Impaired Global Longitudinal Strain Research Articles

Global longitudinal strain by cardiac magnetic resonance is associated with cardiac iron and complications in beta-thalassemia major patients

BackgroundThe aim of this cross-sectional study was to investigate the association of left ventricular (LV) strain parameters with demographics, clinical data, cardiovascular magnetic resonance (CMR) findings, and cardiac complications (heart failure and arrhythmias) in patients with β-thalassemia major (β-TM). MethodWe considered 266 β-TM patients (134 females, 37.08 ± 11.60 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) project and 80 healthy controls (50 females, mean age 39.77 ± 11.29 years). The CMR protocol included cine images for the assessment of global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) using feature tracking (FT) and for the quantification of LV function parameters, the T2* technique for the assessment of myocardial iron overload, and late gadolinium enhancement (LGE) technique. ResultsIn comparison to the healthy control group, β-TM patients showed impaired GLS, GCS, and GRS values.Among β-TM patients, sex was identified as the sole independent determinant of all LV strain parameters. All LV strain parameters displayed a significant correlation with LV end-diastolic volume index, end-systolic volume index, mass index, and ejection fraction, and with the number of segments exhibiting LGE. Only GLS exhibited a significant correlation with global heart T2* values and the number of segments with T2* < 20 ms. Patients with cardiac complications exhibited significantly impaired GLS compared to those without cardiac complications. ConclusionIn patients with β-TM, GLS, GCS, and GRS were impaired in comparison with control subjects. Among LV strain parameters, only GLS demonstrated a significant association with cardiac iron levels and complications.

Myocardial Blood Flow Reserve, Microvascular Coronary Health, and Myocardial Remodeling in Patients With Aortic Stenosis.

Coronary microvascular function and hemodynamics may play a role in coronary circulation and myocardial remodeling in patients with aortic stenosis (AS). We aimed to evaluate the relationship between myocardial blood flow and myocardial function in patients with AS, no AS, and aortic valve sclerosis. We included consecutive patients who had resting transthoracic echocardiography and clinically indicated positron emission tomography myocardial perfusion imaging to capture their left ventricular ejection fraction, global longitudinal strain (GLS), and myocardial flow reserve (MFR). The primary outcome was major adverse cardiovascular event (all-cause mortality, myocardial infarction, or late revascularization). There were 2778 patients (208 with aortic sclerosis, 39 with prosthetic aortic valve, 2406 with no AS, and 54, 49, and 22 with mild, moderate, and severe AS, respectively). Increasing AS severity was associated with impaired MFR (P<0.001) and GLS (P<0.001), even when perfusion was normal. Statistically significant associations were noted between MFR and GLS, MFR and left ventricular ejection fraction, and MFR and left ventricular ejection fraction reserve. After a median follow-up of 349 (interquartile range, 116-662) days, 4 (7.4%), 5 (10.2%), and 6 (27.3%) patients experienced a major adverse cardiovascular event in the mild, moderate, and severe AS groups, respectively. In a matched-control analysis, patients with mild-to-moderate AS had higher rates of impaired MFR (52.9% versus 39.9%; P=0.048) and major adverse cardiovascular event (11.8% versus 3.0%; P=0.002). Despite lack of ischemia, as severity of AS increased, MFR decreased and GLS worsened, reflecting worse coronary microvascular health and myocardial remodeling. Positron emission tomography-derived MFR showed a significant independent correlation with left ventricular ejection fraction and GLS. Patients with prosthetic aortic valve showed a high prevalence of impaired MFR.

Prognostic Implications of Left Ventricular Hypertrophy and Mechanical Function in Fabry Disease: A Longitudinal Cohort Study

The prognostic value of different grades of left ventricular hypertrophy (LVH) and left ventricular (LV) mechanical function in Fabry disease is unclear. We aimed to evaluate the association between the severity of LVH, LV mechanical function, and clinical outcomes in Fabry disease. We conducted a retrospective cohort study from a single-center registry of adult patients with Fabry disease. Left ventricular mass index (LVMI) was measured by echocardiography. The severity of LVH was categorized by LVMI using the sex-specific cutoff values. Left ventricular mechanical function was measured as LV global longitudinal strain (GLS) by speckle-tracking analysis. The primary outcome was a composite of major adverse cardiovascular events (MACE) at 5years, including heart failure hospitalization, sustained ventricular tachycardia, acute ischemic stroke, and all-cause mortality. The study included 268 patients (age 50.4±15.4years, men 46.6%) with Fabry disease (83.2% IVS4+919G>A mutation), and 106 patients (39.6%) had LVH. Patients with mild, moderate, or severe LVH had 5-year MACE rates of 7.4%, 10%, and 30.5%, respectively (P<.001). Moreover, patients with impaired LV GLS (<14.1%) had a higher 5-year MACE rate than those with preserved LV GLS (32.1% vs 2.4%, P<.001). Severe LVH was an independent predictor of MACE compared with absence of LVH (adjusted hazard ratio, 12.73; 95% CI, 1.3-124.71; P=.03), after adjusting for age, sex, hypertension, hyperlipidemia, atrial fibrillation, renal function, average E/e', enzyme replacement therapy, and LV GLS. Patients with severe LVH and impaired LV GLS had the highest incidence for MACE (log-rank P<.05), irrespective of sex, genotypes, and whether receiving enzyme replacement therapy or not. Sex-specific grading of LVH by LVMI is practical for risk stratification in patients with Fabry disease, and impaired LV GLS further refines the prognostication.

