Abstract
OBJECTIVE
To determine changes in health-related quality of life up to 12 months after surgery in dogs with myxomatous mitral valve disease that undergo mitral valve repair.
ANIMALS
54 dogs that underwent mitral valve repair at a United Kingdom referral hospital.
PROCEDURES
Health-related quality of life was assessed with a previously validated, owner-completed questionnaire before and 1, 3, 6, and 12 months after surgery.
Results
There was a significant decrease in total score (corresponding to reduced negative impact of cardiac disease on quality of life) between the preoperative timepoint and all postoperative timepoints. A significant decrease in total score was also demonstrated between the 1- and 3-month timepoints, but no additional significant changes in total score between adjacent timepoints were identified beyond 3 months after surgery. Significant improvements in individual question scores were found up to 12 months after surgery.
CLINICAL RELEVANCE
Health-related quality of life was significantly improved following mitral valve repair in dogs with myxomatous mitral valve disease and this improvement persisted for up to a year after surgery. These results may be useful when counseling owners of dogs considered candidates for this procedure.
Introduction
Myxomatous mitral valve disease (MMVD) is the most common cause of cardiovascular disease in dogs, with murmurs consistent with MMVD identified in 3.54% of all dogs presenting to first-opinion clinics in the United Kingdom in 1 study.1 Although many dogs in which MMVD is diagnosed will remain free from clinical signs, left-sided congestive heart failure can develop in some dogs. This is ultimately fatal, with reported survival times of < 1 year with medical management alone.2–5
In people, Barlow disease is associated with mitral valve regurgitation and mitral valve leaflet prolapse, and the condition shares many similarities with MMVD in dogs, although there are several important differences in pathological changes, genetic predispositions, and disease progression.6 The yearly mortality rate for medically managed human patients classified as New York Heart Association grade 3 or 4 (marked or severe limitation in activities owing to cardiac symptoms) exceeds 30%, and 90% of patients will undergo surgical intervention or die within 10 years of diagnosis.7 In human patients with mitral valve regurgitation, mitral valve repair (MVR) is the only approach with defined clinical success.7,8 Prompt surgical intervention is recommended in instances of severe regurgitation, with a high probability of a durable repair in the hands of an experienced surgical team.9
Although MVR for dogs has limited availability, with only a handful of centers performing the procedure, successful completion of MVR in dogs has been described,10,11 and the latest American College of Veterinary Internal Medicine (ACVIM) consensus guidelines for the management of canine MMVD include surgery as a potential management option.12 Previous authors have reported both objective and subjective outcomes after MVR in dogs, including survival rates, changes in murmur intensity, echocardiographic findings, and medication use.10,11,13,14
In recent years, increasing consideration has been given to health-related quality of life (HRQoL) as a treatment outcome measure in both human and veterinary medicine, and several veterinary studies15–25 have incorporated specific quality-of-life measuring tools for various canine diseases, including canine heart disease. In human medicine, HRQoL is a fundamental outcome measure,26 representing the multidimensional impact of chronic diseases and their treatment on everyday life,27 and has been established as an essential clinical endpoint in many human trials.28 Similarly, several studies investigating the benefit of medical treatment in dogs with cardiac disease have used HRQoL questionnaires to compare treatment arms. For example, improvements in HRQoL measures have been shown with the use of enalapril versus a placebo,29 but not with the use of pimobendan versus ramipril.30
Maintaining a good HRQoL has been shown to be as important as overall survival time for most human patients with chronic heart failure31; however, most people with cardiac disease have substantially impaired HRQoL, compared with HRQoL for patients with noncardiac disease as well as individuals in the general population.32,33 Similarly, HRQoL has been shown to be more important than longevity to owners of both dogs and cats with heart disease.34,35
A questionnaire for assessing HRQoL of dogs with cardiac disease has been previously designed and validated,25 and this questionnaire was previously used to assess HRQoL in 360 dogs, 51% of which had medically managed MMVD ranging in severity from no clinical signs or radiographic evidence of cardiomegaly to severe mitral valve regurgitation and cardiomegaly. Although MVR for dogs with MMVD is receiving increasing attention and demand, as yet no study has reported HRQoL as an outcome measure following this procedure. The objective of the study reported here was to use this previously validated Functional Evaluation of Cardiac Health (FETCH) questionnaire to determine changes in HRQoL up to 12 months after surgery in dogs with MMVD that undergo MVR.
