DISCUSSION
The relevant results of the present study were:
(1) The relevance of the ramp test during follow up for the hemodynamic
optimization in patients implanted with Left ventricular support.
(2) Right ventricle function remains a limiting factor in patients with
LVAD.
(3) The current parameters usually adopted for setting the RPM are not
exhaustive to make the patient’s hemodynamic profile optimal.
(4) This newly designed tool for hemodynamic optimization that we called
hemodynamic index, can support clinicians to easily identify the
hemodynamic profile of individual patients and to optimize medical
treatment aiming to prevent events of right failure and related
rehospitalizations. Based on this model, we recommend maintaining an HI
above 60, during pump speed optimization, to preserve good right
ventricle function while ensuring optimal left ventricle unloading. HI
could provide a useful guide during ramp test, avoiding an excessive
increase in rpm.
Ramp testing during right heart catheterization to optimize the RPM is
recommended in the guidelines of the Society of Heart and Lung
Transplantation to optimize the rpm of the device during the
postoperative course. The current guidelines encourage the use of the
echocardiography as an integral part in determining that adequate
unloading of the left ventricle is obtained while maintaining central
positioning of the septum and minimal mitral regurgitation (class I
recommendation)[8]. Setting the RPM to ensure intermittent opening
of the aortic valve is currently a class IIb recommendation, to prevent
the development of aortic regurgitation or aortic leaflets fusion. These
recommendations are somewhat vague and not standardized, and the
application of right heart catheterization in conditions of clinical
stability is not well defined. Right heart catheterization is currently
recommended (class I) to cope with specific situations, such as when
symptoms of heart failure occur, for evaluation of pulmonary
hypertension in patients eligible for heart transplantation and in the
event of right ventricular failure. When the explant of LVAD is planned,
the hemodynamic evaluation is also recommended (class IIa) to obtain
more data confirming myocardial recovery. Diagnosis of LVAD outflow
obstruction or suspected device thrombosis is another indication for
performing the ramp test during right heart catheterization [9].
Uriel et al. observed that an LV end-diastolic dimension slope less than
an absolute value of 0,16 during a ramp test is a strong predictor of
thrombosis in HeartMate II patients, and evidence not confirmed in
patients implanted with HVAD [10-11]. There is no broad consensus on
the routine use of right heart cathetherization, and it is currently not
recommended in the guidelines. Uriel et al. highlighted in their study
that many patients have abnormal hemodynamic profiles at the set RPM
level, despite no signs or symptoms of heart failure were identified
[12]. Suwa et al. have recently demonstrated that 57% of clinically
stable patients had a significant increase in CVP and PCWP at baseline
LVAD speed [13]. These findings were also confirmed by our study,
which estimated a PCWP value greater than 12 mmHg in 30 % of patients.
In both groups, we achieved a significant reduction in PCWP after speed
optimization. As highlighted by Table 2, the pre- and post- speed
optimization PCWP values were respectively 17.15 ± 4.93 mmHg and 12.55 ±
2.21 mmHg (p <0.001) respectively for the RVF- group. The PCWP
values pre and post speed optimization in RVF + patients were 14.75 ±
3.46 mmHg and 10.16 ± 2.51 mmHg (p <0.001) respectively.
Although PF and CO increases were achieved in both patient groups by
improving the LVAD speed, the CO increased significantly only in the RVF
- group. This finding suggests that current approaches for setting the
optimal LVAD speed are insufficient and that a hemodynamic evaluation
provides important additional information about the clinical condition
of the patient [14]. The hemodynamic profile obtained with ramp
tests during right catheterization might be used to better tailor drug
therapy so that a better hemodynamic profile and a better quality of
life can be achieved. Although further studies are needed, Jung et al.
have highlighted how changes in hemodynamic parameters during RPM
changes can have important clinical implications. Jung pointed out that
a reduction in PCWP during ramp tests in patients implanted with HM II
correlated with a lower NYHA class and that an increase in CO was
related to a better quality of life [15]. In addiction, data are
emerging concerning the effect of pump speed optimization on long-term
outcomes. Sarswat et al. conducted a two-year prospective observational
study of 62 LVAD patients after performing hemodynamic optimization by
invasive ramp test. The rate of hospital readmission was lower in
patients with an optimized hemodynamic profile when compared with
patients in whom the hemodynamic condition had not been optimized.
Couperus also highlighted the effectiveness of speed optimization on the
function of the right ventricle [16]. Our results showed the ramp
test assists in the unloading of the left ventricle but was not so
effective in improving the right heart function. A significant reduction
of CVP was observed only in RVF- (Tab 2). If we consider that only in
RVF - patients there was a significant increase in CO, we can conclude
that despite optimal unloading of the left ventricle, hemodynamic
optimization is substantially conditioned by the residual intrinsic
function of the right ventricle. Despite the results obtained by
Couperus and Coll, the correlation between hemodynamic optimization and
a reduced incidence of right ventricular failure and better survival
remains to be validated. An important aspect to highlight is that many
studies focus on the incidence of early right failure with minimal focus
on late right failure, which however represents an important
complication during support with LVAD. As described by Burke et al.,
late RVF could be mostly related to intrinsic myocardial function, or it
could be secondary to various etiologies such as ventricular arrhythmia,
the progression of tricuspid insufficiency and pulmonary hypertension
[17]. Identifying these risk factors for development of late RVF is
clinically very relevant since planning biventricular support can result
in a better outcome, especially for high-risk BTT patients [18].
