Lower Global Longitudinal Strain Research Articles

Serial measurement of global longitudinal strain among women with breast cancer treated with proton radiation therapy

Abstract Background Conventional photon radiotherapy (RT) for breast cancer is associated with reduction in global longitudinal strain (GLS), an increase in both troponin and N-terminal pro-B type natriuretic peptide (NT-proBNP), and incident heart failure. The cardiac radiation exposure with proton-RT is reduced and, thus may be associated with less cardiotoxicity. Objectives To test the effect of proton-RT on GLS, troponin and NT-proBNP. Methods A prospective observational single center study of 69 women being treated with proton-RT for breast cancer. Serial measurements of GLS, high-sensitivity cardiac troponin-I (hs-cTnI), and NT-proBNP were performed at pre-specified intervals (pre proton-RT, 4 weeks after completion of proton-RT and again at 2 months post proton-RT). Results The mean age was 46±11 years, BMI was 25.6±5.2 kg/m2, 32% had hypertension and mean radiation dose to the heart and left ventricle (LV) were 0.44 Gy and 0.12 Gy respectively. There was no change in LV ejection fraction (pre proton-RT vs. 4-weeks post proton-RT vs. 2 months post proton-RT, 65±5 vs. 66±5 vs. 64±4%, p=0.15), global GLS (−21.7±2.7 vs. −22.7±2.3 vs. −22.8±2.1%, p=0.24) or segmental GLS from pre-to post proton-RT. Similarly, there was no change in hs-cTnI or NT-proBNP with proton-RT. However, post proton-RT, we found that patients with a history of hypertension had lower GLS when compared to women without hypertension (−21.3±3.5 vs. −24.0±2.4%, p=0.006). Conclusion Proton-RT did not impact LV function, or associate with an increase in biomarkers. These data support the potential cardiac benefits of proton-RT compared to conventional RT. Funding Acknowledgement Type of funding sources: None.

Concomitant wild type transthyretin amyloidosis & severe aortic stenosis in elderly Indian population: pilot study

Abstract Background Prevalence of both severe aortic stenosis (AS) and wild-type transthyretin cardiac amyloidosis (wtTTRCA) increases with age. Dual disease (AS+wtTTRCA) occurs in a significant proportion of patients undergoing aortic valve replacement. Prognostic significance of this dual disease is not established. Purpose TTRCA distribution has ethnic variability. This has not been studied in an Indian/Asian population before. India alone has >4.6 million estimated elderly individuals with severe AS. This pilot study was designed as part of a larger study to determine the prevalence of coexistence of severe AS and wtTTRCA in elderly Indian population and identify non-invasive predictors of its diagnosis. Methods Symptomatic severe AS patients aged ≥65 years undergoing surgical aortic valve replacement (SAVR) were enrolled. Detailed 2-D transthoracic echocardiogram including speckle tracking and longitudinal strain assessment was done preoperatively. TTRCA diagnosis was based on preoperative 99m-Technitium pyrophosphate scan (PYP), and intra-operatively obtained basal inter-ventricular septum (IVS) biopsy and excised native aortic valve subjected to histopathological examination (HPE). Congo red staining and immunohistochemistry using TTR monospecific antibodies were performed to identify and sub-type amyloid respectively. Serum/urine protein electrophoresis with serum immunofixation to rule out primary amyloidosis and genetic analysis to rule out mutant TTRCA were also done. Results SAVR was done in 46 severe AS patients (mean age 70±5 years, 70% men), 32 (70%) of whom also underwent PYP scan. Significant PYP uptake (Perrugini grade II or III) was seen in 3 (9%) patients (Figure 1E, F). On HPE, 33 (72%) native aortic valves had amyloid deposits, of which 19 (58%) had TTR deposition (Figure 1A, B, C, D). However, none of the IVS biopsies showed amyloid deposits. None of the patients had evidence of monoclonal protein elevation and mutation in the TTR gene. Non-invasive markers of this dual coexistence included elevated troponin-I (≥26.2 pg/mL, 35% vs 67%), combined elevated troponin-I & NT-ProBNP (≥26.2 pg/mL & ≥400 pg/mL, 24% vs 33%), and significantly low myocardial contraction fraction (≤30%, 72% vs 100%), deceleration time (207±80 msec vs 85±23 msec) and global longitudinal strain (−19.3±4.3% vs −13.6±3.7%). At median follow-up of 12.5 months, 1 patient each had died in TTR negative and TTR positive groups (3% vs 33%). The results are summarised in the central illustration (Figure 2). Conclusion In the Indian context, concomitant existence of severe AS and wtTTRCA is common. This pilot study suggests an absolute burden of >450,000 patients with dual disease of AS and wtTTRCA, in those otherwise believed to have lone severe AS. Further larger studies are thus indicated to establish the prevalence of this dual disease and to assess its prognostic implication. Funding Acknowledgement Type of funding sources: None. Figure 1. Histopathology and PYP scan resultsFigure 2. Central illustration

Myocardial deformation techniques as potential tools to detect arrhythmogenic cardiomyopathy in early stages of the disease

