Left Ventricular Diastolic Function in Hypertension: Relation to Left Ventricular Mass and Systolic Function

Transcription

1 15 JACC Vl. 3. N.6 June 1984: REPORTS ON HYPERTENSION Left Ventricular Diastlic Functin in Hypertensin: Relatin t Left Ventricular Mass and Systlic Functin FETNAT M. FOUAD, MD, FACC, J. MAREK SLOMINSKI, ROBERT C. TARAZI, MD, FACC Cleveland, Ohi Initial studies f diastlic cardiac functin in hypertensin demnstrated that slwing f the maximal rate f left ventricular filling ccurred befre alteratins in either ejectin fractin r cardiac utput. The present study was undertaken t determine: 1) the relatin between hypertensin, increased left ventricular mass and impaired left ventricular filling, and 2) the crrelatin between abnrmalities in left ventricular diastlic functin and its systlic perfrmance. Eleven nrmal subjects (Grup 1), 5 hypertensive patients withut evidence f left ventricular hypertrphy (Grup 2) and 18 hypertensive patients with increased left ventricular mass by echqcardigraphy (Grup 3) were studied by M-mde echcardigraphy, radinuclide (technetium-99m humanserum albumin)first pass technique and gated bld pl scintigraphy. Indexes f systlic functin (ejectin fractin, maximal rate f ejectin and percent left ventricular shrtening) were essentially similar in hypertensive and nrmtensive subjects. N crrelatin was fund between systlic bld pressure and left ventricular mass (r =.2, nt significant). Maximal rate f left ventricular filling (P dv/dt) and fast filling fractin decreased prgressively frm Grup 1 t Grup 3 (2.36 ±.4 [mean ± standard deviatin], 2.17 ±.3 and 1.97 ±.4 S-I, respectively, fr P dv/dt and 46 ± 7,48 ± 9 and 38 ± 11 %, respectively, fr fast filling fractin); the difference frm values in nrmal subjects reached statistical significance in hypertensive patients with left ventricular hypertrphy. Left ventricular maximal filling rate crrelated inversely with left ventricular mass and left ventricular end-systlic diameter (r = -.74), but psitively with left ventricular fractinal shrtening and ejectin fractin (r =.7). These results suggest that impairment f early left ventricular filling develps in relatin t left ventricular hypertrphy in hypertensin and that it can be detected even befre definite evidence f systlic cardiac impairment is present. Recent nninvasive techniques have allwed evaluatin f the diastlic functin f the heart in asymptmatic patients (1-3). A slw left ventricular filling rate was fund in crnary artery disease (1,3) and in hypertensin (2), befre alteratins in systlic functin. Inasmuch as a slw rate f left ventricular filling is related t left ventricular relaxatin, these initial investigatins culd help explain the ccurrence f islated left atrial abnrmality in hypertensin (4,5). Hwever, these early studies f left ventricular filling in hypertensin did nt reprt n the simultaneus structural changes in the left ventricle, particularly the presence r absence f left ventricular hypertrphy. The present study was undertaken t determine the relatin, if any, between the elevatin in arterial pressure with Frm the Research Divisin, Cleveland Clinic Fundatin, Cleveland, Ohi. This study was supprted in part frm a grant f the American Heart Assciatin, Nrtheast Ohi Affiliate, Cleveland, Ohi. Manuscript received Octber 17,1983; revised manuscript received December 19,1983, accepted December 21, Address fr reprints: Fetnat M. Fuad, MD, Research Divisin, The Cleveland Clinic Fundatin, 95 Euclid Avenue, Cleveland, Ohi by the American Cllege f Cardilgy and withut increase in left ventricular mass and the alteratin f left ventricular filling. In particular, it was imprtant t determine whether abnrmalities in diastlic functin f the heart were dependent n structural factrs, such as left ventricular hypertrphy, and whether there was any crrelatin between altered left ventricular filling and variatins in systlic functin. This invlved a cmbined apprach including study f cardiac functin by radinuclide techniques and determinatin f cardiac mass and left ventricular wall stress by echcardigraphy. Thus, bth the functinal and structural aspects f alteratins in left ventricular filling culd be examined nninvasively in patients with hypertensin. Study Grup Methds Thirty-fur cnsecutive subjects were studied: 11 nrmtensive vlunteers and 23 patients with untreated hypertensin wh did nt shw any histry r evidence f cr /84/$3.

