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Left ventricular (LV) wall thickening is the most consistent clinical marker of hypertrophic cardiomyopathy (HC), and characteristically increases substantially during adolescence. In this study, we used 2-dimensional echocardiography to develop a cross-sectional profile of LV wall thicknesses in adult patients with HC. We studied a regional community-based cohort of 239 consecutively enrolled patients (aged 18 to 91 years). On average, maximum LV wall thickness decreased relative to increasing age (p = 0.007) within 4 age groups: 22.8 +/- 5.1 mm (18 to 39 years) to 22.1 +/- 5.1 mm (40 to 59 years) to 21.1 +/- 3.7 mm (60 to 74 years) to 20.8 +/- 3.6 mm (>or=75 years). The LV thickness index (summation of wall thicknesses in all 4 segments) also decreased with age (p = 0.017): 63.0 +/- 12.2 mm to 59.8 +/- 11.9 mm to 58.3 +/- 10.4 mm to 57.9 +/- 9.8 mm. Decreasing magnitude of LV hypertrophy was independently associated with increasing age, but not with other relevant disease variables, such as symptoms and outflow obstruction. However, when separated by gender, this inverse relation between age and LV wall thickness was statistically significant only for women (p = 0.007). In conclusion, in an unselected HC cohort, cross-sectional analysis showed a modest but statistically significant inverse relation between age and LV hypertrophy that was largely gender-specific for women. This association constitutes another facet of the natural history of this complex and heterogenous disease and may reflect disproportionate occurrence of premature death in young patients with HC with marked hypertrophy or possibly gradual LV remodeling. [ABSTRACT FROM AUTHOR]

Background: Motion Picture Experts Group-2 (MPEG2) is a broadcast industry standard that allows high-level compression of echocardiographic data. Validation of MPEG2 digital images compared with super VHS videotape has not been previously reported., Methods: Simultaneous super VHS videotape and MPEG2 digital images were acquired. In all, 4 experienced echocardiographers completed detailed reporting forms evaluating chamber size, ventricular function, regional wall-motion abnormalities, and measures of valvular regurgitation and stenosis in a blinded fashion. Comparisons between the 2 interpretations were then performed and intraobserver concordance was calculated for the various categories., Results: A total of 80 paired comparisons were made. The overall concordance rate was 93.6% with most of the discrepancies being minor (4.1%). Concordance was 92.4% for left ventricle, 93.2% for right ventricle, 95.2% for regional wall-motion abnormalities, and 97.8% for valve stenosis. The mean grade of valvular regurgitation was similar for the 2 techniques., Conclusions: MPEG2 digital imaging offers excellent concordance compared with super VHS videotape.

Because pulmonary venous pressure has never been measured, it is unclear whether pulmonary wedge pressure measures left atrial pressure, as commonly assumed, or pressure more upstream in the pulmonary venous or capillary beds. Fluid-filled mean pulmonary artery and pulmonary wedge pressure were compared with pulmonary venous and left atrial pressure obtained with high-fidelity micromanometer catheters in eight lightly sedated dogs over a physiologic range of filling pressures. In all conditions, mean pulmonary wedge pressure was virtually identical (r = 0.99) to mean left atrial pressure (slope = 0.99; intercept = -0.46 mm Hg). At the same time, mean pulmonary venous pressure (17.1 +/- 6.5 mm Hg) was intermediate between mean pulmonary artery pressure (20.2 +/- 6.2 mm Hg) and mean pulmonary wedge pressure (13.3 +/- 6.2 mm Hg; P < 0.0001) or mean left atrial pressure (13.4 +/- 6.3 mm Hg; P < 0.0001). These relationships were maintained over normal and increased pressure ranges. As measured by conventional flow-directed pulmonary catheters, mean pulmonary wedge pressure accurately reflects left atrial pressure in lightly sedated, spontaneously breathing normal dogs., (Copyright 2002 Wiley-Liss, Inc.)