Abstract Introduction Arrhythmogenic Cardiomyopathy (ACM) is a life-threatening entity which predispose to malignant arrhythmias and sudden cardiac death even in early stages of the disease. Deformation techniques obtained by echocardiography are promising tools which can identify subtle pathologic changes in the myocardial wall. Our aim is to investigate how myocardial deformation parameters may be affected throughout ACM spectrum. Methods A cohort of ACM 45 subjects, was characterized using advanced transthoracic echocardiography and divided into groups according to left ventricle ejection fraction (LVEF). Twenty-three healthy volunteers were also included as control group (CG). We analyzed regional wall motion abnormalities and left ventricular myocardial deformation parameters by 2D Speckle Tracking, such as global longitudinal strain (GLS), mechanical dispersion (MD) [standard deviation (SD) and range (delta)]. Results 23 (51,1%) of the ACM cohort were men, with a mean age of 43,13±16,55 years. Next-generation sequencing identified a potential pathogenic mutation in 37 (82,2%) of the patients. Those ACM subjects with low LVEF (ACM-L) presented lower GLS values when compared to those with normal LVEF (ACM-N) (−16,17±2,68% vs. ACM-N −19,39±2,97%; p<0.001) with no significant differences in MD parameters. ACM-N showed no differences in GLS regarding to CG, but significant differences were found when analyzing MD values, with pathological dispersion times in the ACM-N group (ACM-N DMSD 50,50±20,39ms vs. CG 37,35±17,15ms; p=0,016; ACM-N DMDelta 167,4583±75,07ms vs CG 125±49,13ms; p=0,033). Conclusions MD may be an additive tool for identifying ACM patients in early stages of the disease when LVEF is still preserved. Funding Acknowledgement Type of funding sources: None.

Concomitant Transthyretin Amyloidosis and Severe Aortic Stenosis in Elderly Indian Population: A Pilot Study

BackgroundPrevalence of both degenerative severe aortic stenosis (AS) and transthyretin cardiac amyloidosis (ATTR-CA) increases with age. Dual disease (AS+myocardial ATTR-CA) occurs in significant proportion of patients undergoing surgical aortic valve replacement (SAVR). ObjectivesThis study aimed to determine the prevalence of ATTR-CA in severe AS in the Indian population, identify noninvasive predictors of its diagnosis, and understand its impact on prognosis. MethodsSymptomatic severe AS patients aged ≥65 years undergoing SAVR were enrolled. ATTR-CA diagnosis was based on preoperative 99m-technetium pyrophosphate (PYP) scan and intraoperatively obtained basal interventricular septum biopsy for myocardial ATTR-CA, and excised native aortic valve for isolated valvular ATTR-CA. Primary amyloidosis was excluded by serum/urine protein electrophoresis with serum immunofixation. ResultsSAVR was performed in 46 AS patients (age 70 ± 5 years, 70% men). PYP scan was performed for 32 patients, with significant PYP uptake in 3 (n = 3 of 32, 9.4%), suggestive of myocardial ATTR-CA. On histopathological examination, none of the interventricular septum biopsy specimens had amyloid deposits, whereas 33 (71.7%) native aortic valves showed amyloid deposits, of which 19 (57.6%) had transthyretin deposition suggestive of isolated valvular amyloidosis. Noninvasive markers of dual disease included low myocardial contraction fraction (median [interquartile range], 28.8% [23.8% to 39.1%] vs 15.3% [9.3% to 16.1%]; P = 0.006), deceleration time (215 [144 to 236] ms vs 88 [60 to 106] ms; P = 0.009) and global longitudinal strain (-18.7% [-21.1% to -16.9%] vs -14.2% [-17.0% to -9.7%]; P = 0.030). At 1-year follow-up, 2 patients died (4.3%); 1 each in myocardial ATTR-CA negative and positive groups (3.4% vs 33.3%; P = 0.477). ConclusionsDual disease is not uncommon in India. Isolated valvular amyloidosis in severe AS is much more common.

Aggravating effect of obstructive sleep apnoea on left ventricular remodelling and function disorder in patients with type 2 diabetes mellitus: a case-control study by 3D speckle tracking echocardiography

Objectives The purpose of this study was to evaluate the early alterations of left ventricular (LV) structure and function in type 2 diabetes mellitus (T2DM) patients with or without obstructive sleep apnoea (OSA) using 3 D speckle tracking echocardiography (3DSTE). Methods Eighty T2DM patients with preserved LVEF were included, half of whom had OSA as co-morbidity. Forty age- and sex-matched controls were also enrolled. LV structure and function were evaluated by conventional echocardiography and 3DSTE. LV global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS) were all measured by 3DSTE. Results Four geometric patterns (normal geometry, concentric remodelling, concentric and eccentric hypertrophy) occupied significantly different proportions within the three groups (p = .014). LV remodelling made up higher shares in two T2DM groups than in the controls, whereas LV hypertrophy appeared most frequently in the patients with T2DM and OSA. The patients with T2DM alone had significantly lower GLS and GCS than the controls (both p < .01). The patients with T2DM and OSA had significantly lower GLS, GCS, GAS, and GRS than the controls and the patients with T2DM alone (all p < .01). Fasting plasma glucose (FPG), OSA and BMI had negative impacts on all and part of the strain values in T2DM patients. The T2DM patients with moderate-to-severe OSA showed significantly lower GLS, GCS, GAS, and GRS than those with mild OSA (all p < .05). Conclusions The 3DSTE plus conventional echocardiography could detect the sub-clinical LV alterations in T2DM patients with or without OSA.

