Combination Therapy with Digoxin and Diltiazem Controls Ventricular Rate in Chronic Atrial Fibrillation in Dogs Better than Digoxin or Diltiazem Monotherapy: A Randomized Crossover Study in 18 Dogs

Background: Atrial fibrillation (AF) with excessively high ventricular rates (VR) occurs in dogs with advanced heart disease. Rate control improves clinical signs in these patients. Optimal drug therapy and target VR remain poorly defined.
Hypothesis: Digoxin-diltiazem combination therapy reduces VR more than either drug alone in dogs with high VR AF.
Animals: Eighteen client-owned dogs (>15 kg) with advanced heart disease, AF, and average VR on 24-hour Holter > 140 beats per minute (bpm).
Methods: After baseline Holter recording, dogs were randomized to digoxin or diltiazem monotherapy, or combination therapy. Repeat Holter evaluation was obtained after 2 weeks; dogs were then crossed over to the other arm (monotherapy or combination therapy) for 2 weeks and a third Holter was acquired. Twenty-four hour average VR, absolute and relative VR changes from baseline, and percent time spent within prespecified VR ranges (>140, 100–140, and <100 bpm) were compared. Correlations between serum drug concentrations and VR were examined.
Results: Digoxin (median, 164 bpm) and diltiazem (median, 158 bpm) decreased VR from baseline (median, 194 bpm) less than the digoxin-diltiazem combination (median, 126 bpm) ( P < .008 for each comparison). With digoxin-diltiazem, VR remained <140 bpm for 85% of the recording period, but remained >140 bpm for 88% of the recording period with either monotherapy. Serum drug concentrations did not correlate with VR.
Conclusions and Clinical Importance: At the dosages used in this study, digoxin-diltiazem combination therapy provided a greater rate control than either drug alone in dogs with AF.     

Twenty-Four-Hour Ambulatory Electrocardiography in Normal Cats

Twenty-four-hour ambulatory electrocardiograms were recorded in two age groups of 10 normal cats each: group 1 (1 to 4 years) and group 2 (8 to 14 years), with equal numbers of males and females in each group. Average heart rates over the 24-hour recording period ranged from 114 to 202 beats/minute (bpm). The mean 24-hour average rate did not differ between group 1 and group 2 (157.6 vs. 156.3+/-5.3 bpm, respectively); however, females (both groups combined) had higher average heart rates than males (166.8 vs. 147.1+/-5.3 bpm, respectively). Females also had a higher mean minimum heart rate than males (116.9 vs. 96.5+/-4.2 bpm, respectively); but there were no gender or age group differences in maximum heart rate. Results of hourly analyses of average, minimum, and maximum heart rates were similar. Mean heart rates rose from mid-afternoon to about 9:00 PM and were lowest just after midnight. Although regular sinus rhythm predominated, periods of sinus arrhythmia were evident in most cats, especially in early morning hours. Supraventricular extrasystoles were uncommon. Isolated ventricular extrasystoles occurred more frequently in group 2 cats; multiform configuration was observed in both groups. Repetitive ventricular extrasystoles, which usually consisted of occasional couplets, occurred more frequently in group 2 cats. One older cat had 2 short runs of ventricular tachycardia. Another older cat appeared to have a recurrent accelerated idioventricular rhythm.     

Heart rate turbulence after ventricular premature beats in healthy Doberman pinschers and those with dilated cardiomyopathy

Objectives

To describe the measurement of heart rate turbulence (HRT) after ventricular premature beats and compare HRT in healthy Doberman pinschers and those with dilated cardiomyopathy (DCM), with and without congestive heart failure (CHF).

Size and Shape of Right Heart Chambers in Mitral Valve Regurgitation in Small-Breed Dogs

Background: The contribution of right heart (RH) chamber enlargement to general heart enlargement seen on thoracic radiographs in mitral regurgitation (MR) is not known.
Objectives: To determine the size and shape of the RH chambers in normal dogs and dogs with varying degrees of MR.
Animals: Fifty-four privately owned dogs: 13 normal, 41 with varying degrees of MR including 25 with congestive heart failure (CHF).
Methods: Archived first pass radionuclide angiocardiograms were used to produce static images of the RH and left heart (LH) chambers. Indexes of size and shape of the RH and LH chambers were related to severity of MR determined by heart rate-normalized pulmonary transit time (nPTT), vertebral heart scale (VHS), and clinical status. RH shape was measured by a circularity index of RH short axis/long axis.
Results: A 2nd degree polynomial fit best described the ratios; RH/LH dimension to nPTT ( R ²= 0.62) and to VHS ( R ²= 0.43), RH/LH area to nPTT ( R ²= 0.64) and to VHS ( R ²= 0.58), all P < .001. RH circularity was decreased in CHF, P < .001. In CHF, the RH chambers of 16 dogs were both flattened and enlarged, whereas 9 had convex septal borders.
Conclusions: RH chambers are not significantly dilated in dogs with mild to moderate MR without CHF. In CHF, RH chambers enlarge and also may be compressed by the LH chambers. Pulmonary hypertension probably is present in some dogs with CHF. Increased sternal contact is not a useful sign of right-sided heart dilatation in MR.     

