Aims:A typical left bundle branch block (LBBB) contraction pattern prior to cardiac resynchronization therapy (CRT) has been demonstrated to be highly associated with response beyond QRS morphology and duration. This study investigates whether septal deformation type and lateral wall strain amplitude may be of particular importance for long-term outcome after CRT implantation. Methods:From two centres, 208 CRT candidates with LBBB, New York Heart Association functional class II-IV, left ventricular ejection fraction ≤35%, and QRS duration ≥ 120 ms underwent echocardiography before CRT-defibrillator (CRT-D) implantation. Results:Four septal contraction patterns were identified: 36 patients (17%) had double-peaked systolic pattern (LBBB-1), 51 (25%) had early pre-ejection peak shortening followed by systolic stretch (LBBB-2), 43 (21%) had shortening with one systolic peak inside 70% of the ejection phase (LBBB-3), and 78 (38%) had normal septal peak timing outside early 70% of ejection phase (LBBB-4). The primary outcome (freedom from death, implantation of a left ventricular assist device, and heart transplantation) occurred in 48 patients during a median follow-up of 4 years (interquartile range 3.25-4). The most favourable outcome was associated with LBBB-1 and LBBB-2, which had one-seventh the risk of the primary outcome compared to LBBB-4 (HR: 0.14 [95% confidence interval: 0.06-0.34]; P < 0.001). Patients in the lowest tertile of lateral wall strain (>-7.4%) were at high risk of an event compared to the other patients (HR: 2.57 [1.46-4.55]; P = 0.001). Conclusion:The long-term clinical benefit of CRT-D in patients with LBBB pre-implantation varies. Subtypes of septal contraction patterns and, to a lesser degree, lateral function are important determinants of outcome in patients with CRT-D.

CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, has demonstrated significantly improved overall survival in acute myeloid leukemia (AML) compared with 7 + 3, but its impact on cardiac function remains unclear. In a post hoc analysis of the pivotal clinical trial, we sought to determine the relative cardiotoxicity of CPX-351 vs. 7 + 3 in high-risk AML. We evaluated cardiotoxicity in 102 patients with AML (CPX-351, n = 57; 7 + 3, n = 45) who had normal baseline left ventricular ejection fraction (LVEF) ≥ 53

Background Guideline-directed medical therapy (GDMT) includes an ARNI. However, the relative importance of continuing or initiating ARNI therapy during titration of GDMT on changes in left sided heart function are unknown. Methods Sixty-three HFrEF patients in a GDMT clinic and who had baseline and 3-12 months follow-up transthoracic echocardiography (TTE) were enrolled prospectively between 2020 to 2022. LVEF, LV longitudinal strain (LVGLS), LAVI, and LA peak strain (LAs) were analyzed as left-sided parameters. Patients were divided into three groups: patients with initiation of ARNI (NEW group), continued administration of ARNI before baseline TTE (CON group), and patients who did not initiate ARNI (NON group). Results In all patients, the mean age was 64 years, and the mean time between TTEs was 6.9 months. Regarding LVEF, LVGLS, LAVI, and LAs, significant improvements were observed at follow-up TTEs in NEW and CON groups (p < 0.05). In NON group, only LAVI had a significant difference between the two TTEs. Among the three groups, there were no significant differences in all parameters at baseline. There was a significant difference among the three groups in LVGLS and LAs at follow-up. (p < 0.001 in LVGLS, p = 0.020 in LAs). At follow-up, there were significant differences in LVGLS between CON and NON groups (p = 0.001) and tendencies in LVEF (p = 0.096) and LAs (p = 0.101). However, there were no statistical differences between NEW and CON groups in all four parameters. (Figure) Conclusion Patients initiated or continued on ARNI had significant improvement in multiple echocardiographic measures left heart function, whereas those who did not receive ARNI had little improvement.

