The next heartbeat: Creating dynamic and histographic Poincaré plots for the assessment of cardiac rhythms.

The rhythm of the heart is not a stationary phenomenon, and therefore, incorporation of the dynamic Poincaré plot and tachogram provides additional diagnostic information to complement and expand waveform (P-QRST) analyses from the electrocardiogram. Although pattern assessment of the Poincaré plot and tachogram can provide an appraisal for normal and abnormal rhythms and serve as a potential means for machine-learned rhythm diagnoses, time-selected windows of beat-to-beat variability permit more detailed examination. As such, expanded criteria for rhythm diagnoses, identification of arrhythmic triggers, global appreciation of rhythm changes, and recognition of patterns that provoke mechanistic questions may be gleaned from the use of the methods reviewed in this report. More specifically, these methods demonstrate that limitations exist in the reliance on traditional measures of heart rate variability in the dog due to the non-linear beat-to-beat rhythm of sinus arrhythmia in the species. Behavior of arrhythmias based on coupling intervals, repeating patterns, preceding triggers of beat-to-beat variability, and circumstantial evidence of atrioventricular nodal conduction during atrial flutter and fibrillation are a few examples of discovery founded in these techniques. The open access website, The Next Heartbeat (https://thenextheartbeat.com/), permits anyone to implement these methods in the assessment of long-term electrocardiographic examinations (Holter monitoring) so that, as yet to be revealed, features of the beating heart through time may be discovered.

Instantaneous and averaged heart rate profiles: Developing strategies for programming pacing rates in dogs.

Pacemakers use heart rate histograms (% beats) and sensor indicated rate histograms (% time) to illustrate rate distributions. When programmed to the rate adaptive modes, these data are used to determine the appropriateness of rate response to activity. These histograms are generated from instantaneous heart rate calculations. In humans, such data are compared to known histographic rate profiles. Such rate profiles during 24 h in the dog are not available. Moreover, data representation differ between Holter monitoring and pacemakers making comparisons challenging. The rate distribution in dogs >7-years of age was determined over 24 h using instantaneous and rolling average heart rate. Such data could serve as a guide to programming pacing rates for dogs. Sinus arrhythmia resulted in dissimilar heart rate profiles depending on the method of determining rate. The long intervals of sinus arrhythmia resulted in median values for the percent of time with an instantaneous heart rate of <50 beats/min (bpm) of 15%, whereas a rolling average heart rate of <50 bpm was 0.2%. Based on the cumulative time of the rolling average rate, dogs spent 26.3% of the day between 70-90 bpm with rates <65 bpm and >90 bpm approximating 30% for each. Rates >160 bpm were uncommon (<1%). However, high variability existed between dogs. This study demonstrated the shortcomings of both instantaneous and averaging methods to evaluate heart rate profiles in the dog and that both methods should be incorporated when making pacing rate decisions during programming.

Insights into sinus arrhythmia of the dog: Acetylcholine perfusion of canine right atrium results in beat-to-beat patterns that mimic sinus arrhythmia supporting exit block in the sinoatrial conduction pathways.

Sinus arrhythmia of the dog is unique because of the pronounced alternating beat-to-beat intervals. The clustering of these short (faster rates) and long (slower rates) intervals is not just influenced by autonomic input from breathing; sinus arrhythmia can persist in the panting or apneic dog. The multiplicity of central and peripheral influences on the sinus node complicates the unraveling of the mechanisms of sinus arrhythmia. Studies of the sinus node suggest that acetylcholine can slow cellular depolarization and block sinoatrial conduction. Electrocardiographic monitoring of the dog supports this notion in that abrupt bifurcation into short and long intervals develop at lower heart rates. We sought to determine whether this phenomenon could be recapitulated in canine atrial preparations perfused with acetylcholine and whether selective pharmacologic blockade of the voltage and calcium clocks could provide insight into its mechanism. Spontaneous beat to beat (A-A) intervals were obtained from monophasic action potential recordings of perfused canine right atrial preparations before and during perfusion with acetylcholine (2-5 µM). The calcium clock was blocked with ryanodine (2-3 µM). The membrane clock was blocked with diltiazem hydrochloride (ICa,L blocker; 0.25 µM) and ZD7288 (If blocker; 3 µM). Hyperpolarization was hindered by blockade of IK,Ado/IK,Ach with tertiapin Q (100 nM) before and during acetylcholine perfusion. Acetylcholine resulted in beat clusters similar to those seen in sinus arrhythmia of the dog. Beat clusters were consistent with intermittent 2:1 and 3:1 sinoatrial conduction block. Tertiapin Q abolished this patterning suggesting a role of IK,Ado/IK,ACh in the mechanism of these acetylcholine-induced beat-to-beat patterns.

