Resolution of dynamic left ventricular outflow tract obstruction and reversible left ventricular hypertrophy in 4 cats

Abstract

This case series describes spontaneous resolution of systolic anterior motion of the mitral valve, cessation of a dynamic left ventricular outflow tract obstruction, and reverse cardiac remodeling in 4 young cats. Following initial presentation with or without congestive heart failure, subsequent rechecks documented resolution of systolic anterior motion of the mitral valve and normalization of left heart dimensions. Those cats originally presented with congestive heart failure were successfully weaned off diuretic medications. Atenolol was prescribed to all 4 cats, and all remained on oral atenolol through the final recheck. There was no documented recurrence of progressive heart disease and heart failure in any of the cats. Consideration is given to transient myocardial thickening, spontaneous resolution of mitral valve dysplasia, and response to beta-1 adrenergic antagonism as possible underlying mechanisms.

Key clinical message:

When presented with young cats with hypertrophic obstructive cardiomyopathy, veterinarians should consider multiple differential diagnoses, as lifespan in these cases may be longer than typically expected for cats with primary hypertrophic cardiomyopathy, even with concurrent congestive heart failure.

Hypertrophic cardiomyopathy (HCM) phenotype is characterized echocardiographically by diffuse or regional left ventricular hypertrophy (LVH) with a nondilated left ventricular chamber (1) and is the most common cardiomyopathy affecting felines (2). Systolic anterior motion of the mitral valve (SAM) can be an abnormality in cats diagnosed with HCM phenotype. It is hypothesized that SAM develops secondary to an abnormal mitral valve apparatus, such as papillary muscle hypertrophy or an elongated anterior mitral valve leaflet, and/or a hyperkinetic left ventricle, which commonly results in dynamic obstruction of the left ventricular outflow tract when the anterior mitral valve leaflet abruptly moves towards the interventricular septum during mid-systole (3,4).

Left ventricular outflow tract obstruction (LVOTO) can result in chronic pressure overload of the left ventricle, fibrotic lesions of the proximal interventricular septum, and secondary mitral valve insufficiency (4,5). Furthermore, SAM has also been documented in cats without LVH (2,6), indicating that primary SAM can precede LVH. Therefore, it was speculated that LVH can be a consequence of chronic pressure overload secondary to LVOTO (5). This can make it difficult to distinguish primary SAM with secondary LVH from primary HCM, particularly on first examination of younger patients that may have congenitally abnormal mitral valve apparatus. This case series describes 4 young cats with documented LVH and SAM that all displayed resolution of LVOTO with cardiac dimensions returning to normal.

CASE DESCRIPTIONS

Case 1

A 1-year-old neutered male domestic shorthair cat was brought to the emergency service with a 1-day history of lethargy, anorexia, and dyspnea. On initial assessment, the cat was tachypneic with increased bronchovesicular lung sounds bilaterally and a Grade-3/6 left parasternal systolic murmur. A single lateral thoracic radiograph revealed evidence of cardiomegaly, pleural effusion, and a diffuse, interstitial to alveolar pulmonary pattern. On echocardiogram, LVH, left atrial dilation, and a thickened and irregular anterior mitral valve leaflet with SAM and mild mitral insufficiency were noted (Table 1). The cat was hospitalized overnight and treated with oxygen supplementation (40%), furosemide (2 mg/kg, IV, q8h), enalapril (0.3 mg/kg, PO, q24h), and atenolol (1.6 mg/kg, PO, q24h). Due to improved respiratory rate and effort, the cat was discharged the following morning and prescribed furosemide (1.7 mg/kg, PO, q12h), enalapril (0.3 mg/kg, PO, q24h), and atenolol (1.6 mg/kg, PO, q24h). Thoracic radiographs 3 wk later revealed resolution of the previously noted pulmonary pattern and pleural effusion. The furosemide dosage was reduced (1.7 mg/kg, PO, q24h for 14 d; then 1.7 mg/kg, PO, q48h).

TABLE 1.

Echocardiographic measurements and heart rate before starting atenolol (Initial) and at final examination (Final) for cats in each of the 4 cases.

