Postgrad Med J: first published as 10.1136/pgmj.68.797.180 on 1 March 1992. Downloaded from Postgrad Med J (1992) 68, 180 - 185 i) The Fellowship of Postgraduate Medicine, 1992

Hypertension in aortic valve disease and its response to valve replacement Alexander Zezulkal, John Mackinnon2 and D.G. Beevers' 'University Department ofMedicine and 2Department ofCardiology, Dudley Road Hospital, Birmingham BT18 7QH, UK

Summary: We have investigated the prevalence ofhypertension and the response ofblood pressure to operation in 87 patients with lone aortic valve disease who underwent aortic valve replacement. In patients with aortic stenosis alone 26% were hypertensive pre-operatively (age and sex adjusted blood pressure > 160 systolic and or > 95 mmHg diastolic) and 24% were hypertensive post-operatively. In those with aortic regurgitation alone, hypertension was present in 65% before and 57% after valve replacement using the same criterion. For combined stenosis and regurgitation, the prevalence was 54% and 62%, respectively. The post-operative increase in systolic pressure in patients with aortic stenosis occurred mainly in those with a history of left ventricular failure. In those with aortic regurgitation or combined stenosis with regurgitation, diastolic pressure rose after valve replacement resulting in a prevalence of diastolic hypertension of 44% and 35%, respectively. Blood pressure changes were not predicted by the type of valve inserted nor its size. Our data show that despite severe symptomatic aortic valve disease, systolic hypertension was common

in aortic stenosis and diastolic hypertension was found in aortic regurgitation. This underlines the by copyright. importance of blood pressure monitoring in patients following aortic valve replacement.