Background— Deficiencies of iron-sulfur (Fe-S) clusters, metal complexes that control redox state and mitochondrial metabolism, have been linked to pulmonary hypertension (PH), a deadly vascular disease with poorly defined molecular origins. The BolA Family Member 3 (BOLA3) regulates Fe-S biogenesis, and mutations in BOLA3 result in multiple mitochondrial dysfunction syndrome, a fatal disorder associated with PH. The mechanistic role of BOLA3 in PH remains undefined. Methods— In vitro assessment of BOLA3 regulation and gain and loss of function assays were performed in human pulmonary artery endothelial cells (PAECs) using siRNA and lentiviral vectors expressing the mitochondrial isoform of BOLA3. Polymeric nanoparticle 7C1 was utilized for lung endothelial-specific delivery of BOLA3 siRNA oligonucleotides in mice. Overexpression of pulmonary vascular BOLA3 was performed by orotracheal transgene delivery of adeno-associated virus in mouse models of PH. Results— In cultured hypoxic PAECs as well as lung from human Group 1 and 3 PH patients as well as multiple rodent models of PH, endothelial BOLA3 expression was down-regulated, which involved HIF-2 α -dependent transcriptional repression via HDAC-mediated histone deacetylation. In vitro gain and loss of function studies demonstrated that BOLA3 regulated Fe-S integrity, thus modulating lipoate-containing 2-oxoacid dehydrogenases with consequent control over glycolysis and mitochondrial respiration. In contexts of siRNA knockdown and naturally occurring human genetic mutation, cellular BOLA3 deficiency down-regulated the glycine cleavage system protein H (GCSH), thus bolstering intracellular glycine content. In the setting of these alterations of oxidative metabolism and glycine levels, BOLA3 deficiency increased endothelial proliferation, survival, and vasoconstriction, while decreasing angiogenic potential. In vivo, pharmacologic knockdown of endothelial BOLA3 and targeted overexpression of BOLA3 in mice demonstrated that BOLA3 deficiency promotes histologic and hemodynamic manifestations of PH. Notably, the therapeutic effects of BOLA3 expression were reversed by exogenous glycine supplementation. Conclusions— BOLA3 acts as a crucial lynchpin connecting Fe-S-dependent oxidative respiration and glycine homeostasis with endothelial metabolic re-programming critical to PH pathogenesis. These results provide a molecular explanation for the clinical associations linking PH with hyperglycinemic syndromes and mitochondrial disorders. These findings also identify novel metabolic targets, including those involved in epigenetics, iron-sulfur biogenesis, and glycine biology, for diagnostic and therapeutic development. provide crucial support for the of central dysregulation of Fe-S integrity a biogenesis

Background Right ventricular (RV) dysfunction has been identified as a prognostic marker for adverse events in patients with intermediate‐risk pulmonary embolism. We hypothesized that right‐sided strain parameters have additive value to conventional echocardiographic parameters to further risk‐stratify patients for mortality. Methods and Results This is a retrospective cohort study of patients with intermediate‐risk pulmonary embolism between 2010 and 2018. All‐cause 30‐day mortality was evaluated. Echocardiographic strain parameters and conventional RV measurements were compared between survivors and nonsurvivors. Two hundred fifty‐one patients were analyzed. Mortality at 30 days was 12.4%. Image quality was sufficient for RV strain analysis in 230 patients (91.6%). Right to left ventricular end‐diastolic diameter ratio (RV/LV ratio) (odds ratio [OR], 1.490 [95% CI, 1.120–1.990]) and RV global longitudinal strain (RVGLS) (OR, 0.742 [95% CI, 0.605–0.910]) were independently associated with 30‐day mortality. Using RVGLS and RV/LV ratio in an additive fashion, we found that 99 patients with a high RVGLS (>17.7%) and low RV/LV ratio (<1.03) had a 30‐day mortality of 1.0%. Conversely, 39 patients with a low RVGLS (≤17.7%) and high RV/LV ratio (≥1.03) had a 30‐day mortality of 46.2%. Kaplan–Meier analysis depicted the significantly different prognosis among the groups (P<0.001). Conclusions The combined evaluation of RVGLS and RV/LV ratio is a practical method of evaluating RV dysfunction. Using both parameters in patients with intermediate‐risk pulmonary embolism identifies those at highest and lowest risk of short‐term mortality. This approach offers promise for improved risk stratification and guidance of treatment pathways.

