Presentatie V. Niemeijer, Het falende hart in beweging

Het Falende Hart in Beweging

Victor Niemeijer Sportarts, Elkerliek Ziekenhuis Helmond

CNE Hartfalen en Hartrevalidatie

Nederlandse Vereniging voor Hart en Vaat Verpleegkundigen

Dinsdag 21 april 2015

*  Pathofysiologie

*  Fysieke Training

*  Inspanningsdiagnostiek

Inhoud

CNE Hartfalen en Hartrevalidatie 2

Vraag Score Antwoord Verschil (abs)

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Quiz


*  Hoeveel procent van de patiënten met chronisch hartfalen is in Nederland vijf jaar na diagnose overleden?

Vraag 1


*  Hoeveel procent van de patiënten met chronisch hartfalen die een indicatie hebben voor hartrevalidatie krijgt dit in Nederland daadwerkelijk aangeboden?

Vraag 2


*  Hoeveel procent van de patiënten met chronisch hartfalen verbeteren hun peak VO2 (>109%) door fysieke training?

Vraag 3


*  Hoeveel procent van de patiënten met chronisch hartfalen valt gemiddeld uit tijdens een fysiek trainingsprogramma van 12 weken?

Vraag 4


*  Hoeveel hartslagen (/min) moet men bij inspanning verwijderd blijven van de VT-‐zone van de ICD van een CHF patiënt?

Vraag 5


*  Vanaf welke waarde voor peak VO2

*  wordt een CHF patient geschikt geacht voor hartrevalidatie? (goed genoeg)

*  wordt een CHF patient geschikt geacht voor harttransplantatie? (slecht genoeg)

Vraag 6


Epidemiologie Het Falende Hart in Beweging


Epidemiologie


Pathofysiologie Het Falende Hart in Beweging


*  “A pathophysiological state in which an abnormality of cardiac function is responsible for the failure of the heart to pump blood at a rate commensurate with the requirements of the metabolising tissues” (Braunwald, 1980)

*  Etiologie *  Ischemische cardiomyopathie *  Dilaterende cardiomyopathie *  Hypertensieve cardiomyopathie *  Valvulaire cardiomyopathie

Pathofysiologie CHF


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*  Centraal *  Afgenomen cardiac output (CO = SV X HR) *  Afgenomen LVEF (dilatatie) *  Coronair perfusie *  Sympathetic nerve activity (SNA) *  Systemische inflammatie

Pathofysiologie CHF


*  Perifeer *  Perifere vasoconstric.e (neurohormonaal) *  Skeletspieratrofie *  Shi$ vezeltype (I IIa/b)

*  Calciummetabolisme *  Capillairen *  verminderde RBC flux

*  Compe..eve bloedstromen *  Ademhalingspieren vs locomotor spieren

Pathofysiologie CHF

decrease in muscle pH during exercise, and decreased mitochon-drial density and oxidative enzyme content. Consistent with thehypothesis that the skeletal myopathy in HF limits exercisecapacity, each of these features has been correlated with de-creased exercise capacity in patients with chronic HF.

Controversy in the Role of MitochondrialOxidative Metabolism

Although a compelling and appealing explanation for theexercise dysfunction in HF, the story of the skeletal myopathyof HF as outlined thus far may be incomplete.

Intrinsic Mitochondrial FunctionMettauer et al16 examined the intrinsic mitochondrial functionin situ rather than selective enzyme activity in homogenizedspecimens in intact muscle biopsies from patients withchronic HF on optimal therapy and compared them with truesedentary as well as active control subjects. HF patientscompared with sedentary and active control subjects haddiminished exercise capacity as measured by peak oxygenconsumption and ventilation threshold; selective mitochon-drial enzyme activity was diminished as well. Surprisingly,however, the muscle (mitochondrial) oxidative consumptionwas not different in HF patients compared with the sedentarycontrol subjects(Figure 2). Muscle mitochondrial oxidationwas diminished in both of these groups compared with theactive control group. The investigators point out that themitochondrial oxygen consumption (the tricarboxylic acidcycle) is not limited by a rate limiting enzyme and thatalthough individual enzyme activity levels are diminished inHF, they are apparently still in sufficient quantity to maintainnormal mitochondrial respiration. These findings have beenconfirmed by other investigators.17

These investigators have reopened the question of whatadditional factors in the skeletal musculature, other thanmitochondrial oxidative metabolism, may lead to decreasedexercise capacity in chronic HF patients on optimal therapy.

