Risk Of Left Ventricular Dysfunction Research Articles

Association Between Type 2 Diabetes and Changes in Myocardial Structure, Contractile Function, Energetics, and Blood Flow Before and After Aortic Valve Replacement in Patients With Severe Aortic Stenosis.

Type 2 diabetes (T2D) is associated with an increased risk of left ventricular dysfunction after aortic valve replacement (AVR) in patients with severe aortic stenosis (AS). Persistent impairments in myocardial energetics and myocardial blood flow (MBF) may underpin this observation. Using phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance, this study tested the hypothesis that patients with severe AS and T2D (AS-T2D) would have impaired myocardial energetics as reflected by the phosphocreatine to ATP ratio (PCr/ATP) and vasodilator stress MBF compared with patients with AS without T2D (AS-noT2D), and that these differences would persist after AVR. Ninety-five patients with severe AS without coronary artery disease awaiting AVR (30 AS-T2D and 65 AS-noT2D) were recruited (mean, 71 years of age [95% CI, 69, 73]; 34 [37%] women). Thirty demographically matched healthy volunteers (HVs) and 30 patients with T2D without AS (T2D controls) were controls. One month before and 6 months after AVR, cardiac PCr/ATP, adenosine stress MBF, global longitudinal strain, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and 6-minute walk distance were assessed in patients with AS. T2D controls underwent identical assessments at baseline and 6-month follow-up. HVs were assessed once and did not undergo 6-minute walk testing. Compared with HVs, patients with AS (AS-T2D and AS-noT2D combined) showed impairment in PCr/ATP (mean [95% CI]; HVs, 2.15 [1.89, 2.34]; AS, 1.66 [1.56, 1.75]; P<0.0001) and vasodilator stress MBF (HVs, 2.11 mL min g [1.89, 2.34]; AS, 1.54 mL min g [1.41, 1.66]; P<0.0001) before AVR. Before AVR, within the AS group, patients with AS-T2D had worse PCr/ATP (AS-noT2D, 1.74 [1.62, 1.86]; AS-T2D, 1.44 [1.32, 1.56]; P=0.002) and vasodilator stress MBF (AS-noT2D, 1.67 mL min g [1.5, 1.84]; AS-T2D, 1.25 mL min g [1.22, 1.38]; P=0.001) compared with patients with AS-noT2D. Before AVR, patients with AS-T2D also had worse PCr/ATP (AS-T2D, 1.44 [1.30, 1.60]; T2D controls, 1.66 [1.56, 1.75]; P=0.04) and vasodilator stress MBF (AS-T2D, 1.25 mL min g [1.10, 1.41]; T2D controls, 1.54 mL min g [1.41, 1.66]; P=0.001) compared with T2D controls at baseline. After AVR, PCr/ATP normalized in patients with AS-noT2D, whereas patients with AS-T2D showed no improvements (AS-noT2D, 2.11 [1.79, 2.43]; AS-T2D, 1.30 [1.07, 1.53]; P=0.0006). Vasodilator stress MBF improved in both AS groups after AVR, but this remained lower in patients with AS-T2D (AS-noT2D, 1.80 mL min g [1.59, 2.0]; AS-T2D, 1.48 mL min g [1.29, 1.66]; P=0.03). There were no longer differences in PCr/ATP (AS-T2D, 1.44 [1.30, 1.60]; T2D controls, 1.51 [1.34, 1.53]; P=0.12) or vasodilator stress MBF (AS-T2D, 1.48 mL min g [1.29, 1.66]; T2D controls, 1.60 mL min g [1.34, 1.86]; P=0.82) between patients with AS-T2D after AVR and T2D controls at follow-up. Whereas global longitudinal strain, 6-minute walk distance, and NT-proBNP all improved after AVR in patients with AS-noT2D, no improvement in these assessments was observed in patients with AS-T2D. Among patients with severe AS, those with T2D demonstrate persistent abnormalities in myocardial PCr/ATP, vasodilator stress MBF, and cardiac contractile function after AVR; AVR effectively normalizes myocardial PCr/ATP, vasodilator stress MBF, and cardiac contractile function in patients without T2D.

Assessment of predictors of anthracycline-induced heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Introduction and objectives Chemotherapy-induced cardiotoxicity is a growing clinical problem, which is increasing and has acquire more importance in recent years. The objective of this study was to determine the incidence of anthracycline-induce cardiomyotoxicity in patients with Non-Hodkin´s Lymphoma (NHL), quantified by serial measurements of biomarkers (highly sensitive troponin I and Nt-proBNP) and echocardiophic imaging: 2D left ventricle ejection fraction (LVEF) and myocardial deformation, assessed by global longitudinal strain (GLS). Material and methods Observational, prospective study. We included 50 patients diagnosed with NHL between January 2018-January 2020, with a mean follow-up of 30.2 months. Patients were treated with liposomal doxorubicin and had no history of previous known heart disease. Statistical analysis was performed to evaluate the association between biomarkers, imaging parameters and time to development of cardiomyotoxicity. Results The cumulative incidence of cardiomyotoxicity was 6.3% at 6 months, 10.8% at 1 year, and 16% at 2 years. The median time to development of cardiomyotoxicity was 7.1 months. Both troponin, Nt-proBNP and GLS levels were independently associated with increased risk of cardiomyotoxicity (p &amp;lt; 0.05). Regarding troponin levels, they were found to be elevated in 23.2% of the patients. Elevation in troponin analysis was associated with an increased risk of left ventricular dysfunction (odds ratio OR 10.2). Patients with Nt-proBNP &amp;gt; 680 pg/ml had a 4.1-fold increased risk of presenting cardiomyotoxicity. GLS with a value of -16.1% showed 80% sensitivity and 98.2% specificity for the diagnosis of cardiomyotoxicity. Conclusions Chemotherapy with Doxorubicin is associated with an increased risk of cardiomyotoxicity. IN our study, significant variations in baseline troponin levels, NT-proBNP, and GLS were powerful predictors of its development. These parameters could identify groups of patients with different risk of cardiotoxicity, in whom cardiological evaluation and personalized follow-up should be offered.

