Caval syndrome is a severe variant or a complication of canine heartworm disease, characterized by a heavy worm burden in the right atrium and vena cava (12). Affected dogs have partial inflow obstruction to the right heart, severe pulmonary hypertension, decreased cardiac output, and tricuspid insufficiency by interfering with the valve apparatus (4,12). In caval syndrome, adulticidal treatment has numerous potential complications (e.g., pulmonary thromboembolism and allergic pneumonitis) because of dead worms, resulting in a marked host immune response (13). Therefore, the mainstays for treating dogs with severe infestation are surgical or mechanical removal using retrieval devices (8,13).

In veterinary medicine, mechanical removal using retrieval devices (e.g., flexible alligator forceps, a loop snare device, or a basket device) has been applied successfully (2-4,6-8,10,11,13,14). The first retrieval devices used in the veterinary field were flexible alligator forceps, which improved access to the pulmonary arteries, reduced invasiveness of the procedure by surgical thoracotomy, and had a shorter duration of general anesthesia (7,12). However, there are limitations in removing heartworms in small patients, as their size permits insertion into the right atrium and only the proximal part of the right ventricle (11). Furthermore, the retrieval rate per extraction was 1-3 worms, resulting in a substantial number of extraction trials to remove heartworms remaining in the right heart and pulmonary arteries (14). Also, alligator and tripod forceps are at risk of unintentional intracardiac damage by potentially grasping and tearing the atrial wall or a tricuspid valve leaflet (13,14). The brush method was used for heartworm removal from the pulmonary artery of cats, and modified brushes, which are more flexible and cheaper than conventional brushes, have been developed and used in dogs with a heavy worm burden in the right cardiac chambers (6,9). These techniques are known to minimize intra-cardiac damage and could be used in places where fluoroscopic or endoscopic guidance is not available (9). However, the limitation of this method is that there are no control aids for inserting the brush into the pulmonary artery, and other retrieval devices are necessary when extracting worms from the pulmonary arteries (9). Conversely, the basket device, which was initially developed to extract foreign bodies from the esophagus or uroliths from the urinary tract, has an advantage over other devices in that it is more flexible, has a wide range of diameters, and rarely causes intracardiac or vascular damage (13). Furthermore, baskets can significantly increase the number of captured worms per retrieval, thus shortening the mean time to complete removal compared to those associated with other devices (13). However, unlike flexible alligator forceps, the baskets do not have maneuvering aids for positioning the device tip, making it difficult to remove heartworms residing in the pulmonary arteries. Furthermore, as they are made for medical use in humans, these devices are not applicable to small dogs and cats.

Based on these limitations, a heartworm basket device was developed (S & G Biotech Inc., Seoul, Republic of Korea) (Fig. 1). This device is the first product designed for veterinary use and is known to have an optimal angle for placing the tip in the right atrium, right ventricle, and main pulmonary arteries. This paper reports the efficacy and safety of the newly developed heartworm basket device for removing adult heartworms in three dogs with caval syndrome.

Figure 1. Heartworm basket device. ‘Black hash key’ indicates pusher hub, ‘white arrow’ indicates Y-connector with injection port, ‘white arrowhead’ indicates sheath hub, ‘black arrow’ indicates sheath tube with pusher wire inside, and ‘black arrow head’ indicates basket of the device.

Procedure for interventional heartworm extraction

To reduce the side effects of the procedure, each dog was administered clopidogrel hydrogen sulfate (1 mg/kg PO SID; Pravic Tab., Sinil Pharm Co., Chungju, Korea), prednisolone (0.5 mg/kg PO BID; Solondo Tab., Yuhan Co., Cheongju, Korea), and dalteparin (100 IU/kg SC TID; Fragmin Inj., Pfizer Inc., Seoul, Korea) from days to weeks prior to the heartworm removal procedure. Clopidogrel and dalteparin were discontinued a few days before the procedure depending on the patient’s condition to prevent excessive bleeding during the procedure. Blood transfusion was administered the day prior to the procedure. The dogs were premedicated with atropine (0.02 mg/kg IV; Atropine sulfate Inj., Jeil Pharm Co., Yongin, Korea) and midazolam (0.2 mg/kg, IV; Midazolam, Bukwang Pharm Co., Ansan, Korea), followed by anesthesia induction with propofol (4 mg/kg IV; Provive 1% Inj., Myungmoon Pharm Co., Hwasung, Korea). After tracheal intubation, anesthesia was maintained with isoflurane at a 2-4% concentration depending on the size of the dog. After achieving surgical anesthesia, venipuncture was performed with a 20 G needle at the right femoral vein and artery in patient 1, who also presented with aberrant migration of heartworms to the systemic arteries, but at the right jugular vein in patients 2 and 3. A guidewire (Sungwon Medical Co., Ltd., Seoul, Korea) was inserted into the needle and used to locate the vessels. A vessel dilator (Sungwon Medical Co., Seoul, Korea) was inserted under the guidance of the pre-placed guidewire, and the vessels were dilated through several insertions. The guidewire and dilator were then removed from the vessel. A heartworm basket device (S & G Biotech Inc., Seoul, Korea) was inserted into the vessel and pushed to the vena cava and right atrium using fluoroscopy (Phillips Veradius Unity machine, Bothell, Washington). The tip of the device was advanced to the ventricle and main pulmonary artery (Fig. 2). Once in position, the basket device was spread-folded to catch the heartworms, twisted with complete rotations, and slowly retrieved from the right heart. This was repeated until no worms were visible by echocardiography. After the extraction was completed, the punctured vein was tightly ligated in patient 3 and sutured in patients 1 and 2.

