Basis Of Left Ventricular Ejection Fraction Research Articles

Clinical and echocardiographic impact of physiological estimulation in patients with preserved ejection fraction: a randomized clinical trial

Abstract Introduction Right ventricular stimulation in the apex (RVAS) produce dysynchrony, leading to left ventricle systolic dysfunction (LVSD) in some cases. Circumstances that can worsen the LVSD are a high burden of RVAS, and the presence of previous LVSD and/or intraventricular conduction disease (IVCD). Direct activation of the specialized conduction system with physiological stimulation (PS) can preserve this physiological pattern and shorten de QRS when the impairment is proximal to the pacing site. Most of the studies with PS has been focused on patients with LVSD, with few and scarce evidences regarding pacients without LVSD. Objectives and methods: This is a parallel, single blinded, unicentric, randomized trial of patients with preserved of mild reduced left ventricular ejection fraction (LVEF) submitted to a pacemaker implantation due to atrioventricular block (AVB), with previous IVCD (wide QRS) an anticipated high rate of ventricular pacing. Patients were randomized 1:1 to RVAS vs PS and followed for 6 months. Clinical, ECG, echocardiography and analytic parameters were compared. The primary endpoint was the change in the LVEF at 6 months in each group. The secondary endpoints were the changes in the left ventricular end-diastolic diameter (LVEDD), the QRS duration, the pro–B-type natriuretic peptide (NT-proBNP), the NYHA class, and the Minnesota Living with Heart Failure Questionnaire (MLWHFQ) in each group. Results The study included 57 patients of 77±9,6 years. Of all patients, 53% were treated with RVAS and 47% with PS. There were 2 patients with crossover to RVAS for technical difficulties and 1 patient with crossover to PS due to apical scar. There were no differences in the basal QRS duration (142.08±20,2 ms), LVEF (58.87±7,2%), NT-proBNP (3336,03±7258,68 pg/ml), or MLWHFQ (22,19±14,68), between both groups (Table 1). Acutely significant differences were observed in the change of QRS duration among groups (+16±29 ms in the RVAS group vs -17±25 ms in the PS group, p<0,001). At 6 months follow-up LVEF showed a non-significant reduction of 0.8±1.1% in the PS group compared to a significant reduction of 5.1±1.7% in the RVAS group (difference 4,26% IC 0,1-8,43 p=0,022). No differences were observed regarding the values of the NT-ProBNP and the MLWHFQ between groups at 6 months (Table 2). Conclusions In patients with preserved LVEF requiring pacemaker implantation for AVB, PS shorten the QTS duration and preserves the LVEF compared to RVAS.Basal characteristics of groupsDifferences in outcomes between groups

Physiological stimulation in preserved ejection fraction: A randomized trial

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Right ventricular stimulation in the apex (RVAS) produce dysynchrony, leading to left ventricle systolic dysfunction (LVSD) in some cases. Circumstances that can worsen the LVSD are a high burden of RVAS, and the presence of previous LVSD and/or intraventricular conduction disease (IVCD). Direct activation of the specialized conduction system with physiological stimulation (PS) can preserve this physiological pattern and shorten de QRS when the impairment is proximal to the pacing site. Most of the studies with PS has been focused on patients with LVSD, with few and scarce evidences regarding pacients without LVSD. Objectives and methods This is a parallel, single blinded, unicentric, randomized trial of patients with preserved of mild reduced left ventricular ejection fraction (LVEF) submitted to a pacemaker implantation due to atrioventricular block (AVB), with previous IVCD (wide QRS) an anticipated high rate of ventricular pacing. Patients were randomized 1:1 to RVAS vs PS and followed for 6 months. Clinical, ECG, echocardiography and analytic parameters were compared. The primary endpoint was the change in the LVEF at 6 months in each group. The secondary endpoints were the changes in the left ventricular end-diastolic diameter (LVEDD), the QRS duration, the pro–B-type natriuretic peptide (NT-proBNP), the NYHA class, and the Minnesota Living with Heart Failure Questionnaire (MLWHFQ) in each group. Results The study included 57 patients of 77±9,6 years. Of all patients, 53% were treated with RVAS and 47% with PS. There were 2 patients with crossover to RVAS for technical difficulties and 1 patient with crossover to PS due to apical scar. There were no differences in the basal QRS duration (142.08±20,2 ms), LVEF (58.87±7,2%), NT-proBNP (3336,03±7258,68 pg/ml), or MLWHFQ (22,19±14,68), between both groups (Table 1). Acutely significant differences were observed in the change of QRS duration among groups (+16±29 ms in the RVAS group vs -17±25 ms in the PS group, p<0,001). At 6 months follow-up LVEF showed a non-significant reduction of 0.8±1.1% in the PS group compared to a significant reduction of 5.1±1.7% in the RVAS group (difference 4,26% IC 0,1-8,43 p=0,022). No differences were observed regarding the values of the NT-ProBNP and the MLWHFQ between groups at 6 months (Table 2). Conclusions In patients with preserved LVEF requiring pacemaker implantation for AVB, PS shorten the QTS duration and preserves the LVEF compared to RVAS.

