Medical Rehabilitation in cardiac patients with HF

Salim Thabet PGY3Moderator: Dr. Mahazarin Ginwalla

Case• JD is a 60 y.o male pt. known with 1. HFrEF 35-40% due to ICM2. CAD s/p MIx2 with PCI3. HTN/DLD4. Smoker 30PY5. Dietary non-compliance

Presenting with progressive SOB on exertion of 1wk associated with orthopnea, PNDs and increase abdominal girth and LE edema. When not in HF exac. can usually walk on flat surface with mild SOB

• PE: VS: 120/70 100 SR 25 afebrileJVD to mandibleS4 heard, no murmursCrackles+2 LEE• CXR: Pulmonary edema• ProBNP=10k, Cr=2 with baseline of 1.2• Meds:Lisinopril 20, Metoprolol succinate 100, aspirin 81, atorvastatin 20mg, imdur 30mg and Lasix 40mg

• Pt. was diuresed with 40mg Lasix IVP BID with improvement in symptoms and total I/O -10 lt,

• He was discharged home on Lasix 40 mg BID (with instructions to increase according to weight increase), metoprolol succinate 150 mg and Imdur 60 mg

• Heart failure care path and PCP/Cardiology f/u

• He is readmitted 2 months later with same symptoms

OutlineI. Exercise and the body

A. Exercise physiologyB. Benefits of exerciseC. Risks of exercise

II. Heart failure and the bodyA. Exercise capacity in HFB. Skeletal muscle dysfunction

III. Rehabilitation in HFA. SafetyB. Effect of exercise in HF

1. Readmission2. Morbidity/Mortality3. Psychosocial/Economic

IV. Conclusion and recommendationsV. QI project (HF readmission)

Epidemiology of HF

• Hard to estimate and usually based on symptoms

• 5.1 million in the US in 2006

• Lifetime prevalence 1/5

• Incidence increases with age (8/1,000 50-59yrs and 66/1000 80-89)

• African Americans 25% more than in whites

Exercise physiology• Skeletal muscle metabolism can increase up to

50 xs resting rate

• To preserve tissue oxygenation and PH the heart and lung must react

• Exercise testing yields information on the response to exercise and can determine cardiac and pulmonary limitations to exercise

• Physiologic data include:1. Oxygen uptake (VO2)2. CO2 output3. Tidal volume4. Minute ventilation (VE)5. ECG6. Pulse oximetry

• In certain situations more extensive monitoring (arterial or pulmonary artery catheterization)

• VO2max: symptom-limited max O2 uptake during incremental bilateral leg exercise

• Used to provide overall assessment of exercise capacity

• Normal VO2 means that no serious pathology exists in pulmonary, cardiovascular and neuromuscular systems

• However intra and inter-organ compensation can yield a normal value

1. Med Sci Sports Exerc 1997; 29:5912. Am J Noninvas Cardiol 1987; 1:244

• VO2 increases linearly with work (slope=10ml/min)

• Slope not affected by age, sex or training

• Shifted leftward in obese (increased O2 uptake for same workload)

• VO2max = plateau of VO2 vs Work

• Nl VO2max > 20ml/kg/min ( training, age)

• Can be predicted by age, gender, height and lean weight

Am Rev Respir Dis 1984; 129:S49

Normal VO2 vs. Workload

VO2maxx

Fatigue• Central (not well understood) vs peripheral

• Accumulation of metabolic byproducts (lactate, Ammonia) and depletion of ATP/glycogen

• Lactate threshold (LT): VO2 at which pyruvate exceeds the ability of it being metabolized by the Krebs cycle

• LT better predictor of sustained performance than VO2max

• At VO2 just below LT exercise can be sustained for long periods (steady state) ex: UFC fighters

Muscle Nerve 1989; 12:660

Normal lactate vs VO2 in exercise

Effect of exercise on skeletal muscles

• Training capillary density and mitochondria

• Training is associated with less ammonia and lactate with less fatigue at a set metabolic rate (VO2)

• LT > 40% VO2max in nl. people, less in pts. with CVD and more in athletes

Sports Sci Exchange 1995; 8:1

Circulation• Fick equation: VO2 = CO x (CaO2 – CvO2)

• CO due to HR (autonomic changes) and SV (increased contractility

and LVEDV 20-40%)

• Training results in lower resting HR

• LVEDP up to 20 mm Hg & filling is limited by pericardium (CO + VO2 inc. with pericardiectomy)

• CO limits VO2max in healthy adults with training CO can up to 5 xs resting value

Heart Lungs Tissue metabolism

Systemic circulation• Balance bet muscle chemoreflex and arterial baroreceptors

results in net in SBP whereas DBP remains near resting value

• Rise in SBP is much less than what is expected by rise in CO reflecting in SVR

• PH &PO2, K+, adenosine & NO causes local muscle vasodilatation whereas sympathetic arterial vasoconstriction directs flow to muscles

