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DIAGNOSIS AND TREATMENT OF FELINE HCM Iolanda Navalón Calvo Ars Veterinaria c/.Cardedeu nº3 Barcelona Spain INTRODUCTION Hypertrophic cardiomyopathy (HCM) is characterized by a hypertrophy of the left ventricle due to problems inherent to the myocardium, in absence of other heart or systemic conditions that can lead to a concentric hypertrophy of the myocardium, such as aortic stenosis, blood hypertension, infiltrative myocarditis (neoplastic or infectious), hyperthyroidism or acromegaly. The incidence of heart disease in the cat is estimated around 8-10% and the HCM is the most frequent form, representing approximately 2/3 of the feline CM. Hypertrophy in cats is typically concentric and symmetrical, including the whole left ventricle. However, there are also regional asymmetrical hypertrophies, involving the upper aspect of the septum, the free wall of the ventricle, or papillary muscles. Most of apparently normal cats have a LV < 4.5 mm. 1 Most cases of HCM have an unknown cause and, thus, it is called primary HCM (genetic). It is thought (although this is not completely described) that there may be mutations in the sarcomere of the myocytes that alter the muscle contraction at a molecular level and the replication of the sarcomere may be activated causing an increase of the thickness of the myocytes and hypertrophy. In cats, there is breed prevalence, suggesting a hereditary component of the HCM. It has been described in Siberia, Sphynx, American shorthair, Cornish Rex, Persian, European and British shorthair, Chartreux, Bengal and Norway forest cats. Two distinct mutations of the protein "myosin protein C3 bniding" (MYBPC3) with dominant autosomal traits and incomplete penetrance have been identified in Maine Coon and Ragdoll Mutation A31P (g-c) in the Main Coon and R820W in the Ragdoll 2, 3. Apart from inherited cases of HCM, the rest could be caused by "de novo" sarcomere mutations, as in humans, though there are also cases with unknown cause where the existence of additional mutations are suspected, or even potential environmental causes or other influences. Males are predisposed, and the condition is more frequent in young cats (5 months to 6 years of age), although is has been described in up to 16 years-old cats. In mild to moderate cases, it may be asymptomatic and the diagnosis may be incidental, but they may develop heart failure when there is severe thickening. They may present with lethargy, anorexia, tachypnea and dyspnea due to pulmonary oedema, pleural effusion, or both. It can also cause systemic arterial thromboembolism (SATE) with acute paralysis or paresis, or even sudden death, which is likely to be caused by a coronary embolism, ventricular arrhythmia or by a not diagnosed congestive heart failure (CHF) that causes hypoxia. Auscultation may help: systolic murmur is more frequent (usually on the sternal border) and can be by mitral regurgitation or by left-sided obstructive flow with systolic anterior movement of mitral valve (SAM Systolic Anterior Motion) or gallop sounds (S3, S4). DIAGNOSIS The diagnosis is primarily based on echocardiography: Increased ventricular thickness (≥ 5.5 mm), symmetrical or asymmetrical. Sometimes, hypertrophy is only from papillary m. (early sign). Sometimes, M-mode is not sufficient to detect the asymmetries. Increased LA (Left Atrium), indicating an increase of the pressure in the LV (left ventricle left) at the end of the diastole. It has prognostic significance, since it usually relates to the severity of the diastolic failure or MR and can predict the risk of CHF and SATE. Decreased intraventricular size. Normal or increased systolic shortening fraction. In chronic HCM, LV contractility may decrease, the chamber can be dilated and there may be evidence of progression of the restrictive disease. SATE is observed with relative frequency and can be increased with the sympathetic tone. Its aetiology is controversial, with an initially proposed theory of the Venturi effect (or blood flow), although it is currently recognized that the presence of secondary morphological alterations due to the hypertrophy may be the main cause. It can be identified using 2B and M-mode and colour Doppler, where two turbulent flows originating in the LV outflow are