British Heart_Journal, I972, 34, 605-6I0.

Response of heart murmur intensity toisometric (handgrip) exercise1

D. Bruce McCraw, Wayne Siegel,2 H. Keith Stonecipher, Donald 0. Nutter,Robert C. Schlant, and J. Willis HurstFrom the Division of Cardiology, Department of Medicine, Emory University School ofMedicine and Grady Memorial Hospital, Atlanta, Georgia 30303, U.S.A.

The effects of maximal, voluntary isometric handgrip exercise on the intensity of cardiac mur-murs was evaluated in 36 patients and the results compared with the effects of amyl nitrite andphenylephrine. The isometric handgrip exercise produced immediate, reproducible, and significantincreases in heart rate and blood pressure. It also increased the intensity of murmurs due toaortic and mitral regurgitation and mitral stenosis and attenuated the murmurs of left ventricularoutflow tract obstruction.

It is not always possible to determine theorigin and significance of certain heart mur-murs during cardiac auscultation ofthe restingpatient. A variety of physical manoeuvres orpharmacological interventions are availablefor use in differential diagnosis (Dohan and-Criscitiello, I970).

Isometric handgrip exercise is a form ofsustained voluntary muscle contraction shownby Donald et al. (I967) rapidly to induce sig-nificant increments in heart rate and bloodpressure. These circulatory responses arereadily obtained in the supine position andare related to the intensity of contractionindependent of the muscle mass involved,(Lind and McNicol, I967). A preliminarystudy from our laboratory (Stonecipher et al.,I970) showed that the haemodynamic changesinduced by sustained isometric handgrip pro-'duced predictable alterations in the amplitudeof murmurs in patients with a variety of car-diac anatomical lesions. We have also reportedon the role of isometric stress testing forevoking or accentuating the phonocardiogra-phic and apex cardiographic signs of left ven-tricular dysfunction (Siegel et al., I970). Iso-metric exercise is particularly applicable dur-ing auscultation because of the rapid onsetand offset of the induced tachycardia andpressor response while the examiner is un-

This study was supported by U.S. Public HealthService Grants.2 Dr. Siegel was a Special Research Fellow of theNational Heart and Lung Institute while working onthis project.

Received 13 August I971.

encumbered by patient movement or thenecessity of administering potent pharmaco-logical agents.The purpose of this study was to document

the changes induced by isometric handgripon the amplitude of heart murmurs in 36patients with a variety of valvular and othercardiac defects. In over half of these patientsthe changes in murmur intensity were com-pared during isometric handgrip and amylnitrite inhalation or during phenylephrineadministration.

Subjects and methodsThirty-six patients were studied, of whom 27 hadproven cardiac lesions during previous diagnosticcardiac catheterization. The remaining 9 patientswere felt to have unquestionable clinical evidenceof specific valvular cardiac lesions. The lesionsstudied are listed in Table i, and were predomin-antly aortic and or mitral defects.

Bipolar praecordial electrocardiograms with thecathode over the sternum at the fourth intercostalspace level and the anode at the Vs position(CM5) were recorded simultaneously with phono-cardiograms, carotid pulse tracings, and apexcardiograms on an eight-channel Hewlett-Packardphotographic recorder' at a paper speed of Ioomm/sec. Phonocardiograms were obtained withcrystal microphones' at the cardiac apex using cut-off frequencies of 50 Hz and 200 Hz; and in thesecond left intercostal space at 200 Hz with filterslopes of 24 Db/octave. The apex cardiogram and

1 Model 4578 Poly Beam Recording System, HewlettPackard Co., Waltham, Mass.2Model 2IO5o A, Hewlett Packard Co., Waltham,Mass.

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6o6 McCraw, Siegel, Stonecipher, Nutter, Schlant, and Hurst

TABLE i Response of heart murmur intensity to isometric handgrip exercise, amyl nitrite,and phenylephrine

Cardiac lesion No. of Isometric handgrip exercise Amyl nitrite Phenylephrinepatients

Murmur Murmur Indeterminate Murmur Murmur Indeterminate Murmur Murmur Indeterminateincreased decreased or no change increased decreased or no change increased decreased or no change

Aortic stenosis 4 3 I 2 I IAortic regurgitation I2 9 3 5 4 5 3Mitral stenosis I0 9 I 4 3 2 3Mitral regurgitation I4 II 3 4 5 3 8 2Pulmonary stenosis 3 2 I 2 2Ventricular septal

defect 3 2 I I 2 2Idiopathic hypertrophic

subaortic stenosis I I IMembranous

subaortic stenosis I I I

carotid pulse tracings were obtained using induct-ance displacement transducers' (time constant= cx). AC amplifiers with 4-second time con-stants2 were used for signal conditioning. Record-ings were performed at rest, during the last I5seconds of isometric exercise, and during adminis-tration of amyl nitrite and phenylephrine asdescribed below.

