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Aims: Acute myocarditis, although a rare disease, can be associated with sudden cardiac death or the need for transplantation in both children and young adults. To date, there is no definitive evidence to support the routine use of immunosuppressive therapy or treatment targeting inflammation in patients with myocarditis. Animal models of cardiovascular (CV), as well as neurological diseases, have demonstrated that cannabidiol has significant anti‐inflammatory properties and may represent a promising therapy in acute myocarditis. This efficacy has been shown in a murine model of autoimmune myocarditis as well as in in vitro and in vivo models of heart failure (HF). Methods and results: We present the rationale and design of the ARCHER Trial, an international multicentre, double‐blind, randomized, placebo‐controlled, phase II study examining the safety and efficacy of a pharmaceutically produced cannabidiol formulation, in patients with mild to moderate acute myocarditis. Eligible patients are those with acute myocarditis, randomized within 10 days of the diagnostic cardiac MRI (CMR), which has met defined diagnostic criteria for myocarditis. Oral treatment (cannabidiol or placebo) is titrated from 2.5 mg/kg of body weight up to 10 mg/kg of body weight b.i.d. (or highest tolerated dose) and taken for 12 weeks in addition to standard of care therapy for HF. The primary endpoints are defined as changes in global longitudinal strain (GLS) and extra cellular volume (ECV), measured by CMR at 12 weeks. Assuming 80% power, a 5% alpha risk and 25% missing CMR follow‐up data at Week 12, 100 patients are required to demonstrate the desired treatment effect of 18%. The change in left ventricular ejection fraction (LVEF) from baseline to Week 12 was selected as the secondary endpoint. Additional exploratory endpoints include changes in hs‐troponin, NT‐proBNP, markers of inflammation and endothelial function during the 12‐week treatment period. The trial is ongoing but is now more than 50% recruited. As enrolment in the trial continues, no interim data are available for inclusion in this Design paper. Conclusions: The ongoing ARCHER Trial is an international, multicentre, double‐blind, randomized, placebo‐controlled phase II study, designed to determine the effect of a pharmaceutically produced cannabidiol formulation on CMR parameters in patients presenting with acute myocarditis. Enrolment of 100 patients is expected to conclude in Q3 2024. Study results will be available in early 2025. [ABSTRACT FROM AUTHOR]

Aims: Anthracycline chemotherapy (AC) for breast cancer can cause cancer therapy‐related cardiac dysfunction (CTRCD) with resultant heart failure, traditionally defined as a reduction in left ventricular (LV) ejection fraction on echocardiography. In recent years, global longitudinal systolic strain (GLS) has been used to identify subclinical cardiac dysfunction prior to development of overt CTRCD. Recent harmonized guidelines have incorporated GLS into definitions for CTRCD to identify cardiac dysfunction and inform decisions regarding cardioprotective strategies. Methods and results: We evaluated subclinical dysfunction in breast cancer patients treated with AC and determined the echocardiographic and patient factors associated with significant GLS changes. One hundred fourteen HER2 negative patients treated with AC were prospectively recruited and underwent serial echocardiograms (LVEF and LVGLS) at three time points (prior to AC, 3 months, and 1 year). CTRCD was defined as an asymptomatic reduction in LVEF of 10% or symptomatic drop of 5% to LVEF <53%. Subclinical LV dysfunction was defined as a reduction of ≥10% in GLS compared with baseline, recognizing that this cut off identified an 'at risk cohort' rather than patients with established CTRCD. No participant demonstrated CTRCD by reduction in LVEF. Forty‐three patients (38%) demonstrated a ≥10% relative reduction in GLS at 12 months; 20/43 (47%) had a reduced absolute GLS to <16%, and were older, had hypertension, increased LV mass, lower baseline e′ velocity and GLS. GLS ≥20.5% at baseline yielded a sensitivity of 79% and specificity of 87% for a normal GLS (i.e., ≥16%) at 1 year despite a ≥10% reduction from baseline. Conclusions: We present a stepwise evaluation for subclinical LV dysfunction using both a relative reduction in GLS combined with an absolute reduction in GLS. We believe our findings may re‐stratify patients with a high baseline GLS into a lower risk group despite transient relative GLS decrements ≥10%. [ABSTRACT FROM AUTHOR]

Aims: The COVID‐19 infection has been described as affecting myocardial injury. However, the relation between left ventricular global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS), disease severity and all‐cause mortality in COVID‐19 is unclear. Methods and Results: The study consisted of 220 patients with COVID‐19, including 127 (57.5%) with mild, 43 (19.5%) with moderate and 50 (22.7%) with severe/critical conditions. Myocardial dysfunction was analysed by GLS, GCS and GRS using two‐dimensional speckle‐tracking echocardiography. Hazard ratios and Kaplan–Meier curves were produced to assess the association between strains and cardiac biomarker indices with a composite outcome of all‐cause mortality. With an average follow‐up period of 11 days, 19 patients reached the endpoint (death). Significant associations were found for the three strain parameters and the levels of blood urea nitrogen (BUN) (r = 0.206, 0.221 and 0.355, respectively). Cardiac troponin I (cTnI) was closely related to the GLS and GCS (r = 0.240 and 0.324, respectively). In multivariable Cox regression, GCS > −21.6% was associated with all‐cause death {hazard ratio, 4.007 [95% confidence interval (CI), 11.347–11.919]}. Conclusions: GLS, GCS and GRS are significantly related to myocardial dysfunction in patients with COVID‐19. Worsening GCS poses an increased risk of death in COVID‐19. [ABSTRACT FROM AUTHOR]

Aims: Systemic amyloidosis represents a heterogeneous group of diseases resulting from amyloid fibre deposition. The purpose of this study is to establish a differential diagnosis algorithm targeted towards the two most frequent subtypes of CA. Methods and results: We prospectively included all consecutive patients with ATTR and AL evaluated between 2018 and 2022 in two centres in a score derivation cohort and a different validation sample. All patients had a complete clinical, biomarker, electrocardiographic, and imaging evaluation. Confirmation of the final diagnosis with amyloid typing was performed according to the current international recommendations. The study population included 81 patients divided into two groups: ATTR (group 1, n = 32: 28 variant and 4 wild type) and AL (group 2, n = 49). ATTR patients were younger (50.7 ± 13.9 vs. 60.2 ± 7.3 years, P = 0.0001), and significantly different in terms of NT‐proBNP [ATTR: 1472.5 ng/L (97–4218.5) vs. AL 8024 ng/L (3058–14 069) P = 0.001], hs‐cTn I [ATTR: 10 ng/L (4–20) vs. AL 78 ng/L (32–240), P = 0.0002], GFR [ATTR 95.4 mL/min (73.8–105.3) vs. AL: 68.4 mL/min (47.8–87.4) P = 0.003]. At similar left ventricular (LV) wall thickness and ejection fraction, the ATTR group had less frequently pericardial effusion (ATTR: 15% vs. AL: 33% P = 0.0027), better LV global longitudinal strain (ATTR: −13.1% ± 3.5 vs. AL: −9.1% ± 4.3 P = 0.04), RV strain (ATTR: −21.9% ± 6.2 vs. AL: −16.8% ± 6 P = 0.03) and better reservoir function of the LA strain (ATTR: 22% ± 12 vs. AL: 13.6% ± 7.8 P = 0.02). Cut‐off points were calculated based on the Youden method. We attributed to 2 points for parameters having an AUC > 0.75 (NT‐proBNP AUC 0.799; hs‐cTnI AUC 0.87) and 1 point for GFR (AUC 0.749) and TTE parameters (GLS AUC 0.666; RV FWS AUC 0.649, LASr AUC 0.643). A score of equal or more than 4 points has been able to differentiate between AL and ATTR (sensitivity 80%, specificity 62%, AUC = 0.798). The differential diagnosis score system was applied to the validation cohort of 52 CA patients showing a sensitivity of 81% with specificity of 77%. Conclusions: CA is a complex entity and requires extensive testing for a positive diagnosis. This study highlights a series of non‐invasive checkpoints, which can be useful in guiding the decision‐making process towards a more accurate and rapid differential diagnosis. [ABSTRACT FROM AUTHOR]

Aims: Tafamidis improves clinical outcomes in transthyretin amyloid cardiomyopathy (ATTR‐CM), yet how tafamidis affects cardiac structure and function remains poorly described. This study prospectively analysed the effect of tafamidis on 12‐month longitudinal changes in cardiac structure and function by cardiac magnetic resonance (CMR) compared with the natural course of disease in an untreated historic control cohort. Methods and results: ATTR‐CM patients underwent CMR at tafamidis initiation and at 12 months. Untreated patients with serial CMRs served as reference to compare biventricular function, global longitudinal strain (GLS), LV mass and extracellular volume fraction (ECV). Thirty‐six tafamidis‐treated (n = 35; 97.1% male) and 15 untreated patients (n = 14; 93.3% male) with a mean age of 78.3 ± 6.5 and 76.9 ± 6.5, respectively, and comparable baseline characteristics were included. Tafamidis was associated with preserving biventricular function (LVEF (%): 50.5 ± 12 to 50.7 ± 11.5, P = 0.87; RVEF (%): 48.2 ± 10.4 to 48.2 ± 9.4, P = 0.99) and LV‐GLS (−9.6 ± 3.2 to −9.9 ± 2.4%; P = 0.595) at 12 months, while a significantly reduced RV‐function (50.8 ± 7.3 to 44.2 ± 11.6%, P = 0.028; P (change over time between groups) = 0.032) and numerically worsening LVGLS (−10.9 ± 3.3 to −9.1 ± 2.9%, P = 0.097; P (change over time between groups) = 0.048) was observed without treatment. LV mass significantly declined with tafamidis (184.7 ± 47.7 to 176.5 ± 44.3 g; P = 0.011), yet remained unchanged in untreated patients (163.8 ± 47.5 to 171.2 ± 39.7 g P = 0.356, P (change over time between groups) = 0.027). Irrespective of tafamidis, ECV and native T1‐mapping did not change significantly from baseline to 12‐month follow‐up (P > 0.05). Conclusions: Compared with untreated ATTR‐CM patients, initiation of tafamidis preserved CMR‐measured biventricular function and reduced LV mass at 12 months. ECV and native T1‐mapping did not change significantly comparable to baseline in both groups. [ABSTRACT FROM AUTHOR]

