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Multicenter Study
. 2025 Feb;13(2):332-343.
doi: 10.1016/j.jchf.2024.09.008. Epub 2024 Nov 6.

The Clinical Trajectory of NYHA Functional Class I Patients With Obstructive Hypertrophic Cardiomyopathy

Monica Ahluwalia  1 , Jiankang Liu  2 , Iacopo Olivotto  3 , Victoria Parikh  4 , Euan A Ashley  4 , Michelle Michels  5 , Jodie Ingles  6 , Rachel Lampert  7 , John C Stendahl  7 , Steven D Colan  8 , Dominic Abrams  8 , Alexandre C Pereira  9 , Joseph W Rossano  10 , Thomas D Ryan  11 , Anjali T Owens  12 , James S Ware  13 , Sara Saberi  14 , Adam S Helms  14 , Sharlene Day  12 , Brian Claggett  2 , Carolyn Y Ho  2 , Neal K Lakdawala  15
Affiliations
Multicenter Study

The Clinical Trajectory of NYHA Functional Class I Patients With Obstructive Hypertrophic Cardiomyopathy

Monica Ahluwalia et al. JACC Heart Fail. 2025 Feb.

Abstract

Background: An improved understanding of the natural history in NYHA functional class I patients with obstructive hypertrophic cardiomyopathy (oHCM) is needed.

Objectives: Using a multicenter registry (SHaRe [Sarcomeric Human Cardiomyopathy Registry]), this study described the natural history in patients with oHCM who were classified as NYHA functional class I at the initial visit compared with patients classified as NYHA functional class II and reported baseline characteristics associated with incident clinical events.

Methods: Incident events assessed included a composite of NYHA functional class III to IV symptoms, left ventricular ejection fraction <50%, atrial fibrillation, stroke, ventricular arrhythmias, septal reduction therapy, ventricular assist device or transplantation, or death. Factors associated with incident events were determined using Kaplan-Meier, Cox proportional hazards, and restricted cubic spline models.

Results: Of 7,964 patients with HCM in SHaRe, 1,239 patients with oHCM met inclusion criteria; 598 were in NYHA functional class I at the initial visit (age 48 ± 17 years; 31.1% female; peak gradient, 75 ± 40 mm Hg). At 5-year follow-up, the composite event rate of NYHA functional class I patients was 28% compared with 44% (P < 0.001) in 641 NYHA functional class II patients with oHCM (age 54 ± 16 years; 46.5% female; peak gradient, 83 ± 39 mm Hg). Left atrial (LA) diameter ≥45 mm (HR: 1.56 [95% CI: 1.14-2.12]; P = 0.005), female sex (HR: 1.61 [95% CI: 1.16-2.24]; P = 0.003), and older age (HR: 1.21 per 10 years [95% CI: 1.09-1.34]; P < 0.001), but not the magnitude of left ventricular outflow tract obstruction, were associated with a higher risk of the composite outcome in NYHA functional class I patients.

Conclusions: Although NYHA functional class I patients with oHCM fared better than NYHA functional class II patients, more than one-fourth experienced adverse events over 5-year follow-up, especially if they were older, female, and/or had LA enlargement. Strategies to reduce the rate of clinical outcomes in NYHA functional class I patients warrant further study.

Keywords: atrial fibrillation; heart failure; left atrial dilation; left ventricular outflow tract obstruction; obstructive hypertrophic cardiomyopathy.

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Conflict of interest statement

Funding Support and Author Disclosures Funding for SHaRe has been provided through an unrestricted research grant from Bristol Myers Squibb. Bristol Myers Squibb had no role in approving the content of this manuscript. This work was also supported by the Sir Jules Thorn Charitable Trust [21JTA], the Medical Research Council (UK), the British Heart Foundation [RE/18/4/34215], and the National Institutes of Health R Imperial College Biomedical Research Centre. For the purpose of open access, the authors have applied a Creative Commons Attribution (CC BY) license to any Author Accepted Manuscript version arising. Dr Ahluwalia has received modest consulting income from Bristol Myers Squibb. Dr Olivotto has received research grants from Bristol Myers Squibb, Cytokinetics, Amicus, Genzyme, Shire Takeda, Menarini international, Chiesi, Boston Scientific; and has received consulting income from Bristol Myers Squibb, Cytokinetics, Amicus, Genzyme, Shire Takeda, Chiesi, Boston Scientific, Tenaya, Rocket Pharma, and Lexeo. Dr Owens has received consulting fees from Bristol Myers Squibb, Cytokinetics, Pfizer, Edgewise, Stealth, Lexeo, Lexicon, Tenaya, and BioMarin; and has received research funds from Bristol Myers Squibb. Dr Ware has received research support from Bristol Myers Squibb; and has acted as a consultant for MyoKardia, Pfizer, Foresite Labs, Health Lumen, and Tenaya Therapeutics. Dr Ho has received consulting fees and unrestricted research funding from Bristol Myers Squibb (MyoKardia), Pfizer, Cytokinetics, BioMarin, Tenaya, Lexicon, and Viz.ai. Dr Lakdawala has received consulting income from Bristol Myers Squibb, Pfizer, Cytokinetics, Tenaya, and Akros; and has received research support from Bristol Myers Squibb and Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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