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Influence of valvular insufficiency and recurrent airway obstruction on haemodynamics and therapy in warmblood horses with atrial fibrillation
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Research in Veterinary Science 85 (2008) 333–339 www.elsevier.com/locate/rvsc
Influence of valvular insufficiency and recurrent airway obstruction on haemodynamics and therapy in warmblood horses with atrial fibrillation Heidrun Gehlen a,*, Kirstin Bubeck a, Karl Rohn b, Peter Stadler a b
a Equine Clinic, University of Veterinary Medicine Hanover, Foundation, D-30173 Hanover, Germany Department of Biometry, Epidemiology and Information Processing, University of Veterinary Medicine Hanover, Foundation, D-30173 Hanover, Germany
Accepted 3 November 2007
Abstract The aim of this study was to investigate the potential haemodynamic effects of valvular insufficiency and recurrent airway obstruction (RAO) in horses with atrial fibrillation (AF). Therefore in ten healthy horses (group 1) and 40 horses with AF a clinical examination, a lung examination, echocardiography and right heart catheterization for measurement of intracardic and pulmonary pressures were performed. According to the clinical findings the horses with AF were subdivided into 4 groups (group 2: AF; group 3: AF/valvular insufficiency; group 4: AF/RAO; group 5: AF/valvular insufficiency/RAO). Most of the horses of group 3 and 5 suffered from two valvular insufficiencies (mitral and tricuspid valve insufficiency: n = 11, mitral and aortic valve insufficiency: n = 2). The remaining horses showed a single mitral (n = 6), tricuspid (n = 2) or aortic valve insufficiency (n = 1) or more than two valvular insufficiencies (n = 4). In group 2 right ventricular mean pressure (RVPm) was higher than in group 1 and 4 (P < 0.025); diastolic right ventricular pressure was higher than in group 1; PWP was higher than in group 1 and group 4; PDP was lower compared to group1. Compared to group1 in group 3 left atrial diameter (LA) was greater; the PAPs was higher and the PDP lower (P < 0.05). In group 4 RVPm and PWP was lower compared to group 2. In group 5 LA, fractional shortening and diastolic left ventricular diameter were greater, PWP and PAPs were higher and PDP lower compared to group1. Twenty six of the 40 horses with AF (65%) were treated. Successful cardioversion to sinus rhythm occurred in 15 horses (58%). Therapy was successful in 50% of the treated horses of group 2 and 3, in 67% of the treated horses of group 4 and in 63% of the treated horses in group 5. In conclusion the presence of valvular insufficiency or RAO influences the haemodynamics of horses with AF. Ó 2007 Published by Elsevier Ltd. Keywords: Atrial fibrillation; Warmblood horse; Right heart catheterization; Pulmonary artery wedge pressure; Echocardiography; Heart valve insufficiency; RAO; Equine
1. Introduction Horses with AF alone, which is also known as idiopathic AF, mostly show neither any clinical symptoms of cardiac disease, except the presence of the arrhythmia on auscultation, nor any echocardiographic or hemodynamic
*
Corresponding author. Tel.: +49 511 856 8185; fax: +49 511 856 7671. E-mail address: [email protected] (H. Gehlen).
0034-5288/$ - see front matter Ó 2007 Published by Elsevier Ltd. doi:10.1016/j.rvsc.2007.11.001
anomalies (Deem and Fregin, 1982; Reef et al., 1988). Until now there has been no consensus about the effects of AF on cardiac haemodynamics, especially at rest (Bertone and Wingfield, 1987; Reef et al., 1995). It has been reported that there is not necessarily deterioration of haemodynamics in these horses at rest, as atrial contraction has only little influence on ventricular filling at rest, and that there is a good chance for successful therapy in these horses (Reef et al., 1988, 1995; Muir and Mc Guirk, 1984). On the other hand, several studies on horses have reported changes in
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cardiac haemodynamics at rest before and after successful treatment of AF, so that AF alone seems in some cases to influence haemodynamics at rest (Muir and Mc Guirk, 1984; Killip and Boer, 1964). It seems to be obvious that the extent of hemodynamic changes in horses with AF depends on several accompanying factors, particularly on additional cardiac and/or respiratory diseases. Right heart cardiac pressure measurements provide information on cardiac and pulmonary haemodynamics for the diagnosis and differentiation between valvular insufficiency and RAO in the horse (Muylle et al., 1986). Precapillary hypertension may be caused by interstitial or obstructive pulmonary diseases, thrombemboli, alveolar hypoxia, or left sided heart disease (Nuytten et al., 1988; Nyman et al., 1991). In these cases one could find an increased pulmonary artery pressure (PAP) combined with a normal pulmonary artery wedge pressure (PWP, Buchwalsky, 1994). Postcapillary hypertension may be a result of acute or chronic mitral (MVI) and/or aortic valve insufficiency (AVI) with a progressive pressure increase from the left side of the heart to the pulmonary veins, the lung capillaries, and the lung arterioles and arteries. In these cases there is an increase in both PAP and PWP (Muylle et al., 1986). Pulmonary driving pressure (PDP) is the difference between the mean PAP and PWP. PDP is also used to differentiate between pulmonary hypertension induced primary by valvular insufficiency or RAO, as PDP is increased in the latter (Muylle et al., 1986). As there are no published data about the hemodynamic influences of additional valvular insufficiency and/or RAO on AF and on successful therapy in Warmblood horses, we investigated echocardiographic and cardiac pressure parameters in horses with AF. 2. Materials and methods This study included 10 healthy Warmblood horses (group 1) with neither cardiovascular nor respiratory disease and 40 Warmblood horses with AF (group 2; Table 1). Although the exact duration of AF was unknown, AF had been detected by the referring veterinarian in all cases at least five to six months prior to presentation.(date of the last clinical examination). The animals were subjected to a general physical examination, electrocardiography, echocardiography, and a detailed examination of the respiratory tract.
Table 1 Basic data of the horses Group
Age (yr)
Weight (kg)
Height (cm)
HR (bpm)
1 2 3 4 5
4±1 9±5 8±4 10 ± 5 10 ± 4
554 ± 40 557 ± 48 584 ± 51 560 ± 52 582 ± 51
167 ± 5 172 ± 3 171 ± 5 168 ± 3 170 ± 4
38 ± 5 38 ± 7 38 ± 10 36 ± 4 41 ± 8
(n = 10) (n = 7) (n = 13) (n = 7) (n = 13)
Mean age, weight, height and heart rate at rest.
In addition radiography of the thorax and right heart catheterization were performed in all horses at rest consisting of measurement of intracardiac pressure, pulmonary artery pressure (PAP), and pulmonary artery wedge pressure (PWP). Pulmonary driving pressure (PDP) was then calculated using the following formula: PDP (mmHg) = mean PAP (mmHg) PWP (mmHg). 2.1. Examination of the lungs The diagnosis of RAO was based on clinical signs during auscultation and thoracic percussion, arterial blood gas analysis (ABG), endoscopic examination, cytological evaluation of respiratory tract secretions (TBS) and characteristic radiographic findings. 2.2. Echocardiographic examination Standard long and short axis two-dimensional real-time echocardiograms were performed in all horses. B-mode was used to measure the left atrial diameter (LA) using the left parasternal long axis view and the aortic (AO) and pulmonary diameters (PA). M-mode was used for the echocardiographic measurement of the left ventricular internal diameter during systole (LVDs) and diastole (LVDd), fractional shortening (FS%), interventricular septum during systole (IVSs) and diastole (IVSd), and the left ventricular free wall during systole (LVWs) and diastole (LVWd) using the right parasternal long axis view. Continuous wave and color-flow doppler echocardiography were used for detecting valvular insufficiencies.1 Differentiation between pathological valvular insufficiency and physiological valvular back flows were made by flow velocity and flow duration (Patteson, 1996). 2.3. Right heart catheterization After echocardiography, right atrial mean pressure (RAPm), right ventricular mean pressure (RVPm), right ventricular systolic (RVPs) and diastolic (RVPd) pressure, pulmonary arterial mean (PAPm), systolic (PAPs) and diastolic (PAPd) pressure, pulmonary arterial wedge pressure (PWP) and pulmonary driving pressure (PDP) were measured with a flow-directed balloon catheter (Swan– Ganz catheter2, 7 French, 160 cm length). The catheter was inserted into the right jugular vein through an introducer system.3 The level of the shoulder joint was used as a reference marker for all pressure measurements. The animals were continuously monitored during echocardiography and heart catheterization, with a base-apex lead ECG.4 1 2 3 4
Vingmed 750, Vingmed CFM 800. Arrow, Erding GmbH, Germany. Cook, Peel awayÒ, Brisbane, QLD, Australia. Hellige, Servomed, (SMR 211 and SMK 231, Vicom-sn) Germany.