Transthoracic echo-guided pacemaker implantation reduces fluoroscopic use in dogs.

Echocardiographic guidance provides an alternative method when fluoroscopy is unavailable, equipment or power failure of fluoroscopic equipment during a procedure occurs or to decrease radiation risk. Recently, transthoracic (TTE) and transesophageal echocardiography were reported as an alternative method to guide interventional procedures in dogs. Therefore, we hypothesized that TTE could be used as an alternative method to visualize endocardial leads during pacemaker implantation in dogs, largely avoiding the use of fluoroscopy. A prospective consecutive case series of pacemaker implantation was performed using TTE guidance. The endocardial lead was imaged by TTE during its intracardiac advancement until the lead tip was positioned at the right ventricular apex. Echocardiographic right parasternal views, optimized to visualize the pacing lead, were used, starting with a short axis image of the right atrium and ending with a long axis view of the right ventricle (RV) optimized to image the RV apex. Proper lead placement was confirmed by both capture threshold, impedance and fluoroscopy. Twenty-one pacemaker implantation procedures by TTE monitoring were successfully performed. The TTE guidance provided images of a quality sufficient to clearly monitor implantation in real-time and allowed for immediate corrections to pacing lead malpositioning or excessive looping. Fluoroscopy was used to confirm the correct placement of the lead that was guided echocardiographically in the initial three procedures, after which a single radiographic image (no cine-mode) was used to identify lead placement and redundancy in the remaining eighteen cases. Static imaging (radiography using the fluoroscope) was used to assess the proper lead redundancy in all procedures because this cannot be evaluated echocardiographically. Pacemaker leads were successfully implanted in the RV of dogs using TTE monitoring. A larger cases series is needed for validation of safety and effectiveness of TTE during this interventional procedure in dogs.

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.

Genetic analysis of ventricular arrhythmia in young German Shepherd Dogs.

BACKGROUND: Ventricular arrhythmias (VA) and sudden death are inherited in German Shepherd Dogs (GSDs). OBJECTIVES: To estimate the genetic parameters (heritabilities and correlations) of 3 traits of VA (single premature ventricular complexes (PVCs), 2 consecutive PVCs (couplets), and 3 or more consecutive PVCs-ventricular tachycardia [VT]). ANIMALS: Three hundred and ninety-eight GSDs. METHODS: Prospective, observational, case control study. Dogs were phenotyped by 24-hour ambulatory ECG from 6 to 45 weeks of age. Edited ECG records included the number of incidents of (1) single PVCs, (2) couplets, and (3) VT. RESULTS: A data set of 1,239 Holter records from 398 GSDs was used to estimate genetic variables. Phenotypic correlations for affectedness (binarily coded 0/1) of the 3 traits ranged from 0.55 to 0.74, whereas correlations for severity (continuous values of 24-hour VA counts) ranged from 0.26 to 0.39. Estimates of genetic correlation among the severity traits were 0.06 to 0.27. Estimated heritabilities were 0.54, 0.54, and 0.46 for affectedness and 0.33, 0.69, and 0.69 for severity of PVCs, couplets, and VT, respectively. Month and year of birth and age at ECG recording had significant effects on all 3 traits. Season of ECG recording had a significant effect on the number of single PVCs, but not couplets or incidents of VT. Age of onset differed, with single PVCs appearing an average of 4 days earlier than couplets and VT. CONCLUSION: These results imply a strong genetic component for this disease but suggest that differences in the 3 traits should be taken into consideration in studies to identify the underlying genes.