Background: Intermediate-risk pulmonary embolism (PE) is common and associated with significant mortality. We previously demonstrated that right ventricular global longitudinal strain (RVGLS) predicted short-term outcomes in intermediate-risk PE in a single-center retrospective cohort study using data up to 2018, identifying a best cutoff value of 17.7 %. However, limited evidence exists regarding the prognostic utility of RVGLS in more recent cohorts following the 2019 European Society of Cardiology guideline update. We conducted an external validation study using data from another institution between 2019 and 2022. Methods: Retrospective cohort study of 119 patients with intermediate-risk PE from 2019 to 2022. The primary outcome was all-cause 30-day mortality. Echocardiographic parameters were compared between survivors and non-survivors. RVGLS and right atrial (RA) strain were applied using Philips software. Receiver operating characteristic (ROC) curves analysis and Kaplan-Meier analysis were performed to assess prognostic value. Results: Among patients (mean age: 66.1 years, 48.7 % female), mortality at 30 days occurred in 6 patients (5.0 %). Image quality was sufficient to perform RV and RA strain analysis in 110 patients (92.4 %) and 105 patients (88.2 %). Non-survivors had significantly lower RVGLS (17.3 % vs. 19.6 %, p = 0.013) and RA strain (25.8 % vs. 31.4 %, p = 0.040) than survivors. Univariate analysis showed both RVGLS (odds ratio [OR] 0.567, p = 0.033) and RA strain (OR 0.865, p = 0.046) were associated with 30-day mortality. In ROC curves analysis, RVGLS had a higher area under the curve of 0.802 (Figure 1), compared to 0.751 for RA strain. Applying the previously reported cutoff of 17.7 %, the ROC curve provided 66.7 % sensitivity and 72.1 % specificity. When patients were divided into two groups utilizing the RVGLS value of 17.7 %, Kaplan-Meier curves demonstrated patients with low RVGLS had higher risk of 30-day mortality compared to those with high RVGLS (Log rank P = 0.042. Figure 2). Conclusions: In this external cohort, reduced RVGLS at baseline was associated with increased 30-day mortality in patients with intermediate-risk PE. These data validate the prognostic significance of RVGLS previously reported in a single-center study. Prospective studies are warranted to evaluate whether incorporating RVGLS into treatment algorithms can impact care and improve patient outcomes.

BACKGROUND:Black women with peripartum cardiomyopathy (PPCM) have a higher prevalence of hypertensive disorders of pregnancy (HDP) and worse clinical outcomes compared with non-Black women. We examined the impact of HDP on myocardial recovery in Black women with PPCM. METHODS:A total of 100 women were enrolled into the Investigation in Pregnancy Associated Cardiomyopathy (IPAC) study. Left ventricular ejection fraction (LVEF) was assessed by echocardiography at entry, 6, and 12-months post-partum (PP). Women were followed for 12 months postpartum and outcomes including persistent cardiomyopathy (LVEF ≤35%), left ventricular assist device, (LVAD), cardiac transplantation, or death were examined in subsets based on race and the presence of HDP. RESULTS:Black women with HDP were more likely to present earlier compared to Black women without HDP (days PP HDP: 34 ± 21 vs 54 ± 27 days, P = .03). There was no difference in LVEF at study entry for Black women based on HDP, but better recovery with HDP at 6 (HDP: 52 ± 11% vs no HDP: 40 ± 14%, P = .03) and 12-months (HDP:53 ± 10% vs no HDP:40 ± 16%, P = .02). At 12-months, Black women overall had a lower LVEF than non-Black women (P < .001), driven by less recovery in Black women without HDP compared to non-Black women (P < .001). In contrast, Black women with HDP had a similar LVEF at 12 months compared to non-Black women (P = .56). CONCLUSIONS:In women with PPCM, poorer outcomes evident in Black women were driven by women without a history of HDP. In Black women, a history of HDP was associated with earlier presentation and recovery which was comparable to non-Black women.

