Similar patterns of myocardial metabolism and perfusion in patients with type 2 diabetes and heart disease of ischaemic and non-ischaemic origin.

AIMS/HYPOTHESIS: Type 2 diabetes and insulin resistance are often associated with the co-occurrence of coronary atherosclerosis and cardiac dysfunction. The aim of this study was to define the independent relationships between left ventricular dysfunction or ischaemia and patterns of myocardial perfusion and metabolism in type 2 diabetes. METHODS: Twenty-four type 2 diabetic patients--12 with coronary artery disease (CAD) and preserved left ventricular function and 12 with non-ischaemic heart failure (HF)--were enrolled in a cross-sectional study. Positron emission tomography (PET) was used to assess myocardial blood flow (MBF) at rest, after pharmacological stress and under euglycaemic hyperinsulinaemia. Insulin-mediated myocardial glucose disposal was determined with 2-deoxy-2-[(18)F]fluoroglucose PET. RESULTS: There was no difference in myocardial glucose uptake (MGU) between the healthy myocardium of CAD patients and the dysfunctional myocardium of HF patients. MGU was strongly influenced by levels of systemic insulin resistance in both groups (CAD, r = 0.85, p = 0.005; HF, r = 0.77, p = 0.01). In HF patients, there was an inverse association between MGU and the coronary flow reserve (r = -0.434, p = 0.0115). A similar relationship was observed in non-ischaemic segments of CAD patients. Hyperinsulinaemia increased MBF to a similar extent in the non-ischaemic myocardial of CAD and HF patients. CONCLUSIONS/INTERPRETATION: In type 2 diabetes, similar metabolic and perfusion patterns can be detected in the non-ischaemic regions of CAD patients with normal cardiac function and in the dysfunctional non-ischaemic myocardium of HF patients. This suggests that insulin resistance, rather than diagnosis of ischaemia or left ventricular dysfunction, affects the metabolism and perfusion features of patients with type 2 diabetes.

Apolipoprotein A-I mimetic peptide L-4F prevents myocardial and coronary dysfunction in diabetic mice.

Diabetes is a major health problem associated with adverse cardiovascular outcomes. The apolipoprotein A-I mimetic peptide L-4F is a putative anti-diabetic drug, has antioxidant and anti-inflammatory proprieties and improves endothelial function. In obese mice L-4F increases adiponectin levels, improving insulin sensitivity, and reducing visceral adiposity. We hypothesized that the pleiotropic actions of L-4F can prevent heart and coronary dysfunction in a mouse model of genetically induced Type II diabetes. We treated db/db mice with either L-4F or vehicle for 8 weeks. Trans-thoracic echocardiography was performed; thereafter, isolated hearts were subjected to ischemia/reperfusion (IR). Glucose, insulin, adiponectin, and pro-inflammatory cytokines (IL-1ß, TNF-α, MCP-1) were measured in plasma and HO-1, pAMPK, peNOS, iNOS, adiponectin, and superoxide in cardiac tissue. In db/db mice L-4F decreased accumulation of subcutaneous and total fat, and increased insulin sensitivity and adiponectin levels while lowering inflammatory cytokines (P < 0.05). L-4F normalized in vivo left ventricular (LV) function of db/db mice, increasing (P < 0.05) fractional shortening and decreasing (P < 0.05) LV dimensions. In I/R experiments, L-4F prevented coronary microvascular resistance from increasing and LV function from deteriorating in the db/db mice. These changes were associated with increased cardiac expression of HO-1, pAMPK, peNOS, and adiponectin and decreased levels of superoxide and iNOS (P < 0.01). In the present study we showed that L-4F prevented myocardial and coronary functional abnormalities in db/db mice. These effects were associated with stimulation of HO-1 resulting in increased levels of anti-inflammatory, anti-oxidative, and vasodilatatory action through a mechanism involving increased levels of adiponectin, pAMPK, and peNOS.

Computer simulation of coronary flow waveforms during caval occlusion.