Abstract P142: Factors Associated With Persistent Cardiac Organ Damage In Primary Aldosteronism After One Year Of Treatment

Introduction: Adrenalectomy and medical treatment of primary aldosteronism (PA) both induce regression of left ventricle (LV) hypertrophy, while the effects on LV myocardial function are less investigated. Hypothesis: We hypothesized that persistent cardiac organ damage was more prevalent in medically treated PA patients. Methods: Eighty-four patients (57±11 years, 27% female) with PA underwent echocardiography at time of diagnosis and after 1 year of treatment (49% adrenalectomized, 51% medically treated). Persistent cardiac organ damage was identified as LV hypertrophy or low LV systolic function by midwall shortening or global longitudinal strain (GLS), both at baseline and at follow-up. LV diastolic function was assessed by left atrial enlargement and estimated LV filling pressure (E/e’). Results from logistic regression analyses are reported as odds ratio (OR) with 95% confidence intervals (CI). Results: After 1 year, a significant regression of LV hypertrophy was observed in adrenalectomized patients (44% vs. 22%, p=0.038), but not in medically treated patients (59% vs. 50%, p=0.206). Midwall shortening, E/e’ and prevalence of enlarged left atrium improved significantly in both treatment groups (all p&lt;0.001), while GLS remained unchanged. In multivariable logistic regression analysis, receiving medical treatment for PA (OR 4.98 [95% CI 1.26-18.88] was a strong predictor of persistent LV hypertrophy independent of higher body mass index (OR 1.20 [95% CI 1.04-1.38]) and presence of diabetes (OR 6.48 [95% CI 1.20-34.83], all p&lt;0.05). Important covariables of persistently low midwall shortening were persistent LV hypertrophy (OR 3.50 [95% CI 1.12-10.96]) and suppression of plasma renin activity after 1 year of treatment (OR 4.31 [1.15-16.12], both p&lt;0.05). The strongest predictor of persistently low GLS was higher HbA 1c (OR 2.37[95% CI 1.12-5.02], p=0.024). Conclusions: In PA, LV hypertrophy regression was more common in adrenalectomized patients. Persistent LV hypertrophy and impaired glucose metabolism were the major factors associated with persistent LV myocardial dysfunction independent of treatment.

Prognostic implications of longitudinal strain in hypertensive patients

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): University Hospital of Tlemcen Introduction Hypertension is a well-established risk factor for cardiovascular disease. It causes left ventricular (LV) pressure overload, and, in turn, changes in cardiac geometry and LV hypertrophy (LVH). Early impairment of LV function, detected by a reduced GLS, is associated with long-lasting, uncontrolled HBP, overweight, related metabolic changes, and is more pronounced in patients with LVH. This decline in longitudinal function may be a determining factor in the occurrence of cardiovascular complications and therefore an increase in cardiovascular morbidity and mortality. Purpose : This study sought to investigate the associations of left ventricular (LV) strain and its serial change with major adverse cardiac events in hypertensive patients. Methods We retrospectively studied 400 asymptomatic patients with hypertension of which, 182 patients had abnormal global longitudinal strain(GLS) and 218 patients had normal GLS, between 2016 and 2019. Global longitudinal strain (GLS) was measured using speckle tracking. Patients were followed for admission because of heart failure, myocardial infarction, atrial fibrillation and strokes, over median of 4 years. At the start of study, all patients had preserved LV ejection fraction. Résultats : The control of patients noted 25 cases (6.25%) of attacks of heart failure in the arm hypertension with low GLS against only 4 cases (1%) in the arm hypertension + normal GLS (P &amp;lt;0.001). The same, 19 ( 4.75%) hypertensive patients with low GLS had a stroke compared to only 5 (1.25%) hypertensive patients with normal GLS. A significant difference in the incidence of onset of acute coronary syndromes was also noted in the hypertension arm with abnormal GLS (P = 0.002). As for rhythmic complications, 26 (6.5%) hypertensive patients with abnormal GLS developed atrial fibrillation compared to only 9 (2.25%) hypertensive patients with normal GLS (P &amp;lt;0.0001). Conclusion : GLS and its deterioration are associated with cardiovascular complications in asymptomatic hypertensive heart disease. Although LVEF will remain a cornerstone of LV function assessment, the addition of GLS enables detailed phenotyping and improved risk assessment and is a tool for present and future therapeutic advancement. A risk score incorporating strain was useful for predicting risk of cardiac events.

