AHS Heartworm Hotline , Parasitology

Canine Caval Syndrome Series, Part 1: Understanding Development of Caval Syndrome

Canine Caval Syndrome Series, Part 1: Understanding Development of Caval Syndrome
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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.


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.

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

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

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 inflow tract to the right ventricle (Figure 3), 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.
FIGURE 2. Right view of the thorax depicting adult heartworms in the anterior vena cava (arrows).

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).

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

In the 1980s, a high level of scientific 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 defined.

While it is evident that more scientific 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 Infection

The 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

T1511C06_Table01

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 define specific causes of CS is complicated.

Location of Worms

In 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 first 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 flow 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 flow is reduced and resistance to flow is increased—worms migrate toward the right atrium.

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 flow 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 inflow tract obstruction.2,4,10
  7. Cardiac output falls and acute signs of CS ensue.10

Obstructive Pulmonary Disease

The effects of arterial obstruction on pulmonary arterial flow and its resulting impact on worm location in dogs heavily infected with heartworms were studied by Kitagawa and colleagues, who artificially 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 flow, 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 Collapse

The 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 Flow

Although obstructive pulmonary vascular disease and cardiovascular collapse are entirely different disease processes, both lead to a dramatic decrease in pulmonary flow. If blood flow 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 flow.

WHAT CONTRIBUTES TO CAVAL SYNDROME?

Etiology

Once believed to be the consequence of “too many worms to fit in the pulmonary arteries,” we now know that factors other than worm numbers are involved in the etiology of CS.4 The difficulty has been in defining these other “factors,” especially in dogs with natural infection.

Based on the study findings discussed earlier, the relationship between blood flow and location of adult worms must be considered. Normal pulmonary arterial flow facilitates location of worms almost exclusively within the pulmonary arteries. As pulmonary arterial flow was decreased by artificially creating obstructive disease or by cardiac insufficiency, 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 insufficiency progress.7,12,13

Vascular Obstruction

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

T1511C06_Table02

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

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

T1511C06_Fig05

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

T1511C06_Fig06

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

T1511C06_Fig07

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

T1511C06_Fig08

FIGURE 8. Vascular fibrosis (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.

Cardiac Insufficiency

Cardiac insufficiency can be a pathologic consequence of advanced HWD. Even without overt signs of right-sided heart failure, reduction in cardiac output can significantly impact hemodynamics, decreasing the ejected volume of blood.13 While many unrelated diseases can lead to cardiac insufficiency, HWD alone can notably diminish cardiac function through several mechanisms (Table 3).

T1511C06_Table03

T1511C06_Fig09

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

Obstruction & Insufficiency Combined

Unlike obstructive disease in which blood flow is impacted solely by increased vascular resistance, cardiac insufficiency causes reduced flow due to diminished ejection of blood volume. In either case, because HWD can cause both obstructive disease and cardiac insufficiency simultaneously, a reduction in pulmonary arterial flow can become significant enough to allow heartworms to relocate to the right heart and/or vena cava.

IN SUMMARY

Understanding the pathophysiology of CS is an essential first 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

References

  1. 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 Dirofilaria immitis. J Vet Intern Med 1988; 2(1):36-40.
  5. Kuwahara Y, Kitagawa H, Sasaki Y, Ishihara K. Cardiopulmonary values in dogs with artificial 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 artificial pulmonary arterial embolism or injection of heartworm body fluid. Jpn J Vet Science 1990; 52(3):591-595.
  9. Kitagawa H, Sasaki Y, Ishihara K. Canine dirofilarial hemoglobinuria induced by milbemycin D administration. Jpn J Vet Sci 1986; 48:517-522.
  10. Kitagawa H, Sasaki Y, Ishihara K. Canine dirofilarial 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 dirofilarial 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 dirofilarial hemoglobinuria: Relationship between the presence of heartworm mass at the tricuspid valve orifice 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 dirofilariasis. 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 dirofilariosis. Am J Vet Res 2002; 63(11):1538-1544.
  15. Rawlings CA. The pulmonary arterial response to adult Dirofilaria 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 flexible 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 dirofilariasis. Jpn J Vet Sci 1990; 52(6):1211-1217.

Author_S-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.