Incremental value of mineralocorticoid receptor antagonists in patients with heart failure with reduced ejection fraction treated with sacubitril/valsartan

AimsWe investigated the incremental advantage in terms of N-terminal pro-B-type natriuretic peptide (NT-proBNP) reduction in patients affected by heart failure with reduced ejection fraction (HFrEF) treated with sacubitril/valsartan (S/V) and...

Left bundle branch pacing after transcatheter aortic valve implantation. Initial experience of a center

Abstract Introduction Permanent pacing is often needed in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) due to new onset conduction disorders. Nevertheless, continuous right ventricular pacing may deteriorate left ventricular ejection fraction (LVEF) and lead to poor outcomes. Thus, in last years, more physiological forms of pacing, such as left bundle branch pacing (LBBP) have been developed to prevent pacing induced cardiomyopathy. Purpose The aim of our study is to describe the initial experience in our center, evaluate the safety and feasibility of LBBP after TAVI and describe electrophysiological outcomes in the first months of follow-up. Methods We designed a prospective registry that collected all patients from the TAVI program of our center who developed conduction abnormalities in the immediate postoperative and received LBBP. We analyzed baseline characteristics, complications and procedure time, electrophysiological parameters after the procedure and final QRS interval. During follow-up LVEF, electrophysiological parameters and adverse clinical events (readmissions for heart failure, cardiovascular mortality and all-cause of mortality) were also evaluated at 3rd, 6th and 12th month. Results Between January 2020 and January 2022, twenty patients who developed conduction abnormalities after TAVI underwent LBBP. Seven patients (35%) had a complete atrioventricular block, two patients (10%) alternating bundle branch block and 11 (55%) had a new left bundle branch block. HV electrophysiology study was performed in 8 patients, with a median value of 68ms (66–72). Of the 20 patients, 3 out of 4 patients were male and had history of hypertension. 40% had previous ischemic heart disease and one patient had transthyretin cardiac amyloidosis. Median age was 79 years-old (76–83.5). Balloon-expandable prosthesis was implanted in 11 patients while 9 received a self-expandable prosthesis. Median basal LVEF was 59% (41.5–60) and median NTproBNP was 1722pg/ml (535–5848). LBBP was successful in all of the 20 patients. The median time of the procedure was 60 minutes (45–80) without suffering any complications. The median QRS interval before the procedure was 155ms (140–158) and 116ms (105–125) post-implant. To date, two patients have died of non-cardiac cause 3 and 8 months after LBBP. There have been no readmissions for heart failure. LVEF (pre and post-LBBP) and electrophysiological parameters post-implant and three-month follow-up are shown in Table 1. Conclusions In our experience, LBBP after TAVI is a safe and feasible procedure. Despite the small sample size and short follow-up period, our first results indicate stability of LVEF and pacemaker parameters. Funding Acknowledgement Type of funding sources: None.

Cardiac resynchronization therapy in non-ischemic cardiomyopathy: a comparative non-randomized study of His bundle pacing versus biventricular pacing

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiac resynchronization therapy (CRT) via permanent His bundle pacing (pHBP) has gained acceptance globally, but robust studies comparing pHBP-CRT with classic CRT are lacking. Purpose To compare the improvement in left ventricular ejection fraction (LVEF) after pHBP-CRT vs classic CRT. Methods Single-center study comparing a prospective series of pHBP-CRT with a historical series of CRT via classic biventricular pacing (BVP). Patients with non-ischemic cardiomyopathy, baseline LVEF <35%, left bundle branch block (LBBB), and CRT indications were selected. Results Fifty-one patients underwent classic CRT and 52 patients underwent pHBP-CRT (26.9% selective vs 73.1% non-selective HBP with LBBB correction). In 2 patients, pHBP was not possible: one of them cause of high thresholds and the other because QRS correction was lacking. The baseline characteristics are shown in Table 1. In the classic CRT group, 74.5% of patients were in sinus rhythm (SR) and 25.5% in atrial fibrillation (AF). In the pHBP group, 88.5% were in SR and 11.5% in AF (p=0.07). The median VP was 98.5% (94.3–100%) in the former group and 99% (98–100%) in the latter (p=0.484). Regarding LVEF, the primary objective of this study, in the classic CRT group, the median basal LVEF was 30% (29–35%) before implantation and 40% (35–48%) at follow-up. In the pHBP-CRT group, the median basal LVEF was 30% (28–34%) before implantation and 55% (45–60%) at follow-up (p=0.001). In the classic CRT group, the absolute increase in LVEF was >20%, 10–20%, and 5–10% in 19.6%, 31.4%, and 15.7% of patients, respectively. In the pHBP-CRT group, the absolute increase in LVEF was >20%, 10–20%, and 5–10% in 55.8%, 32.7%, and 7.7% of patients, respectively, (p=0.001). The characteristics of the basal and paced QRS, as well as the His thresholds, are shown in Table 2. Considering the secondary objective of our study, the median long-term (after a year) His recruitment threshold with LBBB correction was 1.25 (1–2.5) V at 0.4 ms in cases where pHBP-CRT was performed, compared to an LV coronary sinus threshold of 1.25 (1–1.75) V at 0.4 ms in cases where classic CRT was performed; there was no significant difference between the two groups (p=0.48). The basal QRS duration was similar in both groups; after CRT, the median paced QRS duration was 135 (120–145) ms for pHBP-CRT and 140 (130–150) ms for BVP-CRT (p=0.586). Considering the concept of effective QRS in patients who underwent pHBP CRT, the median paced QRS was 110 (110–120) ms (p=0.001) compared to the classic CRT. Conclusions The improvement in LVEF was superior in patients who underwent pHBP-CRT than in those that received classic CRT. The threshold levels after 1 year of follow-up period were similar for LBBB correction with pHBP or conventional BVP. Randomized prospective studies with larger populations and longer follow-up periods are needed to verify our results.

