Christopher G Scott

Mayo Clinic - Rochester, Rochester, Minnesota, United States

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Publications (101)630.46 Total impact

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    ABSTRACT: -The goal of this study was to identify genetic determinants of plasma NT-proatrial natriuretic peptide (NT-proANP) in the general community by performing a large-scale genetic association study and to assess its functional significance in in-vitro cell studies and on disease susceptibility. -Genotyping was performed across 16,000 genes in 893 randomly selected individuals, with replication in 891 subjects from the community. Plasma NT-proANP1-98 concentrations were determined using a radioimmunoassay. Thirty-three genome-wide significant single nucleotide polymorphisms (SNPs) were identified in the MTHFR-CLCN6-NPPA-NPPB locus and were all replicated. To assess significance, in-vitro functional genomic studies and clinical outcomes for carriers of a SNP rs5063 (V32M) located in NPPA that represented the most significant variation in this genetic locus, were assessed. The rs5063 variant allozyme in transfected HEK293 cells was decreased to 55±8% of wild-type protein (p=0.01) as assessed by quantitative Western blots. Carriers of rs5063 had lower NT-proANP levels (1427 vs. 2291 pmol/L, p<0.001), higher diastolic blood pressures (75 vs. 73 mmHg, p=0.009) and were at an increased risk for stroke as compared to wild-type subjects independent of age, sex, diabetes, hypertension, atrial fibrillation, and cholesterol levels (hazard ratio 1.6, p=0.004). -This is the first large-scale genetic association study of circulating NT-proANP levels performed with replication and functional assessment that identified genetic variants in the MTHFR-CLCN6-NPPA-NPPB cluster to be significantly associated with NT-proANP levels. The clinical significance of this variation relates to lower NT-proANP levels, higher blood pressures and an increased risk for stroke in the general community.
    Circulation Cardiovascular Genetics 12/2014; · 6.73 Impact Factor
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    ABSTRACT: We sought to investigate the role of aldosterone as a mediator of disease and its relationship with the counter-regulatory natriuretic peptide (NP) system. We measured plasma aldosterone (n=1674; aged≥45 years old) in a random sample of the general population from Olmsted County, MN. In a multivariate logistic regression model, aldosterone analyzed as a continuous variable was associated with hypertension (odds ratio [OR]=1.75; 95% confidence interval [CI]=1.57-1.96; P<0.0001), obesity (OR=1.34; 95% CI=1.21-1.48; P<0.0001), chronic kidney disease (OR=1.39; 95% CI=1.22-1.60; P<0.0001), central obesity (OR=1.47; 95% CI=1.32-1.63; P<0.0001), metabolic syndrome (OR=1.41; 95% CI=1.26-1.58; P<0.0001), high triglycerides (OR=1.23; 95% CI=1.11-1.36; P<0.0001), concentric left ventricular hypertrophy (OR=1.22; 95% CI=1.09-1.38; P=0.0007), and atrial fibrillation (OR=1.24; 95% CI=1.01-1.53; P=0.04), after adjusting for age and sex. The associations with hypertension, central obesity, metabolic syndrome, triglycerides, and concentric left ventricular hypertrophy remained significant after further adjustment for body mass index, NPs, and renal function. Furthermore, aldosterone in the highest tertile correlated with lower NP levels and increased mortality. Importantly, most of these associations remained significant even after excluding subjects with aldosterone levels above the normal range. In conclusion, we report that aldosterone is associated with hypertension, chronic kidney disease, obesity, metabolic syndrome, concentric left ventricular hypertrophy, and lower NPs in the general community. Our data suggest that aldosterone, even within the normal range, may be a biomarker of cardiorenal and metabolic disease. Further studies are warranted to evaluate a therapeutic and preventive strategy to delay the onset and progression of disease, using mineralocorticoid antagonists or chronic NP administration in high-risk subjects identified by plasma aldosterone.