Iosmetric handgrip exercise testing Eachpatient was positioned in the supine or left lateraldecubitus position for all recordings. After restingrecordings were obtained, a sustained maximaleffort handgrip was maintained for one minuteusing a handgrip dynamometer. The strength ofthe handgrip during the last I5 seconds duringwhich recordings were made was approximately75 per cent of the instantaneous peak maximal

'APT-i6, Hewlett Packard Co., Waltham, Mass.2 350 Series, High Gain Amplifier, Hewlett PackardCo., Waltham, Mass.

handgrip strength. Blood pressure was measuredin the non-exercising arm during rest and exerciseusing a standard blood pressure cuff (I13 cm xI3-5 cm). All patients were instructed to breathenormally to avoid performing the Valsalvamanoeuvre. Fig. i illustrates the dynamometerand isometric handgrip exercise technique. All36 patients performed isometric handgrip exer-cise; of these, 27 also received amyl nitrite and,of these, I9 also received phenylephrine. Onepatient of the 36 received phenylephrine afterisometric handgrip exercise without previousamyl nitrite inhalation. Amyl nitrite and phenyl-ephrine were administered to compare the effectupon the murmurs of the tachycardia induced byamyl nitrite with that induced by isometric hand-grip, and to compare the effects of the pressorresponse induced by phenylephrine with that ofisometric handgrip. Amyl nitrite inhalation wasbegun after control tracings were obtained andafter a sufficient period was allowed for the patientto return to the resting state (2 to 5 minutes).

TABLE 2 Mean heart rate and blood pressure responses to isometric handgrip exercise, amylnitrite, and phenylephrine

Cardiac lesion No. of Variable Control Isometric Amyl Phenylephrinepatients handgrip nitrite

exercise

Aortic stenosis 4 Heart rate 82 93 I06 60Blood pressure II3/75 I54/98 I35/88

Aortic regurgitation I2 Heart rate 74 88* I04 67*Blood pressure I29/65 I62*/84* I6l*/74*

Mitral stenosis I0 Heart rate 74 85* III* 57*Blood pressure I19/78 I46*/96* 5Ift/92tMitral regurgitation I4 Heart rate 7I 85* I09* 62*Blood pressure I23/70 I47*/88* 145*/8I*

Pulmonary stenosis 3 Heart rate 77 78 115 73Blood pressure I47/92 I70/IO7 I40/100

Ventricular septal defect 3 Heart rate 78 8I 99 57Blood pressure 115/80 I30/93 I35/95

Blood pressure and heart rate measurements were performed immediately before recording phonocardiogramsand pulse tracings during isometric handgrip exercise, amyl nitrite, and phenylephrine.* P <o-oi.t P <0-02.

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Heart murmurs and isometric exercise 607

FmItG. i The spring loaded handgrip dynamo-meter calibrated in kilogrammnes.

When a reflex tachycardia was induced, inhalationwas stopped and tracings were recorded. Afteragain allowing sufficient time for the patient toreturn to the resting state (5 to IO minutes) astandard dose of o025 mg phenylephrine was slow-ly administered intravenously. If the blood pres-sure response exceeded that of handgrip,xrecordings were purposely delayed until thepressor response (with its associated reflex brady-cardia) approximated that induced by handgrip.If the blood pressure did not exceed that inducedzby handgrip, the dose was not repeated.

ResultsTable i lists the changes in murmur intensityto isometric handgrip exercise and drugs; thetotal of the number of patients listed for eachlesion equals more than the actual number ofpatients tested since many patients had morethan one murmur. Table 2 lists the meanheart rate and blood pressure responses to iso-Wmetric handgrip exercise and drugs.

Aortic stenosis Isometric handgrip exer-cise decreased the murmur of aortic stenosis'in 3 of 4 patients with no significant change ini patient. Amyl nitrite increased the murmurin both patients tested. Phenylephrine de-

creased the murmur in i patient and producedno significant change in another.