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2.4. Therapy Twenty eight horses with AF were treated with an intravenous infusion of quinidine sulphate solution (1%) using a mean dosage of 40 mg/kg quinidine sulphate5 (range from 35 to 45 mg/kg) and an infusion rate of 5 ml/min. A maximum amount of 2 L solution was not exceeded. The infusion was stopped if cardioversion was observed. All horses were monitored continuously with an ECG during the entire infusion. The intravenous infusion of quinidine sulphate solution was used instead of oral application because negative side effects (i.e. colic, sweating, tachycardia) could be avoided. The infusion rate was decreased immediately if tachycardia or additional arrhythmias occurred. 2.5. Statistical analysis All data were included in a descriptive analysis. Normal distribution of the echocardiographic variables was confirmed by visual assessment of normal probability plots and by the Shapiro–Wilk Test. The arithmetic means ðxÞ and standard deviations (s) were calculated for all variables. T-test was performed for comparing the means of the cardiac parameters between horses with and without successful therapy. Differences in the means of the four subgroups of horses with AF and the group of healthy horses were compared using one-way analysis of variance with subsequent Ryan–Einot–Gabriel–Welsch Multiple Range Test for multiple pairwise comparisons of means between two disease levels. Correlation analysis was performed by calculating the Pearson correlation coefficient rho. Analysis was carried out with SAS statistical software, version 9.1. The GLM (General linear models) procedures were used for analysis of the linear models. A P-value of 0.05 was considered statistically significant. 3. Results The control group (group 1) showed no clinical signs of cardiac or pulmonary disease, normal ABG, no mucus accumulation in the lower airways and normal thoracic radiographs. The horses with AF (n = 40) had a characteristic arrhythmia with irregular intervals of the QRS-T complexes and without p-waves. A total of 20 of the 40 horses with AF (50%) were found to be affected with a concurrent RAO. Thirteen of these horses showed recurrent airway obstruction (RAO) and seven horses had RAO combined with pulmonary haemorrhage (PH). The diagnosis of RAO was based on typical clinical signs (tachypnoea, chronic cough, prolonged inand/or expiration), peribronchial infiltrations visible on radiographs, decreased arterial PaO2 in ABG and neutrophilic inflammation and/or Curshmann’s spirals in TBS.
5
Fagron GmbH & Co. Barsbu¨ttel, Germany.
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The diagnosis of PH was based on radiographic alveolar or mixed alveolar-interstitial opacities in the caudodorsal lung field and identification of red blood cells and/or macrophages containing haemosiderin in TBS. Twenty six out of 40 horses with AF showed additional heart murmurs during auscultation and valvular insufficiency in echocardiography (Table 2). The mean echocardiographic parameters of the healthy horses (group 1) were within normal limits (Table 3). Right heart catheterization was tolerated well by all horses. No adverse effects or complications were observed. The pressure values of the healthy horses (group 1) were within the reference range (Table 4). 3.1. Subdivision of the horses with AF For further analysis the 40 horses with AF (n = 40) were divided into four subgroups according to their additional pathological findings (Table 1, 2): Group 2 (n = 7): Group 3 (n = 13): group 4 (n = 7): Group 5 (n = 13):
horses with lone AF horses with AF and concurrent valvular insufficiency horses with AF and RAO horses with AF, concurrent valvular insufficiency, and RAO.
3.1.1. Results in horses with lone AF (group 2) The horses in group 2 showed no clinical signs of pulmonary disease, normal ABG, no mucus accumulation in the lower airways and normal thoracic radiographs. The mean PaO2 in this group was 102 mmHg, the mean PaCO2 was 44 mmHg. The mean echocardiographic parameters of the horses from group 2 were within normal limits (Table 3). Horses from group 2 showed a significantly higher (P < 0.05) RVPd, RVPm and PWP than the control group (group 1). The PDP was significantly lower (P < 0.05) than in the control group (Table 4). Also the RVPm in group 2 was significantly higher (p < 0.05) than in group 4 (horses with AF and RAO). 3.1.2. Results in horses with AF and concurrent valvular insufficiency (group 3) In group 3, eleven horses had a holosystolic heart murmur between grade 2 and 5 out of 6 with the point of maximum intensity on the left thoracic side. Clinical lung examination revealed no pathological findings in this group. Endoscopy revealed no mucus accumulation in the lower airways and the horses had normal thoracic radiographs. The mean PaO2 in this group was 102 mmHg and the mean PaCO2 was 44 mmHg.
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Table 2 Valvular insufficiency of groups 3 and 5 Group
MVI
TVI
AVI
MVI + TVI
MVI + AVI
MVI + TVI + AVI
MVI + PVI + AVI
MVI + TVI + AVI + PVI
3 5
1 5
1 1
– 1
9 2
2 –
– 2
– 1
– 1
MVI = mitral valve insufficiency, TVI = tricuspid valve insufficiency, AVI = aortic valve insufficiency, PVI = pulmonic valve insufficiency.
Table 3 Results of the echocardiographic examination Group 1
Group 2
Group 3
Group 4
Group 5
P < 0.05
LVDd (mm)
109 ± 2
116 ± 13
135 ± 23
124 ± 11
141 ± 17
LVDs (mm) FS (%) IVSd (mm) IVSs (mm) LVWd (mm) LVWs (mm) PA (mm) AO (mm) LA (mm)
69 ± 4 26 ± 4 30 ± 2 43 ± 2 24 ± 3 30 ± 2 57 ± 4 80 ± 3 121 ± 5
68 ± 15 42 ± 9 26 ± 4 39 ± 3 23 ± 4 31 ± 3.6 59 ± 7 80 ± 6 125 ± 6
88 ± 32 34 ± 12 29 ± 5 40 ± 7 22 ± 6 33 ± 6 60 ± 9 81 ± 10 141 ± 14
83 ± 23 34 ± 12 31 ± 7 41 ± 4 22 ± 4 34 ± 7 58 ± 7 73 ± 10 128 ± 6
90 ± 23 36 ± 13 30 ± 5 39 ± 5 23 ± 6 34 ± 7 60 ± 6 80 ± 6 145 ± 18
1?5 1?3 2?5 n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. 1?3 1?5
LVD = left ventricular diameter, FS = fractional shortening, IVS = interventricular septal wall, LVW = left ventricular free wall, 5 = B-mode, PA = pulmonic artery, AO = aortic root, LA = left atrium, d = end diastolic measurement, s = end systolic measurement, MVI = mitral valve insufficiency, TVI = tricuspid valve insufficiency, AVI = aortic valve insufficiency, PVI = pulmonic valve insufficiency, s = systolic, d = diastolic.
