Decrease In Left Ventricular Ejection Fraction Research Articles

Effects of Cardioprotective Tactics on the Myocardial Perfusion and Contractile Function of the Left Ventricular Myocardium in Cancer Patients with Evidence of Doxorubicin-Induced Cardiotoxicity.

Aim To study the effect of cardioprotective tactics on parameters of left ventricular myocardial perfusion and contractility as per data from single-photon emission computed tomography in oncological patients with signs of anthracycline-induced cardiotoxicity.Material and methods The study included patients with oncological diseases (n=61) referred to polychemotherapy (PCT). For patients with signs of anthracycline-induced cardiotoxicity, a cardioprotective tactics was used, which included changing the PCT schedule and administering beta-blockers and angiotensin-converting enzyme inhibitors. For all patients at baseline, after the first four PCH courses, after initiation of the cardioprotective tactics and the next four PTC courses, the level of N-terminal pro-brain natriuretic peptide was measured and echocardiography and perfusion single-photon emission computed tomography were performed with assessment of left ventricular (LV) perfusion heterogeneity, systolic and diastolic function.Results Following four PTC courses, signs of cardiotoxicity were detected in 13 (21.3 %) patients. On the background of the cardioprotective tactics, a further decrease in LV ejection fraction (EF) by -9±2 % (p<0.01) was observed in 4 (30.8 %) patients. In 9 (69.2 %) patients, LV EF increased by 4±2 % (p<0.01). Standard indexes of LV myocardial perfusion did not significantly change. In 7 patients, the cardioprotective tactics was associated with reduced severity of myocardial perfusion disorder, LV∆σТ = -1.37±1.29 (p<0.05), and in 4 patients, with reduced heterogeneity of myocardial perfusion, LV∆σН = -1.20±0.70 (p<0.05).Conclusion The cardioprotective tactics prevents both further disorder of perfusion and decreases in parameters of left ventricular myocardial contractility in patients with anthracycline-induced cardiotoxicity.

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

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

Myocardial work brings a new insight into left ventricule remodelling in cardiooncology patients

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Serial echocardiographic assessment of 2D left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) is the gold standard screening method for cancer therapeutics-related cardiac dysfunction (CTRCD). Non-invasive left ventricular (LV) pressure-strain loop (PSL) provides a novel method of quantifying myocardial work (MW) with potential advantages, as it incorporates measurements of myocardial deformation and LV pressure. Purpose To evaluate the impact of cardiotoxic treatments in MW indices. Methods Prospective study of female breast cancer patients (P) submitted to therapy (TH) who underwent serial monitoring by 2D, 3D transthoracic echocardiography (TTE) and concomitant blood pressure assessment. P were evaluated at T0, T1 and T2 (before, ≥6 and ≥12 months after starting TH). PSL analysis allowed the calculation of the following indices: Global Work Index (GWI), Global Constructive Work (GCW), Global Work Waste (GWW) and Global Work Efficiency (GWE). CTRCD was defined as an absolute decrease in 2D LVEF > 10% to a value < 54% or a relative decrease in 2D GLS > 15%, according to literature. Results 122 patients (mean age 54.7 ± 12.0 years), mostly treated with anthracyclines (77.0%, cumulative dose 268.6 ± 71.8mg/m2), anti-HER (75.4%) and radiotherapy (77.0%) were included. 2D and 3D LVEF were significantly reduced during TH, however remaining within the limits of normality (2D LVEF T0-T1 64.2 ±7.6 vs 61.1 ± 8.2%, p = 0.006 and 3D LVEF T0-T1 60.2 ± 6.7 vs 56.9 ±6.3%, p = 0.022). 2D GLS was also more impaired at T1 (-19.8 ± 2.7% vs -18.5 ± 3.0%, p = 0.003). All MW indices were significantly reduced at T1 compared to baseline (GWI 1756.9 ± 319.2 vs 1614.3 ± 338.5mmHg%, p = 0.005; GCW 2105.6 ± 352.0 vs 1970.5 ± 376.2 mmHg%, p = 0.015; GWW 121.1 ± 66.6 vs 161.1 ± 84.1 mmHg%, p = 0.001; GWE 93.5 ± 3.1 vs 91.1 ± 4.5%, p = 0.001). Between T1 and T2 no statistical difference was found but a partial recovery of parameters was observed when comparing T2 to T0 (GWI (T2) 1650.6 ± 357.5 mmHg%, p = 0.035; GCW (T2) 2013.3 ± 379.3 mmHg%, p = 0.086; GWW (T2) 148.0 ± 85.0 mmHg%, p = 0.02 and GWE (T2) 92.0 ± 4.7%, p = 0.012). During a mean follow-up of 14.9 ± 9.3 months, 36 patients (29.5%) developed CTRCD. P presenting CTRCD revealed a significant decrease in GWI and GWE at T1 comparing with women without CTRCD (GWI 1.8 ± 21.6 vs -14.2 ± 18.5%, p = 0.004 and GWE -1.0 ±3.0 vs -3.6 ±3.9%, p = 0.005). GWW had a substantially increase at T1 in P with cardiotoxicity (27.6 ± 76.3% vs 64.1 ± 68.0%, p = 0.051). Conclusion Left ventricular systolic function study with MW showed a reduction in cardiac performance with a peak at 6 months from the start of chemotherapy and partial recovery after term. Assessment of myocardial deformation parameters, namely MW, proved to be a useful tool for a better characterisation of cardiac remodelling, and could enhance patient selection for cardioprotective therapeutics. Abstract Figure. TTE parameters

