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Non-invasive evaluation of left ventricular hemodynamic force abnormalities in hypertrophic cardiomyopathy:
Chiara Zocchi1, Alessandra Milazzo2, Giorgia Panichella3
1Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy.
Insights
Hypertrophic cardiomyopathy (HCM) impairs heart mechanics. Mavacamten therapy improves left ventricular hemodynamic forces (HDF) in obstructive HCM, suggesting better mechanical coordination and reduced obstruction.
Area of Science:
- Cardiology
- Biomedical Engineering
- Translational Medicine
Background:
- Hypertrophic cardiomyopathy (HCM) involves abnormal myocardial mechanics, potentially with left ventricular outflow tract obstruction (LVOTO).
- Mavacamten, a myosin inhibitor, shows efficacy in reducing LVOTO.
- The impact of mavacamten on left ventricular hemodynamic forces (HDF), a novel marker of myocardial function, remains undefined.
Purpose of the Study:
- Characterize left ventricular HDF patterns in obstructive HCM (oHCM), non-obstructive HCM (noHCM), and healthy controls.
- Evaluate the long-term effects of mavacamten therapy on HDF in oHCM patients.
Main Methods:
- Retrospective analysis of 40 HCM patients (20 oHCM, 20 noHCM) and 20 healthy controls.
- Quantification of HDF parameters using echocardiographic strain imaging software.
- Assessment of six oHCM patients on mavacamten at baseline and after three years of therapy.
Main Results:
- HCM patients exhibited reduced systolic time to peak and diastolic-systolic transition time compared to controls.
- Diastolic force amplitude was significantly lower in oHCM versus noHCM.
- Mavacamten treatment prolonged diastolic-systolic transition and restored longitudinal force dynamics in oHCM patients.
Conclusions:
- HDF analysis reveals distinct mechanical impairments in HCM, irrespective of obstruction.
- Mavacamten favorably modulates HDF, delaying systolic thrust and normalizing force distribution.
- These findings provide mechanistic insights into mavacamten's therapeutic action in HCM.
Background:
Hypertrophic cardiomyopathy (HCM) is characterized by abnormal myocardial mechanics, with or without left ventricular outflow tract obstruction (LVOTO). Myosin inhibitors such as mavacamten have shown clinical efficacy in reducing obstruction, but their effects on left ventricular hemodynamic forces (HDF)-a novel marker of myocardial function-are not yet defined. This study aimed to characterize left ventricular HDF patterns in patients with obstructive (oHCM) and non-obstructive (noHCM) HCM compared to healthy controls, and to evaluate the impact of long-term mavacamten therapy on HDF parameters in oHCM.
Methods:
We retrospectively analyzed 40 HCM patients (20 oHCM, 20 noHCM) and 20 age- and sex-matched healthy controls. HDF parameters were quantified using echocardiographic strain imaging software (Qstrain, Medis Medical Imaging Systems). Parameters included systolic and diastolic force amplitudes and time indices. Six oHCM patients receiving mavacamten were assessed at baseline and after three years of therapy.
Results:
Compared to controls, HCM patients had significantly reduced systolic time to peak (p < 0.001) and diastolic-systolic transition time (p < 0.001), indicating premature systolic thrust and impaired relaxation. Diastolic force amplitude was significantly lower in oHCM than noHCM (p < 0.001). Mavacamten treatment in oHCM patients significantly prolonged diastolic-systolic transition (p = 0.030) and restored longitudinal force dynamics (p = 0.031), suggesting improved mechanical coordination and reduced LVOTO.
Conclusions:
HDF analysis identifies distinct mechanical impairments in HCM regardless of obstruction status. Mavacamten favorably modulates HDF, delaying systolic thrust initiation and normalizing force distribution, offering new mechanistic insights into its therapeutic action in HCM.
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