Table 4 Results of the right heart catheterization Group 1
Group 2
Group 3
Group 4
Group 5
RAPm (mmHg) RVPs (mmHg) RVPd (mmHg) RVPm (mmHg)
6±2 41 ± 7 2±2 17 ± 2
8±4 48 ± 10 8 ± 10 25 ± 9
6±3 45 ± 8 5±4 19 ± 7
7±2 42 ± 18 3±2 15 ± 6
6±3 42 ± 6 3±3 20 ± 4
PAPs (mmHg)
39 ± 2
48 ± 10
52 ± 7
44 ± 12
51 ± 10
PAPd (mmHg) PAPm (mmHg) PWP (mmHg)
15 ± 2 28 ± 2 15 ± 2
18 ± 7 30 ± 5 23 ± 4
14 ± 6 28 ± 5 20 ± 5
15 ± 4 26 ± 4 17 ± 4
18 ± 7 31 ± 6 23 ± 6
PDP (mmHg)
13 ± 2
8±3
8±4
10 ± 2
8±4
P < 0.05
1?2 1?2 2?4 1?3 1?5
1?2 1?5 2?4 1?2 1?3 1?5
RAP = right atrial pressure, RVP = right ventricular pressure, PAP = pulmonary artery pressure, PWP = pulmonary artery wedge pressure, PDP = pulmonary driving pressure, s = systolic, d = diastolic, m = mean, Norm. = normal value.
Horses with AF and concurrent valvular insufficiency (group 3 and 5) had a significantly larger LA than the control group (P < 0.0001; Table 3). Horses with AF and concurrent valvular insufficiency (group 3 and 5) showed significantly higher PAPs and lower PDP than those from the control group (P < 0.05, Table 4). 3.1.3. Results in horses with AF and RAO (group 4) The mean PaO2 in this group was 89 mmHg, the mean PaCO2 was 43 mmHg. The TBS of the horses revealed an
increase of neutrophils and visible Churschman spirals in all horses as well as red blood cells and hemosiderin-laden macrophages in four horses. The thoracic radiographs of these horses showed peribronchial infiltrations in all horses and additional mixed alveolar-interstitial opacity in the caudodorsal lung field in four horses. Three of the seven horses in group 4 were diagnosed with a recurrent airway obstruction (RAO); and four suffered from both RAO and pulmonary haemorrhage (PH). There were no exact informations about the duration of the RAOs.
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The mean echocardiographic parameters of the horses of group 4 were within normal ranges (Table 3). There were differences between horses with AF and concurrent RAOs (group 4) and between horses with lone AF (group 2) in RVPm and PWP which were both significantly higher in horses with lone AF (group 2; RVPm: P < 0.025, PWP: P < 0.002; Table 4). 3.1.4. Results in horses with AF, concurrent valvular insufficiency and RAO (group 5) In group 5, eleven horses had holosystolic heart murmur between grade 1 and 4 out of 6 with the point of maximum intensity on the left thoracic side. Ten of the thirteen horses in group 5 had RAO; and three suffered from both RAO and PH. The duration of the RAO was not known. The mean PaO2 in this group was 92 mmHg, the mean PaCO2 was 43 mmHg. The TBS of the horses showed an increase in neutrophils and Curschman’s spirals in the horses with RAO and additionally red blood cells and haemosiderin-laden macrophages in horses with RAO and PH. The thoracic radiographs of the horses with RAO showed peribronchial infiltrations and additionally mixed alveolarinterstitial opacity in the caudodorsal lung field in the horses with RAO and PH. In this group there were also no exact informations about the duration of the RAOs. Seven horses of group 5 had a single valvular lesion and six horses had multiple valvular lesions. The most frequent heart valve insufficiency was the mitral valve insufficiency (n = 11, Table 2, 2). The LA was significantly (P < 0.05) larger in group 5 compared to the control group (P < 0.0001). The horses of group 5 had also a significantly (P < 0.05) higher FS (P < 0.001) and LVDd (P < 0.0008) than the control group (Table 3). Additionally the LVDd was also significantly higher (P < 0.05) than in the horses with lone AF (group 2, Table 3). There were differences between horses with AF, concurrent valvular insufficiency and RAO (group 5) and between the control group (group 1) in PAPs and PWP which were both significantly higher (P < 0.05) in group 5 and in PDP which was significantly lower (P < 0.05) in group 5 (Table 4). 3.2. Influence of concurrent PH on cardiac parameters Horses with a combination of AF, RAO and PH showed significantly lower LA and PWP values (P < 0.05) compared to horses with AF and lone RAO (Table 5). In group 4 there was a significant positive correlation between PWP and LVDd (P = 0.01). 3.3. Results of therapy In all, 26 of the 40 horses with AF (65%) were treated. Successful cardioversion to sinus rhythm occurred in 15
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horses (58%). In five cases the owners did not consent to any therapy. The left atrial diameter was greater than 14.5 cm in nine horses, which were not treated due to the poor prognosis. Treatment was considered successful if conversion to sinus rhythm took place. Therapy was successful in only 50% of the treated horses of group 2 and 3. However this was the case in 67% of the treated horses of group 4 and in 63% of the treated horses in group 5. 3.3.1. Differences in the cardiac parameters between the horses with and without successful therapy In group 2 the dimension of the IVSs was smaller (P = 0.043) in the horses with successful therapy (36.3 ± 1.5 mm) than in the group of horses without successful therapy (41.3 ± 2.5 mm). In group 3 the PAPd was lower (P = 0.05) in the horses with successful therapy (3 ± 4.2 Hg) than in the group of horses without successful therapy (15 ± 4.2 Hg). In group 5 there were differences in HR (P = 0.035), AO (P = 0.05) and LA (P = 0.003) between the horses with successful therapy (AO = 78.7 ± 3.4 mm; LA = 131 ± 2.6 mm) and the group of horses without successful therapy in which all three parameters were significantly higher (P < 0.05, AO = 84.3 ± 0.6 mm; LA = 142 ± 3.4 mm). 4. Discussion It is clear from the present study that the hemodynamic state of AF is influenced by the concurrent presence of valvular insufficiency and/or RAO. Lone AF is reported in humans and horses, in the absence of structural heart disease. Although in the present study the echocardiographic examination revealed no differences between healthy horses and horses with lone AF, there were differences between the two groups in various pressure values. The present study confirmed that PWP, RVPd and RVPm of horses with lone AF were higher than those of the healthy horses. These increased pressures were not correlated with clinical and/or echocardiographical signs of cardiac disease except of the AF itself. If AF is accompanied by valvular insufficiencies, there has to be an influence on haemodynamics, as valvular insufficiency alone has been shown to cause hemodynamic changes (Patteson, 1996; Reef, 1995). If AF and valvular insufficiencies occur together, the question always arises as to whether the valvular insufficiency is the cause or the result of AF. Our study could not answer this question. But both scenarios are possible and should be taken into consideration, although the conventional view is that valvular insufficiency and left atrial enlargement pre-dates the onset of AF (Patteson, 1996). Significantly increased PWP values, as observed in our study, could be due to either regurgitant volume or AF and following atrial remodelling. In humans with valvular insufficiency an increased PWP is judged a sign of incipient contractility
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Table 5 Differences in echocardiographic and pressure values between horses with AF and RAO and horses with RAO and PH Group
RAO
RAO + PH
P-value RAO ? RAO + PH
4 + 5 (n = 13)
4 (n = 3)
5 (n = 10)
4 + 5 (n = 7)
4 (n = 4)
5 (n = 3)
IVSs LA PWP
37.8 ± 4 144.6 ± 18 23.3 ± 6
38 ± 3 132 ± 7 17 ± 4
38 ± 4 148.4 ± 19 25.2 ± 5
43.1 ± 3 129 ± 7 16 ± 3
43 ± 4 126 ± 5 16 ± 4
43 ± 4 133.7 ± 8 16 ± 1
RVPs
41.4 ± 5
45 ± 7
40.4 ± 4
44.1 ± 19
40 ± 24
49.3 ± 6
4 + 5 ? 4 + 5: 0.007 4 + 5 ? 4 + 5: 0.01 4 + 5 ? 4 + 5: 0.008 5 ? 5: 0.01 5 ? 5: 0.01
RVPs = systolic right ventricular pressure, PWP = pulmonary artery wedge pressure, LA = left atrium, IVSs = systolic interventricular septal wall.