Skeletal Muscle Excitation-Contraction CouplingAfter depolarization of the sarcolemma, calcium is releasedfrom the intracellular calcium storage site, the sarcoplasmicreticulum(SR), through type 1 ryanodine receptors (RyR1)(Figure 3). Intracellular calcium concentration rapidly in-creases, binding troponin C, allowing myosin and actin crossbridges to form, leading to muscle contraction in a processcalled excitation-contraction (E-C) coupling. Calcium is thenrapidly sequestered in an energy-requiring reaction utilizingthe sarco(endo)plasmic reticulum Ca2!-ATPase (SERCA).Abnormalities of E-C coupling have been identified in HF,although much of the work has focused on cardiac but notskeletal muscle E-C coupling.

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Figure 1. A, Fiber type shift correlates with decreased exercisecapacity. Morphometric analyses of muscle biopsies from HFpatients have revealed a shift in fiber type, from slow-twitch,oxidative type I fibers to fast-twitch, glycolytic type IIb fibers.The shift in fiber type correlates with diminished exercise capac-ity as estimated by peak oxygen consumption. B, Decreasedmitochondrial density correlates with decreased exercise capac-ity. Quantified by electron microscopy, volume density of themitochondrial in HF is significantly diminished compared withcontrol subjects. See text for discussion. Filled squares indicateHF and open squares, control subjects. Reprinted with permis-sion from Woltersk Kluwer/Lippincott Williams & Wilkins.9

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Figure 2. Correlation between exercise capacity and muscleoxidative capacity. HF patients have lower exercise capacity butsimilar muscle oxidative capacity compared with sedentary con-trol subjects; both exercise capacity and muscle oxidativecapacity are lower in these groups compared with active controlsubjects. The decreased exercise capacity in HF, therefore, can-not be entirely attributed to decreased muscle oxidative capac-ity. Open circles indicate HF; open triangles, sedentary controlsubjects; and closed triangles, active control subjects. Modifiedfrom Reference 16.

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*  Coordinated adaptation

Pathofysiologie CHF

Exercise necessitates adequate oxygen transport and deliv-ery to meet the increased oxygen requirements in exercisingmuscle. Oxygen transport is a multistep pathway in which thecardiovascular system works alongside the pulmonary, hema-tologic, and metabolic systems to ensure adequate oxygentransport. According to the theory of coordinated adaptation,when an acute, primary cardiac disorder becomes chronic,such as when an acute myocardial infarction progresses tochronic systolic dysfunction, the reserves of oxygen transportcapacity in the periphery are unused and superfluous. In thissetting, maintaining an excessive oxidative muscle mass in apatient with a severely limited cardiac output might imposelarge energetic requirements to maintain a reserve capacityunlikely ever to be utilized. Thus, a system governed bycoordinated adaptation ensures that the overall efficiency ofthe system is optimized by matching all steps at a lowerfunctional level (Figure 5).

The chronic condition of COPD may be an additionalexample of coordinated adaptation,6 in which a skeletalmyopathy, sharing many of the features of the skeletalmyopathy of HF, is present.3,26 Chronic renal failure, al-though more heterogeneous, may be yet another example.27

In these chronic conditions, reduced muscle mass, fiber

atrophy and switch from oxidative to glycolytic fiber types,decreased oxidative enzyme content and mitochondrial den-sity have all been described.

How is the Downregulation of All SystemsInvolved in Oxygen Transport Signaled and

Coordinated Throughout the Body?All of these chronic conditions, HF, COPD, and chronic renaldisease, share the common feature of a stressed system. Ineach case, SNA is chronically elevated, approaching achronic flight or fight condition. Although acutely life-saving, chronic activation of the sympathetic nervous systemhas many deleterious consequences. In chronic HF, I hypoth-esize that sympathetic excitation provides an important signalto the skeletal musculature that there has been a primarycardiac injury (Figure 6). SNA may directly and indirectly,through cytokine release, then lead to the coordinated, sec-ondary downregulation of the other steps in oxygen transport,especially downregulation of the skeletal muscle capacity.

In summary, increased SNA during acute cardiac injurybecomes chronic and may be the signal to other organs andtissues to decrease oxygen transport capacity.