Effect of Transvenous Electrical Cardioversion on Plasma Cardiac Troponin I Concentrations in Horses with Atrial Fibrillation

Background: Whether electrical cardioversion of cardiac arrhythmias results in cardiomyocyte damage is unknown.
Objective: To describe effect of transvenous electrical cardioversion (TVEC) on plasma cardiac troponin I (cTnI) concentration in horses.
Animals: All horses presented to the Cornell University Hospital for Animals for cardioversion of atrial fibrillation between May 2006 and October 2008 were eligible for inclusion in the study. Owners of 14 horses elected for TVEC and each horse was then enrolled (16 procedures).
Methods: Prospective observational study measuring concentrations of plasma cTnI before and after TVEC.
Results: Median cTnI concentration increased from 0.045 ng/mL at baseline (range 0.0–0.20 ng/mL) to 0.11 ng/mL after TVEC (range 0.0–3.73 ng/mL) ( P = .036). This increase was not associated with the number of shocks delivered, maximal energy delivered, cumulative energy delivered, chronicity of atrial fibrillation before cardioversion, or positioning of the pulmonary artery catheter.
Conclusions: The increase in cTnI is unlikely to be clinically important. The increase might be correlated with persistent atrial dysfunction after TVEC, suggesting that a longer convalescent period after the procedure could be warranted.     

Efficacy of Spironolactone on Survival in Dogs with Naturally Occurring Mitral Regurgitation Caused by Myxomatous Mitral Valve Disease

Background: Spironolactone, an aldosterone antagonist, has been demonstrated to decrease mortality in human patients when added to other cardiac therapies. Hypothesis: Spironolactone in addition to conventional therapy increases survival compared with conventional therapy in dogs with naturally occurring myxomatous mitral valve disease (MMVD). Animals: Between February 2003 and March 2005, 221 dogs were recruited in Europe. Nine dogs were excluded from analysis, leaving 212 dogs with moderate to severe mitral regurgitation (MR) caused by MMVD (International Small Animal Cardiac Health Council classification classes II [n = 190] and III [n = 21]). Methods: Double‐blinded, field study conducted with dogs randomized to receive either spironolactone (2 mg/kg once a day) or placebo in addition to conventional therapy (angiotensin converting enzyme inhibitor, plus furosemide and digoxin if needed). Primary endpoint was a composite of cardiac‐related death, euthanasia, or severe worsening of MR. Results: Primary endpoint reached by 11/102 dogs (10.8%) in the spironolactone group (6 deaths, 5 worsening) versus 28/110 (25.5%) in control group (14 deaths, 8 euthanasia, 6 worsening). Risk of reaching the composite endpoint significantly decreased by 55% (hazard ratio [HR] = 0.45; 95% confidence limits [CL], 0.22–0.90; log rank test, P= .017). Risk of cardiac‐ related death or euthanasia significantly reduced by 69% (HR = 0.31; 95% CL, 0.13–0.76; P= .0071). Number of dogs not completing the study for cardiac and other miscellaneous reasons similar in spironolactone (67/102) and control groups (66/110). Conclusion and Clinical Importance: Spironolactone added to conventional cardiac therapy decreases the risk of reaching the primary endpoint (ie, cardiac‐related death, euthanasia, or severe worsening) in dogs with moderate to severe MR caused by MMVD.     

