Restrictive-type hemodynamics following valve surgery for rheumatic heart disease

International Journal of Cardiology, 17 (1987) 257-266 Elsevier

257

IJC 00600

Restrictive-type hemodynamics following valve surgery for rheumatic heart disease Warren Sherman, Eliot J. Lazar, Bruce Goldman, John Ambrose Departments of Medicine and Pathology, Mount Sinai Hospital and Mount Sinai School of Medicine, New York, NY, U.S.A. (Received

7 April 1987; accepted

9 June 1987)

Sherman W, Lazar ET, Goldman B, Ambrose J. Restrictive-type hemodynamics following valve surgery for rheumatic heart disease. Int J Cardiol 1987;17:257-266. Over a six-year period three patients with rheumatic valvular disease presented with congestive heart failure due to abnormalities in myocardial diastolic function. Each patient previously had been operated for mitral stenosis; one patient had additional aortic valve replacement for aortic insufficiency. The mean time for the development of symptoms following surgery was 4.7 years. In all patients, left ventricular systolic function was normal (radionuclide or angiographic ejection fraction greater than 0.50). Abnormalities in diastolic function involved the left ventricle in all patients. Biopsy material from right (one patient) and left (one patient) ventricles was nonspecific in its histologic appearance. Other disease processes, such as constrictive pericarditis and diabetic cardiomyopathy were considered to be clinically unimportant in these patients. Restrictive-type hemodynamics in patients with postoperative rheumatic heart disease may comprise a newly recognized entity.

Key words: Restrictive physiology; Cardiomyopathy

Introduction

Rheumatic heart disease involves a pathologic process directed primarily at valvular structures. Resulting symptoms are a consequence of pulmonary venous hypertension or of a reduction in cardiac output; both of these situations may be Correspondence io: Warren Sherman, Place, New York, NY 10029, U.S.A.

0167-5273/87/$03.50

M.D., Annenberg

0 1987 Elsevier Science Publishers

8-26. Mount

Sinai Hospital,

B.V. (Biomedical

Division)

One Gustave

Levy

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due, in part, to alteration in ventricular performance created by the primary valvular lesion(s). When valvular surgery is undertaken to correct such lesions, symptoms will generally improve if the preoperative functional state of both ventricles is acceptable and if intraoperative myocardial protection has been adequate. As in other disease processes, ventricular function has clear importance for both nonsurgical and post-surgical prognoses. This is particularly true in valvular regurgitation, but also pertains to valvular stenosis, such as mitral stenosis where, barring coronary disease, left ventricular systolic function is generally observed to be normal. While systolic function is usually affected, abnormalities of ventricular diastolic function are also observed in rheumatic heart disease. These are generally a result of decreased compliance secondary to left ventricular hypertrophy, as seen in aortic stenosis. Rheumatic disease itself may be associated with primary ventricular systolic dysfunction [l], a finding noted with curiosity in the past following valve surgery for mitral stenosis. In three patients who underwent surgery for rheumatic valvular disease we observed, at follow-up cardiac catheterization, diastolic left ventricular dysfunction in the absence of significant systolic dysfunction or residual valvular lesions. Our experience with these patients serves as the basis for this report.

Methods The reports of 5375 patients undergoing cardiac catheterization at Mount Sinai Hospital between and including the years 1980-1985 were reviewed. Of these, hospital records of three patients demonstrated diastolic abnormalities of the left ventricle following valvular surgery for rheumatic heart disease. Their medical records were isolated for review. Bight and left heart catheterization and angiography were performed by standard techniques. In Case 3, left atria1 pressure was measured with a Brockenbrough catheter (USCI, Billerica, MA) by the trans-atria1 septal method [2]. Hemodynamic recordings were made with fluid-filled catheters using Statham P23ID transducers (Gould Electronics, Saddle Brook, NJ). Cardiac outputs were performed by either thermodilution or Fick method. Hemodynamic findings compatible with restrictive physiology were defined by the presence of each of the following factors: (1) right ventricular end-diastolic pressure equal to or greater than 10 mm Hg and/or left ventricular end-diastolic pressure equal to or greater than 15 mm Hg, usually with an early diastolic plateau phase; (2) the absence of congenital or significant coronary or residual valvular heart disease following the previous cardiac surgery(ies); and (3) the presence of normal systolic function as determined by an angiographic or radionuclide ejection fraction of greater than 0.50. The clinical course was determined from hospital records and physician contact. The standard New York Heart Association (NYHA) Classification for symptomatic congestive heart failure was used where possible. Case 1. A 56-year-old white male with mitral stenosis was admitted following 4 weeks of progressive dyspnea. At age 10 he was known to have had rheumatic fever

