Fall In Left Ventricular Ejection Fraction Research Articles

Sex-based differences on adverse left ventricular remodeling and clinical outcomes after an ST-segment elevation myocardial infarction in the PCI era

Abstract Background There is conflicting evidence regarding sex-based differences in myocardial salvage and clinical outcome in patients after an ST-segment elevation myocardial infarction (STEMI) in the contemporary era of primary percutaneous coronary intervention (PCI) and optimal medical treatment. Adverse left ventricular remodelling (LVR) after a STEMI worsens outcomes, however, the influence of sex is not yet clear. Aim/Purpose To analyze whether there are sex differences in clinical outcomes and adverse LVR in patients after a STEMI. Methods Patients with STEMI who underwent primary PCI were included and a cardiac magnetic resonance (CMR) was performed during hospitalization (6.2±2.6 days) and after 6 months (6.1±1.8 months). LVR, myocardial salvage (MS), infarct size (IS), microvascular obstruction (MVO), and area at risk (AAR) were quantified. Adverse LVR was defined as a 15% increase in LV end-diastolic volume and a relative fall in LV ejection fraction of 3% at 6 months. The primary outcome was a composite of cardiovascular death, admission for heart failure, or ventricular arrhythmia. Results A total of 1046 patients were included (mean age: 59.8±9 years; 16.6% women), and a second CMR was completed in 589 patients. Women were older (58.8±8 years vs 65.0±10 years, p<0.0001) and presented more cardiovascular risk factors (Table). The primary outcome occurred in 310 patients during follow-up of 75 months (range: 36–112 months) and was more frequent in women than in men (35.8% vs 22.3%, p<0.001). After adjusting for baseline differences (age, diabetes, hypertension, Killip class, and time to reperfusion), female sex was not an independent predictor of major adverse cardiac events (Fig. 1A & B). Although adverse LVR was a strong independent predictor for the primary outcome, no interaction was present between sex and LVR (women 6.4% vs men 8%, p=0.46) (Fig 1B), nor did we find significant differences between sex and other CMR derived variables such as MS, IS, MVO and AAR. Conclusions After a STEMI, women present worse clinical outcomes than men. However, these differences are related to their clinical characteristics and higher incidence of cardiovascular risk factors, and not to a higher incidence of adverse left ventricular remodeling. Funding Acknowledgement Type of funding sources: None.

Myocardial Strain Imaging Using Feature Tracking Method of Cardiac MRI: Our Initial Experience of This Novel Parameter as an Additional Diagnostic Tool.

Background Left ventricular ejection fraction (LVEF) is used as quantitative parameter to evaluate myocardial function. However, interobserver variation, limited reproducibility, and dependence on pre-load and after-load reduces its accuracy. The fall in LVEF occurs very late, when myocardial dysfunction is already advanced. Myocardial strain measurements (especially global longitudinal strain) is a new parameter to detect myocardial dysfunction before derangements in LVEF. The aim of this article is to share our experience of this novel diagnostic tool. Methods Feature tracking method of strain assessment is performed using routine long and short axis cine images of cardiac MRI (CMR). Dedicated post-processing CMR software can perform off-line analysis and provide results in form of color-coded maps, percentage values as well as strain over time curve for each myocardial segments. Results Global longitudinal strain (GLS) is more sensitive than LVEF and can identify sub-clinical left ventricular (LV) dysfunction in various cardiomyopathies. It is also an important prognostic marker in serial assessment of heart failure patients. Regional differences in strain parameters can provide clues in hypertrophic cardiomyopathy as well as amyloidosis. GLS is recommended as routine measurement in patients undergoing chemotherapy to detect LV dysfunction prior to fall in LVEF. Strain imaging can be applied to guide placement of the LV pacing lead in patients receiving cardiac resynchronization therapy. More clinical data is needed to evaluate its role in ischemic heart disease. Conclusion Strain imaging can identify LV dysfunction earlier than conventional methods and this opens a new perspective in risk stratification and therapeutic decision-making of various cardiac pathologies.

Guidelines for the monitoring and management of iron overload in patients with haemoglobinopathies and rare anaemias.

Guidelines for the monitoring and management of iron overload in patients with haemoglobinopathies and rare anaemias.

