clinical profile restrictive cardiomyopathy -...

Clinical Profile of Restrictive CardiomyopathyJOSEPH R. BENOTTI, M.D., WILLIAM GROSSMAN, M.D., AND PETER F. COHN, M.D.

SUMMARY The characteristic hemodynamic features of restrictive cardiomyopathy (normal or reducedcardiac index, normal ventricular systolic function, and "dip and plateau" early in diastole) are traditionallyassociated with pathologic evidence of inflammation, infiltration and fibrosis. Prognosis is usually poor. Ninepatients with restrictive hemodynamic features were recently identified in our laboratory; six were males, threewere females, and ages ranged from 23-57 years (mean 47 years). Only one was asymptomatic. Chest pain,dyspnea on exertion and fatigue were the most common symptoms. Echocardiography revealed various degreesof left ventricular wall thickening, but no significant pericardial effusion, pericardial thickening or calcifica-tion. Mean left ventricular end-diastolic pressure was 25 mm Hg, cardiac index 2.8 1/min/M2 and ejectionfraction 0.63. Endomyocardial and pericardial biopsies, obtained in two patients, were normal. Follow-up(mean 22 months, range 16-42 months) revealed no cardiac deaths. These findings support the hypothesis thatthe restrictive hemodynamic profile does not necessarily indicate the presence of a specific pathologic processin the subendocardium or myocardium and that the prognosis is not necessarily ominous. The commonpathophysiologic feature for this syndrome appears to be reduced ventricular diastolic compliance, but theetiology in many cases is unclear.

CARDIOMYOPATHIES have been divided intocongestive, hypertrophic and restrictive types," 2 and aspecific hemodynamic and clinical profile has beendescribed for each class and correlated with specificetiologies.The hemodynamic pattern ofrestrictive car-

diomyopathy is characterized by an elevated fillingpressure in the ventricles associated with normal ornearly normal systolic function. Ventricular pressuredeclines significantly at the onset of diastole and thenrises abruptly and rapidly in early diastole. This dip-and-plateau filling pattern in the ventricular diastolicpressure tracing is manifest in the atrial pressure trac-ing as a prominent y descent followed by a rapid riseand plateau. The rapid rise and abrupt plateau in earlydiastolic ventricular pressure gives rise to the "square-root" sign. The right and left ventricular diastolicpressures may be superimposable or within 3-4mm Hg of one another when simultaneously recorded.Thus, the hemodynamic findings may closely simulateconstrictive pericarditis.The restrictive physiology has been attributed to

reduced diastolic ventricular compliance, presumablyresulting from fibrotic or infiltrative processes involv-ing the subendocardium and/or myocardium. Specificetiologies have been reported to include amyloidosis,sarcoidosis, hemochromatosis, Loeffler's eosinophilicendomyocardial disease and endomyocardial fibrosis.5Except for hemochromatosis, these conditions have noknown specific therapy and are associated withprogressive deterioration and a grave prognosis.

In contrast, we have found that restrictive car-diomyopathy usually has a stable course, a relatively

From the Department of Medicine, Peter Bent Brigham Hospitaland Harvard Medical School, Boston, Massachusetts.

Supported by USPHS grants HL-7049 and HL-19089.Dr. Grossman is an Established Investigator of the American

Heart Association.Address for correspondence: Peter F. Cohn, M.D., Cardiovas-

cular Division, Peter Bent Brigham Hospital, 721 HuntingtonAvenue, Boston, Massachusetts 02115.

Received July 10, 1979; revision accepted December 21, 1979.Circulation 61, No. 6, 1980.

good prognosis, and no specific etiology. This reportdescribes our experience with restrictive cardio-myopathy at the Peter Bent Brigham Hospital over a3-year period and correlates clinical, hemodynamicand pathologic findings.

MethodsBetween July 1, 1975 and December 31, 1978, ap-

proximately 2000 diagnostic catheterizations wereperformed at the Peter Bent Brigham Hospital.Patients with left- or right-heart catheterization onlyor those without high-quality recordings of both rightand left ventricular pressures were excluded. Recordsof the remaining 1200 patients were reviewed andthose with the following hemodynamic findings, con-sistent with restrictive cardiomyopathy, were selected:1) elevation in both left ventricular end-diastolicpressure (LVEDP) and right ventricular end-diastolicpressure (RVEDP) (normal LVEDP < 12 mm Hg andRVEDP < 8 mm) not explicable by valvular, cor-onary, pericardial or congenital heart disease; 2) nor-mal left ventricular systolic function (ejection fraction> 50%); and 3) characteristic early diastolic dip andsubsequent rapid plateau in both ventricular pressurecurves with abnormal elevation in ventricular pressureachieved with the rapid filling wave.