Abstract Number ‐ 235: Stroke Management in Left Ventricular Non‐Compaction Syndrome (LVNC): Report of 2 Cases

Introduction Left Ventricular Non‐Compaction syndrome is a rare congenital cardiomyopathy that results in prominent endomyocardial trabeculations which increases the risk of left ventricular dysfunction, malignant arrhythmias and thromboembolic events. Its diagnosis is based on morphological changes seen on trans‐thoracic echocardiograph (TTE), which can often be missed as it is user dependent. Objective: To discuss two cases of stroke associated with LVNC at our institution as well as offer further diagnostic and therapeutic recommendations. Methods Case Report Results Case1: A 29‐year‐old gentleman with a history dilated cardiomyopathy of unclear etiology and prior stroke presented to our institution complaining of dizziness and right sided headache. He was found to have a right M2 occlusion resulting in an insular infarct. Patient was out of the window for any chemical or mechanical thrombectomy. Initial TTE showed a depressed ejection fraction of 45‐50‐% with a 6mm LV apical thrombus. Patient was started on anticoagulation with coumadin and follow up TTE 3 months later showed the same EF, but with resolution of the apical thrombus. Given the unclear etiology of his heart failure, he was sent for cardiac MRI which demonstrated deep endomyocardial trabeculae consistent with Left Ventricular Non‐Compaction Syndrome. Given new findings, patient was recommended to continue anticoagulation with coumadin indefinitely. Case 2: A 12‐year old boy with a history of Cerebral Palsy and cardiomyopathy due to a formal diagnosis of Left Ventricular Non‐Compaction syndrome shortly after birth presented with sudden right sided weakness. Patient was admitted to the PICU team for elevated level of care. He underwent an MRI of the brain and found to have a left MCA ischemic stroke. He was out of the window for any mechanical or chemical thrombectomy. He was started on anticoagulation after 4 days with a stable CT scan of the stroke. Conclusions In the first case, several TTE’s in the outpatient setting and two done while the patient was hospitalized did not identify the pathogenic trabeculae. The diagnosis was only made after a cardiac MRI was done, posing a delay in diagnosis and possible treatment that could have prevented thrombogenic environment in the patient’s LV leading to an acute stroke. In the second case, the patient did have a diagnosis of LVNC, but anticoagulation was never started. Currently, there there exists no current accepted guidelines for diagnoses and management of LVNC. We recommend a cardiac MRI if there is a concern for stroke in a patient with cardiac myopathy of unclear etiology. Furthermore, professional opinion based on several meta‐analysis suggests that anticoagulation should be started when LVEF is less than 40% or presence of a prior stroke in patient with LVNC. Given the rarity of this syndrome and the challenge with its diagnosis, further studies are needed to better evaluate its timely diagnosis and proper management.

Obstetric and fetal/neonatal outcomes in pregnant women with frequent premature ventricular complexes and structurally normal heart

BackgroundHigh premature ventricular complex (PVC) burden may increase the risk of left ventricular dysfunction and all-cause mortality. We aimed to evaluate maternal and neonatal outcomes of pregnant women with structurally normal heart having PVC burden ≥1%. MethodsThis retrospective cohort study used data from Chang Gung Research Database. Pregnancies from January 1, 2005, through June 30, 2020, with documented maternal PVC burden ≥1% by 24-h Holter monitor were identified. Pregnant women with a diagnosis of structural heart disease or arrhythmias other than PVC were excluded. We used propensity score matching (PSM) to balance the covariates between the PVC group and normal control group. The PVC group was classified into low-PVC (<10%) and high-PVC burden subgroups. The maternal and neonatal outcomes were assessed through 6 months after delivery or termination. ResultsAfter PSM, there were 214, 61, and 46 pregnant women enrolled in the normal control group, low-PVC burden, and high-PVC burden subgroups, respectively. The high-PVC and low-PVC burden subgroups had composite adverse maternal and neonatal events similar to the control group without use of antiarrhythmic drugs (AADs), but a higher proportion of placental abruption was observed in the high-PVC burden subgroup. Maternal age, diabetes, and overweight were significant predictors of composite adverse maternal events, whereas only maternal age was a significant predictor of composite adverse neonatal events. ConclusionsHigh PVC burden was not associated with poor composite adverse maternal and neonatal outcomes with no need of AADs therapy in pregnant women with structurally normal heart.

