Preclinical Dilated Cardiomyopathy Research Articles

Assessment of right ventricular function in healthy Great Danes and in Great Danes with dilated cardiomyopathy

IntroductionRight ventricular (RV) dysfunction is a significant negative prognostic indicator in human dilated cardiomyopathy (DCM). Many RV indices are weight-dependent, and there is a lack of reference values for the right heart in giant breed dogs (over 50 kg), including Great Danes (GDs). This study aimed to compare indices of RV function in echocardiographically normal GDs, those with preclinical DCM (PC-DCM), and those with DCM and congestive heart failure (DCM-CHF). AnimalsA total of 116 client-owned adult GDs: 74 normal, 31 with PC-DCM, and 11 with DCM-CHF. MethodsA retrospective, single-center cohort study assessed RV function using free-wall RV longitudinal strain (RVLS), strain rate, fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), and pulsed-wave tissue Doppler imaging-derived systolic myocardial velocity of the lateral tricuspid annulus (TDI S’). Relationships between DCM status and RV function indices were analyzed. ResultsRV function, measured by TAPSE (P=0.001), FAC (P<0.001), and TDI S’ (P<0.001), decreased in dogs with PC-DCM and DCM-CHF compared to healthy dogs, with FAC being lower in DCM-CHF compared to PC-DCM (P=0.048). RVLS impairment was more significant in the DCM-CHF group than in the PC-DCM group (P=0.048). RVLS had the highest area under the curve (0.899) for differentiating between normal and DCM-CHF dogs. ConclusionAs DCM progresses, echocardiographic variables of RV function, including TAPSE, FAC, TDI S’, RVLS, and strain rate, worsen, indicating impaired RV systolic function in GDs affected by DCM.

Prospective evaluation of the combined value of physical examination and biomarker variables in screening for preclinical dilated cardiomyopathy in Doberman Pinschers

IntroductionScreening to assess likelihood of preclinical dilated cardiomyopathy (PC-DCM) prior to advanced diagnostic tests in Doberman Pinschers (DP) is desirable. ObjectiveTo investigate the combined value of physical examination (PE), N-terminal pro B-type natriuretic peptide (NTproBNP) and cardiac troponin I (cTnI) for identifying PC-DCM in DP. Animals, materials and methodsAll dogs underwent: PE, echocardiogram, 3-min ECG and cardiac biomarker measurement. Asymptomatic DP (414) were classified based on 3-min ECG and echocardiogram as: No-DCM/MMVD or myxomatous mitral valve disease (MMVD), PC-DCM based on echocardiogram (PC-DCM-Echo), PC-DCM based on arrhythmias with a normal echocardiogram (PC-DCM-ECG), equivocal DCM (EQ-DCM), and MMVD. Receiver operator characteristic curves and prediction models were derived. ResultsHeart murmurs and arrhythmias were rare and gallop sounds were absent in No-DCM/MMVD DP. Dogs ≥ four years old and males had higher probabilities of PC-DCM-Echo. Prediction models incorporating PE variables with NTproBNP had an area under the curve (AUC) of 0.940 for distinguishing between PC-DCM-Echo and all other groups, which was similar to the AUC for NTproBNP (0.939) or cTnI (0.932) alone. Discrimination between No-DCM/MMVD and all other groups was similar for NTproBNP (0.781) and cTnI (0.742) as individual tests, however, models combining PE variables and NTproBNP increased the AUC to 0.812. An NTproBNP cut-off of ≥548 pmol/L, was 100% sensitive and 77.3% specific for detecting PC-DCM-Echo. ConclusionsBoth NTproBNP and cTnI had good utility as sole tests to discriminate PC-DCM-Echo DP from all others. Models differentiating No-DCM/MMVD DP from all other DP were improved by using PE and NTproBNP together.

