Higher Exercise Capacity Research Articles

How to live until 90 – Factors predicting survival in 75-year-olds from the general population

Background: The objective of the study was to explore potential predictors common in a clinical context, for survival to age 90 among 75-year-olds from Sweden’s general population. We performed a prospective community-based cohort study with 15-year follow-up among 75-year-olds from a defined geographical area. Methods: Of 1,100 inhabitants born in 1922 and living in Vasteras in 1997, 618 were invited to participate in a cardiovascular health survey, and 432 individuals accepted participation. Among them, 380 subjects (61% of those originally invited; 191 men and 189 women) had complete records for all examined variables. Variables were categorized into 4 groups: 1) Previous or present disease; 2. Exercise test variables; 3. Conventional risk factors; 4. Other potential risk factors. Through Area Under the Receiver Operating Characteristic (AUROC) curves, strong predictors for survival until age 90 (AUROC≥0.60) in men and women were selected. Results: The strongest individual predictors for reaching the age of 90 were metabolic equivalents and systolic blood pressure (BP) rise during exercise test, QTc interval in resting electrocardiogram (ECG) and peak expiratory flow (PEF) in men, and, for women, white blood cell (WBC) counts and systolic blood pressure BP rise during exercise. The strongest independent predictor in multivariable models were metabolic equivalents in men and WBC counts in women (explained variability 22 and 6%). Conclusions: High exercise capacity in men and low WBC in women were the strongest independent predictors of reaching age 90 among the clinical predictors at 75. The strongest modifiable predictor was exercise capacity in men, which can be improved by physical training.

Abstract 9333: Prognostic Value of Stress Echocardiography In Patients Achieving a High Exercise Workload (=10 Metabolic Equivalents) and Submaximal Heart Rate Response

Background: High exercise capacity (≥10 metabolic equivalents, METS) is a predictor of favorable prognosis. Submaximal studies (<85% maximum predicted heart rate, MPHR) may lead to non-diagnostic results and indeterminate outcomes. The purpose of this study was to examine the prognostic value of stress echocardiography (SEcho) in patients achieving high exercise capacity and submaximal heart rate response. Methods: We evaluated 81 patients (50 ± 13 years; 62% male) achieving nine minutes (≥10 METS) and <85% MPHR with treadmill SEcho. Resting left ventricular ejection fraction and regional wall motion were assessed. The left ventricle was divided into 16 segments and scored on 5-point scale of wall motion. Abnormal SEcho was defined as stress-induced ischemia (wall-motion score of ≥1 grade). Followup (3.4 ± 1.5 years) for non-fatal myocardial infarction and cardiac death (n = 2) were obtained. Results: By univariate analysis, the number of new ischemic wall motion abnormalities (hazard ratio = 2.5, confidence interval 1.2 - 5.3, p = 0.02) was the most significant predictor of cardiac events. Cumulative survival in patients achieving nine minutes (≥10 METS) and <85% MPHR was significantly worse in patients with abnormal (ischemic) vs. normal (nonischemic) SEcho (1.1%/year vs. 0.2%/year, p = 0.02)[Graph]. Conclusions: The ability to achieve nine minutes (≥10 METS), despite <85% MPHR by treadmill SEcho was associated with a benign prognosis (~1.0%/year). In the setting of high achieved exercise capacity and <85% MPHR, SEcho results (presence or absence of ischemia) were further able to sub-stratify this low risk group.

Prognostic Value of Treadmill Stress Echocardiography at Extremes of Exercise Performance: Submaximal <85% Maximum Predicted Heart Rate versus High Exercise Capacity ≥10 Metabolic Equivalents