Introduction All forms of aortic valve disease are known to be The association between hypertension and aortic associated with abnormalities of blood pressure. valve disease is not widely recognized. This prompt- Paul Wood's textbook describes the increased ed us to examine the prevalence of hypertension in pulse pressure with raised systolic and low diastolic patients who underwent cardiac catheterization for http://pmj.bmj.com/ pressures in patients with aortic regurgitation (AR) severe aortic stenosis and/or regurgitation and to and the reduced pulse pressure characteristic of investigate blood pressure changes resulting from aortic stenosis (AS).' Thus AS systolic hyperten- aortic valve replacement. sion might be expected to be uncommon and in AR a raised diastolic pressure should not be encount- ered. However, we have been misled by a patient Patients and methods with severe lone AS who had severe hypertension.2 Furthermore, the murmur ofaortic regurgitation is The records from the catheter laboratory of our on September 28, 2021 by guest. Protected found in a proportion of patients with diastolic district general hospital were examined retrospec- hypertension3 and although this regurgitation was tively for a 10 year period to identify all patients usually minor, progression necessitating aortic with lone aortic valve disease without involvement valve replacement (AVR) has been recorded.4 of other cardiac valves. The present analysis was Transient increases in blood pressure are well confined to those cases who subsequently under- documented immediately following cardiac sur- went AVR. Two patients who died within 6 months gery and in patients with AS raised blood pressure of operation and 5 who developed paraprosthetic has been reported in about 10% of cases in the aortic valve leaks were excluded from the study. immediate post-operative period.5 There are, how- Data on cardiac symptoms, physical signs and the ever, few long-term data on the effects of AVR.6'7 need for diuretic and/or antihypertensive drugs were recorded. For this analysis, only measure- ments of blood pressure obtained during the last outpatient clinic visit within the 6 months prior to Correspondence: D.G. Beevers, M.D., F.R.C.P. cardiac catheterization and at follow-up between Accepted: 9 October 1991 6-12 months after AVR were analysed as these are Postgrad Med J: first published as 10.1136/pgmj.68.797.180 on 1 March 1992. Downloaded from AORTIC VALVE DISEASE AND BLOOD PRESSURE 181 the blood pressure readings upon which clinical m2 (range 0.2-0.52) which confirmed severe steno- decisions are made. If more than one measurement sis. was made the average values were used for analysis. Pre-operatively antihypertensive drugs were Throughout, measurements of semi-recumbent used in one patient although 20 were receiving loop systolic and diastolic phase IV (muffling ofsounds), diuretics which may have reduced their blood blood pressures were recorded mainly by one pressure. After valve replacement, 3 patients were observer using standard mercury sphygmomano- given antihypertensive drugs of whom 2 had AR meters. and one had AS with AR. Nine patients continued Patients with heart failure continued to receive to take loop diuretics. their diuretic treatment as indicated and underwent Mean blood pressure levels before and after cardiac catheterization only when they were surgery are shown in Table II. These data show improved and stable. At left heart catheterization, that, pre-operatively, raised systolic blood pres- the peak systolic gradient across the aortic valve, sures were present in 3 cases (8%) with AS alone, the left ventricular end-diastolic pressure (LVEDP) the diastolic hypertension was seen in 9 cases and ascending aortic pressures were measured. (24%). In patients with AR alone, systolic hyper- Cardiac output (CO) was calculated by the direct tension was, as expected, common being seen in 15 Fick method and total peripheral resistance (TPR) patients (65%). However, diastolic hypertension derived from the CO and the mean intra-arterial was also seen in 2 cases (9%). In patients with blood pressure. combined AS and AR, systolic hypertension was Patients were classified as having AS alone, AR seen in 12 cases (46%) and diastolic hypertension alone or combined AS with AR. The degree of was present in 3 (11%). aortic regurgitation was quantified using a grading The WHO criteria for hypertension which are system based on left ventricular (LV) opacification based on systolic and/or diastolic blood pressures during aortography.8 The criteria for lone AS were were met by 10 (26%) patients with AS alone, 15 a peak systolic gradient of more than 30 mmHg (65%) with AR alone and 14 (54%) with combined across zero or one the aortic valve with grade aortic AS and AR. Of the cases with AS alone, 4 had by copyright. regurgitation. The severity ofAS was confirmed by intra-arterial systolic pressures of 160 mmHg or using Gorlin's formula for aortic valve orifice more, and one had a diastolic pressure of95 mmHg. area.9 Lone AR was defined as grade 2 to 4 aortic In patients with AR alone, intra-arterial systolic regurgitation with less than a 30 mmHg pressure pressures were 160 mmHg or more in 10 cases gradient across the aortic valve. Combined AS and although none had diastolic hypertension. In AR was defined as an aortic valve gradient of patients with combined AS and AR, intra-arterial greater than 30 mmHg and aortic regurgitation of systolic pressures were 160 mmHg or more in 3 grade two or more. cases but again none had diastolic hypertension. In view of the differences in age and sex of the After aortic valve replacement, there was no patients studied and the increase in age of up to 16 significant change in mean systolic or diastolic http://pmj.bmj.com/ months during follow-up, blood pressure readings blood pressures in patients with AS alone (Figure were adjusted for age and sex by the method of 1). Systolic hypertension was now found in 9 Pickering.'" This method was used because his data patients (24%) of whom 2 had had raised systolic were, as in the present study, obtained using phase pressures prior to surgery. In patients with AR IV diastolic pressures in an outpatient survey where alone, average systolic blood pressures were reduced men and women were examined separately. Actual significantly in response to surgery and as expected and adjusted readings the age are (to of 55 years) there was a highly significant rise in average diastolic on September 28, 2021 by guest. Protected presented. pressures (P < 0.001). Ten of these patients (43%) Statistical analysis was performed using Student's now exhibited diastolic hypertension. Patients with t-tests for paired data, Chi-squared with Yates' combined AS and AR showed a significant rise in correction for discontinuity to compare frequen- diastolic (P < 0.05) but not systolic blood pressure cies and Pearson's r for correlation coefficients. in response to AVR and 16 cases (62%) now had hypertension by WHO criteria. Amongst those meeting WHO criteria pre-oper- Results atively, 40% of AS patients remained hypertensive post-operatively compared to 54% of AR cases Of the 87 consecutive patients in the study, 38 had and 58% in the AS/AR group. In those without AS, 26 had AS/AR and 23 AR alone. The clinical pre-operative hypertension, 21% of AS patients features and investigative findings are shown in became hypertensive post-surgery compared to Table I. The cardiac catheter could not be passed 40% of AR cases and 14% in the AS/AR group. into the left ventricle in 2 patients with AS. The No differences in blood pressure, or change in mean aortic valve orifice area in the 28 patients blood pressure after AVR were found in patients with AS who had their CO calculated was 0.38 cm/ with and/or without angina or syncopal attacks. Postgrad Med J: first published as 10.1136/pgmj.68.797.180 on 1 March 1992. Downloaded from 182 A. ZEZULKA et al.