How variable are the volumetric measurements from gated perfusion SPECT when a one-day stress-rest protocol is used?

BackgroundUsing myocardial perfusion scintigraphy (MPS), an increase in left ventricular (LV) volumes or a decrease in ejection fraction (EF) from rest to stress may be clinically important. The variation in these measures between the low-dose stress acquisition and high-dose rest acquisition in a one-day stress-rest protocol has not been established. We assessed the reproducibility of gated volumetric indices between stress and rest and the normal variation in ungated TID ratio for a one-day stress-rest 99mTc-tetrofosmin protocol. MethodsTwo thousand and one hundred and fifty eight (2158) 99mTc-tetrofosmin MPS patient studies were analyzed retrospectively. Studies were excluded for incomplete data, significant technical difficulties, or (for gated analysis but not for analysis of TID ratio) if the LV EF was > 75%. An analysis of gated data was undertaken to establish the reproducibility of ventricular volumes and EF between stress and rest scans. Ungated volume data were analyzed to determine the confidence limits of TID ratio according to ventricular volume. ResultsGated data were analyzed for 621 patients without inducible hypoperfusion. Mean EF at rest was slightly higher than after stress (62.4% ± 10.3% vs 61.2% ± 10.4%, P < 0.001), and the standard deviation of the difference was 5.2% (95% CI 4.9% to 5.5%). Ungated volumes were available for 992 non-ischaemic patients. The upper 95% CI for TID ratio was 1.23. This increased from 1.20 to 1.37 between the highest and lowest deciles of rest ungated volume. ConclusionUsing a one-day stress-rest 99mTc-tetrofosmin protocol, a fall in LV EF between rest and stress of > 11.6% or a TID ratio of > 1.23 is likely to be clinically reliable. The upper limit of normal for TID ratio needs to be increased for patients with small LV chamber volumes.

Prognostic Value of Initial Left Ventricular Remodeling in Patients With Reperfused STEMI

ObjectivesThis study sought to establish the best definition of left ventricular adverse remodeling (LVAR) to predict outcomes and determine whether its assessment adds prognostic information to that obtained by early cardiac magnetic resonance (CMR). BackgroundLVAR, usually defined as an increase in left ventricular end-diastolic volume (LVEDV) is the main cause of heart failure after an ST-segment elevated myocardial infarction; however, the role of assessment of LVAR in predicting cardiovascular events remains controversial. MethodsPatients with ST-segment elevated myocardial infarction who received percutaneous coronary intervention within 6 h of symptom onset were included (n = 498). CMR was performed during hospitalization (6.2 ± 2.6 days) and after 6 months (6.1 ± 1.8 months). The optimal threshold values of the LVEDV increase and the LV ejection fraction decrease associated with the primary endpoint were ascertained. Primary outcome was a composite of cardiovascular mortality, hospitalization for heart failure, or ventricular arrhythmia. ResultsThe study was completed by 374 patients. Forty-nine patients presented the primary endpoint during follow-up (72.9 ± 42.8 months). Values that maximized the ability to identify patients with and without outcomes were a relative rise in LVEDV of 15% (hazard ratio [HR]: 2.1; p = 0.007) and a relative fall in LV ejection fraction of 3% (HR: 2.5; p = 0.001). However, the predictive model (using C-statistic analysis) failed to demonstrate that direct observation of LVAR at 6 months adds information to data from early CMR in predicting outcomes (C-statistic: 0.723 vs. 0.795). ConclusionsThe definition of LVAR that best predicts adverse cardiovascular events should consider both the increase in LVEDV and the reduction in LV ejection fraction. However, assessment of LVAR does not improve information provided by the early CMR.

ST-Segment Elevation Myocardial Infaction Alert During the Night Shift, A Misfortune for the Patient or an Overstatement?

