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Final Program


Program-At-A-Glance

Rapid Fire Session

Session: Rapid Fire Session 3: Tissue Characterization (Monitor 7)

4D Modelling of Sex-Specific Phenotypes in HCM and Future Clinical Outcomes

Friday, February 6, 2026
10:36 AM - 10:43 AM  
Location: Galapagos / Aruba / Ilhabela (2nd Lower Level)

    Presenting Author(s)

  • KA

    Kate Aspinall, BSc

    Undergraduate student
    Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary
    Calgary, Alberta, Canada

    • Primary Author(s)

  • KA

    Kate Aspinall, BSc

    Undergraduate student
    Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary
    Calgary, Alberta, Canada

    • Co-Author(s)

  • RM

    Rylan Marianchuk, BSc

    Masters Student
    University of Calgary
    Calgary, Alberta, Canada

  • Justin J. Tse, PhD, MSc, BSc

    Research Associate
    University of Calgary
    Calgary, Alberta, Canada

  • Sahar Sajjad, BSc

    Graduate Student
    Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary
    Calgary, Alberta, Canada

  • CJ

    Cory R. Jensen, BSc

    Cardiac Machine Learning Developer
    Libin Cardiovascular Institute, University of Calgary, Canada

  • SD

    Steven Dykstra, MSc, BEng

    PhD Candidate
    University of Calgary
    Calgary, Alberta, Canada

  • TB

    Talia A. Beckie, BEng

    Cardiac Imaging Systems Engineer
    Libin cardiovascular Institute, University of Calgary
    Calgary, Alberta, Canada

  • FH

    Fereshteh Hasanzadeh, MSc

    Masters Student
    University of Calgary
    calgary, Alberta, Canada

  • SR

    Sandra Rivest, RN

    Research Coordinator
    Libin Cardiovascular Institute; University of Calgary
    Calgary, Alberta, Canada

  • JF

    Jacqueline Flewitt, MSc

    Manager of Strategic Partnerships
    Libin Cardiovascular Institute; University of Calgary
    Calgary, Alberta, Canada

  • SC

    Stephanie Corriveau, PhD

    Ad Clinical trial lead & Senior Scientific Advisor - CV
    Bristol Myers Squibb
    Montreal, Quebec, Canada

  • YF

    Yuanchao Feng, PhD

    Senior AHS analyst
    Libin Cardiovascular Institute; University of Calgary
    Calgary, Alberta, Canada

  • JN

    Julian B. Neves, MSc

    Junior Data Engineer
    Libin Cardiovascular Institute, University of Calgary, Canada

  • MM

    Michael McDonald, MD

    Associate Professor
    University of Toronto, Canada

  • MK

    Melanie King, PhD

    Director, Program Development and Implementation
    Libin Cardiovascular Institute, University of Calgary, Canada

  • OK

    Omid Kiamanesh, MD

    Cardiologst
    Libin Cardiovascular Institute, University of Calgary, Canada

  • GP

    Grant Peters, MD

    Clinical Assistant Professor
    Libin Cardiovascular Institute, University of Calgary
    Calgary, Alberta, Canada

  • MW

    Meredith Wright, PhD

    Member of the MYCOVACC Study Team / Senior Project Advisor
    Canadian Cardiovascular Society, Canada

  • CL

    Carmen P. P. Lydell, MD

    Clinical Assistant Professor
    Libin Cardiovascular Institute of Alberta, University of Calgary
    Calgary, Alberta, Canada

  • MB

    Michael Bristow, MD

    Clinical Associate Professor
    University of Calgary, Alberta, Canada

  • MG

    Marco J.W Götte, MD, PhD

    MD, PhD
    Stephenson Cardiac Imaging Centre
    Calgary, Alberta, Canada

  • RM

    Robert J.H. Miller, MD

    Clinical Assistant Professor
    Libin Cardiovascular Institute; University of Calgary
    Calgary, Alberta, Canada

  • LK

    Louis Kolman, MD

    Clinical Assistant Professor
    Libin Cardiovascular Institute; University of Calgary
    Calgary, Alberta, Canada

