D. Douglas Miller

Prognostic value of cardiopulmonary exercise testing using percent achieved of predicted peak oxygen uptake for patients with ischemic and dilated cardiomyopathy

OBJECTIVESnWe tested the hypothesis that percent achieved of predicted peak oxygen uptake (predicted VO2max) improves the prognostic accuracy of identifying high risk ambulatory patients with congestive heart failure considered for heart transplantation compared with absolute peak oxygen uptake (VO2max) in 181 patients with ischemic or dilated cardiomyopathy.nnnBACKGROUNDnPeak oxygen uptake during exercise has been shown to be a useful prognostic measurement to risk stratify patients with heart failure. The prognostic value of percent predicted VO2max has not been assessed in these patients.nnnMETHODSnWe retrospectively studied 181 ambulatory patients referred to the Saint Louis University Heart Failure Unit. Clinical, hemodynamic (137 patients) and coronary angiographic (145 patients) data were recorded, and all patients underwent symptom-limited cardiopulmonary exercise.nnnRESULTSnDuring a mean follow-up period of 12 +/- 6 months, 26 patients died, and 18 were listed as Status 1 priority for heart transplantation. The actuarial 1- and 2-year survival of the 89 patients who achieved < or = 50% predicted VO2max was 74% and 43%, respectively, compared with 98% and 90% in the 92 who achieved > 50% predicted VO2max (p = 0.001). Multivariable analysis selected < or = 50% predicted VO2max as the most significant predictor of cardiac death (p = 0.007) and cardiac death or Status 1 priority (p = 0.0005).nnnCONCLUSIONSnPercent achieved of predicted VO2max provides important information that can be used to risk stratify ambulatory patients with heart failure with ischemic or dilated etiology that exceeds that provided by measurement of VO2max alone. Patients who achieve > 50% predicted VO2max have an excellent short-term prognosis when treated medically, and heart transplantation can be safely deferred.

Fatty acid analogue accumulation: a marker of myocyte viability in ischemic-reperfused myocardium.

A 3-methyl substituted radioiodinated long chain fatty acid analogue was evaluated as an agent for the noninvasive detection of altered fatty acid uptake in reperfused, postischemic myocardium. This iodinated fatty acid analogue, 15-(para-iodophenyl)-3-methyl pentadecanoic acid, was given intravenously at 3 hours of reperfusion following 15 minutes (Group 1, n = 5 dogs) or 60 minutes (Group 2, n = 5 dogs) of left anterior descending coronary artery occlusion. Myocardial blood flow (MBF) was measured during occlusion and reperfusion with radiolabeled microspheres administered via the left atrium. Paired ultrasonic subendocardial crystals were placed in the ischemic perfusion bed to assess regional left ventricular systolic function at baseline, during ischemia and reperfusion. Electron microscopic analysis and staining with triphenyltetrazolium chloride (TTC) was performed. Groups 1 and 2 dogs had similar (p = NS) myocardial blood flows during occlusion. TTC positive 1 g endocardial segments from Group 1 (n = 98) and Group 2 (n = 71) had 37% greater fatty acid analogue activity (0.26 +/- 0.04 vs. 0.19 +/- 0.09 percent injected dose per gram; p less than 0.05) compared with TTC negative segments from Group 2 dogs (n = 37). When fatty acid analogue activity was related to near simultaneous reperfusion blood flow, this ratio was 27% greater (p less than 0.05) in TTC positive segments (0.38 +/- 0.1) compared with TTC negative (0.30 +/- 0.16) segments, and 9% greater than normal (0.35 +/- 0.09; p less than 0.05). While ischemic regions from both Groups 1 and 2 dogs became similarly dyskinetic during occlusion (systolic shortening, -11 +/- 6 vs. -11 +/- 2%; p = NS), TTC negative segments remained akinetic (= 1 +/- 7%) at 3 hours of reperfusion while TTC positive zones had recovered partial systolic function (8 +/- 22%). Electron microscopy confirmed the presence of reversible ultrastructural changes in TTC positive regions. A 60-minute occlusion, 3-hour reperfusion model adapted for in vivo single photon emission computed tomography showed a similar excess of 123I fatty acid activity over flow when compared to perfusion (as measured with 201Tl) in the ischemic border zone of 4/4 canine myocardial infarcts. We conclude that the accumulation of this non-beta-oxidized fatty acid analogue noninvasively identifies zones of discordance between fatty acid and flow distribution that are characteristic of ischemically stunned but viable myocardium.

