The efficacy and safety of milrinone for treating heart failure in dogs

Milrinone has been studied in a variety of situations. In experimental dogs it has been documented to increase contractility to a similar degree as beta-receptor agonists and to produce mild arteriolar dilation in dogs. In canine patients with heart failure, milrinone produces demonstrable improvement in echocardiographic ventricular function and hemodynamic variables. In addition, it improves clinical signs in these patients, improving their quality of life. Milrinone is superior to digoxin as evidenced by the improvement in clinical signs noted in dogs that were unresponsive or no longer responding to digoxin administration. There is no doubt that milrinone improves short-term prognosis and in so doing prolongs life. Many of the patients that the author has observed would not have gone home without the benefits of milrinone. Milrinone's effects on long-term survival cannot be assessed, but its effects on survival time are certainly not dramatic enough to be evident without a comparison population. Therefore, milrinone administration should be considered palliative, as is administration of all other cardiovascular medications for heart failure. In addition to its beneficial effects, milrinone also appears to be relatively safe when compared with the alternative of digoxin administration. Fatal events attributable to milrinone administration are rare, and those directly attributable to enhanced ventricular arrhythmia can generally be avoided by monitoring an electrocardiogram after initial milrinone administration commences. Milrinone does not increase the incidence of sudden death in Doberman Pinschers. It is possible that a small number of dogs with mitral regurgitation may develop mitral chordal rupture. For this reason and possibly others, milrinone probably will not be indicated in early heart failure due to mitral regurgitation when heart failure is readily responsive to diuretic administration. The risk-to-benefit ratio turns markedly in the favor of milrinone administration in the dog with mitral regurgitation that is partially or completely refractory to other cardiovascular drugs. Milrinone appears to be a more effective and safer positive inotrope for long-term treatment of dogs with congestive heart failure than drugs currently available. The author and all the investigators involved in the milrinone clinical trials hope that it will soon be available for use by the veterinary community.     

Effects of dopamine, dobutamine, amrinone and milrinone on regional blood flow in isoflurane anesthetized dogs

The effects of cyclic AMP increasing cardiotonics (dopamine, dobutamine, amrinone and milrinone) on the blood flow in most organs were compared using colored microsphere technique in isoflurane-anesthetized dogs. Dopamine increased blood flow in ventricular myocardium. Furthermore dopamine induced the increase in blood flow in intestine and kidney at low to middle dose, but not at high dose. Dobutamine induced the highest increase in blood flow in ventricular myocardium and skeletal muscle among the drugs evaluated at middle and high doses. Amrinone and milrinone increased blood flow in ventricular myocardium almost same with catecholamines, and milrinone decreased vascular resistance moderately in most other organs. Milrinone might be more useful than catecholamines for improvement of congestive heart failure or peripheral circulatory failure accompanied with exceeded vasoconstriction.     

Echocardiographic and clinical effects of milrinone in dogs with myocardial failure

Milrinone is a recently synthesized bypyridine compound with positive inotropic and arteriolar dilating properties in persons and experimental animals. To examine the efficacy and safety of milrinone to treat myocardial failure in dogs, dogs with myocardial failure were selected from the patient populations of 3 veterinary hospitals. Progressively increased dosages of milrinone, from 0.05 to 1.0 mg/kg of body weight, were administered over 14 days, and cardiac responses, as determined by M-mode echocardiography, and clinical responses were recorded. An effective dosage of milrinone was identified for each dog and administered for 4 weeks to evaluate the stability of the cardiac response. A randomized blinded study of drug vs nondrug capsule or nondrug elixer (designated placebo) was performed at the end of 4 weeks to eliminate possible effects of investigator bias or spontaneous regression of the disease. The duration of drug effect was determined by evaluating echocardiographic measurements of left ventricular function for 12 hours after drug administration. Echocardiographic evaluation of left ventricular function improved in dogs given milrinone. The effective dosage was between 0.5 and 1.0 mg/kg. Tolerance to milrinone did not develop during the 4-week study. In dogs given placebo during the randomized blinded study, echocardiographic values decreased significantly. Dogs that were given milrinone remained echocardiographically stable. During the study, 6 dogs improved clinically, 5 remained the same, 1 had a decrease in exercise tolerance, 1 died of severe heart failure, and 1 died of hypoadrenocorticism. Ventricular tachydysrhythmia was exacerbated in 2 dogs, but was not treated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of medical therapy on survival of patients with dilated cardiomyopathy.