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.

Lidocaine converts acute vagally associated atrial fibrillation to sinus rhythm in German Shepherd dogs with inherited arrhythmias.

BACKGROUND: Lidocaine is most frequently used to treat ventricular arrhythmias. However, lidocaine may have an antiarrhythmic effect for certain supraventricular arrhythmias. HYPOTHESIS: We hypothesized that lidocaine would be effective in converting experimentally induced atrial fibrillation (AF) to sinus rhythm and that a decrease in the dominant frequency (DF) and an increase in the organization as judged by the spectral entropy (SE) would occur over the course of the conversion. ANIMALS: Seven German Shepherd (GS) Dogs. METHODS: Dogs were anesthetized with fentanyl and pentobarbital. AF was induced with standard pacing protocols while left and right atrial monophasic action potentials (MAP) were recorded. The power spectra from the MAP recordings were analyzed to determine DF and SE during treatment with boluses of 2 mg/kg lidocaine. RESULTS: Lidocaine converted AF to sinus rhythm in all dogs and all episodes (n = 19). Conversion time was 27-87 seconds. After atropine, sustained AF was not induced; however, 5 episodes of atrial tachycardia resulted, and 3 were converted with lidocaine. Frequency domain analysis of 12 conversion sequences showed that left and right DF of the MAP signals decreased from the time of injection to conversion to sinus rhythm (P < .001). Mean SE indicated a gradient between the left and right atria (P = .003) that did not change during conversion. CONCLUSIONS AND CLINICAL IMPORTANCE: Vagally associated AF in GS dogs is terminated with lidocaine. Lidocaine is likely an effective treatment in clinical dogs with vagally associated AF.

Low-energy ablation of anteroseptal accessory pathways in two dogs.

In humans, accessory pathways (APs) in an anteroseptal and midseptal position are often challenging to ablate because of their close proximity with the conduction pathways of the atrioventricular junction. The use of low-energy ablation techniques can be useful to reduce the risk of permanently damaging the atrioventricular node and the His bundle. This report describes the use of low-energy radiofrequency catheter ablation to successfully and permanently ablate anteroseptal APs in two dogs with orthodromic atrioventricular reciprocating tachycardia. In the first dog, a transient first degree atrioventricular block persisted for 30 s after radiofrequency energy delivery. In the second dog, transient paroxysmal atrioventricular conduction block was observed during the procedure but resolved within 3 days. First degree atrioventricular block was again identified 2 months later. In conclusion, anteroseptal APs can be effectively treated by low-energy radiofrequency catheter ablation with minimal and transient damage to the atrioventricular junction.

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.

Use of 3D printer technology to facilitate surgical correction of a complex vascular anomaly with esophageal entrapment in a dog.

A 10 week old female intact Staffordshire terrier was presented with a total of five congenital cardio-thoracic vascular anomalies consisting of a patent ductus arteriosus (PDA) with an aneurysmic dilation, pulmonic stenosis, persistent right aortic arch, aberrant left subclavian artery and persistent left cranial vena cava. These abnormalities were identified with a combination of echocardiogram and computed tomography angiography (CTA). The abnormalities were associated with esophageal entrapment, regurgitation, and volume overload of the left heart with left atrial and ventricular enlargement. A 2 cm diameter aneurysmic dilation at the junction of the PDA, right aortic arch and aberrant left subclavian artery presented an unusual surgical challenge and precluded simple circumferential ligation and transection of the structure. A full scale three dimensional model of the heart and vasculature was constructed from the CTA and plasma sterilized. The model was used preoperatively to facilitate surgical planning and enhance intraoperative communication and coordination between the surgical and anesthesia teams. Intraoperatively the model facilitated spatial orientation, atraumatic vascular dissection, instrument sizing and positioning. A thoracoabdominal stapler was used to close the PDA aneurysm prior to transection. At the four-month postoperative follow-up the patient was doing well. This is the first reported application of new imaging and modeling technology to enhance surgical planning when approaching correction of complex cardiovascular anomalies in a dog.