BackgroundConflicting data exist regarding the outcomes of primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) based on intervention timings. It is believed that short staffing at night hours may lead to a lapse in the delivery of effective, efficient and timely medical intervention.MethodsA retrospective single-center study was performed, and a total of 436 patients were randomized into two groups. Group A had 279 patients who had the heart catheterization done during the daytime (between 6 am and 6 pm), while group B had 157 patients who had the same intervention performed at night (between 6 pm and 6 am).ResultsDoor to balloon (DTB) time during the day was about 16 min shorter than the DTB time at night (81.29 ± 3.26 vs. 97.30 ± 8.54) with no statistical difference (P = 0.051). The mean troponin rise during the day was 1.94 ± 10.60 SEM (95% confidence interval (CI): -22.70 to 18.90) higher than night troponin levels (71.75 ± 7.18 vs. 69.80 ± 7.18), but P value was 0.85. The left ventricular ejection fraction (LVEF) fall for daytime was 0.93% vs. 0.90% for night time patients (P = 0.94).ConclusionThere is no significant difference in the mean DTB time, the rise in troponin, fall in LVEF, readmission rates, or mortality, and hence no negative effects on patient outcomes based on the patient’s time of presentation between the two groups.

Identification of a Novel microRNA Profile in Pediatric Cancer Patients Following Anthracycline Chemotherapy

Introduction Anthracycline chemotherapy (AC) can be associated with a progressive decline in left ventricular ejection fraction (LVEF), but the contributory mechanisms remain unclear. While changes in microRNAs (miRs), a key translational control point, have been identified in adult cardiovascular disease, whether and to what degree a shift in miR profiles occurs in pediatric AC patients has not been well studied. The goal of this study was to examine miR profiles (unbiased array) in pediatric AC patients compared to age matched referent normal patients. Hypothesis We hypothesize that pediatric AC patients will express a unique miR profile at initiation and completion of therapy and will be related to LVEF. Methods Serum was collected in pediatric patients (n=12, 13-22 years old) with newly diagnosed malignancy requiring AC within 24-48 hours following initiation of therapy (30-60 mg/m2) and approximately one year after completing maximal therapy. A custom microarray of 84 miRs associated with cardiovascular disease pathways was utilized (RT-qPCR) and indexed to referent normal profiles (n=17, 13-17 years old). LVEF was computed by cardiac MRI. Results LVEF fell from AC initiation at one year following AC (64.28% ± 1.78% vs 57.53% ± 0.95% respectively, p=0.004). Of the 84 miRs profiled, significant shifts in 17 miRs occurred relative to referent normal (p ≤ 0.05) where a nearly equivalent number were upregulated and downregulated (41 vs 59%, respectively). Moreover, the functional domain of miRs associated with myocardial differentiation and development fell by over 3-fold at completion of AC (Figure, p ≤ 0.05). Lastly, miRs-143-3p, -499a-5p, and -142-3p were associated with the fall in LVEF (p ≤ 0.05). Conclusions This study demonstrated for the first time that dynamic changes in miR expression occurs in pediatric cancer patients following AC. These findings suggest that miRs are a potential strategy for early identification of patients most susceptible to LV dysfunction following AC exposure, as well as potential targets for protective therapies.

In Vivo Reactive Oxygen Species Detection With a Novel Positron Emission Tomography Tracer, 18F-DHMT, Allows for Early Detection of Anthracycline-Induced Cardiotoxicity in Rodents

Reactive oxygen species (ROS) are involved in doxorubicin-induced cardiotoxicity. The authors investigated the efficacy of 18F-DHMT, a marker of ROS, for early detection of doxorubicin-induced cardiotoxicity in rats. Echocardiography was performed at baseline and 4, 6, and 8 weeks post-doxorubicin initiation, whereas invivo superoxide production was measured at 4 and 6 weeks with 18F-DHMT positron emission tomography. Left ventricular ejection fraction (LVEF) was not significantly decreased until 6 weeks post-doxorubicin treatment, whereas myocardial superoxide production was significantly elevated at 4 weeks. 18F-DHMT imaging detected an elevation in cardiac superoxide production before a fall in LVEF in rodents and may allow for early cardiotoxicity detectionin cancer patients.

