PAD Rehabilitation

PAD rehabilitation Manlio Prior, Sergio De Marchi, Enrico Arosio Angiology and Vascular Rehabilitation Unit University Hospital, Verona - Italy INTRODUCTION Peripheral arterial disease (PAD) is an atherosclerotic disease that, since the early stages, significantly affect both the functional level and quality of life of the patient, resulting in reduction of walking distance, rest pain or ischemic ulcers, and the risk of limb loss. In addition, a particularly important aspect, is due to increased morbidity and mortality from cardiovascular and cerebrovascular ischemic events. In fact, patients with peripheral arterial disease, even asymptomatic, has a very high cardiovascular risk, comparable to that of the patient who has suffered myocardial infarction. It is therefore essential that the treatment is aimed on one side to reduce the symptomatology determined by the altered arterial flow, trying to increase the walking distance and the quality of life of the patient, on the other hand to reduce the progression of the disease and the incidence of ischemic events, such as cardiac and cerebrovascular diseases, to increase patient survival. Because, as we shall see, exercise exerts many beneficial effects in PAD patients, is nowadays considered, according to international guidelines, the first measure to be taken, especially in the early stages of the disease (intermittent claudication or even asymptomatic). However, PAD rehabilitation should not be limited only to exercise training but must include interventions for correction of lifestyle and reducing modifiable risk factors, both through educational and behavioral therapy but also with an intensive drug treatment of risk factors. EFFECTS OF PHYISICAL TRAINING IN PAD PATIENTS Numerous studies have demonstrated the multiple favorable effects that exercise is able to determine also in patients with peripheral arterial disease. Indeed, in addition to the fundamental action on increasing the walking capacity, the training has shown the ability to improve the quality of life of PAD patients, both as regards the performance in daily activities, both as regards the tone of mood. Another aspect highlighted in recent times is the effect of regular exercise in favourably modifying the cardiovascular risk profile, improving the glycolipid metabolism, reducing the arterial pressure and helping to optimize body weight. This, combined with the evidence of a role in improving endothelial dysfunction, is probably the main explanation of its effect on the reduction of cardiovascular mortality and the incidence of amputations in PAD patients. Walking distance Since nearly 20 years it has proven more and more convincing that exercise can increase the walking distance in patients with intermittent claudication. The magnitude of the increase varies depending on the studies by about 50% even up to 200%. Therefore all international guidelines on the management of PAD (European Society of Cardiology, Trans-Atlantic Inter-Society Consensus, American College of Cardiology Foundation / American Heart Association) gave a Level 1 Grade A indication to the use of a program of physical training, preferably supervised, in the initial treatement of intermittent claudication. In fact, the increase in walking distance induced by physical training, especially supervised, is even comparable, according to some recent studies, to that obtained with revascularization, particularly in controls in the medium and long term. This result requires, of course, that the exercise should be continued on a regular basis over time. If not, the benefits are expected to disappear within 6-12 months, while it has been shown that patients who are able to maintain a regular physical activity, retain the results obtained. If there are no doubts about the effectiveness of the training on the walking ability, there is less certainty about what mechanisms are most responsible for this effect. Several possible candidates will be described and it is likely that many of them contribute. (Table 1). TABLE 1 Improvement of endothelial function Reduction of inflammatory processes enhancement of angiogenesis Improvement of muscle metabolism improvement of haemorheology Redistribution of microcirculatory flow Improvement of gait mechanics One of the first hypothesized mechanisms was the increase in the peripheral flow in the limbs determined by the development of collateral circulation induced by training. In fact, some authors have demonstrated increased flow on femoral arteries between 10 and 20%, but usually the ankle brachial pressure index is not changed significantly and, above all, there has never been convincing evidence of an increase in collateral circulation. This assumption, however, may receive new interest following the recent demonstration of possible favorable effects of