2 JACC Vl. 3, N.6 June 1984: 15()()""6 FOUAO ET AL. 151 nary artery disease, diabetes mellitus, renal insufficiency r heart failure. Mre specifically, n patient had electrcardigraphic signs f prir mycardial infarctin r shwed abnrmality f wall mtin n radinuclide examinatin. In all but fur patients, renal functin was within nrmal fr the labratry; in these fur patients, serum creatine level varied between I.7 and 2. I mg/1 ml. The purpse f the study, the nninvasive nature f the tests and the minimal radiactivity expsure were explained in detail t all patients, and they gave free, infrmed cnsent t the study. The prtcl fr investigatin f cardiac perfrmance in hypertensin was apprved by the Institutinal Review Bard. The subjects were classified int three grups, accrding t bld pressure status and echcardigraphic data. Grup 1. This grup cmprised II nrmtensive subjects withut evidence f heart disease r left ventricular hypertrphy, There were six wmen and five men with a mean age f 37 years (range 21 t 62). Grup 2. This grup cmprised five patients with well dcumented established hypertensin and n clinical, electrcardigraphic r echcardigraphic evidence f left ventricular hypertrphy. There were three wmen and tw men with a mean age f 48 years (range 34 t 68). Grup 3. This grup cmprised 18 patients with established essential hypertensin, There were nine wmen and nine men with a mean age f 49 years (range 33 t 72), All patients in this grup had echcardigraphic evidence (Mmde) f left ventricular hypertrphy based n classic criteria (6). All were either untreated r discntinued medicatins fr at least 2 weeks befre the study. Six had cncentric left ventricular hypertrphy and 12 had asymmetric (islated) septal hypertrphy. Study Prtcl The prtcl cnsisted f tw sequential studies perfrmed n the same day r within a 24 hur interval. The first was the determinatin f cardiac utput, ejectin fractin and ther hemdynamic indexes by radinuclide technique. The secnd was M-mde echcardigraphy perfrmed with tw-dimensinal echcardigraphic mnitring fr calculatin f left ventricular mass, left ventricular stress and fractinal shrtening. Radinuclide hemdynamic study. All studies were perfrmed in the mrning after an vernight fast (except fr water). After 3 minutes f supine rest, plasma vlume was determined by 125-idine-Iabeled human serum albumin using 1 minutes f equilibratin, as previusly described in detail (7). Ttal bld vlume was derived frm plasma vlume and simultaneusly determined hematcrit (7). Hemdynamic studies were then perfrmed in duplicate using the radiistpe (technetium-99m human serum albumin) first pass technique. Details f the radiistpe technique and its validatin in ur labratry by cmparisn with the dye-dilutin and thermdilutin methds have been previusly described (8-1). Cuff arterial pressure was determined in the arm by auscultatin, the diastlic pressure was recrded as Krtkff phase V (II). Previus studies frm this center and thers (12,13) have shwn that auscultated systlic brachial pressure crrelated very clsely (r =.9, prbability [p] <,1 in ur experience) with directly btained intraventricular systlic pressure in patients withut artic stensis, Heart rate was btained frm cntinuus recrdings f a lead 11 electrcardigram, At least 1 t 12 bld pressure and heart rate recrdings were btained during the study; average values were used fr derivatin f hemdynamic indexes. Derived hemdynamic indexes were calculated by standardfrmulas; they included mean arterial pressure, cardiac index, strke index and ttal peripheral resistance (8,9), The measurement f pulmnary mean transit time allwed derivatin f cardipulmnary vlume (1). Left ventricular vlume curves and ejectin fractin were btained by imaging (gated bld pl technique) during the equilibrium phase after the first pass study, thus making use f the same circulating radiistpe. The left ventricular vlume curve was analyzed (PDP-15 system) t measure ejectin fractin and maximal rates f left ventricular ejectin (negative = N dv/dt) and left ventricular filling (psitive = P dv/dt) as described previusly in detail (2). In summary, left ventricular ejectin fractin was calculated by subtracting the left ventricular