Materials and Methods
Dogs with MMVD undergoing MVR between October 2017 and January 2020 at the Queen Mother Hospital for Animals, Royal Veterinary College, were enrolled in the study if owner consent was given. Royal Veterinary College ethical approval for the study was obtained.
Owners were asked to complete the FETCH questionnaire25 before surgery (T0) and 1 (T1), 3 (T3), 6 (T6), and 12 (T12) months after surgery. Dogs were excluded from the study if they died prior to hospital discharge or if the questionnaire was not completed prior to surgery and a minimum of once between 1 and 12 months after surgery.
The FETCH questionnaire was designed and validated by Tufts University for the purpose of assessing HRQoL in dogs with cardiac disease and was used in the present study with the authors’ prior approval. The questionnaire comprised 18 questions regarding the impact of specific factors on the dog’s quality of life during the 7 days prior to questionnaire completion. Each question was scored on a Likert scale ranging from 0 (no impact of factor on quality of life) to 5 (quality of life very much affected by factor). Owners were directed to skip either question 5 or question 6, depending on whether exercise restrictions were in place, resulting in a total of 17 completed questions. An additional question (“If your dog coughs, what has the frequency been during the last 7 days”) was added at the end of the original 18 questions, although answers were not used for the purpose of the present study.
A FETCH score was calculated by summing the answers from the 17 questions (considering questions 5 and 6 as 1 question) to give a possible score ranging from 0 to 85, with a higher score indicating a greater overall negative impact on HRQoL and a decrease in score indicating an improvement in HRQoL.
Paper copies of the questionnaire were completed by clients until September 2019, after which time a digital version of the same questionnaire was used. When follow-up examinations were performed at another institution, the digital questionnaire was emailed to clients at the appropriate times.
FETCH questionnaire data were entered into a commercially available spreadsheet program (Excel; Microsoft Corp), alongside medical record data such as signalment, date of surgery, ACVIM stage,12 medications administered, and details of any complications occurring during the study period.
Statistical analysis
Data were analyzed with a commercially available statistical software program (SPSS version 24; IBM Corp) with significance set at values of P < 0.05. Data were assessed for normality with a Shapiro-Wilk test and reported as mean ± SD when normally distributed and median (range) when not normally distributed.
Individual question scores were compared between each time point with the Kendall τ test. Total individual scores were compared between time points with a paired t test. Scores at each time point were compared between dogs with stage C versus D disease with an independent sample t test. For each of these tests, only dogs with completed questionnaires for both of the time points assessed were included. Number of cardiac medications administered was compared between time points with a paired t test.
Results
Signalment
Sixty-two dogs underwent MVR during the study period, but 8 were excluded because they died prior to discharge from the hospital. The remaining 54 dogs were included in the study.
For dogs included in the study, the most common breeds were Chihuahua and Cavalier King Charles Spaniel, each accounting for 11 (20.4%) dogs in the study population. Median age was 10 years (range, 5 to 14 years) and there were 24 (44.4%) neutered males, 16 (29.6%) neutered females, 10 (18.5%) sexually intact males, and 4 (7.4%) sexually intact females. Two (3.7%) dogs were in ACVIM stage B2 of disease, 41 (75.9%) were in stage C, and 11 (20.4%) were in stage D
Medications
All dogs were prescribed a 3-month course of aspirin and clopidogrel following MVR. Other cardiac medications prescribed included pimobendan, spironolactone, furosemide, torasemide, digoxin, benazepril hydrochloride, enalapril, diltiazem, sotalol, propranolol, amiodarone, hydrocodone, sildenafil, and heparin. Drugs given for diseases unrelated to MMVD, topical treatments, and food supplements were not included in the analysis.