    Hypertension 11/2014; · 6.87 Impact Factor
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    ABSTRACT: To determine if ECG repolarization measures can be used to detect small changes in serum potassium levels in hemodialysis patients. Signal-averaged ECGs were obtained from standard ECG leads in 12 patients before, during, and after dialysis. Based on physiological considerations, five repolarization-related ECG measures were chosen and automatically extracted for analysis: the slope of the T wave downstroke (T right slope), the amplitude of the T wave (T amplitude), the center of gravity (COG) of the T wave (T COG), the ratio of the amplitude of the T wave to amplitude of the R wave (T/R amplitude), and the center of gravity of the last 25% of the area under the T wave curve (T4 COG) (Fig. 1). The correlations with potassium were statistically significant for T right slope (P<0.0001), T COG (P=0.007), T amplitude (P=0.0006) and T/R amplitude (P=0.03), but not T4 COG (P=0.13). Potassium changes as small as 0.2mmol/L were detectable. Small changes in blood potassium concentrations, within the normal range, resulted in quantifiable changes in the processed, signal-averaged ECG. This indicates that non-invasive, ECG-based potassium measurement is feasible and suggests that continuous or remote monitoring systems could be developed to detect early potassium deviations among high-risk patients, such as those with cardiovascular and renal diseases. The results of this feasibility study will need to be further confirmed in a larger cohort of patients. Copyright © 2014 Elsevier Inc. All rights reserved.
    Journal of electrocardiology. 10/2014;
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    ABSTRACT: Low-gradient (LG) severe aortic stenosis (AS) and preserved EF with reduced stroke volume are associated with an adverse prognosis, but the relationship of stroke volume index (SVI) with mortality among a range of values is unknown. We investigated the prognostic impact of SVI in this population.
    Heart (British Cardiac Society) 09/2014; · 5.01 Impact Factor
  • Journal of Cardiac Failure 08/2014; 20(8S):S44. · 3.32 Impact Factor
  • Journal of cardiac failure. 08/2014; 20(8S):S45-S46.
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    ABSTRACT: Rationale and Objectives Increased mammographic breast density is a significant risk factor for breast cancer. A reproducible, accurate, and automated breast density measurement is required for full-field digital mammography (FFDM) to support clinical applications. We evaluated a novel automated percentage of breast density measure (PDa) and made comparisons with the standard operator-assisted measure (PD) using FFDM data. Methods We used a nested breast cancer case–control study matched on age, year of mammogram and diagnosis with images acquired from a specific direct x-ray conversion FFDM technology. PDa was applied to the raw and clinical display (or processed) representation images. We evaluated the transformation (pixel mapping) of the raw image, giving a third representation (raw-transformed), to improve the PDa performance using differential evolution optimization. We applied PD to the raw and clinical display images as a standard for measurement comparison. Conditional logistic regression was used to estimate the odd ratios (ORs) for breast cancer with 95% confidence intervals (CI) for all measurements; analyses were adjusted for body mass index. PDa operates by evaluating signal-dependent noise (SDN), captured as local signal variation. Therefore, we characterized the SDN relationship to understand the PDa performance as a function of data representation and investigated a variation analysis of the transformation. Results The associations of the quartiles of operator-assisted PD with breast cancer were similar for the raw (OR: 1.00 [ref.]; 1.59 [95% CI, 0.93–2.70]; 1.70 [95% CI, 0.95–3.04]; 2.04 [95% CI, 1.13–3.67]) and clinical display (OR: 1.00 [ref.]; 1.31 [95% CI, 0.79–2.18]; 1.14 [95% CI, 0.65–1.98]; 1.95 [95% CI, 1.09–3.47]) images. PDa could not be assessed on the raw images without preprocessing. However, PDa had similar associations with breast cancer when assessed on 1) raw-transformed (OR: 1.00 [ref.]; 1.27 [95% CI, 0.74–2.19]; 1.86 [95% CI, 1.05–3.28]; 3.00 [95% CI, 1.67–5.38]) and 2) clinical display (OR: 1.00 [ref.]; 1.79 [95% CI, 1.04–3.11]; 1.61 [95% CI, 0.90–2.88]; 2.94 [95% CI, 1.66–5.19]) images. The SDN analysis showed that a nonlinear relationship between the mammographic signal and its variation (ie, the biomarker for the breast density) is required for PDa. Although variability in the transform influenced the respective PDa distribution, it did not affect the measurement's association with breast cancer. Conclusions PDa assessed on either raw-transformed or clinical display images is a valid automated breast density measurement for a specific FFDM technology and compares well against PD. Further work is required for measurement generalization.