Association between dilated cardiomyopathy and hypothyroidism in dogs

It is a known fact that thyroid hormones have an influence on the heart function. Opinions on hypothyroidism and its effect on dilated cardiomyopathy (DCM) development are controversial and often contradictory. This prospective study examined the potential association between hypothyroidism and DCM in dogs. A total of 35 dogs with DCM were included in the study. Preclinical DCM was diagnosed in 18 patients, and clinical DCM was diagnosed in 17 patients, four of which were also diagnosed with hypothyroidism. There was a positive correlation between the thyroid-stimulating hormone and body weight, left atrium size and the serum NT-proBNP concentration in patients with preclinical DCM. Euthyroid dogs with DCM had higher total thyroxine values and more ventricular premature complexes than hypothyroid dogs. Although our study did not confirm a direct relationship between hypothyroidism and DCM as a possible cause, other correlations were detected that had not yet been described in veterinary medicine.

DETERMINATION OF VERTEBRAL HEART SCALE AND ECHOCARDIOGRAPHIC MEASUREMENTS IN HEALTHY ANESTHETIZED AFRICAN WILD DOGS (LYCAON PICTUS) IN HUMAN CARE.

Cardiac disease is an important cause of mortality in African wild dogs in human care. Vertebral heart scale (VHS) is a well-documented objective measure of cardiac size and is commonly used in domestic dogs. The VHS of 63 clinically healthy African wild dogs housed in zoological institutions was retrospectively calculated. Using the robust method of reference interval (RI) calculation, the RI for VHS in captive African wild dogs was 9.3-10.8. Echocardiographic measurements from 16 clinically healthy and 2 African wild dogs with preclinical dilated cardiomyopathy are reported. The cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) were measured in a subset of African wild dogs. The median plasma NT-proBNP measurement was 845 pM/L (range 366-1,388) and the median serum cTnI measurement was 0.02 ng/ml (0.01-0.04). These data can be used for the assessment and identification of cardiac disease in this endangered species.

Echocardiographic reference intervals in healthy UK deerhounds and prevalence of preclinical dilated cardiomyopathy: a prospective, longitudinal study

BackgroundSighthounds have high echocardiographic (ECHO) left ventricular volumes. Establishing robust breed-specific ECHO reference intervals (RI) for screening is important. End-diastolic volume index (EDVI), end-systolic volume index (ESVI) and ejection fraction (EF) reference ranges derived by Simpson's method of discs are not available for deerhounds. The influence of sex or body weight (BW) on left ventricular diameter during diastole (LVDd) and systole (LVDs) has never been reported. ObjectivesProspectively determine ECHO RI and assess prevalence of dilated cardiomyopathy (DCM) in healthy UK deerhounds. AnimalsNinety-nine deerhounds. MethodsDeerhounds scored on ECHO and ECG variables then classified as normal (NORM), equivocal (EQUIV) or affected (AFF) with DCM. Fifty-nine NORM deerhounds used to determine ECHO RI. ResultsPrevalence of DCM was 21.6%. There were significant differences in BW (P<0.001), LVDd (P<0.001) and LVDs (P<0.05) between female and male deerhounds. Cut-off values for EDVI (≥140.2 mL/m2: 79% sensitivity/97% specificity), ESVI (≥71.9 mL/m2: 94.7% sensitivity/94.2% specificity) and EF (≤42.1%: 84.2% sensitivity/92.8% specificity) were proposed to help diagnose DCM. The most reliable ECHO variables to identify AFF dogs were LVDs indexed to BW by allometric scaling and ESVI; one of the least reliable was sphericity index. Ventricular arrhythmias (VA) were identified in 13.6% of the population, with the highest prevalence in AFF deerhounds (42%). ConclusionsPreclinical DCM in deerhounds is common and VA may be associated with DCM. Healthy deerhounds have higher LVDd, LVDs and EDVI compared with other breeds. This study provides ECHO RIs for deerhounds; sex or BW RIs should be used when screening.