Dogs were receiving a median of 4 cardiac medications (range, 1 to 7; n = 53 dogs) at T0 (ie, prior to surgery), 3 cardiac medications (range, 2 to 4; 49 dogs) at T1 (ie, 1 month after surgery), 0 cardiac medications (range, 0 to 3 medications; 47 dogs) at T3 (ie, 3 months after surgery, 0 cardiac medications (range, 0 to 3 cardiac medications; 45 dogs) at T6 (ie, 6 months after surgery), and 0 cardiac medications (range, 0 to 3; 40 dogs) at T12 (ie, 12 months after surgery).
There were significant decreases in the number of cardiac medications prescribed from T0 to T1 and from T1 to T3 (both P < 0.001). By T12, 30 of the 40 dogs (75%) for which follow-up information was available were receiving no medications, and 8 (20%) were receiving only pimobendan.
HRQoL
FETCH scores at each of the study time points were summarized (Table 1). Thirty-six owners (66.7%) completed questionnaires at both T0 and T1, 28 (51.9%) completed questionnaires at both T1 and T3, 32 (59.3%) completed questionnaires at both T3 and T6, and 36 (66.7%) completed questionnaires at both T6 and T12.
Health-related quality of life (HRQoL), as determined with the owner-completed Functional Evaluation of Cardiac Health (FETCH) questionnaire, in 54 dogs with myxomatous mitral valve disease that underwent mitral valve repair.
| Timepoint | Mean (SD) time (d) | No. of dogs before or after surgery | Median score | Range |
|---|---|---|---|---|
| T0 | 54 | 12.1 (23.7) | 30.5 | 0–82 |
| T1 | 36 | 35.7 (9.3) | 7.5 | 0–58 |
| T3 | 33 | 103.9 (16.8) | 5 | 0–34 |
| T6 | 43 | 190.3 (22.5) | 3 | 0–29 |
| T12 | 45 | 385.6 (33.1) | 1 | 0–25 |
Owners were asked to complete the FETCH questionnaire before (T0) and 1 (T1), 3 (T3), 6 (T6), and 12 (T12) months after surgery. Possible scores for the questionnaire ranged from 0 to 85, with a higher score indicating a greater overall negative impact on HRQoL and a decrease in score indicating an improvement in HRQoL.
Total FETCH scores were significantly decreased at all postoperative time points, compared with preoperative T0 score (P = < 0.001 for all). Scores were also significantly decreased between T1 and T3 (P = 0.006) but not between T3 and T6 (P = 0.104) or between T6 and T12 (P = 0.501).
Results of comparing scores for individual questions between time points were also summarized (Table 2). Eight individual questions had significant decreases in FETCH scores between T0 and T1 and 10 questions had significant decreases between T1 and T3. Scores significantly decreased for 7 questions between T3 and T6 and for 6 questions between T6 and T12.
P values obtained when comparing (Kendall τ test) individual question scores between timepoints for the dogs in Table 1.
