Pregnancy-Associated Congestive Heart Failure in a Cat

Introduction

Pregnancy results in significant stress on the cardiovascular system. Plasma volume and cardiac output may increase up to 50%.¹ Increased cardiac output is the result of increased stroke volume and heart rate. Stroke volume is increased because of plasma volume expansion and a lowered systemic vascular resistance.² During labor and delivery, cardiac output increases further from increased sympathetic tone secondary to pain and increased venous return from the contracting uterus.² In healthy people and animals, the increase in cardiac output and intravascular volume is well tolerated. However, in individuals with underlying cardiovascular disease, the added burden of pregnancy may be accompanied by devastating consequences such as maternal death, preterm birth, intrauterine growth restriction, and stillbirth.²

In women, the estimated prevalence of clinically significant cardiac disease during pregnancy is only 0.1% to 1.4%, but cardiac disease accounts for 15% of pregnancy-related mortality.² A specific cardiac disease that affects previously healthy women is known as peripartum cardiomyopathy (PPCM).^3,4 Peripartum cardiomyopathy appears in the perinatal period and is characterized by an acute onset of dilated cardiomyopathy.^3,4 The cause is unknown but has been postulated to be a selenium deficiency, a sequela to a viral infection, or an immune-mediated phenomenon.^3,4 Women suffering from PPCM may recover completely, suffer from persistent cardiac disease, or die.^3,4 The mortality rate associated with PPCM has been reported to reach 18% to 56% in women.⁴ Additionally, as progress in the management of congenital and acquired cardiac diseases has advanced, there are greater numbers of women in child-bearing years with significant cardiovascular disease. The eagerness of these women to bear children, despite potentially life-threatening risks, has led to the creation of guidelines for patient management.^2,5

In contrast to people, the incidence of cardiac disease in pregnant cats and dogs is unknown. Screening for inherited diseases removes many affected animals from the breeding pool. However, cats may develop cardiomyopathy at any age and may not develop signs of heart failure unless stressed.^6–8 Stresses that have previously been linked to the development of congestive heart failure in cats include treatment with glucocorticoids (particularly the long-acting, deposital forms) and anesthetic agents (especially ketamine).^6–8 To the authors’ knowledge, heart failure associated with pregnancy has not previously been reported in cats, although a reported single case exists in a dog.⁹ Because of the paucity of information in the veterinary literature, no guidelines have been determined for the best management of a pregnant animal in congestive heart failure. Without the benefit of clinical veterinary studies, it is unclear whether the recommendations for women apply to pregnant animals. For women with cardiac disease, assisted vaginal delivery is considered superior to cesarean section.² The purpose of this report is to describe the occurrence of congestive heart failure during late-term pregnancy in a queen, and the subsequent long-term resolution of heart failure following cesarean section and ovariohysterectomy. The decision to proceed with surgery was a difficult one and was made after considering the benefits and risks to both the queen and kittens.

Case Report

A 4-year-old, 3.9-kg, intact female Himalayan was presented for evaluation of dyspnea at the Foster Hospital for Small Animals at Cummings School of Veterinary Medicine at Tufts University. The queen was near term, as it was 63 days since her breeding date. Her previous litter had been delivered uneventfully 1 year earlier. No problems were noted with the current pregnancy until 24 hours prior to admission, when the queen developed anorexia, lethargy, and tachypnea. No signs of active labor were observed. The queen was treated with aminophylline^a (5 mg/kg subcutaneously [SC]) and amoxicillin^b (15 mg/kg SC) prior to referral.

At presentation, the queen was hypothermic (98.6°F) and had a heart rate of 220 beats per minute. A gallop rhythm was auscultated, and mucous membranes were pale. The queen was tachypneic (72 breaths per minute), with an increased inspiratory effort and increased bronchovesicular lung sounds, indicating that air flow was turbulent.¹⁰ Evaluation of radiographs obtained by the primary care veterinarian confirmed the presence of four kittens in the uterus, with none engaged in the birth canal. Cardiomegaly, a moderate volume of pleural effusion, and an increased interstitial pattern consistent with pulmonary edema were also evident on the radiographs.