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and at age 33 was found to be in atria1 fibrillation. His only significant medical illness consisted of diabetes mellitus of four years duration without any clinically apparent end organ damage. His medications included digoxin, furosemide, tolazemide and isosorbide dinitrate. On physical examination there were signs of significant mitral stenosis and mild aortic stenosis. A two-dimensional echocardiogram demonstrated left atrial, mild left ventricular and right atria1 dilation, mitral stenosis (valve area approximately 1.2 cm2) and aortic valvular sclerosis. Cardiac catheterization disclosed the following pressures: mean right atrial 10 mm Hg, right ventricular 50/10 mm Hg, pulmonary arterial 50/30 mm Hg (mean 35 mm Hg), pulmonary artery wedge mean 30 mm Hg, left ventricular 140/12 mm Hg and aortic 140/80. The mitral valvular mean gradient was 17 mm Hg with a cardiac output of 2.9 liters/minute and a calculated valve area of 1.3 cm [2]. At angiography, left ventricular size and function were normal (ejection fraction 0.60) the aortic valve was mildly insufficient and there was two vessel coronary disease. The patient underwent mitral valve and papillary muscle excision, mitral valve replacement (3M Hall-Kaster), tricuspid annuloplasty and two-vessel (left anterior descending and circumflex) coronary bypass grafting, all uneventfully. His inhospital postoperative course was unremarkable. On postoperative day 8 a two-dimensional echocardiogram illustrated normal ventricular systolic function. The patient was discharged on postoperative day 15 on digoxin, furosemide and coumadin. Over the subsequent 10 days the patient worsened symptomatically to the point of NYHA functional class 3 and was readmitted. On examination there were signs of pulmonary and systemic venous congestion with normal prosthetic valve sounds. There had been no significant weight gain. An early diastolic rumble was observed in the mitral area. There were no signs of myocardial infarction, his prothrombin time was in a good therapeutic range and his serum glucose levels remained mildly elevated. Two dimensional echocardiography documented abnormal interventricular septal motion, normal wall thickness, the absence of a pericardial effusion and was otherwise unchanged from previous studies. Repeat catheterization (Table 1, Fig. 1) revealed moderate pulmonary hypertension and a small to moderate sized mitral gradient (valve area 1.5 cm2). Angiography demonstrated normal left ventricular volumes and function (ejection fraction = 0.55), mild mitral regurgitation, mild aortic insufficiency and patent coronary bypass grafts. He was felt to have predominantly diastolic dysfunction of the left ventricle. With medical management he has remained NYHA class 2-3 with 2 years of follow-up. Case 2. A 48-year-old Hispanic female presented with progressive exertional dyspnea. At age 17 she had acute rheumatic fever without known recurrences. Due to dyspnea and syncope she was catheterized at age 38, whereupon moderate mitral stenosis (valve area 1.3 cm*), mild pulmonary hypertension and normal left ventricular function were discovered. Open commissurotomy was performed and her postoperative course was complicated by second degree atrioventricular block with

1

Parentheses m* = square

1 2 3

Case

TABLE

70/20 80/20 90/20 70/30 80/20 90/35

(40) (40) (53)

Pulmonary arterial

(30) (24) pressures

Pulmonary arterial wedge

indicate mean pressures. Ventricular diastolic meter; min = minute; I = liter; - = not available.

(16) (20) (20)

Right

ventricular

Right

(mm Hg)

atria1

Pressures

were

(24)

_ _

measured

Left atria1

at end-diastole.