• NO activity is increased with training

• Acidosis O2 extraction also by shifting oxyhemoglobin dissociation curve to the right

Blood flow distribution with exercise

Maximal exercise (% total) Rest (% total)

1 24 Splanchnic

88 21 Skeletal muscle

1 19 Kidneys

3 13 Brain

2 8 Skin

4 3 Heart

1 10 Other organs

Pulmonary circulation/Ventilation• PAP rarely exceeds 30 mm Hg at peak exercise in

normal individuals

• This is done by PVR by passive dilation and due to NO effect

• Minute ventilation (VE) rises due increase RR

• TV increase in hyperbolic relation with exercise

• Training decreases VE for any given VO2

CO2 and O2• Blood flow is directed more to the lung apices which are more

ventilated

• Improved distribution of blood flow increases diffusing surface area

• More CO2 is produced but CO2 elimination becomes much more efficient (high TV and VE)

• PAO2 = PiO2 – (PACO2/RER)

• Net effect: PaO2 remains near resting value, PvO2 decreases and PaCO2 decreases (compensated metabolic acidosis)

Summary• Intense exercise 15 xs O2 uptake, by 10 xs VE, 5 xs CO & 3

xs VO2

• Microvascular adaptation to increase O2 delivery to the muscles

• Link bet. cardiopulmonary adaptation & changes in muscle metabolism not well understood

• Max CO is what limits aerobic exercise capacity

• Training enhances every step from lung to mitochondria

Study of 5,159 men aged 40-49 yrs followed for 19 yrs showed less CHD in people who perform any physical activity vs inactive

Observational studies

Additional years gained after adoption of certain lifestyle change in 10,269 Harvard alumni from 1977 to 1985

• Moderately vigorous exercise was associated with 23 % decrease in mortality than less exercise

Effect of physical activity level on life expectancy at age 50

• Framingham Heart Study

Benefits of regular physical activity

Reduces the risk of dying prematurely

Reduces the risk of dying from heart disease

Reduces the risk of stroke

Reduces the risk of developing diabetes

Reduces the risk of developing high blood pressure

Helps reduce blood pressure in people who already have high blood pressure

Reduces the risk of colon, prostate and breast cancer

Reduces feelings of depression and anxiety/Delays Alzheimer’s disease

Helps control weight

Helps build and maintain healthy bones, muscles and joints

Helps older adults become stronger and better able to move about without falling

Promotes psychological well-being and helps with smoking cessation

Decreases healthcare costs (estimated at $4,950/life saved in US)

Biologic mechanisms for benefit of exercise

Antiatherogenic effects

Reduction of adiposity, particularly in those with excess upper body and abdominal fat

Reduction of elevated blood pressure

Reduction of elevated plasma TG (and associated small dense LDL particles)

Increase in HDL cholesterol levels

Important in insulin sensitivity and glucose use and reduction in risk of type 2 diabetesAntithrombotic effects

Endothelial function alteration

Autonomic functional changes

Anti-ischemic effects (promotes atheroprotective and decreases atherogenic cytokines)

Antiarrhythmic effect

Risks in normal individuals • Musculoskeletal injury is the most common

⁻ Acute strains, tears, inflammation, chronic strain, stress fractures, traumatic fractures, nerve palsies, tendonitis and bursitis

• Secondary to overuse and can be preventable

• More serious but less common include: ⁻ Arrhythmias, SCD, MI, LVH, rhabdomyolysis,

bronchoconstriction and heat-related problems.• More common in who do not exercise regularly &

suddenly decide to do heavy exercise

How much exercise?• 1 MET = 3.5 mL O2/kg/min consumption (seated adult)

• Based on physical fitness BP reduction, HDL elevation, O2 consumption and weight reduction data; CDC, AHA and Surgeon General recommend 30-60 min moderate intensity exercise (3-6 METs) 4-6 xs/wk

• Pts. should move gradually from sedentary life style to moderate intensity exercise

• Brisk walking, active yard work, dancing, bicycling, jogging and other leisure sports work

• Indicators of adequate exercise include breathlessness, fatigue and sweating

• Strength-developing exercise 2-3 xs a wk add to benefits of endurance-type activities

• Importance of warm up is controversial

• Cool-down for 5 min after exercise is important for lactic acid removal from muscles, slow return from vasodilation and gradual return of blood to other parts

Examples of moderate physical activity

• Moderate amount of physical activity uses roughly 150 Cal/day or 1000 Cal/wk

HF and exercise capacity• Limitations of exercise capacity is one of the

main manifestations of HF

• Varies with severity of disease and correlates with survival

• Ventilatory threshold (VT) or anaerobic threshold: when VE increases disproportionately to VO2 seen at 60-70% VO2max

