„Slow Kill” – adulticide protocol in heartworm treatment! Can we use it? When to use it? How to use it?
veterinary clinic “Vitalis”, Plovdiv, Bulgaria
Heartworm disease is caused by Dirofilaria immitis. The disease is widely distributed throughout Europe. Species susceptible to infection are dogs, wolves, foxes, coyotes, cats, ferrets, muskrats, sea lions, and humans. The parasite is transmitted by over 70 species of mosquitoes.
Adult heartworms reside in pulmonary arteries and in cases of severe infections in the right ventricle. Mature female parasites produce microfilariae and release them into the circulation. The feeding female mosquitoes ingest these microfilariae, and they undergo two molts, L1 – L2 – L3, over an 8 to 17 dаy period. This process is temperature-dependent (at least 18 C are needed). The L3 are infective and are transmitted by the mosquito to the hosts. In the subcutaneous, adipose, and skeletal muscle tissue L3 molt to L4 for 1 to 12 days and L4 molts to S5 – immature adults, for 2 to 3 months. The Immature adults enter the vascular system, migrating to the heart and lungs, where final maturation and mating occur. Under optimal conditions, completion of the life cyclе takes 184 to 210 days.
The adult worms cause the following through mechanical, immune-induced, and through toxic substances: inflammation and proliferation of the pulmonary arteries, pulmonary thromboembolism, pulmonary hypertension, and right-sided heart failure. Clinical signs of the disease are weight loss, exercise intolerance, lethargy, poor condition, cough, dyspnea, syncope, abdominal distention.1
According to the guidelines of the American Heartworm Society2 treatment of the heartworm infection consists of doxycycline 10 mg/kg BID for 28 days, monthly use of macrocyclic lactones, and melarsomine at days 60, 90 and 91.
In other publication3, the authors suggest administration of melarsomine on day 30 , 60 and 61, to make the protocol shorter, and to better comply with the owner’s financial resources.
In certain circumstances, melarsomine dihydrochloride could be contraindicated, unavailable, or not affordable to the owners. In this situation the practicing veterinarian could use the so-called “Slow kill” or “Soft kill” protocol. It consists of the use of macrocyclic lactones in prophylactic doses with and withоut doxycycline to kill adult heartworms4–6. In most of the studies, the results are not satisfactory. L. Venco et al.6 used ivermectin – 6mcg/kg, monthly and had 100% microfilaricidal efficiency after 7 months, and 71% adulticidal efficiency after 24 months. The authors do not recommend this treatment regime in patient with clinical, radiographic or echocardiographic signs. G. Grandi et al.4 used doxycycline – 10 mg/kg/sid for 30 days and ivermectin-pyrantel – 6mcg/kg-14mg/kg every 15 days. By day 90 one hundred percent of the dogs became negative for microfilariae, and 72.7% became antigen-negative by day 300.
The study of Savadelis et al.7from 2017 had results similar to melarsomine treatment for a relatively short period of time. They used topical moxidectin 2.5%+imidacloprid 10% monthly with combination of doxycycline 10mg/kg/bid for 30 days. All treated dogs became negative for microfilariae at day 21. Ten months after the beginning the adulticidal efficacy was 95.6%. Hence, the conclusion of the authors is that this treatment regimen is a relatively quick, reliable and safe option to treat canine heartworm infection as compared to other treatment regimens involving macrocyclic lactones, when the approved drug melarsomine dihydrochloride is unavailable, contraindicated or declined by an owner unable to afford the more costly treatment or concerned about the potential side effects”.
I used this protocol numeral times with very good results. Most of the dogs were with class 4 heartworm disease and caval syndrome. Probably the most severe case was a 10-year-old Bulgarian shepherd dog. At presentation, the dog was cachectic, could not walk, did not eat for several days, and had ascites. Blood work revealed slight leukocytosis, neutrophilia, and thrombocytopenia, slightly increase in ALAT, ASAT, BUN, decrease in albumin, and the test for HW antigens was positive. Echocardiographic examination revealed severely dilated right atrium and right ventricle, with heartworms in the tricuspid valve region(video 1).
The left atrium and ventricle were collapsed due to severe pulmonary hypertension. Of course, in this situation surgical extraction of the worms is the first choise8, but this option was declined by the owners. So we started treatment with doxycycline 10 mg/kg/sid, moxidectin+imidacloprid topically, and sildenafil 1mg/kg/bid. Several days after the start of the treatment the dog was in better condition, and on the echocardiographic examination we found that the left ventricle is relatively dilated, compared with the previous exam, the number of worms in the tricuspid valve region was subjectively lower. However, on m-mode, the systolic motions of Interventricular septum and left ventricular free wall was weak(photo 2). Therefore we suggested that the dog has subclinical dilated cardiomyopathy, which contributed to the development of the caval syndrome. We added pimobendane – 0.25mg/kg/bid and benazepril – 0.5 mg/kg/bid and prednisolone – 0.5mg/kg/sid to the therapy for thromboembolism prophylactic. On the next control examination, the dog was feeling better, there were no heartworms in the right atrium and ventricle and in the pulmonary artery(photo 3,4).
After a month from the diagnosis we stopped the doxycycline and continued with other pimobendane, benazepril, topical moxidectin+imidacloprid, sildenafil, and prednisolone – 0.5 mg/kg/48h. After two more months we gradually stopped the prednisolone. Six months after diagnosis the antigen test for heartworms was negative. The dog still had severe pulmonary hypertension, exercise intolerance and coughed occasionally. We continued treatment with pimobendane, benazepril and sildenafil and monthly moxidectin+imidacloprid for heartworms prophylactic. The dog lived for two more years and died from noncardiogenic reasons. I have similar results with two other large-breed dogs, also with caval syndrome, with complete resolution of clinical signs and withdrawal of all drugs, only continuing with moxidectin+imidacloprid for heartworm prophylactic. A small-bred dog developed severe pulmonary hypertension and tricuspid valve granuloma after the third month probably due to damages of the tricuspid valve from heartworms(photo 5), and untreatable right-side heart failure. Soon after the dog was euthanized.
