Mechanical properties of myxomatous mitral valves.

OBJECTIVE: We sought to characterize the mechanical properties of normal and myxomatous mitral valve tissues. METHODS: We tested 113 mitral valve sections from patients undergoing mitral valve repair or replacement for myxomatous mitral valve prolapse and sections from 33 normal valves obtained at autopsy. RESULTS: Myxomatous mitral valve leaflets were more extensible than normal leaflets when tested parallel to the free edge (41.2% +/- 18.5% vs 17.3% +/- 6.7% circumferential strain [mean +/- SD]; P <.001), as well as perpendicular to the free edge (43.2% +/- 19.4% vs 17.3% +/- 6.7% radial strain; P <.001). Myxoid leaflets were less stiff circumferentially (4.0 +/- 1.6 vs 6.1 +/- 1.4 kN/m; P <.001) and radially (4.5 +/- 1.1 vs 6.1 +/- 1.4 kN/m; P <.001) than normal leaflets. Leaflet strength, however, was similar in both groups. CONCLUSIONS: Myxomatous mitral valve leaflets are physically and mechanically different from normal mitral valve leaflets. They are more extensible and less stiff. Compared with chordae examined previously, however, they are affected much less. Myxomatous mitral valve disease may therefore affect the collagen in the chordae more severely than that in the leaflets.

Current medical management of valvular heart disease.

Drug therapy plays a key role in the management of valvular heart disease, though in many cases it does not alter its course or delay the need for surgery. The importance of drug therapy lies in stabilizing the patient's condition when the disease is due to abnormal valve structure, and in treating the underlying condition when the condition is due to a functional abnormality. Drug therapy also lowers the risk of bacterial endocarditis and rheumatic fever.

Effect of hydroxymethylglutaryl coenzyme a reductase inhibitors on the progression of calcific aortic stenosis.

BACKGROUND: Recent studies have supported the hypothesis that calcific aortic stenosis is the product of an active inflammatory process, with similarities to atherosclerosis. We sought to determine whether therapy with hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) might slow the progression of aortic stenosis. METHODS AND RESULTS: A retrospective study of 174 patients (mean age 68+/-12 years) with mild to moderate calcific aortic stenosis was conducted. Patients required normal left ventricular function, /=2 echocardiograms performed at least 12 months apart. Fifty-seven patients (33%) received treatment with a statin; the remaining 117 (67%) did not. The statin group was older and had a higher prevalence of hypertension, diabetes mellitus, and coronary disease. During a mean follow-up of 21 months, patients treated with statin had a smaller increase in peak and mean gradient and a smaller decrease in aortic valve area. When annualized, the decrease in aortic valve area for the nonstatin group was 0.11+/-0.18 cm(2) compared with 0.06+/-0.16 cm(2) for those treated with a statin (P=0.03). In multivariate analysis, statin usage was a significant independent predictor of a smaller decrease in valve area (P=0.01) and a lesser increase in peak gradient (P=0.02). CONCLUSIONS: Statin-treated patients, despite a higher risk profile for progression, had reduced aortic stenosis progression compared with those not treated with a statin. These data provide justification for a prospective randomized trial to substantiate whether statin therapy slows the progression of aortic stenosis.

Clinical and echocardiographic characteristics of papillary fibroelastomas: a retrospective and prospective study in 162 patients.

BACKGROUND: Cardiac papillary fibroelastoma (CPF) is a primary cardiac neoplasm that is increasingly detected by echocardiography. The clinical manifestations of this entity are not well described. METHODS AND RESULTS: In a 16-year period, we identified patients with CPF from our pathology and echocardiography databases. A total of 162 patients had pathologically confirmed CPF. Echocardiography was performed in 141 patients with 158 CPFs, and 48 patients had CPFs that were not visible by echocardiography (<0.2 cm), leaving an echocardiographic subgroup of 93 patients with 110 CPFs. An additional 45 patients with a presumed diagnosis of CPF were identified. The mean age of the patients was 60+/-16 years of age, and 46.1% were male. Echocardiographically, the mean size of the CPFs was 9+/-4.6 mm; 82.7% occurred on valves (aortic more than mitral), 43.6% were mobile, and 91.4% were single. During a follow-up period of 11+/-22 months, 23 of 26 patients with a prospective diagnosis of CPF that was confirmed by pathological examination had symptoms that could be attributable to embolization. In the group of 45 patients with a presumed diagnosis of CPF, 3 patients had symptoms that were likely due to embolization (incidence, 6.6%) during a follow-up period of 552+/-706 days. CONCLUSIONS: CPFs are generally small and single, occur most often on valvular surfaces, and may be mobile, resulting in embolization. Because of the potential for embolic events, symptomatic patients, patients undergoing cardiac surgery for other lesions, and those with highly mobile and large CPFs should be considered for surgical excision.