end-systlic cunts frm left ventricular end-diastlic cunts, and dividing the result by left ventricular end-diastlic cunts. Fr calculatin f the rates f ejectin and filling, Furier analysis was applied t fit curve t the data pints (16 in ur system) by the methd f least squares. The time derivative f the curve was cmputed by using the Furier transfrm technique as a glbal estimate f the tangent t the curve at each data pint. Because this curve represents the radiactivity cunts as a mathematical functin f time, the derivatives were expressed in cunts per secnd, The negative derivatives crrespnded t the decrease in cunts f ejectin phase and the psitive derivatives crrespnded t the increase in cunts f filling phase. In this analysis, we examined the largest negative and psitive derivatives, These derivatives were scaled by maximal abslute cunts equivalent t the end-diastlic cunts t cmpensate fr variatin in injected dse and efficiency f the acquisitin system. The units f these new variables were, therefre, expressed in units f fractinal change per secnd r hertz (Hz), These variables are prprtinal t the change in vlume/unit time and hence referred t as dv/ dt. The filling phase was further analyzed t measure the fractin f fast filling and the fractin f slw filling by a mdificatin f the index described by Redut et al. (3). Echcardigraphic techniques. The technique fr echcardigraphic recrdings and measurement f relevant indexes has als been previusly described (6). In all hy-

3 152 FOUAD ET AL. lacc Vl. 3. N.6 June 1984: pertensive patients, M-mde echcardigraphy was perfrmed while mnitring the ultrasnic beam directin by tw-dimensinal view n a TV screen using Tshiba apparatus (Tshiba mdel SSH-IOA) and a 2.4 MHz transducer. The examinatins were dne in a slightly tilted psitin t btain bth the septum and psterir wall in the same view at the tip f the mitral valve. Measurements f left ventricular diameters were made at end-diastle, marked by the beginning f the QRS cmplex, and at end-systle, as determined frm the shrtest left ventricular internal diameter. Measurements were btained frm an average f at least six cnsecutive cardiac cycles using a prgrammable calculatr (Numnics mdel 1239). The calculatin f left ventricular meridinal wall stress was based n principles derived by Grssman et al. (14) and verified by Wilsn et al. (13), using the echcardigraphic determinatin f left ventricular diameters and wall thickness and auscultating brachial systlic pressures. Peak systlic wall stress was calculated frm the systlic bld pressure, end-diastlic left ventricular diameter and crrespnding psterir wall thickness. End-systlic wall stress was calculated frm systlic bld pressure, endsystlic left ventricular diameter and crrespnding psterir wall thickness. Nrmal values in ur labratry averaged (mean ± standard deviatin) 6 ± 14 x 1 3 dynesl cm 2 per s fr end-systlic wall stress, and 169 ± 27 x 1 3 dynes/cm 2 per s fr peak systlic wall stress. The diagnsis f left ventricular hypertrphy frm M mde echcardigraphy was based principally n a left ventricular mass index f 95 g/m 2 r greater (>2 standard deviatins frm the nrmal mean in ur labratry) (6,15). The diagnsis was further substantiated by left ventricular psterir end-diastlic wall thickness r end-diastlic septal wall thickness, r bth, f 1.2 cm r greater. Analysis f data. The subdivisin f subjects int grups was used in the first analysis t examine the significance f differences between nrmtensive and hypertensive subjects and between patients with and withut left ventricular hypertrphy. Hwever, because patients with hypertensin frm a cntinuum in relatin t extent f cardiac invlvement, analyses were perfrmed t examine the crrelates f left ventricular filling rate in all patients as a grup. Calculatins f averages, paired and unpaired t tests and crrelatin cefficients were perfrmed by standard methds (16). Values reprted are means ± standard deviatin. Differences were cnsidered statistically significant when prbability (p) was less than.5. Data were analyzed with the help f PROPHET, a natinal cmputer service resurce supprted by the Natinal Institutes f Health. Results Hemdynamic Data (Table 1) Bth