Transient high-output heart failure documented by echocardiographic cardiac index measurement in a pregnant cat

Abstract

A female cat (approximately 3 weeks of gestation) was referred for respiratory distress and pleural effusion. Echocardiography revealed dilation of the left atrium and left ventricle, and the cardiac index was markedly elevated (0.39 L/kg/min), raising suspicion for high-output heart failure (HOHF). The cat was treated with furosemide and enrofloxacin. Pleural effusion completely resolved in late pregnancy, and 45 days after delivery the cardiac index decreased to 0.22 L/kg/min. To our knowledge, this is the first report describing a transient HOHF associated with pregnancy in a cat, highlighting the clinical utility of echocardiographic cardiac index measurement for identifying this condition. Further accumulation of cases is needed to better characterise this condition in feline patients.

High-output heart failure (HOHF) is a rare form of heart failure characterized by eccentric hypertrophy and an abnormally elevated cardiac output (CO) beyond the normal range [8]. Pregnancy is associated with increased circulating blood volume and may contribute to the development of heart failure in humans [1, 10, 15]. Only a few cases have been reported in cats, including two cases of congestive heart failure (CHF) occurring in late pregnancy [7, 14], and detailed clinical characteristics of pregnancy-associated heart failure in cats remain poorly described. This report describes a cat that developed transient HOHF accompanied by increased CO during pregnancy.

A 5.5-year-old female Sphynx cat was presented to a local veterinary clinic with a 3-day history of decreased appetite and tachypnoea. At the referring veterinary clinic, enrofloxacin (4.5 mg/kg q24 hr) had been prescribed empirically because an infection could not be excluded in the presence of an increased serum amyloid A concentration (41.8 mg/L; reference interval, <3.75 mg/L). The cat was subsequently referred to our hospital for evaluation of suspected cardiac disease and possible pericardial effusion. On presentation, the cat weighed 3.3 kg (body condition score 5/9), with a heart rate of 220–230 bpm and a respiratory rate of 44 breaths/min. No cardiac murmur was auscultated. Abdominal distension was noted; however, the cat was approximately 3 weeks pregnant. Thoracic radiography revealed marked cardiomegaly (vertebral heart score, 8.4; cardiothoracic ratio, 81.9%) with increased pulmonary opacity (Fig. 1). Lung ultrasonography (Aplio a Verifia, CANON Medical Systems Corp., Otawara, Japan) revealed echo-free spaces suggestive of pleural effusion (Fig. 2A); however, thoracocentesis was not performed because the volume was minimal. B-lines were observed in the right anterior thoracic region (Fig. 2B), suggesting cardiogenic pulmonary oedema. Electrocardiography revealed sinus tachycardia (220 bpm) without arrhythmias. Blood chemistry (FUJI DRI-CHEM NX600 analyzer, FUJIFILM Medical Co., Ltd., Tokyo, Japan) revealed elevated alkaline phosphatase (148 IU/L; reference interval, <58 IU/L) and creatine phosphokinase (>2,000 IU/L; reference interval, 87–309 IU/L); no other abnormalities were detected. The serum N-terminal pro–B-type natriuretic peptide concentration was 676 pmol/L ([IDEXX Laboratories Japan, Tokyo, Japan]: reference interval; <100 pmol/L). The oscillometric systolic blood pressure was 127 mmHg.

Fig. 1.

Thoracic radiographs obtained at the initial presentation. Left panel: Right lateral view showing marked cardiomegaly (vertebral heart score, 8.4). Right panel: Dorsoventral view showing marked cardiomegaly (cardiothoracic ratio, 81.9%).

Fig. 2.

Lung ultrasonographic images obtained at the initial presentation. (A) Pleural effusion was observed in the ventral region of the left thorax, whereas (B) B-lines were identified in the ventral region of the right anterior thorax.