| Question No. | T0 vs T1 scores | T1 vs T3 scores | T3 vs T6 scores | T6 vs T12 scores |
|---|---|---|---|---|
| 1 (dyspnea) | 0.014 | 0.14 | < 0.001 | 0.005 |
| 2 (coughing) | 0.006 | < 0.001 | < 0.001 | < 0.001 |
| 3 (wheezing) | < 0.001 | 0.029 | 0.062 | 0.169 |
| 4 (fatigue) | 0.083 | 0.017 | < 0.001 | < 0.001 |
| 5 or 6 (activity limitations) | 0.270 | 0.311 | 0.199 | 0.336 |
| 7 (resting during walks) | 0.064 | 0.023 | 0.007 | 0.359 |
| 8 (difficulty with stairs) | < 0.001 | 0.094 | 0.029 | 0.036 |
| 9 (syncope) | 0.301 | ND | 0.465 | ND |
| 10 (discomfort) | 0.015 | 0.005 | 0.032 | 0.123 |
| 11 (sleep disturbance) | < 0.001 | 0.031 | 0.023 | 0.316 |
| 12 (hyporexia) | 0.167 | 0.676 | 0.335 | 0.297 |
| 13 (change in food types) | 0.180 | 0.018 | 0.587 | 0.337 |
| 14 (periruria) | 0.129 | 0.498 | 0.294 | 0.396 |
| 15 (emesis) | 0.052 | 0.186 | 0.056 | 0.132 |
| 16 (limited time with family) | 0.276 | 0.009 | 0.151 | 0.021 |
| 17 (irritability) | 0.001 | 0.051 | 0.120 | ND |
| 18 (dullness) | < 0.001 | 0.027 | 0.123 | 0.030 |
ND = Not determined.
Stage of disease
Mean total score at T0 was 26.3 (SD, 16.1) for dogs with stage C disease and was 45.9 (SD, 20.4) for dogs with stage D disease. Total scores were significantly (P = 0.002) higher (indicating a worse HRQoL) at T0 for dogs with stage D versus stage C disease but did not differ between groups at other time points. Mean scores were significantly higher at T0 for dogs with stage D versus stage C disease for question 1 (P = 0.009), question 2 (P = 0.015), question 3 (P = 0.019), question 4 (P = 0.049), question 5 or 6 (P = 0.021), question 7 (P = 0.039), question 8 (P = 0.045), question 9 (P = 0.003), and question 11 (P = 0.006). Mean scores for individual questions were not significantly different between dogs with stage D versus stage C disease at any time point after surgery (P > 0.50 for all).
Complications
Two (3.7%) dogs were found to have rupture of ≥ 1 artificial chord postoperatively. In 1 dog, this was detected prior to discharge from the hospital. The second dog had no evidence of chord rupture at the time of hospital discharge, but chord rupture was noted at the 3-month follow-up appointment. In the first dog, improved parameters were seen echocardiographically despite the chord rupture, and pimobendan was prescribed. This dog was still receiving pimobendan at T12, but diuretic treatment was not required. In the second dog, chord rupture led to recurrence of congestive heart failure 3 months after surgery and resumption of diuretic treatment. This dog was lost to follow-up after T3.
Three (5.5%) dogs experienced complications suspected to be related to emboli during the hospitalization period. Two of these dogs developed unilateral thoracic limb paralysis, and the third developed cranial nerve deficits. All of these events resolved uneventfully with conservative management by T1.
Discussion
To our knowledge, the present study represents the first attempt to report HRQoL as an outcome measure for dogs undergoing MVR because of MMVD. In this group of dogs, there was a significant decrease in total scores (corresponding to an improvement in HRQoL) between the preoperative time point and all postoperative time points. Furthermore, a significant improvement in total score was demonstrated between the 1- and 3-month time points. Scores did not change significantly between adjacent time points beyond 3 months after surgery, suggesting that there was no deterioration in the initial improvement in HRQoL. It was interesting and hopefully of reassurance to owners considering MVR that improvement is seen so rapidly after surgery and was maintained long-term.
HRQoL is now considered an essential outcome in human medicine when considering the success of an intervention.36 In veterinary patients, understanding the consequences of various treatments on HRQoL is of particular importance given the need for proxy decision-making. Previous work has demonstrated that HRQoL is an important factor for dog owners34; therefore, quantification of HRQoL changes following MVR is expected to have substantial utility for client decision-making.
