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Biomedical subjects

Marcelo F Di Carli

Publications and source records attributed to Marcelo F Di Carli.

At least 19 recordsLinked to original sources
PubMed2006

Characterization of the peri-infarct zone by contrast-enhanced cardiac magnetic resonance imaging is a powerful predictor of post-myocardial infarction mortality.

BACKGROUND: Accurate risk stratification is crucial for effective treatment planning after myocardial infarction (MI). Previous studies suggest that the peri-infarct border zone may be an important arrhythmogenic substrate. In this pilot study, we tested the hypothesis that the extent of the peri-infarct zone quantified by contrast-enhanced cardiac magnetic resonance (CMR) is an independent predictor of post-MI mortality. METHODS AND RESULTS: We studied 144 patients with documented coronary artery disease and abnormal myocardial delayed enhancement (MDE) consistent with MI. A computer-assisted, semiautomatic algorithm quantified the total infarct size and divided it into the core and peri-infarct regions based on signal-intensity thresholds (>3 SDs and 2 to 3 SDs above remote normal myocardium, respectively). The peri-infarct zone was normalized as a percentage of the total infarct size (%MDE(periphery)). After a median follow-up of 2.4 years, 29 (20%) patients died. Patients with an above-median %MDE(periphery) were at higher risk for death compared with those with a below-median %MDE(periphery) (28% versus 13%, log-rank P<0.01). Multivariable analysis showed that left ventricular systolic volume index and %MDE(periphery) were the strongest predictors of all-cause mortality (adjusted hazard ratio [HR] for %MDE(periphery), 1.45 per 10% increase; P=0.002) and cardiovascular mortality (adjusted HR, 1.51 per 10% increase; P=0.009). Similarly, after adjusting for age and left ventricular ejection fraction, %MDE(periphery) maintained strong and independent associations with all-cause mortality (adjusted HR, 1.42; P=0.005) and cardiovascular mortality (adjusted HR, 1.49; P=0.01). CONCLUSIONS: In patients with a prior MI, the extent of the peri-infarct zone characterized by CMR provides incremental prognostic value beyond left ventricular systolic volume index or ejection fraction. Infarct characteristics by CMR may prove to be a unique and valuable noninvasive predictor of post-MI mortality.

Aged↗
PubMed2006

Myocardial oxidative metabolic supply-demand relationships in patients with nonischemic dilated cardiomyopathy.

BACKGROUND: Nonischemic dilated cardiomyopathy (NIDCM) is associated with left ventricular remodeling, hypertrophy, and mitochondrial metabolic abnormalities in vitro. We evaluated the hypothesis that energy supply, as judged by the rate of myocardial oxidative metabolism, is inadequate to meet oxygen demand in patients with NIDCM compared with normal subjects. METHODS AND RESULTS: We used positron emission tomography to determine the myocardial carbon 11 acetate decay rate (kmono) as an index of energy supply, and we compared kmono with the rate-pressure product (RPP) as an index of metabolic demand in 7 patients with NIDCM and 7 normal subjects. The mean kmono value (SEM) was 0.060 +/- 0.006 min(-1) in NIDCM patients versus 0.054 +/- 0.002 in normal subjects (P = not significant). The RPP was 9949 +/- 931 beats/min.mm Hg in NIDCM patients and 6521 +/- 476 in normal subjects (P = .007). The relationship of kmono to this index of demand (kmono/RPP) was 6.2 x 10(-6) in NIDCM patients but was 8.5 x 10(-6) in normal subjects (P = .003). Thus RPP, as an index of myocardial oxygen demand, was poorly matched by the rate of oxidative metabolism in those patients with NIDCM. The kmono was closely related to RPP in normal subjects (r = 0.83, P = .02) but not in NIDCM patients. Furthermore, there was no significant relationship between kmono and wall stress as another index of oxygen demand. CONCLUSIONS: These results are consistent with a mitochondrial metabolic abnormality in heart failure. This metabolic mismatch detected by positron emission tomography may contribute to the pathophysiology of congestive heart failure and left ventricular remodeling.