The “slow kill” protocol is arguably more suitable for large and giant breed dogs, where the surgical extraction is more challenging, and the treatment with melarsomine is more expensive. In caval syndrome, the worms could be moved back in the pulmonary artery with a combination of pimobendane and sildenafil. Sildenafil is a phosphodiesterase 5 inhibitor, and pimobendane is a phosphodiesterase 3 inhibitor. The combination leads to more profound reduction in pulmonary artery pressure. The pimobendane has positive inotropic effect, hence the combination of improved myocardial function and lower pulmonary artery pressure helps in movement of the heartworms from right heart in pulmonary artery9(photo 6, 7 – before and after administration of pimobendane and sildenafil).
In small and medium dog breeds the surgical extraction, when possible, is the best choice, however, do not exclude the use of macrocyclic lactones and melarsomine.
In conclusion, when we treat a dog with dirofilariosis, we should first rely on the American heartworm society guidelines2. When we decide to use the Slow kill protocol, the macrocyclic lactone of choice is topical moxidectin. It has a unique pharmacokinetic, establishing a peak several days after application, long half-life about 28 days, and steady-state levels after four monthly applications, ensuring constant and high exposure of the parasites to the drug10,11. Of course doxycycline is also mandatory for adulticide therapy. Last but not least, we always have to think of the patient, we have to treat the patient rather than the disease, and to ensure good quality of life to them.
FIRST REPORTED CASE OF SYMPTOMATIC DIROFILARIA IMMITIS INFECTION IN A HOUSOLED DOMESTIC FERRET (MUSTELA PUTORIUS FURO) IN BULGARIA.
1Veterinary surgeon in United Veterinary Clinic Bulgaria Varna 9000,
Heartworm disease in dogs and cats is well known in many European countries including Bulgaria. There are furthermore studies confirming dirofilariosis in wild foxes and Canis aureus i reports about heartworm disease in domestic ferrets in our country.
A 5 year old male, entire, pet ferret (Mustela putorius furo), weight 0,9 Kg was presented with labored abdominal breathing. The owner reported reduced appetite, difficulty breathing and restlessness. The ferret was not able to sleep or lie down for more than few minutes. The ferret was used to live mainly indoor and allowed during the summer to be outside in the garden, for just few hours during the day, to be exposed to natural sunlight.
Clinical presentation and collateral exams
On presentation ferret was lethargic with abdominal breathing and breathing rate up to 90/minute. There was clear subcutaneous edema more prominent on the front and hind legs and ventral part of the abdomen. Mucous membranes were pale, while CRT was not possible to be assessed. Heart rate ranged in between 120-180 bpm. Pulses were weak even if assessing on the femoral artery was difficult due to the subcutaneous edema. Abdominal palpation was unremarkable, lymph nodes were normal in size. Thoracic radiograph showed loss of detail into thoracic cavity consistent with pleural effusion. Thoracic US was performed confirming pleural effusion and one hundred and twenty ml of modified transudate was drained. Brief screening echocardiography showed normal left atrium and left ventricle and severely dilated right atrium containing double line hyperechoic objects suggesting the presence of few adult Heartworms. (Fig 1). Right atrium was larger than left atrium. Doppler study and any further detailed investigation of the heart were not possible to be performed due the fact ferret became aggressive and owner declined any sedation or anesthesia. Snap® HTWM Antigen test (Idexx) on blood yielded negative result and at fresh blood smear examination no microfilariae were possible to be identified. Knott test was not possible to be performed due to limited amount of sampled blood.
On the basis of echocardiography findings diagnosis of HW disease was done. Negative HW antigen test was assumed to be due probably due to juvenile D.immitis worms and right atrium localization to the small size of pulmonary arteries as described in cats and ferrets.
Therapy and Follow up
The ferret was treated with Advocate® spot on >4kg (half tube), Furosemide 2mg/kg twice a day and Prednisolone 1mg/kg daily both of them orally. The ferret was stable on that therapy. He was eating and drinking well regain the normal body weight 1.5 kg. no breathing difficulties were reported. He was rechecked 35 days after initial presentation. Echocardiography showed right mildly dilated atrium but no presence of HW (Fig 2). Only 10 ml of fluid was drained from the thoracic cavity. From that time he was stable with no owners complain for 6 month. Suddenly he developed respiratory distress and on presentation was with cyanotic membrane. Pulmonary thromboembolism connects to HW disease was suspected Owner elected euthanasia and no more investigations. Necropsy was declined.
This case shows the in endemic area even indoor domestic ferrets may be infected by Dirofilaria immitis. and that the disease is difficult to be diagnosed and can lead to death. Suspicion about this problem and monthly chemoprophylaxis should be warranted in this situation as in dogs and cats.
Diagnosis and therapeutic management in a a dog with severe cardiac dilatation associated with complex arrhythmias – A case report.
Radu Andrei BAISAN, Vasile VULPE
Clinics Department, Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine “Ion Ionescu de la Brad”, Iași, Romania
Cardiac dilatation is a common finding in dogs with heart disease. Chronic myocardial stress and volume overload are the main reasons for cardiac remodeling. These changes are encountered in most of chronic diseases such as dilated cardiomyopathy, mitral valve disease or congenital disease that develop volume overload. Cardiac dilatation should not be confused with dilated cardiomyopathy (DCM), which is known to be a myocardial disease induced by several specific factors such as genetic or familial predispositions. In the absence of specific signs, such as mitral valve degeneration or congenital heart diseases, cardiac dilatation should be carefully evaluated and additional tests must be performed before deciding the diagnosis and therapy. In veterinary medicine, there is insufficient data regarding the differential diagnosis of cardiac dilatation when specific sins are absent.
The aim of this paper is to report and discuss a patient with congestive heart failure due to severe cardiac dilatation associated with multiple arrhythmias and to describe the diagnostic protocol, therapy and evolution of the disease.
An eleven years male, German Shorthaired Pointer dog, weighing 38 kg, was referred for a second opinion to our Cardiology Service from the Teaching Hospital of the Veterinary Faculty of Iași, because of chronic abdominal fluid accumulation, severe effort intolerance and weight loss for the past few months. The dog was receiving cardiac therapy assigned by the referring clinician and consisted of pimobendane (Vetmedin® Boehringer Ingelheim), 0.25 mg/kg P.O. BID and furosemide (Furosoral, Artesan Pharma GmbH & Co.), 2 mg/kg P.O. BID. The owner reported that the dog had been treated for Babesia canis for four times in the past few years.
