Submaximal oxygen uptake kinetics, functional mobility, and physical activity in older adults with heart failure and reduced ejection fraction.

BACKGROUND: Submaximal oxygen uptake measures are more feasible and may better predict clinical cardiac outcomes than maximal tests in older adults with heart failure (HF). We examined relationships between maximal oxygen uptake, submaximal oxygen kinetics, functional mobility, and physical activity in older adults with HF and reduced ejection fraction. METHODS: Older adults with HF and reduced ejection fraction (n = 25, age 75 ± 7 years) were compared to 25 healthy age- and gender-matched controls. Assessments included a maximal treadmill test for peak oxygen uptake (VO2peak), oxygen uptake kinetics at onset of and on recovery from a submaximal treadmill test, functional mobility testing [Get Up and Go (GUG), Comfortable Gait Speed (CGS), Unipedal Stance (US)], and self-reported physical activity (PA). RESULTS: Compared to controls, HF had worse performance on GUG, CGS, and US, greater delays in submaximal oxygen uptake kinetics, and lower PA. In controls, VO2peak was more strongly associated with functional mobility and PA than submaximal oxygen uptake kinetics. In HF patients, submaximal oxygen uptake kinetics were similarly associated with GUG and CGS as VO2peak, but weakly associated with PA. CONCLUSIONS: Based on their mobility performance, older HF patients with reduced ejection fraction are at risk for adverse functional outcomes. In this population, submaximal oxygen uptake measures may be equivalent to VO2 peak in predicting functional mobility, and in addition to being more feasible, may provide better insight into how aerobic function relates to mobility in older adults with HF.

Activation of the homeostatic intracellular repair response during cardiac surgery.

BACKGROUND: The homeostatic intracellular repair response (HIR2) is an endogenous beneficial pathway that eliminates damaged mitochondria and dysfunctional proteins in response to stress. The underlying mechanism is adaptive autophagy. The purpose of this study was to determine whether the HIR2 response is activated in the heart in patients undergoing cardiac surgery and to assess whether it is associated with the duration of ischemic arrest and predicted surgical outcomes. STUDY DESIGN: Autophagy was assessed in 19 patients undergoing coronary artery bypass or valve surgery requiring cardiopulmonary bypass. Biopsies of the right atrial appendage obtained before initiation of cardiopulmonary bypass and after weaning from cardiopulmonary bypass were analyzed for autophagy by immunoblotting for LC3, Beclin-1, autophagy 5-12, and p62. Changes in p62, a marker of autophagic flux, were correlated with duration of ischemia and with the mortality/morbidity risk scores obtained from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (version 2.73). RESULTS: Heart surgery was associated with a robust increase in autophagic flux indicated by depletion of LC3-I, LC3-II, Beclin-1, and autophagy 5-12; the magnitude of change for each of these factors correlated significantly with changes in the flux marker p62. In addition, changes in p62 correlated directly with cross-clamp time and inversely with the mortality and morbidity risk scores. CONCLUSIONS: These findings are consistent with preclinical studies indicating that HIR2 is cardioprotective and reveal that it is activated in patients in response to myocardial ischemic stress. Strategies designed to amplify HIR2 during conditions of cardiac stress might have a therapeutic use and represent an entirely new approach to myocardial protection in patients undergoing heart surgery.

Evaluation of a nurse practitioner disease management model for chronic heart failure: a multi-site implementation study.

While disease management appears to be effective in selected, small groups of CHF patients from randomized controlled trials, its effectiveness in a broader CHF patient population is not known. This prospective, quasi-experimental study compared patient outcomes under a nurse practitioner-led disease management model (intervention group) with outcomes under usual care (control group) in both primary and tertiary medical centers. The study included 969 veterans (458 intervention, 511 control) treated for CHF at six VA medical centers. Intervention patients had significantly fewer (p<0.05) CHF and all-cause admissions at one-year follow-up, and lower mortality at both one- and two-year follow-up. These data provide support for the potential effectiveness of the intervention, and suggest that the evidence from RCTs of disease management models for CHF can be translated into clinical practice, even without the benefits of a selected patient population and dedicated resources often found in RCTs.