Myocardial interstitial fibrosis assessed by extracellular volume quantification is a determinant of symptoms in aortic valve regurgitation with preserved ejection fraction

Abstract Funding Acknowledgements Type of funding sources: None. Introduction According to current guidelines indication for surgery is straightforward with a class I recommendation in case of severe symptomatic aortic regurgitation (AR) and/or left ventricular ejection fraction (LVEF) decrease ≤50%. However, the management of patients with asymptomatic severe AR with preserved LVEF remains debated, with a cruel lack of prognostic factors to identify patients who may benefit from early intervention. An explanation to the absence of such factors is that the determinants of symptoms, a strong prognostic parameter, have been poorly identified. Beyond LV dilation and systolic dysfunction, which are both recognized prognostic factors in chronic AR, we hypothesized that interstitial myocardial fibrosis, as an early indicator of LV remodeling, may also influence the occurrence of symptoms. Cardiovascular magnetic resonance (CMR)-based myocardial extracellular volume (ECV) quantification by T1 mapping has emerged as a valuable tool to quantify diffuse myocardial fibrosis. Objective To study the relationship between myocardial interstitial fibrosis quantified by T1 mapping and the symptomatic status of patients with chronic aortic valve regurgitation. Methods We retrospectively included 38 consecutive patients with chronic, isolated, mild to severe AR who underwent a CMR at our institution. Exclusion criteria were the presence of any other heart condition that may induce myocardial fibrosis, ≥ mild associated valve disease, AR secondary to endocarditis, genetic, inflammatory or congenital disease except bicuspid aortic valve. T1 mapping of the basal segments was performed before and after contrast administration measuring native and post-contrast T1 relaxation time and ECV. Results Mean age was 56 ± 20 years, 30 patients (79%) were males, and symptoms were reported in 11 patients (29%). Mean LVEF was 57 ± 9% and ≥50% in 30 patients (79%). Aortic valve regurgitation fraction (RF) was 25 ± 13%, ECV 0.27 ± 0.04%, indexed LV end-diastolic volume (LVEDVi) 98 ± 32 ml/m2, end-systolic volume (LVESVi) 46 ± 19 ml/m2, and LV mass 79 ± 21 g/m2. LVESVi (r = 0.41,p = 0.01), LVEF (r=-0.59,p = 0.0001), and ECV (r = 0.42,p = 0.008) were correlated with symptoms, whereas age (r = 0.16,p = 0.33), gender (r=-0.24,p = 0.15), LVEDVi (r = 0.28,p = 0.09), LV mass index (r = 0.08,p = 0.62), and RF (r = 0.31,p = 0.06) were not. In the subgroup of patients with preserved LVEF (≥50%), after adjustment for LVESVi and RF, only ECV remained independently associated with symptoms (p = 0.046). Interestingly, when including the patients with a reduced LVEF < 50% in the multivariable analysis only LVESVi was an independent determinant of symptoms (p = 0.04) and ECV was not (p = 0.07) Conclusion myocardial fibrosis quantified by ECV calculation is a determinant of symptoms in AR with preserved LVEF. Further studies are warranted to determine the prognostic value of ECV that may justify earlier intervention. Abstract Figure. ECV in AR with preserved LVEF

Doxorubicin-induced and trastuzumab-induced cardiotoxicity in mice is not prevented by metoprolol.