Abstract P5-20-17: Safety of continuing chemotherapy in overt left ventricular dysfunction using antibodies to human epidermal growth factor receptor-2: A retrospective study

Abstract Introduction: Trastuzumab is a monoclonal antibody that targets the human epidermal growth factor receptor (HER)-2 and significantly improves survival in HER-2 positive early stage breast cancer. However, trastuzumab is also known to cause cardiotoxicity. Guidelines recommend withholding or discontinuing trastuzumab if left ventricular ejection fraction (LVEF) falls ≥15% from baseline, or to &amp;lt;50%, but there is little evidence to support this strategy. Additionally, premature discontinuation of trastuzumab may lead to poorer cancer outcomes. Trastuzumab cardiotoxicity is frequently reversible, and the use of angiotensin converting enzyme-inhibitors (ACE-I) and beta blockers is highly effective at treating impaired LVEF in other patient populations. We therefore hypothesize that it is safe to continue trastuzumab in patients with asymptomatic or mildly symptomatic fall in LVEF, when concomitantly treated with ACE-I and beta blockers. Methods: In this retrospective chart review, we identified 18 consecutive patients with stage 1-3 HER-2 positive breast cancer patients who had a decline in LVEF meeting the criteria above to withhold trastuzumab, and who were referred to our cardio-oncology service from the beginning of 2015 to March 2017. These patients were offered and consented to receive ongoing trastuzumab accompanied by ACE-I and/or beta blocker. Data on patient demographics, cancer therapies, clinical features, LVEF, and cardiac medications were extracted from medical charts. Results: Among the 18 patients identified, all were women, 12 (67%) were estrogen receptor positive, and 7 progesterone receptor positive (39%). 11 (61%) of patients had a left-sided breast cancer, 6 (33%) had right-sided breast cancer, and 1 (5%) had an unspecified side breast cancer. 17 (94%) of patients had previously undergone radiation therapy, and 4 (22%) had experienced a recurrence. 16 patients had received a prior anthracycline regimen (10 sequentially, 6 concurrently). The patients were treated with one or a combination of the following medications: carvedilol (n=13), ramipril (n=12), bisoprolol (n=1), candesartan (n=2), rosuvastatin (n=2), atorvastatin (n=2). The patients were followed up for an average of 7 months after starting cardiac therapy. Table 1 summarizes the mean±SD LVEF values over the follow up time period. All patient except one (94%) completed trastuzumab treatment successfully. This patient with concomitant moderate-severe mitral regurgitation was hospitalized for pulmonary edema. Trastuzumab was discontinued and LVEF has subsequently returned to normal values. Table 1: LVEF progression from baseline to end of follow-upMean±SD LVEF at baseline57.59±5.49%Mean±SD LVEF on referral to cardio-oncology clinic50.75±4.76%Mean±SD LVEF at end of follow-up56.35±3.50% Conclusion: Treating cardiac dysfunction related to trastuzumab in a cardio-oncology clinic, using beta blockers and ACE-I may enable completion of trastuzumab therapy. Randomized trials are necessary before it can be widely recommended, however findings from our experience suggest this may be a promising new treatment strategy. Citation Format: Bharaj UK, Leong D, Dhesy-Thind S, Ellis P, Mukherjee S, Bordeleau L, Phillips C, Brown M, Kumar Tyagi N. Safety of continuing chemotherapy in overt left ventricular dysfunction using antibodies to human epidermal growth factor receptor-2: A retrospective study [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 P5-20-17.

Combination of Trastuzumab and Radiotherapy in the Adjuvant Treatment of Breast Cancer: A Single Center Experience and Focus on the Cardiac Safety

Background: The main toxicity of trastuzumab, is the alteration of cardiac function. The objective of this study is to examine the acute cardiotoxicity of the combination of Radiotherapy (RT) and trastuzumab in the adjuvant treatment of breast cancer. Materials and Methods: This is a retrospective study of 41 patients followed for localized breast cancer, treated by multimodal strategy combining chemotherapy, Radiotherapy and trastuzumab as adjuvant treatment in the medical oncology department at the Ibn Sina Military hospital of Marrakesh. Results: All patients underwent adjuvant RT on the wall, including 17 on the left side. The median value of the Left Ventricular Ejection Fraction (LVEF) before starting treatment was 64%. The median value of the absolute decrease of LVEF, after the end of RT, was of the order of 4%. All patients received treatment with trastuzumab, during irradiation at usual doses for twelve months. Trastuzumab was stopped temporarily in seven patients, because of the fall in LVEF of more than 10%. After a median followup of 13 months, one patient developed congestive heart failure, imposing the definitive cessation of trastuzumab. Conclusion: The association RT and trastuzumab, does not appear to increase the risk of acute cardiac toxicity, whatever the irradiated side.