Figure 2. The procedure for heartworm interventional extraction. (A) After achieving surgical anesthesia, venipuncture was performed with a 20 G needle. (B) A guidewire was inserted into the needle. (C, D) A vessel dilator was inserted with guidance of a pre-placed guidewire and the vessels were dilated through several insertions. The guide wire and vessel dilator were then removed from the vessel. (E) After the guide wire and vessel dilator was removed, heartworm basket device was inserted into the right atrium and ventricle with fluoroscopic guidance.

After heartworm removal, all dogs were treated with prednisolone (0.5 mg/kg PO BID; Solondo Tab., Yuhan Co., Cheongju, Korea), doxycycline (10 mg/kg PO BID; Doxycycline hydrate Tab., Youngpoong Pharm Co., Incheon, Korea), sildenafil (1 mg/kg PO BID; Viagra Tab., Pfizer Inc., Seoul, Korea), clopidogrel (1 mg/kg PO SID; Pravic Tab., Sinil Pharm Co., Chungju, Korea), and furosemide (1 mg/kg PO BID; Lasix Tab., Handok Inc., Eumseong, Korea) for days to weeks. Subsequent follow-up studies were performed after the mechanical extraction of the heartworms.

Patient 1

A 6-year-old intact female Pointer dog weighing 17.2 kg was presented to the Chungbuk National University Veterinary Medical Center with a 1-month history of pigmenturia and non-weight-bearing lameness of the left hindlimb. Physical examination revealed severe lethargy, exercise intolerance, pale mucous membranes, and abdominal distension. Peripheral perfusion in the left hindlimb was remarkably decreased, as evidenced by coldness of extremities, loss of deep pain sensation, and a weak femoral pulse. The main laboratory findings were anemia, leukocytosis, markedly increased hepatic enzymes (alanine transaminase, 1327 IU/L; alkaline phosphatase, 470 IU/L), and elevated D-dimer levels (>10,000 ng/mL; reference interval = 0-250 ng/mL). Heartworm antigen testing yielded positive results, and microfilaria was observed on a direct smear. Thoracic radiography revealed a moderately enlarged main pulmonary artery and caudal vena cava, severe enlargement of the pulmonary arteries, right-sided cardiomegaly, and ascites (Fig. 3A, B). Echocardiograms were acquired using one of the two machines with varying transducer arrays based on patient size (Philips EPIQ7, Bothell, Washington, USA or Aloka Prosound Alpha 7, Wallingford, Connecticut, USA). Echocardiography revealed moderate right ventricular and atrial enlargement, severe infestation of heartworms in the right heart, flattening of the interventricular septum, and tricuspid regurgitation (Fig. 4A, B). During abdominal ultrasonography, double-walled linear echoic structures indicating adult heartworms were also confirmed in the distal part of the abdominal aorta and femoral arteries (Fig. 5). Three days after the initial hospital visit, the left hindlimb spontaneously fell off due to severe ischemic necrosis, and the necrotic wounds were managed with surgical debridement and daily bandage changes until the procedure. Under fluoroscopic guidance, 20 heartworms were removed from the heart after seven attempts, 10 from the abdominal aorta after five attempts, and the extraction procedure took approximately 2 h. Adulticidal therapy (melarsomine, 2.5 mg/kg IM; Immiticide Inj., Merial Inc., Nanchang, China) was administered 1 week after heartworm removal. Radiography performed 5 weeks after the extraction revealed moderate decrease in enlargement of the main pulmonary artery and right-sided cardiomegaly (Fig. 3C, D. No heartworms were visible in the right heart, and echocardiography tricuspid regurgitation was resolved (Fig. 4C, D). The patient received a continuous anticoagulant prescription (clopidogrel; 1 mg/kg PO SID; Pravic Tab., Sinil Pharm Co., Chungju, Korea) after the procedure; however, necrosis of the peripheral hindlimb continued due to persistent thromboembolism. As a result of the owner’s opposition to complete hindlimb amputation, additional partial amputation under the right tarsal joint and left tibia was performed approximately 2 and 3 months, respectively, after the interventional heartworm extraction. The patient’s condition was well-maintained for 1 year without additional necrosis or complications.