Initial Treatment of Multisystem Inflammatory Syndrome

Source: Son MBF, Murray N, Friedman K, et al Multisystem inflammatory syndrome in children—initial therapy and outcomes. N Engl J Med. 2021;385(1):23-34; doi:10.1056/NEJMoa2102605Investigators from multiple institutions conducted a retrospective study to evaluate the effectiveness of initial immunomodulatory treatments of children with multisystem inflammatory syndrome (MIS-C). For the study, they abstracted data from the Overcoming COVID-19 surveillance registry, which includes data on children diagnosed with MIS-C at participating US hospitals. At each participating site, demographic data and information on underlying conditions, signs and symptoms at presentation, clinical course, laboratory and medications, and outcomes were entered into a central database on patients meeting CDC criteria for MIS-C (serious illness leading to hospitalization in patients <21 years old, fever, laboratory evidence of inflammation, multisystem organ involvement, and evidence of SARS-CoV-2 infection).For the study, the investigators focused their analyses on patients whose initial immunomodulatory treatment was either intravenous immunoglobulin (IVIG) alone or IVIG plus glucocorticoids (initial day of treatment designated as Day 0). The primary study outcome was evidence of left ventricular dysfunction, defined as left ventricular ejection fraction <55%, echocardiogram, or shock treated with vasopressors, documented anytime between Day 2 of treatment until discharge. Secondary outcomes included recurrent fever (after Day 2), use of other therapies (second dose of IVIG, glucocorticoids in those in the IVIG alone group, or biologics), and length of ICU stay. Multiple baseline variables were combined to develop a propensity score on study patients, then those treated with IVIG plus glucocorticoids were propensity score matched 1:1 with those receiving IVIG alone and the outcomes assessed with regression analyses.A total of 518 patients with MIS-C received an immunomodulatory treatment. The median age of these children was 8.7 years, 58% were male, 75% were previously healthy, and 9 died. The most common initial treatments (on Day 0) were IVIG alone in 192 (37%) and IVIG plus glucocorticoids in 157 (30%); 34 patients received a biologic on Day 0 and were excluded from the analysis. Outcomes were compared in 206 patients (103 treated with IVIG plus glucocorticoids and 103 who received IVIG alone on Day 0) who could be propensity score 1:1 matched. Among these children, those receiving IVIG plus glucocorticoids had significantly less left ventricular dysfunction than those receiving IVIG alone (17% and 31%, respectively; risk ratio [RR], 0.56; 95% CI, 0.34, 0.94). Among those treated with IVIG plus glucocorticoids, 34% received adjunctive therapies vs 70% of those initially treated with IVIG alone (RR, 0.49; 95% CI, 0.36, 0.65). There were no significant differences between groups for rate of recurrent fever or length of ICU stay.The authors conclude that among patients with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of left ventricular dysfunction than treatment with IVIG alone.Dr Bratton has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.MIS-C is a rare complication of COVID-19 in children and teenagers with some similarities to Kawasaki Disease (KD) (See AAP Grand Rounds. 2020;44[3]:30.)1, but it typically occurs in older children.2 Because children and teenagers may have asymptomatic infections, the rate of MIS-C is difficult to ascertain accurately. Two prospective observational studies of MIS-C were published in the same journal edition.2,3 The authors of the current study included only patients from the US who met CDC criteria for MIS-C, while McArdle et al, authors of the second report, included children from 32 countries who met the slightly different WHO criteria.4 The current investigators reported that treatment with IVIG and glucocorticoids was associated with lower risk of left ventricular dysfunction. McArdle et al, however, did not find additional benefit in patients treated with IVIG and glucocorticoids compared to IVIG alone. Why these different findings? First, the description of MIS-C has evolved, and coronavirus variants have emerged. The 2 groups of investigators examined somewhat different time periods. Likewise, differing criteria for study selection may impact the findings, and these reports are observational and at risk for bias if treatment selection and these or other factors are associated with myocardial dysfunction. Disease presentation and response to therapy also may differ in US patients due to genetic differences. In summary, the rate of MIS-C may be changing with the development of new virus strains; refinement of criteria for disease diagnosis and therapy also likely will change.Among US children and adolescents with MIS-C, IVIG plus glucocorticoids appear to be associated with a lower risk of cardiovascular dysfunction than IVIG alone. The long-term health of MIS-C affected children remains to be ascertained.Of note, the safety and efficacy of targeted biologic agents (eg, infliximab) in addition to or instead of IVIG and glucocorticoids were not evaluated in either of the 2 New England Journal of Medicine studies.2,3

NT-proBNP/BNP ratio for prognostication in European Caucasian patients enrolled in a heart failure prevention programme.