Background: The prognostic value of infarct size quantification by technetium 99m sestamibi single-photon emission computed tomography (SPECT) in patients with chronic coronary artery disease (CAD) has not been established. Methods And Results Between September 1994 and May 1995, 1323 patients with known or suspected CAD were referred for perfusion imaging for clinical reasons and had infarct size determined by quantitative SPECT imaging. Patients underwent exercise stress (61%), pharmacologic stress (37%), and rest imaging (3%). Patients were excluded if they had cardiomyopathy, valvular heart disease, or myocardial infarction within 3 weeks of the SPECT study. There were 1224 patients who formed the study group. Follow-up was 94% complete at a median of 1.9 +/- 0.4 years. Sixty-five percent of patients had no measurable infarct. Among the patients with measurable infarcts, the mean infarct size by sestamibi imaging was 15.0% +/- 14.5% of the left ventricle (25% of infarcts /=19% of the left ventricle). By using stepwise regression analysis, age, diabetes, and hypercholesterolemia were all clinical predictors of overall death (P <.05). For cardiac death, only age and diabetes were significant. After adjusting for these clinical variables, infarct size remained an independent predictor of overall death (P =. 001) and survival free of cardiac death (P =.0002). However, when first-pass left ventricular ejection fraction was added to the models, infarct size was no longer significant., Conclusions: Infarct size determination by SPECT (99m)Tc sestamibi can predict subsequent death in patients with chronic CAD, although ejection fraction appears to have greater prognostic value.

Objective: To derive a clinically useful, noninvasive determination of right atrial pressure. Noninvasive assessment of right ventricular systolic pressure from Doppler-derived tricuspid regurgitant velocity requires an accurate assumption of right atrial pressure., Patients and Methods: Seventy-one patients were studied in the cardiac catheterization laboratory, comparing right atrial pressure (measured at mid systole) with simultaneous 2-dimensional echocardiographic measurement of inferior vena cava diameter and Doppler recordings of hepatic vein systolic, diastolic, and atrial reversal velocities. The initial 28 patients were used to derive a clinical algorithm to predict right atrial pressure, which was tested in the subsequent 43 patients., Results: Inferior vena cava dimension correlated directly with right atrial pressure (r2=0.74; P<.001). The systolic filling fraction of the hepatic vein velocity curves correlated poorly with right atrial pressure. However, the correlation between the hepatic vein Doppler sum of systolic forward flow velocity and atrial reversal velocity and right atrial pressure was inverse (r2=0.32; P=.002). With a combination of variables from both inferior vena cava diameter and hepatic vein velocity curves, patients can be divided into those with normal right atrial pressure, mildly increased right atrial pressure, and severely increased right atrial pressure., Conclusion: The combined information from inferior vena cava diameter and hepatic vein velocity curves can be used to assess right atrial pressure.

A consecutive series of patients underwent exercise thallium imaging and coronary angiography that identified single-vessel right coronary artery disease. Redistribution in the left anterior descending territory was significantly associated with the presence of left-to-right collaterals, whereas collaterals were significantly less frequent in individuals who did not exhibit redistribution.

The present study retrospectively identified 367 patients who had restrictive physiology as defined by deceleration time < or = 130 msec; 293 were in sinus rhythm (SR) (194 men and 99 women; mean age 64 +/- 14 years) and 74 were in atrial fibrillation (AF) (51 men and 23 women; mean age 72 +/- 11 years; p < 0.001). Both groups had similar underlying diagnoses and no significant difference in Doppler indices (E wave, 96 +/- 23 vs 99 +/- 22 cm/sec in SR and AF, respectively; deceleration time, 116 +/- 12 vs 116 +/- 13 msec; and left ventricular outflow tract time velocity integral, 14.8 +/- 4.8 vs 14.5 +/- 4.4 cm). Left ventricular ejection fraction was significantly lower in SR patients (29% +/- 16% vs 39% +/- 20%; p = 0.0003). There were 120 deaths (41%) in the SR group and 35 (47%) in the AF group (median follow-up for both groups, 2.2 years). Restrictive physiology as defined by Doppler echocardiography (deceleration time < or = 130 msec) appears to predict a similar poor prognosis with AF as with SR.

