Abnormal Left Ventricular Ejection Fraction Research Articles

Cardioprotective Diet to Prevent Anthracycline-Induced Cardiotoxicity in Patients with Breast Cancer: A Randomized Open-Label Controlled Trial.

Objectives: Several studies have indicated that dietary interventions may offer protection against the development of cardiac damage in the case of anthracycline-induced cardiomyopathy (AIC). The goal of this study was to assess whether an evidence-based cardioprotective diet can be effective in preventing AIC in patients with breast cancer. Design: Randomized, open-label, controlled trial. The study period was set for 18 weeks, and the data were analyzed by generalized estimating equation modeling and one-way repeated measures analysis of variance. Setting/Location: Shahid Rajaie Hospital affiliated (Tehran, Iran). Subjects: Fifty anthracycline-treated patients with breast cancer. Interventions: Patients were randomized to receive either a 2-hour training in evidence-based cardio-protective diet or Carvedilol 6.25 mg bid. Outcome Measures: The primary outcome was the number of patients with abnormal left ventricular ejection fraction (LVEF) after 18 weeks. Results: At week 18, 12 (48%) out of 25 participants in the cardioprotective diet group had abnormal LVEF in comparison with 21 (84%) out of 25 in the carvedilol group (p = 0.007). Also, 2 (8%) out of 25 in the cardioprotective diet group compared with 7 (28%) out of 25 participants in the carvedilol group had abnormal global longitudinal strain (p = 0.066). The diet group showed significant improvements in the quality-of-life dimensions named "health change" and "general health" compared with the carvedilol group using the Short Form-36 Health Survey questionnaire. Conclusions: This study suggests that an evidence-based cardioprotective diet can contribute to the prevention of AIC. Although current treatments for AIC can be effective, further research is mandatory for more options.

Associations of cardiac function and arterial stiffness with cerebrovascular disease

BackgroundWhite matter hyperintensities (WMHs) represent diffuse small vessel disease implicating the cardiac, systemic, and cerebral vasculatures. As the brain may be the end-organ of cumulative vascular disease, and higher education is protective of both cardiovascular and brain health, we aim to clarify their intertwining relationships. MethodsWe evaluated participants (mean age = 64) from the UK Biobank with neuroimaging measures of WMHs, left ventricular ejection fraction (LVEF) quantified using cardiovascular MRI, and arterial stiffness index (ASI) quantified using finger photoplethysmography. We used multiple regression to evaluate the basic, independent, and interactive relationships of LVEF status (n = 27,512) and ASI (n = 33,584) with WMHs. Moderated mediation analysis was used to determine whether the relationship between LVEF status and WMH was mediated by ASI and moderated by education. ResultsAbnormal LVEF (β = −0.082, p < 0.001) and higher ASI (β = 0.02, p < 0.001) were associated with greater WMHs separately and independently, but not interactively. Moderated mediation analyses revealed that the relationship between abnormal LVEF and WMH was mediated by ASI, for individuals with lower education (β = −0.004, p < 0.001). Abnormal LVEF was associated with lower cortical thickness in 16 predominantly frontotemporal and select parietal regions (FDR, q < 0.05). ConclusionsCardiovascular dysfunction is associated with regional cerebral atrophy and may precipitate cerebrovascular disease via stiffening of systemic vasculatures, particularly for individuals with lower education. Integrative approaches to study biophysiological vascular systems can elucidate the complex interplay between biological and social determinants of brain and cerebrovascular health.

Presence and utility of electrocardiographic abnormalities in long-term childhood cancer survivors

BackgroundWe assessed the prevalence and diagnostic value of ECG abnormalities for cardiomyopathy surveillance in childhood cancer survivors.MethodsIn this cross-sectional study, 1381 survivors (≥5 years) from the Dutch Childhood Cancer Survivor...

Identifying left ventricular dysfunction using prospective electrocardiogram-triggered coronary computed tomography angiography

