Kyle W. Klarich

Association of cholesterol levels, hydroxymethylglutaryl coenzyme-A reductase inhibitor treatment, and progression of aortic stenosis in the community.

OBJECTIVES This study was designed to analyze the association among cholesterol levels, lipid-lowering treatment, and progression of aortic stenosis (AS) in the community. BACKGROUND Aortic stenosis is a progressive disease for which there is no known medical treatment to prevent or slow progression. Despite plausible pathologic mechanisms linking hypercholesterolemia to AS progression, clinical studies have been inconsistent and affected by referral bias, and the role of lipid-lowering therapy is uncertain. METHODS We determined the association between blood cholesterol levels and progression of native AS (assessed by Doppler echocardiography at baseline and at least six months later; mean interval, 3.7 +/- 2.3 years) in a community-based study of 156 patients (age 77 +/- 12 years; 90 men). Thirty-eight patients received statin treatment during follow-up. RESULTS In untreated subjects, mean gradient increased from 22 +/- 12 mm Hg to 39 +/- 19 mm Hg, and aortic valve area (AVA) decreased from 1.20 +/- 0.35 cm(2) to 0.91 +/- 0.33 cm(2) (both p < 0.001). The annualized change in AVA was -0.09 +/- 0.17 cm(2)/year (-7% +/- 13%/year). Neither total cholesterol (r = -0.01, p = 0.92) nor low-density lipoprotein cholesterol (r = 0.01; p = 0.88) showed a significant correlation to AS progression. Nevertheless, progression of AS was slower in patients receiving statins compared with untreated patients (decrease in AVA -3 +/- 10% vs. -7 +/- 13% per year, respectively; p = 0.04), even when adjusted for age, gender, cholesterol, and baseline valve area (p = 0.04). The association of statin treatment with slower progression was confirmed when analysis was restricted to patients coming for a systematic follow-up (p=0.02). The odds ratio of AS progression with statin treatment was 0.46 (95% confidence interval, 0.21 to 0.96). CONCLUSIONS In the community, progression of AS shows no trend of association with cholesterol levels. Statin treatment, however, is associated with slower progression, suggesting that the effects of statin treatment on progression of AS should be pursued with appropriate clinical trials.

Papillary Fibroelastoma: Echocardiographic Characteristics for Diagnosis and Pathologic Correlation

OBJECTIVES We sought to determine the clinical and echocardiographic characteristics of papillary fibroelastoma (PFE). BACKGROUND PFE is a rarely encountered cardiac tumor about which relatively little is known. METHODS Institutional records were reviewed for the years 1980 to 1995 for patients with pathologic or echocardiographic diagnosis of PFE. Group 1 included 17 patients with the pathologic diagnosis of PFE who also underwent echocardiography. Echocardiographic features of PFE were established in group 1. Group 2 included 37 patients with only echocardiographic evidence of PFE. RESULTS In group 1, 7 (41.2%) of 17 patients had symptoms related to PFE. Neurologic events occurred in 5 (29.4%) of 17 patients. All patients had the tumor surgically removed. During follow-up, no new embolic events occurred. Echocardiographic characteristics of PFE included a small tumor (12.1 +/- 6.5 x 9.0 +/- 4.3 mm), usually pedunculated (14 [94%] of 17 patients) and mobile, with a homogeneous speckled pattern and a characteristic stippling along the edges. PFEs were most common on valvular surfaces (12 [60%] of 20 PFEs) but were not uncommon on other endocardial surfaces (8 [40%] of 20 PFEs). The tumor did not cause valvular dysfunction. In group 2, 16 (43%) of 37 patients were asymptomatic. Five patients (13.5%) had a previous neurologic event. During follow-up (mean 31 months, range 1 to 77), nine neurologic events occurred. CONCLUSIONS PFEs are associated with embolism, can be diagnosed with echocardiography, are often an incidental clinical finding and do not cause valvular dysfunction.

Assessment of Right Atrial Pressure With 2-Dimensional and Doppler Echocardiography: A Simultaneous Catheterization and Echocardiographic Study

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.

Prognostic value of exercise echocardiography in 2,632 patients ≥65 years of age

Abstract OBJECTIVES We sought to determine the prognostic value of exercise echocardiography in the elderly. BACKGROUND Limited data exist regarding the prognostic value of exercise testing in the elderly, a population which may be less able to exercise and is at increased risk of cardiac death. METHODS Follow-up (2.9 ± 1.7 years) was obtained in 2,632 patients ≥65 years who underwent exercise echocardiography. RESULTS There were 1,488 (56%) men and 1,144 (44%) women (age 72 ± 5 years). The rest ejection fraction was 56 ± 9%. Rest wall motion abnormalities were present in 935 patients (36%). The mean work load was 7.7 ± 2.3 metabolic equivalents (METs) for men and 6.5 ± 1.9 METs for women. New or worsening wall motion abnormalities developed with stress in 1,082 patients (41%). Cardiac events included cardiac death in 68 patients and nonfatal myocardial infarction in 80 patients. The addition of the exercise electrocardiogram to the clinical and rest echocardiographic model provided incremental information in predicting both cardiac events (chi-square = 77 to chi-square = 86, p = 0.003) and cardiac death (chi-square = 71 to chi-square = 86, p CONCLUSIONS Exercise echocardiography provides incremental prognostic information in patients ≥65 years of age. The best model included clinical, exercise testing and exercise echocardiographic variables.