    Academic Radiology. 08/2014; 21(8):958–970.
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    ABSTRACT: High-sensitivity cardiac troponin assays have potent prognostic value in stable cardiovascular disease cohorts. Our objective was to assess the prognostic utility of a novel cardiac troponin I (cTnI) high-sensitivity assay, independently and in combination with amino-terminal pro-B-type natriuretic peptide (NT-proBNP), for the future development of heart failure and mortality in the general community.
    Clinical chemistry. 07/2014;
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    ABSTRACT: Transthyretin (ATTR) cardiac amyloidosis may be because of mutant transthyretin causing familial amyloid cardiomyopathy (FAC) or wild-type transthyretin causing systemic senile amyloidosis (SSA). Histologic confirmation is often challenging and may require endomyocardial biopsy (EMB). The purpose of this study was to determine the frequency of amyloid protein deposition in positive noncardiac organ biopsy or fat aspiration in patients with ATTR cardiac amyloidosis. The medical records of 286 patients (mean age 66 ± 11, 85% men) with a diagnosis of ATTR cardiac amyloidosis at our institution who underwent noncardiac biopsy or subcutaneous fat aspiration were reviewed, including 186 patients (65%) with FAC and 100 patients (35%) with SSA. One hundred and thirty-one patients (46%) had EMB, all of which were positive. There were 210 patients (73%) with positive noncardiac tissue sampling, including 175 patients (94%) with FAC and 35 patients (35%) with SSA (p <0.001). There were 141 patients (76%) with FAC and 84 patients (84%) with SSA who underwent fat aspiration, and 67% and 14% were positive, respectively, whereas 100 (54%) and 64 (64%) underwent bone marrow biopsy, and 41% and 30% were positive, respectively. Rectal and sural nerve biopsies were performed in 52 (28%) and 54 (29%) patients with FAC and were positive in 81% and 83%, respectively. Biopsy of other noncardiac sites was performed with relatively lower frequency. In conclusion, although EMB is more commonly required to establish the diagnosis of SSA than FAC, noncardiac biopsy or fat aspiration could be considered as initial testing in patients evaluated for ATTR cardiac amyloidosis with characteristic echocardiography findings.
    The American Journal of Cardiology. 05/2014; 113(10):1723–1727.
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    ABSTRACT: Breast density has been established as a major risk factor for breast cancer. We have earlier demonstrated that mammographic texture resemblance (MTR), recognizing the local texture patterns of the mammogram, is also a risk factor for breast cancer, independent of percent breast density. We examine if these findings generalize to another population. Texture patterns were recorded in digitalized pre-diagnosis (3.7 years) film-mammograms of a nested case-control study within the Dutch screening program (S1) comprising of 245 breast cancers and 250 matched controls. The patterns were recognized in the same study using cross-validation to form resemblance scores associated with breast cancer. Texture patterns from S1 were examined in an independent nested case-control study within the Mayo Mammography Health Study cohort (S2) of 226 cases and 442 matched controls: mammograms on average 8.5 years prior to diagnosis, risk factor information and percent mammographic density (PD) estimated using Cumulus were available. MTR scores estimated from S1, S2 and S1 + S2 (the latter two as cross-validations) were evaluated in S2. MTR scores were analyzed as both quartiles and continuously for association with breast cancer using odds ratios (OR) and adjusting for known risk factors including age, body mass index (BMI), and hormonal usage RESULTS: The mean ages of S1 and S2 were 58.0 +/- 5.7 years and 55.2 +/- 10.5 years, respectively. The MTR scores on S1 showed significant capability to discriminate cancers from controls (area under the operator characteristics curve (AUC) = 0.63 +/- 0.02, p < 0.001), which persisted after adjustment for PD. S2 showed an AUC of 0.63, 0.61, and 0.60 based on PD, MTR scores trained on S2, and MTR scores trained on S1, respectively. When adjusted for PD, MTR scores of S2 trained on S1 showed an association with breast cancer for the highest quartile alone: OR in quartiles of controls of ref; 1.04 (0.59-1.81); 0.95 (0.52-1.74); 1.84 (1.10-3.07) respectively. The combined continuous model with both PD and MTR scores based on S1 had an AUC of 0.66 +/- 0.03. The local texture patterns associated with breast cancer risk in S1 were also an independent risk factor in S2. Additional textures identified in S2 did not significantly improve risk segregation. Hence, the textural patterns that indicated elevated risk persisted under differences in x-ray technology, population demographics, follow up time and geography.
