Global Longitudinal Strain and Left Ventricular Mechanical Dispersion in Patients With Preserved Ejection Fraction and Sudden Cardiac Arrest

Specific tools are lacking for sudden cardiac arrest (SCA) risk assessment in patients with preserved left ventricular ejection fraction (LVEF) and nonhypertrophic ventricles. We hypothesized that echocardiographic global longitudinal strain (GLS) and left ventricular mechanical dispersion (LVMD) identify patients at risk of SCA in subjects with preserved LVEF. In this case-control study, patients evaluated in the electrophysiology clinic due to SCA between 2017 and 2022 were identified and matched 1:2 by age and sex with controls without SCA. Subjects were included if they had preserved LVEF (≥50%). GLS and LVMD (standard deviation of time to peak regional longitudinal strain from 16 segments) were computed offline using speckle-tracking echocardiography. For patients without coronary artery disease (CAD) or ischemic stroke, we calculated atherosclerotic cardiovascular disease and PREVENT risk scores. In 129 subjects (43 SCA, 86 controls) CAD was more frequent in the SCA group (48% vs 29%, p = 0.039). GLS, and LVMD significantly differed between the groups. Impaired GLS (≥–14%), prolonged LVMD (≥75 ms) and CAD were associated with SCA. Yet, GLS and LVMD were independent and incremental to the association between CAD and SCA. Adding GLS increased the strength of the association between CAD and SCA (Chi-square = 13.2, p = 0.001), and adding both GLS and LVMD further strengthened this association (Chi-square = 16.3, p <0.001). In patients without overt cardiovascular disease, GLS and LVMD remained significantly associated with SCA independently of atherosclerotic cardiovascular disease and PREVENT risk scores. In patients with preserved LVEF, GLS and LVMD appear to be promising SCA risk markers beyond CAD.

Clinical Perspectives

1. Global longitudinal strain (GLS) and left ventricular mechanical dispersion (LVMD) provide additional insight into left ventricular mechanical performance beyond left ventricular ejection fraction (LVEF).

2. These parameters reflect subtle myocardial abnormalities that may precede overt deterioration in LVEF.

3. GLS and LVMD are impaired in individuals who develop sudden cardiac arrest despite preserved LVEF, independent of the presence of coronary artery disease.

4. Integration of GLS and LVMD into current risk stratification approaches may improve identification of patients at increased risk of sudden cardiac arrest despite preserved LVEF.

5. These imaging markers have the potential to refine clinical decision-making and inform future preventive strategies in this population.

Reduced left ventricular ejection fraction (LVEF) is an established risk marker for sudden cardiac arrest (SCA), but, approximately 48% of SCA events occur in patients with preserved LVEF, for whom there is currently no validated means of risk stratification. In patients without overt cardiovascular disease, such as those without coronary artery disease (CAD) or ischemic stroke, 10-year risk estimation for major adverse cardiovascular and cerebrovascular events is commonly performed using the atherosclerotic cardiovascular disease (ASCVD) risk score, which is currently recommended by the most recent primary prevention guidelines. More recently, the PREVENT score emerged as an alternative to the pooled cohort equations such as ASCVD risk score. However, these scores do not specifically assess arrhythmic risk or the risk of SCA in patients with preserved LVEF and nonhypertrophic ventricles. ,

Speckle-tracking echocardiography derived global longitudinal strain (GLS) and left ventricular mechanical dispersion (LVMD), a metric of regional heterogeneous contraction, may reflect vulnerability to SCA in subjects with preserved LVEF. Previous studies have suggested the association of these parameters with arrhythmic outcomes across various cardiac conditions, but their value beyond CAD and conventional risk calculators has not been fully explored in patients with preserved LVEF. ,,

We aimed to test the hypothesis that impaired GLS and prolonged LVMD are associated with SCA in subjects having preserved LVEF independently of CAD, ASCVD and PREVENT scores.

Methods

Study population

We identified patients with hospital discharge ICD-10 diagnosis code (I49.01, I49.02, I47.2, I46.2, I46.8, or I46.9) between April 2017 and August 2022. From this eligible population, a convenience sample of 103 adult (age >18 years) patients with a transthoracic echocardiogram before the SCA that were suitable for postprocessing using the EchoPAC software were selected. Patients were excluded if they had LVEF <50% (n = 36), hypertrophic cardiomyopathy (obstructive or nonobstructive) (n = 6), severe aortic stenosis (n = 6), atrial fibrillation (n = 8) or paced rhythm (n = 4) at time of echocardiography. Final population comprised 43 SCA patients. The majority of excluded patients were excluded for LVEF <50%. The control group consisted of individuals from the same source population who underwent complete transthoracic echocardiography (TTE) during the same period and met the same inclusion criteria but did not have subsequent SCA. Controls were matched by age and sex to SCA survivors in a 2:1 ratio. The study protocol complied with the Declaration of Helsinki and was approved by the Institutional Review Board.