Few studies have been conducted that focus on survival as the end point of medical therapy of CHF. No vigorous studies have been conducted in dogs. It is generally accepted that diuretic therapy is an essential component of the therapy of CHF in cardiomyopathic dogs. Significant symptomatic improvement is afforded by diuretics, and acute death may be prevented. In this context diuretics can be said to improve survival. However, diuretics do not alter the natural progression of cardiomyopathy and in this context do not favorably influence long-term survival. Digitalis glycosides have been shown in humans to improve various parameters of CHF in a subset of patients with either atrial fibrillation or third heart sounds. In dogs, these gallop heart rhythms due to third heart sounds are usually associated with myocardial failure due to dilated cardiomyopathy. In spite of symptomatic improvement, no study has demonstrated an unequivocal favorable effect of digoxin on survival of patients with dilated cardiomyopathy. Likewise, there is no convincing evidence of an adverse effect on survival. Newer, powerful inotropes, such as milrinone, often demonstrate impressive short-term improvements in left ventricular function, clinical signs, and exercise tolerance in patients with CHF. However, their long-term benefits are much less impressive, they are arrhythmogenic, and they have not been shown to prolong survival. In fact, long-term milrinone therapy in humans has had an unfavorable influence on mortality. Vasodilators offer the potential advantage of increasing left ventricular performance without an associated increase in myocardial oxygen demand and cardiac rhythm disturbances. The only vigorous survival study that unequivocally demonstrated improved survival of patients with advanced CHF due to myocardial failure, including dilated cardiomyopathy, was the Consensus Trial. Survival of patients receiving enalapril was significantly better than those receiving placebo. In fact, the trial was stopped prematurely by the ethical review committee when it became obvious that the results favored the enalapril group. Although the use of beta-adrenergic blocking drugs in cardiomyopathic patients with CHF is controversial and associated with a risk of short-term deterioration of left ventricular function, their use in human medicine is gaining acceptance. Although hemodynamic and clinical evidence of improvement has been demonstrated along with withdrawal-associated deterioration, the only study purporting a beneficial effect on survival used retrospective controls.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of 4 classes of cardiovascular drugs on ventricular function in dogs with mitral regurgitation

BACKGROUND: There have been few trials in which dogs with mitral regurgitation (MR) have been treated with various cardioactive drugs to determine effects on left ventricular (LV) function. HYPOTHESIS: Four classes of cardiovascular drugs may improve LV function in dogs with MR without increasing MR. ANIMALS: Nine mature dogs were included in the study. METHODS: MR was produced in 9 dogs. Five months later under butorphanol narcosis, parameters of LV function and left atrial dimension (LAD) were monitored by LV micromanometry and echocardiography/Doppler. Dogs were given (in random order) enalaprilat, nitroglycerine, ouabain, milrinone, and placebo. RESULTS: Nitroglycerin produced no significant change; milrinone and ouabain increased contractility; ouabain decreased heart rate; and there was evidence that enalaprilat and milrinone decreased LAD. Milrinone and ouabain decreased isovolumetric contraction time and therefore the time available for MR. There was no evidence that a positive inotrope increased MR despite increasing LV contractility and stroke volume. CONCLUSION AND CLINICAL IMPORTANCE: This study contradicts the hypotheses that (1) strengthening the left ventricle may increase MR and (2) treatment of MR (even before symptoms of heart failure develop) may decrease LAD. It is reasonable that strengthening the force of LV contraction should increase the driving pressure for MR; however, this effect did not appear to increase MR. Although some investigators believe that treating dogs with MR with afterload reducers and decreasing hindrance to ejection of blood from the LV to aorta may lengthen life by decreasing MR, there did not appear to be a reduction in MR, at least in response to the angiotensin-converting enzyme (ACE) inhibitor.     

