Ventricular performance related to transmural filling pressure in clinical cardiac tamponade

Transcription

1 PAHOPHYOLOGY AND NAURAL HORY CARDAC AMPONADE Ventricular erformance related to transmural filling ressure in clinical cardiac tamonade CHEER M. BOLWOOD, JR., M.D. Downloaded from htt://ahajournals.org by on October 1, 1 ABRAC n clinical cardiac tamonade, oen-catheter intraericardial ressure (PP) may be used to estimate left ventricular transmural filling ressure (MFP). However, it has been suggested recently that right atrial ressure (RAP) is suerior to PP in assessing true extracardiac ressure during ericardial drainage. n 1 atients with subacute cardiac tamonade, ulmonary wedge ressure (PWP), RAP, and PP were measured along with indexes of systolic function. o test the relative merits of PP and RAP in assessing true ericardial ressure, three MFP estimates were analyzed: MFP1 = (PWP PP); MFP - = (PWP 1/ RAP / PP); and MFP - - = (PWP - RAP). An accurate MFP resumably should increase during ericardiocentesis and correlate with left ventricular stroke work. n addition, to test the role of reload variation in ulsus aradoxus, resiratory variation in MFP was analyzed. n the initial tamonade state, RAP and PP were essentially equal, so all three MFP estimates gave equivalent results. For instance, MFP1 averaged ± mm Hg but fell to mm Hg during insiration ( <.1 vs exiration) and showed beat-by-beat correlation with ulse arterial ressure. After intermediate ericardiocentesis ( ± 1 ml), the PP of ± mm Hg fell significantly below the RAP of 1 ± mm Hg ( <.1), but with a + ml residual effusion suggesting continued PP measurement accuracy. By comlete ericardiocentesis (1 ± ml) there was a significant increase in MFP1 to ± mm Hg ( <. vs tamonade) but not in the MFP of 1 ± mm Hg. Encomassing tamonade and ericardiocentesis data, left ventricular stroke work index showed ositive correlation with MFP1 (r =.) and MFP (r =.) but not with MFP. hus cardiac tamonade often may be diagnosed with a MFP averaging well above zero, and diastolic equalization of PWP, RAP, and PP may be a redominantly insiratory finding ("insiratory tracking"). his suorts the role of reload variation in the genesis of ulsus aradoxus. On the other hand, true ericardial ressure may fall substantially below RAP in the course of ericardial drainage. his may be reconciled with the concet that normal ericardial ressure nearly equals RAP by hyothesizing an increased ericardial caacity in subacute tamonade so that ericardiocentesis roduces a state analogous to removal of normal ericardial constraint. Circulation, No., 1-, 1. HE FORCE BALANCE affecting a hollow chamber may be described by the transmural difference between intracavitary and extramural ressures. Accordingly, transmural ventricular diastolic ressure is an aroriate correlate of diastolic volume' and of corresonding systolic erformance.' Desite the concetual ad- From the Deartment of Medicine, University of California chool of Medicine and VA Medical Center, West Los Angeles. uorted in art by the VA Medical Center Research ervice, Wadsworth Division, Los Angeles. his work was erformed during Dr. Boltwood's tenure (11-1) as a Merck Fellow of the American College of Cardiology and during his tenure as a Clinician cientist of the American Heart Association, Greater Los Angeles Alfiliate. Address for corresondence: Chester M. Boltwood, Jr., M.D., Cardiology 1/11 11E, West Los Angeles VA Medical Center, Wilshire and awtelle Blvds., Los Angeles, CA. Received June 11, 1; revision acceted Feb. 1, 1. Presented in art at the th and th cientific essions of the American Heart Association, 1 and 1. Vol., No., May 1 vantage of transmural diastolic ressure, measuring extracardiac ressure in the intact state generally is imossible, and ventricular erformance often has been related simly to intracavitary diastolic ressure, tacitly neglecting forces external to the heart. Recent work suggests that the constraint ressure exerted by the normal ericardium generally is not negligible and often may nearly equal right ventricular diastolic ressure or right atrial ressure (RAP) in magnitude. '- However, oen-catheter intraericardial ressure (PP) often falls markedly below RAP during ericardial drainage for cardiac tamonade.i One answer to this aradox offered by miseth et al. is that true ericardial ressure equals RAP during ericardiocentesis and that oen-catheter PP underestimates constraint when there is insufficient free effusion. A roblem with this hyothesis is that the RAP 1