Moderate alcohol feeding attenuates postinjury vascular cell proliferation in rabbit angioplasty model

Our studies in the cholesterol-fed rabbit model indicate that moderate alcohol consumption reduces the risk of restenosis by preventing low-density lipoprotein (LDL) oxidation. Eighteen hypercholesterolemic rabbits underwent arterial injury by Fogerty balloon endothelial denudation of iliac arteries. Two weeks later, balloon angioplasty of atherogenic or atherosclerotic arterial segments was performed. Nine rabbits (control) received water ad lib, whereas nine rabbits (moderate alcohol treated) received an average of 2.5 ml alcohol per 500 ml water daily, from the day of feeding hypercholesterolemic diet until they were killed, 10 weeks later. There was a 26% increase in lumen size of the moderate alcohol-treated group compared with the control group. The percentage neointima formation (NI) values of the moderate alcohol-treated and control groups were 77 +/- 2.1 and 61 +/- 1.9, respectively (p < 0.001). The lumen/neointima (L/NI) ratio of the moderate alcohol-treated group was 0.71 +/- 0.07 compared with the control group, 0.33 +/- 0.04 (p < 0.001). The number of foam cells in the moderate alcohol-treated group was threefold less than the control group [i.e., 1.4 +/- 0.4 and 3.9 +/- 0.8, respectively (p = 0.005)]. The arterial lesion malondialdehyde (MDA) values of the control and the moderate alcohol-treated groups were 13.6 +/- 2.8 and 4.4 +/- 0.5 (p = 0.004), respectively. By radioimmunoassay, the moderate alcohol-treated group had less macrophage chemotactic protein-1 (MCP-1; 3,277 cpm/microg protein) and platelet-derived growth factor (PDGF; 2,261 cpm/microg protein) compared with the controls (MCP-1, 4,529 cpm/microg protein; PDGF, 3,583 cpm/microg protein). Thus we conclude that low concentrations of alcohol reduce neointimal formation, and the extent of lipid oxidation, the number of foam cells in the neointimal area and may decrease the expression of MCP-1 and PDGF by reducing LDL oxidation in an animal model of postangioplasty restenosis.

Prognostic value of computer-quantitated exercise thallium imaging early after percutaneous transluminal coronary angioplasty.

To develop an approach to predicting adverse events after percutaneous transluminal coronary angioplasty (PTCA), 50 patients had thallium-201 exercise testing within 1 month after successful single vessel coronary angioplasty and were followed up for a mean of 18 months. Adverse events were: 1) clinical events consisting of recurrent angina (17 patients) and myocardial infarction (1 patient); 2) treatment events consisting of repeat coronary angioplasty (10 patients) and coronary bypass surgery (1 patient); and 3) restenosis, defined as a greater than 30% increase in luminal stenosis (15 of 38 recatheterized patients). There were no deaths. Of the clinical, exercise, angiographic and thallium scan variables analyzed by stepwise logistic regression, postangioplasty gradient greater than 20 mm Hg predicted clinical events and treatment events, and the number of segments with slower thallium clearance predicted clinical events, treatment events and restenosis. Using Cox Hazards model regression of survival without events, the number of transient qualitative thallium defects also predicted clinical events and restenosis. At 1 year after angioplasty, 24% of patients with these variables had restenosis compared with only 6% of those without these variables and 36% of patients with these variables had a clinical or treatment event compared with 8% of patients without these variables. Three measures of the adequacy of myocardial perfusion (post-angioplasty gradient, reduced thallium clearance and transient thallium defects) were additive predictors of adverse events after coronary angioplasty with the relative risk being approximately four times greater in patients with these variables than in those without. Such adverse events, therefore, are usually a consequence of inadequate revascularization.

