The longitudinal outcome of canine (K9) myxomatous mitral valve disease (LOOK-Mitral) registry: Baseline treatment characteristics.

OBJECTIVES: To describe the medical treatment prescribed or modified by veterinary cardiologists at the enrollment visit in dogs included in the longitudinal outcome of canine (K9) myxomatous mitral valve disease (MMVD) registry (LOOK-mitral registry) and to evaluate the influence of the EPIC trial and other selected variables on cardiologist prescription habits. ANIMALS: The medical records of 6,102 dogs enrolled in the LOOK_mitral registry between 2015 and 2018 were retrospectively reviewed and 6,016 dogs were included. RESULTS: A medical treatment was prescribed by a cardiologist to 2,599 dogs (15% Stage-B1, 90% Stage-B2 and to all dogs in Stage-C). Angiotensin converting enzyme inhibitors (Ace-i) were the treatment most commonly prescribed for dogs in Stage-B1 (n = 352, 9%). The combination of pimobendan and an Ace-i was the most common treatment in Stage-B2 dogs (n = 367, 41%). Furosemide, an Ace-i, and pimobendan was the most common cardiac medical treatment prescribed for ACVIM Stage-C dogs (n = 704, 57%). Within each stage, dogs with larger left atrial and left ventricular dimensions were more likely to receive Ace-i, pimobendan or spironolactone. There was a four-fold increase in pimobendan prescription in Stage-B2 dogs after the publication of the EPIC trial. Moreover, a 15% reduction in Ace-i prescription and a 30% reduction in spironolactone prescription occurred after EPIC. In 974 dogs, a medical treatment was prescribed by the referring veterinarian. This was not changed (12%), modified (74%), or discontinued (14%) by the cardiologist. CONCLUSIONS: The EPIC trial and the echocardiographic assessment of left atrial and ventricular dimensions influence cardiologists' prescription habits.

The Longitudinal Outcome Of Canine (K9) myxomatous mitral valve disease (LOOK-Mitral registry): Baseline characteristics.

INTRODUCTION: The Longitudinal Outcome Of Canine (K9) myxomatous mitral valve disease (MMVD) registry (LOOK-Mitral registry) was established to describe the natural history and predictors of outcome in dogs affected by MMVD. This study was intended to describe the baseline characteristics of dogs in the LOOK-mitral registry. ANIMALS: Dogs with echocardiographic evidence of MMVD were prospectively enrolled by thirteen referral centers. RESULTS: A total of 6102 dogs with MMVD were included. The median age was 10 years (1-19 years), and mixed breed was the most common breed (n = 1,360, 22%). Concomitant diseases were reported in 2459 dogs with chronic respiratory diseases occurring most frequently (14%), followed by the presence of azotemia (6%) and orthopedic diseases (5%). Regarding disease severity, 65% of dogs were in ACVIM Stage-B1, 15% in Stage-B2, and 20% in Stage-C. Dogs in Stage-B1 were younger (p<0.001) than dogs in other stages. Murmur intensity, heart rate during physical examination, and radiographic vertebral heart score were positively associated with the stage. Dogs in Stage-C were more likely to have tachypnea (p<0.001), dyspnea (p<0.001), cough (p<0.001), syncopal episodes (p<0.001), and tachyarrhythmias (p<0.001) compared to dogs in Stage-B1 and B2. Echocardiographic indices of left atrial and ventricular size were positively correlated with the ACVIM stage. Interestingly, 4% of dogs that weighed <20 kg had an increased normalized end-systolic left ventricle internal diameter (>1.26). CONCLUSIONS: This study contributes to a better understanding of the clinical characteristics of dogs affected by MMVD and provides new findings that may be of clinical relevance.

Accuracy of echocardiographically estimated pulmonary artery pressure in dogs with myxomatous mitral valve disease.

