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Force-frequency relation in patients with left ventricular hypertrophy and failure
1Division of Cardiology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
Insights
Patients with ventricular hypertrophy and heart failure experience reduced systolic function as heart rate increases. This dysfunction, linked to excitation-contraction coupling, limits cardiovascular reserve and causes exertional intolerance.
Area of Science:
- Cardiology
- Physiology
Background:
- Ventricular hypertrophy (LVH) is associated with impaired cardiac function and congestive heart failure symptoms.
- Patients with LVH often experience limited cardiovascular reserve and exertional intolerance.
Purpose of the Study:
- To investigate the impact of increasing heart rate on systolic function in patients with LVH and heart failure.
- To explore the underlying mechanisms of impaired cardiac force-frequency response in LVH.
Main Methods:
- Assessed systolic contractile enhancement with increasing heart rate.
- Evaluated diastolic function, post-rest potentiation, recirculation fraction, and mechanical restitution.
- Examined ventriculo-vascular coupling efficiency in LVH hearts.
Main Results:
- Demonstrated a loss of systolic contractile enhancement with increased heart rate in LVH patients.
- Observed no worsening of diastolic function, suggesting mechanisms beyond ischemia.
- Identified abnormalities in excitation-contraction coupling and impaired ventriculo-vascular coupling.
Conclusions:
- Dysfunctional cardiac force-frequency behavior contributes to limited cardiovascular reserve in LVH.
- Abnormalities in excitation-contraction coupling, not SR Ca2+ release, are implicated.
- Enhancing the force-frequency response may improve exercise capacity in LVH patients.
Abstract:
Our study demonstrated a loss of normal systolic contractile enhancement with increasing heart rate in patients with ventricular hypertrophy and symptoms of congestive heart failure. This decline in systolic reserve was not accompanied by worsening of diastolic function, and would therefore not seem to reflect underlying ischemia. Rather, it was more likely related to abnormalities of excitation-contraction coupling, particularly in light of findings of both increased post-rest potentiation and a reduced recirculation fraction. In contrast, mechanical restitution was unchanged, suggesting that alterations in Ca2+ release from the SR did not play a major role. Finally, we showed that increasing heart rate adversely affects the efficiency of ventriculo-vascular coupling in LVH hearts. This suggested another explanation of how dysfunction of cardiac force-frequency behavior can lead to limited cardiovascular reserve and contribute to clinical symptoms of exertional intolerance. Future efforts aimed at enhancing the force-frequency response, perhaps by enhancing the SR-ATPase, or manipulating its regulation, should prove helpful in ameliorating the limitations of LVH patients associated with rapid heart rate.