Adult↗
PubMed2006

Coronary vasodilator reserve and Framingham risk scores in subjects at risk for coronary artery disease.

BACKGROUND: The relationship between coronary vasodilator reserve and risk of coronary heart disease (CHD) in subjects without coronary artery disease (CAD) is not well known. METHODS AND RESULTS: We studied 289 subjects (mean age, 58 +/- 10 years) without overt CAD and at low (< 10%) to intermediate risk (10%-20%) for CHD based on Framingham risk scores (RAMPART [Relative and Absolute Myocardial Perfusion changes as measured by Positron Emission Tomography to Assess the Effects of ACAT Inhibition: A Double-Blind, Randomized, Controlled, Multicenter Trial]). Coronary flow reserve (CFR) and coronary vascular resistance (CVR) were calculated from rest and adenosine nitrogen 13 ammonia positron emission tomography studies. Framingham-estimated CHD risk was used to as a surrogate for outcomes. Compared with subjects with low-risk scores (n = 150), those with intermediate-risk scores (n = 139) had a higher minimal CVR (49.3 +/- 17.41 mm Hg x mL(-1) x min(-1) x g(-1) vs 52.4 +/- 16.4 mm Hg x mL(-1) x min(-1) x g(-1), P = .05) and lower CFR (2.8 +/- 1.0 vs 2.5 +/- 0.8, P = .02). CFR was inversely related to CHD risk (R = -0.2, P = .006), and CVR was directly related to CHD risk (R = 0.2, P < .001). The mean CFR was significantly lower in patients in the first quartile of CHD risk compared with those in the fourth quartile (2.3 +/- 0.7 vs 2.8 +/- 1.0, P = .02), and the minimal CVR was significantly higher (44 +/- 15 mm Hg x mL(-1) x min(-1) x g(-1) vs 53 +/- 14 mm Hg x mL(-1) x min(-1) x g(-1), P < or = .05). CONCLUSIONS: In subjects without clinical CAD and at low to intermediate risk, CFR assessed by positron emission tomography is inversely related to estimated 10-year CHD risk.

Adenosine↗
PubMed2005

Safety and feasibility of autologous myoblast transplantation in patients with ischemic cardiomyopathy: four-year follow-up.

BACKGROUND: Successful autologous skeletal myoblast transplantation into infarcted myocardium in a variety of animal models has demonstrated improvement in cardiac function. We evaluated the safety and feasibility of transplanting autologous myoblasts into infarcted myocardium of patients undergoing concurrent coronary artery bypass grafting (CABG) or left ventricular assist device (LVAD) implantation. In addition, we sought to gain preliminary information on graft survival and any associated changes in cardiac function. METHODS AND RESULTS: Thirty patients with a history of ischemic cardiomyopathy participated in a phase I, nonrandomized, multicenter pilot study of autologous skeletal myoblast transplantation concurrent with CABG or LVAD implantation. Twenty-four patients with a history of previous myocardial infarction and a left ventricular ejection fraction <40% were enrolled in the CABG arm. In a second arm, 6 patients underwent LVAD implantation as a bridge to heart transplantation, and patients donated their explanted native hearts for testing at the time of heart transplantation. Myoblasts were successfully transplanted in all patients without any acute injection-related complications or significant long-term, unexpected adverse events. Follow-up positron emission tomography scans showed new areas of glucose uptake within the infarct scar in CABG patients. Echocardiography measured an average change in left ventricular ejection fraction from 28% to 35% at 1 year and of 36% at 2 years. Histological evaluation in 4 of 6 patients who underwent heart transplantation documented survival and engraftment of the skeletal myoblasts within the infarcted myocardium. CONCLUSIONS: These results demonstrate the survival, feasibility, and safety of autologous myoblast transplantation and suggest that this modality offers a potential therapeutic treatment for end-stage heart disease.

Adult↗
PubMed2005

Quantitative relation between hemodynamic changes during intravenous adenosine infusion and the magnitude of coronary hyperemia: implications for myocardial perfusion imaging.