Aims: Clinical trials in heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) commonly have detailed eligibility criteria. This may contribute to challenges with efficient enrolment and questions regarding the generalizability of trial findings. Methods and results: Patients with HFmrEF/HFpEF from a large US healthcare system were identified through a computable phenotype applied in linked imaging and electronic health record databases. We evaluated shared eligibility criteria from five recent/ongoing HFmrEF/HFpEF trials (PARAGON‐HF, EMPEROR‐Preserved, DELIVER, FINE‐ARTS, and SPIRRIT‐HFpEF) and compared clinical and echocardiographic features as well as outcomes between trial‐eligible and trial‐ineligible patients. Among 5552 patients with HFpEF/HFmrEF, 792 (14%) were eligible for trial consideration, having met all criteria assessed. Causes of ineligibility included lack of recent loop diuretics (37%), significant pulmonary disease (24%), reduced estimated glomerular filtration rate (17%), recent stroke/transient ischaemic attack (13%), or low natriuretic peptides (12%); 53% of ineligible patients had >1 reason for exclusion. Compared with eligible patients, ineligible patients were younger (age 71 vs. 75 years, P < 0.001) with higher rates of coronary artery disease (66% vs. 59%, P < 0.001) and peripheral vascular disease (40% vs. 33%, P < 0.001), but less mitral regurgitation, lower E/e′ ratio, and smaller left atrial sizes. Both eligible and ineligible patients demonstrated high rates of structural heart disease consistent with HFpEF [elevated left atrial size or left ventricular (LV) hypertrophy/increased LV mass], although this was slightly higher among eligible patients (95% vs. 92%, P = 0.001). The two cohorts demonstrated similar LV global longitudinal strain along with a similar prevalence of atrial fibrillation/flutter, hypertension, and obesity. Ineligible patients had similar all‐cause mortality (33% vs. 33% at 3 years) to those eligible but lower rates of heart failure hospitalization (20% vs. 28% at 3 years, P < 0.001). Conclusions: Among patients with HFmrEF/HFpEF from a large health system, approximately one in seven were eligible for major trials based on key criteria applied through a clinical computable phenotype. These findings highlight the large proportion of patients with HFmrEF/HFpEF ineligible for contemporary trials for whom the generalizability of trial findings may be questioned and further investigation would be beneficial. [ABSTRACT FROM AUTHOR]

This article discusses a case report of two sisters with hypertrophic cardiomyopathy (HCM) who exhibit differences in genetic mutations and clinical presentation. HCM is a genetic disorder characterized by thickening of the heart muscle. The sisters both experienced symptoms such as chest pain and palpitations, but one sister also had a cerebral infarction. Genetic testing revealed mutations in the MYH7 and RYR2 genes in both sisters, while the younger sister carried an additional mutation in the AKAP9 gene. The findings suggest that different mutations can lead to variations in the severity and clinical manifestations of HCM. Further research is needed to understand the role of AKAP9 in HCM. [Extracted from the article]

Aims: There are minimal data on the prognostic impact of right atrial strain during the reservoir phase (RASr) in patients with immunoglobulin light‐chain (AL) cardiac amyloidosis. Methods and results: Among 78 patients who were diagnosed with AL cardiac amyloidosis at Kumamoto University Hospital from 2007 to 2022, 72 patients with sufficient two‐dimensional speckle tracking imaging data without chemotherapy before the diagnosis were retrospectively analysed. During a median follow‐up of 403 days, 31 deaths occurred. Age and the rate of male sex were not significantly different between the all‐cause death group and the survival group (age, 70.4 ± 8.8 years vs. 67.0 ± 10.0 years, P = 0.14, male sex, 65% vs. 66%, P = 0.91). The estimated glomerular filtration rate (eGFR) was significantly lower, and B‐type natriuretic peptide (BNP) and high sensitivity cardiac troponin T (hs‐cTnT) were significantly higher, in the all‐cause death group versus the survival group (eGFR, 48.2 ± 21.0 mL/min/1.73 m2 vs. 59.4 ± 24.4 mL/min/1.73 m2, P < 0.05, BNP, 725 [360–1312] pg/mL vs. 123 [81–310] pg/mL, P < 0.01, hs‐cTnT, 0.12 [0.07–0.18] ng/mL vs. 0.05 [0.03–0.08] ng/mL, P < 0.01). Left ventricular (LV) global longitudinal strain (GLS) (LV‐GLS), left atrial strain during the reservoir phase (LASr), right ventricular GLS (RV‐GLS), and RASr were significantly lower in the all‐cause death group versus the survival group (LV‐GLS, 8.5 ± 4.3% vs. 11.8 ± 3.8%, P < 0.01, LASr, 8.8 ± 7.1% vs. 14.3 ± 8.1%, P < 0.01, RV‐GLS, 11.6 ± 5.1% vs. 16.4 ± 3.9%, P < 0.01, RASr, 10.2 ± 7.3% vs. 20.7 ± 9.5%, P < 0.01). RASr was significantly associated with all‐cause death after adjusting for RV‐GLS, LV‐GLS and LASr (hazard ratio [HR]: 0.91, 95% confidence interval [95% CI]: 0.83–0.99, P < 0.05). RASr and log‐transformed BNP were significantly associated with all‐cause death after adjusting for log‐transformed troponin T and eGFR (RASr, HR: 0.93, 95% CI: 0.87–1.00, P < 0.05; log‐transformed BNP, HR: 2.10, 95% CI: 1.17–3.79, P < 0.05). The optimal cut‐off values were RASr: 16.4% (sensitivity: 66%, specificity: 84%, area under curve [AUC]: 0.81) and BNP: 311.2 pg/mL (sensitivity: 83%, specificity: 78%, AUC: 0.82) to predict all‐cause mortality using ROC analysis. Kaplan–Meier analysis revealed that patients with low RASr (<16.4%) or high BNP (>311.2 pg/mL) had a significantly high probability of all‐cause death (both, P < 0.01). We devised a new staging score by adding 1 point if RASr decreased or BNP levels increased more than each cut‐off value. The HR for all‐cause death using score 0 as a reference was 5.95 (95% CI: 1.19–29.79; P < 0.05) for score 1 and 23.29 (95% CI: 5.37–100.98; P < 0.01) for score 2. Conclusions: The new staging system using RASr and BNP predicted prognosis in patients with AL cardiac amyloidosis. [ABSTRACT FROM AUTHOR]

Abstract Aims To assess the different imaging characteristics between corticosteroid‐sensitive (CS) and corticosteroid‐refractory (CR) immune checkpoint inhibitor‐associated myocarditis (ICIaM) with cardiac magnetic resonance (CMR) and the potential CMR parameters in the early detection of CR ICIaM. Methods and results Thirty‐five patients diagnosed with ICIaM and 30 age and gender‐matched cancer patients without a history of ICI treatment were enrolled. CMR with contrast was performed within 2 days of clinical suspicion. Left ventricular ejection fraction (LVEF) and late gadolinium enhancement (LGE) were assessed by CMR. LV sub‐endocardial (GLSendo) and sub‐epicardial (GLSepi) global longitudinal strains were quantified by offline feature tracking analysis. CS and CR ICIaM were defined based on the trend of Troponin I and clinical course during corticosteroid treatment. All 35 patients presented with non‐fulminant symptoms upon initial assessment. Twenty patients (57.14%) were sensitive, and 15 (42.86%) were refractory to corticosteroids. Compared with controls, 22 patients (62.86%) with ICIaM developed LGE. LVEF decreased in CR ICIaM compared with the CS group and controls. GLSendo (−14.61 ± 2.67 vs. −18.50 ± 2.53, P

Aims: The early diagnosis of cardiac amyloidosis (CA) is paramount, since there are effective therapies that improve patient survival. The diagnostic accuracy of classical electrocardiographic (ECG) signs, such as low voltage, pseudoinfarct pattern, and conduction disturbances in the diagnosis of CA, is inferior to that of the echocardiographic myocardial deformation criteria; therefore, our aim was to find more accurate novel ECG criteria for this purpose. Methods: We tested the diagnostic value of five novel ECG criteria, two of them devised by us, in 34 patients with confirmed CA (20 transthyretin amyloidosis and 14 AL amyloidosis) and 45 control patients with left ventricular hypertrophy on echocardiography due to hypertension, valvular aortic stenosis and hypertrophic cardiomyopathy. The following novel ECG criteria, that suggested CA, were tested: QRS amplitude in lead I < 0.55 mV (I < 0.55); QRS amplitude in lead aVR < 0.5 mV (aVR < 0.5); average QRS amplitude of leads I + aVR < 0.575 mV [(I + aVR) < 0.575]; average QRS amplitude of leads I + aVR/average QRS amplitude of leads V1–4 < 0.375 [(I + aVR)/(V1–4) < 0.375]; average QRS amplitude of leads I + aVR/longest intrinsicoid deflection in leads I,aVL,V1–6 < 0.0115 [(I + aVR)/I,aVL,V1–6ID < 0.0115]. Results: The I < 0.55, aVR < 0.5, (I + aVR) < 0.575, (I + aVR)/(V1–4) < 0.375, (I + aVR)/I,aVL,V1–6ID < 0.0115 test accuracy (TA) were 81%, 84.8%, 82.3%, 84.8%, and 83.3%, respectively; the sensitivity (SE): 76.5%, 82.4%, 85.3%, 82.4%, and 76.9%; specificity (SP): 84.4%, 86.7%, 80%, 86.7%, and 87.5%; positive predictive values (PPV): 78.8%, 82.4%, 76.3%, 82.4%, and 80%; negative predictive values (NPV): 82.6%, 86.7%, 87.8%, 86.7%, and 85.4%; area under curve (AUC) values: 0.8922, 0.8794, 09016, 0.8824, and 0.8462 were respectively. These parameters of the novel ECG criteria were at least as good as those reported by other authors in the literature of the qualitative (TA: 67%, SE: 80%, SP: 34%, PPV: 75%, NPV: 42%, AUC: 0.57) and quantitative apical sparing (TA: 64–80%, SE: 66–81.3%, SP: 55–78.3%, PPV: 33–83.9%, NPV: 41–75%, AUC: 0.62–0.68) and left ventricular ejection fraction/global longitudinal strain >4.1 (TA: 77%, SE: 93%, SP: 38%, PPV: 79%, NPV: 69%, AUC: 0.65) echocardiographic criteria. Among the classical criteria, the low voltage in limb leads criterion was present most frequently (in 73.5%) in patients with CA, with slightly worse diagnostic value than the novel ECG criteria (TA: 78.5%, SE: 73.5%, SP: 82.2%, PPV: 75.8%, NPV: 80.4%). Conclusions: The novel ECG criteria [mostly the aVR < 0.5, (I + aVR)/(V1–4) < 0.375] seem at least as reliable in the diagnosis of CA as the best echocardiographic myocardial deformation criteria and might be used either together with the echocardiographic criteria or as stand‐alone criteria to diagnose CA in the future. [ABSTRACT FROM AUTHOR]