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Figure 5. Coordinated adaptation in oxy-gen transport. Arrow size indicatescapacity; shaded arrows indicate sites ofgreatest limitation. The number of plussigns indicates the effect of changingcapacity on changing maximal oxygenflux. The athlete has matched capacitiesat all steps. The untrained person is lim-ited by cardiovascular delivery and mus-cle extraction. The patient with chroniclung disease is limited by pulmonary dif-fusion. In chronic HF, the limited maxi-mal cardiac output leads to downregula-tion of muscle oxygen extraction andmitochondrial utilization. Modified fromReference 6.

Figure 6. Mechanisms by which SNAmay contribute to the skeletal myopathyof HF. See text for discussion.

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Fysieke training Het Falende Hart in Beweging


Centrale effecten reverse remodelling



Centrale effecten reverse remodelling


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Centrale effecten coronaire perfusie



Perifere effecten skeletspierdoorbloeding

24 CNE Hartfalen en Hartrevalidatie

Perifere effecten skeletspiermetabolisme


Perifere effecten neurohormonaal


crine hyperactivity associated with CHF, but the neurohor-monal activation in response to strenuous exercise stressappears to be unaltered.

Neurohormone concentrations in health and disease.The neurohormone assays used in the present study havebeen used reliably in our laboratory for numerous experi-ments with human subjects (24–26). Thus, intralaboratorycomparisons are possible that are not limited by the con-founding problems associated with interlaboratory compar-isons of biochemical data. In an attempt to interpret thephysiologic significance of the relative reductions in plasmaneurohormone levels in our trained CHF patients, wecompared results from the present study with neurohor-mone levels in two reference groups: 1) age-matchedhealthy subjects, and 2) age-matched orthotopic hearttransplant recipients recently studied in our laboratory (Figs.2 and 3). The 16-week exercise training period used in ourCHF patients was associated with reductions in concentra-tions of ANG II, ALDO and AVP to levels that arecomparable (p ! 0.05) with those observed in age-matchedsedentary reference subjects (no medications) and stableheart transplant recipients (“standard transplant care”) (Figs.2 and 3). Plasma ANP in trained CHF patients was alsoreduced to levels observed in age-matched healthy subjects(p ! 0.05) (Fig. 3).

Mechanism of neuroendocrine activation in CHF. Twoprincipal mechanisms are recognized in neurohormonalactivation in CHF patients, and both may be modulated byendurance exercise training. One contends that neuroendo-crine hyperactivity in CHF is triggered by baroreflex dys-function in association with a prolonged exposure to lowcardiac output and reduced blood pressure. Sinoaortic andcardiac baroreceptors normally exert a tonic inhibitoryinfluence on resting sympathetic activity, the kidney RAAS,and AVP release (27). In CHF patients, tonic inhibitorybaroreflexes are depressed and contribute to sympathetic

excitation and elevated circulating neurohormone levels(27–33).

An alternative but physiologically related mechanism forneuroendocrine hyperactivity in CHF is associated with theexcitatory effects of circulating ANG II. Plasma ANG IIlevels initially become elevated owing to renal underperfu-sion, the primary stimulus for ANG II production by therenal RAAS. Elevated ANG II exerts excitatory effects atthe level of the brain (34), ganglionic transmission (35) andat adrenergic nerve terminals (36,37).

Exercise and baroreflex sensitivity. The present study wasnot designed to investigate the possible mechanisms respon-sible for neuroendocrine modulation in heart failure, butseveral studies have suggested that strenuous enduranceexercise may improve baroreflex sensitivity. Convertino etal. (19,20) have repeatedly observed that a single bout ofintense dynamic exercise increased the sensitivity ofbaroreceptor-cardiac reflexes (i.e., heart rate regulation) andbaroreceptor-vascular reflexes (i.e., peripheral vascular resis-tance regulation), independent of blood volume changes.Pagani et al. (21) used a crossover design to investigate theeffects of exercise training (6 months of jogging) and nottraining (4 months without jogging) on baroreceptor sensi-tivity in 11 subjects with mild hypertension. The authors

Figure 1. Relative changes in angiotensin II (ANG II), aldoste-rone (ALDO), arginine vasopressin (AVP), and atrial natriureticpeptide (ANP) after four months of endurance exercise training orcontrol period. Data are mean ! SEM. *p " 0.05 After trainingversus before training.

