Hypertrophic cardiomyopathy is the most common heart disease of cats, and for decades it has been defined by the left ventricle: a thickened muscular wall, measured in millimetres, that gives the condition its name. A new narrative review published in Frontiers in Veterinary Science argues that this ventricle-anchored view is systematically late to the disease it is meant to detect. The authors, Sumade Kongchatree and Jatuporn Rattanasrisomporn of Kasetsart University in Thailand, contend that the clinical events which actually determine how long and how well an affected cat lives are atrial in their proximate pathophysiology, and that diagnostic frameworks, prognostic models and even the regulatory endpoint behind a newly approved drug remain anchored on the wrong chamber.
The argument rests on a striking longitudinal finding. In the CatScan II cohort, 107 cats from rehoming centres were followed for a median of 5.6 years, during which 19 developed hypertrophic cardiomyopathy. The independent predictor of that outcome on multivariable Cox proportional hazards analysis was not any measure of the left ventricle but a lower left atrial fractional shortening at baseline. Cats whose baseline value was at or below 25 per cent were more likely to develop the disease phenotype, while those whose value exceeded 25 per cent were reported to be 91 per cent less likely to do so. Crucially, many of these cats had ventricular walls that were normal or equivocal at study entry, meaning atrial dysfunction was detectable before the wall-thickness criterion registered anything abnormal. The authors caution that the estimate rests on only 19 events and that the hazard ratios were presented graphically rather than tabulated, but the temporal pattern is difficult to dismiss.
A parallel signal exists in humans. Sarcomere mutation carriers who have not yet developed left ventricular hypertrophy show measurable abnormalities of left atrial structure and function on cardiac magnetic resonance imaging. The two study designs differ in important ways: the human carriers were genotype-positive and phenotype-negative, whereas the CatScan II cats were phenotypically equivocal and not genotyped. Still, in two species, with different methods and observers, atrial dysfunction preceded ventricular hypertrophy. Whether this reflects truly upstream atrial pathology or a disease process that the wall-thickness criterion simply has not yet caught remains unresolved. On either reading, the review argues, a framework anchored to wall thickness arrives late.
The scale of the problem is considerable. Hypertrophic cardiomyopathy affects an estimated 14.7 per cent of apparently healthy cats screened in rehoming centres, with a case definition of left ventricular wall thickness of 6 millimetres or more and hypertensive and hyperthyroid cats excluded. Yet the events that matter clinically are atrial: congestive heart failure arises from elevated left atrial pressure transmitted to the pulmonary venous bed, and arterial thromboembolism arises from blood stasis in a remodelled, dysfunctional left atrial appendage. Left atrial size and function are retained as independent predictors of survival in multivariable models, and severe left atrial enlargement remains the strongest single echocardiographic predictor of imminent heart failure and thromboembolism.
The thromboembolic endpoint is particularly grim. In the largest international longitudinal cohort of preclinical cats with hypertrophic cardiomyopathy, arterial thromboembolism occurred in 11.6 per cent of cats over the observed study period, with a Kaplan–Meier estimated risk of 11.3 per cent at 10 years after diagnosis. That figure derives from preclinical disease; risk rises once congestive heart failure or marked atrial enlargement is established. Clinical cohorts document high mortality, frequent euthanasia at presentation and substantial disability and recurrence among survivors. The thrombus typically forms in the left atrial appendage, where stagnant flow, endocardial dysfunction and hypercoagulability complete Virchow’s triad. Notably, laboratory criteria of hypercoagulability were found in 50 per cent of cats with left atrial enlargement plus spontaneous echo contrast or thrombus, and in 56 per cent of cats with thromboembolism, but in none of the cats with left atrial enlargement alone.
Modern echocardiography offers a layered toolkit for reading the atrium. Beyond the traditional left atrium-to-aortic root ratio, clinicians can measure atrial ejection fraction and fractional area change, quantify deformation with two-dimensional speckle-tracking strain, and calculate atrial stiffness as the ratio of the E/e′ filling-pressure index to reservoir strain. In one feline study, peak atrial longitudinal strain averaged 13.16 per cent in cats with hypertrophic cardiomyopathy versus 28.54 per cent in healthy controls, and atrial stiffness was roughly sevenfold higher in affected cats. Left atrial appendage flow velocity below 0.20 metres per second proved the only independent predictor of spontaneous echo contrast, with an odds ratio of 30.1. The review stresses, however, that strain and stiffness data come from a small number of centres, that vendor-specific algorithms produce non-interchangeable values, and that independent multicentre replication remains an outstanding methodological gap.