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value='Honduras' >Honduras</option><option value='Hong Kong' >Hong Kong</option><option value='Hungary' >Hungary</option><option value='Iceland' >Iceland</option><option value='India' >India</option><option value='Indonesia' >Indonesia</option><option value='Iran' >Iran</option><option value='Iraq' >Iraq</option><option value='Ireland' >Ireland</option><option value='Isle of Man' >Isle of Man</option><option value='Israel' >Israel</option><option value='Italy' >Italy</option><option value='Jamaica' >Jamaica</option><option value='Japan' >Japan</option><option value='Jersey' >Jersey</option><option value='Jordan' >Jordan</option><option value='Kazakhstan' >Kazakhstan</option><option value='Kenya' >Kenya</option><option value='Kiribati' >Kiribati</option><option value='Kuwait' >Kuwait</option><option value='Kyrgyzstan' >Kyrgyzstan</option><option value='Lao People&#039;s Democratic Republic' >Lao People&#039;s Democratic Republic</option><option value='Latvia' >Latvia</option><option value='Lebanon' >Lebanon</option><option value='Lesotho' >Lesotho</option><option value='Liberia' >Liberia</option><option value='Libya' >Libya</option><option value='Liechtenstein' >Liechtenstein</option><option value='Lithuania' >Lithuania</option><option value='Luxembourg' >Luxembourg</option><option value='Macau' >Macau</option><option value='Macedonia' >Macedonia</option><option value='Madagascar' >Madagascar</option><option value='Malawi' >Malawi</option><option value='Malaysia' >Malaysia</option><option value='Maldives' >Maldives</option><option value='Mali' >Mali</option><option value='Malta' >Malta</option><option value='Marshall Islands' >Marshall Islands</option><option value='Martinique' >Martinique</option><option value='Mauritania' >Mauritania</option><option value='Mauritius' >Mauritius</option><option value='Mayotte' >Mayotte</option><option value='Mexico' >Mexico</option><option value='Micronesia' >Micronesia</option><option value='Moldova' >Moldova</option><option value='Monaco' >Monaco</option><option value='Mongolia' >Mongolia</option><option value='Montenegro' >Montenegro</option><option value='Montserrat' >Montserrat</option><option value='Morocco' >Morocco</option><option value='Mozambique' >Mozambique</option><option value='Myanmar' >Myanmar</option><option value='Namibia' >Namibia</option><option value='Nauru' >Nauru</option><option value='Nepal' >Nepal</option><option value='Netherlands' >Netherlands</option><option value='New Caledonia' >New Caledonia</option><option value='New Zealand' >New Zealand</option><option value='Nicaragua' >Nicaragua</option><option value='Niger' >Niger</option><option value='Nigeria' >Nigeria</option><option value='Niue' >Niue</option><option value='Norfolk Island' >Norfolk Island</option><option value='North Korea' >North Korea</option><option value='Northern Mariana Islands' >Northern Mariana Islands</option><option value='Norway' >Norway</option><option value='Oman' >Oman</option><option value='Pakistan' >Pakistan</option><option value='Palau' >Palau</option><option value='Palestine, State of' >Palestine, State of</option><option value='Panama' >Panama</option><option value='Papua New Guinea' >Papua New Guinea</option><option value='Paraguay' >Paraguay</option><option value='Peru' >Peru</option><option value='Philippines' >Philippines</option><option value='Pitcairn' >Pitcairn</option><option value='Poland' >Poland</option><option value='Portugal' >Portugal</option><option value='Puerto Rico' >Puerto Rico</option><option value='Qatar' >Qatar</option><option value='Réunion' >Réunion</option><option value='Romania' >Romania</option><option value='Russia' >Russia</option><option value='Rwanda' >Rwanda</option><option value='Saint Barthélemy' >Saint Barthélemy</option><option value='Saint Helena' >Saint Helena</option><option value='Saint Kitts and Nevis' >Saint Kitts and Nevis</option><option value='Saint Lucia' >Saint Lucia</option><option value='Saint Martin' >Saint Martin</option><option value='Saint Pierre and Miquelon' >Saint Pierre and Miquelon</option><option value='Saint Vincent and the Grenadines' >Saint Vincent and the Grenadines</option><option value='Samoa' >Samoa</option><option value='San Marino' >San Marino</option><option value='Sao Tome and Principe' >Sao Tome and Principe</option><option value='Saudi Arabia' >Saudi Arabia</option><option value='Senegal' >Senegal</option><option value='Serbia' >Serbia</option><option value='Seychelles' >Seychelles</option><option value='Sierra Leone' >Sierra Leone</option><option value='Singapore' >Singapore</option><option value='Sint Maarten' >Sint Maarten</option><option value='Slovakia' >Slovakia</option><option value='Slovenia' >Slovenia</option><option value='Solomon Islands' >Solomon Islands</option><option value='Somalia' >Somalia</option><option value='South Africa' >South Africa</option><option value='South Georgia' >South Georgia</option><option value='South Korea' >South Korea</option><option value='South Sudan' >South Sudan</option><option value='Spain' >Spain</option><option value='Sri Lanka' >Sri Lanka</option><option value='Sudan' >Sudan</option><option value='Suriname' >Suriname</option><option value='Svalbard and Jan Mayen Islands' >Svalbard and Jan Mayen Islands</option><option value='Sweden' >Sweden</option><option value='Switzerland' >Switzerland</option><option value='Syria' >Syria</option><option value='Taiwan' >Taiwan</option><option value='Tajikistan' >Tajikistan</option><option value='Tanzania' >Tanzania</option><option value='Thailand' >Thailand</option><option value='Timor-Leste' >Timor-Leste</option><option value='Togo' >Togo</option><option value='Tokelau' >Tokelau</option><option value='Tonga' >Tonga</option><option value='Trinidad and Tobago' >Trinidad and Tobago</option><option value='Tunisia' >Tunisia</option><option value='Turkey' >Turkey</option><option value='Turkmenistan' >Turkmenistan</option><option value='Turks and Caicos Islands' >Turks and Caicos Islands</option><option value='Tuvalu' >Tuvalu</option><option value='Uganda' >Uganda</option><option value='Ukraine' >Ukraine</option><option value='United Arab Emirates' >United Arab Emirates</option><option value='United Kingdom' >United Kingdom</option><option value='United States' >United States</option><option value='Uruguay' >Uruguay</option><option value='US Minor Outlying Islands' >US Minor Outlying Islands</option><option value='Uzbekistan' >Uzbekistan</option><option value='Vanuatu' >Vanuatu</option><option value='Venezuela' >Venezuela</option><option value='Vietnam' >Vietnam</option><option value='Virgin Islands, British' >Virgin Islands, British</option><option value='Virgin Islands, U.S.' >Virgin Islands, U.S.</option><option value='Wallis and Futuna' >Wallis and Futuna</option><option value='Western Sahara' >Western Sahara</option><option value='Yemen' >Yemen</option><option value='Zambia' >Zambia</option><option value='Zimbabwe' 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