BACKGROUND:Right ventricular (RV) systolic dysfunction has been identified as a prognostic marker for adverse clinical events in patients presenting with acute pulmonary embolism (PE). However, challenges exist in identifying RV dysfunction using conventional echocardiography techniques. Strain echocardiography is an evolving imaging modality which measures myocardial deformation and can be used as an objective index of RV systolic function. This study evaluated RV Global Longitudinal Strain (RVGLS) in patients with intermediate risk PE as a parameter of RV dysfunction, and compared to traditional echocardiographic and CT parameters evaluating short-term mortality. METHODS:Retrospective single center cohort study of 251 patients with intermediate-risk PE between 2010 and 2018. The primary outcome was all-cause mortality at 30 days. Statistical analysis evaluated each parameter comparing survivors versus non-survivors at 30 days. Receiver operating characteristic (ROC) curves and Kaplan-Meier curves were used for comparison of the two cohorts. RESULTS:Altogether 251 patients were evaluated. Overall mortality rate was 12.4%. Utilizing an ROC curve, an absolute cutoff value of 17.7 for RVGLS demonstrated a sensitivity of 93% and specificity of 70% for observed 30-day mortality. Individuals with an RVGLS ≤17.7 had a 25 times higher mortality rate than those with RVGLS above 17.7 (HR 25.24, 95% CI = 6.0-106.4, p < .001). Area under the curve was (.855), RVGLS outperformed traditional echocardiographic parameters, CT findings, and cardiac biomarkers on univariable and multivariable analysis. CONCLUSIONS:Reduced RVGLS values on initial echocardiographic assessment of patients with intermediate-risk PE identified patients at higher risk for mortality at 30 days.

Aims Heart failure (HF) outcomes remain poor despite optimal guideline-directed medical therapy (GDMT). We assessed safety, effectiveness, and transthoracic echocardiographic (TTE) outcomes during the 12 months after Ventura shunt implantation in the RELIEVE-HF open-label roll-in cohort. Methods and results Eligibility required symptomatic HF despite optimal GDMT with >= 1 HF hospitalization in the prior year or elevated natriuretic peptides. The safety endpoint was device-related major adverse cardiovascular or neurological events at 30 days, compared to a prespecified performance goal. Effectiveness evaluations included the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline, 1, 3, 6, and 12 months and TTE at baseline and 12 months. Overall, 97 patients were enrolled and implanted at 64 sites. Average age was 70 +/- 11 years, 97% were in New York Heart Association class III, and half had left ventricular ejection fraction (LVEF) <= 40%. The safety endpoint was achieved (event rate 0%, p < 0.001). KCCQ overall summary score was improved by 12-16 points at all follow-up timepoints (all p < 0.004), with similar outcomes in patients with reduced and preserved LVEF. At 12 months, left ventricular end-systolic and end-diastolic volumes were reduced (p = 0.020 and p = 0.038, respectively), LVEF improved (p = 0.009), right ventricular end-systolic and end-diastolic areas were reduced (p = 0.001 and p = 0.030, respectively), and right ventricular fractional area change (p < 0.001) and tricuspid annular plane systolic excursion (p < 0.001) improved. Conclusion Interatrial shunting with the Ventura device was safe and resulted in favourable clinical effects in patients with HF, regardless of LVEF. Improvements of left and right ventricular structure and function were consistent with reverse myocardial remodelling. These results would support the potential of this shunt device as a treatment for HF.