insufficiency due to myocardial remodelling (Davy et al., 2000). Our findings of a correlation between MVI and the LAdiameter confirm those of other studies (Patteson, 1996). Interestingly in our study, PWP was significantly higher in the horses with MVI and a normal left atrium than in those with MVI and an enlarged left atrium. This may support the hypothesis that on the one hand dilatation would tend to allow intracardiac pressure to remain within normal limits for longer and on the other hand that elevated PWP and left atrial pressure may be due not only to the insufficiency of the blood volume, but also to other, additional factors like atrial myocardial remodelling (Davy et al., 2000). The compliance of the left atrium and its influence by cardiac remodelling seems to be an important factor in the pathomechanism of AF in humans (Davy et al., 2000). In horses with AF and MVI, increased PWP could be a sign of incipient cardiac decompensation and/or myocardial fibrosis of the left atrium; this has been described for horses with MVI alone during exercise (Reef, 1995). In contrast to our findings, one would expect that the increase in PWP in cases of AF and MVI would be significantly higher in horses with dilated atria than in cases of AF and MVI without atrial dilation because of overloading of the atrium due to the lack of end diastolic emptying and to the high systolic insufficiency volume. However, it is possible in chronic cases of AF and MVI that a dilated and elastic (compliant) atrium is able to withstand a larger insufficiency volume without any or with only little increase in pressure. This phenomenon has been described by Greenberg (1994) as an important adaptation to chronic volume overload in humans. Increased atrial and ventricular myocardial compliance may thus also mask an increase in PWP in horses. AF without concurrent heart disease is often accompanied by RAO, particularly PH. It is has been suggested that some cases of AF may be induced by primary RAO. Four cases of horses with primary pulmonary hypertension and secondary right-sided cardiac ventricular hypertrophy and dilatation, AF, and heart failure have been described in the literature (Gelberg et al., 1991). It has been reported that chronic RAO with hypoxemia in humans can reduce the myocardial metabolism due to reduced myocardial contractility (Szam, 1975). Maybe the same pathophysiology can also occur in horses and may induce AF.
There were no significant differences in echocoardiographic and pressure values between group 4 and the healthy horses of the present study. However, PWP and RVPm were significantly higher in group 2 (lone AF) than in group 4. Changes in PWP and thus in left atrial haemodynamics are consequences of AF itself and not of pulmonary diseases, as PWP is a specific parameter of cardiac haemodynamics. The significantly higher RVPm in group 2 than in group 4 seems to indicate influence of RAO on the right side of the heart. PAP and PDP are haemodynamic parameters for the differentiation between pulmonaryinduced, pre-capillary hypertonia and cardiac-induced post-capillary hypertonia (Gelberg et al., 1991). A significant increase in PAP and PDP has been described in the literature in horses with RAO alone (Goetz and Manohar, 1986). However, PWP is a haemodynamic parameter only for left ventricular and left atrial function and thus for left cardiac preload (Sapru et al., 1968). PWP is significantly increased in horses with cardiac diseases. However, in the present study, neither PDP, PAP nor PWP of the horses of group 4 were significantly different from those of healthy ones. Interestingly, there was a positive correlation between PH and PWP, and between RAO and left atrial size. Deem and Fregin (1982) reported the high prevalence of epistaxis in race horses with AF and its elimination in some by conversion to normal sinus rhythm, and a probable relation between the two conditions. The greatest changes in echocardiographic and pressure parameters were found in horses with AF, valvular insufficiency, and concurrent RAO. In these horses, echocardiography revealed a significantly enlarged LA and LVDd, with a significant correlation between the two parameters. PAP and PWP were significantly higher, and PDP was significantly lower than in healthy horses. Increased PWP has also been described in humans with AF (Shapiro and Klein, 1968). In this group of horses it must be recalled that valvular insufficiencies could also have had a haemodynamic effect on the lung. A left side cardiac pressure increase could result in an right side cardiac pressure increase (Pape et al., 1991). Thus it appears that secondary lung tissue remodelling with interstitial and/or alveolar oedema could result from venous congestion in the pulmonary circuit. This blood accumulation and secondary oedema of the capillary alveolar endothelium has been shown to induce pulmonary fibrosis (Billingham, 1994).
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Thus a combination of AF, heart valve insufficiency and RAO is not uncommon. Especially PH should be taken into consideration as a disease secondary to AF and left cardiac valvular diseases. Although it has been reported that there was a favorable therapeutic response to quinidine therapy (oral application route) in more than 80% of horses with AF (Deem and Fregin, 1982), in our study treatment was successful in only 50% of the Warmblood horses with lone AF and in horses with AF and concurrent valvular insufficiency. Therapeutic success in horses with AF mainly depends on how long the horses have been fibrillating before therapy and if the horses suffered from atrial dilatation. In our study horses with high-grade atrial dilation had already been excluded from therapy, but all horses in our study had a long history of AF for more than five months. This could be one reason for the poor results of therapy. The success rate of therapy for AF could also possibly be improved by oral quinidine application (Reef et al., 1995) or electrical cardioversion (McGurrin et al., 2005) instead of transvenous application (Davy et al., 2000). But the risks of negative side effects are higher using this methods. Taken together these findings may indicate that the pathomechanism of lone AF and AF with concurrent lung and/or heart valve disease is not the same. Additional RAO seems not to decrease successful therapy in the present study. The rate for long-term success may have other results, as atrial size and structural diseases are thought to be predisposing factors for the onset and persistence of AF. In conclusion, our results confirm the hypothesis that AF, leads to haemodynamic changes at rest, especially if there are additional heart disease and/or RAO. Unfortunately the results of our study unable us further to answer the final question about which disease was the cause and which the result in horses with AF and concurrent cardiac and/or pulmonary diseases and in which way concurrent diseases influences successful therapy. References Bertone, J.J., Wingfield, W.E., 1987. Atrial fibrillation in horses. Compend. Contin. Educ. Pract. Vet. 9, 261–265. Billingham, M.E., 1994. The pathology of congestive heart failure. In: Hosenpud, J.D., Greenberg, B.H. (Eds.), Congestive Heart Failure. Springer Verlag, New York, Berlin, pp. 301–322. Buchwalsky, R., 1994. Belastungsuntersuchungen in Rahmen von Einschwemm- katheteruntersuchungen. In: Mager, G., Winter, U.J. (Eds.), Belastungsuntersuchungen bei Herz- Kreislauf-, Gefa¨ß- und
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Lungenerkrankungen. Verlag Georg Thieme, Stuttgart, New York, pp. 76–89. Davy, J.M., Beck, L., Pons, M., Piot, C., 2000. Electrophysiologic and anatomic atrial remodeling: an atrial rhythmic cardiomyopathy. Arch. Mal. Coeur. Vaiss. 93, 39–45. Deem, D.A., Fregin, G.F., 1982. Atrial fibrillation in horses: a review of 106 clinical cases with consideration of prevalence, clinical signs, and prognosis. J. Am. Vet. Med. Assoc. 180, 261–265. Gelberg, H.B., Smetzer, D.L., Foreman, J.H., 1991. Pulmonary hypertension as a cause of atrial fibrillation in young horses: four cases (1980–1989). J. Am. Vet. Med. Assoc. 198, 679–682. Goetz, T.E., Manohar, M., 1986. Pressures in the right side of the heart and oesophagus (pleura) in ponies during exercise before and after furosemid administration. Am. J. Vet. Res. 47, 270–275. Greenberg, B.H. Con, 1994. Congestive heart failure as a consequence of valvular heart disease. In: Hosenpud, J.D., Greenberg, B.H. (Eds.), Congestive Heart Failure. Springer Verlag, New York, Berlin, pp. 234– 345. Killip, T., Boer, R.A., 1964. Cardiac function before and after electrical reversion from atrial fibrillation to sinus rhythm. Clin. Res. 12, 105– 112. McGurrin, M.K., Physick-Sheard, P.W., Kenney, D.G., Kerr, C., Hanna, W.J., 2005. Transvenous electrical cardioversion of equine atrial fibrillation: technical considerations. J. Vet. Int. Med. 19, 695–702. Muir, W.W., Mc Guirk, S.M., 1984. Hemodynamics before and after conversion of atrial fibrillation to normal sinus rhythm in horses. J. Am. Vet. Med. Assoc. 184, 965–970. Muylle, E., Nutten, J., Deprez, P., van den Hende, C., Oyaert, W., 1986. Pulmonary driving pressure as a pulmonary function test in horses. Equine Vet. Sci. 4, 57–59. Nuytten, J., Deprez, P., Picavet, T., Van Den Hende, C., Muylle, E., 1988. Heart failure in horses: haemodynamic monitoring and determination of LDH1-concentration. Equine Vet. Sci. 8, 214–216. Nyman, G., Lindberg, R., Weckner, D., Bjo¨rk, M., Kvart, C., Persson, S.G., Gustafsson, H., Hedenstierna, G., 1991. Pulmonary gas exchange correlated to clinical signs and lung pathology in horses with chronic bronchiolitis. Equine Vet. J. 23, 253–260. Pape, L.A., Price, J.M., Alpert, J.S., Ockene, I.S., Weiner, B.H., 1991. Relation of left atrial size to pulmonary capillary wedge pressure in severe mitral insufficiency. Cardiology 78, 297–303. Patteson, M., 1996. Equine Cardiology. Blackwell Wissenschaftsverlag, Berlin, pp. 12–52. Reef, V.B., Levitan, C.W., Spencer, P.A., 1988. Factors affecting prognosis and conversion in equine atrial fibrillation. J. Vet. Int. Med. 2, 1–6. Reef, V.B., 1995. Heart murmurs in horses: determining their significance with echocardiography. Equine Vet. J. Suppl. 19, 71–80. Reef, V.B., Reimer, J.M., Spencer, P.A., 1995. Treatment of atrial fibrillation in horses: new perspectives. J. Vet. Int. Med. 9, 57–67. Sapru, R.P., Taylor, S.H., Donald, K.W., 1968. Comparison of the pulmonary wedge pressure with the left ventricular end-diastolic pressure in man. Clin. Sci. 34, 125–140. Shapiro, W., Klein, G., 1968. Alterations in cardiac function immediately following electrical conversion of atrial fibrillation to normal sinus rhythm. Circulation 38, 1074–1084. Szam, I., 1975. Cor Pulmonale Chronicum. Schattauer Verlag, Stuttgart, New York, pp. 7–74.