Parameter	Case 1		Case 2		Case 3		Case 4
	Initial	Final	Initial	Final	Initial	Final	Initial	Final
IVSd (mm)	7.0	4.3	4.9	3.9	7.4	3.8	6.5	3.5
LVFWd (mm)	8.0	4.7	6.4	4.8	9.5	4.9	6.4	3.3
LVIDd (mm)	14.0	14.1	9.4	14.8	11.0	16.0	12.5	14.2
LAD (LAX, mm)	18.0	12.0	18.7	11.3	14.0	14.8	14.0	14.2
LA/Ao	1.8	1.1	2.0	1.6	1.7	1.3	0.9	1.5
HR (bpm)	130	160	220	160	180	190	200	160

HR — Heart rate; IVSd — Interventricular septal thickness at end-diastole; LA/Ao — Left atrium to aorta ratio; LAD — Maximum left atrial diameter; LAX — Right parasternal long axis 4-chamber view; LVFWd — Left ventricular free wall thickness at end-diastole; LVIDd — Left ventricular internal diameter at end-diastole.

On reevaluation 1 mo later, echocardiography revealed unchanged LVH, SAM, and mitral valve insufficiency with a normal left atrial diameter. The cat was discharged and prescribed furosemide (1.7 mg/kg, PO, q48h), enalapril (0.3 mg/kg, PO, q24h), and an increased dosage of atenolol (1.6 mg/kg, PO, q12h).

On reevaluation 3 mo later, a Grade-2/6 left parasternal heart murmur was auscultated. Echocardiography revealed resolved SAM, persistent LVH, and normal left atrial diameter. The furosemide and enalapril were discontinued. The cat was discharged on atenolol as previously prescribed.

On final evaluation 6 mo later, the cat had been doing clinically well at home, with no relapse of congestive heart failure. Echocardiography did not reveal evidence of LVH or left atrial dilation (Table 1). A Grade-3/6 left parasternal heart murmur persisted. This cat continued to receive atenolol but was lost to follow-up.

Case 2

A 7-month-old neutered male ragdoll cat was brought to the emergency service with a 2-day history of tachypnea and lethargy. On initial assessment, the cat was dyspneic with crackles bilaterally, and had a Grade-3/6 left parasternal murmur. Thoracic radiographs revealed evidence of cardiomegaly, minimal pleural effusion, and a diffuse, interstitial to alveolar pulmonary pattern. On echocardiography, hypertrophy of the left ventricular free wall, left atrial dilation (Figure 1), SAM, and mild mitral insufficiency were noted (Table 1). The cat was hospitalized and treated with oxygen supplement (40%) and furosemide (2 mg/kg, IV, q8h). The cat was discharged 2 d later and prescribed furosemide (2.1 mg/kg, PO, q12h).

FIGURE 1.

Echocardiography: Right parasternal short-axis basilar view for the cat presented in Case 2. A — Dilated left atrium as shown by an increased left atrium to aorta ratio at the time of diagnosis of congestive heart failure, hypertrophic cardiomyopathy, and systolic anterior motion of the mitral valve. B — Resolution of the previously noted left atrial enlargement at 9 mo after initial diagnosis.

Ao — Aorta; LA — Left atrium.

On reevaluation 1 wk later, echocardiography revealed unchanged LVH and left atrial dilation, SAM, and mitral valve insufficiency. Treatment with clopidogrel (6.25 mg/kg, PO, q24h) and atenolol (2.1 mg/kg, PO, q12h) was added. When the cat was reevaluated 4 mo later, echocardiography revealed resolved SAM, normal left ventricular wall thickness, and normal left atrial diameter. The furosemide dosage was decreased (2.1 mg/kg, PO, q24h) with no changes to the other medications.

On reevaluation 5 mo later, echocardiography revealed findings similar to those of the previous echocardiogram (Table 1; Figure 1). No murmur was auscultated. Furosemide and clopidogrel were discontinued while atenolol was continued at the same dosage. At the time of this report (1 y after discontinuation of furosemide), the cat was doing clinically well at home with no relapse of congestive heart failure.