Structural and molecular pathology of the atrium in boxer arrhythmogenic right ventricular cardiomyopathy.

OBJECTIVE: To investigate the expression and distribution of desmosomal and gap junction proteins of the intercalated disc in the atria of boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC). ANIMALS: Nineteen control dogs and 13 boxers with histopathologically confirmed ARVC. METHODS: Right and left atrial samples were examined using immunofluorescence and Western blots. The intercalated disc proteins investigated included total and phosphorylated connexin43 (Cx43 and pCx43), connexin45, connexin40, plakoglobin, plakophilin-2, desmoplakin, and N-cadherin. RESULTS: Histopathological changes characteristic of ARVC were present in the left or right atrium of 12 out of 13 boxers and were absent in all control dogs. When compared to the 19 control dogs, immunofluorescence analysis revealed a decrease in signal intensity for pCx43 and plakoglobin in the left (p = 0.03 and p = 0.014, respectively) and right atrium (p = 0.015 and p = 0.002, respectively) of affected boxers. Connexin43 and pCx43 Western blot band density was significantly decreased in the left (p = 0.025 and p = 0.027, respectively) and right atrium (p = 0.001 and p = 0.044, respectively) of affected boxers. CONCLUSION: Altered intercalated disc and gap junction proteins were identified in atrial myocardium of ARVC boxers, supporting atrial involvement as part of this disorder. Reduction in pCx43 in conjunction with histological changes could represent the substrate for atrial arrhythmias associated with ARVC. Furthermore, these findings detected in boxer dogs, lend support for the broader term, arrhythmogenic cardiomyopathy, as preferred nomenclature used to describe this disease in humans.

Intracardiac echocardiography: use during transcatheter device closure of a patent ductus arteriosus in a dog.

Intracardiac echocardiography (ICE) is used in humans for percutaneous interventional procedures, such as transcatheter device closures. Intracardiac echocardiography provides high-resolution imaging of cardiac structures with two-dimensional, M-mode, Doppler, and also three-dimensional modalities. The present report describes application of ICE during transcatheter occlusion of patent ductus arteriosus using a canine ductal occluder in a dog for which transesophageal echocardiography could not provide an optimal acoustic window.

Canine pulmonary vein-to-pulmonary artery ratio: echocardiographic technique and reference intervals.

OBJECTIVES: The size of the pulmonary veins (PVs) and pulmonary arteries (PAs) changes in response to hemodynamic alterations caused by physiological events and disease. We sought to create standardized echocardiographic methods for imaging the right ostium of the pulmonary veins (RPVs) and the right pulmonary artery (RPA) using specific landmarks and timing to quantify vessel diameters and phasic changes during the cardiac cycle. ANIMALS: Fifty client-owned healthy dogs prospectively recruited. METHODS: M-mode and 2-dimensional images were obtained from modified right parasternal long and short axis views. Right ostium of the pulmonary veins and RPA measurements were timed with electrical [peak of the QRS complex (RPVQRS and RPAQRS) and end of T wave (RPVT and RPAT)] or mechanical events [RPV and RPA vessels at their respective maximal (RPVMAX; RPAMAX) and minimal (RPVMIN; RPAMIN) diameters]. Right ostium of the pulmonary veins and RPA measurements were also indexed to the aorta. RESULTS: In normal dogs regardless of the echocardiographic view or time in the cardiac cycle, the RPV/RPA ratio approximated 1.0. Mechanically timed fractional changes (distensibility indices) in RPV and RPA diameters did not differ (p=0.99; 36.9% and 36.8%, respectively). ECG-timed fractional changes (distensibility indices) in RPV and RPA diameter were at least 50% smaller than mechanically timed changes (p<0.05). RPV:Ao and RPA:Ao ranged between 0.3 and 0.6, with lower values obtained in diastole and larger values in systole (p<0.0001). Multiple positive and negative deflections were identified on the RPV and RPA M-mode tracings. CONCLUSION: This study provides detailed methodology and 2D and M-mode reference intervals for the RPV and RPA dimensions and the phasic changes during the cardiac cycle of the dog using echocardiography.

