Cardio2.5- Heartworms

L3 within the mosquito

mosquito picks up microfilaria from dog--> larvae develop into infective L3 within the mosquito--> mosquito takes another blood meal and deposits L3 into the skin--> larvae molt from L3 toL4 and L4 to L5 within subQ tissues--> L5 migrate to the vascular system--> migrate to the pulmonary vasculature, where they mature into adults (5 months)--> adult worms reproduce and release microfilaria into the blood--> repeat

L3/L4 subQ stage, adults in pulmonary vessels, microfilaria

migrating L5, young adults; takes 5 months for migration and  maturation from L5 to adult, which produce Ag and are susceptible to adulticides

intracellular, symbiotic gram negative rickettsial species that enhance the development of filarial parasites

the males have a screwed up head

canines, cats, ferrets, muskrats, sea lions, and coatimundi

coin lesions in lungs, subcutaneous, or ocular lesions

• innate resistance of the cat
• higher level of aberrant migration in the cat
• adult worm bigger relative to the cat than the dog
• lighter worm burden in cats
• microfilaremia very brief in cats
• cats have a marked pulmonary reaction to parasites
• difficult to definitively diagnose in cats
• lack of safe adulticide therapy for cats
• higher preventative doses in cats

the worms undergo abberant migration and cannot develop properly

when an adult worm dies (even just 1), it creates a pulmonary embolism and a SEVERE parenchymal reaction

because the worms are so large relative to the size of the heart and lungs, so you have a higher chance of actually finding the worms

eyes, brain (ventricles), systemic arterial system

while the L5 are maturing; this is before we can detect the infection, so we can't stop it from happening

endothelial swelling, WBC and platelet activation--> arteritis, thrombi

damage to pulmonary arteries, injury to lung parenchyma

villous arteritis; pulmonary hypertension

increased D-dimers

the caudal lung lobes

villous arteritis and thrombosis--> increased pressure and pulmonary hypertension--> pulmonary arteries dilate from increased pressure--> pulmonary arteries become stiffer--> pressure increases further--> RV mixed hypertrophy b/c it must overcome higher pressure (RV not designed to work at high pressures)--> right heart failure

dilated caudal right and left lobar pulmonary arteries- seen with PHT and HWD

with HWD, there is no pressure gradient b/w the main pulmonary artery and the RV; in pulmonic stenosis, there pressure is much higher in the RV than in the pulmonary circulation

pulmonary infarction from thrombosis, hypersensitivity pneumonitis (from parasites sequestered in lungs), inflammatory pulmonary edema, HARD in cats, lung fibrosis, hemosiderosis (from RBC injury or hemorrhage)

you don't get pulmonary edema from R-CHF, therefore, if you get pulmonary edema with HWD, it must be from inflammation and increased vascular permeability (HWD does NOT cause L-CHF)

Heartworm Associated Respiratory Disease: hyper-reactive response of bronchiolar smooth muscle, causing medial hypertrophy and severe inflammation

cor pulmonale and RV dysfunction/failure; respiratory signs

cough, respiratory distress, abnormal lung sounds- loud bronchial sounds or crackles

vomiting, coughing, dyspnea, chylothorax (prob from R-CHF), CNS disease, spontaneous pneumothorax

caval syndrome, acute pulmonary embolism, sudden death

• [due to decreased CO] weakness, exercise intolerance, syncope
• [when it become R-CHF] increased jugular venous pressure, hepatomegaly, ascites

• tympanic second heart sound
• S2 splitting into separate aortic and pulmonic components
• jugular venous pulse
• soft ejection murmur (flow into dilated PA)
• tricuspid regurg (relating to PHT)

separate aortic and pulmonary components because PHT causes the pulmonic valve to snap shut under high pressure

PHT and dilated main pulmonary artery--> ejection murmur

History, clinical exam, and thoracic radiography

• RV enlargement (if cor pulmonale)
• bulging of main PA
• enlarged pulmonary arteries
• increased interstitial opacity
• patchy alveolar infiltrates
• coin lesions (small granulomas)

• Dx of caval syndrome 
• Dx of HWD in cats (can see worms more easily)

tortuous lobar pulmonary arteries

abrupt stoppage of blood flow (seen with contrast) due to thrombosis with worms

adult parasites: double echoic lines with a hypoechoic center (lumen of worm)

• eosinophilia, basophilia, monocytosis, +/- mild non-regenartive anemia
• inc globulins, decreased albumin (renal loss), +/- incr liver enzymes (if congestion)

caval syndrome--> hemolysis--> pigment nephropathy--> glomerular disease--> protein-losing nephropathy

• Ag test prior to starting preventative (dog)
• Ag test annually in dogs (to identify resistance to macrocyclic lactones)
• (?????) positive HW antigen test

Antigen test directed against adult female antigen; negative predictive value (neg. test very reliable)

• single sex infection (hopefully its just F, we can still detect them with antigen test but they can't produce mf without males)
• immune -mediated destruction of mf
• chronic treatment with a preventative drug

combined antibody test and antigen test; Ab test is specific for HW exposure, Ag test is specific for HW infection

Ag tests detect Ag from F worms; you often get neg Ag tests in cats, even when they have HWI; Ab tests tell us if the cat has been exposed, but there may not be any worms in the cat (aberrant migration and failure to initiate an infection)

microfilaria MUST go through a mosquito to develop to L3

adult A. reconditum live in the SQ tissues, non-pathogenic, IH is flea

Knott's test or Millipore Filter test

try to distinguish it from A. reconditum: D. immitus is wider and has a tapering head (as opposed to a blunt head); A. reconditum has button hook tail

• Asymptomatic 
• Symptomatic for HWD: respiratory signs, cor pulmonale, R-CHF
• Concurrent dz or aged patient
• Acute Syndromes of HWD: acute PE, caval syndrome, death

• immiticide (adulticide)- Melarsomine dihydrochloride
• slow kill adults

Wolbachia improve fertility of adult worms; prior killing of Wolbachia with Doxycycline for 4 weeks prior to adulticide therapy

• 2 stage therapy:
• 4 weeks of Doxy therapy
• initial injection of Immiticide followed 1 month later with 2 injections 24 hours apart

• strict cage rest for 2-4 weeks, observe for PE
• treat PE with prednisolone
• follow up with Ag test 4-6 months later

treat for 7-14 days with prednisolone and doxycycline; then 2 stage treatment of adulticide therapy

• Pimobendan (dog), furosemide, sildenafil, ACEi, spironolactone, STRICT cage rest, prednisone--> stabilize CHF for 2-4 wk prior to adulticide therapy
• 2 stage adulticide therpay

causes caval syndrome because the worms migrate backwards due to high pressure

immediately (Ivermectin, moxidectin)

• takes too long- continued pulmonary damage
• not cost effective (given twice monthly)
• macrocyclic lactone resistance is emerging

ivermectin (oral), milbemycin oxime (oral), selamectin (topical), moxidectin (topical), moxidectin (injectable- every 6 months)

large worm burden with severe pulmonary hypertension--> worms move retrograde into tricuspid valve orifice, RA, and caudal vena cava--> low cardiac output and hepatic congestion

hemoglobinuria (due to RBC fragmentation and hemolysis), DIC, severe hepatocellular injury

TR murmur + echo; forceps/snare removal of worms

corticosteroids, oxygen, rest, analgesics

avoid selective pressure on microfilaria or adult worms by not using slow kill methods for txt