[Show abstract][Hide abstract] ABSTRACT: The recent guidelines for preventing atherosclerotic cardiovascular events are an important advancement. For primary prevention, statins are recommended if the ten-year risk is ≥ 5% (consideration for therapy) or ≥ 7.5% (definitive treatment unless contraindication after discussion). We rationalized that a significant cohort with ten-year risk below the treatment thresholds would predictably surpass them within the recommended 4-6 year window for reassessing the ten-year risk. As atherosclerosis is a progressive disease, these individuals may therefore benefit with more aggressive therapies even at baseline.
PLoS ONE 01/2014; 9(8):e104478. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: -There is currently no therapy proven to attenuate left ventricular (LV) dilatation and dysfunction in the volume overload induced by isolated mitral regurgitation (MR). To better understand molecular signatures underlying isolated MR, we performed LV gene expression analyses and overlaid regulated genes into Ingenuity Pathway Analysis in patients with isolated MR.
-Gene arrays from LV tissue of 35 patients, taken at the time of surgical repair for isolated MR, were compared to 13 normal controls. Cine-magnetic resonance imaging (MRI) was performed in 31 patients before surgery to measure LV function and volume from serial short axis summation. LV end-diastolic volume was 2-fold (p=0.005) higher than normals and LV ejection fraction (EF) was 64±7% (50-79%) in MR patients. Ingenuity pathway analysis identified significant activation of pathways involved in β-adrenergic, cyclic AMP, and G-protein coupled signaling; while there was downregulation of pathways associated with complement activation and acute phase response. SERCA2a and phospholamban protein were unchanged in MR vs. control LVs. However, mRNA and protein levels of the sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA) regulatory protein sarcolipin, which is predominantly expressed in normal atria, were increased 12- and 6-fold respectively. Immunofluorescence analysis confirmed the absence of sarcolipin in normal LVs and its marked upregulation in MR LVs.
-These results demonstrate alterations in multiple pathways associated with β-adrenergic signaling and sarcolipin in the LVs of patients with isolated MR and LVEF > 50%,suggesting a beneficial role for β-adrenergic blockade in isolated MR.
[Show abstract][Hide abstract] ABSTRACT: How the left ventricle remodels in response to a high-volume stimulus is important in evaluating the endurance athlete's heart. Marathoners and patients with isolated, moderate chronic compensated mitral regurgitation (MR) represent physiologic and pathologic forms of eccentric left ventricular (LV) remodeling in response to intermittent and chronic volume overload, respectively. Thus, in this study, magnetic resonance imaging with tissue tagging and 3-dimensional data analysis at rest were performed in 19 marathoners (mean age 39 ± 10 years, 47% women), 17 patients with isolated MR without coronary artery disease or medical therapy (mean age 46 ± 5 years, 53% women), and 24 controls (mean age 45 ± 8 years, 50% women). Marathoners and patients with MR had approximately 35% greater LV end-diastolic volume indexes, approximately 50% greater end-systolic volume indexes, and approximately 34% greater LV stroke volume indexes (p <0.0001) compared to controls. However, marathoners' hearts had increased long-axis length, while those of patients with MR did not differ from the hearts of controls. The hearts of patients with MR had greater LV global and apex sphericity compared to those of marathoners and controls (p <0.0001). Marathoners had normal LV mass/volume ratios and wall thicknesses, whereas these were significantly decreased in the MR group. In marathoners, the baseline LV work rate was similar to that in controls and higher in patients with MR compared to controls. In conclusion, marathoners' hearts achieve elevated stroke volume at rest with adherence to an elliptical shape defined by 3-dimensional geometry and mass/volume ratio. Thus, a comprehensive evaluation of LV geometry and mass/volume ratio may be important in the evaluation of the athlete's heart.
The American journal of cardiology 01/2013; · 3.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of the study was to evaluate the effect of long-term β(1)-aderergic receptor (AR) blockade on left ventricular (LV) remodeling and function in patients with chronic, isolated, degenerative mitral regurgitation (MR).
Isolated MR currently has no proven therapy that attenuates LV remodeling or preserves systolic function.
Thirty-eight asymptomatic subjects with moderate to severe, isolated MR were randomized either to placebo or β(1)-AR blockade (Toprol-XL, AstraZeneca, London, United Kingdom) for 2 years. Magnetic resonance imaging with tissue tagging and 3-dimensional analysis was performed at baseline and at 6-month intervals for 2 years. Rate of progression analysis was performed for endpoint variables for primary outcomes: LV end-diastolic volume/body surface area, LV ejection fraction, LV end-diastolic (ED) mass/ED volume ratio, LV ED 3-dimensional radius/wall thickness; LV end-systolic volume/body surface area, LV longitudinal strain rate, and LV early diastolic filling rate.