The role of aetiology in cardiac manifestations of chronic kidney disease: the CPH-CKD ECHO study.

We investigated the associations between cardiac parameters and aetiologies of CKD in an exploratory study. The study population consisted of 883 participants, 174 controls and 709 patients with aetiologies of CKD including diabetic nephropathy/renovascular KD in diabetes mellitus, hypertensive/renovascular nephropathy, tubulointerstitial nephritis, glomerulonephritis/vasculitis, polycystic KD (PKD), and CKD of unknown origin. Echocardiographic measures included left ventricular (LV) ejection fraction, global longitudinal, area, and radial strain, E/e' ratio, and LV mass index. These were compared between each aetiological group and controls in unadjusted and adjusted analysis. In unadjusted analysis, patients with diabetic nephropathy/renovascular KD in diabetes mellitus, had impaired LV ejection fraction (Median [IQR]: 56% [49.9,60.69] vs. 60.8% [57.7,64.1]), global longitudinal (mean ± SD: 13.1 ± 3.5% vs. 15.5 ± 2.6%), area (24.1 ± 5.8% vs. 28.5 ± 4.2%), and radial strain (36.2 ± 11.2% vs. 44.1 ± 9.7%), and increased LV mass index (89.1g/m2 [71.8,104.9] vs. 69,0g/m2 [57.9,80.8]) and E/e' ratio (10.6 [8.5,12.6] vs. 7 [5.8,8.3], p < 0.001 for all) compared with controls. Associations were similar for CKD of unknown origin. Patients with hypertensive/renovascular nephropathy had impaired global longitudinal and area strain, and higher E/e' ratio. Patients with glomerulonephritis/vasculitis had higher LV mass index, while patients with PKD had better global longitudinal strain than controls. All findings remained significant in adjusted analysis, except for the impaired global longitudinal strain in hypertensive/renovascular nephropathy. Glomerulonephritis/vasculitis, hypertensive/renovascular nephropathy, CKD of unknown origin, and diabetic nephropathy/renovascular KD in diabetes mellitus were increasingly associated with adverse cardiac findings, while PKD and tubulointerstitial nephritis were not. Aetiology might play a role regarding the cardiac manifestations of CKD.

Evaluation of left ventricular function in patients with mitral annular disjunction using speckle tracking echocardiography.

Mitral annular disjunction (MAD) is a structural abnormality characterized by the systolic detachment of the posterior mitral annulus and the ventricular myocardium. It is usually observed coexistent with mitral valve prolapse (MVP) and associated with a mechanical dysfunction despite preserved electrical isolation function of the mitral annulus. This study aimed to evaluate left ventricular (LV) function using speckle tracking echocardiography in MVP patients with MAD. This study was designed as a prospective, single-center study including 103 patients with MVP and 40 age- and sex-matched control subjects. Transthoracic echocardiography and cardiac magnetic resonance imaging were performed to assess LV function and MAD presence. MAD (+) MVP (n=34), MAD (-) MVP (n=69), and control (n=40) groups were enrolled in the study. Among the MVP patients, 34 (33%) had MAD. T-negativity in the inferior leads on electrocardiography was more frequent in the MAD (+) group than in the MAD (-) patients (4.3%vs. 20.6%, p=.014). Mitral regurgitation degree, Pickelhaube sign (17.6%vs. 1.4%, p=.005), and late gadolinium enhancement frequency (35.3%vs. 10.6%, p=.002) were significantly higher in MAD (+) patients. MAD (+) patients had significantly impaired global longitudinal strain (-23.1±2.1vs. -23.5±2.3, p<.001), basal longitudinal strain (BLS) (-19.6±1.5vs. -20.5±1.9, p<.001), Mid-Ventricular Longitudinal Strain (-22.2±1.7vs. -23.2±2.2, p<.001) and LA strain (-24.5±3.9vs. -27.2±3.6, p<.001) when compared to MAD (-) MVP patients, despite similar LV ejection fraction. All these values of MVP patients were also significantly lower than the control group. The mean MAD distance was 7.8±3.2mm in MAD (+) patients. Patients with two or more symptoms were higher in the MAD (+) group than in the MAD (-) group (4.3%vs. 44.1%, p<.001). This study demonstrated a significant decrease in longitudinal strain in MVP patients with MAD, indicating myocardial dysfunction. These findings suggest that MAD may contribute to LV dysfunction and highlight the importance of early detection in younger patients. Further research is needed to explore the functional implications and long-term outcomes of MAD.

Characterization of anthracycline-induced cardiotoxicity by diffusion tensor magnetic resonance imaging.