Peripartum cardiomyopathy (PPCM) is an idiopathic form of pregnancy-induced heart failure associated with preeclampsia. Circulating factors in late pregnancy are thought to contribute to both diseases, suggesting a common underlying pathophysiological process. However, what drives this process remains unclear. Using serum proteomics, we identified the senescence-associated secretory phenotype (SASP), a marker of cellular senescence associated with biological aging, as the most highly up-regulated pathway in young women with PPCM or preeclampsia. Placentas from women with preeclampsia displayed multiple markers of amplified senescence and tissue aging, as well as overall increased gene expression of 28 circulating proteins that contributed to SASP pathway enrichment in serum samples from patients with preeclampsia or PPCM. The most highly expressed placental SASP factor, activin A, was associated with cardiac dysfunction or heart failure severity in women with preeclampsia or PPCM. In a murine model of PPCM induced by cardiomyocyte-specific deletion of the gene encoding peroxisome proliferator–activated receptor γ coactivator-1α, inhibiting activin A signaling in the early postpartum period with a monoclonal antibody to the activin type II receptor improved heart function. In addition, attenuating placental senescence with the senolytic compound fisetin in late pregnancy improved cardiac function in these animals. These findings link senescence biology to cardiac dysfunction in pregnancy and help to elucidate the pathogenesis underlying cardiovascular diseases of pregnancy.

AbstractAimsOne third of patients do not improve after cardiac resynchronization therapy (CRT). Septal flash (SF) and apical rocking (ApRock) are deformation patterns observed on echocardiography in most patients eligible for CRT. These markers of mechanical dyssynchrony have been associated to improved outcome after CRT in observational studies and may be useful to better select patients. The aim of this trial is to investigate whether the current guideline criteria for selecting patients for CRT should be modified and include SF and ApRock to improve therapy success rate, reduce excessive costs and prevent exposure to device‐related complications in patients who would not benefit from CRT.MethodsThe AMEND‐CRT trial is a multicentre, randomized, parallel‐group, double‐blind, sham‐controlled trial with a non‐inferiority design. The trial will include 578 patients scheduled for CRT according to the 2021 ESC guidelines who satisfy all inclusion criteria. The randomization is performed 1:1 to an active control arm (‘guideline arm’) or an experimental arm (‘echo arm’). All participants receive a device, but in the echo arm, CRT is activated only when SF or ApRock or both are present. The outcome of both arms will be compared after 1 year. The primary outcome measures are the average change in left ventricular end‐systolic volume and patient outcome assessed using a modified Packer Clinical Composite Score.ConclusionsThe findings of this trial will redefine the role of echocardiography in CRT and potentially determine which patients with heart failure and a prolonged QRS duration should receive CRT, especially in patients who currently have a class IIa or class IIb recommendation.

Background: Right atrial (RA) function contributes 15 - 30% to right ventricular stroke volume. However, limited studies have evaluated RA function in the setting of submassive pulmonary embolism (PE). We investigated whether the severity of right atrial dyssynchrony was associated with short-term mortality in patients with submassive PE. Methods: We performed a retrospective cohort study of 251 patient with submassive PE. Strain analysis was applied retroactively using TomTec software. 201 patients had images sufficient for RA strain analysis. RA dyssynchrony was defined as absolute max opposing wall delay (maxOWD) which was the time interval between peak lateral and septal wall strain in RA (Figure1) The primary outcome was 30-day all-cause mortality. The severity of dyssynchrony was defined according to max OWD and divided into four groups; no delay, first tertile (mild), second tertile (moderate), and third tertiles (severe). Results: The patient groups were defined as follows: no delay (0 ms; n = 40), first tertile/mild delay (> 0 ms, ≤ 4.49 ms; n = 52), second tertile/moderate delay (> 4.49 ms, ≤ 13.1 ms; n = 51), and third tertile/severe delay (> 13.1 ms; n = 52). Of 201 patients, 23 patients (11 %) died within 30 days after diagnosis. Kaplan-Meier curves showed significant difference among the four groups (p < 0.001). Additionally, there were significant differences between no delay and moderate delay groups (p = 0.0321) and between moderate and severe delay groups (p=0.010). (Figure2) Moreover, patients with severe RA dyssynchrony had 7.3 times higher risk of 30-day mortality compared to patients in other groups (p < 0.001). Conclusions: The severity of RA dyssynchrony on presentation was associated with mortality in patients with submassive PE. Assessment of RA dyssynchrony on presentation could risk stratify patients with submassive PE.