hypertensive grups had, by definitin, higher systlic and diastlic arterial pressure than the nrmal vlunteers, but there was n significant difference in pressure between the tw hypertensive grups. N significant difference was fund amng all grups in cardiac index, mean transit time r cardipulmnary vlume. The increase in arterial pressure in hypertensive subjects was therefre related t an increase in ttal peripheral resistance (3 flm2 in Grup I (nrmal subjects), 52 flm2 in Grup 2 (hypertensin withut left ventricular hypertrphy) and 49 flm2 in Grup 3 (hypertensin with left ventricular hypertrphy; p <.1, between Grup 1 and either Grup 2 r 3). Heart rate was higher in the hypertensive patients than in the nrmtensive vlunteers (Table 2). Strke index was significantly lwer in the hypertensive patients cmpared with nrmal subjects, as has been frequently nted previusly (17). Indexes f systlic functin (aside frm strke vlume) shwed n significant difference between nrmtensive and hypertensive grups. Thus, ejectin fractin, mean rate f left ventricular ejectin and left ventricular percent shrtening were essentially similar in hypertensive patients and nrmtensive subjects (Tables I and 2). The lwer strke index was therefre related either t the mre rapid heart rate r t the increased pressure in hypertensive patients rather than t mycardial dysfunctin (17). Left Ventricular Diastlic Functin Indexes f left ventricular filling rate. The mst marked difference between the nrmtensive and hypertensive patients was nted in the varius indexes f left ventricular filling (Table 2). Maximal rate f left ventricular filling (P dv/dt) decreased prgressively: values in the nrmtensive subjects (Grup I) were higher than in hypertensive patients withut left ventricular hypertrphy (Grup 2) (2.36 ±.37 versus 2.17 ±.27 Hz) and reached a minimum f 1.97 ±.44 Hz in Grup 3 patients (hypertensive patients with left ventricular hypertrphy). The reductin in P dv/dt frm nrmal reached statistical significance nly in Grup 3 (p <.5); hwever, patients in Grup 2 had values intermediate between thse f nrmal subjects and hypertensive patients with left ventricular hypertrphy, s that their grup average was nt significantly different frm that f the ther tw grups. Crrectin fr heart rate did nt alter these results. In fact, the reductin in dvidt in Grup 2 attained brderline statistical significance frm nrmal (Table 3). Fast filling fractin als prgressively declined frm Grup 1 t Grup 3. In cntrast, the slw filling fractin increased prgressively amng the three grups: II % in Grup I, 15% in Grup 2 and 21 % in Grup 3 (Table 2). Crrelates f altered left ventricular filling in hypertensive patients. A highly significant negative crrelatin was fund between P dvidt and end-systlic left ventricular wall stress (Fig. 1). This dependence f left ventricular filling n end-systlic wall stress was further studied in relatin t each f the values entering in the calculatin f

4 JACC Vl. 3, N.6 June 1984: 15-6 FOUAD ET AL. LEFT VENTRICULAR RELAXAnON IN HYPERTENSION 153 Table 1. Systemic Hemdynamics Grup SBP DBP CI SI TPR MTT CPV Grup I: 114 ± ± ± ± ± ± ± 129 (nrmal subjects; n = II) Grup 2: 174* ± 31 17* ± * ± * ± * ± 8 9.2* ± ± 264 (hypertensive subjects withut LVH; n = 5) Grup 3: 156* ± 25 13* ± * ± * ± * ± 1 8.5* ± ± 225 (hypertensive subjects with LVH; n = 18) *Prbability (p) <.1 versus nrmal subjects; differences between the tw hypertensive grups were nt significant. CI = cardiac index (liters/ min per m 1 ); CPV = cardipulmnary vlume (ml); DBP = diastlic bld pressure (mm Hg); LVH = left ventricular hypertrphy; MTT = pulmnary mean transit time (secnds); SBP = systlic bld pressure (mm Hg); SI = strke index (mllm 2 ); TPR = ttal peripheral resistance (U m 1 ). stress, namely systlic pressure, end-systlic vlume r left ventricular diameter and left ventricular wall thickness in end-systle. N crrelatin was fund between peak psitive dv/dt and systlic bld pressure (Fig. 2). End-systlic left ventricular diameter crrelated significantly with psitive dv/dt (r = -.74) (Fig. 3). We have chsen t base ur crrelatin n left ventricular diameter at end-systle diameter (LVESD) rather than left ventricular