Aims: To assess the different imaging characteristics between corticosteroid‐sensitive (CS) and corticosteroid‐refractory (CR) immune checkpoint inhibitor‐associated myocarditis (ICIaM) with cardiac magnetic resonance (CMR) and the potential CMR parameters in the early detection of CR ICIaM. Methods and results: Thirty‐five patients diagnosed with ICIaM and 30 age and gender‐matched cancer patients without a history of ICI treatment were enrolled. CMR with contrast was performed within 2 days of clinical suspicion. Left ventricular ejection fraction (LVEF) and late gadolinium enhancement (LGE) were assessed by CMR. LV sub‐endocardial (GLSendo) and sub‐epicardial (GLSepi) global longitudinal strains were quantified by offline feature tracking analysis. CS and CR ICIaM were defined based on the trend of Troponin I and clinical course during corticosteroid treatment. All 35 patients presented with non‐fulminant symptoms upon initial assessment. Twenty patients (57.14%) were sensitive, and 15 (42.86%) were refractory to corticosteroids. Compared with controls, 22 patients (62.86%) with ICIaM developed LGE. LVEF decreased in CR ICIaM compared with the CS group and controls. GLSendo (−14.61 ± 2.67 vs. −18.50 ± 2.53, P < 0.001) and GLSepi (−14.75 ± 2.53 vs. −16.68 ± 2.05, P < 0.001) significantly increased in patients with CR ICIaM compared with the CS ICIaM. In patients with CS ICIaM, although GLSepi (−16.68 ± 2.05 vs. −19.31 ± 1.80, P < 0.001) was impaired compared with the controls, GLSendo was preserved. There was no difference in CMR parameters between LGE‐positive and negative groups. LVEF, GLSendo, and GLSepi were predictors of CR ICIaM. When LVEF, GLSendo, and GLSepi were included in multivariate analysis, only GLSendo remained an independent predictor of CR ICIaM (OR: 2.170, 95% CI: 1.189–3.962, P = 0.012). A GLSendo of ≥−17.10% (sensitivity, 86.7%; specificity, 80.0%; AUC, 0.860; P < 0.001) could predict CR ICIaM in the ICIaM cohort. Kaplan–Meier analysis showed that in patients with impaired GLSendo of ≥−17.10%, cardiovascular adverse events (CAEs) occurred much earlier than in patients with preserved GLSendo of <−17.10% (Log‐rank test P = 0.017). Conclusions: CR and CS ICIaM demonstrated different functional and morphological characteristics in different myocardial layers. An impaired GLSendo could be a helpful parameter in early identifying corticosteroid‐refractory individuals in the ICIaM population. [ABSTRACT FROM AUTHOR]

Aims: Transthyretin amyloid cardiomyopathy (ATTR‐CM) is characterized by increased wall thickness, diastolic dysfunction and progressive heart failure symptoms. The disease may infiltrate the conduction system leading to conduction disturbances requiring an implantation of permanent cardiac pacemaker (PM), but the extent is unknown. Here, we report the prevalence of ATTR‐CM in patients ≥65 years with PM. Methods and results: In this prospective, cross‐sectional single‐centre study patients were recruited from our out‐patient pacemaker clinic. Eligibility criteria were age above 65 years, permanent cardiac pacemaker and competent to give informed consent. Patients underwent echocardiography at the pacemaker visit and were referred to 99mTc‐DPD‐scintigraphy (DPD) and blood samples if septum thickness was ≥12 mm, defined as left ventricular hypertrophy (LVH). Fifty eight of the 128 patients had LVH on echocardiography. Eleven patients had a DPD‐scintigraphy based diagnosis of ATTR‐CM, which represent 19% of patients with LVH and 9% of the total cohort. Patients diagnosed with ATTR‐CM had higher concentrations of cardiac biomarkers (P < 0.001), higher E/E′ (P = 0.001), and lower global longitudinal strain (P = 0.003) on echocardiography and more heart failure symptoms (P = 0.001). Conclusions: The prevalence of ATTR‐CM in elderly patients with PM and LVH on echocardiography was 19%. [ABSTRACT FROM AUTHOR]

Aims: Left ventricular reverse remodelling (LVRR) is an important objective of optimal medical management for dilated cardiomyopathy (DCM) patients, as it is associated with favourable long‐term outcomes. Cardiac magnetic resonance (CMR) can comprehensively assess cardiac structure and function. We aimed to assess the CMR parameters at baseline and investigate independent variables to predict LVRR in DCM patients. Methods and results: Nighty‐eight initially diagnosed DCM patients who underwent CMR and echocardiography examinations at baseline were included. CMR parameters and feature tracking (FT) based left ventricular (LV) global strain (nStrain) and nStrain indexed to LV cardiac mass index (rStrain) were measured. The predictors of LVRR were determined by multivariate logistic regression analyses. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of CMR parameters and were compared by the DeLong test. At a median follow‐up time of 9 [interquartile range, 7–12] months, 35 DCM patients (36%) achieved LVRR. The patients with LVRR had lower LV volume, mass, LGE extent and stroke volume index (LVSVi) and higher left ventricular remodelling index (LVRI), nStrains, rStrains, and peak systolic strain rate (PSSR) in the longitudinal direction and rStrains in the circumferential direction at baseline (all P < 0.05). In the multivariate logistic regression analyses, LVRI [per SD, odds ratio (OR) 1.79; 95% confidence interval (CI) 1.08–2.98; P = 0.024] and the ratio of global longitudinal peak strain (rGLPS) (per SD, OR 1.88; 95% CI 1.18–3.01; P = 0.008) were independent predictors of LVRR. The combination of LVSVi, LVRI, and rGLPS had a greater area under the curve (AUC) than the combination of LVSVi and LVRI (0.75 vs. 0.68), but not significantly (P = 0.09). Conclusions: Patients with LVRR had a lower LV volume index, lower LVSV index, lower LGE extent, higher LVRI, and preserved myocardial deformation in the longitudinal direction at baseline. LVRI and rGLPS at baseline were independent determinants of LVRR. [ABSTRACT FROM AUTHOR]

Abstract Background The predictive value of left ventricular (LV) global longitudinal strain (GLS) to predict outcomes in different left ventricular ejection fraction (LVEF) cohorts is not well known. We aimed to assess the role of LV GLS predicting outcomes in HF patients by LVEF. Methods In the Multicenter Automatic Defibrillator Implantation Trial Cardiac Resynchronization Therapy (MADIT‐CRT), we studied 1077 patients (59%) with 2D speckle tracking data available, 437 patients with LVEF > 30% and 640 with LVEF ≤ 30%. Baseline LV GLS was stratified in tertiles in both LVEF subgroups. The primary endpoint was ventricular tachycardia/fibrillation (VT/VF) or death; the secondary endpoint was heart failure (HF) or death. Results In patients with LVEF ≤ 30%, a higher tertile GLS (T3, less contractility) was associated with a higher rate of VT/VF/death (P 30% (P = 0.057). In patients with LVEF ≤ 30%, a higher tertile GLS was also associated with a higher rate of HF/death. In multivariable models, LV GLS predicted VT/VF or death in the LVEF ≤ 30% subgroup [T1 vs. T2/3 HR = 1.67 (1.16–2.38), P = 0.005], but not in those with LVEF > 30% [T1 vs. T2.3 HR = 1.32 (0.86–2.04), P = 0.21]. LV GLS predicted HF/death in the LVEF ≤ 30% subgroup [T1 vs T2/3 HR = 2.00 (1.30–3.13), P = 0.002], but not in in those with LVEF > 30%. Conclusions In this MADIT‐CRT sub‐study, LV GLS identified patients at higher risk of VT/VF, HF/death risk independently of conventional clinical parameters in patients with LVEF ≤ 30%, but not in patients with LVEF > 30%.

