Diffusing Capacity Decreases After Heart Transplantation

Diffusing Capacity Decreases After Heart Transplantation* Jill Ohar, M . D . , F.C.C.E;Joan Ostedoh, B . S . N . ; Nudeem Ahnled, M.D.; and Leslie Miller, M.D.

We evaluated the following spirometric values: forced vital capacity (FVC), first second expiratory volume (FEV,), FEV,/FVC, the lung volumes, total lung capacity (TLC), residual volume (RV), and single breath diffusing capacity for C O in 22 patients, before and after heart transplant. We found abnormal pulmonary function in 21 patients before heart transplantation. Despite postoperative increases in lung volumes in 10 patients, abnormal pulmonary function persisted in 20 patients after heart transplant. Mean values for lung volumes and flow rates did not change but diffusion for C O decreased significantly after heart transplantation. Diffusion failed to correlate with ejection fraction, pulmonary arterial pressure, pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance; however, in a subset of patients with improved postoperative lung volumes, preoperative diffusion for C O correlated with preoperative PCWP. We conclude that pulmonary function abnormalities a r e common among heart transplant recipients. Diffusion abnormalities are not

linearly related to indices of cardiac function measured before transplantation and diffusion abnormalities appear to be multifactorial in cause. The posttransplant decrease in diffusion appears to result from the combined effects of decreased postoperative lung volumes in some patients and relief of heart failure induced pulmonary vascular engorgement in others. Improvement in lung volumes and flow rates may occur but cannot be expected after heart transplantation, and diffusion decreases after heart transplantation. The fact that pulmonary function and lung volumes do not improve following heart transplantation implies to underlying lung disease or permanent lung alterations result (Chest 1993; 103:857-61) from chronic heart failure.

transplantation has become a viable therapy Cardiac for end-stage heart disease regardless of etiology.

tation. Based on the report by Hoseopnd e t a19 of increased lung volumes, we hypothesized that pulmonary function might improve after heart transplantation and that patients may be arbitrarily denied transplantation based on poor preoperative pulmonary function. However, Hosenpud et a19 analyzed only spirometric data and did not study the diffi~sion abnormalities noted in the preliminary findings of Egan et allr and Casan et al."' We therefore evaluated pulmonary function before and after heart transplantation to determine if postoperative improvement in lung volumes, flow rates or diffusion could be espected.

The number of hearts transplanted annually is in excess of 2,000, with one-year survival surpassing 85 percent.[ Heart transplants are limited by the availability of suitable donors, which underscores the extreme importance of appropriate recipient selection. Selection criteria for cardiac transplant candidates based on pulmonary function have been publishedZ but these criteria have not been ~ a l i d a t e d .Patients ~ with heart failure commonly have pulmonary function a b n ~ r m a l i t i e s .Reduction ~-~ in lung volumes, flo\v rates, and difi~sionhave all been shown to be associated with heart The subset of patients with heart failure who are awaiting heart transplantation also ~~ et have pulmonary function a b n o r m a l i t i e ~ .Wright aln noted dfii~sionabnormalities in 67 percent of 132 patients awaiting heart transplantation and restriction in 21 percent. Hosenpud et a19 observed a reduced FVC and FEV, consistent with restriction, which improved after transplantation in a study of 17 cardiac transplant candidates. Casan et a1I0alsonoted improvement in lung volumes after heart transplantation. However, reports by Egan et allr and Casan et alMJ described worsening of diffusion after heart transplan*From the Department of Internal Medicine, St. Louis University Medical Center. St Louis. ~ ~ ~ , ,b\.~~~~~i~~~ ~ ) ~ t tieart ~ d~ ~ ~ c r a n t~- i n - ~ii d91014760, ~ t ~ ; c i ; s c r i ~r;ceived t June 30. revision accepted September 23.

Dm = single-breath diffusin capacity for carbon monoxide; DLVA= ratio of Dm to alveofar volume; EF = ejection fraction; LAO = left anterior obli ue; PCWP= pulmonary capillary wedge pressure; PPA= parnonary arterial pressure; PVR = pulmonary vascular resistance; Q = cardiac output; VA =

alveolar volume.

Twenty-two patients who had rindergone cardiac transp1;rnt;ction were recn~itedinto this str~dyInfornred c~)nsentw;is obtained and the protoc~)lwas approved by St. Lor~isUniversity Mtdical Center institr~tionalreview 1x)ard. Diagnoses for which patients undem~ent transp1;ents included ischemic," idiopathic.* ;end v:ilvr~l:cr' cardiomyopathies. Two patients received ;I heart transpla~rtfor c~)npenital heart disease. The study popr11;ction rwnstitr~ted 17 men and 5 women. The me:cn nge ;ct the time of heart transp1:cntation was 53 + 2 years (range, 40 to 61 years). All patients were evalr~;ctedfor potential c;crdiac transp1;intation as inpatients according to the St. Lollis University prot(xoI. Pretransplantation evalrr;etion was performed 5 + 1 months Iwfore the transpliint prtxedure. A cwmplete history wos taken and a physic;il examination was performed as pert of the evalr~ation. Smokillg st;etus wes defint,d as either ..never- smoked Or ..formerw i sneokers. ~ ~ Patients were not considered for transplantation in orlr program until they hied abstained from ttr1);eccr) pr(K111ctsfor :ct leiest CHEST I 103 I 3 I MARCH. 1993