Cardiac resynchronization therapy in non-ischemic cardiomyopathy: a comparative non-randomized study of His Bundle pacing versus biventricular pacing.

Cardiac resynchronization therapy (CRT) via permanent His bundle pacing (pHBP) has gained acceptance globally, but robust studies comparing pHBP-CRT with classic CRT are lacking. In this study, we aimed to compare the improvement in left ventricular ejection fraction (LVEF) after pHBP-CRT versus classic CRT. This was a single-center study comparing a prospective series of pHBP-CRT with a historical series of CRT via classic biventricular pacing (BVP). Patients with non-ischemic cardiomyopathy, baseline LVEF < 35%, left bundle branch block (LBBB), and CRT indications were selected. Fifty-one patients underwent classic CRT and 52 patients underwent pHBP-CRT. In the classic CRT group, the median (interquartile range) basal LVEF was 30% (IQR, 29-35%) before implantation and 40% (35-48%) at follow-up. In the pHBP-CRT group, the median basal LVEF was 30% (28-34%) before implantation and 55% (45-60%) at follow-up, with significant differences between both modalities at follow-up (p = 0.001). The median long term His recruitment threshold with LBBB correction was 1.25 (1-2.5) V at 0.4ms in cases of pHBP-CRT, compared to a left ventricular coronary sinus threshold of 1.25 (1-1.75) V in cases of classic CRT (p = 0.48). After CRT, the median paced QRS was 135 (120-145) ms for pHBP-CRT versus 140 (130-150) ms for BVP-CRT (p = 0.586). The improvement in LVEF was superior with pHBP-CRT than with classic CRT. The thresholds at follow-up were similar in both groups.

Effects of acute ischemia and hypoxia in young and adult calsequestrin (CSQ2) knock-out and wild-type mice

Calsequestrin (CSQ2) is the main Ca2+-binding protein in the sarcoplasmic reticulum of the mammalian heart. In order to understand the function of calsequestrin better, we compared two age groups (young: 4–5 months of age versus adult: 18 months of age) of CSQ2 knock-out mice (CSQ2(−/−)) and littermate wild-type mice (CSQ2(+/+)). Using echocardiography, in adult mice, the basal left ventricular ejection fraction and the spontaneous beating rate were lower in CSQ2(−/−) compared to CSQ2(+/+). The increase in ejection fraction by β-adrenergic stimulation (intraperitoneal injection of isoproterenol) was lower in adult CSQ2(−/−) versus adult CSQ2(+/+). After hypoxia in vitro (isolated atrial preparations) by gassing the organ bath buffer with 95% N2, force of contraction in electrically driven left atria increased to lower values in young CSQ2(−/−) than in young CSQ2(+/+). In addition, after global ischemia and reperfusion (buffer-perfused hearts according to Langendorff; 20-min ischemia and 15-min reperfusion), the rate of tension development was higher in young CSQ2(−/−) compared to young CSQ2(+/+). Finally, we evaluated signs of inflammation (immune cells, autoantibodies, and fibrosis). However, whereas no immunological alterations were found between all investigated groups, pronounced fibrosis was found in the ventricles of adult CSQ2(−/−) compared to all other groups. We suggest that in young mice, CSQ2 is important for cardiac performance especially in isolated cardiac preparations under conditions of impaired oxygen supply, but with differences between atrium and ventricle. Lack of CSQ2 leads age dependently to fibrosis and depressed cardiac performance in echocardiographic studies.