AimsGuidelines support the role of B‐type natriuretic peptide (BNP) and amino‐terminal pro‐BNP (NT‐proBNP) for risk stratification of patients in programmes to prevent heart failure (HF). Although biologically formed in a 1:1 ratio, the ratio of NT‐proBNP to BNP exhibits wide inter‐individual variability. A report on an Asian population suggests that molar NT‐proBNP/BNP ratio is associated with incident HF. This study aims to determine whether routine, simultaneous evaluation of both BNP and NT‐proBNP is warranted in a European, Caucasian population.Methods and ResultsWe determined BNP and NT‐proBNP levels for 782 Stage A/B HF patients in the STOP‐HF programme. The clinical, echocardiographic, and biochemical associates of molar NT‐proBNP/BNP ratio were analysed. The primary endpoint was the adjusted association of baseline molar NT‐proBNP/BNP ratio with new‐onset HF and/or progression of left ventricular dysfunction (LVD). We estimated the C‐statistic, integrated discrimination improvement, and the category‐free net reclassification improvement metric for the addition of molar NT‐proBNP/BNP ratio to adjusted models. The median age was 66.6 years [interquartile range (IQR) 59.5–73.1], 371 (47.4%) were female, and median molar NT‐proBNP/BNP ratio was 1.91 (IQR 1.37–2.93). Estimated glomerular filtration rate, systolic blood pressure, left ventricular mass index, and heart rate were associated with NT‐proBNP/BNP ratio in a linear regression model (all P < 0.05). Over a median follow‐up period of 5 years (IQR 3.4–6.8), 247 (31.5%) patients developed HF or progression of LVD. Log‐transformed NT‐proBNP/BNP ratio is inversely associated with HF and LVD risk when adjusted for age, gender, diabetes, hypertension, vascular disease, obesity, heart rate, number of years of follow‐up, estimated glomerular filtration rate, and baseline NT‐proBNP (odds ratio 0.71, 95% confidence interval 0.55–0.91; P = 0.008). However, molar NT‐proBNP/BNP ratio did not increase the C‐statistic (Δ −0.01) and net reclassification improvement (0.0035) for prediction of HF and LVD compared with NT‐proBNP or BNP alone. Substitution of NT‐proBNP for BNP in the multivariable model eliminated the association with HF and LVD risk.ConclusionsThis study characterized, for the first time in a Caucasian Stage A/B HF population, the relationship between NT‐proBNP/BNP ratio and biological factors and demonstrated an inverse relationship with the future development of HF and LVD. However, this study does not support routine simultaneous BNP and NT‐proBNP measurement in HF prevention programmes amongst European, Caucasian patients.

Case Report: Novel Likely Pathogenic ACTN2 Variant Causing Heterogeneous Phenotype in a Korean Family With Left Ventricular Non-compaction

Left ventricular non-compaction (LVNC) is a very rare primary cardiomyopathy with a genetic etiology, resulting from the failure of myocardial development during embryogenesis, and it carries a high risk of left ventricular dysfunction, thromboembolic phenomenon, and malignant arrhythmias. Here, we report the first case of familial LVNC in Korea, caused by a novel ACTN2 missense variant. We performed duo exome sequencing (ES) to examine the genome of the proband and his father. A 15-year-old boy was admitted for the evaluation of exertional dyspnea for 2 weeks. He was diagnosed with LVNC with a dilated cardiomyopathy phenotype [left ventricular end-diastolic dimension 60 mm, interventricular septal dimension 8.2 mm by transthoracic echocardiography (TTE)]. For the screening of familial cardiomyopathy, TTE and cardiac magnetic resonance imaging (cMRI) were performed, which revealed hypertrophic and isolated LVNC in the proband's father and sister, respectively. In particular, the cMRI revealed dense hypertrabeculation with focal aneurysmal changes in the apical septal wall in the proband's father. ES of the father–son duo identified a novel heterozygous c.668T>C variant of the ACTN2 gene (NM_001103.3:c.668T>C, p.Leu223Pro; no rsID) as the candidate cause of autosomal dominant LVNC. Sanger sequencing confirmed this novel variant in the proband, his father, and sister, but not in the proband's grandmother. Even within families harboring the same variant, a variable risk of adverse outcomes is common. Therefore, familial screening for patients with LVNC associated with ACTN2 variant should be performed for early detection of the LVNC phenotype associated with poor outcomes, such as dilated LVNC.

33-Year-Old Woman With Postpartum Acute Shortness of Breath

33-Year-Old Woman With Postpartum Acute Shortness of Breath

Cardiac biomarkers for the detection of cardiotoxicity in childhood cancer-a meta-analysis.