observed, one regurgitating into de LA and the other into the aorta. Spectral Doppler can be used to determine the pressure gradient through the dynamic stenosis. The assessment of the LV diastolic dysfunction is important. The main functional features include the assessment of the global function, relaxation and "untwist", the elasticity of the chamber, filling volume and pressures. Filling pressures can be evaluated in a semiquantitative way using echocardiography, as well as other variable such as the transmitral flow, the LVRT (left ventricular relaxation time), pulmonary veins flow, Tissue Doppler tissue or filling pressures ratios E/E' or E/LVRT as most important values allowing us to make a classification of the LV diastolic dysfunction.4 ECG: it may be abnormal. Abnormalities of ventricular conduction (left bundle branch block, left anterior fascicular block pattern and preexcitation syndrome) can be seen. Arrhythmias are uncommon. X-rays may be normal, but may show cardiomegaly (elongation) and dilation of the left atrium in advanced cases. The assessment of lung patterns, such as prominent vascular patterns that may indicate secondary pulmonary hypertension, high LV diastolic pressure, or increased lung densities (patched interstitial and alveolar patterns) that are compatible with pulmonary oedema or signs of pleural effusion, which are rather frequent in cases of ICC, will also be useful. Blood tests, as well as the measurement of blood pressure, are used to rule out other systemic diseases that may cause phenotypical HCM. Cardiac biomarkers such as NT-ProBNP or inhibitory cardiac troponin (cTnI) have diagnostic and 5, prognostic value. NT-ProBNP is useful to differentiate patients with respiratory disease vs. heart disease 6 and as screening test for asymptomatic patients. Its increase has also been described in cardiac derived 7 pleural effusion. Troponin has more prognostic value (values > 0.7ng / ml), increasing the value proportionally to the increase of the risk of death, regardless of the presence of heart failure or left atrial 8 dilatation. Anatomical pathology Histopathology reveals: Myocyte hypertrophy. (Increased size of cells, enlarged nuclei, rectangular and hyperchromic). Some show degenerative changes such as myofibrillar lysis, sarcoplasmic vascularization, agglutination of the Z line material and abundant lipofucsin granules. Disorders of the myocardial myofibers, with groups of muscle cells that are aligned at right angles or obliquely. Interstitial fibrosis. Abnormalities in the intramyocardial small vessels, with fibromuscular dysplasia of the intramural coronary artery. 9 TREATMENT It must be taken into account that here are no extensive and controlled studies indicating benefits with the treatment in cases of asymptomatic disease, cats with recurrent episodes of CHF or for the evolution of the heart failure itself. Therefore, treatment is based on recommendations and the experience of different authors, experimental or retrospective studies in cats, or extrapolated evidences from canine or human medicine. A persistent problem in HCM is the prevention of the arterial thromboembolism. In case of asymptomatic patients with SATE with potentially negative effects, it is not clear that the reduction of the gradient has beneficial effects due to the lack of efficacy assays. However, treatment with β blockers (atenolol), calcium channel blockers (diltiazem) and sinoatrial node I f current blockers (Ivabradine)10 are proposed. In cases of acute HCF, it is important to minimize the stress, so it is advisable to give time to calm down before performing diagnostic tests. In general, we would start with a sedation (buprenorphine, butorphanol, midazolam), together with oxygen therapy and furosemide. As the IV administration can be stressful, we can use the IM route. The starting dose would be 1 - 4 mg/Kg, depending on the degree of 11 HF decompensation, and repeated every 1 or 2 hours. In the case of large amounts of pleural effusion, diuretics will not be sufficient and a thoracocentesis will usually be needed. In addition, the analysis of the fluid will be useful to confirm that the nature of it is compatible with CHF. Positive inotropes, like pimobendan, are not registered for cats, although compared with what we know in