training in promoting neo angiogenesis through the production of VEGF, induced by HIF, due to the ischemic stimulus. However, it is likely that most of the vascular changes occur at the microcirculatory level. Exercise in fact seems to counteract the endothelial dysfunction described on PAD patients, through the release of NO, induced by activation of NO synthase and also increasing the production of prostacyclin. The training regular aerobic also is able to reduce the production of free radicals, unlike in acute strenuous physical exercise which determines a marked increase. These effects of improved endothelial function may have favorable effects on plaque stabilization and then on its evolution. Even at muscular level changes occur that allow a more efficient metabolism. Have in fact been described improvements homeostasis system acyl-carnitine, increases the cellular enzyme activity and especially an increase in muscle oxidative capacity that allows the muscle to work longer under aerobic conditions. As regard as haemoreology properties, viscosity and erythrocyte aggregation tend to decrease, improving blood fluidity. One aspect that can definitely play a role in the benefits induced by exercise training, is the improvement of the gait mechanics. This may be due to the effect of exercise on muscle tone and on articular flexibility, that improves walking stability, especially if the treadmill workouts are associated with specific proprioceptive exercises. Finally, a possible reduction of pain perception induced by physical activity, probably mediated by an increase in the release of endorphins, has been described. Quality of life The quality of life of PAD patients, due to functional limitation determined by the reduced walking capacity, is significantly compromised, like other chronic diseases such as COPD. The physical training is able to favorably influence this aspect, not only thanks to the recovery of an adequate walking distance, but also through an improved ability to perform everyday activities. An important component is definitely the psychological motivation linked to participation in structured programs that counteract the sedentary habits and stimulate the resumption of an active life. Several studies have investigated these effects on quality of life, using questionnaires such as the 36-Item Short Form Health Survey (SF-36) and have shown how all these aspects are improved after rehabilitation programs. Cardiovascular risk factors As we will see the correction of modifiable cardiovascular risk factors is an important component in a PAD rehabilitation program. A very interesting aspect of exercise is the emerging evidence about his ability to favorably modify the risk profile of the PAD patient. In several studies it is shown that regular exercise is able to reduce LDL cholesterol and triglycerides and increasing HDL cholesterol. It has also favorable effects in improving glycemic control in diabetic and in reducing blood pressure. Exercise has been described to increase weight loss, especially if associated with dietary treatment. Finally the patient followed regularly as part of a training program has a better chance of success in quitting smoking. Cardiovascular morbidity and mortality Although PAD rehabilitation was in the past mainly focused to achieve symptomatic improvement, in recent years they are coming confirmation of an important effect of exercise training on cardiovascular morbidity and mortality, as has long been known for cardiac rehabilitation. This is not unexpected, considering on the one hand the improvement of endothelial function induced by exercise training, on the other, the beneficial changes in risk factors just described. Some years ago a study had shown that PAD patients who practiced regular physical activity had a significant reduction in 5-year mortality than sedentary ones. More recently the results of the follow up to 5 years of a group of participants in a supervised training program were published. A 50% reduction in cardiovascular mortality and 30% in morbidity was found in exercise trained, compared with not trained patients. Safety of exercise Exercising, especially at the intensity commonly used in vascular rehabilitation, is associated with very low risks. A problem may be that of any falls, patients should be assessed for the presence of orthopedic or neurological disorders associated to gait imbalance. In such cases the training must be done with caution and with continuous care, possibly exercising on cycle-ergometer. The presence of rheumatologic diseases may be a contraindication to the treadmill training, this is another case to be considered for training on cycle-ergometer that may reduce the load on the joints of the lower limbs. Attention should be made to diabetic patients, where in addition to verifying the adequacy of