AimsOur objectives were to validate a murine model of chronic cardiotoxicity induced by Doxorubicin (Dox) and Trastuzumab (Trast) and to test the potential cardio‐protective effect of metoprolol.Methods and resultsMale C57Bl6 mice were intraperitoneally injected during 2 weeks with Dox (24 mg/kg) or saline, and then with Trast (10 mg/kg) or saline for two more weeks. Half of the mice received metoprolol (100 mg/kg). Cardiotoxicity was defined by a decline in left ventricular ejection fraction (LVEF) ≥ 10 points. At Day 42, Dox + Trast‐treated mice exhibited a 13‐points decline in LVEF (74 ± 2.6% vs. 87 ± 0.8% for control mice, P < 0.001) and a severe cardiac atrophy (heart weight: 105 ± 2.7 mg vs. 119 ± 3.9 mg for control mice, P < 0.01). This cardiac atrophy resulted from an excess of cardiac necrosis (assessed by plasma cardiac troponin I level: 3.2 ± 0.4 ng/L vs. 1.3 ± 0.06 ng/L for control mice, P < 0.01), an increase in apoptosis (caspase 3 activity showing a six‐fold increase for Dox + Trast‐treated mice vs. controls, P < 0.001), and cardiomyocyte atrophy (myocyte size: 0.67 ± 0.08 μm2 vs. 1.36 ± 0.10 μm2 for control mice, P < 0.001). In addition, Dox + Trast‐treated mice were shown to have an increased cardiac oxidative stress (164 ± 14 dihydroethidine‐marked nuclei per area vs. 56 ± 9.5 for control mice, P < 0.01) and increased cardiac fibrosis (the semi‐quantitative fibrosis score was three‐fold higher for Dox + Trast‐treated mice as compared with controls, P < 0.01). Metoprolol was not able to prevent either the decrease in LVEF or the severe cardiac atrophy, the cardiac necrosis, and the cardiac remodelling induced by chemotherapies.ConclusionA murine model of chronic cardiotoxicity induced by Dox and Trast was characterized by a decrease in cardiac function, a cardiac apoptosis and necrosis leading to cardiomyocyte atrophy. Metoprolol did not prevent this cardiotoxicity.

Risk Factors for Left Ventricular Dysfunction Following Surgical Management of Cardiac Fibroma.

Surgical resection of cardiac fibromas in children reduces hemodynamic and arrhythmia burden; however, little is known about postoperative left ventricular (LV) function. We aimed to evaluate factors associated with postoperative LV dysfunction. In this retrospective observational cohort study, imaging data were reviewed from 41 patients who had undergone surgical resection of a cardiac fibroma. Tumor volume was indexed to body surface area (tumor volume index). Right ventricular tumors were excluded from analysis of postoperative ventricular function. Postoperative regional wall motion abnormality score was defined as number of wall segments with regional wall motion abnormality, and LV dysfunction was defined as LV ejection fraction <50%. Cardiovascular magnetic resonance-derived strain was low if <5%ile by previously published normative data. Of 41 patients who underwent resection at a median age of 2.1 years (range, 0.5-19), 37 fibromas were in the LV, (29 free wall and 8 septal), and 4 in the right ventricle. Preoperative median tumor volume index was 66 mL/m2 (range, 11-376). Of 37 patients with LV tumors, younger patients had larger tumor volume index and higher grades of preoperative mitral regurgitation (P<0.001). Larger tumor volume index correlated with higher postoperative regional wall motion abnormality score (P<0.001). By paired pre- and post-operative cardiovascular magnetic resonance (n=14), LV end-diastolic volume increased (mean 76 versus 101 mL/m2, P=0.011), with decreased LV ejection fraction (mean 60% versus 55%, P=0.014), a higher prevalence of low global circumferential strain (36% versus 64%, P=0.045), and decreased cardiac index (mean 4.8 versus 3.9 L/[min·m2], P=0.039). More than mild preoperative mitral regurgitation was the only independent predictor of predischarge LV dysfunction (odds ratio, 22 [95% CI, 2.8-179], P=0.008). Surgical resection of LV fibroma is associated with regional wall motion abnormality, increased LV volume, and reduced systolic function. Children with significant preoperative mitral regurgitation are at highest risk for LV dysfunction and warrant ongoing close surveillance.

Clinical Characteristics of Hypertensive Patients with Obstructive Sleep Apnoea Syndrome Developing Different Types of Left Ventricular Geometry.

Objective The objective of the study was to compare polygraphic parameters and selected laboratory parameters in patients with obstructive sleep apnoea (OSA) who develop various types of left ventricular (LV) geometry. Material and Methods. The research covered 122 patients with obstructive sleep apnoea and coexisting effectively treated systemic hypertension (95 men, 27 women, average age: 54 ± 10.63). Overnight polygraphy, echocardiography, carotid artery ultrasonography, and laboratory measurements were performed. The patients were classified into four groups, depending on LV geometry. Group 1 comprised patients with normal LV geometry, group 2 included those with LV concentric remodelling. Group 3 and group 4 were patients with LV hypertrophy, concentric or eccentric, respectively. Results The most frequent type of LV geometry in the examined population was eccentric hypertrophy (36%). The highest average values of BMI and T-Ch were observed in the group of patients with concentric remodelling (group 2). The most severe respiratory disorders were found in the group of patients developing LV concentric hypertrophy (group 3); however, these differences were not statistically significant in comparison to other groups. Patients with LV eccentric hypertrophy had significantly decreased LV ejection fraction (p = 0.0008). Conclusions LV eccentric hypertrophy is the most frequent type of LV geometry in OSA patients. Patients with severe sleep-disordered breathing are more likely to develop concentric hypertrophy, while concentric remodelling occurs more frequently among OSA patients with other coexisting conditions, such as obesity or lipid-related disorders.