Anthracyclines are highly potent anti-cancer drugs, but their clinical use is limited by severe cardiotoxic side effects. The impact of anthracycline-induced cardiotoxicity (AIC) on left ventricular (LV) microarchitecture and diffusion properties remains unknown. This study sought to characterize AIC by cardiovascular magnetic resonance diffusion tensor imaging (DTI). Mice were treated with Doxorubicin (DOX; n = 16) for induction of AIC or saline as corresponding control (n = 15). Cardiac function was assessed via echocardiography at the end of the study period. Whole hearts (n = 8 per group) were scanned ex vivo by high-resolution DTI at 7T. Results were correlated with histopathology and mass spectrometry imaging. Mice with AIC demonstrated systolic dysfunction (LVEF 52 ± 3% vs. 43 ± 6%, P < 0.001), impaired global longitudinal strain (-19.6 ± 2.0% vs. -16.6 ± 3.0%, P < 0.01), and cardiac atrophy (LV mass index [mg/mm], 4.3 ± 0.1 vs. 3.6 ± 0.2, P < 0.01). Regional sheetlet angles were significantly lower in AIC, whereas helix angle and relative helicity remained unchanged. In AIC, fractional anisotropy was increased (0.12 ± 0.01 vs. 0.14 ± 0.02, P < 0.05). DOX-treated mice displayed higher planar and less spherical anisotropy (CPlanar 0.07 ± 0.01 vs. 0.09 ± 0.01, P < 0.01; CSpherical 0.89 ± 0.01 vs. 0.87 ± 0.02, P < 0.05). CPlanar and CSpherical yielded good discriminatory power to distinguish between mice with and without AIC (c-index 0.91 and 0.84, respectively, P for both <0.05). AIC is associated with regional changes in sheetlet angle but no major abnormalities of global LV microarchitecture. The geometric shape of the diffusion tensor is altered in AIC. DTI may provide a new tool for myocardial characterization in patients with AIC, which warrants future clinical studies to evaluate its diagnostic utility.

Speckle-tracking global longitudinal strain predicts death and cardiovascular events in patients with systemic sclerosis.

Albeit often asymptomatic, heart involvement in systemic sclerosis (SSc) represents a negative prognostic factor, accounting for nearly one-fourth of all deaths. Global longitudinal strain (GLS) is accurate in detecting heart involvement in patients with SSc and no overt cardiac disease and allows early detection and longitudinal monitoring, but its association with clinical endpoints has not been tested so far. The primary outcome was the association between left and right GLS and mortality for all causes. The secondary outcome was the association between left and right GLS and hospitalizations. A prospective longitudinal study enrolling all consecutive patients with SSc without structural heart disease or previous cardiovascular event.A total of 164 patients were enrolled, of whom 19 (11.5%) died during follow-up and 48 (29.3%) were hospitalized. Both left (LV) and right ventricle (RV) GLS at enrolment were independently associated with an increased risk of death for all causes and hospitalizations. Patients with biventricular GLS impairment, respectively, had a 4.2-, 4.9-, and 13.9-fold increased risk of death when compared with patients with only LV, only RV, or no impairment (P < 0.001). The incidence of hospitalization in patients with biventricular GLS impairment was nearly four times higher when compared with patients with only LV or only RV impairment, and nine times higher when compared with normal biventricular GLS (P < 0.001). Biventricular GLS is associated with an increased risk of death and hospitalization in patients with SSc during a median of 3-year follow-up, acting as a reliable and accurate prognostic tool in everyday practice.

Evaluation of the Relationship Between Vitamin D Deficiency and Subclinical Cardiac Dysfunction Using 2D/3D Strain Echocardiography in Healthy People.

Vitamin D deficiency has a high prevalence in the population and is highly associated with cardiovascular diseases. The aim of this study was to evaluate subclinical left ventricular (LV) function using strain analysis in healthy individuals with vitamin D deficiency. 113 healthy volunteers were enrolled in the study (age, 44.1±7 yrs, 34 male). All volunteers underwent two-dimensional (2D) and three-dimensional (3D) speckle tracking echocardiography after conventional echocardiographic evaluation. The subjects were divided into two groups according to their vitamin D concentrations. 61 subjects with vitamin D less than 20 ng / ml were included in the vitamin D deficiency group. The baseline clinical characteristics, laboratory measurements, echocardiographic data, including 2D and 3D global longitudinal strain (GLS) values, were compared between the groups. The 2D GLS values of the subjects with vitamin D deficiency were lower (mathematically less negative) than subjects with normal vitamin D (-16.1±3.4 vs -19.3±4.2, p&lt;0.001). Similarly, the 3D GLS results were lower in subjects with vitamin D deficiency (-18.3±5.2 vs -24.1±6.9, p&lt;0.001). A significant correlation was detected between the vitamin D concentrations and the 2D and 3D GLS measurements. (r=0.765 and r=0.628, respectively, p&lt;0.001). Vitamin D was found to be an independent predictor of impaired 2D and 3D LV GLS (p=0.031, p=0.023, respectively). Subclinical LV dysfunction in healthy individuals with vitamin D deficiency was demonstrated by 3D and 2D strain analysis. Due to potential negative effects of vitamin D deficiency on cardiac function, more attention should be paid to healthy individuals with vitamin D deficiency.