Assessment of the study of longitudinal systolic function by 2D strain in hypertensive patients

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): University Hospital Center of Tlemcen Introduction Hypertension is a well-established risk factor for cardiovascular disease. It causes left ventricular (LV) pressure overload, and, changes in cardiac geometry and LV hypertrophy(LVH). LVH as well as patterns of abnormal geometry have been associated with adverse outcomes. Global longitudinal strain (GLS) has been used to detect early subclinical myocardial dysfunction in a broad spectrum of cardiac conditions and thereby provides a novel approach for LV risk assessment in patients with hypertension. Purpose This study is intended to assess the clinical and echocardiographic factors associated with and predictive for early impairment of left ventricular function as assessed using GLS evaluation in hypertensive patients. Methods Cross-sectional descriptive study, with a total number of 130 hypertensive and with the objective of evaluating the study of longitudinal function by 2D strain in patients with systemic hypertension with preserved LVEF and the determination of predictors the decrease GLS in this population. A complete study echo cardiographic, including LVEF biplane Simpson method, calculation of left ventricular mass indexed and relative parietal thickness to differentiate the eccentric and concentric LVH, analysis diastolic function and finally the study of longitudinal strain of the LV by the speckle tracking technique (calculation of GLS) to seek a possible decline in the GLS and establish a possible correlation between this drop and power and LVH the diagnosis of subclinical hypertensive heart disease. Results The prevalence of left ventricular hypertrophy (LVH) was found in (66%) in this population. half of the patients (49%) presented a concentric hypertrophy, It was clearly noted that 73%of the patients had a relative wall thickness (RWT)&amp;gt;0.42. Alterations in diastolic function were detected in 89% of the group, 18% had severe diastolic dysfunction with elevation in filling pressure. Analysis of the longitudinal systolic function of the left ventricle took the average GLS as a reference value. The mean GLS was found to be -16.9 ± 3.2%, within a range between -25% and-11.6%. Low GLS values (&amp;gt;-17%) were found in 45.5% of the general population. In particular, 34.4% of the patients had no left ventricular hypertrophy (LVH) and 50.7% of them presented LVH. The average systolic and diastolic blood pressures, taken at the time of echocardiographic analysis, were found higher in the subgroup of hypertensive patients with low GLS. Very low GLS values (&amp;gt;-13%) were found in 11% of the general population. Statistical analysis revealed significant correlation between the decrease in GLS and diabetes the values of blood pressure and elevated filling pressures. Conclusion The evaluation of longitudinal systolic function provides new insight of myocardial function in hypertension that could improve the pathophysiological understanding and identify high-risk heart failure patients eligible for preventive strategies.

Elevated Plasma Homocysteine Level Associated with Further Left Ventricular Structure and Function Damages in Type 2 Diabetic Patients: A Three-Dimensional Speckle Tracking Echocardiography Study.

Aims: The aims of this study were to explore the left ventricular (LV) structural remodeling and its risk factors in type 2 diabetes mellitus (T2DM) patients with or without hyperhomocysteinemia (hHcy) and to detect the accompanied LV dysfunction using three-dimensional speckle tracking echocardiography (3DSTE). Methods: There were totally 80 T2DM patients with undamaged LV ejection fraction (≥55%) in this study, 40 of whom were also diagnosed with hHcy as co-morbidity. Forty age- and gender-matched controls were also recruited. The risk factors and corresponding diagnostic values for LV remodeling (LVR) were, respectively, determined using logistic regression and area under the receiver operating characteristic curves (AUC). The 3DSTE was used to measure global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS). Results: The constituent ratio of LV geometry showed significant differences among the study populations (P = 0.01). Compared with the controls, three types of LVR accounted for larger proportion in the two T2DM groups, whereas LV hypertrophy was most prevalent in those with T2DM and hHcy. Glycosylated hemoglobin (HbA1c), total plasma homocysteine (tHcy), and HbA1c plus tHcy were all significant risk factors associated with LVR in T2DM patients (AUC values: 0.741, 0.746 and 0.851, respectively). The patients with T2DM alone had significantly lower GLS and GAS than the controls (both P < 0.05). The patients with T2DM and hHcy had significantly lower GLS, GCS, GAS, and GRS than the controls (all P < 0.001), and also had significantly lower GLS, GCS, and GRS than the patients with T2DM alone (all P < 0.05). Conclusions: The 3DSTE plus conventional echocardiography could be used as an effective supplement for detecting early and occult cardiac damages in T2DM patients with plasma homocysteine at normal or elevated levels.

Correlation of left ventricular longitudinal strain and E/e’ ratio in primary hypertension patients

ABSTRACT Objectives: The aim of this study is to explore and compare the relationships of both global longitudinal strain (GLS) and strain (SR) with E/e’ ratio in a population of asymptomatic patients with systemic hypertension. Methods: Retrospectively included 210 cases of essential hypertension patients. Dynamic images were analyzed for left ventricular myocardial systolic global longitudinal strain (GLS), left ventricular longitudinal peak systolic strain rate (SRs), early diastolic peak strain rate (SRe), late diastolic peak strain rate (SRa). According to the 2012 baseline E/e’ ratio, the population was divided into three groups, group A (E/e’<8), group B (8 ≤ E/e’≤14), and group C (E/e’>14). Results: Systolic function parameters left ventricular ejection fraction (LVEF) remained at normal rage and no different, but patients with elevated E/e’ ratio had significantly lower GLS, lower early diastolic strain rate(SRe), lower ratio of early diastolic strain rate to late diastolic strain rate (SRe/a) and higher E/SRe. Positive relationships were observed between GLS, E/SRe and E/e’ ratio, inverse relationships were observed between SRe, SRe/a and E/e’ ratio. E/SRe >0.73 had a sensitivity of 87.7% and a specificity of 38.2% for predicting an elevated E/e’ ratio (E/e’>14). In multivariable analysis, IVS-e’ <7 cm/s showed almost 2.5-fold increased risk for decreased GLS (OR 2.48[95% CI 1.36–4.53]; p = 003). Conclusions: Our current study demonstrated that hypertensive patients with preserved LVEF and elevated E/e’ ratio have systolic and diastolic abnormalities in longitudinal directions as detected by speckle imaging. E/SRe correlates well with E/e’ and predicted elevated left ventricular filling pressure.

