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tvpjournal.com | November/December 2015 | TODAY’S VETERINARY PRACTICE AHS HEARTWORM HOTLINE Peer Reviewed 63 According to the American Heartworm Society, over one million dogs in the United States are currently infected with Dirofilaria immitis (heartworms). If diagnosed in a timely fashion, most infections can be managed medically with good results. However, a small percentage of dogs harboring heartworms develop caval syndrome (CS), an acute phase, severe form of heartworm disease (HWD) that is fatal without prompt surgical intervention. Most commonly seen in dogs heavily infected with heartworms, CS often presents acutely and progresses rapidly (Figure 1). CS is a life threatening condition; therefore, it is extremely important that clinicians recognize and understand this syndrome. WHAT IS CAVAL SYNDROME? CS is a specific condition that develops when a mass of heartworms becomes situated in the right ventricle, right atrium, and often, the vena cava (Figure 2). These worms partially obstruct the Canine Caval Syndrome Series PART 1: UNDERSTANDING DEVELOPMENT OF CAVAL SYNDROME Stephen L. Jones, DVM Lakeside Animal Hospital, Moncks Corner, South Carolina The Heartworm Hotline column is presented in partnership between Today’s Veterinary Practice and the American Heartworm Society (heartwormsociety.org). The goal of the column is to communicate practical and timely information on prevention, diagnosis, and treatment of heartworm disease, as well as highlight current topics related to heartworm research and findings in veterinary medicine. FIGURE 1. Classic caval syndrome in a dog with a high worm burden. FIGURE 2. Right view of the thorax depicting adult heartworms in the anterior vena cava (arrows). FIGURE 3. A mass of adult heartworms lodged within the tricuspid valve of a dog presented with caval syndrome (view from the right ventricle).

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Page 1: TVP 2015-1112 HH caval syndrome - Today’s Veterinary

tvpjournal.com | November/December 2015 | TODAY’S VETERINARY PRACTICE

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According to the American Heartworm Society, over one million dogs in the United States are currently infected with Dirofi laria immitis (heartworms). If diagnosed in a timely fashion, most infections can be managed medically with good results.

However, a small percentage of dogs harboring heartworms develop caval syndrome (CS), an acute phase, severe form of heartworm disease (HWD) that is fatal without prompt surgical intervention. Most commonly seen in dogs heavily infected with heartworms, CS often presents acutely and progresses rapidly (Figure 1).

CS is a life threatening condition; therefore, it is extremely important that clinicians recognize and understand this syndrome.

WHAT IS CAVAL SYNDROME?CS is a specifi c condition that develops when a mass of heartworms becomes situated in the right ventricle, right atrium, and often, the vena cava (Figure 2). These worms partially obstruct the

Canine Caval Syndrome Series

PART 1: UNDERSTANDING DEVELOPMENT OF CAVAL SYNDROMEStephen L. Jones, DVMLakeside Animal Hospital, Moncks Corner, South Carolina

The Heartworm Hotline column is presented in partnership between Today’s Veterinary Practice and the American Heartworm Society (heartwormsociety.org). The goal of the column is to communicate practical and timely information on prevention, diagnosis, and treatment of heartworm disease, as well as highlight current topics related to heartworm research and fi ndings in veterinary medicine.

FIGURE 1. Classic caval syndrome in a dog with a high worm burden.

FIGURE 2. Right view of the thorax depicting adult heartworms in the anterior vena cava (arrows).

FIGURE 3. A mass of adult heartworms lodged within the tricuspid valve of a dog presented with caval syndrome (view from the right ventricle).

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infl ow tract to the right ventricle (Figure 3, page 63), interfering with closure of the tricuspid valve and consequently resulting in:1-5

• Significant tricuspid regurgitation• Compromised right ventricular filling• In some patients, the onset of circulatory

collapse.In the 1980s, a high level of scientifi c interest

in CS led to an expanded—albeit incomplete—understanding of the condition’s etiology. Unfortunately, enthusiasm for the subject waned, and even today the etiology of CS remains incompletely defi ned.

While it is evident that more scientifi c studies are needed to completely explain this unique manifestation of a complex disease, information from earlier studies combined with more recent pictorial and clinical evidence allows formulation of a working hypothesis for the development of CS.