PurposeCoronary computed tomography angiography (CCTA) is an important non-invasive tool for the assessment of coronary artery disease and the delivery of information incremental to coronary anatomy. CCTA measured left ventricular (LV) mid-diastolic volume (LVMDV) and LV mass (LVMass) have important prognostic information but the utility of prospectively ECG-triggered CCTA to predict reduced left ventricular ejection fraction (LVEF) is unknown. The objective of this study was to determine if indexed LVMDV (LVMDVi) and the LVMDV:LVMass ratio on CCTA can identify patients with reduced LVEF. Materials/methods8179 patients with prospectively ECG-triggered CCTA between November 2014 and December 2019 were reviewed. A subset derivation cohort of 4352 healthy patients was used to define normal LVMDVi and LVMDV:LVMass. Sex-specific thresholds were tested in a validation cohort of 1783 patients, excluded from the derivation cohort, with cardiac disease and known LVEF. The operating characteristics for 1 SD above the mean were tested for the identification of abnormal LVEF, LVEF≤35 ​% and ≤30 ​%. ResultsThe derivation cohort had a mean LVMDVi of 61.0 ​± ​13.7 ​mL/m2 and LVMDV:LVMass of 1.11 ​± ​0.24 ​mL/g. LVMDVi and LVMDV:LVMass were both higher in patients with reduced LVEF than those with normal LVEF (98.8 ​± ​40.8 ​mL/m2 vs. 63.3 ​± ​19.7 ​mL/m2, p ​< ​0.001, and 1.32 ​± ​0.44 ​mL/g vs. 1.05 ​± ​0.28 ​mL/g, p ​< ​0.001). Both mean LVMDVi and LVMDV:LVMass increased with the severity of LVEF reduction. Sex-specific LVMDVi thresholds were 79 ​% and 80 ​% specific for identifying abnormal LVEF in females (LVMDVi ​≥ ​69.9 ​mL/m2) and males (LVMDVi ​≥ ​78.8 ​mL/m2), respectively. LVMDV:LVMass thresholds had high specificity (87 ​%) in both females (LVMDVi:LVMass ​≥ ​1.39 ​mL/g) and males (LVMDVi:LVMass ​≥ ​1.30 ​mL/g). ConclusionOur study provides reference thresholds for LVMDVi and LVMDV:LVMass on prospectively ECG-triggered CCTA, which may identify patients who require further LV function assessment.

Artificial intelligence electrocardiogram as a novel screening tool to detect a newly abnormal left ventricular ejection fraction after anthracycline-based cancer therapy.

Cardiotoxicity is a serious side effect of anthracycline treatment, most commonly manifesting as a reduction in left ventricular ejection fraction (EF). Early recognition and treatment have been advocated, but robust, convenient, and cost-effective alternatives to cardiac imaging are missing. Recent developments in artificial intelligence (AI) techniques applied to electrocardiograms (ECGs) may fill this gap, but no study so far has demonstrated its merit for the detection of an abnormal EF after anthracycline therapy. Single centre consecutive cohort study of all breast cancer patients with ECG and transthoracic echocardiography (TTE) evaluation before and after (neo)adjuvant anthracycline chemotherapy. Patients with HER2-directed therapy, metastatic disease, second primary malignancy, or pre-existing cardiovascular disease were excluded from the analyses as were patients with EF decline for reasons other than anthracycline-induced cardiotoxicity. Primary readout was the diagnostic performance of AI-ECG by area under the curve (AUC) for EFs < 50%. Of 989 consecutive female breast cancer patients, 22 developed a decline in EF attributed to anthracycline therapy over a follow-up time of 9.8 ± 4.2 years. After exclusion of patients who did not have ECGs within 90 days of a TTE, 20 cases and 683 controls remained. The AI-ECG model detected an EF < 50% and ≤ 35% after anthracycline therapy with an AUC of 0.93 and 0.94, respectively. These data support the use of AI-ECG for cardiotoxicity screening after anthracycline-based chemotherapy. This technology could serve as a gatekeeper to more costly cardiac imaging and could enable patients to monitor themselves over long periods of time.

Abstract 19087: Cardiac Magnetic Resonance Imaging Increased Utilization of Cardiac Treatment in Young Duchenne Muscular Dystrophy Patients

Introduction: Duchenne muscular dystrophy (DMD), an X-linked recessive disorder affecting up to 1 in 6000. DMD-associated cardiomyopathy (DMD-C) is universal and starts as young as 6 years of age by cardiac magnetic resonance imaging (CMR) with presence of late gadolinium enhancement (LGE). Heart failure signs and symptoms are vague due to skeletal muscle myopathy. Echocardiogram only detects global dysfunction by left ventricular ejection fraction (LVEF) which rarely occur before 10 years of age. The current DMD cardiac care consideration guidelines (CCCG) recommends initiation of cardiac medication around 10 years of age or if there is LGE and/or LVEF abnormalities . Hypothesis: We hypothesized young DMD were more likely to have cardiac therapy initiated after CMR compared to only TTE evaluation. Methods: Electronic medical records for DMD patients (6 to &lt; 10 years) who underwent routine TTE or CMR evaluation between 2014-2023 were included. Demographic data at the time of the study and initiation of cardiac medication including angiotensin-converting-enzyme inhibitor (ACE-I), Angiotensin II receptor blockers (ARB) and/or Mineralocorticoid Receptor Antagonists (MRA) were recorded. Results: 150 patients met inclusion criteria, of these 81 patients underwent TTE only and 69 underwent CMR evaluation in lieu of TTE with no difference in age (8.4±1.1 versus 8.6±0.8 years, P = 0.07). Of those with TTE evaluation 10/81 (12.3%) was initiated with ACE-I or ARB ( 3/10 (33%) had LVEF &lt; 55% (average 53.5%), 4/10 (40%) turned 10 on the follow-up visit and 3/10 (30%)) because family requested. Of the 69 patients with CMR, 51/69 (73.9%) had cardiac therapy initiated (28/51 (54.9%) because of new LGE, 6/51 (11.8%) due to isolated LVEF &lt; 55% (average 53%), 12/51 (23.5%) would turn 10 on follow-up and 5/51 (9.8%)) the family requested. All patients with LGE on CMR also had MRA therapy started. Conclusions: DMC-C is universal and the use of CMR improved disease specific treatment of both ACE-I/ARB and MRA. Duboc et al, in a placebo control study showed that in 9.5 - 13.5 year old DMD patients treated with ACE-I had fewer patients develop dysfunction with reduced mortality at 10 years. Early and aggressive treatment may attenuate DMD-C. Future longitudinal study is needed.