Baseline LV magnetic resonance imaging or demographic variables did not differ between the 2 groups. Significant treatment effects were found on LV ejection fraction (p = 0.006) and LV early diastolic filling rate (p = 0.001), which decreased over time in untreated patients on an intention-to-treat analysis and remained significant after sensitivity analysis. There were no significant treatment effects found on LV ED or LV end-systolic volumes, LV ED mass/LV ED volume or LV ED 3-dimensional radius/wall thickness, or LV longitudinal strain rate. Over 2 years, 6 patients treated in the placebo group and 2 patients in the β(1)-AR blockade group required mitral valve surgery (p = 0.23).
β(1)-AR blockade improves LV function over a 2-year follow-up in isolated MR and provides the impetus for a large-scale clinical trial with clinical outcomes. (Molecular Mechanisms of Volume Overload-Aim 1 [SCCOR in Cardiac Dysfunction and Disease]; NCT01052428).
Journal of the American College of Cardiology 07/2012; 60(9):833-8. · 14.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although surgery is indicated in patients with mitral regurgitation (MR) when left ventricular (LV) end-systolic (LVES) dimension is >40 mm, LV ejection fraction may decrease after mitral valve surgery. We hypothesize that significant LV remodeling before surgery is not reflected by standard echocardiographic parameters measured at the base of the heart.
Ninety-four patients (age, 54 ± 11 years; 38% female) with degenerative isolated MR underwent cine magnetic resonance imaging with tissue tagging and 3-dimensional analysis. In 51 control subjects (age, 44 ± 14 years; 53% female), the relation between LVES volume (LVESV) and LVES dimension was quadratic, whereas in 94 MR patients, this relation was cubic, indicating a greater increase in LVESV per LVES dimension among MR patients. Moreover, magnetic resonance imaging LVESV from summated serial short-axis slices was significantly greater than LVESV assessed with the Bullet formula in MR patients, attributed to a more spherical remodeling distal to the tips of the papillary muscles (P<0.001). Thirty-five patients underwent mitral valve repair per current guideline recommendations. LV ejection fraction decreased from 61 ± 7% to 54 ± 8% (P<0.0001) and maximum shortening decreased significantly below normal at 1 year postoperatively (P<0.0001). Despite normalization of LV stroke volume and LV end-diastolic volume/mass ratio, there was a persistent significant increase in distal LVES 3-dimensional radius/wall thickness ratio and LVESV index after surgery.
Despite apparently preserved LVES dimension, MR patients demonstrate significant spherical mid to apical LVES remodeling that contributes to higher LVESV than predicted by standard geometry-based calculations. Decreased LV strain after surgery suggests that a volumetric analysis of LV remodeling and function may be preferred to evaluate disease progression in isolated MR.
[Show abstract][Hide abstract] ABSTRACT: Mechanisms of left ventricular (LV) dysfunction in isolated mitral regurgitation (MR) are not well understood. Vasodilator therapy in other forms of LV dysfunction reduces LV wall stress and improves LV function; however, studies in isolated MR show no beneficial effect on LV remodeling using vasodilator drugs or renin-angiotensin system blockade. Therefore, the search for new therapies that improve LV remodeling and function in isolated MR is clinically significant. Recent work in the authors' laboratory has demonstrated increased oxidants from a number of sources including the enzyme xanthine oxidase (XO) in the LV of patients with isolated MR. In addition to being a major source of reactive oxygen species, XO is linked to bioenergetic dysfunction because its substrates derive from adenosine triphosphate catabolism. Correspondingly, there was also evidence of aggregates of small mitochondria in cardiomyocytes, which is generally considered a response to bioenergetic deficit in cells. Future studies are required to determine whether XO and persistent oxidative stress are causative in maladaptive LV remodeling and offer potential therapeutic targets in ameliorating LV damage in patients with isolated MR.
The American Journal of the Medical Sciences 08/2011; 342(2):114-9. · 1.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To validate a method called bi-ventricular strain unwrapped phase (BiSUP) for reconstructing three-dimensional plus time (3D+t) biventricular strain maps from phase-unwrapped harmonic phase (HARP) images derived from tagged cardiac magnetic resonance imaging (MRI).
A set of 30 human subjects were imaged with tagged MRI. In each study, HARP phase was computed and unwrapped in each short-axis and long-axis image. Inconsistencies in unwrapped phase were resolved using branch cuts manually placed with a graphical user interface. The 3D strain maps were computed independently in each imaged time frame through systole and mid diastole in each study. The BiSUP strain and displacements were compared with those estimated by a 3D feature-based (FB) technique and a 2D+t HARP technique.
The standard deviation of the difference between strains measured by the FB and the BiSUP methods was less than 4% of the average of the strains from the two methods. The correlation between peak minimum principal strain measured using the BiSUP and HARP techniques was over 83%.
The BiSUP technique can reconstruct full 3D+t strain maps from tagged MR images through the cardiac cycle in a reasonable amount of time and user interaction compared with other 3D analysis methods.
Journal of Magnetic Resonance Imaging 07/2011; 34(4):799-810. · 2.57 Impact Factor