OBJECTIVES: Mathematical modeling of the cardiovascular system is a powerful tool to extract physiologically relevant information from multi-parametric experiments. The purpose of the present work was to reproduce by means of a computer simulator, systemic and coronary measurements obtained by in vivo experiments in the pig. METHODS: We monitored in anesthetized open-chest pig the phasic blood flow of the left descending coronary artery, aortic pressure, left ventricular pressure and volume. Data were acquired before, during, and after caval occlusion. Inside the software simulator (CARDIOSIM) of the cardiovascular system, coronary circulation was modeled in three parallel branching sections. Both systemic and pulmonary circulations were simulated using a lumped parameter mathematical model. Variable elastance model reproduced Starling's law of the heart. RESULTS: Different left ventricular pressure-volume loops during experimental caval occlusion and simulated cardiac loops are presented. The sequence of coronary flow-aortic pressure loops obtained in vivo during caval occlusion together with the simulated loops reproduced by the software simulator are reported. Finally experimental and simulated instantaneous coronary blood flow waveforms are shown. CONCLUSIONS: The lumped parameter model of the coronary circulation, together with the cardiovascular system model, is capable of reproducing the changes during caval occlusion, with the profound shape deformation of the flow signal observed during the in vivo experiment. In perspectives, the results of the present model could offer new tool for studying the role of the different determinants of myocardial perfusion, by using the coronary loop shape as a "sensor" of ventricular mechanics in various physiological and pathophysiological conditions.

Microvascular dysfunction in collateral-dependent myocardium.

OBJECTIVES: The aim of this study was to evaluate myocardial blood flow regulation in collateral-dependent myocardium of patients with coronary artery disease. BACKGROUND: Despite great clinical relevance, perfusion correlates of collateral circulation in humans have rarely been estimated by quantitative methods at rest and during stress. METHODS: Nineteen patients with angina and isolated occlusion of the left anterior descending (n = 14) or left circumflex (n = 5) coronary artery were evaluated. Using positron emission tomography and nitrogen-13 ammonia, we obtained flow measurements at baseline, during atrial pacing-induced tachycardia and after intravenous administration of dipyridamole (0.56 mg/kg body weight over 4 min). Flow values in collateral-dependent and remote areas were compared with values in 13 normal subjects. RESULTS: Flow at rest was similar in collateralized and remote myocardium (0.61 +/- 0.11 vs. 0.63 +/- 0.17 ml/min per g, mean +/- 1 SD), and both values were lower than normal (1.00 +/- 0.20 ml/min per g, p < 0.01). During pacing, blood flow increased to 0.83 +/- 0.25 and 1.11 +/- 0.39 ml/min per g in collateral-dependent and remote areas, respectively (p < 0.05 vs. baseline); both values were lower than normal (1.86 +/- 0.61 ml/min per g, p < 0.01). Dipyridamole induced a further increase in perfusion in remote areas (1.36 +/- 0.57 ml/min per g, p < 0.01 vs. pacing) but not in collateral-dependent regions (0.93 +/- 0.37 ml/min per g, p = NS vs. pacing); again, both values were lower (p < 0.01) than normal (3.46 +/- 0.78 ml/min per g). Dipyridamole flow in collateral-dependent myocardium was slightly lower in patients with poorly developed than in those with well developed collateral channels (0.75 +/- 0.29 vs. 1.06 +/- 0.38 ml/min per g, respectively, p = 0.06); however, the former showed higher flow inhomogeneity (collateral/control flow ratio 0.58 +/- 0.10 vs. 0.81 +/- 0.22, respectively, p < 0.02). A linear direct correlation was observed between flow reserve of collateral-dependent and remote regions (r = 0.83, p < 0.01). CONCLUSIONS: Despite rest hypoperfusion, collateral-dependent myocardium maintains a vasodilator reserve that is almost fully utilized during increases in oxygen consumption. A global microvascular disorder might hamper adaptation to chronic coronary occlusion.

Homogeneously reduced versus regionally impaired myocardial blood flow in hypertensive patients: two different patterns of myocardial perfusion associated with degree of hypertrophy.