Left ventricular ejection fraction response during exercise in asymptomatic systemic hypertension

To study the effect of mild-to-moderate elevations in diastolic blood pressure (BP) on systolic left ventricular (LV) function, 28 hypertensive patients and 20 normal subjects underwent upright exercise first-pass radionuclide angiography. All were asymptomatic, had normal rest and exercise electrocardiographic findings and no evidence of LV hypertrophy or coronary artery disease. LV function at rest was similar in the 2 groups, but with exercise hypertensive patients had a greater end-systolic volume (69 +/- 19 vs 51 +/- 19 ml, p less than 0.002) and lower ejection fraction (EF) (0.59 +/- 0.09 vs 0.72 +/- 0.07, p less than 0.0001), stroke volume (101 +/- 28 vs 130 +/- 36 ml, p less than 0.005) and peak oxygen uptake (23 +/- 7 vs 33 +/- 9 ml/kl/min, p less than 0.05). Hypertensive patients were separated into 3 groups: group 1-12 patients with an increase in EF with exercise greater than or equal to 0.05; group 2-7 patients with a change in EF with exercise less than 0.05; and group 3-9 patients with a decrease in EF with exercise greater than or equal to 0.05. Group 3 hypertensive patients were older, had a higher heart rate at rest and lower peak oxygen uptake. Rest LV function was similar in the 3 hypertensive subgroups, but exercise end-systolic volumes were higher in groups 2 and 3. Exercise thallium-201 images was normal in all but 1 of 14 hypertensive group 2 or 3 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Nifedipine, but not propranolol, improves left ventricular systolic and diastolic function in patients with hypertension

The effects of nifedipine and propranolol on cardiac function both at rest and at peak exercise were compared in 22 hypertensive patients whose diastolic blood pressures remained in excess of 95 mm Hg despite diuretic therapy. In this double-blind, placebo-controlled study, left ventricular systolic and diastolic function at rest and at peak exercise during bicycle ergometry was assessed by first-pass radionuclide angiography using the Baird Scinticor before and after treatment with either nifedipine or propranolol. Both agents effectively reduced blood pressure in the supine and upright positions and at peak exercise. Nifedipine was associated with a significant increase in cardiac output and stroke volume at rest and at peak exercise, while propranolol decreased cardiac output at rest and at peak exercise. Systemic vascular resistance decreased with nifedipine treatment at rest and at peak exercise, but increased significantly with propranolol. Nifedipine increased ejection fraction in patients at rest and also increased maximal oxygen consumption at peak exercise, while propranolol decreased maximal oxygen consumption at peak exercise. At rest and at peak exercise, nifedipine increased peak filling rate, but time to peak filling rate was not affected by either drug. The fraction of total diastolic filling at the midpoint of diastole was significantly increased by nifedipine therapy at rest but was not affected by propranolol therapy. Nifedipine significantly decreased atrial filling volume while propranolol had no effect. Propranolol therapy did not result in any improvement in left ventricular function. In contrast, nifedipine improved left ventricular systolic and diastolic function at rest and peak exercise. Future selection of an antihypertensive agent should include consideration of the impact of therapy on left ventricular function.

Effect of hyperosmotic mannitol on magnetic resonance relaxation parameters in reperfused canine myocardial infarction

To determine how administration of a hyperosmotic agent alters regional nuclear magnetic resonance (NMR) relaxation parameters and imaging characteristics in ischemic-reperfused myocardium, 7 dogs were infused with mannitol for 15 minutes before and after the release of a 3 hour left anterior descending coronary artery (LAD) occlusion. Nine control animals received normal saline during the 3 hour occlusion and 1 hour reperfusion periods. Normal posterior left ventricular (LV) wall and the ischemic anterior LV wall (risk area) myocardium was sampled for calculation of segmental microsphere myocardial blood flow, % tissue water content, NMR relaxation times (T1, T2) and myocyte ultrastructure using electron microscopy. Mean infarct T1 values were 14% greater than normal segments in saline-treated controls, but only 5% greater after mannitol. The difference in tissue water content between infarcted and normal segments was 4% in saline-treated (83 vs. 79%) compared to 2% in mannitol-treated dogs (79 vs. 77%). T1, T2 and % water content of control infarct segments were greater than treated infarcts (p less than 0.01). T1 and T2 rose as occlusion flow fell below 0.5 ml/min/g in control hearts but did not rise until flows were reduced to 0.1 ml/min/g in mannitol-treated hearts. Areas of increased signal in T1 and T2 NMR images correlated well with histochemical infarct volume (r = 0.98, SEE = 1.1 cc) in mannitol-treated dogs, but infarct borders were qualitatively less well-defined than in controls. We concluded that mannitol (1) diminishes tissue edema and reduces NMR relaxation parameters (T1, T2) in infarcted myocardium; and (2) attenuates the rise in T1 and T2 and ultrastructural myocyte injury in ischemic-reperfused myocardium.