Left ventricular ejection fraction decrease related to BRAF and/or MEK inhibitors in metastatic melanoma patients: a retrospective analysis

BRAF and MEKis have revolutionized the management of BRAF V600 -mutated melanoma patients. Left ventricular ejection fraction decrease (LVEF-D) related to these treatments has not been thoroughly evaluated to date. The main objective of this study was to describe characteristics of LVEF-D in melanoma patients treated with BRAF and/or MEKis. Metastatic melanoma patients treated with BRAF and/or MEKis between March 1, 2012 and May 18, 2018 were included retrospectively (XXX University Hospital, XXX). LVEF-D was defined as a reduction in LVEF 3 10 % from baseline to a value < 55 %; normalization was defined as a value ≥ 55 %. Among the 88 patients included, 12 (13.6 %) experienced a LVEF-D, including 10 grade 2 and 2 grade 3. The median onset of which was 11 months [IQR (3–21)]. No patient previously treated with beta-blockers ( N = 12) experienced a LVEF-D. Analysis of laboratory parameters, electrocardiogram, and transthoracic echocardiography during the follow-up did not find any predictive marker of LVEF-D. All patients who benefited from a specific treatment of LVEF-D had a normalization of LVEF at the end of follow-up. LVEF recovery was significantly better for patients treated with angiotensin converting enzyme inhibitors and beta-blockers than those who did not ( P = 0.019). Ophthalmological adverse events were significantly more frequent in patients who experienced a LVEF-D ( P = 0.006) and the latter did not influence overall-survival ( P = 0.117) or progression-free-survival ( P = 0.297). LVEF-D is a common and easily manageable adverse event due to BRAF and MEKis. Its association with ocular toxicity suggests a close ophthalmological monitoring when LVEF-D occurs.

The Association between Changes in Low Parathyroid Hormone Levels and Cardiac Function Decline in Maintenance Hemodialysis Patients: A Prospective Observational Study

Objectives: The aim of this study was to investigate a possible association between changes in low parathyroid hormone (PTH) levels and cardiac function decline in maintenance hemodialysis (MHD) patients. Methods: A total of 150 MHD patients were included and followed for 24 months. The enrolled patients were divided into 3 groups based on their PTH status at baseline and 24 months. Factors potentially involved in changes in the PTH level and cardiac function were compared using multivariate logistic regression analysis. Results: At 24 months, the presence of low PTH levels increased by 26.7%. The main independent factors for low PTH levels were a low BMI, hemoglobin, and serum albumin and high serum calcium (p < 0.05). A persistently low PTH level at 24 months was associated with a decrease in the left ventricular ejection fraction (LVEF) and increase in valvular calcification (p < 0.05). Additionally, a decrease in PTH levels from normal or high to low values was associated with a decrease in LVEF and cardiac output (CO) and an increase in valvular calcification (p < 0.05). Furthermore, compared with those of the persistently low PTH level group, LVEF values were lower at 24 months in the group with a decrease from high/normal to low PTH level (p < 0.05). Conclusion: Persistently low PTH levels and changes in the PTH level from high/normal to low were associated with cardiac function decline in MHD patients. Moreover, a PTH level change from high/normal to low showed a stronger correlation with cardiac function decline.

СТИМУЛЯЦИЯ ЭКСТРАКАРДИАЛЬНОЙ РЕВАСКУЛЯРИЗАЦИИ ПРИ КОРОНАРНОМ ШУНТИРОВАНИИ У БОЛЬНЫХ ИБС С ДИФФУЗНЫМ ПОРАЖЕНИЕМ ВЕНЕЧНОГО РУСЛА

Objective: Clinical observations of the use of complex myocardial revascularization (YurLeon III technique) and traditional coronary artery bypass graft (CABG) in patients with diffuse atherosclerotic lesions of the coronary network are presented. A year after CABG+YurLeon III surgery, left ventricular ejection fraction (LVEF) increased from 45% to 57%, the perfusion defect according to synchro-single-photon emission computed tomography (synchro-SPECT) decreased from 30% to 5%, the overall index of total physical well-being increased from 23.81 to 53.97 and general mental well-being elevated from 46.97 to 47.57 points. With isolated CABG, the patient had an improvement in contractility, perfusion, and key indicators of quality of life (QoL) in the early stages after surgery. However, the dynamics after a year revealed a slight decrease in LVEF, and an increase of the zone of myocardial perfusion defect. Keywords: Atherosclerosis, coronary artery disease, coronary artery bypass graft, diffuse coronary artery disease, YurLeon technique.