metabolic control, should be carefully examined for possible foot-risk areas of injury. In the case adequate unloading orthoses should be used. Severe heart disease, such as unstable angina, decompensated heart failure, uncontrolled cardiac arrhythmias, severe symptomatic valvular heart disease or uncontrolled hypertension are all contraindications to exercise training. A particularly relevant problem is the frequent coexistence of ischemic heart disease in PAD patients. It should however be noted that aerobic training is not only not contraindicated in ischemic heart disease, but it is part of all cardiac rehabilitation programs post-myocardial infarction. Before engaging in an exercise training program all patients should undergo a full cardiological assessment, including history, physical examination, and resting ECG. In patients with suspected myocardial ischemia an exercise testing should be performed. A continous electrocardiographic monitoring of the training sessions should be considered in ischemic patients. In all patients heart rate and blood pressure at baseline and end of session are monitored. It is of course always made available to the emergency cart with drugs and instruments (complete with defibrillator). Components of PAD rehabilitation program - Training fisico - terapia educazionale per correzione stile di vita e riduzione fattori di rischio o cessazione fumo o dieta o attività fisica - trattamento intensivo fattori di rischio Exercise training The most important component of a PAD rehabilitation program is definitely the physical training, which, as we have seen, plays multiple favorable effects in patients with intermittent claudication, and also in the asymptomatic ones. Anyway, since the main effect we want to achieve is to increase the walking distance it is essential that this parameter is defined and measured as exactly as possible to monitoring the results. o valutazione funzionale o o o protocolli di esercizio  treadmill  cyclette  palestra  esercizi propriocettivi  esercizi di potenziamento muscolare  o altre modalità  ginnastica respiratoria  mobilizzazione passiva  drenaggio linfatico (massaggio connettivale)  elettrostimolazione muscolare  balneo crenoterapia? EXERCISE PROTOCOLS Although they are now several clinical studies that evaluated the role of training in the treatment of PAD patients, there is still no unanimous agreement on the type of training to be preferred. Many training protocols have been used, in fact, ranging from corridor walking, treadmill walking, cycle-ergometer exercising, arm-ergometer, steppers, nordic walking, circuit exercise, or muscle strengthening. Another aspect of it is not easy to define the intensity of the exercise workout load. There is indeed a risk that loads too light are not able to induce an optimal response. On the other hand workloads more intense, that can activate the mechanisms of ischemic preconditioning, ie favorable adaptations induced by ischemia, may cause damage by ischemia-reperfusion, free radicals production, activation of inflammation and progression of atherosclerosis. The difficulty is thus to identify the intensity of training more effective to induce the desired adaptations, without there being an excessive production of harmful metabolites. One aspect that seems particularly relevant for the best results is the execution of the exercise program in a controlled environment under the guidance of trained staff (supervised training). The programs conducted self-administered at home (home training) would be less effective, but could be a cheaper alternative from a management perspective. Treadmill After the publication of the Gardner meta-analysis in 1995, it was considered that the treadmill training is to be able to ensure the best results. This is particularly true, especially if we limit to evaluate the impact on the walking distance. Usually the treadmill training is performed in 3-5 sessions per week, for a period ranging from 6 to 26 weeks, for a duration of each session between 30 and 60 minutes. As there is evidence that a supervised protocol for 6 weeks allows results similar to those of longer duration, the Consensus Document on Intermittent Claudication suggests a training program as described in Table 2. The main characteristics of the proposed scheme are: 1. the determination of the exercise load with a test at a reduced intensity (called submaximal test) than the treadmill test that is performed to monitor the training effectiveness (maximal test), so avoid arrests too close together. 