    Breast cancer research: BCR 04/2014; 16(2):R37. · 5.87 Impact Factor
  • Journal of the American Society of Hypertension 04/2014; 8(4):e4. · 2.84 Impact Factor
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    ABSTRACT: Transthyretin (ATTR) cardiac amyloidosis may be because of mutant transthyretin causing familial amyloid cardiomyopathy (FAC) or wild-type transthyretin causing systemic senile amyloidosis (SSA). Histologic confirmation is often challenging and may require endomyocardial biopsy (EMB). The purpose of this study was to determine the frequency of amyloid protein deposition in positive noncardiac organ biopsy or fat aspiration in patients with ATTR cardiac amyloidosis. The medical records of 286 patients (mean age 66 ± 11, 85% men) with a diagnosis of ATTR cardiac amyloidosis at our institution who underwent noncardiac biopsy or subcutaneous fat aspiration were reviewed, including 186 patients (65%) with FAC and 100 patients (35%) with SSA. One hundred and thirty-one patients (46%) had EMB, all of which were positive. There were 210 patients (73%) with positive noncardiac tissue sampling, including 175 patients (94%) with FAC and 35 patients (35%) with SSA (p <0.001). There were 141 patients (76%) with FAC and 84 patients (84%) with SSA who underwent fat aspiration, and 67% and 14% were positive, respectively, whereas 100 (54%) and 64 (64%) underwent bone marrow biopsy, and 41% and 30% were positive, respectively. Rectal and sural nerve biopsies were performed in 52 (28%) and 54 (29%) patients with FAC and were positive in 81% and 83%, respectively. Biopsy of other noncardiac sites was performed with relatively lower frequency. In conclusion, although EMB is more commonly required to establish the diagnosis of SSA than FAC, noncardiac biopsy or fat aspiration could be considered as initial testing in patients evaluated for ATTR cardiac amyloidosis with characteristic echocardiography findings.
    The American journal of cardiology 03/2014; · 3.58 Impact Factor
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    ABSTRACT: Severe aortic stenosis (SAS) is a major risk factor for death after non-cardiac surgery, but most supporting data are from studies over a decade old. We evaluated the risk of non-cardiac surgery in patients with SAS in contemporary practice. SAS patients (valve area ≤1 cm(2), mean gradient ≥40 mmHg or peak aortic velocity ≥4 m/s) undergoing intermediate or high-risk surgery were identified from surgical and echo databases of 2000-2010. Controls were matched for age, sex, and year of surgery. Post-operative (30 days) death and major adverse cardiovascular events (MACE), including death, stroke, myocardial infarction, ventricular tachycardia/fibrillation, and new or worsening heart failure, and 1-year survival were determined. There were 256 SAS patients and 256 controls (age 76 ± 11, 54.3% men). There was no significant difference in 30-day mortality (5.9% vs. 3.1%, P = 0.13). Severe aortic stenosis patients had more MACE (18.8% vs. 10.5%, P = 0.01), mainly due to heart failure. Emergency surgery, atrial fibrillation, and serum creatinine levels of >2 mg/dL were predictors of post-operative death by multivariate analysis [area under the curve: 0.81, 95% confidence intervals: 0.71-0.91]; emergency surgery was the strongest predictor of 30-day mortality for both SAS and controls. Severe aortic stenosis was the strongest predictor of 1-year mortality. Severe aortic stenosis is associated with increased risk of MACE. In contemporary practice, perioperative mortality of patients with SAS is lower than previously reported and the difference from controls did not reach statistical significance. Emergency surgery is the strongest predictor of post-operative death. These results have implications for perioperative risk assessment and management strategies in patients with SAS.
