Acute and chronic angiotensin-1 receptor antagonism reverses endothelial dysfunction in atherosclerosis.

BACKGROUND: The renin-angiotensin system may contribute to atherogenesis through the promotion of endothelial dysfunction. The present study was performed to determine whether angiotensin-1 (AT(1)) receptor inhibition improves endothelial dysfunction. METHODS AND RESULTS: In the femoral circulation of 19 patients with atherosclerosis and of 9 control subjects, we studied microvascular responses to reactive hyperemia, angiotensin II, acetylcholine, and sodium nitroprusside before and after the administration of intra-arterial losartan (10 mg). Femoral artery flow velocity was measured with a Doppler flow wire, and the femoral vascular resistance index (FVRI) was calculated as mean arterial pressure divided by flow velocity. Losartan induced a minor (5.9+/-2%, P=0. 02) reduction in FVRI and inhibited angiotensin II-mediated vasoconstriction in both patient groups (P<0.01). After the administration of losartan, acetylcholine-mediated vasodilation was augmented in patients (44+/-5% to 58+/-4% reduction in FVRI with infusion at a rate of 150 microgram/min, P<0.001) but not control subjects. Vasodilation during reactive hyperemia was also greater after AT(1) receptor inhibition (P=0.03) in patients, but the response to sodium nitroprusside remained unchanged. In a separate group of 31 patients with atherosclerosis, we investigated the effect of 8 weeks of oral losartan therapy on brachial artery flow-mediated vasodilation with the use of high-resolution ultrasound. Oral losartan therapy improved flow-mediated brachial artery dilation (1.4+/-0.9% to 3.2+/-0.8%, P=0.03) but had no effect on the nitroglycerin response. Serum nitrogen oxide levels increased from 21.6+/-1.7 to 26.7+/-2.4 micromol/L (P=0.008). CONCLUSIONS: The results of the present study indicate that inhibition of the AT(1) receptor in patients with atherosclerosis reverses endothelial dysfunction by improving NO availability and therefore may have long-term therapeutic benefits.

Benefits and risks of sauna bathing.

Although sauna bathing causes various acute, transient cardiovascular and hormonal changes, it is well tolerated by most healthy adults and children. Sauna bathing does not influence fertility and is safe during the uncomplicated pregnancies of healthy women. Some studies have suggested that long-term sauna bathing may help lower blood pressure in patients with hypertension and improve the left ventricular ejection fraction in patients with chronic congestive heart failure, but additional data are needed to confirm these findings. The transient improvements in pulmonary function that occur in the sauna may provide some relief to patients with asthma and chronic bronchitis. Sauna bathing may also alleviate pain and improve joint mobility in patients with rheumatic disease. Although sauna bathing does not cause drying of the skin-and may even benefit patients with psoriasis-sweating may increase itching in patients with atopic dermatitis. Contraindications to sauna bathing include unstable angina pectoris, recent myocardial infarction, and severe aortic stenosis. Sauna bathing is safe, however, for most people with coronary heart disease with stable angina pectoris or old myocardial infarction. Very few acute myocardial infarctions and sudden deaths occur in saunas, but alcohol consumption during sauna bathing increases the risk of hypotension, arrhythmia, and sudden death, and should be avoided.

Determination of pretest probability for detection of a cardiovascular source of emboli by transesophageal echocardiography using clinical and transthoracic echocardiographic data.

Transesophageal echocardiographic findings and their effect on disease management were evaluated in 216 patients with suspected cardiovascular source of emboli. Clinical and transesophageal echocardiographic findings were useful in defining pretest probability for finding a probable cardiovascular source of emboli on transesophageal echocardiography.

Immediate effect of Biosense guided percutaneous direct myocardial revascularization with holmium:yttrium aluminium garnet laser on myocardial contractility assessed by transesophageal echocardiography.