OBJECTIVES: The goal of this study was to determine the relationship between changes in cardiac hemodynamics during intravenous adenosine (ADO) infusion, and myocardial blood flow (MBF). BACKGROUND: The relationship between changes in MBF and the peripheral hemodynamic effects during peak adenosine infusion is unknown. METHODS: We studied 348 (age 57 +/- 11 years; 106 females) without evidence of obstructive coronary artery disease by positron emission tomography (PET). Patients underwent [(13)N]ammonia PET imaging to measure MBF and coronary vascular resistance (CVR) at rest and during a standard 6-min ADO infusion. Changes in heart rate (HR) and mean arterial pressure (MAP) were measured at baseline and during peak hyperemia. RESULTS: During ADO, HR increased (delta: 24 +/- 11 beats/min) and MAP decreased (delta: -2 +/- 10 mm Hg). Overall, delta HR correlated poorly with hyperemic MBF (R = 0.10, p = 0.06) and with CVR (R = 0.11, p = 0.04). Delta MAP also showed a weak correlation with hyperemic MBF (R = 0.04, p = 0.44) and with CVR (R = 0.11, p = 0.04). Patients in the lowest tertile for delta HR showed a 7% lower hyperemic MBF (1.84 +/- 0.6 ml/min/g vs. 1.98 +/- 0.6 ml/min/g, p = 0.022) and an 8% higher CVR (54 +/- 20 mm Hg/ml/min/g vs. 50 +/- 17 mm Hg/ml/min/g, p = 0.056) compared with those in the highest tertile. Patients in the lowest tertile for delta MAP (i.e., greatest decline) showed similar hyperemic MBF, and an 8% lower CVR compared with those in the highest tertile (p = NS for both). These small differences between tertiles remain, even after adjusting for differences in age, gender, smoking status, and lipid profile. CONCLUSIONS: Changes in cardiac hemodynamics during intravenous ADO are generally poor predictors of changes in MBF and CVR during peak hyperemia, and, thus, they should not be used to assess the effectiveness of vasodilator stress in myocardial perfusion imaging.

Adenosine↗
PubMed2005

Should we screen for occult coronary artery disease among asymptomatic patients with diabetes?

Diabetes mellitus predisposes people to premature atherosclerotic coronary artery disease (CAD). The risk of a myocardial infarction in diabetics without overt evidence of obstructive CAD matches that of patients without diabetes who have had a previous myocardial infarction. The available data suggest that occult CAD is a common finding among asymptomatic diabetics, ranging from 20% to >50%. The diagnostic accuracy of myocardial perfusion single-photon emission computed tomography (SPECT) in diabetics appears to be comparable to that observed in nondiabetic individuals. As shown in other patient groups, the ischemic burden assessed by stress SPECT in subjects with diabetes is also linked to their increased risk of adverse cardiovascular events. Among patients with normal stress SPECT, however, those with diabetes are at significantly greater risk than non-diabetics. Testing diabetics with an abnormal resting electrocardiogram or with evidence of peripheral or carotid occlusive arterial disease appears to result in an excellent yield of abnormal SPECT findings, as does testing in the setting of dyspnea. However, recent evidence suggests that achieving an adequate yield in asymptomatic diabetics without overt evidence of CAD is a greater challenge. Further investigation of sequential testing strategies is needed in order to identify an efficient means for screening asymptomatic patients with diabetes.

Coronary Disease↗
PubMed2005

Electrocardiographic infarct size assessment after thrombolysis: insights from the Acute Myocardial Infarction STudy ADenosine (AMISTAD) trial.

