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J Vet Clin 2022; 39(6): 366-372

https://doi.org/10.17555/jvc.2022.39.6.366

Published online December 31, 2022

Type 4 Tetralogy of Fallot with Pulmonary Hypertension in an American Shorthair Cat

Hyeon-Jin Kim1,2 , Jihyun Kim1,2 , Tae Jung Kim3 , Ha-Jung Kim1,2

1Department of Veterinary Internal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea
2BK 21 Project Team, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea
3College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea

Correspondence to:*kimhj614@jnu.ac.kr (Ha-Jung Kim), tjkim@chonnam.ac.kr (Tae Jung Kim)

Received: September 8, 2022; Revised: November 1, 2022; Accepted: November 23, 2022

Copyright © The Korean Society of Veterinary Clinics.

A 2-year-old, spayed female, American shorthair cat presented with acute weight loss, tachypnea, and dyspnea. The cat had grade V holosystolic murmur and systemic hypotension. Echocardiography showed a 9 mm defect in the ventricular septum, left-to-right dominant bi-directional shunt, right ventricular hypertrophy, pulmonary stenosis, pulmonary hypertension, and overriding aorta. The cat was diagnosed with a Tetralogy of Fallot. The cat was treated with furosemide, pimobendan, ramipril, and sildenafil. Treatment reduced pulmonary infiltration, pulmonary vessel enlargement, and main pulmonary artery bulging. However, right-to-left flow increased over time and right ventricular outflow tract velocity was elevated. Currently, the patient has maintained an improved state for 1 year. This case report described a severe inherited feline Tetralogy of Fallot case that was successfully managed for a long time.

Keywords: cat, congenital heart disease, eisenmenger syndrome, tetralogy of fallot, ventricular septal defect.

Tetralogy of Fallot (TOF) is a congenital heart disease (CHD), which occurs during embryogenesis. It is associated with underdevelopment of the subpulmonary infundibulum that results in pulmonary stenosis (PS), overriding aorta, ventricular septal defect (VSD), and right ventricular (RV) hypertrophy (24). TOF accounts for 0.6% to 6.9% of all congenital heart diseases in dogs and cats (16,22). The most common clinical signs of TOF are exercise intolerance, respiratory signs (e.g. dyspnea and panting), and cyanosis (6). In case of humans, TOF is divided into 5 types based on severity of PS and VSD (17). Classically, TOF is a cyanotic heart disease, whereas type 4 is acyanotic with symptoms of slight-to-moderately decreased exercise tolerance, despite a loud heart murmur and generalized cardiomegaly (17). In most cases, surgical intervention is needed and supportive medical drugs can help to delay disease progression in dogs (20). The prognosis depends on the degree of PS and other complications (4).

This case describes a rare case of type 4 TOF with pulmonary artery hypertension (PAH) in a cat, which was managed adequately with medication for 1 year without obvious clinical signs.

A 2-year-old, spayed female, American shorthair cat presented with acute weight loss and tachypnea (90/min, 20-30/min). Thoracic auscultation revealed a grade V holosystolic murmur in the left apex area with a precordial thrill. Systolic blood pressure was 105 mmHg (normal, 120 mmHg-130 mmHg) with a Doppler, suggesting systemic hypotension. Herat rate was 190 (normal, 160-220). Electrocardiographic examination showed right axis deviation, deep notching Q wave, elevated T wave, and short P-R interval (Fig. 1). No remarkable abnormalities were observed in complete blood count (Hematocrit 43%; normal range, 30.3-52.3%) and serum chemistry.

Figure 1.Electrocardiogram during the first visit revealed right axis deviation, deep notching Q wave (black arrowhead), elevated T wave (white arrowhead), and short P-R interval (arrow).

Thoracic radiology showed generalized cardiomegaly (VHS = 9.0 vertebrae; normal range, 6.8-8.1 vertebrae) with bulging MPA, and slight enlargement of the left atrium. Mild infiltration of entire lung lobes, and remarkable enlargement of the pulmonary blood vessels indicated pulmonary overcirculation (Fig. 2A). To identify the cause of pulmonary overcirculation, we ruled out heartworm infection via the SNAP 4Dx Plus Test (IDEXX Laboratories, Inc., Westbrook, ME).