Figure 2. Angiotensin II (top panel) and aldosterone (bottompanel) concentrations drawn at rest in the standing posture forage-matched healthy control subjects; heart transplant recipients;heart failure patients before four months’ exercise training; andheart failure patients after four months’ exercise training. Data aremean ! SEM. *p " 0.05 heart failure before training versus theother three groups. †p " 0.05 versus heart failure after training andnormal control group.

1173JACC Vol. 34, No. 4, 1999 Braith et al.October 1999:1170–5 Neurohormones in Heart Failure

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used IV phenylephrine to study the effects of training on theheart rate–blood pressure relationship and reported a netimprovement in the tonic inhibitory activity of the majorconstituents of the sympathetic-vagal balance. The mecha-nism responsible for exercise-induced improvements inbaroreflex sensitivity is not understood. Investigators havestudied all components of the reflex arc, but specific mech-anisms have not been identified because of the complexity ofthe neural circuitry.

Baroreflex sensitivity and exercise capacity and survivalrate are also improved in CHF patients by administration ofACE inhibitors (9,11,12,37,38). In aggregate, theangiotensin-converting enzyme (ACE) inhibitor data sug-gest that ANG II plays an important role in the centralintegration of baroreflex information. Grassi et al. (9)recently provided the first direct evidence, via muscle mi-croneurography, that chronic ACE inhibitor treatment inCHF patients caused both a reduction in central sympa-thetic nerve traffic and an improved baroreceptor restrainton sympathetic traffic. Thus, a reduction in circulatingANG II achieved through exercise training may act favor-ably on baroreflex control of sympathetic activity (9,39).

Cardiac output and renal perfusion. The exercise-induced reduction of plasma neurohormones observed inthe present study could possibly be taken as a marker ofimproved cardiac pump function. Certainly increased car-

diac output would augment renal perfusion and therebydiminish the primary stimulus for activation of the kidneyRAA system. Although we did not measure cardiac outputin the present study, results from previous long-term train-ing studies in CHF patients do not reveal evidence ofincreased cardiac output. Sullivan et al. (40) reported a 23%increase in VO2peak in patients with CHF (left ventricularejection fraction [LVEF] 24 ! 10%) after four months ofexercise training, but there were no changes in rest orexercise stroke volume, cardiac output or LVEF. Mostexercise training studies in CHF patients reporting im-provements in VO2peak observe no changes in rest orexercise measurements of left ventricular performance orcentral hemodynamics. Rather, the beneficial elements ofthe training response are attributed to peripheral adapta-tions (41,42).

Study limitations. This study was limited by small samplesize, relatively brief duration of exercise training and absenceof outcome data. In addition, the study would be strength-ened by inclusion of either direct (intraneural recordings) orindirect (plasma norepinephrine or epinephrine data) in-dexes of efferent sympathetic nerve traffic at study entry andafter 16 weeks. Finally, the CHF patients in the presentstudy were carefully selected, and they received very expertheart failure and exercise training care that may not begeneralized.

Conclusions. It is generally believed that the neurohor-monal activation in heart failure has an adverse prognosticsignificance and that reduction in circulating neurohor-monal levels by treatment represents a favorable therapeuticeffect. Thus, demonstration that endurance exercise trainingis accompanied by a marked reduction ("25% to 30%) inresting levels of plasma ANG II, ALDO, AVP, and ANPhas clinical implications. Currently, this demonstration hasonly been provided in one small cohort of CHF patientswho trained for a period of 16 weeks.

AcknowledgmentThe authors wish to acknowledge the late Michael L.Pollock, PHD, for his contributions in the design andimplementation of this study.

Reprint requests and correspondence: Dr. Randy W. Braith,P.O. Box 118206, Center for Exercise Science, University ofFlorida, Gainesville, Florida 32611. E-mail: [email protected].

REFERENCES

1. Cohn JN, Levine TB, Olivari MT, et al. Plasma norepinephrine as aguide to prognosis in patients with chronic congestive heart failure.N Engl J Med 1984;311:819–23.

2. Francis GS, Benedict C, Johnstone DE, et al., for SOLVD Investi-gators. Comparison of neuroendocrine activation in patients with leftventricular dysfunction with and without congestive heart failure.Circulation 1990;82:1724–9.