Aortic regurgitation Isometric handgripexercise increased the murmur of aortic re-gurgitation in 9 of I2 patients with no signifi-cant change in 3 patients. Amyl nitrite de-creased the murmur in 5 of 9 patients testedwith no significant change in 4 patients.Phenylephrine increased the murmur in 5 of8 patients tested with no significant change in3 patients. The effect of isometric handgripexercise on the murmurs of aortic stenosis andregurgitation is graphically illustrated inFig. 2 and 3.

Mitral stenosis Isometric handgrip exer-cise increased the murmur of mitral stenosisin 9 of IO patients with no significant changein one patient. Amyl nitrite increased themurmur in 4 of 7 patients tested with nosignificant change in 3 patients. Phenyl-ephrine decreased the murmur in 2 of 5patients tested with no significant change in

3 patients.

FIG. 2 Graphic recordings at rest and duringa maximal voluntary handgrip contraction(Ioo% MVC)from a woman with moderatevalvular aortic stenosis and regurgitation.Handgrip increased the heart rate from 83 to93 beats/minute and the blood pressure from120/90 to 170/100 mnmHg. The systolic mur-mur of aortic stenosis decreases and the diastolicmurmur of aortic regurgitation is accentuatedduring Ioo per cent MVC;

2 LICS

APEX200

APEX50

REST

II01%MVC'' S .

100% MVC

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6o8 McCraw, Siegel, Stonecipher, Nutter, Schlant, and Hurst

Mitral regurgitation Isometric handgripexercise increased the murmur of mitral re-gurgitation in ii of I4 patients with no sig-nificant change in 3 patients. Amyl nitriteincreased the murmur in 4 of I2 patientstested, decreased the murmur in 5 patients,and gave no significant change in 3 patients.Phenylephrine increased the murmur in 8 ofI0 patients tested with no significant changein 2 patients. The graphic recordings frompatients with mitral stenosis and mitral re-gurgitation obtained before and during iso-metric handgrip exercise are shown in Fig. 4and 5.

Pulmonary stenosis Isometric handgripexercise increased the murmur ofvalvular pul-monary stenosis in 2 of 3 patients with nosignificant change in one patient. Amyl nitriteincreased the murmur in both patients testedand phenylephrine produced no significantchange in both patients tested.

Ventricular septal defect Three patients,two with congenital defects and one with atraumatic defect, were studied. None of thesedefects was associated with pulmonary hyper-tension. Isometric handgrip exercise increasedthe murmur in 2 of 3 patients and producedno significant change in i patient. Amyl nitritedecreased the murmur in I of 3 patients withno significant change in 2 patients. Phenyl-ephrine produced no significant change ineither of two patients tested.

Idiopathic hypertrophic subaortic steno-sis (hypertrophic obstructive cardio-myopathy) Isometric handgrip exercisedecreased the murmur and amyl nitrite in-creased the murmur in the one patient studied.A similar response in association with adecrease in the left ventricular outflow ob-struction was observed in two additionalpatients studied during cardiac catheteriza-tion.

Membranous subaortic stenosis In onepatient all three procedures produced nochange.

DiscussionThe results of this study indicate that theblood pressure and heart rate increase occur-ring during isometric handgrip exercise sig-nificantly affect the intensity of certain typesof heart murmurs.

Isometric exercise in normal subjects re-sults in a potent cardiovascular reflex charac-terized by tachycardia, an increase in cardiac

2 LICS . ,, .

Apex 20C

Apex 50C-.

REST 100%MVCFIG. 3 Graphic recordings (from left to right)at rest, during a maximal voluntary handgripcontraction (ioo% MVC), and I0 seconds afterrelease of I00 per cent MVCfrom a patientwith moderately severe aortic regurgitation.The I00 per cent MVC increased the heartrate from 65 to 80 beats/minute and the bloodpressure from 120/48 to 152/55 mmHg. Notethe obvious accentuation of the aortic diastolicmurmur during I00 per cent MVC and therapid return to normal intensity after handgriprelease.