2 BOLWOOD Downloaded from htt://ahajournals.org by on October 1, 1 - PP difference may occur in the resence of a large residual effusion,' suggesting continued PP accuracy.' An alternative exlanation for the RAP - PP difference, therefore, is that the ericardial caacity is enlarged above normal in certain cases of tamonade, so that ericardiocentesis results in abnormally high transmyocardial diastolic ressures. n the current study, hemodynamic data from a grou of atients with cardiac tamonade were analyzed to test two chief hyotheses. First, if PP accurately measures true extracardiac ressure during ericardiocentesis, then ulmonary wedge ressure (PWP) - PP should increase during this rocedure and correlate with the resulting imrovement in left ventricular stroke work. his is true because the increase in cardiac erformance during ericardiocentesis resumably reflects an increase in ventricular filling that should correlate with transmural filling ressure (MFP). econd, if ulsus aradoxus is caused chiefly by changes in left ventricular reload, then there should be corresonding resiratory changes in an accurate MFP that become attenuated during ericardiocentesis. More general aims were to examine the relation between ventricular erformance and MFP over a range of filling states and to reexamine the hemodynamics of cardiac tamonade within the new context of the ericardial constraint hyothesis." Methods Patients. en consecutive atients undergoing right heart catheterization and ericardiocentesis for diagnosis and/or treatment of ericardial disease with evidence of tamonade were ABLE 1 Clinical rofile studied between Aril 11 and May 1. Written informed consent for these clinically indicated rocedures was obtained in all cases. An eleventh atient in the series was excluded from analysis because adhesions allowed drainage of only 1 ml of ericardial fluid, in the face of a much larger effusion on echocardiograhy. able 1 details clinical data on the atients studied, each of whom was male and had a large ericardial effusion on echocardiograhy and an insiratory decrease in arterial systolic ressure greater than 1 mm Hg. Right ventricular diastolic collase was detected on echocardiograhy as early diastolic invagination of the free wall, often seen at the outflow tract. 1 imilarly, right atrial collase was detected as invagination of its free wall during late diastole.' wo atients each received raid intravenous infusion of aroximately liters of crystalloid and/or colloid before study (atient, the subject of a rior reort, 1 and atient, who develoed hyotension comlicating low-ressure tamonade,' and who also required latelet transfusions for thrombocytoenia before undergoing ericardiocentesis). hree atients had underlying heart disease: atient with severe hyertension and a history of heart failure after myocardial infarction, atient with mild aortic insufficiency, history of non-q wave myocardial infarction, and a ermanent ventricular acemaker (redominantly normal sinus rhythm throughout this study), and atient with advanced catheterization-documented dilated cardiomyoathy. Patients and were relatively asymtomatic and underwent ericardiocentesis chiefly to diagnose the cause of ericardial effusion. he remaining atients were moderately to severely symtomatic, chiefly from dysnea. Hemodynamics. Right heart catheterization was erformed in the routine manner with a balloon-tied thermodilution ulmonary arterial catheter. he ericardial sace was cannulated via the subxyhoid aroach with a No. F end- and six sideholed Cook UCLA traight ecial catheter' by means of the eldinger technique. wo equisensitive transducers allowed simultaneous stri-chart recordings of PWP, RAP, and PP. n atients 1,,,, and one of these transducers then was used to measure arterial ressure via a radial artery cannula. n atients and an arterial cannula was not laced, and a shygmomanometer was used to measure systemic arterial ressure. n atients,, and 1 a third transducer allowed simultaneous Age Patient (yr) Presentation Diagnosis Rhythm RVDC RAC 1 Dysnea Polycythemia vera, thrombocytosis + A Dysnea Chronic idioathic ericarditis A A 1: AVC Mild dysnea, friction rub, fever Viral ericarditis VP, R + A Dysnea Metastatic bronchogenic carcinoma + + Mild dysnea Metastatic bronchogenic carcinoma R + A Dysnea Metastatic bronchogenic carcinoma MFA B B Chest ain, dysnea, friction rub, fever Viral ericarditis + A Friction rub, hyotension tahlococcal ericarditis, + A myelofibrosis Dysnea Metastatic bronchogenic carcinoma, PVC Dysnea, fever Metastatic bronchogenic carcinoma + + RVDC = right ventricular diastolic collase; RAC = right atrial collase; = sinus tachycardia; A = atrial tachycardia; AVC = atrioventricular conduction; VP = ventricular demand acer; R = normal sinus rhythm; MFA = multifocal atrial tachycardia; PVC = remature ventricular contractions. ARight atrial free wall not well visualized. raid tachycardia making RVDC, RAC difficult to interret. Bwinging heart, CRCULAON

3 PAHOPHYOLOGY AND NAURAL HORY-CARDAC AMPONADE Downloaded from htt://ahajournals.org by on October 1, 1 recording of systemic arterial ressure with a radial arterial cannula. Patient was studied semielectively in the catheterization laboratory and agreed to lacement of an esohageal catheter, which was a saline-filled ediatric nasogastric tube inserted aroximately cm from the nostrils and attached to a fourth transducer. he transducers were zeroed at the same fourth intercostal sace, at mid-chest height before each recording. rilicate thermodilution cardiac outut (CO) values were averaged, and ressure data were recorded in the control (tamonade) state and immedately after intermediate and comlete ericardiocentesis. he intermediate ericardiocentesis state was defined as a oint during ericardial drainage when significant imrovement in cardiac outut had occurred, but with removal of less total ericardial fluid than estimated on revious echocardiograhy. he comlete ericardiocentesis state was defined as the oint where no more fluid could be drained from the ericardial catheter, even after ulling the catheter back slightly. Mean PWP, RAP, and PP were obtained by averaging the hasic stri-chart tracings manually at. sec intervals over one to two resiratory cycles ( to data oints er average) and were rounded to the nearest millimeter of mercury. he results agreed with digital average readouts within 1 to mm Hg, but this method was used for maximal accuracy. f after comlete ericardiocentesis PP went off the lower scale limit during insiration, the digital average readout was taken as the mean value. he systolic and diastolic systemic arterial ressures were averaged over to 1 beats, and mean arterial ressure (AP) calculated as 1/ systolic + ¾ diastolic. Mean ulmonary arterial ressure (PAP) was derived similarly in some atients. Pulsus aradoxus was measured as the decrease from maximum to minimum systolic arterial ressure during insiration and was averaged over at least four resiratory cycles. n atients and shygmomanometry was used to measure ulsus aradoxus as the cuff ressure decrement between first intermittent and consistent Korotkoff sounds audible throughout the resiratory cycle. Cardiac index (C) and stroke volume index (V) were calculated as: C (liters/min/m) = CO/body surface area; V (ml/beat/m) = Cl/heart rate. Left (LV) and right ventricular (RV) stroke work indexes (W) were calculated as: LVW (g-m/m) = (AP - PWP) x V X.1; RVW (g-m/m) = (PAP - RAP) x V x.1. ystemic (VR) and ulmonary vascular resistance (PVR) were calculated as: VR (dyne-sec-cm-) = x (AP - RAP)/CO; PVR (dyne-seccm-) = x (PAP - PWP)/CO. ransmural filling ressure estimates. Encomassing mean or instantaneous data during tamonade and after intermediate and comlete ericardiocentesis, three estimates of left ventricular transmural filling ressure were calculated: MFP = (PWP - PP); MFP = (PWP - 1/ RAP - / PP); and MFP = (PWP - RAP). MFP, assumes a redominant influence of ericardial ressure on the left ventricular free wall and that oen-lumen PP accurately measures true extracardiac ressure even after intermediate and comlete ericardiocentesis. MFP accounts for otentially different ressures exerted outside the setum by right ventricular diastolic ressure- RAP, and outside the free wall by PP, and assumes that the setal external area is aroximately one-third of the total external left ventricular surface, 1 with aroximately equal comliances for the setum and free wall. 1 MFP assumes that true extracardiac ressure continues to equal RAP, even when PP aarently falls below RAP, hyothetically due to underestimation of true constraint in the resence of limited free effusion.' 1 n situations where PP RAP, the three MFP estimates would give equivalent results. Resiratory measurements. nstantaneous measurements Vol., No., May 1 during the resiratory cycle were taken at end-diastole (i.e., eak of the ECG R wave). his oint was chosen because atrial ressure essentially equals ventricular ressure at end-diastole and because ventricular reload conventionally is measured at end-diastole. ince PWP is an indirect measure of left atrial ressure, which is somewhat delayed through the ulmonary vasculature, the PWP delay was estimated from the timing of the A or C wave with resect to the ECG (ranging to 1 msec) and used to measure the hase-corrected PWP at enddiastole. he three instantaneous estimates then were calculated by hase-corrected PWP, PP, and RAP. An event marker was ushed manually during the atient's chest exansions to identify the insiratory ortions of the ressure recordings, which always corresonded to the descending ortion of the PWP tracing. Midexiratory MFP estimates therefore were obtained at ECG R waves where PWP was maximal. ince the insiratory ortion of the resiratory cycle was often shorter than the exiratory ortion, it was not always ossible to find an ECG R wave that was timed exactly with the PWP nadir, but R waves closest to this oint were used to obtain the midinsiratory MFP estimates. All such instantaneous estimates were averaged over three to four resiratory cycles and rounded to the nearest millimeter of mercury. Note that because three channels rarely were available for simultaneous PWP, RAP, and PP recordings, instantaneous MFP often was calculated as ( MFP1 + 1/ MFP), where MFP and MFP were obtained from simultaneous PWP-PP and PWP-RAP recordings erformed in close temoral sequence. he insiratory decrease in PP from midexiration to midinsiration also was measured at end-diastole and averaged over four resiratory cycles. he resiratory rate was measured from event marks or the PWP tracing and averaged over three to four resiratory cycles. o test the beat-by-beat deendence of left ventricular erformance on reload, in atients,, and 1 ulse arterial ressure was related to the immediately receding end-diastolic (hase corrected PWP - PP) over multile cardiac cycles during the atient's sontaneous resiration. n addition, in these three atients afterload was assessed by calculating transmural systolic ressure across the left ventricular free wall as arterial ressure - PP, averaged over end-diastole, eak-systole, and end-systole, and averaged again over three midexirations and three midinsirations. n these measurements the delay in the arterial waveform from central aortic ressure was corrected by assuming onset of raid systolic ustroke at the ECG R wave. Data analysis. All grou data are reorted as mean + D. Whereas ressure data generally were rounded to the nearest millimeter of mercury (the robable measurement resolution), the mean grou results in resiratory MFP estimates were reorted to the nearest.1 mm Hg to more exactly secify the sread around zero of these variables during insiration. ignificant differences among mean hemodynamic results from tamonade and intermediate and comlete ericardiocentesis conditions were tested by reeated measures analysis (BMDP V).' f this analysis suggested a significant difference among the three conditions, then searate airwise tudent t tests were erformed, but with values multilied by according to the Bonferroni correction. Paired tudent t tests were used to assess differences among mean PWP and RAP in the tamonade state, mean RAP and PP searately in tamonade and intermediate and comlete ericardiocentesis conditions, mean exiratory and insiratory MFP estimates, and mean exiratory and insiratory left ventricular afterload estimates. he null hyothesis was excluded at the. robability level. Least-squares linear regression analysis (BMDP 1R)1 was used to test correlation between RAP and PP in the tamonade