160/28 120/20 110/30

Left ventricular

(94) (80) (75) F= Fick

160/80 120/60 110/60

Aortic

method;

3.4 2.8 1.4

Cardiac index (I/min/m2)

T = thermodilution

6.0 F 4.8 T 2.7 F

(Win)

Cardiac output

method;

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100 75 mmHg 50 25 0

Fig. 1. Simultaneous

left ventricular

(Lv) and right ventricular

(RV) pressure

tracings

from Case 1.

bradycardia, pulmonary edema and bacterial pneumonia. Her serum glucose determinations were normal. Treatment included permanent transvenous pacemaking. Her mild congestive symptoms worsened over the subsequent four months, prompting reevaluation. Hemodynamics at that time indicated mild to moderate pulmonary hypertension (pulmonary arterial pressure 42/12 mm Hg), mean right atrial pressure of 5 mm Hg, mean pulmonary artery wedge pressure of 16 mm Hg, left ventricular pressure of 120/9 mm Hg and a cardiac output of 5.0 liters/mm. The mitral valvular mean gradient was 11 mm Hg. Angiographic left ventricular function was normal (ejection fraction = 0.58) as were her coronary arteries. There was mild mitral regurgitation. At age 42, progression of symptoms again led to cardiac catheterization at another institution. Described at that time were moderate pulmonary hypertension (pulmonary arterial pressure 65/20 mm Hg), right ventricular pressure 65/15 mm Hg, “moderate” mitral stenosis (13.7 mm Hg mitral valve gradient, a cardiac output of 4.5 liters/mm and a calculated minimal valve area of 1.1 cm2), mild mitral regurgitation (ventricular-paced rhythm) and possible restrictive cardiomyopathy. Left ventricular systolic function was normal (ejection fraction = 0.71). A thoracotomy to evaluate pericardial const,riction revealed adhesions without thickening or effusion. Myocardial biopsy showed fibrosis and focal vascularization of myofibers without evidence of amyloid. Pericardial biopsy demonstrated only nonspecific degenerative changes. She was diagnosed as having restrictive cardiomyopathy of uncertain cause and was treated medically. Her dyspnea worsened over the ensuing 6 years, the last year of which being also marked by hyperglycemia. Mild mitral stenosis (valve area 1.7 cm2) with normal ventricular size and function was observed at echocardiography and normal pericardial thickness was demonstrated by computed tomographic scanning. Cardiac catheterization (Table 1) revealed mild mitral stenosis, moderately severe pulmonary hypertension, mild mitral regurgitation and mild aortic insufficiency, normal coronary arteries and normal left ventricular systolic function (ejection fraction = 0.58). There was angiographic mild tricuspid regurgitation and mild right ventricular

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100

75 .RV mmHg 50

\

25 I

0

Fig. 2. Simultaneous left ventricular (LV) and right ventricular (RV) pressure tracings from Case 2.

dilatation with normal systolic function. There were elevated right and left ventricular diastolic filling pressures (Fig. 2). Her hyperglycemia came under control with dietary measures and insulin. Two years later the patient is alive with NYHA class 3 symptoms on medical therapy. Case 3. A 62-year-old white male with a history of Type-2 diabetes mellitus was admitted for evaluation and treatment of left and right-sided congestive heart failure. He first developed congestive symptoms at age 45. Five years subsequently, he was found to have moderately severe mitral stenosis (mitral valve gradient of 17 mm Hg), moderate aortic insufficiency and mild aortic stenosis, with pulmonary hypertension (pulmonary arterial pressure 71/26 mm Hg, cardiac output of 2.4 liters/mm) and normal ventricular filling pressures (left ventricular end-diastolic pressure of 8 mm Hg and mean right atria1 pressure of 3 mm Hg). Aortic valve (Starr-Edwards 2320) and, following papillary muscle excision, mitral valve (StarrEdwards 6320) replacements were performed. Although his postoperative course was marked by persistently elevated filling pressure (left atria1 pressure lo-20 and right atrial pressure lo-15 mm Hg) and transfusion related hepatitis, there was good functional recovery. At age 60 his dyspnea began to worsen and over the course of 2 years reached NYHA functional class 3, in spite of treatment with furosemide, digoxin and zaroxylin, in addition to diabinese and coumadin. Clinical examination indicated primarily right-sided congestive heart failure, normal prosthetic function and severe tricuspid insufficiency. A nonfasting serum glucose was mildly elevated. An electrocardiogram revealed atrial fibrillation and left bundle branch block. On gated blood pool imaging his left ventricular ejection fraction was 0.56. An echocardiogram

263

mmM50_

25 -

I

i

1 set Fig. 3. Simultaneous

left ventricular

(LV) and right ventricular

(RV) pressure

tracings

from Case 3.

