[Show abstract][Hide abstract] ABSTRACT: Frailty is prevalent in patients with cardiovascular disease, but few studies have evaluated relations between frailty and echocardiographically determined cardiac indexes. To assess the prevalence of frailty and its association with echocardiographic characteristics, we prospectively measured frailty in 257 patients ≥65 years who underwent echocardiography (transthoracic echocardiography [TTE]) from June 2012 to February 2013. Deficits of weight loss, exhaustion, physical activity, gait speed, and handgrip strength were used to categorize patients as frail (≥3 features), intermediately frail (1 or 2 features), or nonfrail (0 features). Pearson correlation was used to examine bivariate associations between TTE variables and frailty. Kaplan-Meier methods were used to estimate overall survival based on frailty status. A multivariable model was used to examine TTE indexes associated with frailty while accounting for age and baseline cardiac co-morbidities. Of the 257 patients studied, 40 (15.6%) were nonfrail, 167 (65.0%) intermediately frail, and 50 (19.4%) frail. Left atrial volume (r = 0.14; p = 0.03), stroke volume (r = -0.19; p <0.01), E/A ratio (r = 0.26; p <0.001), and pulmonary artery systolic pressure (r = 0.33; p <0.001) correlated with fraility. After age and baseline cardiac comorbidities were accounted for, larger left atrial volumes, lower stroke volumes, and higher pulmonary artery systolic pressures remained independently associated with frailty. Frail patients had worse survival compared with nonfrail and intermediately frail patients (p = 0.016 by log-rank). In conclusion, 1/5 of older patients who underwent clinically indicated TTE were frail, with worse survival and a unique fingerprint of TTE findings distinguishing them from nonfrail patients.
The American journal of cardiology 09/2015; DOI:10.1016/j.amjcard.2015.08.023 · 3.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aims:
Blood pressure (BP) responses during dobutamine stress echocardiography (DSE) have not been systematically studied. Consequently, it is not known what constitutes a normal or an abnormal BP response to dobutamine stress. We sought to define the typical BP response during DSE of patients not known to have cardiovascular disease.
Methods and results:
Of 24 134 patients who underwent DSE from November 2003 to December 2012 at Mayo Clinic, Rochester, MN, 2968 were selected for inclusion in this retrospective study. Excluded were patients with a history of hypertension, diabetes, or coronary artery disease, and those taking vasoactive medications. Patients who had baseline and/or stress-induced wall motion abnormalities were also excluded. The distribution of the study population's BP responses during DSE was Gaussian; we defined cut-point values for normative BP responses at 2 SD for each decade of age and for the whole study population. During DSE, systolic BP (SBP) increased from baseline to peak stress (Δ +2.9 ± 24 mmHg, P < 0.0001) and diastolic BP (DBP) decreased (Δ -7.4 ± 14 mmHg). BP changes were age and sex dependent; men and younger patients had greater ΔSBP and lesser ΔDBP, compared with women and older patients. Patients who received atropine had higher peak BP values than patients who did not receive atropine, due to greater ΔSBP (+7.4 ± 26 vs. -0.5 ± 22 mmHg, P < 0.0001) and lesser ΔDBP (-4 ± 14 vs. -9.7 ± 12 mmHg, P < 0.0001). This atropine effect was present in men and women, and was more pronounced in younger patients. The normative peak SBP values ranged from 82 to 182 mmHg.
BP responses during DSE vary and depend on patients' age, gender, and the use of atropine. We describe the typical BP responses seen during DSE and report normative reference values, which can be used for defining normal and abnormal BP responses to dobutamine stress.
[Show abstract][Hide abstract] ABSTRACT: Percent mammographic density (PD) estimates the proportion of stromal, fat, and epithelial breast tissues on the mammogram image. Adjusted for age and body mass index (BMI), PD is one of the strongest risk factors for breast cancer . Inherited factors are hypothesized to explain between 30 and 60% of the variance in this trait [2-5]. However, previously identified common genetic variants account for less than 6% of the variance in PD, leaving much of the genetic contribution to this trait unexplained. We performed the first study to examine whether germline copy number variation (CNV) are associated with PD. Two genome-wide association studies (GWAS) of percent density conducted on the Illumina 660W-Quad were used to identify and replicate the association between candidate CNVs and PD: the Minnesota Breast Cancer Family Study (MBCFS) and controls from the Mayo Venous Thromboembolism (Mayo VTE) Case-Control Study, with 585 and 328 women, respectively. Linear models were utilized to examine the association of each probe with PD, adjusted for age, menopausal status and BMI. Segmentation was subsequently performed on the probe-level test statistics to identify candidate CNV regions that were associated with PD.
Sixty-one probes from five chromosomal regions [3q26.1 (2 regions), 8q24.22, 11p15.3, and 17q22] were significantly associated with PD in MBCFS (p-values <0.0001). A CNV at 3q26.1 showed the greatest evidence for association with PD; a region without any known SNPs. Conversely, the CNV at 17q22 was largely due to the association between SNPs and PD in the region. SNPs in the 8q24.22 region have been shown to be associated with risk of many cancers; however, SNPs in this region were not responsible for the observed CNV association. While we were unable to replicate the associations with PD, two of the five CNVs (3q26.1 and 11p15.3) were also observed in the Mayo VTE controls.
CNVs may help to explain some of the variability in PD that is currently unexplained by SNPs. While we were able to replicate the existence of two CNVs across the two GWAS studies, we were unable to replicate the associations with PD. Even so, the proximity of the identified CNV regions to loci known to be associated with breast cancer risk suggests further investigation and potentially shared genetic mechanisms underlying the PD and breast cancer association.