Figure 2.Ventrodorsal view (A) and right lateral view (a) of thoracic radiology during the first visit. Cardiomegaly (VHS = 9.0 vertebrae; normal, 6.8-8.1 vertebrae)- with MPA bulge (black arrowhead), slight enlargement of the left atrium, mild infiltration of entire lung lobes, and remarkable enlargement of the pulmonary blood vessels (black arrows) indicating pulmonary overcirculation. Ventrodorsal view (B) and right lateral view (b) of thoracic radiology at 2 months. Cardiomegaly, pulmonary vessel dilatation, and lung infiltration were significantly improved.

Two-dimensional echocardiography revealed a region of discontinuity between the upper portion of the interventricular septum and the base of the aorta. The size of VSD was 9.91 mm (VSD: Ao ratio = 0.9, large VSD) (Fig. 3A). Further echocardiographic studies revealed right ventricular free wall hypertrophy (8.16 mm, 2.4 ± 0.4) and thickened interventricular septum (8.94 mm, 4.66 ± 0.21) with suspected overriding aorta (Fig. 3B) (14,25). L-R shunt flow was observed on color Doppler echocardiography and its velocity (3.3 m/sec) was revealed on continuous Doppler echocardiography of the right parasternal long axis (5-chamber view). There was an increased pulmonary artery flow rate (3.7 m/sec [normal, 1.02 ± 0.15 m/sec]) (18). Pulmonary regurgitation was associated with elevated velocity (4.7 m/sec) (Fig. 3C, Table 1). Based on these findings, the case was diagnosed as TOF with L-R shunt, compatible with PH. Considering the patient’s respiratory distress, initial echocardiology was brief and no bubble study was performed, so, there was no accurate shunt flow analysis. Based on clinical signs, radiology, and continuous doppler examination of VSD, the dominant direction of the shunt was assumed.

Table 1 Serial echocardiologic measurements

ParameterFirst visit3 months later6 months laterReference interval
LVIDD (mm)22.6119.927.414.2 ± 1.8
LVIDS (mm)10.4510.2012.556.7 ± 1.5
Fractional shortening (%)53.848.754.253.1 ± 7.2
RVOT flow (m/s)3.73.74.31.02 ± 0.15
PR flow (m/s)4.74.34.0
Shunt flow (m/s)3.34.232.7
Shunt size (mm)9.919.79.7
IVS (mm)8.947.87.24.66 ± 0.21
RV free wall (mm)8.168.98.22.4 ± 0.4

LVIDD, left ventricular internal dimension at end-systole; LVIDS, left ventricular internal dismension at end-diastole; RVOT, right ventricular outflow tract; PR, pulmonary regurgitation; IVS, interventricular septum; RV, right ventricle.



Figure 3.Echocardiogram of the cat. Two-dimensional echocardiography was performed along the right parasternal long-axis (5-chamber view) during the first visit. (A) 9.91 mm VSD is placed in the upper portion of the interventricular septum. (B) Right ventricular free wall hypertrophy (8.16 mm, 2.4 ± 0.4) and thickened interventricular septum (8.94 mm, 4.66 ± 0.21) with suspected overriding aorta are observed. Continuous doppler echocardiography involved the right parasternal (short-axis view). (C) Pulmonary regurgitation flow rate was severely elevated with a velocity of 4.7 m/sec, due to PH. LV, left ventricle; RV, right ventricle; LA, left atrium; IVS, interventricular septum; RVFW, right ventricular free wall; AO, aorta; RVOT, right ventricular outflow tract; MPA, main pulmonary artery.

Considering the status of pulmonary edema, the cat was treated with furosemide (1 mg/kg every 8 hr, IV; Lasix tab, Handok Pharm, Seoul, Korea) with oxygen supplementation. In addition, a 1 day of hospitalization significantly improved cardiomegaly and pulmonary vessel dilatation (Fig. 2B). Tachypnea was improved from 90/min to 40/min (20-30/min). After discharge, the cat was managed at home with oral drugs: furosemide (2 mg/kg PO bid; Lasix tab, Handok Pharm, Seoul, Korea), pimobendan (0.25 mg/kg PO bid; Vetmedin tab, Meda Manufacturing GmbH, Cologne, Germany), ramipril (0.125 mg/kg PO sid; Tritace tab, Handok Pharm, Seoul, Korea) were prescribed for the congestive heart condition; and sildenafil (1 mg/kg PO bid; Palpal tab, HanmiParhm, Seoul, Korea) was prescribed for PAH.