A venous blood gas analysis demonstrated acidosis (pH 7.15, reference range 7.277 to 7.409; HCO₃ 16 mmol/L, reference range 18 to 23.2 mmol/L; PCO₂ 46 mm Hg, reference range 32.7 to 44.7 mm Hg). Abnormalities on a complete blood count included leukocytosis (20,500 cells/μL, reference range 5500 to 19,500 cells/μL) characterized by a mature neutrophilia (15,200 cells/μL, reference range 2500 to 12,800 cells/μL) and a microcytic, hypochromic anemia (hematocrit 23.8%, reference range 24% to 45%). The only abnormality documented on serum biochemical analysis was hypoalbuminemia (2.81 g/dL, reference range 2.9 to 3.9 g/dL).

A thoracocentesis was performed, and 100 mL of a clear, pale yellow fluid was removed. The total protein of this fluid was 2.9 gm/dL; the specific gravity was 1.021; and cytological evaluation identified low numbers of neutrophils, macrophages, lymphocytes, and rare erythrocytes. The pleural fluid was diagnosed as a modified transudate and was consistent with a clinical diagnosis of congestive heart failure. The initial therapy included diuresis with furosemide^c (1.9 mg/kg intramuscularly [IM] q 6 hours), vasodilatation with nitroglycerin^d (1/8 inch applied to the aural pinna q 6 hours), and supplemental oxygen. The systolic blood pressure was 108 mm Hg as measured by Doppler 6 hours after the initial doses of furosemide and nitroglycerin.

Twelve hours after admission, the queen remained tachypneic (64 breaths per minute) and had a moderate increase in respiratory effort. There was no jugular vein distension. The heart rate was 160 beats per minute, and body temperature (100.2°F) had normalized. Further laboratory tests documented hemoconcentration, as the hematocrit had risen to 35% and plasma total solids were 10.1 g/dL (reference range 6.0 to 8.4 g/dL). Electrolyte changes were compatible with diuretic therapy (sodium 142 mEq/L, reference range 143 to 153 mEq/L; chloride 96 mEq/L, reference range 108 to 128 mEq/L; potassium 3.2 mEq/L, reference range 3.5 to 5.2 mEq/L). An electrocardiogram documented a left axis shift.

Echocardiographic findings, obtained 18 hours after initial furosemide administration, included moderate left atrial enlargement [see Figure], mitral regurgitation, moderate right heart enlargement, and good left ventricular systolic function [see Table]. The cardiac changes were consistent with a clinical diagnosis of congestive heart failure. It could not be determined whether the cardiac changes were secondary to the pregnancy and volume overload or whether the queen had a restrictive or unclassified form of cardiomyopathy.

A theriogenologist recommended a cesarean section for several reasons. The repeated use of furosemide had resulted in dehydration of the queen, which, in combination with reduced cardiac output from heart failure, could have resulted in reduced perfusion of the fetuses. Despite this dehydration, the queen remained dyspneic. Topical nitroglycerin was used as a vasodilator because of its action as a smooth-muscle relaxant. Similarly, it is a tocolytic in women, and its use in the cat reported here may have prevented myometrial contractions necessary for parturition.¹¹ In addition, the cat had been anorexic for 2 days; natural labor for a queen suffering from congestive heart failure was considered potentially dangerous; and continued calcium diuresis induced by furosemide may have contributed to uterine inertia. After consideration of these factors and with little improvement in the queen’s condition following 17 hours of medical therapy, the decision was made to proceed with en bloc ovariohysterectomy and cesarean section.

The queen was premedicated with butorphanol^e (0.1 mg/kg intravenously [IV]), induced with ketamine^f (3.8 mg/kg IV) and diazepam^g (0.2 mg/kg IV), and general anesthesia was maintained with isoflurane^h in oxygen. During the surgery, the queen received IV fluids (0.45% sodium chloride [NaCl] supplemented with 2.5% dextrose at 5 mL/kg per hour). An en bloc ovariohysterectomy of the gravid uterus was performed using a standard midline approach. Anesthesia time was 52 minutes, and surgical time was 31 minutes. All four kittens were viable at the time of delivery. However, one kitten did not respond to resuscitative efforts and died immediately.