3. Packer M. The neurohormonal hypothesis: a theory to explain the

Figure 3. Arginine vasopressin (top panel) and atrial natriureticpeptide (ANP) (bottom panel) concentrations drawn at rest in thestanding posture for age-matched healthy control subjects; hearttransplant recipients; heart failure patients before four months’exercise training; and heart failure patients after four months’exercise training. Data are mean ! SEM. *p ! 0.05 heart failurebefore training versus the other three groups. †p ! 0.05 versusheart failure after training and normal control group.

1174 Braith et al. JACC Vol. 34, No. 4, 1999Neurohormones in Heart Failure October 1999:1170–5

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*  Inspanningscapaciteit

*  Kwaliteit van leven

*  Prognose

Fysieke training




HF-‐ACTION (Flynn 2009 JAMA)


Fysieke training kwaliteit van leven

CHANGE (Wielenga 2008 Heart Fail Rev)


Fysieke training prognose

Training 3-‐7x / week 8 weken – 1 jaar 60-‐80% peak VO2 / HF Interventie: 88 overleden (mediane tijd tot

event: 618 dagen)

Controle: 105 overleden (mediane tijd tot

event: 421 dagen)

NNT: 17 (2 jaar)


Training 5x / week, na 3 maanden home-‐based 60% heart rate reserve, 3x30 min

*  Aerobe en interval training

*  Krachttraining

*  Inspiratory muscle training

Trainingsvormen


*  HF-‐ACTION (2009) *  Moderate Intensity Continuous Training (MIT of CT)

*  Meyer (1996) *  Supra Hoog-‐intensieve Interval Training (HIIT)

*  Wisløff (2007) *  Aerobe Interval Training (AIT)

Aerobe en interval training maakt intensiteit uit?


CT (HF-‐ACTION)


HIIT (Meyer)

Interval training in pa-ents with severe chronic heart failure: analysis and recommenda-ons for exercise procedures. MEYER, KATHARINA; SAMEK, LADISLAUS; SCHWAIBOLD, MATTHIAS; WESTBROOK, SAMUEL; HAJRIC, RAMIZ; BENEKE, RALPH; LEHMANN, MANFRED; ROSKAMM, HELMUT Medicine & Science in Sports & Exercise. 29(3):306-‐312, March 1997.


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Hoe werkt AIT? Exitatie – Contractie Koppeling


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Hoe werkt AIT? Hartspierfunctie


Hoe werkt AIT? Hartspiermetabolisme


Vergelijking HIT


HIT vs beweegadvies


HIT vs MIT / CT


Randomized trial of progressive resistance trainingto counteract the myopathy of chronic heart failure

CHARLES T. PU,1,2,3 MEREDITH T. JOHNSON,1,3 DANIEL E. FORMAN,3,4

JEFFREY M. HAUSDORFF,5 RONENN ROUBENOFF,1 MONA FOLDVARI,1ROGER A. FIELDING,1,6 AND MARIA A. FIATARONE SINGH1,3,7

1Nutrition, Exercise Physiology, and Sarcopenia Laboratory, Jean Mayer United States Departmentof Agriculture, Human Nutrition Research Center on Aging, Tufts University, Boston 02111;2Brockton West Roxbury Veterans Affairs Medical Center, Division on Aging, Harvard MedicalSchool, Boston 02132; 3Hebrew Rehabilitation Center for Aged, Division on Aging, Harvard MedicalSchool, Boston 02131; 6Department of Health Sciences, Sargeant College of Health RehabilitationSciences, and 4Department of Cardiology, Boston University, and 5Gerontology Division, Beth IsraelDeaconess Hospital, Boston, Massachusetts 02215; and 7School of Exercise and Sport Science,University of Sydney, Sydney, Australia 2141Received 25 April 2000; accepted in final form 10 January 2001