Submaximal stress testing or achieving <85% maximum predicted heart rate (MPHR) may lead to nondiagnostic results and indeterminate outcomes. High exercise capacity (≥ 10 metabolic equivalents, METS) is a predictor of favorable prognosis. The purpose of this study was to evaluate the prognostic value of submaximal or high exercise capacity stress echocardiography. We evaluated 1781 patients (55 ± 13 years; 59% male) undergoing treadmill stress echocardiography divided into 811 patients with submaximal (<85% MPHR) and 970 patients with high exercise capacity (≥ 10 METS). Resting left ventricular ejection fraction and regional wall motion were assessed. The left ventricle was divided into 16 segments and scored on 5-point scale of wall motion. Abnormal stress echocardiography was defined as stress-induced ischemia (wall-motion score of ≥ 1 grade). Follow-up (3.3 ± 1.5 years) for nonfatal myocardial infarction (MI) (n = 40) and cardiac death (n = 52) were obtained. By univariate analysis, echocardiographic variables of ejection fraction, peak wall-motion score index (WMSI) and number of new ischemic wall-motion abnormalities were significant predictors of cardiac events. Cumulative survival was significantly worse in patients with abnormal (ischemic) versus normal (nonischemic) stress echocardiography in submaximal (4.4%/year vs. 1.3%/year, P < 0.0001) and high exercise capacity (1.5%/year vs. 0.2%/year, P < 0.0001) studies. Multivariate Cox proportional hazards analysis identified number of new ischemic wall-motion abnormalities as the strongest predictor of cardiac events (P < 0.05) in both groups. Despite normal stress echocardiography, the inability to achieve 85% MPHR conferred a higher, intermediate cardiac event rate of 2.9%/year. The ability to achieve 9 minutes (≥ 10 metabolic equivalents, METS) conferred an overall low cardiac event rate of 0.4%/year. However, the absence or presence of ischemia by stress echocardiography was able to further risk stratify patients with either submaximal or high exercise capacity studies.

Value of an Exercise Workload ≥10 Metabolic Equivalents for Predicting Inducible Myocardial Ischemia

We sought to identify extensive ischemia on exercise echocardiography (ExE) relative to workload in patients without known coronary artery disease and to investigate whether ExE is useful in predicting outcomes in those with high exercise capacity (≥10 metabolic equivalents [METs]) plus a maximal test (≥85% of their maximal age-predicted heart rate [MAPHR]). The analysis was performed on 4269 patients who underwent ExE, of whom 3995 achieved ≥85% of their MAPHR. These patients were divided according to the reached workload (<7, 7-9, or ≥10 METs) and compared for ExE results. Outcomes in the group achieving ≥10 METs plus ≥85% of their MAPHR (n=2221) were specifically assessed. Ischemia was defined as new/worsening wall motion abnormalities with exercise. ExE results were different between groups because the METs were lower. Still, among patients achieving ≥10 METs plus ≥85% of their MAPHR, 9.3% had extensive ischemia and 6% multiterritory disease. During follow-up in this subgroup, 108 patients died and 42 had a major cardiac event. Annualized mortality and major cardiac event rates were 0.84% and 0.32% in patients without ischemia versus 2.26% and 0.84% in those with ischemia, respectively (P<0.001 and P=0.002, respectively). Ischemia was an independent predictor of mortality (hazard ratio, 1.88; 95% confidence interval, 1.23-2.89; P=0.004) and major cardiac event (hazard ratio, 2.39; 95% confidence interval, 1.22-4.71; P=0.01). Patients without known coronary artery disease achieving ≥10 METs plus ≥85% of their MAPHR may still have ischemia. However, the low event rates even in those with ischemia limit the usefulness of imaging for assessing outcomes in this group.

Value of an exercise workload higher or equal to 10 metabolic equivalents for predicting low risk of inducible myocardial ischemia

Objectives: To identify the prevalence of extensive ischemia on exercise echocardiography (ExE) relative to workload in patients without known coronary artery disease (CAD), and to investigate whether ExE is useful to assess outcome in those with high exercise capacity (≥10 metabolic equivalents (METs) plus a maximal test (≥85% of their Maximal Age-Predicted Heart Rate (MAPHR). Background: Recent work has suggested low reach of imaging in patients who achieve ≥10 METs and ≥85% of their MAPHR during exercise. Methods: Retrospective analysis on 4,269 patients who underwent ExE, of whom 3,995 achieved ≥85% of their MAPHR. These patients were divided according to the reached workload (<7, 7 to 9, or ≥10 METs) and were compared for ExE results, particularly the prevalence of extensive ischemia (≥3 ischemic segments). Outcome in the group achieving ≥10 METs plus ≥85% of their MAPHR (n=2,221) was specifically assessed. Ischemia was defined as the development of new/worsening wall motion abnormalities with exercise. Results: ExE results were significantly different between groups as the achieved METs were lower. Still, among patients achieving ≥10 METs plus ≥85% of their MAPHR, 6% had extensive ischemia and 9.3% multiterritory disease. During follow-up of 4.3±3.4 years in this group, 108 patients died and 42 had a MACE. The 5-year mortality and MACE rates were 4.2% and 1.6% in patients without ischemia vs. 11.3% and 4.2% in those with ischemia (p <0.001, and p=0.002, respectively). Ischemia was an independent predictor of mortality (hazard ratio [HR] 1.88, 95% confidence interval [CI] 1.23-2.89, p=0.004) and MACE (HR 2.39, 95% CI 1.22-4.71, p=0.01). Conclusions: Patients with theoretically good prognosis by exercise testing, such those without known CAD achieving ≥10 METs plus ≥85% of their MAPHR may still have significant risk. Switching these patients to exercise ECG testing alone could deny important medical treatment or revascularization procedures.

