Peak Mitral Inflow Velocity Predicts Mitral Regurgitation Severity 11All editorial decisions for this article, including selection of referees, were made by a Guest Editor. This policy applies to all articles with authors from the University of California San Francisco.22To discuss this article on-line, visit the ACC Home Page at www.acc.org/membersand click on the JACC Forum

AbstractObjectives. Mitral regurgitation (MR) is a common echocardiographic finding; however, there is no simple accurate method for quantification. The aim of this study was to develop an easily measured screening variable for hemodynamically significant MR.Background. The added regurgitant volume in MR increases the left atrial to left ventricular gradient, which then increases the peak mitral inflow or the peak E wave velocity. Our hypothesis was that peak E wave velocity and the E/A ratio increase in proportion to MR severity.Methods. We performed a retrospective analysis of 102 consecutive patients with varying grades of MR seen in the Adult Echocardiography Laboratory at the University of California, San Francisco. Peak E wave velocity, peak A wave velocity, E/A ratio and E wave deceleration time were measured in all patients. The reference standard for MR was qualitative echocardiographic evaluation by an expert and quantitation of regurgitant fraction using two-dimensional and Doppler echocardiography.Results. Peak E wave velocity was seen to increase in proportion to MR severity, with a significant difference between the different groups (F = 37, p < 0.0001). Peak E wave velocity correlated with regurgitant fraction (r = 0.52, p < 0.001). Furthermore, an E wave velocity >1.2 m/s identified 24 of 27 patients with severe MR (sensitivity 86%, specificity 86%, positive predictive value 75%). An A wave dominant pattern excluded the presence of severe MR. The E/A ratio also increased in proportion to MR severity. Peak A wave velocity and E wave deceleration time showed no correlation with MR severity.Conclusions. Peak E wave velocity is easy to obtain and is therefore widely applicable in clinical practice as a screening tool for evaluating MR severity

Proteomic analysis of heart failure hospitalization among patients with chronic kidney disease: The Heart and Soul Study.

BACKGROUND:Patients with chronic kidney disease (CKD) are at increased risk for heart failure (HF). We aimed to investigate differences in proteins associated with HF hospitalizations among patients with and without CKD in the Heart and Soul Study. METHODS AND RESULTS:We measured 1068 unique plasma proteins from baseline samples of 974 participants in The Heart and Soul Study who were followed for HF hospitalization over a median of 7 years. We sequentially applied forest regression and Cox survival analyses to select prognostic proteins. Among participants with CKD, four proteins were associated with HF at Bonferroni-level significance (p&lt;2.5x10(-4)): Angiopoietin-2 (HR[95%CI] 1.45[1.33, 1.59]), Spondin-1 (HR[95%CI] 1.13 [1.06, 1.20]), tartrate-resistant acid phosphatase type 5 (HR[95%CI] 0.65[0.53, 0.78]) and neurogenis locus notch homolog protein 1 (NOTCH1) (HR[95%CI] 0.67[0.55, 0.80]). These associations persisted at p&lt;0.01 after adjustment for age, estimated glomerular filtration and history of HF. CKD was a significant interaction term in the associations of NOTCH1 and Spondin-1 with HF. Pathway analysis showed a trend for higher representation of the Cardiac Hypertrophy and Complement/Coagulation pathways among proteins prognostic of HF in the CKD sub-group. CONCLUSIONS:These results suggest that markers of heart failure differ between patients with and without CKD. Further research is needed to validate novel markers in cohorts of patients with CKD and adjudicated HF events

The flail mitral valve: Echocardiographic findings by precordial and transesophageal imaging and doppler color flow mapping

