The Predictive Role of Left and Right Ventricular Speckle-Tracking Echocardiography in COVID-19.

A recent study shows that left ventricular ejection fraction (LVEF) is preserved in most patients with coronavirus disease-2019 (COVID-19) infection, but LV diastolic and right ventricular (RV) function are impaired (1). We assessed left and right myocardial systolic function by speckle-tracking echocardiography (STE) in 100 consecutive patients with COVID-19 and analyzed their prognostic value on survival and need for intubation.

All patients had a diagnosis of COVID-19 confirmed by a polymerase chain reaction assay for severe acute respiratory syndrome-coronavirus-2 and underwent STE examination within 24 h of admission. Demographic, clinical, and laboratory data were systematically recorded. Patients were risk stratified according to their COVID-19 Modified Early Warning Score (1). Routine computed tomography was not done due to the risk of contamination of the computed tomography area. All patients who experienced clinical deterioration (need for intubation or hemodynamic deterioration) underwent repeated STE. Median time between consecutive measurements was 3.5 days (interquartile range: 3 to 5 days). To reduce exposure and contamination, STE was assessed off-line. Nonadjusted and adjusted Cox proportional hazards models for mortality or combined event (death or new need for intubation) hazard ratios (HRs) were calculated for STE parameters. Analysis for survival was obtained for all patients. Analyses for the combined event were done, excluding 9 patients who were mechanically ventilated before baseline STE. The ethics committee of the Tel Aviv Medical Center approved the study (Institutional Review Board number 0196-20-TLV) and voided the requirement of informed consent for the echocardiographic assessment.

A total of 100 patients with COVID-19 infection (age 64.3 ± 20.7 years, 64% male) underwent routine echocardiographic evaluation, and subsequent off-line STE evaluation was feasible in 93 (93%), 83 (83%), and 78 (78%) patients for the LV, RV, or both ventricles, respectively. At the time of baseline STE, 61, 26, and 13 patients had mild, moderate, or severe disease, respectively. The latter had high troponin I (763 ng/l), B-type natriuretic peptide (BNP) (75 pg/ml), and C-reactive protein (162.3 mg/l). Although only 11% of patients had EF ≤50%, abnormal LV (based on peak LV global longitudinal strain [GLS] ≤16.6) and RV free wall longitudinal strain (RVFWLS) (≤20.0) were observed in 42% and 38%, respectively. In 35 of 78 (45%) of patients assessed for both ventricles, all strain parameters were in the normal range. The lowest RV strain values were for the mid and apical septal segments (p < 0.0001 for trend). Patients with poorer clinical grade levels had worse LVGLS, LVFWLS, RVGLS, and RVFWLS (p < 0.05 for all). Of note, septal strain parameters and routine echocardiographic parameters of the LV were not different between the groups. All strain measurements had good intraobserver and interobserver reproducibility. The peak LVGLS intraclass correlation was 0.89 and 0.86, respectively, and for RVFWLS was 0.90 and 0.88, respectively.

Second echocardiography was required in 19% of patients. In these patients, the most common pattern was RV STE deterioration, mostly in the mid segments with apical sparing (p < 0.05). At the end of follow-up (27 [18, 40] days) 23 patients died and 14 patients needed intubation, or both. The impact of clinical and STE characteristics on mortality and clinical event rate is summarized in Table 1 . Survival was reduced with abnormal LVGLS (74 ± 7% vs. 92 ± 8% at 30-day follow-up; p = 0.05). Survival was reduced with abnormal RVFWLS (76 ± 7% vs. 92 ± 5% at 30-day follow-up; p = 0.03). LVGLS was associated with mortality (HR 0.8; p = 0.003] and combined events (HR: 0.80; p = 0.005) when adjusted for EF, or if adjusted for tricuspid annular plane systolic excursion and BNP (HR for mortality: 0.56; 95% confidence interval: 0.19 to 0.95; p = 0.02; HR for combined event: 0.70; 95% confidence interval: 0.48 to 0.94; p = 0.01). RVFWLS was associated with combined events (HR: 0.84; p = 0.008) after adjustment for RV S′ or age and Modified Early Warning Score (HR: 0.90; p = 0.05) but not if adjusted for tricuspid annular plane systolic excursion and BNP.