4 Downloaded from htt://ahajournals.org by on October 1, 1 BOLWOOD state in three different ways: (1) end-diastolic RAP was related to end-diastolic PP in consecutive beats er atient in all atients studied (total n = ), () mean RAP was related to mean PP in all atients studied (n = 1), and () mean instantaneous exiratory and insiratory values for PWP - RAP were related to corresonding values for PWP - PP in all atients studied (n = ). imilar linear regression analysis was used to test correlations between ulse arterial ressure and the receding hase-corrected PWP - PP searately in atients,, and 1 over multile end-diastolic oints during sontaneous resiration (n = 1 to er individual atient regression), and LVW and each of the mean MFP estimates for all atients studied, including tamonade and intermediate and comlete ericardiocentesis conditions (n = er individual MFP regression, since intermediate ericardiocentesis data were not obtained in atient ). Results here were no significant comlications from the invasive hemodynamic monitoring and ericardiocenteses erformed in this study. able details individual and grou hemodynamic findings in the tamonade and intermediate and comlete ericardiocentesis states. (n atient no intermediate ericardiocentesis data were collected.) he intermediate state was reached after removing ± 1 ml of ericardial fluid, while the comlete ericardiocentesis state was reached after removing 1 ± ml total. n the tamonade state, an PP of 1 ± mm Hg, an RAPof 1 ± mmhg,andapwpofl ± mmhg were all above normal, but the mean arterial ressure of ± mm Hg and the cardiac index of. ±. liters/min/m were normal. he difference between PWP and RAP in the tamonade state was highly significant ( <.1). Pulsus aradoxus of 1 ± mm Hg and the heart rate of 1 ± beats/min were both elevated (normal ulsus generally is assumed to be less than 1 mm Hg), and the LVW of ± 1 g-m/m and the RVW of g-m/m were both below normal. (Low normal LVW is g-m/m, and assuming a mean PAP of 1 mm Hg, an RAP of mm Hg, and an V of ml/beat/m, low normal RVW may be about g-m/m.) he tamonade VR was normal at 1 ± dyne-sec-cm-, but PVR was somewhat elevated at 1 ± dyne-sec-cm. n the tamonade state all three MFP estimates agreed with each other within 1 to mm Hg in individual atients, and each averaged to ± mm Hg overall. Resonse to ericardiocentesis. n the intermediate ericardiocentesis state, PP fell to ± mm Hg, RAP to 1 ± mm Hg, PWP to 1 ± mm Hg, ulsus aradoxus to ± mm Hg, and VR to 11 ± dyne-sec-cm-, whereas cardiac index rose to. ± 1. liters/min/m, LVW to ± 1 g-m/m, and RVW to. ±.1 g-m/m. All these changes from the tamonade state were statistically significant. Mean arterial ressure remained unchanged at ± mm Hg, however, and the changes in heart rate to 1 ± beats/min and PVR to 1 ± dyne-sec-cm- were not significant. he increase of MFP, from ± to + mm Hg was statistically significant, but the increase in MFP to ± 1 mm Hg and decrease in MFP to ± mm Hg were not. After comlete ericardiocentesis there were further significant decreases in PP to 1 + mm Hg, in RAP to ± mm Hg, and in PWP to ± mm Hg. However, comared with the intermediate ericardiocentesis state, mean arterial ressure was essentially unchanged at ± 1 mm Hg, as were ulsus aradoxus of ± mm Hg, heart rate of 1 ± beats/min, cardiac index of. ±. liters/min/m, LVW of 1 ± 1 g-m/m, RVW of. ± 1. g-m/ mi, VR of 1 ± dyne-sec-cm -, and PVR of 1 ± dyne-sec-cm-. Comared with the intermediate ericardiocentesis state, the increases in MFP to ± mm Hg and in MFP to ± mm Hg and the decrease in MFP to 1 ± mm Hg were not statistically significant. n atients,, and the RAP remained above mm Hg even after comlete ericardiocentesis, erhas reflecting a comonent of visceral ericardial constriction. Right atrial-intraericardial ressure relation. n the tamonade state there was relatively close hasic correlation between RAP and PP throughout the cardiac and resiratory cycles. Figure 1 shows reresentative simultaneous tracings. Patients 1,,, and showed the attern on anel A with near equality during mid to late diastole, but with RAP somewhat greater than PP during ventricular systole. Patients and showed the attern on anel B with strikingly exact hasic equality in RAP and PP (excet erhas during atrial systole when RAP may slightly exceed PP). Four atients had 1 to mm Hg systematic differences between RAP and PP as illustrated in anel C (atients and 1 with RAP > PP; and with RAP < PP), erhas reflecting errors in zeroing or calibration. With data from the tamonade state, end-diastolic RAP was related to end-diastolic PP, as illustrated in figure, yielding the regression equation RAP =.1 PP +.1 (r =.). n addition, mean RAP was related to mean PP yielding RAP =. PP (r =.). hus, although the difference in grou means between RAP (1 ± mm Hg) and PP (1 ± mm Hg) was significant ( <.), mean RAP was nearly identical to mean PP excet for a systematic offset of about 1 mm Hg. Finally, mean instantaneous PWP - RAP was related to PWP - PP at midexiration and midinsiration, yielding PWP - RAP =. (PWP CRCULAON