Postoperative treatment for the queen included continued supplemental oxygen therapy, IV fluids (0.45% NaCl supplemented with 2.5% dextrose at 1 mL/kg per hour), nitroglycerin as previously described, and furosemide (1.9 mg/kg IM once). The kittens were encouraged to suckle on the queen; however, they would not suckle, and the queen displayed no interest in nursing the kittens. The kittens were fed kitten milk replacerⁱ by bottle and were stimulated to defecate and urinate. All kittens were noted in the first 12 hours to be eating, urinating, and defecating with normal activity and respiratory rates. The birth weights of the kittens were 82 g, 59 g, and 56 g. The two smaller kittens failed to thrive and developed cardiopulmonary arrest between 18 and 22 hours after birth. The larger kitten continued to thrive, and the owner elected to take the kitten home at 24 hours after birth. That kitten continued to gain weight and lived to adulthood.

Twelve hours after surgery, the queen’s respiratory rate and effort improved significantly, although she remained mildly tachypneic (48 breaths per minute). Throughout the day, the respiratory rate and effort normalized, and the cat began to eat and drink. By 14 hours postoperatively, she was normothermic (102.4°F), had a normal heart rate (180 beats per minute), and her weight had dropped to 3.1 kg. All medications and supportive therapies were discontinued during the day. On the third postoperative day, treatment with enalapril^j (0.4 mg/kg per os [PO] q 24 hours) and aspirin^k (26 mg/kg PO three times per week) was initiated, and the cat was discharged from the hospital.

Following discharge, congestive heart failure did not recur, and the owners stopped administering all medications 4 months after surgery. An echocardiogram was repeated 9 months after surgery. The left and right atria were subjectively normal in size based on two-dimensional echocardiography. The left ventricle was mildly dilated based on subjective evaluation of the two-dimensional echocardiogram. The left ventricular internal diastolic dimension on M-mode echocardiography was 1.7 cm and was slightly larger than that seen on the previous echocardiographic examination [see Table]. Left ventricular systolic function was mildly decreased, and the fractional shortening was 32%. Several measurements of interventricular septal or left ventricular wall thickness were decreased compared to the original echocardiogram. No medical therapy was considered necessary, but serial echocardiograms were recommended. Communication with the owner and the referring veterinarian 9 years after the heart failure episode indicated that the queen never again developed clinical signs of cardiac disease.

Discussion

In cats with cardiomyopathy, congestive heart failure is often preceded by a stressful event such as hospitalization and IV fluid therapy, anesthesia, surgery, trauma, and corticosteroid injections.^6–8 In the cat reported here, the lack of signs referable to cardiac disease both before and after pregnancy, and the normalization of left atrial chamber size suggested that the pregnancy itself was the antecedent stressor that initiated congestive heart failure. It was also possible that this cat had no pre-existing myocardial disease and that the development of heart failure was, instead, a PPCM or a PPCM-like syndrome. In people, a diagnosis of PPCM requires the following criteria: no pre-existing heart failure, echocardiographic evidence of idiopathic cardiomyopathy, onset during the 5 months before and 1 month after parturition, decreased ejection fraction (<45%) or fractional shortening (<30%), and an increased left ventricular end-diastolic dimension.³ The cat of this report fulfilled the first three criteria. However, the original echocardiographic findings, obtained 18 hours after administration of furosemide and other medications, did not support a diagnosis of PPCM as described in humans. In some women, hypertension develops during pregnancy and may be accompanied by several complications, including heart failure.¹² Blood pressure measurements were not obtained from the cat reported here until 6 hours after admission and may have been altered by furosemide and nitroglycerin therapy.