AimsChildhood cancer therapy is associated with a significant risk of therapy‐related cardiotoxicity. This meta‐analysis aims to evaluate cardiac biomarkers for the detection of cancer therapy‐related left ventricular (LV) dysfunction in childhood cancer patients.Methods and resultsPubMed, Cochrane Library, Wiley Library, and Web of Science were screened for studies investigating brain natriuretic peptide (BNP)/N‐terminal proBNP (NT‐proBNP) or cardiac troponin in childhood cancer patients. The odds ratios (OR) for elevation of cardiac biomarkers and association with LV dysfunction were calculated using a random‐effects model. Data from 27 studies with 1651 subjects were included. BNP/NT‐proBNP levels were higher post‐treatment compared with controls or pre‐treatment values [standardized mean difference = 1.0; 95% confidence interval (CI) = 0.6–1.4; n = 320; P < 0.001]. LV dysfunction was present in 11.76% of included patients, and risk for LV dysfunction was increased in patients with elevated BNP/NT‐proBNP (OR = 7.1; 95% CI = 2.0–25.5; n = 350; P = 0.003). The sensitivity of BNP/NT‐proBNP for the detection of LV dysfunction was 33.3%, and the specificity was 91.5%. Sensitivity increased when selecting for studies that assessed patients < 5 years after anthracycline exposure and for studies including high cumulative anthracycline doses. Anthracycline chemotherapy was associated with an increased frequency of elevated troponin (OR = 3.7; 95% CI = 2.1–6.5; n = 348; P < 0.001). The available evidence on the association between elevated troponin and LV dysfunction was insufficient for an adequate analysis. In five included studies, the frequency of LV dysfunction was not increased in patients with elevated troponin (OR = 2.5; 95% CI = 0.5–13.2; n = 179; P = 0.53).ConclusionsBNP/NT‐proBNP is associated with cardiotoxicity in paediatric cancer patients receiving anthracycline therapy, but owing to low sensitivity, BNP/NT‐proBNP has to be evaluated in the context of further parameters including clinical assessment and echocardiography. Future studies are needed to determine whether troponin serves as a marker for cardiotoxicity in children. Standardized recommendations for the application of cardiac biomarkers in children undergoing cardiotoxic cancer therapy may benefit management and clinical outcome.

Angiographic pattern of patients with left bundle branch block: A comparative cross-sectional study

Objectives: We purposed to determine the relationship between left bundle branch block (LBBB) and coronary artery disease (CAD) site, severity, and CAD risk factors. Methods: Eighty patients with LBBB were sorted into two groups based on coronary angiography (CA) findings: Group 1: 56 patients with CAD (stenosis ≥70% in ≥1 epicardial vessel) and Group 2: 24 patients with normal coronaries. Results: Our observations confirm male preponderance of LBBB and affirm hypertension and diabetes as common risk factors for CAD within this subpopulation. Hence, these risk factors can be considered a strong predictor of CAD in LBBB. Cardiac echocardiography data suggest that LBBB and CAD are associated with regional hypokinesia and decreased ejection fraction. The most frequently diseased vessel was left anterior descending (LAD), followed by left circumflex then right coronary artery. Our study CA showed single-vessel disease (SVD) in 37 participants (46.3%), two-vessel disease in 16 subjects (20%), three-vessel disease in 3 subjects (3.8%), and normal vessels in 24 participants (30%). Hence, SVD frequency was high in our study. Conclusion: The risk for left ventricular dysfunction and SVD more commonly LAD artery involvement had increased in the presence of LBBB in electrocardiogram. CA present only in tertiary centers, which considered a major and invasive diagnostic tool for CAD, so selection criteria are required to predict patients with LBBB who are prone to be at risk of CAD and need this invasive procedure, on the other hand, avoid CAD overdiagnosis, unnecessary admissions to hospital, and antianginal drugs consumption.

354P - Anti-HER-2 therapies and left ventricular dysfunction the renaissance study

BackgroundThe Anti-Her 2 (AH2) drugs [trastuzumab (T.) and ertuzumab (P.)] are essential components in HER2 + Breast Cancer treatment. Although these kinds of therapies represent a breakthrough in different studies, a group of patients (p.) presented left ventricular dysfunction (LVD) in the follow-up. The vast majority recovered the left ventricular ejection fraction (LVEF) after withdrawal of treatment. We analysed prospectively a group of p. who presented a LVD after AH2 treatment. We propose that the early treatment with beta-blockers (BB), angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blockers (ARB), aldosterone antagonist (AA); could help an early recovery of LVEF and allow the reintroduction of the AH2 therapy without a new risk of LVD. MethodsWe evaluated 587 consecutive p. with HER2+ breast cancer who received T. alone or with P. from January 2017 to August 2018. We evaluated LVEF with ultrasonography (US.) before treatment (t). 43 p. had developed LVD and started t. with BB [Carvedilol (C.], ACEI [Enalapril (E.)] or ARB [Valsartan (V.)], AA [eplerenone (EP.)] at the moment of HF diagnosis and kept under t. after LVEF recovery. AH2 therapies were reintroduced when the patients improved their LVEF. Follow-up was with US.: 30 days, 60 days, 3 and 6 months (m.). We used SPSS for the statistical analysis. Results43 p. aged 54 +/- 8, 100% female. Risk Factors: arterial hypertension 10 p., diabetes 5 p, dyslipidemia 6 p., smoking 9 p. Previous oncological therapies: doxorubicin - cyclophosphamide 22 p., paclitaxel 22 p. Median of the basal LVEF was 61.4 % and at HF diagnosis was 39.3 %. Patient's New York Heart Association (NYHA) at diagnosis moment class was: I 15 %, II 60% and III 25%. All of the p. stopped the AH2 therapy. HF t. was: C 42 patients, E 33 patients, V. 10 patients and EP. 42 patients. LVEF recovery at 30 days was 81.39 % of p, at 60 days 95.34 %, at 3 and 6 m 97.67 %. When p. recuperated the LVEF we restarted the AH2 therapy. No patients had a new LVD at 3 m. and 6 m.. Patient's NYHA class at 6 m was: I 30%, II 25% and asymptomatic 45%. ConclusionsWhile the LVD related with AH2 therapies is a real problem in HER2+ breast cancer patients’ care, a timely diagnosis and t. with therapies for HF can allow LVEF recovery and specific oncological therapy continuance. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Cost-effectiveness of screening guidelines to prevent heart failure in childhood cancer survivors: A report from the Childhood Cancer Survivor Study (CCSS).