Clinical implications of subclinical left ventricular dysfunction in heart failure with preserved ejection fraction: The PARAGON-HF study.

Left ventricular (LV) subclinical impairment has been described in heart failure with preserved ejection fraction (HFpEF). We assessed the relationship between LV myocardial deformation by strain imaging and recurrent hospitalization for heart failure (HF) or cardiovascular death in a large international HFpEF population. We assessed two-dimensional speckle-tracking based global longitudinal strain (GLS) in 790 patients (mean age 74 ± 8 years, 54% female) with adequate image quality enrolled in the PARAGON-HF echocardiography study. We examined the relationship of GLS with total HF hospitalizations and cardiovascular death (the primary composite outcome) after accounting for clinical confounders. Approximately 47% of the population had evidence of LV subclinical dysfunction, defined as absolute GLS <16%. Impaired GLS was significantly associated with higher values of circulating baseline N-terminal pro-B-type-natriuretic peptide. After a median follow-up of 3.0 years, there were 407 total HF hospitalizations and cardiovascular deaths. After multivariable adjustment, worse GLS was associated with a greater risk for the primary composite outcome (adjusted hazard ratio per 1% decrease: 1.06; 95% confidence interval 1.02-1.11; p = 0.008). GLS did not modify the treatment effect of sacubitril/valsartan compared with valsartan for the composite outcome (p for interaction >0.1). In a large HFpEF population, impaired LV function was observed even among patients with preserved ejection fraction, and was associated with an increased risk of total HF hospitalizations or cardiovascular death, accounting for clinical confounders. These findings highlight the key role of subtle LV systolic impairment in the pathophysiology of HFpEF.

The relationship between coronary artery calcium and layer-specific global longitudinal strain in patients with suspected coronary artery disease.

Layer-specific global longitudinal strain (GLS) may provide important insights in patients with suspected coronary artery disease (CAD). We aimed to investigate the association between layer-specific GLS and coronary artery calcium score (CACS) in patients suspected of CAD. We performed a retrospective study of patients suspected of CAD who underwent both an echocardiogram and cardiac computed tomography (median 42 days between). Layer-specific (endocardial-, whole-layer-, and epicardial-) GLS was measured using speckle tracking echocardiography. We assessed the continuous association between layer-specific GLS and CACS by negative binomial regression, and the association with high CACS (≥400) using logistic regression. Of the 496 patients included (mean age 59 years, 56% male), 64 (13%) had a high CACS. Those with high CACS had reduced GLS in all layers compared to those with CACS<400 (endocardial GLS: -20.5vs. -22.7%, whole-layer GLS: -17.7vs. -19.4%, epicardial GLS: -15.3vs. -16.9%, p<.001 for all). Negative binomial regression revealed a significant continuous association showing increasing CACS with worsening GLS in all layers, which remained significant after multivariable adjustment including SCORE chart risk factors. All layers of GLS were associated with high CACS in univariable analyses, which was consistent after multivariable adjustment (endocardial GLS: OR=1.11 (1.03-1.20); whole-layer GLS: OR=1.14 (1.04-1.24); epicardial GLS: OR=1.16 (1.05-1.29), per 1% absolute decrease). In this study population with patients suspected of CAD and normal systolic function, impaired layer-specific GLS was continuously associated with increasing CACS, and decreasing GLS in all layers were associated with presence of high CACS.

Association of global longitudinal strain by feature tracking cardiac magnetic resonance imaging with adverse outcomes among community-dwelling adults without cardiovascular disease: The Dallas Heart Study.

Left ventricular (LV) global longitudinal strain (GLS) may detect subtle abnormalities in myocardial contractility among individuals with normal LV ejection fraction (LVEF). However, the prognostic implications of GLS among healthy, community-dwelling adults is not well-established. Overall, 2234 community-dwelling adults (56% women, 47% Black) with LVEF ≥50% without a history of cardiovascular disease (CVD) from the Dallas Heart Study who underwent cardiac magnetic resonance (CMR) with GLS assessed by feature tracking CMR (FT-CMR) were included. The association of GLS with the risk of incident major adverse cardiovascular events (MACE; composite of incident myocardial infarction, incident heart failure [HF], hospitalization for atrial fibrillation, coronary revascularization, and all-cause death), and incident HF or death were assessed with adjusted Cox proportional hazards models. A total of 309 participants (13.8%) had MACE during a median follow-up duration of 17 years. Participants with the worst GLS (Q4) were more likely male and of the Black race with a history of tobacco use and diabetes with lower LVEF, higher LV end-diastolic volume, and higher LV mass index. Cumulative incidence of MACE was higher among participants with worse (Q4 vs. Q1) GLS (20.4% vs. 9.0%). In multivariable-adjusted Cox models that included clinical characteristics, cardiac biomarkers and baseline LVEF, worse GLS (Q4 vs. Q1) was associated with a significantly higher risk of MACE (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.07-2.24, p = 0.02) and incident HF or death (HR 1.57, 95% CI 1.03-2.38, p = 0.04). Impaired LV GLS assessed by FT-CMR among adults free of cardiovascular disease is associated with a higher risk of incident MACE and incident HF or death independent of cardiovascular risk factors, cardiac biomarkers and LVEF.

