Clinical Trial: Multicenter Prospective Study of Low-Flow Low-Gradient Aortic Stenosis (TOPAS Study)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Multicenter Prospective Study of Low-Flow Low-Gradient Aortic Stenosis (TOPAS Study Phase III)

Brief Summary:

Low-flow, low-gradient (LF-LG) aortic stenosis (AS) may occur with depressed (i.e. Classical LF; CLF) or preserved (i.e. Paradoxical LF; PLF) LV ejection fraction (LVEF) and both situations are amongst the most challenging encountered in patients with valvular heart disease. Although, CLF-LG AS is recognized has an important clinical entity, current ACC/AHA-ESC guidelines however do not provide precise recommendations for clinical management of these patients . PLF-LG AS is a new entity recently described by our group, which is characterized by more pronounced LV concentric remodeling with smaller LV cavity size and a restrictive physiology leading to impaired LV filling, altered myocardial function, and a low-flow state. Up to recently, this entity was often misdiagnosed, leading to underestimation of AS severity and inappropriate delays for aortic valve replacement surgery (SAVR). The two main challenges in patients with CLF- or PLF- LG AS are to distinguish between a true-severe (TS) versus a pseudo-severe (PS) stenosis and to accurately quantify the extent of myocardial impairment. Unfortunately, the traditional resting and stress echocardiographic parameters currently used to assess the severity of valvular and myocardial dysfunction in patients with LF-LG AS are far from being optimal, and as a consequence, quantification of disease severity and therapeutic management may not be appropriate in a substantial proportion of these patients.

THE GENERAL OBJECTIVES of the TOPAS study are to develop and validate new parameters and biomarkers to improve the assessment of stenosis severity and myocardial impairment, the risk-stratification, and the clinical decision making in patients with LF-LG AS and to assess the impact of the different therapeutic strategies on patient outcomes.


Detailed Summary:

Low-flow, low-gradient (LF-LG) aortic stenosis (AS) may occur with depressed (i.e. Classical LF; CLF) or preserved (i.e. Paradoxical LF; PLF) LV ejection fraction (LVEF) and both situations are amongst the most challenging encountered in patients with valvular heart disease. Although, CLF-LG AS is recognized has an important clinical entity, current ACC/AHA-ESC guidelines however do not provide precise recommendations for clinical management of these patients because there is an important lack of data on this condition. PLF-LG AS is a new entity recently described by our group, which is characterized by more pronounced LV concentric remodeling with smaller LV cavity size and a restrictive physiology leading to impaired LV filling, altered myocardial function, and a low-flow state. Up to recently, this entity was often misdiagnosed, leading to underestimation of AS severity and inappropriate delays for aortic valve replacement surgery (SAVR). The two main challenges in patients with CLF- or PLF- LG AS are to distinguish between a true-severe (TS) versus a pseudo-severe (PS) stenosis and to accurately quantify the extent of myocardial impairment. Unfortunately, the traditional resting and stress echocardiographic parameters currently used to assess the severity of valvular and myocardial dysfunction in patients with LF-LG AS are far from being optimal, and as a consequence, quantification of disease severity and therapeutic management may not be appropriate in a substantial proportion of these patients. Furthermore, it remains uncertain which is the optimal timing and mode of treatment (SAVR vs. Transcatheter Aortic Valve Implantation [TAVI] vs. Medical) for the different subsets of patients with LF-LG AS patients (CLF- vs. PLF- LG AS; TS vs. PS AS; absence vs. presence of myocardial contractile reserve etc.) THE GENERAL OBJECTIVES of the TOPAS study are to develop and validate new parameters and biomarkers to improve the
Sponsor: Laval University

Current Primary Outcome: all-cause mortality [ Time Frame: Patients will be followed for 5 years, with an average of 3.5 years ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 30-day mortality (for patients treated by SAVR or TAVR) [ Time Frame: Patients will be followed for 5 years, with an average of 3.5 years ]
  • cardiovascular mortality [ Time Frame: Patients will be followed for 5 years, with an average of 3.5 years ]
  • new major cardiovascular events as defined by VARC: myocardial infarction, stroke, vascular complications, and re-hospitalization for heart failure composite end-point of cardiovascular mortality and hospitalization for heart failure [ Time Frame: Patients will be followed for 5 years, with an average of 3.5 years ]
  • composite end-point of cardiovascular mortality and hospitalization for heart failure [ Time Frame: Patients will be followed for 5 years, with an average of 3.5 years ]


Original Secondary Outcome: Same as current

Information By: Laval University

Dates:
Date Received: April 16, 2013
Date Started: June 2002
Date Completion: January 2019
Last Updated: August 31, 2016
Last Verified: August 2016