Figure 3. Radiographic evaluation of patient 1 before and after the heartworm removal. (A, B) Radiography revealed moderately enlarged main pulmonary artery and caudal vena cava, severe enlargement of the pulmonary arteries, right-sided cardiomegaly, and ascites. (C, D) On the radiography taken 5 weeks after heartworm removal, the enlargement of main pulmonary artery and right-sided cardiomegaly was moderately decreased.

Figure 4. Echocardiographic evaluation of patient 1 before and after the heartworm removal (right parasternal long axis view, 4-chamber view) (A, B) Before the procedure, many heartworms (arrowheads) were visible in the right atrium and ventricle, and tricuspid regurgitation was detected by color Doppler sonography (arrow). (C, D) After the procedure, no heartworms were visible in the right atrium and ventricle, and tricuspid regurgitation was resolved.

Figure 5. Longitudinal (A) and transverse (B) ultrasonographic images of the abdominal aorta in patient 1. Note the heartworms as double-walled, linear echoic structures.

Patient 2

An 8-year-old intact male Jindo dog weighing 16.5 kg was referred to the Chungbuk National University Veterinary Medical Center for anorexia, diarrhea, and tachypnea. The clinical signs included exercise intolerance, mild dehydration, pale mucous membrane, and grade III systolic murmur on thoracic auscultation. Hemogram and blood biochemistry revealed hemolytic anemia, leukocytosis, mildly increased hepatic enzyme levels (alanine transaminase, 203 IU/L; aspartate transaminase, 556 IU/L; alkaline phosphatase, 391 IU/L), markedly elevated D-dimer levels (>10,000 ng/mL; reference interval = 0-250 ng/mL), and prerenal azotemia (blood urea nitrogen, 104.2 mg/dL; creatinine, 4.3 mg/dL). Immunological tests were positive for adult worms and microfilaria. Thoracic radiography revealed enlargement of the main pulmonary artery, caudal vena cava, and peripheral pulmonary arteries. Additionally, right-sided cardiomegaly and ascites were observed. Echocardiography revealed hyperechoic parallel lines in the enlarged right atrium and pulmonary artery with regurgitation of blood flow at the tricuspid valve area. During interventional extraction, 58 heartworms were extracted from the right heart and main pulmonary artery after 12 attempts, and the procedure took 1 hour and 10 minutes. One day after the procedure, hematoma occurred at the surgical site and the anticoagulant treatment was stopped. The hematoma lasted about 2 weeks, but completely improved after 3 weeks. Anticoagulants (clopidogrel; 1 mg/kg PO SID) were prescribed, and melarsomine treatment (2.5 mg/kg IM; Immiticide Inj., Merial Inc., Nanchang, China) was administered after the patient’s condition stabilized. D-dimer level decreased to approximately one-third of that before the procedure, and no other complications were observed.

Patient 3

A 7-year-old intact female Welsh Corgi dog weighing 11.8 kg was referred to the Chungbuk National University Veterinary Medical Center for anorexia. The dog showed clinical signs of exercise intolerance, dehydration, and tachypnea. Hematology revealed anemia, thrombocytopenia, and leukocytosis. Blood chemistry tests revealed increased hepatic enzyme levels (alanine transaminase, 190 IU/L; aspartate transaminase, 443 IU/L; alkaline phosphatase, 122 IU/L), markedly elevated D-dimer levels (>10,000 ng/mL; reference interval = 0-250 ng/mL), and prerenal azotemia (blood urea nitrogen, 120.6 mg/dL; creatinine, 1.5 mg/dL). Amylase (3439 IU/L; reference interval = 200-2000 IU/L) and lipase (5079 IU/L; reference interval = 200-1800 IU/L) levels were high due to hypoxic damage to the pancreas. Positive findings of microfilariae were observed in antigen tests and direct smears. Thoracic radiography revealed moderate enlargement of the main pulmonary artery, severe enlargement of the pulmonary arteries, right-sided cardiomegaly, and ascites. Right atrial and ventricular enlargement, interventricular septal flattening, tricuspid regurgitation, and presence of heartworms were confirmed by echocardiography. Sixteen heartworms were extracted from the right heart and pulmonary artery after seven attempts, and the procedure took approximately 40 minutes. One day after the procedure, the dog regained her appetite, and her respiratory rate returned to the normal range (20-30/min). Three days after the procedure, an echocardiography revealed the disappearance of the flattening of the interventricular septum and absence of heartworms in the right atrium and ventricle. The patient received three doses of immiticide (2.5 mg/kg IM; Immiticide Inj., Merial Inc., Nanchang, China) during the subsequent 2-month follow-up, and the D-dimer level returned to the normal range without any complications.