Subsequent rechecks were performed every month, via radiology and blood tests (CBC, Chemistry). Echocardiological examination was performed 3 months later. CBC revealed a normal level of erythrocytes. There was a mild uptrend of creatinine which was attributed to the prescribed diuretics. Radiographic examination confirmed proper maintenance of cardiomegaly and pulmonary vessel dilatation. Tachypnea and weight loss improved gradually.

A progression of hemodynamic disorder was observed after 3 months and details that could not be detected in the initial examination were confirmed. Aorta was positioned over VSD. RV wall hypertrophy progressed to 8.9 mm (Fig. 4A). The interventricular septum bulged toward LA following increased RA pressure. PS caused by hypoplastic annulus was accompanied by post-stenotic dilation (Fig. 4B). Continuous Doppler echocardiography revealed a shunt flow velocity of 4.2 m/sec in the left-to-right direction, suggesting disease progression compared with 3 months ago (Fig. 4C). Pulmonary artery flow rate (3.7 m/sec) and pulmonary regurgitation (4.3 m/sec) were similar to those of 3 months ago. Bubble study of the right parasternal long axis (5-chamber view) revealed VSD shunt flow direction. L-R shunt was dominant, but during the early diastole, a partial flow along the right-to-left direction was detected, which established a bi-directional shunt flow (Table 1).

Figure 4.Two-dimensional echocardiography performed after 3 months. (A) Right parasternal long-axis 5-chamber view. The size of the defect in the interventricular septum was 9 mm, the same as the initial value. Aorta was positioned over VSD. RV wall hypertrophy progressed slightly to 8.9 mm. (B) Right parasternal short-axis view. Hypoplastic annulus was accompanied by post-stenotic dilation inducing pulmonary stenosis. Valve forms a dome shape in systole (arrowhead). (C) Continuous Doppler echocardiography in the right parasternal long-axis 5-chamber view revealed a shunt flow velocity of 4.2 m/sec in the left-to-right direction, which progressed compared with that of 3 months ago. RVFW, right ventricular free wall; PV, pulmonary valve; MPA, main pulmonary artery; VSD, ventricular septal defect.

Two months after the initial treatment, prerenal azotemia was confirmed by elevated creatinine (2.0 mg/dL; normal, 0.6-1.6 mg/dL). Continuous fluid therapy led to a decrease in creatinine level below 2.0 mg/dL. Since then, the dose of furosemide was adjusted from 2 mg/kg PO bid to 1.5 mg/kg PO bid based on periodical blood work and thoracic radiology results.

In the most recent re-evaluation, the patient did not exhibit erythrocytosis, lung infiltration, and pulmonary overcirculation, and cardiomegaly was also maintained. Echocardiology showed no significant change in cardiac structural disorders or hemodynamic measurements. A recent bubble study revealed a dominant L-R shunt, but a slightly increasing partial R-L shunt. The patient continues to maintain stable clinical symptoms. 1 year has passed since the first visit and the cat is being monitored every two months.

TOF is divided into 5 types based on the severity of PS and VSD (17). Classically, TOF is a cyanotic heart disease, whereas type 4 is acyanotic with symptoms of slight-to-moderately decreased exercise tolerance, despite a loud heart murmur and generalized cardiomegaly. Typical TOF does not accompany PAH. However, in type 4, the pressure in the pulmonary artery is usually elevated accompanied by systemic hypotension due to the L-R shunt (17,27). According to the American College of Veterinary Internal Medicine (ACVIM) consensus of PH in dogs, PH associated with a congenital cardiac shunt is classified as group 1d1 (21).

This is the first case of a cat with type 4 TOF that developed pulmonary edema in Korea and is important in that it was well managed with medication. Based on the human classification of TOF, the present case is Type 4 which is defined by a large VSD with L-R shunt and infundibular stenosis (17); since the patient’s VSD/aortic root ratio was greater than 0.7, it was classified as large VSD (11,12). Based on the criteria for the size of VSD involving human children, the case had a dominant L-R shunt flow. L-R shunt plays a key role in normal oxygen saturation, followed by the absence of cyanosis or hyperviscosity syndrome (17).

Further, this patient manifested PAH-CHD associated with shunt flow. According to the human classification of PAH-CHD (13,23), L-R flow was dominant in the latest examination, therefore, the PAH-CHD was classified as type 2, but we found an increase in R-L bubbles. At a certain point, R-L flow will reverse to L-R flow, and the PAH-CHD type will be changed to type 3 (Table 2) (13).