Table I Pre-operative clinical and investigation characteristics of patients with aortic stenosis, regurgitation or combined valve disease Aortic Aortic Stenosis and stenosis regurgitation regurgitation Number of patients 38 23 26 Male/female 22/16 18/5 21/5 Mean age (years) at operation 57 (9) 53 (11) 43 (10) Symptoms (%) Angina 63 39 58 Exertional dyspnoea 76 78 100 Syncope 11 4 12 Symptomless 5 9 0 Previous left ventricular 74 74 96 failure (%) Mean ECG size (mm) 48 (17) 55 (13) 54 (19) (SVY or2+RV5 or6) n = 36 n = 21 Average grade of aortic 0.3 3.8 2.9 regurgitation Mean aortic valve peak 100 (25) 6 (4) 67 (32) systolic gradient (mmHg) n = 36 Range 69-180 0-10 30-138 Mean left ventricular end 18 (8) 16 (6) 17 (7) diastolic pressure (mmHg) n = 36 Mean cardiac output 5 (1.6) 5 (1.6) 4.2 (1.3) (1/min) n = 28 n= 19 n = 21 Mean total peripheral 19 (5) 18 (7) 23 (8) resistance (mmHg/min/l) n = 28 n= 19 n = 21 by copyright. Figures in parentheses are standard deviations.

Aortic Aor;t.; CombinI stis The rise in corrected systolic pressure following steosis rgurpitation and r gon valve replacement in AS patients was confined to those with previous left ventricular failure (125 to

143 mmHg, P < 0.001; n = 28). In those without http://pmj.bmj.com/ failure systolic pressures were little changed (141 to .9.. 147 mmHg; n = 10). In AS patients with prior left heart failure, the diastolic pressures were non- 100 .2. significantly reduced following AVR (84 to 80 mmHg) and were unchanged in those without heart s.2. failure (90 mmHg). In patients with AR, systolic pressure dropped and diastolic rose in response to surgery in both those with and without left ventric- on September 28, 2021 by guest. Protected ular failure. Most cases with combined AS and AR

*0 had cardiac failure prior to surgery. ..Pos Minor grades of aortic regurgitation associated *; Pra. Post. Pro Post Pro Post with aortic stenosis did not influence systolic or diastolic pressure changes. Neither were they Figure 1 Individual systolic (0) and diastolic (0) different in those given Bjork-Shiley (n = 58) or age-corrected blood pressures measured in the outpatient Starr-Edwards prosthetic valves (n = 27) in any clinic before and at least 6 months after aortic valve disease category. The remaining 2 patients had replacement for aortic stenosis, aortic regurgitation and homograft valves. No correlation emerged between combined stenosis and regurgitation. Horizontal bars valve size and pre- or post-operative blood pres- represent the means. The fall in average systolic blood sure. As expected, those with AR required larger pressure following surgery in patients with aortic regur- valves. gitation was statistically significant (P < 0.05) as was the rise in diastolic blood pressure in cases with aortic In patients with aortic stenosis a positive correla- regurgitation alone (P < 0.01) and combined stenosis and tion was observed between the cardiac output and regurgitation (P < 0.05). the height of the diastolic pressure (r = 0.54, Postgrad Med J: first published as 10.1136/pgmj.68.797.180 on 1 March 1992. Downloaded from AORTIC VALVE DISEASE AND BLOOD PRESSURE 183

Table II Mean and (standard deviation) ofblood pressure (mmHg) before and after aortic valve replacement and the percentages for cases in excess of various levels of blood pressure Aortic Aortic Stenosis and stenosis regurgitation regurgitation Number of patients 38 23 26 Pre-operative blood pressure Systolic 128 (21) 168 (34) 150 (31) Diastolic 85 (12) 62 (19) 77 (16) Systolic A 130 (23) 177 (37) 162 (49) Diastolic A 85 (13) 63 (19) 77 (20) % systolic A> 160 mmHg 8 65 46 % diastolic A> 95 mmHg 24 9 11 % A> 160 and/or 95mmHg 26 65 54 Post-operative blood pressure Systolic 142 (24) 155 (26) 145 (26) Diastolic 82 (11) 89 (12) 84 (15) Systolic A 144 (25) 161 (24) 156 (34) Diastolic A 83 (12) 92 (13) 87 (16) % systolic A> 160 mmHg 24 44 54 % diastolic A > 95 mmHg 16 44 54 % A> 160 and/or 95 mmHg 24 57 62 Suffix A indicates pressures adjusted to age 55 years by the method of Pickering. A systolic blood pressure > 160 and/or a diastolic pressure of 95 mmHg or more is the WHO criterion for hypertension. by copyright.

