Steven R. Bergmann

Augmentation of myocardial blood flow in hypertensive heart disease by angiotensin antagonists: a comparison of lisinopril and losartan.

OBJECTIVESnThe goal of this study was to compare myocardial perfusion reserve (MPR) before and after long-term treatment with lisinopril and losartan in patients with hypertension and left ventricular hypertrophy (LVH).nnnBACKGROUNDnStudies have suggested that treatment with angiotensin-converting enzyme inhibitors (ACEIs) improves MPR in patients with hypertension by potentiating endogenous bradykinins. Because angiotensin receptor blockers (ARBs) lack a direct effect on bradykinins, we hypothesized that they may not improve MPR.nnnMETHODSnWe measured pre- and post-treatment myocardial blood flow (MBF) by positron emission tomography in 17 patients (lisinopril: 9 patients, losartan: 8 patients) with hypertension and LVH at baseline and after coronary vasodilation with intravenous dipyridamole. In addition, we measured rest and hyperemic blood flow in eight normotensive controls.nnnRESULTSnPost-treatment maximal coronary blood flow and MPR in the lisinopril group increased significantly compared with pretreatment values (3.5 +/- 1.2 vs. 2.6 +/- 1.1 ml/min/g, p = 0.02; 3.7 +/- 1.1 vs. 2.4 +/- 1 ml/min/g, respectively, p = 0.002, respectively). Post-treatment hyperemic flow in the patients treated with lisinopril was not significantly different from corresponding measurements in controls (3.5 +/- 1.2 vs. 3.9 +/- 1 ml/min/g, respectively, p = NS). In the patients treated with losartan, there was no difference between pre- and post-treatment MBF values and MPR.nnnCONCLUSIONSnMyocardial perfusion reserve and maximal coronary flow improved in asymptomatic patients with hypertension-induced LVH after long-term treatment with lisinopril but not with losartan. Thus, ACEIs, but not ARBs, might be effective in repairing the coronary microangiopathy associated with hypertension-induced LVH.

Absolute quantitation of coronary steal induced by intravenous dipyridamole

OBJECTIVEnThe study was done to determine whether coronary steal (defined as an absolute decrease in perfusion from resting blood flow) is induced by intravenous (IV) dipyridamole in patients with severe coronary artery disease (CAD).nnnBACKGROUNDnMyocardial ischemia during coronary vasodilation is usually attributed to coronary steal. However, there is limited data on the absolute magnitude of coronary steal in humans.nnnMETHODSnEighteen patients with multivessel CAD underwent dynamic positron emission tomography (PET) imaging with 13NH3 at rest and after infusion of IV dipyridamole. Eight myocardial sectors were analyzed per short axis slice and myocardial blood flow calculated with a two-compartment model in absolute terms.nnnRESULTSnCoronary steal occurred in 8 of the 18 patients. In the 8 patients with coronary steal, myocardial blood flow decreased from 90 +/- 18 ml/100 g/min at rest to 68 +/- 27 ml/100 g/min following dipyridamole in the segments with steal, and increased from 87 +/- 19 to 138 +/- 16 ml/100 g/min following dipyridamole in the segments without steal. Significant clinical correlates of coronary steal were either ST elevation or the combination of ST depression and angina.nnnCONCLUSIONSnCoronary vasodilation with IV dipyridamole is associated with significant reductions in blood flow to collateral-dependent myocardium consistent with coronary steal in about 45% of patients with severe CAD.

Utility of positron emission tomography in predicting cardiac events and survival in patients with coronary artery disease and severe left ventricular dysfunction.

that many patients referred for transplantation can actually safely undergo coronary artery bypass grafting if they have viable myocardium identified with positron emission tomography (PET). The delineation of viable from nonviable myocardium is critically important, especially in patients with severe left ventricular (LV) dysfunction because they derive the most benefit from surgical interventions, but also have the highest perioperative risk. 4‐ 7 The purpose of this study was to determine the utility of PET in predicting cardiac events in patients with coronary artery disease and severe LV dysfunction and the outcome of these patients based on the choice of medical therapy or revascularization. ••• A retrospective analysis of all patients who had

Partial loading of the left ventricle during mechanical assist device support is associated with improved myocardial function, blood flow and metabolism and increased exercise capacity☆