AbstractTo determine the echocardiographic and Doppler characteristics of mitral regurgitation associated with a flail mitral valve, precordial and transesophageal echocardiography with pulsed wave and Doppler color flow mapping was performed in 17 patients with a flail mitral valve leaflet due to ruptured chordae tendineae (Group I) and 22 patients with moderate or severe mitral regurgitation due to other causes (Group II). Echocardiograms were performed before or during cardiac surgery; cardiac catheterization was also performed in 28 patients (72%). Mitral valve disease was confirmed at cardiac surgery in all patients.By echocardiography, the presence of a flail mitral valve leaflet was defined by the presence of abnormal mitral leaflet ccaptation or ruptured chordae. Using these criteria, transesophageal imaging showed a trend toward greater sensitivity and specificity than precordial imaging in the diagnosis of flail mitral valve leaflet. By Doppler color flow mapping, a flail mitral valve leaflet was also characterized by an eccentric, peripheral, circular mitral regurgitant jet that closely adhered to the walls of the left atrium. The direction of flow of the eccentric jet in the left atrium distinguished a flail anterior from a flail posterior leaflet. By transesophageal echocardiography with Doppler color flow mapping, the ratio of mitral regurgitant jet arc length to radius of curvature was significantly higher in Group I than Group II patients (5.0 ± 2.3 versus 0.7 ± 0.6, p < 0.001); all of the Group I patients and none of the Group II patients had a ratio >2.5.Thus, transesophageal imaging with Doppler color flow mapping of mitral regurgitation is complementary to precordial echocardiography in the diagnosis and localization of flail mitral valve leaflet due to ruptured chordae tendineae

Fibroblast Growth Factor–23 and Cardiac Structure and Function

Background: Fibroblast growth factor–23 (FGF‐23) is a phosphaturic factor previously associated with left ventricular hypertrophy and systolic dysfunction among individuals with chronic kidney disease. Whether FGF‐23 acts directly to induce left ventricular hypertrophy, potentially independent of its klotho coreceptor, remains uncertain. We investigated associations of FGF‐23 with cardiac structural abnormalities among individuals with a broad range of kidney function and explored potential biological mechanisms using cardiac magnetic resonance imaging and histology in klotho‐null mice, an established model of constitutively elevated FGF‐23. Methods and Results: Among 887 participants with coronary artery disease in the Heart and Soul Study, FGF‐23 was modestly associated with worse left ventricular ejection fraction (−1.0% per standard deviation increase in lnFGF‐23; standard error, 0.4%), but was not associated with the overall prevalence of concentric hypertrophy (odds ratio, 1.5; CI, 0.9 to 2.4) or eccentric hypertrophy (odds ratio, 1.1; CI, 0.9 to 1.3). FGF‐23 was only associated with concentric hypertrophy among individuals with diminished kidney function (eGFR <60 mL/min per 1.73 m2; odds ratio, 2.3; CI, 1.0 to 5.3; P‐interaction=0.28). Comparing klotho‐null with wild‐type mice, null mice did not have greater left ventricular mass (P=0.37) or a lower ejection fraction (P=0.94). Conclusions: Together, our results suggest that FGF‐23 is unlikely to have major effects on cardiovascular structure and function among patients free of substantial chronic kidney disease, and these effects may not be independent of the klotho coreceptor

Remote second-hand tobacco exposure in flight attendants is associated with systemic but not pulmonary hypertension

Background: Second-hand tobacco smoke has been associated with cardiopulmonary dysfunction. We sought to examine the residual effects of remote second-hand smoke exposure on resting and exercise cardiopulmonary hemodynamics. We hypothesized that remote secondhand smoke exposure results in persistent cardiopulmonary hemodynamic abnormalities. Methods: Participants were non-smoking flight attendants who worked in airline cabins prior to the in-flight tobacco ban. Participants underwent clinical evaluations and completed smoke exposure questionnaires. We used Doppler echocardiography to measure pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR) at rest and during supine bicycle ergometer exercise, using the validated formula TRV/VTIRVOT × 10 + 0.16, where VTIRVOT is the velocity time integral at the right ventricular outflow tract and TRV is the tricuspid regurgitation velocity. The group was divided into quartiles according to the degree of smoke exposure. Analysis of variance was used to determine the differences in hemodynamic outcomes. Results: Seventy-nine flight attendants were included in our analysis. Baseline characteristics among participants in each quartile of smoke exposure were similar except for history of systemic hypertension, which was more prevalent in the highest quartile. Peak exercise PASP rose to the same degree in all test groups (mean PASP 44 mm Hg, p = 0.25), and PVR increased by approximately 27% in all quartiles. There was no significant difference in pulmonary artery systolic pressure or pulmonary vascular resistance among quartiles of smoke exposure. Conclusions: We found that remote heavy second-hand smoke exposure from in-flight tobacco is associated with systemic hypertension but does not have demonstrable pulmonary hemodynamic consequences