A prospective study examining the role of myocardial Fibrosis in outcome following mitral valve repair IN DEgenerative mitral Regurgitation: rationale and design of the mitral FINDER study

BackgroundThe optimal management of chronic severe primary degenerative mitral regurgitation (MR) is to repair the valve but identification of the optimal timing of surgery remains challenging. Current guidelines suggest ‘watchful waiting’ until the onset of symptoms or left ventricular (LV) dysfunction but these have been challenged as promoting ‘rescue surgery’. Better predictors are required to inform decision-making in relation to the necessity and timing of surgery. Chronic volume overload is a stimulus for adverse adaptive LV remodelling. Subclinical reduction in LV strain before mitral repair predicts a fall in LV ejection fraction following surgery and is thought to reflect the development of myocardial fibrosis in response to chronic volume overload. Myocardial fibrosis can be detected non-invasively using cardiac magnetic resonance (CMR) imaging techniques as an expansion of the extracellular volume (ECV).Methods/designThis study investigates whether: 1) patients with above median ECV will have smaller reduction in end-systolic volume index (as a measure of the degree of reverse LV remodelling) on CMR following mitral valve repair, compared to those with below median ECV; and 2) higher ECV on CMR, validated through histology, adversely impacts upon post-operative complications and symptomatic improvement following surgery.This is a multi-centre, prospective, cross-sectional comparison of patients prior to and 9 months following surgery for chronic severe primary degenerative MR. To establish the natural history of ECV in MR, an additional cohort of patients with asymptomatic MR who do not wish to consider early repair will be followed. Investigations include CMR, cardiopulmonary exercise test, stress echocardiography, signal-averaged electrocardiogram, 24-h electrocardiogram monitoring, laboratory tests and patient-reported outcome measures. Patients undergoing surgery will have cardiac biopsies performed at the time of mitral valve repair for histological quantification of fibrosis.DiscussionThis study will advance our understanding of ventricular remodelling in MR, its impact on patient symptoms and ventricular response following surgery. Establishing the link between myocardial fibrosis (measured on CMR and validated through histology), with early ventricular dysfunction, will offer physicians a novel non-invasive biomarker that can further inform the timing of surgery.Trial registrationThis trial was registered at ClinicalTrials.gov (NCT02355418) on 30th November 2015.

Intracoronary delivery of recombinant TIMP-3 after myocardial infarction: effects on myocardial remodeling and function.

Ischemia-reperfusion (IR) and myocardial infarction (MI) cause adverse left ventricular (LV) remodeling and heart failure and are facilitated by an imbalance in matrix metalloproteinase (MMP) activation and the endogenous tissue inhibitors of metalloproteinase (TIMPs). We have identified that myocardial injections of recombinant TIMP-3 (rTIMP-3; human full length) can interrupt post-MI remodeling. However, whether and to what degree intracoronary delivery of rTIMP-3 post-IR is feasible and effective remained to be established. Pigs (25 kg) underwent coronary catheterization and balloon occlusion of the left anterior descending coronary artery (LAD) for 90 min whereby at the final 4 min, rTIMP-3 (30 mg, n = 9) or saline was infused in the distal LAD. LV echocardiography was performed at 3-28 days post-IR, and LV ejection fraction (EF) and LV end-diastolic volume were measured. LV EF fell and LV end-diastolic volume increased from baseline (pre-IR) values (66 ± 1% and 40 ± 1 ml, respectively, means ± standard deviation) in both groups; however, the extent of LV dilation was reduced in the rTIMP-3 group by 40% at 28 days post-IR (P < 0.05) and the fall in LV EF was attenuated. Despite equivalent plasma troponin levels (14 ± 3 ng/ml), computed MI size at 28 days was reduced by over 45% in the rTIMP-3 group (P < 0.05), indicating that rTIMP-3 treatment abrogated MI expansion post-IR. Plasma NH2-terminal pro-brain natriuretic peptide levels, an index of heart failure progression, were reduced by 25% in the rTIMP-3 group compared with MI saline values (P < 0.05). Although the imbalance between MMPs and TIMPs has been recognized as a contributory factor for post-MI remodeling, therapeutic strategies targeting this imbalance have not been forthcoming. This study is the first to demonstrate that a relevant delivery approach (intracoronary) using rTIMP can alter the course of post-MI remodeling.NEW & NOTEWORTHY Myocardial ischemia and reperfusion injury remain significant causes of morbidity and mortality whereby alterations in the balance between matrix metalloproteinase and tissue inhibitor of metalloproteinase have been identified as contributory biological mechanisms. This novel translational study advances the concept of targeted delivery of recombinant proteins to modify adverse myocardial remodeling in ischemia-reperfusion injury.