Sudden cardiac arrest and risk definitions

SCA was defined as a sudden loss of cardiac function resulting in hemodynamic collapse, requiring resuscitation or leading to death within one hour of symptom onset. SCA events were identified based on hospital discharge ICD-10 codes consistent with sudden cardiac arrest or malignant ventricular arrhythmia. Patients’ characteristics were recorded from medical charts. CAD was defined as >50% stenosis in any proximal or mid coronary artery distribution. For patients without overt cardiovascular disease (no CAD or ischemic stroke), the 10-year risk of major adverse cardiovascular and cerebrovascular events was estimated using the ASCVD risk score, calculated according to current guidelines for individuals aged 40 to 79 years. In addition, ASCVD and PREVENT risk scores were calculated in line with recent recommendations. A high-risk category was defined as a 10-year estimated risk of ≥20% for both ASCVD and PREVENT risk scores. ,

Electrocardiography data analysis

Twelve-lead electrocardiograms (ECGs) were retrospectively collected from patient charts. For each patient, the ECG recording closest in time to the echocardiographic examination was selected. Heart rate, QRS duration, and QT interval were recorded. The QT interval was defined as the time from the onset of the Q wave to the end of the T wave. Heart rate correction of the QT interval was performed using the Fridericia formula: QTc = QT interval/³√ RR.

Echocardiography data processing

Echocardiograms were performed using Vivid E9 and Vivid E95 ultrasound systems (GE Healthcare, Horten, Norway and Chicago, USA). Left ventricular (LV) geometry was categorized according to the recommendations of the American Society of Echocardiography. An increased LV mass index was defined as ≥134 g/m² in males and ≥110 g/m² in females. Increased relative wall thickness (RWT) was defined as ≥0.45. Based on the combination of LV mass index and RWT, 4 geometric patterns were identified: normal (normal LV mass index and normal RWT), concentric remodeling (normal LV mass index with increased RWT), concentric hypertrophy (increased LV mass index and increased RWT), and eccentric hypertrophy (increased LV mass index with normal RWT). Concentric remodeling, concentric hypertrophy, and eccentric hypertrophy were collectively classified as abnormal LV geometry.

Speckle-tracking strain analysis was computed from cine-loops acquired at 40 to 90 frames/second during sinus rhythm. Speckle-tracking echocardiography was conducted in accordance with the recommendations of the strain standardization task force using the Automated Function Imaging tool. Postprocessing was performed using commercially available dedicated software (EchoPAC version 2.06, GE Healthcare, Horten, Norway). Time to peak longitudinal strain was defined as the interval from the onset of the QRS complex on the ECG to the peak negative longitudinal strain. LVMD was calculated as the standard deviation of the time to peak negative strain from 16 left ventricular segments. Mechanical dysfunction was defined as the combination of impaired GLS and prolonged LVMD as defined from the receiver-operating characteristics (ROC) curve analysis by Youden index.

Statistics

Standard statistical software programs (SPSS, version 30, SPSS, Inc. Chicago, IL) and R Project for Statistical Computing (version 4.4.0, Vienna, Austria) were used. Propensity scores were estimated using age and sex, and 1:2 nearest-neighbor matching was performed to create balanced population for the comparison of groups with and without SCA. Balanced cohorts by 1:2 propensity score matching was conducted using the MatchIt package in R, with logistic regression to estimate the propensity score for each patient based on age and gender. Nearest-neighbor matching was applied with a caliper width of 0.1 and a 1:1 ratio, without replacement. Covariate balance between groups was assessed using standardized mean differences, with values <0.1 indicating good balance. The normal distribution of the data was tested by the Kolmogorov-Smirnov test, with a p-value <0.05 indicating a non-normal distribution. For comparison of 2 independent groups, Student’s t test was used for normally distributed continuous variables, the Mann-Whitney U test for non-normally distributed variables. For categorical variables, the Pearson Chi-Square test was used to assess associations between groups. Fisher’s exact test (2-sided) was additionally applied for the ASCVD and PREVENT subgroup analysis, given the smaller sample size. Median of LVEF (60%) was used for purposes of dichotomization in logistic regression models as all the patients had preserved LVEF. The optimal discriminatory GLS and LVMD thresholds were determined from the ROC curves and Youden Index. Stratified logistic regression analysis was further performed to assess effect modification by CAD for the associations of GLS ≥–14% and LVMD ≥75 ms with SCA. Likelihood ratio tests were used to assess the incremental value of GLS LVMD to CAD, ASCVD and PREVENT risk scores (≥20%). A p-value <0.05 was considered statistically significant.