INTRODUCTION: Echocardiographically identified pulmonary hypertension is an independent predictor of poor outcome in dogs affected by myxomatous valvular degeneration (MMVD). Systolic pulmonary arterial pressure is routinely estimated based on its relationship with the Doppler-determined velocity of tricuspid regurgitation as defined by the simplified Bernoulli equation (sPAP_D). Experimental studies suggest that the method is imperfect, but its accuracy in dogs with MMVD is not known. ANIMALS: Twenty dogs affected by MMVD that had cardiac remodeling and measurable tricuspid regurgitation. METHODS: A flow-directed thermodilution monitoring catheter was percutaneously placed in the right external jugular vein and advanced to the main pulmonary artery. Pulmonary arterial systolic pressure was recorded (systolic pulmonary arterial pressure obtained by right heart catheterization [sPAP_C]). A second operator contemporaneously acquired tricuspid regurgitant velocity spectra to calculate sPAP_D. Each operator was blinded to the result of the other techniques. RESULTS: Technical difficulties prevented the analysis of catheterization data in two dogs. Eighteen measurement pairs were therefore used for comparison of sPAP_C and sPAP_D through correlation and Bland-Altman analysis. A statistically significant bias between sPAP_C and sPAP_D (mean difference = 0.5 mmHg; confidence interval = -6.5 mmHg, +7.5 mmHg) was not detected. The interval of agreement between the techniques was wide (-27.3 mmHg, +28.2 mmHg). A significant linear association between the two techniques was not identified (r = 0.11, p=0.17). CONCLUSION: Echocardiographically estimated pulmonary artery pressure poorly agrees with sPAP_C measurement in dogs affected by MMVD and cardiac remodeling with or without previously diagnosed congestive heart failure. In these dogs, sPAP_D could under- or over-estimate sPAP_C by more than 20 mmHg, and therefore caution should be used when interpreting sPAP_D.

Predictors of reoccurrence of congestive signs within 180 days after successful treatment of the first episode of congestive heart failure in dogs with myxomatous mitral valve disease.

INTRODUCTION: Myxomatous mitral valve disease (MMVD) is the most common cause of left-sided congestive heart failure in dogs. We sought to identify predictors of first reoccurrence of congestive signs (CS) within 180 days in dogs with MMVD and clinically stable heart failure. ANIMALS: A total of 445 dogs affected by stable American College of Veterinary Internal Medicine (ACVIM)-Stage-C MMVD were included, 106 in the reoccurrence group (RG) and 339 in no reoccurrence group (NRG). Patients were considered "stable" if medical treatment had been unchanged for at least 4 weeks since the first identification of CS. METHODS: Medical records of dogs with stable ACVIM-Stage-C MMVD included in a registry of dogs affected by MMVD were reviewed. Follow-up was required for inclusion in this investigation. Logistic regression was used to identify clinical and echocardiographic variables that independently predict first reoccurrence of CS. RESULTS: Baseline left atrial-aortic ratio (p=0.022, OR: 1.89, 90% CI: 1.20-2.98), left ventricular internal diameter at end-diastole (LVIDd_N) (p=0.014, OR: 2.84, 90% CI: 1.41-5.77), peak velocity of early diastolic transmitral flow (p=0.049, OR: 1.81, 90% CI: 1.10-3.00) and furosemide daily dosage (p=0.039, OR: 1.19, 90% CI: 1.04-1.37) were associated with reoccurrence of CS in univariable analyses. The LVIDd_N (p=0.014) remained significant in the multivariable analysis, but the area under the receiver operator characteristic curve was 0.57. CONCLUSION: This study failed to identify accurate predictors of reoccurrence of CS. However, dogs with larger value of LVIDd_N are more likely to have reoccurrence of CS within 180 days.

Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study.

BACKGROUND: Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described. OBJECTIVES: To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF. ANIMALS: Three hundred and fifty-four dogs with MMVD and cardiomegaly. MATERIALS AND METHODS: Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored. RESULTS: At day 35, heart size had reduced in the pimobendan group: median change in (Δ) LVIDDN -0.06 (IQR: -0.15 to +0.02), P < 0.0001, and LA:Ao -0.08 (IQR: -0.23 to +0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in ΔLVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in ΔLA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo.

Endometriosis fertility index predicts live births following surgical resection of moderate and severe endometriosis.