Aims: Mechanical function of the left atrium (LA) and the left ventricle (LV) has been demonstrated to be a prognostic factor in patients with hypertrophic cardiomyopathy (HCM). We explore whether myocardial mechanical function can be improved by septal reduction therapy in symptomatic obstructive HCM. Methods and results: Among 65 patients who underwent septal myectomy for symptomatic obstructive HCM from 2006 to 2022, 44 were analysed after excluding those who underwent simultaneous valve repair or replacement or maze operation. LA and LV functional variables including LA strain and LV global longitudinal strain were evaluated by two‐dimensional and speckle‐tracking echocardiography and compared before and 1 year after surgery. After septal myectomy, LA volume index (58.1 ± 18.3 vs. 45.3 ± 14.6 mL/m2, P = 0.001) decreased significantly. As LV end‐systolic dimension increased after surgery, the LV ejection fraction decreased (73.8 ± 6.7 vs. 62.9 ± 8.3%, P < 0.001). LA strain (24.4 ± 9.3 vs. 30.5 ± 13.6%, P = 0.004) improved after septal myectomy, but LV global longitudinal strain deteriorated (−12.6 ± 3.6 vs. −11.6 ± 4.3%, P = 0.033), mainly related to worsening non‐septal longitudinal strain (−14.4 ± 4.3 vs. −10.9 ± 8.4%, P = 0.005). Conclusions: As haemodynamic loads due to LV outflow tract obstruction was relieved through surgical septal reduction therapy in patients with symptomatic obstructive HCM, there was a significant reduction in LA volume and restoration of LA mechanical dysfunction. However, LV mechanical dysfunction deteriorated even after surgical septal reduction therapy. [ABSTRACT FROM AUTHOR]

Aims: The presence of anti‐human leucocyte antigen (HLA) antibodies has been implicated in a higher incidence of complications as well as mortality rate in heart transplantation. The aim of the study was to identify through non‐invasive parameters early signs of myocardial dysfunction in the presence of anti‐HLA antibodies but without evidence of antibody‐mediated rejection (AMR) and its possible prognostic impact. Methods and results: A total of 113 heart‐transplanted patients without acute cellular rejection (ACR) and AMR or cardiac allograft vasculopathy (CAV) were prospectively enrolled and divided into two groups ['HLA+' (50 patients) and 'HLA−' (63 patients)], based on the presence of anti‐HLA antibodies. Each patient was followed for 2 years after the enrolment, recording episodes of AMR, ACR, CAV, and mortality. Clinical characteristics were similar between the two groups. Among laboratory data, N‐terminal pro‐B‐type natriuretic peptide and high‐sensitivity cardiac troponin values were significantly higher in the presence of anti‐HLA antibodies (P < 0.001 and P = 0.003, respectively). The echocardiographic parameters that showed a statistically significant difference between the two groups were deceleration time of E wave (DecT E, P < 0.001), left ventricular global longitudinal strain (P < 0.001), tricuspid annular plane systolic excursion (P = 0.011), tricuspid S′ wave (P = 0.002), and free wall right ventricular longitudinal strain (fwRVLS, P = 0.027), whereas left atrial strain did not differ significantly (P = 0.408). Univariate analysis showed that anti‐HLA antibodies were associated with the development of CAV at both 1 and 2 year follow‐up [odds ratio (OR) 11.90, 95% confidence interval (CI) 1.43–90.79, P = 0.022 and OR 3.37, 95% CI 1.78–9.67, P = 0.024, respectively]. Bivariate analysis demonstrated that both fwRVLS and DecT E were predictors of CAV development independently from HLA status. Conclusions: The presence of circulating anti‐HLA antibodies is correlated with a mild cardiac dysfunction, even in the absence of AMR, and CAV development. Interestingly, reduced values of DecT E and fwRVLS were predictors of future development of CAV, independently from anti‐HLA antibody. [ABSTRACT FROM AUTHOR]

Aims: Transplant services were imposed to the multiple challenges of insufficient facilities and resources during the COVID‐19 pandemic. Thus, each centre modified and altered its routine practice to maintain the service. We report our experience in Iran's single‐centre paediatric heart transplantation unit during the 2 year pandemic in transplant rate and early transplant outcomes. Methods and results: We retrospectively reviewed all paediatric heart transplants performed at our centre between 19 February 2020 and February 2022. We studied the number and percentage of paediatric transplanted patients who developed COVID‐19, in‐hospital outcome, 30 day survival and left ventricular function during the first month of the follow‐up visit. From February 2020 to February 2022, 59 transplants were performed compared with 62 patients from February 2018 to 2020. Compared with the year before the pandemic, the heart transplant rate was reduced by 34% in the first year of the pandemic; however, it bounced back in the second year with a 19% increase. The in‐hospital mortality rate during the 2 year pandemic was (11.8%). One death occurred related to COVID‐19 acute respiratory distress syndrome. The in‐hospital COVID‐19 infection rate was 11 patients (18%). In the 30 day follow‐up, the overall 30 day survival rate was 88%, and the 30 day rejection rate was 10%. The mean left ventricular ejection fraction was (53.6 ± 4.9), the mean left ventricular global longitudinal strain was −16.9 ± 3.3, and the mean right ventricular global longitudinal strain was −17.0 ± 3.8 with no significant difference between patients with in‐hospital COVID and other recipients (P = 0.1, P = 0.2 and P = 0.2). Conclusions: Throughout the pandemic, although we experienced a reduction in the transplant rate in the first year, with the increasing vaccination rate in health care and later in the general population, we continued to maintain our transplant rate by incorporating safety protocols and more resources. [ABSTRACT FROM AUTHOR]

Aims: Coronary microvascular dysfunction (CMD) has been proposed as an important pathophysiological mechanism in Takotsubo syndrome (TTS). Our aims were (i) to evaluate and compare levels of CMD in patients with TTS and patients with ischaemia and no obstructive coronary arteries (INOCA) and (ii) to investigate associations between CMD and clinical parameters, left ventricular function, and coronary atherosclerosis in TTS. Methods and results: We conducted a prospective study of 27 female TTS patients and an equally sized, age‐ and gender‐matched, cohort of INOCA patients. Coronary microvascular function was quantified invasively using the index of microcirculatory resistance (IMR), coronary flow reserve (CFR), and resistive reserve ratio (RRR). CMD was defined as IMR ≥ 25 and/or CFR ≤ 2. In the TTS patients, left ventricular function was assessed with echocardiography and cardiovascular magnetic resonance (CMR) imaging, and coronary atherosclerosis was visualized with intravascular ultrasound with near‐infrared spectroscopy (IVUS‐NIRS). The incidence of CMD was higher in the TTS patients than in the INOCA cohort (78% vs. 44%, P = 0.01), with higher IMR (30 vs. 14, P = 0.002), lower CFR (1.8 vs. 2.8, P = 0.009), and lower RRR (2.1 vs. 3.5, P = 0.003). In apical compared with midventricular TTS, IMR was numerically higher (50 vs. 28, P = 0.20), whereas CFR and RRR were lower (1.5 vs. 2.5, P = 0.003 and 1.6 vs. 2.7, P = 0.01, respectively). Global longitudinal strain and global circumferential strain, assessed with CMR imaging, were more impaired in apical than in midventricular TTS (−11 vs. −14, P < 0.001 and −12 vs. −15, P = 0.049, respectively). In the TTS patients, CFR and RRR correlated with echocardiography‐derived (R2 = 0.15, P = 0.002 and R2 = 0.18, P = 0.007, respectively) and CMR‐derived (R2 = 0.09, P = 0.025 and R2 = 0.10, P = 0.038, respectively) ejection fraction. CFR and RRR correlated inversely with CMR‐derived end‐diastolic volume index, end‐systolic volume index, and left ventricular mass index. IMR, CFR, and RRR were not associated with measures of coronary atherosclerosis derived by IVUS‐NIRS. Conclusions: Coronary microvascular dysfunction is common in patients with TTS and more frequent than in patients with INOCA. CMD in TTS is more severe in the apical compared with the midventricular phenotype of the syndrome, is associated with left ventricular function, but is unrelated to coronary atherosclerosis. Our results support the notion of CMD as a key mediator in TTS. [ABSTRACT FROM AUTHOR]

Background: The predictive value of left ventricular (LV) global longitudinal strain (GLS) to predict outcomes in different left ventricular ejection fraction (LVEF) cohorts is not well known. We aimed to assess the role of LV GLS predicting outcomes in HF patients by LVEF. Methods: In the Multicenter Automatic Defibrillator Implantation Trial Cardiac Resynchronization Therapy (MADIT‐CRT), we studied 1077 patients (59%) with 2D speckle tracking data available, 437 patients with LVEF > 30% and 640 with LVEF ≤ 30%. Baseline LV GLS was stratified in tertiles in both LVEF subgroups. The primary endpoint was ventricular tachycardia/fibrillation (VT/VF) or death; the secondary endpoint was heart failure (HF) or death. Results: In patients with LVEF ≤ 30%, a higher tertile GLS (T3, less contractility) was associated with a higher rate of VT/VF/death (P < 0.001), with similar association in patients with LVEF > 30% (P = 0.057). In patients with LVEF ≤ 30%, a higher tertile GLS was also associated with a higher rate of HF/death. In multivariable models, LV GLS predicted VT/VF or death in the LVEF ≤ 30% subgroup [T1 vs. T2/3 HR = 1.67 (1.16–2.38), P = 0.005], but not in those with LVEF > 30% [T1 vs. T2.3 HR = 1.32 (0.86–2.04), P = 0.21]. LV GLS predicted HF/death in the LVEF ≤ 30% subgroup [T1 vs T2/3 HR = 2.00 (1.30–3.13), P = 0.002], but not in in those with LVEF > 30%. Conclusions: In this MADIT‐CRT sub‐study, LV GLS identified patients at higher risk of VT/VF, HF/death risk independently of conventional clinical parameters in patients with LVEF ≤ 30%, but not in patients with LVEF > 30%. [ABSTRACT FROM AUTHOR]

Abstract Aims Fabry disease (FD) is often associated with heart failure (HF). However, data on HF prevalence, prognosis, and applicability of echocardiographic criteria for HF diagnosis in FD remain uncertain. Methods and results We evaluated patients with genetically proven FD for symptoms and natriuretic peptides indicating HF. We then analysed the diagnostic utility of the currently recommended European Society of Cardiology (ESC) echocardiographic criteria for HF diagnosis and their relationship to natriuretic peptides. Finally, we examined the association between HF and echocardiographic criteria with mortality and cardiovascular events during follow‐up. Of 116 patients with FD, 48 (41%) had symptomatic HF (mean age 58 ± 11 years, 62% male). HF with preserved ejection fraction (HF‐pEF) was diagnosed in 43 (91%) patients, representing the dominant phenotype. Left ventricular mass index (LVMi) had the highest diagnostic utility (sensitivity 71% and specificity 83%) for HF diagnosis in FD, followed by E/e′ > 9 (sensitivity 76% and specificity 78%) and global longitudinal strain (GLS) 9, and GLS