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Abstract 294: Association Between Exercise Frequency, Performance, and Health-Related Quality of Life in Heart Failure Patients

Background: Heart failure (HF) is one of the leading causes of morbidity and mortality in the United States. Exercise intolerance and impaired quality of life (QOL) are common limitations. Cardiopulmonary exercise test (CPX) is used for risk stratification and diagnosis of ischemia in HF patients. In HF patients interested in rehabilitation protocols, higher exercise capacity has been linked to better QOL. The primary objective is to determine the association between QOL and exercise parameters in an unselected HF population. Methods: English-speaking HF patients scheduled for routine CPX were approached prospectively. Each consenting person completed 2 page survey on home environment, exercise routine, and QOL. Disease-specific QOL was measured using the Minnesota Living with Heart Failure Questionnaire (MLHF), a 21-item instrument that assesses perceptions of QOL related to their HF (scored 0 to 105 with lower score representing better QOL). Generic QOL was measured using a one-item visual analog scale (VAS), scored 0 to 100 with higher score representing better QOL. Patients were stratified by age, disability, exercise routine, HRR &gt; 18 at 1minute, working status, emotional support, gender, live alone, and peak RER&gt;1. Results of CPX were measured [e.g., heart rate recovery in 1 minute (HRR), peak oxygen uptake (peakVO2), respiratory exchange ratio (RER)]. Data was analyzed with Chi-square, t-test, and ANOVA using STATA. Results: We enrolled 167 patients (Mean age 54 + 11, Female 26%, peakVO2 15.7±6, peak RER 1.2±.12). The MLHF score was 44 + 28 and mean VAS score was 61.9±22. QOL is worse among patients who are younger (P=0.0042), non-working (51.3 VS. 34.1, P-0.001), and disabled (54.7 VS. 38.3). There is no association between QOL and exercise frequency, gender, emotional support, or living alone. Patients with HRR &gt; 18 had better MLHF scores (38.0±28 vs. 52.9±26, p&lt;0.001). PeakVO2 is moderately correlated to MLHF scores in all age categories; however, patients who lived alone did not have a strong correlation between peakVO2 and MLHF (r2=-0.256, p=0.21 vs. r2=-0.47, p&lt;0.001). Conclusion: Routine exercise is not associated with better QOL in an unselected HF population. Performance on CPX was associated with QOL regardless of age. Although emotional support is not linked with QOL, those getting support from siblings tended to have a worse QOL than others. Strategies to improve QOL among HF patients should focus on factors beyond exercise.

Abstract 9509: Prognostic Value of Treadmill Stress Echocardiography at Extremes of Exercise Workload: Submaximal, &lt;85% Maximum Predicted Heart Rate and High Exercise Capacity, ≥10 Metabolic Equivalents

Background: Submaximal stress testing, &lt;85% maximum predicted heart rate (MPHR) may be non diagnostic and high exercise capacity (≥10 metabolic equivalents, METS) is a predictor of favorable prognosis. The purpose of this study was to evaluate the prognostic value of submaximal and high exercise capacity stress echocardiography (EXSE). Methods: We evaluated 1781 patients (55 ± 13 years; 59% male) undergoing EXSE divided into 811 with submaximal (&lt;85% MPHR) and 970 with high exercise capacity (≥10 METS). Resting left ventricular ejection fraction and wall motion was assessed. The left ventricle was divided into 16 segments and scored on a 5-point scale of wall motion. Abnormal EXSE was defined as stress-induced ischemia (wall-motion score of ≥1 grade). Follow-up (3.3 ± 1.5 years) for non-fatal myocardial infarction (n = 40) and cardiac death (n = 52) were obtained. Results: By univariate analysis, exercise work load (p&lt;0.0001), ejection fraction (p&lt;0.0001) and number of new ischemic wall motion abnormalities (p&lt;0.0001) were significant predictors of cardiac events. Cumulative survival was significantly worse in patients with abnormal vs. normal EXSE in submaximal (4.5%/year vs. 1.4%/year, p&lt;0.0001) and high exercise capacity groups (1.1%/year vs. 0.2%/year, p=0.001) (Graph). Multivariate logistic regression analysis identified number of new ischemic wall motion abnormalities as the best predictor of cardiac events (p&lt;0.05) in both groups. Conclusions: Despite normal EXSE, inability to achieve 85% MPHR conferred a higher, intermediate event rate of 3.0%/year. The ability to achieve nine minutes (≥10 METS) on EXSE conferred a benign prognosis (1.0%/year) regardless of EXSE results. In either group (submaximal or high exercise capacity), EXSE results (absence or presence ischemia) were useful in further, effectively risk stratifying patients.

