Optimising exercise training in peripheral arterial disease

Peripheral arterial disease (PAD) is an obstructive condition where the flow of blood through peripheral arteries is impeded. During periods of increased oxygen demand (e.g. during exercise), peripheral limb ischaemia occurs, resulting in the sensation of muscle pain termed 'claudication'. As a result of claudication, subjects' ability to exercise is greatly reduced affecting their quality of life. Although many treatment options for patients with PAD exist, exercise training is an effective and low-cost means of improving functional ability and quality of life. Currently, there are limited specific recommendations to assist the exercise prescription and programming of these individuals. This review summarises data from 28 exercise training studies conducted in patients with PAD and formulates recommendations based on their results. Exercise training for patients with PAD should involve three training sessions per week comprising 45 minutes of intermittent treadmill walking in a supervised environment for a time period of 20 weeks or more. Encouragement and direction is given to further research aimed at investigating the effectiveness of training programmes in these patients.

A clinical and echocardiographic score for assigning risk of major events after dobutamine echocardiograms

OBJECTIVES We sought to develop and validate a risk score combining both clinical and dobutamine echocardiographic (DbE) features in 4,890 patients who underwent DbE at three expert laboratories and were followed for death or myocardial infarction for up to five years. BACKGROUND In contrast to exercise scores, no score exists to combine clinical, stress, and echocardiographic findings with DbE. METHODS Dobutamine echocardiography was performed for evaluation of known or suspected coronary artery disease in 3,156 patients at two sites in the U.S. After exclusion of patients with incomplete follow-up, 1,456 DbEs were randomly selected to develop a multivariate model for prediction of events. After simplification of each model for clinical use, the models were internally validated in the remaining DbE patients in the same series and externally validated in 1,733 patients in an independent series. RESULTS The following score was derived from regression models in the modeling group (160 events): DbE risk = (age (.) 0.02) + (heart failure + rate-pressure product <15,000) (.) 0.4 + (ischemia + scar) (.) 0.6. The presence of each variable was scored as 1 and its absence scored as 0, except for age (continuous variable). Using cutoff values of 1.2 and 2.6, patients were classified into groups with five-year event-free survivals >95%, 75% to 95%, and <75%. Application of the score in the internal validation group (265 events) gave equivalent results, as did its application in the external validation group (494 events, C index = 0.72). CONCLUSIONS A risk score based on clinical and echocardiographic data may be used to quantify the risk of events in patients undergoing DbE. (C) 2004 by the American College of Cardiology Foundation.

Alterations of left ventricular myocardial characteristics associated with obesity

Background-Obesity is associated with heart failure, but an effect of weight, independent of comorbidities, on cardiac structure and function is not well established. We sought whether body mass index (BMI) and insulin levels were associated with subclinical myocardial disturbances. Methods and Results-Transthoracic echocardiography, myocardial Doppler-derived systolic (sm) and early diastolic velocity ( em), strain and strain rate imaging and tissue characterization with cyclic variation (CVIB), and calibrated integrated backscatter (cIB) were obtained in 109 overweight or obese subjects and 33 referents (BMI35) and the referent patients (P

Co-existing conditions for deaths from infectious and parasitic diseases in Australia

Objective: To examine the frequency distribution of co-existing conditions for deaths where the underlying cause was infectious and parasitic diseases. Materials and methods: Besides the underlying cause of death, the distributions of co-existing conditions for deaths from infectious and parasitic diseases were examined in total and by various age and sex groups, at individual and chapter levels, using 1998 Australian mortality data. Results: In addition to the underlying cause of death, the average number of reported co-existing conditions for a single infectious and parasitic death was 1.62. The most common co-existing conditions were respiratory failure, acute renal failure non-specific causes, ischaemic heart disease, pneumonia and diabetes. When studying the distribution of co-existing conditions at the ICD-9 chapter level, it was found that the circulatory system diseases were the most important. There was an increasing trend in the number of reported co-existing conditions from 60 years of age upwards. Gender differences existed in the frequency of some reported co-existing conditions. The most common organism types of co-existing conditions were other bacterial infection and other viruses. Conclusions: The study indicated that the quality of death certificates is less than satisfactory for the 1998 Australian mortality data. The findings may be helpful in clarifying the ICD coding rules and the development of disease prevention strategies. (C) 2003 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Diabetic cardiomyopathy: Evidence, mechanisms, and therapeutic implications