OBJECTIVE: To evaluate immediate changes in left ventricular wall motion in patients treated using Biosense direct myocardial revascularization laser system. METHODS: Regional wall motion in 10 patients undergoing catheter-based direct myocardial revascularization using a holmium:yttrium aluminium garnet laser was assessed by transesophageal echocardiography before and immediately after the procedure. RESULTS: Mild deterioration in wall-motion score occurred rarely for only three of 160 (1.9%) segments and did not induce clinical heart failure. CONCLUSION: With the current catheter-based laser myocardial revascularization strategy, mild deterioration in wall motion of treated segments was rarely observed and did not effect overall left ventricular function or induce clinical congestive heart failure.

Electromechanical characterization of myocardial hibernation in a pig model.

BACKGROUND: This study attempted to assess in-vivo electromechanical changes following gradual coronary artery occlusion in a pig ameroid constrictor model using a novel three-dimensional left ventricular mapping system. METHODS AND RESULTS: We measured unipolar and bipolar voltage potentials and local endocardial shortening in the ischemic lateral and non-ischemic anterior zones in animals at rest (n = 9) 5 weeks after the implantation of ameroid constrictors around the left circumflex artery. Echocardiography was used to assess regional contractility (percentage myocardial thickening), and an echo-contrast perfusion study was performed using acoustic densitometry methods. The ischemic lateral zone showed reduced myocardial perfusion at rest (peak intensity; 3.4 +/- 1.7 versus 20.7 +/- 14.8, P = 0.005), impaired mechanical function (percentage wall thickening 22 +/- 19% versus 40 +/- 11%, P = 0.03; local endocardial shortening 2.9 +/- 5.5% versus 11.7 +/- 2.1%, P = 0.002), and preserved electrical activity (unipolar voltage 12.4 +/- 4.7 versus 14.4 +/- 1.9 mV, P = 0.25; bipolar voltage 4.1 +/- 1.1 versus 3.8 +/- 1.5 mV, P = 0.62), compared with the anterior region. CONCLUSIONS: Gradual coronary artery occlusion resulting in regional reduced perfusion and function at rest (i.e. hibernating myocardium) is characterized by preserved electrical activity. An electromechanical left ventricular mapping procedure such as the one described here may be of diagnostic value for identifying the hibernating myocardium.

Intravenous Optison (FS069) enhances pulmonary vein flow velocity signals: a multicenter study.

BACKGROUND: Pulmonary vein spectral Doppler signals to characterize ventricular diastolic and systolic function, though often difficult to obtain, can be enhanced using contrast agents. HYPOTHESIS: The objective of this study was to determine the efficacy of the intravenous contrast agent Optison for enhancement of Doppler signals in patients with poor signals on two-dimensional echocardiographic examinations. METHODS: Enhancement of pulmonary venous flow was evaluated in 191 patients at 0.2, 0.5, 3.0, and 5.0 ml per injection. RESULTS: Greatest contrast enhancement for right and left pulmonary veins was observed at the highest doses. At 0.5 ml, conversion from inadequate to adequate was observed in right and left pulmonary veins in 48.0 and 79.3% of patients, respectively, while any degree of improvement was 54.4 and 65.8%, respectively. The adverse event rate (6.5%) was similar to a first-generation agent. CONCLUSION: The results demonstrate that Optison is a safe and effective contrast agent for improving visualization of pulmonary Doppler signals, especially the left pulmonary vein.

Hyperthyroid heart disease.

The heart is an organ sensitive to the action of thyroid hormone, and measurable changes in cardiac performance are detected with small variations in thyroid hormone serum concentrations. Most patients with hyperthyroidism experience cardiovascular manifestations, and the most serious complications of hyperthyroidism occur as a result of cardiac involvement. Recent studies provide important insights into the molecular pathways that mediate the action of thyroid hormone on the heart and allow a better understanding of the mechanisms that underlie the hemodynamic and clinical manifestations of hyperthyroidism. Several cardiovascular conditions and drugs can interfere with thyroid hormone levels and may pose a difficulty in interpretation of laboratory data in patients with suspected thyroid heart disease. The focus of this report is a review of the current knowledge of thyroid hormone action on the heart and the clinical and hemodynamic laboratory findings as well as therapeutic management of patients with hyperthyroid heart disease.