Table 1

Impact of Clinical and Echocardiographic Characteristics on Mortality and Clinical Event Rate

	Outcome
	Death (n = 23)	p Value	Intubation (n = 14)	p Value	Combined (n = 30)	p Value
Age	1.04 (1.02–1.06)	0.001	1.00 (0.98–1.03)	0.70	1.03 (1.01–1.05)	0.001
Male	1.02 (0.36–3.20)	0.90	1.40 (0.46–5.00)	0.60	1.06 (0.47–2.60)	0.90
Modified Early Warning Score	1.30 (1.17–1.50)	<0.001	1.35 (1.16–1.60)	<0.001	1.40 (1.26–1.56)	<0.001
Temperature	1.18 (0.65–2.04)	0.50	1.89 (1.03–3.30)	0.04	1.80 (1.18–2.70)	0.005
O2 saturation	0.85 (0.78–0.92)	<0.001	0.87 (0.79–0.97)	0.01	0.85 (0.79–0.91)	<0.001
Heart rate	1.00 (0.97–1.03)	0.60	1.04 (1.00–1.07)	0.02	1.03 (1.00–1.05)	0.05
Systolic blood pressure	0.98 (0.96–1.01)	0.40	0.98 (0.95–1.01)	0.20	0.99 (0.98–1.02)	0.90
Diastolic blood pressure	0.97 (0.95–1.00)	0.20	0.99 (0.96–1.03)	0.70	0.99 (0.97–1.02)	0.90
C-reactive protein	1.00 (0.99–1.01)	0.10	1.01 (1.00–1.02)	<0.001	1.01 (1.00–1.01)	0.002
D-dimers	1.07 (0.91–1.18)	0.30	1.18 (1.06–1.30)	0.005	1.12 (0.99–1.22)	0.06
Troponin I	1.00 (0.99–1.00)	0.80	1.00 (1.00–1.01)	0.03	1.00 (0.99–1.00)	0.20
B-type natriuretic peptide	1.00 (1.00–1.02)	0.02	1.00 (0.99–1.01)	0.90	1.00 (0.99–1.01)	0.08
LV assessment
Ejection fraction	0.93 (0.86–1.04)	0.20	1.00 (0.89–1.18)	0.90	0.96 (0.90–1.06)	0.40
LV end-diastolic diameter	0.97 (0.94–1.01)	0.20	0.98 (0.95–1.03)	0.50	0.98 (0.95–1.01)	0.20
LV end-systolic diameter	0.97 (0.92–1.03)	0.40	0.99 (0.93–1.07)	0.80	0.97 (0.93–1.02)	0.30
E/A	0.28 (0.02–2.00)	0.20	0.02 (0.001–0.30)	0.004	0.44 (0.10–1.60)	0.20
E/e′ average	1.04 (0.96–1.10)	0.20	0.94 (0.78–1.05)	0.40	1.04 (0.98–1.09)	0.10
Peak LV global longitudinal strain	0.84 (0.73–0.96)	0.01	0.88 (0.75–1.03)	0.10	0.83 (0.74–0.93)	0.001
End-systolic LV global longitudinal strain	0.87 (0.76–1.00)	0.05	0.88 (0.75–1.03)	0.10	0.83 (0.74–0.93)	0.001
Peak LV free wall longitudinal strain	0.90 (0.79–1.01)	0.09	0.86 (0.74–0.99)	0.04	0.87 (0.79–0.96)	0.007
End-systolic LV free wall longitudinal strain	0.90 (0.80–1.01)	0.08	0.83 (0.74–0.98)	0.03	0.87 (0.79–0.96)	0.005
Peak LV septal wall longitudinal strain	0.89 (0.78–1.02)	0.10	0.94 (0.81–1.08)	0.40	0.86 (0.77–0.95)	0.003
RV assessment
Right atrial pressure	1.03 (0.87–1.16)	0.60	1.06 (0.88–1.20)	0.50	1.03 (0.91–1.13)	0.50
RV end-diastolic area	1.02 (0.91–1.14)	0.70	1.04 (0.92–1.19)	0.50	0.97 (0.89–1.06)	0.60
RV end-systolic area	1.05 (0.90–1.19)	0.50	1.10 (0.94–1.20)	0.20	1.02 (0.90–1.15)	0.60
RV fractional area change	0.96 (0.90–1.03)	0.30	0.96 (0.89–1.04)	0.30	0.96 (0.92–1.02)	0.20
Tricuspid annular plane systolic excursion	0.17 (0.07–0.45)	0.005	0.45 (0.15–1.44)	0.20	0.32 (0.15–0.73)	0.008