• VT is a reflection of lactic acid production by muscles

• If a patient fatigues before reaching VT, it means that the cause in noncardiac

• 6 min walk test has also been used (simple and inexpensive)

• Measures distance covered in 6 min on a flat surface and correlates well with VO2max and outcome (distinguish better bet. NYHA class 3 &4 than 1 & 2)

Cardiac dysfunction

• CO might be nl at rest but unable to increase adequately with even mild exertion

• Decreased CO would lead to less perfusion of muscles, early anaerobic metabolism, fatigue and eventual wasting

• HF patients are not able to attain VO2max and peak VO2 is used instead

Impaired hemodynamic response to exercise in CHF

• By definition HF is a high chatecholamine state which will lead to down regulation of beta receptors and desensitization

• Starling mechanism is altered due to DHF and possible pericardial constraint with inability to increase SV

• With exercise PCWP is significantly increased which causes more lung congestion

• With time PAP will rise and will contribute to decrease in CO

• Mitral regurgitation complicates the picture

Skeletal muscle dysfunction

• Acute and chronic (more important) hypoperfusion

• Apoptosis is seen in SM of HF pts. correlating with exercise limitation and muscle wasting

• Capillary density is decreased in HF which means less oxidative capacity

• Oxidative stress in the muscles with production of ROS has been implicated in pathophysiology of HF

• Muscle fiber type changes to more fatigable

• Intrinsic SM metabolic defects (lower PH, less PCr, reduced mitochondrial size and function)

• leading to less efficient use of energy and rapid accumulation of lactic acid

Functional abnormalities

• SM ergo and metaboreceptors are enhanced in HF resulting in increased ventilation and sensation of dyspnea with exercise

• Increased sympathetic tone with decreased effective renal perfusion (more Na and H2O)

• Inducible NO synthase increases with decrease in CK needed in energy transfer from mit. to cytosol

Skeletal muscle dysfunction in HF

Left ventricular dysfunction

Decreased perfusion

Decreased activity

Catabolic factorsInsulin resistance

Increased vascular resistance

Sympathetic activation

Baroreflex downregulation

Ergoreflex activation

Increased VE/VCO2

Breathlessness

Respiratory muscle changes

Fatigue

Muscle fatigueMuscle wasting

Decreased aerobic capacity

Pulmonary dysfunction

• Respiratory muscle dysfunction is part of general myopathy in HF (fatigue and dyspnea)

• Diaphragm on the contrary shows increase in slow high endurance fibers (increased work)

• Impaired pulmonary diffusion with increase in VE due to ventilation/ perfusion mismatch severity of which is related to degree of HF

Peak VO2 and prognosis

• Most objective of functional capacity in HF

• Important predictor for transplant

• Peak VO2 ≤10-12 & no malignancy/advanced lung ds were accepted for transplant

• Survival varied with peak VO2

Peak VO2 and survival

Limitations• Data was published before era of B-blockers

• PVD, muscular deconditioning, arthritis, angina pectoris and low motivation can terminate the test prematurly

• Peak VO2 less useful in women than men but prognosis is better; a better variable would be % predicted VO2 for age and wt.

Additional predictors

• The value of peak VO2 can be enhanced by:

1. 3 yr survival of pts with VO2< 14 unable to reach a SBP of 120mm Hg was 55% vs 83%

2. Ability to have a CO (by invasive techniques) adequate with exercise had better prognosis

Peak VO2 + BP predict outcome in CHF

3. VT or AT < 11 mL/Kg/min in a study was more predictive of 6 mo mortality than VO2

4. Another non invasive test is dobutamine stress echocardiography, with increase in LVED diam. and wall stress indicating higher mortality

5. VE/VCO2 slope (>34 bad) is easier to obtain and better predictor than VO2max, NYHA class and LVEF

6. Another parameter is O2 uptake efficiency slope (OUES) derived from VO2 and VE

7. Peak stroke work index (> 30gm/m2 good) by Swan-Ganz is most predictive of prognosis

Ventilatory response to exercise predicts survival

Stroke work index and survival

Recommendations

• 2009 ACC/AHA class 1 recommendation to the use of exercise testing and ventilation gas analysis before transplantation

• Peak VO2 should be interpreted in the context of age, lifestyle, goals and current treatment

Rehabilitation in HF

• Old recommendation was to decrease activity in HF (1970s)

• Now well known that inactivity increases symptoms of HF

• Exercise training HF patients improves symptoms, exercise tolerance, quality of life and may impact outcome

Plot of individual values of anaerobic threshold pre and post-training

• No relationship bet. LVEF and peak exercise performance

• Treatment with Inotropes, and vasodilators such as ACEI, nitrates and hydralazine did not acutely improve exercise tolerance