STUDY QUESTION: Can live birth be accurately predicted following surgical resection of moderate-severe (Stage III-IV) endometriosis? SUMMARY ANSWER: Live births can accurately be predicted with the endometriosis fertility index (EFI), with adnexal function being the most important factor to predict non-assisted reproductive technology (non-ART) fertility or the requirement for ART (www.endometriosisefi.com). WHAT IS KNOWN ALREADY: Fertility prognosis is important to many women with severe endometriosis. Controversy persists regarding optimal post-operative management to achieve pregnancy and the counselling of patients regarding duration of conventional treatments before undergoing ART. The EFI is reported to correlate with expectant management pregnancy rate, although external validation has been performed without specifically addressing fertility in women with moderate and severe endometriosis. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study of 279 women from September 2001 to June 2016. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: We included women undergoing laparoscopic resection of Stage III-IV endometriosis who attempted pregnancy post-operatively. The EFI was calculated based on detailed operative reports and surgical images. Fertility outcomes were obtained by direct patient contact. Kaplan-Meier model, log rank test and Cox regression were used for analyses. MAIN RESULTS AND THE ROLE OF CHANCE: The follow-up rate was 84% with a mean duration of 4.1 years. A total of 147 women (63%) had a live birth following surgery, 94 of them (64%) without ART. The EFI was highly associated with live births (P < 0.001): for women with an EFI of 0-2 the estimated cumulative non-ART live birth rate at five years was 0% and steadily increased up to 91% with an EFI of 9-10, while the proportion of women who attempted ART and had a live birth, steadily increased from 38 to 71% among the same EFI strata (P = 0.1). A low least function score was the most significant predictor of failure (P = 0.003), followed by having had a previous resection (P = 0.019) or incomplete resection (P = 0.028), being older than 40 compared to <35 years of age (P = 0.027), and having leiomyomas (P = 0.037). LIMITATIONS REASONS FOR CAUTION: The main limitation of this study is its retrospective design. Imprecision was higher with low EFI due to smaller sample size in this subgroup. Finally, the EFI is somewhat subjective and could be prone to intra- and inter-observer variations. WIDER IMPLICATIONS OF THE FINDINGS: Women with a high EFI score have excellent fertility prognosis and may be advised to try to become pregnant with timed intercourse compared to women with a low score, for which prompt referral to ART seems more reasonable. Other prognostic factors can be used to guide the management of women with an intermediate EFI score. These data follow women over many years post-resection and represent longitudinal fertility data rarely demonstrated in such a cohort. The location and impact of lesions on the ability of the adnexa to function seems crucial for the fertility prognosis and should be further investigated. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the GRACE Research funds. S.M.-L. is the recipient of a Training Award from the Fonds de Recherche Quebec-Sante. D.A. is the primary author of the Endometriosis Fertility Index. All authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Mitral valve repair in dogs using an ePTFE chordal implantation device: a pilot study.

OBJECTIVE: Mitral valve (MV) regurgitation due to degenerative MV disease is the leading cause of cardiac death in dogs. We carried out preliminary experiments to determine the feasibility and short-term effects of beating-heart MV repair using an expanded polytetrafluorethylene (ePTFE) chordal implantation device (Harpoon TSD-5) in dogs. ANIMALS: This study involved six healthy purpose-bred Beagles (weight range 8.9-11.4 kg). MATERIAL AND METHODS: Following a mini-thoracotomy performed under general anesthesia, the TSD-5 was used to place 1 or 2 artificial ePTFE cords on the anterior MV leaflet or the posterior MV leaflet via a left-ventricular transapical approach. The procedure was guided and monitored by transesophageal echocardiography. Postoperative antithrombotic treatment consisted of clopidogrel or a combination of clopidogrel and apixaban. Dogs were serially evaluated by transthoracic echocardiography at day 1, 7, 14, 21, and 30. The hearts were then examined for evaluation of tissues reactions and to detect signs of endothelialization. RESULTS: One or two chords were successfully implanted in five dogs. Four dogs completed the 30 days follow-up. One dog died intra-operatively because of aortic perforation. One dog died early post-operatively from a hemorrhagic pleural effusion attributed to overly aggressive antithrombotic treatment. One dog developed a thrombus surrounding both the knot and the synthetic cord. Postmortem exam confirmed secure placement of ePTFE knots in the mitral leaflets in all dogs and the presence of endothelialization of the knots and chords. CONCLUSIONS: These preliminary results demonstrate the feasibility of artificial chordal placement using an ePTFE cordal implantation device in dogs.