  • James A. White, MD

    Professor
    Libin Cardiovascular Institute; University of Calgary
    Calgary, Alberta, Canada

  • Dina Labib, MD, PhD, FSCMR

    Associate Scientific Director, Personalized Diagnostics Program; Adjunct Assistant Professor
    University of Calgary
    Calgary, Alberta, Canada

Background: Women with hypertrophic cardiomyopathy (HCM) experience elevated risk of major adverse cardiovascular events (MACE) versus males despite lower perceived disease severity. This may reflect the limitations of non-sex-specific definitions of wall thickness. We investigated an automated, deep-learning-based phenomics tool, 4Deep, for the characterization of phenotypes using sex-specific, z-score normalization. We investigated whether this technique identifies sex-specific phenotypes, and if observed differences explain differences in event-free survival.

Methods: A total of 551 patients with HCM were identified from the Cardiovascular Imaging Registry of Calgary (CIROC). All underwent CMR with routine 2D cine and late gadolinium enhancement (LGE) imaging. 4Deep analysis was batch run (no user interaction) on routine 2D cine images to deliver a bi-layer 4D mesh model of the left ventricle (LV) with 480 spatially registered elements upon which maximal wall thickness, 3D mass, and 3D principal strain markers were calculated. Elements belonging to each AHA segment were used to calculate maximal or mean values, these normalized to sex-specific reference values (103 healthy volunteers). Patients were followed for a composite MACE outcome of all-cause mortality, heart failure hospitalization, new onset atrial fibrillation, or sustained ventricular arrhythmia. A multivariable Cox model was used to study associations of sex-specific and 4Deep LV mass and future MACE.

Results: Baseline characteristics are shown in Table 1 (median age 59.0; 31% females). Despite lower indexed LV mass (67.0 vs 80.4 g/m2, p< 0.001), females had significantly greater 4Deep-derived max wall thickness (5.5 vs 4.4; p < 0.001) and BSA-indexed LV mass (4.8 vs. 3.2; p < 0.001). Geographic increases in sex-normalized mass were seen for all AHA segments with the exception of non-septal apical segments (Figure 1). Females showed a greater degree of hypercontractility by z-scored normalized 3D maximum principal strain (93.6 vs 82.7%, p=0.006). Over a median follow-up of 5.4 years, 78 patients (14%) experienced the primary outcome (19% females vs 12% males, p=0.044). Kaplan-Meier curves are shown in Figure 2. A multivariable Cox model demonstrated BSA-indexed 4Deep indexed LV mass to remain an independent predictor of MACE (aHR 1.69 per 1g/m2, p=0.038), following adjustment for age, sex, diabetes, BSA-indexed LA volume, and LGE percent burden (Figure 2). Female sex remained an independent predictor of MACE in this model.

Conclusion: Automated 4Deep phenomics identified evidence of sex-specific phenotypic expression in patients with HCM, showing a disproportionately greater severity of hypertrophy and hypercontractility in females. Ongoing and expanded investigation into contributive factors surrounding worse clinical outcomes in this patient group is required.

Table 1. Patient Clinical Characteristics, CMR Imaging Characteristics and Z-Score Metrics
     
 CLINICAL CHARACTERISTICS BY SEX    
 Clinical CharacteristicOverallN = 551MaleN = 379 (69%)FemaleN = 172 (31%) p - value
 Age, yrs 59.0 (47.0, 68.0)  57.0 (45.0, 66.0)  63.0 (50.0, 72.0)  < 0.001 
 EQ5D Health Score 80.0 (70.0, 90.0)  80.0 (70.0, 90.0)  75.0 (60.0, 87.5)  0.026 
 NYHA Class, n (%)    0.001 
    Class I 413 (76%)  302 (80%)  111 (67%)  
    Class II 128 (24%)  74 (20%)  54 (33%)  
 Hypertension, n (%) 263 (48%)  184 (49%)  79 (46%)  0.57
 Diabetes, n (%) 123 (22%)  88 (23%)  35 (20%)  0.45
 HCM Subtype, n (%)    0.43
    Septal 363 (66%)  246 (65%)  117 (68%)  
    Apical 137 (25%)  100 (26%)  37 (22%)  
    Mixed 51 (9%)  33 (9%)  18 (10%)  
 Composite Outcome, n (%) 78 (14%)  46 (12%)  32 (19%) 0.044
     