Dilated Cardiomyopathy in Paediatric Population: A Review

Dilated cardiomyopathy (DCM) is a common cardiac diagnosis in children that may result as a consequence of diverse genetic and environmental insults. The differential diagnosis remains quite broad and as a result the approach to diagnosis and management may, at times, be quite difficult. A rigorous work-up can exclude alternative causes of left ventricular (LV) dilation and dysfunction, identify etiologies that may respond to specific treatments, and guide family screening. Assessment of myocardial detection of pre-clinical DCM could significantly reduce morbidity and mortality by allowing early instigation of cardio protective therapy. This review article discusses genetic and acquired causes of DCM, diagnostic modalities and therapeutic implications in the hope of informing physicians of a clinical entity that afflicts a substantial number of children worldwide.&#x0D; Cardiovasc. j. 2019; 12(1): 64-74

Dilated cardiomyopathy in 151 Irish Wolfhounds: Characteristic clinical findings, life expectancy and causes of death

Dilated cardiomyopathy (DCM) is an important cause of morbidity in Irish Wolfhounds (IW), a breed also predisposed to neoplastic and orthopedic diseases that shorten life expectancy. The objective of this study was to investigate survival and causes of death in IW with DCM and to characterise the clinical findings of DCM over time. Data from cardiovascular examinations performed in 1591 IW, including echocardiography and electrocardiography, were retrospectively evaluated. IW with DCM on medical therapy with long term longitudinal follow-up were included in this study (n=151; 95 males, 56 females). Based on their clinical status at initial diagnosis, IW were classified into one of three groups: preclinical DCM with sinus rhythm (PC-DCM-SR, n=35), preclinical DCM with atrial fibrillation (PC-DCM-AF, n=87), and congestive heart failure with DCM and AF (CHF-DCM-AF, n=29). Survival data were analyzed using cumulative incidence functions, Kaplan–Meier and Cox regression.CHF was predominantly characterized by chylous pleural and mild pericardial effusions. Causes of death were cardiac (CD) in 73/151 and non-cardiac (non-CD) in 62/151; 16 dogs remained alive at study end. The majority of deaths in both preclinical DCM groups were non-CD (PC-DCM-AF=51.9% non-CD, 48.1% CD; PC-DCM-SR, 65.5% non-CD, 34.5% CD). In the CHF-DCM-AF group most dogs (89.6%) experienced a CD. Median survival of the CHF-DCM-AF group (7.3 months) was significantly shorter than in the PC-DCM-AF group (21.9 months) or PC-DCM-SR group (29.1 months, P=0.001).CHF-DCM-AF in IW was associated with reduced life expectancy and CD, while most IW with preclinical DCM died from non-cardiac causes.

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

ObjectivesTo 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). AnimalsSixty-five client-owned Dobermans: 20 healthy (NORMAL), 31 with preclinical DCM and 14 with DCM and CHF (DCM + CHF). MethodsA retrospective study of data retrieved from clinical records and ambulatory ECG (Holter) archives, including data collected previously for a large-scale prospective study of Dobermans with preclinical DCM. Holter data were reanalysed quantitatively, including conventional time-domain heart rate variability and the HRT parameters turbulence onset and turbulence slope. ResultsHeart rate turbulence could be measured in 58/65 dogs. Six Holter recordings had inadequate ventricular premature contractions (VPCs) and one exhibited VPCs too similar to sinus morphology. Heart rate turbulence parameter, turbulence onset, was significantly reduced in DCM dogs, whereas conventional heart rate variability measures were not. Heart rate variability and HRT markers were reduced in DCM + CHF dogs as expected. ConclusionsHeart rate turbulence can be measured from the majority of good quality standard canine 24-hour Holter recordings with >5 VPCs. Turbulence onset is significantly reduced in Dobermans with preclinical DCM which indicates vagal withdrawal early in the course of disease. Heart rate turbulence is a powerful prognostic indicator in human cardiac disease which can be measured from standard 24-hour ambulatory ECG (Holter) recordings using appropriate computer software. Further studies are warranted to assess whether HRT may be of prognostic value in dogs with preclinical DCM and in other canine cardiac disease.

PRELIMINARY CHARACTERIZATION OF DILATED CARDIOMYOPATHY IN A CAPTIVE POPULATION OF BANDED MONGOOSES (MUNGOS MUNGO).