e-TC: Development and pilot testing of a web-based intervention to reduce anxiety and depression in survivors of testicular cancer.

e-TC is an online intervention designed to address common psychosocial concerns of testicular cancer survivors. It aims to reduce anxiety, depression and fear of cancer recurrence by providing evidence-based information and psychological intervention. This paper details the development and pilot testing of e-TC. During pilot testing, 25 men (with varying psychological profiles) who had completed treatment for testicular cancer, 6 months to 5 years ago (which had not recurred), used e-TC over a 10-week period and provided quantitative and qualitative feedback on the feasibility and acceptability of the programme. Six men also completed a qualitative interview to provide detailed feedback on their experiences using e-TC. Fourteen men (56%) completed at least 80% of the programme. Participants reported a high level of satisfaction with the programme. Men's limited time was a barrier to programme use and completion, and participants suggested that men with a more recent diagnosis and a higher level of distress may be more likely to engage with the programme. e-TC appears to be a feasible and acceptable online intervention for survivors of testicular cancer. Findings from this study are currently being used to refine e-TC and guide the design of a larger efficacy study.

Mitral valve morphology assessed by three-dimensional transthoracic echocardiography in healthy dogs and dogs with myxomatous mitral valve disease.

OBJECTIVE: To assess differences in morphology of the mitral valve (MV) between healthy dogs and dogs affected by myxomatous mitral valve disease (MMVD) using real-time transthoracic three-dimensional echocardiography (RT3DE). ANIMALS: Thirty-four were normal dogs and 79 dogs were affected by MMVD. METHODS: Real-time transthoracic three-dimensional echocardiography mitral datasets were digitally recorded and analyzed using dedicated software. The following variables were obtained and compared between healthy dogs and dogs with MMVD at different stages: antero-posterior annulus diameter, anterolateral-posteromedial annulus diameter, commissural diameter, annulus height, annulus circumference, annulus area, anterior leaflet length, anterior leaflet area, posterior leaflet length, posterior leaflet area, non-planar angle, annulus sphericity index, tenting height, tenting area, tenting volume, the ratio of annulus height and commissural diameter. RESULTS: Dogs with MMVD had a more circular MV annulus compared to healthy dogs as demonstrated by an increased annulus sphericity index (p=0.0179). Affected dogs had a less saddle-shaped MV manifest as a decreased annulus height to commissural width ratio (p=0.0004). Tenting height (p<0.0001), area (p<0.0001), and volume (p<0.0001) were less in affected dogs. CONCLUSIONS: Real-time transthoracic three-dimensional echocardiography analysis demonstrated that dogs affected by MMVD had a more circular and less saddle-shaped MV annulus, as well as reduced tenting height area and volume, compared to healthy dogs. Multiple variables differed between dogs at different stages of MMVD. Diagnostic and prognostic utility of these variables, and the significance of these changes in the pathogenesis and natural history of MMVD, require further attention.

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial.

BACKGROUND: Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. HYPOTHESIS/OBJECTIVES: Administration of pimobendan (0.4-0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac-related death, or euthanasia. ANIMALS: 360 client-owned dogs with MMVD with left atrial-to-aortic ratio ≥1.6, normalized left ventricular internal diameter in diastole ≥1.7, and vertebral heart sum >10.5. METHODS: Prospective, randomized, placebo-controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac-related death, or euthanasia. RESULTS: Median time to primary endpoint was 1228 days (95% CI: 856-NA) in the pimobendan group and 766 days (95% CI: 667-875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47-0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952-NA) in the pimobendan group and 902 days (95% CI: 747-1061) in the placebo group) (P = .012). CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit.

The effects and effectiveness of laparoscopic excision of endometriosis: a prospective study with 2-5 year follow-up.