Concordance analysis between practice and algorithm recommendations for cardiac screening in a cohort of high-risk lymphoma survivors.

498 Background: Cardiovascular disease (CVD) is a leading cause of mortality among cancer survivors, with the risk peaking five or more years post-diagnosis. Among survivors, lymphoma patients receiving cardio-toxic therapies such as anthracyclines and mediastinal radiation exhibit an elevated risk for CVD-related complications and mortality. To address this concern, we have implemented lymphoma survivorship care algorithms that outline recommended cardiovascular health monitoring for these patients. Methods: In 2021, 387 patients were seen in the Lymphoma Survivorship clinic. Of these, 53 were previously treated with both an anthracycline and thoracic radiation. We conducted a review of cardiac screening tests and visits for this high-risk group, with the aim of evaluating the concordance between their survivorship care and the algorithm recommendations. Specifically, we assessed the frequency and type of cardiac screening received by these patients at risk for cardiac late effects from treatment, and the prevalence of cardiac abnormalities in the cohort. Results: The mean age of the patients at their most recent survivorship appointment was 53 years, while the median time since the last radiation therapy was 11.67 years. Of the patients studied, 84.9% had a post-treatment cardiology consultation, with 69.8% receiving cardiology services at MD Anderson. An echocardiogram (ECHO) was available for 90.5% of patients, with no abnormal left ventricular ejection fraction (LVEF) reported. The average number of cardiology visits was 3.08 per patient, and the average time between the most recent ECHO and the latest survivorship appointment was 1.26 years. A lipid profile was performed for 98% of the cohort, typically during their survivorship appointment or a subsequent cardiology visit. Body Mass Index (BMI) and blood pressure were assessed in all patients, with an average BMI of 29 and hypertension reported in 28% of cases. Conclusions: We identified a high level of concordance in survivorship care and our algorithm’s recommendations for a cohort of lymphoma survivors with a high risk of cardiovascular late effects post-treatment. We conclude the algorithm was beneficial in guiding care in this patient population. Collaboration with cardiology services is crucial for identifying and monitoring high-risk survivors, updating cardiology care guidelines, and continuously monitoring long-term cardiovascular outcomes.

Diagnostic accuracy of point-of-care ultrasound with artificial intelligence-assisted assessment of left ventricular ejection fraction

Focused cardiac ultrasound (FoCUS) is becoming standard practice in a wide spectrum of clinical settings. There is limited data evaluating the real-world use of FoCUS with artificial intelligence (AI). Our objective was to determine the accuracy of FoCUS AI-assisted left ventricular ejection fraction (LVEF) assessment and compare its accuracy between novice and experienced users. In this prospective, multicentre study, participants requiring a transthoracic echocardiogram (TTE) were recruited to have a FoCUS done by a novice or experienced user. The AI-assisted device calculated LVEF at the bedside, which was subsequently compared to TTE. 449 participants were enrolled with 424 studies included in the final analysis. The overall intraclass coefficient was 0.904, and 0.921 in the novice (n = 208) and 0.845 in the experienced (n = 216) cohorts. There was a significant bias of 0.73% towards TTE (p = 0.005) with a level of agreement of 11.2%. Categorical grading of LVEF severity had excellent agreement to TTE (weighted kappa = 0.83). The area under the curve (AUC) was 0.98 for identifying an abnormal LVEF (<50%) with a sensitivity of 92.8%, specificity of 92.3%, negative predictive value (NPV) of 0.97 and a positive predictive value (PPV) of 0.83. In identifying severe dysfunction (<30%) the AUC was 0.99 with a sensitivity of 78.1%, specificity of 98.0%, NPV of 0.98 and PPV of 0.76. Here we report that FoCUS AI-assisted LVEF assessments provide highly reproducible LVEF estimations in comparison to formal TTE. This finding was consistent among senior and novice echocardiographers suggesting applicability in a variety of clinical settings.