OBJECTIVES: The aim of this study was to quantitatively measure regional and global myocardial blood flow and coronary reserve in hypertensive patients without coronary artery disease and to assess the correlation with left ventricular mass. BACKGROUND: The effect of left ventricular hypertrophy on regional vasodilating coronary capability in arterial hypertension is controversial, and no quantitative method has been applied to assess a possible correlation. METHODS: Positron emission tomography was performed in 50 untreated hypertensive patients and 13 normotensive subjects. Blood flow at baseline and after dipyridamole was globally and regionally measured by using nitrogen-13 ammonia; coronary reserve and resistance were calculated. Left ventricular mass was assessed by two-dimensional echocardiography. RESULTS: In hypertensive patients, flow at baseline was similar to that of normotensive subjects (p = 0.21), but values were reduced after pharmacologic vasodilation (p < 0.05). This impairment of maximal coronary flow was not correlated with left ventricular mass (p = 0.13). Among hypertensive patients, we identified a group with a homogeneous distribution of perfusion and a group with a heterogeneous flow pattern. Flow was globally reduced in the former group, but it was abnormal only at the site of perfusion defects in the latter. Patients with regional defects showed the highest likelihood of having an increased left ventricular mass. CONCLUSIONS: In arterial hypertension, left ventricular mass is not correlated with global myocardial blood flow. Nevertheless, patients with ventricular hypertrophy are likely to show a heterogeneous flow pattern with regional defects and almost normal blood flow in nonaffected regions. In hypertensive patients with a homogeneous perfusion pattern during stress, myocardial blood flow frequently shows a diffuse reduction.

Novel organ-specific circulating cardiac autoantibodies in dilated cardiomyopathy.

To determine whether organ-specific cardiac autoantibodies are present in dilated cardiomyopathy, indirect immunofluorescence on human heart and skeletal muscle was used to test sera from 200 normal subjects and from 65 patients with dilated cardiomyopathy, 41 with chronic heart failure due to myocardial infarction and 208 with other cardiac disease. Three immunofluorescence patterns were observed: diffuse cytoplasmic on cardiac tissue only (organ-specific), fine striational on cardiac and, to a lesser extent, skeletal muscle (cross-reactive 1) and broad striational on both cardiac and skeletal muscle (cross-reactive 2). Cardiac specificity of the cytoplasmic pattern was confirmed by absorption studies with homogenates of human atrium, skeletal muscle and rat liver. Organ-specific cardiac antibodies (IgG; titer range 1/10 to 1/80) were more frequent in patients with dilated cardiomyopathy (17 [26%] of 65) than in those with other cardiac disease (2 [1%] of 208, p less than 0.0001) or heart failure (0 [0%] of 41, p less than 0.001) or in normal subjects (7 [3.5%] of 200, p less than 0.0001). Organ-specific cardiac antibodies were more common in patients with dilated cardiomyopathy and in those with fewer symptoms (8 of 15 in New York Heart Association functional class I versus 9 of 50 in classes II to IV, p less than 0.01) and more recent (less than 2 years) onset of disease (9 of 19 versus 8 of 46, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial and forearm blood flow reserve in mild-moderate essential hypertensive patients.

BACKGROUND: Structural readaptation of systemic resistance-sized arterioles in response to an elevated blood pressure reduces the forearm vasodilator reserve in patients with essential hypertension. The development of a similar process at the coronary microvascular level has frequently been hypothesized, but little information about coronary remodeling during the uncomplicated stage of hypertension has been obtained, and the relationship with concomitant changes in forearm blood flow reserve is not known. OBJECTIVE: To assess the minimal myocardial resistance and its relationship with the minimal forearm resistance in a group of male patients with mild-to-moderate uncomplicated hypertension and carefully matched controls. MATERIAL AND METHODS: The minimal myocardial resistance (Rmin(myocardia), the mean arterial pressure: hyperemic myocardial flow ratio after administration of 0.84 mg/kg dipyridamole, measured by using positron emission tomography and [3N]-ammonia), minimal forearm vascular resistance (Rmin(forearm), a hemodynamic index of arteriolar structure derived from the mean blood pressure and maximal postischemic forearm blood flow by venous plethysmography), echocardiographic cardiac mass and wall thickness were measured in 25 male patients with mild-to-moderate uncomplicated essential hypertension, most of whom had previously been treated, and in seven sex- and age-matched normotensive controls. RESULTS: Rmin(myocardial) (and hyperemia: baseline myocardial flow ratios) did not differ significantly between the two groups, whereas Rmin(forearm) was significantly higher in hypertensives. There was no significant intra-individual correlation between the two parameters. The left ventricular mass index was greater in patients and was related previously to Rmin(forearm) but not to Rmin(myocardial) for the overall sample. In a subgroup analysis, Rmin(forearm) values were 2SD above control values in nine patients and within the normal range in the remaining 16. The myocardial reserve was very similar in the two subgroups. CONCLUSIONS: The myocardial vasodilator reserve appeared to be preserved in these mild-to-moderate uncomplicated hypertensive patients, whereas the forearm vasodilator capacity was reduced, suggesting that the hypertensive readaptation process was not distributed homogeneously over the two vascular beds.

