[Show abstract][Hide abstract] ABSTRACT: Objectives To evaluate the individual and interacting impacts of the continuous variables (age, total cholesterol (total-C), high-density lipoprotein cholesterol (HDL-C) and systolic blood pressure(BP)) on 10-year atherosclerotic cardiovascular disease (ASCVD) risk and better understand the pattern of predicted 10-year risk with change of each variable using recently published new pooled cohort equations.
Design Simulation analysis was performed across the whole range of the boundary limits suggested for the continuous variables for groupings based on race and gender in the pooled cohort 10-year risk equations.
Setting Computer-based simulation analysis.
Participants Data were generated by simulation using prespecified variable ranges.
Intervention Data simulation and visual display of the hazard analysis.
Main outcome measures Interactions of age with other variables were analysed using multidimensional visualisation and hazard analysis.
Results In African–American females, due to the interaction of age with HDL-C, treated BP and untreated BP, increasing age may not always increase 10-year risk. Furthermore, in the same cohort, increasing HDL-C level may result in higher 10-year risk for older individuals. For Caucasian females, due to square of Ln (age) term in the equation, the age-risk curve does not monotonically increase with age. The vertex is within the given age range of 40–79 years for a certain range of total-C and HDL-C, indicating that age may not always result in increased predicted 10-year risk.
Conclusions The new pooled cohort equations are sophisticated as they take into account the interactions of the continuous variables in predicting 10-year risk. We find situations where the estimated 10-year risk does not follow the general secular trends. The impact of such interesting patterns may be substantial and therefore further exploration is needed as it has direct implications in clinical management for primary prevention.
BMJ Open 05/2015; 5(4):e006468. DOI:10.1136/bmjopen-2014-006468 · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Marathon runners (MTH) and patients with mitral regurgitation (MR) exhibit left ventricular (LV) overload, and LV geometric changes in these groups have been reported. In this study, right ventricular (RV) adaptation to chronic volume overload was evaluated in MTH and MR and normal controls together with interventricular septal remodeling and tricuspid annulus (TA) motion. Methods: A total of 60 age-matched subjects (including 19 MTH, 17 isolated chronic compensated MR patients and 24 normal subjects) underwent conventional cine and tagged cardiac magnetic resonance imaging. Myocardial strain and curvature were computed on the interventricular septum and RV free wall. A dual-propagation technique was applied to construct RV volume-time curves for a single cardiac cycle. Similarly, the tricuspid annulus was tracked throughout the cardiac cycle to create displacement over time curve. Results: Septal curvature was significantly lower in MTH and MR compared to controls. No significant differences in RV free wall strain or RV ejection fraction were noted amongst the 3 groups. However, longitudinal TA excursion was significantly higher in MTH compared to controls (p=0.0061). The peak late diastolic TA velocity in MR was significantly faster than MTH (p=0.0031) and controls (p=0.020). Conclusions: Increased TA kinetics allows for improved RV performance in MTH. Septal remodeling was observed in both MR and MTH, therefore a direct relationship of septal remodeling to TA kinetics in athlete’s heart could not be elucidated in this study.
[Show abstract][Hide abstract] ABSTRACT: Background:
Torsion shear angle φ is an important measure of left ventricular (LV) systolic and diastolic functions. Here we provide a novel index utilizing LV normalized torsion shear angle φ ^ volume V ^ loop to assess LV diastolic functional properties. We defined the area within φ ^ V ^ loop as torsion hysteresis area, and hypothesized that it may be an important global parameter of diastolic function. We evaluated the φ ^ changes to increased V ^ during early diastole - d φ ^ / d V ^ as a potential measure of LV suction.
Sixty resistant hypertension patients (HTN), forty control volunteers were studied using cardiovascular magnetic resonance with tissue tagging. Volumetric and torsional parameters were evaluated.
HTN demonstrated concentric remodeling with preserved ejection fraction. HTN had significantly decreased normalized early filling rate, early diastolic mitral annulus velocity and E/A (1.33 ± 1.13 vs. 2.19 ± 1.07, P < 0.0001) vs. control. Torsion hysteresis area was greater (0.11 ± 0.07 vs. 0.079 ± 0.045, P < 0.001) and peak - d φ ^ / d V ^ at early diastole was higher (10.46 ± 8.51 vs. 6.29 ± 3.85, P = 0.002) than control. Torsion hysteresis area was significantly correlated with E/A (r = -0.23, P = 0.025). Thirteen HTN patients had both E/A ratio < 1.12 (Control mean E/A-1SD) and torsion hysteresis area > 0.12 (Control mean torsion hysteresis area + 1SD).