Patients or their physicians were contacted to assessclinical status, New York Heart Associationclassification and therapeutic program. The clinicalpresentation, noninvasive studies, catheterization dataand follow-up information on patients with thediagnosis of restrictive cardiomyopathy according tothe above hemodynamic criteria are the basis of thisreport.

ResultsClinical Characteristics

Nine of 79 patients with the diagnosis of car-diomyopathy met the criteria for diagnosis of restric-tive cardiomyopathy and were selected for review.Table 1 summarizes the clinical presentation and non-invasive data. There were six males and three females.

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RESTRICTIVE CARDIOMYOPATHY/Benotti et al.

TABLE 1. Clinical and Noninvasive Data for the Patients with Restrictive Myopathy

Age NYHAPt (years) Sex History class Exam Chest x-ray ECG Echocardiogram

1 40 M AF, DOE III Apical HSM, S3 Left ventricular AF, Thickened septum,prominence NSSTTWAS no evident obstruc-

tion to left ventricu-lar outflow

2 45 M Anginal CP, DOE III SEM, S4 WNI WNL WNL

3 56 M von Reekling- IV Elevated JVP, Cardiomegaly Low-voltage Thickened LV wall,hausen's syndrome, SEM, ankle edema RYH LVE, LAE, RVECOPD, biventric-ular CHF

4 39 F Atypical CP III SEM WNL WNL WNL

5 54 M Alcohol abuse, IV Elevated JVP, Cardiomegaly, AF Not doneliver disease, ascites, edema, PVRbiventricular S3, SEMCHF

6 56 F Atypical CP, III APCs, elevated WNL APCs Late systolic prolapseatrial arrhythmia JVP of the posterior

mitral valve leaflet

7 53 F COPD, IV Cyanosis, in- Four-chamber RVH Thickened RV wallbiventricular CHF creased JVP, cardiac enlarge- and dilation

rales, HSMA at ment, prominentLLSB, edema central pulmonary

arteries

8 23 M Noonan's syn- I Cardiovascular Biventricular LAE, RAE, Thickened LV walldrome, asympto- exam normal enlargement, PVR LVH, RVHmatic

9 57 M Atypical CP IV SEM Cardiomegaly LVH with Systolic anteriorstrain motion of the mitral

valve, no obstructionto left ventricularoutflow demonstratedat rest or with pro-vocative maneuvers

Abbreviations: NYHA = New York Heart Association; AF = atrial fibrillation; DOE = dyspnea on exertion; HSM = holo-systolic murmur; NSSTTWAS = nonspecific ST- and T-wave changes; JVP = jugular venous pressure; PVR = pulmonary vascu-lar redistribution; LVII = left ventricular hypertrophy; LAE = left atrial enlargement; SEMI = systolic ejection murmur; WNL- within normal limits; COPD = chronic obstructive pulmonary disease; ClIF = congestive heart failure; RVHI = right ven-tricular hypertrophy; LVE = left ventricular enlargement; RVE = right ventricular enlargement; CP = chest pain; APCs =atrial premature contractions; LLSB = lower left sternal border.

Mean age at the time of presentation was 47 years(range 23-57 years). Patients presented with a varietyof complaints that were related to the cardiovascularsystem. These included dyspnea on exertion andfatigue (five patients), peripheral edema (threepatients), angina (one patient) and atypical chest pain(three patients). In these patients, the pain was notconsistently related to exertion nor a substernal loca-tion and was more a stabbing than pressure sensation.One patient presented with new atrial arrhythmias.Two patients had associated chronic obstructive lungdisease and one had von Recklinghausen's syndrome.One asymptomatic patient was studied because he hada diagnosis of Noonan's syndrome, evidence of ahypertrophic cardiomyopathy, and required completecardiovascular evaluation before he underwentgeneral anesthesia. In summary, five patients hadsymptoms of dyspnea or congestive heart failure, fourhad chest pain and one was asymptomatic.At the time of presentation, these patients were

receiving a variety of cardiovascular medications. Fivewere taking digoxin and diuretics (including furose-

mide and spironolactone), four were taking variousnitrate preparations and two were taking /3-blockingagents. Two patients were on no medications.