Prevalence and prognostic significance of left ventricular myocardial late gadolinium enhancement in severe aortic stenosis

BackgroundMyocardial fibrosis occurs in aortic stenosis (AS) as part of the hypertrophic response. It can be detected by LGE, which is associated with an adverse prognosis in the form of increased mortality and morbidity. ObjectivesTo assess the prevalence of LGE patterns using cardiac magnetic resonance (CMR) in severe AS patients and to study its prognostic significance. MethodsPatients enrolled into the study from June 2012 to November 2014. All the patients underwent CMR and various patterns of LGE studied. These patients if symptomatic were advised AVR and others were managed conservatively. All patients were followed up and watched for outcomes like mortality, heart failure/hospitalization for cardiovascular cause, fall in left ventricular ejection fraction (LVEF) ≥20% and arrhythmia. ResultsA total of 109 patients (mean age-57.7±12.5yrs) underwent CMR with 63 males. These patients were followed up for a mean of 13 months. Among 38 patients who underwent AVR, 6 died (5–cardiovascular cause, 1–non cardiovascular). 71 patients were managed conservatively out of which 18 died (17-cardiovascular cause, 1-non cardiovascular cause). LGE patterns were seen in 46 patients (43%); mid myocardial enhancement was seen in 31.1% of cases (33 patients). No LGE pattern was seen in 57%(63 patients). Basal and mid regions were maximally involved with mid myocardial enhancement in 66% & 68.3% respectively. LV ejection fraction (p=0.002), peak aortic systolic velocity (p=0.01) and peak aortic systolic gradient (p=0.02) were the main predictors of LGE. Main predictors of primary outcome were NYHA class [OR- 13.4(2.8–26.1), p≤0.001], age- 62± 9.6yrs(p=0.001), EF simpson-50.9±13%(p≤ 0.001), LGE[OR 2.8 (1.27–6.47),p=0.01], number of segments involved [2.37±2.1,P≤0.001] & CMR LV mass (151.73±32gms, p=0.007). LGE predicted heart failure/hospitalization for cardiovascular cause [OR- 3.8(1.2–11.9), p=0.01] and fall in LVEF [OR- 5.8(1.5–22.5), p=0.005]. Patients with LGE had 2.87 times risk of adverse outcomes and patients with more than 3 segment LGE involvement had again increased chances for adverse outcomes. ConclusionsLGE was detected by CMR in 43% of patients with severe AS. It predicted recurrent heart failure, hospitalization for cardiovascular cause and fall in LV ejection fraction. Our study has laid a path to larger prospective studies with long term follow up to assess the prognostic impact of CMR in patients with severe AS.

PP.LB01.01] HIGH VALUE OF ARTERIAL STIFFNESS AS A PREDICTOR OF A LESS EFFECTIVE RECOVERY OF LEFT VENTRICULAR SYSTOLIC FUNCTION AFTER ACUTE MYOCARDIAL INFARCTION