Table 2 Clinical classification of congenital heart disease associated with pulmonary arterial hypertension (12)

Classification
Eisenmenger syndrome
Left to right shunts
PAH with co-incidental CHD
Post operative PAH


Type 3 PAH-CHD is designated as Eisenmenger Syndrome (ES). ES may be defined as PH due to reversed or bidirectional shunt caused by congenital heart defects (28). In human ES patients, desaturated blood circulates systemically due to R-L flow, and consequently, clinical signs develop (26). Morbidity and mortality in human ES patients are usually related to chronic hypoxemia, erythrocytosis, and coagulopathy (1,10,26).

Clinical management of patients with PAH-CHD has focused on palliative and supportive treatment even in humans (2). Increasing clinical evidence suggests that therapies targeted at ES and PAH improve symptoms and survival (29). The ES targeted therapies include prostaglandin I2, phosphodiesterase inhibitor type-5 (PDE-5) inhibitor, and endothelin receptor agonist. The cat in the present case was treated with sildenafil, PDE-5 inhibitor (2,3). In previous studies which used sildenafil in ES cases of small animals and humans, 5 cats were reported as ES, and only one case received sildenafil (7-9,15). Sildenafil therapy resulted in symptomatic relief in dogs, and improved oxygen saturation in humans (5,19).

The prognosis of feline type 4 TOF is hard to predict because the progress of hemodynamic disorders varies in every case due to variant structure disorder. The goal of treatment, in this case, was two-fold: 1) to decrease congestive status, and 2) to delay the point of shunt reversal to prevent cyanosis. Loop diuretics, ACE inhibitors, and positive inotropes were used considering the patient’s congestive status.

The present case has been managed well with no surgical intervention required for 1 year now. The congestive status is being periodically monitored. In addition, targeted therapy has been used to prevent aggravation of PH and thereby manage the shunt flow well in L-R and maintain systemic blood flow under saturated conditions. Accordingly, it is expected that the onset of clinical symptoms will be delayed for as long as possible in this patient. The cat in this report may be valuable as a rare case of a long-living animal with TOF with a good quality of life.

The reported cases of CHD and ToF involving small animals are fewer than in humans, and therefore no specific classification exists. Some human data were used to understand the degree of hemodynamic and structural disorders via specific classification (17). This case elucidates CHD in small animals based on human classification. Further studies of CHD classification in small animals are needed.

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (NRF-2020R1A2C2005364).

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF), which is funded by the Ministry of Education (NRF-2020R1A2C2005364).

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Article

Case Report

J Vet Clin 2022; 39(6): 366-372

Published online December 31, 2022 https://doi.org/10.17555/jvc.2022.39.6.366

Copyright © The Korean Society of Veterinary Clinics.

Type 4 Tetralogy of Fallot with Pulmonary Hypertension in an American Shorthair Cat

Hyeon-Jin Kim1,2 , Jihyun Kim1,2 , Tae Jung Kim3 , Ha-Jung Kim1,2

1Department of Veterinary Internal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea
2BK 21 Project Team, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea
3College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea

Correspondence to:*kimhj614@jnu.ac.kr (Ha-Jung Kim), tjkim@chonnam.ac.kr (Tae Jung Kim)

Received: September 8, 2022; Revised: November 1, 2022; Accepted: November 23, 2022

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A 2-year-old, spayed female, American shorthair cat presented with acute weight loss, tachypnea, and dyspnea. The cat had grade V holosystolic murmur and systemic hypotension. Echocardiography showed a 9 mm defect in the ventricular septum, left-to-right dominant bi-directional shunt, right ventricular hypertrophy, pulmonary stenosis, pulmonary hypertension, and overriding aorta. The cat was diagnosed with a Tetralogy of Fallot. The cat was treated with furosemide, pimobendan, ramipril, and sildenafil. Treatment reduced pulmonary infiltration, pulmonary vessel enlargement, and main pulmonary artery bulging. However, right-to-left flow increased over time and right ventricular outflow tract velocity was elevated. Currently, the patient has maintained an improved state for 1 year. This case report described a severe inherited feline Tetralogy of Fallot case that was successfully managed for a long time.

Keywords: cat, congenital heart disease, eisenmenger syndrome, tetralogy of fallot, ventricular septal defect.