5 Downloaded from htt://ahajournals.org by on October 1, 1 ABLE Hemodynamic data PAHOPHYOLOGY AND NAURAL HORY-CARDAC AMPONADE Patient PVOL PP RAP PWP AP Pulsus HR Cl LVW RVW VR PVR MFP1 MFP MFP D ± ± vs A B 1E + 1 ± ± vs P B B P 1 1 E ± ± ± P vs A A F 1 1 ± ± ± ± B A 1 1 ± + ± ± A 1 ± ±1 ± ± A A ±. B. ± A ±1 ±1. ± ± ± ± +1 B c B B ± 1 ±.1 ± ± ± ± 1 ± ±1 ±1. ± + ± ± ± A B B c = tamonade; = intermediate ericardiocentesis; P = comlete ericardiocentesis; PVOL = ericardiocentesis volume (ml); PP = mean intraericardial ressure (mm Hg); RAP = mean right atrial ressure (mm Hg); PWP = mean ulmonary wedge ressure (mm Hg); AP = mean arterial ressure (mm Hg); Pulsus = ulsus aradoxus (mm Hg); HR = heart rate (beats/min); C = cardiac index (1/min/m); LVW = left ventricular stroke work index (g-m/m); RVW = right ventricular stroke work index (g-m/m); VR = systemic vascular resistance (dyne-seccm-); PVR = ulmonary vascular resistances (dyne-sec-cm-); MFP (transmural filling ressure) = (PWP - PP) (mm Hg); MFP = (PWP- 1/ RAP - / PP) (mm Hg); MFP = (PWP - RAP) (mm Hg). A <.1; B <.1; C <.; D <. vs PP; E <.1 vs PP; F <.1 vs RAP. Vol., No., May 1

6 BOLWOOD mm Hg A mm Hg 1 -Anb ECG h seco--nds seconds - RAP... PP _ A, A, A A ~, A,~ A, A,ECG C, CL. cc H 1OH Y=. 1X+.1 O m * a n a a / /,, DENY PAEN 1 1 o Downloaded from htt://ahajournals.org by on October 1, 1 B C seconds seconds - RAP... PP ECG FGURE 1. imultaneous RAP and PP tracings. A, From atient 1; B, from atient ; C, from atient 1. - PP) +. (r =.). he results of this regression analysis are further detailed in table. After intermediate ericardiocentesis the resulting difference in RAP (1 + mm Hg) and PP ( + mm Hg) was quite significant ( <.1). his difference develoed while a large ericardial effusion was still resent (i.e., ml in the intermediate ericardiocentesis state, range to 1 ml, derived in each atient as the difference between comlete and intermediate ericardiocentesis volumes). As shown on a reresentative tracing in figure, in the intermediate state RAP and PP were often close during exiration, but PP fell notably below RAP during insiration. his attern was resent during the intermediate ericardiocentesis state in atients 1,,,,, and 1. n atients and, RAP and PP were searated throughout the resiratory cycle, while in atient they were still suerimosable in the intermediate ericardiocentesis state. After comlete ericardiocentesis the difference between grou mean RAP ( + mm Hg) and PP (1 + mm Hg) was even more striking ( <.1), and the ressures were searated throughout the resiratory cycle in all 1 atients. Resiratory efects. Figure shows simultaneous 1. A A A 1 PP (mm Hg) FGURE. Regression of end-diastolic RAP versus end-diastolic PP ( consecutive beats in each of the 1 atients). PWP and PP tracings along with systemic arterial and esohageal ressures obtained in the tamonade state. o a greater or lesser degree, nine atients demonstrated such a resiratory attern during tamonade, where the midexiratory PWP was significantly above PP but tended to merge with or fall slightly below PP during insiration. his resiratory attern in PWP- PP or in PWP-RAP has been termed "insiratory tracking." n only atient was continuous nearequalization of PWP and PP found (see figure ). Averaged over the resiratory cycle in the whole grou, the insiratory tracking attern resulted in the significant difference between mean PWP 1 + mm HgandmeanPPorRAPof 1to 1 + mmhg( <.1), imlying a mean MFP in the tamonade state significantly above zero at to mm Hg. mm Hg 1 seconds AK&& RAP... PP ECG FGURE. imultaneous RAP and PP tracings in atient 1 after intermediate ericardiocentesis ( ml removed, with remaining). Although RAP and PP are close during exiration, there is notable searation during insiration coincident with deeening of the X and Y descents (which suggests an increase in ulsatile systemic venous flow). A i CRCULAON