10052 Background: Childhood cancer survivors treated with anthracyclines or chest radiation therapy (RT) are at risk for left ventricular dysfunction (LVD) and subsequent heart failure (HF). The International Guideline Harmonization Group (IGHG) recommends risk-based screening echocardiograms for LVD, but evidence supporting its frequency and cost-effectiveness is limited. Methods: Using data from the CCSS, we developed a microsimulation model of the clinical course of LVD and HF to estimate long-term health and economic outcomes associated with screening for IGHG-defined risk groups (low [anthracycline 1-99 mg/m2 and/or RT &lt; 15 Gy], moderate [100 to &lt; 250 mg/m2 or 15 to &lt; 35 Gy], high [≥ 250 mg/m2 or ≥ 35 Gy or (≥ 100 mg/m2 and ≥ 15 Gy)]). We compared 1, 2, and 5-year interval-based screening to no screening. Screening performance and pharmacological treatment effectiveness were based on published studies. Costs and quality of life weights were based on US averages and published studies. Outcomes included lifetime HF risk, quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs). Strategies with ICERs &lt; $100,000/QALY gained were considered cost-effective. Results: Among the IGHG risk groups, the lifetime HF risk in the absence of screening was 37% (high), 25% (moderate) and 17% (low). Screening every 2 or 5 years was cost-effective for the high-risk group, and every 5 years for the moderate-risk group. In contrast, routine screening may not be cost-effective for the low risk group, representing ~40% of those for whom screening is currently recommended. Conclusions: Our findings can inform screening guidelines and suggest that LVD/HF surveillance for low-risk survivors warrants careful consideration. [Table: see text]

P6180Cardiometabolic risk factors and left ventricular dysfunction risk in adult survivors of childhood cancers: a report from the St Jude lifetime cohort (SJLIFE) study

P6180Cardiometabolic risk factors and left ventricular dysfunction risk in adult survivors of childhood cancers: a report from the St Jude lifetime cohort (SJLIFE) study

Protection from late-occurring anthracycline-related cardiotoxicity among childhood cancer survivors with a RARG coding variant.

130 Background: Susceptibility to late-occurring anthracycline-related left ventricular (LV) dysfunction is poorly understood. While higher dose of anthracyclines, radiation therapy, and younger age at exposure are relevant, heterogeneity persists. A recent report suggests that survivors with the rs2229774 retinoic acid receptor γ (RARG) variant represent a high-risk group. We sought to replicate this finding in our population of adult survivors of childhood and young adult cancer. Methods: We collected germline DNA among 455 survivors of childhood and young adult cancer seen in the Memorial Sloan Kettering Long-Term Follow-Up Programs. Participants were 48% male and more that 90% were white, non-Hispanic. Median age at diagnosis was 15 years and median time from diagnosis was 17.8 years. The most common diagnosis was Hodgkin Lymphoma (31%) followed by sarcoma (29%) and leukemia (10%). Initial genetic testing was performed using a low density SNP array (Illumina Exomearray), followed by full gene analysis by LD block testing. LV dysfunction was defined as ventricular ejection fraction less than 55%. Bonferroni-adjusted p values were used to determine significance in a multivariate model. Results: Of 455 participants, 120 did not have a history of anthracycline exposure, 1 was excluded for lack of echo data, and 17 were excluded due to poor genotyping quality control. Out of the remaining 317 participants, 41 had LV dysfunction. On initial testing, survivors with the rs2229774 variant were at lower risk for LV dysfunction (OR 0.14; 95% CI 0.02-0.99; p = 0.02), compared to survivors with other variants. Of note, the allele frequency in those without LV dysfunction was similar to reported studies and public data. In full gene analysis, those with a missense variant in ESPL1 (separase), within LD block but upstream of RARG, were at significantly increased risk of LV dysfunction (OR 5.61; 95% CI 1.48-21.3; p=0.005) compared to those without the ESPL1 variant. Conclusions: Based on these findings, rs2229774 RARG variant does not appear to confer genetic susceptibility to left ventricular dysfunction. ESPL1, a nearby candidate, may be the risk-conferring variant. Replication efforts are ongoing.

Late cardiac effects of chemotherapy in breast cancer survivors treated with adjuvant doxorubicin: 10-year follow-up.