Introduction

Tetralogy of Fallot (TOF) is a congenital heart disease (CHD), which occurs during embryogenesis. It is associated with underdevelopment of the subpulmonary infundibulum that results in pulmonary stenosis (PS), overriding aorta, ventricular septal defect (VSD), and right ventricular (RV) hypertrophy (24). TOF accounts for 0.6% to 6.9% of all congenital heart diseases in dogs and cats (16,22). The most common clinical signs of TOF are exercise intolerance, respiratory signs (e.g. dyspnea and panting), and cyanosis (6). In case of humans, TOF is divided into 5 types based on severity of PS and VSD (17). Classically, TOF is a cyanotic heart disease, whereas type 4 is acyanotic with symptoms of slight-to-moderately decreased exercise tolerance, despite a loud heart murmur and generalized cardiomegaly (17). In most cases, surgical intervention is needed and supportive medical drugs can help to delay disease progression in dogs (20). The prognosis depends on the degree of PS and other complications (4).

This case describes a rare case of type 4 TOF with pulmonary artery hypertension (PAH) in a cat, which was managed adequately with medication for 1 year without obvious clinical signs.

Case Report

A 2-year-old, spayed female, American shorthair cat presented with acute weight loss and tachypnea (90/min, 20-30/min). Thoracic auscultation revealed a grade V holosystolic murmur in the left apex area with a precordial thrill. Systolic blood pressure was 105 mmHg (normal, 120 mmHg-130 mmHg) with a Doppler, suggesting systemic hypotension. Herat rate was 190 (normal, 160-220). Electrocardiographic examination showed right axis deviation, deep notching Q wave, elevated T wave, and short P-R interval (Fig. 1). No remarkable abnormalities were observed in complete blood count (Hematocrit 43%; normal range, 30.3-52.3%) and serum chemistry.

Figure 1. Electrocardiogram during the first visit revealed right axis deviation, deep notching Q wave (black arrowhead), elevated T wave (white arrowhead), and short P-R interval (arrow).

Thoracic radiology showed generalized cardiomegaly (VHS = 9.0 vertebrae; normal range, 6.8-8.1 vertebrae) with bulging MPA, and slight enlargement of the left atrium. Mild infiltration of entire lung lobes, and remarkable enlargement of the pulmonary blood vessels indicated pulmonary overcirculation (Fig. 2A). To identify the cause of pulmonary overcirculation, we ruled out heartworm infection via the SNAP 4Dx Plus Test (IDEXX Laboratories, Inc., Westbrook, ME).

Figure 2. Ventrodorsal view (A) and right lateral view (a) of thoracic radiology during the first visit. Cardiomegaly (VHS = 9.0 vertebrae; normal, 6.8-8.1 vertebrae)- with MPA bulge (black arrowhead), slight enlargement of the left atrium, mild infiltration of entire lung lobes, and remarkable enlargement of the pulmonary blood vessels (black arrows) indicating pulmonary overcirculation. Ventrodorsal view (B) and right lateral view (b) of thoracic radiology at 2 months. Cardiomegaly, pulmonary vessel dilatation, and lung infiltration were significantly improved.

Two-dimensional echocardiography revealed a region of discontinuity between the upper portion of the interventricular septum and the base of the aorta. The size of VSD was 9.91 mm (VSD: Ao ratio = 0.9, large VSD) (Fig. 3A). Further echocardiographic studies revealed right ventricular free wall hypertrophy (8.16 mm, 2.4 ± 0.4) and thickened interventricular septum (8.94 mm, 4.66 ± 0.21) with suspected overriding aorta (Fig. 3B) (14,25). L-R shunt flow was observed on color Doppler echocardiography and its velocity (3.3 m/sec) was revealed on continuous Doppler echocardiography of the right parasternal long axis (5-chamber view). There was an increased pulmonary artery flow rate (3.7 m/sec [normal, 1.02 ± 0.15 m/sec]) (18). Pulmonary regurgitation was associated with elevated velocity (4.7 m/sec) (Fig. 3C, Table 1). Based on these findings, the case was diagnosed as TOF with L-R shunt, compatible with PH. Considering the patient’s respiratory distress, initial echocardiology was brief and no bubble study was performed, so, there was no accurate shunt flow analysis. Based on clinical signs, radiology, and continuous doppler examination of VSD, the dominant direction of the shunt was assumed.

Table 1 . Serial echocardiologic measurements.

ParameterFirst visit3 months later6 months laterReference interval
LVIDD (mm)22.6119.927.414.2 ± 1.8
LVIDS (mm)10.4510.2012.556.7 ± 1.5
Fractional shortening (%)53.848.754.253.1 ± 7.2
RVOT flow (m/s)3.73.74.31.02 ± 0.15
PR flow (m/s)4.74.34.0
Shunt flow (m/s)3.34.232.7
Shunt size (mm)9.919.79.7
IVS (mm)8.947.87.24.66 ± 0.21
RV free wall (mm)8.168.98.22.4 ± 0.4

LVIDD, left ventricular internal dimension at end-systole; LVIDS, left ventricular internal dismension at end-diastole; RVOT, right ventricular outflow tract; PR, pulmonary regurgitation; IVS, interventricular septum; RV, right ventricle..



