Validation of New Non-Invasive Parameters of Diastolic Suction in the Left Ventricle
Information source: University Hospital Inselspital, Berne
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Diastolic Heart Failure
Phase: N/A
Status: Recruiting
Sponsored by: University Hospital Inselspital, Berne Official(s) and/or principal investigator(s): Christian Seiler, Prof, Study Chair Stefano de Marchi, MD, Principal Investigator, Affiliation: Departement of Cardiology, Bern University Hospital
Overall contact: Stefano de Marchi, MD, Phone: +41316322111, Email: stefano.demarchi@insel.ch
Summary
It is known that, at the end of the cardiac ejection period, potential energy is stored in
elastic fibers of the heart, which promotes the suction of blood from the atria during early
filling. The investigators have developed a new ultrasound-based method to quantify this
suction effect. Here, it is necessary to reduce the complex 3-dimensional cardiac mechanics
in a 1-dimensional (piston-like) pump system. In the study, several steps of model reduction
will be tested. Each reduction is intended to allow non-invasive measurements to become
increasingly simple and feasible at reduced echo quality. The reference method is the
invasive data obtained from a pressure-volume conductance catheter. To increase the supply
of potential energy in the elastic fibers, a substance (dobutamine) is administered for
transient strengthening of the force of contraction.
Hypothesis: There is a good agreement between the new, non-invasive parameters and the
invasive reference method for the quantification of the suction effect of the left
ventricle, and the good correlation persists even with increasing model simplification.
Clinical Details
Official title: Validation of New Non-Invasive Parameters of Diastolic Suction in the Left Ventricle
Study design: Observational Model: Case-Only, Time Perspective: Prospective
Primary outcome: Composite outcome measure: absolute suction work using MAPSE (Mitral annular plane systolic excursion) and IVPG (Intraventricular pressure gradients)
Secondary outcome: Composite outcome measure: absolute suction work using MAPSE and catheter-derived invasive pressureComposite outcome measure: absolute suction work using impedance catheter-derived volumes and IVPG Absolute suction work using tissue velocities (e'/s') Absolute suction work using tissue velocities (s'/L0, L0 = end-systolic ventricular length)
Detailed description:
Background
1. Clinical Background: Heart failure is a widespread cause of morbidity and mortality
worldwide. Despite their similar clinical manifestation, systolic and diastolic heart
failure are two distinct entities that differ with regard to pathophysiology, diagnosis,
prognosis and treatment.
Diastolic dysfunction occurs early in the onset of heart failure. In the past, diastolic
dysfunction has often been defined per exclusionem as heart failure in the absence of
evidence of systolic dysfunction. This definition may be appropriate for clinical diagnosis
if concentric or eccentric LV hypertrophy co-exists, but it is physiologically misleading,
since diastolic dysfunction continues to persist or even worsens with the onset of systolic
dysfunction. It should be considered that symptoms in heart failure are more closely related
to diastolic than to systolic dysfunction. Furthermore, also prognosis of heart failure
seems to be more closely related to the underlying degree of diastolic rather than systolic
dysfunction. Despite its clinical importance, however, large trials on treatment outcome for
diastolic heart failure (such as the CHARM-preserved and PEP-CHF trials) are scarce and
disappointing. Among numerous others, three important reasons for this data scarcity are:
overestimation of end-point events in the power analyses of the respective trials, lack of
therapeutic agents that specifically target diastolic dysfunction, and lack of simple
echocardiographic parameters capable of measuring diastolic function independently from
loading conditions. The latter will be addressed in the study presented here. As will be
detailed below, early-diastolic function is inextricably linked to the end-systolic
conditions of the ventricle. An echocardiographic parameter describing an early-diastolic
mechanical event is therefore very likely to vary with changes in end-systolic conditions.
The present study will investigate new parameters of early-diastolic function by provoking
contractility changes.
1. 2 Physiological Background: There is no doubt that the human heart is a suction-pump
capable of aspirating blood before expelling. There is a concept of early-diastolic suction:
systolic myocardial shortening is believed to store potential energy in elastic fibers and
myocyte filaments that are released in early-diastole to produce a suction effect, thus
contributing to quick LV filling.
In 1930, Katz et al. first published a study describing a suction phenomenon in an in-vitro
preparation of an isolated beating turtle ventricle. They showed that the early-diastolic
volume increase of the ventricle coincides with a pressure fall, which is consistent with
the concept of suction. He concluded that contraction and relaxation alters the elastic
state of the ventricle between two limits (end-systolic and - diastolic), and proposed a
suction effect produced by elastic recoil. This view represented a paradigm change, as
filling was previously considered the result of atrial pressure. If suction is defined
according to Katz, i. e. filling during pressure decay, then it is observed in all ejecting
hearts, regardless of contractility, end-systolic volume or filling pressure. This type of
suction corresponds to what early physiologists may have called the ventricular filling 'vis
a fronte': a filling mechanism generated by the heart. It constitutes a suction effect
relative to the filling reservoir. It can occur as a result of both, elastic recoil and
relaxation.