Gluino Pair Production at Linear e^+e^- Colliders

We study the potential of high-energy linear $e^+e^-$ colliders for the production of gluino pairs within the Minimal Supersymmetric Standard Model (MSSM). In this model, the process $e^+e^-\to\tilde{g}\tilde{g}$ is mediated by quark/squark loops, dominantly of the third generation, where the mixing of left- and right-handed states can become large. Taking into account realistic beam polarization effects, photon and $Z^0$-boson exchange, and current mass exclusion limits, we scan the MSSM parameter space for various $e^+e^-$ center-of-mass energies to determine the regions, where gluino production should be visible.Comment: 22 pages, 9 figure

The echo-transponder electrode catheter: A new method for mapping the left ventricle

AbstractThe ability to locate catheter position in the left ventricle with respect to endocardial landmarks might enhance the accuracy of ventricular tachycardia mapping. An echotransponder system (Telectronics, Inc.) was compared with biplane fluoroscopy for left ventricular endocardial mapping. A 6F electrode catheter was modified with the addition of a piezoelectric crystal 5 mm from the tip. This crystal was connected to a transponder that received and transmitted ultrasound, resulting in a discrete artifact on the two-dimensional echocardiographic image corresponding to the position of the catheter tip.Catheters were introduced percutaneously into the left ventricle of nine anesthetized dogs. Two-dimensional echotransponder and biplane fluoroscopic images were recorded on videotape with the catheter at multiple endocardial sites. Catheter location was marked by delivering radiofrequency current to the distal electrode, creating a small endocardial lesion. Catheter location by echo-transponder and by fluoroscopy were compared with lesion location without knowledge of other data. Location by echo-transponder was 8.7 ± 5.1 mm from the center of the radiofrequency lesion versus 14 + 7.8 mm by fluoroscopy (n = 15, p = 0.023). Echo-transponder localization is more precise than is biplane fluoroscopy and may enhance the accuracy of left ventricular eledrophysiologic mapping

A Functional Polymorphism in Renalase (Glu37Asp) Is Associated with Cardiac Hypertrophy, Dysfunction, and Ischemia: Data from the Heart and Soul Study

Renalase is a soluble enzyme that metabolizes circulating catecholamines. A common missense polymorphism in the flavin-adenine dinucleotide-binding domain of human renalase (Glu37Asp) has recently been described. The association of this polymorphism with cardiac structure, function, and ischemia has not previously been reported.We genotyped the rs2296545 single-nucleotide polymorphism (Glu37Asp) in 590 Caucasian individuals and performed resting and stress echocardiography. Logistic regression was used to examine the associations of the Glu37Asp polymorphism (C allele) with cardiac hypertrophy (LV mass>100 g/m2), systolic dysfunction (LVEF<50%), diastolic dysfunction, poor treadmill exercise capacity (METS<5) and inducible ischemia.Compared with the 406 participants who had GG or CG genotypes, the 184 participants with the CC genotype had increased odds of left ventricular hypertrophy (OR = 1.43; 95% CI 0.99-2.06), systolic dysfunction (OR = 1.72; 95% CI 1.01-2.94), diastolic dysfunction (OR = 1.75; 95% CI 1.05-2.93), poor exercise capacity (OR = 1.61; 95% CI 1.05-2.47), and inducible ischemia (OR = 1.49, 95% CI 0.99-2.24). The Glu37Asp (CC genotype) caused a 24-fold decrease in affinity for NADH and a 2.3-fold reduction in maximal renalase enzymatic activity.A functional missense polymorphism in renalase (Glu37Asp) is associated with cardiac hypertrophy, ventricular dysfunction, poor exercise capacity, and inducible ischemia in persons with stable coronary artery disease. Further studies investigating the therapeutic implications of this polymorphism should be considered