A Higher Estimated Glomerular Filtration Rate Is Associated with Better Survival in Subjects with Coronary Artery Disease and Heart Failure with a Mildly Reduced Ejection Fraction.

Subjects with coronary artery disease (CAD) have myocardial ischemia and associated abnormal left ventricular ejection fraction (EF). Heart failure with mildly reduced EF (41-49%) (HFmrEF) is a new subgroup of EF for heart failure. Although prognostic factors for CAD and HF with reduced EF are well known, fewer studies have been conducted on factors related to the survival of CAD and HFmrEF. We recruited study subjects with significant CAD and HFmrEF from our cardiac catheterization data bank. Data were recorded from traceable chart records from our hospital. All-cause and cardiovascular mortality were recorded until December 2019 and served as a follow-up outcome. A total of 348 subjects with CAD and HFmrEF were analyzed. The median duration of follow-up was 37 months. Seventy-eight subjects died during the follow-up period and 30 of them were due to cardiovascular causes. In univariate analyses, those who died were of older ages, and with a lower estimated glomerular filtration rate (eGFR) (47 ± 30 versus 71 ± 30 mL/minute/1.73 m2, P < 0.001), and lower usage of percutaneous coronary intervention (PCI) and beta blockers. In the Cox survival regression analysis, a higher eGFR (hazard ratio 0.980, P < 0.001) was protective, while older age and a higher serum total cholesterol (hazard ratio 1.006, P = 0.048) were related to all-cause mortality for CAD with HFmrEF. Furthermore, a higher eGFR was also associated with less cardiovascular mortality. In conclusion, for subjects with CAD and HFmrEF, a higher eGFR was protective and associated with a lower all-cause and cardiovascular mortality.

Tracking Changes in Global Longitudinal Strain in Lung Cancer Patients Receiving Thoracic Radiation

Thoracic radiation improves survival in many lung cancer patients. However, radiation-induced cardiotoxicity is a major source of morbidity and mortality in such patients. Global longitudinal strain (GLS), a novel echocardiography (ECHO) method of assessing left ventricular function, has been shown to predict long-term adverse cardiovascular risk in diverse patient populations. We hypothesized that receipt of thoracic radiation is associated with GLS changes in lung cancer patients. We retrospectively identified patients with lung cancer treated at our institution between 2005-2020 who had ECHOs performed both before and after RT, and in whom GLS was extractable. ECHO Board-Certified cardio-oncologists measured GLS and left ventricular ejection fraction (LVEF) from these ECHOs. A total of 40 patients met inclusion criteria. Median time to ECHO was 78 days prior and 172 days after RT. Two chamber (2C), 3C, 4C, and average GLS were significantly decreased after RT on paired t-test [mean difference (SD) 2.23 (3.29), 2.99 (2.78), 2.25 (3.63), 2.51 (2.66) respectively, all p < 0.001]. Thirteen patients (32.5%) had abnormal GLS (<18%) prior to RT. 5 of those 13 patients (38.5%) had abnormal LVEF (< 50%). 27/40 patients (67.5%) had an abnormal GLS or clinically significant (≥15%) drop in GLS after RT. This difference (32.5% patients pre-RT vs 67.5% post-RT) was statistically significant (p < 0.01). Among patients (n = 27) who had normal LVEF before RT, 1 patient (3.7%) developed abnormal LVEF (<50%) after RT. Backwards logistic regression showed significant interaction between heart volume receiving 5 Gray and change in GLS. This cohort exhibited a significant decrease in 2C, 3C, 4C, and average GLS after RT. ∼1/3 of patients had abnormal GLS at baseline (suggesting a high-risk group for cardiac complications) and 67.5% of patients had clinically significant decrease in GLS after RT. Among the patients with normal GLS before RT, although 51.9% of patients demonstrated a clinically significant drop in GLS after RT, only 3.7% of patients developed abnormal LVEF, suggesting that this is a late occurrence. GLS changes may serve as a valuable tool for early identification of patients who are at high risk for future cardiac complications after receiving thoracic radiation.