During the first visit, the dog was subjected for complete cardiologic examination consisting of physical examination, five minutes six leads electrocardiography (PolySpectrum veterinary device), blood pressure measurement (Vet-HDO blood pressure device), cardiac ultrasonography (Logiq V5, General Electric), cardio-thoracic radiography (Intermedical Basic 4006 X-ray machine and Examion X-CR smart digital developing machine) and biochemical and CBC blood analyses as previously described [1-4].
Physical examination showed pink mucosal membranes, with a CRT of 3 seconds, abdominal distension, breathlessness, with a normal respiratory rate (28 bpm), strong and arrhythmic cardiac beats, without precordial thrill. The palpation of the femoral artery revealed weak asynchronous arterial pulse. Auscultation revealed an arrhythmic rhythm and III/VI systolic plateau left apical murmur. Auscultation of the lungs revealed crackles in both sides of the caudal lung lobes.
Electrocardiography revealed an arrhythmic rhythm with a median heart rate of 130 bpm, with more types of arrhythmias present over the five minutes ECG tracing. The predominant rhythm was accelerated idioventricular rhythm, with a heart rate of 168 bpm, interrupted by runs of supraventricular tachycardia, with a heart rate of 240 bpm and sinus tachycardia with a heart rate of 165 bpm (Fig no 1).
There were also present runs o junctional beats with a retro-conducted P-wave. Between these sequences of arrhythmias, there were present 25 left ventricular premature complexes, with the same morphology, with a negative polarity in DII, DIII, and aVF and positive polarity aVR and aVL. These complexes had a length of 120 msec and a tall, opposed T-wave. Multiple fusion beats were also present (Fig no 2 and 3).
The blood pressure measurement was performed with a D1 cuff placed on the tail and simultaneous recording of the pulsating-wave graphic. However, measurements of the blood pressure were not accurate due to the differences in the pulsating wave.
Cardiac ultrasonography revealed severe left ventricular dilatation during systole (39.6 mm 95%CI 15.8-17.18 mm) and diastole (64.2 mm, 95% CI 37.64-39.1 mm), with thinned interventricular septum and ventricular free wall and severe left atrial dilatation, with a LA/Ao ratio of 2.54 (normal upper limit 1.6). Also, the left auricular cavity was visibly enlarged. The mitral valve was thin with normal echoic appearance and abnormal motion due to the hemodynamic changes induced by the underlying arrhythmia and a regurgitating jet was observed by color doppler. The left ventricle systolic function was within normal limit, when assessed during supraventricular rhythm (SF%=38, EF%=67). The pulmonary and aortic flow were laminar, within normal ranges. There were no signs of pulmonary hypertension. The pericardium was normal, without fluid accumulation (Fig no 4-6).
Fig nr. 4 Echocardiographic left parasternal long axis apical four chamber view of an eleven years old dog with signs of congestive heart failure. The LA and LV are visible enlarged and the mitral valve leaflets appear normal. LV-left ventricle; LA-left atrium; RV-right ventricle; RA-right atrium;
Fig nr. 5 Echocardiographic right parasternal long axis oblique four chamber view optimized for the left atrium of the same dog with signs of congestive heart failure. The LA and Lau appear visible enlarged. LV-left ventricle; LA-left atrium; LAu-left auricle
A left lateral thoracic X-ray was available for examination and revealed severe cardiomegaly, with a VHS of 13.3v. The trachea was dorsally displaced and a perihilar pulmonary interstitial and alveolar pattern was visible in the caudal lung lobes consistent with moderate cardiogenic pulmonary edema. A round radiopaque area was present over the gallbladder topography and a gallbladder stone was suspected (Fig no 7).
Blood biochemical analyses were within normal ranges except a moderate hypoalbuminemia (2.5 g/dL normal ranges 2.6-4 g/dL) and moderate increased alanine aminotransferase (58 UI/L, normal ranges 8-57 UI/L). Cell blood count was within normal ranges.
The diagnosis consisted of idiopathic dilated cardiomyopathy with supraventricular and ventricular arrhythmias. The current therapy was maintained and amiodarone (Amiodaronă LPH, LABORMED PHARMA S.A.), was added as following: 15 mg/kg P.O. BID for 7 days, followed by 7.5 mg/kg P.O. BID for the next seven days and 7.5 mg/kg P.O. QD for the next fourteen days. The dog was released from the hospital the same day with effort and salt restriction. The reevaluation was scheduled after 2 weeks if no event required a sooner visit.
Three weeks later, the owner called for a reevaluation. The medication was administered according to recommendation and no events were observed during this period. aA significant improvement in the quality of life of the patient was reported.
The dog was alert and active during physical examination, with pink mucosal membranes, CRT of 3 seconds, moderate decreased respiratory rate (36 bpm) and effort, and a less distended abdomen. Palpation of the thorax revealed a strong cardiac beat and the arterial pulse was synchronous with the cardiac beat. Cardiac auscultation showed rhythmic rhythm, with a heart rate of 114 bpm and III/VI systolic plateau left apical murmur.
The five minutes six lead ECG tracing revealed a predominant sinus rhythm, interrupted by 107 single supraventricular complexes and only one right ventricular premature complex with positive polarity in DII, DIII and aVF and negative in DI, aVR and aVL. No sequences of supraventricular tachycardia or accelerated idioventricular rhythm were present on the five minutes tracing. The abnormalities in morphology of the sinus beats revealed a mitral P-wave (78 msec), increased amplitude of the R-wave (3.34 mV) and increased length of the QRS complex (91 msec) (Fig no 8).
There were no improvements seen during the echocardiographic examination. The owners were instructed to administer the therapy with pimobendane and furosemide continuously and amiodarone until the end of protocol. Eight weeks after the first examination, owners reported by telephone that the patient is alive and the quality of life remained improved.