Observations on the development of congestive heart failure in Irish wolfhounds with dilated cardiomyopathy

Records of previous electrocardiographic (ECG) and echocardiographic examinations of 39 Irish wolfhounds with cardiac failure, obtained during a 10-year survey, were examined to establish whether previously detected abnormalities might be prognostic indicators for the development of congestive heart failure (CHF) due to dilated cardiomyopathy (DCM) in later life. Eighteen dogs (46 per cent) had had atrial fibrillation (AF) at their first examination. Other ECG abnormalities detected at previous examinations were ventricular and supraventricular premature contractions, first and second degree atrioventricular block, P mitrale and left anterior fascicular and right bundle branch blocks. All 39 dogs had developed AF by the time of onset of CHF. The mean age at which CHF was diagnosed was 77 months in males and 86 months in females. The mean age at which AF was first detected was 45 months in males and 59 months in females, and the mean time from the first detection of AF to CHF was 27 months in males and 24 months in females. Previous echocardiographic examinations in eight dogs, over a period of up to five years, revealed progressive left atrial and left ventricular dilatation. Fractional shortening was reduced to below the normal range at the onset of CHF compared with previous examinations in three cases but increased in five. It appears, therefore, that certain ECG abnormalities, especially AF, and/or progressive ventricular and atrial dilatation, may be indicators of 'occult' DCM in wolfhounds.     

Estimation of left ventricular filling pressure by Doppler echocardiography in dogs with pacing-induced heart failure

BACKGROUND: Congestive heart failure (CHF) is a common clinical syndrome characterized by elevated filling pressure. HYPOTHESIS: Doppler echocardiographic (DE) variables of left ventricular (LV) filling can predict a decline of LV end-diastolic pressure (LVEDP) induced by acute preload reduction in dogs with compensated CHF. ANIMALS: Five male hound dogs. METHODS: Dogs previously instrumented with a transvenous cardiac pacemaker and a LV pressure gauge were paced at 160-180 bpm to induce mild CHF characterized by LVEDP > 20 mmHg. LVEDP and 9 DE variables of LV filling derived from diastolic time intervals, transmitral and pulmonary venous flow, and tissue Doppler imaging were measured simultaneously at baseline and 30, 60, 120, and 240 minutes after furosemide (4 mg/kg, IV) or placebo (0.9% saline, IV). Repeated measures analysis of variance and correlation analysis were used to determine the association between the decline of LVEDP after furosemide and DE measures of LV filling pressure (LVFP). RESULTS: Furosemide but not placebo decreased LVEDP (P < .001). The ratio of early transmitral flow velocity to LV isovolumic relaxation time (E : IVRT) predicted LVEDP best (R(2)= .50; P < .001). Correlations were also found between LVEDP and IVRT, E, ratio between E and late diastolic transmitral flow velocity (E : A), and early diastolic velocity of the mitral annulus (Ea). The ratio of E to Ea (E : Ea) was not useful in the prediction of LVEDP in this model. CONCLUSION AND CLINICAL IMPORTANCE: E : IVRT can be used to predict LVFP in dogs with mild left-sided CHF induced by rapid pacing.     

Plasma endothelin-1 immunoreactivity in normal dogs and dogs with acquired heart disease