output, and an increase in both systolic anddiastolic pressure. Freyschuss (I970) hasshown the tachycardia to be mediated by therelease of vagal tone and the pressor responseto result from both the increase in heart rateand cardiac output and an increase in sys-temic vascular resistance mediated by thesympathetic nervous system. We have demon-strated similar reflex increases in heart rate,cardiac output, and systemic and pulmonaryarterial pressure during isometric handgripexercise performed during cardiac catheteriza-tion in over 60 patients with a variety ofacquired and congenital cardiovascular lesions(manuscript in preparation).The basic pharmacological action of amyl

nitrite is to relax smooth muscle. Amyl nitritecauses a decrease in systemic vascular resist-ance and systemic arterial pressure accom-panied by a reflex increase in heart rate andprobable venoconstriction with an increasedvenous return (Beck et al., I96I). The cardiacoutput and ejection velocity are increasedwhereas little change occurs in stroke volume(Perloff et al., I963).Phenylephrine is a potent pressor agent

acting through vascular sympathetic alphareceptors to produce an obvious increase insystemic vascular resistance (Innes andNickerson, I970). The pressor response to

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Heart murmurs and isometric exercise 6099

phenylephrine is accompanied by reflexbradycardia, little change in stroke volume,and a resultant decrease in cardiac output(Beck et al., I96I).The increased intensity of aortic and mitral

regurgitant murmurs with isometric handgripexercise can be explained by the significantelevation of aortic diastolic and left ventricularpsystolic pressures that accompanies isometricexercise. Phenylephrine also increased aorticand left ventricular pressure and increased theintensity of aortic and mitral regurgitationmurmurs in our patients as previously notedby Luisada and Madoery (I966). The obser-vation in our patients that amyl nitrite eitherdecreases or does not alter the murmur ofraortic regurgitation while exerting a variableeffect, including a 'paradoxical' increase, onthe murmur of mitral regurgitation is inaccord with Luisada and Madoery (I966).

Although only 4 patients with valvularaortic stenosis were studied, isometric hand-grip decreased the systolic murmur in 3,patients. This effect may result from thedecrease in systolic gradient that has beendescribed when systemic resistance is raised(Perloff et al., I967; Silove, Vogel, and Gro-ver, I968), and during dynamic exercise(Anderson et al., I969). The murmur re-sponse, in 2 patients with aortic stenosis, toamyl nitrite and phenylephrine was expected,based on the haemodynamic action of theseagents.The diastolic rumble of mitral stenosis in-

creased in intensity during isometric hand-grip exercise. The shorter diastolic fillingperiod associated with tachycardia during iso-metric handgrip may explain the increase inmurmur intensity. A similar increase in the,mitral rumble with dynamic exercise can beexplained by an increase in mitral valve flowrate that results during tachycardia and anincrease in cardiac output (Kasalicky et al.,x1968). Amyl nitrite is also thought to augmentthe rumble ofmitral stenosis by causing tachy-cardia and an increase in cardiac output(Tavel, I967). The failure of amyl nitrite toincrease the mitral rumble in 3 of 7 patientstested in this study is unexplained. Thoughphenylephrine might be expected to decreasethe rumble of mitral stenosis, by increasingdiastolic filling time and reducing cardiac out-put, this was observed in only 2 of 5 patientstested.The problems and danger of isometric exer-

cise testing deserve comment. Patient co-operation, in order to achieve maximal volun-tary contractions, is more important thanduring pharmacological intervention, and caremust be taken to avoid a Valsalva manoeuvre

RESTF IG . 4 Graphic recordings from a youngwoman with mild mitral stenosis (mitral valvearea= 2I cm2). Maximal handgrip exercise(I00% MVC) increased the heart rate from86 to 100 beats/minute and increased theintensity of the mitral diastolic murmur (DM).OS =opening snap.

100 % MVC

FIG. 5 Graphic recordings from a patientwith mild mitral regurgitation illustrating theobvious accentuation of the systolic murmurduring maximal handgrip exercise (ioo%MVC).

100% MVC

LICS

EX

50 '

REST

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during the test. Matthews et al. (I97I) havereported dangerous dysrhythmias in patientswith cardiac disease during performance ofisometric handgrip exercise. Though we haveprecipitated ventricular ectopic rhythms inonly 3 subjects, all of which reverted spon-taneously, during approximately 200 tests ina variety of cardiac patients, it is recommen-ded that electrocardiographic monitoring beused during isometric exercise in patients withleft ventricular dysfunction or rhythm dis-orders. Obvious arterial hypertension, recentmyocardial infarction, and cerebrovasculardisease, including vascular malformations, arecontraindications to the use of sustained iso-metric exercise of any muscle group.