Complex disease and phenotype mapping in the domestic dog.

The domestic dog is becoming an increasingly valuable model species in medical genetics, showing particular promise to advance our understanding of cancer and orthopaedic disease. Here we undertake the largest canine genome-wide association study to date, with a panel of over 4,200 dogs genotyped at 180,000 markers, to accelerate mapping efforts. For complex diseases, we identify loci significantly associated with hip dysplasia, elbow dysplasia, idiopathic epilepsy, lymphoma, mast cell tumour and granulomatous colitis; for morphological traits, we report three novel quantitative trait loci that influence body size and one that influences fur length and shedding. Using simulation studies, we show that modestly larger sample sizes and denser marker sets will be sufficient to identify most moderate- to large-effect complex disease loci. This proposed design will enable efficient mapping of canine complex diseases, most of which have human homologues, using far fewer samples than required in human studies.

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.

Triggered activity as a mechanism for inherited ventricular arrhythmias in German shepherd Dogs.

OBJECTIVES: This study sought to determine whether early afterdepolarization-induced triggered activity is responsible for the initiation of ventricular arrhythmias in dogs with an inherited predisposition to sudden death. BACKGROUND: We have identified a colony of German shepherd dogs that display inherited ventricular ectopic activity and sudden cardiac death. The arrhythmias in these animals are pause dependent but are not associated with a prolonged QT interval, suggesting that they might be initiated by early afterdepolarization-induced triggered activity in Purkinje fibers. METHODS: Cardiac Purkinje fibers obtained from dogs that either did or did not exhibit ventricular tachyarrhythmias at the time of study were superfused in vitro with normal Tyrode solution (extracellular potassium ion concentration 4 mmol/liter) and were studied using standard microelectrode techniques. RESULTS: Early afterdepolarizations and triggered activity occurred spontaneously in Purkinje fibers obtained from affected dogs (n = 7) but not in fibers obtained from unaffected dogs (n = 13). Exit conduction block of triggered responses occurred to varying degrees within the Purkinje fiber but not at the Purkinje-muscle junction. Overdrive pacing suppressed triggered activity. The reemergence of triggered activity after cessation of pacing was both time and rate dependent. Triggered activity in fibers obtained from affected dogs was potentiated by phenylephrine and epinephrine and was suppressed by isoproterenol. Triggered activity was not induced by phenylephrine or epinephrine in fibers obtained from unaffected dogs. CONCLUSIONS: These results support the hypothesis that early afterdepolarization-induced triggered activity in Purkinje fibers is responsible for the initiation of ventricular arrhythmias in this canine model of inherited sudden death.

Electropharmacological characterization of cardiac repolarization in German shepherd dogs with an inherited syndrome of sudden death: abnormal response to potassium channel blockers.

OBJECTIVES: This study sought to determine whether abnormal ventricular repolarization is implicated in cardiac arrhythmias of German shepherd dogs with inherited sudden death. BACKGROUND: Moïse et al. (9) have identified German shepherd dogs that display pause-dependent lethal ventricular arrhythmias. METHODS: Ventricular repolarization was studied both in vivo using electrocardiogram recordings on conscious dogs and in vitro with a standard microelectrode technique performed on endomyocardial biopsies and Purkinje fibers. Pharmacological manipulation was used to evaluate the role of potassium channels. RESULTS: In control conditions, electrocardiogram parameters were similar in both groups of dogs, except for the PR interval (18% longer in affected dogs, p < 0.05). Injection of d,l-sotalol (2 mg/kg) prolonged QT interval more in affected dogs (+14%, n = 9) than it did in unaffected dogs (+6%, n = 6, p < 0.05) and increased the severity of arrhythmias in affected dogs. In vitro, in control conditions, action potential duration (APD90) of endomyocardial biopsies and Purkinje fibers were significantly longer in affected dogs (respectively 209 +/- 3 ms, n = 30 and 352 +/- 15 ms, n = 17) than they were in unaffected dogs (197 +/- 4 ms, n = 25 and 300 +/- 9 ms, n = 30) at a pacing cycle length (PCL) of 1,000 ms. This difference increased with PCL. The kinetics of adaptation of APD90 to a change in PCL was faster in affected dogs. D,l-sotalol (10(-5) and 10(-4)M) increased APD90 in both groups of dogs, but this increase was greater in affected dogs, with the occurrence of triggered activity on Purkinje fibers. E-4031 (10(-7) and 10(-6) M), an I(Kr)-blocker, increased APD90 similarly in both groups of dogs. Chromanol 293B (10(-6) and 10(-5)M), an I(Ks)-blocker, increased significantly APD90 in unaffected dogs but had no effect in affected dogs. CONCLUSIONS: These results support the hypothesis of an abnormal cardiac repolarization in affected dogs. The effects of 293B suggest that I(Ks) may be involved in this anomaly.