Physical findings were variable. One patient had anapical holosystolic murmur, one patient had aholosystolic murmur at the lower left sternal border,five patients had ejection systolic murmurs, two hadthird heart sounds, and one patient had a fourth heartsound. Three patients had evidence of systemic venouscongestion with jugular venous distension. Threepatients had peripheral edema; one of these patientsalso had ascites. Two patients were in atrial fibrilla-tion, which was well controlled on digoxin therapy,and seven patients were in sinus rhythm.

Electrocardiogram

A variety of electrocardiographic findings werepresent that were consistent with enlargement orhypertrophy of one or more cardiac chambers. Onepatient had left ventricular hypertrophy withassociated ST-T-wave changes consistent with digoxin

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therapy or a "strain" pattern. Two patients demon-strated electrocardiographic evidence of isolated rightventricular hypertrophy and one patient demonstratedbiventricular hypertrophy. Two patients had nonspe-cific abnormalities of the ST segments and T wavesand three had normal ECGs except for the presence ofoccasional atrial premature contractions in one of thethree.

Chest X-ray

The roentgenographic examination revealed avariety of pulmonary and cardiomediastinal abnor-malities. Five patients had cardiomegaly (car-diothoracic ratio > 0.50), though the specificchambers that were enlarged could not be determinedin two of these patients. One patient demonstrated leftventricular enlargement and two showed biventricularenlargement. Two patients demonstrated pulmonaryvascular redistribution, and one patient had prom-inence of the pulmonary artery.

Echocardiography

Echocardiographic findings in these patients were

variable. One patient demonstrated asymmetric septalthickening and one showed abnormal systolic motionof the anterior mitral leaflet, but had no evidence ofresting or provocable outflow tract obstruction byechocardiographic examination or systolic time inter-val analysis. Two patients demonstrated left ven-tricular wall thickening, one showed left ventricularenlargement and two had right ventricular enlarge-ment. One patient had left atrial enlargement. Theechocardiogram was completely normal in two pa-tients. In summary, echocardiograms demonstratedvarying degrees of left ventricular wall thickening, leftand/or right ventricular enlargement, but no signifi-cant thickening or calcification of the pericardium oreffusion.

Cardiac Catheterization

All patients underwent diagnostic biventricularcatheterization and left ventriculography. Coronaryarteriography was performed in eight patients. Thehemodynamic and angiographic findings are sum-marized in table 2. The cardiac index was normal infour patients (> 2.8 1/min/M2) and depressed in theother five patients, including one with an index of1.7 1/min/m2. Four patients had systolic arterial

TABLE 2. Hemodynamic and A ngiographic Data

Mean MeanCO (l/min)/ SAP LVSP/LVEDP PCWP RVSP/RVEDP RAP Coronary

Pt CI (l/min/m2) (mm Hg) (mm Hg) (mm Hg) (mm Hg) (mm Hg) EF LVgram arteriogram1 3.5/1.7 110/815 110/18 (10)* 18 32/13 (6)* 13 0.68 Increased LV Not done

free wallthickness

2 6.0/3.1 120/70 120/24 (0) 20 36/16 (6) 14 0.62 WNL 25% narrowingof the mid-LADand proximalCFX

3 8.0/3.7 160/65 160/28 (0) 18 80/25 (0) 14 0.60 Increased LV WNLfree wallthickness

4 4.4/2.9 165/80 165/17 (5) 14 32/10 (2) 10 0.68 WNL WNL5 5.4/2.7 125/60 125/20 (10) 14 70/24 (8) 21 0.53 Anteroapical 50% narrowing

hypokinesis of an LADdiagonal branch

6 7.2/4.2 120/64 120/24 (5) 16 36/16 (4) 16 0.68 Mild LV WNLenlargement,mild MR

7 4.3/2.4 166/86 166/31 (14) 34 78/16 (0) 16 0.52 Mild LV WNLenlargement



Mean 5.4 1.4/ 139 - 23/ 20 49 - 21/ 14 0.63SD 2.8 0.8 25 -6 -6 16 5 -4 = 0.08

Figures in parentheses indicate beginning diastolic pressure.Abbreviations: CO = cardiac output; CI - cardiac index; SAP = systemic arterial pressure; LVSP = left ventricular systolic

pressure; LVEDP = left ventricular end-diastolic pressure; PCWP = pulmonary capillary wedge pressure; RVSP = right ven-tricular systolic pressure; RVEDP = right ventricular end-diastolic pressure; RAP = right atrial pressure; EF = ejection fracton;LVgram = left ventriculogram; LV = left ventricular; LAI) = left anterior descending coronary artery; CFX = circumflexcoronary artery; WNL = within normal limits.

