Single echocardiographic parameters and association with
hospital mortality
Regarding the secondary outcomes focusing on the association between
single echocardiographic parameters and hospital mortality, we found
that non-survivors had higher lateral E/e’ ratio (p=0.03). A trend
towards higher average E/e’ ratio was also found (p=0.08), whilst septal
values were not significantly different (p=0.31). Deceleration Time, a
parameter used in previous guidelines (ASE/EACVI 2009) for the
assessment of LVDD31,
was significantly different according to hospital survival (p=0.01). The
only other echocardiographic parameter significantly associated with
hospital survival was the TDI s’ wave. This result was consistent with
all measurements performed as septal, lateral and average (p=0.02;
p=0.02; and p=0.01, respectively).
PRICES Checklist for reporting echocardiography studies are provided as
Supplementary Digital Contents (1, for the checklist of the common
items; 2, for checklist of the echocardiography variables studied). All
the essential items of the LV diastolic function domain were reported,
together with several items of the LV systolic function and RV function
ones.
DISCUSSION In this small single center study conducted in patients with COVID-19
admitted to ICU, full assessment of LV diastolic function according to
the ASE/EACVI 2016
guidelines20 was
feasible in roughly three quarter of the population. The challenge of
performing this assessment in the remaining patients is not entirely
surprising as the assessment requires a good apical four-chamber
acoustic window with proper alignment, recording and calculation of
several parameters. Several factors may contribute to the challenges of
properly assessing LVDD in COVID-19 patients. First, considering the
severe respiratory impairment of this population of patients and the use
of high positive end-expiratory pressures (median 10
cmH2O in our study), it is not unusual to experience
suboptimal acoustic windows. Second, performing advanced CCE under
hazardous conditions wearing personal protective equipment and double
gloves may be challenging, especially during a period of unprecedented
clinical workload; in such cases, advanced assessment of LVDD may be
perceived as cumbersome and time-consuming, and it is unlikely to become
a priority in a busy and understaffed ICU. Further, severe COVID-19
patients are frequently treated with prone position, which may render
more complex the assessment with
CCE32,33.
With several limitations, this study is probably one of the few
available experiences reporting full LVDD assessment according to the
current ASE/EACVI 2016
guidelines20. Indeed,
whilst several studies reported behavior of one or more echocardiography
variables used for the assessment of LVDD, it seems no studies have
reported full LVDD assessment according to latest
guidelines20, as shown
by a systematic review9.
From an overview of the literature on COVID-19 patients, we also could
not find any experiences comparing the full and the simplified
assessment of LVDD.
Unfortunately, our study is severely underpowered for detecting
influence of LVDD on the outcome of severe COVID-19 patients. This was
behind our control as the ICU served as COVID-ICU for the Trust only for
a brief period of time (~4 months, n=102 COVID-19
admissions); moreover, the workload did not always allow timely
assessment with advanced CCE for the purpose of this study, as only one
operator had advanced CCE skills and joined the ECHO-COVID study.
Therefore, all together with the risk of statistical error, it is likely
that an inevitable selection bias took place.
We found that almost half of COVID-19 patients were diagnosed with LVDD
according to ASE/EACVI 2016
guidelines20 (n=12/26,
46%). LVDD was associated with a trend towards higher mortality in
those with LVDD according to ASE/EACVI 2016
guidelines20 (hospital,
p=0.11; ICU, p=0.13). Conversely, the assessment of LVDD according to
simplified Lanspa
criteria30 showed no
statistical differences; of note, LVDD diagnosis with the latter
criteria was made in over 80% of patients (n=21/26), demonstrating
significant differences with the assessment according to ASE/EACVI 2016
guidelines20. The
reason of this striking difference relies probably in the large amount
of patients with depressed TDI e’ wave values in the overall population;
indeed, depressed e’ velocity is the only criteria adopted by Lanspa et
al.30 for the diagnosis
of LVDD. Moreover, applying the simplified Lanspa criteria for LVDD
grading30 (based on
values of E/e’ ratio) over half of patients had grade III LVDD (n=11/21)
followed by grade II (n=7) and grade I (n=3). Taken together, these
results show huge differences in the assessment of LVDD and probably the
use of the simplified criteria for diagnosis and grading of LVDD in
patients with severe COVID-19 should be considered cautiously as likely
to produce some degree of overestimation. For instance, half of the
patients diagnosed with normal LV diastolic function according to the
ASE/EACVI 201620, had
grade II (n=3) or III (n=4) LVDD according to the simplified
definition30.
Bearing in mind the limitations of the study, we think that our analysis
is in line with previous experience reporting the possible importance of
LVDD in the context of critical illness. Different phenotypes of
cardiovascular dysfunction have been described in critically ill
patients34, and LVDD
has received attention for its association both with mortality in septic
patients21,22and for weaning
failure23. Conversely,
LVSD has not shown the same association when evaluated by means of
LVEF35 or s’
wave24 in critically
ill patients. It was somewhat unexpected to find that TDI s’ wave was
significantly lower in hospital (and ICU) non-survivors, as this
parameter has not been found associated with prognosis in critically ill
patients (i.e. septic
patients24); moreover,
the population we studied was mostly free from cardiovascular support
(77%), and those on norepinephrine received a very low dose (0.04
mcg/kg/min). However, considering that a myocarditis-like pattern has
been found in cardiac magnetic resonance imaging after COVID-19 also in
cohorts of asymptomatic and mildly symptomatic
patients12,36,37,
it is possible that the lower TDI s’ values are related with an impaired
longitudinal LV systolic function not detected by assessment of LVEF.
We also found that lateral E/e’ ratio was significantly higher in
non-survivors at hospital discharge, followed by a trend in average E/e’
ratio (p=0.08). The mean difference between survivors and non-survivors
was just over 3 points, opening the possibility that higher left atrial
pressure contributes to poorer prognosis in patients with severe
COVID-19. However, the overall values of E/e’ ratio were not very high
(median value of average E/e’ was 10.8), and non-survivors presented
median values of 11, well-below the cut-off suggested by the ASE/EACVI
2016 guidelines (E/e’
14)20. From clinical
perspectives, this finding is in line with lung edema and impaired gas
exchange mainly triggered by interstitial pneumonia, with left atrial
pressure playing a marginal role in these cases. In our opinion, it is
reasonable that E/e’ ratio does not play a major role also in
consideration of the gradual course of the COVID-19 disease. Indeed, in
most of the cases evolving towards severe interstitial patterns, the
progression happens over days or weeks. During this period, the patient
has already experienced fever and dehydration. The admission to the
Emergency Department or to other COVID-19 areas with prolonged oxygen
support (high-flow or non-invasive ventilation) increases the likelihood
of intravascular volume depletion due to sweating (fever) and poor water
intake. In such cases, the presence of normal left atrial pressure may
be related to a reduced circulating volume for the above-described
reasons, and it does not necessarily reflect intrinsic myocardial
relaxation. On the contrary, the TRvel (other parameter used for
assessing LVDD) could increase during severe COVID-19 due to the
occurrence of micro- or macro-vascular thrombosis/embolism in the
pulmonary circulation or for the effects of mechanical ventilation,
rather than as a reflection of an ongoing impaired LV relaxation
(post-capillary). Therefore, there are several adjunctive differences
and peculiarities that may render the evaluation of LVDD even more
complex as compared to the usual ICU patient. Among these, COVID-19
usually has a more gradual evolution of the critical illness as compared
to typical septic shock evolving more rapidly.