AbstractAimsInteratrial shunts are under evaluation as a treatment for heart failure (HF); however, their in vivo flow performance has not been quantitatively studied. We aimed to investigate the fluid dynamics properties of the 0.51 cm orifice diameter Ventura shunt and assess its lumen integrity with serial transesophageal echocardiography (TEE).Methods and resultsComputational fluid dynamics (CFD) and bench flow tests were used to establish the flow‐pressure relationship of the shunt. Open‐label patients from the RELIEVE‐HF trial underwent TEE at shunt implant and at 6 and 12 month follow‐up. Shunt effective diameter (Deff) was derived from the vena contracta, and flow was determined by the continuity equation. CFD and bench studies independently validated that the shunt's discharge coefficient was 0.88 to 0.89. The device was successfully implanted in all 97 enrolled patients; mean age was 70 ± 11 years, 97% were NYHA class III, and 51% had LVEF ≤40%. Patency was confirmed in all instances, except for one stenotic shunt at 6 months. Deff remained unchanged from baseline at 12 months (0.47 ± 0.01 cm, P = 0.376), as did the trans‐shunt mean pressure gradient (5.1 ± 3.9 mmHg, P = 0.316) and flow (1137 ± 463 mL/min, P = 0.384). TEE measured flow versus pressure closely correlated (R2 ≥ 0.98) with a fluid dynamics model. At 12 months, the pulmonary/systemic flow Qp/Qs ratio was 1.22 ± 0.12.ConclusionsWhen implanted in patients with advanced HF, this small interatrial shunt demonstrated predictable and durable patency and performance.

Background: Initiation of Guideline-Directed Medical Therapy (GDMT) in patients who have heart failure with reduced ejection fraction (HFrEF) has been shown to improve left ventricular EF, decrease hospitalizations, and reduce mortality. GDMT includes an angiotensin receptor/neprilysin inhibitor (ARNI). However, the relative importance of initiating or maintaining ARNI therapy during titration of GDMT and the impact on changes in left ventricular (LV) and right ventricular (RV) function is unknown. Methods: We enrolled 173 patients with HF in a GDMT clinic prospectively between 2020 to 2022. Of 173 patients, 63 HFrEF patients with baseline and 3-12 months follow-up transthoracic echocardiography (TTE) were included in this post-hoc analysis. Patients were divided into three groups; patients with initiation of ARNI after baseline TTE (Group 1), patients with continuation of ARNI that was started before baseline TTE (Group 2), patient who were not on ARNI during evaluation period (Group 3). LVEF as calculated by volumetric assessment, LV global longitudinal strain (LVGLS), RV fraction area change (RVFAC), and RV global longitudinal strain (RVGLS) were evaluated in this study. Strain analysis of LVGLS and RVGLS were applied using TomTec. Results: The mean age was 64 years, the mean time between TTEs was 6.9 months. Improvement in biventricular function and strain were noted between baseline and follow up data. (Figure 1) Changes of the four parameters for each group between the two TTEs are shown in Figure 2. In patients initiated on ARNI therapy (Group 1) there was a significant improvement from baseline to follow up TTEs in all parameters. (LVEF; p < 0.001, LVGLS; p < 0.001, RVFAC; p = 0.003, and RVGLS; p = 0.003) In group 2, we noted significant improvements in LVEF, LVGLS, and RVGLS from baseline to follow up. (LVEF; p < 0.001, LVGLS; p < 0.001, and RVGLS; p = 0.005) In those not on ARNI (Group 3), there was no statistical difference noted in any of the 4 parameters between baseline and follow up TTE. Conclusion: In patients with HFrEF, who had routing follow-up in a GDMT clinic, those initiated or continued on ARNI had significant improvement in biventricular function and biventricular strain measurements, compared to those who were not taking an ARNI.