Aims: A causal link between non‐ischaemic heart failure (HF) and humoral autoimmunity against G‐protein‐coupled receptors (GPCR) remains unclear except for Chagas' cardiomyopathy. Uncertainty arises from ambiguous reports on incidences of GPCR autoantibodies, spurious correlations of autoantibody levels with disease activity, and lack of standardization and validation of measuring procedures for putatively cardio‐pathogenic GPCR autoantibodies. Here, we use validated and certified immune assays presenting native receptors as binding targets. We compared candidate GPCR autoantibody species between HF patients and healthy controls and tested associations of serum autoantibody levels with serological, haemodynamic, metabolic, and functional parameters in HF. Methods: Ninety‐five non‐ischaemic HF patients undergoing transcatheter endomyocardial biopsy and 60 healthy controls were included. GPCR autoantibodies were determined in serum by IgG binding to native receptors or a cyclic peptide (for β1AR autoantibodies). In patients, cardiac function, volumes, and myocardial structural properties were assessed by cardiac magnetic resonance imaging; right heart catheterization served for determination of cardiac haemodynamics; endomyocardial biopsies were used for histological assessment of cardiomyopathy and determination of cardiac mitochondrial oxidative function by high‐resolution respirometry. Results: Autoantibodies against β1 adrenergic (β1AR), M5‐muscarinic (M5AR), and angiotensin II type 2 receptors (AT2R) were increased in HF (all P < 0.001). Autoantibodies against α1‐adrenergic (α1AR) and angiotensin II type 1 receptors (AT1R) were decreased in HF (all P < 0.001). Correlation of alterations of GPCR autoantibodies with markers of cardiac or systemic inflammation or cardiac damage, haemodynamics, myocardial histology, or left ventricular inflammation (judged by T2 mapping) were weak, even when corrected for total IgG. β1AR autoantibodies were related inversely to markers of left ventricular fibrosis indicated by T1 mapping (r = −0.362, P < 0.05) and global longitudinal strain (r = −0.323, P < 0.05). AT2R autoantibodies were associated with improved myocardial mitochondrial coupling as measured by high‐resolution respirometry in myocardial biopsies (r = −0.352, P < 0.05). In insulin‐resistant HF patients, AT2R autoantibodies were decreased (r = −.240, P < 0.05), and AT1R autoantibodies were increased (r = 0.212, P < 0.05). Conclusions: GPCR autoantibodies are markedly altered in HF. However, they are correlated poorly or even inversely to haemodynamic, metabolic, and functional markers of disease severity, myocardial histology, and myocardial mitochondrial efficiency. These observations do not hint towards a specific cardio‐pathogenic role of GPCR autoantibodies and suggest that further investigations are required before specific therapies directed at GPCR autoantibodies can be clinically tested in non‐ischaemic HF. [ABSTRACT FROM AUTHOR]

Right ventricular (RV) function and its adaptation to increased afterload [RV–pulmonary arterial (PA) coupling] are crucial in various types of pulmonary hypertension, determining symptomatology and outcome. In the course of disease progression and increasing afterload, the right ventricle undergoes adaptive remodelling to maintain right‐sided cardiac output by increasing contractility. Exhaustion of compensatory RV remodelling (RV–PA uncoupling) finally leads to maladaptation and increase of cardiac volumes, resulting in heart failure. The gold‐standard measurement of RV–PA coupling is the ratio of contractility [end‐systolic elastance (Ees)] to afterload [arterial elastance (Ea)] derived from RV pressure–volume loops obtained by conductance catheterization. The optimal Ees/Ea ratio is between 1.5 and 2.0. RV–PA coupling in pulmonary hypertension has considerable reserve; the Ees/Ea threshold at which uncoupling occurs is estimated to be ~0.7. As RV conductance catheterization is invasive, complex, and not widely available, multiple non‐invasive echocardiographic surrogates for Ees/Ea have been investigated. One of the first described and best validated surrogates is the ratio of tricuspid annular plane systolic excursion to estimated pulmonary arterial systolic pressure (TAPSE/PASP), which has shown prognostic relevance in left‐sided heart failure and precapillary pulmonary hypertension. Other RV–PA coupling surrogates have been formed by replacing TAPSE with different echocardiographic measures of RV contractility, such as peak systolic tissue velocity of the lateral tricuspid annulus (S′), RV fractional area change, speckle tracking‐based RV free wall longitudinal strain and global longitudinal strain, and three‐dimensional RV ejection fraction. PASP‐independent surrogates have also been studied, including the ratios S′/RV end‐systolic area index, RV area change/RV end‐systolic area, and stroke volume/end‐systolic volume. Limitations of these non‐invasive surrogates include the influence of severe tricuspid regurgitation (which can cause distortion of longitudinal measurements and underestimation of PASP) and the angle dependence of TAPSE and PASP. Detection of early RV remodelling may require isolated analysis of single components of RV shortening along the radial and anteroposterior axes as well as the longitudinal axis. Multiple non‐invasive methods may need to be applied depending on the level of RV dysfunction. This review explains the mechanisms of RV (mal)adaptation to its load, describes the invasive assessment of RV–PA coupling, and provides an overview of studies of non‐invasive surrogate parameters, highlighting recently published works in this field. Further large‐scale prospective studies including gold‐standard validation are needed, as most studies to date had a retrospective, single‐centre design with a small number of participants, and validation against gold‐standard Ees/Ea was rarely performed. [ABSTRACT FROM AUTHOR]

Aims: Sacubitril/valsartan has changed the treatment of heart failure with reduced ejection fraction (HFrEF), due to the positive effects on morbidity and mortality, partly mediated by left ventricular (LV) reverse remodelling (LVRR). The aim of this multicenter study was to identify echocardiographic predictors of LVRR after sacubitril/valsartan administration. Methods and results: Patients with HFrEF requiring therapy with sacubitril/valsartan from 13 Italian centres were included. Echocardiographic parameters including LV global longitudinal strain (GLS) and global peak atrial longitudinal strain by speckle tracking echocardiography were measured to find the predictors of LVRR [= LV end‐systolic volume reduction ≥10% and ejection fraction (LVEF) improvement ≥10% at follow‐up] at 6 month follow‐up as the primary endpoint. Changes in symptoms [New York Heart Association (NYHA) class] and neurohormonal activations [N‐terminal pro‐brain natriuretic peptide (NT‐proBNP)] were also evaluated as secondary endpoints; 341 patients (excluding patients with poor acoustic windows and missing data) were analysed (mean age: 65 ± 10 years; 18% female, median LVEF 30% [inter‐quartile range: 25−34]). At 6 month follow‐up, 82 (24%) patients showed early complete response (LVRR and LVEF ≥ 35%), 55 (16%) early incomplete response (LVRR and LVEF < 35%), and 204 (60%) no response (no LVRR and LVEF < 35%). Non‐ischaemic aetiology, a lower left atrial volume index, and a higher GLS were all independent predictors of LVRR at multivariable logistic analysis (all P < 0.01). A baseline GLS < −9.3% was significantly associated with early response (area under the curve 0.75, P < 0.0001). Left atrial strain was the best predictor of positive changes in NYHA class and NT‐proBNP (all P < 0.05). Conclusions: Speckle tracking echocardiography parameters at baseline could be useful to predict LVRR and clinical response to sacubitril–valsartan and could be used as a guide for treatment in patients with HFrEF. [ABSTRACT FROM AUTHOR]

Aims: Fabry disease (FD) is often associated with heart failure (HF). However, data on HF prevalence, prognosis, and applicability of echocardiographic criteria for HF diagnosis in FD remain uncertain. Methods and results: We evaluated patients with genetically proven FD for symptoms and natriuretic peptides indicating HF. We then analysed the diagnostic utility of the currently recommended European Society of Cardiology (ESC) echocardiographic criteria for HF diagnosis and their relationship to natriuretic peptides. Finally, we examined the association between HF and echocardiographic criteria with mortality and cardiovascular events during follow‐up. Of 116 patients with FD, 48 (41%) had symptomatic HF (mean age 58 ± 11 years, 62% male). HF with preserved ejection fraction (HF‐pEF) was diagnosed in 43 (91%) patients, representing the dominant phenotype. Left ventricular mass index (LVMi) had the highest diagnostic utility (sensitivity 71% and specificity 83%) for HF diagnosis in FD, followed by E/e′ > 9 (sensitivity 76% and specificity 78%) and global longitudinal strain (GLS) <16% (sensitivity 54% and specificity 88%). Log N‐terminal pro‐brain natriuretic peptide correlated significantly with LVMi (r = 0.60), E/e′ (r = 0.54), and GLS (r = 0.52) (all Ps < 0.001) but not with left ventricular ejection fraction (r = −0.034, P = 0.72). During follow‐up (mean 1208 ± 444 days), patients diagnosed with HF had a higher rate of all‐cause mortality and worsening HF (33% vs. 1.5%, P < 0.001). Abnormal LVMi, E/e′ > 9, and GLS < 16% were all associated with higher all‐cause mortality and worsening HF. Conclusions: This study found a high prevalence of symptomatic HF in FD patients. HF‐pEF was the dominant phenotype. LVMi, E/e′, and GLS yielded the highest diagnostic utility for HF diagnosis and were significantly correlated with natriuretic peptides levels. Echocardiographic criteria proposed by current ESC HF guidelines apply to Fabry patients and predict cardiovascular events. At follow‐up, Fabry patients with HF diagnosis had high event rates and significantly worse prognosis than patients without HF. [ABSTRACT FROM AUTHOR]

Abstract Aims To evaluate echocardiographic and biomarker changes during chemotherapy, assess their ability to early detect and predict cardiotoxicity and to define the best time for their evaluation. Methods and results Seventy‐two women with breast cancer (52 ± 9.8 years) treated with anthracyclines (26 also with trastuzumab), were evaluated for 14 months (6 echocardiograms/12 laboratory tests). We analysed: high‐sensitivity cardiac troponin T, NT‐proBNP, global longitudinal strain (GLS), left ventricle end‐systolic volume (LVESV), left ventricle end‐diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF). Cardiotoxicity was defined as a reduction in LVEF>10% compared with baseline with LVEF

Abstract Aims This study aimed to determine the relationship of low birth weight (LBW) with adult cardiac structure and function and investigate potential causal pathways. Methods and results A population‐based sample of 925 Australians (41.3% male) were followed from childhood (aged 7–15 years) to young adulthood (aged 26–36 years) and mid‐adulthood (aged 36–50 years). Left ventricular (LV) global longitudinal strain (GLS, %), LV mass index (LVMi, g/m2.7), LV filling pressure (E/e′), and left atrial volume index (g/m2) were measured by transthoracic echocardiography in mid‐adulthood. Birth weight category was self‐reported in young adulthood and classified as low (≤5 lb or ≤2270 g), normal (5–8 lb or 2271–3630 g), and high (>8 lb or >3630 g). Of the 925 participants, 7.5% (n = 69) were classified as LBW. Compared with participants with normal birth weight, those with LBW had 2.01‐fold (95% confidence interval: 1.19, 3.41, P = 0.009) higher risks of impaired GLS (GLS > −18%) and 2.63‐fold (95% confidence interval: 0.89, 7.81, P = 0.08) higher risks of LV hypertrophy (LVMi > 48 g/m2.7 in men or >44 g/m2.7 in women) in adulthood, independent of age, sex, and any socio‐economic factors. Participants with LBW significantly increased body fat from childhood to adulthood relative to their peers and had greater levels of triglycerides, fasting glucose, and arterial stiffness in adulthood. These risk factors were the strongest mediators and explained 54% of the LBW effect size on adult GLS and 33% of the LBW effect size on LVMi. The remaining of these associations was independent of any of the measured risk factors. Conclusions Low birth weight was associated with impaired cardiac structure and function in mid‐adulthood. This association was only partially explained by known risk factors.