Correlation of Cardiac Troponin I with Left Ventricular Systolic Function in Patients with Acute ST-segment Elevated Myocardial Infarction

Myocardial infarction is one of the leading cause of death globally and following acute myocardial infarction prognosis depends on extent of myocardial damage. This study was aimed to correlate cardiac troponin I level with the left ventricular systolic function in patients with acute ST-elevated myocardial infarction. A total of 104 patients of acute ST-segment elevated myocardial infarction receiving streptokinase therapy within 12 hours of onset of chest pain were studied. Cardiac troponin I concentration was measured by immunometric assay and echocardiographic left ventricular ejection fraction was calculated by modified biplane Simpson's method. Left ventricular ejection fraction (LVEF) was compared with serum cardiac troponin I concentration. Study subjects were divided into two groups on the basis of LVEF. In group I, there were 54 patients with LVEF &lt; 50% and in group II, there were 50 patients with LVEF &gt;_ 50%. The mean cTnI within 12 hours of onset was 129 ± 8.7 ng/ml in group I and11 ± 2.1 ng/ml group II and the difference was statistically significant (p&lt;0.001). Serum cardiac troponin I concentration has a strong negative correlation with left ventricular ejection fraction after first acute myocardial infarction. A level of serum cardiac troponin I &gt;_ 6.6 ng/ml provided a good indication for LVEF &lt;50% and this can be used to detect patients with higher risk. Faridpur Med. Coll. J. 2021;16(1):34-38

Left Ventricular Systolic Function in Patients with Systemic Lupus Erythematosus and Its Association with Cardiovascular Events

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with potential cardiovascular involvement. The aim of this study was to assess left ventricular (LV) systolic function in a large cohort of patients with SLE using standard echocardiographic measurements and global longitudinal strain (GLS) by two-dimensional speckle-tracking analysis. Furthermore, the association between echocardiographic parameters and the occurrence of cardiovascular events was assessed. A total of 102 patients with SLE (88% women; mean age, 43±14years) undergoing a dedicated multidisciplinary assessment were analyzed, including echocardiography, at the time of their first visit. A control group consisted of 50 age- and sex-matched healthy subjects. Compared with control subjects, patients with SLE showed impaired LV systolic function on the basis of LV ejection fraction (51±6% vs 62±6%, P<.001) and by LV GLS (-15±3% vs -19±2%, P<.001). During a median follow-up period of 2years (interquartile range, 1-6years), 38 patients (37%) developed cardiovascular events. Kaplan-Meier survival curves showed that patients with SLE with more impaired LV GLS (on the basis of the median value of -15%) experienced higher cumulative rates of cardiovascular events compared with those with less impaired LV GLS (χ2=8.292, log-rank P=.004). On multivariate Cox regression analysis, LV GLS demonstrated an independent association with cardiovascular events (hazard ratio, 2.171; 95% CI, 1.015-4.642; P=.046), whereas LV ejection fraction was not significantly associated with the outcome. In patients with SLE, LV systolic function as measured by LV GLS is significantly impaired and associated with cardiovascular events, potentially representing a new tool to improve risk stratification in these patients.

Long-Term Mortality Comparison of Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock and Treated With Culprit-Only or Multivessel Percutaneous Coronary Intervention

ObjectivesWe sought to determine whether, in a real word context of patients with Acute Myocardial Infarction (AMI), multivessel disease (MVD) and cardiogenic shock (CS), the successful treatment with primary percutaneous coronary intervention (p-PCI) of only culprit lesions (OC-PCI) is associated with better long-term mortality rates than multivessel PCI (MV-PCI) of all significant lesions. MethodsFrom our registry of all consecutive patients admitted for AMI between January 1995 and December 2016 we selected those presenting with CS and MVD successfully treated with p-PCI, and compared those who underwent OC-PCI against MV-PCI, either during the p-PCI (MV-pPCI) or by staged revascularization (Staged-PCI) during hospitalization. The primary endpoint was 2-year all-cause death. ResultsAmong 4210 patients with AMI, 406 (9.6%) presented CS (Killip class IV). A total of 292 patients had MVD. Of them, 252 (86.3%) were successfully treated with p-PCI, 159 patients with OC-PCI and 93 with MV-PCI, either in the same (n = 29) or staged procedure (n = 64). At 2-year follow-up the overall mortality was 47.6%, lower in MV-PCI group (37.6% vs 53.5% in OC-PCI, p = 0.019). Diabetes (HR = 1.50, 1.01–2.22), three vessel disease (HR = 1.49, 1.02–2.17) and basal left ventricular ejection fraction <15% (HR = 3.39, 2.41–6.27) were independent predictors of mortality, while MV-PCI was the only variable associated with improved survival (HR = 0.54, 0.36–0.81). ConclusionsIn this real world registry of AMI patients with MVD presenting CS, MV-PCI was associated with better long-term survival.