Research in Veterinary Science 85 (2008) 333–339 www.elsevier.com/locate/rvsc
Influence of valvular insufficiency and recurrent airway obstruction on haemodynamics and therapy in warmblood horses with atrial fibrillation Heidrun Gehlen a,*, Kirstin Bubeck a, Karl Rohn b, Peter Stadler a b
a Equine Clinic, University of Veterinary Medicine Hanover, Foundation, D-30173 Hanover, Germany Department of Biometry, Epidemiology and Information Processing, University of Veterinary Medicine Hanover, Foundation, D-30173 Hanover, Germany
Accepted 3 November 2007
Abstract The aim of this study was to investigate the potential haemodynamic effects of valvular insufficiency and recurrent airway obstruction (RAO) in horses with atrial fibrillation (AF). Therefore in ten healthy horses (group 1) and 40 horses with AF a clinical examination, a lung examination, echocardiography and right heart catheterization for measurement of intracardic and pulmonary pressures were performed. According to the clinical findings the horses with AF were subdivided into 4 groups (group 2: AF; group 3: AF/valvular insufficiency; group 4: AF/RAO; group 5: AF/valvular insufficiency/RAO). Most of the horses of group 3 and 5 suffered from two valvular insufficiencies (mitral and tricuspid valve insufficiency: n = 11, mitral and aortic valve insufficiency: n = 2). The remaining horses showed a single mitral (n = 6), tricuspid (n = 2) or aortic valve insufficiency (n = 1) or more than two valvular insufficiencies (n = 4). In group 2 right ventricular mean pressure (RVPm) was higher than in group 1 and 4 (P < 0.025); diastolic right ventricular pressure was higher than in group 1; PWP was higher than in group 1 and group 4; PDP was lower compared to group1. Compared to group1 in group 3 left atrial diameter (LA) was greater; the PAPs was higher and the PDP lower (P < 0.05). In group 4 RVPm and PWP was lower compared to group 2. In group 5 LA, fractional shortening and diastolic left ventricular diameter were greater, PWP and PAPs were higher and PDP lower compared to group1. Twenty six of the 40 horses with AF (65%) were treated. Successful cardioversion to sinus rhythm occurred in 15 horses (58%). Therapy was successful in 50% of the treated horses of group 2 and 3, in 67% of the treated horses of group 4 and in 63% of the treated horses in group 5. In conclusion the presence of valvular insufficiency or RAO influences the haemodynamics of horses with AF. Ó 2007 Published by Elsevier Ltd. Keywords: Atrial fibrillation; Warmblood horse; Right heart catheterization; Pulmonary artery wedge pressure; Echocardiography; Heart valve insufficiency; RAO; Equine
1. Introduction Horses with AF alone, which is also known as idiopathic AF, mostly show neither any clinical symptoms of cardiac disease, except the presence of the arrhythmia on auscultation, nor any echocardiographic or hemodynamic
*
Corresponding author. Tel.: +49 511 856 8185; fax: +49 511 856 7671. E-mail address: [email protected] (H. Gehlen).
0034-5288/$ - see front matter Ó 2007 Published by Elsevier Ltd. doi:10.1016/j.rvsc.2007.11.001
anomalies (Deem and Fregin, 1982; Reef et al., 1988). Until now there has been no consensus about the effects of AF on cardiac haemodynamics, especially at rest (Bertone and Wingfield, 1987; Reef et al., 1995). It has been reported that there is not necessarily deterioration of haemodynamics in these horses at rest, as atrial contraction has only little influence on ventricular filling at rest, and that there is a good chance for successful therapy in these horses (Reef et al., 1988, 1995; Muir and Mc Guirk, 1984). On the other hand, several studies on horses have reported changes in
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cardiac haemodynamics at rest before and after successful treatment of AF, so that AF alone seems in some cases to influence haemodynamics at rest (Muir and Mc Guirk, 1984; Killip and Boer, 1964). It seems to be obvious that the extent of hemodynamic changes in horses with AF depends on several accompanying factors, particularly on additional cardiac and/or respiratory diseases. Right heart cardiac pressure measurements provide information on cardiac and pulmonary haemodynamics for the diagnosis and differentiation between valvular insufficiency and RAO in the horse (Muylle et al., 1986). Precapillary hypertension may be caused by interstitial or obstructive pulmonary diseases, thrombemboli, alveolar hypoxia, or left sided heart disease (Nuytten et al., 1988; Nyman et al., 1991). In these cases one could find an increased pulmonary artery pressure (PAP) combined with a normal pulmonary artery wedge pressure (PWP, Buchwalsky, 1994). Postcapillary hypertension may be a result of acute or chronic mitral (MVI) and/or aortic valve insufficiency (AVI) with a progressive pressure increase from the left side of the heart to the pulmonary veins, the lung capillaries, and the lung arterioles and arteries. In these cases there is an increase in both PAP and PWP (Muylle et al., 1986). Pulmonary driving pressure (PDP) is the difference between the mean PAP and PWP. PDP is also used to differentiate between pulmonary hypertension induced primary by valvular insufficiency or RAO, as PDP is increased in the latter (Muylle et al., 1986). As there are no published data about the hemodynamic influences of additional valvular insufficiency and/or RAO on AF and on successful therapy in Warmblood horses, we investigated echocardiographic and cardiac pressure parameters in horses with AF. 2. Materials and methods This study included 10 healthy Warmblood horses (group 1) with neither cardiovascular nor respiratory disease and 40 Warmblood horses with AF (group 2; Table 1). Although the exact duration of AF was unknown, AF had been detected by the referring veterinarian in all cases at least five to six months prior to presentation.(date of the last clinical examination). The animals were subjected to a general physical examination, electrocardiography, echocardiography, and a detailed examination of the respiratory tract.