Aims: To evaluate echocardiographic and biomarker changes during chemotherapy, assess their ability to early detect and predict cardiotoxicity and to define the best time for their evaluation. Methods and results: Seventy‐two women with breast cancer (52 ± 9.8 years) treated with anthracyclines (26 also with trastuzumab), were evaluated for 14 months (6 echocardiograms/12 laboratory tests). We analysed: high‐sensitivity cardiac troponin T, NT‐proBNP, global longitudinal strain (GLS), left ventricle end‐systolic volume (LVESV), left ventricle end‐diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF). Cardiotoxicity was defined as a reduction in LVEF>10% compared with baseline with LVEF<53%. High‐sensitivity troponin T levels rose gradually reaching a maximum peak at 96 ± 13 days after starting chemotherapy (P < 0.001) and 62.5% of patients presented increased values during treatment. NT‐proBNP augmented after each anthracycline cycle (mean pre‐cycle levels of 72 ± 68 pg/mL and post‐cycle levels of 260 ± 187 pg/mL; P < 0.0001). Cardiotoxicity was detected in 9.7% of patients (mean onset at 5.2 months). In the group with cardiotoxicity, the LVESV was higher compared with those without cardiotoxicity (40 mL vs. 29.5 mL; P = 0.045) at 1 month post‐anthracycline treatment and the decline in GLS was more pronounced (−17.6% vs. −21.4%; P = 0.03). Trastuzumab did not alter serum biomarkers, but it was associated with an increase in LVESV and LVEDV (P < 0.05). While baseline LVEF was an independent predictor of later cardiotoxicity (P = 0.039), LVESV and GLS resulted to be early detectors of cardiotoxicity [odds ratio = 1.12 (1.02–1.24), odds ratio = 0.66 (0.44–0.92), P < 0.05] at 1 month post‐anthracycline treatment. Neither high‐sensitivity troponin T nor NT‐proBNP was capable of predicting subsequent cardiotoxicity. Conclusions: One month after completion of anthracycline treatment is the optimal time to detect cardiotoxicity by means of imaging parameters (LVESV and GSL) and to determine maximal troponin rise. Baseline LVEF was a predictor of later cardiotoxicity. Trastuzumab therapy does not affect troponin values hence imaging techniques are recommended to detect trastuzumab‐induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

Abstract Aims Global longitudinal strain (GLS) has become an alternative to left ventricular ejection fraction (LVEF) to determine systolic function of the heart. The absence of cut‐off values is one of the limitations preventing full clinical implementation. The aim of this study is to determine a cut‐off value of GLS for an increased risk of adverse events in individuals with a normal LVEF. Methods and results Echocardiographic images of 502 subjects (52% female, mean age 48 ± 15) with an LVEF ≥ 55% were analysed using speckle tracking‐based GLS. The primary endpoint was cardiovascular death or cardiac hospitalization. The analysis of Cox models with splines was performed to visualize the effect of GLS on outcome. A cut‐off value was suggested by determining the optimal specificity and sensitivity. The median GLS was −22.2% (inter‐quartile range −20.0 to −24.9%). In total, 35 subjects (7%) had a cardiac hospitalization and/or died because of cardiovascular disease during a follow‐up of 40 (5–80) months. There was a linear correlation between the risk for adverse events and GLS value. Subjects with a normal LVEF and a GLS between −22.9% and −20.9% had a mildly increased risk (hazard ratio 1.01–2.0) for cardiac hospitalization or cardiovascular mortality, and the risk was doubled for subjects with a GLS of −20.9% and higher. The optimal specificity and sensitivity were determined at a GLS value of −20.0% (hazard ratio 2.49; 95% confidence interval: 1.71–3.61). Conclusions There is a strong correlation between cardiac adverse events and GLS values in subjects with a normal LVEF. In our single‐centre study, −20.0% was determined as a cut‐off value to identify subjects at risk. A next step should be to integrate GLS values in a multi‐parametric model.

Abstract Aims This study aimed to investigate the functional correlate, clinical relevance, and prognostic implications of novel left ventricular (LV) deformations in patients with atrial fibrillation (AF). Methods and results LV deformational indices, including peak global longitudinal strain (GLS), systolic strain rates (SRs), and early diastolic strain rates (SRe) were measured in a large‐scale AF population. We related such measures to key clinical heart failure (HF) markers, conventional echocardiographic ventricular parameters, and clinical outcomes. Among 1483 subjects with newly diagnosed AF (mean age, 71.6 ± 12.4 years; 55.5% male), worsened GLS (mean, − 12.6 ± 3.9%) and strain rates (SRs and SRe: mean, − 0.86 ± 0.27 and 1.25 ± 0.41 1/s, respectively) by our three‐beat measures were independently correlated with higher C‐reactive protein, N‐terminal pro‐B‐type natriuretic peptide, higher E/e′, more impaired LV ejection fraction (LVEF − 14.7%) was common in our cohort (67.8%) despite an averaged preserved LVEF (58.4 ± 14.2%), with worse GLS and SRe being associated with higher composite HF re‐admissions/death during the 2.9 year follow‐up (inter‐quartile range, 1.6–4.1 years) in multivariate models incorporating key LV indices (LVEF, LV mass index, and E/e′) (all P

Abstract Aims Obesity doubles the lifetime risk of developing heart failure. Current knowledge on the role of obesity in causing cardiac dysfunction is insufficient for optimal risk stratification. The aim of this study was first to estimate the prevalence of subclinical cardiac dysfunction in obesity patients and second to investigate the underlying pathophysiology. Methods and results The CARDIOBESE study is a cross‐sectional multicentre study of 100 obesity patients [body mass index (BMI) ≥ 35 kg/m2] without known cardiovascular disease and 50 age‐matched and gender‐matched non‐obese controls (BMI ≤ 30 kg/m2). Echocardiography was performed, blood samples were collected, and a Holter monitor was affixed. Fifty‐nine obesity patients [48 (42–50) years, 70% female] showed subclinical cardiac dysfunction: 57 patients had decreased global longitudinal strain (GLS), and two patients with normal GLS had either diastolic dysfunction or increased brain natriuretic peptide (BNP). Only one non‐obese control had diastolic dysfunction, and none had another sign of cardiac dysfunction. Multivariable logistic analysis identified male gender and standard deviation of all NN intervals (SDNN) index, which is a measure of autonomic dysfunction, as independent significant risk factors for subclinical cardiac dysfunction in obesity patients. Conclusions There was a high prevalence (61%) of subclinical cardiac dysfunction in obesity patients without known cardiovascular disease, which appeared to be best identified by GLS. Subclinical cardiac dysfunction in obesity was linked to autonomic dysfunction and male gender, and not to the presence of traditional cardiac risk factors, increased C‐reactive protein, increased BNP, increased high‐sensitivity troponin I, or increased left ventricular mass.

Abstract Aims The present study had two aims: (i) compare echocardiographic parameters in COVID‐19 patients with matched controls and (2) assess the prognostic value of measures of left (LV) and right ventricular (RV) function in relation to COVID‐19 related death. Methods and results In this prospective multicentre cohort study, 214 consecutive hospitalized COVID‐19 patients underwent an echocardiographic examination (by pre‐determined research protocol). All participants were successfully matched 1:1 with controls from the general population on age, sex, and hypertension. Mean age of the study sample was 69 years, and 55% were male participants. LV and RV systolic function was significantly reduced in COVID‐19 cases as assessed by global longitudinal strain (GLS) (16.4% ± 4.3 vs. 18.5% ± 3.0, P

Aims: This study aimed to determine the relationship of low birth weight (LBW) with adult cardiac structure and function and investigate potential causal pathways. Methods and results: A population‐based sample of 925 Australians (41.3% male) were followed from childhood (aged 7–15 years) to young adulthood (aged 26–36 years) and mid‐adulthood (aged 36–50 years). Left ventricular (LV) global longitudinal strain (GLS, %), LV mass index (LVMi, g/m2.7), LV filling pressure (E/e′), and left atrial volume index (g/m2) were measured by transthoracic echocardiography in mid‐adulthood. Birth weight category was self‐reported in young adulthood and classified as low (≤5 lb or ≤2270 g), normal (5–8 lb or 2271–3630 g), and high (>8 lb or >3630 g). Of the 925 participants, 7.5% (n = 69) were classified as LBW. Compared with participants with normal birth weight, those with LBW had 2.01‐fold (95% confidence interval: 1.19, 3.41, P = 0.009) higher risks of impaired GLS (GLS > −18%) and 2.63‐fold (95% confidence interval: 0.89, 7.81, P = 0.08) higher risks of LV hypertrophy (LVMi > 48 g/m2.7 in men or >44 g/m2.7 in women) in adulthood, independent of age, sex, and any socio‐economic factors. Participants with LBW significantly increased body fat from childhood to adulthood relative to their peers and had greater levels of triglycerides, fasting glucose, and arterial stiffness in adulthood. These risk factors were the strongest mediators and explained 54% of the LBW effect size on adult GLS and 33% of the LBW effect size on LVMi. The remaining of these associations was independent of any of the measured risk factors. Conclusions: Low birth weight was associated with impaired cardiac structure and function in mid‐adulthood. This association was only partially explained by known risk factors. [ABSTRACT FROM AUTHOR]

