Heartworm disease is defined as the presence of heartworms (Dirofilaria immitis) in the pulmonary artery and/or right heart with the presence of clinical signs.  These parasites are transmitted from the bite of an infected mosquito and their lifecycle completes within in the canine and feline heart.  The consequences of these parasites are inflammation of the pulmonary vasculature and lung parenchyma.   Pulmonary arteries become dilated and tortuous and this scenario can lead to decreased oxygenation of the blood within the lungs.  Pulmonary hypertension results from the aforementioned changes as the right heart has to generate higher pressures to pump blood through the altered pulmonary vasculature.  As a result, the right heart eccentrically hypertrophies in response to an acquired pressure overload.   Eventually due to the combined effects of right heart dilation and pulmonary hypertension, right heart failure can occur.  Other complications seen with heartworm disease include chronic immune stimulation which can result in immune-complex glomerulonephritis of the kidneys, vasculitis and polyarthropathies.  In addition, the pulmonary parenchyma can undergo detrimental changes as well.  Allergic pneumonitis is a pulmonary parenchymal disease that can occur in dogs infected with heartworms.   Rarely, a form of non-infectious pneumonia (pulmonary eosinophilic granulomatosis) can occur from excessive infiltration of inflammatory cells into the lung in response to the parasite.  Thromboembolic events (most commonly pulmonary thromboembolisms) can also result.    Cardiac arrhythmias can also occur as a result of myocardial changes with dilation.  

Clinical signs and staging
Heartworm disease has four distinct clinical stages and treatment is initiated specifically for the stage diagnosed:    

• Class 1 heartworm positive animals have a positive antigen test but are generally asymptomatic.  They cough rarely and may show slight exercise intolerance. They may have very mild changes evident on thoracic radiographs.  Blood work is normal other than a positive heartworm antigen test.
• Class 2 heartworm positive animals also have a positive antigen test but have clinical signs associated with moderate disease.  Clinical signs can be occasional coughing, exercise intolerance and fever.  A split 2nd heart sound may be heard on physical examination due to delayed closure of the pulmonic valve compared to the aortic valve due to pulmonary hypertension.  Blood work may reveal a mild anemia and urinalysis may show mild to moderate protein loss.   Thoracic radiographs may reveal moderate disease such as dilated pulmonary arteries and right heart enlargement.  
• Class 3 heartworm positive animals also have a positive antigen test but have clinical signs associated with severe disease.  Clinical signs include difficulty breathing without exercise, frequent cough, weight loss, inappetance, lethargy, coughing up blood and abdominal distension due to ascites.  Blood work can show a moderate to severe anemia and urinalysis can show severe protein loss.  Thoracic radiographs show signs of severe disease with tortuous and dilated pulmonary arteries, enlarged right heart and other pulmonary parenchymal changes such as an interstitial pattern from allergic pneumonitis or pleural effusion secondary to right heart failure.   A split 2nd heart sound may be heard on physical examination due to delayed closure of the pulmonic valve compared to the aortic valve due to pulmonary hypertension.  
• A syndrome called Caval Syndrome defines Class 4 heartworm positive dogs.  Clinical signs include a very sick patient that can be weak or collapsing due to shock.  All clinical signs of a class 3 heartworm dog can be present.  In addition, urinalysis will reveal a dark brown urine signifying hemoglobinuria secondary to red blood cell lysis from the shearing forces as blood is forced across the tricuspid valve which is entangled with worms.   Thoracic radiographs are similar to class 3 animals.  Echocardiogram can reveal the presence of many adult heartworms in the right heart and pulmonary artery.   A loud systolic murmur heard best of over the right apex can be present due to tricuspid valve regurgitation.  A split 2nd heart sound may be heard on physical examination due to delayed closure of the pulmonic valve compared to the aortic valve due to pulmonary hypertension.  
• Cats with heartworm disease fall into a class all of their own.  Cats often have very low worm burdens and can have very severe inflammatory responses to this very small worm number.  The most common clinical sign in cats is respiratory distress.  They often don’t cough like dogs do and have difficulty breathing most commonly due to the inflammation caused by heartworms.
  

Treatment
Treatment for heartworm disease depends upon the classification aforementioned. In general, all animals that are heartworm positive should be started on an ivermectin-based once monthly oral preventative to help kill of the immature larvae and microfilaria) to halt the lifecycle and prevent a reservoir for disease. An ivermectin-based product should be chosen rather than milbemycin based products in this situation in order to kill the microfilaria slowly rather than all at once which could lead to an anaphylactic shock state. For class 1 heartworm positive patients, it is recommended to start an ivermectin-based preventative for at least 2-3 months before melarsomine dihydrochloride (Immiticide®) administration.  Additionally, doxycyline, an antibiotic is administered for one month after diagnosis for the treatment of Wolbachia, a parasite that lives within the heartworms.  The melarsomine is administered as a deep intramuscular injection into the muscles of the lower back. One injection should be administered to kill the most sensitive adult worms and the patient should be strictly cage rested for one month to try to prevent thromboembolic events from the dying worms. The patient should then return in one month after the first injection of melarsomine for two more injections 24 hours apart. Again the patient must be strictly cage-rested for one month. The patient should then have an antigen heartworm test performed six month after treatment and then on an annual basis. For Class 2 and 3 heartworm positive dogs, the same protocol should be followed as for Class 1 patients with some important alteration in treatment. The oral ivermectin-based preventative should be given for 2-3 months prior to adulticide (melarsomine) treatment. In addition, an antibiotic called Doxycycline and/or steroids may also be prescribed during this time frame. These patients may also have evidence of right-sided heart failure and may require medical treatment such as diuretics, angiotensin inhibitors and pulmonary arterial vasodilators. After 2-3 months of treating the microfilaria and immature larvae, adulticide treatment will be initiated as for Class 1 with heartworm testing performed 6 months after the final treatment with melarsomine. Class 4 heartworm patients with Caval Syndrome require immediate attention and hospitalization. These animals require heartworm embolectomy, which is surgical removal of the adult heartworms from the right heart. This procedure is performed through intravenous access through the jugular vein and special instruments are placed through this vein into the right heart to remove the adult worms. These patients are unstable and are not the best candidates for anesthesia; however, the worms need to be removed. These patients require intense monitoring and support in an ICU setting post embolectomy and may require blood transfusions, oxygen therapy and medications for right-sided heart failure. If this patient recovers, the same treatment for a Class 3 heartworm positive patient will be necessary.

Cats with heartworm disease should never be administered adulticide treatment as this can cause a severe life-threatening systemic shock response.  Cat’s clinical signs are controlled by anti-inflammatory doses of steroids and once monthly ivermectin-based preventatives to stop the heartworm life cycle.  Adult heartworms are not killed and are left to die on their own.  Cats require both antibody and antigen heartworm testing because they often have low burden infections with mostly single sex (female) worms.  The antibody test can show exposure and the antigen test can confirm an active infection.  

Follow up
Dogs should be tested every 12 months for heartworm disease, as this is a preventable disease.  Once a dog is infected, the recheck examinations will be based upon which class your pet falls into.