Abstract 310: Aerobic Exercise Training Improves Blood Pressure Variability in Obese Female Mice.

Background: Clinical issues related with obesity and diabetes are focused not only on metabolic dysfunctons, but also on cardiovascular pathologies which are the likely cause of morbidity and mortality in these patients. In this sense, blood pressure variability (BPV) has been reported to be associated with an adverse cardiovascular prognosis. Ob/ob mice have been used as a model of type 2 diabetes and obesity. However, the effects of aerobic exercise training on cardiovascular parameters in this model are unknown. Objective: The aim of this study was to evaluate the blood pressure variability in trained youth obese mice. METHODS: Female ob/ob mice (4 weeks) were randomized into sedentary (OS, n=11) or trained (OT, n=8) (treadmill,5 days/w, 60 min/d, during 8 wks) groups. Blood glucose was measured by reagent strips. Arterial pressure signals were recorded using a data acquisition system. Results: The OT group had higher exercise capacity compared to the OS group. OT group had reduced body weight and blood glucose (45±2g, 133±3 mg/dL) compared to OS group (50±2g e 169±8 mg/dL). Mean arterial pressure and heart rate were similar between groups (OS: 106 ± 4mmHg and 513± 18bpm vs. OT: 104 ± 6 mmHg and 514±28bpm). The BPV and the low frequency band of BPV were higher in the OS (23 ± 3mmHg2 and 7 ± 1 mmHg2) compared to the OT group (15 ± 2 mmHg2 and 5 ± 1 mmHg2). Moreover, the spontaneous baroreflex sensitivity, represented by alpha index, was lower in the sedentary group (1.2 ± 0.3 ms/mmHg) compared to the trained group (1.9 ± 0.2 ms/mmHg). Conclusion: Our results suggest that early physical training in obese mice can be effective in attenuating the increase in weight and blood glucose in addition to improving blood pressure variability in these animals. Sources of funding: FAPESP,CNPq

Muscular exercise capacity and body fat predict VO2peakin heart transplant recipients

Heart transplant (HTx) recipients usually have reduced exercise capacity, with reported VO2peak levels of 50-70% of predicted values. This study aimed to evaluate central and peripheral factors predictive of VO2peak. Fifty-one clinically stable HTx recipients >18 years old and 1-8 years after HTx, underwent maximal exercise testing on a treadmill. Clinical laboratory, haemodynamic and echocardiographic data, lung function, and isokinetic muscle strength and muscular exercise capacity were recorded. The mean ± SD age was 52 ± 16 years, 71% were male, and time from HTx was 4.1 ± 2.2 years. The patients were assigned to one of two groups: VO2peak ≤or >27.3 ml/kg/min, which was the median value, corresponding to 80% of predicted value. The group with the higher VO2peak had significantly lower body mass index, body fat, and triglycerides, and significantly higher body water, muscular exercise capacity, high-density lipoprotein (HDL) cholesterol, lung function, mitral annular velocity, peak ventilation, O2 pulse, and VE/VCO2 slope. Donor age, recipient age, sex, medication, ischaemic time, cardiac dimensions, systolic function, and chronotropic responses during exercise were similar. Multiple regression analysis showed that muscular exercise capacity and body fat were the strongest VO2peak predictors. Chronotropic incompetence is not a limiting factor for exercise capacity in a population of relatively fit HTx patients. The most significant predictors, representing only peripheral factors, are similar to those often determining VO2peak in healthy, non-athletic individuals. Our findings emphasize the importance of a low percentage of body fat and high muscular exercise capacity in order to attain a sufficient VO2peak level after HTx.