Table 1 Basic data of the horses Group
Age (yr)
Weight (kg)
Height (cm)
HR (bpm)
1 2 3 4 5
4±1 9±5 8±4 10 ± 5 10 ± 4
554 ± 40 557 ± 48 584 ± 51 560 ± 52 582 ± 51
167 ± 5 172 ± 3 171 ± 5 168 ± 3 170 ± 4
38 ± 5 38 ± 7 38 ± 10 36 ± 4 41 ± 8
(n = 10) (n = 7) (n = 13) (n = 7) (n = 13)
Mean age, weight, height and heart rate at rest.
In addition radiography of the thorax and right heart catheterization were performed in all horses at rest consisting of measurement of intracardiac pressure, pulmonary artery pressure (PAP), and pulmonary artery wedge pressure (PWP). Pulmonary driving pressure (PDP) was then calculated using the following formula: PDP (mmHg) = mean PAP (mmHg) PWP (mmHg). 2.1. Examination of the lungs The diagnosis of RAO was based on clinical signs during auscultation and thoracic percussion, arterial blood gas analysis (ABG), endoscopic examination, cytological evaluation of respiratory tract secretions (TBS) and characteristic radiographic findings. 2.2. Echocardiographic examination Standard long and short axis two-dimensional real-time echocardiograms were performed in all horses. B-mode was used to measure the left atrial diameter (LA) using the left parasternal long axis view and the aortic (AO) and pulmonary diameters (PA). M-mode was used for the echocardiographic measurement of the left ventricular internal diameter during systole (LVDs) and diastole (LVDd), fractional shortening (FS%), interventricular septum during systole (IVSs) and diastole (IVSd), and the left ventricular free wall during systole (LVWs) and diastole (LVWd) using the right parasternal long axis view. Continuous wave and color-flow doppler echocardiography were used for detecting valvular insufficiencies.1 Differentiation between pathological valvular insufficiency and physiological valvular back flows were made by flow velocity and flow duration (Patteson, 1996). 2.3. Right heart catheterization After echocardiography, right atrial mean pressure (RAPm), right ventricular mean pressure (RVPm), right ventricular systolic (RVPs) and diastolic (RVPd) pressure, pulmonary arterial mean (PAPm), systolic (PAPs) and diastolic (PAPd) pressure, pulmonary arterial wedge pressure (PWP) and pulmonary driving pressure (PDP) were measured with a flow-directed balloon catheter (Swan– Ganz catheter2, 7 French, 160 cm length). The catheter was inserted into the right jugular vein through an introducer system.3 The level of the shoulder joint was used as a reference marker for all pressure measurements. The animals were continuously monitored during echocardiography and heart catheterization, with a base-apex lead ECG.4 1 2 3 4
Vingmed 750, Vingmed CFM 800. Arrow, Erding GmbH, Germany. Cook, Peel awayÒ, Brisbane, QLD, Australia. Hellige, Servomed, (SMR 211 and SMK 231, Vicom-sn) Germany.
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2.4. Therapy Twenty eight horses with AF were treated with an intravenous infusion of quinidine sulphate solution (1%) using a mean dosage of 40 mg/kg quinidine sulphate5 (range from 35 to 45 mg/kg) and an infusion rate of 5 ml/min. A maximum amount of 2 L solution was not exceeded. The infusion was stopped if cardioversion was observed. All horses were monitored continuously with an ECG during the entire infusion. The intravenous infusion of quinidine sulphate solution was used instead of oral application because negative side effects (i.e. colic, sweating, tachycardia) could be avoided. The infusion rate was decreased immediately if tachycardia or additional arrhythmias occurred. 2.5. Statistical analysis All data were included in a descriptive analysis. Normal distribution of the echocardiographic variables was confirmed by visual assessment of normal probability plots and by the Shapiro–Wilk Test. The arithmetic means ðxÞ and standard deviations (s) were calculated for all variables. T-test was performed for comparing the means of the cardiac parameters between horses with and without successful therapy. Differences in the means of the four subgroups of horses with AF and the group of healthy horses were compared using one-way analysis of variance with subsequent Ryan–Einot–Gabriel–Welsch Multiple Range Test for multiple pairwise comparisons of means between two disease levels. Correlation analysis was performed by calculating the Pearson correlation coefficient rho. Analysis was carried out with SAS statistical software, version 9.1. The GLM (General linear models) procedures were used for analysis of the linear models. A P-value of 0.05 was considered statistically significant. 3. Results The control group (group 1) showed no clinical signs of cardiac or pulmonary disease, normal ABG, no mucus accumulation in the lower airways and normal thoracic radiographs. The horses with AF (n = 40) had a characteristic arrhythmia with irregular intervals of the QRS-T complexes and without p-waves. A total of 20 of the 40 horses with AF (50%) were found to be affected with a concurrent RAO. Thirteen of these horses showed recurrent airway obstruction (RAO) and seven horses had RAO combined with pulmonary haemorrhage (PH). The diagnosis of RAO was based on typical clinical signs (tachypnoea, chronic cough, prolonged inand/or expiration), peribronchial infiltrations visible on radiographs, decreased arterial PaO2 in ABG and neutrophilic inflammation and/or Curshmann’s spirals in TBS.
5
Fagron GmbH & Co. Barsbu¨ttel, Germany.
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The diagnosis of PH was based on radiographic alveolar or mixed alveolar-interstitial opacities in the caudodorsal lung field and identification of red blood cells and/or macrophages containing haemosiderin in TBS. Twenty six out of 40 horses with AF showed additional heart murmurs during auscultation and valvular insufficiency in echocardiography (Table 2). The mean echocardiographic parameters of the healthy horses (group 1) were within normal limits (Table 3). Right heart catheterization was tolerated well by all horses. No adverse effects or complications were observed. The pressure values of the healthy horses (group 1) were within the reference range (Table 4). 3.1. Subdivision of the horses with AF For further analysis the 40 horses with AF (n = 40) were divided into four subgroups according to their additional pathological findings (Table 1, 2): Group 2 (n = 7): Group 3 (n = 13): group 4 (n = 7): Group 5 (n = 13):
horses with lone AF horses with AF and concurrent valvular insufficiency horses with AF and RAO horses with AF, concurrent valvular insufficiency, and RAO.
3.1.1. Results in horses with lone AF (group 2) The horses in group 2 showed no clinical signs of pulmonary disease, normal ABG, no mucus accumulation in the lower airways and normal thoracic radiographs. The mean PaO2 in this group was 102 mmHg, the mean PaCO2 was 44 mmHg. The mean echocardiographic parameters of the horses from group 2 were within normal limits (Table 3). Horses from group 2 showed a significantly higher (P < 0.05) RVPd, RVPm and PWP than the control group (group 1). The PDP was significantly lower (P < 0.05) than in the control group (Table 4). Also the RVPm in group 2 was significantly higher (p < 0.05) than in group 4 (horses with AF and RAO). 3.1.2. Results in horses with AF and concurrent valvular insufficiency (group 3) In group 3, eleven horses had a holosystolic heart murmur between grade 2 and 5 out of 6 with the point of maximum intensity on the left thoracic side. Clinical lung examination revealed no pathological findings in this group. Endoscopy revealed no mucus accumulation in the lower airways and the horses had normal thoracic radiographs. The mean PaO2 in this group was 102 mmHg and the mean PaCO2 was 44 mmHg.
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Table 2 Valvular insufficiency of groups 3 and 5 Group
MVI
TVI
AVI
MVI + TVI
MVI + AVI
MVI + TVI + AVI
MVI + PVI + AVI
MVI + TVI + AVI + PVI
3 5
1 5
1 1
– 1
9 2
2 –
– 2
– 1
– 1
MVI = mitral valve insufficiency, TVI = tricuspid valve insufficiency, AVI = aortic valve insufficiency, PVI = pulmonic valve insufficiency.