We sought to measure plasma endothelin-1 (ET-1) concentrations in normal dogs and to compare them with those measured in dogs with acquired heart disease with or without pulmonary edema. A sandwich enzyme-linked immunosorbent assay kit was validated and used to measure ET-1 immunoreactivity in plasma samples obtained from 32 normal dogs and 46 dogs with either dilated cardiomyopathy (DCM, n = 27) or degenerative valvular disease (CDVD, n = 19) with (n = 30) or without (n = 16) overt congestive heart failure (CHF). Plasma ET-1 concentrations (geometric mean, 95% confidence interval of geometric mean) were 1.17 (1.04-1.32) fmol/mL in the 32 normal control dogs, 1.25 (0.981-1.60) fmol/mL in 16 dogs with DCM (n = 9) or CDVD (n = 7) without CHF, and 2.51 (2.10-3.01) fmol/mL in 30 dogs with DCM (n = 18) and CDVD (n = 12) with CHE Plasma immunoreactivity of ET-1 was significantly higher in dogs with CHF in comparison with normal dogs (P < .001) and dogs with heart disease without CHF (P < .001). No significant difference was found between normal dogs and dogs with heart disease but without CHF (P > .05). Significant correlations were between plasma ET-I concentrations and left atrial:aortic ratio (P < .0001, r2 = .39), left ventricular internal dimension at end-diastole indexed to aortic diameter (P < .0001, r2 = .30) or body surface area (BSA) (P = .0071, r2 = .10), and left ventricular internal dimension at end-systole indexed to aortic diameter (P = .0003, r- = .17) or BSA (P = .0008, r2 = .15).     

Echocardiographic characterization of dilatation cardiomyopathy in the English cocker spaniel

The echocardiographic characterization of a dilatation cardiomyopathy in small-breed dogs is reported. Twelve clinically healthy adult English Cocker Spaniel dogs (between 2 and 9 years old and weighing 11.5 to 15.4 kg [mean 12.9 +/- 1.00 kg]) from a kennel population with a history of cardiomyopathy were assessed, using M-mode echocardiography. The dogs were selected on ECG and/or radiographic evidence of ventricular enlargement. Nine dogs had R-wave amplitude in lead 11 of greater than 3.0 mV. Two dogs had an unusual right-axis deviation, the result of deep Q waves in the limb leads and deep S waves in chest leads CV6LL and CV6LU, indicating that there was right ventricular enlargement. All dogs had increased end-systolic dimensions (mean 3.0 +/- 0.6 cm). End-diastolic dimensions were increased in 9 dogs (mean 4.0 +/- 0.5 cm), and there was a decrease of left ventricular (LV) function as measured by fractional shortening in 8 dogs. Mean fractional shortening for the 12 dogs was 25.4 +/- 5.7%. There was significant correlation between LV dimensions and age at echocardiographic assessment, indicating that LV dilatation was progressive. Three of the oldest dogs had severe dilatation of the LV, and in 2 of these, LV function was severely decreased. Left ventricular function in the 3rd dog, however, was within the acceptable range. Fractional shortening and thickness of the LV caudal wall and interventricular septum were significantly correlated (P less than 0.01 for interventricular system and P less than 0.05 for LV caudal wall).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of milrinone on hemodynamics and regional blood flow in the hypoxic dog

Milrinone, a therapeutic agent for acute congestive heart failure, has both inotropic and vasodilatory effects, but investigations of these effects of milrinone were almost all conducted under normoxia, and few reports have investigated how milrinone affects the hemodynamics and redistribution of regional blood flow under severe hypoxia. By using colored microspheres, we investigated how milrinone affects hemodynamics and the redistribution of regional blood flow under severe hypoxia. Twelve healthy mongrel dogs were divided into 2 groups. The milrinone group was infused with milrinone cumulatively at 25, 75 and 250 microg/kg for 5 min each. The intact group was infused with saline instead of milrinone. We measured the hemodynamics and cerebrum, cerebellum and kidney blood flow in both groups. Both groups were inspired with 10% oxygen. Milrinone induced significant decrease in mean pulmonary artery and pulmonary vascular resistance, compared with the intact group. In both groups slight decreases in mean arterial pressure, systemic vascular resistance and double-product were seen. In regional blood flow, milrinone-induced increases in blood flow were seen in the cerebrum, cerebellum, and especially in the kidneys. Milrinone's vasodilatory effects were sufficient even under hypoxia. And milrinone increased regional blood flow slightly in the cerebrum and cerebellum, and significantly in the kidneys. These results suggested that milrinone protects against hypoxia-induced organ damage especially in the kidneys. In addition, milrinone is very potent in improving severe congested hemodynamics which complicates hypoxic pulmonary vasoconstriction.     