Pu, Charles T., Meredith T. Johnson, Daniel E. For-man, Jeffrey M. Hausdorff, Ronenn Roubenoff, MonaFoldvari, Roger A. Fielding, and Maria A. FiataroneSingh. Randomized trial of progressive resistance trainingto counteract the myopathy of chronic heart failure. J ApplPhysiol 90: 2341–2350, 2001.—Chronic heart failure (CHF)is characterized by a skeletal muscle myopathy not optimallyaddressed by current treatment paradigms or aerobic exer-cise. Sixteen older women with CHF were compared with 80age-matched peers without CHF and randomized to progres-sive resistance training or control stretching exercises for 10wk. Women with CHF had significantly lower musclestrength (P , 0.0001) but comparable aerobic capacity towomen without CHF. Exercise training was well toleratedand resulted in no changes in resting cardiac indexes in CHFpatients. Strength improved by an average of 43.4 6 8.8% inresistance trainers vs. 21.7 6 2.8% in controls (P 5 0.001),muscle endurance by 299 6 66% vs. 1 6 3% (P 5 0.001), and6-min walk distance by 49 6 14 m (13%) vs. 23 6 19 m (23%)(P 5 0.03). Increases in type I fiber area (9.5 6 16%) andcitrate synthase activity (35 6 21%) in skeletal muscle wereindependently predictive of improved 6-min walk distance(r2 5 0.78; P 5 0.0024). High-intensity progressive resistancetraining improves impaired skeletal muscle characteristicsand overall exercise performance in older women with CHF.These gains are largely explained by skeletal muscle and notresting cardiac adaptations.

exercise; aging; type I fibers

CHRONIC SYSTOLIC HEART FAILURE (CHF) is the only car-diac diagnosis that is continuing to increase in preva-lence in the United States due to the prolonged sur-vival of those with hypertension and ischemic heartdisease, as well as improved average life span of the

population (35, 42). The clinical hallmark of the dis-ease is exercise intolerance, manifested as fatigue anddyspnea during increasingly minimal activities (21).

Mounting evidence suggests that peripheral skeletalmuscle abnormalities figure prominently in the exer-cise intolerance associated with CHF (15–17, 26, 40,53, 54), whereas central hemodynamic parameters,such as ejection fraction, are far less predictive ofclinical symptoms or mortality (34). These peripheralabnormalities include a skeletal muscle myopathycharacterized by preferential loss and atrophy of type I(slow, oxidative) fibers, decreased oxidative enzymecapacity and mitochondrial volume density, early acti-vation of glycolytic pathways of ATP generation duringwork, and reduced muscle endurance, strength, power,and overall exercise tolerance compared with healthy,age-matched individuals (39). The selective loss of ox-idative fibers distinguishes this condition from type IIfiber selectivity of muscle atrophy common to agingand disuse syndromes (29, 47, 66) and suggests that adifferent pathogenetic mechanism may be operative.

The degree of exercise intolerance in CHF correlatesstrongly with both mortality and quality of life (69, 70);yet current medical therapies often fail to specificallyaddress many of the potential mechanisms that under-lie these symptoms (25). Aerobic exercise interventionshave been shown to be tolerable in middle-aged andyoung-old patients with stable CHF and result in im-proved aerobic capacity without improving central he-modynamic features (contractility, stroke volume, ejec-tion fraction, chamber diameter, filling times) of thedisease (1, 18–20, 24, 62), as well as improved survival,quality of life, and reduced rate of hospitalizations (5,27). However, the limited experience reported from the

Address for reprint requests and other correspondence: M. A. F.Singh, Nutrition, Exercise Physiology and Sarcopenia Laboratory,Jean Mayer USDA Human Nutrition Research Center on Aging atTufts Univ., 711 Washington St., Boston, MA 02111 (E-mail:[email protected]).

The costs of publication of this article were defrayed in part by thepayment of page charges. The article must therefore be herebymarked ‘‘advertisement’’ in accordance with 18 U.S.C. Section 1734solely to indicate this fact.

J Appl Physiol90: 2341–2350, 2001.

8750-7587/01 $5.00 Copyright © 2001 the American Physiological Societyhttp://www.jap.org 2341