Figure 3. Echocardiogram of the cat. Two-dimensional echocardiography was performed along the right parasternal long-axis (5-chamber view) during the first visit. (A) 9.91 mm VSD is placed in the upper portion of the interventricular septum. (B) Right ventricular free wall hypertrophy (8.16 mm, 2.4 ± 0.4) and thickened interventricular septum (8.94 mm, 4.66 ± 0.21) with suspected overriding aorta are observed. Continuous doppler echocardiography involved the right parasternal (short-axis view). (C) Pulmonary regurgitation flow rate was severely elevated with a velocity of 4.7 m/sec, due to PH. LV, left ventricle; RV, right ventricle; LA, left atrium; IVS, interventricular septum; RVFW, right ventricular free wall; AO, aorta; RVOT, right ventricular outflow tract; MPA, main pulmonary artery.

Considering the status of pulmonary edema, the cat was treated with furosemide (1 mg/kg every 8 hr, IV; Lasix tab, Handok Pharm, Seoul, Korea) with oxygen supplementation. In addition, a 1 day of hospitalization significantly improved cardiomegaly and pulmonary vessel dilatation (Fig. 2B). Tachypnea was improved from 90/min to 40/min (20-30/min). After discharge, the cat was managed at home with oral drugs: furosemide (2 mg/kg PO bid; Lasix tab, Handok Pharm, Seoul, Korea), pimobendan (0.25 mg/kg PO bid; Vetmedin tab, Meda Manufacturing GmbH, Cologne, Germany), ramipril (0.125 mg/kg PO sid; Tritace tab, Handok Pharm, Seoul, Korea) were prescribed for the congestive heart condition; and sildenafil (1 mg/kg PO bid; Palpal tab, HanmiParhm, Seoul, Korea) was prescribed for PAH.

Subsequent rechecks were performed every month, via radiology and blood tests (CBC, Chemistry). Echocardiological examination was performed 3 months later. CBC revealed a normal level of erythrocytes. There was a mild uptrend of creatinine which was attributed to the prescribed diuretics. Radiographic examination confirmed proper maintenance of cardiomegaly and pulmonary vessel dilatation. Tachypnea and weight loss improved gradually.

A progression of hemodynamic disorder was observed after 3 months and details that could not be detected in the initial examination were confirmed. Aorta was positioned over VSD. RV wall hypertrophy progressed to 8.9 mm (Fig. 4A). The interventricular septum bulged toward LA following increased RA pressure. PS caused by hypoplastic annulus was accompanied by post-stenotic dilation (Fig. 4B). Continuous Doppler echocardiography revealed a shunt flow velocity of 4.2 m/sec in the left-to-right direction, suggesting disease progression compared with 3 months ago (Fig. 4C). Pulmonary artery flow rate (3.7 m/sec) and pulmonary regurgitation (4.3 m/sec) were similar to those of 3 months ago. Bubble study of the right parasternal long axis (5-chamber view) revealed VSD shunt flow direction. L-R shunt was dominant, but during the early diastole, a partial flow along the right-to-left direction was detected, which established a bi-directional shunt flow (Table 1).

Figure 4. Two-dimensional echocardiography performed after 3 months. (A) Right parasternal long-axis 5-chamber view. The size of the defect in the interventricular septum was 9 mm, the same as the initial value. Aorta was positioned over VSD. RV wall hypertrophy progressed slightly to 8.9 mm. (B) Right parasternal short-axis view. Hypoplastic annulus was accompanied by post-stenotic dilation inducing pulmonary stenosis. Valve forms a dome shape in systole (arrowhead). (C) Continuous Doppler echocardiography in the right parasternal long-axis 5-chamber view revealed a shunt flow velocity of 4.2 m/sec in the left-to-right direction, which progressed compared with that of 3 months ago. RVFW, right ventricular free wall; PV, pulmonary valve; MPA, main pulmonary artery; VSD, ventricular septal defect.