Background: Submassive pulmonary embolisms (sPE) are common and carry significant mortality. Strain imaging presents a novel method of assessing right atrial (RA) function. However, there are less reports focused on the feature of RA strain in patients with sPE. This study examines whether RA strain has different cutoff values according to aging in patients with sPE. Method: We performed a retrospective cohort study of 221 patients with sPE. The primary outcome was 30-day all-cause mortality. RA strain was analyzed retrospectively using TOMTEC ®. All patients were divided into three age groups according to tertiles. Receiver operating characteristic (ROC) curves were performed for evaluation. Result: Median age was 65 years and 31 patients died within 30 days. Of 221 patients, 84 patients (38%) were elder group (70 ≤ age), 66 patients (30%) were middle-aged group (58 ≤ age ≤ 69), and 71 patients (32%) were young group (age < 58). In all patients, statistical difference was observed in RA strain among the three groups (p = 0.042). ROC curve to predict 30-day mortality depicted area under the curve (AUC) and best cutoff value (BCV) were 0.688 and 27.7, respectively. (sensitivity [SE] 0.704, specificity [SP] 0.642) In elder group, ROC demonstrated AUC of 0.656 and BCV of 28.9 (SE 0.480, SP 0.889). In middle-aged group, ROC showed AUC of 0.647 and BCV of 27.7 (SE 0.636, SP 0.694). Interestingly, in young group, ROC demonstrated the lowest BCV of 17.4 with AUC of 0.75 (SE 0.571, SP 0.984) (Figure). Conclusion: RA strain as best cutoff shows different values among different age groups, especially low value in young groups. Further validation is needed to determine the role and utility of strain in patients with submassive PE.

Introduction and Hypothesis: Right ventricular (RV) dysfunction has been identified as a prognostic marker for adverse clinical events in patients with submassive pulmonary embolism (PE). We hypothesized that combination of right-sided strain analysis and conventional parameters can further risk stratify patients at high risk for mortality. Methods: Retrospective cohort study of patients with submassive PE between 2010 and 2018. The primary outcome was all-cause mortality at 30 days. Echocardiographic parameters including right to left ventricular end-diastolic diameter ratio (RV/LV ratio), RV global longitudinal strain (RVGLS), RV free wall strain and right atrium strain were compared between survivors and non-survivors. Multivariable analysis and receiver operator characteristic (ROC) curves analysis were used to demonstrate the predictive value of baseline measurements. Results: 251 patients were analyzed. Overall mortality rate at 30 days was 12.4 %. Multivariable analysis revealed RV/LV ratio was an independent predictor of 30-day mortality in conventional parameters, and RVGLS was also an independent predictor among the three strain parameters. ROC curves indicated that the best cutoff values for RVGLS and RV/LV ratio to predict mortality were 17.7 % and 1.03. When the 230 patients with measurable RVGLS and RV/LV ratio were divided into four groups using both cutoff values, patients with both high RVGLS and low RV/LV ratio had the lowest mortality (1.0 % at 30 days; n = 99) while patients with both low RVGLS and high RV/LV ratio had the highest mortality (46.2 % at 30 days; n = 39). Kaplan-Meier curves depicted the significantly different prognosis among the four groups (p < 0.001. Figure). Conclusions: The combination of RVGLS and RV/LV ratio can help further risk stratify patients with submassive PE. This may identify patients at highest risk of mortality and ultimately alter treatment pathways.