Permanent longitudinal strain damage of cardiotoxic drugs in childhood cancer: What is the safe level?

Anthracycline administration in children is associated with cardiac dysfunction. Speckle-tracking echocardiography (STE) can detect subclinical cardiac damage that may go undetected by conventional two-dimensional (2D) echocardiography. This study aims to investigate medium-term anthracycline cardiotoxicity using STE and determine a safer administrable level of anthracyclines (ACs). This observational case-control study enrolled 37 healthy controls and 78 pediatric cancer survivors who received chemotherapy. The patients were divided into two groups: cardiotoxic received (CR) and cardiotoxic free (CF). Data on segmental longitudinal strain (LS), global LS (GLS), and 2D echocardiographic parameters were collected after a drug-free period of at least one year. A total of 115 children with a mean age of 108 ± 55 months, of whom 66% were males, were included in the study. Both the groups of cancer survivors exhibited significantly reduced GLS compared to healthy controls (CR vs. controls, P = 0.001; CF vs. controls, P = 0.013), but no significant difference in left ventricular ejection fraction (LVEF) was observed (P = 0.75). Overall, cancer survivors treated with ACs demonstrated a significant reduction in strain in 10 left ventricular segments, particularly in the basal segments (P < 0.05). Among CR patients, those with impaired GLS (n = 43, GLS worse than -21.9) had significantly higher mean age and cumulative anthracycline dose compared to CR patients with normal GLS (age, P = 0.024; anthracycline dosage, P = 0.036). Using an anthracycline cutoff of 223 mg/m2 resulted in a higher detection rate (49% vs. 25%) and fewer missed cases (51% vs. 74%) compared to the 360 mg/m2 anthracycline cutoff. Childhood cancer survivors demonstrate significantly reduced GLS while preserving a normal LVEF, which does not differ significantly from reference values of healthy children. The reduction in strain appears to be associated with higher anthracycline doses and older age. Lowering the anthracycline threshold to 223 mg/m2 may improve the predictability of a decline in cardiac function using strain imaging at medium-term follow-up.

Left Ventricular Dysfunction in Hypertensive Patients and Inter-arm Pressure Difference

Background: Systolic inter-arm pressure difference (SIAD) is considered as cardiovascular risk. We aimed to ascertain whether the presence of (SIAD) is associated with impaired left ventricular (LV) functions or not. Methods: Blood pressure (BP) was measured on both arms of 81 participants, echocardiographic parameters of LV functions; ejection fraction, mitral E, A, eˋ, aˋand tricuspid regurgitant velocities, left atrial volume index, E/A and E/eˋ ratio, LV stiffness index and myocardial performance index (MPI) were measured, and global longitudinal strain (GLS) was assessed. Results: Higher SIAD level had good positive correlations with age, body mass index (BMI), duration of hypertension (HTN), MPI, and LV end-systolic volume. SIAD had good negative correlations with mitral E wave velocity, E/A ratio, eˋ and sˋ wave velocities, and with the average GLS. Impaired LV average GLS is independently associated with: Years from HTN discovery followed by BMI, gender, and age. Conclusion: BP reading in both arms on the first visit is not sufficient; hypertensive patients need evaluation of the SIAD on follow up. We need to consider the SIAD on risk stratification and BP control. This will be simple to follow in primary care and areas with low resources.

Lifestyle and Cardiac Structure and Function in Healthy Midlife Population

AimThe association between lifestyle and cardiac structure and function measures such as global longitudinal strain (GLS) and diastolic function (E/e’) in a healthy midlife general population is not well known. MethodsA subpopulation of the Northern Finland Birth Cohort 1966 took part in follow-up, including echocardiography (n = 1155) at the age of 46. All antihypertensive medication users (n=164), diabetes patients (n=70), subjects with any cardiac diseases (n=24) and subjects with echocardiography abnormalities (n=21) were excluded. Moderate to vigorous physical activity (MVPA) was recorded with a wrist-worn accelerometer over 14 days and categorized into high, moderate, and low MVPA groups. Similarly, alcohol consumption was categorized as low, moderate, and high dose users of alcohol and smoking as non-smokers, former and current smokers. The total number of healthy subjects included in the study was 715 (44 % males). ResultsLeft ventricular mass index (LVMI) and left atrial end-systolic volume index (LA ESVI) were significantly higher in the high MVPA group compared to the low MVPA group (adjusted main effect p=0.002 and p<0.001, respectively). Cardiac function did not differ among PA groups. High alcohol consumption was associated with impaired GLS and E/e’ (adjusted main effect p=0.002 and p=0.004, respectively) but not with any cardiac structure variables. Smoking was not associated with cardiac structure or function. ConclusionIn healthy middle-aged adults, MVPA was independently associated with structural changes in the heart but not with cardiac function. High alcohol consumption was associated with impaired modern cardiac function measures but not with cardiac structure.