Abstract Aims Currently, the ejection fraction [left ventricular ejection fraction (LVEF)] is the main criterion used for implanting implantable cardioverter defibrillators (ICDs) for primary prevention. However, many of ICD receivers would not have an event and do not have any gains from the device. Consequently, improving the discrimination strategies is needed. Here, we aimed at assessing the role of global longitudinal strain (GLS) for such purpose. Methods and results Seventy ischaemic or dilated cardiomyopathy cases characterized by LVEF ≤ 40% with a previously implanted ICD were enrolled. LVEF and GLS amounts were evaluated using 3D echocardiography. The occurrence of ventricular arrhythmias was checked by analysing the ICD history. Mean follow‐up period of patients was 1.8 ± 0.6 years. There was a significant difference in the amount of GLS in arrhythmic cases compared with non‐arrhythmic ones (−6.97 ± 3.06 vs −11.82 ± 4.25; P

Abstract Aims The angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan reduces mortality and hospitalizations in patients with heart failure and reduced ejection fraction (HFrEF). Favourable effects on haemodynamic and functional parameters have been observed in patients with HFrEF undergoing ARNI therapy, using standard transthoracic echocardiography. Global longitudinal strain (GLS) assessment uses a semi‐automatic procedure to provide a reliable and repeatable method that improves the detection of early changes of contractile function. We aimed to assess the effects of ARNI on GLS and myocardial mechanics in patients with HFrEF. Methods and results Thirty patients with New York Heart Association class II–III HFrEF were treated with ARNI and monitored using standard echocardiographic examination and GLS measurements at baseline, 3 months, and 6 months. ARNI therapy resulted in a significant reduction of ventricular volumes and a significant increase in left ventricular ejection fraction at 6 months but not 3 months by standard transthoracic echocardiography (left ventricular ejection fraction from 28 ± 8% at baseline to 34 ± 12% at 6 months, P

Abstract Aims Although serum uric acid (SUA) level is correlated with oxidative stress and serves as a marker of poor prognosis in heart failure patients, its possible association with subclinical left ventricular (LV) dysfunction has not been evaluated. This study aimed to investigate the association between SUA and subclinical LV dysfunction in a sample of a general population without overt cardiac disease. Methods and results We examined 1175 participants who underwent extensive cardiovascular health check‐up including laboratory tests and speckle‐tracking echocardiography to assess LV global longitudinal strain (GLS). The association of SUA concentration, as a continuous variable and a categorical variable using quartiles, with the presence of abnormal LVGLS was assessed. Mean age was 62 ± 12 years, and 656 (56%) were male participants. Mean SUA was 5.6 ± 1.3 mg/dL (25th–75th percentile, 4.6–6.5 mg/dL). The prevalence of abnormal LVGLS (greater than –18.6%) was greatest in the upper quartile of SUA. In multivariable analysis, SUA as a continuous variable was significantly associated with abnormal LVGLS [adjusted odds ratio (OR), 1.26 per 1 mg/dL; P = 0.008] independent of traditional cardiovascular risk factors, pertinent laboratory parameters and echocardiographic measures, and medications. In the categorical analysis, the upper quartile of SUA was independently associated with abnormal LVGLS in a fully adjusted model (adjusted OR, 2.28 vs. lowest quartile; P = 0.020). Conclusions In a sample of the general population, an elevated SUA was independently associated with subclinical LV dysfunction. Assessment of LVGLS may add important prognostic information in individuals with elevated SUA, even in the absence of overt cardiac disease.

Aims: The present study had two aims: (i) compare echocardiographic parameters in COVID‐19 patients with matched controls and (2) assess the prognostic value of measures of left (LV) and right ventricular (RV) function in relation to COVID‐19 related death. Methods and results: In this prospective multicentre cohort study, 214 consecutive hospitalized COVID‐19 patients underwent an echocardiographic examination (by pre‐determined research protocol). All participants were successfully matched 1:1 with controls from the general population on age, sex, and hypertension. Mean age of the study sample was 69 years, and 55% were male participants. LV and RV systolic function was significantly reduced in COVID‐19 cases as assessed by global longitudinal strain (GLS) (16.4% ± 4.3 vs. 18.5% ± 3.0, P < 0.001), tricuspid annular plane systolic excursion (TAPSE) (2.0 ± 0.4 vs. 2.6 ± 0.5, P < 0.001), and RV strain (19.8 ± 5.9 vs. 24.2 ± 6.5, P = 0.004). All parameters remained significantly reduced after adjusting for important cardiac risk factors. During follow‐up (median: 40 days), 25 COVID‐19 cases died. In multivariable Cox regression reduced TAPSE [hazard ratio (HR) = 1.18, 95% confidence interval (CI) [1.07–1.31], P = 0.002, per 1 mm decrease], RV strain (HR = 1.64, 95%CI[1.02;2.66], P = 0.043, per 1% decrease) and GLS (HR = 1.20, 95%CI[1.07–1.35], P = 0.002, per 1% decrease) were significantly associated with COVID‐19‐related death. TAPSE and GLS remained significantly associated with the outcome after restricting the analysis to patients without prevalent heart disease. Conclusions: RV and LV function are significantly impaired in hospitalized COVID‐19 patients compared with matched controls. Furthermore, reduced TAPSE and GLS are independently associated with COVID‐19‐related death. [ABSTRACT FROM AUTHOR]

Aims: Obesity doubles the lifetime risk of developing heart failure. Current knowledge on the role of obesity in causing cardiac dysfunction is insufficient for optimal risk stratification. The aim of this study was first to estimate the prevalence of subclinical cardiac dysfunction in obesity patients and second to investigate the underlying pathophysiology. Methods and results: The CARDIOBESE study is a cross‐sectional multicentre study of 100 obesity patients [body mass index (BMI) ≥ 35 kg/m2] without known cardiovascular disease and 50 age‐matched and gender‐matched non‐obese controls (BMI ≤ 30 kg/m2). Echocardiography was performed, blood samples were collected, and a Holter monitor was affixed. Fifty‐nine obesity patients [48 (42–50) years, 70% female] showed subclinical cardiac dysfunction: 57 patients had decreased global longitudinal strain (GLS), and two patients with normal GLS had either diastolic dysfunction or increased brain natriuretic peptide (BNP). Only one non‐obese control had diastolic dysfunction, and none had another sign of cardiac dysfunction. Multivariable logistic analysis identified male gender and standard deviation of all NN intervals (SDNN) index, which is a measure of autonomic dysfunction, as independent significant risk factors for subclinical cardiac dysfunction in obesity patients. Conclusions: There was a high prevalence (61%) of subclinical cardiac dysfunction in obesity patients without known cardiovascular disease, which appeared to be best identified by GLS. Subclinical cardiac dysfunction in obesity was linked to autonomic dysfunction and male gender, and not to the presence of traditional cardiac risk factors, increased C‐reactive protein, increased BNP, increased high‐sensitivity troponin I, or increased left ventricular mass. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to investigate the functional correlate, clinical relevance, and prognostic implications of novel left ventricular (LV) deformations in patients with atrial fibrillation (AF). Methods and results: LV deformational indices, including peak global longitudinal strain (GLS), systolic strain rates (SRs), and early diastolic strain rates (SRe) were measured in a large‐scale AF population. We related such measures to key clinical heart failure (HF) markers, conventional echocardiographic ventricular parameters, and clinical outcomes. Among 1483 subjects with newly diagnosed AF (mean age, 71.6 ± 12.4 years; 55.5% male), worsened GLS (mean, − 12.6 ± 3.9%) and strain rates (SRs and SRe: mean, − 0.86 ± 0.27 and 1.25 ± 0.41 1/s, respectively) by our three‐beat measures were independently correlated with higher C‐reactive protein, N‐terminal pro‐B‐type natriuretic peptide, higher E/e′, more impaired LV ejection fraction (LVEF < 50%), lower estimated glomerular filtration rate, permanent AF, and prevalent HF (all P < 0.05). LV deformations by three‐beat analysis well correlated with the respective results of traditional methods. Abnormal GLS (>− 14.7%) was common in our cohort (67.8%) despite an averaged preserved LVEF (58.4 ± 14.2%), with worse GLS and SRe being associated with higher composite HF re‐admissions/death during the 2.9 year follow‐up (inter‐quartile range, 1.6–4.1 years) in multivariate models incorporating key LV indices (LVEF, LV mass index, and E/e′) (all P < 0.001). Sensitivity analysis by excluding those with regional wall motion abnormality showed broadly similar findings. An improved risk reclassification was observed when GLS and SRe were separately added to the LVEF. Comparison of the AF cohort with a fully matched independent non‐AF cohort at the same baseline LVEF level showed a substantially lower GLS [− 13.2 ± 3.8% (AF) vs. 18.1 ± 3.2% (non‐AF)] and higher clinical events rate (hazard ratio, 1.41 [95% confidence interval, 1.14–1.75]; log‐rank P = 0.002) in the AF cohort. Conclusions: Impaired LV function defined by myocardial deformation was common in patients with AF and provides independent prognostic values over conventional measures with improved risk prediction. Our data highlight the need for implementing cardiac deformations in daily practice for patients with AF. [ABSTRACT FROM AUTHOR]