Myxomatous mitral valve chordae. I: Mechanical properties.

BACKGROUND AND AIM OF THE STUDY: Chordal rupture is the most common reason for severe mitral regurgitation requiring surgery. The features that predispose myxomatous chordae to rupture, however, have not been studied. Thus, the physical and mechanical properties of normal and myxomatous mitral valve chordae were measured. METHODS: Chordae from 24 normal and 59 myxomatous mitral valves were cut into 10 mm-long segments and mechanically tested to measure extensibility, modulus, failure stress, failure strain, and failure load. After testing, the specimens were weighed and their cross-sectional area and volume measured. RESULTS: Chordae from myxoid mitral valves were larger (1.9 +/- 0.1 mm2 versus 0.8 +/- 0.1 mm2, p < or = 0.001) and heavier (16.6 +/- 1.0 mg versus 6.5 +/- 0.4 mg, p < or = 0.001) than normal chordae. Myxoid chordae had significantly lower moduli (40.4 +/- 10.2 MPa versus 132 +/- 15 MPa, p < or = 0.001) and failed at significantly lower tensile stress (6.0 +/- 0.6 MPa versus 25.7 +/- 1.8 MPa, p < or = 0.001) and absolute load (728 +/- 50 g versus 1,450 +/- 135 g, p < or = 0.001) than normal chordae. Normal and myxoid chordae had similar measurements of extensibility and failure strain. CONCLUSION: Myxomatous degeneration severely affects the mechanical properties of mitral valve chordae. Most notably, myxoid chordae failed at loads one-half of those of normal chordae. This may explain why chordal rupture is the main indication for repair of myxoid mitral valves. These findings also suggest that chordal preservation should be carried out with caution, as myxoid chordae are clearly abnormal with compromised mechanical strength.

Myxomatous mitral valve chordae. II: Selective elevation of glycosaminoglycan content.

BACKGROUND AND AIM OF THE STUDY: Chordal rupture in myxomatous mitral valves is the leading cause of leaflet prolapse and regurgitation. Increased glycosaminoglycan (GAG) content has been reported in these valves. Therefore, the biochemical differences between myxomatous and control mitral valve chordae were investigated. METHODS: The contents of hexuronic acid, DNA, water, and collagen in chordae from 45 myxomatous valves and 10 control valves were measured. Collagen and hexuronic acid quantities were normalized to wet and dry weights, and to DNA content. Different GAG classes were measured using fluorophore-assisted carbohydrate electrophoresis (FACE). RESULTS: Myxomatous chordae contained significantly more GAGs than controls after quantities were normalized for wet weight, dry weight, and DNA content. The FACE assay showed that the myxomatous chordae contained significantly more chondroitin/dermatan 6-sulfate when normalized to both wet and dry weight, and slightly more hyaluronan. In contrast to leaflets, which contain predominantly hyaluronan, the predominant GAG class in chordae was chondroitin/dermatan sulfate. Keratan sulfate, a GAG class previously unreported in valve tissues, was also discovered in the chordae. Myxomatous chordae contained more water and less collagen than control chordae, but equal quantities of DNA when normalized for wet weight. CONCLUSION: Cells in the chordae of myxomatous valves may produce more GAGs than cells in the chordae of control valves. The resulting accumulation of GAGs and bound water likely gives myxomatous valves their characteristic thickening and floppy, gelatinous nature, and may account for their reported mechanical weaknesses.

Calculation of mitral regurgitant orifice area with use of a simplified proximal convergence method: initial clinical application.