Survival and echocardiographic data in dogs with congestive heart failure caused by mitral valve disease and treated by multiple drugs: a retrospective study of 21 cases

This retrospective study reports the survival time [onset of congestive heart failure (CHF) to death from any cause] of 21 dogs with mitral regurgitation (MR) and CHF treated with a combination of furosemide, angiotensin-converting enzyme inhibitor (ACEI, benazepril, or enalapril), pimobendan, spironolactone, and amlodipine. Baseline echocardiographic data: end-systolic and end-diastolic volume indices (ESVI and EDVI), left atrium to aorta ratio (LA/Ao), and regurgitant fraction (RF) are reported. Median survival time (MST) was 430 d. Initial dosage of furosemide (P = 0.0081) and LA/Ao (P = 0.042) were negatively associated with survival. Baseline echocardiographic indices (mean ± standard deviation) were 40.24 ± 16.76 for ESVI, 161.48 ± 44.49 mL/m(2) for EDVI, 2.11 ± 0.75 for LA/Ao, and 64.71 ± 16.85% for RF. Combining furosemide, ACEI, pimobendan, spironolactone, and amlodipine may result in long survival times in dogs with MR and CHF. Severity of MR at onset of CHF is at least moderate.     

Echocardiographic assessment of left ventricular dimensions in clinically normal English cocker spaniels

Seventeen clinically normal adult English Cocker Spaniels from a kennel population with a history of cardiomyopathy were assessed, using M-mode echocardiography, to establish reference values for left ventricular (LV) dimensions for this breed of dog. Echocardiographic measurements were compared with postmortem measurements in 10 of 17 dogs. The LV weight calculated from the echocardiographic measurements correlated significantly with LV weight at postmortem (P less than 0.05). Echocardiographic measurements of end diastolic and end systolic diameters for the 17 dogs correlated significantly with body surface area (P less than 0.01). Measurements of the interventricular septum were in close agreement with values in clinically normal dogs and were significantly correlated with postmortem measurements (r = 0.94, P less than 0.01). However, 76% of the measurements for LV caudal wall thickness in this group of dogs were above the normal range. Calculation of fractional shortening values identified a group of 5 dogs with reduced fractional shortening (mean +/- SD, 20.97 +/- 3.66%), which indicates that a depression in contractility may be present in some apparently healthy dogs of this kennel population. The remaining 12 dogs had fractional shortening values of mean +/- SD, 34.26 +/- 4.54%.     

Therapeutic trial of granulocyte-colony stimulating factor for dilated cardiomyopathy in three dogs

Three dogs were presented to us for evaluation of cardiac problems. Electrocardiographic recordings revealed severe tachyarrhythmia and atrial fibrillation with ventricular tachycardia in 2 of the 3 dogs. The echocardiographic findings of the 3 dogs revealed markedly decreased fractional shortening and a marked increase in E-point septal separation. Based on the results of electrocardiographic and echocardiographic evaluation, the 3 dogs were diagnosed as dilated cardiomyopathy (DCM). The dogs were treated with conventional cardiac medication, but cardiac function did not improve and the clinical signs remained. We subsequently attempted treatment with granulocyte-colony stimulating factor (G-CSF; 10 microg/kg, subcutaneously). The specific purpose of G-CSF therapy for DCM was to improve cardiac function and a significant improvement in cardiac function was confirmed. The three dogs had no treatment side effects. This case report suggests that G-CSF might have therapeutic effects for medically refractory DCM in dogs.     

