Moderate Cardiorespiratory Fitness Is Positively Associated With Resting Metabolic Rate in Young Adults

ObjectiveTo determine whether moderate cardiorespiratory fitness (CRF) or moderate to vigorous physical activity (MVPA) is associated with elevations in resting metabolic rate (RMR) similar to findings previously observed in endurance athletes.Participants and MethodsUsing a cross-sectional design, we measured CRF, RMR, body composition, energy expenditure, and time in MVPA via an arm-based activity monitor in 423 young adults (mean age, 27.6 years). Based on the results of a fitness test, participants were classified into CRF tertiles (low, moderate, or high) by sex.ResultsThere were significant differences among the low-, moderate-, and high-CRF groups for mean ± SD body mass index (calculated as the weight in kilograms divided by the height in meters squared) (28.1±4.1, 25.1±3.4, and 23.6±2.5, respectively; P<.001) and fat mass (28.8±9.7, 20.5±8.2, and 14.8±6.5 kg, respectively; P<.001) but not fat-free mass (53.1±11.5, 53.5±12.4, and 54.7±12.1 kg, respectively; P=.49). There were no differences in mean ± SD unadjusted RMR among the groups (1533.2±266.2, 1519.7±267.6, and 1521.9±253.9 kcal/d, respectively). However, after statistical adjustment for differences in body composition, the moderate- and high-CRF groups had a higher RMR compared with low-CRF individuals by 39.7 and 59.9 kcal/d, respectively (P<.05). After further adjustment for MVPA, RMR was higher in the high-CRF group compared with the low-CRF group by 51.2 kcal/d (P<.05).ConclusionIn this large sample of young adults representing a range of CRF, there was a positive stepwise gradient in RMR across tertiles of CRF independent of body composition. Also, MVPA was independently associated with RMR, although this relationship was modest. These findings underscore the multidimensional role of CRF and MVPA on health.Trial Registrationclinicaltrials.gov Identifier: NCT01746186     

Safety and Efficacy of Extracorporeal Shock Wave Myocardial Revascularization Therapy for Refractory Angina Pectoris

ObjectiveTo assess the safety and efficacy of extracorporeal shockwave myocardial revascularization (ESMR) therapy in treating patients with refractory angina pectoris.Patients and MethodsA single-arm multicenter prospective trial to assess safety and efficacy of the ESMR therapy in patients with refractory angina (class III/IV angina) was performed. Screening exercise treadmill tests and pharmacological single-photon emission computed tomography (SPECT) were performed for all patients to assess exercise capacity and ischemic burden. Patients were treated with 9 sessions of ESMR to ischemic areas over 9 weeks. Efficacy end points were exercise capacity by using treadmill test as well as ischemic burden on pharmacological SPECT at 4 months after the last ESMR treatment. Safety measures included electrocardiography, echocardiography, troponin, creatine kinase, and brain natriuretic peptide testing, and pain questionnaires.ResultsFifteen patients with medically refractory angina and no revascularization options were enrolled. There was a statistically significant mean increase of 122.3±156.9 seconds (38% increase compared with baseline; P=.01) in exercise treadmill time from baseline (319.8±157.2 seconds) to last follow-up after the ESMR treatment (422.1±183.3 seconds). There was no improvement in the summed stress perfusion scores after pharmacologically induced stress SPECT at 4 months after the last ESMR treatment in comparison to that at screening; however, SPECT summed stress score revealed that untreated areas had greater progression in ischemic burden vs treated areas (3.69±6.2 vs 0.31±4.5; P=.03). There was no significant change in the mean summed echo score from baseline to posttreatment (0.4±5.1; P=.70). The ESMR therapy was performed safely without any adverse events in electrocardiography, echocardiography, troponins, creatine kinase, or brain natriuretic peptide. Pain during the ESMR treatment was minimal (a score of 0.5±1.2 to 1.1±1.2 out of 10).ConclusionIn this multicenter feasibility study, ESMR seems to be a safe and efficacious treatment for patients with refractory angina pectoris. However, larger sham-controlled trials will be required to confirm these findings.     