7 ABLE Results of linear regression analysisa PAHOPHYOLOGY AND NAURAL HORY-CARDAC AMPONADE Deendent variable (Y) ndeendent variable (X) n Regression relation r EE value End-diastolic RAP End-diastolic PP Y=.1 x <.1 Mean RAP Mean PP 1 Y =. X <.1 PWP -RAP PWP - PP Y=.x <.1 Pulse AP PWP - PP Patient 1 Y=.x +... <.1 Patient Y= 1.1 X <.1 Patient 1 Y=.1x +... <.1 LVW MFP1 Y=.1 x <.1 LVW MFP Y=.x <.1 LVW MFP -.1.B n = number of data oints analyzed; r = standard correlation coefficient; EE = standard error of the estimate (in units of the deendent variable); = robability of no linear correlation between deendent and indeendent variables; other abbreviations as in table. Aee second aragrah of Data Analysis subsection for detailed descrition of the variables analyzed. BNo significant correlation. Downloaded from htt://ahajournals.org by on October 1, 1 able details individual and grou resiratory measurements. With the excetion of atients and, significant tachynea was resent with a grou resiratory rate of + 1/min, and this variable did not decrease significantly with ericardial drainage. As detailed under MFP1, in the tamonade state PWP - PP was. +. mm Hg at midexiration (range 1 to mm Hg) and fell to mnm Hg at midinsiration ( <.1; range -1 to mm Hg). With RAP- PP in the tamonade state, the findings in MFP and MFP were very similar to those in MFP,. n atients,, and 1 during tamonade, ulse arterial ressure was related to the immediately receding (hase-corrected PWP - PP) over multile beats. As detailed in table, these two hemodynamic variables showed significant linear correlation in each atient so studied, with r values ranging. to.. n the intermediate ericardiocentesis state, MFP1 ECG decreased from.1 ±. mm Hg at midexiration to.1 ±. mm Hg at midinsiration ( <.1). n contrast, because of the inequality of RAP and PP, MFP decreased from. ±. mm Hg at midexiration to the lower value of -. ±. mm Hg at midinsiration ( <.1). MFP showed intermediate findings between MFP1 and MFP. Note that the insiratory value for MFP1 after intermediate ericardiocentesis of.1 ±. mm Hg was significantly higher than that during tamonade of. ± 1. mm Hg ( <.). n the comlete ericardiocentesis state, MFP1 could be evaluated in only four atients (PP went off scale in the others). Nevertheless, the change from. ±. mm Hg at midexiration to. ±. mm Hg at midinsiration was significant ( <.1). MFP, on the other hand, could be evaluated in all atients in the comlete ericardiocentesis state, and became notably negative during insiration in six of the 1 atients. On the average, MFP fell from. ±. mm Hg at mm Hg AP PWP 1 Fl%L_.c w..,pp seconds FGURE. imultaneous arterial (AP), ulmonary wedge (PWP), intraericardial (PP), and esohageal ressure (EOP) tracings during tamonade in atient. ee text for discussion. Vol., No., May 1 - Hg 1-_ FGURE.. a1 a seconds PWP... PP imultaneous PWP and PP during tamonade in atient

8 BOLWOOD ABLE Resiratory measurements MFP MFP MFP Afterload PP Patient RR Ex n (Ex -n) Ex n (Ex - n) Ex n (Ex - n) Ex n (Ex - n) P P P Downloaded from htt://ahajournals.org by on October 1, 1 1 P vs P vs P c +1. B.1c ±..D ±.. ± O.OC c. ±. ±..Oc. ±. ± c C c ±. ± ± E + ±1 B 1 E + 1 ±1 A A E +1 ±1 RR = resiratory rate (er min); Afterload = AP - PP (mm Hg, averaged over end-diastole, eak systole, and end-systole); Ex = midexiratory; n = midinsiratory; other abbreviations as in table. A <.1; B <.; C <.1 vs Ex; D <.1 vs Ex; E vs Ex. 1. ±.. ±.. +. CRCULAON