BACKGROUNDnMyocardial recovery has been observed after placement of left ventricular assist devices in some patients awaiting cardiac transplantation. Left ventricular assist devices provide profound volume and pressure unloading while restoring systemic blood flow. However, the optimal degree of left ventricular unloading during left ventricular assist device support is unknown. The purpose of this study was to assess the effect of the degree of left ventricular decompression, during left ventricular assist device support, on myocardial function and exercise capacity.nnnMETHODSnTwenty patients with a left ventricular assist device performed cardiopulmonary exercise testing with simultaneous echocardiographic and hemodynamic measurements during full, and then partial, device support. Eleven patients underwent positron emission tomographic scanning for measurement of myocardial blood flow and oxygen consumption.nnnRESULTSnPatients were divided into two groups based on the degree of left ventricular decompression as assessed by echocardiographic measurements. Patients with partially decompressed ventricles (n = 13, LVEDD = 4.8 +/- 1.0 cm) as compared to those with fully decompressed ventricles (n = 10, LVEDD = 3.0 +/- 0.3 cm) demonstrated significant improvements in: peak oxygen consumption (16.8 +/- 4.3 versus 12.8 +/- 3.0 ml/kg.min), native left ventricular index during exercise (2.5 +/- 1.4 versus 0.8 +/- 0.8 liters/min.m(2)); ability to exercise with the device weaned (10 of 13 versus 1 of 10 patients); resting myocardial blood flow (0.55 +/- 0.11 versus 0.21 +/- 0.13 ml/g.min); and myocardial oxygen consumption (0.04 +/- 0.01 versus 0.02 +/- 0.001 min-1) (all p < 0.05).nnnCONCLUSIONSnThese results suggest that partial loading of the left ventricle during left ventricular assist device support may be beneficial. Further study of optimal ventricular decompression during device support is needed, as this may be important in improving myocardial recovery.

Cardiac positron emission tomography

Positron emission tomography (PET) is an intrinsically quantitative tool that provides a unique and unparalleled approach for clinicians and researchers to interrogate the heart noninvasively. The ability to label substances of physiological interest with positron-emitting radioisotopes has permitted insight into normal blood flow and metabolism and the alterations that occur with disease states. The efficacies of interventional therapies also have been demonstrated with cardiac PET. PET is unequaled in establishing the presence or absence of coronary artery disease (CAD) as well as for assessment of myocardial viability. Using mathematically and physiologically appropriate models, myocardial blood flow, metabolism, and ligand density and flux can be measured noninvasively, providing physicians and researchers with an exceptional window to the heart. Future advances in both instrumentation as well as radiochemistry and image processing will improve our understanding of the heart under normal conditions as well as with disease and should provide therapeutic approaches to enhancing the treatment of patients with heart disease of diverse etiologies.

Value of definitive diagnostic testing in the evaluation of patients presenting to the emergency department with chest pain

The optimal diagnostic evaluation of patients presenting to the emergency department (ED) with chest pain but without myocardial infarction or unstable angina is controversial. We performed a prospective, nonrandomized, observational study of 1,195 consecutive patients presenting to the ED with chest pain but who had normal or nondiagnostic electrocardiograms and negative cardiac biomarkers. Patients (mean +/- SD age 61 +/- 15 years; 55% women) were admitted to the hospital and a standard protocol for evaluation and treatment was suggested. The use of stress myocardial perfusion imaging (MPI) or cardiac catheterization during their index hospitalization, and the 3-month incidence of coronary angiography, percutaneous cardiac intervention, coronary artery bypass surgery, re-presentation to our institutions ED for chest pain, myocardial infarction, or death were followed. Five hundred nine of 1,195 patients (43%) underwent provocative stress MPI during their index hospitalization; 37% had perfusion defects (predominantly ischemia). Fifty-six of 1,195 patients (4%) underwent cardiac catheterization without stress MPI for their primary diagnostic evaluation. Six hundred thirty of 1,195 patients (53%) had neither MPI or cardiac catheterization during their index hospitalization. During the 3-month follow-up period, patients with a normal stress perfusion study during their index hospitalization had fewer return visits (4%) compared with patients with abnormal perfusion studies (19%), those who underwent catheterization directly (16%), or patients with no initial diagnostic evaluation (15%) (p <0.001). In addition, patients who had a diagnostic evaluation during their index hospitalization had a lower incidence of either acute myocardial infarction (0.9% vs 2.1%) or death (0.4% vs 3.0%, p <0.001) in the 3-month follow-up period. Accordingly, we strongly advocate provocative stress MPI early after presentation for chest pain in all patients with risk factors for coronary artery disease.