Left ventricular speckle-tracking-derived mechanical dispersion in patients with transthyretin amyloidosis and their first-degree relatives

Abstract Background Mechanical dispersion has shown to predict ventricular (LV) arrhythmias and sudden cardiac death in populations with established cardiac diseases, such as cardiomyopathies and heart failure. Transthyretin amyloid (ATTR) cardiomyopathy arises from deposition of misfolded, insoluble transthyretin (TTR) in extracellular matrix. The disease impacts profoundly cardiac tissue architecture and its mechanical properties. Purpose The aim of this prospective study was assessment of LV speckle-tracking-derived mechanical dispersion in patients with ATTR cardiomyopathy and their first-degree relatives. Methods We present data based on evaluation of 85 patients, including 34 (group 1) index patients with ATTR and 51 (group 2) first-degree relatives who were studied between June 2020 and January 2023. Study protocol included clinical data, free light chain blood immunoglobulins and urine immunofixation, transthoracic echocardiography (TTE) with global longitudinal strain (GLS) analysis, hybrid technique single-photon emission computed tomography and computed tomography (SPECT/CT) with [99mTc] Tc 3,3-disphono-1,2-propanodicarboxylic acid (DPD), genetic testing by an amplicon-based next-generation TTR sequencing approach, and in selected cases cardiac or soft tissue biopsy. Mechanical dispersion was calculated manually from GLS measurements and defined as the standard deviation (SD) of contraction duration from R on the electrocardiogram (ECG) to peak negative longitudinal strain of all LV segments. Results In group 1 patients were older (66.6±11 vs. 50.7±14) and presented with higher New York Heart Association (NYHA) class (2.4± 1 vs. 1.1± 0.6) (p&amp;lt;0.05). Overall, there were detected following types of TTR variants - Phe53Leu, Ala101Val, Glu112Lys, Glu109Lys, Glu122Lys, Glu82Lys. Compared to group 2, group 1 presented with higher N-terminal (NT)-pro hormone BNP (NT-proBNP) value (5859±7320 vs. 281±990 pg/ml), greater intraventricular septum thickness (19±4 vs. 12±3 mm) and LV mass index values (199±69 vs.111±42 g/m2), impaired LV ejection fraction (44±13 vs. 59±10 %) and GLS (-12.7±6 vs. -18.7±4 %) (p&amp;lt;0.05). Moreover, patients with ATTR cardiomyopathy had significantly higher value of LV speckle-tracking-derived mechanical dispersion compared to their first-degree relatives (96.2±22.3 vs. 77.9±23.3 ms, p=0.0007). Conclusions Patients with ATTR cardiomyopathy present with significantly higher LV mass index value, impaired GLS and higher value of LV speckle-tracking-derived mechanical dispersion compared to their first-degree relatives (p&amp;lt;0.05). Assessment of LV speckle-tracking-derived mechanical dispersion may in future translate into further enhancement of disease evaluation and improving prognosis in the group of patients.

Comparative prognostic value of different echocardiographic parameters of the subpulmonary left ventricle in adults with a systemic right ventricle

Abstract Introduction Adults with complex congenital heart disease and a systemic right ventricle (SRV) are at increased risk of SRV dysfunction, heart failure, and premature death. In the systemic left ventricle (LV), impaired global longitudinal strain (GLS) is a strong predictor of adverse outcome. In the subpulmonary LV, however, echocardiographic assessment lacks standardisation and the relative prognostic significance of metrics of subpulmonary LV function remain unknown. Purpose To assess the correlation and relative prognostic power of quantitative metrics of subpulmonary LV function in adults with an SRV. Methods All adults with an SRV who underwent echocardiography in 2011-2019 at our specialist centre and had sufficient data for quantitative multiparametric subpulmonary LV assessment were included. LV systolic function was assessed by fractional area change (FAC), 4-chamber global longitudinal strain (GLS) and free wall longitudinal strain (FWLS). Linear regression was used to assess the correlation between echocardiographic variables of subpulmonary LV function. Cox regression analysis was used to assess the relation between echocardiographic predictors and the combined endpoint of death or transplantation. TimeROC analysis was performed to assess risk variable performance. Results In total, 120 patients (43.5±12.1 years, 60.0% male, 37.5% congenitally corrected transposition of the great arteries) were included. Most patients (94, 79.0%) were in NYHA functional class I/II and two-thirds (79, 66.4%) were receiving ≥1 heart failure therapy. One half of patients (63, 52.5%) had at least moderate systolic SRV dysfunction at baseline assessment with a median SRV FAC of 27[22-32]%. Subpulmonary LV function was visually preserved in most patients (98, 81.7%), with a LV FAC of 47.0[40.0-52.9]%. Median GLS was -15.2[-19.7–11.8]% and LV FWLS -19.9[-24.4–12.8]%. There was a weak correlation between LV FAC and GLS (r=0.25). During a median follow-up of 4.9[3.4-5.6] years, 24(20.0%) patients died and 3(2.5%) underwent heart or heart-lung transplantation. The 5-year transplant-free survival was 78.9%, (95%CI: 71.7-86.8%). On univariable Cox analysis, LV FAC (/5%, HR 0.55, 95%CI:0.47-0.65, p&amp;lt;0.0001) and GLS (/5%, HR 1.6, 95%CI:1.1-2.31, p=0.01), but not LV FWLS (/5%, HR 1.25, 95%CI:0.99-1.58, p=0.06) emerged as predictors of death or transplantation. LV GLS did not remain predictive in a bivariable model including LV FAC. LV FAC outperformed GLS on timeROC analysis (5-year AUC 0.87 vs. 0.64, p&amp;lt;0.0001; Figure). Conclusions Impaired systolic function of the subpulmonary LV strongly associated with mortality and heart or heart-lung transplantation in adults with an SRV. Both LV FAC and GLS are related to outcomes and should be a part of comprehensive echo assessment. LV FAC, a marker longitudinal and radial contraction, may better reflect pathophysiological mechanisms of subpulmonary LV failure and has greater prognostic significance in SRV patients.5-year ROC curves of LV FAC and GLS