Premature ventricular contraction-induced cardiomyopathy: a treatable condition.

Premature ventricular contractions (PVCs) are early depolarizations of the myocardium originating in the ventricle. They are often seen in association with structural heart disease and represent increased risk of sudden death,1 yet they are ubiquitous, even in the absence of identifiable heart disease.1,2 They may cause troubling and sometimes incapacitating symptoms such as palpitations, chest pain, presyncope, syncope, and heart failure.3 Traditionally, they have been thought to be relatively benign in the absence of structural heart disease.4,5 Over the last decade, however, PVC-induced cardiomyopathy has been a subject of great interest and the evidence for this entity is rapidly emerging. ### Epidemiology PVCs are common with an estimated prevalence of 1% to 4% in the general population.5 In a normal healthy population, PVCs have been detected in 1% of subjects on standard 12-lead electrocardiography and between 40% and 75% of subjects on 24- to 48-hour Holter monitoring.6 Their prevalence is generally age-dependent,1 ranging from 75 years.8 Commonly thought to be a benign entity,4,5 the concept of PVC-induced cardiomyopathy was proposed by Duffee et al9 in 1998 when pharmacological suppression of PVCs in patients with presumed idiopathic dilated cardiomyopathy subsequently improved left ventricular (LV) systolic dysfunction. Many of these patients often have no underlying structural heart disease and subsequently develop LV dysfunction and dilated cardiomyopathy; in cases of those with an already impaired LV function from underlying structural heart disease, worsening of LV function may occur.10,11 The exact prevalence of PVC-induced cardiomyopathy is not known; it is an underappreciated cause of LV dysfunction, and it is primarily observed in older patients.12 This observation could be due to the fact that the prevalence of …

Intracardiac thrombosis and anticoagulation therapy in cardiac amyloidosis.

Background— Primary amyloidosis has a poor prognosis as a result of frequent cardiac involvement. We recently reported a high prevalence of intracardiac thrombus in cardiac amyloid patients at autopsy. However, neither the prevalence nor the effect of anticoagulation on intracardiac thrombus has been evaluated antemortem. Methods and Results— We studied all transthoracic and transesophageal echocardiograms of cardiac amyloid patients at the Mayo Clinic. The prevalence of intracardiac thrombosis, clinical and transthoracic/transesophageal echocardiographic risks for intracardiac thrombosis, and effect of anticoagulation were investigated. We identified 156 patients with cardiac amyloidosis who underwent transesophageal echocardiograms. Amyloidosis was the primary type (AL) in 80; other types occurred in 76 patients, including 56 with the wild transthyretin type, 17 with the mutant transthyretin type, and 3 with the secondary type. Fifth-eight intracardiac thrombi were identified in 42 patients (27%). AL amyloid had more frequent intracardiac thrombus than the other types (35% versus 18%; P=0.02), although the AL patients were younger and had less atrial fibrillation. Multivariate analysis showed that atrial fibrillation, poor left ventricular diastolic function, and lower left atrial appendage emptying velocity were independently associated with increased risk for intracardiac thrombosis, whereas anticoagulation was associated with a significantly decreased risk (odds ratio, 0.09; 95% CI, 0.01 to 0.51; P<0.006). Conclusions— Intracardiac thrombosis occurs frequently in cardiac amyloid patients, especially in the AL type and in those with atrial fibrillation. Risk for thrombosis increased if left ventricular diastolic dysfunction and atrial mechanical dysfunction were present. Anticoagulation therapy appears protective. Timely screening in high-risk patients may allow early detection of intracardiac thrombus. Anticoagulation should be carefully considered.