Bosentan and the endothelin system in congestive heart failure.

The endothelin system appears to play an important role in the pathophysiology of congestive heart failure (CHF). Endothelin receptor antagonists represent a novel class of agents that are being evaluated for their potential benefits in treating various cardiovascular disorders. Bosentan is an orally active endothelin receptor antagonist that has been studied for the treatment of CHF. Early clinical experience with bosentan has confirmed some benefits on hemodynamic parameters in patients with CHF. Its role in slowing the progression of the disease and improving survival remains to be elucidated.

Radiation-induced coronary artery disease.

Excessive unprotected radiation to the heart appears to lead to the development of CAD, even in the absence of significant cardiovascular risk factors. The coexistence of such factors may enhance the probability of CAD. The presence of hypercholesterolemia and concomitant or sequential use of chemotherapeutic agents (especially doxorubicin) could further increase this risk. Therapeutic decisions, as with any other manifestation of CAD, relate to the extent of myocardium at jeopardy and to the overall diffuseness of CAD. Management options possible are PTCA or coronary artery bypass surgery. The latter may be required in left main artery stenosis and complicated ostial lesions. Use of shielding should decrease the associated risk of radiation-induced CAD in future years. However, clinicians should continue to have a high degree of suspicion of CAD in patients treated with thoracic radiation without cardiac shielding.

The intrarenal endothelin system and hypertension.

The kidney is both a source of endothelin (ET) generation and an important target organ of this peptide. The highest concentrations of ET-1 in the body exist in the renal medulla, where it mediates natriuretic and diuretic effects through the ET(B) receptor subtype. It is proposed that aberrations in the renal ET system may lead to sodium and water retention and subsequently to the development of hypertension.

Preliminary animal and clinical experiences using an electromechanical endocardial mapping procedure to distinguish infarcted from healthy myocardium.

BACKGROUND: A catheter-based left ventricular (LV) endocardial mapping procedure using electromagnetic field energy for positioning of the catheter tip was designed to acquire simultaneous measurements of endocardial voltage potentials and myocardial contractility. We investigated such a mapping system to distinguish between infarcted and normal myocardium in an animal infarction model and in patients with coronary artery disease. METHODS AND RESULTS: Measurements of LV endocardial unipolar (UP) and bipolar (BP) voltages and local endocardial shortening were derived from dogs at baseline (n=12), at 24 hours (n=6), and at 3 weeks (n=6) after occlusion of the left anterior descending coronary artery. Also, 12 patients with prior myocardial infarction (MI) and 12 control patients underwent the LV endocardial mapping study for assessment of electromechanical function in infarcted versus healthy myocardial regions. In the canine model, a significant decrease in voltage potentials was noted in the MI zone at 24 hours (UP, 42. 8+/-9.6 to 29.1+/-12.2 mV, P=0.007; BP, 11.6+/-2.3 to 4.9+/-1.2 mV, P<0.0001) and at 3 weeks (UP, 41.0+/-8.9 to 13.9+/-3.9 mV, P<0.0001; BP, 11.2+/-2.8 to 2.4+/-0.4 mV, P<0.0001). No change in voltage was noted in zones remote from MI. In patients with prior MI, the average voltage was 7.2+/-2.7 mV (UP)/1.4+/-0.7 mV (BP) in MI regions, 17.8+/-4.6 mV (UP)/4.5+/-1.1 mV (BP) in healthy zones remote from MI, and 19.7+/-4.4 mV (UP)/5.8+/-1.0 mV (BP) in control patients without prior MI (P<0.001 for MI values versus remote zones or control patients). In the canine model and patients, local endocardial shortening was significantly impaired in MI zones compared with controls. CONCLUSIONS: These preliminary data suggest that infarcted myocardium could be accurately diagnosed and distinguished from healthy myocardium by a reduction in both electrical voltage and mechanical activity. Such a diagnostic electromechanical mapping study might be clinically useful for accurate assessment of myocardial function and viability.