Phase II study of liposomal doxorubicin, docetaxel and trastuzumab in combination with metformin as neoadjuvant therapy for HER2-positive breast cancer.

Background:The aim of this study was to improve activity over single human epidermal growth factor receptor 2 (HER2)-blockade sequential neaodjuvant regimens for HER2-positive breast cancer, by exploiting the concomitant administration of trastuzumab, taxane and anthracycline, while restraining cardiac toxicity with use of liposomal doxorubicin, and by adding metformin, based on preliminary evidence of antitumor activity.Patients and methods:This multi-center, single-arm, two-stage phase II trial, assessed the safety and the activity of a new treatment regimen for HER2-positive, early or locally advanced breast cancer. Patients received six 21-day cycles of non-pegylated liposomal doxorubicin, 50 mg/m2 intravenously (i.v.) on day 1, docetaxel, 30 mg/m2 i.v. on days 2 and 9, trastuzumab, 2 mg/kg/week i.v. on days 2, 9, and 16 (with 4 mg/kg loading dose), in association with metformin 1000 mg orally twice daily. The primary endpoint was the rate of pathological complete response (pCR) in the breast and axilla (ypT0/is ypN0). A subgroup of patients performed a 3-deoxy-3-18F-fluorothymidine positron emission tomography (FLT-PET) at baseline and after one cycle.Results:Among 47 evaluable patients, there were 18 pCR [38.3%, 95% confidence interval (CI) 24.5–53.6%]. A negative estrogen-receptor status, high Ki67, and histological grade 3 were related with pCR, although only grade reached statistical significance. FLT-PET maximum standardized uptake value after one cycle was inversely related to pCR in the breast (odds ratio 0.29, 95% CI 0.06–1.30, p = 0.11). Toxicity included grade 3–4 neutropenia in 70% and febrile neutropenia in 4% of patients, grade 1–2 nausea/vomiting in 60%/38%, and grade 3 in 4%/2%, respectively, grade 1–2 diarrhea in 72%, and grade 3 in 6%. There were two cases of reversible grade 2 left-ventricular ejection-fraction decrease, and one case of sharp troponin-T increase.Conclusions:The concomitant administration of trastuzumab, liposomal doxorubicin, docetaxel, and metformin is safe and shows good activity, but does not appear to improve activity over conventional sequential regimens.

Aspects of chronic heart failure in patients with type 2 diabetes mellitus after implantation of a permanent pacemaker, depending on body weight

The course of chronic heart failure (CHF) had been analyzed in patients with type 2 diabetes mellitus (DM) who had undergone pacemaker implantation, depending on body mass index (BMI). A retrospective analysis of echocardiographic data was carried out in 203 CHF patients who underwent pacemaker implantation, among whom 102 had concomitant type 2 diabetes (main group) and 101 participants did not have this metabolic pathology (control group). Pacemaker implantation was considered effective when the left ventricular end-diastolic volume (LV EDV) increased by 15 % after 12 months after operation. Patients who did not reach the target value of LV EDV were considered non-responders; analyzed the left ventricular ejection fraction (LVEF). In the main group, 22 patients (21,57 %) did not respond to implantation of the pacemaker, in the control group 12 people (11,9 %) did not respond to implantation of the pacemaker. Among the nonresponders, obese persons of the I, II and III degrees predominated. In the cohort of persons who responded to the establishment of the pacemaker, patients with a normal and increased BMI predominated; recorded a significant (p&lt;0,001) increase in the mean values of LVEF in patients with normal BMI from (52,0±0,8) % to (61,4±0,8) %. Similar changes were noted in overweight patients: LVEF significantly (p&lt;0,05) increased from (47,7±1,4) % to (55,1±1,3) %. Patients with CHF with concomitant type 2 diabetes, requiring pacemaker, have an inherent decrease in LVEF, which progressively decreases with increasing BMI. Low LVEF values are characteristic to patients with chronic heart failure, type 2 diabetes and morbid obesity. A good response to pacemaker implantation is associated with a normal, elevated BMI; failure to achieve the target value of LV EDV and insufficient growth of LVEF is more often recorded in the presence of concomitant obesity, especially of the II and III degrees. Keywords: heart failure, pacemaker, diabetes mellitus, left ventricular ejection fraction.