Effects of physical exercise and high fructose diet on cardiac autonomic control in rats

The aim of this study was to evaluate the cardiovascular autonomic control in trained youth male rats fed with high fructose diet. Weaned male Wistar rats (21 days) fed with fructose in drinking water (10%, 8wks) were randomized into sedentary (FS, n=5) and trained (FT, n=8), treadmill running,5 days/w, 60 min/d, during 8 wks) groups. Insulin resistance was evaluated by Glucose Tolerance Test. Arterial pressure signals were recorded using a data acquisition system (Windaq, 2KHz) in conscious and freely animals. Vagal and sympathetic tonus were measured by pharmacological blockade. The FT group had higher exercise capacity and lower insulin resistance compared to the FS group. Mean arterial pressure was similar between groups (FS: 124 ± 6 vs. FT: 125 ± 3 mmHg), however, the FT group presented resting bradycardia (339 ± 10 bpm) compared to the FS group (366 ± 13bpm). The sympathetic tone was lower in the FT group (41 ± 13bpm) compared to the FS (80 ± 6 bpm), however vagal tone was similar between groups. Thus, our results suggest that physical training during lifespan can be effective in attenuating the autonomic dysfunction resulting from high fructose consumption.

Comparison of Exercise Treadmill Testing With Cardiac Computed Tomography Angiography Among Patients Presenting to the Emergency Room With Chest Pain

Background— The aims of our study were to (1) examine how data from exercise treadmill testing (ETT) can identify patients who have coronary plaque or stenosis, using CT angiography (CTA) as the reference standard, and (2) identify patient characteristics that may be used in selecting ETT versus CTA. Methods and Results— The Rule Out Myocardial Infarction Using Computer-Assisted Tomography (ROMICAT) trial was an observational cohort study of acute chest pain patients presenting to the emergency department with normal initial troponin and a nonischemic ECG. Univariate and multivariable analyses were performed to assess the relationship of baseline clinical data and ETT parameters with coronary plaque and stenosis on CTA. Of the 220 patients who had ETT (mean age, 51 years; 63% men), 21 (10%) had positive results. A positive ETT had a sensitivity of 30% and specificity of 93% to detect &gt;50% stenosis. The sensitivity increased to 83% after excluding uninterpretable segments and evaluating the ability to detect a &gt;70% stenosis. Predictors of plaque included older age, male sex, diabetes, hypertension, hyperlipidemia, lower functional capacity, and a lower Duke Treadmill Score. Both a positive ETT and a low Duke Treadmill Score were significant univariate and multivariable predictors of stenosis &gt;50% on CTA Whereas the prevalence of stenosis by CTA was greater among patients with more risk factors, coronary stenosis was not present among men &lt;40 years old or women &lt;50 years old or individuals who achieved at least 13 metabolic equivalents on ETT. Conclusions— Among low- to intermediate-risk patients with acute chest pain, a positive ETT has a limited sensitivity but high specificity for the detection of &gt;50% stenosis by CTA. Although patients with a high number of clinical risk factors are more likely to have obstructive coronary artery disease, those who are young or who would be expected to have a very high exercise capacity are unlikely to have coronary stenosis and therefore may benefit from initial ETT testing instead of CTA.

Physical fitness affects the quality of single operator cardiocerebral resuscitation in healthcare professionals

Sustained external chest compressions during cardiocerebral resuscitation (CCR) are physically demanding. It might be hypothesized that a high cardiopulmonary exercise capacity and/or muscle strength delays the development of physical fatigue and, consequently, preserves CCR quality. We intended to assess the impact of cardiopulmonary exercise capacity and muscle strength on CCR quality. Fifteen healthcare professionals (10 men and five women, mean age 34±9 years) performed a 15-min hands-on CCR session on an adult training manikin. CCR compression depth (from which CCR quality was calculated) and frequency were monitored. During CCR we assessed serial blood lactate concentrations, and provided continuous heart rate monitoring. Relationships were examined between participant characteristics, peak cardiopulmonary exercise capacity, ventilatory threshold, maximal muscle strength, muscle strength endurance and CCR quality. Significant univariate correlations were found between 15-min CCR quality and body height (r=0.53), ventilatory threshold (r=0.67), peak oxygen uptake capacity (r=0.54), peak cycling power output (r=0.54), and maximal isometric elbow extension strength (r=0.55) (P<0.05). CCR quality was significantly lower in females, when compared with males (P<0.05). Within different timeframes, CCR quality was mainly related to the ventilatory threshold up to the first 5 min (P<0.05), whereas CCR quality was mainly related to maximal isometric elbow extension strength after 5 min (P<0.05). In healthcare professionals, the ventilatory threshold is significantly related to CCR quality during the first few min. Healthcare professionals who are regularly involved in CCR should therefore aim to achieve/sustain a high aerobic exercise capacity. Study registration number: ISRCTN70447230, www.controlled-trials.com/ISRCTN70447230.