Dilated cardiomyopathy (DCM) can occur as a primary cardiomyopathy such as genetic, or familial DCM , or secondary to myocardial stress, such as drug- or toxin-induced, infiltrative, ischaemic, metabolic, nutritional, or inflammatory myocardial diseases . In both cases, DCM is expressed through a disease of the myocardium associated with ventricular systolic and diastolic dysfunction and development of congestive heart failure . According to ESVC Taskforce for Dilated Cardiomyopathy, 2003, scoring system, the score in this dog was above 6 points, which is consistent with the presence of DCM . The left ventricular internal diameter in both systole and diastole were above the 95% CI based on the regression formula , the sphericity index was under the lowest recommended limit and left atrial enlargement was present. However, there were some changes that did not seem to be associated with primary DCM. The shortening and ejection fraction were within normal ranges and the large range of arrhythmias was not consistent with specific morphologic and rhythm changes in primary DCM. It has been suggested that atrial fibrillation is the most common arrhythmia in dogs with DCM and also, increased number of ventricular premature complexes may have diagnostic value [5, 8]. Nevertheless, it must be considered that the dog was treated with positive inotropic medication which may have influenced the systolic function of the heart. Another unexpected result was the intense positive response to arrhythmic therapy. Amiodarone is an antiarrhythmic agent with primarily class 3 action, but also potent class one. This agent prolongs the action potential duration and the effective refractory period in all cardiac tissues. It is recommended in dogs with ventricular arrhythmias and has also been used to convert atrial fibrillation to sinus rhythm .
The differential diagnosis for cardiac dilatation should include secondary DCM due to cardio-toxicosis, drug-induced, metabolic or nutritional factors, chronic myocarditis or tachycardia-induced cardiomyopathy (TIC). Secondary DCM is difficult to diagnose due to the multiple factors of environment and microclimate. A large series of pathogens have been reported to induce chronic myocarditis, including canine babesiosis [10-15]. However, in most studies, the etiological diagnosis was reached through histopathological examination of the cardiac tissue after patient’s death . Considering the four episodes of clinical manifestation of canine babesiosis in this patient, cardiac enlargement may be related to this. Tachycardia-induced cardiomyopathy is characterized by cardiac dilatation and systolic and diastolic dysfunction due to long-term increased heart rate, however these changes may be easily confused with DCM. Clinical studies in human medicine have suggested that the left ventricle internal diameter and volume are significantly smaller in patients with TIC than in those with DCM . Another difference between the two pathologies is that the ventricle remodeling during TIC may benefit from partial or total reversibility once the arrhythmia control is achieved . In the patient discussed in this paper, we observed a significant improvement in controlling the rhythm and heart rate after the antiarrhythmic therapy but not in the cardiac remodeling. It remains unclear whether the arrhythmias were induced by the myocardial structural changes during the progression of heart remodeling or if the dilatation was induced by a chronic supraventricular tachyarrhythmia which later developed ventricular complexes and accelerated idioventricular rhythm.
Dilated cardiomyopathy is a common cardiac disease in large breed dogs, however differential diagnosis must be considered when cardiac dilatation is present, in the absence of any certain factors. The dog from this report had cardiac dilatation associated with severe arrhythmia. Although an etiologic diagnosis could not be established, we succeeded to improve the quality of life by controlling the heart rate and the rhythm.
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Open heart surgery for a left atrial mass extraction during cardio-pulmonary bypass (CPB) in a 9 yoa Labrador dog
Ranko Georgiev1, Stoyan Nikolov2, Nadezhda Petrova3
Georgi Ignatov4, MD Thoracic Surgery
1,2,3 DVM, Central Veterinary Clinic, Sofia, Bulgaria
4 MD, City Clinic Cardiovascular Center, Sofia, Bulgaria
Open heart surgery during a cardiopulmonary bypass is the only effective approach for some diseases that require an access to the heart chambers or the great vessels; even when a temporary inflow occlusion is chosen as an alternative, only a very few “time restricted” procedures could be done on a beating heart. However, when considering an open heart surgery, the high risk of intra- and post- procedure complications often outweighs the benefits. In veterinary medicine the financial weight of such a procedure is also a limiting factor.
We would like to share a case where a temporary sinus arrest was induced during a cardiopulmonary bypass and a huge mass was successfully extracted from the left atrium of a dog with an open heart approach.
Arthur is a 9 year old MC Labrador, trained like a guide dog for a blind person, admitted because of increasingly frequent exercise intolerance episodes during the past few months. Furthermore, the last week the patient was very weak and experienced several syncopal episodes. On a clinical presentation with the referring vet а tachycardia and dyspnea were noted and the patient was referred to us for a Cardiology consult.
On physical examination, the dog weighted 25 kg, with a history of a rapid body mass loss for the last couple of months. His “normal” weight has always been around 32 kg according to the owners. The body condition was poor (score 2/5) and the dog had a grade II/VI left sided apical soft diastolic heart murmur. Lung auscultation was unremarkable, but the respiratory rate (RR) was more than 50 breaths per minute.
The X-rays of the chest were highly suggestive for e left sided congestive heart failure and showed mild generalized cardiomegaly with a VHS of 11.5 with enlarged left atrium and left ventricle. The pulmonary veins were slightly larger than the pulmonary arteries; the lung parenchyma with diffuse interstitial pattern in the area of the hilus. The patient was already on Furosemide in a low dose – 2mg/kg twice a day for the last two weeks with no improvement of the clinical signs.
A transthoracic echocardiography was done with the patient in lateral recumbence through the right and left parasternal windows. A huge echogenic mass with irregular shape was observed in the area of the left atrium – attached to the intra atrial septum and prolapsing through the mitral valve during diastole towards the left ventricle. The mass was creating almost full diastolic obstruction of the valve, allowing only a tiny fraction of the blood in.
Complete blood count, electrolytes and biochemical profile were normal. During the abdominal US study no further abnormalities were noted and no more masses found. On the ambulatory ECG a normal sinus rhythm was recorded with multiple atrial premature complexes. The blood pressure was normal. A hemo-culture and a urine culture were obtained and came back negative for a bacterial growth. The bleeding time and the Pt/APtT were normal.
A diagnosis of an intra atrial mass with clinical signs of a progressing left sided congestive heart failure was made and a surgery was discussed. Because of the location of the mass no surgical or interventional approach was possible without the aid of a cardiopulmonary bypass (CPB) and cardioplegia. All the risks and possible complications were discussed with the owner and a decision for such a surgery was made. The team for the surgery was from a veterinary surgeon, human cardiovascular surgeon, cardiovascular perfusionist, veterinary and human anesthetists, and nurses. The procedure was done in Central Vet Clinic, Sofia on 3rd of December 2016.