2. exercise load established in order to induce a moderate level of pain 3. the recalculation of the exercise load after 3 weeks in order to adapt it to the improvement of walking ability (incremental protocol of the training program) SUPERVISED TRAINING PROGRAM 6 WEEKS, 3 DAYS WEEKLY Day 0 (the day before to start Physical Training Program) 1) Warm-up 10 min of bicycle exercise without load; 2) Maximal Treadmill (diagnostic) Test: constant load (speed: 3.2 km/h; slope:12-15%); parameters: ICD, ACD, recovery time(RT); 3) assessment of walking capacity: 1 h after maximal Treadmill Test, submaximal Treadmill(speed: 1.5 km/h; slope: 6±2%) or spontaneous walking without slope, measuring the absolute walking capacity; the same settings will be used for training session. Day 1 1) Warm-up 10 min of bicycle exercise without load; 2) single training session: patient walks until 60-70% of measured walking capacity (sub maximal test); 3) resting and restore period: standing or sitting for 1 min or until the patient can restart the walking (indicative setting could be a period equal to RT measured during the maximal treadmill test); 4) daily training session: exercise-rest-exercise pattern should be repeated, reaching the 1-2 km of walk, or at least 30 min of effective walking time; 5) cool-down: sitting resting until the normalization of all cardiovascular parameters. Day 9 1) New assessment of walking capacity: submaximal treadmill test or spontaneous walking without slope (same setting utilized the day0); 2) recalculate the single exercise load: patient walks until 60-70% of new walking performance(incremental protocol of the training program);3) resting and restore period and daily training session remain unchanged. Day 18 (6 weeks) Maximal treadmill test to assess the new ICD, ACD, RT. -------------------- Cycle ergometer Training on erogmeter differs from the one on treadmill regarding muscles groups involved ; in fact the muscles exerted are those acting on proximal portions of the limb, mainly of the thigh and gluteus. Furtheromore the exercise on ergometer determines a greater cardio-respiratory workoload. Respiratory improvement is surely of advantage but this type of exercise implies some cautions in patients with ischemic heart disease. The ergometer has also the advantage to be significantly less hurting on articulations avoiding the charge; this make it more suitable for patients with some orthopedical or neurological limitations. Nevertheless the pedaling movement needs a good knee function and may be relatively contraindicated in case of knee arthrosis. Initial Test:  To measure maximum padaling capacity (startning with 50 W , incresing with 10 W every 2 minutes till pain onset)  To calculate 70% of maximum capacity Training sessions:  Warming for 10 min (5 min stretching and 5 min ergometer without load)  Pedaling at 70% of maximum capacity for 30 min (1 min rest if pain at the limb appears)  5 min cool-down (stretching)  Recalculate pedaling maximum capacity at the beginning of a new week of training. Arm Ergometry An alterative type of training in patients unsuitable for treadmill, is training with arm ergometer . Arm muscles workoload determins systemic effects on cardiovascular apparatus that reflect favourably on lower limbs circulation. Some studies highlighted that this type of training increases walking ability similarly to treadmill training. Nordic Walking Free walking is a training regularly prescribed in rehabilitaiton programmes with home based training, a new method that is spreading in Nordic Walking, i.e. walking with the use of sticks. Nordic Walking offers a walking tecnique with a higher stability, less prone to falls, and may be prescribed to patients with some light neurological and orthjopedic co-morbilities. Arms movements due to sticks increase cardiometabolic effetcs of training and allows a stronger thrust to every single path, improving performance. Increase in walking distance, for some authors, is significant and somehow comparable to that obtained on treadmill. Strengthening Exercises A different approach to training is the on strenthening of diffferent muscles with specific exercises against resistance by means of machines. In recent times an increasing interest is growing for this type of training, in particular for the recover of muscolar mass that is lost in PAD for detraining and reduction of activity. This training is often inserted in a more extensive programme and in particular types of training called “stations in circuit” , this last type allows the involvement of an highe number of patients. Proprioception Exercises A useful completing element of treadmill training may be the adding of a program of exercises aiming to improve proprioception, articular mobility, mucrolar tone and walking scheme. This type of trianing is particularly important in more ageing subjects with co-morbility that may cause a instable march. Respiratory Training Obstructive pulmonary disease has an high prevalence in PAD patients cohort (often due to ageing and smoke) with a reduction in respiratory function. Hence introducing exercises for improving respiratory