    European Heart Journal 02/2014; · 14.72 Impact Factor
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    ABSTRACT: Central sleep apnea (CSA) is common amongst heart failure (HF) patients and is promoted by elevated CO2 chemosensitivity. Left atrial size is a marker of the hemodynamic severity of HF. The aim of this study was to determine if left atrial size predicts chemosensitivity to carbon dioxide (CO2) and central sleep apnea (CSA) in HF patients. HF patients with left ventricular ejection fraction (LVEF) ≤35% underwent PSG for detection of CSA, echocardiography and measurement of CO2 chemosensitivity. CSA was defined as an apnea-hypopnea index ≥15 with ≥50% central apneic events. The relation of clinical and echocardiographic parameters to chemosensitivity and CSA were evaluated by linear regression, estimation of odds ratios (OR) and receiver operator characteristics (ROC). Forty-six subjects without obstructive sleep apnea had complete data for analysis, of whom 25 had CSA. The only parameter that significantly correlated with chemosensitivity was left atrial volume index (LAVI, r = 0.40, P < 0.01). LAVI was greater in those with CSA than those without CSA (59.2 vs 36.4 mL/m2, P < 0.001) and significantly correlated with log-transformed AHI (r = 0.46, P = 0.001). LAVI was the best predictor of CSA (area under the curve = 0.83). A LAVI of ≤33 mL/m2 was associated with 22% risk of CSA while LAVI ≥53 mL/m2 was associated with 92% risk of CSA. Increased LAVI is associated with heightened CO2 chemosensitivity and greater frequency of CSA. LAVI may be useful to guide referral for PSG for detection of CSA in HF patients.
    Chest 02/2014; · 7.13 Impact Factor
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    ABSTRACT: Objective To assess the diagnostic capability of handheld echocardiography (HHE) compared with transthoracic echocardiography (TTE) performed and evaluated by experienced sonographers and expert echocardiographers. Patients and Methods We conducted a prospective study of adult outpatients undergoing comprehensive TTE between July 9, 2012, and April 3, 2013. Experienced sonographers performed a detailed, standardized examination using a handheld ultrasound device that included 2-dimensional and color Doppler images from standard imaging windows. Images from TTE and HHE were independently interpreted by expert echocardiographers to whom the other study was masked. Agreement between the standard TTE and the HHE reports was analyzed. Results The study group contained 190 patients (mean ± SD age, 62±17 years; 49% male [n=93]). The κ values were 0.52 for left ventricular (LV) enlargement, 0.52 for right ventricular enlargement, 0.62 for regional wall motion abnormalities, 0.73 for aortic stenosis, and 0.61 for mitral regurgitation. Lin concordance correlation coefficients ranged from 0.89 for LV end-systolic diameter to 0.78 for LV end-diastolic diameter. In 51 patients (27%), echocardiographic findings were discordant between HHE and standard TTE. The most common discordant finding was the presence vs absence of any regional wall motion abnormalities. In discordant cases, HHE tended to underestimate, rather than overestimate, the severity of abnormal findings. Conclusion In experienced hands, HHE shows moderate correlation with standard TTE, but discordant findings were present in 27% of patients. Even when performed and interpreted by experienced operators, HHE should not be used as a surrogate for standard TTE. Trial Registration clinicaltrials.gov Identifier: NCT01558518
    Mayo Clinic Proceedings 01/2014; · 5.79 Impact Factor