Table 3 Results of the echocardiographic examination Group 1
Group 2
Group 3
Group 4
Group 5
P < 0.05
LVDd (mm)
109 ± 2
116 ± 13
135 ± 23
124 ± 11
141 ± 17
LVDs (mm) FS (%) IVSd (mm) IVSs (mm) LVWd (mm) LVWs (mm) PA (mm) AO (mm) LA (mm)
69 ± 4 26 ± 4 30 ± 2 43 ± 2 24 ± 3 30 ± 2 57 ± 4 80 ± 3 121 ± 5
68 ± 15 42 ± 9 26 ± 4 39 ± 3 23 ± 4 31 ± 3.6 59 ± 7 80 ± 6 125 ± 6
88 ± 32 34 ± 12 29 ± 5 40 ± 7 22 ± 6 33 ± 6 60 ± 9 81 ± 10 141 ± 14
83 ± 23 34 ± 12 31 ± 7 41 ± 4 22 ± 4 34 ± 7 58 ± 7 73 ± 10 128 ± 6
90 ± 23 36 ± 13 30 ± 5 39 ± 5 23 ± 6 34 ± 7 60 ± 6 80 ± 6 145 ± 18
1?5 1?3 2?5 n.s. n.s. n.s. n.s. n.s. n.s. n.s. n.s. 1?3 1?5
LVD = left ventricular diameter, FS = fractional shortening, IVS = interventricular septal wall, LVW = left ventricular free wall, 5 = B-mode, PA = pulmonic artery, AO = aortic root, LA = left atrium, d = end diastolic measurement, s = end systolic measurement, MVI = mitral valve insufficiency, TVI = tricuspid valve insufficiency, AVI = aortic valve insufficiency, PVI = pulmonic valve insufficiency, s = systolic, d = diastolic.
Table 4 Results of the right heart catheterization Group 1
Group 2
Group 3
Group 4
Group 5
RAPm (mmHg) RVPs (mmHg) RVPd (mmHg) RVPm (mmHg)
6±2 41 ± 7 2±2 17 ± 2
8±4 48 ± 10 8 ± 10 25 ± 9
6±3 45 ± 8 5±4 19 ± 7
7±2 42 ± 18 3±2 15 ± 6
6±3 42 ± 6 3±3 20 ± 4
PAPs (mmHg)
39 ± 2
48 ± 10
52 ± 7
44 ± 12
51 ± 10
PAPd (mmHg) PAPm (mmHg) PWP (mmHg)
15 ± 2 28 ± 2 15 ± 2
18 ± 7 30 ± 5 23 ± 4
14 ± 6 28 ± 5 20 ± 5
15 ± 4 26 ± 4 17 ± 4
18 ± 7 31 ± 6 23 ± 6
PDP (mmHg)
13 ± 2
8±3
8±4
10 ± 2
8±4
P < 0.05
1?2 1?2 2?4 1?3 1?5
1?2 1?5 2?4 1?2 1?3 1?5
RAP = right atrial pressure, RVP = right ventricular pressure, PAP = pulmonary artery pressure, PWP = pulmonary artery wedge pressure, PDP = pulmonary driving pressure, s = systolic, d = diastolic, m = mean, Norm. = normal value.
Horses with AF and concurrent valvular insufficiency (group 3 and 5) had a significantly larger LA than the control group (P < 0.0001; Table 3). Horses with AF and concurrent valvular insufficiency (group 3 and 5) showed significantly higher PAPs and lower PDP than those from the control group (P < 0.05, Table 4). 3.1.3. Results in horses with AF and RAO (group 4) The mean PaO2 in this group was 89 mmHg, the mean PaCO2 was 43 mmHg. The TBS of the horses revealed an
increase of neutrophils and visible Churschman spirals in all horses as well as red blood cells and hemosiderin-laden macrophages in four horses. The thoracic radiographs of these horses showed peribronchial infiltrations in all horses and additional mixed alveolar-interstitial opacity in the caudodorsal lung field in four horses. Three of the seven horses in group 4 were diagnosed with a recurrent airway obstruction (RAO); and four suffered from both RAO and pulmonary haemorrhage (PH). There were no exact informations about the duration of the RAOs.
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The mean echocardiographic parameters of the horses of group 4 were within normal ranges (Table 3). There were differences between horses with AF and concurrent RAOs (group 4) and between horses with lone AF (group 2) in RVPm and PWP which were both significantly higher in horses with lone AF (group 2; RVPm: P < 0.025, PWP: P < 0.002; Table 4). 3.1.4. Results in horses with AF, concurrent valvular insufficiency and RAO (group 5) In group 5, eleven horses had holosystolic heart murmur between grade 1 and 4 out of 6 with the point of maximum intensity on the left thoracic side. Ten of the thirteen horses in group 5 had RAO; and three suffered from both RAO and PH. The duration of the RAO was not known. The mean PaO2 in this group was 92 mmHg, the mean PaCO2 was 43 mmHg. The TBS of the horses showed an increase in neutrophils and Curschman’s spirals in the horses with RAO and additionally red blood cells and haemosiderin-laden macrophages in horses with RAO and PH. The thoracic radiographs of the horses with RAO showed peribronchial infiltrations and additionally mixed alveolarinterstitial opacity in the caudodorsal lung field in the horses with RAO and PH. In this group there were also no exact informations about the duration of the RAOs. Seven horses of group 5 had a single valvular lesion and six horses had multiple valvular lesions. The most frequent heart valve insufficiency was the mitral valve insufficiency (n = 11, Table 2, 2). The LA was significantly (P < 0.05) larger in group 5 compared to the control group (P < 0.0001). The horses of group 5 had also a significantly (P < 0.05) higher FS (P < 0.001) and LVDd (P < 0.0008) than the control group (Table 3). Additionally the LVDd was also significantly higher (P < 0.05) than in the horses with lone AF (group 2, Table 3). There were differences between horses with AF, concurrent valvular insufficiency and RAO (group 5) and between the control group (group 1) in PAPs and PWP which were both significantly higher (P < 0.05) in group 5 and in PDP which was significantly lower (P < 0.05) in group 5 (Table 4). 3.2. Influence of concurrent PH on cardiac parameters Horses with a combination of AF, RAO and PH showed significantly lower LA and PWP values (P < 0.05) compared to horses with AF and lone RAO (Table 5). In group 4 there was a significant positive correlation between PWP and LVDd (P = 0.01). 3.3. Results of therapy In all, 26 of the 40 horses with AF (65%) were treated. Successful cardioversion to sinus rhythm occurred in 15
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horses (58%). In five cases the owners did not consent to any therapy. The left atrial diameter was greater than 14.5 cm in nine horses, which were not treated due to the poor prognosis. Treatment was considered successful if conversion to sinus rhythm took place. Therapy was successful in only 50% of the treated horses of group 2 and 3. However this was the case in 67% of the treated horses of group 4 and in 63% of the treated horses in group 5. 3.3.1. Differences in the cardiac parameters between the horses with and without successful therapy In group 2 the dimension of the IVSs was smaller (P = 0.043) in the horses with successful therapy (36.3 ± 1.5 mm) than in the group of horses without successful therapy (41.3 ± 2.5 mm). In group 3 the PAPd was lower (P = 0.05) in the horses with successful therapy (3 ± 4.2 Hg) than in the group of horses without successful therapy (15 ± 4.2 Hg). In group 5 there were differences in HR (P = 0.035), AO (P = 0.05) and LA (P = 0.003) between the horses with successful therapy (AO = 78.7 ± 3.4 mm; LA = 131 ± 2.6 mm) and the group of horses without successful therapy in which all three parameters were significantly higher (P < 0.05, AO = 84.3 ± 0.6 mm; LA = 142 ± 3.4 mm). 4. Discussion It is clear from the present study that the hemodynamic state of AF is influenced by the concurrent presence of valvular insufficiency and/or RAO. Lone AF is reported in humans and horses, in the absence of structural heart disease. Although in the present study the echocardiographic examination revealed no differences between healthy horses and horses with lone AF, there were differences between the two groups in various pressure values. The present study confirmed that PWP, RVPd and RVPm of horses with lone AF were higher than those of the healthy horses. These increased pressures were not correlated with clinical and/or echocardiographical signs of cardiac disease except of the AF itself. If AF is accompanied by valvular insufficiencies, there has to be an influence on haemodynamics, as valvular insufficiency alone has been shown to cause hemodynamic changes (Patteson, 1996; Reef, 1995). If AF and valvular insufficiencies occur together, the question always arises as to whether the valvular insufficiency is the cause or the result of AF. Our study could not answer this question. But both scenarios are possible and should be taken into consideration, although the conventional view is that valvular insufficiency and left atrial enlargement pre-dates the onset of AF (Patteson, 1996). Significantly increased PWP values, as observed in our study, could be due to either regurgitant volume or AF and following atrial remodelling. In humans with valvular insufficiency an increased PWP is judged a sign of incipient contractility
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Table 5 Differences in echocardiographic and pressure values between horses with AF and RAO and horses with RAO and PH Group
RAO
RAO + PH
P-value RAO ? RAO + PH
4 + 5 (n = 13)
4 (n = 3)
5 (n = 10)
4 + 5 (n = 7)
4 (n = 4)
5 (n = 3)
IVSs LA PWP
37.8 ± 4 144.6 ± 18 23.3 ± 6
38 ± 3 132 ± 7 17 ± 4
38 ± 4 148.4 ± 19 25.2 ± 5
43.1 ± 3 129 ± 7 16 ± 3
43 ± 4 126 ± 5 16 ± 4
43 ± 4 133.7 ± 8 16 ± 1
RVPs
41.4 ± 5
45 ± 7
40.4 ± 4
44.1 ± 19
40 ± 24
49.3 ± 6
4 + 5 ? 4 + 5: 0.007 4 + 5 ? 4 + 5: 0.01 4 + 5 ? 4 + 5: 0.008 5 ? 5: 0.01 5 ? 5: 0.01
RVPs = systolic right ventricular pressure, PWP = pulmonary artery wedge pressure, LA = left atrium, IVSs = systolic interventricular septal wall.