Alteration in regulation of myocardial blood flow in one-vessel coronary artery disease determined by positron emission tomography.

The behavior of myocardial blood flow (MBF) regulation in territories supplied by angiographically normal vessels of patients with coronary artery disease (CAD) has been poorly investigated. Resting MBF and coronary reserve were evaluated in 32 patients with stable angina, no previous myocardial infarction, and isolated left anterior descending or left circumflex coronary artery stenosis (> or = 50% diameter narrowing). MBF was measured, in the absence of any medical therapy, by means of dynamic positron emission tomography and 13N-ammonia. MBF measurements at baseline and after intravenous dipyridamole (0.56 mg/kg administered over 4 minutes), were obtained both in the stenosis-related regions and in contralateral territories. As a control group, 14 normal subjects were evaluated according to the same protocol. At rest, the 32 patients with CAD had similar MBF values in the stenotic and remote regions (0.76 +/- 0.21 and 0.77 +/- 0.19 ml/min/g, respectively, p = NS); both these values were significantly (p < 0.01) reduced with respect to mean MBF in normal subjects (1.03 +/- 0.25 ml/min/g). The dipyridamole study was completed in 30 patients; these patients had lower values of maximal MBF in the stenotic than in the remote regions (1.52 +/- 0.65 vs 1.76 +/- 0.68 ml/min/g, p < 0.05); however, both these values were significantly reduced (p < 0.01) with respect to mean dipyridamole MBF in normal subjects (3.66 +/- 0.92 ml/min/g). Thus, in patients with CAD, resting and maximal MBF can be reduced not only in myocardial territories supplied by stenotic arteries, but also in territories supplied by angiographically normal arteries.

Does the myocardium become "stunned" after episodes of angina at rest, angina on effort, and coronary angioplasty?

To assess whether myocardial stunning occurs after brief periods of ischemia, global and regional ventricular function assessed by radionuclide angiography was studied in 52 patients. Patients were divided into 3 groups according to the type of ischemic episodes. Group 1 consisted of 15 patients studied before, during and after episodes of angina at rest. Seventeen patients studied immediately before and after coronary angioplasty constituted group 2. Group 3 consisted of 20 patients with stable angina studied before, during and after exercise-induced ischemia. Medical therapy was discontinued 48 hours before the study in all patients except those undergoing coronary angioplasty who were receiving diltiazem 180 mg/day. No difference in baseline ejection fraction was found between groups, whereas peak filling rate was statistically lower in group 3 patients. Evidence of left ventricular dysfunction during ischemia was seen in patients in groups 1 and 3, whereas transient ischemia was documented by ST-segment displacement and/or typical chest pain during balloon inflation in group 2. Persistence of systolic or diastolic dysfunction was not observed in any of the 3 groups in the recovery phase after ischemia. In conclusion, transient ischemia caused either by a primary reduction in oxygen supply (angina at rest, coronary angioplasty) or by an increase in oxygen demand (angina on effort) did not reproduce the phenomenon of systolic and diastolic stunning observed in animal experiments, although in all patients the ischemia was of sufficient duration and severity to induce marked ventricular dysfunction. The search for stunned myocardium should be extended to other different clinical models characterized by prolonged ischemia such as unstable angina or myocardial infarction.

Regional myocardial blood flow and coronary reserve in hypertensive patients. The effect of therapy.