Transthoracic echocardiography was performed by a board-certified cardiologist (Y.H.). Right parasternal long-axis and short-axis views were obtained with the cat in right lateral recumbency. The left atrial-to-aortic root (LA:Ao) ratio was measured from the right parasternal basal short-axis view according to the Swedish method. Left ventricular internal diameter at end-diastole (LVIDd) and fractional shortening were obtained from M-mode recordings in the right parasternal short-axis view at the level of the papillary muscles. Echocardiographic measurements are summarized in Table 1. Dilation of the left atrium and left ventricle was observed (Fig. 3A, 3B), and left ventricular fractional shortening was increased at 69.7%. No ventricular wall hypertrophy, pericardial effusion, or abnormal intracavitary structures were identified. Colour Doppler examination showed no intracardiac shunt flow or abnormal valvular flow. Based on these findings, the cat was tentatively diagnosed with an unclassified cardiomyopathy phenotype. In addition, stroke volume and CO were calculated using both left and right ventricular outflow tract methods, as previously described [2, 9]. For calculation of stroke volume, the aortic velocity–time integral was obtained by pulsed-wave Doppler from the left apical long-axis view at the level of the aortic valve, whereas the pulmonary velocity–time integral was obtained from the right parasternal short-axis view at the level of the pulmonary valve. Briefly, stroke volume was calculated as outflow tract cross-sectional area × velocity–time integral. Cardiac output was calculated as stroke volume × heart rate, and cardiac index (CI) was calculated by dividing CO by body weight or body surface area. Pulmonary-to-systemic blood flow ratio (Qp/Qs) was calculated using Doppler-derived flow measurements as previously described [11]. Pulmonary and systemic blood flow were derived from the right and left ventricular outflow tracts, respectively, and Qp/Qs was calculated as the ratio of pulmonary to systemic blood flow. The left ventricular CI calculated from the body weight at presentation was 0.39 L/kg/min, which exceeds the normal feline CI (0.112 ± 0.038 L/kg/min, [2]), and was therefore considered elevated. The Qp/Qs ratio was within the normal range (Table 1). Thus, HOHF was suspected.

Table 1. Serial echocardiographic changes in a cat with transient high-output heart failure.

	Day 1	Day 89	Day 1,033	Reference Value	Ref No
Heart rate (bpm)	220	194	185	180 (160–195)	[5]
Left atrial diameter (mm)	16.6	13.4	13.4	10.0 (7.6–13.4)	[5]
LA/AO ratio	2.37	1.6	1.64	1.15 (0.87–1.42)	[5]
IVSd (mm)	3.2	4.4	5.4	3.7 (2.8–4.9)	[5]
LVIDd (mm)	18.8	17.3	17	14.8 (11.9–18.5)	[5]
LVPWd (mm)	4.1	4.3	4.7	3.6 (2.7–4.7)	[5]
Fractional shortening (%)	69.7	46.7	51.7	45 (28–62)	[5]
RV diameter (mm)	8.2	6.5	4.4	4.85 ± 1.27	[11]
E wave velocity (cm/sec)	-	110.9	66.9	70 ± 10	[4]
AOF velocity (cm/sec)	232.1	148.8	128.9	110 ± 20	[4]
Left ventricular stroke volume (mL)	5.8	4	3.9	5.0–5.5	[3]
Right ventricular stroke volume (mL)	5.3	3.7	3.1	4.26 (3.60–4.77)	[6]
Left ventricular CO (L/min)	1.28	0.78	0.72	1.0–1.15	[3]
Right ventricular CO (L/min)	1.16	0.71	0.58	0.76 (0.62–0.91)	[6]
Left ventricular CI (L/kg/min)	0.39	0.22	0.2	0.112 ± 0.038	[2]
Left ventricular CI (L/min/m2)	5.79	3.30	1.89	No reference	-
Right ventricular CI (L/kg/min)	0.35	0.2	0.16	No reference	-
Qp:Qs ratio	0.9	0.93	0.75	0.71–1.29	[12]

AOF: aortic outflow; CI: cardiac index; CO: cardiac output; E wave: early diastolic transmitral flow velocity; IVSd: interventricular septal thickness at end-diastole; LA/Ao ratio: left atrium–to–aorta ratio; LVIDd: left ventricular internal diameter at end-diastole; LVPWd: left ventricular posterior wall thickness at end-diastole; Qp:Qs ratio: pulmonary-to-systemic blood flow ratio; RV: right ventricle.

Fig. 3.

Echocardiographic images obtained at the initial presentation and on day 89. Left panel: At the initial presentation, the (A) long-axis four-chamber view and (B) short-axis view at the heart base demonstrated marked enlargement of the left atrium and left ventricle. The imaging depth was set at 5 cm for all images. Right panel: On day 89, the (C) long-axis four-chamber view and (D) short-axis view at the heart base showed improvement in enlargement of the left atrium, left ventricle, and right ventricle. The imaging depth was set at 5 cm for all images.

Initial treatment consisted of furosemide (1.52 mg/kg q12 hr) and enrofloxacin (4.5 mg/kg q24 hr) administered for 7 days. After 7 days, the cat’s respiratory status and appetite had improved; therefore, the furosemide dosage was gradually reduced to q24 hr. In late pregnancy, the pulmonary oedema and pleural effusion had completely resolved; therefore, furosemide was discontinued. Forty-three days after the first presentation, the cat delivered seven kittens, one of which was stillborn.

On day 89 (45 days after delivery), ultrasonographic examination showed improvement in dilation of both atria and ventricle (Fig. 3C, 3D). The CI calculated from the left ventricular outflow tract decreased from 0.39 L/kg/min at baseline to 0.22 L/kg/min (Table 1). Following the present pregnancy, the cat underwent three additional pregnancies without recurrence of CHF. At the most recent recheck on day 1,033, the cat was in good general condition. Thoracic radiography showed reduced cardiac size (vertebral heart score, 8.0; Fig. 4), and echocardiography demonstrated that cardiac morphometric variables remained within the normal range (Table 1). The serum N-terminal pro–B-type natriuretic peptide concentration was <24 pmol/L.