Abstract 9888: Is There Additional Prognostic Value of Stress Echocardiography in Patients Achieving a High Exercise Capacity (≥10 Metabolic Equivalents)?

Background: High exercise capacity is a predictor of favorable prognosis in patients with known or suspected coronary artery disease. The purpose of this study was to examine the prognostic value of stress echocardiography (SEcho) in patients achieving high exercise workload. Methods: We evaluated 970 patients (51 ± 11 years; 62% male) achieving nine minutes (≥10 metabolic equivalents) on a Bruce protocol by treadmill SEcho. Resting left ventricular ejection fraction and regional wall motion were assessed. The left ventricle was divided into 16 segments and scored on 5-point scale of wall motion. Abnormal SEcho was defined as stress-induced ischemia (wall-motion score of ≥1 grade). Followup (3.4 ± 1.5 years) for non-fatal myocardial infarction (n = 11) and cardiac death (n = 3) were obtained. Results: By univariate analysis, both peak wall motion score index (p=0.002) and number of new ischemic wall motion abnormalities (p&lt;0.0001) were significant predictors of cardiac events. Cumulative survival in patients achieving nine minutes (≥10 metabolic equivalents) was signficantly worse in patients with abnormal (ischemic) vs. normal (nonischemic) SEcho (1.1%/year vs. 0.2%/year, p=0.001)(Graph). Multivariate logistic regression analysis identified number of new ischemic wall motion abnormalities as the strongest predictor of cardiac events (RR 1.27, 95% CI 1.0-1.6, p=0.01). Conclusions: The ability to achieve nine minutes (≥10 metabolic equivalents) by treadmill stress echocardiography confers a benign prognosis (~1.0%/year). In the setting of high achieved exercise capacity, stress echocardiography (absence or presence of ischemia) is further able to effectively risk stratify a low risk group.

Cardiorespiratory fitness in young adults with a history of renal transplantation in childhood

Limited knowledge exists on cardiorespiratory fitness (CR fitness) in adults having a renal transplant (Rtx) during childhood. Our aim was to assess CR fitness (V0(2peak)) with a maximal treadmill test in former Rtx children reaching adulthood (ped-tx, n = 31), compared to patients Rtx as adults (adult-tx, n = 17) and healthy controls (HC, n = 36). Median age was 26.9 (19-41), 28.6 (23.5-34) and 33.5 (20-42) years, respectively. Median time since first Rtx was 18.1 (7-29) and 3.7 (1.2-12.6) years. Body composition was measured by dual-energy X-ray absorptiometry (DXA). V0(2peak) was median 37.9 (12.5-56.3), 40.8 (26.5-57.5), and 44.4 (29.5-65.6) ml kg (-1)min (-1) in the ped-tx, adult-tx, and HC, respectively. Ped-tx had significantly lower V0(2peak) compared to HC (p = 0.01). Adult-tx had higher exercise capacity (test duration) compared to ped-tx (median 10.5 (7.5-16) and 9 (6-14) min, respectively (p = 0.016). In multiple linear regression analysis, test duration, fat-free mass (FFM, kg) and Hgb (g/dl) were significant predictors of V0(2peak) explaining 86% of its variance. There was no significant difference between ped-tx and adult-tx in V0(2peak.) CR fitness depicts long-term health outcome in Rtx patients both in regard to physical functioning and is a plausible indirect marker of CV health.

Expression of angiogenic regulators and skeletal muscle capillarity in selectively bred high aerobic capacity mice