Echocardiographic Determinants of Ventricular Arrhythmia in Sickle Cell Disease Adults

Unexplained sudden death remains one of the leading causes of death in sickle cell disease (SCD) adults. Ventricular arrhythmia is a well-known risk factor for sudden death but its prevalence and determinants in the context of SCD remain understudied. From January 2019 to March 2021, consecutive adult patients with SCD referred to ambulatory cardiology department for possible cardiac involvement were prospectively included (Drepacoeur cohort). All patients that had 24-hour ECG monitoring (24h-holter) and thransthoracic echocardiography (TTE) on the same day were analysed. The primary end point was the occurrence of ventricular arrhythmia, defined as sustained or non-sustained ventricular tachycardia (VT), more than 500 premature ventricular contractions (PVC) on 24h-holter, or history of VT ablation. Overall, 90 patients were included and 54 (60%) were analysed. Mean age was 47.6 ± 11.6 years (range 21-69), 53% were male. Heart function was mainly preserved with a mean left ventricular ejection fraction (LVEF) of 57.9 ± 4.9% and a mean global longitudinal strain (GLS) of -18 ± 2.8%. Mean tricuspid regurgitation velocity was 2.6 ± 0.4 m/s. Ventricular arrhythmia was observed in 13 (24.1%) patients (4 non-sustained VT, 9 with more than 500 PVC and 1 history of VT ablation). Ventricular arrhythmia was associated with lower GLS (−15.8 ± 1.8% vs. −19 ± 2.7%, P < 0,001), lower tricuspid annular plane systolic excursion (TAPSE, 23 ± 5.7 mm vs. 26.9 ± 4.6 mm, P = 0,02) and more dilated right ventricle assessed by tricuspid annulus diameter (38.2 ± 6.1 mm vs. 34.2 ± 4.5 mm, P = 0,02). In multivariate analysis, GLS was independently associated with ventricular arrhythmia (OR = 2,1 CI95% [1,3; 3,3], P = 0,004) with a moderate exponential correlation with PVC load on 24h-holter (R = 0,5, P < 0,001). In SCD adults with preserved LVEF, GLS was the only independent echocardiographic predictor of ventricular arrhythmia.

Myocardial strain analysis as a non-invasive screening test in the diagnosis of stable coronary artery disease

BackgroundCoronary artery disease (CAD) is one of the most prevalent diseases around the world; however, finding the best noninvasive, low-cost, and more easily accessible test for its screening has been a challenge for several years. Eighty-nine patients suspected of stable CAD underwent 2D-speckle-tracking echocardiography (2DSTE) at resting position and offline longitudinal myocardial strain analysis, followed by coronary angiography. The correlation of the global longitudinal strain (GLS) and territorial longitudinal strain (TLS) with significant CAD (70% and more stenosis in at least one coronary artery) was then evaluated.ResultsThe statistical analysis showed a significant correlation between low GLS and significant CAD (P=0.0001). The results also showed a significant correlation between low TLS and significant CAD in the left and right coronary artery territories. The optimal cut-off point of GLS for the detection of significant CAD was −19.25, with a sensitivity of 76.5% and specificity of 76.6%.ConclusionThis study confirmed the usefulness of 2DSTE myocardial strain analysis in diagnosis of CAD for detecting the affected coronary arteries using GLS and SLS.

Generalizability of HFA-PEFF and H2FPEF Diagnostic Algorithms and Associations With Heart Failure Indices and Proteomic Biomarkers: Insights From PROMIS-HFpEF

BackgroundDiagnosing heart failure with preserved ejection fraction (HFpEF) remains challenging. We aimed to evaluate the generalizability of the HFA-PEFF (Heart Failure Association Pre-test assessment, Echocardiography & natriuretic peptide, Functional testing, Final etiology) and weighted H2FPEF (Heavy, 2 or more Hypertensive drugs, atrial Fibrillation, Pulmonary hypertension, Elder age > 60, elevated Filling pressures) diagnostic algorithms and associations with HF severity, coronary microvascular dysfunction and proteomic biomarkers. Methods and ResultsDiagnostic likelihood of HFpEF was calculated in the prospective, multinational PROMIS-HFpEF (Prevalence of microvascular dysfunction in HFpEF) cohort using current European Society of Cardiology recommendations, HFA-PEFF and H2FPEF algorithms. Associations between the 2 algorithms and left atrial function, Doppler-based coronary flow reserve, 6-minute walk test, quality of life, and proteomic biomarkers were investigated. Of 181 patients with an EF of ≥50%, 129 (71%) and 94 (52%) fulfilled criteria for high likelihood HFpEF as per HFA-PEFF and H2FPEF, and 28% and 46% were classified as intermediate likelihood, requiring additional hemodynamic testing. High likelihood HFpEF patients were older with higher prevalence of atrial fibrillation and lower global longitudinal strain and left atrial reservoir strain (P < .001 for all variables). left atrial reservoir strain and global longitudinal strain were inversely associated with both HFA-PEFF and H2FPEF scores (TauB = –0.35 and –0.46 and –0.21 and –0.31; P < .001 for all). There were no associations between scoring and 6-minute walk test, quality of life, and coronary flow reserve. Both scores were associated with biomarkers related to inflammation, oxidative stress, and fibrosis. ConclusionsAlthough the HFA-PEFF and H2FPEF scores were associated with measures of HF severity and biomarkers related to HFpEF, they demonstrated a modest and differential ability to identify HFpEF noninvasively, necessitating additional functional testing to confirm the diagnosis.