Case 3

A 1-year-old spayed female calico cat was presented for further evaluation for congestive heart failure previously diagnosed by the emergency service, at which time the cat was prescribed furosemide (1.75 mg/kg, PO, q12h). Physical examination revealed a Grade-3/6 left parasternal systolic murmur. Echocardiography revealed LVH (Figure 2), left atrial dilation, and SAM (Table 1). The cat was discharged and prescribed a decreased furosemide dose (1.5 mg/kg, PO, q12h), atenolol (1.25 mg/kg, PO, q12h), and enalapril (0.3 mg/kg, PO, q24h). On recheck examination 1 mo later, a Grade-2 to 3/6 parasternal murmur was auscultated. On echocardiography, SAM had resolved while LVH and left atrial dilation persisted. On subsequent recheck examinations over 6 mo, the heart murmur, LVH (Figure 2), and left atrial dilation resolved, with no recurrence of SAM. Over the course of 1 y, the furosemide dose was gradually decreased until it was discontinued, and the cat continued receiving atenolol as previously prescribed. At the time of this report (10 y after initial presentation), the cat had no relapse of congestive heart failure with no evidence of recurrent LVH on echocardiography (Table 1).

FIGURE 2.

Echocardiography: Right parasternal short-axis apical view at the end of diastole for the cat presented in Case 3. A — Hypertrophy of the IVS and LVFW at the time of diagnosis of hypertrophic cardiomyopathy and systolic anterior motion of the mitral valve. B — Resolution of the previously noted left ventricular hypertrophy.

IVS — Interventricular septum; LV — Left ventricle; LVFW — Left ventricular free wall.

Case 4

A 3-year-old spayed female domestic longhair cat previously diagnosed with hypertrophic obstructive cardiomyopathy phenotype (2 y earlier) by another cardiologist was presented for recheck examination. The cat had a Grade-4/6 left parasternal murmur, persistent and static LVH, and evidence of SAM (Table 1), with a systolic blood pressure of 110 mmHg. Atenolol was prescribed (1.3 mg/kg, PO, q12h). An echocardiogram conducted 6 mo later revealed resolution of SAM. A Grade-1/6 left parasternal murmur was auscultated at that time. Over the course of 1 y, resolution of the heart murmur and return to normal left ventricular wall thickness were noted (Table 1). The cat received yearly examinations for the following 3 y while receiving atenolol at the same dosage. No recurrent LVH was noted.

DISCUSSION

The 4 cats described in this series were all 1 year of age or younger when first presented for evaluation of potential heart disease. All cats demonstrated echocardiographic changes consistent with dynamic LVOTO from SAM and LVH, both of which resolved in all cases. In 3 of 4 cats, resolution of SAM was documented before reverse cardiac remodeling. Also of note, the 3 of 4 cats initially diagnosed with cardiogenic pulmonary edema were successfully weaned off diuretic medication and remained stable without recurrence of congestive heart failure. Only a small number of cases describing joint resolution of SAM and LVH have previously been documented in cats (7–10).

Transient myocardial thickening (TMT), a clinical entity characterized by reversible LVH, has been described in young cats (9,10). The cats in this series shared clinical features similar to those in cats with TMT. Approximately 20 to 30% of cats with TMT in previous reports had SAM (9,10). Furthermore, co-resolution of LVH and LVOTO was specifically noted in 6 cats with TMT and SAM (9). All but 2 cats in the previous reports were in congestive heart failure, and most cats were weaned off diuretic medication and remained stable (9,10). The cats described herein that had congestive heart failure similarly remained stable following reverse cardiac remodeling without diuretic medication. Of note, the cat in Case 4 did not present in congestive heart failure, and SAM and LVH in that cat persisted for 2 y. This case contrasted with those involving TMT, as TMT spontaneously resolved in all previous cases in < 5 mo (9,10). Transient myocardial thickening has also been associated with higher circulating cardiac troponin I concentrations compared to HCM (10); however, cardiac troponin I was not measured and could not be used to further evaluate the likelihood of TMT in these cases. Importantly, most cats with TMT did not experience recurrence of LVH or clinical signs (9,10), similar to the cats described herein.