Selective breeding for high voluntary wheel running in untrained mice has resulted in a 'mini muscle' (MM) phenotype, which has increased skeletal muscle capillarity compared with muscles from non-selected control lines. Vascular endothelial growth factor (VEGF) and thrombospondin-1 (TSP-1) are essential mediators of skeletal muscle angiogenesis; thus, we hypothesized that untrained MM mice with elevated muscle capillarity would have higher basal VEGF expression and lower basal TSP-1 expression, and potentially an exaggerated VEGF response to acute exercise. We examined skeletal muscle morphology and skeletal muscle protein expression of VEGF and TSP-1 in male mice from two (untrained) mouse lines selectively bred for high exercise capacity (MM and Non-MM), as well as one non-selected control mouse line (normal aerobic capacity). In the MM mice, gastrocnemius (GA) and plantaris (PLT) muscle capillarity (i.e. capillary-to-fibre ratio and capillary density) were greater compared with control mice (P < 0.05). In Non-MM mice, only muscle capillarity in PLT was greater than in control mice (P < 0.001). The soleus (SOL) showed no statistical differences in muscle capillarity among groups. In the GA, MM mice had 58% greater basal VEGF (P < 0.05), with no statistical difference in basal TSP-1 when compared with control mice. In the PLT, MM mice had a 79% increase in basal VEGF (P < 0.05) and a 39% lower basal TSP-1 (P < 0.05) compared with the control animals. Non-MM mice showed no difference in basal VEGF in either the GA or the PLT compared with control mice. In contrast, basal TSP-1 was elevated in the PLT, but not in the GA, of Non-MM mice compared with control mice. Neither VEGF nor TSP-1 was significantly different in SOL muscle among the three mouse lines. In response to acute exercise, MM mice displayed a 41 and 28% increase (P < 0.05) in VEGF in the GA and PLT, respectively, whereas neither control nor Non-MM mice showed a significant VEGF response to acute exercise. In contrast, TSP-1 levels were decreased by 90% in GA (P < 0.05) but increased by 50% in PLT (P < 0.05) in response to acute exercise in MM mice. The SOL showed no response to exercise for either VEGF or TSP-1 for any of the mouse lines. These data, with the exception of the Non-MM plantaris muscle, suggest that elevated capillarity is associated with altered balance between positive and negative angiogenic regulators (i.e. VEGF versus TSP-1, respectively). Based on the greater capillarity and significant VEGF response to exercise in MM mice, these data suggest that VEGF expression may, at least in part, be genetically determined.

Lung Volume Reduction Surgery Using the NETT Selection Criteria

The National Emphysema Treatment Trial (NETT) proved that lung volume reduction surgery (LVRS) was safe and effective in patients with certain clinical characteristics and using defined inclusion-exclusion criteria. Based on the selection criteria developed in that trial, we performed bilateral LVRS on 49 patients during the period of February 2004 until May 2009. Forty-nine patients underwent lung volume reduction by either median sternotomy (10) or video-assisted thoracoscopic surgery (39) selected according to NETT described parameters. Preoperative characteristics were the following: mean (±SD) age 62.5±6.6 years, preoperative FEV1 (forced expiratory volume in the first second of expiration) 691 cc (±159), % of predicted FEV1 25.3 (±6.2), preoperative Dlco (diffusing capacity of lung for carbon monoxide) 7.6 (±2.7), and % of predicted DLCO 27% (±7.3). All patients had upper lobe predominant disease and either low exercise capacity (n=23) or high exercise capacity (n=26) as defined by the NETT. There was no operative or 90-day mortality. Median length of stay was 8 days (interquartile range=6 to 10). Two patients required reintubation and tracheostomy but were decannulated prior to discharge. The BODE index (body mass index, airflow obstruction, dyspnea, and exercise capacity), a multidimensional predictor of survival in chronic obstructive pulmonary disease, improved -2.3 (±1.5, p<0.0001) (missing data: 5 of 42, 11.9%) and the FEV1 improved 286 cc (±221, p<0.0001), both 1 year after surgery. Probability of survival was 0.98 (95% CI [confidence interval]=0.94 to 1) at 1 year, and 0.95 (95% CI=0.88 to 1) at 3 years. Surgical lung volume reduction for emphysema can be performed in patients using selection criteria developed by the NETT with very low surgical risk and excellent midterm results. Surgical LVRS is the standard against which other nonsurgical treatments for advanced emphysema should be judged.