Objective: To evaluate the potential utility of transthoracic two-dimensional echocardiography as an aid in the technique of transseptal catheterization., Design: We performed a prospective study of 58 patients (29 men and 29 women; mean age, 64.2 years) referred for cardiac catheterization, in whom a systematic approach was used with selective application of two-dimensional echocardiography., Material and Methods: The study group of 58 patients had the following diagnoses: mitral stenosis in 17, hypertrophic cardiomyopathy in 13, dilated cardiomyopathy in 13, aortic stenosis in 13, and prosthetic valve dysfunction and pulmonary hypertension in 1 each. With use of only fluoroscopic guidance, initial gentle pressure on the dilator alone was attempted for left atrial access. If the catheter resisted entry into the left atrium, two-dimensional echocardiography was performed to assess the catheter's position relative to the atrial septum, and adjustments were made accordingly. Transseptal puncture with a Brockenbrough needle was performed only after confirmation of the catheter position at the region of the fossa ovalis with two-dimensional echocardiography., Results: The catheterization procedure was performed without complication in all 58 patients; the mean time to catheter placement was 5.6 +/- 3.5 minutes (range, 3 to 20). Two-dimensional echocardiography was used in 33 patients (57%) when left atrial access was not obtained. On the basis of echocardiographic images, the transseptal catheter had to be repositioned in 16 of these 33 patients (48%)., Conclusion: Two-dimensional echocardiography offers value in demonstrating catheter position during transseptal catheterization and may be used in some patients to ensure transseptal puncture at the region of the fossa ovalis.

A 79-yr-old man received thrombolytic therapy for acute myocardial infarction after injection with 99mTc-sestamibi and died shortly thereafter. Postmortem in situ SPECT imaging of the heart was performed. The heart was then removed and sectioned into short-axis slices, which were placed directly on the SPECT camera face for imaging, and examined by routine gross and microscopic pathologic methods. Pathologic findings were consistent with a small acute inferoseptal myocardial infarction, as demonstrated on both SPECT imaging of the intact heart and imaging of the heart slices. This case report provides further evidence of the validity of SPECT sestamibi imaging for the determination of myocardium at risk during acute myocardial infarction.

Objectives: The aim of this study was to demonstrate the usefulness of preload alterations in assessing left ventricular filling pressures with transmitral Doppler velocity curves., Background: Doppler mitral inflow velocities, used to estimate left ventricular filling pressures noninvasively, are limited in predicting left ventricular filling pressures, especially in patients with normal systolic function and a "pseudonormal" mitral filling pattern., Methods: Forty-nine patients were studied in the cardiac catheterization laboratory with simultaneous Doppler echocardiography using high fidelity catheters to compare left ventricular diastolic filling pressures (pre-A wave left ventricular pressure) and Doppler mitral inflow at baseline and during reduction of preload during the strain phase of the Valsalva maneuver (n = 27) or sublingual nitroglycerin (n = 36), or both (n = 14). Doppler measurements consisted of E (initial peak velocity), A (velocity at atrial contraction), deceleration time (time from E velocity to deceleration of flow extrapolated to baseline) and absolute A wave velocity (A' [peak A wave velocity minus velocity at onset of atrial contraction])., Results: In patients with high pre-A wave pressure (> or 15 mm Hg), there was a greater change in the E/A' ratio during the Valsalva maneuver than in patients with a normal pre-A wave pressure (-1.22 +/- 1.1 vs. -0.35 +/- 0.17; p = 0.02). A similar change was seen when comparing the change in the E/A' ratio after administration of nitroglycerin in patients with a high versus a normal pre-A wave pressure (0.81 +/- 0.49 vs. 0.18 +/- 0.17; p < 0.001). These differences were present in patients with a normal E/A ratio at baseline., Conclusions: Alterations in preload during assessment of Doppler echocardiographic indexes may be useful in noninvasively assessing left ventricular filling pressures.