Effect of Sacubitril/Valsartan and enalapril on left ventricular function in patients with hematologic malignancies after bone marrow transplantation

Abstract Background and Aims Optimizing treatment for heart failure early after initiation of chemotherapy may prevent myocardial dysfunction. We hypothesized that early initiation of treatment with sacubitril/valsartan (sac/val) or enalapril (ena) may prevent cardiotoxicity. Patients and methods 90 patients (mean age 45.7 ± 14,1 years old, 52 male) with normal LV ejection fraction, who suffered from hematologic malignancies (lymphoma, leukemia) and underwent bone marrow transplantation, were randomized to receive sacubitril/valsartan 24/26 mg bid daily or enalapril 5 mg bid daily or placebo. We measured at baseline, before transplantation and after six months: i) Global Longitudinal Strain (GLS) of left ventricle (LV) by speckle tracking imaging, ii) myocardial global work index (GWI), global constructive work (GCW), global wasted work (GWW) and myocardial global work efficiency (GWE), by longitudinal strain-peripheral blood pressure loops, and iii) Left Ventricular Ejection Fraction (LVEF). Results The 3 treatment groups had similar age, sex, risk factors and cardiotoxic medication before and after bone marrow transplantation. Compared to baseline, patients treated with sacubitril/valsartan or enalapril for six months did not show a deterioration of LV GLS (-19.8±2.8 vs -19.3±4.1%, p=0.403 for sac/val, -20.3±2.8 vs -20.0±3.6%, p=0.634 for ena). Conversely, patients treated with placebo for six months, presented a significant impairment of LV GLS (-20.9±2.1% vs -18.5±2.2, p=0,001). No significant changes were found in LVEF after treatment with sacubitril/valsartan or enalapril for six months (57.5±4.9 vs 57.9±6.8%, p=0.826 for sac/val, 58.8±5.4 vs 60.7±7.1%, p=0.419, for ena), while a borderline deterioration was noticed after treatment with placebo (60.6±5.4 vs 57.7±6.7%, p=0.045). Moreover, in the sacubitril/valsartan group, we noticed a significant reduction of left ventricular end diastolic and end-systolic volume [(102.3±26.9 vs 93.9±21.5 ml, p=0.042 and 44.5±15.4 vs 38.6±9.6ml, p=0.012), respectively]. At 6 months, we did not observe any alteration in GWi, GCW, GWW, GWE in patients treated with enalapril (p&amp;gt;0.05). Conversely, in patients treated with sacubitril/valsartan GWE was improved (94.2±3.1 vs 95.8±1.8 %, p=0.030) and GWW was reduced (111.5±75.7 vs 86.4±43.1 mmHg%, p=0.045), while GWI and GCW did not show any significant alteration. Conversely, in the placebo group, GWI was reduced (1909.9±336.4 vs 1727.9±340.9 mmHg%, p=0.027), GWW was increased (80.7±60.6 vs 110.6±65.1 mmHg%, p=0.045), GWE was also reduced (94.2±3.1 vs 95.8±1.8 %, p=0.030) and GCW did not change at 6 months. Conclusions Treatment with sacubitril/valsartan or enalapril prevented deterioration of myocardial function six months after bone marrow transplantation in patients with hematologic malignancies and preserved LV ejection fraction. Moreover, sacubitril/valsartan showed a more favorable effect on myocardial work.