Bone Mass in Individuals With Chronic Spinal Cord Injury: Associations With Activity-Based Therapy,Neurologic and Functional Status,a Retrospective Study

ObjectiveTo describe the prevalence of osteoporosis and its association with functional electrical stimulation (FES) use in individuals with spinal cord injury (SCI)-related paralysis.DesignRetrospective cross-sectional evaluation.SettingClinic.ParticipantsConsecutive persons with SCI (N=364; 115 women, 249 men) aged between 18 and 80 years who underwent dual-energy x-ray absorptiometry (DXA) examinations.InterventionsNot applicable.Main Outcome MeasurePrevalence of osteoporosis defined as DXA T score ≤−2.5.ResultsThe prevalence of osteoporosis was 34.9% (n=127). Use of FES was associated with 31.2% prevalence of osteoporosis compared with 39.5% among persons not using FES. In multivariate adjusted logistic regression analysis, FES use was associated with 42% decreased odds of osteoporosis after adjusting for sex, age, body mass index, type and duration of injury, Lower Extremity Motor Scores, ambulation, previous bone fractures, and use of calcium, vitamin D, and anticonvulsant; (adjusted odds ratio [OR]=.58; 95% confidence interval [CI], .35–.99; P=.039). Duration of injury >1 year was associated with a 3-fold increase in odds of osteoporosis compared with individuals with injury <1 year; (adjusted OR=3.02; 95% CI, 1.60–5.68; P=.001).ConclusionsFES cycling ergometry may be associated with a decreased loss of bone mass after paralysis. Further prospective examination of the role of FES in preserving bone mass will improve our understanding of this association.     

Imaging Pandora's Box: Incidental Findings in Elderly Patients Evaluated for Transcatheter Aortic Valve Replacement

ObjectiveTo determine the frequency and clinical impact of noncardiovascular incidental findings (IFs) detected on preoperative computed tomographic angiography (CTA) of the chest/abdomen/pelvis performed in elderly patients with severe aortic stenosis being considered for transcatheter aortic valve replacement (TAVR).Patients and MethodsThe CTA studies for 424 consecutive patients being evaluated for TAVR between January 1, 2009, through January 24, 2012, were reviewed for noncardiovascular IFs (62.0% male; median ± SD age, 82±8.3 years). The electronic medical record was reviewed to assess for subsequent clinical management and survival.ResultsPotentially pathologic IFs (PPIFs) were present in 285 patients (67.2%). The mean ± SD number of PPIFs per patient was 1.1±1.0 (range, 0-4). Factors associated with higher numbers of PPIFs were reduced ejection fraction (P=.02) and history of smoking (P=.06). Potentially pathologic incidental findings prompted clinical work-up in 39 patients (9.2%) and delayed or canceled treatment plans for aortic stenosis in 7 patients (1.7%). The number needed to image to diagnose a new malignancy or medical condition was 19. The number of PPIFs was predictive of poor overall survival before (hazard ratio, 1.58; 95% CI, 1.31-1.88) and after (hazard ratio, 1.45; 95% CI, 1.19-1.76) adjustment for baseline clinical variables (P<.001 for both).ConclusionThis investigation found that PPIFs are common in elderly patients undergoing TAVR-CTA scans and, once discovered, commonly generate further clinical evaluation. Higher numbers of PPIFs may be predictive of poorer survival, but further study is required to guide the appropriateness of pursuing diagnostic evaluations for asymptomatic PPIFs in this elderly population.     

[18F]-Fluorodeoxyglucose–Positron Emission Tomography in Patients With Active Myelopathy

ObjectiveTo report and compare spinal cord [¹⁸F]-fluorodeoxyglucose–positron emission tomography (FDG-PET) metabolism in 51 patients with active myelopathy.Patients and MethodsWe retrospectively identified patients from January 1, 2001, through December 31, 2011, with active myelopathy in whom FDG-PET was performed. Inclusion criteria were (1) intramedullary myelopathy, (2) neoplastic/inflammatory etiology, and (3) FDG-PET performed after myelopathy onset. Exclusion criteria were (1) extramedullary myelopathy, (2) radiation-associated myelopathy, (3) no pathological confirmation of neoplasm, and (4) inactive myelopathy. Diagnostic categories of nonsarcoid inflammatory, neoplastic, and neurosarcoid were based on their final myelopathic diagnosis. Two radiologists who independently assessed FDG-PET for spinal cord hypermetabolism and maximum standardized uptake value (SUVmax) were blinded to the underlying etiology.ResultsFifty-one patients (53% women) with a median age of 60 years (range, 20-82 years) were included. Inflammatory myelopathic diagnoses (n=24) were as follows: paraneoplastic (n=13), autoimmune/other (n=5), inflammatory demyelinating (n=4), and transverse myelitis (n=2). Neoplastic diagnoses (n=21) were as follows: intramedullary metastases (n=12), intramedullary lymphoma/leukemia (n=7), and primary intramedullary neoplasm (n=2). Six patients had neurosarcoid myelopathy. Spinal cord hypermetabolism was more common with neoplastic myelopathy than with nonsarcoid inflammatory myelopathy (17 of 21 [81%] vs 6 of 24 [25%]; P<.001). Agreement between radiologist’s assessments was excellent (κ=0.88). Median SUVmax was greater in neoplastic than in nonsarcoid inflammatory causes of myelopathy (3.3 g/mL vs 1.9 g/mL; P<.001). The FDG-PET hypermetabolism was seen in 3 of the 6 patients (50%) with neurosarcoid myelopathy (median SUVmax, 2.6 g/mL; range, 1.8-12.2 g/mL).ConclusionSpinal cord FDG-PET hypermetabolism in patients with active myelopathy may be reliably detected and was more common in neoplastic than in inflammatory myelopathies in this study. Future investigation of spinal cord FDG-PET is indicated to assess its potential contributions in evaluating active myelopathies.     

