Acute afterload relief with TAVI reveals preserved dynamic systolic and lusitropic reserve in severe aortic stenosis, demonstrating that impaired frequency-dependent myocardial reserve in pressure-overload remodeling is functionally reversible and tightly linked to loading conditions.
Key Findings
Results
Before TAVI, incremental atrial pacing produced only a modest increase in systolic contractility (dP/dtmax) without improvement in relaxation parameters.
Pacing from 80 to 100 beats/min produced a delta increase in dP/dtmax of only +150 mmHg/s (P = 0.004)
No improvement was observed in dP/dtmin (P = 0.329) or the relaxation constant τ (P = 0.182) with pacing before TAVI
This blunted response occurred despite preserved left ventricular ejection fraction (LVEF)
Study involved 46 patients with severe normal-flow, high-gradient AS who completed the pacing protocol
Results
Immediately after TAVI, incremental atrial pacing produced significant improvements in both systolic and diastolic (lusitropic) reserve indices.
Lusitropic reserve emerged post-TAVI: dP/dtmin improved (delta +56 mmHg/s; P = 0.050) and τ improved (P = 0.033)
LVEDP was reduced with pacing after TAVI (P = 0.017), indicating improved diastolic filling pressures
Correlation analyses supported the emergence of physiological force-frequency relationships (FFR) and relaxation-frequency relationships (RFR) after valve implantation
Results
At 3-month follow-up, echocardiography demonstrated group-level improvement in diastolic function and pulmonary hemodynamics.
Pulmonary artery systolic pressure was significantly lower at 3 months compared to baseline (P = 0.002)
Left atrial reservoir strain improved at 3 months
Diastolic dysfunction grade was lower at 3-month follow-up (P = 0.006)
Echocardiography was performed at baseline and 3 months post-TAVI
Methods
The study used invasive left ventricular pressure recording during controlled incremental atrial pacing to assess frequency-dependent myocardial reserve before and immediately after TAVI.
This was a prospective study with invasive LV pressure recording during pacing at 80 and 100 beats/min
Systolic reserve was assessed using dP/dtmax and preload-adjusted indices (dP/dtmax/LVEDP and LVSP/LVEDP)
Lusitropic reserve was assessed using dP/dtmin, the relaxation constant τ, and LVEDP
Patients included had severe normal-flow, high-gradient AS with preserved LVEF
Discussion
Impaired frequency-dependent myocardial reserve in pressure-overload remodeling due to severe aortic stenosis is functionally reversible and tightly linked to loading conditions.
Both systolic (force-frequency) and diastolic (relaxation-frequency) responses were blunted before TAVI despite preserved LVEF
Restoration of both FFR and RFR occurred acutely—immediately after valve implantation—following afterload reduction
The authors conclude that the impairment is 'functionally reversible and tightly linked to loading conditions' rather than reflecting irreversible myocardial damage
These findings provide 'direct invasive human evidence' that frequency-dependent myocardial reserve is acutely restored after TAVI
What This Means
This research suggests that patients with severe aortic stenosis (a narrowing of the heart's main outflow valve) have a hidden impairment in how their heart muscle responds to increased workload, even when standard measures of heart function appear normal. In a healthy heart, the muscle gets stronger and relaxes more efficiently when the heart beats faster. In patients with severe aortic stenosis, this normal 'reserve' response was blunted—the heart muscle showed only a modest increase in pumping strength and no improvement in relaxation when pacing was increased from 80 to 100 beats per minute. This occurred despite preserved ejection fraction, meaning conventional tests would not have detected this problem.
Strikingly, this research found that simply replacing the diseased valve with a transcatheter aortic valve (TAVI procedure) immediately restored this frequency-dependent reserve. Right after the procedure, when the heart was paced faster, it showed significant improvements in both pumping strength and relaxation—responding the way a healthy heart should. By 3 months after the procedure, patients also showed improvements in diastolic (filling) function, lower pressures in the lungs, and better left atrial function on echocardiography.
These findings matter because they demonstrate that the heart muscle impairment seen in severe aortic stenosis is not permanent or structural damage—it is reversible and directly caused by the excessive pressure load the diseased valve places on the heart. This supports the idea that early valve replacement may restore normal heart function before lasting damage occurs, and it provides a more nuanced understanding of why patients with aortic stenosis can have symptoms and functional limitations even when their ejection fraction appears preserved on standard testing.
Fiori E, Buytaert D, Viscusi M, Mistrulli R, Corradetti S, Storozhenko T, et al.. (2026). Restoration of frequency-dependent myocardial reserve after TAVI in severe aortic stenosis: an invasive hemodynamic study.. American journal of physiology. Heart and circulatory physiology. https://doi.org/10.1152/ajpheart.00441.2026