• There must be other reasons than just cardiac dysfunction

Ejection fraction vs peak VO2 in HF

Ejection fraction

Peak

VO

2 (m

L/Kg

/min

SM theory of HF

• Inactivity leads to muscle atrophy

• In HF high energy phosphates are used inefficiently

• Lactic acid accumulates more rapidly contributing to fatigue and limited exercise capacity

• Respiratory muscles are involved which adds to dyspnea

Skeletal muscle hypothesis of HF

LV dysfunction

Reduced peripheral blood flow

Increased ergoreceptor activity

Increased ventilation

Dyspnea

Skeletal and respiratory

Catabolic state

TNF, insulin resistance, malnutrition, inactivity

Muscle fatigueSympatho-excitationVagal-withdrawal

VasoconstrictionIncreased afterload

Effect of exercise in HF• No benefit at all in acute setting

• In compensated HF it has the following benefits:

1. Improves diastolic function with increase in peak early diastolic filling rate both at rest and during exercise which enhances peak VO2 and CO

2. Improves SM energetics allowing pts. To perform same work at lower HR, rate-pressure product and VE

3. Symptomatic improvement in dyspnea and fatigue

4. Reduces sympathetic tone and increases vagal tone at rest with resultant decrease in SVR and improved CO

5. Reduces resting levels of angiotensin, aldosterone, ADH and BNP

6. Improves endothelial function with more NO production and AC mediated vasodilation

7. Reduction of TNFa, IL6 and their receptors is addition to apoptotic mediators (Fas and FasL)

• Nothing predicts outcome of exercise training in HF pts. except in pts. with hibernating cardiomyopathy who always benefit

Effect on mortality and morbidity Response to exercise training Organ system/Tissue

Peak VO2 survival hospitalization

in cardiac output; in peak VO2; reverse chronotropic incompetence; regional blood flow

Improve central transport and regional blood flow

HRV arrhythmia survival hospitaliz. plasma NE survival

HRV; plasma NE (rest) Autonomic nervous system

Change in muscle composition QOL hospitalization

aerobic enzymes; mitochondria size/density; capillary density; relative type 1 fibers

Skeletal muscle

Coronary blood flow survival Ischemia and MI hospitaliz.

vascular reactivity Peripheral vasculature

Potential mechanism of how exercise training improves survival

Effect on hemodynamics• In a meta-analysis of RCTs of exercise in HF aerobic

training was associated with sig. improvement in LVEF, EDV and ESV

• May be due to decreased SVR

• Also BNP is reduced meaning improved hemodynamics

• Type of exercise training may be imp (interval vs continuous)

Effect on functional capacity• Different studies have shown sig improvement in exercise

time, peak VO2 and NYHA class after 1-6 mo of exercise training

• This means that pts. can participate in their daily activities more easily and comfortably

• In a review aerobic plus strength training was not more effective in terms of VO2max

• Some evidence that strength training might actually obliterate benefits gained by aerobic exercise

• High intensity interval aerobic exercise up to 95% peak HR was associated with better outcome concerning remodeling and improvement in VO2max than moderate continuous exercise training up to 70% peak HR

• Since HF pts. rarely exert themselves to maximal capacity, a more important result was reported in a study which showed a 25% increase in VT and 52% increase in submaximal exercise time after 4-6 months 3-5 hrs/wk training (walking, biking & jogging)

Other benefits reported

• Sig. increase in 6 min walk distance (mean of 41 m in 2003 Cochrane review)

• 16-52% reduction of resting catecholamines indicating better hemodynamics demonstrated also by better heart rate variability and lower resting HR

Effect on outcome

• Meta-analysis of 9 RCT (801 pts.)

• Supervised exercise for at least 8wks to at least 60% peak HR or 50% peak VO2

• Average 2 yr F/U showed sig. reduced mortality (22 vs 26%) and combined end points of death or hospitalization (32 vs 43%)

HF ACTION study• Most previous studies are small and single center

• Meta-analyses are retrospective & prone to error

• Negative trials are less likely to be published

• Necessitated RCT: HF ACTION study which enrolled 2,331 pts. in the US and Canada to see if exercise training will reduce mortality and hospitalization in NYHA 2-4 HF pts (95% NYHA 2-3)

• Modest but significant improvement in all-cause mortality and hospitalizations

Cost-effectiveness• Assessed over 14 mo training period in pts with stable

HF

• 1.82 yrs/person increase in life expectancy over 15.5 yrs

• Cost of $1,773/ life-yr saved

• HF ACTION compared hospitalization costs vs cost of exercise training

• Medical costs were lower with exercise training

Recommendations

• ACC/AHA 2009 update of 2005 Class 1 recommendation to cardiac rehabilitation in NYHA 2&3 with no advanced arrhythmias and other limitations

• Benefits are seen in high or low levels of training and as early as 3 wks

• Not enough data to recommend it for NYHA 4

QI project