Results

Forty-three eligible SCA subjects were matched with 86 controls, resulting in a final analytic cohort of 129 patients. Standardized mean differences for age and sex were reduced from 0.067 and 0.094 to 0.055 and 0.000, respectively. Time from transthoracic echocardiogram to SCA was median 4 months (IQR: 1 to 12 months, range: 0.5 to 35 months). Patients’ characteristics are presented in Table 1 . The prevalence of CAD was significantly higher in the SCA group as compared to controls (48% vs 29%, p = 0.039), while no significant differences were observed in the history of myocardial infarction, other comorbidities or the use of antiarrhythmic therapies. In patients with CAD, 40% had a history of percutaneous coronary intervention (PCI). SCA occurred in 61.1% of patients with PCI and 33.3% of patients without PCI history (p = 0.066). Furthermore, ECG measurements and echocardiographic metrics other than GLS (SCA:–14.3 ± 4.3% vs non-SCA: −16.5 ± 3.7%, p = 0.003) and LVMD (SCA: 77.9 ± 37.2 ms vs non-SCA: 62.7 ± 21.9 ms, p = 0.004) were similar between subjects with and without SCA ( Figure 1 , Table 2 ) LVEF was also significantly different between the groups (SCA: 58 ± 5% vs non-SCA: 61 ± 5%; p = 0.021).

Table 1

Baseline characteristics

All population Population without CVD
SCA (−) SCA (+) SCA (−) SCA (+)
n = 86 n = 43 n = 51 n = 20
Age (years) 70 ± 13 69 ± 14 67 ± 10 67 ± 7
Male gender (%) 53 59 57 70
Coronary artery disease (%) 29 48 None
History of myocardial infarction (%) 22 21 None
Diabetes mellitus (%) 29 12 31 35
Hypertension (%) 81 74 74 75
Systolic blood pressure (mmHg) 132 ± 20 131 ± 22 131 ± 19 132 ± 22
Diastolic blood pressure (mmHg) 74 ± 12 74 ± 11 75 ± 11 74 ± 11
Ischemic stroke (%) 13 11 None
Paroxysmal atrial fibrillation (%) 24 26 None
β-Blocker (%) 52 61 49 50
Amiodarone/dronedarone (%) 3 2 None
ACE-i/ARB (%) 44 47 47 50
Creatinine (mg/dL) 1.25 ± 1.03 1.22 ± 0.85 1.01 ± 0.52 1.35 ± 1.1
HbA1C (%) 6.2 ± 1.5 6.0 ± 0.9 6.2 ± 1.5 5.9 ± 0.6
Non-HDL cholesterol (mg/dL) 103 ± 39 112 ± 47 107 ± 37 110 ± 34
HDL (mg/dL) 46 ± 12 44 ± 16 46 ± 12 45 ± 16
High ASCVD score (%) 47 40
High PREVENT score (%) 43 35

ACE-I = angiotensin converting enzyme inhibitor; ARB = angiotensin receptor blocker; ASCVD = atherosclerotic cardiovascular disease; CVD = cardiovascular disease; SCA = sudden cardiac arrest.

Data presented as mean ± SD.

Figure 1

Global longitudinal strain (GLS) and left ventricular mechanical dispersion (LVMD) in a patient with sudden cardiac arrest (SCA) ( left panels) and a patient without SCA ( right panels).

Table 2

Comparison of electrocardiographic and echocardiographic parameters between patients with and without SCA

All population Population without CVD
SCA (−) SCA (+) SCA (−) SCA (+)
n = 86 n = 43 n = 51 n = 20
HR (bpm) 73 ± 14 81 ± 18 73 ± 16 81 ± 18
QRS (ms) 105 ± 36 97 ± 21 111 ± 33 104 ± 26
Corrected QT (Fridericia) (ms) 440 ± 32 438 ± 30 444 ± 37 440 ± 32
IVS thickness (cm) 1.1 ± 0.3 1.2 ± 0.3 1.1 ± 0.3 1.2 ± 0.2
LVEF (%) 61 ± 5 58 ± 5 * 61 ± 5 57 ± 5
GLS (%) −16.5 ± 3.7 −14.3 ± 4.3 −16.3 ± 3.8 −13.7 ± 3.4 *
LVMD (ms) 63 ± 22 78 ± 37 66 ± 25 88 ± 38
EDVI (ml/m 2) 52 ± 15 54 ± 14 53 ± 14 59 ± 17
ESVI (ml/m 2) 21 ± 7 23 ± 8 21 ± 7 26 ± 9 *
LVMI (mg/m 2) 98 ± 43 105 ± 39 99 ± 49 102 ± 27
RWT 0.50 ± 0.12 0.48 ± 0.16 0.50 ± 0.13 0.45 ± 0.09
Abnormal geometry (%) 68 58 71 55
TR velocity (m/s) 2.7 ± 0.5 2.6 ± 0.5 2.6 ± 0.5 2.5 ± 0.5
E/e’ 13 ± 5 15 ± 7 12 ± 5 14 ± 6
LAVImax (ml/m 2) 41 ± 18 37 ± 16 39 ± 15 32 ± 14
Reservoir LA strain (%) 23.3 ± 11.1 23.7 ± 10.9 24 ± 11 23 ± 9
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Aug 8, 2026 | Posted by in CARDIOLOGY | Comments Off on Global Longitudinal Strain and Left Ventricular Mechanical Dispersion in Patients With Preserved Ejection Fraction and Sudden Cardiac Arrest

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