Freeman et al25 demonstrated a significant association between deteriorating cardiac disease and increasing total FETCH score, with decreasing FETCH score found in the population of dogs for which International Small Animal Cardiac Health Council (ISACHC)37 classification improved over the study period. Our findings were reflective of this, with higher scores found in dogs with ACVIM stage D (ISACHC stage 3) disease than in dogs with stage C (ISACHC stage 2) disease.
The median FETCH score of the population studied by Freeman et al25 was 7, which was comparable to the median score of 7.5 found at T1 in our study. This finding was expected, as > 75% of the animals in that study were classified as ISACHC stage 1a or 1b disease (ie, dogs without clinical signs, with or without cardiomegaly, respectively), which was consistent with the degree of disease in our postoperative population. In our population, only 1 dog had clinical signs of heart failure at T3 and was lost to follow-up thereafter. All other dogs would be classified as ISACHC stage 1a or 1b disease.
Significant improvements in respiratory abnormalities (wheezing and dyspnea) were reported between 1 and up to 12 months postoperatively in our study. Successful MVR abolishes or minimizes the mitral regurgitant jet severity, leading to a reversal of cardiac remodeling and subsequent improvement in clinical signs relating to pulmonary edema.10
Similarly, improvement in coughing was seen throughout the study period. The etiology of cough in dogs with MMVD is multifactorial, particularly in small-breed dogs that are predisposed to airway diseases such as tracheal collapse. One study38 found that the presence of cardiogenic pulmonary edema was not a risk factor for cough in dogs with MMVD, although left atrial enlargement was significantly associated with coughing. A second study39 failed to demonstrate a difference in the severity of airway collapse between dogs with severe or negligible left atrial enlargement. That study also demonstrated left cranial lobar bronchial collapse in all dogs and left caudal and right middle lobar bronchial collapse in most. Thus, it was suggested that in most dogs with MMVD, coughing is likely secondary to concomitant respiratory disease, such as generalized tracheobronchomalacia.
Fatigue and the need to rest during walks did not significantly improve between the preoperative and 1-month postoperative time points in the present study, but an improvement was seen from 1 month and up to 6 months postoperatively for the latter and up to 12 months postoperatively for the former. The delay in improvement may relate to postoperative exercise restrictions and soft tissue healing in the immediate postoperative period. Difficulty in using stairs improved between all time points throughout the study period, which could suggest an earlier improvement in ability to perform light exercise. In human patients, significant increases in maximal oxygen intake, peak oxygen pulse, and maximal exercise tolerance capacity have been demonstrated by 4 months after MVR.40
Some of our results were not anticipated. For example, both sleep disruptions and inability to find a comfortable position when resting significantly improved up to 6 months after surgery. These findings are interesting because the impact of chronic disease on sleep quality is rarely discussed in veterinary medicine, although it is being given increasing consideration in relation to brachycephalic dogs.41 The influence of certain chronic diseases on sleep quality is well recognized in human medicine, with up to 56% of heart failure patients reporting sleeping difficulties.42 Central sleep apnea is reported in over a third of patients with CHF and is associated with an increased mortality rate.43 In this syndrome, stretching of the pulmonary J receptors owing to pulmonary edema leads to dysregulation of Paco2, cyclic periods of apnea, and subsequent disturbed rest.44 A similar syndrome has not yet been characterized in dogs but could account for part of the increase in preoperative sleep disturbances reported between dogs with stage D versus stage C disease. This finding further highlights the importance of studies assessing HRQoL in dogs. Equally, although the impact of periuria did not change significantly throughout the study period, diuretic treatment had been withdrawn in nearly all dogs by the time of discharge, and a reduced frequency of nocturia may have contributed to these findings.
