Precision Phenotyping in Heart Failure and Pattern Clustering of Ultrasound Data for the Assessment of Diastolic Dysfunction.

OBJECTIVES: The aim of this study was to investigate whether cluster analysis of left atrial and left ventricular (LV) mechanical deformation parameters provide sufficient information for Doppler-independent assessment of LV diastolic function. BACKGROUND: Medical imaging produces substantial phenotyping data, and superior computational analyses could allow automated classification of repetitive patterns into patient groups with similar behavior. METHODS: The authors performed a cluster analysis and developed a model of LV diastolic function from an initial exploratory cohort of 130 patients that was subsequently tested in a prospective cohort of 44 patients undergoing cardiac catheterization. Patients in both study groups had standard echocardiographic examination with Doppler-derived assessment of diastolic function. Both the left ventricle and the left atrium were tracked simultaneously using speckle-tracking echocardiography (STE) for measuring simultaneous changes in left atrial and ventricular volumes, volume rates, longitudinal strains, and strain rates. Patients in the validation group also underwent invasive measurements of pulmonary capillary wedge pressure and LV end diastolic pressure immediately after echocardiography. The similarity between STE and conventional 2-dimensional and Doppler methods of diastolic function was investigated in both the exploratory and validation cohorts. RESULTS: STE demonstrated strong correlations with the conventional indices and independently clustered the patients into 3 groups with conventional measurements verifying increasing severity of diastolic dysfunction and LV filling pressures. A multivariable linear regression model also allowed estimation of E/e' and pulmonary capillary wedge pressure by STE in the validation cohort. CONCLUSIONS: Tracking deformation of the left-sided cardiac chambers from routine cardiac ultrasound images provides accurate information for Doppler-independent phenotypic characterization of LV diastolic function and noninvasive assessment of LV filling pressures.

In vitro antischistosomal activity of venom from the Egyptian snake Cerastes cerastes.

INTRODUCTION:: We studied the potential in vitro antischistosomal activity of Cerastes cerastes venom on adult Schistosoma mansoni worms. METHODS:: Live specimens of the horned viper snake, C. cerastes were collected from the Aswan Governorate (Egypt). Venom was collected from snakes by manual milking. Worms of S. mansoni were obtained from infected hamsters by perfusion and isolated from blood using phosphate buffer. Mortality rates of worms were monitored after 3 days of exposure to snake venom at LC50 and various sublethal concentrations (10, 5, 2.5µg/ml). Scanning electron microscopy was used to investigate tegumental changes in treated worms after exposure to LC50 doses of venom. RESULTS:: The LC50 of C. cerastes venom was 21.5µg/ml. The effect of C. cerastes venom on Schistosoma worms varied according to their sex. The mortality rate of male and female worms after 48-h exposure was 83.3% and 50%, respectively. LC50 of C. cerastes venom induced mild to severe tegumental damage in Schistosoma worms in the form of destruction of the oral sucker, shrinkage and erosion of the tegument, and loss of some tubercle spines. CONCLUSIONS:: The present study demonstrated that C. cerastes venom exerts potential in vitro antischistosomal activity in a time and dose-dependent manner. These results may warrant further investigations to develop novel schistosomicidal agents from C. cerastes snake venom.

In vitro antischistosomal activity of venom from the Egyptian snake Cerastes cerastes

Abstract INTRODUCTION: We studied the potential in vitro antischistosomal activity of Cerastes cerastes venom on adult Schistosoma mansoni worms. METHODS: Live specimens of the horned viper snake, C. cerastes were collected from the Aswan Governorate (Egypt). Venom was collected from snakes by manual milking. Worms of S. mansoni were obtained from infected hamsters by perfusion and isolated from blood using phosphate buffer. Mortality rates of worms were monitored after 3 days of exposure to snake venom at LC50 and various sublethal concentrations (10, 5, 2.5µg/ml). Scanning electron microscopy was used to investigate tegumental changes in treated worms after exposure to LC50 doses of venom. RESULTS: The LC50 of C. cerastes venom was 21.5µg/ml. The effect of C. cerastes venom on Schistosoma worms varied according to their sex. The mortality rate of male and female worms after 48-h exposure was 83.3% and 50%, respectively. LC50 of C. cerastes venom induced mild to severe tegumental damage in Schistosoma worms in the form of destruction of the oral sucker, shrinkage and erosion of the tegument, and loss of some tubercle spines. CONCLUSIONS: The present study demonstrated that C. cerastes venom exerts potential in vitro antischistosomal activity in a time and dose-dependent manner. These results may warrant further investigations to develop novel schistosomicidal agents from C. cerastes snake venom.

Radius of proximal isovelocity surface area in the assessment of rheumatic mitral stenosis: Connecting flow to anatomy and hemodynamics.

BACKGROUND: Echocardiographic assessment of left atrial pressure (LAP) in mitral stenosis (MS) is controversial. We sought to examine the role of the radius of the proximal isovelocity surface area (PISA-r) in the assessment of the hemodynamic status of MS after fixing the aliasing velocity (Val). METHODS AND RESULTS: We studied 42 candidates of balloon mitral valvuloplasty (BMV), for whom pre-BMV echocardiography was done and LAP invasively measured before dilatation. PISA-r was calculated after fixing aliasing velocity to 33 cm/s. In addition, the ratio IVRT/Te'-E was also measured, where IVRT was isovolumic relaxation time, and Te'-E was the time difference between the onset of mitral flow E-wave and mitral annular early diastolic velocity. IVRT/Te'-E and PISA-r showed a strong correlation with LAP (r = -0.715 and -0.637, all p < 0.001) and with right-sided pressures. In addition, PISA-r correlated with mitral valve area by planimetry method (MVA) and with left ventricular outflow tract stroke volume (r = 0.66 and 0.71, all p < 0.001). Receiver operator characteristic curve (ROC-curve) showed that PISA-r was not inferior to IVRT/Te'-E in differentiating LAP ⩾25 from <25 mmHg. CONCLUSION: Provided that Val is set to a constant of 33 cm/s, PISA-r can assess the hemodynamic status of MS, and seems a simple alternative to the tedious IVRT/Te'-E for estimation of LAP.

Tissue Doppler-Derived Myocardial Acceleration during Isovolumetric Contraction Predicts Pulmonary Capillary Wedge Pressure in Patients with Significant Mitral Regurgitation.

The aim of this study was to determine whether isovolumic contraction velocity (IVV) and acceleration (IVA) predict pulmonary capillary wedge pressure (PCWP) in mitral regurgitation. Forty-four patients with mitral regurgitation were studied. PCWP was invasively measured. IVV, IVA and the ratio IVRT/Te'-E (where IVRT = isovolumic relaxation time, and Te'-E = time difference between the onset of mitral annular e' and mitral flow E waves) were measured. Mean age was 59.2 ± 13.3 y. Twenty-six patients had an ejection fraction ≥55%, and 18 patients had an ejection fraction <55%. IVRT/Te'-E was impossible in 11 patients because Te'-E = zero. PCWP correlated with IVV, IVA and IVRT/Te'-E; overall (r = -0.714, -0.892 and, -0.752, all p < 0.001), ejection fraction ≥55 (r = -0.467, -0.749, -0.639, p = 0.016, <0.001, 0.003) and ejection fraction <55% (r = -0.761, -0.911 and -0.833, all p < 0.001). Similar correlations were found for sinus and atrial fibrillation. Our study suggests that IVV and IVA correlate with PCWP in patients with mitral regurgitation irrespective of systolic function or rhythms and, thus, can be alternatives to the tedious IVRT/Te'-E, especially when impossible because Te'-E = 0.