function may be of grat importance. Strengthening respiratory muscles and of the arms may exerts fovourable effects on breathing. This type of exerciseses is particularly useful in patients with critical limb ischemia, as we will see later, since they suffer more severely from deconditioning and greatly on respiratory function. Counselling for healthy lifestyle and risk factors reduction. A reduction of risk factors within a healthy lifestyle must always be associatetd to training programme, because the aim of PAD rehabilitation goes beyond the improvement of walking ability focusing on the reduction of desease progression and of mortality. Smoking is the main risk factor for PAD and must be avoided; the involvement of specialists in smoking cessation my often be necessary for appropriate counselling and even the use of specific therapies. Smoking cessation is correalted to increase in walking distance, reduction of cardiovascular morbidity and mortality, furthemore a lower rate of re-occlusion after revascularization procedures. In particular a trial conducted in 2014 on a cohort of 800 PAD pacients folowed for 5 years, showed a 50% reduction of total mortality and a 40% increase of amputaion free survival in those subjects who stopped smoking compared to the smoking group. These results may be obtained more easily if smoking cessation is part of a more general educational program for healthy lifestyle, involving alimentary counselling and exercise prescription. Several scientific papers demonstrate the efficacy of this type of approach, necessarily asscociated to training. Intensive risk factors control Pharmacological intervention is generally necessary in PAD patients to achieve goals. All subjects with PAD, even if asymptomatic, should be on treatment with statins to reach the target of LDL cholesterol (<100 mg/dL), a tighter control (<70 mg/dl) in patients with higher risk profile. LADL reduction has been demonstrated efficacious in reducing cardiovascular morbidity and mortality. In several trials , statins have improved walking ability. In order to reduce cardiovascular events hypertension should be treated to reach the target (<140/90 mmHg), with a lower one in case of diabetes or renal function impairment (< 130/80 mmHg). In addition, ramipril seems to have contributed to improve walking distance. It is important, as well, to obtain a good control of diabetes; even if, a deep reduction of levels of glicated haemoglobin should be avoided in those most aged patients and with comorbidites. The opinions and trial focus on a 7% glicated hemoglobin target. Other interventions on hyperomociteinemia or Lpa lipoprotein seem not to have obtained significant results on cardiovascular events. Rehabilitation in Critical limb ischemia. Revascularization is obviuosly the pivotal treatment in these patients, since CLI is a limb survival treatening condition; furthermore CLI increase vascular morbidity in PAD patients. However some patients are considered not suitable for vascular surgery and excluded from revascularization. In addition , some patients revascularized still present a critical vascular condition with residual functional impairment and pain. Data from literatura have shown that , 6 months after revascularization, 50% of patients walk with a recover of ischemic dmage. Hence also in patients with CLI ischemia can be proposed a rehabilitative program, in addition to revasculrization or in those cases not “surgical”. Interventions on risk factors is mandatory , acting also in improving microvascular function. Cardiac function must be improved with pharmacological on interventional prcedure, in order to increase inflow. Nutritional status should be analysed with an good balance in proteic and energetic foods; CLI patients often suffer from inparropriate alimentary habits with reduction in proteins and vitamins. Before exercise prescription a cardiological evaluation should be performed, and, if necessary, ECG monitoring could be proposed during exercise. Pain control is another corner-stone in managing CLI; rest pain relief is important for quality of live but also for avoidining lowered position of the limb during the night. In fact this position causes swelling with worsening of perfusion. It is generally necessary to prescribe analgesic drugs, following a gradual increase in power. The main criteria is “to cover” the patient with a long lasting drug , adding a short effect drug for outbreaking pain. Often the association of two drugs with complmentary actions is requestested for pain control. 1. Stewart KJ, Hiatt WR, Regensteiner JG, Hirsch AT. Exercise training for claudication. N Engl J Med 2002; 347: 1941-51 2. Hirsch AT, Haskal ZJ, Hertzer NR et al. ACC/AHA 2005 practice guidelines for the management of patients with peripheral arterial disease. Circulation. 2006;113: e463– e654