Under-prescribing and non-adherence to medications after coronary bypass surgery in older adults: strategies to improve adherence.

The focus for this clinical review is under-prescribing and non-adherence to medication guidelines in older adults after coronary artery bypass grafting (CABG) surgery. Non-adherence occurs in all age groups, but older adults have a unique set of challenges including difficulty hearing, comprehending, and remembering instructions; acquiring and managing multiple medications; and tolerating drug-drug and drug-disease interactions. Still, non-adherence leads to increased morbidity, mortality, and costs to the healthcare system. Factors contributing to non-adherence include failure to initiate therapy before hospital discharge; poor education about the importance of each medication by hospital staff; poor education about medication side effects; polypharmacy; multiple daily dosing; excessive cost; and the physician's lack of knowledge of clinical indicators for use of medications. To improve adherence, healthcare systems must ensure that (i) all patients are prescribed the appropriate medications at discharge; (ii) patients fill and take these medications post-operatively; and (iii) patients continue long-term use of these medications. Interventions must target central administrative policies within healthcare institutions, the difficulties facing providers, as well as the concerns of patients. Corrective efforts need to be started early during the hospitalization and involve practitioners who can follow patients after the date on which surgical care is no longer needed. A solid, ongoing relationship between patients and their primary-care physicians and cardiologists is essential. This review summarizes the post-operative medication guidelines for CABG surgery, describes barriers that limit the adherence to these guidelines, and suggests possible avenues to improve medication adherence in older cardiac surgery patients.

Dominance of traditional cardiovascular risk factors over renal function in predicting arterial stiffness in subjects with chronic kidney disease.

BACKGROUND: The predictors of arterial stiffness across the spectrum of renal function are unclear. These predictors were investigated across a wide range of estimated glomerular filtration rates (eGFR). METHODS: Carotid-femoral pulse wave velocity (PWV; an index of arterial stiffness) was measured in 264 subjects with chronic kidney disease (CKD) stages 3-5 from three nephrology clinics ('lower GFR group'). PWV was also measured in 149 subjects without previously recognized CKD ('higher GFR group') including n = 26 with eGFR between 30 and 60 ml/min/1.73 m(2) and n = 123 with eGFR between 60 and 100 ml/min/1.73 m(2). The association between PWV and eGFR was investigated using linear regression. RESULTS: The 413 subjects had a mean age of 61.9 years, were 51% male, 28% diabetic and 79% hypertensive. In age-adjusted analyses within the 'lower GFR group', 'higher GFR group' and combined group, PWV correlated with higher systolic blood pressure (SBP), pulse pressure (PP), diabetes mellitus, body mass index (BMI) and resting heart rate (all P < 0.0008). In addition, PWV correlated inversely with eGFR in the 'higher GFR group' (P = 0.03) and combined group (P < 0.0001). In multivariable regression analyses of the combined group (n = 413), PWV was independently predicted by eGFR (P < 0.05). However, eGFR explained at most 4% of the variability in PWV in age-adjusted analyses (compared with 13-15% explained by SBP, PP or diabetes) and <1% of PWV variability in models adjusting for age, SBP, diabetes, heart rate and BMI (P < 0.0001). CONCLUSION: Although eGFR may independently predict PWV, the contribution of GFR per se does not appear to be clinically meaningful when compared with traditional cardiovascular risk factors.

Quantification of myocardial iron overload by cardiovascular magnetic resonance imaging T2* and review of the literature.

Heart failure due to myocardial iron overload remains the leading cause of death in patients with transfusion-dependent anemias. Iron overload-induced cardiomyopathy is reversible if intensive chelation therapy is instituted on time. Thus, early detection of myocardial iron deposition is imperative to prevent overt heart failure. Conventional cardiac monitoring, including physical examination, electrocardiography, echocardiography or serum ferritin levels fail to predict manifest or subclinical myocardial involvement resulting from iron overload. Cardiovascular magnetic resonance imaging T2* (cMRI-T2*, pronounced T2 star) times correlate well with myocardial iron levels. This timely review focuses on the utility of cMRI-T2*, for the preclinical detection of myocardial iron overload and monitoring of myocardial iron content during chelation therapy.