BACKGROUND: Noninvasive methods are needed to evaluate reperfusion success in patients with acute myocardial infarction (MI). The AMISTAD trial was analyzed to compare MI size and myocardial salvage determined by electrocardiogram (ECG) with technetium Tc 99m sestamibi single-photon emission computerized tomography (SPECT) imaging. METHODS: Of 236 patients enrolled in AMISTAD, 166 (70 %) with no ECG confounding factors and no prior MI were included in this analysis. Of these, group 1 (126 patients, 53%) had final infarct size (FIS) available by both ECG and SPECT. Group 2 (56 patients, 24%) had myocardium at risk, FIS, and salvage index (SI) assessed by both SPECT and ECG techniques. Aldrich/Clemmensen scores for myocardium at risk and the Selvester QRS score for final MI size were used. Salvage index was calculated as follows: SI = (myocardium at risk-FIS)/(myocardium at risk). RESULTS: In group 1, FIS was 15% (6, 24) as measured by ECG and 11% (2, 27) as measured by SPECT. In the adenosine group, FIS was 12% (6, 21) and 11% (2, 22). In the placebo group, FIS was 16.5% (7.5, 24) and 11.5% (3.0, 38.5) by ECG and SPECT, respectively. The overall correlation between SPECT and ECG for FIS was 0.58 (P = .0001): 0.60 in the placebo group (P = .0001) and 0.54 (P = .0001) in the adenosine group. In group 2, myocardium at risk was 23% (17, 30) and 26% (10, 50) with ECG and SPECT, respectively (P = .0066). Final infarct size was 17% (6, 21) and 12% (1, 24) (P < .0001). The SI was 29% (-7, 57) and 46% (15, 79) with ECG and SPECT, respectively (P = .0510). CONCLUSIONS: The ECG measurement of infarct size has a moderate relationship with SPECT infarct size measurements in the population with available assessments. This ECG algorithm must further be validated on clinical outcomes.

Adenosine↗
PubMed2005

Quantitative dynamic cardiac 82Rb PET using generalized factor and compartment analyses.

UNLABELLED: We have addressed 2 major challenges of (82)Rb cardiac PET, noninvasive estimation of an accurate input function and absolute quantitation of myocardial perfusion, using a generalized form of least-squares factor analysis of dynamic sequences (GFADS) and a novel compartment analysis approach. METHODS: Left and right ventricular (LV + RV) time-activity curves (TACs) were generated from 10 rest/stress studies, and 30 myocardial TACs were modeled to cover a range of clinical values. Two-dimensional PET Monte Carlo simulations of the LV, RV, myocardium, and other organs were generated separately and combined using the above TACs to form 30 realistic dynamic (82)Rb studies. LV and RV TACs were estimated by GFADS and used as input to a 2-compartment kinetic analysis that estimates parametric maps of myocardial tissue extraction (k(1)) and egress (k(2)), as well as LV + RV contributions (f(v), r(v)), by orthogonal voxel grouping. In addition, 13 patients were injected with 2.22 +/- 0.19 GBq (60 +/- 5 mCi) of (82)Rb and imaged dynamically for 6 min at rest and during dipyridamole stress. RESULTS: In Monte Carlo simulations, GFADS yielded estimates of the 3 factors and corresponding factor images, with average errors of -4.2% +/- 6.3%, 3.5% +/- 4.3%, and 2.0% +/- 5.5% in the LV, RV, and myocardial factor estimates, respectively. The estimates were significantly more accurate and robust to noise than those obtained using TACs based on manually drawn volumes of interest (P < 0.01). The 2-compartment approach yielded accurate k(1), k(2), f(v), and r(v) parametric maps; the average error of estimates of k(1) was 6.8% +/- 3.6%. In all patient studies, our approach yielded robust estimates of k(1), k(2), f(v), and r(v), which correlated very well with the status of the subject and the catheterization results. CONCLUSION: Quantitative dynamic (82)Rb PET using generalized factor analysis of dynamic sequences and compartmental modeling yields estimates of parameters of absolute myocardial perfusion and kinetics with errors of <9%.

Adult↗
PubMed2004

Quantitative relation of ST-segment depression during exercise to the magnitude of myocardial ischemia as assessed by single-photon emission computed tomographic myocardial perfusion imaging.