Our anesthesia protocol with this patient started routinely for the procedure of a thoracic surgery – premedication with Midazolam and Buprenorphine, induction with Etomidate, intubation and maintenance with Isoflurane. Additionally we put a bladder catheter for urine production measurement, central venous catheter, an intra-arterial catheter for a direct blood pressure measurement and tree peripheral intra-venous catheters. Many more drugs were used during the anesthesia and the long post-operative recovery period like Nitroglycerin, Atracurium, Protamine, Amantadine, Pyracetam, Efedrin, Dopamine, Methylprednisolone, Fraxiparin, Clopidogrel, antibiotics, etc.)
The surgical approach was through the left fifth intercostal space with a standard lateral thoracotomy. Additionally the left carotid artery was approached and prepared in case it is needed for the CPB blood return. The pericardium was excised and the left atrium, the big vessels and the left ventricle visualized. Then three cannulas were put – the one collecting the venous blood inside the right atrium (through the right atrium auricle), the one returning the oxygenated blood from the CPB machine into the ascending aorta and one small cardioplegique cannula into the aortic root over the coronary arteries. Then a bolus of Heparin was injected iv in a dose of 800UI/kg and 5 minutes later the patient was switched to the heart-lung machine (Sorin 5 and a pediatric oxygenator with 360 ml prime). Then we started a controlled cooling of the patient using a chiller, connected to the CPB machine. When the target body temperature of 28o C was reached the ascending aorta was cross clamped and a 600 ml of cooled to 4o C crystalloid cardioplegique infusion rich in potassium was infused through the coronary cannula producing complete heart arrest. We stopped the active ventilation of the lungs and the patient became fully dependent of the heart-lung machine. The heart was open through a 5 cm cut into the left atrial wall starting from the auricle tip. The mass was directly visualized and excised. It was connected to the intra atrial septum with a relatively small neck. We removed it without creating an ASD. The air from the heart was evacuated and the surgical cut closed with a 5-0 Polypropylene suture in a continuous way. The mass was a solid and well defined structure with irregular shape and was admitted for histology. The size was 8/6/4 cm.
We started a slow rewarming of the patient with a target body temperature of 38o C. Two epicardial electrodes were embedded and connected with an external pacemaker. Once closed and warmed, the heart was gently massaged manually for a couple of minutes and then hit with a direct pediatric defibrillator. We used 5 to 20J of energy shocks and got a slow and then faster rhythm after the 9th try. The external pacemaker was switched on and put on a 100 bpm rate for the next 12 hours. The surgical closure was uncomplicated and no significant bleeding was noted. The patient received slowly iv Protamin (1mg/100IU Heparin) as a Heparin antidote and the heart-lung machine was gradually restricted and then switched off. Two chest drains were put and connected to a sterile active suction. The total machine time was 130 min, the sinus arrest time – 22 min, total surgery time – close to 5 hours. Immediately after the CPB machine was stopped a hemotransfusion with two units of fresh blood was done.
Arthur recovered from the general anesthesia slowly over the next 12 hours, but he was unable to stand on his feet for additional 5 days. The electrolyte levels, liver and kidney values were monitored almost every hour for the first 2 days and then three to five times a day; our main concern was the potassium blood level and we tried to maintain it stable at all times. The urine production was also constantly monitored and tailored to be in the normal range – with diuretics and blood pressure control drugs. From all the possible complications after a CPB we saw only a transient neurological signs attributed to some degree of brain injury – interpreted after the neurological exam as left sided forebrain lesion – ischemic or hemorrhagic. Arthur recovered completely both physically and mentally for the next two weeks with a lot of supportive care and physiotherapy. On discharge from the clinic he was able again to do all the things a blind person guide dog is trained to do. The histology report was made in a referral laboratory in Germany – Laboklin, and after the immunohistochemistry stain came back as a Neurofibrosarcoma.
CPB is a routine everyday procedure in the human hospitals, usually carrying a good to excellent prognosis and very low mortality rate. On the other hand in the veterinary medicine field is still an exotic and very risky one. Although very demanding both for the clinical team and the patient himself, the cardiopulmonary bypass is the only option for cardiac diseases requiring an open heart surgery. We believe that a close relationship between a human medicine cardio surgical team and a small animal hospital team could make this type of procedures safer and better recognized.
We have done regular monthly rechecks on the patient with echocardiography and X-rays since then and now six months later Arthur is doing great, no drugs or any supportive therapy needed. He gained back his usual weight and is working like a guide dog every day.
Dr Todor Kalinov
ZaraVet- city of Plovdiv, Bulgaria
Degenerative mitral valve disease (DMVD) is the most common cardiologic disorder in canine population. It has been estimated to account for 75% to 80% of canine cardiac disease1. It is common in small breed dogs, but also can be encountered in large breeds like german shepherd and other . The disease characterizes with thickening and enlarging of the mitral leaflets, elongation of chrdae tendineae and mitral regurgitation. Histopathologic features are expansion of extracellular matrix with glycosaminoglycans and proteoglycans; valvular interstitial cell alteration; and attenuation or loss of the collagen-laden fibrosa layer2. Because of the mitral regurgitation the usual course of this disorder represents volume overloud of the left atrium and left ventricle , eccentric hypertrophy of the left ventricle , dilation of the left atrium ,and left sided congestive heart failure . Increased pressure in left atrium and pulmonary veins leads to pulmonary edema . Often complication is so called passive pulmonary hypertension , consequence of increased pressure in pulmonary veins. Really rare complication is left atrial rupture .
Richka is 12 years old mixed breed dog with history of DMVD , threated only with enalapril . She was admitted in our clinic for cardiologic examination, because recently increasing in coughing and exercise intolerance. During the examination she was tachypneic , normal mucous membrane color , alert and responsive .She had increased heart rate. Auscultation revealed right and left apex systolic heart murmurs. The abdomen was swollen with palpable fluid thrill. We have made echocardiographic examination, with the patient on left and right lateral recumbency, with all parasternal views according to the accepted standards. We found eccentric hypertrophy of the left and right ventricles, left and right atrial dilation, thickening and prolapse of the mitral valve. Doppler examination shows mitral and tricuspid regurgitation with pressure gradient of 162 mmHg and 62 mmHg respectively (figures 1,2,3) . Abdominal echography revealed ascites. So we diagnosed degenerative mitral valve disease with secondary pulmonary hypertension. We prescribed following: pimobendan – 0.25 mg/kg/bid , furozemid – 4.0 mg/kg/bid , spironolactone – 1.0 mg/kg bid enalapril – 0.5 mg/kg/bid , sildenafil – 1.0 mg/kg/tid.
