Validation of New Non-Invasive Parameters of Diastolic Suction in the Left Ventricle
Validation of New Non-Invasive Parameters of Diastolic Suction in the Left Ventricle
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.
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).
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)