Clinical Features and Impact on One Year Prognosis of Prescribing Low Doses of Direct Oral Anticoagulant Agents in a Middle Eastern Population with Atrial Fibrillation: Analysis from the Jordan Atrial Fibrillation Study

IntroductionDirect oral anticoagulant agents (DOACs) are indicated for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). Reduced doses of DOACs are indicated in patients who have renal impairment and according to age and weight criteria. The aim of this study was to investigate the frequency, clinical factors, and impact on 1-year prognosis of underdosing DOACs. MethodsData of patients enrolled in the Jordan AF (JoFib) study and who were followed for 1 year was used to compare patients prescribed standard dose with those who were underdosed. ResultsThere were 672 patients (76.2%) who were prescribed standard dose and 210 patients (23.8%) who were underdosed. Baseline characteristics were similar between the 2 groups. Factors associated with underdosing were enrollment from an outpatient vs hospital site, moderate- or high-risk HAS-BLED score, an abnormal left ventricular ejection fraction (LVEF <50%), a history of heart failure, or current use of diuretics. At 1 year, the incidence of all-cause mortality was 12.2% in standard dose vs 13.3% in the underdose group (P = .82), stroke or systemic embolism was 3.6% in the standard dose vs 3.8% in the underdose group (P = .67), and major bleeding was 2.2% in the standard dose vs 3.3% in the underdose group (P = .35). ConclusionsAbout (25%) of patients were underdosed. Factors associated with underdosing were outpatient (vs hospital) center enrollment, moderate- or high-risk HAS-BLED score, abnormal LVEF (<50%), history of heart failure, and current use of diuretics. There were no significant differences in the incidence of adverse events of mortality and major morbidity at 1-year follow-up between the standard dose and the underdose groups.

Extensive Cardiac Function Analyses Using Contemporary Echocardiography in Childhood Cancer Survivors: A DCCSS LATER Study.

Childhood cancer survivors (CCS) are at risk for cardiotoxicity. We sought to assess how cardiac dysfunction measurements in CCS overlap and are differentially influenced by risk factors. This cross-sectional Dutch Childhood Cancer Survivor Study evaluated echocardiograms of 1,397≥5-year CCS and 277 siblings. Of CCS, n=1,254 received cardiotoxic (anthracyclines/mitoxantrone/radiotherapy involving the heart region [RTheart]) and n=143 received potentially cardiotoxic (cyclophosphamide, ifosfamide, or vincristine) therapy. We assessed demographic, treatment-related, and traditional cardiovascular risk factors for cardiac dysfunction using multivariable logistic regression. CCS were a median of 26.7 years after diagnosis; 49% were women. Abnormal left ventricular ejection fraction (LVEF) (defined as<52% in men,<54% in women) occurred most commonly in CCS treated with anthracyclines and RTheart combined (38%). Age/sex-specific abnormal global longitudinal strain (GLS) occurred most commonly in CCS treated with RTheart, either with (41%) or without (38%) anthracyclines. Of CCS with normal LVEF, 20.2% showed abnormal GLS. Diastolic dysfunctiongrade ≥II was rare. Abnormal LVEF was mainly associated with female sex, anthracycline dose, and only in women, RTheart dose. Abnormal GLS was associated with female sex, RTheart dose, diastolic blood pressure, and only in women, anthracycline dose. Cyclophosphamide, ifosfamide, and vincristine were not associated with LVEF or GLS. Compared with siblings, CCS showed higher risk of abnormal LVEF (OR: 2.9; 95% CI: 1.4-6.6) and GLS (OR: 2.1; 95% CI: 1.2-3.7), independent of (potentially) cardiotoxic treatment-related and cardiovascular risk factors. Abnormal LVEF and GLS constitute complementary measures of systolic dysfunction among long-termCCS. Their diagnostic value may differ according to cardiotoxic exposures. Also, CCS have residual, unexplained riskof cardiac dysfunction. (Early Detection of Cardiac Dysfunction in Childhood Cancer Survivors, a DCOG LATERstudy; NTR7481).

Abnormal Left Ventricular Strain Correlates with Left Ventricular Dysfunction but not Aortic Pathology in Marfan Syndrome in Children.

Cardiomyopathy is a complication in adults with Marfan syndrome (MFS). Early recognition of MFS patients at high risk of cardiomyopathy could impact monitoring and treatment. Abnormal ventricular strain has been associated with impaired ventricular function among adults with MFS but remains understudied in children. We retrospectively analyzed a cohort of patients with MFS undergoing cardiac magnetic resonance imaging (CMR) performed in 2003-2018 at age < 19years. Correlations were evaluated between initial global circumferential strain (GCS) and global longitudinal strain (GLS) and the outcomes of left ventricular ejection fraction (LVEF), aortic root z-score, and vertebral artery tortuosity index corrected for height (VTI-h), all measured from CMR, using Spearman correlation. In those with serial CMR, the ability of ventricular strain to predict development of abnormal LVEF within a 5-year period was assessed. A total of 31 subjects were included (median age at initial CMR 13.5 years, Q1Q3 10.7-16.2 years), with 48% (n = 15) having LVEF < 55%. Worse GCS and worse GLS were associated with lower LVEF (ρ = - 0.629, p < 0.001 and ρ = - 0.411, p = 0.030, respectively). A clinical cutoff of GCS = - 34% predicted LVEF < 55% with sensitivity = 80% and specificity = 50%. Neither GCS nor GLS was associated with aortic root z-score (GCS: p = 0.524; GLS: p = 0.624) nor VTI-h (GCS: p = 0.949; GLS: p = 0.593). Of those with LVEF ≥ 55%, initial GCS and GLS did not differ between those with later normal versus abnormal LVEF (GCS: p = 0.505; GLS: p = 0.232). In this cohort, abnormal LV strain was associated with abnormal LVEF, but not with aortic dilation or low LVEF within the 5years post-CMR.