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EKG

LV

100

_-- - _-I

E

U!)W

FIGURE 1. Simultaneous recordings ofleft ventricular (LV) and right ventricular (R V)pressures in patient6 illustrating the early diastolic dip and plateau and near-equilibration ofdiastolic pressures characteristic ofrestrictive myopathy. Although diastolic pressures ofboth ventricles are elevated, the diastolic plateau in the

left ventricle is higher than in the right ventricle.

hypertension (systolic aortic pressure 150 mm Hg),but it was mild (< 170 mm Hg) in each case. Left andright ventricular end-diastolic pressures were elevatedin all patients, with a group mean ± SD of 25 ± 6 mmHg and 16 ± 5 mm Hg, respectively. All patients had

PA

ECG

1 ~ A A

11 T W _0-

AV

a prominent dip and rapid plateau in the left and rightventricular pressure tracings during diastole (fig. 1).There was a corresponding prominent y descent in thepulmonary capillary wedge and right atrial pressuretracings (fig. 2). In all but patients 3 and 5, the left

RA

FIGURE 2. Near-equalization ofpulmonary artery (PA) diastotic, right ventricular (R V) diastolic, mean

right atrial (RA) and mean pulmonary capillary wedge (PCW) pressures in patient 6.

0

An

71 71

-I\ ^r

t

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ventricular end-diastolic pressure exceeded the rightventricular end-diastolic pressure by at least 5 mmHg. The mean pulmonary capillary wedge pressurewas elevated in all patients (20 ± 6 mm Hg), consis-tent with the patients' complaints of dyspnea. Themean right atrial pressure was elevated in eightpatients. (14 ± 4 mm Hg), thereby explaining thesymptoms and signs of systemic congestion. Pul-monary and systemic vascular resistances were variedfrom patient to patient, and no consistent patternwas evident.

Figure 1 shows the simultaneous right and left ven-

tricular pressure recordings for patient 6. Itdemonstrates the characteristic early diastolic dip andrapid plateau in ventricular pressures that arecharacteristic of restrictive cardiomyopathy or con-strictive pericarditis. The near-equality of these right-and left-sided pressures in diastole is also demon-strated in figure 2. In the patient shown, diastolicpressures remained nearly equal during leg raisingand supine exercise, maneuvers that have beenreported to cause a disproportionate elevation in leftventricular end-diastolic pressure in patients withrestrictive cardiomyopathy. Because ventriculardiastolic pressures were nearly equal - except at end-diastole and left ventricular end-diastolic pressurecould not be selectively elevated by any hemodynamicmaneuver, the question of a pericardial constrictiveprocess was raised in this patient. Right ventricularendomyocardial biopsy was obtained. The myocar-dium, stained with hematoxylin and eosin, Congo redand Prussian blue, was normal; there was no evidenceof amyloid or iron deposition. The patient subse-quently underwent thoracotomy for insertion of an

epicardial pacemaker (to treat her atrial brady-arrhythmias), at which time pericardial biopsy wasobtained. The pericardium demonstrated no thicken-ing or fibrosis. This differential diagnosis - restrictivecardiomyopathy vs constrictive pericarditis alsowas raised in patients 3 and 5, whose left and rightventricular end-diastolic pressures were within 3-4 mmHg of each other.

Patient 3 underwent a right ventricular en-

domyocardial biopsy at the time of catheterizationand an open pericardial biopsy a few days later. Thepericardium was normal and the myocardium, studiedby similar histochemical techniques, was also free ofinfiltrative processes. Patient 5 had a history ofalcohol abuse, Laennec's cirrhosis and biventricularcongestive heart failure. At catheterization, thehemodynamic findings were consistent with restrictivecardiomyopathy or constrictive pericarditis. Furtherdiagnostic procedures were not undertaken because ofthe severity of hepatic decompensation. He died 1month after catheterization. A postmortem examina-tion was not performed.