Electrocardiographic findings in dogs with motor vehicle-related trauma

Motor vehicle-related injury is the most common form of trauma incurred by dogs, and cardiac arrhythmias are a well-recognized complication. Although posttraumatic arrhythmias are often observed, little is known regarding their frequency. This study utilized continuous ambulatory electrocardiography (i.e., Holter monitoring) to describe the cardiac rhythm disturbances in 30 dogs sustaining trauma in motor vehicle accidents. Ventricular ectopy was identified by Holter monitoring in 29 of 30 dogs, although the initial electrocardiogram (EKG) only documented ventricular ectopic complexes (VECs) in four dogs. Ventricular ectopy was infrequent in most dogs (i.e., 62% of the dogs had less than 100 VECs per day for the entire study), but 16% developed frequent arrhythmias (greater than 4,000 VECs per day). In all cases, the VECs were observed within 24 hours of injury. Forty-three percent of dogs had at least one episode of ventricular tachycardia, including several dogs that had an overall infrequent rate of VECs (i.e., less than 100 or 100 to 1,000 VECs per day). Although baseline EKGs are useful in identifying arrhythmias in most dogs, the length of the recording should be increased to improve the likelihood of observing an abnormal EKG event. Most importantly, additional EKGs should be obtained or continuous EKG monitoring should be performed in dogs that display clinical signs that could be attributed to ventricular arrhythmias.     

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.

     

The effect of 7.2% hypertonic saline solution on m-mode echocardiographic indices in normovolemic dogs

This study investigated whether a small volume of 7.2% hypertonic saline solution (HSS) could affect M-mode echocardiographic indices in dogs. HSS induced significant increase in heart rate, stroke volume and cardiac index, when the fluid infusion was completed (P<0.05). In the HSS group, the left ventricular end-diastolic volume index, as an index of preload, significantly increased (P<0.05), whereas left ventricular end-systolic volume index were not altered. HSS induced slight increases in ejection fraction at end of infusion despite significantly differences were not observed. In conclusion, HSS did not induce a demonstrable effect on M-mode echocardiographic indices of systolic function-enhance cardiac contractility, but it caused preload augmentation that may contribute to an abrupt and transient increase in cardiac output just after HSS infusion.     

Evaluation of techniques and outcomes of mitral valve repair in dogs

OBJECTIVE: To describe surgical techniques for and assess outcome of treatment of mitral regurgitation in dogs. DESIGN: Uncontrolled prospective study. ANIMALS: 18 dogs with naturally occurring mitral regurgitation. PROCEDURE: All dogs weighed > 5 kg (11 lb) and had severe mitral regurgitation, congestive heart failure (CHF), and no serious noncardiac disease. Left ventricular volume indices, left atrial size, and degree of mitral regurgitation were determined echocardiographically before and after surgery. Repair techniques included circumferential annuloplasty, placement of artificial chordae, chordal fenestration and papillary muscle splitting, and edge-to-edge repair. Factors predictive for surgery survival and resolution of CHF were determined. RESULTS: 12 dogs survived surgery. Factors predictive for surgery survival included weight > 10 kg (22 lb) and CHF of less than 6 months' duration. In 9 dogs, CHF resolved for a median period of 1 year (range, 4 months to 3 years) after surgery. One dog had stable CHF at 12 months. One dog died as a result of progressive CHF; another was euthanatized for a noncardiac reason. Left ventricular diastolic volume index was 226.9 +/- 117.7 cm3/m2 before surgery and 134.9 +/- 70.4 cm3/m2 at 6 months after surgery (n = 10). Factors predictive for resolution of CHF included left ventricular diastolic volume index < 250 cm3/m2 and systolic volume index < 70 cm3/m2. CONCLUSION AND CLINICAL RELEVANCE: Mitral valve repair may resolve CHF in dogs with severe mitral regurgitation, particularly in dogs that weigh > 10 kg and are treated within 6 months of the onset of CHF.     