Aims: Currently, the ejection fraction [left ventricular ejection fraction (LVEF)] is the main criterion used for implanting implantable cardioverter defibrillators (ICDs) for primary prevention. However, many of ICD receivers would not have an event and do not have any gains from the device. Consequently, improving the discrimination strategies is needed. Here, we aimed at assessing the role of global longitudinal strain (GLS) for such purpose. Methods and results: Seventy ischaemic or dilated cardiomyopathy cases characterized by LVEF ≤ 40% with a previously implanted ICD were enrolled. LVEF and GLS amounts were evaluated using 3D echocardiography. The occurrence of ventricular arrhythmias was checked by analysing the ICD history. Mean follow‐up period of patients was 1.8 ± 0.6 years. There was a significant difference in the amount of GLS in arrhythmic cases compared with non‐arrhythmic ones (−6.97 ± 3.06 vs −11.82 ± 4.25; P < 0.001). This difference was found in both ischaemic and dilated cardiomyopathy groups. A GLS below −10 cm/s could predict the occurrence of a ventricular event by 90% specificity and 72.2% sensitivity (area under the curve = 0.84, P < 0.001). While 27.39 (69.2%) patients with GLS below −10 cm/s had a ventricular event, only 3.31 (9.6%) of the patients with GLS above −10 had an event) P < 0.001). Those patients with a GLS ≥ 17 cm/s never experienced a ventricular arrhythmia. Conclusions: Global longitudinal strain is a more accurate predictor of ventricular arrhythmias in patients with reduced LVEF. Whether it may help in selecting more appropriate patients for ICD implantation or not should be evaluated within a randomized trial in the future. [ABSTRACT FROM AUTHOR]

Aims: Although serum uric acid (SUA) level is correlated with oxidative stress and serves as a marker of poor prognosis in heart failure patients, its possible association with subclinical left ventricular (LV) dysfunction has not been evaluated. This study aimed to investigate the association between SUA and subclinical LV dysfunction in a sample of a general population without overt cardiac disease. Methods and results: We examined 1175 participants who underwent extensive cardiovascular health check‐up including laboratory tests and speckle‐tracking echocardiography to assess LV global longitudinal strain (GLS). The association of SUA concentration, as a continuous variable and a categorical variable using quartiles, with the presence of abnormal LVGLS was assessed. Mean age was 62 ± 12 years, and 656 (56%) were male participants. Mean SUA was 5.6 ± 1.3 mg/dL (25th–75th percentile, 4.6–6.5 mg/dL). The prevalence of abnormal LVGLS (greater than –18.6%) was greatest in the upper quartile of SUA. In multivariable analysis, SUA as a continuous variable was significantly associated with abnormal LVGLS [adjusted odds ratio (OR), 1.26 per 1 mg/dL; P = 0.008] independent of traditional cardiovascular risk factors, pertinent laboratory parameters and echocardiographic measures, and medications. In the categorical analysis, the upper quartile of SUA was independently associated with abnormal LVGLS in a fully adjusted model (adjusted OR, 2.28 vs. lowest quartile; P = 0.020). Conclusions: In a sample of the general population, an elevated SUA was independently associated with subclinical LV dysfunction. Assessment of LVGLS may add important prognostic information in individuals with elevated SUA, even in the absence of overt cardiac disease. [ABSTRACT FROM AUTHOR]

Aims: The angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan reduces mortality and hospitalizations in patients with heart failure and reduced ejection fraction (HFrEF). Favourable effects on haemodynamic and functional parameters have been observed in patients with HFrEF undergoing ARNI therapy, using standard transthoracic echocardiography. Global longitudinal strain (GLS) assessment uses a semi‐automatic procedure to provide a reliable and repeatable method that improves the detection of early changes of contractile function. We aimed to assess the effects of ARNI on GLS and myocardial mechanics in patients with HFrEF. Methods and results: Thirty patients with New York Heart Association class II–III HFrEF were treated with ARNI and monitored using standard echocardiographic examination and GLS measurements at baseline, 3 months, and 6 months. ARNI therapy resulted in a significant reduction of ventricular volumes and a significant increase in left ventricular ejection fraction at 6 months but not 3 months by standard transthoracic echocardiography (left ventricular ejection fraction from 28 ± 8% at baseline to 34 ± 12% at 6 months, P < 0.001). Non‐significant differences in the size of the left atrium, right ventricular function, and pulmonary pressures were found at 6 months. By using GLS, there was a progressive improvement of all strain parameters by 3 months. The improvement showed a progressive trend over time and maintained significance at 6 months: GLS 4ch −7.2 ± 4.8% at baseline vs. −7.5 ± 3.9% at 3 months (P = 0.025) and − 9.2 ± 5.2% at 6 months (P = 0.0001); AVG GLS −6.9 ± 4.3 at baseline vs. −7.9 ± 4.2 at 3 months (P = 0.04) and − 8.8 ± 4.4 at 6 months (P = 0.035); GLS endo 8.2 ± 4.8 at baseline vs. −9.0 ± 4.8 at 3 months (P = 0.05) and − 10.1 ± 5.1 at 6 months (P = 0.001). Conclusions: Sacubitril/valsartan induces an early benefit on left ventricular remodelling, which is captured by myocardial strain and not by standard echocardiography. Strain method represents a practical tool to assess early and minimal variations of left ventricular systolic function. [ABSTRACT FROM AUTHOR]

Aims Global longitudinal strain (GLS) has become an alternative to left ventricular ejection fraction (LVEF) to determine systolic function of the heart. The absence of cut-off values is one of the limitations preventing full clinical implementation. The aim of this study is to determine a cut-off value of GLS for an increased risk of adverse events in individuals with a normal LVEF. Methods and results Echocardiographic images of 502 subjects (52% female, mean age 48 ± 15) with an LVEF ≥ 55% were analysed using speckle tracking-based GLS. The primary endpoint was cardiovascular death or cardiac hospitalization. The analysis of Cox models with splines was performed to visualize the effect of GLS on outcome. A cut-off value was suggested by determining the optimal specificity and sensitivity. The median GLS was -22.2% (inter-quartile range -20.0 to -24.9%). In total, 35 subjects (7%) had a cardiac hospitalization and/or died because of cardiovascular disease during a follow-up of 40 (5–80) months. There was a linear correlation between the risk for adverse events and GLS value. Subjects with a normal LVEF and a GLS between -22.9% and -20.9% had a mildly increased risk (hazard ratio 1.01–2.0) for cardiac hospitalization or cardiovascular mortality, and the risk was doubled for subjects with a GLS of -20.9% and higher. The optimal specificity and sensitivity were determined at a GLS value of -20.0% (hazard ratio 2.49; 95% confidence interval: 1.71–3.61). Conclusions There is a strong correlation between cardiac adverse events and GLS values in subjects with a normal LVEF. In our single-centre study, -20.0% was determined as a cut-off value to identify subjects at risk. A next step should be to integrate GLS values in a multi-parametric model. [ABSTRACT FROM AUTHOR]

2022 May 19. i We read with great interest the study by Muehlberg I et al i .[1] where the authors attempted to characterize sepsis-associated cardiomyopathy using cardiovascular magnetic resonance imaging (cMRI). I Letter on the article: Characterization of critically ill patients with septic shock and sepsis-associated cardiomyopathy using cardiovascular MRI. [Extracted from the article]

Abstract: Aims: We aimed to explore the burden of frequent premature ventricular contractions (PVCs) associated with myocardial dysfunction in patients with outflow tract arrhythmia (OTA). We hypothesized that this threshold is lower than the previously suggested threshold of 24 000 PVCs/24 h (24%PVC) when systolic function is assessed by strain echocardiography. Furthermore, we aimed to characterize OTA patients with malignant arrhythmic events. Methods and results: We included 52 patients referred for OTA ablation (46 ± 12 years, 58% female). Left ventricular global longitudinal strain (GLS) and mechanical dispersion were assessed by speckle tracking echocardiography. A subset underwent cardiac magnetic resonance imaging. PVC burden (%PVC) was assessed by Holter recording. Sinus rhythm QRS duration and PVC QRS duration were recorded from electrocardiogram, and the ratio was calculated (PVC QRS duration / sinus rhythm QRS duration). Median %PVC was 7.2 (0.2–60.0%). %PVC correlated with GLS (R = 0.44, P = 0.002) and with mechanical dispersion (R = 0.48, P < 0.001), but not with ejection fraction (R = 0.22, P = 0.12). %PVC was higher in patients with impaired systolic function by GLS (worse than −18%) compared with patients with normal function (22% vs. 5%, P = 0.001). Greater than 8%PVC optimally identified patients with abnormal GLS (area under the curve 0.79). Serious arrhythmic events occurred in 11/52 (21%) patients characterized by high QRS ratios (1.56 vs. 1.91, P < 0.001). Conclusions: More than 8%PVC was associated with impaired systolic function by GLS, which is a lower threshold than previously reported. Patients with serious arrhythmic events had higher QRS ratios, which may represent a more malignant phenotype of OTA. [ABSTRACT FROM AUTHOR]

Abstract: Aims: While abnormal resting LV GLS has been described in patients with chronic heart failure with preserved ejection fraction (HFpEF), its prognostic significance when measured during an acute heart failure hospitalization remains unclear. We assessed the association between left ventricular global longitudinal strain (LV GLS) and outcomes in patients hospitalized with acute HFpEF. Methods and results: We studied patients discharged alive for acute HFpEF from Duke University Medical Center between 2007 and 2010. Among patients with measurable LV GLS, we performed 2D, speckle‐tracking analysis and Cox proportional hazards models assessed the association between continuous LV GLS and outcomes. Baseline characteristics were stratified by normal (≤−16%) or abnormal (>−16%) LV GLS for comparison. Among 463 patients, the median LV GLS was −12.8% (Interquartile range, −15.8 to −10.8%) and was abnormal in 352 (76%). Overall patients in the cohort were generally elderly, female and had hypertension. After multivariable adjustment, worse outcomes were noted between LV GLS and mortality (HR 1.19 per 1% increase; 95% CI 1.00–1.42; P = 0.046) and a composite endpoint of mortality or rehospitalization at 30 days (HR 1.08 per 1% increase; 95% CI 0.99–1.18; P = 0.08). There was no association between LV GLS and mortality or a composite of mortality or rehospitalization at 1 year. Conclusions: A high prevalence of patients hospitalized with acute HFpEF have abnormal LV GLS suggesting unrecognized myocardial systolic dysfunction. Furthermore, worse LV GLS is associated with worse clinical outcomes at 30 days but not by1 year. [ABSTRACT FROM AUTHOR]