RV S'	0.82 (0.72–0.96)	0.02	0.86 (0.74–1.04)	0.10	0.81 (0.71–0.93)	0.003
Tei index	6.10 (1.19–24.00)	0.03	0.93 (0.04–7.20)	0.90	4.00 (1.08–12.2)	0.04
Peak RV 4-chamber longitudinal strain	0.89 (0.76–1.03)	0.10	0.85 (0.71–1.00)	0.05	0.85 (0.75–0.96)	0.008
End-systolic RV 4-chamber longitudinal strain	0.88 (0.74–1.02)	0.09	0.86 (0.72–1.01)	0.07	0.85 (0.74–0.95)	0.007
Peak RV free wall longitudinal strain	0.91 (0.81–1.02)	0.10	0.88 (0.78–1.00)	0.06	0.83 (0.75–0.93)	0.0006
End-systolic RV free wall longitudinal strain	0.87 (0.77–0.98)	0.03	0.85 (0.71–1.00)	0.05	0.85 (0.75–0.96)	0.008
Peak RV septal wall longitudinal strain	0.94 (0.81–1.08)	0.40	0.86 (0.73–1.01)	0.07	0.91 (0.82–1.02)	0.10
End-systolic RV septal wall longitudinal strain	0.93 (0.81–1.07)	0.40	0.90 (0.78–1.04)	0.10	0.92 (0.84–1.02)	0.10
Peak RV apical septal segment longitudinal strain	0.93 (0.83–1.05)	0.30	0.95 (0.84–1.09)	0.50	0.95 (0.87–1.05)	0.40
Peak RV mid septal segment longitudinal strain	0.89 (0.79–1.00)	0.05	0.97 (0.85–1.09)	0.60	0.91 (0.83–0.99)	0.04
Peak RV basal septal segment longitudinal strain	1.02 (0.94–1.11)	0.60	0.90 (0.83–1.02)	0.10	0.96 (0.90–1.030	0.30
Peak RV apical free wall segment longitudinal strain	0.97 (0.90–1.05)	0.50	0.90 (0.82–0.98)	0.01	0.95 (0.89–1.00)	0.09
Peak RV mid free wall segment longitudinal strain	0.93 (0.83–1.05)	0.30	0.95 (0.84–1.09)	0.50	0.95 (0.87–1.05)	0.40
Peak RV basal free wall segment longitudinal strain	1.02 (0.94–1.11)	0.50	0.92 (0.83–1.01)	0.10	0.96 (0.90–1.03)	0.30

Values are hazard ratio (95% confidence interval).

E/A = E wave velocity divided by A wave velocity; E/e′ = E wave velocity divided by E prime velocity; LV = left ventricular; RV = right ventricular.

A recent report (2) showed that RV strain predicts mortality in patients with COVID-19 infection. However, RV assessment was limited to RVFWLS, and LV strain analyses and repeated exams were not performed. We are the first to show the segmental nature of RV dysfunction, with patterns typical for pulmonary embolism or other types of acute cor pulmonale (3, 4, 5). Furthermore, we are the first to evaluate LV strain in patients with COVID-19 infection. We show that abnormal LV longitudinal strain is more common than reduced EF, and that LV STE is superior to LVEF for predicting adverse outcome in patients with COVID 19 infection.

In conclusion, with COVID-19 infection, LV and RV STE are abnormal in ∼40% of patients. Poorer clinical grade and clinical deterioration are mostly associated with worsening RV segmental STE, in pattern suggestive of acute cor pulmonale. LV and RV STE are strong predictors of mortality and need for intubation in patients with COVID-19 infection.