Long-Term Implications of Abnormal Left Ventricular Strain During Sepsis.

Septic cardiomyopathy develops frequently in patients with sepsis and likely increases short-term mortality. However, whether septic cardiomyopathy is associated with long-term outcomes after sepsis is unknown. We investigated whether septic patients with septic cardiomyopathy have worse long-term outcomes than septic patients without septic cardiomyopathy. Retrospective cohort study. Adult ICU. Adult ICU patients with sepsis. None. Left ventricular global longitudinal systolic strain was our primary measure of septic cardiomyopathy. We employed a suite of multivariable survival analyses to explore linear and nonlinear associations between left ventricular global longitudinal systolic strain and major adverse cardiovascular events, which included death, stroke, and myocardial infarction. Our primary outcome was major adverse cardiovascular event through 24 months after ICU discharge. Among 290 study patients, median left ventricular global longitudinal systolic strain was -16.8% (interquartile range, -20.4% to -12.6%), and 38.3% of patients (n = 111) experienced a major adverse cardiovascular event within 24 months after discharge. On our primary, linear analysis, there was a trend (p = 0.08) toward association between left ventricular global longitudinal systolic strain and major adverse cardiovascular event (odds ratio, 1.03; CI, < 1 to 1.07). On our nonlinear analysis, the association was highly significant (p < 0.001) with both high and low left ventricular global longitudinal systolic strain associated with major adverse cardiovascular event among patients with pre-existing cardiac disease. This association was pronounced among patients who were younger (age < 65 yr) and had Charlson Comorbidity Index greater than 5. Among patients with sepsis and pre-existing cardiac disease who survived to ICU discharge, left ventricular global longitudinal systolic strain demonstrated a U-shaped association with cardiovascular outcomes through 24 months. The relationship was especially strong among younger patients with more comorbidities. These observations are likely of use to design of future trials.

Role of myocardial deformation analysis in the early detection of subclinical Left Ventricular dysfunction in breast cancer under anthracyclines and trastuzumab

Abstract Funding Acknowledgements Type of funding sources: None. Introduction : Cardio-oncology field has notably raised interest this past decade, it considerably improved cancer patients’ quality of care by monitoring and preventing complications of cardiotoxic treatment like anthracyclines and trastuzumab. Transthoracic echocardiography (TEE) plays a major role in the baseline assessment and follow-up of cardio-oncology patients. While left ventricular ejection fraction (LVEF) still has its place in cardiac monitoring, new modalities like myocardial deformation imaging with speckle tracking strain analysis, show great potential for early detection of subclinical LV dysfunction. Purpose : The aim of this study was to evaluate the role of Global Longitudinal Strain (GLS) in the early detection of cardiotoxicity and its correlation to LVEF. Methods : We conducted a longitudinal prospective study including all the breast cancer patients treated with anthracyclines and/or trastuzumab followed in the Casablanca cardio-oncology unit from January 2017 to December 2019. All patients underwent baseline TEE, and were followed-up every 3 months after that, with GLS assessment whenever it was possible. We evaluated the frequency of GLS drop and its correlation to LVEF reduction. Results : Out of a total of 793 patients, 677 had available LV GLS assessment. Among them, 83 (12,3%) decreased their GLS during follow-up, 67% of which had no concomitant drop in LVEF. In these patients, impaired LV GLS values were noted at 1 month after chemotherapy and at 3, 6, and 12 months compared with baseline (-22,3 ± 1.8% at baseline, -18.1 ± 2.3% at 1 month, -17.7 ± 2.1% at 3 months, -17.1 ± 2.2% at 6 months, and -16.9 ± 2.1% at 12 months (p &amp;lt; 0,0001). LV GLS at 3 months was strongly correlated to cardiotoxicity (LVEF &amp;lt; 50%) at 12 months (p &amp;lt; 0,0001). A cut-off LV GLS value of -17,7% was then retained to identify LVEF alteration at the end of follow-up. Moreover, lower GLS values were observed in patients under Doxorubicin with a mean cumulative dose &amp;gt;180 mg/m2 (p = 0,0019), while LVEF remained normal. Finally, our study found that GLS at 1 month and 3 months had a prognostic value, since the lower GLS was, the poorest the patient’s clinical outcome was, with further development of symptomatic heart failure (p = 0,0038). Conclusion : Our study demonstrates that myocardial deformation analysis enables detection of early and progressive subclinical cardiac dysfunction, and GLS at 3 month was positively correlated to LVEF drop at 12 months. Thus, routine GLS should be used in patients undergoing cardiotoxic chemotherapy in order to early detect cardiotoxicity and prevent irreversible cardiac dysfunction by early initiating cardio-protective treatment.