In a physically more stringent concept, suction is defined as filling at negative LV
transmural pressure. According to this definition, the ventricular wall performs work to
pull blood into the cavity. There are two important conditions for such a suction event.
First, the end-systolic volume must be lower than the volume of elastic ventricular
equilibrium, otherwise no elastic energy would be stored. Second, early diastolic relaxation
must be quick enough to allow restoring forces to prevail over the vanishing active forces.
The process of suction lasts until the equilibrium volume is reached. Atrial pressure then
stretches the ventricle to a volume where a force balance between filling pressure and
ventricular passive stress impedes any further flow (diasthasis). Diasthasis volume is
probably higher than the elastic equilibrium volume, which is a ventricular material
property. Because LV filling itself very quickly abolishes any negative transmural
pressures, and the equilibrium volume of the LV is probably small, suction according to this
definition has been measured almost exclusively under particular circumstances, such as in
nearly empty ventricles (e. g. artificially low afterload), during artificial absence of
filling, or during inotropic stimulation.
1. 3 Concept of Testing New Parameters: In the current study, several steps of model
reduction will be tested. Each reduction is intended to allow non-invasive measurements to
become increasingly simple and feasible at reduced echo quality. The comparison with the
gold standard will then reveal the costs of model reductions in terms of precision and
predictive power. Since direct pressure measurements are not feasible non-invasively, some
simplifications of the pump model are mandatory. The most useful is to reduce the heart to a
1-dimensional, piston-like pump system moving only in apico-basal direction (longitudinal
function). In such a model, not only contractions, but also flow directions are
longitudinal. The 1-dimensional Euler equation can then be used to calculate instantaneous
atrio-ventricular pressure gradients from Color Doppler M-Mode echocardiograms. Similarly,
apico-basal displacement of the 'piston' can easily be measured by M-Mode echocardiograms of
the mitral annulus (mitral annular plane systolic excursion, MAPSE). When combined, the
suction effect of the ventricle relative to the left atrium can be assessed. A further
simplification consists of replacing MAPSE by the widely used Doppler tissue imaging (DTI)
- parameters of systolic (s') and early-diastolic (e') velocity. The reference method of this
study will consist of invasively measured suction work, against which the new parameters
will directly be compared.
Objective
The study is performed to prospectively test novel, non-invasive parameters of early
diastolic function with respect to their ability to quantify the physiological phenomenon of
LV suction.
Hypothesis: The following parameters correlate significantly with LV suction work, but in
descending order of magnitude (r2): absolute suction work from pressure/MAPSE, relative
suction work from IVPG/MAPSE, e'/L0, e'/s', (at rest and under Dobutamin).
Methods
Reference for LV suction work: conductance-catheter is introduced through the aortic valve
and placed along the longitudinal axis of the LV. Continuous conductance are transformed
into LV volume data and simultaneous pressure measurements are performed.
Echo parameters:
IVPG (intraventricular pressure gradients)is calculated from Color-Doppler M-Mode
echocardiograms. This imaging modality produces a color-coded, longitudinal forward-flow
velocity profile (y-axis) over time (x-axis). Such velocity maps can then be processed to
retrieve instantaneous pressure gradients between any two points on the longitudinal axis.
MAPSE (mitral annular plane systolic excursion)is performed with M-Mode echocardiogram of
the septal and lateral mitral annulus.
Tissue velocity: peak systolic velocity (s') and the peak early-diastolic negative velocity
(e')of septal and lateral mitral anulus are measured by pulsed-wave Doppler tissue imaging
(DTI).
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- 1. Patients referred to elective percutaneous coronary angiography
- Stable cardio-pulmonary conditions
- Sinus rhythm
- Written informed consent to participate to the study
Exclusion Criteria
- Patients referred to emergency coronary intervention
- 2. Prior myocardial infarction, wall-motion-abnormalities, stenosis ≥50%
- Prior cardiac surgery
- More than mild left-sided valve disease
- Documented pulmonary disease leading to dyspnea NYHA II or more, including history of
asthma bronchiale
- Any restrictive LV filling pattern without eccentric LV hypertrophy, such as in
infiltrative myocardial diseases
- Pericardial diseases, including prior pericardiotomy and pericardial effusions.
- Pacemaker, implantable cardioverter-defibrillator (ICD) or cardiac resynchronization
therapy device (CRT)
- Known adverse reactions to Dobutamin or Esmolol
- Women who are pregnant or breast feeding (β-HCG > 10 IU/L)
Locations and Contacts
Stefano de Marchi, MD, Phone: +41316322111, Email: stefano.demarchi@insel.ch
Departement of Cardiology, Bern University Hospital, Bern 3010, Switzerland; Recruiting Stefano de Marchi, MD, Principal Investigator
Additional Information
Starting date: December 2014
Last updated: August 3, 2015
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