Evaluation of a technique to measure heart rate variability in anaesthetised cats

Analysis of heart rate (HR) and heart rate variability (HRV) are powerful tools to investigate cardiac diseases, but current methods, including 24-h Holter monitoring, can be cumbersome and may be compromised by movement artefact. A commercially available data capture and analysis system was used in anaesthetised healthy cats to measure HR and HRV during pharmacological manipulation of HR. Seven healthy cats were subjected to a randomised crossover study design with a 7 day washout period between two treatment groups, placebo and atenolol (1 mg/kg, IV), with the efficacy of atenolol to inhibit β₁ adrenoreceptors challenged by epinephrine. Statistical significance for the epinephrine challenge was set at P < 0.0027 (Holm–Bonferroni correction), whereas a level of significance of P < 0.05 was set for other variables.Analysis of the continuous electrocardiography (ECG) recordings showed that epinephrine challenge increased HR in the placebo group (P = 0.0003) but not in the atenolol group. The change in HR was greater in the placebo group than in the atenolol group (P = 0.0004). Therefore, compared to cats pre-treated with placebo, pre-treatment with atenolol significantly antagonised the tachycardia while not significantly affecting HRV. The increased HR in the placebo group following epinephrine challenge was consistent with a shift of the sympathovagal balance towards a predominantly sympathetic tone. However, the small (but not significant at the critical value) decrease in the normalised high-frequency component (HF_norm) in both groups of cats suggested that epinephrine induced a parasympathetic withdrawal in addition to sympathetic enhancement (increased normalised low frequency component or LF_norm). In conclusion, this model is a highly sensitive and repeatable model to investigate HRV in anaesthetised cats that would be useful in the laboratory setting for short-term investigation of cardiovascular disease and subtle responses to pharmacological agents in this species.     

Association of Tricuspid Annular Plane Systolic Excursion with Survival Time in Boxer Dogs with Ventricular Arrhythmias

Background

Tricuspid annular plane systolic excursion (TAPSE) is a useful estimate of right ventricular function in humans. Reference intervals for dogs have been generated, but the value of measuring TAPSE in other diseases, or investigating the association between TAPSE and outcome, is unknown.

Hypothesis

TAPSE is lower in Boxer dogs with ≥50 VPCs/24 h on Holter than in dogs with fewer ventricular ectopics, and lower TAPSE is associated with a shorter survival time.

Animals

Fifty Boxer dogs that presented for investigation of syncope or suspected arrhythmogenic right ventricular cardiomyopathy (ARVC) at a veterinary teaching hospital (2004–2011).

Methods

Retrospective study. Clinical records, Holter, and echocardiographic data were reviewed. TAPSE was measured in a blinded manner on stored echocardiographic cine‐loops using anatomic M‐mode. Outcome information was obtained and death was classified as cardiac or noncardiac. Survival analysis was performed using Kaplan‐Meier curves and Cox proportional hazards models.

Results

TAPSE was lower in Boxers with ≥50 VPCs/24 h (13.9 ± 4.04 mm) than Boxers with <50 VPCs/24 h (16.8 ± 3.21 mm; P < .001). TAPSE <15.1 mm was associated with shorter cardiac survival time in all dogs (P = .004) and also in dogs without left ventricular dysfunction (P = .035). When controlling for other variables, including ventricular tachycardia on Holter and left ventricular systolic dysfunction, multivariable analysis showed that TAPSE remained an independent predictor of time to cardiac death (HR >4.09, 95%CI 1.15–16.9, P < .029).

Conclusions and Clinical Importance

TAPSE offers prognostic value for Boxer dogs, including those with apparently normal systolic function and ≥50 VPCs/24 h on Holter analysis.     

Longitudinal Electrocardiographic Evaluation of Dogs with Degenerative Mitral Valve Disease

Background

Increased heart rate (HR) and decreased heart rate variability (HRV) are evident in some dogs with degenerative mitral valve disease (DMVD).

Objectives

Evaluation of the factors influencing HR and HRV (assessed by the vasovagal tonus index; VVTI) and their change over time in dogs with DMVD.

Animals

Client‐owned dogs (n = 257) with DMVD recruited from first opinion practice.

Methods

Prospective longitudinal follow‐up at six‐monthly intervals of dogs with DMVD. Dogs followed up for at least 18 months (n = 102) were grouped according to their outcome as dogs dying/euthanized because of cardiac disease (n = 28; Group 1), noncardiac disease (n = 40; Group 2) and dogs alive (n = 34; Group 3). HR and VVTI were measured on 1‐minute ECG recordings. Repeated measures linear models were constructed to investigate the factors that influence HR and VVTI and their changes over time.

Results

Heart rate and VVTI were affected by disease severity and were different in Cavaliers compared to other breeds. Group 1 and Group 2 dogs underwent an increase in HR and decrease in VVTI, evident at least 18 months before death. Group 1 had a further decrease in VVTI followed by an increase in HR approximately 1 year and 6 months before death, respectively.