Implantation of a permanent pacemaker is an accepted mode of therapy for symptomatic bradyarrhythmias. Application of pacemaker technology for the treatment of cardiomyopathies has generated considerable interest and enthusiastic support in recent years. In both hypertrophic cardiomyopathy and dilated cardiomyopathy, dual-chamber pacing has been shown to decrease symptoms and improve hemodynamics; however, not all patients will benefit from dual-chamber pacing. Technical considerations must be acknowledged in order to obtain optimal benefit with dual-chamber pacing. In addition, other more accepted therapies are available for patients with symptomatic cardiomyopathies. The purposes of this article are to review critically the current literature on the use of dual-chamber pacemakers in patients with either hypertrophic or dilated cardiomyopathy and to provide a clinical perspective based on current knowledge.

This report describes two patients who were treated for obstruction of St. Jude tricuspid valve prostheses. In the patient with the hypereosinophilic syndrome, right heart failure developed 15 days after valve replacement. The other patient had symptoms of right heart failure for 8 weeks; these occurred 15 months after valve implantation. In both patients, thrombolytic therapy was successful and without major sequelae. Herein we review the literature on the use of thrombolysis for obstructed mechanical prosthetic valves and completely summarize the English literature; the efficacy of thrombolysis for obstructed prosthetic valves and the associated morbidity and mortality are emphasized. Recommendations for thrombolysis in clinical practice are provided.

Background: Conventional cardiac catheterization criteria for the diagnosis of constrictive pericarditis (CP) rely on equalization of intracardiac pressures and have many recognized limitations. Recently, Doppler echocardiographic methods have been used to examine dynamic respiratory changes of increased ventricular interdependence and dissociation of intrathoracic and intracardiac pressures for the diagnosis of CP. These pathophysiological features may be best delineated by cardiac catheterization. Therefore, we studied the accuracy of these dynamic respiratory changes in left ventricular and right ventricular pressure for the diagnosis of CP at cardiac catheterization., Methods and Results: High-fidelity manometric catheters and respirometry were used to study 36 patients: 15 patients with surgically proven CP (group 1) and 21 patients with other causes of heart failure (group 2). Conventional cardiac catheterization variables used to establish the diagnosis of CP lacked sensitivity and specificity and failed to distinguish between these groups. However, the finding of discordance between right ventricular and left ventricular pressures during inspiration, a sign of increased ventricular interdependence, accurately distinguished patients in group 1 from those in group 2 (P < .05)., Conclusions: Examination of dynamic respiratory changes indicating increased ventricular interdependence may be helpful in the diagnosis of CP in the cardiac catheterization laboratory.