The effect of estrogen compared to estrogen plus progesterone on the exercise electrocardiogram

OBJECTIVESnThe objective of this study was to evaluate the effect of estrogen compared to estrogen plus progesterone on the stress electrocardiogram (ECG) in relationship to stress-gated myocardial perfusion imaging (MPI) in postmenopausal women.nnnBACKGROUNDnIt is generally recognized that estrogen may cause false positive ST depressions on the stress ECG. The effects of estrogen plus progesterone are not known. This study was performed to define the effects of these agents on the stress ECG correlated with results from MPI.nnnMETHODSnWe evaluated 140 postmenopausal women-31 not taking any hormone replacement therapy (HRT); 75 taking estrogen alone; and 34 taking estrogen plus progesterone. Women with a history of coronary artery disease (CAD), cardiomyopathy, or an abnormal resting ECG were excluded. All women underwent a symptom-limited treadmill test and MPI.nnnRESULTSnThe overall sensitivity and specificity of the stress ECG compared to MPI in women not taking HRT was 54% and 78%, respectively. In women taking estrogen or estrogen plus progesterone, the sensitivity was unchanged. The power to detect clinically meaningful sensitivity difference (10%) was poor (p = 0.09). The specificity was reduced to 46% (p < 0.01) in women on estrogen therapy. In women taking estrogen plus progesterone, specificity was 80%.nnnCONCLUSIONSnOur results suggest that estrogen increases the false positive rate of the stress ECG. This decreased specificity is countered by co-administration of progesterone. Nonetheless, because the sensitivity of the stress ECG is only 50% to 57% in postmenopausal women, women at risk should have imaging in conjunction with stress for the optimal detection of CAD.

Protection of ischemic hearts perfused with an anion exchange inhibitor, DIDS, is associated with beneficial changes in substrate metabolism.

OBJECTIVEnMetabolic interventions that promote glucose use during ischemia have been shown to protect the myocardium and improve functional recovery on reperfusion. In this study we evaluated if cardioprotection can be accomplished by inhibiting fatty acid uptake, which would be expected to increase glycolytic metabolism.nnnMETHODSnDiisothiocyanostilbene sulfonic acid (DIDS), commonly used to inhibit Band-3 mediated anion exchanger, and has also been demonstrated to inhibit fatty acid transport in adipocytes, was used to inhibit fatty acid uptake prior to ischemia. Isolated rat hearts were perfused with buffer containing 5 mM glucose, 70 mU/l insulin, 0.4 mM palmitate, and 0.4 mM albumin, paced at 300 beats/min, and subjected to 50 min of low-flow ischemia followed by 60 min of reperfusion.nnnRESULTSnIschemic injury, as assessed by creatine kinase release, was diminished in hearts perfused with DIDS (334+/-72 in DIDS vs. 565+/-314 IU/g dry wt in controls, P<0.04). Increases in LVEDP during ischemia were attenuated (8+/-3 mmHg in DIDS vs. 15+/-18 mmHg in controls, P<0.03) and the % recovery of LV function with reperfusion was enhanced in DIDS-treated hearts (78+/-10% of baseline in DIDS vs. 62+/-19% of baseline in controls, P<0.04). These beneficial effects of DIDS were associated with increased glucose metabolism and ATP content during ischemia and reperfusion. Furthermore, treatment with DIDS lowered the accumulation of long chain acyl carnitines.nnnCONCLUSIONSnThis study demonstrates that DIDS protects ischemic myocardium, and is associated with inhibition of fatty acid uptake, improved glucose metabolism, and enhanced functional recovery on reperfusion. The data presented here suggest a potential role for therapeutic agents that lower fatty acid uptake as a metabolic adjunct in the treatment of myocardial ischemia.

Usefulness of positron emission tomography in defining myocardial viability in patients referred for cardiac transplantation

Positron emission tomography imaging detected evidence of viability in 17 of 33 patients with evidence of infarction only on their thallium scans who were referred for transplant evaluation. Eleven of these 17 underwent revascularization with excellent outcome.

Silent ischemia: unsafe at any time*

Percutaneous coronary intervention (PCI) using balloon angioplasty with stenting has become a mainstay in the treatment of patients with coronary artery disease (CAD). Over one million PCI procedures were performed in the U.S. alone in 2000, nearly one-half of which involved placement of a coronary