New radionuclides for cardiac imaging.

T WO RADIONUCLIDES, thallium-201 and technetium-99m, have assumed preeminence in cardiovascular nuclear medicine because their photon energies, kinetics, and dosimetry are well-suited to make three major physiologic measurements: perfusion, function, and viability. The photon energies of these nuclides are well matched to the characteristics of the Anger camera, which has optimum efficiency and resolution for energies between 100 and 200 keV. The spatial resolution of the “system” for the average cardiovascular nuclear medicine study (radiopharmaceutical, collimator, camera, and computer) at the depth of the heart is approximately 1 cm full width half maximum (FWHM). Against this background, new radiopharmaceuticals suggested for the evaluation of the heart (Table 1) must offer an improvement in dosimetry and resolution, or provide data on a previously unmeasurable parameter. This review will concentrate on the new radiopharmaceuticals that have met two criteria: (1) experience with the radiopharmaceutical in human subjects, and (2) some likelihood of commercial production of the agent for widespread clinical use. Although equilibrium studies provide high quality data for evaluation of regional and global cardiac function, a high photon flux first pass approach, which could evaluate ventricular function during breathholding (to eliminate respiratory motion), would improve resolution. The ideal first pass radionuclide should have a short physical halflife, have no particulate emissions, produce photons of 100 to 200 keV, and decay to a stable daughter. Such an agent would permit multiple measurements to be performed in each view and would allow repetitive determinations of ventricular function during the action of drugs, exercise, or physiologic maneuvers (Valsalva, etc). The following agents have some of these properties and may supplant Tc-99m as the radionuclide for first pass studies.

Coronary artery disease: diagnostic and prognostic models for reducing patient risk.

Early and accurate diagnostic testing is a critical factor in the detection and optimal management of coronary artery disease (CAD); thus, noninvasive cardiac imaging has become a central tool for CAD evaluation. Currently, tests used for evaluating CAD include conventional resting and stress electrocardiogram, echocardiography, and myocardial perfusion imaging--the most widely used imaging test for evaluation of suspected myocardial ischemia. Emerging techniques for noninvasive assessment of myocardial perfusion and coronary angiography include cardiac computed tomography, cardiac magnetic resonance imaging, and positron emission tomography. The distinctive pathophysiology of atherosclerosis can be used together with imaging techniques to diagnose and assess risk for CAD. Imaging modalities for cardiac risk stratification include a diverse array of tools, such as noninvasive tests that visualize presymptomatic atherosclerosis to sophisticated radionuclide protocols that identify myocardial viability. Of the noninvasive imaging tests, gated SPECT is the most accurate method for risk stratification of CAD. Myocardial perfusion imaging with SPECT has improved accuracy and image quality such that a shift from diagnostic to prognostic use has occurred. Radionuclide myocardial perfusion imaging has played an important role in CAD evaluation since the introduction of thallium-201 (Tl-201) in the 1970s. Although Tl-201 has high sensitivity, specificity, and reproducibility, it also has physical properties that limit its use and affect image quality. Currently, Tc-99m tetrofosmin and sestamibi are the most commonly used agents for a variety of resting and stress protocols, both have similar diagnostic accuracy profiles. The field of nuclear cardiology has grown steadily over the past few decades, as more practitioners recognize its clinical applications and value in managing cardiovascular disease. There is abroad spectrum of noninvasive and invasive testing available for the diagnosis and management of patients with cardiovascular disease. Advances in computer technology have made sophisticated devices, such as the gated SPECT, a routine part of cardiology.

Safety of dipyridamole testing in patients with cerebrovascular disease

Abstract Severe undiagnosed coronary artery disease is a major cause of morbidity and mortality in patients with carotid stenoses. 22,23 Our study demonstrates that dipyridamole testing carries a very low risk of neurologic complications in patients with cerebrovascular disease.