9 PAHOPHYOLOGY AND NAURAL HORY-CARDAC AMPONADE Downloaded from htt://ahajournals.org by on October 1, 1 midexiration to mm Hg at midinsiration ( <.1). MFP again showed intermediate results between MFP1 and MFP. he afterload variable evaluated in atients,, and 1 showed no significant change from midexiration to midinsiration in the tamonade or ericardiocentesis states. However, the increase from ± mm Hg in tamonade to ± 1 mm Hg after comlete ericardiocentesis at midexiration was significant ( <.1), with a similar significant increase in midinsiratory values. Finally, the insiratory decrease (Ex - n) in PP averaged. ±. mm Hg in the tamonade state and did not change significantly with ericardiocentesis. n atient the insiratory decrease in esohageal ressure was about mm Hg (see figure ). ince this atient was relatively asymtomatic, it may be resumed that the average insiratory decrease in esohageal ressure was greater than or equal to mm Hg for the entire grou. ransericardial ressure may be defined as PP - P, where P is intrathoracic ressure. ince changes in esohageal ressure reflect changes in P, this suggests an exiratory-insiratory change in PP - P of at least. - = - 1. mm Hg, i.e., an insiratory increase of several millimeters of mercury in transericardial ressure. troke work-transmural filling ressure relations. As shown in figure, A, the best correlate of LVW encomassing tamonade and ericardiocentesis data was MFP1 (r =.). Most atients showed a ositively monotonic increase in LVW with PWP - PP after intermediate and comlete ericardiocentesis. However, there was an unexected decrease in PWP - PP from intermediate to comlete ericardiocentesis in atients and. he correlation between LVW and MFP was nearly as good (r =., see anel B), with similar overall features. n contrast, there was no significant overall correlation between LVW and MFP (see anel C). A ositively monotonic increase in LVW with MFP occurred only in atients and, with many of the remainder showing nonhysiologic decreases in MFP desite increases in LVW. Results of this regression analysis are further detailed on table. Discussion Pathohysiology and diagnosis of cardiac tamonade. Cardiac tamonade is a comlex circulatory state in which an abnormal ericardial effusion reduces cardiac filling below the normal range of oeration. he volume available for cardiac filling is the difference between total intraericardial and effusion volumes. otal intraericardial volume in turn deends on the ericardial ressure-volume relation. ince acute ericardial effusions of only ml may cause hyotensive tamonade, normal ericardial caacity aarently is not that much greater than normal total cardiac volume. As illustrated in this and other series, however, resentations with large effusions imly sufficient chronicity for ericardial caacity to enlarge substantially above normal. A consistent finding in tamonade is the nearly exact equality of PP and RAP throughout the cardiac and resiratory cycles (see figure 1).,1 Although the regression relation between PP and RAP at end-diastole was not exact identity, there was considerable overla with the identity line within the scatter of the data (see figure ). he relation between mean PP and mean RAP was more nearly identity (see table ), erhas because of reduction in random measurement error by averaging. Other frequent findings in cardiac tamonade such as right atrial and right ventricular diastolic collase have been attributed to negative transmural diastolic ressure (i.e., PP > RAP). However, measurably negative transmural ventricular diastolic ressures have been reorted only in late stages of exerimental cardiac tamonade.1 he critical buckling ressure for a thin-walled cylinder (which may be an aroriate geometry for ortions of the right ventricular free wall) is: (Pextema - Pintemal)= E (h/r) (1 - v) where E is Young's modulus, v is Poisson's ratio, and h is the thickness and R the radius of the cylindrical shell. Here buckling is defined as a collase or shae change inward from the equilibrium configuration that exists at zero transmural ressure. With E values of 1 to g/mm from initial linear myocardial stress-strain data, incomressibility with v =., and a reresentative diastolic (h/r) -. cm/ cm -. for the right ventricular free wall (from atient ), the theoretical buckling ressure is. to.1 mm Hg. hus the negative transmural ressure gradient causing right ventricular diastolic collase may be too small in absolute magnitude to measure unless collase is extreme. n situations where PP -right ventricular diastolic ressure or RAP, the ressures outside the left ventricular free wall and setum during diastole are similar, so a relatively uniform MFP may be estimated as PWP - PP or as PWP - RAP. he equality of mean PWP, RAP, and PP conventionally sought in cardiac tamonade, therefore, would imly oeration with a mean MFP of zero, i.e., near the left ventricular Vol., No., May 1

10 BOLWOOD equilibrium volume. he current study demonstrates that cardiac tamonade often may be diagnosed with a mean MFP significantly above zero but that this gradient tyically falls to zero or slightly below during insiration, correlating with ulsus aradoxus (see figure ). An insiratory movement of the intraventricular setum toward the free wall also is observed frequently in tamonade. ince diastolic setal osition has been shown to deend on the transsetal gradient, the resiratory variation in PWP - RAP shown here would rovide the hemodynamic basis of this echocardiograhic finding. Other reorts have acceted diastolic equalization within several millimeters of mercury as comatible with tamonade, ' so the current findings do not necessarly add to the diagnosis of this disorder. As an indeendent criterion, in fact, diastolic equalization of PWP and RAP within mm Hg is not that helful because these ressures often normally agree within this range. amonade therefore remains a clinical diagnosis tyically featuring dysnea, jugular venous distension, and ulsus aradoxus in the resence of an abnormal ericardial effusion. he hemodynamic criteria of PP -RAP and imroved cardiac erformance after ericardial drainage robably are redicted by right atrial or right ventricular diastolic collase, although false negatives may occur in the resence of right heart or ulmonary disease. Asymtomatic atients with such echocardiograhic findings simly demonstrate the sectrum of cardiac tamonade. r F F =. X + 1. r =.1 E cj', E. E cmek so F h Downloaded from htt://ahajournals.org by on October 1, 1 A (PWP - PP) (mm Hg) cm E E E 1 B F 1 No Correlation A * * * * At j 1 a 1 1 (PWP - 1/ RAP - / PP) (mm Hg) 1-1 (PWP - RAP) (mm Hg) C FGURE. Regression lots with the deendent variable left ventricular stroke work index (LVW) vs the three MFP estimates shown resectively in anels A, B, and C. n each lot the initial tamonade oints are labeled with atient number, and arrows connect to intermediate and comlete ericardiocentesis oints in each case. CRCULAON