BMC Research Notes 07/2015; 8(1):297. DOI:10.1186/s13104-015-1212-y
[Show abstract][Hide abstract] ABSTRACT: Among patients with severe aortic stenosis (sAS) and preserved LVEF, those with low-flow, low-gradient sAS (LFLG-sAS) have an adverse prognosis. It has been proposed that LFLG-sAS represents an end-stage point of sAS, but longitudinal information has not been described. The aim was to determine whether LFLG-sAS represents an end-stage consequence of normal-flow, high-gradient sAS (NFHG-sAS) or a different entity.
From our transthoracic echocardiogram (TTE) database, we identified patients with sAS (aortic valve area <1 cm(2)) and preserved LVEF (≥50%), and from these, patients with LFLG-sAS (stroke volume index <35 mL/m(2) and mean transvalvular gradient <40 mm Hg) who had ≥1 additional TTE within five years prior to the index TTE. Patients were age/sex/date matched 2:1 with patients with NFHG-sAS and normal-flow, low-gradient (NFLG)-sAS who also had ≥1 TTE. Included were 1203 TTEs (383 index studies and 820 preceding studies).
In 78 patients with LFLG-sAS, an HG stage preceded the index TTE in only 4 (5%). During the five years preceding the index TTE, patients with LFLG-sAS developed increasing relative wall thickness (0.42 to 0.49; p<0.001) without change in LV mass index. Patients with NFHG-sAS had a marked increase in LV mass index (87 to 115 g/m(2); p<0.001). Patients with LFLG-sAS demonstrated the greatest reduction in LV end-diastolic diameters (-3 vs -1 for NFLG-sAS vs +2 mm for NFHG-sAS; p=0.001), deceleration time (-55 vs -3 vs +3 ms, respectively; p<0.01) and LVEF (-4 vs 0 vs 0%, respectively; p=0.01).
LFLG-sAS is a distinct presentation of sAS preceded by a unique remodelling pathway and is uncommonly preceded by an HG stage.
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[Show abstract][Hide abstract] ABSTRACT: Increased carbon dioxide (CO2) chemosensitivity and augmented exercise ventilation are characteristic of heart failure (HF) patients with central sleep apnea (CSA). The aim of this study was to test the hypothesis that decreased end-tidal CO2 by cardiopulmonary exercise testing predicts CSA in HF patients.
Consecutive ambulatory NYHA II-III HF patients were prospectively evaluated by CO2 chemosensitivity by rebreathe, cardiopulmonary exercise testing and polysomnography (PSG). Subjects were classified as either CSA (n=20) or no sleep apnea (n=13) by PSG; a central apnea-hypopnea index ≥5 defined CSA. Subgroups were compared by t-test or Mann Whitney test and data summarized as mean ± SD; p<0.05 was considered significant.
At rest, subjects with CSA had higher CO2 chemosensitivity (∆V.E/∆PETCO2) (2.3±1.0 vs. 1.6±0.4L/min/mmHg; p=0.02), minute ventilation (V.E) (15±7 vs. 10±3L/min; p=0.02) and lower end-tidal CO2 (PETCO2) (31±4 vs. 35±4mmHg; p<0.01) compared to controls. At peak exercise, the ratio of ventilatory equivalents to expired CO2 (V.E/V.CO2) was higher (43±9 vs. 33±6; p<0.01) and PETCO2 lower (29±6 vs. 36±5mmHg; p<0.01) in CSA subjects. In addition, CO2 chemosensitivity, peak exercise V.E/V.CO2, and PETCO2 were independently correlated to CSA severity as quantified by the apnea hypopnea index (p<0.05). Peak exercise PETCO2 was the measure most strongly associated with CSA with odds ratio of 1.29 (95% confidence interval 1.08-1.54; p=0.01) and AUC of 0.88.
In HF patients with CSA ventilatory drive is increased while awake at rest and during exercise and associated with heightened CO2 chemosensitivity and decreased arterial CO2 setpoint.
[Show abstract][Hide abstract] ABSTRACT: A women-based formula for calculation of age-predicted maximum heart rate [age-predicted maximum heart rate=206-(0.88×age)] was established in asymptomatic volunteer women undergoing treadmill exercise tolerance testing (ETT). We sought to perform a comparison of the performance of this women-based formula for prediction of peak heart rate to the traditional formula [220-age] and our own database-generated prediction formula in a large database of women undergoing ETT.
We performed a retrospective analysis of all consecutive women who underwent symptom-limited Bruce protocol ETT at the Mayo Clinic from 1994 to 2010. Women with known cardiovascular disease or those using beta blockers, calcium channel blockers, or digitalis were excluded. Separate analyses were performed according to symptomatic status.
The study included 11,029 women (89.4% Caucasian) with a mean age 52±12 years; 3,632 (33%) were referred specifically for evaluation of symptoms. Age-predicted maximum heart rate calculated by the traditional formula was achieved by 49.7% of women versus 69.9% by the women-based formula with most of the underestimation observed in older women. Average absolute deviation between achieved and predicted peak heart rate (HR) was 10.85±9.18 bpm for traditional versus 11.98±9.00 for women-based formulas (dependent t=-16.64, p<0.0001). The linear regression line calculated from our population [HR=201-(0.67×age)] was closer to the women-based formula, both in terms of intercept and slope than the traditional formula. Peak HR was shown to be slightly affected (-2.5 bpm) by symptom status at referral, whereas smoking and diabetes more significantly reduced achieved peak HR.
The women-based formula underestimated peak HR, especially in older women, but was observed to be closer in both intercept and slope to the regression line determined from our study in this large population of female patients. These sex-unique observations should be taken into account when determining adequacy and targets for ETT in women.
Journal of Women's Health 03/2015; 24(3):174-81. DOI:10.1089/jwh.2014.4935 · 2.05 Impact Factor