Software-Guided Insulin Dosing: Tight Glycemic Control and Decreased Glycemic Derangements in Critically Ill Patients

ObjectiveTo determine whether glycemic derangements are more effectively controlled using software-guided insulin dosing compared with paper-based protocols.Patients and MethodsWe prospectively evaluated consecutive critically ill patients treated in a tertiary hospital surgical intensive care unit (ICU) between January 1 and June 30, 2008, and between January 1 and September 30, 2009. Paper-based protocol insulin dosing was evaluated as a baseline during the first period, followed by software-guided insulin dosing in the second period. We compared glycemic metrics related to hyperglycemia, hypoglycemia, and glycemic variability during the 2 periods.ResultsWe treated 110 patients by the paper-based protocol and 87 by the software-guided protocol during the before and after periods, respectively. The mean ICU admission blood glucose (BG) level was higher in patients receiving software-guided intensive insulin than for those receiving paper-based intensive insulin (181 vs 156 mg/dL; P=.003, mean of the per-patient mean). Patients treated with software-guided intensive insulin had lower mean BG levels (117 vs 135 mg/dL; P=.0008), sustained greater time in the desired BG target range (95-135 mg/dL; 68% vs 52%; P=.0001), had less frequent hypoglycemia (percentage of time BG level was <70 mg/dL: 0.51% vs 1.44%; P=.04), and showed decreased glycemic variability (BG level per-patient standard deviation from the mean: ±29 vs ±42 mg/dL; P=.01).ConclusionSurgical ICU patients whose intensive insulin infusions were managed using the software-guided program achieved tighter glycemic control and fewer glycemic derangements than those managed with the paper-based insulin dosing regimen.     

Activity-Based Therapy for Recovery of Walking in Individuals With Chronic Spinal Cord Injury: Results From a Randomized Clinical Trial

ObjectiveTo examine the effects of activity-based therapy (ABT) on neurologic function, walking ability, functional independence, metabolic health, and community participation.DesignRandomized controlled trial with delayed treatment design.SettingOutpatient program in a private, nonprofit rehabilitation hospital.ParticipantsVolunteer sample of adults (N=48; 37 men and 11 women; age, 18–66y) with chronic (≥12mo postinjury), motor-incomplete (ASIA Impairment Scale grade C or D) spinal cord injury (SCI).InterventionsA total of 9h/wk of ABT for 24 weeks including developmental sequencing; resistance training; repetitive, patterned motor activity; and task-specific locomotor training. Algorithms were used to guide group allocation, functional electrical stimulation utilization, and locomotor training progression.Main Outcome MeasuresNeurologic function (International Standards for Neurological Classification of Spinal Cord Injury); walking speed and endurance (10-meter walk test, 6-minute walk test, and Timed Up and Go test); community participation (Spinal Cord Independence Measure, version III, and Reintegration to Normal Living Index); and metabolic function (weight, body mass index, and Quantitative Insulin Sensitivity Check).ResultsSignificant improvements in neurologic function were noted for experimental versus control groups (International Standards for Neurological Classification of Spinal Cord Injury total motor score [5.1±6.3 vs 0.9±5.0; P=.024] and lower extremity motor score [4.2±5.2 vs −0.6±4.2; P=.004]). Significant differences between experimental and control groups were observed for 10-meter walk test speed (0.096±0.14m/s vs 0.027±0.10m/s; P=.036) and 6-minute walk test total distance (35.97±48.2m vs 3.0±25.5m; P=.002).ConclusionsABT has the potential to promote neurologic recovery and enhance walking ability in individuals with chronic, motor-incomplete SCI. However, further analysis is needed to determine for whom ABT is going to lead to meaningful clinical benefits.     