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.

Prevalence and Prognostic Impact of Septal Late Gadolinium Enhancement in Acute Myocarditis With or Without Preserved Left Ventricular Function

Recent data suggest that myocardial septal late gadolinium enhancement (LGE) may have an independent prognostic value in patients with acute myocarditis undergoing cardiac magnetic resonance (CMR). Aim of the present study is to evaluate its prevalence and prognostic implications in these patients with or without preserved LV function. Retrospective cohort study including all cases of clinically suspected acute myocarditis referred for CMR. A diagnosis of acute myocarditis was confirmed by CMR according to Lake Louise Criteria. Cardiovascular mortality, heart failure, heart transplantation, and sustained ventricular arrhythmias were considered adverse events at follow-up. Seventy-one patients were included in the present study (mean age 47 years 95% confidence intervals 42 to 51, 53 males; 75%). Left Ventricular Ejection Fraction (LVEF) was preserved in 45 cases (63%) and pericardial effusion was detected in 26 cases (38%). CMR was performed at a mean time of 11 days (95% confidence intervals 7.5 to 14.4) from symptoms onset. Myocardial hyperemia and edema were detected in 53 cases (75%), myocardial LGE in 66 cases (93%). Septal LGE was reported in 21 cases (30%). After a mean follow-up of 60.8 months, the mean LVEF increased from 51.6 ± 14.0% to 56.6 ± 10.9% (p = 0.021) and combined adverse events were only recorded in 4 patients (6%) with reduced basal LVEF. These patients had more commonly septal LGE (respectively 58% vs13%, p <0.0001). However, on multivariable analysis septal LGE had no additional predictive value over reduced basal LVEF. In conclusion, our study suggests that septal LGE is not uncommon in patients with acute myocarditis but has no added prognostic value over reduced LVEF at presentation.

Abstract P3-14-07: Early detection of chemotherapy-induced cardiotoxicity in breast cancer patients

Abstract BACKGROUND The incidence of cardiotoxicity in patients receiving treatment for breast cancer is unknown. There is not enough evidence about early detection and appropriate management of cardiotoxicity. The aim of this study is to identify early markers of risk of cardiac toxicity. MATERIAL AND METHOD Prospective study was conducted between 2014 and 2017 based on a cohort of 97 patients diagnosed with breast cancer treated with chemotherapy. Analytical biomarkers (natriuretic peptide, ultra-sensitive T troponin), echocardiogram parameters (left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS)) and electrocardiogram were performed. Analytical biomarkers were measured each chemotherapy cycle and cardiology test were performed before starting chemotherapy, 3 months afterwards, and then every six months during 5 years. Cardiotoxicity was defined as a reduction in basal LVEF &amp;gt;10% with LVEF&amp;lt;55% in asymptomatic patients or &amp;gt;5% with LVEF&amp;lt;55% in symptomatic patients. RESULTS Patients characteristics are shown in table 1 Patients characteristicsVariablesNo cardiotoxicity (n=88)Cardiotoxicity (n=12)Gender (women/men)88/012/0Median age (range)53 years (29-79)47 years (37-70)Smoker (former smoker)13 (3)2 (2)Arterial hypertension202Dyslipemia160Diabetes62Previous chemotherapy11Prior mediastinal radiation therapy01 . All patients had the basal LVEF in normal range. Median follow-up was 26.5 months (13,5-39,6 months). A total of 10.3% had cardiotoxicity with reduction in basal LVEF &amp;gt;10% with LVEF&amp;lt;55% being asymptomatic and 2.1% were symptomatic. Five of these patients were treated with heart failure therapy: 5 with ACE (angiotensin converting enzyme) inhibitors and 3 with beta- blockers. Two of those (40%) who received specific treatment recovered basal LVEF-levels, 2 maintained LVEF dysfunction, and 1 died during follow-up due to tumor-related causes. In 83.3% of patients, cardiotoxicity occurred within the first year of follow-up. In 50 patients SLG was calculated, in 30% it was lower than -12% in some measurement phase. In 5 cases the LVEF fell below 55% and the LRP decreased by 12% coincided. The others patients, although they did not develop cardiotoxicity according to the established criteria, a decrease of the LVEF is observed during the treatment and in the first control, between 3-7%, which subsequently tends to recover spontaneously. miRNA 21-5p, miRNA-133b, miRNA 210-3p, miRNA 423-5p, and miRNA-663b were analyzed. A model has been evaluated where a correlation between the levels of miRNA-133b, miRNA-21-5p and miRNA-210-3p and the decrease of LVEF in relation to treatment was observed. CONCLUSIONS Control by echocardiography and serum markers allowed us to detect early cardiotoxicity events and provide us an opportunity to start heart failure therapy on time with the aim of improving the control and evolution of it.Levels of miR-133b, miR-21-5p and miR-210 may alert for a risk of cardiotoxicity and can help to make decisions about treatments. Acknowledgements: Project funded by European Comission (Hecatos FP7-HEALTH-2013-INNOVATION-1. Reference: CP-IP 602156-1) and RETICS program (RD12/0019/0025) cofunded by FEDER "una manera de hacer Europa”. Citation Format: Salvador-Coloma C, Hernándiz A, Tejedor S, Miró V, Palomar L, Salvador A, Sepúlveda P, Santaballa A. Early detection of chemotherapy-induced cardiotoxicity in breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-14-07.