Caval syndrome is a relatively uncommon but severe complication of heartworm disease, resulting from a relocated worm burden to the tricuspid valve orifice causing large volume regurgitant flow, obstruction to the right ventricular inflow, and pulmonary hypertension (1,12). Without treatment, death frequently occurs within 24-72 h due to cardiogenic shock complicated by anemia, metabolic acidosis, and disseminated intravascular coagulation (12). Therefore, in cases of caval syndrome, prompt decisive action by owners and veterinarians is required (4). Worm extraction using removal devices is safer and more efficient than that performed via melarsomine administration in patients with caval syndrome. Worm removal devices also produce fewer complications and are useful in de-bulking the infection and reducing the risk of subsequent adulticidal therapy (1,8). In a previous report, dogs with caval syndrome undergoing transvenous heartworm extraction exhibited a mortality rate of 29%, and 67% of the dogs successfully underwent the procedure and exhibited good long-term prognosis (4).

In this study, a heartworm basket device, the first product designed for veterinary use, was used in three dogs with heartworm infection and caval syndrome. Post removal of the heartworms, all of them exhibited good prognosis of clinical symptoms as indicated by imaging analyses. The heartworm basket device is easy to manipulate, has an optimal angle for entering the right cardiac chambers, and is protected by a catheter sheath, which makes it less likely to damage the endothelial surface during the manipulation. Furthermore, it has an extra Y-shaped hub inlet through which the contrast medium or emergency drugs could be injected mid-procedure. Additionally, access to the right atrium via femoral venotomy, which is an uncommon approach to the cardiac chambers, was successful, as described in patient 1. However, the maximum diameter is 20 mm when the basket is unfolded, and its minimum diameter is 2 mm when folded and replaced in the sheath tube. This is a limitation for its application to blood vessels of 5 French or less and patients of 2 kg or less.

Regarding the procedure time in the three dogs, it was approximately 2 h in patient 1 even though it was an interventional procedure and not a laparotomy, considering the initial application of the device by the surgeon and the removal of the worms by approaching from both the femoral artery and vein. However, in patients 2 and 3, the procedure time was significantly less because of the jugular vein approach. In addition, in the case of patient 3, although the number of worms and the attempts for removal were higher than those of patient 2, the procedure took a shorter time. Hence, the experience of the surgeon played a crucial role in the easier and faster completion of the procedure.

Considering the previously reported complications of interventional extraction of heartworms and the cases in this report, the main complications of the procedure were pulmonary thromboembolism and inflammation resulting from rapid release of the antigen from the macerated heartworms (5,13). To reduce complications and destroy the remaining worms, anticoagulants (clopidogrel) and anti-inflammatory agents (prednisolone) were administered before the procedure, and adulticidal therapy with melarsomine injection was administered at a minimum of 1-month after the extraction. However, in patient 1 with aberrant systemic migration of the heartworm, although the worms in the abdominal aorta were removed by approaching through the femoral artery, the worms that had already migrated to the peripheral vessels were impossible to remove. This resulted in long-lasting necrosis of both hind legs despite the administration of melarsomine.

Another complication of the procedure was hematoma formation at the surgical site. Punctured veins can be tightly ligated or sutured after worm removal. When the vein is sutured without ligation, hematoma can occasionally occur, as in patient 2. Although hematoma can resolve over time, vein ligation is recommended to reduce its risk.

Although the heartworm retrieval was successful, there were a few limitations associated with the procedure. First, while the rigidity and torque of the device were sufficient for selecting the vessels, they limited the surgeon’s ability to place the tip at an acute angle (when accessing the main pulmonary artery) due to its rigidity. Second, repeated heartworm retrieval and basket device reinsertion were inconvenient. However, in a previous report with a basket device applied to a preplaced flexible introducer, the worms were often stuck at the introducer, making it impossible to extract the entire filaria intact (13). Therefore, repeated removal is necessary to prevent the complications associated with macerated worms. Third, cardiac damage to the intracardiac structures is a potential risk factor because of the blinded retrieval from the right heart or pulmonary vasculature. The fluoroscopic guidance during the procedure only visualizes the device and not the worms (4,8,13). Another potential risk factor innately associated with the retrieval procedure is crushing or transecting the heart, which can induce a fatal shock reaction from rapid antigen release and pulmonary thromboembolism (5,13). Therefore, gradual and cautious extraction is needed, especially if the retrieval device catches too many heartworms. Lastly, this study is retrospective and the number of cases enrolled is small. In addition, this is a case report; hence, a controlled study with other extraction devices was not performed. Further investigations with a diverse variety of breeds and weights of dogs, and controlled studies with other devices are needed.

This research was supported by Chungbuk National University Korea National University Development Project (2021).

The authors have no conflicting interests.