Duchenne's cardiomyopathy in a canine model: electrocardiographic and echocardiographic studies.

Thirteen dogs affected with X-linked Duchenne's muscular dystrophy and 11 female carrier dogs were studied by electrocardiography (ECG) and echocardiography. Twelve of the affected dogs were studied as immature animals and followed at 1 to 6 month intervals until they were 7 to 46 months of age. Compared with control dogs, affected dogs had significantly increased (p less than 0.02) Q/R ratios in ECG leads II, III, aVF, CV6LL (V2) and CV6LU (V4). Carrier dogs had significantly increased (p less than 0.02) Q/R ratios in leads V2 and V4. The Q/R ratio increased in three of six dogs followed up from age 6 months to greater than 2 years. The PR intervals were significantly shorter (p less than 0.02) in affected dogs. Ventricular arrhythmias were identified in four of six mature affected dogs. Two-dimensional echocardiography revealed distinctive hyperechoic lesions in 12 of the 13 affected dogs and in 6 of the 11 carrier dogs. Hyperechoic lesions corresponded to calcified myocardium and surrounding dense connective tissue. This study establishes the dog affected with Duchenne's muscular dystrophy as an animal model of Duchenne's cardiomyopathy and demonstrates that the heart in carrier dogs is affected by the dystrophic process.

Inherited ventricular arrhythmias and sudden death in German shepherd dogs.

OBJECTIVES: This report describes a unique group of German shepherd dogs with inherited ventricular arrhythmias and sudden death. Before death, these dogs have no evidence of cardiovascular failure. BACKGROUND: There are few spontaneous animal models of sudden death that permit intensive investigation. METHODS: To determine the temporal evolution of ventricular arrhythmias and to characterize the syndrome of sudden cardiac death in these dogs, 24-h ambulatory electrocardiographic (ECG) monitoring, echocardiograms, electrophysiologic testing and breeding studies were conducted. RESULTS: The 24-h ambulatory ECGs from dogs that died showed frequent ventricular arrhythmias with rapid polymorphic ventricular tachycardia (rates > 480 beats/min). Affected dogs had a window of vulnerability for arrhythmias, with the highest incidence and severity of arrhythmias between 20 to 30 and 40 to 50 weeks of age. Affected dogs that died did not have prolongation of the QT interval over a spectrum of heart rates compared with unaffected dogs. The clinical arrhythmia was not induced in dogs during programmed electrical stimulation. Severely affected dogs monitored > 5 years did not develop any evidence of heart failure or cardiomyopathy, and no histopathologic abnormalities existed. Seventeen dogs died suddenly (age 4 to 30 months) and were either 1) found dead at first observation in the morning (n = 8), 2) observed to die during sleep (n = 4), 3) observed to die while resting after exercise (n = 3), or 4) observed to die during exercise (n = 2). All sudden deaths occurred between the end of September and April, with most (n = 11) during January and February. CONCLUSIONS: The cause of the inherited severe ventricular arrhythmias and sudden death in these young German shepherd dogs is still undetermined. A purely arrhythmic disorder is supported by the lack of cardiac pathology. Moreover, the window of vulnerability to ventricular arrhythmias and the age and circumstances of death invite speculation about the role of the autonomic nervous system.