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Krachttraining


Effect of Resistance Exercise on SkeletalMuscle Myopathy in Heart

Transplant RecipientsRandy W. Braith, PhD, Peter M. Magyari, PhD, Gary L. Pierce, MS,David G. Edwards, PhD, James A. Hill, MD, Lesley J. White, PhD,

and Juan M. Aranda, Jr., MD

The purpose of this study was to determine the efficacyof resistance exercise in reversing skeletal muscle my-opathy in heart transplant recipients. Myopathy, engen-dered by both heart failure and immunosuppressionwith glucocorticoids, is a post-transplant complication.The sequelae of myopathic disease includes fiber-typeshifts and deficits in aerobic metabolic capability. Werandomly assigned patients to either 6 months of resis-tance exercise (training group; n ! 8) or a control(control group; n ! 7) group. Exercise was initiated at 2months after transplant. Biopsy of the right vastus late-ralis was performed before and after the 6-month inter-vention. Myosin heavy chain (MHC) composition wasassessed using sodium dodecyl sulfate-polyacrylamidegel electrophoresis. Biochemical assays were performedto determine citrate synthase, 3-hydroxyacyl-CoA-dehydrogenase, and lactate dehydrogenase activity.There were no group differences (p >0.05) in MHCcomposition and enzymatic reserve at baseline. Im-

provements in the training group for citrate cynthase("40%), 3-hydroxyacyl-CoA-dehydrogenase ("10%),and lactate dehydrogenase activity ("48%) were signif-icantly greater (p <0.05) than in the control group("10%, #15%, and "20%, respectively). Oxidativetype 1 MHC isoform concentration increased signifi-cantly in the training group ("73%, p <0.05) but de-creased in the control group (#28%; p <0.05). Glyco-lytic type 2x MHC isoform increased significantly (17%;p <0.05) in the control group but decreased (#33%;p <0.05) in the training group. This is the first study todemonstrate that resistance training elicits myofibrillarshifts from less oxidative type II fibers to more oxidativefatigue-resistant type I fibers in heart transplant recipients.Resistance exercise initiated early in the post-transplantperiod is efficacious in changing skeletal muscle phenotypethrough increases in enzymatic reserve and shifts in fibermorphology. !2005 by Excerpta Medica Inc.

(Am J Cardiol 2005;95:1192–1198)

Skeletal muscle myopathy is a hallmark of end-stage heart failure involving both morphologic

shifts in fiber type1–4 and histochemical changes inenzymatic reserve.5,6 After orthotopic heart transplan-tation, immunosuppression regimens using bolus glu-cocorticoids cause further de novo deleterious effectson skeletal muscle.7–11 No therapeutic intervention hasbeen developed to prevent myopathic disease in hearttransplant recipients. The purpose of this study was todetermine if an intervention consisting of progressiveresistance exercise, initiated early in the post-trans-plant period, would be efficacious in changing skeletalmuscle phenotype through increases in enzymatic re-serve and shifts in fiber morphology in heart transplantrecipients. We used skeletal muscle biopsy to prospec-tively assess skeletal muscle morphology and enzy-matic reserve in heart transplant recipients at 2 monthsafter transplant and repeated the measurements after 6

months of progressive resistance exercise training or acontrol period.

METHODSSubjects: Fifteen patients (n ! 15) were recruited to

participate in the study at the time they were listedwith the United Network for Organ Sharing as candi-dates for orthotopic heart transplantation. Descriptivecharacteristics of heart transplant recipients are listedin Table 1. Before transplantation, patients were ran-domly and prospectively assigned either to a groupthat would participate in a 6-month program of resis-tance exercise training (n ! 8) or to a control groupthat would not participate in resistance exercise (n !7). Before transplantation, all subjects participated in ahospital-based physical therapy program consisting ofmild walking and resistance exercises. After trans-plantation, all subjects participated in standard carehome-based walking programs that were comparablein intensity and duration, but only the resistance train-ing group performed specific supervised resistanceexercises.

All heart transplant recipients had biatrial anasto-mosis at the time of transplantation and were receivingtriple-drug immunosuppression therapy with cyclo-sporine, prednisone, and azathioprine. Cyclosporinedose was titrated to maintain whole blood troughlevels of approximately 300 ng/ml. No subject re-

From the Center for Exercise Science, College of Health andHuman Performance and the College of Medicine, University ofFlorida, Gainesville, Florida; Lynchburg College, Lynchburg,Virginia; and the Department of Kinesiology, University of NewHampshire, Durham, New Hampshire. This report was supportedby a grant from the American Heart Association, Dallas, Texas, toDr. Braith. Manuscript received September 13, 2004; revised manu-script received and accepted January 10, 2005.

Address for reprints: Randy W. Braith, PhD, PO Box 118206,Center for Exercise Science, University of Florida, Gainesville, Florida32611. E-mail: [email protected].