Results of ambulatory electrocardiography in overtly healthy Doberman Pinschers with equivocal echocardiographic evidence of dilated cardiomyopathy

OBJECTIVE: To determine results of ambulatory electrocardiography in and outcome of overtly healthy Doberman Pinschers with equivocal echocardiographic evidence of dilated cardiomyopathy. DESIGN: Case series. ANIMALS: 44 overtly healthy (25 male, 19 female) Doberman Pinschers. PROCEDURE: 24-hour ambulatory electrocardiographic (Holter) recordings with > 90% scan quality obtained the same day that echocardiography was performed were reviewed. RESULTS: Holter recordings from 42 of 44 (95%) dogs contained ventricular premature complexes (VPC). Fifteen of 44 (34%) dogs had > 100 VPC, 9 (20%) had > 500 VPC, and 5 (11%) had > 1,000 VPC. Nonsustained (< 30 seconds) ventricular tachycardia was detected in 4 dogs. Eighteen of 27 (67%) dogs with > 100 VPC, any couplets or triplets of VPC, or ventricular tachycardia developed dilated cardiomyopathy within 1 year, compared with 8 of 17 (47%) dogs with < 100 VPC, no couplets or triplets of VPC, and no ventricular tachycardia. Of the 18 dogs that did not develop dilated cardiomyopathy within 1 year, 11 (61%) did so within 3 years. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that a high percentage of Doberman Pinschers with equivocal echocardiographic evidence of dilated cardiomyopathy will be found to have VPC during 24-hour ambulatory electrocardiography and that most will develop echocardiographic abnormalities indicative of cardiomyopathy.     

Association between results of ambulatory electrocardiography and development of cardiomyopathy during long-term follow-up of Doberman pinschers

OBJECTIVE: To characterize ambulatory electrocardiographic results of overtly healthy Doberman Pinschers and determine associations between those results and development of dilated cardiomyopathy. DESIGN: Cohort study. ANIMALS: 114 (58 male, 56 female) overtly healthy Doberman Pinschers without echocardiographic evidence of cardiac disease on initial examination. PROCEDURE: Echocardiograms and 24-hour ambulatory electrocardiograms (Holter recordings) were obtained initially and at variable intervals. The status (live vs dead) of all dogs was known at least 2 years and as long as 10 years after initial examination (mean [+/- SD] follow-up time, 4.33 +/- 1.84 years). Associations between development of dilated cardiomyopathy and number of ventricular premature contractions (VPC), age, and sex were determined. RESULTS: 55 dogs (48%) did not have VPC on initial Holter recordings, and only 8 dogs had > 50 VPC/24 hours. The likelihood that a dog would have VPC was associated with increasing age and being male. At least 1 VPC/24 hours, and in particular, > 50 VPC/24 hours or > or = 1 couplet or triplet of VPC/24 hours, were predictive of subsequent development of dilated cardiomyopathy. Fifty-four dogs (47%) developed dilated cardiomyopathy; 12 were still alive at the end of the study, and 42 had died. Twenty-five of these 42 dogs died after the onset of congestive heart failure (CHF), 15 died suddenly before the onset of overt CHF, and 2 died of noncardiac causes. More males developed dilated cardiomyopathy than females, and dogs that died suddenly were approximately 1 year younger than those that developed CHF. CONCLUSIONS AND CLINICAL RELEVANCE: Results of high-quality Holter recordings may be used to identify overtly healthy Doberman Pinschers that are at a high risk for dilated cardiomyopathy.     

Cardiovascular effects of a phosphodiesterase III inhibitor in the presence of carvedilol in dogs

The aim of this study was to determine whether dobutamine, dopamine, or milrinone (a phosphodiesterase [PDE] III inhibitor) would support cardiac function that had been attenuated by administration of the beta-blocker, carvedilol (0.2, 0.4, or 0.8 mg/kg). Hemodynamic and cardiac parameters including the heart rate (HR), left-ventricular fractional shortening (FS), and arterial pressure were measured in six healthy dogs without cardiac disease. Carvedilol did not affect FS or arterial pressure, but decreased the HR significantly. The positive inotropic and chronotropic responses to dobutamine and dopamine were attenuated by carvedilol, whereas arterial pressure was unaffected. Milrinone did not affect the HR and decreased arterial pressure, whereas FS was significantly greater both in the control and carvedilol-treated groups. Although milrinone affect the negative chronotropic effects of carvedilol, milrinone increased FS and prevented the decrease in arterial pressure. These results suggest that inhibition of PDE III preserves cardiac contractility and hemodynamic function in the presence of carvedilol.