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    ABSTRACT: To determine the frequency and prognostic significance of abnormal exercise echocardiographic results for patients achieving a workload of 10 or more metabolic equivalents during treadmill exercise echocardiography. Patients who underwent treadmill exercise echocardiography from November 1, 2003, through December 31, 2008, and exercised for 9 or more minutes using the Bruce protocol (N=7236) were included. Clinical and exercise echocardiographic characteristics and outcomes were evaluated. Variables associated with abnormal exercise echocardiographic results and mortality were identified. Exercise echocardiographic results were positive for ischemia in 862 patients (12%). Extensive ischemia developed in 265 patients (4%). For patients with normal exercise echocardiographic results, all-cause and cardiovascular mortality rates were 0.30% and 0.05% per person-year of follow-up, respectively. For patients who had extensive ischemia, all-cause and cardiovascular mortality rates were 0.84% and 0.25% per person-year of follow-up, respectively. Patients at highest risk were those who had extensive and severe regional wall motion abnormalities at rest (n=58), and their all-cause and cardiovascular mortality rates were 2.65% and 0.76% per person-year of follow-up. Exercise echocardiographic variables did not identify sizable patient subgroups at risk for death and did not provide incremental prognostic information (C statistic was 0.74 compared with 0.73 for the clinical plus exercise electrocardiography model). Patients achieving a workload of 10 or more metabolic equivalents during treadmill exercise testing do not often have extensive ischemic abnormalities on exercise echocardiography. Although exercise echocardiographic results provide some prognostic information, it is not of incremental value for these patients, whose short-term and medium-term prognosis is excellent.
    Mayo Clinic Proceedings 12/2013; 88(12):1408-19. · 5.79 Impact Factor
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    ABSTRACT: Understanding whether mammographic density (MD) is associated with all breast tumor subtypes and whether the strength of association varies by age is important for utilizing MD in risk models. Data were pooled from six studies including 3414 women with breast cancer and 7199 without who underwent screening mammography. Percent MD was assessed from digitized film-screen mammograms using a computer-assisted threshold technique. We used polytomous logistic regression to calculate breast cancer odds according to tumor type, histopathological characteristics, and receptor (estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2)) status by age (<55, 55--64, and >=65 years). MD was positively associated with risk of invasive tumors across all ages, with a two-fold increased risk for high (>51%) versus average density (11-25%). Women ages <55 years with high MD had stronger increased risk of ductal carcinoma in situ (DCIS) compared to women ages 55--64 and >=65 years (Page-interaction = 0.02). Among all ages, MD had a stronger association with large (>2.1 cm) versus small tumors and positive versus negative lymph node status (P's < 0.01). For women ages <55 years, there was a stronger association of MD with ER-negative breast cancer than ER-positive tumors compared to women ages 55--64 and >=65 years (Page-interaction = 0.04). MD was positively associated with both HER2-negative and HER2-positive tumors within each age group. MD is strongly associated with all breast cancer subtypes, but particularly tumors of large size and positive lymph nodes across all ages, and ER-negative status among women ages <55 years, suggesting high MD may play an important role in tumor aggressiveness, especially in younger women.
