This work is structured as follows:
In Section 1 we discuss the clinical problem of heart failure. In particular, we
present the phenomenon known as ventricular mechanical dyssynchrony: its
impact on cardiac function, the therapy for its treatment and the methods for
its quantification. Specifically, we describe the conductance catheter and its
use for the measurement of dyssynchrony. At the end of the Section 1, we
propose a new set of indexes to quantify the dyssynchrony that are studied
and validated thereafter.
In Section 2 we describe the studies carried out in this work: we report the
experimental protocols, we present and discuss the results obtained.
Finally, we report the overall conclusions drawn from this work and we try to
envisage future works and possible clinical applications of our results.
Ancillary studies that were carried out during this work mainly to investigate
several aspects of cardiac resynchronization therapy (CRT) are mentioned in
Appendix.
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Ventricular mechanical dyssynchrony plays a regulating role already in normal
physiology but is especially important in pathological conditions, such as
hypertrophy, ischemia, infarction, or heart failure (Chapter 1,2.).
Several prospective randomized controlled trials supported the clinical
efficacy and safety of cardiac resynchronization therapy (CRT) in patients with
moderate or severe heart failure and ventricular dyssynchrony. CRT
resynchronizes ventricular contraction by simultaneous pacing of both left and
right ventricle (biventricular pacing) (Chapter 1.).
Currently, the conductance catheter method has been used extensively to
assess global systolic and diastolic ventricular function and, more recently,
the ability of this instrument to pick-up multiple segmental volume signals has
been used to quantify mechanical ventricular dyssynchrony. Specifically,
novel indexes based on volume signals acquired with the conductance
catheter were introduced to quantify dyssynchrony (Chapter 3,4.).
Present work was aimed to describe the characteristics of the conductancevolume
signals, to investigate the performance of the indexes of ventricular
dyssynchrony described in literature and to introduce and validate improved
dyssynchrony indexes. Morevoer, using the conductance catheter method
and the new indexes, the clinical problem of the ventricular pacing site
optimization was addressed and the measurement protocol to adopt for
hemodynamic tests on cardiac pacing was investigated.
In accordance to the aims of the work, in addition to the classical time-domain
parameters, a new set of indexes has been extracted, based on coherent
averaging procedure and on spectral and cross-spectral analysis (Chapter 4.).
Our analyses were carried out on patients with indications for
electrophysiologic study or device implantation (Chapter 5.). For the first time,
besides patients with heart failure, indexes of mechanical dyssynchrony
based on conductance catheter were extracted and studied in a population of
patients with preserved ventricular function, providing information on the
normal range of such a kind of values.
By performing a frequency domain analysis and by applying an optimized
coherent averaging procedure (Chapter 6.a.), we were able to describe some
characteristics of the conductance-volume signals (Chapter 6.b.).
We unmasked the presence of considerable beat-to-beat variations in
dyssynchrony that seemed more frequent in patients with ventricular
dysfunction and to play a role in discriminating patients. These non-recurrent
mechanical ventricular non-uniformities are probably the expression of the
substantial beat-to-beat hemodynamic variations, often associated with heart
failure and due to cardiopulmonary interaction and conduction disturbances.
We investigated how the coherent averaging procedure may affect or refine
the conductance based indexes; in addition, we proposed and tested a new
set of indexes which quantify the non-periodic components of the volume
signals.
Using the new set of indexes we studied the acute effects of the CRT and the
right ventricular pacing, in patients with heart failure and patients with
preserved ventricular function.
In the overall population we observed a correlation between the hemodynamic
changes induced by the pacing and the indexes of dyssynchrony, and this
may have practical implications for hemodynamic-guided device implantation.
The optimal ventricular pacing site for patients with conventional indications
for pacing remains controversial. The majority of them do not meet current
clinical indications for CRT pacing. Thus, we carried out an analysis to
compare the impact of several ventricular pacing sites on global and regional
ventricular function and dyssynchrony (Chapter 6.c.). We observed that right
ventricular pacing worsens cardiac function in patients with and without
ventricular dysfunction unless the pacing site is optimized. CRT preserves left
ventricular function in patients with normal ejection fraction and improves
function in patients with poor ejection fraction despite no clinical indication for
CRT. Moreover, the analysis of the results obtained using new indexes of
regional dyssynchrony, suggests that pacing site may influence overall global
ventricular function depending on its relative effects on regional function and
synchrony.
Another clinical problem that has been investigated in this work is the optimal
right ventricular lead location for CRT (Chapter 6.d.). Similarly to the previous
analysis, using novel parameters describing local synchrony and efficiency,
we tested the hypothesis and we demonstrated that biventricular pacing with
alternative right ventricular pacing sites produces acute improvement of
ventricular systolic function and improves mechanical synchrony when
compared to standard right ventricular pacing. Although no specific right
ventricular location was shown to be superior during CRT, the right ventricular
pacing site that produced the optimal acute hemodynamic response varied
between patients.
Acute hemodynamic effects of cardiac pacing are conventionally evaluated
after stabilization episodes. The applied duration of stabilization periods in
most cardiac pacing studies varied considerably.
With an ad hoc protocol (Chapter 6.e.) and indexes of mechanical
dyssynchrony derived by conductance catheter we demonstrated that the
usage of stabilization periods during evaluation of cardiac pacing may mask
early changes in systolic and diastolic intra-ventricular dyssynchrony. In fact,
at the onset of ventricular pacing, the main dyssynchrony and ventricular
performance changes occur within a 10s time span, initiated by the changes
in ventricular mechanical dyssynchrony induced by aberrant conduction and
followed by a partial or even complete recovery.
It was already demonstrated in normal animals that ventricular mechanical
dyssynchrony may act as a physiologic modulator of cardiac performance
together with heart rate, contractile state, preload and afterload. The present
observation, which shows the compensatory mechanism of mechanical
dyssynchrony, suggests that ventricular dyssynchrony may be regarded as an
intrinsic cardiac property, with baseline dyssynchrony at increased level in
heart failure patients.
To make available an independent system for cardiac output estimation, in
order to confirm the results obtained with conductance volume method, we
developed and validated a novel technique to apply the Modelflow method (a
method that derives an aortic flow waveform from arterial pressure by
simulation of a non-linear three-element aortic input impedance model,
Wesseling et al. 1993) to the left ventricular pressure signal, instead of the
arterial pressure used in the classical approach (Chapter 7.).
The results confirmed that in patients without valve abnormalities, undergoing
conductance catheter evaluations, the continuous monitoring of cardiac output
using the intra-ventricular pressure signal is reliable. Thus, cardiac output can
be monitored quantitatively and continuously with a simple and low-cost
method.
During this work, additional studies were carried out to investigate several
areas of uncertainty of CRT. The results of these studies are briefly presented
in Appendix: the long-term survival in patients treated with CRT in clinical
practice, the effects of CRT in patients with mild symptoms of heart failure and
in very old patients, the limited thoracotomy as a second choice alternative to
transvenous implant for CRT delivery, the evolution and prognostic
significance of diastolic filling pattern in CRT, the selection of candidates to
CRT with echocardiographic criteria and the prediction of response to the
therapy.
| Identifer | oai:union.ndltd.org:unibo.it/oai:amsdottorato.cib.unibo.it:400 |
| Date | 19 April 2007 |
| Creators | Valsecchi, Sergio <1974> |
| Contributors | Salinari, Serenella |
| Publisher | Alma Mater Studiorum - Università di Bologna |
| Source Sets | Università di Bologna |
| Language | English |
| Detected Language | English |
| Type | Doctoral Thesis, PeerReviewed |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
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