dogs, they seem to have a longer elimination time and a greater maximum blood concentration, although the therapeutic dose is still not well defined12. However, there are clinicians who prescribe them in acute CHF, especially if there is systolic dysfunction, severe pleural effusion, severe lung oedema, renal failure, 13, 14 or in refractory cases. Pimobendan has also vasodilation effects by inhibiting the action of the phosphodiesterase 3. Pimobendan (0.625-1.25 mg/cat/12 h IV or PO). Dobutamine could also be used as inotropic, although with a very strict monitoring of the blood pressure and the possibility of tachyarrhythmias, as most relevant adverse effects. Other vasodilators like nitroglycerin, have no clear therapeutic benefit. For nitroprusside, its significant hypotensive effect could limit its use. Arrhythmias can contribute to the morbidity and mortality of the HF. Studies in human medicine show that the treatment with antiarrhythmic drugs has increased the mortality of the population instead of being beneficial in many cases. For this reason, in the case of low grade arrhythmias, treatment is not recommended and we only consider it in situations where there is evidence of hemodynamic alterations. In the case of chronic CHF, diuretics can be used, like the minimum effective dose of furosemide, ideally once a day, monitoring the respiratory rate at home (Sleep Respiratory Rate SRR). 15 ACE inhibitors could also be used, based on the fact that diuretics increase the activity of the RAAS and also because they have a renoprotective effect, which could be interesting in animals that also have kidney disease. 16 (0.25 0.5 mg/Kg/12 - 24 h PO) There are authors who use β blockers such as atenolol, especially in cats with LVOTO (left ventricular outflow tract obstruction) with a gradient > 50mmHg and especially at risk of sinus tachycardia and normal left atrial function. It is recommended to start with low doses (6.25 mg / cat / 12 h PO) once the clinical congestive signs are corrected, and subsequently increased if necessary. However, there is a study which shows no benefit in cases of HCM.17 The administration of pimobendan could be recommended in combination with the rest of the conventional treatment in cases with a history of CHF characterized by systolic dysfunction and without LVOTO as determined by ultrasound. There is a study where the administration of pimobendan in HCM increased the survival time. 14 However, there are authors who reserve it as salvage therapy, in very critical situations where the treatment is not working and as the last resort. 16 Antiplatelet agents are commonly used for the prevention of thrombotic disease 18 . Clopidogrel has shown to be superior to aspirin in the FAT CAT Study, with a lower recurrence rate of SATE and also a reduced 19 rate of recurrence after one year. PROGNOSIS The prognosis can be very variable, with animals remaining asymptomatic lifelong and patients that progress to CHF, sudden death or SATE. Clinical signs of CHF, with or without the presence of SATE, the dilatation of the left atrium, senior life stage, predisposed breeds as Ragdoll or Maine Coon and gallop rhythm or arrhythmias could be considered negative prognostic factors. Negative echocardiographic prognostic values: severe hypertrophy > 9 mm, diastolic dysfunction with FS < 30%, regional hypokinesis, decreased atrial function, positive contrast or intracardiac thrombi and advanced diastolic dysfunction, with restrictive pattern. 20-22 REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. Petric AD, Rishniw M, Thomas WP. Two-dimensionally-guided M-mode and pulsed wave Doppler echocardiographic evaluation of the ventricles of apparently healthy cats. Journal of veterinary cardiology. 2012;14:423-430. Meurs KM, Norgard MM, Ederer MM, Hendrix KP, Kittleson MD. A substitution mutation in the myosin binding protein C gene in ragdoll hypertrophic cardiomyopathy. Genomics. 2007;90:261264. Casamian-Sorrosal D, Chong SK, Fonfara S, Helps C. Prevalence and demographics of the MYBPC3-mutations in ragdolls and Maine coons in the British Isles. The Journal of small animal practice. 2014;55:269-273. Schober KE, Chetboul V. Echocardiographic evaluation of left ventricular diastolic function in cats: Hemodynamic determinants and pattern recognition. Journal of veterinary cardiology. 