end-systlic vlume (ESV) because: I) it is this diameter that enters in the calculatin f left ventricular end-systlic wall stress, and 2) it is a directly determined value rather than a calculated number (ESV = [LVESDF). Hwever, the same crrelatin (r = -.71, P :s.1) was btained when left ventricular end-systlic vlume was used. Finally, left ventricular mass crrelated inversely with peak dv/dt (Fig. 4), meaning that the maximal rate f left ventricular filling was slwer when the left ventricular mass was higher; crrelatins with left ventricular wall thickness (r = -.39 at best when septal wall in end-diastle was used) did nt reach statistical significance. Similarly, n significant crrelatin was fund between peak psitive dv/dt and either diastlic bld pressure (r = -.21) r peak systlic stress (r = -.22). Relatin fdiastlic Filling t Systlic Perfrmance Left ventricular systlic perfrmance was evaluated frm tw indexes, the standard left ventricular fractinal shrtening (%Sh) and a mre recently intrduced index f "cntractility" end-systlic pressure/end-systlic vlume (ESP/ ESV). In this study we utilized the rati f systlic bld pressure t left ventricular end-systlic diameter t avid the inaccuracies assciated with calculatins f end-systlic vlume frm end-systlic diameter btained frm the shrt axis nly. We and thers (12,13) have previusly fund a significant crrelatin between brachial cuff systlic pressure and left ventricular systlic pressure. Bth indexes f systlic perfrmance crrelated significantly (p <. I), with the maximal rate f left ventricular filling: r =.7 fr the crrelatin between peak psitive Table 2. Cardiac Functin Indexes Ejectin Indexes LV Filling Indexes Grup EF N dv/dt FF SF P dv/dt HR Grup I: (nrmal subjects; 51 ± ± ± 7 II ± ±,37 59 ± 8 n = II) Grup 2: (hypertensive subjects 54 ± 1 2,68 ± ± 9 15 ± ± ± 8 withut LVH; n = 5) Grup 3: (hypertensive subjects 48 ± ±.42 38t ± II 21* ± 9 J.97t ±.44 68* ± 8 with LVH; n = 18) *p <.1, tp <.5 versus nrmal subjects; differences between the tw hypertensive grups were nt significant. EF = ejectin fractin (%); FF = fast filling fractin (%); HR = heart rate (beats/min); LV = left ventricular; LVH = left ventricular hypertrphy; N dv/dt and P dv/dt = maximal rate f left ventricular ejectin (negative) and maximal rate f left ventricular filling (psitive). respectively (Hz); SF = slw filling fractin (%).

5 154 FOUAO ET AL. LEFr VENTRICULAR RELAXATION IN HYPERTENSION JACC Vl. 3. N.6 June 1984:15-6 Table 3. Effect f Crrectin fr Heart Rate n Maximal Left Ventricular Diastlic Filling P dy/dt (Hz) Nnnalized Nrmalized fr fr RR Grup Uncrrected Heart Rate Interval Grup I: (nnnal subjects) 2.36 ± ± ±.41 Grup 2: (hypertensive subjects 2.17 ± ± ±.17 withut LVH) Grup 3: (hypertensive subjects 1.97 ± ± ±.45 with LYH) p Value 1 vs. 2 NS <.5.8 (NS) I vs. 3 <.5 <.1 <.1 2 vs. 3 NS NS NS LVH = left ventricular hypertrphy; NS = nt significant; P dy/dt = maximal left ventricular diastlic filling rate. dv/dt and fractinal shrtening f the left ventricle (Fig. 5), and r =.69 fr the crrelatin between peak psitive dv/dt and the left ventricular cntractility index (rati f systlic bld pressure t left ventricular systlic end diameter) (Fig. 6). Discussin The present study has cnfirmed in a larger number f patients the first reprts (2) f early impairment f left ventricular filling in hypertensin, an impairment ften fund befre any evidence f reduced cardiac utput r ejectin fractin. In additin, the cncmitant determinatin f ventricular vlume curves and f echcardigraphic left ven- Figure 1. Crrelatin between peak rate f left ventricular filling (PDVIDT) and left ventricular end-systlic stress (ESS) in patients with hypertensin. Clsed circles indicate 5 hypertensive patients withut evidence f left ventricular hypertrphy (Grup 2) and pen circles indicate 18 hypertensive patients with such evidence (Grup 3). p = prbability; r = crrelatin cefficient. tricular indexes has allwed an examinatin f the crrelates f that impairment. The reductin in peak rate f early left ventricular filling was related t left ventricular mass and left ventricular end-systlic diameter, nt t arterial pressure levels themselves. Althugh the degree f systlic