Perioperative Doses of Ondansetron or Dolasetron Do Not Lengthen the QT Interval

ObjectiveTo test the primary hypothesis that ondansetron or dolasetron extends the rate-corrected QT electrocardiographic interval (QTc) greater than 60 milliseconds or increases the fraction of patients with QTc greater than 500 milliseconds in patients having noncardiac surgery, and the secondary hypothesis that QTc prolongation is worse in diabetic patients.Patients and MethodsWe extracted data from the Cleveland Clinic's Perioperative Health Documentation System between March 25, 2006, and September 30, 2010, and additional perioperative medications from Cleveland Clinic pharmacy's Epic Cost of Goods Sold (COGS) system. We searched for patients who had a preoperative electrocardiogram within 1 month of surgery and postoperatively within 2 hours. We excluded patients given an antiemetic drug other than ondansetron or dolasetron perioperatively, and those given amiodarone.ResultsA total of 1429 patients given serotonin-3 receptor (5HT3R) antagonists and 1022 controls met the enrollment criteria. Seventeen percent of patients given 5HT3R antagonists (n=242) and 22% of controls (n=220) had postoperative QTc exceeding 500 milliseconds. Mean ± SD presurgical and postsurgical QTc, respectively, were 438±37 milliseconds and 464±41 milliseconds for 5HT3R antagonist patients and 443±40 milliseconds and 469±47 milliseconds for control patients. Univariable mean ± SD perioperative increases in QTc were 26±39 and 26±48 milliseconds in the 2 groups. After adjusting for confounding variables, there were no differences in the mean increase in QTc in patients who were and were not given 5HT3R antagonists: –0.1 milliseconds (97.5% CI, –5.2 to 5.0 milliseconds; multivariable P=.97). The QTc was prolonged, but not significantly, in diabetic patients given 5HT3R antagonists (P=.16).ConclusionsThe average QTc prolongation from baseline was only 6%. Perioperative use of ondansetron or dolasetron was not associated with extended QT prolongation, and these results did not vary by diabetic status. Perioperative use of 5HT3R antagonists does not produce potentially dangerous perioperative electrocardiographic changes and does not seem to warrant a drug safety warning from the Food and Drug Administration.     

Maternal Inactivity: 45-Year Trends in Mothers’ Use of Time

ObjectiveTo examine 45-year trends in time use and physical activity energy expenditure (PAEE) in a nationally representative sample of US mothers.Participants and MethodsWe quantified time allocation to physical activity (PA), sedentary behaviors (SED), and PAEE from 1965 to 2010 in mothers with older children (MOC) (>5 to ≤18 years) and mothers with younger children (MYC) (≤5 years). Physical activity was the sum of time allocated to housework, child care, laundry, food preparation, postmeal cleanup, and exercise. Sedentary behavior was the sum of time spent in a vehicle and using screen-based media. Physical activity energy expenditure was calculated using body weights from national surveys and metabolic equivalents.ResultsFrom 1965 to 2010, the time allocated to PA decreased by 11.1 h/wk (from 32.0 to 20.9 h/wk) in MOC and by 13.9 h/wk (from 43.6 to 29.7 h/wk) in MYC. The time spent in SED increased by 7.0 h/wk in MOC (from 17.7 to 24.7 h/wk) and increased by 5.7 h/wk in MYC (from 17.0 to 22.7 h/wk). Physical activity energy expenditure decreased by 1237.6 kcal/wk (176.8 kcal/d) in MOC (from 5835.3 to 4597.7 kcal/wk), and in MYC, PAEE decreased by 1572.5 kcal/wk (224.6 kcal/d), from 7690.5 to 6118.0 kcal/wk.ConclusionThere was a significant reallocation of time by mothers from PA (eg, housework) to SED (eg, watching television) between 1965 and 2010. Given the essential role of PA for health and the potential for the intergenerational transmission of obesity and obesogenic behaviors, these results suggest that maternal inactivity may be an important target for the primary prevention of chronic noncommunicable diseases and obesity.     

Antineutrophil Cytoplasmic Antibody-Associated Renal Vasculitis Treated With Autologous Mesenchymal Stromal Cells: Evaluation of the Contribution of Immune-Mediated Mechanisms

We report the first case of renal antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis treated with autologous mesenchymal stromal cells (MSCs). A 73-year-old man was admitted to the hospital for malaise, weight loss, and oliguria. His serum creatinine level was 2.7 mg/dL but it rapidly increased to 7.8 mg/dL; urinalysis showed proteinuria and hematuria, and the ANCA to myeloperoxidase with a perinuclear pattern (pANCA) titer was high (132 IU/mL). Renal biopsy showed necrotizing crescentic glomerulonephritis. Standard immunosuppressive therapy (cyclophosphamide and corticosteroids) was ineffective. Rituximab therapy was started, but it was discontinued after the third dose to minimize the risk of systemic spread of a severe oral Candida infection and to prevent superinfections that were facilitated by leukopenia. The patient received autologous MSCs, 1.5 × 10⁶ cells/kg body weight, intravenously. After 7 days, his serum creatinine level decreased to 2.2 mg/dL, pANCA titer decreased to 75 IU/mL, and urinalysis findings normalized. Eight months later, he received a second MSC infusion because his serum creatinine level increased. In 1 week, his creatinine level decreased to 1.9 mg/dL and his pANCA titer decreased to 14 IU/mL. Immunosuppressive therapy was subsequently withdrawn. At the last follow-up visit, 12 months after the second MSC infusion, the patient remained in clinical remission without any therapy. Infusion of MSCs induced expansion of the T-lymphocyte subset expressing a regulatory T-cell phenotype (CD4⁺CD25⁺Foxp3⁺) and a notable reduction in interferon-γ, interleukin 6, and tumor necrosis factor serum levels.     