2015;17 Suppl 1:S102-133. Fox PR, Oyama MA, Reynolds C, Rush JE, DeFrancesco TC, Keene BW, Atkins CE, Macdonald KA, Schober KE, Bonagura JD, Stepien RL, Kellihan HB, Nguyenba TP, Lehmkuhl LB, Lefbom BK, Moise NS, Hogan DF. Utility of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) to distinguish between congestive heart failure and non-cardiac causes of acute dyspnea in cats. Journal of veterinary cardiology. 2009;11 Suppl 1:S51-61. Connolly DJ, Magalhaes RJ, Syme HM, Boswood A, Fuentes VL, Chu L, Metcalf M. Circulating natriuretic peptides in cats with heart disease. Journal of veterinary internal medicine. 2008;22:96-105. Humm K, Hezzell M, Sargent J, Connolly DJ, Boswood A. Differentiating between feline pleural effusions of cardiac and non-cardiac origin using pleural fluid NT-proBNP concentrations. The Journal of small animal practice. 2013;54:656-661. Langhorn R, Tarnow I, Willesen JL, Kjelgaard-Hansen M, Skovgaard IM, Koch J. Cardiac troponin I and T as prognostic markers in cats with hypertrophic cardiomyopathy. Journal of veterinary internal medicine. 2014;28:1485-1491. Marz I, Wilkie LJ, Harrington N, Payne JR, Muzzi RA, Haggstrom J, Smith K, Luis Fuentes V. Familial cardiomyopathy in Norwegian Forest cats. Journal of feline medicine and surgery. 2015;17:681-691. Riesen SC, Schober KE, Cervenec RM, Bonagura JD. Effects of treatment with ivabradine and atenolol on reproducibility of echocardiographic indices of left heart size and function in healthy cats. Journal of veterinary cardiology. 2012;14:323-332. Ferasin L, DeFrancesco T. Management of acute heart failure in cats. Journal of veterinary cardiology. 2015;17 Suppl 1:S173-189. Hanzlicek AS, Gehring R, Kukanich B, Kukanich KS, Borgarelli M, Smee N, Olson EE, Margiocco M. Pharmacokinetics of oral pimobendan in healthy cats. Journal of veterinary cardiology. 2012;14:489-496. Gordon SG, Saunders AB, Roland RM, Winter RL, Drourr L, Achen SE, Hariu CD, Fries RC, Boggess MM, Miller MW. Effect of oral administration of pimobendan in cats with heart failure. Journal of the American Veterinary Medical Association. 2012;241:89-94. 14. 15. 16. 17. 18. 19. 20. 21. 22. Reina-Doreste Y, Stern JA, Keene BW, Tou SP, Atkins CE, DeFrancesco TC, Ames MK, Hodge TE, Meurs KM. Case-control study of the effects of pimobendan on survival time in cats with hypertrophic cardiomyopathy and congestive heart failure. Journal of the American Veterinary Medical Association. 2014;245:534-539. Ljungvall I, Rishniw M, Porciello F, Haggstrom J, Ohad D. Sleeping and resting respiratory rates in healthy adult cats and cats with subclinical heart disease. Journal of feline medicine and surgery. 2014;16:281-290. Gordon SG, Cote E. Pharmacotherapy of feline cardiomyopathy: Chronic management of heart failure. Journal of veterinary cardiology. 2015;17 Suppl 1:S159-172. Schober KE, Zientek J, Li X, Fuentes VL, Bonagura JD. Effect of treatment with atenolol on 5year survival in cats with preclinical (asymptomatic) hypertrophic cardiomyopathy. Journal of veterinary cardiology. 2013;15:93-104. Tablin F, Schumacher T, Pombo M, Marion CT, Huang K, Norris JW, Jandrey KE, Kittleson MD. Platelet activation in cats with hypertrophic cardiomyopathy. Journal of veterinary internal medicine. 2014;28:411-418. Hogan DF, Fox PR, Jacob K, Keene B, Laste NJ, Rosenthal S, Sederquist K, Weng HY. Secondary prevention of cardiogenic arterial thromboembolism in the cat: The double-blind, randomized, positive-controlled feline arterial thromboembolism; clopidogrel vs. aspirin trial (FAT CAT). Journal of veterinary cardiology. 2015;17 Suppl 1:S306-317. Payne J, Luis Fuentes V, Boswood A, Connolly D, Koffas H, Brodbelt D. Population characteristics and survival in 127 referred cats with hypertrophic cardiomyopathy (1997 to 2005). The Journal of small animal practice. 2010;51:540-547. Payne JR, Borgeat K, Connolly DJ, Boswood A, Dennis S, Wagner T, Menaut P, Maerz I, Evans D, Simons VE, Brodbelt DC, Luis Fuentes V. Prognostic indicators in cats with hypertrophic cardiomyopathy. Journal of veterinary internal medicine. 2013;27:1427-1436. Spalla I, Locatelli C, Riscazzi G, Santagostino S, Cremaschi E, Brambilla P. Survival in cats with primary and secondary cardiomyopathies. Journal of feline medicine and surgery. 2015.