Takeda et al. found that comparing the non-RHF and RHF group, similar
hemodynamic values were found, including CVP and CVP / PCWP ratio
[19]. These variables are commonly representative markers of
intrinsic right ventricular dysfunction. Similarly Kormos et al.
reported CVP and CVP/PCWP ratio values similar in those patients who did
not develop RHF when compared to patients who developed late RHF. on the
other hand, patients developing early RHF showed significantly higher
CVP and CVP/PCWP ratio values when compared with data from the non-RHF
population [20]. From these results, it emerges that the
preoperative hemodynamic evaluation is not sensitive enough to identify
patients at risk of late RVF after LVAD implantation. Once the right
ventricle adapts to the new physiological state guaranteed by the
continuous flow pump support, other factors like the intrinsic right
ventricular dysfunction can result in right hear failure. Hence the
purpose of our study was to develop a new hemodynamic index calculated
on hemodynamic parameters obtained after speed optimization at
follow-up. Since the normal parameters such as CVP and CVP / wedge, as
previously anticipated, are not adequate to identify patients at risk of
RVF, we developed a parameter that integrates the filling pressures of
the right and left sections, the afterload represented by the MAP, and
the ratio between the optimized RPM and the maximum RPM available. The
latter parameter was intended as a correction factor and expressed the
support level of the device. The main purpose of this hemodynamic index
is to identify a reference parameter to guide the RPM setting during
ramp tests in order to optimally balance all the variables involved,
thus reducing the risk of right failure. Suboptimal unloading of the
left ventricle and right dysfunction are the major determinants of
long-term mortality in patients with LVAD [21-22]. The LVAD pump
speed can influence both factors. A high LVAD speed increases the
unloading of the left ventricle and increases the cardiac output and
exercise capacity [23]. However, elevated speed has been associated
with aortic valve dysfunction. In particular, a reduction in the opening
of the valve due to the increased pump speed results in the fusion of
the valve leaflets, thrombus formation and valve insufficiency which
reduces survival in patients with long-term LVAD support [24-25].
LVAD speed also has an important effect on the function of the right
ventricle, the degree of unloading of the VS, pulmonary arterial
pressures, and the right ventricle afterload. A higher level of pump
speed might improve right function by reducing the afterload on the
right ventricle. However, excessive LVAD speed can also compromise right
ventricular function because of increased preload, the leftward shift of
the interventricular septum, and modification of the right ventricle’s
geometry. Therefore, the optimal hemodynamic balance during support with
LVAD is the result of several variables that interact with each other.
When considered individually, these variables fail to precisely identify
a patient’s hemodynamic profile and showed poor correlation with the
incidence of right ventricular failure. The hemodynamic balance of
patients with continuous-flow LVAD support is much more complex, and
more than a single variable should be considered. The HI attempts to
summarize the effects of the different variables by combining them into
a single parameter that could represent a reference for the hemodynamic
optimization of LVAD patients. By retrospectively evaluating our 38
patients, a HI of 51,66 ± 5,28 was found in those who required
re-hospitalization with the diagnosis of late RVF and resulted
significantly lower when compared with the group of patients who had not
experienced a right failure episode, HI 80,10 ± 13,45
(p<0,001). In the RVF + group, the lower HI, according to our
formula, was the result of a lower PCWP / CVP ratio, a reduced MAP, and
a lower ratio between the RPM set/ RPM max. The reduced ratio between
PCWP / CVP at a reduced RPM / RPM max ratio is due to a poor function of
the right ventricle, illustrating a clear relationship between this
hemodynamic feature and high risk of right failure. When a low
hemodynamic index was found in conjunction with a low MAP, then the
right dysfunction could have been explained by excessive unloading of
the left ventricle and significant leftward shift of the septum and
modified geometry of the right ventricle. In this case, attention should
be paid to reduce antihypertensive therapy to restore normal afterload.
According to our results, a ROC analysis identified a cut off level for
HI of 55, a level significantly predictive of late right failure.
Our study shows that this new hemodynamic index can be used for various
purposes:
1) Hemodynamic and pump speed optimization by aiming for a minimum HI of
at least 55.
2) Identification of different hemodynamic profiles with stratification
of patients according to the risk of late RVF. In these patients, a
different strategy should be adopted by anticipating the inclusion in
the transplant list or proceed with an emergency transplant.
3) Medical therapy optimization in patients with a very high HI. A very
high HI is an expression of high PAM, a high value of the PCWP / CVP
ratio, and high RPM set/max RPM ratio, indicative of poor left
ventricular unloading. In such patients, an increase in antihypertensive
therapy to reduce the afterload of the ventricle is certainly
recommended (see algorithm Fig 4).