS tended to improve (1.42+/-0.38 vs 1.32+/-0.39; p = 0.09). The proportion of dysfunctional segments (72% vs 32%; p <0.0001) and FDG uptake in these segments (0.44+/-0.15 vs 0.34+/-0.15 micromol/g/min, p <0.0001) were greater in group 1 than in group 2. The baseline EF influenced the predictive accuracy of PET, with highest positive predictive accuracy in group 2 and highest negative predictive accuracy in group 1. Thus, coronary revascularization has the potential for greatest benefit in patients with the most severe dysfunction, but with evidence of viability, and the entity of LV dysfunction affects the predictive accuracy of viability studies.

Adult↗