showed left atria1 enlargement, normal valve appearance, normal left ventricular function without hypertrophy and a normal appearing pericardium. Cardiac catheterization (Table 1) demonstrated severe pulmonary hypertension and elevated but unequal diastolic pressures. Fig. 3 illustrates the ventricular pressure tracings. There were no important valvular gradients and at angiography there was mild aortic insufficiency. In that the presumptive diagnosis was restrictive cardiomyopathy involving both ventricles, a right ventricular endomyocardial biopsy was performed which demonstrated myocyte hypertrophy and diffuse interstitial fibrosis. Histochemical stains for amyloid were negative. The patient has been maintained on medical therapy and is alive at age 63. Discussion The three patients in this report illustrate a clinical state not previously described: restrictive-type hemodynamics in the setting of postoperative rheumatic heart disease. All patients had been operated for mitral stenosis (2 with valve replacements, 1 with commissurotomy) and one for mixed aortic regurgitation and stenosis. Congestive symptoms referable to restrictive-type hemodynamics developed within 18 days to 10 (mean 4.7) years of operation. Restrictive cardiomyopathy is diagnosed when restrictive physiology is observed in the presence of normal ventricular systolic function. Diastolic pressures in both ventricles are elevated and their tracings often take on an appearance of a “squareroot” configuration, with an immediate diastolic trough followed by an early plateau phase. The absolute levels of diastolic pressure may be disparate among chambers, since the left ventricle normally has higher diastolic pressures than the right ventricle, and since the left ventricle may be more affected than the right ventricle in this disease process.

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The degree of diastolic dysfunction in our patients was variable. Left ventricular end diastolic pressure ranged from moderately elevated (Case 2) to markedly elevated (Cases 1 and 3). In no patient was there evidence of other diseases known to result in such left ventricular pressures: no patient had hypertension, aortic stenosis or left ventricular hypertrophy, nor did any patient have aortic or mitral regurgitation severe enough to account for such pressures. Right ventricular and right atria1 pressures were elevated in all three patients. These were unquestionably related to pulmonary hypertension and in Case 3, in part, to tricuspid regurgitation. As no patient was known to have pulmonary parenchymal or interstitial disease, the pulmonary hypertension was assumed to be a consequence of the longstanding pulmonary venous hypertension induced by elevated left ventricular and left atrial filling pressures. It is known that right ventricular, and probably right atrial, volume overload or dysfunction can adversely influence left ventricular function [3]. This phenomenon has been observed in a variety of circumstances, especially as is seen with acute changes in right ventricular function (with chamber dilatation) or with severe right ventricular hypertrophy (presumably due to septal hypertrophy). Quantitative assessment of right ventricular systolic function was not available but was described as echocardiographically normal in all three patients. Severe right ventricular hypertrophy was not noted in any patient. Since moderate pulmonary hypertension and mitral and/or tricuspid insufficiency are known to accompany restrictive cardiomyopathy, it may be difficult to distinguish myopathic from valvular processes in certain situations. The hemodynamic findings in our patients are not distinctive for restrictive cardiomyopathy, and in part resemble those seen in patients with constrictive pericarditis. However, from hemodynamic and anatomic data, chronic pericardial disease is extremely unlikely in our patients. In two patients (Cases 1 and 3) right and left ventricular diastolic pressures were fairly discrepant and in all patients pulmonary systolic pressures exceeded 50 mm Hg. Additionally, in all patients right ventricular diastolic pressure was less than one third of systolic pressure, also making constrictive pericarditis unlikely. In Case 2 constrictive pericarditis was disproven by way of direct surgical inspection of the pericardia, and in Cases 1 and 3 the pericardia as well as other findings indicative of pericardial constriction were normal at echocardiography. The time course for the development of symptoms due to diastolic abnormalities in our patients was variable, ranging from 18 days (Case 1) to 10 years (Case 3) with a mean of 4.7 years. Case 1 is unique in this regard since congestive symptoms recurred very early following surgery. In this patient it is quite possible that left ventricular diastolic abnormalities existed preoperatively but were masked by the mitral stenosis. Unfortunately, the effects of surgery’ or anesthesia cannot be dismissed in this patient (see below). Therefore, the process leading to diastolic dysfunction in our patients appears to be a slow and chronic one. Myocardial biopsies were taken in two of our patients and, from these specimens, infiltrating diseases were excluded. The myocellular hypertrophy and limited fibrosis observed are not specific and can occur in a variety of disease processes, including rheumatic disease. Therefore, even though there appears to be a clinical