Critical congenital heart disease screening does not predict car seat tolerance screen outcomes

BackgroundCar Seat Tolerance Screening (CSTS) and Critical Congenital Heart Disease (CCHD) screens were both implemented to identify infants with cardiorespiratory distress. We hypothesized that the CCHD screen would be poorly sensitive to predict a failed CSTS for many reasons.MethodsRetrospective record review of infants in 2013 who qualified for CSTS. Calculated sensitivity, specificity, predictive value (PV) of a failed CCHD screen to identify those infants who failed their CSTS.Results270 subjects underwent both screens and 14 failed a CSTS (5.2%). Of these, 1 failed the CCHD and 1 had an equivocal result. None were diagnosed with CCHD. An abnormal CCHD (failed or equivocal) had a sensitivity = 14.3% and a PV = 40% for predicting CSTS failure.ConclusionsCCHD screening is poorly sensitive and has poor PV for identifying those infants who are at risk of failing a CSTS. We therefore cannot recommend replacement of the CSTS with routine CCHD screening.     

Cardiorespiratory Fitness and the Paradoxical BMI-Mortality Risk Association in Male Veterans

ObjectiveTo assess the effect of fitness status on the paradoxical body mass index (BMI)-mortality risk association.Patients and MethodsFrom February 1, 1986, through December 30, 2011, we assessed fitness and BMI in 18,033 male veterans (mean age, 58.4±11.4 years) in 2 Veterans Affairs Medical centers. We established 3 fitness categories on the basis of peak metabolic equivalents achieved during an exercise test as well as 5 BMI categories. The primary outcome was all-cause mortality.ResultsDuring the follow-up period (median, 10.8 years, comprising a total of 207,168 person-years), 5070 participants (28%) died. After adjusting for age, risk factors, muscle-wasting diseases, medications, and year of entry, mortality risk was higher for individuals with a BMI of 20.1 to 23.9 kg/m² (hazard ratio [HR], 1.21; 95% CI, 1.12-1.30) and 18.5 to 20.0 kg/m² (HR, 1.56; 95% CI, 1.37-1.77) than for those with a BMI of 24.0 to 27.9 kg/m²; mortality risk was not increased for those with a BMI of 28.0 kg/m² or greater. When stratified by fitness, the trend was similar for low-fit and moderate-fit individuals. However, mortality risk was not increased for high-fit individuals across BMI categories. When fitness status was considered within each BMI category, mortality risk increased progressively with decreased fitness and was more pronounced for moderate-fit (HR, 2.52; 95% CI, 2.06-3.08) and low-fit (HR, 2.48; 95% CI, 2.0-3.06) individuals with a BMI of 18.5-20.0 kg/m². Mortality risk was not significantly increased for high-fit individuals (HR, 1.17; 95% CI, 0.78-1.78; P=.45).ConclusionA high mortality risk associated with low BMI levels was observed only in moderate-fit and low-fit individuals, and not in high-fit individuals. Thus, fitness greatly affects the paradoxical BMI-mortality risk association. Furthermore, our findings indicate that lower BMI levels do not increase the risk for premature death as long as they are associated with high fitness. Thus, the paradoxically higher mortality risk observed with lower body weight as represented by lower BMI is likely the result of unhealthy reduction in body weight and, perhaps most importantly, considerable loss of lean body mass.     

Influence of Self-Efficacy and Coping on Quality of Life and Social Participation After Acquired Brain Injury: A 1-Year Follow-Up Study

