The aim of the study was to assess the impact of mitral regurgitation (MR) on left ventricular (LV) anatomic and molecular remodeling and function and to determine whether early LV remodeling and function predict long-term outcome in experimental organic MR. A new rodent model of chronic MR was created. Twenty-eight rats had surgically induced MR, twelve rats had a sham operation, and twelve rats had no operation. LV diameters, volume, and mass and LV ejection fraction (LVEF) and LV fractional shortening (LVFS) were assessed using echocardiography in the early stage of MR (6 and 12 wk after induction of MR). LV hemodynamics was assessed invasively. Cardiac alpha- and beta-myosin heavy chains and sarco(endo)plasmic reticulum Ca(2+)-ATPase 2 (SERCA2) were measured to assess molecular remodeling and contractility. Cox's proportional hazard ratios (HR) were used to identify outcome predictors. Early LV dilation was demonstrated in rats with MR when LVEF and LVFS were still normal. LV remodeling was associated with an increase in LV end-diastolic pressure and decrease in maximal change in pressure over time. Shifting of alpha- to beta-myosin and reduced SERCA2 were observed in rats with MR. Cox's proportional hazard analysis showed that LV end-diastolic diameters (HR, 1.2-2.4; P = 0.007) and LV end-diastolic volume (HR, 1.1-1.4; P = 0.005) at 6 wk and LV mass index (HR, 1.1-2.0; P = 0.004) at 12 wk after induction of MR were significantly associated with 1-yr mortality. However, LVEF (HR, 0.7-6.8 for the 6 wk, P > 0.05; and HR, 0.4-3.2 for the 12 wk, P > 0.05) and LVFS (HR, 0.4-1.4 for the 6 wk; and 0.4-3.1 for the 12 wk, P > 0.05) did not predict late death. Chronic MR leads to LV anatomic and cellular remodeling and impaired contractility. The time course of LV remodeling and function changes in the rat model of MR is similar to humans. Prediction of outcome may be achieved by assessments of early LV remodeling.

Although conventional TTE variables show preserved LV size and function, LV longitudinal strain suggests subclinical myocardial dysfunction in patients with GDM. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:20-27, 2017.

Background-Mitral regurgitation (MR) produces sympathetic nervous system activation which is detrimental in other causes of heart failure. However, whether β-blockade is beneficial in MR has not been determined. Methods and Results-Eighty-seven rats with significant organic MR were randomized to the β-blockade group (n=43) or the control group (n=44). Carvedilol was started in week 2 post MR induction and given for 23 to 35 weeks in the β-blockade group. Echocardiography was performed at baseline and at weeks 2, 6, 12, 24, 30, and 36 after MR induction. After 23 weeks of β-blockade, heart rates were significantly reduced by carvedilol (308±25 versus 351±31 beats per minute; P<0.001). Left ventricular end-diastolic (2.2±0.7 versus 1.59±0.6 mL; P<0.001), end-systolic volumes (0.72±0.42 versus 0.40±0.19 mL; P<0.001), and mass index (2.40±0.55 versus 2.06±0.62 g/kg; P<0.001) were significantly higher, and left ventricular fraction shortening (33±7% versus 38±7%; P<0.001) and ejection fraction (69±11% versus 75±7%; P<0.001) were significantly lower in the β-blockade group than in the control group. Systolic blood pressure was lower in the β-blockade group than in the control group (114±10 versus 93±12 mm Hg; P<0.005). Survival probability was significantly lower in the early β-blockade group than in the control group (88% versus 96%; P=0.03). 14 This dissociation creates a possible pathophysiological contradiction because adverse LV remolding is often associated with LV dysfunction and poor long-term outcome in all forms of congestive heart failure. Therefore, it is important to determine whether beneficial effects of β-blockade could be demonstrated if chronic organic MR was treated in the early stages before the development of LV dysfunction and if treatment is long-term. It is also imperative to determine whether LV remodeling associated with β-blocker therapy could ultimately have a negative impact on LV function in chronic organic MR or if the early improvement in LV function and myocardial contractility observed in prior studies could lead to improvement in LV remodeling if treatment was initiated early and long-term. To clarify this important issue, we performed a prospective study to determine the effects of early, late, and long-term β-blockade on LV remodeling, systolic function, and survival in experimental chronic MR. The study design had the following unique characteristics: (1) the study used a unique rat model of chronic MR developed in our laboratory, 15 allowing us to use a large numbers of animals to test the hypothesis; (2) carvedilol (a nonselective β-adrenergic blocking agent with α 1 -blocking activity) was administered early before the development of LV systolic dysfunction; and (3) a long-term treatment strategy was applied. Conclusions-Early Methods Rat Model of MRThe study protocol was approved by the Institution's Animal Care and Use Committee of the Pennsylvania State University College of Medicine (assurance number A3045-01). The study was performed according to the guidelines of the Amer...