Reliability of Left Ventricular Ejection Fraction from Three-Dimensional Echocardiography for Cardiotoxicity Onset Detection in Patients with Breast Cancer

Cardiotoxicity is a well-known adverse effect of various chemotherapeutic agents that can be monitored by echocardiography. A decrease in left ventricular ejection fraction (LVEF) triggers consideration for therapy modification or interruption. The aim of this study was to evaluate how variability in LVEF estimates computed using three-dimensional echocardiography could influence cardiotoxicity onset detection. One hundred eighty one patients with breast cancer treated with anthracycline and trastuzumab were analyzed. LVEF was computed using two commercial software packages. In a subgroup of 40 patients, three-dimensional echocardiographic data were reanalyzed to assess intra- and interobserver variability by two expert investigators using both packages. Global longitudinal strain (GLS) imaging was evaluated in 64 patients. End-diastolic volume, end-systolic volume, and LVEF measurements obtained applying the two software packages were in good agreement, with small bias and acceptable limits of agreement. Intra- and interobserver variability was smaller using one of the two software packages. However, for both packages, variability indexes were in the range of affecting LVEF estimates at a level that could lead to an inaccurate assessment of cardiac adverse effects of cancer therapeutic drugs. On the basis of LVEF, 11 of 181 patients (6.1%) had cardiotoxicity at 3-month follow-up. The absolute value of GLS was smaller in 16 of 64 patients (25%) thought to have cardiotoxicity on the basis of GLS results, including six of seven patients who had cardiotoxicity considering LVEF in this subgroup. Following clinical definition of cardiotoxicity onset, variability in LVEF computation by three-dimensional echocardiography could be a confounding factor for cardiotoxicity diagnosis, and different software packages should not be used interchangeably for LVEF monitoring. GLS confirms its predictive value for subsequent cardiotoxicity.

Early Detection of Chemotherapy- Induced Cardiotoxicity in Hematological Patients: A Prospective Study

Introduction: Chemotherapy-induced cardiotoxicity is an important concern in the long-term survivors era, especially in those younger patients who may suffer excess cardiovascular morbidity and worse outcomes. There is no consensus on monitoring criteria for this phenomenon and prompt therapy has not been yet properly established. We aim to evaluate prospectively early detection of cardiotoxicity, incidence, timing of occurrence and pre-existing factors during two years.Methods: This prospective study is being conducted at La Paz University Hospital in the period 2012-2013 (n=80) (age 18-84) based on anthracycline chemotherapy. A second phase of the study is ongoing, pending completion of the two year follow-up. Patients’ levels of analytical biomarkers cardiac troponin (cTnl) and B type natriuretic peptid (NT pro BNP), echocardiogram parameters left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were measured before starting chemotherapy, 3 weeks and 3 months afterwards, and then every six months during 2 years. In the first visit different clinical variables were also measured, including age, sex, body mass index, cardiovascular risk factors and previous treatments with chemotherapy and radiotherapy. Cardiotoxicity was defined as a reduction in LVEF <50% or >10% with basal >50%. Another cardiotoxicity conditions such as ischemic cardiomyopathy, arrhythmia, pericarditis and valvular heart disease were also considered. The cumulative dose of chemotherapy was measured in every visit.Results: Eighty patients were included; 49% women; 53.75% non-Hodgkin lymphoma, 22.5% Hodgkin lymphoma and 23.75% acute myeloid leukemia. Fifteen patients died (18.75%), 100% due to tumour related causes. Nine patients did not attend follow-up (11.25%). A total of 14 cardiotoxicity events occurred (17.5%): the most frequent event was reduction in LVEF (78,5%). Ischemic events and valvular disease were also observed. No hospitalization was needed in any of the events. Two of them recovered LVEF-levels spontaneously in the next visit. The other 9 were treated with heart failure therapy: 8 with ACE (angiotensin converting enzyme) inhibitors and beta- blockers and 1 with ACE inhibitors. Six (66.6%) of those who received specific treatment recovered basal LVEF-levels, 2 maintained LVEF dysfunction, and 1 died during follow-up due to tumour-related causes. In 85.7% of patients, cardiotoxicity occurred within the first year of follow-up. Basal LVEF and previous treatment with chemotherapy were significant predictors of subsequent cardiotoxicity (Cox regression model).Conclusions: early detection of cardiotoxic events provides an opportunity to start heart failure therapy on time to prevent progression to established heart failure. Previous chemotherapy treatment points to an increased risk of cardiotoxicity, so more intensive surveillance is necessary. Extended analysis of patients being included in the ongoing study will extend the information about cumulative anthracycline dose and cardiotoxicity induced by non-anthracycline chemotherapy. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