Intracardiac Thrombosis and Embolism in Patients With Cardiac Amyloidosis

Background— Patients with primary amyloidosis (AL type) have a poor prognosis, in part due to frequent cardiac involvement. Although intracardiac thrombus has been reported in anecdotal cases, neither its frequency nor its role in causing mortality is known. Furthermore, the clinical and echocardiographic variables that may be associated with thromboembolism in cardiac amyloidosis have not been defined. Methods and Results— A total of 116 autopsy or explanted cases of cardiac amyloidosis (55 AL and 61 other type) were identified in the Mayo Clinic. Forty-six fatal nonamyloid trauma cases served as controls. Each heart was examined for intracardiac thrombus. The cause of death was determined from autopsy and clinical notes. Intracardiac thrombosis was identified in 38 hearts (33%). Twenty-three had 1 thrombus, whereas 15 had 2 to 5 thrombi. Although subjects in the AL group were younger and had less atrial fibrillation than those with other types of amyloidosis, the AL group had significantly more intracardiac thrombus (51% versus 16%, P<0.001) and more fatal embolic events (26% versus 8%, P<0.03). Control hearts had no intracardiac thrombus. The presence of both atrial fibrillation and AL was associated with an extremely high risk for thromboembolism (odds ratio 55.0 [95% confidence interval 8.1 to 1131.4]). By multivariate analysis, AL type (odds ratio 8.4 [95% confidence interval 1.8 to 51.2]) and left ventricular diastolic dysfunction (odds ratio 12.2 [95% confidence interval 2.7 to 72.7]) were independently associated with thromboembolism. Conclusions— A high frequency of intracardiac thrombosis was present in cardiac amyloidosis. Furthermore, thromboembolism caused significant fatality. Several risk factors for thromboembolism were identified. Early screening, especially in high-risk patients, and early anticoagulation might reduce morbidity and mortality.

Usefulness of harmonic imaging for left ventricular opacification and endocardial border delineation by optison.

Harmonic and fundamental imaging techniques were directly compared in 20 patients undergoing intravenous contrast echocardiography for enhancement of left ventricular endocardial border definition. Harmonic imaging demonstrated significantly enhanced left ventricular endocardial border detection and improved the duration and intensity of a contrast effect despite a reduced dosing requirement.

A contemporary case series of lupus myocarditis

Objectives: The purpose of this study was to describe clinical phenotype and treatment outcomes in lupus myocarditis (LM), an uncommon but serious manifestation of systemic lupus erythematosus (SLE). Methods: The study involved a 10-year retrospective case series of hospitalized patients with LM, with a search of a diagnosis database using systemic lupus erythematosus and either myocarditis, cardiomyopathy, or congestive heart failure, and of a pathology database for biopsy-proved LM. Results: Twenty-four patients met the study criteria, with 79% female and 82% white (age: mean (SD), 47.6 (20.4) years; follow-up: mean (SD), 9.2 (6.1) months). The frequency of antibodies SS-A (69%) and anti-RNP (62%) was greater than in published lupus populations (25%–40%). On echocardiography, the mean initial left ventricular ejection fraction was 33.8%, improving to 49.5% after a mean of 7.2 months. All patients received immunosuppression, most with high-dose corticosteroid treatment and subsequent corticosteroid taper. One patient died of cardiogenic shock during hospitalization; two patients died within one year posthospitalization. Conclusions: A high index of suspicion is necessary in suspected LM. Higher frequency of elevated SS-A and anti-RNP antibody levels in our series than in the literature is suggestive of an LM association. Echocardiography is a useful initial investigation for LM, but patients should be referred early for cardiac magnetic resonance imaging or endomyocardial biopsy to confirm diagnosis if it is clinically indicated in difficult cases.

Variability Between Methods of Calculating Mitral Valve Area: Simultaneous Doppler Echocardiographic and Cardiac Catheterization Studies Conducted Before and After Percutaneous Mitral Valvuloplasty

The purpose of this study was to assess the variability of measuring the mitral valve area (MVA) by the cardiac catheterization (Gorlin) method and two Doppler echocardiographic methods, the pressure half-time and continuity equation methods. The determinants of MVA were measured simultaneously before and after percutaneous mitral balloon valvuloplasty (PBMV). Thirty-three patients with severe mitral stenosis underwent simultaneous measurements of MVA by the three methods immediately before and within 15 minutes after PBMV. After combining all data, the correlation between the catheterization and pressure half-time methods was significant (r = 0.65; p < 0.001), as was that between the catheterization and continuity equation methods (r = 0.64; p < 0.001). However, there was a large degree of variability among the measurements with the three techniques. The mean difference between the catheterization and pressure half-time methods of measuring MVA before PBMV was -0.2 +/- 0.4 cm2 and 0.1 +/- 0.3 cm2 between the catheterization and continuity equation methods. This variability was even more marked after PBMV: -0.5 +/- 0.9 cm2 between the catheterization and pressure half-time methods and 0.4 +/- 0.6 cm2 between the catheterization and continuity equation methods. Although previous studies have shown a good correlation between MVA as measured with the catheterization and two Doppler echocardiographic methods, they included a wide range of MVAs. In our study of patients with hemodynamically significant mitral stenosis, there was a large degree of variability between the catheterization and simultaneously performed Doppler echocardiographic methods. The calculated MVA by any method should not be used as the single measure of severity of stenosis.