Patients with essential arterial hypertension demonstrate abnormal vasodilator capacity either during increased cardiac metabolic demand or during pharmacological vasodilation. Structural and functional damage to the coronary microcirculation has been proposed as one of the major causes of impaired coronary reserve in this disease. To assess the role of microvascular impairment in regional myocardial blood flow (MBF), 27 patients with essential hypertension were evaluated by dynamic positron emission tomography (PET) at rest, during atrial pacing and after dipyridamole infusion and compared with 13 healthy subjects. All patients had normal coronary arteries, 17 had moderate to severe hypertension and 10 had mild hypertension. Baseline mean MBF of 0.97 +/- 0.25 ml/min/g was significantly increased to 1.60 +/- 0.38 during atrial pacing and 2.35 +/- 0.95 after dipyridamole infusion (p < 0.01); however, mean flow during atrial pacing and after dipyridamole infusion was significantly lower than in healthy subjects (2.15 +/- 0.73 and 3.71 +/- 0.86 ml/min/g, p < 0.05 and p < 0.01, respectively). The MBF response to atrial pacing and dipyridamole infusion was similarly depressed in patients with mild and severe hypertension. The study was repeated after 6 months of antihypertensive treatment with the calcium antagonist verapamil or the angiotensin converting enzyme (ACE) inhibitor enalapril in a subgroup of 20 patients as part of a randomised, single-blind clinical trial. This study is still in progress; the initial 16 patients treated with verapamil or enalapril showed an obvious improvement in MBF values during atrial pacing and after dipyridamole infusion after 6 months of therapy (mean MBF: 2.10 +/- 0.64 and 2.99 +/- 1.63 ml/min/g, respectively, p < 0.05 vs pretreatment values). In conclusion, obvious impairment of MBF during atrial pacing and after dipyridamole infusion was observed in hypertensive patients with normal coronary arteries and this appeared unrelated to the severity of hypertension. Therapy with verapamil or enalapril improved coronary reserve and MBF response to an increase in myocardial oxygen demand.

Increased circulating levels of ouabain-like factor in patients with asymptomatic left ventricular dysfunction.

BACKGROUND: Much evidence has been accumulated that human plasma contains digitalis-like factor(s) with Na/K ATPase inhibitor properties. Increased concentrations of ouabain-like factor (OLF) have been reported in patients with moderate to severe hypertension and in patients with overt congestive heart failure due to dilated cardiomyopathy. AIM: The presence of circulating OLF has not been investigated in borderline to mild hypertension or in the early stage of dilated cardiomyopathy. METHODS AND RESULTS: The study population consisted of 18 normal volunteers, 24 patients with borderline to mild hypertension, 47 patients with asymptomatic left ventricular dysfunction (ALVD) due to dilated cardiomyopathy and 26 patients with cardiac arrhythmias but normal left ventricular function. OLF values (pM ouabain equivalent) were assayed in extracted plasma, using a radioimmunoassay for ouabain. OLF was, respectively, 29.4+/-20.6 pM in normal controls, 39.1+/-23.8 pM in hypertensives, 35+/-18 pM in patients with cardiac arrhythmias, 52.3+/-25.8 pM in ALVD patients not treated with digoxin and 64.6+/-29.6 pM in ALVD patients treated with digoxin. Patients with ALVD, both treated and not treated with digoxin, had OLF significantly higher (P<0.05) than all the other groups. In patients with ALVD no correlation between OLF and left ventricular ejection fraction was observed. In the hypertensive group no correlation between OLF and both diastolic and systolic pressure was found. CONCLUSION: Increased concentrations of OLF were observed in patients with left ventricular dysfunction due to dilated cardiomyopathy, before the occurrence of overt heart failure, suggesting that OLF may be an early marker of the disease.

Significance of both negative T waves and stress-induced normalization of the repolarization phase in infarcted patients: a positron-emission-tomography assessment of regulation of myocardial blood flow and viability of myocardium.