Association between clinical risk factors and left ventricular function in patients with breast cancer following chemotherapy

Abstract Funding Acknowledgements Type of funding sources: None. Background The sequential or concurrent use of two different types of agents such as anthracyclines and trastuzumab may increase myocardial injury and cancer therapeutics-related cardiac dysfunction (CTRCD), which is often the result of the combined detrimental effect of the two therapies for breast cancer patients. For risk stratification to detect the development of CTRCD, the current position paper from the European Society of Cardiology (ESC) lists several factors associated with risk of cardiotoxicity. Purpose Our purpose was to investigate the impact of baseline risk factors on left ventricular (LV) function in patients with preserved LV ejection fraction (LVEF) who have undergone chemotherapy for breast cancer. Methods We studied 86 breast cancer patients treated with anthracyclines, trastuzumab, or both. Mean age was 59 ± 13 years and LVEF was 67 ± 5%. In accordance with the current definition, CTRCD was defined as a decline in LVEF of &amp;gt;10% to an absolute value of &amp;lt;53% after chemotherapy. Based on the 2016 ESC position paper, clinical risk factors for CTRCD were defined as: (1) a cumulative total doxorubicin dose of ≥ 240mg/m², (2) age ≥ 65-year-old, (3) body mass index ≥ 30kg/m², (4) a previous history of radiation therapy to chest or mediastinum, (5) B-type natriuretic peptide ≥ 100pg/mL, (6) a previous history of cardiovascular disease, (7) atrial fibrillation, (8) hypertension, (9) diabetes mellitus, (10) current or ex-smoker. Results The relative decrease in LVEF after chemotherapy for patients with more than four risk factors was significantly greater than that for patients without (-9.3 ± 10.8% vs. -2.2 ± 10.2%; p = 0.02). However, this finding did not apply to patients with more than one, two or three risk factors. Patients with more than four risk factors also tended to show a higher prevalence of CTRCD than those without (14.3% vs. 2.8%, p = 0.12). Moreover, patients with more than four risk factors were more likely to have higher LV mass index (109.3 ± 29.0g/m² vs. 83.2 ± 21.0g/m², p &amp;lt; 0.001), lower global longitudinal strain (18.4 ± 2.8% vs. 20.0 ± 2.6%, p = 0.06) and higher E/e’ (10.4 (8.9-13.0) vs. 9.0 (7.4-10.9), p = 0.06) compared to those without. Furthermore, receiver-operator characteristics curve analysis showed that an optimal cut off value of a cumulative total doxorubicin dose for developing LV dysfunction in patients with more than any of four risk factors was lower than that in those without (180 mg/m² vs. 280 mg/m²). Conclusions Association between clinical risk factors and LV dysfunction following chemotherapy became stronger with an increase in the number of risk factors in breast cancer patients, and was especially strong for patients treated with chemotherapy who had more than four risk factors. Our findings can thus be expected to have clinical implications for better management of patients with breast cancer referred for chemotherapy. Abstract Figure.

Association of maximal stress ergometry performance with troponin T and abdominal aortic calcification score in advanced chronic kidney disease

BackgroundCardiac biomarkers Troponin T (TnT) and N-terminal pro-B-type natriuretic peptide (proBNP) and abdominal aortic calcification score (AAC) are associated with cardiovascular events and mortality in patients with chronic kidney disease (CKD). The effects of cardiac biomarkers and AAC on maximal exercise capacity in CKD are unknown and were studied.MethodsOne hundred seventy-four CKD 4–5 patients not on maintenance dialysis underwent maximal bicycle ergometry stress testing, lateral lumbar radiograph to study AAC, echocardiography and biochemical assessments.ResultsThe subjects with proportional maximal ergometry workload (WMAX%) less than 50% of the expected values had higher TnT, proBNP, AAC, left ventricular end-diastolic diameter, left ventricular mass index, E/e’ and pulse pressure, and lower global longitudinal strain compared to the better performing patients. TnT (β = − 0.09, p = 0.02), AAC (β = − 1.67, p < 0.0001) and diabetes (β = − 11.7, p < 0.0001) remained significantly associated with WMAX% in the multivariable model. Maximal ergometry workload (in Watts) was similarly associated with TnT and AAC in addition to age, male gender, hemoglobin and diastolic blood pressure in a respective multivariate model.AAC and TnT showed fair predictive power for WMAX% less than 50% of the expected value with AUCs of 0.70 and 0.75, respectively.ConclusionsTnT and AAC are independently associated with maximal ergometry stress test workload in patients with advanced CKD.Trial registrationhttp://www.ClinicalTrials.gov NCT04223726.