Doxorubicin (Dox), a mainstay of adjuvant breast cancer treatment, is associated with cardiac toxicity in the form of left ventricular dysfunction (LVD), LV diastolic dysfunction, or LV systolic dysfunction. Study objectives were to evaluate the prevalence of LVD in long-term breast cancer survivors treated with Dox and determine if brain-type natriuretic peptide (BNP) may help identify patients at risk for LVD. Patients who participated in prospective clinical trials of adjuvant Dox-based chemotherapy for breast cancer with a baseline left ventricular (LV) ejection fraction evaluation from 1999 to 2006 were retrospectively identified from the St Vincent's University Hospital database. Patients were invited to undergo transthoracic echocardiography, BNP analysis, and cardiovascular (CV) risk factor assessment. LVDD was defined as left atrial volume index >34 mL/m(2) and/or lateral wall E prime <10 m/s, and LVSD as LVEF <50 %. Of 212 patients identified, 154 participated, 19 patients had died (no cardiac deaths), and 39 declined. Mean age was 60.7 [55:67] years. A majority of the patients (128, 83 %) had low CV risk (0/1 risk factors), 21 (13.6 %) had 2 RFs, and 5 (3.2 %) ≥3 RFs. BMI was 27.2 ± 4.9 kg/m(2). Median Dox dose was 240 mg/m(2) [225-298]; 92 patients (59.7 %) received ≤240 mg/m(2) and 62 (40.3 %) > 240 mg/m(2). Baseline LVEF was 68.2 ± 8 %. At follow-up of 10.8 ± 2.2 years, LVEF was 64.4 ± 6 %. Three (1.9 %) subjects had LVEF <50 % and one (0.7 %) had LVDD. Dox >240 mg/m2 was associated with any LVEF drop. BNP levels at follow-up were 20.3 pg/ml [9.9-36.5] and 21.1 pg/ml [9.8-37.7] in those without LVD and 61.5 pg/ml [50-68.4] in those with LVD (p = 0.04). Long-term prospective data describing the impact of Dox on cardiotoxicity are sparse. At over 10 years of follow-up, decreases in LVEF are common, and dose related, but LVD as defined is infrequent (2.6 %). Monitoring with BNP for subclinical LVD needs further evaluation.

Abstract 9947: Predictors of Left Ventricular Dysfunction After Aortic Valve Replacement in Patients With Mixed Aortic Valve Disease

Objectives: Predictors of left ventricular dysfunction (LVD) after aortic valve replacement (AVR) in mixed aortic valve disease (MAVD) have not been studied. Objective was to determine prevalence and predictors of early and late LVD at 1 and 5 years post-AVR. Methods: Retrospective review of 247 patients (Age 63±8 years, males 81%) with moderate/severe MAVD who underwent AVR at the Mayo Clinic from 1994-2013. Only patients with follow-up data at 1 year post AVR were included (n=239). Cohort divided into 3 groups based on data collected prior to AVR, 1 and 5 years post AVR. LVD was defined as ejection fraction &lt;50%. Results: LVD was present in 11/239 at baseline. At 1-year post AVR, 181 had normal EF (group 1) while 58/239 (24%) had early LVD (group 2). Predictors of LVD were atrial fibrillation (hazard ratio [HR] 1.83 confidence interval [CI] 1.59-1.98, p=0.001), age &gt;70 years (HR: 3.12, CI: 2.33-4.18, p= &lt;0.0001), CABG (HR: 2.17, CI: 2.24-5.93, p= &lt;0.0001), and severe MAVD pre-operatively (HR: 2.87, CI: 2.33-3.17, p= 0.01), and hypertension (HR: 1.83, CI: 1.35-2.46, p= &lt;0.0001). Prevalence of late LVD was 24% (47/197-group 3) and LVMI at 1 year post AVR was predictive of late LVD (HR 1.65, CI 1.11-3.8 per 10 g/ m 2 increment, p= 0.04)). Group 2 had less reverse LV remodeling compared to group 1 at 1 year post AVR (142±39 vs 129±42 g/ m 2 , p=0.02). Conclusions: Risk of LVD was significant even in subset of patients with moderate MAVD. Risk stratification of MAVD should be based on both clinical and echocardiographic parameters. Our data suggest earlier surgical intervention may be required in the MAVD population to prevent postoperative LVD but further studies are needed. Figure legend: FU: follow up

Update on Cardiovascular Safety of Tyrosine Kinase Inhibitors: With a Special Focus on QT Interval, Left Ventricular Dysfunction and Overall Risk/Benefit.