BACKGROUND: The clinical correlation of stress-induced normalization of previously negative T waves (NNTW) to regulation of regional myocardial blood flow (MBF) and tissue viability is still being debated. OBJECTIVE: To clarify its meaning. METHODS: We studied 25 patients, who had previously suffered anterior myocardial infarction and for whom negative T waves were recorded on baseline electrocardiographic precordial leads, by means of positron emission tomography. We obtained MBF in the infarcted myocardial regions under resting conditions for all patients, during infusion of dipyridamole (17 patients) and dobutamine (20 patients), using [13N]-ammonia as a flow tracer. RESULTS: During stress tests, 13 patients exhibited NNTW (group 1) whereas the remaining 12 presented persistent negative T waves (group 2). NNTW was observed in 18 stress studies (for 10 and eight patients during administration of dobutamine and dipyridamole, respectively) whereas persistent negative T waves occurred 19 times (for 10 patients during infusion of dobutamine and nine patients during administration of dipyridamole). A complete concordance of the modifications of the repolarization phase was observed for patients who were subjected both to dipyridamole and to dobutamine studies. Furthermore, we assessed viability of myocardium in 20 of 25 patients using [18F]-fluorodeoxyglucose. For the remaining five patients not subjected to metabolic imaging, a coronary reserve of 1.65 was considered a cut-off of viability. Resting MBF for patients in groups 1 and 2 were similar (0.53 +/- 0.20 versus 0.47 +/- 0.17 ml/min per g, respectively, NS) whereas during pharmacological stress, MBF of patients in group 1 was significantly higher than that for patients in group 2 (0.99 +/- 0.41 versus 0.56 +/- 0.26 ml/min per g, respectively, P < 0.0001). Coronary vasodilating capability, expressed as stress/resting MBF ratio, turned out to be 1.88 +/- 0.49 and 1.16 +/- 0.37 for patients in groups 1 and 2, respectively (P < 0.0001). We observed no difference in mean exercise work load (9.6 +/- 2.80 versus 8.46 +/- 2.18 min, NS) and rate- pressure product (24230 +/- 6425 versus 24207 +/- 8146 mmHg beats/ min, NS) at peak for the two categories of patients. All 13 patients in group 1 (100%) had viable myocardium in the anterior infarcted areas whereas only one of 12 patients in group 2 did (9%, P< 0.0001 versus group 1). Finally, a subanalysis for the specific pharmacological agent used was performed and it gave similar results. CONCLUSION: Regardless of the specific stress test able to elicit the electrocardiographic sign, infarcted dysfunctional areas with stress-induced NNTW were demonstrated to have a higher coronary vasodilating capability and a greater probability of viability of myocardium than had persistent negative T wave regions. Therefore, detection of NNTW appears to be a cheap first-line method for the identification both of a better preserved coronary microcirculatory function and of the persistence of viability of myocardium in the infarcted areas.

Clinical application of monitoring techniques: radioisotopic methods.

The availability of mobile gamma cameras or the nearness of nuclear medicine devices to the coronary care unit make the assessment of transient myocardial ischemia by radioisotopic techniques practical. Nuclear cardiology provides information on the presence, site and extent of ischemia and helps the clinician in the evaluation of myocardial functional impairment and recovery. Monitoring of myocardial wall motion by radionuclide ventriculography demonstrates that during angina at rest; global ejection fraction is not always sensitive to regional ischemia; episodes of angina with undetectable electrocardiographic signs of ischemia can be associated with severe myocardial dysfunction; separate left and right phase analysis of radionuclide ventriculography is a sensitive tool to assess segmental dyssynergy localized to the left or the right ventricle; a prevalent right ventricular impairment during ischemia, not measurable by Thallium scintigraphy, is possible; the recovery of function after ischemia is usually fast and apparently complete. In addition, useful diagnostic information can be derived by left ventricular injection of radioactive microspheres during cardiac catheterization followed by gated acquisitions of the intramyocardial radioactivity. Gated microsphere acquisitions, providing diastolic and systolic images, avoid blurring of images due to cardiac motion and enhance contrast between myocardium and background: the overall result is an improved detection and definition of small perfusion defects. Furthermore, this technique permits simultaneous assessment of regional perfusion and wall motion. An appraisal of potential mismatches between flow and function after revascularization procedures can be recognized by this approach. The development of technology is improving the performance of nuclear medicine instrumentation, hampered, at present, by limited spatial and temporal resolution.(ABSTRACT TRUNCATED AT 250 WORDS)

When the electrocardiogram fails to define site and extent of myocardial ischemia.