The presence of a diabetic cardiomyopathy, independent of hypertension and coronary artery disease, is still controversial. This systematic review seeks to evaluate the evidence for the existence of this condition, to clarify the possible mechanisms responsible, and to consider possible therapeutic implications. The existence of a diabetic cardiomyopathy is supported by epidemiological findings showing the association of diabetes with heart failure; clinical studies confirming the association of diabetes with left ventricular dysfunction independent of hypertension, coronary artery disease, and other heart disease; and experimental evidence of myocardial structural and functional changes. The most important mechanisms of diabetic cardiomyopathy are metabolic disturbances (depletion of glucose transporter 4, increased free fatty acids, carnitine deficiency, changes in calcium homeostasis), myocardial fibrosis (association with increases in angiotensin II, IGF-I, and inflammatory cytokines), small vessel disease (microangiopathy, impaired coronary flow reserve, and endothelial dysfunction), cardiac autonomic neuropathy (denervation and alterations in myocardial catecholamine levels), and insulin resistance (hyperinsulinemia and reduced insulin sensitivity). This review presents evidence that diabetes is associated with a cardiomyopathy, independent of comorbid conditions, and that metabolic disturbances, myocardial fibrosis, small vessel disease, cardiac autonomic neuropathy, and insulin resistance may all contribute to the development of diabetic heart disease.

Echocardiographic detection of early diabetic myocardial disease

OBJECTIVES We sought to determine whether disturbances of myocardial contractility and reflectivity could be detected in diabetic patients without overt heart disease and whether these changes were independent and incremental to left ventricular hypertrophy (LVH). BACKGROUND Left ventricular (LV) dysfunction is associated with diabetes mellitus, but LVH is common in this population and the relationship between diabetic LV dysfunction and LVH is unclear. METHODS We studied 186 patients with normal ejection fraction and no evidence of CAD: 48 with diabetes mellitus only (DM group), 45 with LVH only (LVH group), 45 with both diabetes and LVH (DH group), and 48 normal controls. Peak strain and strain rate of six walls in apical four-chamber, long-axis, and two-chamber views were evaluated and averaged for each patient. Calibrated integrated backscatter (113) was assessed by comparison of the septal or posterior wall with pericardial IB intensity. RESULTS All patient groups (DM, DH, LVH) showed reduced systolic function compared with controls, evidenced by lower peak strain (p < 0.001) and strain rate (p = 0.005). Calibrated 113, signifying myocardial reflectivity, was greater in each patient group than in controls (p < 0.05). Peak strain and strain rate were significantly lower in the DH group than in those in the DM alone (p < 0.03) or LVH alone (p = 0.01) groups. CONCLUSIONS Diabetic patients without overt heart disease demonstrate evidence of systolic dysfunction and increased myocardial reflectivity. Although these changes are similar to those caused by LVH, they are independent and incremental to the effects of LVH. (C) 2003 by the American College of Cardiology Foundation.

Effect of aldosterone antagonism on myocardial dysfunction in hypertensive patients with diastolic heart failure

Background - Specific treatments targeting the pathophysiology of hypertensive heart disease are lacking. As aldosterone has been implicated in the genesis of myocardial fibrosis, hypertrophy, and dysfunction, we sought to determine the effects of aldosterone antagonism on myocardial function in hypertensive patients with suspected diastolic heart failure by using sensitive quantitative echocardiographic techniques in a randomized, double-blinded, placebo-controlled study. Methods and Results - Thirty medically treated ambulatory hypertensive patients (19 women, age 62 +/- 6 years) with exertional dyspnea, ejection fraction >50%, and diastolic dysfunction (E/A 250m/sec) and without ischemia were randomized to spironolactone 25 mg/d or placebo for 6 months. Patients were overweight (31 +/- 5 kg/m(2)) with reduced treadmill exercise capacity (6.7 +/- 2.1 METS). Long-axis strain rate (SR), peak systolic strain, and cyclic variation of integrated backscatter (CVIB) were averaged from 6 walls in 3 standard apical views. Mean 24-hour ambulatory blood pressure at baseline (133 +/- 17/80 +/- 7mm Hg) did not change in either group. Values for SR, peak systolic strain, and CVIB were similar between groups at baseline and remained unchanged with placebo. Spironolactone therapy was associated with increases in SR (baseline: -1.57 +/- 0.46 s(-1) versus 6-months: -1.91 +/- 0.36 s(-1), P < 0.01), peak systolic strain (-20.3 &PLUSMN; 5.0% versus -26.9 &PLUSMN; 4.3%, P < 0.001), and CVIB (7.4 +/- 1.7dB versus 8.6 +/- 1.7 dB, P = 0.08). Each parameter was significantly greater in the spironolactone group compared with placebo at 6 months (P = 0.05, P = 0.02, and P = 0.02, respectively), and the increases remained significant after adjusting for baseline differences. The increase in strain was independent of changes in blood pressure with intervention. The spironolactone group also exhibited reduction in posterior wall thickness (P = 0.04) and a trend to reduced left atrial area (P = 0.09). Conclusions - Aldosterone antagonism improves myocardial function in hypertensive heart disease.