Evaluation of heart chambers and left ventricular geometry in civil aviation pilots of senior age groups according to echocardiography data

The structural- functional changes of heart chambers (changes in size, volume, shape and function of the heart) are the basis of the cardiac remodeling — an important element of the cardiovascular continuum, which is a key mechanism for the progression of the main cardiovascular diseases. Echocardiography is the main and available method for its assessment.Material and methods. 1189 civil aviation pilots aged 54–68 who underwent routine in-patient examination at the Central Clinical Hospital of Civil Aviation were examined on a regular basis with further medical assessment at the Central Medical Flight Expert Commission of Civil Aviation of the Russian Federation in 2009–2010. The average age was 56.75 ± 0.07. Transthoracic echocardiography was performed for evaluation of the structural-functional indicators of the cardiovascular system in 1170 of flight personnel (98.4%).Results. Enlarged size of the heart chambers was minor and moderate without heart failure and was detected in 4.8% of civil aviation pilots of senior age group. Abnormal geometry of left ventricular (LV) was revealed in 61.7% of the examined civil aviation pilots of senior age group: left ventricular hypertrophy (LVH) — in 1% of pilots (concentric LVH — 0.6 % and eccentric LVH — 0.4% cases), concentric remodeling of the LV — in 60.7% pilots. The decrease in LV ejection fraction was observed only in one pilot with EF— 53%. Pilots inapt for flying had enlarged chambers more often than pilots with fitness to fly (9.8% vs 3.35% pilots; p &lt; 0,0001) and LVH (2.9% vs 0.45%; p &lt; 0,001).Conclusions. Echocardiography is an important method for cardiac chambers evaluation, including determination of type LVH geometry. It can be used in the medical assessment of civil aviation pilots of the senior age group.

Effect of intramyocardial haemorrhage on structural and functional echocardiographic parameters of myocardium after ST-segment elevation myocardial infarction with

Aim. To analyze the effect of intramyocardial haemorrhage (IMH) on the structural and functional echocardiographic parameters of myocardium in patients with primary ST-segment elevation myocardial infarction (STEMI).Material and methods. The study included 60 patients with primary STEMI reperfused within 12 hours after symptom onset. On the second day after the event, all subjects underwent gadolinium-enhanced cardiac magnetic resonance imaging (MRI). IMH was visualized as T2-weighted hypointense areas. Subsequently, all patients underwent the standard echocardiography on the 7th day after MI.Results. IMH was revealed in 31 patients (51,6%). In 22 patients (70,9%), IMH was accompanied by microvascular obstruction (MVO). In the remaining 9 patients (29%), an isolated IMH phenomenon was visualized. Lower values of left ventricular ejection fraction (LVEF) and LV volume parameters were associated with a combination of MVO and IMH. At the same time, the indices of volumetric characteristics and LVEF in isolated IMH were the same as in the group without IMH and MVO. It was demonstrated that the IMH occupies 1% (1-3%) of the LV myocardium. Correlation analysis showed a moderate inverse correlation between the IMH area and LV contractile function: the larger the area, the lower the LVEF (R=-0,35; p=0,007).Conclusions. The analysis of the influence of different IMH phenotypes on the structural and functional echocardiographic parameters of myocardium in the short-term period after STEMI has shown that the combination of IMH with MVO and isolated IMH have different effects on LV contractile function. The combination of IMH with MVO is a predictor of a decrease in LVEF and increase of end-systolic volume (ESV), while an isolated IMH does not affect these parameters. Correlations between the IMH area and a decrease in LVEF, as well as an increase in ESV, have been demonstrated.

Impact of obesity on safety outcomes and treatment modifications with ado-trastuzumab emtansine in breast cancer patients

Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate indicated for the treatment of HER2-positive breast cancer. The 2012 American Society of Clinical Oncology guidelines on chemotherapy dosing in obesity recommend using full weight-based cytotoxic chemotherapy doses to treat obese patients with cancer. These guidelines were published prior to the advent of anticancer antibody-drug conjugates. There is a need to investigate the safety of T-DM1 in obese patients. This retrospective chart review included adult patients with breast cancer receiving T-DM1. The primary endpoint was a composite of the incidence of T-DM1 treatment modifications secondary to an adverse event. Secondary outcomes included the incidence of dose reductions, dose delays, treatment discontinuations, and adverse events. A total of 119 patients with HER2-positive breast cancer who received T-DM1 therapy were included in this study: 44 obese patients and 75 non-obese patients. The composite outcome of treatment modifications due to toxicity was significantly higher in obese patients compared to non-obese patients (45% vs 25%, p = 0.024). Treatment delays were significantly higher in obese patients (36% vs 16%, p = 0.011). All-grade adverse events with a higher incidence in obese patients included left ventricular ejection fraction decrease (11% vs 5%), bilirubin increase (32% vs 12%), thrombocytopenia (61% vs 55%), and peripheral neuropathy (34% vs 27%). This study suggests obese patients receiving T-DM1 may require more treatment modifications secondary to adverse events compared to non-obese patients. Larger studies are needed to determine if obese patients are at higher risk for specific T-DM1-induced adverse events.