11 PAHOPHYOLOGY AND NAURAL HORY-CARDAC AMPONADE Downloaded from htt://ahajournals.org by on October 1, 1 he insiratory tracking attern was observed in the resence or absence of dysnea and underlying cardiac disease. hus the currently reorted atients are not secial cases but may exemlify a common intermediate tamonade state between severely comromised cases in which an average MFP of zero would be exected and the rare case of "right heart tamonade" in which MFP is consistently above zero. ince cardiac outut is well maintained in this intermediate tamonade state, dysnea rather than fatigue or hyotension is the cardinal symtom. nterestingly, since PWP is not always very elevated and since dysnea has been described in low-ressure tamonade,' the mechanism of this symtom may not be simly ulmonary venous congestion. ince right heart tamonade has been described in only four atients, this subset deserves further study. ecifically, the resence or absence of right atrial and right ventricular diastolic collase would be ertinent to the roer inclusion of this subset in the tamonade sectrum.' Mechanisms of ulsus aradoxus. Although the transmission of negative intrathoracic ressure to the aorta may cause a decrease in arterial ressure measured with reference to atmosheric ressure, an insiratory decrease in arterial ulse ressure imlies a decrease in left ventricular stroke volume. his has been attributed to a decrease in left ventricular reload'" or an increase in afterload. he insiratory decrease in PWP - PP reorted here strongly suorts reload reduction as an imortant mechanism of ulsus aradoxus in cardiac tamonade. f left heart filling decreases while right heart outut is maintained, ooling in the ulmonary circuit necessarily occurs but attributing this effect chiefly to lung mechanics or right-left cometition is difficult. As demonstrated by habetai et al.," the reduction of ulsus aradoxus by holding systemic venous return constant and the sudden decrease in aortic ressure 1 beat after an increment in right heart filling rovide exerimental evidence for right-left diastolic cometition in tamonade. As discussed above, the current tamonade data imly an increase in transericardial ressure with insiration. ince recent literature suggests a negligible effect by diahragmatic traction on ericardial caacity,' this imlies an increase in total ericardial volume with insiration in the tamonade state. his suggests that in tamonade the insiratory increment in right heart filling is greater than the insiratory decrement in left heart filling. his would not fit with urely assive underfilling of the left ventricle and suggests sufficient right heart filling to comete with that of the left heart. However, this is highly inferential. n addi- Vol., No., May 1 tion, in the intermediate ericardiocentesis state, in which tamonade was largely relieved but PP resumably was accurate, there was still a significant insiratory decrease in PWP - PP (see table ). ince rightleft diastolic interaction may be much less imortant in the absence of ericardial limitation, this suggests that some reload reduction may occur indeendent of a cometitive effect. ince the right and left hearts are connected in series, an insiratory increase in right heart filling and outut reaches the left heart within several beats. Guntheroth et al.', in fact, suggested that ulsus aradoxus is caused by nadirs in left ventricular filling between these insiratory series increments rather than by direct insiratory effects on reload. However, Katz and GauchatO areciated the very close timing between insiration and subsequent fall in aortic ressure, and Ruskin et al.' later demonstrated an immediate effect by instructing tamonade atients temorarily to sto and then restart breathing. Figure shows the results of a similar maneuver in atient. During held exiration cardiac ressures were stable and PWP was significantly above PP. Just with the onset of insiration, PWP merged with PP, and the immediately following arterial waveform showed a decrease in systolic and ulse ressure. his emhasizes the very direct effect of insiration on left ventricular filling and erformance. However, the increase in PWP - PP several beats later resumably reflects the series effect of increased right heart outut reaching the left heart. Once the resiratory cycle is reestablished, series and direct effects intermix, but tracking of PWP and PP consistently occurs with each insiration. A decrease in intrathoracic ressure has been hyothesized to constitute an increased afterload for left ventricular ejection. Exressed as systolic wall stress, left ventricular afterload resumably deends on transmural ressure and ventricular geometry. ECG A B C 1, mm t j y n AP 1- mm Hg P seconds FGURE. imultaneous arterial ressure (AP), PWP, and PP tracings in atient. A = held end-exiration; B = onset of insiration; C = reestablished resiration. ee text for discussion. 1

12 Downloaded from htt://ahajournals.org by on October 1, 1 BOLWOOD ince PP is the ressure immediately outside the left ventricle in tamonade, the failure of the arterial ressure-pp difference to rise significantly with insiration in tamonade argues against a significant insiratory afterload effect in this disorder (see table ). Although this variable does not take left ventricular geometry or extrasetal ressure into account, since left ventricular cross-sectional area may decrease and right ventricular systolic ressure may increase with insiration in tamonade, an overall insiratory increase in left ventricular systolic wall stress in this disorder is unlikely. he afterload effect of very negative intrathoracic ressure may be more imortant when the ericardium is normal. However, roer measurement of normal ericardial constraint may also change interretation of the afterload effect in this setting. Ventricular erformance and transmural diastolic ressure-volume curves. he stroke work-mfp lots in figure show considerable scatter, suggesting heterogeneity in contractile state and other factors. Nevertheless, there was a rough overall correlation between left ventricular stroke work index and MFP1 or MFP. ndividual curves often showed flattening when the MFP estimates reached to mm Hg. he decrease in MFP from intermediate to comlete ericardiocentesis oints in atients and was surrising, since left ventricular diastolic volume resumably increases monotonically during ericardial drainage. A theoretical consideration is that diastolic stress relaxation may occur when the ventricle is exosed to a larger oerating volume. he curve relating transmural diastolic ressure to ventricular diastolic volume may be relatively flat in the vicinity of zero ressure, with a nearly exonential rise in ressure above this range and negative ressures at the volumes below the equilibrium range. 1 Careful measurements have shown nearly exact equality of left ventricular, right ventricular, and intraericardial ressures throughout diastole in certain cases of tamonade, confirming that a range of ventricular volumes from early to late diastole may occur at nearly zero transmural diastolic ressure. he flat ortion of the transmural diastolic ressure-volume curve may exlain the asymtotic hemodynamic behavior around zero MFP observed in the current study. Other workers have described dee negative insiratory swings in PWP - PP during cardiac tamonade.' n subjects more comromised than those reorted here erhas insiration may reduce left ventricular filling sufficiently to reach the negative transmural ressure range temorarily. On the other hand, oeration with MFP consistently above zero in right heart tamonade would be consistent with the relatively high cardiac outut, arterial hyertension, and absence of ulsus aradoxus in such atients Pulsus aradoxus seems to be a manifestation of at least insiratory oeration near zero MFP. ndeed, in the intermediate ericardiocentesis state in which ulsus was reduced to normal, the otentially accurate MFP1 and MFP, both still fell significantly with insiration, but not to the zero insiratory levels found in tamonade (see table ). f left ventricular stroke work is a linear function of diastolic volume, then the flat ortion of the transmural ressure-volume curve would redict a raidly ascending limb of the curve relating stroke work to transmural diastolic ressure. n some situations, cardiac function is surrisingly well maintained at nearly zero transmural diastolic ressure. his suorts the concet that myocardial fibers may still shorten considerably from the equilibrium volume down to the end-systolic volume and contradicts the contention of Glower et al. that equilibrium and dead volumes are equivalent. Reddy found that cardiac erformance did not imrove further with ericardial drainage once intracavitary diastolic and intraericardial ressures searated. his is surrising because it imlies ventricular function curves that are flat above zero transmural diastolic ressure. Although this descrition may be exaggerated because cardiac outut rather than stroke work was analyzed, it emhasizes that ventricular erformance may be most sensitive to transmural diastolic ressure as this gradient aroaches zero. Comments on method. A major limitation of this study was the lack of directly measured left ventricular ressure, which was not considered clinically indicated. However, ulmonary wedge ressure is a reasonably accurate indirect measurement of left atrial ressure, although the waveform may be somewhat damed and hase-delayed in the ulmonary circuit. Mean PWP correlates well with mean middiastolic left ventricular ressure (i.e., just before atrial systole), and the mean PWP A wave, which correlates with mean left ventricular end-diastolic ressure, is similar in timing to the hase-corrected end-diastolic PWP used here. o test the beat-by-beat correlation of left ventricular enddiastolic ressure and hase-corrected end-diastolic PWP during sontaneous resiration, simultaneous tracings in six coronary atients were analyzed by least-squares linear regression (1 consecutive beats er regression). Overall, there was reasonably good correlation during sontaneous resiration, with an average sloe of 1. (range. to 1.), an intercet of. mm Hg (range -. to. mm Hg), and a CRCULAON