Ventriculography revealed a normal ejection frac-tion (range 0.52-0.76) in all patients. Four patientshad evidence of an increase in left ventricular free wallthickness, two had mild left ventricular enlargement,one had anteroapical hypokinesis and one patient hadmild mitral regurgitation. Wall motion, wall thick-

ness, aortic valve mobility and mitral valve coaptationwere normal in the rest of the group.

Follow-up

Available follow-up information for this group withrestrictive cardiomyopathy is presented in table 3.Most demonstrated clinical improvement. Patient 5

died of hepatic failure secondary to Laennec'scirrhosis 1 month after catheterization. Patient 2 was

lost to follow-up. The remaining patients are alive at a

mean follow-up interval of 22 months (range 16-42months). Six patients have improved by at least one

New York Heart Association classification, and twoare unchanged. Predominant symptoms, New YorkHeart Association functional status, and medicalregimen at follow-up are summarized in table 3.

DiscussionRestrictive cardiomyopathy reportedly results from

a variety of pathologic processes that may involve themyocardium or endocardium.4 This hemodynamicprofile can results from amyloidosis, hemochroma-tosis, glycogen deposition, and fibrosis from a numberof diverse etiologies. These processes reduce ventric-ular diastolic compliance and restrict inflow of blood.Stroke volume is accommodated by the stiffened ven-tricle only through an abnormal rise in diastolicpressure, which accounts for the congestive symp-toms as well as the characteristic hemodynamic signs.

In some cases of restrictive cardiomyopathy, aspecific infiltrative process such as amyloidosis can beidentified. In the few cases that have been reported,the prognosis has been uniformly poor.6 In other in-stances, this clinical and hemodynamic profile may be

TABLE 3. Follow-up Data

Follow-upduration

Pt (months) Status NYHA

1 28 AF, DOE, on digoxin IIand diuretics

2 lost to follow-up3 20 DOE III4 33 Occasional atypical CP II

on long-acting nitrates

5 1 Died of liver disease6 17 Recurrent episodic CP II

7 21 DOE, fatigue, on IIIdigoxin and diuretics

8 16 Asymptomatic, on no Imedications

9 42 Occasional chest pain, IIon no medication

MeanSD 22 10

Abbreviations: AF - atrial fibrillation; DOE = dyspneaon exertion; CP = chest pain.

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associated only with nonspecific ventricular hyper-trophy and/or fibrosis.7 Can certain patients with con-gestive cardiomyopathy develop restrictive physiologywhen myocardial fibrosis becomes sufficient to reducediastolic compliance? Our study suggests that evolu-tion from congestive to restrictive cardiomyopathy isunlikely because all of our patients demonstratedpreservation of ventricular systolic function (e.g., leftventricular ejection fraction 52-76%) at a time whenthere was a clear abnormality in both right and leftventricular filling pressures indicative of restrictivephysiology.

In our series, patients with restrictive car-diomyopathy presented with symptoms of left and/orright ventricular failure, chest pain in the absence ofsignificant narrowing of any epicardial coronaryartery and/or symptoms from atrial arrhythmias.Physical findings were nonspecific, and evidence ofsystemic venous congestion was present in fewer thanhalf the cases. Electrocardiographic findings, thoughnonspecific, may be compatible with restrictivemyopathic process if evidence of left and/or right ven-tricular hypertrophy with or without a strain pattern ispresent. The echocardiogram is helpful in ruling outthickening or calcification within the pericardium orthe presence of pericardial fluid, and may suggest arestrictive myopathic process if there is evidence ofleft and/or right ventricular wall thickening orasymmetric septal thickening. In no patient in ourseries was any pattern of abnormal ventricular dias-tolic wall motion suggestive of restrictive cardiomy-opathy observed on the echocardiogram.

Patients with restrictive cardiomyopathy requirebiventricular catheterization with thorough hemo-dynamic evaluation to differentiate this conditionfrom the more common causes of chest pain, con-gestive heart failure or arrhythmias. Coronary arteri-ography will establish or rule out the presence ofepicardial coronary artery disease. However, acareful, more complete hemodynamic evaluation isrequired to identify more obscure cardiac causes ofchest pain, such as pulmonary hypertension or restric-tive cardiomyopathy.A normal endomyocardial biopsy does not rule out

the presence of restrictive cardiomyopathy, as il-lustrated by patients 3 and 6. Despite hemodynamicfindings that were typical for restrictive car-diomyopathy, including similarity of right ventricularand left ventricular end-diastolic pressures in patient3, they both had normal endomyocardial biopsies.Thus, at times, pericardial exploration with biopsymay be required to differentiate between restrictivecardiomyopathy and constrictive pericarditis. In gen-eral, however, patients with restrictive physiologyhave dissimilar left and right ventricular end-diastolicpressures. Furthermore, cardiac murmurs are also un-common in constrictive disease.