Two months after the initial treatment, prerenal azotemia was confirmed by elevated creatinine (2.0 mg/dL; normal, 0.6-1.6 mg/dL). Continuous fluid therapy led to a decrease in creatinine level below 2.0 mg/dL. Since then, the dose of furosemide was adjusted from 2 mg/kg PO bid to 1.5 mg/kg PO bid based on periodical blood work and thoracic radiology results.

In the most recent re-evaluation, the patient did not exhibit erythrocytosis, lung infiltration, and pulmonary overcirculation, and cardiomegaly was also maintained. Echocardiology showed no significant change in cardiac structural disorders or hemodynamic measurements. A recent bubble study revealed a dominant L-R shunt, but a slightly increasing partial R-L shunt. The patient continues to maintain stable clinical symptoms. 1 year has passed since the first visit and the cat is being monitored every two months.

TOF is divided into 5 types based on the severity of PS and VSD (17). Classically, TOF is a cyanotic heart disease, whereas type 4 is acyanotic with symptoms of slight-to-moderately decreased exercise tolerance, despite a loud heart murmur and generalized cardiomegaly. Typical TOF does not accompany PAH. However, in type 4, the pressure in the pulmonary artery is usually elevated accompanied by systemic hypotension due to the L-R shunt (17,27). According to the American College of Veterinary Internal Medicine (ACVIM) consensus of PH in dogs, PH associated with a congenital cardiac shunt is classified as group 1d1 (21).

Discussion

This is the first case of a cat with type 4 TOF that developed pulmonary edema in Korea and is important in that it was well managed with medication. Based on the human classification of TOF, the present case is Type 4 which is defined by a large VSD with L-R shunt and infundibular stenosis (17); since the patient’s VSD/aortic root ratio was greater than 0.7, it was classified as large VSD (11,12). Based on the criteria for the size of VSD involving human children, the case had a dominant L-R shunt flow. L-R shunt plays a key role in normal oxygen saturation, followed by the absence of cyanosis or hyperviscosity syndrome (17).

Further, this patient manifested PAH-CHD associated with shunt flow. According to the human classification of PAH-CHD (13,23), L-R flow was dominant in the latest examination, therefore, the PAH-CHD was classified as type 2, but we found an increase in R-L bubbles. At a certain point, R-L flow will reverse to L-R flow, and the PAH-CHD type will be changed to type 3 (Table 2) (13).

Table 2 . Clinical classification of congenital heart disease associated with pulmonary arterial hypertension (12).

Classification
Eisenmenger syndrome
Left to right shunts
PAH with co-incidental CHD
Post operative PAH


Type 3 PAH-CHD is designated as Eisenmenger Syndrome (ES). ES may be defined as PH due to reversed or bidirectional shunt caused by congenital heart defects (28). In human ES patients, desaturated blood circulates systemically due to R-L flow, and consequently, clinical signs develop (26). Morbidity and mortality in human ES patients are usually related to chronic hypoxemia, erythrocytosis, and coagulopathy (1,10,26).

Clinical management of patients with PAH-CHD has focused on palliative and supportive treatment even in humans (2). Increasing clinical evidence suggests that therapies targeted at ES and PAH improve symptoms and survival (29). The ES targeted therapies include prostaglandin I2, phosphodiesterase inhibitor type-5 (PDE-5) inhibitor, and endothelin receptor agonist. The cat in the present case was treated with sildenafil, PDE-5 inhibitor (2,3). In previous studies which used sildenafil in ES cases of small animals and humans, 5 cats were reported as ES, and only one case received sildenafil (7-9,15). Sildenafil therapy resulted in symptomatic relief in dogs, and improved oxygen saturation in humans (5,19).

The prognosis of feline type 4 TOF is hard to predict because the progress of hemodynamic disorders varies in every case due to variant structure disorder. The goal of treatment, in this case, was two-fold: 1) to decrease congestive status, and 2) to delay the point of shunt reversal to prevent cyanosis. Loop diuretics, ACE inhibitors, and positive inotropes were used considering the patient’s congestive status.

The present case has been managed well with no surgical intervention required for 1 year now. The congestive status is being periodically monitored. In addition, targeted therapy has been used to prevent aggravation of PH and thereby manage the shunt flow well in L-R and maintain systemic blood flow under saturated conditions. Accordingly, it is expected that the onset of clinical symptoms will be delayed for as long as possible in this patient. The cat in this report may be valuable as a rare case of a long-living animal with TOF with a good quality of life.