P<0.01) but not the systolic blood pressure. The sure if the prevalence of hypertension was unduly systolic and diastolic pressures were not related to common or if the two diseases simply co-existed. the gradient across the aortic valve, valve orifice The true prevalence of hypertension might be area, LVEDP or TPR. higher since some patients pressures may have been In aortic regurgitation, diastolic pressures were lowered by depressed left ventricular function or positively correlated with LVEDP (r = 0.45, P < diuretic therapy. However, the aetiology of aortic

0.05) and the LVEDP correlated with the cardiac valve stenosis could be the key to a genuine http://pmj.bmj.com/ output (r = 0.54, P <0.05). In patients with com- association. The underlying pathology of AS in bined AS and AR, systolic pressure was negatively middle age is most commonly congenital bicuspid related to aortic valve gradient (r = - 0.57, P < valves whilst senile degenerative calcification of 0.01) but unrelated to TPR, CO or LVEDP. tricuspid aortic valves predominates in the elder- The aetiology of aortic valve disease in relation ly.'2"3 Both valvular and vascular degeneration, to the type of lesion was as follows; those classified with decreased large artery compliance and in- as ofdegenerative aetiology all had tricuspid aortic creasing systolic blood pressure, might therefore valves with variable leaflet thickening, distortion, co-exist and accelerate the degeneration in both on September 28, 2021 by guest. Protected degeneration and calcification. The other rarer sclerotic tricuspid and congenitally bicuspid aortic causes of AR included Reiter's disease (1), Mar- valves. In addition, the increased peripheral arte- fan's syndrome (1), syphilis (1), chronic aortic riolar resistance which occurs in hypertension dissection (1) and subacute bacterial endocarditis could lead to dilatation of the aortic root and in previously normal valves (4). produce regurgitant flow which might then acce- lerate aortic valve degeneration. Aortic root dilata- tion has been associated with myxoid degeneration Discussion ofthe aortic cusps. 4 However, the similar aetiology of the valve disease but different blood pressures These data show that even in the presence of severe seen here in those with AS and AS with AR symptomatic aortic valve disease, both systolic and suggests that the haemodynamic disturbances diastolic hypertension are common. Others have caused by the valve disease itself may be responsi- reported that 10% of their patients requiring AVR ble for the blood pressure changes seen after AVR. for calcific AS were receiving treatment for hyper- In AS, patients with prior heart failure showed tension." Due to limited numbers it is difficult to be significant increases in systolic and reductions in 184 A. ZEZULKA et al. Postgrad Med J: first published as 10.1136/pgmj.68.797.180 on 1 March 1992. Downloaded from diastolic pressure. Left ventricular contractility is patients with combined AS and AR than in those impaired in aortic valve disease with heart failure with AR alone and this may offset the effects of and following AVR this often returns to normal so cyclic stress. The high velocity blood jet creates a that subsequent improved ventricular ejection 'Venturi' effect which reduces the aortic wall lateral could then explain rises in systolic pressure."5-17 pressure as the pulse wave develops. Whilst a Hypertension immediately following cardiac similar effect is seen in AS, the ejected systolic surgery appears to be mediated via cardiac reflexes volume is smaller and aortic pressure rises more and sympathetic nervous system, although the slowly. This may explain the differences in post- renin-angiotensin system and circulating vaso- operative blood pressure in patients with AS pressin levels have been implicated.'820 Hyperten- compared with AR and AS with AR. sion following repair of aortic coarctation is Elevation of blood pressure in patients with associated with reduced arterial compliance, aortic valve disease is common, and may remain abnormalities of baroreceptor function and abnor- after AVR. Hypertension has its own associated mal vascular reactivity consistent with a myogenic morbidity and mortality and may also accelerate abnormality.2-23 It is not known if these mechan- deterioration of homograft valves although it is isms are responsible for the long-term elevations in unlikely to affect mechanical valves. These data blood pressure seen in AVD. emphasize the value of routine blood pressure The highest age-adjusted blood pressures follow- monitoring at follow-up in patients undergoing ing AVR were seen in patients with either AR or AS aortic valve replacement. Our data suggest that with AR. Although the aetiology ofthese two types ejection systolic murmurs in hypertensive patients of valve malfunction was different, widened pre- may occasionally be associated with significant operative pulse pressure is a common factor. An in aortic stenosis and aortic regurgitation may be seen vitro arterial wall model suggests that elastic and in patients with raised diastolic blood pressures. collagen fibres are damaged more rapidly by pulsa- tile than continuous stress.24 In AR, high peak wall stress and maximal rate of change of the large Acknowledgements arteries would produce increased cyclic stress over by copyright. a long period which could result in arterial hyper- We wish to thank Ms Fay Cox for secretarial assistance tension. Peak aortic flow velocity is higher in and Mrs Dilys Thomas for preparing the illustration.

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