    Breast cancer research: BCR 11/2013; 15(6):R104. · 5.87 Impact Factor
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    ABSTRACT: Increased serum leptin concentration has been linked to increased ventilation in patients with mild heart failure (HF). However, in animal models the absence of leptin has also been associated with increased ventilation. This study evaluated the relationship of circulating leptin concentration with exercise ventilation in HF patients. Fifty-eight consecutive ambulatory HF patients were stratified by quintiles of leptin concentration, with a lowest quintile of mean leptin concentration of 1.8 ± 8.9 ng/mL and a highest of 33.3 ± 30.3 ng/mL. Peak exercise ventilatory efficiency (VE/VCO2) was significantly elevated in the lowest (46 ± 6 vs 34 ± 4; P < .01) as well as in the highest (38 ± 8 vs 34 ± 4; P < .05) leptin concentration quintiles compared with the reference middle quintile. Multiple regression analysis adjusted for confounders such as age, sex, and body mass index showed leptin concentration to be independently inversely correlated to VE/VCO2 in the low-to-normal quintiles (β = -0.64; P < .01), positively in the normal-to-high quintiles (β = 0.52; P = .02), and positively correlated to PETCO2 in the low-to-normal quintiles (β = 0.59; P = .01) and inversely in the normal-to-high quintiles (β = -0.53; P = .02). In HF patients, both high and low leptin concentrations are associated with increased VE/VCO2 and decreased PETCO2 with a nonlinear U-shaped relationship, suggesting that either leptin deficiency or leptin resistance may modulate ventilatory control in HF patients.
    Journal of cardiac failure 11/2013; 19(11):756-761. · 3.25 Impact Factor
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    ABSTRACT: Abstract Background: More than 100 transthyretin (TTR) variants have been identified which cause familial systemic amyloidosis. It has been increasingly recognized that TTR variants of familial systemic amyloidosis contribute to clinical characteristics, including age at diagnosis, cardiac phenotype and survival. Methods: Two hundred and eighty-two patients who underwent genotyping for TTR variants were identified. This study focused on 116 patients representing the three most common TTR variants; T60A (n = 58), V30M (n = 37) and V122I (n = 21). The remaining subjects (n = 61) were distributed amongst 33 different genotypes and excluded from analysis. Results: Age at diagnosis was similar by genotype. Septal, posterior wall thickness, right ventricular systolic pressure and left ventricular mass index were greater and LVEF lower in the V122I subgroup. At mean follow up of 3.0 ± 2.6 years there were 62 deaths. V30M patients had the best survival. Survival was similar between V122I and T60A patients. The association of genotype with mortality persisted after adjustments for clinical variables. Conclusions: For familial TTR amyloidosis cardiac involvement is frequent and mortality high for T60A, V122I and V30M genotypes. Specific genotype predicted severity of phenotypic expression as measured by echocardiography and survival.
    Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis 10/2013; · 2.51 Impact Factor
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    ABSTRACT: Among patients with severe aortic stenosis (AS) and preserved ejection fraction (EF), those with low-gradient and reduced stroke volume may have an adverse prognosis. We investigated the prognostic impact of stroke volume using the recently proposed flow-gradient classification. We examined 1,704 consecutive patients with severe AS (aortic valve area <1.0 cm(2)) and preserved EF (≥50%) using 2-D and Doppler echocardiography. Patients were stratified by stroke volume index (<35 ml/m(2) (LF) vs. ≥35 ml/m(2) (NF)) and aortic gradient (<40 mmHg (LG) vs. ≥40 mmHg or (HG)) into 4 groups (NF/HG, NF/LG, LF/HG, LF/LG). NF/LG (n=352, 21%), was associated with favorable survival with medical management (2 year estimate 82% vs. 67% in NF/HG, p<0.0001). LF/LG severe AS (n=53, 3%), was characterized by lower EF, more prevalent atrial fibrillation and heart failure, reduced arterial compliance, and reduced survival (2 year estimate 60% vs. 82% in NF/HG, p<0.001). By multivariable analysis, LF/LG pattern was the strongest predictor of mortality (HR 3.26 (1.71, 6.22) p<0.001 vs. NF/LG). Aortic valve replacement (AVR) was associated with a 69% mortality reduction (HR 0.31 (0.25, 0.39) p<0.0001) in LF/LG and NF/HG, with no survival benefit associated with AVR in NF/LG and LF/HG. NF/LG severe AS with preserved EF exhibits favorable survival with medical management and impact of AVR on survival was neutral. LF/LG severe AS is characterized by a high prevalence of atrial fibrillation, heart failure and reduced survival, and AVR was associated with improved survival. These findings have implications for evaluation of AS severity and subsequent management.
    Circulation 09/2013; · 15.20 Impact Factor