HOW DOES CAVAL SYNDROME DEVELOP?Clinical Presentations of Heartworm InfectionThe pathogenesis of HWD and the chain of events that leads to illness is quite complex. Dogs with natural infection may remain asymptomatic for extended periods of time, or may present with a variety of clinical signs (Table 1).6

The wide variety of clinical presentations for heartworm infection (HWI) is expected due to the complex relationship between worm numbers, extent of vascular pathology, and individuality of each dog’s physiologic response, all of which result in the clinical variability observed between individual animals. Therefore, it is not surprising that trying to defi ne specifi c causes of CS is complicated.

Location of WormsIn CS, heartworms are typically found in the right heart and/or vena cava, whereas in heavy HWIs

without CS, worms are normally found in the pulmonary arteries rather than the heart.7

If we are to appreciate how adult worms relocate from the pulmonary arteries to the heart, as they do in CS, it may be necessary to fi rst understand why heartworms normally live in the pulmonary arteries.• Adult heartworms live freely within the lumen of

the pulmonary arteries, with no ability to attach or swim.

• Adult worms move quite slowly and it seems logical that they have a limited ability to freely, or at least quickly, move from one location to another.

• As a result, heartworms live where blood flow forces them to live.One logical explanation as to why heartworms

may normally remain in the pulmonary arteries is:• During systole, as blood is ejected into the

pulmonary arteries, the volume and velocity of blood flow force heartworms to the more distal aspects of the arteries.8-11

• Because adult heartworms move quite slowly, they may be unable to significantly move back toward the heart before the next contraction again pushes them distally, forcing them to reside in the pulmonary arteries.If we assume that blood fl ow is the primary

factor keeping adult heartworms constrained to the pulmonary arteries, it is logical to ask what condition—or series of conditions—might allow or cause multiple heartworms to retrogradely move into the right ventricle, atrium, and/or vena cava, as they do in CS.

WHY DO HEARTWORMS MIGRATE?Studies in heartworm-infected dogs have shown that when hemodynamics are altered—forward fl ow is reduced and resistance to fl ow is increased—worms migrate toward the right atrium.

TABLE 1. Clinical Signs of Heartworm DiseaseWeight lossExercise intoleranceMild to severe coughPolypnea or dyspneaHemoptysisRight-sided heart failureSigns consistent with CS*

*To be discussed in Part 2 of this series

TABLE 2. Disease Processes Associated with Heartworm-Induced Vascular Obstruction• Physical obstruction by adult worms (Figure 4)*• Intimal thickening of vascular walls (Figure 5)*• Microvascular disease• Dead worm obstruction (Figure 6)• Thrombus formation (Figure 7)• Arterial fi brosis and scarring (Figure 8)* Most evidence implies that presence of adult worms

and intimal thickening, individually, are unlikely to have a dramatic impact on vascular � ow. However, in the presence of mild to severe arterial lesions, removal and reinsertion of live heartworms has been shown to decrease and increase pulmonary arterial pressures, respectively.

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FIGURE 7. Active thrombosis secondary to a dead heartworm (A); adult worms with active clotting, reorganizing emboli, and well organized area of fi brosis representing 3 separate events (B); organized obstruction in a distal pulmonary artery containing necrotic heartworm remnants and debris (C).

A

B

C

FIGURE 4. Adult heartworms occupying the lumen of a smaller branch of the pulmonary artery.

FIGURE 5. Severe endothelial proliferation and rufus endarteritis secondary to heartworm infection.

FIGURE 8. Vascular fi brosis (arrows) found in a dog presented with caval syndrome. Interestingly, only 6 worms were present, 5 of which were located in the right heart and vena cava.

FIGURE 6. Dead heartworm embolism obstructing distal pulmonary artery; note the surrounding fi brosis indicating a previous insult (arrows).

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Obstructive Pulmonary DiseaseThe effects of arterial obstruction on pulmonary arterial fl ow and its resulting impact on worm location in dogs heavily infected with heartworms were studied by Kitagawa and colleagues, who artifi cially induced obstructive disease by surgically placing silicone tubes, similar in size to adult heartworms, into the pulmonary arteries of infected dogs.8

A similar study utilized dead adult worms placed in the pulmonary arteries to mimic a more natural thromboembolic episode. In both scenarios, obstruction of the distal pulmonary arteries caused increased vascular resistance, reduction in blood fl ow, and resultant decrease in cardiac output. The live adult worm population subsequently moved or were forced, in a retrograde manner, toward the right atrium, thereby inducing CS.