Fig. 4.

Thoracic radiographs obtained on day 1,033. Left panel: Right lateral view showing mild reduction in cardiac size (vertebral heart score, 8.0). Right panel: Ventrodorsal view showing reduction in cardiac size (cardiothoracic ratio, 67.0%).

The most notable finding in this case was a markedly elevated CI measured using Doppler echocardiography, which strongly suggested HOHF. HOHF is a rare form of CHF characterised by eccentric hypertrophy induced by volume overload and a CO abnormally elevated beyond the normal range [8]. In a previously published box plot, the interquartile ranges of stroke volume and CO derived from the left ventricular outflow tract in healthy cats appear to be approximately 5.0–5.5 mL and 1.0–1.15 L/min, respectively [3]. The CI derived from the left ventricular outflow tract in healthy cats has been reported as 0.112 ± 0.038 L/kg/min [2]. Although direct comparison is not possible, the CO and CI in the present case were approximately 1.2- and 3.5-fold higher, respectively, than previously reported values. Because the CI is normalised to body weight, this marked increase reflects a disproportionately high CO relative to body size. Although definitive diagnostic criteria for HOHF in cats have not been established, the development of oedema despite increased CO is consistent with HOHF as defined in human medicine [8].

Other causes of increased CO, such as hyperthyroidism, arteriovenous fistula, and sepsis, were considered unlikely based on the clinical course and resolution after delivery. Serum thyroxine concentration was not measured in this case because hyperthyroidism is uncommon in cats of this age and because the clinical signs resolved completely after delivery.

Pregnancy is associated with increased circulating blood volume, which may contribute to elevated CO [1]. In healthy cats, stroke volume increases from approximately 5.5 mL to 6–7 mL and CO from approximately 1.0 L/min to 1.4–1.8 L/min from mating to the first and second trimesters [3]. In two previously reported cats with pregnancy-associated CHF, these variables were not assessed [7, 14]. Although baseline CO and CI were unknown in the present case, CO and CI at the initial visit were approximately 1.6–2.0 times higher than the postpartum values, when clinical signs and cardiac enlargement had resolved. Taken together, pregnancy-associated volume overload likely contributed to CHF and pleural effusion through a marked increase in CO.

In human medicine, peripartum cardiomyopathy develops in late pregnancy or the postpartum period and is characterized in part by left ventricular systolic dysfunction [13]. In the present case, fractional shortening was higher than normal reference values, consistent with previous case reports [7, 14], and may reflect pregnancy-related volume overload in cats [3]. This finding suggests that the pathophysiology of CHF during pregnancy in cats may differ from that of human peripartum cardiomyopathy [13]. In addition, unlike previously reported cats that developed CHF in late pregnancy [7, 14], the present cat developed CHF during mid-pregnancy. The reason for this discrepancy remains unclear but may reflect individual variation in cardiovascular adaptation to pregnancy.

In a previously reported cat, pimobendan was administered during late pregnancy and discontinued after resolution of CHF postpartum [7]. In the present case, although both furosemide and enrofloxacin may pose potential risks to fetuses, treatment was considered necessary because CHF represented a greater immediate risk to both the queen and the fetuses. Enrofloxacin had been prescribed by the referring veterinarian because infection could not be excluded. Although enrofloxacin has been associated with abnormalities in articular cartilage development in juvenile animals, no apparent musculoskeletal abnormalities were observed in the surviving kittens; however, one kitten was stillborn. Diuretics such as furosemide are commonly used for the management of peripartum cardiomyopathy in human medicine [16]. Furosemide was discontinued after resolution of CHF, and enrofloxacin after completion of the treatment course. These findings suggest that pregnancy-associated CHF in cats may resolve with minimal medical intervention. However, because safe and effective treatment protocols have not been established, treatment duration should be minimized whenever possible.

The cat in this case has remained asymptomatic without treatment for approximately 3 years following the initial visit. Similarly, in two previously reported cats with pregnancy-associated CHF, heart failure resolved postpartum, with asymptomatic periods of 9 years and 688 days [7, 14], consistent with the present case. These findings suggest that pregnancy-associated CHF in cats may have a favorable long-term prognosis; however, continued long-term follow-up may be warranted.

In conclusion, this case describes a cat that exhibited transient HOHF associated with increased circulating blood volume during pregnancy. This case highlights the potential utility of echocardiographic CI measurement for identifying HOHF in cats.

Conflicts of Interest

The authors have no conflicts of interest to disclose.