Dynamic LVOTO due to SAM was shown in cats to result in increased plasma NT-proBNP, and consequently increased myocardial strain, in the absence of LVH or left atrial dilation (6). Similarly, cats with HCM and SAM had markedly increased LVH compared to cats with HCM alone (4). Therefore, it is reasonable to infer that LVH may occur secondary to SAM, presumably resulting from an abnormal mitral valve apparatus. Given that these cats were all young, and that resolution of SAM preceded resolution of LVH in 3 cases, we can speculate that mitral valve dysplasia resulted in SAM and subsequent LVH in the present cases. In particular, the cat in Case 1 had documented abnormalities of the mitral valve leaflet. Congenital mitral valve malformations resulting in LVOTO and secondary LVH have been reported in both human (11,12) and veterinary literature (7,13,14). However, an antemortem diagnosis of mitral valve dysplasia could not be confirmed in at least 3 of 4 cases, and pathological evaluation of the mitral valve in any case has not been done. Moreover, though resolution of SAM secondary to an abnormal mitral valve apparatus and secondary LVH has been reported in dogs (15), spontaneous resolution of mitral valve dysplasia and secondary LVH has not been documented in cats.

Resolution of dynamic LVOTO and LVH was reported in young dogs; most dogs in those reports were prescribed a beta-1 adrenergic antagonist (15,16). Beta-1 adrenergic antagonism has been shown to reduce left ventricular outflow tract velocity, and therefore the degree of LVOTO, in both cats (17) and humans (18,19) with HCM. In humans with LVOTO, administration of a beta-1 adrenergic antagonist reportedly improved symptoms and quality of life (18–20); but in cats with HCM, the presence of LVOTO did not alter the risk of cardiovascular morbidity or mortality (21), indicating there is no proven clinical benefit of reducing LVOTO. In cases of LVH secondary to SAM, we can hypothesize that, if the LVOTO is reduced, thereby lowering the pressure in the left ventricle, then the secondary LVH may resolve. This was documented in a single case report on a cat (7). However, though all cats described herein received atenolol through the final recheck, reduction in the maximum velocity of blood flow, and therefore the pressure gradient between the left ventricle and aorta, before and following beta-1 adrenergic antagonism was not consistently assessed. Therefore, reduction of LVOTO could not be established in these cats. Consequently, a cause-effect relationship among atenolol therapy, resolution of SAM, and reverse cardiac remodeling could not be determined in these cases.

A recent retrospective study noted short-term resolution of SAM in 47% of young cats treated with atenolol, but SAM remained absent long term in only 9% of cats (8). By contrast, half of the present cases (2/4) were followed long term. One cat (Case 3) received annual examinations for 8 y following discontinuation of furosemide without recurrence of SAM. Another cat (Case 4) was followed for an additional 4 y after normalization of left ventricular wall thickness without recurrence of SAM. Cats in the other cases (2/4) did not receive follow-up past 1 y. Of note, dynamic LVOTO and LVH resolved in all previously reported cases of young dogs, regardless of whether they received a beta-1 adrenergic antagonist (15,16).

It has also been shown experimentally that left ventricular wall thickness increases with increasing heart rate in healthy cats (22). It is consequently possible that beta-1 adrenergic antagonism decreases wall thickness independent of its effects in reducing LVOTO. This phenomenon has not been evaluated in cats with LVOTO and/or LVH, but a direct and isolated effect of atenolol on left ventricular wall thickness in these cats could not be excluded. Likewise, blood pressure measurements were not documented in 3 of 4 cases; therefore, whether systemic hypertension contributed to LVH in these cats could not be determined.

This case series report describes combined spontaneous resolution of LVOTO and LVH. Notably, these cases demonstrated potential differential diagnoses for young cats diagnosed with hypertrophic obstructive cardiomyopathy phenotype. For cases in which LVH resolves, there is a better prognosis than expected in cats with primary HCM, even with concurrent congestive heart failure. The recognition of this possibility could have important effects on clinical decisions and owner willingness to treat.