insufficiency due to myocardial remodelling (Davy et al., 2000). Our findings of a correlation between MVI and the LAdiameter confirm those of other studies (Patteson, 1996). Interestingly in our study, PWP was significantly higher in the horses with MVI and a normal left atrium than in those with MVI and an enlarged left atrium. This may support the hypothesis that on the one hand dilatation would tend to allow intracardiac pressure to remain within normal limits for longer and on the other hand that elevated PWP and left atrial pressure may be due not only to the insufficiency of the blood volume, but also to other, additional factors like atrial myocardial remodelling (Davy et al., 2000). The compliance of the left atrium and its influence by cardiac remodelling seems to be an important factor in the pathomechanism of AF in humans (Davy et al., 2000). In horses with AF and MVI, increased PWP could be a sign of incipient cardiac decompensation and/or myocardial fibrosis of the left atrium; this has been described for horses with MVI alone during exercise (Reef, 1995). In contrast to our findings, one would expect that the increase in PWP in cases of AF and MVI would be significantly higher in horses with dilated atria than in cases of AF and MVI without atrial dilation because of overloading of the atrium due to the lack of end diastolic emptying and to the high systolic insufficiency volume. However, it is possible in chronic cases of AF and MVI that a dilated and elastic (compliant) atrium is able to withstand a larger insufficiency volume without any or with only little increase in pressure. This phenomenon has been described by Greenberg (1994) as an important adaptation to chronic volume overload in humans. Increased atrial and ventricular myocardial compliance may thus also mask an increase in PWP in horses. AF without concurrent heart disease is often accompanied by RAO, particularly PH. It is has been suggested that some cases of AF may be induced by primary RAO. Four cases of horses with primary pulmonary hypertension and secondary right-sided cardiac ventricular hypertrophy and dilatation, AF, and heart failure have been described in the literature (Gelberg et al., 1991). It has been reported that chronic RAO with hypoxemia in humans can reduce the myocardial metabolism due to reduced myocardial contractility (Szam, 1975). Maybe the same pathophysiology can also occur in horses and may induce AF.
There were no significant differences in echocoardiographic and pressure values between group 4 and the healthy horses of the present study. However, PWP and RVPm were significantly higher in group 2 (lone AF) than in group 4. Changes in PWP and thus in left atrial haemodynamics are consequences of AF itself and not of pulmonary diseases, as PWP is a specific parameter of cardiac haemodynamics. The significantly higher RVPm in group 2 than in group 4 seems to indicate influence of RAO on the right side of the heart. PAP and PDP are haemodynamic parameters for the differentiation between pulmonaryinduced, pre-capillary hypertonia and cardiac-induced post-capillary hypertonia (Gelberg et al., 1991). A significant increase in PAP and PDP has been described in the literature in horses with RAO alone (Goetz and Manohar, 1986). However, PWP is a haemodynamic parameter only for left ventricular and left atrial function and thus for left cardiac preload (Sapru et al., 1968). PWP is significantly increased in horses with cardiac diseases. However, in the present study, neither PDP, PAP nor PWP of the horses of group 4 were significantly different from those of healthy ones. Interestingly, there was a positive correlation between PH and PWP, and between RAO and left atrial size. Deem and Fregin (1982) reported the high prevalence of epistaxis in race horses with AF and its elimination in some by conversion to normal sinus rhythm, and a probable relation between the two conditions. The greatest changes in echocardiographic and pressure parameters were found in horses with AF, valvular insufficiency, and concurrent RAO. In these horses, echocardiography revealed a significantly enlarged LA and LVDd, with a significant correlation between the two parameters. PAP and PWP were significantly higher, and PDP was significantly lower than in healthy horses. Increased PWP has also been described in humans with AF (Shapiro and Klein, 1968). In this group of horses it must be recalled that valvular insufficiencies could also have had a haemodynamic effect on the lung. A left side cardiac pressure increase could result in an right side cardiac pressure increase (Pape et al., 1991). Thus it appears that secondary lung tissue remodelling with interstitial and/or alveolar oedema could result from venous congestion in the pulmonary circuit. This blood accumulation and secondary oedema of the capillary alveolar endothelium has been shown to induce pulmonary fibrosis (Billingham, 1994).
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Thus a combination of AF, heart valve insufficiency and RAO is not uncommon. Especially PH should be taken into consideration as a disease secondary to AF and left cardiac valvular diseases. Although it has been reported that there was a favorable therapeutic response to quinidine therapy (oral application route) in more than 80% of horses with AF (Deem and Fregin, 1982), in our study treatment was successful in only 50% of the Warmblood horses with lone AF and in horses with AF and concurrent valvular insufficiency. Therapeutic success in horses with AF mainly depends on how long the horses have been fibrillating before therapy and if the horses suffered from atrial dilatation. In our study horses with high-grade atrial dilation had already been excluded from therapy, but all horses in our study had a long history of AF for more than five months. This could be one reason for the poor results of therapy. The success rate of therapy for AF could also possibly be improved by oral quinidine application (Reef et al., 1995) or electrical cardioversion (McGurrin et al., 2005) instead of transvenous application (Davy et al., 2000). But the risks of negative side effects are higher using this methods. Taken together these findings may indicate that the pathomechanism of lone AF and AF with concurrent lung and/or heart valve disease is not the same. Additional RAO seems not to decrease successful therapy in the present study. The rate for long-term success may have other results, as atrial size and structural diseases are thought to be predisposing factors for the onset and persistence of AF. In conclusion, our results confirm the hypothesis that AF, leads to haemodynamic changes at rest, especially if there are additional heart disease and/or RAO. Unfortunately the results of our study unable us further to answer the final question about which disease was the cause and which the result in horses with AF and concurrent cardiac and/or pulmonary diseases and in which way concurrent diseases influences successful therapy. References Bertone, J.J., Wingfield, W.E., 1987. Atrial fibrillation in horses. Compend. Contin. Educ. Pract. Vet. 9, 261–265. Billingham, M.E., 1994. The pathology of congestive heart failure. In: Hosenpud, J.D., Greenberg, B.H. (Eds.), Congestive Heart Failure. Springer Verlag, New York, Berlin, pp. 301–322. Buchwalsky, R., 1994. Belastungsuntersuchungen in Rahmen von Einschwemm- katheteruntersuchungen. In: Mager, G., Winter, U.J. (Eds.), Belastungsuntersuchungen bei Herz- Kreislauf-, Gefa¨ß- und
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