To validate a previously proposed simplified proximal flow convergence method for calculating mitral regurgitant orifice area (ROA), a prospective study was conducted in ambulatory patients and in patients undergoing open heart surgery. Assuming a pressure difference between the left ventricle and left atrium of approximately 100 mm Hg (jet velocity [v(p)] 500 cm/s) and setting the color aliasing velocity (v(a)) to 40 cm/s, we simplified the conventional proximal convergence method formula (ROA = 2pi(r2)v(a)/v(p)) to r2/2, where r is the radius of the proximal convergence isovelocity hemisphere. For 57 ambulatory patients with a wide range of mitral regurgitant severity (1 to 4+), ROA was calculated by the conventional (x) and simplified (y) methods, demonstrating excellent accuracy (r = 0.92; P <.001; DeltaROA [y - x] = 0.004 +/- 0.08 cm2). For 24 intraoperative patients, ROA calculated by the simplified formula (y) correlated well with the pulsed Doppler-thermodilution method (x) (r = 0.84; P <.01; DeltaROA [y - x] = -0.002 +/- 0.08cm2). This simplified proximal convergence formula yields an accurate assessment of ROA for a wide range of regurgitant severity, while the time required for this measurement is shortened by half (1.5 +/- 0.5 minutes versus 3.2 +/- 0.7 minutes). This may increase the frequency of calculating ROA in the clinical laboratory.

Localization of needle tip with color doppler during pericardiocentesis: In vitro validation and initial clinical application.

This study evaluates a new device that uses color Doppler ultrasonography to enable real-time image guidance of the aspirating needle, which has not been possible until now. The ColorMark device (EchoCath Inc, Princeton, NJ) induces high-frequency, low-amplitude vibrations in the needle to enable localization with color Doppler. We studied this technique in 25 consecutive patients undergoing pericardiocentesis, and in vitro, in a urethane phantom with which the accuracy of color Doppler localization of the needle tip was compared with that obtained by direct measurement. Tip localization was excellent in vitro; errors axial to the ultrasound beam (velocity Doppler -0.13 +/- 0.90 mm, power Doppler -0.05 +/- 1.7 mm) were less than lateral errors (velocity -0.36 +/- 1.8 mm, power -0.02 +/- 2.8 mm). In 18 of 25 patients, the needle was identified and guided into the pericardial space with the ColorMark technique, and it allowed successful, uncomplicated drainage of fluid. Initial failures were the result of incorrect settings on the echocardiographic machine and inappropriate combinations of the needle puncture site and imaging window. This study demonstrates a novel color Doppler technique that is highly accurate at localizing a needle tip. The technique is feasible for guiding pericardiocentesis. Further clinical validation of this technique is required.

Comparison of cardiovascular risk and lipid profiles in patients undergoing aortic valve surgery versus those undergoing coronary artery bypass grafting.

BACKGROUND AND AIM OF THE STUDY: Hyperlipidemia is a risk factor for the progression of coronary artery disease, and possibly also valvular aortic stenosis. Thus, patients with aortic stenosis, coronary disease (or both) might be expected to have more abnormal lipid profiles than those without these two conditions. METHODS: The lipid profiles of patient subsets undergoing aortic valve replacement (AVR) with or without concomitant coronary artery bypass grafting (CABG), as well as those undergoing isolated CABG, between 1987 and 1997 were analyzed retrospectively. Four surgical groups were identified: AVR for aortic regurgitation (n = 370); AVR for predominant aortic stenosis (n = 1,072); AVR for aortic stenosis (AS) with CABG (n = 914); and isolated CABG (n = 11,156). The complete fasting lipid profiles of patients were collected, analyzed by group, and compared. RESULTS: Analysis by Spearman's correlation showed that total cholesterol levels, triglycerides and low-density lipoproteins (LDL-C) were modestly, yet significantly, increased in each successive group, while high-density lipoproteins were decreased. AS patients undergoing isolated AVR had significantly higher total cholesterol (215 versus 201 mg/dl; p <0.0001), triglycerides (125 versus 104 mg/dl; p <0.0001) and LDL-C (139 versus 132 mg/dl; p = 0.003) than those undergoing AVR for aortic regurgitation. Total cholesterol >200 mg/dl was significantly associated with AS, even after adjusting for differences in age, sex, diabetes mellitus and hypertension, with an odds ratio of 1.5 (95% confidence interval, 1.2-2.0; p = 0.001). CONCLUSION: Progressively abnormal lipid profiles are associated with AS and coronary disease in patients undergoing AVR. This evidence helps to extend the link between dyslipidemia and AS in a large consecutive series of patients.