Between 2006 and 2015, a high incidence of dilated cardiomyopathy (DCM) was diagnosed in a captive population of banded mongooses (Mungos mungo) at Chester Zoo, United Kingdom. The aim of this study was to characterize DCM in these mongooses in order to raise awareness of this condition and help inform management and clinical decisions. Prospective clinical assessments, including echocardiography, radiography, and cardiac biomarkers, were carried out in four mongooses remaining in the collection. Radiographs from 15 mature mongooses were reviewed and cardiac size and metrics assessed. Ten postmortem reports and the histologic sections from nine of these cases were reviewed for cardiac lesions. Echocardiographic findings were consistent with a diagnosis of preclinical DCM in one out of the four cases assessed, and it was considered equivocal in a second case. Taurine levels were within normal limits for domestic carnivores. Radiographs in seven mongooses showed right-sided or generalized cardiomegaly. The width of the heart in intercostal spaces and vertebral-tracheal angle on the lateral view were the most-discriminatory radiographic variables for diagnosis of cardiac disease. At necropsy, there was gross pathological evidence consistent with DCM in seven out of 10 mongooses examined. Histopathologically, mild multifocal fibrosis and rare intermyofiber edema were observed. This study provides preliminary evidence that DCM occurs in captive banded mongoose, but etiology and wider prevalence need to be determined.

Preclinical dilated cardiomyopathy and advances in treatment

Preclinical dilated cardiomyopathy and advances in treatment

Long-term Outcome of Irish Wolfhound Dogs with Preclinical Cardiomyopathy, Atrial Fibrillation, or Both Treated with Pimobendan, Benazepril Hydrochloride, or Methyldigoxin Monotherapy.

BackgroundDilated cardiomyopathy (DCM) is a common cause of morbidity and mortality in the Irish Wolfhound (IW). However, the benefit of medical treatment in IW dogs with preclinical DCM, atrial fibrillation (AF), or both has not been demonstrated.ObjectivesCompare the time to develop congestive heart failure (CHF) or sudden death in IW dogs with preclinical DCM, AF, or both receiving monotherapy with pimobendan, methyldigoxin, or benazepril hydrochloride.AnimalsSeventy‐five client‐owned IW dogs.MethodsIrish Wolfhound dogs were prospectively randomized to receive pimobendan (Vetmedin®)1, benazepril HCl (Fortekor®)2, or methyldigoxin (Lanitop®)3 monotherapy in a 1:1:1 ratio in a blinded clinical trial. The prospectively defined composite primary endpoint was onset of CHF or sudden death. To assure stringent evaluation of treatment effect, data from dogs complying with the study protocol were analyzed.ResultsSixty‐six IW fulfilling the study protocol included 39 males, 27 females; median (interquartile range) age, 4.0 years (3.0–5.0 years) and weight, 70.0 kg (63.0–75.0 kg). Primary endpoint was reached in 5 of 23 (21.7%) IW receiving pimobendan, 11 of 22 (50.0%) receiving benazepril HCl, and 9 of 21 (42.9%) receiving methyldigoxin. Median time to primary endpoint was significantly longer for pimobendan (1,991 days; 65.4 months) compared to methyldigoxin (1,263 days; 41.5 months; P = .031) or benazepril HCl‐(997 days; 32.8 months; P = .008) treated dogs.Conclusions and Clinical ImportanceIn IW dogs with preclinical DCM, AF or both, pimobendan monotherapy significantly prolonged time to onset of CHF or sudden death than did monotherapy with benazepril HCl or methyldigoxin.