The primary cardiomyopathy of systemic sclerosis on cardiovascular magnetic resonance imaging.

Cardiac disease in systemic sclerosis (SSc) may be primary or secondary to other disease manifestations of SSc. The prevalence of the primary cardiomyopathy of SSc is unknown. Cardiovascular magnetic resonance (CMR) imaging can help accurately determine the presence and cause of cardiomyopathy. We aimed to investigate the prevalence, the CMR features, and the prognostic implications of the primary cardiomyopathy of SSc. We conducted a retrospective cohort study of consecutive patients with SSc who had a clinical CMR for suspected cardiac involvement. We identified the prevalence, the CMR features of the primary cardiomyopathy of SSc, and its association with the long-term incidence of death or major adverse cardiac events (MACEs): heart failure hospitalization, ventricular assist device implantation, heart transplantation, and sustained ventricular tachycardia. Of 130 patients with SSc, 80% were women, and the median age was 58 years. On CMR, 22% had an abnormal left ventricular ejection fraction, and 40% had late gadolinium enhancement (LGE). The prevalence of the primary cardiomyopathy of SSc was 21%. A third of these patients had a distinct LGE phenotype. Over a median follow-up of 3.6 years after the CMR, patients with the primary cardiomyopathy of SSc had a greater incidence of death or MACE (adjusted hazard ratio 2.01; 95% confidence interval 1.03-3.92; P = 0.041). The prevalence of the primary cardiomyopathy of SSc was 21%, with a third demonstrating a distinct LGE phenotype. The primary cardiomyopathy of SSc was independently associated with a greater long-term incidence of death or MACE.

Longitudinal strain analysis for assessment of early cardiotoxicity during anthracycline treatment in childhood sarcoma: A single center experience.

The growing population of long-term childhood cancer survivors encounter a substantial burden of cardiovascular complications. The highest risk of cardiovascular complications is associated with exposure to anthracyclines and chest radiation. Longitudinal cardiovascular surveillance is recommended for childhood cancer patients; however, the optimal methods and timing are yet to be elucidated. We aimed to investigate the feasibility of different echocardiographic methods to evaluate left ventricular systolic function in retrospective datasets, including left ventricular ejection fraction (LVEF), fractional shortening (FS), global longitudinal strain (GLS) and longitudinal strain (LS) as well as the incidence and timing of subclinical left ventricular dysfunction detected by these methods. A retrospective longitudinal study was performed with re-analysis of longitudinal echocardiographic data, acquired during treatment and early follow-up, including 41 pediatric sarcoma patients, aged 2.1-17.8 years at diagnosis, treated at Astrid Lindgren Children's Hospital, Stockholm, Sweden, during the period 2010-2021. All patients had received treatment according to protocols including high cumulative doxorubicin equivalent doses (≥250 mg/m2 ). In 68% of all 366 echocardiograms, LS analysis was feasible. Impaired LS values (<17%) was demonstrated in >40%, with concomitant impairment of either LVEF or FS in 20% and combined impairment of both LVEF and FS in <10%. Importantly, there were no cases of abnormal LVEF and FS without concomitant LS impairment. Our findings demonstrate feasibility of LS in a majority of echocardiograms and a high incidence of impaired LS during anthracycline treatment for childhood sarcoma. We propose inclusion of LS in pediatric echocardiographic surveillance protocols.

Cardiac safety and efficacy for patients with early-stage breast cancer treated with pegylated liposomal doxorubicin (PLD) or doxorubicin.