It is probable that when restrictive cardiomyopathyis associated with a specific infiltrative or fibroticprocess, it carries a poor prognosis.5 However, inour series, in which no specific etiology for the restric-tive hemodynamic profile could be identified, several

patients noted significant symptomatic improvementover the follow-up interval. This suggests that inpatients with restrictive cardiomyopathy, endomyo-cardial biopsy may be of prognostic importance.We could not identify the etiologic agents and

pathologic processes that resulted in the restrictivehemodynamic profile in our patients and can onlyspeculate on the causes of this condition. In view ofthe somewhat reversible nature of the process, assuggested by the clinical improvement, the initialpresentation and hemodynamic pattern may haveresulted from myocardial edema and/or scattered in-flammatory cell infiltration resulting from a subacuteinfectious or toxic etiology. Myocarditis has beenshown experimentally to cause reduction in ven-tricular diastolic compliance and cause elevation infilling pressures and atrial distention.8 There may alsobe a subtle increase in the total cardiac volume con-tained within the confines of the as yet unyielding non-compliant pericardial sac. Such hemodynamicalterations may precipitate symptoms of pulmonaryand systemic venous congestion, and if there is epicar-ditis as well, there may be atrial arrhythmias and/orchest pain. Conversely, with resolution of the subtleinflammatory changes, diastolic compliance increases,atrial distention is relieved, pericardial tension slack-ens and symptoms improve or resolve completely.

Possible alterations in diastolic cardiac tone ormyocardial relaxation should also be considered. Thesimilarity of hemodynamic findings in hypertrophicand restrictive cardiomyopathies are of interest in thisregard. Slow-calcium-channel blockers such asverapamil have alleviated symptoms in patients withhypertrophic obstructive cardiomyopathy, presum-ably by reducing diastolic ventricular tone and in-creasing compliance.9 Such agents might be of sometherapeutic benefit in patients with restrictive car-diomyopathy in whom no specific infiltrative processcan be identified by histologic examination. Such astudy, though important, would be difficult to performbecause restrictive cardiomyopathy is infrequent, itsclinical presentation nonspecific, and biventricularcatheterization with careful hemodynamic evaluationis required for diagnosis.

References1. Goodwin JF: Prospects and predictions for the car-

diomyopathies. Circulation 50: 210, 19742. Oakley CM: Clinical recognition of the cardiomyopathies. Circ

Res 35 (suppl II): II-152, 19743. Hetzel PS, Wood EH, Burchell HP: Pressure pulses in the right

side of the heart in a case of amyloid disease and in a case ofidiopathic heart failure stimulating constrictive pericarditis.Mayo Clin Proc 28: 107, 1953

4. Meaney E, Shabetai R, Bhargava V, Shearer M, Weidner C,Mangiardi LM, Smalling R, Peterson K: Cardiac amyloidosis,constrictive pericarditis and restrictive cardiomyopathy. Am JCardiol 38: 547, 1976

5. Hurst JW, Logue RB, Schlant RC, Wenger NK: Obliterativeand restrictive cardiomyopathies. In The Heart, 4th ed, edited byHurst JW. New York, McGraw-Hill, 1978, pp 1580-1590

6. Chew C, Ziady GM, Raphael MJ, Oakley CM: The functionaldefect in amyloid heart disease: "the stiff heart syndrome." Am JCardiol 36: 438, 1975

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7. Chew CYC, Ziady GM, Raphael MJ, Nellen M, Oakley CM:Primary restrictive cardiomyopathy. Non-typical endomyocar-dial fibrosis and hypereosinophilic heart disease. Br Heart J 39:399, 1977

8. Morales DD, Wagner RL, Abelmann WH: Right and left ven-tricular compliance in acute and subacute trypanosomal myocar-

ditis. Cardiovasc Res 7: 201, 19739. Kaltenbach M, Hopf R, Kober G, Bussman WD, Keller M,

Petersen Y: Verapamil treatment of hypertrophic obstructivecardiomyopathy. In Cardiomyopathy and Myocardial Biopsyedited by Kalterbach M, Loogen F, Olsen EGJ. Heidelberg, NewYork, Springer-Verlag, 1978, pp 316-331

Beneficial Effects of Afterload Reduction Therapyin Patients with Congestive Heart Failure

and Moderate Aortic StenosisBARRY H. GREENBERG, M.D., AND BARRY M. MASSIE, M.D.