perfrmance and the rate f early left ventricular filling crrelated significantly with each ther, ejectin fractin and left ventricular fractinal shrtening remained within nrmal limits in mst patients, whereas the rate f left ventricular filling was significantly reduced. Thus, we culd again determine that cardiac abnrmalities in patients with hypertensin had their first measurable expressin in abnrmalities f left ventricular filling rather than in systlic perfrmance. These findings further underline the early cardiac invlvement in hypertensin recently described in experimental mdels (18) and hypertensive adlescents (19). Figure 2. Lack f crrelatin in hypertensive patients between peak rate f left ventricular filling (PDV/DT) and systlic bld pressure (SBP). Symbls and abbreviatins as in Figure I. N J: ~ c... > c (l, L----' '_-'----'-_L----' '_-'---UJ r =-.6 p=.2 ESS (13 dynes/cm 2 ) N 2.2 J: ~ c > C Q SBP (mmhg) r= -.2 p=o.io

6 JACC Vl. 3, N, 6 June 1984:15-6 FOUAD ET AL 155 2, N 2.2 :I:, 1Il > 1.8 ~ t> ei f- 2..c.32 ll I.2 '---'----'-----'---'-----'_'---'------'-----'-...>.L-J r =-.74 p=o.ooi LV-ESD(cm) Figure 3. Inverse crrelatin fechcardigraphically determined left ventricular end-systlic diameter (LV-ESD) and peak rate f left ventricular filling (PDVIDT) determined by radinuclide technique in hypertensive patients. Symbls and abbreviatins as in Figure I, , =.7 p=.5 PDV/DT (Hz) Figure 5. Crrelatin between an index f left ventricular diastlic functin (PDVIDT) and an index f left ventricular systlic perfrmance (%Sh = left ventricular percent shrtening) in hypertensive patients. Symbls and abbreviatins as in Figure I. Functinal crrelates f left ventricular filling rate. The reductin in early left ventricular filling was crrelated significantly with left ventricular mass (Fig. 4) and t a lesser degree with left ventricular wall thickness. This implies that it was influenced nt nly by structural changes (wall thickness), but als by the functinal cnditin f the left ventricle. In that regard, the influence f left ventricular endsystlic diameter was fund t be significantly higher than that f systlic bld pressure levels. Hwever, the rle f systlic bld pressure might have been underrated by the fact that nly peak systlic pressure was recrded by auscultatin and nt left ventricular end-systlic pressure. Whatever the case, ur findings cnfirm the cnclusins f Brutsaert (2) regarding the imprtance f end-systlic events in determining the rate f left ventricular relaxatin in human beings. Figure 4. Inverse crrelatin between left ventricular mass (LVM) in g/m 2 and peak rate f left ventricular filling (PDVIDT) in hypertensive patients. Symbls and abbreviatins as in Figure I N 2.2 :I: f- 2, > 1.8 ll Relatin t systlic functin. The imprtance f diastlic relaxatin and filling t adequate systlic functin has nt always been sufficiently appreciated. Systlic perfrmance depends t a large degree n adequate filling, which is related t the rapidity, extent and hmgeneity f relaxatin during the preceding diastle. T these relatins, which may be cnsidered as "mechanical" r "pump priming" factrs, ne can add mre subtle influences fvarius factrs n mycardial cntractility (21). Althugh the impact f adrenergic factrs n ventricular cntractin is well knwn, their influence n ventricular relaxatin is less well recgnized. Snnenblick et al. (22) shwed the marked influence f sympathetic tne n relaxatin f papillary muscles. Fuad et al. (23) shwed the practical imprtance f these adre- Figure 6. Crrelatin between an index f left ventricular cntractility (systlic bld pressure/left ventricular end-systlic diameter [SBP/LVESD J) and peak rate f left ventricular filling (PDVIDT) Ul E t.l u 6 >'.Jf, 55 ll. E CIIE 5 Ul ,= -.56 p=.6 LVM (Qm/M 2 ),=,47 p.2 PDV/DT ( Hz)