BACKGROUND: This study investigates the outcomes for women up to 5 years after laparoscopic excision of endometriosis. METHODS: In this prospective observational cohort study, 254 women with chronic pelvic pain were referred to two units specializing in minimal access surgical management of endometriosis. Of these, 216 women underwent surgical assessment and 176 were confirmed to have endometriosis. Questionnaires and visual analogue scale (VAS) scores for dysmenorrhoea, non-menstrual pelvic pain, dyspareunia and dyschesia as well as quality of life instruments; the EQ-5Dindex and EQ-5Dvas, Short-Form 12 (SF-12) and sexual activity questionnaires were completed pre-operatively. Intra-operative details of revised American Fertility Society (rAFS) stage, site of disease, associated tests, duration of surgery and complications were noted. Follow-up was performed by postal questionnaire and chart review. For women who had further surgery, rAFS stage, site of disease, other procedures and histology were all recorded. RESULTS: Pain scores were all significantly reduced at 2-5 years for dysmenorrhoea (median VAS baseline versus follow-up 2-5 years); 9 versus 3.3 (P < 0.0001), non-menstrual pelvic pain 8 versus 3 (P < 0.0001), dyspareunia 7 versus 0 (P < 0.0001) and dyschesia 7 versus 2 (P < 0.0001). Quality of life was improved for the EQ-5Dindex (P = 0.008 and the EQ-5Qvas (P = 0.03) and for sexual function with pleasure (P = 0.001) and habit (P = 0.012) being improved and discomfort being decreased (P = 0.001). The chance of requiring further surgery as determined by the Kaplan-Meier survival curve was 36%. A rAFS score of >70 was predictive of requiring further surgery (P = 0.03). Of women who had further surgery, endometriosis was found histologically in 68%. CONCLUSIONS: Laparoscopic excision of endometriosis significantly reduces pain and improves quality of life for up to 5 years. The probability of requiring further surgery is 36%. Return of pain following laparoscopic excision is not always associated with clinical evidence of recurrence.

Usefulness of adenosine in augmenting ventricular preexcitation for noninvasive localization of accessory pathways.

Adenosine was administered to test the hypothesis that it would maximize preexcitation and facilitate noninvasive localization of accessory pathways in 22 patients with suspected accessory pathway-mediated tachycardias. Twelve-lead electrocardiograms and 2-dimensional echocardiograms were recorded at baseline and during adenosine-augmented ventricular preexcitation to localize the accessory pathway. Phase analysis was performed on digitized 4-chamber and short-axis views using a first harmonic Fourier transformation. At baseline, 15 patients had manifest preexcitation. In 14 of these patients (93.3%), preexcitation became more prominent after adenosine. Four patients without preexcitation at baseline clearly had it after adenosine. In patients who had preexcitation in response to adenosine, the electrocardiogram correctly identified the accessory pathway locations in 18 of 19 patients at a regional level and was incorrect in 1 of 19 patients. Echocardiographic phase analysis correctly identified the accessory pathway location in all 17 patients, who had technically adequate studies, at a regional level. In conclusion, administration of adenosine accentuates preexcitation, allowing for more accurate electrocardiographic and echocardiographic accessory pathway localization.

Late sequelae of penetrating cardiac wounds.

Physiological and psychological parameters of 20 survivors of penetrating wounds of the heart were examined 7 to 52 months after recovery. All survivors had cardiac complaints. The psychological parameters for hypochondriasis, compulsiveness, and internalization were much greater in the patients than in control subjects but were similar to those in victims of violent major abdominal trauma. Physiological abnormalities were present in 19, although no particular pattern or abnormality could be related with certainty to the type of wound, operative procedure, or postoperative course. One recovered and re-employed victim required late surgical repair of a traumatic ventricular septal defect and ventricular diverticulum. Although functional work capacity measured by stress testing was normal in 90 percent, only eight survivors resumed employment. Complete rehabilitation was impaired by a residual traumatic neurosis. Management goals for patients with penetrating cardiac wounds should be broadened to include prevention of psychological disabilities.