ObjectivesTo investigate the relations linking self-efficacy and coping to quality of life (QOL) and social participation and what effect self-efficacy, changes in self-efficacy, and coping style have on long-term QOL and social participation.DesignProspective clinical cohort study.SettingGeneral hospitals, rehabilitation centers.ParticipantsPatients with newly acquired brain injury (ABI) (N=148) were assessed at baseline (start outpatient rehabilitation or discharge hospital/inpatient rehabilitation; mean time since injury, 15wk) and 1 year later (mean time since injury, 67wk).InterventionsNot applicable.Main Outcome MeasuresQOL was measured with the EuroQuol 5D (the EQ-5D index and the EQ-5D visual analog scale [EQ VAS]) and the 9-item Life Satisfaction Questionnaire (LiSat-9), social participation with the modified Frenchay Activities Index, coping with the Coping Inventory for Stressful Situations, and self-efficacy with the Traumatic Brain Injury Self-efficacy Questionnaire.ResultsAt baseline, self-efficacy moderated the effect of emotion-oriented coping on the EQ-5D index and of avoidance coping on the EQ VAS. Self-efficacy mediated the relation between emotion-oriented coping and LiSat-9. An increase in self-efficacy over time predicted better scores on the EQ-5D index (β=.30), the EQ VAS (β=.49), and LiSat-9 (β=.44) at follow-up. In addition, higher initial self-efficacy (β=.40) predicted higher LiSat-9 scores at follow-up; higher initial emotion-oriented coping (β=−.23) predicted lower EQ VAS scores at follow-up. Higher modified Frenchay Activities Index scores at follow-up were predicted by higher self-efficacy (β=.19) and higher task-oriented coping (β=.14) at baseline (combined R²=5.1%).ConclusionsSelf-efficacy and coping predict long-term QOL but seem less important in long-term social participation. High self-efficacy protects against the negative effect of emotion-oriented coping. Enhancing self-efficacy in the early stage after ABI may have beneficial long-term effects.     

Relationship Between Exercise Heart Rate and Age in Men vs Women

ObjectiveTo analyze a large cohort of patients who underwent exercise testing and also report sex differences in other exercise heart rate (HR) parameters to determine whether separate sex-based equations to predict peak HR are indicated.Patients and MethodsPatients aged 40 to 89 years who performed treadmill exercise tests (Bruce protocol) from September 21, 1993, to December 20, 2010, were included. Patients with cardiovascular disease or taking HR-attenuating drugs were excluded. After analyses on preliminary cohort, peak HR–modifying factors were eliminated to obtain a pure data set. Analysis of variance was used to test difference in HR responses by sex with age adjustment.ResultsA total of 37,010 patients (67.3% men) were included in the preliminary cohort. Men had higher peak HR (166±17 vs 163±16 beats/min [bpm]; P<.001), HR reserve (90±19 vs 84±17 bpm; P<.001), and HR recovery (19±8 vs 18±9 bpm; P<.03). Poor exercise capacity, current smoking, diabetes, and obesity had significant peak HR–lowering effects (all P<.001). In a pure cohort of 19,013 patients (51.3% of full cohort) without these factors, regression lines approximated more closely the traditional line of 220 – age. For men, the regression line in our final cohort was peak HR = 220 – 0.95 × age. For women, both slope (0.79 bpm/y) and intercept (210 bpm) were still substantially different from those obtained with the traditional formula.ConclusionThe HR responses to exercise are different in men and women. The HR response of men was close to that obtained with the traditional formula, but peak HR in women had a lower intercept and decreased more slowly with age. A separate formula for peak HR in women appears to be appropriate.     

Cardiac Amyloidosis Without Increased Left Ventricular Wall Thickness

ObjectivesTo determine how often left ventricular wall thickness (LVWT) is normal and to assess the effect of LVWT on clinical outcomes of patients with immunoglobulin light chain (AL) cardiac amyloidosis.Patients and MethodsA total of 117 patients with systemic AL amyloidosis were retrospectively categorized from April 1, 1995, to September 15, 2012; group A included cardiac amyloidosis patients with an LVWT greater than 12 mm (45 patients); group B, cardiac amyloidosis patients with an LVWT of 12 mm or less (25 patients); and group C, no evidence of cardiac amyloidosis (47 patients). We compared echocardiographic parameters and survival rates among the 3 groups.ResultsNo differences were found between groups A and B in the following parameters: left ventricular ejection fraction (median, 56% [interquartile range (IQR), 46%-63%] vs 56% [IQR, 49%-63%], P=.76), left arterial volume index (median, 44.5 [IQR, 38.5-59.7] vs 43.9 [IQR, 33.8-57.1] mL/m², P=.79), eˈ (median, 0.04 [IQR, 0.03-0.05] vs 0.05 [IQR, 0.04-0.06] m/s, P=.10), and E/eˈ (early diastolic mitral inflow velocity (E)/eˈ) (median, 18.4 [IQR, 12.0-23.3] vs 18.0 [IQR, 13.6-25.0], P=.98). Patients in group C exhibited significantly different values for these parameters (median, 65% [IQR, 61%-69%], 23.4 [IQR, 18.0-29.0] mL/m², 0.08 [IQR, 0.06-0.09] m/s, and 8.8 [IQR, 7.2-10.5], respectively; all P<.001). The survival rates were statistically different, with median survival times of 422, 729, and 2080 days in groups A, B, and C, respectively (P=.002). Using multivariate Cox proportional hazards regression analysis, we found that age, an N-terminal pro–B-type natriuretic peptide level of 1800 pg/mL or greater, E/eˈ, and complete hematologic remission were significant predictors of survival.ConclusionsA third of patients with AL cardiac amyloidosis were diagnosed as having an LVWT of 12 mm or less. Because appropriate therapy can improve the survival of patients with AL cardiac amyloidosis, early detection by sensitive diagnostic methods should be pursued even when LVWT is not increased.     