Accuracy of two-dimensional echocardiographic planimetry of the mitral valve area before and after balloon valvuloplasty.

The purpose of this study was to assess the accuracy of planimetry after percutaneous balloon mitral valvuloplasty (PBMV). The mitral valve area (MVA) was estimated in 34 patients before and after PBMV, using two-dimensional echocardiographic planimetry, Doppler pressure half-time (PHT), and the Gorlin formula. There was no significant difference in the correlation of planimetry and PHT before (r = 0.53, p = 0.001) and after PBMV (r = 0.56, p < 0.001). A similar correlation was found between planimetry and the Gorlin formula (r = 0.44, p = 0.01 before PBMV, r = 0.37, p = 0.03 after PBMV). The concordance between planimetry, PHT, and the Gorlin formula in classifying patients into mild, moderate, or severe mitral stenosis was not worse after PBMV. Planimetry-derived MVA was not less accurate after PBMV than before PBMV. However, the correlation between the two echocardiographic measurements and the Gorlin formula was only moderate.

Catheter-based electromechanical mapping to assess regional myocardial function: a comparative analysis with transthoracic echocardiography.

Recent studies using a nonfluoroscopic three-dimensional left ventricular mapping system showed considerable changes in voltage potentials and mechanical activity detected in ischemic and infarcted myocardial regions with mechanical dysfunction. This study examined the electromechanical characteristics in relation to regional wall motion assessed by echocardiography in patients with coronary artery disease. A 12-segment model of mapping (apical, mid, basal of septal, anterior, lateral, and inferior/posterior segments) was compared to echo wall motion score in 74 patients (836 segments). Unipolar voltage and local endocardial shortening signals were distinguished according to graded echo segmental rest scores (0 = normal, 1 = mild hypokinesis, 2 = moderate hypokinesis, 3 = severe hypokinesis, 4 = akinesis). Results show a significant difference in voltage potentials and shortening values in groups distinguished according to echocardiography motion score. The average voltage potentials and shortening values were highest in myocardial segments with normal or slightly reduced contractility and lowest in myocardial segments with moderate to severely impaired contractility scores (voltage: 12.3 +/- 5.0, 12.1 +/- 5.3, 10.7 +/- 5.4, 8.7 +/- 3.9, 7.1 +/- 3.0 mV, P = 0.0001; local shortening: 9.7 +/- 6.5, 8.4 +/- 5.9, 8.0 +/- 5.4, 5.6 +/- 6.3, 5.1 +/- 4.6%, P = 0.0001 in regions with segmental scores of 0, 1, 2, 3, 4 by echo, respectively). Using receiver-operating curve calculations, the area under the curve was 0.72 +/- 0.06 (voltage) and 0.67 +/- 0.05 (local shortening) without a significant difference between the two curves. The 90% thresholds for defining preserved vs. impaired contractility were 12.8 and 5.6 mV for voltage and 12.6% and 1.6% for local shortening. We conclude that electromechanical mapping correlates with regional changes in wall motion scores assessed by echo, showing a gradual proportional decrease in measured voltage and shortening signals in segments with impaired function.

Medical complications of cocaine: possible relationship to low plasma cholinesterase enzyme.

What predisposes some cocaine users to its complications is not known. Because cocaine is metabolized by plasma cholinesterase enzyme, we evaluated this enzyme in 14 patients with cocaine-induced complications, 11 long-term cocaine users from Bolivia, 14 persons in the United States without any documented cocaine-induced complications, and 14 subjects who have not used cocaine. The enzyme was found to be significantly lower in patients with cocaine-induced complications as compared to other groups (p < 0.05). A low level of plasma cholinesterase enzyme may predict complications from cocaine use.