Effects of revascularisation and contractile reserve on left ventricular remodelling in patients with impaired left ventricular function

Objective: We sought to define the influence of revascularisation and contractile reserve on left ventricular (LV) remodelling in patients with LV dysfunction after myocardial infarction. Revascularisation of viable myocardium is associated with improved regional function, but the effect on remodelling is undefined. Methods: We studied 70 patients with coronary artery disease and LV dysfunction, 31 of whom underwent revascularisation. A standard dobutamine stress echocardiogram (DbE) was carried out. All patients underwent standard medical treatment; the decision to revascularise was made clinically, independent of this study. LV volumes and ejection fraction were measured by 3D echocardiography at baseline and after an average of 40 weeks. Results: There was no significant difference in baseline ejection fraction or volumes between patients who underwent revascularisation and the remainder. Compared to medically treated patients, revascularised patients had significant improvements in ejection fraction and end-systolic volume in follow-up. The impact of baseline variables on remodelling was assessed by dividing patients into tertiles of LV ejection fraction and volumes. Revascularised patients in the lowest tertile of ejection fraction at baseline (<38%) had a significant improvement in end-systolic volume and ejection fraction, larger than obtained in medically treated patients with low ejection fraction. Revascularised patients with an ejection fraction >38% did not show significant improvement in volumes compared to baseline. Revascularised patients in the largest tertiles of end-systolic (>88 ml) or end-diastolic volume (>149 ml) at baseline had a significant improvement in end-systolic volume. Conclusion: Remodeling appears to occur independent of the presence of regional contractile reserve but does correlate with the volume response to low-dose dobutamine. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Exercise training for patients with heart failure: A systematic review of factors that improve mortality and morbidity

PURPOSE: To determine the efficacy of exercise training and its effects on outcomes in patients with heart failure. METHODS: MEDLINE, Medscape, and the Cochrane Controlled Trials Registry were searched for trials of exercise training in heart failure patients. Data relating to training protocol, exercise capacity, and outcome measures were extracted and reviewed. RESULTS: A total of 81 studies were identified: 30 randomized controlled trials, five nonrandomized controlled trials, nine randomized crossover trials, and 37 longitudinal cohort studies. Exercise training was performed in 2387 patients. The average increment in peak oxygen consumption was 17% in 57 studies that measured oxygen consumption directly, 17% in 40 studies of aerobic training, 9% in three studies that only used strength training, 15% in 13 studies of combined aerobic and strength training, and 16% in the one study on inspiratory training. There were no reports of deaths that were directly related to exercise during more than 60,000 patient-hours of exercise training. During the training and follow-up periods of the randomized controlled trials, there were 56 combined (deaths or adverse events) events in the exercise groups and 75 combined events in the control groups (odds ratio [OR] = 0.98; 95% confidence interval [Cl]: 0.61 to 1.32; P = 0.60). During this same period, 26 exercising and 41 nonexercising subjects died (OR = 0.71; 95% CT: 0.37 to 1.02; P = 0.06). CONCLUSION: Exercise training is safe and effective in patients with heart failure. The risk of adverse events may be reduced, but further studies are required to determine whether there is any mortality benefit. (C) 2004 by Excerpta Medica Inc.