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association, we are unable to prove that a histologic relationship exists between restrictive-type hemodynamics observed here and rheumatic heart disease. To date, restrictive cardiomyopathy has not been linked to rheumatic heart disease. While acute rheumatic fever may result in myocarditis, chronic rheumatic heart disease is believed largely to spare the ventricular myocardium from any direct involvement. The secondary effects of rheumatic valvular lesions upon the ventricles are well described and are believed to result from conditions of chronic elevations in preload and/or afterload. However, reports of left ventricular dysfunction in mitral stenosis have also appeared [l]. An abnormality in posterobasal left ventricular contraction due to fibrosis has been proposed to account for a reduction in cardiac output following surgery for mitral stenosis [4]. Alternatively, Ahmed et al. [5] concluded that the decrements in left ventricular ejection reported in previous papers may be due to abnormalities in loading states, rather than as a primary myocardial condition. In their patients, indices of left ventricular isovolumic relaxation and contraction were normal in those with subnormal left ventricular ejection fractions, thereby making an abnormality of myocardial function less likely. Finally, what other etiologies besides rheumatic heart disease could have led to restrictive-type hemodynamics in our patients? The only other characteristics shared by all patients in this report are diabetes mellitus and cardiac surgery. The effects of diabetes mellitus on the heart have been broadly discussed [6]. Primary myocardial abnormalities have recently been recognized, but the nature of the myocardial insult has not been elucidated. Ryndiewicz et al. [7] and Mildenberger et al. [8] demonstrated abnormalities in systolic and diastolic left ventricular function by noninvasive means (gated blood pool scanning and echocardiography) in groups of asymptomatic diabetics. Most of these patients were young and insulin requiring; some had evidence for microvascular disease. Our patients do not fit well into the above categories of patients with diabetes mellitus. Only one patient (Case 2) was insulin requiring and in this patient the development of restrictive-type hemodynamics predated that of diabetes mellitus. Additionally, biopsy data from two of our patients contained no findings which could be considered characteristic of diabetes mellitus. Nonetheless, the effects of diabetes mellitus in our patients may be more pronounced than we can measure. In terms of cardiac surgery as a cause of restrictive cardiomyopathy, there is no such phenomenon described in the literature. To date, neither cardioplegia nor anesthesia, in all of their forms, has ever been correlated with the induction of restrictive cardiomyopathy or long term effects on ventricular diastolic function. One report by Roberts et al. [9] describes endocardial fibrosis as an outcome of Starr-Edwards mitral prosthetic implantation. The mechanism in that particular account was speculative and never again reported. Of our patients, only two had mitral prostheses, one of the ball-cage type. The other two had undergone mitral commissurotomies prior to the development of clinically apparent restrictive-type hemodynamics. In summary, we have described in this report what appears to be a new clinical entity: hemodynamics resembling restrictive cardiomyopathy following valve surgery in patients with rheumatic heart disease. Its importance lies in its recognition as a

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cause of postoperative congestive heart failure in such patients. Clearly further work is needed regarding the pathophysiology and pathogenesis of this entity. References 1 Harvey RM, Ferrer MI, Samet P, et al. Mechanical and myocardial factors in rheumatic heart disease with mitral stenosis. Circulation 1955;11:531-551. 2 Brockenbrough EC, Braunwald E. A new technique for transseptal left ventricular angiocardiography and transseptal left heart catheterization. Am J Cardiol 1960;6:1062. 3 Kelly DT, Spotnitz HM, Beiser GD, et al. Effects of chronic right ventricular volume and pressure loading on left ventricular performance. Circulation 1971;44:403-410. 4 Heller SJ, Carleton RA. Abnormal left ventricular contraction in patients with mitral stenosis. Circulation 1970;17:1099-1110. 5 Ahmed SS, Regan TJ, Fiore JJ, Levinson GF. The state of the left ventricular myocardium in mitral stenosis. Am Heart J 1977;94:28-39. 6 Regan TJ. Cardiac decompensation in diabetes mellitus. Cardiovasc Rev Rep 1985;6:1117-1126. 7 Ryndiewicz A, et al. Systolic and diastolic time intervals in young diabetics. Br Heart J 1980;44:280-283. 8 Mildenberger RR, Bar-SchIomo B, Druch MN, et al. Clinically unrecognized ventricular dysfunction in young diabetic patients. J Am Co11Cardiol 1984;4:234-238. 9 Roberts WC, Morrow AG. Secondary left ventricular endocardial fibroelastosis following mitral valve replacement. Circulation 1968;37 and 38 (suppl II):lOl-109.