Case report: outer sheath rupture may precede complete chordal rupture in fibrotic mitral valve disease.

Rupture mechanics of mitral valve chordae have been difficult to elucidate because most surgical repairs and pathological examinations are performed after the rupture. In an excised anterior leaflet from a fibrotic mitral valve, chordae were observed in an initial phase of rupture. Microscopic sections showed that thinned, nearly ruptured chordal segments were actually chordal cores, containing highly aligned collagen fibers. The outer sheath of elastic fibers, disorganized circumferentially oriented collagen fibers, and endothelial cells that normally surrounds the collagen core apparently had retracted to the extreme ends of the thinned segment, resulting in a bulbous shape, as noted in the chordal rupture literature. In conclusion, these new observations lead us to propose that the rupture of mitral valve chordae is not spontaneous, but may occur over time. The failure of the outer sheath may represent the first phase in a slow, two-part process leading to eventual chordal rupture.

Comparison of quantitative and semiquantitative methods for assessing mitral regurgitation by transesophageal echocardiography.

Semiquantitative grading of mitral regurgitation (MR) by transesophageal echocardiography (TEE) is widely used for clinical decision making. However, the relation between semiquantitative grading by biplane or multiplane TEE and quantitative measures remains undetermined. Biplane or multiplane TEE was performed in 113 patients in the operating room. MR severity was graded from 1 to 4+ by Doppler color flow mapping. MR was quantified using the thermodilution-Doppler method as mitral regurgitant stroke volume (RSV) derived from the difference between total mitral inflow measured by pulsed Doppler and forward flow measured by thermodilution. Mitral regurgitant orifice area (ROA) was calculated by RSV divided by mitral regurgitant velocity. RSV and ROA were also calculated using the proximal isovelocity surface area method. RSV and ROA significantly correlated with the semiquantitative grading either by TEE or angiogram in a nonlinear fashion, with the best fit being given by an exponential model with correlation coefficients from 0.73 to 0.87 (p <0.001). Substantially increased RSV and ROA were observed in MR grades of > or =3+. In the same grades of 3+ or 4+ MR, the largest RSV was 4 times larger than the smallest (190 to 220 vs 44 to 45 ml), and the largest ROA (1.82 to 2.0 vs 0.26 to 0.27 cm2) was sixfold larger than the smallest. Patients with 2 to 3+ MR had significantly variable RSV and ROA (range 21 to 91 ml and 0.12 to 0.65 cm2, respectively). Color flow mapping by biplane or multiplane TEE or angiography is able to categorize precisely mild (< or =2+) and severe (> or =3+) MR, but cannot accurately determine actual hemodynamic load of MR in more severe degrees of MR.

Echocardiographic assessment of the mechanisms of correction of bileaflet prolapse causing mitral regurgitation with only posterior leaflet repair surgery.

Recent data suggest that posterior leaflet repair alone corrects mitral regurgitation in patients with bileaflet prolapse and normal anterior chordae. The purpose of this study was to use echocardiography to define the anatomic differences between posterior and bileaflet prolapse and to determine if posterior leaflet repair alone leads to correction of bileaflet prolapse. We studied patients who underwent quadrangular resection of the posterior mitral valve leaflet to treat bileaflet prolapse (group I, n = 20) or isolated posterior leaflet prolapse (group II, n = 20). Echocardiographic characteristics were compared before and after the procedure. There were no differences in the left ventricular end-diastolic or end-systolic dimensions or function between the 2 groups. However, anterior leaflet length was greater in patients with bileaflet prolapse (3.3 +/- 0.6 cm vs 2.6 +/- 0.4 cm, p = 0.003). In group I, posterior leaflet repair changed anterior leaflet displacement from -0.8 +/- 0.2 to 0.5 +/- 0.4 cm (p <0.001) and posterior leaflet displacement from -0.8 +/- 0.3 cm below to 0.5 +/- 0.4 cm (p <0.001) in front of the mitral annular plane. In group II, anterior leaflet displacement was unchanged from 0.2 +/- 0.1 to 0.3 +/- 0.2 cm (p = 0.22), whereas posterior leaflet displacement changed from -0.7 +/- 0.2 to 0.4 +/- 0.2 cm (p <0.001). Thus, patients with bileaflet prolapse and no ruptured chords have excessive anterior leaflet length. In such patients, posterior leaflet repair alone corrects anterior and posterior leaflet prolapse.