Cardiac pathology in Irish wolfhounds with heart disease

ObjectivesTo evaluate gross and histopathologic lesions in Irish wolfhounds (IWs) with atrial fibrillation (AF) and/or primary dilated cardiomyopathy (DCM) in different stages of disease. MethodsTwenty-six formalin-fixed IW hearts were studied. Clinical diagnosis was based upon results of their most recent cardiovascular examinations including electrocardiography and echocardiography and categorized as normal (n = 4); preclinical (asymptomatic) DCM with AF (n = 6); DCM with congestive heart failure and AF (n = 4); AF with left ventricular reverse remodeling after DCM diagnosis (n = 3); AF without DCM (n = 7); and DCM with sinus rhythm (n = 2). All hearts were evaluated by one pathologist (HA) blinded to the clinical diagnosis. ResultsTen of 15 DCM hearts showed mild to moderate multifocal myocardial fibrosis with variable diffuse adipocyte infiltration within the left and right ventricular myocardium. In five DCM hearts, there were no histopathological findings identified. Right atrial appendages from AF dogs with and without DCM had significantly more myocardial fibrosis and adipocyte infiltration compared with normal hearts and compared to left atrial appendages. ConclusionsGross and histological findings in the ventricular myocardium of IWs with clinical diagnosis of DCM were variable; in some dogs, histopathology was normal. In IWs, the etiology of DCM might be different from that in other breeds with conditions causing functional impairment rather than evident histological changes. Right and left atrial appendages from IWs with AF displayed substantial pathology (interstitial fibrosis and adipocytes) most prevalent in the right atrial appendages which may be correlated to the pathogenesis of AF. These preliminary findings merit further study.

Altered regional cardiac wall mechanics are associated with differential cardiomyocyte calcium handling due to nebulette mutations in preclinical inherited dilated cardiomyopathy

Nebulette (NEBL) is a sarcomeric Z-disk protein involved in mechanosensing and force generation via its interaction with actin and tropomyosin–troponin complex. Genetic abnormalities in NEBL lead to dilated cardiomyopathy (DCM) in humans and animal models. The objectives of this study are to determine the earliest preclinical mechanical changes in the myocardium and define underlying molecular mechanisms by which NEBL mutations lead to cardiac dysfunction. We examined cardiac function in 3-month-old non-transgenic (non-Tg) and transgenic (Tg) mice (WT-Tg, G202R-Tg, A592E-Tg) by cardiac magnetic resonance (CMR) imaging. Contractility and calcium transients were measured in isolated cardiomyocytes. A592E-Tg mice exhibited enhanced in vivo twist and untwisting rate compared to control groups. Ex vivo analysis of A592E-Tg cardiomyocytes showed blunted calcium decay response to isoproterenol. CMR imaging of G202R-Tg mice demonstrated reduced torsion compared to non-Tg and WT-Tg, but conserved twist and untwisting rate after correcting for geometric changes. Ex vivo analysis of G202R-Tg cardiomyocytes showed elevated calcium decay at baseline and a conserved contractile response to isoproterenol stress. Protein analysis showed decreased α-actinin and connexin43, and increased cardiac troponin I phosphorylation at baseline in G202R-Tg, providing a molecular mechanism for enhanced ex vivo calcium decay. Ultrastructurally, G202R-Tg cardiomyocytes exhibited increased I-band and sarcomere length, desmosomal separation, and enlarged t-tubules. A592E-Tg cardiomyocytes also showed abnormal ultrastructural changes and desmin downregulation. This study showed distinct effects of NEBL mutations on sarcomere ultrastructure, cellular contractile function, and calcium homeostasis in preclinical DCM in vivo. We suggest that these abnormalities correlate with detectable myocardial wall motion patterns.

Efficacy of Pimobendan in the Prevention of Congestive Heart Failure or Sudden Death in Doberman Pinschers with Preclinical Dilated Cardiomyopathy (The PROTECT Study)