1. The purpose of this study was to elucidate the cellular mechanism of the positive inotropic effect of hydralazine, a vasodilator widely used for afterload reduction in patients with heart failure that has also been reported to have positive inotropic effects on the heart. After isolation, right ventricular papillary muscles from the ferret were maintained in bicarbonate-buffered salt solution (30 degrees C). A concentration-response relationship was obtained for hydralazine (10(-6) to 10(-3) M). In order to mimic different levels of catecholamine release found in heart failure, we utilized two methods of stimulation: (a) threshold punctate pulses and (b) suprathreshold punctate stimulation with voltage approximately 10% above threshold. 2. In a first group of muscles (n = 16), a maximally effective concentration of hydralazine (10(-3) M) increased peak isometric tension by 39 +/- 9% (P < 0.05). Doses lower than 10(-5) M had no significant effect. The bioluminescent Ca2+ indicator, aequorin, was loaded into a subset of these muscles (n = 7). A significant increase in peak light (i.e., intracellular Ca2+) developed, concurrently with an increase in peak tension (38 +/- 5% to 66 +/- 8%). This inotropic response was associated with a decrease in time to peak tension (ms), 221 +/- 7 to 186 +/- 5 (P < 0.05), and time to peak light, 65 +/- 4 to 52 +/- 2 (P < 0.05). These effects were markedly attenuated by pretreatment with autonomic blocking agents. 3. In a second group of muscles (n = 12), histamine was used to stimulate cyclic AMP production in the presence of propranolol. Hydralazine (3 x 10-4 M) led to a shift in the pD2 (i.e. the negative log of the concentration of histamine producing 50% of the maximal response) from 6.1 +/- 0.1 to 5.9 +/- 0.1(P <0.05), thus increasing the sensitivity of the muscles to histamine. Hydralazine also increased maximum tension from 160 +/- 77% to 195 +/- 57% (P <0.05) above baseline. Thus, hydralazine altered the potency and efficacy of histamine despite the presence of beta-adrenoceptor blockade.4. A third group of muscles were chemically skinned to examine the effects of hydralazine on myofilament Ca2+ responsiveness. Pretreatment of ferret papillary muscles with hydralazine (10-3 M)before skinning did not shift the force-pCa curve after skinning (n = 16). However, hydralazine added to previously skinned fibres desensitized the myofilaments, as indicated by a rightward shift of the force-pCa curve (n = 12). Maximum tension development was not changed.5. The pharmacological effects of hydralazine are characteristic of inotropic drugs that act mainly via cyclic AMP; however, the increase in peak tension demonstrated with histamine in the presence of hydralazine also suggests an effect on cyclic AMP-independent second messenger pathways. These data are consistent with reports that large doses of hydralazine may increase cellular levels of cyclic AMP, as well as other second messengers, by direct cardiac and indirect neuronal mechanisms.

Obesity is associated with insulin resistance and type II diabetes mellitus. In the present study, we have characterized hepatic insulin receptor function in two animal models of obesity: the Zucker fatty rat (ZFR), a model of genetic obesity with severe hyperinsulinemia, and the Sprague-Dawley rat with dietary obesity, a model of acquired obesity. Zucker fatty rats were also treated with streptozotocin (STZ) in an effort to examine the effects of relative insulin deficiency and hyperglycemia in the setting of obesity. Using wheat germ agglutinin-purified insulin receptor extracted from liver, no significant difference in insulin binding was identified in either model of obesity. beta-Subunit autophosphorylation was significantly decreased in both obese models relative to that in controls (72% in the obese ZFR and 49% in the overfed Sprague-Dawley model). Kinase activity, as measured by phosphorylation of the 1142-1153 synthetic peptide, was also decreased in both models of obesity by 22% and 64%, respectively. In the Zucker rat, STZ treatment led to an 80% increase in receptor concentration and a further 70% increase in beta-subunit autophosphorylation per receptor, whereas tyrosine kinase activity toward substrate was not altered. Since kinase activity is closely linked to autophosphorylation, we determined the fraction of autophosphorylated (activated) receptors vs. non-phosphorylated (inactive) receptors by using antiphosphotyrosine antibody to precipitate receptors bound with [125I]insulin. There was no significant difference in the percentage of activated insulin receptors in the dietary obese, ZFR, or STZ-treated Zucker rat vs. that in the controls. In all models, the percentage of activated receptors ranged from 32-46% of the total receptor pool. These data suggest that in genetic and acquired obesity, autophosphorylation of the beta-subunit is reduced and is a limiting factor in insulin receptor activation. A similar fraction of all receptors appears to undergo some level of autophosphorylation; however, full autophosphorylation and, thus, activation of the receptor do not occur, and this results in a decrease in kinase activity. This block in autophosphorylation may account for significant reductions in insulin receptor kinase function in obesity.