550 Background: Anthracyclines play an important role in the treatment of breast cancer (BC) while cardiotoxicity, a serious side effect, limits the clinical application. Pegylated liposomal doxorubicin (PLD) is a new dosage form of doxorubicin encapsulated in liposomes, which can reduce the plasma free level of doxorubicin and drug to normal tissue delivery, thereby reducing cardiotoxicity. The aim of this study was to evaluate the cardiac safety and efficacy of PLD compared with doxorubicin as adjuvant therapy in breast cancer patients. Methods: This is an open-label, randomized trial involving patients with operable breast cancer who were at high risk of recurrence after radical sugery (NCT03949634). Patients were randomized (1:1) to receive adjuvant PLD or doxorubicin (A) and cyclophosphamide followed by taxanes ± trastuzumab. The primary endpoint was cardiotoxicity, which was defined as congestive heart failure (CHF) with clinical symptoms, or no symptoms but with an abnormal left ventricular ejection fraction (LVEF). Secondary endpoints included 5-year disease-free survival (DFS) rate, 5-year overall survival (OS) rate and safety. Results: Between November 2017 and September 2019, 247 patients were randomized and received study treatment (PLD arm, 131; A arm, 116). The median age was 49 years (range, 26-67) in PLD arm and 48 years (range, 25-70) in A arm. The pathological stages were 18.3% stage I, 58.0% stage II, and 22.1% stage III in PLD arm, while those of A arm were 20.7% stage I, 59.5% stage II, and 19.8% stage III. The median follow-up time was 43.0 months. The incidence of abnormal LVEF was 0 in the PLD arm and 1.7% the A arm (P = 0.220). The incidence of CHF was 0 in the PLD arm and 0.9% the A arm (P = 0.470). Survival data analysis is immature. The exploratory analysis of cardiac-related biomarkers showed that the incidence of high-sensitivity cardiac troponin-T (hs-cTnT) was lower in PLD arm than in A arm (3.8% vs. 30.2%, P &lt; 0.001). Grade 3/4 adverse events (AEs) occurred in 42.7% patients in PLD arm and in 61.2% patients in A arm. The most common grade 3/4 AEs in PLD arm and A arm included neutropenia (34.4% vs. 55.2%), leukopenia (30.5% vs. 39.7%), and hand-foot syndrome (4.6% vs. 0.0%). Conclusions: Hs-cTnT elevation may have a role in the AE prediction of antharcycline. PLD usage may present lower incidence of cardiotoxicity than doxorubicin in the adjuvant treatment of patients with early-stage breast cancer. Clinical trial information: NCT03949634 .

Echocardiographic Features Beyond Ejection Fraction and Associated Outcomes in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction.

Heart failure (HF) guidelines recommend assessment of left ventricular ejection fraction (LVEF) to classify patients and guide therapy implementation. However, LVEF alone may be insufficient to adequately characterize patients with HF, especially those with mildly reduced or preserved LVEF. Recommendations on additional testing are lacking, and there are limited data on use of echocardiographic features beyond LVEF in patients with heart failure with mildly reduced or preserved LVEF. In patients with HF with mildly reduced or preserved LVEF identified in a large US health care system, the association of the following metrics with mortality was evaluated: LV global longitudinal strain (LV GLS>-16), left atrial volume index (>28 mL/m2), left ventricular hypertrophy (LVH), and E/e´>13 and e´<9. A multivariable model for mortality was constructed including age, sex, and key comorbidities followed by stepwise selection of echocardiographic features. Characteristics and outcomes of subgroups with normal versus abnormal LV GLS and LVEF were evaluated. Among 2337 patients with complete echocardiographic data assessed between 2017 and 2020, the following features were associated with all-cause mortality on univariate analysis over 3 years of follow-up: E/e´+e´, LV GLS, left atrial volume index (all P<0.01). In the multivariable model (C-index=0.65), only abnormal LV GLS was independently associated with all-cause mortality (HR, 1.35 [95% CI, 1.11-1.63]; P=0.002). Among patients with LVEF>55%, 498/1255 (40%) demonstrated abnormal LV GLS. Regardless of specific LVEF, patients with abnormal LV GLS demonstrated a higher burden of multiple comorbidities and higher event rates compared with patients with normal LV GLS. In a large, real-world HF with mildly reduced or preserved LVEF population, echocardiographic features, led by LV GLS, were associated with adverse outcomes irrespective of LVEF. A large proportion of patients demonstrate adverse myocardial function by LV GLS despite preserved LVEF and may represent a key cohort of interest for HF medical therapies and future clinical studies.

Link between myocardial deformation phenotyping using longitudinal and circumferential strain and risk of incident heart failure and cardiovascular death.