Week later on control examination Richka was better, ascites resolved , mitral and tricuspid regurgitation was with gradient 125 mmHg and 43 mmHg respectively. So we decreased the dose of furosemide to 2.0 mg/kg/bid, and the other drugs were continued with the same doses.
Several months later the owners noticed again swelling of the abdomen and the dog collapsed after exercise. When they came in the clinic Richka was tachypneic with cyanotic mucous membrane. On auscultation we have found 5/6 systolic murmur on the right haemithorax with palpable precordial thrill. Electrocardiography revealed sinus tachycardia – 156 bpm , with premature supraventricular and multifocal ventricular complexes (fig 4). We have made roentgenography in right lateral (fig 5) and dorsoventral (fig 6) position. There was generalized cardiomegaly with dilation of the pulmonary vessels. On echocardiographic examination we have found eccentric hypertrophy of the left and right ventricles, paradoxical motion of the ventricular septum (fig 7), mitral and tricuspid regurgitation with gradient – 118 mmHg and 42 mmHg respectively. Abdominal ultrasonography showed ascites with no collapse of the caudal vena cava with respiration (fig 8). Despite the medications and lower then before pulmonary pressure in this dog the signs of right heart failure were predominant. Because of that and the palpable precordial thrill on the right side we suggested right to left intracardiac shunt. The presence of ventricular septal rupture is less possible, so we decide to search for rupture of the atrial septum. On the right parasternal 4 chambers view modified for better visualization of the right and left atrium with atrial septum, we have found rupture of the septum in the region of the fossa ovalis with left to right shunt.
Video 1 and 2 are same loops with and without colour Doppler demonstrating the defect and shunt of the blood. In this region very often because of the echo dropout on 2d image can be seen a hole in the atrial septum. To be sure that this is a real defect we decided to make a bubble contrast study. We injected 10 ml of agitated saline in v.cephalica antebrachii thru i.v. catheter. When there is right to left shunt the microbubbles are seen in left atrim, left ventricle or arterial circulation – usually the abdominal aorta. But in left to right shunt the goal of the bubble study is to notice contrast washout during right atrium passing of the bubbles. Video 3 and 4 show right parasternal short axis view of the base of the heart with cranial vena cava. We can see the entrance of the contrast and the following washout like a flame because of the left to right shunting of the blood.
In this situation sildenafil makes the pulmonary pressure lower and facilitate the shunt from high pressure left atrium to low pressure right atrium. So we decided to use pulmonary hypertension properly and make the dose of sildenafil lower – 1 mg/kg/24 h. with presumption that higher right ventricle and right atrium pressure will make the amount of the shunt lower. 72 hours after this change the ascites resolves and the condition of the dog became better. On the time of the written of the article Richka is about half year on this medications with sildenafil once per day and no changes in other medications and the only clinical sign is exercise intolerance.
Rupture of the atrial septum is really rare complication of mitral valve disease. Most commonly the rupture occurs in caudal weaker part of atrial wall. In a study of Buchanan JW from 30 dogs only in 4 was found rupture of the interatrial septum with signs of right heart failure3. In another study from the same investigator from 50 dogs 7 have acquired ASD4. The еtiology for rupture of the left atrium is uncleаr , but probably is related with the high pressure in the left and right atrium and the so called jet lesions from the mitral and tricuspid regurgitation. Usually the mitral regurgitation jet is toward lateral wall of the left atrium like in this case (video 5). Tricuspid regurgitation jet was directed to interatrial septum so probably contributed to rupture of the septum. The thin fossa ovalis is weak and suitable place for this kind of lesions. In human medicin rupture of the septum is reported after blunt chest trauma , most often accompanied with rupture of the tricuspid valves 5,6. The proposed reason is that compressivе force occurred during isovolumic contractiоn with maximally dilated ventricles and closed atrioventricular valves5. In humans right ventriсle is right behind the sternum , and this predispоse it to injury. In those cаses when there is rupture of the tricuspid valve and massive regurgitation , the increased pressure in right atrium leads to rupture of the septum and right to left shunt. In canine patients with degenerative mitral valve disease after the rupture of caudal atrial wall and following haemopericardium the clinical signs are collapse and sudden death. After rupture of the atrial septum the predominant signs are of right heart failure. In this case the right atrium and ventricle serves as a low pressure “sink” for severely dilated left atrium.
There are several publications about echocardiographic diagnosis of acquired atrial septal defect and rupture of the atrial septum with haemopericardium3,4. The bubble contrast study has been validated in veterinary echocardiography for diagnosis of congenital and acquired intra and extra cardiac defect and shunt7,8. In this case we have demonstrated the usefulness of so called contras washout – result of bubbles free blood entering contrast rich compartment.
In conclusion in any dog with degenerative mitral valve disease and predominated signs of right heart failure we have to look echocardiographically for atrial septal rupture. More we scan , more we find , and more we learn.
Todor Kalinov, DVM, Zaravet veterinary clinic, city of Plovdiv, Bulgaria, e-mail firstname.lastname@example.org
Patent Ductus Arteriosus(PDA) is one of the most frequently encountered congenital heart disease in dogs , ranging in prevalence from about 25 to 32 % from reported malformations 1 , and lest frequently in cats – about 11 % . The ductus arteriosus is normal foetal structure that shunts blood from pulmonary artery to aorta 2. Before the birth , it divers approximately 80 to 90 % of the right ventricular output back to the left side of the circulation. After parturition and the onset of breathing , pulmonary vascular resistance falls, flow in the ductus reverses , and the resulting rise in arterial oxygen tension inhibits local prostaglandin release causing constriction of the vascular smooth muscle within the vessel wall and functional closure of the ductus arteriosus3.
The ductal wall usually contains a loose branching pattern of circumferential smooth muscle in normal pups. The increasing genetic liability to PDA represents extension of the noncontractile wall structure of the aorta to an increasing segment of the ductus arteriosus, progressively impairing its capacity to undergo physiologic closure1.