Examining the Function In Sitting Test for Validity,Responsiveness, and Minimal Clinically Important Difference in Inpatient Rehabilitation

ObjectivesTo determine the responsiveness of the Function In Sitting Test (FIST), compare scores at admission and discharge from inpatient rehabilitation (IPR) with other balance and function measures, and determine the minimal clinically important difference (MCID).DesignProspective, nonblinded, reference-standard comparison study.SettingFour accredited inpatient rehabilitation units.ParticipantsPopulation-based sample of adults (N=125) with sitting balance dysfunction, excluding persons with spinal cord injury, significant bracing/orthotics, and inability to perform testing safely.InterventionsNot applicable.Main Outcome MeasuresFIST, FIM, and Berg Balance Scale (BBS) at admission and discharge, and Global Rating of Change for function and balance at discharge.ResultsThe FIST demonstrated good to excellent concurrent validity with the BBS and FIM at admission and discharge (Spearman ρ=.71–.85). Significant improvement (P<.000; 95% confidence interval [CI], 10.73–15.41) occurred in the FIST from admission (mean ± SD: 36.81±15.53) to discharge (mean ± SD: 49.88±6.90). The standard error of measurement for the FIST was 1.40, resulting in a minimal detectable change of 5.5 points. The receiver operator characteristic curve differentiated participants with meaningful balance changes (area under the curve, .78; P>.000; 95% CI, .66–.91), with a change in FIST score of ≥6.5 points designating the MCID. Findings support the strong responsiveness of the FIST during IPR as evidenced by the large effect size (.83), standardized response mean (1.04), and index of responsiveness (1.07).ConclusionsIn this study, the FIST correlated well with balance and function measures (concurrent validity) and was responsive to change during IPR. A clinically meaningful change was indicated by an increase in score of ≥6.5 points.     

Prognostic Value of Exercise Capacity in Patients With Coronary Artery Disease: The FIT (Henry Ford ExercIse Testing) Project

ObjectiveTo examine the prognostic value of exercise capacity in patients with nonrevascularized and revascularized coronary artery disease (CAD) seen in routine clinical practice.Patients and MethodsWe analyzed 9852 adults with known CAD (mean ± SD age, 61±12 years; 69% men [n=6836], 31% black race [n=3005]) from The Henry Ford ExercIse Testing (FIT) Project, a retrospective cohort study of patients who underwent physician-referred stress testing at a single health care system between January 1, 1991, and May 31, 2009. Patients were categorized by revascularization status (nonrevascularized, percutaneous coronary intervention [PCI], or coronary artery bypass graft [CABG] surgery) and by metabolic equivalents (METs) achieved on stress testing. Using Cox regression models, hazard ratios for mortality, myocardial infarction (MI), and downstream revascularizations were calculated after adjusting for potential confounders, including cardiac risk factors, pertinent medications, and stress testing indication.ResultsThere were 3824 all-cause deaths during median follow-up of 11.5 years. In addition, 1880 MIs, and 1930 revascularizations were ascertained. Each 1-MET increment in exercise capacity was associated with a hazard ratio (95% CI) of 0.87 (0.85-0.89), 0.87 (0.85-0.90), and 0.86 (0.84-0.89) for mortality; 0.98 (0.96-1.01), 0.88 (0.84-0.92), and 0.93 (0.90-0.97) for MI; and 0.94 (0.92-0.96), 0.91 (0.88-0.95), and 0.96 (0.92-0.99) for downstream revascularizations in the nonrevascularized, PCI, and CABG groups, respectively. In each MET category, the nonrevascularized group had similar mortality risk as and higher MI and downstream revascularization risk than the PCI and CABG surgery groups (P<.05).ConclusionExercise capacity was a strong predictor of mortality, MI, and downstream revascularizations in this cohort. Furthermore, patients with similar exercise capacities had an equivalent mortality risk, irrespective of baseline revascularization status.     