Torsion hysteresis area and peak early diastolic - d φ ^ / d V ^ were significantly increased in hypertensive concentric remodeling. The φ ^ V ^ loop takes into account the active and passive recoil processes of LV diastolic and systolic phases, therefore provides a new global description of LV diastolic function.
Journal of Cardiovascular Magnetic Resonance 09/2014; 16(1):70. DOI:10.1186/s12968-014-0070-4 · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We have previously shown rapid reversal of left ventricular hypertrophy (LVH) with 6 months of spironolactone therapy in patients with resistant hypertension (HTN), preserved left ventricular ejection fraction and no history of heart failure. In this substudy, we investigated the effect of mineralocorticoid receptor blockade with spironolactone on pre-clinical diastolic dysfunction. Thirty-four patients (19 with high and 15 with normal aldosterone levels) were treated with spironolactone and followed with cardiac magnetic resonance with tissue tagging at baseline, 3 and 6 months of treatment. Serum markers of collagen turnover (C-propeptide of type-I procollagen and carboxy-terminal telopeptide of type-I collagen) were measured at baseline and at 6 months. At baseline, patients demonstrated reduced E/A ratio (volumetric normalized peak early filling rate/late filling rate, normalized to left ventricular end-diastolic volume), lower peak early-diastolic mitral annular velocity and lower peak early-diastolic circumferential strain rates compared to the reference values obtained from 45 normal controls without HTN or cardiac disease (all comparisons, P<0.01). No significant change occurred in diastolic filling, relaxation parameters or collagen markers with spironolactone therapy at 6 months irrespective of aldosterone status despite significant reduction in left ventricular mass index in both high- and normal-aldosterone groups. In conclusion, resistant HTN patients with LVH demonstrate significant pre-clinical diastolic dysfunction. Short-term spironolactone therapy may not lead to improvement in diastolic function despite rapid reversal of LVH.Journal of Human Hypertension advance online publication, 18 September 2014; doi:10.1038/jhh.2014.83.
Journal of Human Hypertension 09/2014; 29(4). DOI:10.1038/jhh.2014.83 · 2.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
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.
Methods and Findings
We used publicly available NHANES dataset for ten-year risk calculation. There were 1805 participants. To evaluate the ten-year risk change at five years, we considered two scenarios: no change in the baseline parameters except increased age by five (No Change) and alternatively 10% improvement in systolic BP, total and HDL-c, no smoking with five-year increase in age (Reduced Risk Profile). Amongst non-diabetics with <5% risk at baseline, 35% reached or exceeded 5% risk in five years (5% reached or exceed the 7.5% risk) with No Change and 9% reached or exceeded 5% risk in five years (none reached 7.5% risk) with Reduced Risk Profile; furthermore, 94% of the non-diabetic cohort with baseline risk between 3.5%–5% would exceed the 5% and/or 7.5% boundary limit with No Change. Amongst non-diabetics with 5–7.5% baseline risks, 87% reached or exceeded 7.5% with No Change while 30% reached or exceeded 7.5% risk with Reduced Risk Profile.
A significant population cohort at levels below the treatment thresholds will predictably exceed these limits with time with or without improvement in modifiable risk factors and may benefit with more aggressive therapy at baseline. We provide an improved risk calculator that allows for integrating expected risk modification into discussion with an individual. This needs to be prospectively tested in clinical trials.
PLoS ONE 08/2014; 9(8):e104478. DOI:10.1371/journal.pone.0104478 · 3.23 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; 111(7). DOI:10.1016/j.amjcard.2012.12.027 · 3.28 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. DOI:10.1016/j.jacc.2012.04.029 · 16.50 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: 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 10/2011; 34(4):799-810. DOI:10.1002/jmri.22665 · 3.21 Impact Factor
[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. DOI:10.1097/MAJ.0b013e318224ab93 · 1.39 Impact Factor