Abstract 18184: Association Between Impaired Global Longitudinal Strain and Long-Term Mortality in Patients With Moderate Aortic Stenosis: A Meta-Analysis

Background: Impaired left ventricular (LV) global longitudinal strain (GLS) is associated with worse outcomes in patients with severe aortic stenosis (AS). However, its prognostic value in patients with moderate AS is still unknown. The aim of this study is to investigate the impact of LV GLS on outcomes of patients with moderate AS. Methods: PubMed/Medline, Scopus, and Google Scholar databases were systematically reviewed to find relevant studies through June 2023 reporting data on the relationship between the LV GLS and long-term mortality in patients with moderate AS. Binary random effects models were used to estimate pooled odds ratios (OR) and 95% confidence intervals (CI). I2 statistics were used to interpret heterogeneity, with I2&gt;75% indicating substantial inter-study variation. Leave-one-out meta-analysis was performed to evaluate the effect of each study on the overall estimate. A p&lt;0.05 was considered statistically significant. Results: A total of 172 studies were reviewed, and 4 studies between 2000-2023 were included in our meta-analysis with a median follow-up of 48.5 months and GLS cut-off varying from 11% to 16%. The pooled univariate analysis revealed a significant association between LV GLS and long-term mortality in patients with moderate AS with a pooled OR of 2.02 (95CI 1.04-3.93) p=0.04, I2=94.25%. The multivariate analysis, after adjusting for overall modifiable risk factors, yielded significant results, with an adjusted odds ratio (aOR) of 1.56 (95CI 1.21-2.01) p&lt;0.01, I2=89.48%. Sensitivity analysis, using leave-one-out method, demonstrated robustness and stability of the results with aOR 1.56 (95CI 1.21-2.01) p&lt;0.01. Conclusions: In patients with moderate AS, impaired LV GLS is associated with an increased risk for all-cause mortality. If further randomized studies confirm the prognostic ability of impaired GLS, moderate AS can be redefined, and GLS can be considered in determining the optimal timing for aortic valve intervention.

Abstract 14155: Handgrip Exercise Provoked High Sensitivity Cardiac Troponin I Increase in Women With No Obstructive Coronary Artery Disease: Relations to Myocardial Function

Background: Among women with signs and symptoms of ischemia and no obstructive coronary arteries (INOCA) around 10% develop heart failure with preserved ejection fraction (HFpEF). Mechanisms contributing to AMI and HFpEF progression in INOCA are poorly understood. Purpose: To characterize clinical profile and stress cardiac magnetic resonance imaging (CMRI) myocardial features of INOCA patients with and without increased troponin levels in response to handgrip exercise. Methods: Women with suspected INOCA underwent cardiac MRI and invasive coronary function testing (CFT), including coronary sinus (CS) cannulation, handgrip exercise testing, and serial CS plasma sampling before, after 3 minutes of isometric handgrip stress at 30% of maximal voluntary contraction, and after 5 minutes of recovery. High sensitivity cardiac troponin I (hsTnI) was measured using commercial immunoassay (R-PLEX, Meso Scale Discovery, Rockville, MD) and compared using t-tests. Results: A total of 51 women with complete data were included, of whom 31 (60.7%) had handgrip provoked increases in hsTnI levels from baseline, while 20 (39.2%) did not. Baseline characteristics are shown in Table. Patients with increased hsTnI levels had greater impaired global longitudinal strain rates and early diastolic strain rates (radial and circumferential) compared to those without increased hsTnI. No significant differences were observed in myocardial perfusion reserve index (MPRI). Conclusion: Women with INOCA demonstrating objective evidence of handgrip exercise provoked myocardial injury exhibit evidence of myocardial dysfunction not related to myocardial perfusion. Further prospective research is needed to understand the sequence of relations between coronary microvascular dysfunction contribution to HFpEF progression.

Osteoprotegerin is associated with subclinical left ventricular systolic dysfunction in non-dipper hypertensive patients: a 2D speckle tracking echocardiographic study.

Past studies have shown that non-dipper hypertensive patients have more frequent subclinical left ventricular (LV) systolic dysfunction compared to dippers. Many different parameters have been examined to predict subclinical LV dysfunction. The role of osteoprotegerin (OPG) in the pathogenesis of heart failure and LV systolic dysfunction through different mechanisms had well described. In the present study, we hypothesized that increased OPG levels could predict subclinical LV systolic dysfunction in non-dipper hypertensive patients. Hypertensive patients were divided into two groups according to the results of ambulatory blood pressure (BP) monitoring. Non-dipper patients were subsequently divided into two further groups (normal LV function and impaired LV function) according to LV global longitudinal strain (GLS). A total of 103 hypertensive patients (51 dippers, 52 non-dippers) were included in the study. In the non-dipper group, LV GLS was normal in 21 patients and impaired in 31 patients. Based on the results of the multivariate logistic regression test, it was determined that OPG levels (OR: 2.413, 95% CI: 1.284-4.535, P = 0.006) and LVMI (OR: 1.086, 95% CI: 1.013-1.165, P = 0.021) were independently associated with impaired GLS. Higher OPG values were associated with subclinical LV systolic dysfunction in non-dipper hypertensive patients. It could be used for the early diagnosis of subclinical LV systolic dysfunction, which would allow for strategies to be designed to reduce the cardiovascular event rate in this patient population.