Use of Functional Aerobic Capacity Based on Stress Testing to Predict Outcomes in Normal,Overweight, and Obese Patients

ObjectiveTo determine the poorly studied relationship between functional aerobic capacity (FAC) as measured by treadmill stress testing and mortality in normal, overweight, and obese patients.Patients and MethodsPatients were identified retrospectively from the stress testing database at Mayo Clinic in Rochester, Minnesota. We selected 5328 male nonsmokers (mean ± SD age, 51.8±11.5 years) without baseline cardiovascular disease who were referred for treadmill exercise testing between January 1, 1986, and December 31, 1991, and classified them by body mass index (BMI) into normal-weight (18.5-24.9 kg/m²), overweight (25.0-29.9 kg/m²), and obese (≥30 kg/m²) categories. Functional aerobic capacity was assessed by maximal exercise test results based on age- and sex-specific metabolic equivalents, and patients were stratified into fitness quintiles. Cox proportional hazards analysis was used to determine the relationship of all-cause mortality to fitness in each BMI category.ResultsThere were 322 deaths during 14 years of follow-up. After adjustment for age and exercise confounders, FAC predicted mortality in the 3 BMI groups. Hazard ratios for FAC less than 80% of predicted vs a reference group with normal BMI and fitness (FAC ≥100%) were 1.754 (95% CI, 0.874-3.522), 1.962 (1.356-2.837), and 1.518 (1.056-2.182) for the normal, overweight, and obese groups, respectively. The CIs of the hazard ratios overlapped with no statistically significant differences (P>.05).ConclusionA significant increase in mortality occurs with FAC below 80% of predicted for overweight and obese subjects and below 70% for normal weight subjects. Our results suggest that clinicians need not adjust the standard for low fitness in obese patients.     

Serum Polyclonal Immunoglobulin Free Light Chain Levels Predict Mortality in People With Chronic Kidney Disease

ObjectiveTo determine whether elevated serum polyclonal free light chain (FLC) levels predict mortality in a population of individuals with chronic kidney disease (CKD).Patients and MethodsFrom January 2, 2006, through July 31, 2007, we recruited a cohort of 848 people with CKD who were not receiving renal replacement therapy and did not have monoclonal gammopathy. We measured serum kappa FLC and lambda FLC isotype levels to determine combined FLC (cFLC) levels. The cohort was prospectively followed up for a median of 63 months (interquartile range, 0-93 months). Cox regression analysis was performed to determine variables predictive of mortality.ResultsHigh cFLC levels were an independent risk factor for death (hazard ratio [HR], 2.71; 95% CI, 1.98-3.70; P<.001). Other independent risk factors were age (HR, 1.79; 95% CI, 1.52-2.10; P<.001), South Asian ethnicity (HR, 0.33; 95% CI, 0.14-0.64; P=.02), preexisting cardiovascular disease (HR, 1.59; 95% CI, 1.09-2.31; P=.02), and high-sensitivity C-reactive protein (HR, 1.13; 95% CI, 1.00-1.28; P=.04). Neither estimated glomerular filtration rate nor albuminuria was an independent risk factor for death.ConclusionHigh cFLC levels independently predict mortality in people with CKD.     

Characterization of a Phenotype-Based Genetic Test Prediction Score for Unrelated Patients With Hypertrophic Cardiomyopathy

ObjectivesTo determine the prevalence and spectrum of mutations and genotype-phenotype relationships in the largest hypertrophic cardiomyopathy (HCM) cohort to date and to provide an easy, clinically applicable phenotype-derived score that provides a pretest probability for a positive HCM genetic test result.Patients and MethodsBetween April 1, 1997, and February 1, 2007, 1053 unrelated patients with the clinical diagnosis of HCM (60% male; mean ± SD age at diagnosis, 44.4±19 years) had HCM genetic testing for the 9 HCM-associated myofilament genes. Phenotyping was performed by review of electronic medical records.ResultsOverall, 359 patients (34%) were genotype positive for a putative HCM-associated mutation in 1 or more HCM-associated genes. Univariate and multivariate analyses identified the echocardiographic reverse curve morphological subtype, an age at diagnosis younger than 45 years, a maximum left ventricular wall thickness of 20 mm or greater, a family history of HCM, and a family history of sudden cardiac death as positive predictors of positive genetic test results, whereas hypertension was a negative predictor. A score, based on the number of predictors of a positive genetic test result, predicted a positive genetic test result ranging from 6% when only hypertension was present to 80% when all 5 positive predictor markers were present.ConclusionIn this largest HCM cohort published to date, the overall yield of genetic testing was 34%. Although all the patients were diagnosed clinically as having HCM, the presence or absence of 6 simple clinical/echocardiographic markers predicted the likelihood of mutation-positive HCM. Phenotype-guided genetic testing using the Mayo HCM Genotype Predictor score provides an easy tool for an effective genetic counseling session.