Early Cardiac Effects of Contemporary Radiation Therapy in Patients With Breast Cancer

To characterize the early changes in echocardiographically derived measures of cardiac function with contemporary radiation therapy (RT) in breast cancer and to determine the associations with radiation dose-volume metrics, including mean heart dose (MHD). In a prospective longitudinal cohort study of 86 patients with breast cancer treated with photon or proton thoracic RT, clinical and echocardiographic data were assessed at 3 time points: within 4 weeks before RT initiation (T0), within 3 days before 6 weeks after the end of RT (T1), and 5 to 9 months after RT completion (T2). Associations between MHD and echocardiographically derived measures of cardiac function were assessed using generalized estimating equations to define the acute (T0 to T1) and subacute (T0 to T2) changes in cardiac function. The median estimates of MHD were 139 cGy (interquartile range, 99-249 cGy). In evaluating the acute changes in left ventricular ejection fraction (LVEF) from T0 to T1, and accounting for the time from RT, age, race, preexisting cardiovascular disease, and an interaction term with anthracycline or trastuzumab exposure and MHD, there was a modest decrease in LVEF of borderline significance (0.22%; 95% confidence interval [CI], -0.44% to 0.01%; P = .06) per 30-day interval for every 100 cGy increase of MHD. Similarly, there was a modest worsening in longitudinal strain (0.19%; 95% CI, -0.01% to 0.39%; P = .06) per 30-day interval for each 100 cGy increase in MHD. We did not find significant associations between MHD and changes in circumferential strain or diastolic function. With modern radiation planning techniques, there are modest subclinical changes in measures of cardiac function in the short-term. Longer-term follow-up studies are needed to determine whether these early changes are associated with the development of overt cardiac disease.

Microcirculation disorders and structural and functional left ventricular abnormalities in patients with type 1 diabetes complicated by ketoacidosis

Aim. To assess the patterns of microcirculation disorders and its effect on the left ventricular (LV) structure and function in patients with type 1 diabetes (T1D) complicated by diabetic ketoacidosis (DKA).Material and methods. The study included 128 patients with T1D complicated by DKA. Echocardiography was performed according to the standard technique. To study the microcirculation and vascular tone regulation, we used a laser Doppler flowmetry (LDF) using the LAKK-02 machine (Lazma, Russia).Results. In patients with T1D complicated by DKA, there was an increase in thepassive blood flow modulation with a depression of active factors. The most pronounced changes are recorded in 1-5 days of the disease. Along with this, a spectral redistribution in favour of respiratory and cardiac microcirculation ranges was demonstrated. With DKA, the myocardial remodelling is recorded: an increase in left atrial (LA) size by 5,6%, LV end systolic and diastolic dimension and volume by 5,3% and 6,7%, respectively, LV mass by 17,3% and LV mass index by 17,8%. Decreased LV ejection fraction (EF) in comparison with healthy individuals was obtained. Significant unidirectional changes in these parameters were revealed in comparison with the T1D patients without DKA.Conclusion. In patients with T1D complicated by DKA, the microcirculation decreases, as a result of which the adequate tissue supply is limited, vascular resistance and hemodynamic load increases, which leads to LV structural and functional changes.

Abstract 13441: D-dimmer is a Predictor of Cancer Therapeutics-related Cardiac Dysfunction in Patients Treated With Cardiotoxic Chemotherapy

Background: D-dimer is a sensitive biomarker for cancer-associated thrombosis, but little is known about its significance on cancer therapeutics-related cardiac dysfunction (CTRCD). Methods and Results: Consequtive 202 patients planned for cardiotoxic chemotherapy (anthracyclines, monoclonal antibodies, tyrosine kinase inhibitors, and proteasome inhibitors) were enrolled and followed up for 12 months. Cancer types were as follows: breast cancer (n=112), lymphoma (n=37), ovarian or uterine cancer (n=18), leukemia (n=13), multiple myeloma (n=6), bone cancer (n=4), and others (n=12). All patients underwent echocardiography and blood test at baseline, 3-month, 6-month, and 12-month. The patients were divided into 2 groups based on the value of D-dimer (&gt;1.5 μg/ml or ≦1.5 μg/ml) at baseline before chemotherapy: High D-dimer group (n=52) and Low D-dimer group (n=150). At baseline, left ventricular ejection fraction (LVEF), left ventricular end-systolic volume index, and B-type natriuretic peptide levels were similar between two groups. Time-dependent decrease in LVEF was observed after chemotherapy in high D-dimer group (baseline, 66±5%; 3-month, 63±7%; 6-month, 62±7%; 12-month 62±6%; P=0.005, figure), but not in low D-dimer group. Time-dependent increase in troponin I was similarly observed after chemotherapy in both groups. The occurrence of CTRCD was higher in high D-dimer group than in low D-dimer group (11.5% vs. 4.0%, P=0.048). When we set the cut-off value of baseline D-dimer at 1.65 μg/ml from ROC analysis, sensitivity, specificity, and area under the curve to predict CTRCD were 50%, 77%, and 0.679, respectively. Multivariable logistic analysis revealed that baseline D-dimer was an independent factor to predict the decrease in LVEF more than 10% after cardiotoxic chemotherapy (odds ratio 1.210, 95% confidence interval [1.020-1.440], P=0.025). Conclusion: Baseline D-dimer is a pivotal parameter to predict CTRCD.