In typical cases because of the lower pressure in pulmonary circulation there is continuous flow thru the ductus arteriosus from aorta to pulmonary artery. Clinical impact from this is volume overload of the structures in the shunt pathway : the main pulmonary artery, lungs, left atrium, left ventricle, and back to the ascending aorta up to the level of the ductus4. In that shunt direction the dogs show signs of left-sided congestive heart failure – exercise intolerance, coughing, eventually pulmonary edema. In rare instances when the ductus still wide after birth, the flow is really enormous and this leads to increase in pulmonary vascular resistance and change in direction of the shunt, so-called Eisenmengers physiology and reversed PDA . This pattern of pulmonary hypertension and reversed (right to left) shunting usually develops within the first few weeks of life3. Clinical signs in reversed PDA are shortness of breath, differential cyanosis – pink mucous membranes in cranial part of the body and cyanosis in caudal membranes, polycythemia , pelvic limb weakness, collapse, and seizures. The changes in pulmonary vasculature are irreversible and closure of the PDA is not suggested.
Many dogs with left to right PDA do not show any clinical signs, but if left heart failure has developed in first year of life, up to 65 % would die if left untreated. In most of the dogs clinical signs are apparent before the third year of age. The appearance of signs in older dogs is unusual2.
Buky was 7 years old springer spaniel admitted in our clinic with severe respiratory distress. He had history of heart murmur noted on routine examination , several episodes with increasing respiratory rate, and one presyncopal event with rear limb weakness. All clinical signs were apparent past several months.
The dog breathed with open mouth, mucus membranes were cyanotic , respiration rate increased, and on auscultation we have founded continued heart murmur, and crackles on the both side of the thorax. On the X-ray there was severe generalized cardiomegaly, pulmonary overcirculation with dilation if the pulmonary arteries and veins, interstitial to alveolar lung pattern (Figure 1 – L/L projection, Figure 2 – D/V projection). We have applied initial therapy for congestive heart failure with:
Furozemide – 4mg/kg/hour i.v.
Pimobendan – 0.25mg/kg p.os.
Enalapri – 0.5mg/kg p.os.
Sodium nitroprusside – i.v. constant rate infusion
Oxygen – via mask .
After several hours there was a reduction in respiratory rate, and efforts and an ECG and echocardiography were made.
ECG findings :
Sinus tachycardia – 163 bpm
Wide and tall P wave – suggestive of left atrium enlargement
Tall R wave – suggestive of left ventricular enlargement (Figure 8)
Atrial premature complexes (Figure 3)
Ventricular premature complexes(VPC) with origin in left ventricle (Figure 4)
Fusion beats – intermediate morphology between normal complexes and VPC (Figures 5, 6, 7).
We have made echocardiography at left and right lateral recumbency of the patient with all parasternal views according to accepted standards. From the exam we have found severe left heart volume overloud with eccentric hypertrophy of the left ventricle. Left atrium was dilated with rightward excursion of the atrial septum. Left ventricle was dilated with thin free wall and interventricular septum, dooming of the septum to the right ventricle, and reduced systolic motion of the free wall and the septum (video 1).
Left atrium and aorta was measured on right parasternal short axis view at the heart base and the ratio LA/AO was estimated with results showing at Figure 11. Normal LA/AO ratio have to be < 1,6. Main pulmonary artery was dilated compared to aortic root (video 2)
, and blowing of the pulmonary valve was noted (Figure 12).
On Color Doppler exam there was mild mitral regurgitation with central jet , probably because the dilation of the mitral annulus (Figure 13), and in pulmonary artery was noted typical for PDA continuous flow (video 3).
With CW Doppler the aortic flow velocity was measured 2,19 m/s , with normal speed les then 2.0 m/s. In pulmonary artery CW Doppler show typical continuous bidirectional flow (Figure 14).
On the basis of this findings the dog was diagnosed with Patent Ductus Arteriousus with left to right shunt. Because of the dramatic structural and functional changes in heart, the already developed left heart failure and increased anesthetic risks the owners refused surgical ligation of the ductus. At the time of the diagnosis in our country we did not have the chance for transcatheter coil embolisation. So the only opportunity was to treat congestive heart failure with medications. We have prescribed :
Pimobendan – 0.25 mg/kg/12 h. p.os
Enalapril – 0.5 mg/kg/12 h. p.os
Furozemid – 1.0 mg/kg/12 h. p.os
Spironolacton – 1.0 mg/kg/12 h. p.os
Supplements with L carnitine, taurine, and coenzyme q10.
The dog was very well after the beginning of the therapy and had only exercise intolerance. After about 1 year he had improvement in some echocardiographyc parameters of systolic function – normal fractional shortening, normal pre ejection period, normal ejection time, but the left atrium was bigger then year ago (Figures 15, 16, 17).
Video 4 – right parasternal four and five chamber view year after diagnosis ,
video 5 – modified left parasternal short axis view of heart base with color Doppler of the pulmonary artery showing continuous flow with small turbulent jet in opposite direction.
The treatments for Patent Ductus Arteriosus are surgical ligation or transcatheter device closure. Because of the technical factors and price in our country no one does make device closure but in many clinics surgical procedure can be done with great success. In this case the owners decline surgery, but mine opinion is also that the dog was not appropriate candidate for operation. Despite the fact that in most cases there is dramatic improvement in clinical status and cardiac function after surgical closure, the age ,the already developed heart failure, and concurrent heart disease, affect negatively survival period after PDA closure5. In adult dogs one of the major surgical complications is haemorrhage due to ductus friability2. Mitral valve endocardiosis is also an important factor affecting the survival period. On video 1 and 4 we can see the slight thickening and prolapsed mitral valve leaflets, so I supposed that the dog had degeneration of the mitral valve. Conduction instability of the heart is another reason for anesthetic complications. Actually the dog has died suddenly during routine walk without any other signs, about two years after the diagnosis, so malignant arrhythmia can be the reason. Despite this facts in most of the literature, the authors suggest closure of the PDA, even in adult dogs, only important contraindication for not closing is right to left shunt.
It is not known why some animals with PDA do not show any signs until adulthood. One of the reasons could be the small diameter of the ductus. In human medicine the maintenance of normal pulmonary vascular resistance is important factor for survival of the older patients2. It is certain that the adult dogs with congenital heart diseases are more then we expect, and always when we examine adult animal for some heart disease, we have to think not only for degenerative valve disease and cardiomyopathies but also for congenital and inherited problems. And of course rare things do happen everyday.