Conclusions

The reported cases of CHD and ToF involving small animals are fewer than in humans, and therefore no specific classification exists. Some human data were used to understand the degree of hemodynamic and structural disorders via specific classification (17). This case elucidates CHD in small animals based on human classification. Further studies of CHD classification in small animals are needed.

Source of Funding

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (NRF-2020R1A2C2005364).

Acknowledgements

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF), which is funded by the Ministry of Education (NRF-2020R1A2C2005364).

Conflicts of Interest

The authors have no conflicting interests.

Fig 1.

Figure 1.Electrocardiogram during the first visit revealed right axis deviation, deep notching Q wave (black arrowhead), elevated T wave (white arrowhead), and short P-R interval (arrow).
Journal of Veterinary Clinics 2022; 39: 366-372https://doi.org/10.17555/jvc.2022.39.6.366

Fig 2.

Figure 2.Ventrodorsal view (A) and right lateral view (a) of thoracic radiology during the first visit. Cardiomegaly (VHS = 9.0 vertebrae; normal, 6.8-8.1 vertebrae)- with MPA bulge (black arrowhead), slight enlargement of the left atrium, mild infiltration of entire lung lobes, and remarkable enlargement of the pulmonary blood vessels (black arrows) indicating pulmonary overcirculation. Ventrodorsal view (B) and right lateral view (b) of thoracic radiology at 2 months. Cardiomegaly, pulmonary vessel dilatation, and lung infiltration were significantly improved.
Journal of Veterinary Clinics 2022; 39: 366-372https://doi.org/10.17555/jvc.2022.39.6.366

Fig 3.

Figure 3.Echocardiogram of the cat. Two-dimensional echocardiography was performed along the right parasternal long-axis (5-chamber view) during the first visit. (A) 9.91 mm VSD is placed in the upper portion of the interventricular septum. (B) Right ventricular free wall hypertrophy (8.16 mm, 2.4 ± 0.4) and thickened interventricular septum (8.94 mm, 4.66 ± 0.21) with suspected overriding aorta are observed. Continuous doppler echocardiography involved the right parasternal (short-axis view). (C) Pulmonary regurgitation flow rate was severely elevated with a velocity of 4.7 m/sec, due to PH. LV, left ventricle; RV, right ventricle; LA, left atrium; IVS, interventricular septum; RVFW, right ventricular free wall; AO, aorta; RVOT, right ventricular outflow tract; MPA, main pulmonary artery.
Journal of Veterinary Clinics 2022; 39: 366-372https://doi.org/10.17555/jvc.2022.39.6.366

Fig 4.

Figure 4.Two-dimensional echocardiography performed after 3 months. (A) Right parasternal long-axis 5-chamber view. The size of the defect in the interventricular septum was 9 mm, the same as the initial value. Aorta was positioned over VSD. RV wall hypertrophy progressed slightly to 8.9 mm. (B) Right parasternal short-axis view. Hypoplastic annulus was accompanied by post-stenotic dilation inducing pulmonary stenosis. Valve forms a dome shape in systole (arrowhead). (C) Continuous Doppler echocardiography in the right parasternal long-axis 5-chamber view revealed a shunt flow velocity of 4.2 m/sec in the left-to-right direction, which progressed compared with that of 3 months ago. RVFW, right ventricular free wall; PV, pulmonary valve; MPA, main pulmonary artery; VSD, ventricular septal defect.
Journal of Veterinary Clinics 2022; 39: 366-372https://doi.org/10.17555/jvc.2022.39.6.366

Table 1 Serial echocardiologic measurements

ParameterFirst visit3 months later6 months laterReference interval
LVIDD (mm)22.6119.927.414.2 ± 1.8
LVIDS (mm)10.4510.2012.556.7 ± 1.5
Fractional shortening (%)53.848.754.253.1 ± 7.2
RVOT flow (m/s)3.73.74.31.02 ± 0.15
PR flow (m/s)4.74.34.0
Shunt flow (m/s)3.34.232.7
Shunt size (mm)9.919.79.7
IVS (mm)8.947.87.24.66 ± 0.21
RV free wall (mm)8.168.98.22.4 ± 0.4

LVIDD, left ventricular internal dimension at end-systole; LVIDS, left ventricular internal dismension at end-diastole; RVOT, right ventricular outflow tract; PR, pulmonary regurgitation; IVS, interventricular septum; RV, right ventricle.


Table 2 Clinical classification of congenital heart disease associated with pulmonary arterial hypertension (12)

Classification
Eisenmenger syndrome
Left to right shunts
PAH with co-incidental CHD
Post operative PAH

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