Conclusions and Clinical Importance

Dogs with DMVD have an increase in HR and decrease in HRV over a year before death, with greater changes in those dogs dying/euthanized because of cardiac disease. Both HR and VVTI can potentially be regarded as biomarkers for all‐cause mortality.     

棉籽糖对东方蜜蜂存活率的影响

用不同浓度棉籽糖的蔗糖溶液与纯蔗糖溶液分别饲喂东方蜜蜂（Apiscerana）,比较棉籽糖及其不同浓度对东方蜜蜂存活情况的影响,结果表明：对照组蜜蜂的平均寿命（6．49±0．23d）显著高于试验组;用不同浓度的棉籽糖饲喂蜜蜂,其中在5％棉籽糖条件下,蜜蜂的平均寿命最短（2．63±0．21d）,而在1％棉籽糖条件下最长（5．01±0．19d）,二者差异显著。用5％棉籽糖饲喂蜜蜂时,其存活率下降最快,在5d内全部死亡。     

Acute Effect of Pimobendan and Furosemide on the Circulating Renin-Angiotensin-Aldosterone System in Healthy Dogs

Background: The renin-angiotensin-aldosterone system (RAAS) is activated in states of decreased cardiac output and by certain cardiovascular therapeutic agents, such as loop diuretics and vasodilators.
Hypothesis: Short-term treatment with the inodilator, pimobendan, will not activate the circulating RAAS because its vasodilatory action will be offset by its positive inotropic property, thereby ameliorating RAAS stimulation at the juxtaglomerular apparatus. Furthermore, pimobendan will suppress RAAS activation produced by furosemide.
Animals: Nine healthy laboratory dogs were used in this study.
Methods: Experimental, cross-over study. Dogs were administered pimobendan (0.5 mg/kg q12h) for 4 days followed by furosemide (2 mg/kg q12h) and then, after a wash-out period, a combination of the drugs. Aldosterone : creatinine (A : Cr) was measured at the end of each treatment cycle.
Results: There was no significant increase in the average urinary A : Cr with the administration of pimobendan (control urinary A : Cr = 0.46, standard deviation (SD) 0.33; pimobendan A : Cr = 0.48, SD 0.28). There was a significant increase in the average urinary A : Cr after administration of furosemide (urinary A : Cr = 1.3, SD 0.70) and with the combination of furosemide and pimobendan (urinary A : Cr = 2.9, SD 1.6).
Conclusions and Clinical Relevance: Short-term administration of high-dose pimobendan, does not activate the RAAS in healthy dogs. Pimobendan did not prevent RAAS activation associated with furosemide therapy. These results in healthy dogs suggest that furosemide therapy, with or without pimobendan, should be accompanied by RAAS suppressive therapy.     

Heart rate and arrhythmia frequency of normal cats compared to cats with asymptomatic hypertrophic cardiomyopathy

ObjectivesTo compare heart rate and arrhythmia frequency and complexity in a normal population of cats to a population of cats with hypertrophic cardiomyopathy (HCM).Animals17 cats with HCM and 15 cats with normal echocardiograms.MethodsResults for echocardiography, electrocardiography, Doppler blood pressure, and 24-h Holter monitoring were compared between groups.ResultsThere was no difference in heart rate between HCM cats and normal cats regardless of modality used. All (17/17) HCM cats had ventricular arrhythmias (geometric mean 124 complexes/24 h) with 82% (14/17) exhibiting complex arrhythmias (couplets, triplets, or ventricular tachycardia). Most (14/15) normal cats had ventricular arrhythmias (geometric mean 4 complexes/24 h), but only 20% (3/15) exhibited complexity. HCM cats had significantly more total ventricular complexes, ventricular premature complexes and accelerated idioventricular rhythm than normal cats (P < 0.0001, P < 0.0001, and P = 0.01, respectively). Eighty eight percent (15/17) of HCM cats had supraventricular arrhythmias (geometric mean 9 complexes/24 h) with 23% (4/17) exhibiting complexity. Sixty percent (9/15) of normal cats had supraventricular arrhythmias (geometric mean 1 complex/24 h) with 13% (2/15) exhibiting complexity. Cats with hypertrophic cardiomyopathy had significantly more supraventricular complexes than normal cats (P = 0.0148).ConclusionCats with asymptomatic HCM have more frequent and complex ventricular and supraventricular arrhythmias than normal cats but do not have different overall heart rates compared to normal cats. Further studies are needed to determine if these arrhythmias are associated with an increased risk of sudden cardiac death or influence long-term survival.