Cardiovascular CollapseThe retrograde movement of heartworms and development of CS were similarly observed when cardiovascular collapse was experimentally induced. • A whole-worm extract concocted from dead

worms was administered intravenously and, through an unexplained mechanism, profound vasodilation resulted in circulatory collapse.8

• In a separate study, when milbemycin D was administered to heartworm-infected dogs with high microfilaria numbers, anaphylaxis was induced.9

• In a third study, a dramatic reduction in cardiac output was induced by administration of a potent beta-1 blocker.10 In each of these studies, a resultant shock-like

reaction led to cardiovascular collapse, and as

cardiac output decreased, worms moved into the right atrium.

Role of Blood FlowAlthough obstructive pulmonary vascular disease and cardiovascular collapse are entirely different disease processes, both lead to a dramatic decrease in pulmonary fl ow. If blood fl ow is indeed responsible for keeping adult heartworms constrained to the pulmonary arteries, it is plausible that the development of CS may be potentiated by any condition that causes a reduction in the normal velocity and/or volume of pulmonary blood fl ow.

WHAT CONTRIBUTES TO CAVAL SYNDROME?EtiologyOnce believed to be the consequence of “too many worms to fi t in the pulmonary arteries,” we now know that factors other than worm numbers are involved in the etiology of CS.4 The diffi culty has been in defi ning these other “factors,” especially in dogs with natural infection.

Based on the study fi ndings discussed earlier, the relationship between blood fl ow and location of adult worms must be considered. Normal pulmonary arterial fl ow facilitates location of worms almost exclusively within the pulmonary arteries. As pulmonary arterial fl ow was decreased by artifi cially creating obstructive disease or by cardiac insuffi ciency, worms relocated to the proximal right heart.8-11

These experimental scenarios correlate directly with the progressive disease observed in natural infection as HWI-induced pulmonary vascular obstruction and cardiac insuffi ciency progress.7,12,13

Vascular Obstruction Vascular obstruction commonly occurs in HWD and can result from several disease processes (Table 2, page 64).7,13-15 Individually, each of these obstructive conditions can cause increased resistance to blood fl ow, but when they occur in combination, the additive effect can be quite dramatic.

Cardiac Insuf� ciency Cardiac insuffi ciency can be a pathologic consequence of advanced HWD. Even without overt signs of right-sided heart failure, reduction in cardiac output can signifi cantly impact hemodynamics, decreasing the ejected volume of blood.13 While many unrelated diseases can

Potential Development of Caval Syndrome 1. Heartworms mature in the pulmonary arteries, prompting formation

of antigen:antibody complexes and resulting in microvascular disease and, thus, increased vascular resistance.14

2. Adult worms incite intimal thickening; the combination of worm mass along with a narrowed vascular lumen continue to increase pulmonary vascular resistance.13,16,17

3. An adult worm spontaneously dies, causing a thromboembolic event, which further increases vascular resistance.

4. Dead worm vasomediators are released, impacting cardiac function.8

5. Arterial blood fl ow is reduced, allowing heartworms to migrate toward the heart.8

6. One or more worms move into the right ventricle, interfering with the tricuspid valve and simultaneously causing tricuspid regurgitation and infl ow tract obstruction.2,4,10

7. Cardiac output falls and acute signs of CS ensue.10

Potential Development of Caval Syndrome

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lead to cardiac insuffi ciency, HWD alone can notably diminish cardiac function through several mechanisms (Table 3).

Obstruction & Insuf� ciency CombinedUnlike obstructive disease in which blood fl ow is impacted solely by increased vascular resistance, cardiac insuffi ciency causes reduced fl ow due to diminished ejection of blood volume. In either case, because HWD can cause both obstructive disease and cardiac insuffi ciency simultaneously, a reduction in pulmonary arterial fl ow can become signifi cant enough to allow heartworms to relocate to the right heart and/or vena cava.

IN SUMMARYUnderstanding the pathophysiology of CS is an essential fi rst step to diagnosing and treating this serious and complex condition. While CS is not common, practitioners who see HWD should be prepared to identify patients with CS.

CS = caval syndrome; HWD = heartworm disease; HWI = heartworm infection

References1. Atkins CE. Caval syndrome in the dog. Semin Vet Med Surg

(Small Anim) 1987; 2(1):64-71.2. Atkins CE. Heartworm caval syndrome. In Kirk RW, Bonagura

JD (eds): Current Veterinary Therapy XI Small Animal Practice. Philadelphia: WB Saunders, 1992 pp 721-725.