Impact of scar thickness on the assessment of viability using dobutamine echocardiography and thallium single-photon emission computed tomography - A comparison with contrast-enhanced magnetic resonance imaging

OBJECTIVES We sought to determine whether the transmural extent of scar (TES) explains discordances between dobutamine echocardiography (DbE) and thallium single-photon emission computed tomography (Tl-SPECT) in the detection of viable myocardium (VM). BACKGROUND Discrepancies between DbE and Tl-SPECT are often attributed to differences between contractile reserve and membrane integrity, but may also reflect a disproportionate influence of nontransmural scar on thickening at DbE. METHODS Sixty patients (age 62 +/- 12 years; 10 women and 50 men) with postinfarction left ventricular dysfunction underwent standard rest-late redistribution Tl-SPECT and DbE. Viable myocardium was identified when dysfunctional segments showed Tl activity >60% on the late-redistribution image or by low-dose augmentation at DbE. Contrast-enhanced magnetic resonance imaging (ceMRI) was used to divide TES into five groups: 0%, 75% of the wall thickness replaced by scar. RESULTS As TES increased, both the mean Tl uptake and change in wall motion score decreased significantly (both p < 0.001). However, the presence of subendocardial scar was insufficient to prevent thickening; >50% of segments still showed contractile function with TES of 25% to 75%, although residual function was uncommon with TES >75%. The relationship of both tests to increasing TES was similar, but Tl-SPECT identified VM more frequently than DbE in all groups. Among segments without scar or with small amounts of scar (50% were viable by SPECT. CONCLUSIONS Both contractile reserve and perfusion are sensitive to the extent of scar. However, contractile reserve may be impaired in the face of no or minor scar, and thickening may still occur with extensive scar. (C) 2004 by the American College of Cardiology Foundation.

Increased platelet-derived microparticles in the coronary circulation of percutaneous transluminal coronary angioplasty patients

Platelet-derived microparticles that are produced during platelet activation are capable of adhesion and aggregation. Endothelial trauma that occurs during percutaneous transluminal coronary angioplasty (PTCA) may support platelet-derived microparticle adhesion and contribute to development of restenosis. We have previously reported an increase in platelet-derived microparticles in peripheral arterial blood with angioplasty. This finding raised concerns regarding the role of platelet-derived microparticles in restenosis, and therefore the aim of this study was to monitor levels in the coronary circulation. The study population consisted of 19 angioplasty patients. Paired coronary artery and sinus samples were obtained following heparinization, following contrast administration, and subsequent to all vessel manipulation. Platelet-derived microparticles were identified with an anti-CD61 (glycoprotein IIIa) fluorescence-conjugated antibody using flow cytometry. There was a significant decrease in arterial platelet-derived microparticles from heparinization to contrast administration (P=0.001), followed by a significant increase to the end of angioplasty (P=0.004). However, there was no significant change throughout the venous samples. These results indicate that the higher level of platelet-derived microparticles after angioplasty in arterial blood remained in the coronary circulation. Interestingly, levels of thrombin-antithrombin complexes did not rise during PTCA. This may have implications for the development of coronary restenosis post-PTCA, although this remains to be determined.

Incremental benefit of myocardial contrast to combined dipyridamole-exercise stress echocardiography for the assessment of coronary artery disease

Background-Although assessment of myocardial perfusion by myocardial contrast echocardiography (MCE) is feasible, its incremental benefit to stress echocardiography is not well defined. We examined whether the addition of MCE to combined dipyridamole-exercise echocardiography (DExE) provides incremental benefit for evaluation of coronary artery disease (CAD). Methods and Results-MCE was combined with DExE in 85 patients, 70 of whom were undergoing quantitative coronary angiography and 15 patients with a low probability of CAD. MCE was acquired by low-mechanical-index imaging in 3 apical views after acquisition of standard resting and poststress images. Wall motion, left ventricular opacification, and MCE components of the study were interpreted sequentially, blinded to other data. Significant (>50%) stenoses were present in 43 patients and involved 69 coronary territories. The addition of qualitative MCE improved sensitivity for the detection of CAD (91% versus 74%, P=0.02) and accurate recognition of disease extent (87% versus 65% of territories, P=0.003), with a nonsignificant reduction in specificity. Conclusions-The addition of low-mechanical-index MCE to standard imaging during DExE improves detection of CAD and enables a more accurate determination of disease extent.