Left ventricular myocardial strain assessed by cardiac magnetic resonance feature tracking in patients with rheumatoid arthritis

PurposeThe aim of the study was to assess a relationship between the occurrence of rheumatoid arthritis (RA) and its selected clinical parameters, and left ventricular myocardial strain.Material and methodsFifty-six subjects were qualified for the study: 30 RA patients and 26 subjects without rheumatoid diseases. The study design included taking medical history, assessment of the disease activity using selected scales of activity, collecting samples of venous blood to assess selected laboratory parameters and the assessment of cardiac magnetic resonance (CMR). Using the feature tracking method, the following parameters of the left ventricular myocardial strain were assessed: longitudinal strain (LS), radial strain (RS) and circumferential strain (CS).ResultsRegarding global values, peak LS and peak CS were statistically significantly lower in RA patients than in the control group. In the whole study group, the factors independently related to low global LS peaks were as follows: occurrence of RA, occurrence of arterial hypertension, increased activity of antibodies against cyclic citrullinated peptide and increased concentration of neutrophil gelatinase-associated lipocalin. The occurrence of RA, occurrence of diabetes, tobacco smoking, higher activity of antibodies against cyclic citrullinated peptide and current use of methotrexate are the risk factors for low peak of global CS. The current use of steroids constitutes a protecting factor against low global CS peaks.ConclusionIn subjects with no clinically manifested cardiac damage, RA is associated with a deteriorated left ventricular systolic function assessed by left ventricular myocardial strain measured by CMR feature tracking.

Pre-implant global longitudinal strain as an early sign of pacing-induced cardiomyopathy in patients with complete atrioventricular block.

IntroductionLong‐term right ventricular pacing is the only treatment for patients with a complete atrioventricular block (CAVB); however, it frequently triggers ventricular dys‐synchrony with left ventricular (LV) dysfunction. Previous studies showed that an early decline of LV global longitudinal strain (GLS) predicts pacing‐induced LV dysfunction. We aimed to investigate the potential ability of the initial LV strain to predict pacing‐induced cardiomyopathy (PICM) through long‐term follow‐ups.MethodsWe retrospectively enrolled 80 patients with CAVB with normal LV function who were implanted with dual‐chamber pacemakers between 2008 and 2018. Echocardiographic data and parameters (including longitudinal, radial, and circumferential strain based on speckle‐tracking) were analyzed for the pre‐implant (≤6 months) and post‐implant periods. PICM was defined as a ≥10% reduction in the left ventricular ejection fraction (LVEF) resulting in an LVEF of <50% during the post‐implant period. Predictors of PICM were identified using Cox proportional hazard models.ResultsPatients who developed PICM were more likely to exhibit lower baseline LV GLS, as well as wider native and pacing QRS durations, than those who did not develop PICM (P = .016, P = .011, and P = .026, respectively). In the multivariate analysis, pre‐implant LV GLS (hazard ratio: 1.27; 95% confidence interval 1.009–1.492; P = .004) was independently associated with the development of PICM.ConclusionA lower baseline LV GLS predicts an increased risk of PICM. Patients with CAVB exhibiting low GLS are at increased risk of PICM. More frequent follow‐up visits are warranted in these patients, who may also require de novo His‐bundle pacing or an upgrade to biventricular pacing.

Early Mechanical Alterations in Phospholamban Mutation Carriers: Identifying Subclinical Disease Before Onset of Symptoms

ObjectivesThis study aimed to explore echocardiographic characteristics of phospholamban (PLN) p.Arg14del mutation carriers to investigate whether structural and/or functional abnormalities could be identified before onset of symptoms. BackgroundCarriers of the genetic PLN p.Arg14del mutation may develop arrhythmogenic and/or dilated cardiomyopathy. Overt disease is preceded by a pre-symptomatic phase of variable length in which disease expression seems to be absent. MethodsPLN p.Arg14del mutation carriers with an available echocardiogram were included. Mutation carriers were classified as pre-symptomatic if they had no history of ventricular arrhythmias (VAs), a premature ventricular complex count of <500/24 h, and a left ventricular (LV) ejection fraction of ≥45%. In addition, we included 70 control subjects with similar age and sex distribution as the pre-symptomatic mutation carriers. Comprehensive echocardiographic analysis (including deformation imaging) was performed. ResultsThe final study population consisted of 281 PLN p.Arg14del mutation carriers, 139 of whom were classified as pre-symptomatic. In comparison to control subjects, pre-symptomatic mutation carriers had lower global longitudinal strain and higher LV mechanical dispersion (both p < 0.001). In addition, post-systolic shortening (PSS) in the LV apex was observed in 43 pre-symptomatic mutation carriers (31%) and in none of the control subjects. During a median follow-up of 3.2 years (interquartile range: 2.1 to 5.6 years) in 104 pre-symptomatic mutation carriers, nonsustained VA occurred in 13 (13%). Presence of apical PSS was the strongest echocardiographic predictor of VA (multivariable hazards ratio: 5.11; 95% confidence interval [CI]: 1.37 to 19.08; p = 0.015), which resulted in a negative predictive value of 96% (95% CI: 89% to 98%) and a positive predictive value of 29% (95% CI: 21% to 40%). ConclusionsGlobal and regional LV mechanical alterations in PLN p.Arg14del mutation carriers precede arrhythmic symptoms and overt structural disease. Pre-symptomatic mutation carriers with normal deformation patterns in the apex are at low risk of developing VA within 3 years, whereas mutation carriers with apical PSS appear to be at higher risk.