Abstract 13583: Secondary Findings of Loss-of-function Variants in FLNC Are Associated With Arrhythmogenic Cardiomyopathy Phenotypes in a General Clinical Population

Introduction: The FLNC gene, encoding the Filamin C sarcomere protein, has gained recent attention as a potential cause of severe cardiomyopathy and arrhythmia phenotypes through genetic testing of individuals with known inherited heart disease. We sought to characterize the phenotypes associated with rare, putative loss-of-function variants in FLNC ascertained through secondary findings of exome sequencing in a large clinical population. Methods: We reviewed exome data from the first 135,878 sequenced participants in the Geisinger MyCode Community Health Initiative with linked electronic health records (EHR; the DiscovEHR cohort) to identify rare frameshift, stop gain, or canonical splice site variants in FLNC (FLNC LOF ). We compared data on diagnoses and cardiac diagnostic testing (i.e., ECG and echocardiography, when available) from the EHR between individuals with and without FLNC LOF using SAIGE mixed linear models adjusted for age, sex, and ancestry. Results: We observed 46 individuals (0.03%) carrying one of 24 distinct FLNC LOF variants. These individuals had significantly increased odds for diagnoses of dilated cardiomyopathy (OR: 49, 95% CI: [4-560]), ventricular tachycardia (OR: 170, [5-6317]), and supraventricular tachycardia (OR: 11, [2-77]). We also observed significantly increased left ventricular (LV) diameter (5.1 ± 0.8 cm vs. 4.6 ± 0.7 cm, p = 0.001) and decreased LV ejection fraction (Figure) by echocardiography (available in 50% of FLNC LOF individuals), and a trend toward higher prevalence of inverted T waves in any precordial lead beyond V2 (23% vs. 7%, p = 0.06). Conclusion: Loss-of-function variants in FLNC are extremely rare in a general clinical population but are associated with a clinically significant and potentially actionable, yet incompletely penetrant, cardiac phenotype marked by ventricular dysfunction and dysrhythmia. Consideration for screening and return of secondary findings may be warranted.

Abstract 15180: Myeloid Differentiation Factor 2 Inhibitor Improves Left Ventricular Function And Heart Rate Variability Via Attenuating Cardiac Mitochondrial Dysfunction In Pre-diabetic Rats

Introduction: Systemic inflammation is known as a key mediator of left ventricular (LV) dysfunction in pre-diabetic models including obese-insulin resistance. In obese rats, lipopolysaccharide activates myeloid differentiation factor 2 (MD2)/toll-like receptor 4 complex, leading to systemic inflammation. Previously, MD2 inhibitor L6H21 (20 mg/kg) was shown to effectively reduce systemic inflammation in obese mice. However, its potential benefits on the heart and the underlying mechanisms in pre-diabetic obese-insulin resistant rats are unknown. Hypothesis: L6H21 exerts cardiometabolic protection in pre-diabetic rats by improving LV function and heart rate variability (HRV) via reducing cardiac mitochondrial dysfunction. Methods: Male Wistar rats were fed either a normal diet (n=8) or high-fat diet (HFD, n=40) for 12 weeks. In HFD group, rats were divided into 5 groups (n=8/group): 1) vehicle (1% Na-carboxymethyl cellulose), 2) metformin (300 mg/kg, positive control), 3-5) L6H21 at 10, 20, and 40 mg/kg. After 4 weeks of treatments, LV function and HRV were examined. Heart tissue was assessed for mitochondrial function. Results: Pre-diabetic rats had impaired glucose tolerance, depressed HRV, and decreased LV ejection fraction (LVEF), indicating cardiac autonomic imbalance and LV dysfunction. Cardiac mitochondrial dysfunction was also observed, shown by increased mitochondrial ROS levels, mitochondrial depolarization, and mitochondrial swelling. Although L6H21 at 20 and 40 mg/kg improved insulin sensitivity, cardiac autonomic balance, LV function, and mitochondrial function, L6H21 at 40 mg/kg exerted the highest cardioprotective effects, compared to metformin, in pre-diabetic rats by restoring LV function, HRV, and cardiac mitochondrial function (Fig) . Conclusions: L6H21 exerted cardiometabolic protection in pre-diabetic rats by improving insulin sensitivity and cardiac mitochondrial function, leading to restoring LV function.