857

two months. Nine patients never smoked and 13 were former smokers. Among former smokers, the mean duration of time from smoking cessation to transplant evaluation was 3 3 t 13 months (range, 2 to 156 months). Routine pretransplant evaluation included pulmonan hinction testing, right heart catheterization, and estimation of left ventricrilar ejection fraction (EF) by cardiac gated pnl scan or echocardiogram. Twrentv mCi of -Tc-labeled red blocd cells were utilized for the gated pnol examination. Images were obtained in the 45" left anterior oblique (LAO), anterior, and left lateral pn)jections using a 5 million count endpoint per acquisition. On the 45" LAO view, regions of interest were manllally placed around the left ventricle at end-diastole and end-systole. Left ventricular E F was calculated according to the following formula: EF=

LV end-diastolic cr)unts - LV end-systolic munts LV end-diastolic cu)rlnts

Gated pw)l scan E F values were available on 19 patients. Ejection fraction calculated from two-dimensional echocardiography was used in the analysis for the remaining three patients.12 Right heart catheterization with a 7.5 French Swan-Canz ballcw)n-tipped thermodilution catheter yielded values for mean pulmonary arterial pressure (PYA),cardiac output (Q) and pulmonary capillary wedge pressure (PCWP). Pulmonary vasclllar resistance (PVR) was calculated from these values accujrding to the following equation: PVR = (PYA- PCWP)/Q. Vasclilar pressures were measured at endexpiration and zero-referenced to the level of the right atrium. Cardiac output was determined by thermtdilution of a 10-ml bolus of iced saline ~ o l u t i o n using '~ a cardiac output cumputer (Abbntt Swan Oximetric 111). Pulmonary function testing included measurements of spirometry, Iring volumes, and single-breath diffusion capacity for carbon monoxide (Dco). Forced expired volumes and flow rates were determined using a volume-displacement spirometer with up to eight repetitions to obtain reproducibility Reproducibility was defined as the best of three acceptable maneuvers of FVC that varied by less than 5 percent. Spirometric indices were calculated from the best of three satisfactory breaths, acn~rdingto the American Thoracic Striety guidelinesMand were compared with published predicted values.'" Subdivisions of lung volumes were determined by the helium dilution methtd and expressed as actual values and percent predicted values.lh The single-breath D m was determined in duplicate by the method of Forster et all7 as mtdified by Jones and Meade.ln Patients were classified as having an obstructive ventilatory defect if the observed FEV,/FVC x 100 was less than 70 percent. A restrictive defect was judged to be present if the total I~lngcapacity was less than 80 percent of predicted. Diffi~sionwas cnrrected for hemoglobin accwrding to the following equation:

The result was expressed as actual value" and percent predicted. In this study, a corrected D m of less than 80 percent of predicted was considered abnormal. The ratio of D m to alveolar volume (VA) was also assessed (DL\.A). Posttransplant hemodynamic variables were measured at the time of discontinuation of postoperative hemodynamic monitoring (two to four days posttransplant). Posttransplant pulmonary function was evaluated 5 t 1 months after transplantation. Posttransplant E F was measured from the ventriculogram taken during left heart catheterization just prior to hospital discharge."' Significance of the differences between variables measured before and after transplant was determined by paired Student's t test. A p value less than 0.05 was considered significant. N o statistical c~)mparisonof before and after transplant E F was made because E F was measured by different methods postoperatively and preoperatively. Correlation of two variables was performed by linear regression. Values are expressed as mean t SE.

Before and Afier Transplant

When comparing pretransplant and posttransplant pulmonary function, two significant differences were noted (Table 1). Both Dco and DLVAwere significantly lower in patients after cardiac transplantation than before transplant. The Dco decreased from a mean pretransplant value of 18.662 1.40 to a mean posttransplant value of 14.49+ 1.37 mVmin/mm Hg. Similarly, DLVAdecreased from 3.8k0.26 to 2.94 + 0.21 mVmin/mm Hg/L. Values for Dco decreased in 19 patients and increased in 3. DLVA decreased postoperatively in 18 patients and increased in 4 patients. Lung volumes increased after heart transplant in 10 patients and decreased in 12. Therefore no significant change in mean values for FVC, FEV,, FEV,/FVC, TLC, and FRC was observed after heart transplant. Predictably, hemodynamic variables significantly improved with heart transplantation (Table 2). PPA decreased from 27.64 + 2.09 to 21.62 + 4.21 mm Hg. PVR decreased from 2.1 + 0.27 to 1.48 2 0.17 mm Hg/ LJmin. PCWP also decreased from 18.95+ 1.59 to 13.3k0.5 mm Hg. Although E F improved substantially after heart transplant, use of a different method of measurement before cardiac transplant precluded statistical comparison of these values. The magnitude Table 1 -Pulmonury Function With Percent Predicted Values Before and @ r Transplant* FEV,/FVC,

Pretransplant value + S E (n) % predicted Posttransplant value t SE (n) % predicted

FVC. L

FEV,, L

3.11+0.18 (22) 69 2 3

2.32t0.17 (22) 7024

8

74+2 (22) -

TLC, L

FRC, L

Dm, mvmidmm H g

DLva, mvmidmm H g f l

5.3050.23 (20) 8323

2.86t0.15 (20) 82 2 6

18.662 1.40 (22) 6924

3.8020.26 (22)

-

*FVC =forced vital capacih; FEV, =first secund forced expiratory volume; TLC = total lung capacity; D a ) = single breath diffi~singcapacity ; =alveolar volume. for carbon monoxide; DLVA= D c ~ f l . +VA tp