13 PAHOPHYOLOGY AND NAURAL HORY-CARDAC AMPONADE Downloaded from htt://ahajournals.org by on October 1, 1 standard correlation coefficient of. (range. to.), suorting the use of PWP in the current study. his study makes exacting comarisons of several ressures, requiring a resolution of aroximately 1 mm Hg. Differences in catheter ti heights were accounted for automatically by zeroing all the fluid-filled strain gauges recisely at the same height telative to the atient." he suerimosition of RAP and PP in the tamonade state, desite otentially large differences in vertical height of the right atrial and ericardial catheter tis, demonstrates the internal consistency of this zeroing method. Although this series included consecutive atients coming to the author's attention, there may have been a bias toward atients well enough to undergo detailed hemodynamic evaluatiori. Desite a ossible bias and the resence of underlying cardiac disease in three atients, this series has similarities with other reorts in which overt hyotension was rare and subacute disease redominated.,, Comarison with normal ericardial constraint. n the current study PP fell significantly below RAP in the intermediate ericardiocentesis state (PP ± mm Hg vs RAP 1 + mm Hg; <.1). ecause this occurred in the resence of a large residual ericardial effusion (i.e., + ml), the PP measurement resumably was accurate. n the dog, for instance, only to ml of free effusion is required for accurate measurement of ericardial ressure with an oenended catheter. 1 he searation of RAP and PP in the intermediate ericardiocentesis state occurred in nine of 1 atients and did not deend on the resence of visceral constriction, which was suggested in only three atients. n addition, the resiratory variation in RAP - PP observed in this state is consistent with the increase in right heart filling caused by insiration (see figure ). Furthermore, encomassing tamonade and ericardiocentesis data, PWP - PP increased r C,' E E -ar CO F- P>.1 O NORMAL PERCARDUM (CLOED- OPEN) * AMPONADE (PERCARDOCENE--*) C,' E (n significantly with ericardial drainage and correlated with LVW, whereas PWP - RAP did not (see tables and and figure ). Overall, then, true ericardial ressure aarently may fall substantially below RAP during ericardiocentesis. o reconcile these findings with the concet that normal ericardial ressure nearly may equal RAP,', it is necessary to hyothesize an increase in ericardial caacity above normal so that ericardiocentesis roduces a state analogous to removal of normal ericardial constraint. However, in acute cardiac tamonade in which ericardial caacity has not increased yet, true ericardial ressure may continue to nearly equal RAP during the course of ericardial drainage. 1 n short-term observations with the normal ericardium intact, the near equality of RAP and ericardial ressure (PP) over a range of ressure and volume states has been attributed to a highly comliant right ventricle.' An alternative exlanation for the RAP PP relation is that the normal ericardium generally limits deformation of the right ventricular free wall to its equilibrium range and that changes in right ventricular volume occur chiefly as a result of setal shift rather than free wall distension.' ince right ventricular diastolic collase may imly oeration below the equilibrium volume as discussed above, and since this is an early finding in tamonade, 1 it seems lausible that the right ventricular free wall normally may oerate near its equilibrium configuration. On the other hand, once ericardial constraint is removed, substantial transmural diastolic ressures across the right ventricular free wall may result. Figure comares the grou left and right ventricular function curves from the current atients with those obtained in 1 atients studied intraoeratively, before and after oening the normal ericardium. As described elsewhere (as grou ), the intraoerative grou consisted chiefly of coronary atients with angi- FGURE. Grou ventricular function lots comaring intraoerative data in atients before and after oening the normal ericardium (oen circles) with data from the current study (closed circles). he bars give the standard deviation in the ordinate. At the oints of ordinate comarison (oen arrows), there were no significant differences in the grou abscissas (by unaired t test). ee text for discussion. 1 1 PWP - PP (mm Hg) Vol., No., May 1 1 RAP - PP (mm Hg)

14 Downloaded from htt://ahajournals.org by on October 1, 1 BOLWOOD na but no congestive heart failure, with chest radiograh cardiothoracic ratio of. ±. and left ventricular ejection fraction of. ±.1; in this study PP was measured with secially designed balloon catheters. Just before oening the ericardium, this intraoerative grou had an RAP of ± mm Hg, a PP of ± mm Hg, a PWP of ll ± mm Hg, a mean arterial ressure of ± 1 mm Hg, and a cardiac index of. +. liters/min/m. Although the data are not directly comarable because of anesthetic and vasodilator medications in the intraoerative grou and other factors, the significantly lower LVW in tamonade at the same PWP - PP as the intraoerative grou raises the question of decreased contractile function (the intraoerative and tamonade systemic vascular resistances were not significantly different). he difference in LVW was even more significant when the three tamonade atients with underlying cardiac disease were excluded (atient had unusually elevated LVW). However, contractile function is believed to be reserved or increased in cardiac tamonade, and radionuclide ejection fraction measurements suort this concet. One objection to the intraoerative data is that balloon catheters may overestimate constraint. However, recent validation arguments for balloon measurements are ersuasive. 1 A seculation is that the left ventricular volumes may have been smaller in the tamonade than intraoerative grou but with comarable transmural diastolic ressures due to a form of ventricular remodeling. nterestingly, however, both left and right ventricular function curves in the atients with tamonade seemed to merge with the oen-ericardium intraoerative data during ericardial drainage, suorting the analogy between ericardiocentesis and removal of normal constraint. Dr. Pravin M. hah rovided encouragement and critical review of this manuscrit. Dr. Y. C. Fung rovided helful discussion. Drs. Kenton W. Gregory, Peter Y. Lee, Bryce Morrice, Daniel E. Rieders and other cardiology trainees rovided assistance in the invasive rocedures. 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