96-35: Long term follow-up of the hisian pacing: a single centre experience

Introduction: Long-term His bundle pacing aims at preventing the detrimental hemodynamic consequences of right ventricular (RV) apical stimulation but long-term results are limited. Methods: We analyzed 322 patients (age 75 ± 8 years; 60% males; 48% IIor III degrees AV block, 25% sinus node disease, 27% atrialfibrillation with slow ventricular rate) who received an Hisian (57.4%) or paraHisian lead (3830 Medtronic) from April 2004 to July2011. The mean basal left ventricular ejection fraction (LVEF) was 54 ± 12%. The Hisian lead was connected to the ventricular port of aCRT-P device in 149 (46.2%) patients, to the atrial or ventricular ports of a DR PM in 157 (48.7%) patients, or to the single entry of an SR device in 16 (4.9%) patients. A back up lead was inserted in RV apex or septum in 194 (60.2%) patients. Results: The mean length of follow up was 6.70 ± 2.34 years (median 6.90years). Mean LVEF at follow-up was 55.5 ± 12.3%. At the last ambulatory interrogation 237 (73.9%) patients showed ventricular pacing ≥90%. The mean longevity of the first implanted devices was 5.32 ± 2.02 (median5.03) years. 184 (57.1%) patients had at least one device replacement, for end-of-life behaviour in 92.3% patients. It was necessary to add an RV lead or to turn off the Hisian lead in 8.6 % patients, due to high threshold or lead failure. In 2 patients the back-up RV lead was switched off due to malfunction. During the follow up 75 (23.2%) patients died, no death was pacemaker related.

Long-term effects of pegvisomant on comorbidities in patients with acromegaly: a retrospective single-center study.

ContextThe effect of pegvisomant on IGF1 levels in patients with acromegaly is well documented, but little is known of its long-term impact on comorbidity.AimThe aim of this retrospective study was to evaluate the effects of long-term pegvisomant therapy on cardiorespiratory and metabolic comorbidity in patients with acromegaly.Patients and methodsWe analyzed the long-term (up to 10 years) effect of pegvisomant therapy given alone (n=19, 45%) or in addition to somatostatin analogues and/or cabergoline (n=23, 55%) on echocardiographic, polysomnographic and metabolic parameters in respectively 42, 12 and 26 patients with acromegaly followed in Bicêtre hospital.ResultsAt the first cardiac evaluation, 20±16 months after pegvisomant introduction, IGF1 levels normalized in 29 (69%) of the 42 patients. The left ventricular ejection fraction (LVEF) improved significantly in patients whose basal LVEF was ≤60% and decreased in those whose LVEF was >70%. The left ventricular mass index (LVMi) decreased from 123±25 to 101±21 g/m2 (P<0.05) in the 17 patients with a basal LVMi higher than the median (91 g/m2), while it remained stable in the other patients. Pegvisomant reduced the apnoea–hypopnea index and cured obstructive sleep apnea (OSA) in four of the eight patients concerned. Long-term follow-up of 22 patients showed continuing improvements in cardiac parameters. The BMI and LDL cholesterol level increased minimally during pegvisomant therapy, and other lipid parameters were not modified.ConclusionsLong-term pegvisomant therapy not only normalizes IGF1 in a large proportion of patients but also improves cardiac and respiratory comorbidity.

Predictors and Outcome of Sustained Improvement in Left Ventricular Function in Dilated Cardiomyopathy

Improvement in the left ventricular ejection fraction (LVEF) may occur in patients with dilated cardiomyopathy (DCM). There are different implications of persistent versus transient improvement in LVEF among DCM patients receiving contemporary therapy. We studied 188 patients with nonischemic DCM. Persistent improvement in LVEF (PIEF) was defined as LVEF increase by at least 10% compared to baseline, and found in 2 separate echo-Doppler exams performed at least 12 months apart. Increased LVEF in echo 2, which was not sustained in echo 3, was defined as transient improvement in LVEF (TIEF). Over an average follow-up of 6.8 years, PIEF occurred in 61 (33%) patients, predicting a better long-term outcome (P < 0.001) in a combined end-point comprising death, heart transplantation, or the need for a ventricular assist device. The TIEF group had an intermediate course and were closer to nonimprovers (P = 0.003 vs PIEF). Multivariate logistic regression identified the following independent predictors of PIEF: shorter disease duration, pregnancy-associated disease, left ventricular hypertrophy, and baseline LVEF ≤ 25%. A score to predict PIEF assigned 1 point to each of the following: disease duration < 3 years and no familial cardiomyopathy; pregnancy-associated presentation; basal LVEF ≤ 25%; and left ventricular wall thickness ≥ 12. A score of ≥ 3 was present in 44% of the patients, reliably predicting PIEF in 91% (P = 0.01). Persistent improvement in LVEF is associated with improved long-term prognosis. Baseline clinical parameters can be used to identify patients likely to demonstrate PIEF, thereby allowing tailored management in this population.