We previously reviewed the cardiovascular safety of 16 tyrosine kinase inhibitors (TKIs), approved for use in oncology as of 30 September 2012. Since then, the indications for some of them have been widened and an additional nine TKIs have also been approved as of 30 April 2015. Eight of these nine are indicated for use in oncology and one (nintedanib) for idiopathic pulmonary fibrosis. This report is an update on the cardiovascular safety of those 16 TKIs, including the post-marketing data concerning their pro-arrhythmic effects, and reviews the cardiovascular safety of the nine new TKIs approved since (afatinib, cabozantinib, ceritinib, dabrafenib, ibrutinib, lenvatinib, nintedanib, ponatinib, and trametinib). As before, we focus on specific aspects of cardiovascular safety, namely their potential to induce QT interval prolongation, left ventricular (LV) dysfunction and hypertension but now also summarise the risks of arterial thromboembolic events (ATEs) associated with these agents. Of the newer TKIs, cabozantinib and ceritinib have been shown to induce a mild to moderate degree of QTc interval prolongation while cardiac dysfunction has been reported with the use of afatinib, dabrafenib, lenvatinib, ponatinib and trametinib. The label for axitinib was revised to include a new association with cardiac dysfunction. Hypertension is associated with cabozantinib, lenvatinib, nintedanib, ponatinib and trametinib. Ponatinib, within 10 months of its approval in December 2012, required voluntary (temporary) suspension of its marketing until significant safety revisions (restricted indication, additional warnings and precautions about the risk of arterial occlusion and thromboembolic events and amended dose) were made to its label. Compared with the previous 16 TKIs, more of the recently introduced TKIs are associated with the risk of LV dysfunction, and fewer with QT prolongation. Available data on morbidity and mortality associated with TKIs, together with post-marketing experience with lapatinib and ponatinib, emphasise the need for effective pharmacovigilance and ongoing re-assessment of their risk/benefit after approval of these novel agents. If not adequately managed, these cardiovascular effects significantly decrease the quality of life and increase the morbidity and mortality in a population already at high risk. Evidence accumulated over the last decade suggests that their clinical benefit, although worthwhile, is modest and extends only to progression-free survival and complete response without any effect on overall survival. During uncontrolled use in routine clinical practice, their risk/benefit is likely to be inferior to that perceived from highly controlled clinical trials.

Screening for cardiac dysfunction in anthracycline-exposed childhood cancer survivors.

To examine the utility and reliability of obtaining early echocardiographic measurements of left ventricular (LV) remodeling as well as blood biomarkers of cardiac injury in asymptomatic childhood cancer survivors at risk for LV dysfunction and congestive heart failure due to past exposure to anthracycline chemotherapy. Using a cross-sectional design, anthracycline-exposed childhood cancer survivors with preserved ejection fraction (EF; ≥50%) were evaluated using early echocardiographic indices and blood biomarkers of LV dysfunction. Survivors treated with ≥300 mg/m(2) anthracyclines [high risk (HR): n = 100] were compared with those treated with <300 mg/m(2) anthracyclines [low risk (LR): n = 50] and matched healthy controls (HC: n = 50). All echocardiograms were interpreted by an institutional cardiologist and a study cardiologist blinded to risk status. Time from diagnosis was comparable for HR (12.0 years) and LR (13.2 years, P = 0.8) survivors. Echocardiograms: HR had lower LV thickness-dimension ratio (Z-score: HR: -0.62, LR: -0.03, HC: -0.02; P < 0.001), increased LV wall stress (HR: 66.7 g/cm(2), LR: 56.6 g/cm(2), HC: 54.2 g/cm(2); P < 0.01), and higher myocardial performance index (HR: 0.51, LR: 0.46, HC: 0.46; P < 0.01). Interobserver correlation (clinical/blinded reading) for all echocardiographic indices was excellent (range: R = 0.76-0.97, P < 0.001). Blood biomarkers: With the exception of NT-proBNP (r = 0.28, P < 0.01), there was no correlation between blood biomarkers (B-type natriuretic peptide, Troponin-T, ST-2, Galectin-3) and LV dysfunction. Childhood cancer survivors with preserved EF 10+ years from anthracycline exposure had dose-dependent changes in echocardiographic markers of LV dysfunction.

Screening for Left Ventricular Dysfunction in Childhood Cancer Survivors Who Received Anthracyclines

Because childhood cancer survivors who were treated with anthracyclines are at high risk for left ventricular dysfunction and subsequent congestive

Detection of Left Ventricular Dysfunction Using Early Diastolic Mitral Annular Velocity in Patients Undergoing Mitral Valve Repair for Mitral Regurgitation

Ejection fraction (EF) is considered an unreliable index in patients with mitral regurgitation (MR). Left ventricular dysfunction (LVD) frequently occurs after mitral valve repair (MVR), with the incidence being 15% to 34%. This study aimed at investigating whether preoperative early diastolic mitral annular velocity (E') is associated with LVD after MVR. Retrospective study. University hospital. Sixty-three patients undergoing MVR for severe MR. None. LVD was defined by a postoperative EF of<50%. Receiver operating characteristic (ROC) analysis and separate multivariate logistic regression models were used to examine the independent effects of echocardiographic variables on LVD risk. LVD occurred in 20 patients (31.7%). E' was correlated significantly with perioperative EF change (p = 0.019, r = 0.293). The area under the ROC curve was 0.777 (95% confidence interval [CI]: 0.644-0.911) for E', and the optimal threshold value of E' for predicting LVD was 6.5 cm/s (sensitivity, 80%; specificity, 67.4%). The frequency of LVD was 33.3% for a preoperative EF< 65%; 44.4% for preoperative EF< 65% and left ventricular end-systolic diameter>32 mm; and 88.9% for preoperative EF< 65%, left ventricular end-systolic diameter>32 mm, and E'< 6.5 cm/s (p = 0.006). Multivariate logistic regression models analysis revealed that E' was an independent risk factor for LVD (odds ratio: 1.98, 95% CI: 1.22-3.22). Preoperative E' value was an independent risk factor of LVD after mitral valve repair in patients with severe MR.