Is lung volume reduction surgery effective in the treatment of advanced emphysema?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether lung volume reduction surgery (LVRS) might be superior to medical treatment in the management of patients with severe emphysema. Overall 497 papers were found using the reported search, of which 12 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results are tabulated. We conclude that LVRS produces superior patient outcomes compared to medical treatment in terms of exercise capacity, lung function, quality of life and long-term (>1 year postoperative) survival. A large proportion of the best evidence on this topic is based on analysis of the National Emphysema Treatment Trial (NETT). Seven studies compared LVRS to medical treatment alone (MTA) using data generated by the NETT trial. They found higher quality of life scores (45.3 vs. 27.5, P<0.001), improved maximum ventilation (32.8 vs. 29.6 l/min, P=0.001) and lower exacerbation rate per person-year (0.27 vs. 0.37%, P=0.0005) with LVRS than MTA. Mortality rates for LVRS were greater up to one year (P=0.01), equivalent by three years (P=0.15) and lower after four years (P=0.06) postoperative compared to MTA. Patients with upper-lobe-predominant disease and low exercise capacity (0.36 vs. 0.54, P=0.003) benefited the most from undergoing LVRS rather than MTA in terms of probability of death at five years compared to patients with non-upper-lobe disease (0.38 vs. 0.45, P=0.03) or upper-lobe-disease with high exercise capacity (0.33 vs. 0.38, P=0.32). Five studies compared LVRS to MTA using data independent from the NETT trial. They found greater six-minute walking distances (433 vs. 300 m, P<0.002), improved total lung capacity (18.8 vs. 7.9% predicted, P<0.02) and quality of life scores (47 vs. 23.2, P<0.05) with LVRS compared to MTA. Even though LVRS has a much greater cost per person over five years ($137,000 vs. $100,200, P<0.001), its improved lung function, greater exercise capacity and better quality of life scores make it a preferable treatment option to MTA, with particular indications for patients with upper-lobe-predominant disease and low exercise capacity.

A 14-year follow-up study of chest pain patients including stress hormones and mental stress at index event

Background Knowledge of long-term outcome in chest pain patients is limited. We reinvestigated patients who 14 years earlier had visited the emergency department due to chest pain, and were discharged without hospitalization. Extensive examinations were made at that time on 484 patients including full medical history, exercise test, a battery of stress questions and stress hormone sampling. Methods From a previously conducted chest pain study patients still alive after 14 years were approached. Hospitalization or deaths with a diagnosis of ischemic heart disease or cerebrovascular disease were used as end point. Results During the follow-up period 24 patients had died with a diagnosis of ischemic heart or cerebrovascular disease, and 50 patients had been given such a diagnosis at hospital discharge. Age (OR 1.12, CI 1.06–1.19), previous history of angina pectoris (OR 9.69, CI 2.06–71.61), pathological ECG at emergency department visit (OR 3.27, CI 1.23–8.67), hypertension (OR 5.03, CI 1.90–13.76), smoking (OR 3.04, CI 1.26–7.63) and lipid lowering medication (OR 14.9, CI 1.60–152.77) were all associated with future ischemic heart or cerebrovascular events. Noradrenalin levels were higher in the event group than in the non-event group, mean (SD) 2.44 (1.02) nmol/L versus 1.90 (0.75) nmol/L. When noradrenalin was included in the regression model high maximal exercise capacity was protective of an event (OR 0.986, CI 0.975–0.997). Conclusion In chest pain patients previous history of angina pectoris, hypertension, smoking, pathological ECG at primary examination, and age were the main risk factors associated with future cardiovascular or cerebrovascular events.

QT restitution properties of middle-aged women with different exercise capacities

Background Framingham Study data indicate an incremental risk of cardiovascular death in relation to low exercise capacity in women. The reason for death is still not clear. Methods QT restitution properties in 80 middle-aged women were investigated to confirm whether the cardiac restitution property was affected by the exercise capacity. Exercise tests were performed according to the Bruce protocol. Seventy cases were divided into the low–exercise capacity group (LEC group) and high–exercise capacity group (HEC group) by median exercise capacities. Sequential QT intervals and their preceding TQ intervals were measured, and the QT restitution curve (QTRC) was constructed. Two exponential equations were used to match the data and calculate the maximum slope (Smax) of QTRC, respectively. Results With elevation in the exercise level, the women in the LEC group had a higher change rate of QT intervals (41 ± 10 vs 29 ± 3 ms/Met, P = .001) and TQ intervals (46 ± 12 vs 41 ± 7 ms/Met, P = .046); and the ratio of QT interval alterations to TQ interval alterations increased (0.41 ± 0.09 vs 0.36 ± 0.07, P = .003). The Smax of the QTRC in the LEC group was higher than that in the HEC group (1.43 ± 0.44 vs 1.13 ± 0.34, P = .002). There was an inverse relationship between Smax and exercise capacity ( r = −0.43, P = .001). Conclusion Middle-aged women with low exercise capacity have steeper QTRCs than those with high exercise capacity, denoting a more unstable alternation of QT interval with elevation in exercise level.