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e22071 Background: Cholesterol is an essential component for normal cell growth. However, epidemiological studies show cholesterol levels may be associated with cancer incidence. The Multiple Risk Factor Intervention Trial reported a significant inverse relationship between cholesterol levels and lung cancer. The effects of cholesterol on cancer growth and metastasis have not been established. The aim of the present study was to determine if cholesterol alters cancer growth or metastasis. Methods: The study used 48 wild-type mice and 18 LDL receptor knockout mice (LDLR-/-). Mice were randomized into 3 groups: Group I (wild-type mice fed normal chow, n=23); Group II (wild-type mice fed high lipid chow, n=25); Group III (LDLR-/- mice fed high lipid chow, n=18). Human melanoma cells were injected subcutaneously for the assessment of growth and intravenously for metastasis. Mice were followed for 4 weeks. At the end of the study, mice were weighed and autopsy was performed. Melanoma weight, metastasis, and blood cholesterol levels were evaluated. Data was analyzed using One-way ANOVA and Chi-square. Results: LDL-cholesterol level was significantly higher in Group III than Group I (1103±472 vs.28±6; p<0.01). There was no significant difference in melanoma weight (2.74g ±1.77, 2.98g±1.98 vs. 2.18g±1.59, P=0.56) among the three subcutaneous injection groups. Lung metastasis was observed in all intravenous injection groups (11/11 vs. 10/10 vs. 8/8). There was no difference in melanoma weight or metastasis between male and female mice (P>0.05). There was no difference in net weight gain among the subcutaneous injection groups (4.12g±2.50 vs. 2.64g±2.79 vs. 3.66g±1.96, P=0.30). However, among the intravenous injection groups, weight gain was observed in Group II (2.78g±2.67) and Group III (2.36g±1.73) and weight loss in Group I (-0.32g±1.34, P<0.003). Conclusions: Cholesterol has no effect on melanoma growth or metastasis in mice. A high cholesterol diet may reduce weight loss in animals with metastatic melanoma. Further study is warranted to determine whether similar results exist in other types of cancers and to evaluate a possible beneficial effect of high lipid diets on patients with metastatic cancers.

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Introduction: Recurrence rates of atrial fibrillation (AF) following catheter ablation remain substantial. Studies on cardiac magnetic resonance imaging (cMRI) assessment of predictors of AF recurrence following pulmonary vein (PV) isolation have centered on left atrial volume and fibrosis. We sought to identify other anatomic predictors of recurrent AF following PV isolation by cMRI. Methods: Eighty-seven consecutive patients (72 [83%] male; age 61 ± 10 yrs) who underwent PV isolation for symptomatic AF (63% paroxysmal) and baseline cMRI were evaluated. Baseline left ventricular (LV) mass, LV end-diastolic and end-systolic volumes, LV size, LV ejection fraction, left atrial diameter and area, right atrial sizes, right ventricular size and function and presence of left common PV and right middle PV were assessed by cMRI. Recurrent AF (defined as AT/AF ≥ 30 seconds) during follow up was noted. Results: Over mean follow-up of 372 ± 109 days, a total of 30 (35%) patients had evidence of recurrent AF. Patients with LV enlargement (≥ mild) by cMRI had significantly reduced AF-free survival (53% vs. 73% at 1 year; p = 0.012) and patients with LV mass index ≥ 74.5 g/m 2 had significantly reduced AF-free survival (54% vs. 72% at 1 year; p = 0.031). There was no difference in AF-free survival among patients with and without left atrial, right atrial, and right ventricular enlargement. Patients with and without recurrent AF had similar right ventricular function and LV ejection fractions. In a multivariate analysis of cMRI parameters of cardiac anatomy, LV enlargement was the only significant independent predictor of recurrent AF (HR 2.78; 95% CI 1.26-6.11; p=0.011). Conclusion: Left ventricular enlargement assessed by cMRI is a significant independent predictor of recurrent AF following PV isolation. In addition to abnormal left atrial substrate, negative LV remodeling may also be an important marker of increased susceptibility to AF after ablation.