In conclusion, isometric exercise produceshaemodynamic alterations that include themajor characteristics of both amyl nitrite andphenylephrine administration, i.e. tachycardiaand a significant increase of systemic arterialpressure. Isometric handgrip exercise hasproved to be a simple, noninvasive bedsidemanoeuvre for amplifying the murmurs ofaortic and mitral regurgitation and mitralstenosis. This manoeuvre attenuates murmursoriginating from outflow tract obstruction ofthe left ventricle.

ReferencesAnderson, F. L., Tsagaris, T. J., Tikoff, G., Thorne,

J. L., and Schmidt, A. M. (I969). Hemodynamiceffects of exercise in patients with aortic stenosis.American Journal of Medicine, 46, 872.

Beck, W., Schrire, V., Vogelpoel, L., Nellen, M., andSwanepoel, A. (I96I). Hemodynamic effects ofamyl nitrite and phenylephrine on the normalhuman circulation and their relation to changes incardiac murmurs. American Journal of Cardiology,8, 34I.

Dohan, M. C., and Criscitiello, M. G. (I970). Physio-logical and pharmacological manipulations of heartsounds and murmurs. Modern Concepts of Cardio-vascular Disease, 39, I21.

Donald, K. W., Lind, A. R., McNicol, G. W., Hum-phreys, P. W., Taylor, S. H., and Staunton, H. P.(I967). Cardiovascular responses to sustained(static) contractions. Circulation Research, 20,

Suppl. I, I5.

Freyschuss, U. (I970). Elicitation of heart rate andblood pressure increase on muscle contraction.Journal of Applied Physiology, z8, 758.

Innes, I. R., and Nickerson, M. (I970). Drugs actingon postganglionic adrenergic nerve endings andstructures innervated by them (sympathomimeticdrugs). In The Pharmacological Basis of Thera-peutics, 4th ed., p. 478. Ed. by L. S. Goodmanand A. Gilman. MacMillan, New York.

Kasalicky, J., Hurych, J., Widimsky, J., Dejdar, R.,Metys, R., and Stan6k, V. (I968). Left heart haemo-dynamics at rest and during exercise in patientswith mitral stenosis. British Heart Journal, 30, I88.

Lind, A. R., and McNicol, G. W. (i967). Muscularfactors which determine the cardiovascular re-sponses to sustained and rhythmic exercise.Canadian Medicine Association Journal, 96, 706.

Luisada, A. A., and Madoery, R. J. (I966). Functionaltests as an aid to cardiac auscultation. MedicalClinics of North America, 50, 73.

Matthews, 0. A., Atkins, J. M., Houston, J. D.,Blomqvist, G., and Mullins, C. B. (I97i). Arrhyth-mias induced by isometric exercise. Clinical Re-search, 19, 23.

Perloff, J. K., Binnion, P. F., Caulfield, W. H., andDeLeon, A. C. (I967). The use of angiotensin inthe assessment of left ventricular function in fixedorifice aortic stenosis. Circulation, 35, 347.

Perloff, J. K., Calvin, J., DeLeon, A. C., and Bowen,P. (I963). Systemic hemodynamic effects of amylnitrite in normal man. American Heart Journal,66, 460.

Siegel, W., Gilbert, C. A., Nutter, D. 0., Schiant,R. C., and Hurst, J. W. (I970). A comparison ofisometric and treadmill exercise responses inatherosclerotic heart disease. American Journal ofCardiology, 26, 660.

Silove, E. D., Vogel, J. H. K., and Grover, R. F.(I968). The pressure gradient in ventricular out-flow obstruction: influence of peripheral resistance.Cardiovascular Research, 2, 234.

Stonecipher, H. K., Siegel, W., Gilbert, C. A., Nutter,D. 0., Schlant, R. C., and Hurst, J. W. (I970).Response of heart murmur to isometric handgripexercise. Circulation, 42, Suppl. III, 30.

Tavel, M. E. (1967). Clinical Phonocardiography andExternal Pulse Recording, Chapter 6. Year BookMedical Publishers, Chicago.

Requests for reprints to Dr. Donald 0. Nutter,School of Medicine, Woodruff Medical Center ofEmory University, Thomas K. Glenn MemorialBuilding, 69 Butler Street, S.E., Atlanta, Georgia30303, U.S.A.

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