303P - Cardiac Safety Assessment of Adjuvant Nonpegylated Liposomal Doxorubicin (Npld) Plus Cyclophosphamide (C) Followed By Paclitaxel (P) in Elderly Breast Cancer (Ebc) Women

ABSTRACT Background: doxorubicin is effective in early breast cancer but concerns about higher incidence of cardiac toxicity in older patients (pts) (Swain SM, Cancer 2003) have contributed to limit its use in this setting. NPLD is active in advanced disease and has much less cardiotoxicity than doxorubicin. Methods: In order to explore the feasibility of adjuvant NPLD in terms of cardiac safety, we are conducting a phase II pilot study in high risk EBC pts older than 65 years with NPLD 60mg/sqm day 1 plus C 600mg/sqm day 1 q 21 for 3 cycles followed by P 80 mg/sqm weekly for 9 weeks. Hormonal therapy and radiotherapy post chemotherapy when indicated. Cardiac safety is evaluated by comparison between the basal left ventricular ejection fraction (LVEF) assessed with echocardiogram (ECHO) and LVEF at the end of NPLD + C, after P and every 6 months for 2 years. Cardiac events are defined as appearance of congestive heart failure and/or grade 3-4 LVEF decline, asymptomatic LVEF decline below 50% or an absolute drop > 15%. Results: Up to today 47 pts have been enrolled with a median follow up of 11.0+ months (range 2.3+ - 28.0 +) Main pts characteristics are: median age = 73 (range, 67-83), ECOG-PS 0/1 = 38/9, basal LVEF >50% in all pts and no relevant cardiac co-morbidities. Basal median LVEF is 60% (range, 55%-76%). 141 cycles of NPLD + C have been administered. After NPLD + C the median LVEF is unchanged with a value of 60% (range, 56%-74%), as well as median LVEF after weekly P, with a value of 60% (range, 50%-72%). 18 pts were evaluable for LVEF at 6 months after the end of chemotherapy: median LVEF is unchanged with a value of 60% (range, 50%-69%). No pts had cardiac events as above defined. One patient discontinued NPLD + C after the first cycle for an episode of asymptomatic arrhythmia and one patient had a 10% drop of LVEF above 50%. Toxicities ≥3 were not observed. Conclusions: These preliminary data suggest the feasibility of adjuvant NPLD + C followed by P in EBC pts older than 65 years of age. Disclosure: All authors have declared no conflicts of interest.

Terapia com inibidor da ECA com dosagens relativamente altas e risco de agravamento renal na insuficiência cardíaca crônica

Renoprotective effect of ACE-inhibitors has been questioned in case of decreased effective circulating volume, like in right or biventricular chronic heart failure. To detect clinical predictors of renal worsening in CHF patient population characterized by two types of ACE-inhibitor dosing regimens. According to a retrospective cohort design, we followed 2 groups of patients with CHF - whether right or biventricular -, all in III NYHA class treated with ACE-inhibitors (enalapril or lisinopril), and with left ventricular ejection fraction (LVEF) < 50%, by distinguishing them by ACE-inhibitor dosing: average-low (<10 mg per day) or "high" dose (>10 mg per day) of enalapril or lisinopril. Worsened renal failure (ARD) was defined by Cr increase >30% from baseline. Cox proportional hazards model was used to identify the predictors of ARD among the following variables: ACE-inhibitors "high" dose, age, basal LVEF, history of repeated intensive intravenous loop diuretic therapies (IV diur), diabetes, basal Cr, history of hypertension, systolic blood pressure < 100 mm Hg. 57 patients were recruited, of whom 15 were treated with ACE-inhibitor "high" dose. During a mean follow-up of 718 days, ARD occurred in 17 (29.8%) patients. Only ACE-inhibitor "high" dose (HR: 12.4681 C.I.: 2.1614-71.9239 p=0.0050) and basal Cr (HR: 1.2344 C.I.: 1.0414-1.4632 p=0.0157) were shown to predict ARD. Moreover, ACE-inhibitor "high" doses were shown to fail to predict ARD in both CHF without IV diur and CHF with diabetes. In III NYHA class CHF, ACE-inhibitor "high" doses and a higher basal Cr predicted ARD. Nephrotoxicity related to ACE-inhibitor "high" doses was increased by IV diur, whereas it was not detected in CHF patients with diabetes.