Cocaine-induced chest pain and beta-blockade: an inner city experience.

BACKGROUND: Cocaine is the most common illicit drug used in patients presenting with chest pain to emergency departments. Data on beta-blockers in cocaine-related chest pain syndrome are sparse. We sought out to study the causal and detrimental effects of beta-blockers in cocaine-related chest pain in a large inner city cohort of patients. METHODS AND RESULTS: All patients presenting to a large inner city emergency department with chest pain, with positive urine drug screen for cocaine were included. The group comprised predominantly young (mean age 46.8 +/- 8.2 years), African American (90.6%) males (73.4%). Evidence of myocardial infarction in the form of elevation of troponin-I was noted in 7.3%. Evidence of myonecrosis (MN) was significantly more likely in those who were taking beta-blockers at presentation as compared with those who were not (14% versus 4.4%, P < 0.01). In the absence of prospective controlled data, our observational findings seem to suggest that routine initiation or continuation or of beta-blockers after admission increased the likelihood of developing MN (23.3% versus 10.7%, P < 0.01) during the course of hospitalization. CONCLUSIONS: MN as reflected by elevation of cardiac biomarkers is uncommon in patients presenting with cocaine-related chest pain. Preexisting use of beta-blockers seems to render a higher risk of myocardial injury in patients presenting with cocaine-related chest pain. In addition initiation or continuation of beta-blockers during hospitalization should be discouraged.

Therapeutic potential of vasopressin receptor antagonists.

Arginine vasopressin (AVP) is a neuropeptide hormone that plays an important role in circulatory and sodium homeostasis, and regulating serum osmolality. Several clinical conditions have been associated with inappropriately elevated levels of AVP including heart failure, cirrhosis of the liver and the syndrome of inappropriate secretion of antidiuretic hormone. Three receptor subtypes that mediate the actions of AVP have been identified (V(1A), V(2) and V(1B)). Activation of V(1A) receptors located in vascular smooth muscle cells and the myocardium results in vasoconstriction and increased afterload and hypertrophy. The V(2) receptors located primarily in the collecting tubules mediate free water absorption. The V(1B) receptors are located in the anterior pituitary and mediate adrenocorticotropin hormone release. The cardiovascular and renal effects of AVP are mediated primarily by V(1A) and V(2) receptors. Antagonism of V(1A) receptors results in vasodilatation and antagonism of V(2) receptors resulting in aquaresis, an electrolyte-sparing water excretion. Several non-peptide AVP antagonists (vasopressin receptor antagonists [VRAs]) also termed 'vaptans' have been developed and are vigorously being studied primarily for treating conditions characterised by hyponatraemia and fluid overload. Conivaptan is a combined V(1A)/V(2)-receptor antagonist that induces diuresis as well as haemodynamic improvement. It has been shown in clinical trials to correct euvolaemic and hypervolaemic hyponatraemia, and has been approved by the US FDA for the treatment of euvolaemic hyponatraemia as an intravenous infusion. Tolvaptan, a selective V(2)-receptor antagonist, has undergone extensive clinical studies in the treatment of hyponatraemia and heart failure. It has been shown to effectively decrease fluid in volume overloaded patients with heart failure and to correct hyponatraemia. A large outcome study (n = 4133 patients) will define its role in the management of heart failure. Lixivaptan and satavaptan (SR-121463) are other selective V(2)-receptor antagonists being evaluated for the treatment of hyponatraemia. In addition, a potential role for the vaptans in attenuating polyuria in nephrogenic diabetes insipidus and cyst development in polycystic kidney disease is being explored. Ongoing clinical trials should further define the scope of the potential therapeutic role of VRAs.

Does increased arterial stiffness increase the risk for postural hypotension?