Left ventricular (LV) systolic deformation is altered early in the ventricular disease process despite normal LV ejection fraction (LVEF). These alterations seem to be characterized by decreased global longitudinal strain (GLS) and augmented global circumferential strain (GCS). This study aimed to investigate the link between myocardial deformation phenotyping using longitudinal and circumferential strain and risk of incident heart failure (HF) and cardiovascular death (CD). The study sample was based on the prospective cohort study the 5th Copenhagen City Heart Study (2011-15). All participants were examined with echocardiography following a pre-defined protocol. A total of 2874 participants were included. Mean age was 53±18 years and 60% were female. During a median follow-up of 3.5 years, a total of 73 developed HF/CD. A U-shaped relationship between GCS and HF/CD was observed. LVEF significantly modified the association between GCS and HF/CD (P for interaction <0.001). The optimal transition point for the effect modification was LVEF < 50%. In multivariable Cox regressions, increasing GCS was significantly associated with HF/CD in participants with LVEF ≥ 50% (hazard ratio [HR]=1.12 [95% confidence interval (CI): 1.02; 1.23] per 1% increase), while decreasing GCS was associated with a higher risk of HF/CD in individuals with LVEF < 50% [HR=1.18 (95% CI: 1.05; 1.31) per 1% decrease]. The prognostic utility of GCS is modified by LVEF. In participants with normal LVEF, higher GCS was associated with increased risk of HF/CD, while the opposite was observed in participants with abnormal LVEF. This observation adds important information to our understanding of the pathophysiological evolution of myocardial deformation in cardiac disease progression.

Screening left ventricular systolic dysfunction in children using intrinsic frequencies of carotid pressure waveforms measured by a novel smartphone-based device

Objective. Children with heart failure have higher rates of emergency department utilization, health care expenditure, and hospitalization. Therefore, a need exists for a simple, non-invasive, and inexpensive method of screening for left ventricular (LV) dysfunction. We recently demonstrated the practicality and reliability of a wireless smartphone-based handheld device in capturing carotid pressure waveforms and deriving cardiovascular intrinsic frequencies (IFs) in children with normal LV function. Our goal in this study was to demonstrate that an IF-based machine learning method (IF-ML) applied to noninvasive carotid pressure waveforms can distinguish between normal and abnormal LV ejection fraction (LVEF) in pediatric patients. Approach. Fifty patients ages 0 to 21 years underwent LVEF measurement by echocardiogram or cardiac magnetic resonance imaging. On the same day, patients had carotid waveforms recorded using Vivio. The exclusion criterion was known vascular disease that would interfere with obtaining a carotid artery pulse. We adopted a hybrid IF- Machine Learning (IF-ML) method by applying physiologically relevant IF parameters as inputs to Decision Tree classifiers. The threshold for low LVEF was chosen as <50%. Main results. The proposed IF-ML method was able to detect an abnormal LVEF with an accuracy of 92% (sensitivity = 100%, specificity = 89%, area under the curve (AUC) = 0.95). Consistent with previous clinical studies, the IF parameter was elevated among patients with reduced LVEF. Significance. A hybrid IF-ML method applied on a carotid waveform recorded by a hand-held smartphone-based device can differentiate between normal and abnormal LV systolic function in children with normal cardiac anatomy.

Artificial intelligence based left ventricular ejection fraction and global longitudinal strain in cardiac amyloidosis.

Assessment of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) plays a key role in the diagnosis of cardiac amyloidosis (CA). However, manual measurements are time consuming and prone to variability. We aimed to assess whether fully automated artificial intelligence (AI) calculation of LVEF and GLS provide similar estimates and can identify abnormalities in agreement with conventional manual methods, in patients with pre-clinical and clinical CA. We identified 51 patients (age 80±10 years, 53% male) with confirmed CA according to guidelines, who underwent echocardiography before and/or at the time of CA diagnosis (median (IQR) time between observations 3.87 (1.93, 5.44 years). LVEF and GLS were quantified from the apical 2- and 4-chamber views using both manual and fully automated methods (EchoGo Core 2.0, Ultromics). Inter-technique agreement was assessed using linear regression and Bland-Altman analyses and two-way ANOVA. The diagnostic accuracy and time for detecting abnormalities (defined as LVEF ≤ 50% and GLS ≥ -15.1%, respectively) using AI was assessed by comparisons to manual measurements as a reference. There were no significant differences in manual and automated LVEF and GLS values in either pre-CA (p=.791 and p=.105, respectively) or at diagnosis (p=.463 and p=.722). The two methods showed strong correlation on both the pre-CA (r=.78 and r=.83) and CA echoes (r=.74 and r=.80) for LVEF and GLS, respectively. The sensitivity and specificity of AI-derived indices for detecting abnormal LVEF were 83% and 86%, respectively, in the pre-CA echo and 70% and 79% at CA diagnosis. The sensitivity and specificity of AI-derived indices for detecting abnormal GLS was 82% and 86% in the pre-CA echo and 100% and 67% at the time of CA diagnosis. There was no significant difference in the relationship between LVEF (p=.99) and GLS (p=.19) and time to abnormality between the two methods. Fully automated AI-calculated LVEF and GLS are comparable to manual measurements in patients pre-CA and at the time of CA diagnosis. The widespread implementation of automated LVEF and GLS may allow for more rapid assessment in different disease states with comparable accuracy and reproducibility to manual methods.