7 156 FOUAD ET AL. JACC Vl. 3. NO.6 June 1984: 15-6 nergic effects during treatment f hypertensin by betaadrenergic blckade. In this study, the clse crrelatin fund between indexes f verall systlic functin r left ventricular cntractility (systlic bld pressure/end-systlic diameter) and left ventricular filling rate (Fig. 5 and 6) implies that left ventricular relaxatin and systle can be influenced by the same neurhumral factrs. Hence, an increased sympathetic tne that imprves left ventricular cntractin will als enhance relaxatin rate and filling. Clinically, the abnrmality assciated with hypertensin appears first in measures f early r maximal rate f left ventricular filling. Clearly, mre studies are needed t determine if measures designed t imprve left ventricular filling will als lead t better left ventricular perfrmance. In summary, slwing f maximal left ventricular filling rate was fund t be cmmn in hypertensive patients, even befre signs f decreased systlic perfrmance. The reductin in maximal filling rate was related t bth left ventricular structural changes assciated with hypertensin and t the alteratins in ventricular systlic perfrmance. In particular, the cnditins determining left ventricular end-systlic stress played a significant rle in determining the rate f early left ventricular filling. We are grateful t Brun Sufka and Steve Sverna fr their expert help in cmputer analysis f the ventricular vlume curves, and t Mary Kay DePaul, RN, Kathy Rjc, RN, Sue Vaughn, RN and Jay Clgy, BS, CNMT fr assistance in the hemdynamic and echcardigraphic studies. References 1. Quereshi S, Wagner HN, Aldersn PP. Evaluatin f left ventricular functin in nrmal persns and patients with heart disease. J Nucl Med 1978;19: Fuad FM, Tarazi RC, Gallagher JH, MacIntyre WJ, Ck SA. Abnrmal left ventricular relaxatin in hypertensive patients. Clin Sci 198;59:411s Redut LA, Wickenmeyer WJ, Yung JB. Left ventricular diastlic perfrmance at rest and during exercise in patients with crnary artery disease. Circulatin 1981;63: Sdi-Pallaris D, Calder RM. New Basis f Electrcardigraphy. St. Luis: CV Msby, 1958: Tarazi RC, Miller A, Frhlich ED, Dustan HP. Electrcardigraphic changes reflecting left atrial abnrmality in hypertensin. Circulatin 1966;34: Abi-Samra F, Fuad FM, Tarazi RC. Determinants f left ventricular hypertrphy and functin in hypertensive patients: an echcardigraphic study. Am J Med 1983;75: Tarazi RC, Ibrahim MM, Dustan HP, Ferrari CM. Cardiac factrs in hypertensin. Circ Res 1974;25,26 (suppll):i Fuad FM, Tarazi RC, MacIntyre WJ. Venus delay, a majr surce f errr in istpic cardiac utput determinatin. Am Heart J 1979;97: Fuad FM, Huser T, MacIntyre WJ. Autmated cmputer prgram fr radinuclide cardiac utput determinatin. J Nucl Med 1979;2: Fuad FM, MacIntyre WJ, Tarazi RC. Nn-invasive measurement f cardipulmnary bld vlume. Evaluatin f the centrid methd. J Nucl Med 1981 ;22: Kirkendall WM, Burtn AC, Epstein FH, Freis ED. Recmmendatins fr human bld pressure determinatin by sphygmmanmeters. Circulatin 1967;36: El-Tbgi S, Fuad FM, Kramer JR, Rincn G, Sheldn WC, Tarazi RC. Left ventricular functin in crnary artery disease. Evaluatin f E max and systlic PlV es rati. J Am Cli Cardil 1984:3: Wilsn JR, Reichek N, Hirshfeld J. Nn-invasive assessment f lad reductin in patients with asymptmatic artic regurgitatin. Am J Med 198;68: Grssman W, Jnes D, Mclaurin LP. Wall stress and patterns f hypertrphy in the human left ventricle. J Clin Invest 1975;56: Reichek N, Devereux RB. Left ventricular hypertrphy: relatinship f anatmic, echcardigraphic and electrcardigraphic findings. Circulatin 1981;63: Dixn WJ, Massey FJ Jr. Intrductin t Statistical Analysis. New Yrk: McGraw-Hili, 1969: Frhlich ED, Tarazi RC, Dustan HP. Re-examinatin f the hemdynamics f hypertensin. Am J Med Sci 1969;257: Sen S, Tarazi RC, Khairallah PA, Bumpus FM. Cardiac hypertrphy in spntaneusly hypertensive rats. Circ Res 1974;35: Culpepper WS, Sdt PC, Messerli FH, Ruschhaupt DG, Arcilla RH. Early cardiac invlvement in adlescents with hypertensin. Ann Intern Med 1983;98: Brutsaert DL, Husmans PR, Gethals MA. Dual cntrl f relaxatin. Its rle in the ventricular functin in the mammalian heart. Circ Res 198;47: Tarazi RC, Levy M. Cardiac respnses t increased afterlad. State f the art review. Hypertensin 1982;4(suppl 11): Snnenblick EH. Siegel JR, Sarnff SY. Ventricular distensibility and pressure-vlume curve during sympathetic stimulatin. Am J Physil 1963;24: Fuad FM, Slminski JM, Tarazi RC, Gallagher JH. Alteratins in left ventricular filling with beta-adrenergic blckade. Am J Cardil 1983;51:161-4.