3. Strickland KN. Canine and feline caval syndrome. Clin Tech Small Anim Pract 1998; 13(2):88-95.

4. Atkins CE, Keene BW, McGuirk SM. Investigation of caval syndrome in dogs experimentally infected with Dirofi laria immitis. J Vet Intern Med 1988; 2(1):36-40.

5. Kuwahara Y, Kitagawa H, Sasaki Y, Ishihara K. Cardiopulmonary values in dogs with artifi cial model of caval syndrome in heartworm disease. J Vet Med Sci 1991; 53(1):59-64.

6. McCall JW, Genchi C, Kramer LH, et al. Heartworm disease in animals and humans. Adv Parasitol 2008; 66:193-285.

7. Kitagawa H, Kubota A, Yasuda K, et al. Cardiopulmonary function in dogs with serious chronic heartworm disease. J Vet Med Sci 1992; 54(4):751-756.

8. Kitagawa H, Sasaki Y, Ishihara K, Kawakami M. Heartworm migration toward right atrium following artifi cial pulmonary arterial embolism or injection of heartworm body fl uid. Jpn J Vet Science 1990; 52(3):591-595.

9. Kitagawa H, Sasaki Y, Ishihara K. Canine dirofi larial hemoglobinuria induced by milbemycin D administration. Jpn J Vet Sci 1986; 48:517-522.

10. Kitagawa H, Sasaki Y, Ishihara K. Canine dirofi larial hemoglobinuria: Changes in right heart hemodynamics and heartworm migration from pulmonary artery towards right atrium following B1-blocker administration. Jpn J Vet Sci 1987; 49:1081-1086.

11. Kitagawa H, Sasaki Y, Ishihara K. Canine dirofi larial hemoglobinuria: Changes in right heart hemodynamics inducing heartworm migration from pulmonary artery. Jpn J Vet Science 1987; 49:485-489.

12. Kitagawa H, Sasaki Y, Ishihara K. Clinical studies on canine dirofi larial hemoglobinuria: Relationship between the presence of heartworm mass at the tricuspid valve orifi ce and plasma hemoglobin concentration. Jpn J Vet Science 1986; 48(1):99-103.

13. Sasaki Y, Kitagawa H, Hirano Y. Relationship between the pulmonary arterial pressure and lesions in the pulmonary arteries and parenchyma, and cardiac valves in canine dirofi lariasis. J Vet Med Sci 1992; 54(4):739-744.

14. Ninomiya H, Wakao Y. Scanning electron microscopy of vascular corrosion casts and histologic examination of pulmonary microvasculature in dogs with dirofi lariosis. Am J Vet Res 2002; 63(11):1538-1544.

15. Rawlings CA. The pulmonary arterial response to adult Dirofi laria immitis. In Heartworm Disease in Dogs and Cats. Philadelphia: WB Saunders, 1986, pp 1-39.

16. Ishihara K, Kitagawa H, Sasaki Y, Yokoi H. Changes in cardiopulmonary values after heartworm removal from pulmonary artery using fl exible alligator forceps. Jpn J Vet Sci 1988; 50(3):731-738.

17. Kitagawa H, Sasaki Y, Hirano Y. Contribution of live heartworms harboring in pulmonary arteries to pulmonary hypertension in dogs with dirofi lariasis. Jpn J Vet Sci 1990; 52(6):1211-1217.

STEPHEN L. JONESStephen L. Jones, DVM, is the President of the American Heartworm Society and a general practitioner/practice partner at Lakeside Animal Hospital, Moncks Corner, South Carolina. He received his DVM from University of Georgia. Read more about Dr. Jones at lahmc.com/veterinarians.php.

FIGURE 9. View from the right ventricle showing a dead heartworm intertwined in the chordae tendineae of the tricuspid valve.

TABLE 3. Mechanisms of Diminished Cardiac Function in Heartworm Disease• Reduced cardiac output against high pulmonary

artery pressure• Tricuspid insuffi ciency secondary to increased

pulmonary artery pressure• Tricuspid interference by worm entanglement

(Figure 9)• Tricuspid regurgitation due to worm intrusion

through the valve orifi ce• Vasoactive substance release associated

with worm death and subsequent systemic cardiovascular compromise