1192 ©2005 by Excerpta Medica Inc. All rights reserved. 0002-9149/05/$–see front matterThe American Journal of Cardiology Vol. 95 May 15, 2005 doi:10.1016/j.amjcard.2005.01.048

doi:10.1136/hrt.2008.159582 published online 1 Apr 2009; Heart

and Nicole Uszko-Lencer Martijn A Spruit, Rose-Miek Eterman, Valery Hellwig, Paul Janssen, Emiel Wouters

patients with chronic heart failuremoderate-to-high intensity resistance training in A systematic review on the effects of

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HIT vs HIT + krachttraining


*  Inspiratory muscle training *  Pi max *  < 70% Pi max predicted

*  Training *  30 min/dag *  2-‐3x/week *  20-‐40% Pi max

Ademhalingstraining


Inspanningsdiagnostiek Het Falende Hart in Beweging


1.  Objectiveren inspanningsvermogen / aansturen training

2.  Vaststellen eventuele contra-‐indicaties voor training

3.  Vaststellen aard beperking (co-‐morbiditeit)

4.  Evalueren prognose

Spiro-‐ergometrie bij CHF


1.  Zwakke correlatie subjectieve beleving inspanningstolerantie en

objectieve inspanningscapaciteit

2.  Geen correlatie LVEF en objectieve inspanningscapaciteit

3.  Maximale aërobe capaciteit bij CHF niet goed te voorspellen

door maximale vermogen

Objectiveren inspanningsvermogen


1.  Zwakke correlatie subjectieve beleving inspanningstolerantie en objectieve inspanningscapaciteit (Wilson et al. Circulation 1995)


2. Geen correlatie LVEF en objectieve inspanningscapaciteit (Smith et al. Circulation 1993)

V-HeFT I V-HeFT II

Peak VO2 (ml/kg/min)Peak VO2 (ml/kg/min)

LV-E

F (%

)

LV-E

F (%

)


3. Maximale aërobe capaciteit bij CHF niet goed te voorspellen door maximale vermogen

CHF

0

200

400

600

800

1000

1200

1400

1600

0 20 40 60 80 100 120

Workload

VO2

ΔVO2 / Δwork rate ratio: 7.9

Gezond

0

500

1000

1500

2000

2500

3000

3500

4000

0 50 100 150 200 250 300 350

Workload

VO2

ΔVO2 / Δwork rate ratio: 10.1


*  Peak VO2

*  gemiddelde VO2 in laatste 20-‐30 sec van een RAMP test

*  Bij goed uitgevoerde test objectieve reproduceerbare maat voor het maximale inspanningsvermogen

Objectiveren inspanningsvermogen


1.  Percentage peak VO2

2.  Percentage ventilatoire drempel

Aansturen training


Hartfrequentie is vaak niet bruikbaar!

60

70

80

90

100

110

120

Tijd

Hartf

requ

entie

(bts

/min

)

Maximale inspanningstest

RER max 1.25

Position paper European Society Cardiology 2009:


Meten van trainingseffecten -‐ welke parameters? -‐

Kemps et al. Eur J Appl Physiol 2010


*  ICD *  20 slagen onder interventie zone (cave

AFib) *  Schoudermobiliteit

*  CRT *  Instellingen bij inspanning (positief

complex V1) *  LVAD *  Pulsatile vs continuous flow

*  Hart transplantatie *  Chronotrope incompetentie (denervatie)

Specifieke aanbevelingen


*  Spier is ook ziek in CHF *  Krachttraining werkt echter slechts beperkt

*  Individueel voorschrijven trainingsvorm *  Hoog intensief training is mogelijkheid *  HR alleen bruikbaar bij chronotrope competentie *  Cave ICD

*  Spiro-‐ergometrie is zinvol en sterk aanbevolen *  Richtlijn hartrevalidatie

Take home message


*  Meyer 2013 Current heart failure reports: *  “analogous to opamizing pharmacotherapy, combining and tailoring different exercise training modaliaes according to each paaent’s baseline exercise capacity, personal needs, preferences and goals seem the most judicious approach to exercise prescripaon”

Advies


Vraag Score Antwoord Verschil (abs)

1

2

3

4

5

6a

6b

som

Antwoorden


Documents

Presentatie V. Niemeijer, Het falende hart in beweging