The therapeutic stakes have sharpened with the arrival of disease-modifying therapy. The RAPACAT trial, a multicentre, placebo-controlled, double-blinded study, randomised 43 client-owned cats with subclinical, non-obstructive hypertrophic cardiomyopathy to placebo or delayed-release rapamycin at two weekly doses. At day 180, the low dose significantly slowed progression of maximum left ventricular wall thickness compared with placebo, against a prespecified exploratory alpha of 0.10; the day 60 comparison and the high-dose arm did not reach significance. On the strength of these results, the FDA granted conditional approval to Felycin-CA1 in March 2025 for management of ventricular hypertrophy in cats with subclinical disease. Conditional approval means a reasonable expectation of effectiveness has been shown while full demonstration remains pending, and the review is explicit that a single 180-day trial of 43 cats with 36 completers cannot establish efficacy; it establishes a hypothesis for the larger HALT HCM trial to test.
What the review finds most consequential is what RAPACAT did not measure. Maximum left atrial diameter was tracked as a secondary outcome, but as a unidimensional structural measurement only. Left atrial fractional shortening, ejection fraction, peak atrial longitudinal strain and atrial stiffness were not reported as primary or secondary endpoints, and no atrial functional index was assessed. Whether mTOR inhibition alters atrial remodelling, atrial fibrosis, appendage flow, or the atrial-driven outcomes of heart failure and thromboembolism is simply not addressed by the available data. The direction of any effect is genuinely uncertain: mTORC2 supports contractile function of the pressure-loaded heart in mice, raising the possibility that chronic rapamycin exposure could harm an atrium already under sustained load, while an aged-mouse model found rapamycin attenuated atrial remodelling and reduced atrial fibrillation inducibility. Neither direction has been examined in cats. The authors regard an adverse atrial effect as unproven but not excluded.
The review also emphasises that antithrombotic therapy remains the one existing treatment whose rationale is unambiguously atrial. The FAT CAT trial established clopidogrel as superior to aspirin for secondary prevention of cardiogenic thromboembolism, and the 2020 ACVIM consensus recommends clopidogrel for at-risk cats, with addition of a factor Xa inhibitor in the highest-risk or post-event cases. A cat with significant atrial enlargement, low appendage flow velocity or visible spontaneous echo contrast remains an antithrombotic candidate whether or not it is receiving rapamycin. Ventricle-aimed disease-modifying therapy, the authors warn, should not be misconstrued as reducing the cat’s atrial-driven thromboembolic risk.
Practically, the authors propose an atrial-centric consultation framework operating within the existing ACVIM staging scaffold: a minimum dataset of atrial size, an atrial functional measure and tissue Doppler, supplemented by strain, stiffness and appendage interrogation, with serial tracking of the atrial trajectory guiding surveillance intervals. They are careful to frame the more provocative suggestions, such as managing cats with normal atrial dimensions but impaired atrial function as closer to stage B2, as hypotheses for prospective testing rather than recommendations. The HALT HCM trial, sponsored by TriviumVet and currently enrolling approximately 300 cats across more than 20 United States centres over 12 months, has not publicly specified its primary endpoint or any atrial functional endpoint. The review’s limitations are acknowledged plainly: it is a narrative rather than systematic review, its therapeutic sections rest on a single exploratory trial, and its consultation framework is an unvalidated synthesis. But its central proposition is measured and evidence-based: the atrium has been part of the feline hypertrophic cardiomyopathy evidence base for decades, and it should now be at the centre of the disease rather than at its periphery.
Subject of Research: The role of left atrial structure and function in feline hypertrophic cardiomyopathy diagnosis, prognosis and emerging therapy
Article Title: Beyond the ventricle: the atrial contribution to feline hypertrophic cardiomyopathy and implications for diagnosis, prognosis, and emerging therapy
Article References: Kongchatree, S., & Rattanasrisomporn, J. (2026). Beyond the ventricle: the atrial contribution to feline hypertrophic cardiomyopathy and implications for diagnosis, prognosis, and emerging therapy. Frontiers in Veterinary Science, 13, Article 1979805. https://doi.org/10.3389/fvets.2026.1979805
Image Credits: AI Generated
DOI: 10.3389/fvets.2026.1979805
Keywords: feline hypertrophic cardiomyopathy, left atrium, cats, echocardiography, arterial thromboembolism, congestive heart failure, rapamycin, sirolimus, RAPACAT trial, atrial strain, ACVIM consensus, veterinary cardiology
News Source: William Thompson. (October 29, 2026). The Left Atrium May Hold the Key to Feline Heart Disease Outcomes. Scienmag.