This study tests the hypothesis that increased arterial stiffness is associated with postural hypotension in older adults. Aortic pulse wave velocity and postural blood pressure (BP) response were assessed in 49 nondiabetic community-dwelling normotensive (n=27) and hypertensive (n=22) older adults (mean age+/-SD, 71+/-6.7 years) who were not receiving vasoactive medications. During the 5-minute period of upright posture, 13 subjects had no change or a postural increase in systolic BP (SBP)(+10.6+/-14.6 mm Hg), 27 had a postural decrease of <20 mm Hg (-9.3+/-4.2 mm Hg), and nine had a postural decrease of >20 mm Hg (-29.1+/-8.1 mm Hg). Contrary to the proposed hypothesis, pulse wave velocity was significantly greater in subjects with a postural increase in SBP than in those with a postural decrease in SBP<20 mm Hg (10.2+/-0.68 m/sec vs. 8.3+/-0.37 m/sec; p=0.03) and tended to be greater than in those with a postural decrease in SBP>20 mm Hg (10.2+/-0.68 m/s vs. 8.5+/-0.73 m/sec; p=0.11). Higher pulse wave velocity was associated with a more positive postural SBP response at 1 minute (r=0.42; p=0.024), 3 minutes (r=0.38; p=0.007), and 5 minutes (r=0.45; p=0.001). This study does not support a relationship between arterial stiffness and a postural decrease in BP among healthy older adults; other age-related factors regulating BP homeostasis likely play a greater role.

Walking may be related to less vascular stiffness in the Activity Counseling Trial (ACT).

BACKGROUND: The ACT was a clinical trial of various patient education and counseling interventions to increase physical activity in sedentary primary care populations. It provided the opportunity to measure the effect of increasing physical activity on aortic pulse wave velocity (APWV), a measure of vascular stiffness, in a relatively healthy middle-aged population. The effects of the interventions, as well as the impact of walking and correlates such as older age and maximal oxygen uptake (VO2max), on APWV were assessed. METHODS: The participants in this study were a subset of the 874 persons recruited for the ACT. Information about self-reported physical activity and disease status was collected at baseline (464 persons), 6-month (528 persons), and 24-month (555 persons) intervals. Physiological measures included APWV, systolic blood pressure, and other correlates. RESULTS: In multivariate analyses, the various treatment arms did not have a significant effect on APWV. However, walking in hours per day was associated with slower APWV times or less stiffness (P = .03). This was significant for women and consistent but not significant for men. In addition, age, clinic site, race, systolic blood pressure, and VO2max were independently associated with APWV. CONCLUSIONS: Increased walking frequency over a 24-month period was predictive of reduced vascular stiffness in ACT. The more significant result for walking frequency in women than in men might be caused by the presence of a low Vo2max or physical activity threshold for an effect of walking on APWV, which most women achieved but most men had surpassed at the start of the study. Although needing confirmation because this was a secondary analysis, modest physical activity may have a beneficial effect on large vessel structure.

Arterial stiffness is related to insulin resistance in nondiabetic hypertensive older adults.

Hypertension, diabetes, obesity, and aging are associated with increased arterial stiffness. Both insulin resistance and hyperglycemia may contribute to the development of arterial stiffness. Older nondiabetic hypertensive adults were recruited to test the following hypotheses: (1) insulin resistance is associated with arterial stiffness, and (2) this relationship is independent of glucose tolerance status. Aortic pulse wave velocity (PWV), pulse pressure (PP), insulin sensitivity index (S(I), measured by insulin-assisted frequently sampled iv glucose test), glucose tolerance status, and abdominal fat mass were assessed in 37 older (23 male, 14 female, mean age 69.4 +/- 5.9 yr), nondiabetic, hypertensive adults after a 4-wk antihypertensive medication withdrawal. Both PWV and PP were negatively correlated with S(I) (r = -0.49, P = 0.002, and r = -0.38, P = 0.02, respectively). The mean PWV and PP in those with normal glucose tolerance were not significantly different from those with impaired glucose tolerance (9.8 +/- 2.4 vs. 10.0 +/- 3.1 m/sec, P = 0.79 and 71 +/- 17 vs. 72 +/- 18 mm Hg, P = 0.80, respectively). In multiple regression analysis, PWV and PP remained independently correlated with S(I) (P < 0.05) after adjusting for age, gender, fasting glucose, glucose tolerance status, body mass index, or abdominal fat mass. These results suggest that in hypertensive, nondiabetic, older adults, insulin resistance is associated with arterial stiffness independent of glucose tolerance status.