BackgroundThe benefit of pimobendan in delaying the progression of preclinical dilated cardiomyopathy (DCM) in Dobermans is not reported.HypothesisThat chronic oral administration of pimobendan to Dobermans with preclinical DCM will delay the onset of CHF or sudden death and improve survival.AnimalsSeventy-six client-owned Dobermans recruited at 10 centers in the UK and North America.MethodsThe trial was a randomized, blinded, placebo-controlled, parallel group multicenter study. Dogs were allocated in a 1:1 ratio to receive pimobendan (Vetmedin capsules) or visually identical placebo.The composite primary endpoint was prospectively defined as either onset of CHF or sudden death. Time to death from all causes was a secondary endpoint.ResultsThe proportion of dogs reaching the primary endpoint was not significantly different between groups (P = .1). The median time to the primary endpoint (onset of CHF or sudden death) was significantly longer in the pimobendan (718 days, IQR 441–1152 days) versus the placebo group (441 days, IQR 151–641 days) (log-rank P = 0.0088). The median survival time was significantly longer in the pimobendan (623 days, IQR 491–1531 days) versus the placebo group (466 days, IQR 236–710 days) (log-rank P = .034).Conclusion and Clinical ImportanceThe administration of pimobendan to Dobermans with preclinical DCM prolongs the time to the onset of clinical signs and extends survival. Treatment of dogs in the preclinical phase of this common cardiovascular disorder with pimobendan can lead to improved outcome.

Assessment of mechanical ventricular synchrony in Doberman Pinschers with dilated cardiomyopathy

Objectives Loss of temporal synchrony of myocardial contraction has been shown to reduce systolic function and be responsible for disease progression in people. The objective of this study is the assessment of inter- and intra ventricular synchrony in healthy Doberman Pinschers and those with dilated cardiomyopathy (DCM) by use of conventional Doppler and tissue velocity imaging. Animals A total of 60 scans from 35 client-owned Doberman Pinschers presented for cardiac evaluation were analysed. Methods Retrospective analysis of data. Using the European Society of Veterinary Cardiology DCM taskforce scoring system, Doberman Pinschers were classified into 4 groups: Control (Group 1; n = 12), depressed systolic function other than DCM (Group 2; n = 9), preclinical DCM (Group 3; n = 8) and symptomatic DCM (Group 4; n = 6). The time intervals between the beginning of the QRS complex and the peak velocity of pulmonic flow (Q-P) and the peak aortic flow (Q-Ao) were used to assess global synchrony between both ventricles. The time intervals between the beginning of the QRS complex and the peak myocardial systolic velocity (Q-peak S) and the onset of myocardial systolic velocity (Q-start S) were measured at the base of the right and left ventricular free wall (RVFW and LVFW) and interventricular septum (IVS), and used to determine segmental longitudinal inter- and intra ventricular synchrony. Results No significant loss of global or segmental longitudinal inter- or intra ventricular synchrony was identified between the groups. Conclusion Impairment of longitudinal fibre synchrony does not appear to be significantly associated with clinical status of DCM in Doberman Pinschers, although it was identified in certain individuals.

Toxicity in Doberman Pinchers with Ventricular Arrhythmias Treated with Amiodarone (1996–2005)

Asymptomatic Doberman Pinschers with dilated cardiomyopathy (DCM) often die suddenly owing to ventricular tachycardia that degenerates into ventricular fibrillation. A safe and effective antiarrhythmic drug treatment is needed. This will require a large, well-controlled, prospective study. Amiodarone toxicity is common in Dobermans with occult DCM and ventricular tachyarrhythmias refractory to antiarrhythmia therapy. Infrequent monitoring of hepatic function is inadequate. Frequent monitoring may be useful to determine dogs in which the dosage should be decreased or the drug withdrawn. Medical records from the University of Georgia and Cornell University were searched for Doberman Pinschers diagnosed with preclinical DCM that received amiodarone for severe ventricular arrhythmias refractory to other antiarrhythmic agents. Echocardiographic data, Holter recording data, hepatic enzyme serum activity, and serum amiodarone concentrations were recorded. The presence of clinical signs of toxicity was recorded. Serum amiodarone concentrations were obtained in some dogs. Reversible toxicity was identified in 10 of 22 (45%) dogs. Adverse effects from amiodarone were common and were, in part, dosage related. Patients should be monitored for signs of toxicity and liver enzyme activity should be measured at least monthly.

