Sex‐Related Differences in Genetic Cardiomyopathies

Figures

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  Figure 1. Clinical characteristics of pathogenic variants in women compared with men with dilated cardiomyopathy. AF indicates atrial fibrillation; CV, cardiovascular; DCM, dilated cardiomyopathy; DMD, dystrophin; DSP, desmoplakin; FLNC, filamin C; LMNA, lamin A/C; MYH7, myosin heavy chain 7; TNNC1, troponin C1; TNNT2, troponin T2; TPM1, tropomyosin alpha‐1 chain; TTNtv, titin truncating variants; and VA, ventricular arrhythmia.

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  Figure 2. Women are older than men at the time of hypertrophic cardiomyopathy (HCM) diagnosis and were more likely to have a sarcomere mutation. Left: Age at HCM diagnosis for all women (shaded pink) and men (shaded blue), irrespective of sarcomere variant status. Where age of diagnosis overlaps, the frequency of female patients is represented by the darker color. Mean age of diagnosis labeled and indicated by line. Right: Frequency of pathogenic/likely‐pathogenic sarcomere variants in patients who had undergone genetic testing, excluding patients with multiple variants. 10 MYBPC3 indicates myosin‐binding protein C; MYH7, beta‐myosin heavy chain; and MYL2&3, myosin regulatory light chains 2 and 3.

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  Figure 3. Women show lower left ventricular (LV) mass and dimensions indexed to BSA compared with men. As a consequence, a relatively greater degree of hypertrophy is needed in women to reach the diagnostic criteria for hypertrophic cardiomyopathy (HCM); this might contribute to a delay in diagnosis and treatment. Reproduced with permission from van Driel et al. 74 ©2019 Wolters Kluwer Health, Inc.

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  Figure 4. Channels and pumps as targets of 17β‐estradiol in human cardiomyocytes. The rapidly activating component of the delayed rectifier K+ current (IKr), coded by KCNH2, is modulated by sex hormones. A greater expression of L‐type cardiac calcium channel, sodium‐calcium exchanger NCX1 and a slower decay of the calcium transient have been detected in women compared with men. A higher frequency of calcium sparks and sarcoplasmic reticulum leakage has been described in men compared with women. Increased levels of detyrosinated microtubules may contribute to the worse diastolic function in women with hypertrophic cardiomyopathy. HCMSMP indicates hypertrophic cardiomyopathy sarcomere mutation‐positive.

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  Figure 5. Sex‐related differences in cardiomyopathies. “Sex” refers to the biological differences between men and women. AL indicates light chain amyloidosis; CMP, cardiomyopathy, and DCM, dilated cardiomyopathy.