SUMMARY Patients with congestive heart failure have improved cardiac performance when afterload isreduced by drugs that lower systemic vascular resistance. However, in the presence of mild-to-moderate aorticstenosis, the response to such drugs is uncertain because the major impedance to left ventricular emptying mayoccur at the level of the aortic valve. To determine whether vasodilator therapy is useful in this setting, weevaluated the response to afterload reduction in 11 patients with severe congestive heart failure and reducedaortic valve area.

All patients underwent catheterization to document the severity of stenosis before study. Reduced valve areawas due to native valve stenosis in three patients and to the presence of aortic prostheses in eight patients. Atransvalvular gradient was measured in all patients. The peak gradient was 17 3 mm Hg (mean ± SEM), andthe aortic valve area index was 0.7 ± 0.1 cm2/m2.

After optimal doses of either hydralazine (nine patients) or prazosin (two patients), cardiac index increasedfrom 2.2 ± 0.1 to 3.3 ± 0.2 I/min/m2 (p < 0.001) and stroke volume index increased from 28 ± 2 to 38 ± 2m1/m2 (p < 0.001). Systemic vascular resistance fell from 1649 ± 94 to 1061 ± 68 dyn-sec-cm-6 (p < 0.001),and mean arterial pressure decreased from 93 ± 4 to 88 ± 4 mm Hg (p < 0.01). Hemodynamics were im-proved in all 11 patients regardless of valve area.We conclude that patients with heart failure and mild-to-moderate aortic stenosis respond favorably to

drugs that lower systemic vascular resistance. In such patients, resistance to ventricular emptying is deter-mined predominantly by systemic vascular resistance rather than by aortic valve area.

A COMPENSATORY INCREASE in systemicvascular resistance frequently occurs in response tolow cardiac output in patients with congestive heartfailure. Recently, the potentially deleterious effect ofincreased afterload in patients with left ventriculardysfunction has been appreciated.' Afterload reduc-tion, using drugs that lower systemic vascularresistance, facilitates emptying of the impaired leftventricle and frequently results in improved cardiacperformance and symptomatic improvement in suchpatients. 1-6

Patients with congestive heart failure may also haveaortic stenosis that is not sufficiently severe to indicatevalve replacement. Reduced aortic valve area may be

From the Division of Cardiology, Department of Medicine,University of Oregon Health Sciences Center, Portland, Oregon,and the Department of Medicine, Veterans AdministrationHospital and the University of California, San Francisco, Califor-nia.Address for correspondence: Barry H. Greenberg, M.D., Division

of Cardiology OPC 7304, University of Oregon Health SciencesCenter, 3181 SW Sam Jackson Park Road, Portland, Oregon97201.

Received October 24, 1979; accepted December 21, 1979.Circulation 61, No. 6, 1980.

due to disease of the native valve or to the presence ofan aortic prosthesis. In such cases, the response toafterload reduction therapy is uncertain becauseresistance at the level of the aortic valve may con-tribute substantially to left ventricular afterload. Ifthis were true, drugs that lower systemic vascularresistance would be expected to have little beneficialeffect on cardiac performance and might be harmful.To determine whether afterload reduction therapy

is beneficial in patients with reduced aortic valve area,we evaluated the response of a group of patients withsevere congestive heart failure and mild-to-moderateaortic stenosis to hydralazine9g 10, 12, 16 or prazosin,11drugs whose predominant effect is to reduce systemicvascular resistance.

MethodsPatient Population

Eleven patients with severe congestive heart failureand reduced aortic valve area were evaluated. Theirclinical and hemodynamic profile is shown in table 1.There were nine males and two females whose meanage was 59 ± 3 years (SEM). Three patients had nativevalve stenosis and eight had an aortic valve prosthesis.

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J R Benotti, W Grossman and P F CohnClinical profile of restrictive cardiomyopathy.

Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 1980 American Heart Association, Inc. All rights reserved.

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