The mechanism of ST-segment depression during exercise electrocardiographic treadmill testing (ETT) is unknown. The relatively good correlation between the results of ETT and myocardial perfusion imaging suggests that ST-segment depression may be related to the magnitude of ischemia. Previous studies that investigated this relation have produced conflicting results. We evaluated 1,006 patients who underwent symptom-limited ETT and technetium-99m single-photon emission computed tomographic myocardial perfusion imaging at rest and during stress at a single institution. The magnitude, extent, and duration of ST-segment depression were each strongly associated with the magnitude of myocardial ischemia (p <0.001 for all). The magnitude, extent, and duration of ST-segment depression were highly correlated with each other and had similar relations to the magnitude of ischemia. After adjustment for significant clinical and ETT parameters, these relations remained highly significant. The location of myocardial ischemia was unrelated to ST-segment depression. This large study found that ST-segment depression during ETT is strongly associated with the magnitude of ischemia. These data support a causative role for the magnitude of ischemia in the generation of ST-segment depression.

Chi-Square Distribution↗
PubMed2003

Role of chronic hyperglycemia in the pathogenesis of coronary microvascular dysfunction in diabetes.

OBJECTIVES: We sought to determine the differences in coronary microvascular function between patients with type 1 (insulin-deficient) and type 2 (insulin-resistant) diabetes mellitus (DM). BACKGROUND: Coronary vascular function is impaired in patients with DM. However, it is unclear whether the type and/or severity of this vascular dysfunction are similar in patients with type 1 and type 2 DM. METHODS: We studied 35 young subjects with DM (18 with type 1 and 17 with type 2), who were free of overt cardiovascular complications, and 11 age-matched healthy controls. Positron emission tomography imaging was used to measure myocardial blood flow (MBF) at rest, during adenosine-induced hyperemia (reflecting primarily endothelium-independent vasodilation), and in response to cold pressor test (CPT) (reflecting primarily endothelium-dependent vasodilation). RESULTS: The two groups of diabetics were similar with respect to age and glycemic control. The duration of diabetes was longer and high-density lipoprotein cholesterol levels were higher in type 1 than in type 2 diabetics. Basal MBF was similar in the three groups studied. The increase (from baseline) in MBF with adenosine was similar in the subjects with type 1 (161 +/- 18%) and type 2 (185 +/- 19%) DM, but lower than in the controls (351 +/- 43%) (p < 0.001 for the comparison with both groups of diabetics). Similarly, the increase in MBF during the CPT was comparable in the subjects with type 1 (23 +/- 4%) and type 2 (19 +/- 3%) DM, but lower compared with the controls (66 +/- 12%) (p < 0.0001 for the comparison with both groups of diabetics). These differences persisted after adjusting for the duration of diabetes, insulin treatment, metabolic abnormalities, and autonomic neuropathy. CONCLUSIONS: These results demonstrate markedly reduced and similar endothelium-dependent and -independent coronary vasodilator function in subjects with both type 1 and type 2 DM. These results suggest a key role of chronic hyperglycemia in the pathogenesis of vascular dysfunction in diabetes.

Adult↗
PubMed2003

Single photon emission computed tomography perfusion imaging for assessment of myocardial viability and management of heart failure.

In the setting of coronary artery disease, some areas of dysfunctional myocardium may realize significant improvement in function as a consequence of revascularization. These areas represent viable myocardium, encompassing a spectrum of pathophysiology ranging from chronic stunning, in which resting blood flow is preserved, to hibernating myocardium, in which resting blood flow is decreased. The accurate preoperative evaluation of viable myocardium helps identify those patients with left ventricular dysfunction who will most benefit from coronary revascularization. Of the various modalities available for viability assessment, the nuclear medicine techniques (201)Thallium and (18)Fluorodeoxyglucose positron emission tomography have emerged as the most sensitive. It has been consistently shown that in patients with a significant amount of viable myocardium, there is a substantial survival benefit in revascularization versus medical therapy. The likelihood of affecting a significant improvement decreases with time to revascularization, however, particularly in the setting of an enlarged left ventricle secondary to ventricular remodeling.

Cardiomyopathies↗