The impact of left ventricular ejection time (LVET) in patients with hypertrophic cardiomyopathy with different sarcomeric mutations

Isabell Yan (Hamburg)1, Z. Möhring (Hamburg)1, J. Münch (Hamburg)1, R. Woitschach (Hamburg)2, L. Carrier (Hamburg)3, P. Kirchhof (Hamburg)1, T. Eschenhagen (Hamburg)3, M. Patten (Hamburg)1

1Universitäres Herz- und Gefäßzentrum Hamburg Klinik für Kardiologie Hamburg, Deutschland; 2Universitätsklinikum Hamburg-Eppendorf Hamburg, Deutschland; 3Universitätsklinikum Hamburg-Eppendorf Institut für Klinische Pharmakologie und Toxikologie Hamburg, Deutschland



Hypertrophic cardiomyopathy (HCM) is considered a monogenic disease, typically caused by mutations in sarcomeric genes in MYBPC3 or MYH7. These mutations commonly cause left ventricular hypercontractility, linked to a higher actin-myosin crossbridge cycling rate. Cardiac myosin inhibitors can reverse the increase in cycling rate and are currently entering clinical practice. In addition to peak force, reflected by left ventricular ejection fraction (LVEF), left ventricular ejection time (LVET) is an important echocardiographic marker of contractile function, that is not yet included in routine diagnostic testing. A lack of MYBPC3 in mice leads to reduced LVET, raising the hypothesis that LVET in HCM may be a specific alteration in MYBPC3-related HCM. We tested this hypothesis by a retrospective echocardiographic analysis in a cohort of genotype-defined HCM patients.


Methods and Results

LVET was analysed in transthoracic echocardiography of 77 HCM patients diagnosed with a genetically confirmed mutation (46 MYBPC3 and 31 MYH7) and 44 healthy controls. LVET was corrected for heart rate, resulting in the LVET Index (LVETI). Patients with MYBPC3 mutations had significantly shorter LVETI than controls and especially compared to the MYH7 carriers (Figure). Other echocardiographic parameters, such as LVEF, septal wall thickness (IVS), left ventricular outflow tract (LVOT) gradient and cardiac markers, such as NT-proBNP, were not significantly different between the mutation groups (Table).



These hypothesis-generating data provide the first evidence that MYBPC3, but not MYH7 mutations lead to reduced LVET in humans, indicating a specific deficit in the late contraction/early relaxation phase. The data need confirmation in a larger cohort, but indicate that genotyping in HCM may have an impact on therapeutic approaches affecting contractility.

Figure Left ventricular ejection time index (LVETI) in control and different sarcomeric mutation groups. LVETI mean (SD) are shown below the figure. *p<0.05, ***p<0.001







(n = 44)

(n = 46)


(n = 31)

Age, years, mean (SD)

43 (12)

51 (17)


45 (16)

Female sex, n (%)

22 (50)

22 (47.8)


19 (61,3)

LVEF, %, mean (SD)

62 (4)

56 (7)


56 (7)

LVS, mm, mean (SD)

10 (1) 

20.7 (7)


21 (6)

LVOT gradient max, mm Hg, mean (SD)


15.6 (19.6)


20.3 (23.4)

NT-proBNP, ng/L, mean (SD)

44 (14.1)

1382 (327.7)


1030 (225)

Table Baseline characteristics. Values were shown as total number =n (%) or mean (SD).

Diese Seite teilen