Effects of aerobic exercise training in community-based subjects aged 80 and older: a pilot study.

OBJECTIVES: To assess the ability of sedentary, frail subjects aged 80 and older to train in a community-based exercise program and to evaluate clinical factors that predict improvements in peak oxygen consumption (VO2peak). DESIGN: Pretest, posttest. SETTING: Charlestown Retirement Community, Catonsville, Maryland PARTICIPANTS: Twenty-two (11 male, 11 female; mean age +/- standard deviation = 84 +/- 4.0, range 80-92) self-referred. INTERVENTION: Six months of moderate-intensity aerobic exercise training, two to three sessions/week, 20 to 30 minutes per session. Training modes included treadmill walking and/or stationary cycling. MEASUREMENTS: Baseline and follow-up maximal exercise treadmill tests (ETTs) with electrocardiogram monitoring and respiratory gas analysis. RESULTS: Six months of aerobic exercise training resulted in significant increases (mean +/- standard deviation) in ETT duration (11.9 +/- 3.3 vs 15.9 +/- 4.3 minutes; P =.01), VO2peak (1.23 +/- 0.37 vs 1.31 +/- 0.36 L/min; P =.04), and oxygen pulse (9.3 +/- 2.8 vs 10.1 +/- 3.2; P =.03). Mean heart rate was significantly lower during submaximal ETT stages 1 through 4 (P <.05), and resting systolic blood pressure decreased (146 +/- 18 vs 133 +/- 14 mmHg; P =.01) after training. Multiple regression analysis indicated that baseline VO2peak (r = 0.75, P =.002) and the total amount of time spent in exercise training (r = 0.55, P =.008) were independent predictors of the training-related improvements in VO2peak. CONCLUSION: Subjects aged 80 and older can increase aerobic capacity and reduce systolic blood pressure in a community-based exercise program of moderate intensity. The most important predictors of change in VO2peak were baseline VO2peak and the time spent in exercise training. Subjects with a lower baseline VO2peak had the greatest improvements in VO2peak after training.

Correlates of aortic stiffness in elderly individuals: a subgroup of the Cardiovascular Health Study.

BACKGROUND: Arterial stiffness has been associated with aging, hypertension, and diabetes; however, little data has been published examining risk factors associated with arterial stiffness in elderly individuals. METHODS: Longitudinal associations were made between aortic stiffness and risk factors measured approximately 4 years earlier. Aortic pulse wave velocity (PWV), an established index of arterial stiffness, was measured in 356 participants (53.4% women, 25.3% African American), aged 70 to 96 years, from the Pittsburgh site of the Cardiovascular Health Study during 1996 to 1998. RESULTS: Mean aortic pulse wave velocity (850 cm/sec, range 365 to 1863) did not differ by ethnicity or sex. Increased aortic stiffness was positively associated with higher systolic blood pressure (SBP), age, fasting and 2-h postload glucose, fasting and 2-h insulin, triglycerides, waist circumference, body mass index, truncal fat, decreased physical activity, heart rate, and common carotid artery wall thickness (P < .05). After controlling for age and SBP, the strongest predictors of aortic stiffness in men were heart rate (P = .001) and 2-h glucose (P = .063). In women, PWV was positively associated with heart rate (P = .018), use of antihypertensive medication (P = .035), waist circumference (P = .030), and triglycerides (P = .081), and was negatively associated with physical activity (P = .111). Results were similar when the analysis was repeated in nondiabetic individuals and in those free of clinical or subclinical cardiovascular disease in 1992 to 1993. CONCLUSIONS: In these elderly participants, aortic stiffness was positively associated with risk factors associated with the insulin resistance syndrome, increased common carotid intima-media thickness, heart rate, and decreased physical activity measured several years earlier.