 NON-Z-SCORE CMR IMAGING CHARACTERISTICS    
 Imaging Metric Overall N = 551 Male N = 379 (69%) Female N = 172 (31%) p - value
 LVEDV index (mL/m2) 74.4 (64.2, 84.9)  76.7 (66.2, 86.4)  69.0 (59.7, 78.8)  < 0.001 
 LVESV index (mL/m2) 25.2 (20.2, 30.3)  26.0 (22.2, 30.8)  21.9 (17.3, 27.9)  < 0.001 
 LVEF (%) 65.9 (61.0, 70.9)  65.6 (61.0, 70.2)  67.3 (61.0, 73.7)  0.031
 LV mass index (g/m2) 76.5 (65.0, 91.7)  80.4 (68.2, 94.7)  67.0 (55.5, 83.2)  < 0.001 
 LA volume index (mL/m2) 44.2 (35.0, 53.9)  44.0 (35.0, 53.9)  44.2 (35.3, 54.1)  0.89
 LGE fibrosis/ scar burden (%) 5.9 (1.5, 11.8)  5.9 (2.9, 13.2)  4.4 (1.5, 10.3)  0.020
 LGE midwall patchy 408 (74%)  283 (75%)  125 (73%)  0.49 
 4Deep max. wall thickness, mm 20.7 (17.8, 24.3)  20.8 (17.8, 24.3)  20.2 (17.6, 24.0)  0.31
 4Deep LV mass index (g/m2) 79.6 (67.2, 96.2)  81.7 (70.5, 100.4)  73.2 (59.8, 89.4)  < 0.001 
 4Deep max. principal strain (%) 85.9 (65.5, 113.1)  82.7 (65.2, 106.5)  93.6 (68.1, 122.9)  0.006
 4Deep min. principal strain (%) -23.2 (-25.7, -20.8) -22.5 (-24.8, -20.1)  -24.7 (-27.1, -22.2) < 0.001 
     
 Z-SCORE CMR IMAGING CHARACTERISTICS    
 Z-Score Metric  Overall N = 551 Male N = 379 (69%) Female N = 172 (31%) p - value
 LVEDV index (mL/m2) 74.4 (64.2, 84.9)  76.7 (66.2, 86.4)  69.0 (59.7, 78.8)  < 0.001 
 LVESV index (mL/m2) 25.2 (20.2, 30.3)  26.0 (22.2, 30.8)  21.9 (17.3, 27.9)  < 0.001 
 LVEF (%) 65.9 (61.0, 70.9)  65.6 (61.0, 70.2)  67.3 (61.0, 73.7)  0.031
 LA volume index (z-score) 0.7 (-0.3, 1.9)  0.6 (-0.3, 1.6)  1.1 (-0.1, 2.5)  0.005
 LV mass index (z-score) 2.3 (1.2, 4.1)  2.0 (0.9, 3.2)  3.9 (2.2, 6.4)  < 0.001 
 4Deep max. wall thickness (z-score) 4.7 (3.2, 6.6)  4.3 (2.7, 6.1)  5.5 (4.1, 7.8)  < 0.001 
 4Deep LV mass index (z-score) 3.6 (2.1, 6.1)  3.2 (1.8, 5.5)  4.8 (2.7, 7.4)  < 0.001 
 4Deep max. principal strain (z-score) 0.6 (-0.3, 1.9)  0.4 (-0.3, 1.4)  1.4 (-0.1, 3.1)  < 0.001 
 4Deep min. principal strain (z-score) -0.3 (-0.9, 0.4)  -0.3 (-0.9, 0.4)  -0.3 (-0.9, 0.3)  0.95
     
 Data are presented as median (Q1, Q3)     
Figure 1. Bull’s eyeplots of the AHA segmental distribution of z-score based LV mass indexed to BSA in males and females. Asterisks denote a significant difference between both sexes (p < 0.05)
Figure 2. Univariable (panel A) and multivariable (panel B) associations of female sex with the composite outcome