Equally interesting were the trends in improving irritability during the first month after surgery and improvement in dullness over the entire study period. These results are likely to be multifactorial, with better sleep quality, reduced postoperative discomfort, reduced need for medication, and resolution of preoperative clinical signs all playing a role. In human patients with cardiovascular disease, mood changes are commonly reported, and the prevalence of depression is twice that in the general population.45 Previous human studies have reported depression in up to 48% of patients with heart failure46 and increased feelings of irritability and sadness in 50% and 80%, respectively.47
It is noteworthy that there was no significant improvement in total FETCH scores after the 3-month time point in the present study, although scores for many individual questions did significantly improve between time points throughout the follow-up period, indicating ongoing improvement in HRQoL in more specific areas. In a study48 of human patients undergoing MVR or mitral valve replacement, significant improvements in both physical and psychological parameters were seen between the 3- and 12-month postoperative time points. This continued improvement may be due to physiological factors, such as ongoing cardiac remodeling, or management factors, such as exercise restrictions being lifted and home care becoming less intense.
Comparison of scores at T0 between dogs with stage C and stage D disease in the present study confirmed the greater impact on overall HRQoL and various components of HRQoL in dogs with more severe disease, as would be expected. Interestingly, we found that by 1 month after surgery, there were no differences in individual question or total scores between dogs with stage C versus stage D disease, and this did not change throughout the course of the study. This suggests that the impact of MVR in terms of improved HRQoL is not affected by disease stage, although the immediate postoperative survival rate is lower for dogs with stage D disease compared with stage C disease.11 This finding may help guide owners of dogs in more advanced stages of disease, although results need to be interpreted in light of the inherent study limitations and in combination with data on survival and complication rates.
There were several limitations of the present study. In veterinary medicine, as in pediatrics, we must rely on secondary assessments of HRQoL, which in this case involved owner evaluations. This requires that owners accurately identify the severity of the disease’s impact on their pet’s HRQoL. In dogs with more slowly progressing disease, the true impact on HRQoL immediately after surgery may have been underestimated. Furthermore, MMVD is typically a disease of middle-aged to older dogs, and the impact of progressing age and comorbidities could potentially be a confounding factor. However, the impact of this when comparing different time points was minimized in this study by using each dog as its own control. It should also be noted that owing to the high financial and temporal commitments necessitated by surgery, the population of owners in this study may not reflect the general population. This likely impacted the reported FETCH scores, and results must be extrapolated with this in mind.
Likewise, because we did not define terms used in the questionnaire, owner interpretation of certain terms may have varied. For example, owners were asked to score the impact of irritability and reduction in “peppiness” on their pet’s quality of life. Again, because dogs were used as their own controls, the impact of variability in owner interpretation as well as dog personality was reduced. However, this does limit our ability to compare scores between individuals.
As with all studies relying on questionnaire completion, the response rate in the present study was not 100%, and it is possible that a selection bias existed, either with owners more likely to fill in the questionnaire if their dog was clinically better or more likely to fill in the questionnaire if their dog was doing less well clinically.
It is beyond the scope of this study to assess HRQoL changes in the more immediate postoperative period and, thus, to investigate the negative impact on HRQoL expected from surgical trauma and postoperative hospitalization. Further tools would need to be designed and validated to assess this in the future for MVR as well as for other interventions.
Further work to assess postoperative HRQoL following MVR in dogs may involve comparing the FETCH questionnaire results with results for a control population of age- and breed-matched dogs without MMVD to evaluate whether HRQoL in dogs undergoing MVR returns to a baseline of normal postoperatively.
This was, to our knowledge, the first study to investigate the impact of MVR on changes in HRQoL and provides useful information for owners and veterinarians when considering this surgery. Furthermore, as different modalities for canine MMVD management become available, this questionnaire could serve as a tool to help aid comparisons between techniques in the future.
Acknowledgments
No third-party funding or support was received in connection with this study or the writing or publication of the manuscript. The authors declare that there were no conflicts of interest.
The authors thank Alison Young and Sarah Carey for assistance with data collection. The authors would also like to thank all of the clinicians, nurses and referring veterinarians involved in the management and care of these patients, as well as all the owners.
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