Prediction of thrombus-related mechanical prosthetic valve dysfunction using transesophageal echocardiography.

Identification of thrombus-related mechanical prosthetic valve dysfunction (MPVD) has important therapeutic implications. We sought to develop an algorithm, combining clinical and echocardiographic parameters, for prediction of thrombus-related MPVD in a series of 53 patients (24 men, age 52 +/- 16 years) who had intraoperative diagnosis of thrombus or pannus from 1992 to 1997. Clinical and echocardiographic parameters were analyzed to identify predictors of thrombus and pannus. Prevalence of thrombus and diagnostic yields relative to the number of predictors were determined. There were 22 patients with thrombus, 19 patients with pannus, and 12 patients with both. Forty-two of 53 masses were visualized using transesophageal echocardiography (TEE), including 29 of 34 thrombi or both thrombi and panni and 13 of 19 isolated panni. Predictors of thrombus or mixed presentation include mobile mass (p = 0.009), attachment to occluder (p = 0.02), elevated gradients (p = 0.04), and an international normalized ratio of < or = 2.5 (p = 0.03). All 34 patients with thrombus or mixed presentation had > or = 1 predictor. The prevalence of thrombus in the presence of < or = 1, 2, and > or = 3 predictors is 14%, 69%, and 91%, respectively. Thus, TEE is sensitive in the identification of abnormal mass in the setting of MPVD. An algorithm based on clinical and transesophageal echocardiographic predictors may be useful to estimate the likelihood of thrombus in the setting of MPVD. In the presence of > or = 3 predictors, the probability of thrombus is high.

Psychological aspects of chronic tonic and clonic stuttering: suggested therapeutic approaches.

A comparison of the personality profiles and intellectual functioning of 12 tonic and 18 clonic stutterers indicated that the groups could be discriminated on measures of verbal IQ, object relations, social isolation, somatization, and cognitive processing. Findings are examined in terms of the impact of type of functioning on maintenance of stuttering, and implications for treatment are discussed.

Elevated circulating levels of serum tumor necrosis factor-alpha in patients with hemodynamically significant pressure and volume overload.

OBJECTIVES: We sought to determine whether serum tumor necrosis factor-alpha (TNF-alpha) levels are elevated in patients with hemodynamically significant pressure and volume overload. BACKGROUND: It has been previously shown that TNF-alpha messenger ribonucleic acid (mRNA) and protein are rapidly expressed in the hearts of animal models subjected to abrupt hemodynamic overloading. The clinical significance of these experimental findings has not been tested in pathophysiologically relevant clinical models in human subjects. METHODS: We prospectively measured serum TNF-alpha levels and serum TNF receptor 1 and 2 levels in 21 patients with severe aortic stenosis (AS), in 26 patients with 3+ to 4+ mitral regurgitation (MR) and in normal age- and gender-matched control subjects. Patients with AS and MR were either in New York Heart Association (NYHA) functional class I or II and had no significant coronary disease. We compared the cytokine levels among the groups using analysis of variance. We related cytokine levels to the severity of AS using simple regression analysis. RESULTS: Serum TNF-alpha levels in patients with AS (2.1 +/- 1.6 pg/ml, n = 21) and MR (1.3 +/-0.7 pg/ml, n = 26) were significantly higher than those in the control subjects (0.7 +/-0.2 pg/ml, n = 28). Serum TNF receptor 1 and 2 levels were also higher in patients with AS and MR than in control subjects. Cytokine levels were higher in patients in NYHA class II than in those in class I. In patients with a normal ejection fraction (>50%, n = 16), there was a mild positive correlation (r = 0.56, p = 0.025) between serum TNF-alpha levels and the mean gradient across the aortic valve. CONCLUSIONS: This study demonstrates that serum TNF-alpha is elevated in patients with chronic hemodynamic overloading and early cardiac decompensation. Furthermore, these findings suggest not only that peripheral TNF-alpha levels correlate with the severity of the hemodynamic pressure overload, but also that peripheral TNF-alpha and TNF receptor levels increase in direct relation to deteriorating NYHA functional class.