JHLT open · 2025
Living myocardial slices retain patient-specific features: Insights into etiology and therapeutic history.
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van der Geest Jort S A, van Ham Willem B, Benavente Ernest Diez, El Amrani Mohsin, Mokhles M Mostafa, Oerlemans Marish I F J, Doevendans Pieter A, de Boer Teun P, Sluijter Joost P G, van Laake Linda W, Sampaio-Pinto Vasco
Аннотация
BACKGROUND: Living myocardial slices (LMS) are an emerging translational ex vivo model for studying myocardial function, disease mechanisms, and therapeutics. However, the extent to which ex vivo findings correlate with clinical characteristics is unknown. This study aimed to evaluate whether LMS retain patient-specific functional and pathological characteristics, reflecting diverse etiologies, pharmacological regimens, and clinical interventions.
METHODS: 300-µm-thick LMS were prepared from myocardial biopsies of end-stage heart failure patients (N = 12, n = 138). Functional assessment of freshly prepared LMS included refractory period, stimulation threshold, force-frequency relationship, post pause potentiation, contractile force, alongside simultaneous optical recordings of calcium transients and action potentials. Variability and grouping analyses were conducted to identify features linked to patient-specific parameters, such as etiology and therapeutic history, including prior left ventricular assist device (LVAD) implantation and amiodarone usage.
RESULTS: LMS exhibited lower intrapatient variability (LMS from the same patient) compared to interpatient variability (LMS from different patients), confirming their ability to retain patient-specific functional properties. LMS from LVAD-treated patients exhibited reduced intrapatient variability and reduced diastolic tension, correlated with lower N-terminal pro-B-type natriuretic peptide levels. Stratification by etiology revealed distinct functional characteristics, including enhanced contractile force in titin-mutant LMS and a positive force-frequency relationship in ischemic cardiomyopathy-derived LMS. LMS derived from amiodarone-treated patients demonstrated prolonged action potential duration, reduced excitability at higher pacing frequencies, and enhanced post pause potentiation, reflecting the drug's established pharmacological effects.
CONCLUSIONS: LMS effectively capture distinct functional parameters associated with patient-specific features. These findings establish LMS as a valuable translational platform for personalized cardiac research, therapeutic testing, and precision medicine.
METHODS: 300-µm-thick LMS were prepared from myocardial biopsies of end-stage heart failure patients (N = 12, n = 138). Functional assessment of freshly prepared LMS included refractory period, stimulation threshold, force-frequency relationship, post pause potentiation, contractile force, alongside simultaneous optical recordings of calcium transients and action potentials. Variability and grouping analyses were conducted to identify features linked to patient-specific parameters, such as etiology and therapeutic history, including prior left ventricular assist device (LVAD) implantation and amiodarone usage.
RESULTS: LMS exhibited lower intrapatient variability (LMS from the same patient) compared to interpatient variability (LMS from different patients), confirming their ability to retain patient-specific functional properties. LMS from LVAD-treated patients exhibited reduced intrapatient variability and reduced diastolic tension, correlated with lower N-terminal pro-B-type natriuretic peptide levels. Stratification by etiology revealed distinct functional characteristics, including enhanced contractile force in titin-mutant LMS and a positive force-frequency relationship in ischemic cardiomyopathy-derived LMS. LMS derived from amiodarone-treated patients demonstrated prolonged action potential duration, reduced excitability at higher pacing frequencies, and enhanced post pause potentiation, reflecting the drug's established pharmacological effects.
CONCLUSIONS: LMS effectively capture distinct functional parameters associated with patient-specific features. These findings establish LMS as a valuable translational platform for personalized cardiac research, therapeutic testing, and precision medicine.