Information on the anatomical site of myocardial ischemia and infarction is commonly derived from the 12-lead electrocardiogram; however, correspondence between an electrocardiogram lead, showing ischemic changes and actual location of ischemia is not always present. In our experience, a good correspondence between the electrocardiogram and perfusion defects was found in patients with angina at rest and anterior ST segment elevation or normalization of negative T wave while patients with transient ST segment depression showed perfusion defects which correlated less with electrocardiographic changes. In addition, patients with ischemic episodes at rest and with inferior ST segment elevation, right or left ventricular ischemia were indistinguishable on the basis of the electrocardiogram as documented by Thallium-201 scintigraphy and radionuclide ventriculography. In effort angina, the site and extension of ST segment depression, even in patients with single vessel disease, failed to localize the actual anatomical location of myocardial ischemia. In patients with persistent ST segment depression and/or negative T waves, and clinically documented myocardial necrosis, transmural and non-transmural persistent perfusion defects were found in spite of absence of Q waves. In these patients, late normalization of the electrocardiogram did not correspond to normalization of flow. In conclusion, electrocardiographic changes do not always provide correct information regarding the presence, location and extent of myocardial ischemia and a multiparametric approach is often required in order to characterize ischemic and/or necrotic areas.

Clinical application of monitoring techniques: hemodynamic monitoring.

In the diagnosis of myocardial ischemia continuous hemodynamic monitoring may contribute to detection of transient ischemia, to definition of location and to elimination of its pathogenesis, and to characterization of hemodynamic response to ischemia. It can be helpful in investigating the significance of negligible, non specific and/or short-lasting electrocardiographic changes accompanying typical anginal symptoms. Simultaneous right ventricular and left ventricular pressure monitoring gives information regarding biventricular interaction during episodes of transient ischemia: an early left ventricular dysfunction, with or without a late right ventricular impairment, a selective right dysfunction, and a simultaneous left ventricular and right ventricular impairment all represent the hemodynamic patterns associated with left, right and biventricular ischemia respectively. Monitoring of hemodynamic parameters related to myocardial oxygen consumption and the study of their changes preceding the onset of ischemia during both spontaneous and provoked episodes of ischemia, may help in identifying whether functional or organic factors or both are involved in the pathogenesis of transient ischemia in individual patients. Two principal hemodynamic patterns appear to be associated with transient ischemia: a) left ventricular and/or right ventricular impairment, usually beginning shortly before the onset of electrocardiographic changes, followed by a rapid recovery and often an overshooting, b) a sudden and sustained increase in systolic pressure and heart rate, simultaneous with the onset of ST-T changes. In both cases, the 'excitatory' pattern appears to be unrelated to pain.(ABSTRACT TRUNCATED AT 250 WORDS)

Safety, feasibility and long term follow-up of a non-thoracotomy defibrillation system in patients with inducible sustained ventricular tachycardia/fibrillation.

UNLABELLED: A non-thoracotomy lead system CPI-ENDOTAK, a transvenous lead used alone or combined with a subcutaneous patch (SQ-P), was evaluated as an alternative to epicardial patches/electrodes in patients at high risk for sudden cardiac death undergoing implantable cardioverter-defibrillator (ICD) surgery. Fifty nine patients, 62 +/- 11.4 years with CAD (83.0%) cardiomyopathy (11.9%) other (5.1%), mean ejection fraction 31.8 +/- 14%, with inducible sustained VT/VF underwent testing of either lead alone or lead/SQ-P. Four configurations of NTL were tested. Fifty one patients had NTL implanted (lead alone = 60.8% and lead/SQ-P = 39.2%). Eight patients required non-NTL approaches, due to high DFT (7) or anatomic anomaly (1). DFT's were 19.1J (lead alone) and 20.8J (lead/SQ-P). Acute complications: pulmonary embolism 1, lead dislodgement 3, sensing malfunction 1. [table: see text] CONCLUSION: A NTL system using either a single transvenous lead alone or combined with SQ-P can be implanted successfully in high risk patients with a low incidence of acute complications. Non-arrhythmic survival is lowest in patients receiving defibrillation shocks. Arrhythmic survival is high in all patients.

Radionuclide PET and PET/CT in coronary artery disease.

In the present review, the basis of non invasive assessment of CAD, the most recent technical developments and results obtained by PET in cardiovascular research and clinical cardiology are described. PET has provided a wealth of new information in the field of cardiac pathophysiology and remains the gold standard for non-invasive measurements of MBF and CFR against which new techniques should be tested. The possibility to combine this relevant functional information with the anatomic details on luminal and arterial wall abnormalities, provided by multislice CT with or without the use of "hybrid" scanners, offers new opportunities for comprehensive non-invasive assessment of CAD and efficacy of new treatments.