Surgical extraction of adult D. immitis filariae from the pulmonary arteries of a patient with stage III heartworm disease
Ranko Georgiev1, Hristina Shukerova2, Nadezhda Petrova3(anesthetist)
1,2,3 DVM, Central Veterinary Clinic, Sofia, Bulgaria; 2016
An “exotic” diagnosis for Bulgaria just 5 years ago, Heartworm Disease (HWD) is a parasitic infestation that we nowadays see regularly in our small animal practice. Due to climate change and spreading of intermediate vectors, ever more dogs are getting affected. Other major contributing factors are the infrequency of preventive measures in the country and the high number of undiagnosed and subclinical patients, leading to a reservoir of hosts in the general canine population.
Rem is a 25kg, 10 years old MC mix breed dog admitted because of ascites and exercise intolerance during the past few weeks. Most prominent of the clinical signs was the severely distended, fluid-filled abdomen – assessed as modified transudate on abdominocenthesis (more than 4 liters were drained because of the labored breathing).
Thoracic X-rays revealed right-sided cardiomegaly and severely distended tortuous and blunt-ended pulmonary arteries. On echocardiography, right heart pathology was mainly observed – including a distended right atrium and ventricle, dilated pulmonary artery and evidence of pulmonary hypertension, as well as many tubular echoic structures in the lumen of the main pulmonary artery, typically identified as adult parasites.
Serology was positive for D. immitis (IDEXX 4D snap test) and the dog was classified as stage III HWD.
Because of the high worm burden and ascites, the possibility of interventional removal of the worms, before the adulticide treatment, was suggested to the owner, who gave his informed consent.
The patient was scheduled for surgery several days after hospitalization and treatment of right congestive heart failure and pulmonary hypertension using the following therapeutic protocol:
Torasemide: 0.2mg/kg/12h, IV and PO
Sildenafil: 2mg/kg/12h, PO
Ivermectin: 6ug/kg monthly, subcutaneously
Surgical extraction of worms was routinely performed using the right jugular vein approach. The area was scrubbed aseptically and a small skin incision was made over it. The vein was dissected free from the surrounding tissue and ligated proximally. A small transverse cut in its wall was made, through which a forceps was advanced into the heart under fluoroscopic control.
The anesthetic protocol we used was typical for this procedure; in particular premedication with Atropine, Butorphanol and Midazolam; induction with Etomidate; and finally Isoflurane maintenance.
After nearly 20 attempts, we extracted 25 adult worms. The overall fluoroscopic time of the procedure was less than 5 minutes. The recovery of the patient was uneventful and a day later we started the adulticide protocol for HWD treatment, as recommended by the American Heart Worm Association.
In all cases with stage III or IV HWD it is advisable to discuss the possibility of surgical extraction of some of the worms as a pre-adulticide step. This will lower the risk of fatal pulmonary thromboembolism after the injection of Immiticide and will likely improve the symptoms of existing pulmonary hypertension.
It should be noted that if a different extraction device is used (endoscopic loops and baskets, rigid or semi-rigid alligator forceps, different types of graspers, etc.), the success rate of the procedure is much lower, at least in our experience. The Ishihara forceps could be actively maneuvered into the RVOT, hence providing faster and easier access to the PA.
Surgical extraction of a heavy worm burden is possible and clinically important before adulticide treatment, in patients with end-stage HWD.
Rem, the dog of our study, successfully completed the treatment protocol for HWD without any evidence of pulmonary thromboembolism; meanwhile the symptoms of RCHF have slowly abated.
Pacemaker implantation (PMI) as treatment for AVB III and very slow ventricular escape rhythm in a geriatric canine patient
Ranko Georgiev1, Hristina Shukerova2, Nadezhda Petrova3
1,2,3 DVM, Central Veterinary Clinic, Sofia, Bulgaria
Pacemaker implantation is the most effective treatment for ‘syncope and severe exercise intolerance’ – related arrhythmias; however when searching for the best clinical decision for some older dogs, the risk of anesthesia often outweighs the benefits. We would like to share a case where the old age was not a problem.
Larry was a 17-year old MI mix breed dog admitted because of increasingly frequent exercise intolerance episodes during the past few months. Furthermore, the last week the patient was very week, unable to stand on his feet and with a depressed overall clinical status. On a clinical presentation with the referring vet а bradycardia was noted and the patient referred to us for a Cardiology consult.
During auscultation, a slow regular rhythm was detected with heart rate of 20 bpm classified as ventricular escape rhythm during the normal ECG. A 24hour Holter monitor revealed complete AV block (AVB III) throughout the study with an average rate of 31 bpm, occasional VE beats with some pairs, triplets and short runs; no pauses greater than 5 sec were noted. The slowest heart rate detected was 20 bpm.
Complete blood count and biochemical profile were normal. Radiography and echocardiography revealed generalized cardiomegaly, with mild-to-moderate mitral and tricuspid regurgitation and decreased contractility. During the abdominal FAST study a small amount of free fluid was noted – defined as a transudate on diagnostic abdominocenthesis. Lari_20150811163929_1640560
A diagnosis of complete AV block with clinical signs of right sided congestive heart failure was made and pacemaker implantation was decided. A VVI, bipolar, passive lead was fluoroscopically placed, under anesthesia, through the right jugular vein into the right ventricle, where it was successfully lodged.Lari_20150814181226_1819550 The lead was connected to a generator, which was later fixed in the subcutaneous tissue dorsally to the cervical vertebrae. A temporary pacemaker was used when the dog developed asystole during the procedure. Recovery from the surgery was uneventful, with the pacemaker capturing normally. The pacing rate was set to 100 bpm. The system used was a ‘St Jude’ one.
Our anesthesia protocol with this patient was routine for the procedure of a PMI – premedication with Midazolam and Buprenorphine, induction with Etomidate, intubation and maintenance with Isoflurane. The post procedure treatment was only with Cefazolin iv for the next few days.
The use of a temporary lead and/or an external pacemaker is highly advisable in patients who are depended on their escape rhythm.
Even though Larry recovered from the general anesthesia normally he was unable to stand on his feet for additional 5 days. He was bright, alert and responsive, with good appetite and normal consciousness, but with an impaired proprioception. We attributed this to the long period with severe bradycardia (HR of 20 bpm) and potential vasoconstriction/reperfusion complications. There is some data in the human medicine literature concerning PMI in old people with preexisting severe bradycardia, who reported pain in the extremities post the procedure.