Vasopressin, cortisol, and catecholamine concentrations in dogs with dilated cardiomyopathy

To evaluate plasma concentrations and urinary excretion of vasopressin and cortisol and urinary excretion of catecholamines in dogs with dilated cardiomyopathy (DCM). 15 dogs with clinical signs of DCM, 15 dogs with preclinical DCM, and 15 control dogs. Physical examinations, thoracic radiography, ECG, and echocardiography were performed on all dogs. Blood and urine samples were collected. Plasma concentration of vasopressin and the urine cortisol-to-urine creatinine ratio were significantly increased in dogs with clinical signs of DCM and dogs with preclinical DCM, compared with control dogs. Plasma vasopressin concentration was significantly higher in dogs with clinical signs of DCM, compared with dogs with preclinical DCM. Urine vasopressin-to-urine creatinine ratio was significantly increased in dogs with clinical signs of DCM, compared with dogs with preclinical DCM and control dogs. Urine epinephrine-to-urine creatinine ratio and urine norepinephrine-to-urine creatinine ratio were significantly increased in dogs with clinical signs of DCM, compared with control dogs. Plasma concentration of cortisol and urine dopamine-to-urine creatinine ratio did not differ significantly among groups. According to this study, the neuroendocrine pattern is changed in dogs with preclinical DCM. These changes are even more pronounced in dogs with clinical signs of DCM. Analysis of concentrations of vasopressin, cortisol, and catecholamines may aid in identification of the clinical stages of DCM. These findings may also provide a basis for additional studies of the possible beneficial effects of vasopressin antagonists and beta-adrenergic receptor antagonists in the treatment of dogs with congestive heart failure and DCM.

Proposed Guidelines for the Diagnosis of Canine Idiopathic Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) is a major cause of morbidity and mortality in various dog breeds. The diagnosis of overt DCM is not normally problematic, although the importance of active exclusion of other causes of the dilated, hypokinetic heart is emphasised. Recent interest in human familial DCM has prompted a number of researchers to investigate the genetic basis of canine DCM. Prospective screening of dogs from lines with familial prevalence of DCM may identify dogs with pre-clinical (“occult”) DCM. Dogs with other echocardiographic abnormalities or arrhythmias may also be identified. It is clear that dogs, like humans, have a prolonged pre-symptomatic phase of the disease extending over years. The ESVC DCM taskforce was established to provide the veterinary cardiology community with guidelines for the diagnosis of DCM, predominantly based on 2D and M-mode echocardiography. Diagnosis of DCM requires all of the following: (i) Left ventricular dilatation (ii) Reduced systolic function (iii) Increased sphericity of the left ventricle. We propose a scoring system for the identification of dogs in the pre-clinical stages. These include a number of major criteria and minor criteria. Future prospective longitudinal studies are required to test these in different breed populations to assess their predictive power and further refinements may be required. The importance of post mortem confirmation of disease is emphasised, and the two major histopathological features associated with DCM, the attenuated wavy fibre and the fibro-fatty infiltration-degenerative forms, require further investigation to identify the different aetiopathogenetic factors which may be involved.

Organ-specific cardiac autoantibodies in dilated cardiomyopathy--an update.

Autoimmune disease is characterized by the presence of organ- and disease-specific autoantibodies in patients and first degree relatives; antibody detection may precede disease onset by several years. We investigated potential involvement of organ-specific autoimmunity in dilated cardiomyopathy (DCM). Using indirect immunofluorescence and absorption studies, organ- and disease-specific IgG cardiac antibodies were found in one-third of DCM patients. Antibody status at diagnosis was associated with better exercise capacity; at 1-year follow-up two-thirds of antibody-positive patients became negative. These findings suggest that antibodies are early markers; their absence in the majority of patients at diagnosis may relate to long-standing pre-clinical DCM. Antibody screening was performed in asymptomatic DCM relatives, 177 from 33 families with > 1 affected individual (familial DCM) and 165 from 31 pedigrees with non-familial DCM. Antibodies were detected in 37 (58%) pedigrees and were more common among relatives than in normals (20% vs 3.5%, P = 0.0001). Antibody-positive relatives were younger, had larger left ventricular end-systolic dimension and reduced % fractional shortening compared to antibody-negative relatives. These findings provide evidence for autoimmunity in a subset (58%) including both familial and non-familial DCM; cardiac-specific antibodies may identify relatives at risk of developing DCM.