In humans, pregnancy is associated with a 30% to 50% increase in intravascular volume, a similar increase in cardiac output, and a 20% reduction in systemic vascular resistance.^1,2,5 Labor, accompanied by sympathetic stimulation from pain and increased blood flow from active abdominal and uterine contractions, is associated with even more pronounced changes in cardiovascular parameters.^2,5,13 Women with pre-existing cardiac disease often have difficulty tolerating the cardiovascular alterations that accompany pregnancy and labor.^2,5,13 Therapeutic guidelines have been created to minimize the detrimental cardiopulmonary effects of cardiac disease to both the mother and the fetus before, during, and after labor.^2,5 Recommendations are based on the type and severity of cardiac disease and may include invasive corrective procedures (e.g., valvuloplasty, valve replacement) prior to conception or during pregnancy, and medical management throughout pregnancy (which may consist of reduced physical activity, avoidance of excessive salt, cautious diuretic therapy, vasodilatory therapy, heart rate control, anti-arrhythmia medications, and anticoagulation).^2,5 In the case of PPCM, medical management as for dilated cardiomyopathy is recommended. Vaginal delivery with epidural pain control to eliminate pain-related hypertension is preferable to cesarean section because of a faster return to mobility and, therefore, a reduction of thromboembolic risk.² Assisted delivery devices may be utilized to shorten the duration of labor.^2,5

Animals known to have heart disease are rarely purposefully bred. If such animals do become pregnant, similar therapeutic strategies to those listed above may be helpful. However, in light of species differences, cesarean section may be an acceptable alternative for those pregnant animals that develop congestive heart failure. Cats that undergo cesarean section recover more rapidly than women and, because they are relatively immobile for less time, have a reduced risk of thromboembolism.^14,15 For those animals with heart disease manifesting as failure and those that are refractory to medical management, termination of the pregnancy may be warranted to relieve congestion in a timely manner.

The use of ketamine in this particular case could be debated. Some authors have proposed that ketamine be avoided in cats affected with hypertrophic cardiomyopathy, as it has been implicated as a cause of myocardial damage.⁷ The events of this case occurred almost 10 years ago. Anesthetic protocols were different then, and ketamine was one of the recommended anesthetic agents for feline cesarean sections.¹⁶ Twelve hours after admission, the cat had hemoconcentration but was persistently dyspneic. These findings suggested that despite diuresis, the cat remained in congestive heart failure. The concurrent use of furosemide and IV fluids is also controversial, but the plan was to use furosemide for the congestive heart failure and simultaneously administer IV fluids to improve intravascular volume in the immediate postoperative period.

The hematological abnormalities identified in this cat were consistent with pregnancy. Anemia is a common hematological finding during pregnancy, and a 20% reduction in hematocrit or red cell count can be found in pregnant cats.¹⁸ Such anemia occurs as a result of volume expansion and iron deficiency.^17–19 Hypoalbuminemia occurs in normal pregnancy in people, despite an increase in total body albumin because of the accompanying increase in intravascular volume.²⁰ Hypoalbuminemia was present in the cat reported here; however, total solids rose to above the normal range following administration of furosemide.

In women, cardiac disease during pregnancy can lead to stillbirth.² Because necropsy examinations were not performed on the three kittens that died, it was not possible to definitively state the cause of death. Poor placental perfusion secondary to reduced cardiac output from heart failure or from diuretic therapy may have reduced oxygen delivery to the fetuses. Other documented causes of feline neonatal death that may have contributed to the neonatal mortality in this case include dehydration, insufficient nutritional intake, viral or bacterial infections, and fading kitten syndrome.²¹ Normal birth weights of kittens are reported to be between 75 and 150 g on average, with mean birth weight approximately 105 to 110 g.²¹ The fact that the two kittens that died in the first 24 hours were underweight at the time of birth suggests these kittens were affected by a process that was ongoing during the pregnancy, such as maternal cardiac disease.

Conclusion

Congestive heart failure was diagnosed in a 4-year-old, late-term, pregnant cat and resolved rapidly after ovariohysterectomy and cesarean section. The queen of this report may have developed congestive heart failure as a direct result of pregnancy, or the pregnancy may have acted indirectly as a stressor on a heart already affected by mild cardiomyopathy. Although clear therapeutic recommendations exist for the management of pregnant women with cardiac disease, similar recommendations are lacking for cats. Further studies are needed to determine the modes of therapy that are appropriate once congestive heart failure has developed during pregnancy in the cat.