Objective: Left ventricular global-longitudinal strain (LV GLS) is an important predictor of adverse outcomes in patients with myocardial infarction (MI). GLS is more sensitive than LV ejection fraction (LVEF) as a measure of systolic function and may be used to detect reduction in LV-function prior to fall in LVEF. Pulse wave velocity (PWV), a marker of arterial stiffness, can predict cardiovascular events. The aim of the study was to investigate the relations between GLS and carotid-femoral PWV in patients with MI successfully treated with percutaneous coronary intervention (PCI). Design and method: 93 patients with first MI and primary (PCI) (70% male, age 61.5 ± 10.1 years (M ± SD), 57 (61,3%) with ST-Elevation Myocardial Infarction (STEMI), smokers 25%, arterial hypertension 20%, blood pressure 129 ± 6/82 ± 7 mmHg, left ventricular ejection fraction (LVEF) 47.4 ± 4.3%. Arterial stiffness was assessed using applanation tonometry. GLS by speckle tracking echocardiography (STE) was calculated in a 16-segment LV-model as the average segmental value on the basis of three apical imaging planes. Mann-Whitney and Spearman tests were considered significant if p Results: Baseline GLS >18% was not detected in any patient. GLS increased from 14.3 ± 2.3 to 15.6 ± 2.4%, p 18%) in 24 (25%) patients. Achieved GLS differed significantly in patients without vs with normalization (14.5 ± 1.8 vs 18.6 ± 0.3%, p Conclusions: Improvement of systolic function assessed by GLS was revealed in 25% of patients with first MI treated with PCI. Higher baseline PVW was associated with less improvement of GLS. Arterial stiffening may result in a less effective recovery of LV longitudinal function after MI.

Anthracycline- and trastuzumab-induced cardiotoxicity: a retrospective study.

Some chemotherapeutic agents cause cardiotoxic effects including reduction in left ventricular ejection fraction (LVEF) and occasionally congestive heart failure. Anthracyclines and HER2 monoclonal antibodies are common offenders, but clinical practice data on LVEF changes, risk factors and acute recovery is lacking. We retrospectively examined the electronic medical record at an academic medical center for receipt of anthracyclines and/or trastuzumab from 2000 to 2013 in cancer patients. Patient characteristics and serial LVEF assessments were collected. Patients with and without LVEF decline were analyzed by univariate and multivariate analysis. A total of 549 patients were identified with anthracycline/trastuzumab use and 216 had multiple LVEF assessments. Only 27 of the 216 patients who had multiple LVEF assessments at multiple occasions suffered a clinically significant LVEF fall (12.5%), and symptomatic CHF was rare (0.5%). Compared to unaffected patients, those with a fall in LVEF were more likely to have hypertension, hyperlipidemia or coronary artery disease (CAD). Concomitant trastuzumab and anthracycline use was a risk factor (36 vs 9.5% for anthracycline alone, p<0.001). The median time from start of chemotherapy to reduced LVEF was 202days (5-3008). On multivariate analysis, hypertension and use of trastuzumab remained independent predictors of LVEF fall. Acute recovery in LVEF was observed in 44% of patients. LVEF changes from cancer therapies are frequent and hard to predict. Hypertension, hyperlipidemia and CAD are associated with LVEF decline. Acute recovery of LVEF is observed in those experiencing treatment-related cardiotoxicity. Attention to timely interruption of cardiotoxic chemo is recommended.

Cardiotoxicity of the adjuvant trastuzumab in a Saudi population: clinical experience of a single institution

AbstractPurposeAdjuvant trastuzumab is currently an internationally standard for the treatment of localised breast cancer that over express HER2 with the most adverse effect being cardiotoxicity. We conducted this study to evaluate the cardiac safety of trastuzumab in clinical practice.MethodsThis study is a retrospective observational single institutional study conducted in the Oncology Center of King Abdulla Medical City (KAMC), Makkah, Saudi Arabia, from June 2011 to January 2014. We evaluated the incidence of cardio toxicity and associated risk factors during adjuvant trastuzumab treatment.ResultsOf 57 patients, 20 patients (35%) exhibited cardiotoxicity. About 14% of patients had drop of left ventricular ejection fraction (LVEF) below 50%, whilst 10% and 15% drop of LVEF below their baseline levels were found in 30% and 5% of patients, respectively. About 98.3% of our patients have completed treatment, of whom 21% had a provisional interruption because of a fall in LVEF. A definitive trastuzumab discontinuation has been made in 1.75% of cases because of a nonregressive reduction in LVEF. Analysis of risk factors related to trastuzumab cardio toxicity found that patients older than 40 years were more likely to develop cardio toxicity compared to those younger than 40 years. This difference was statistically significant (p = 0.042).ConclusionIn our study, the cardiac safety seems comparable with the literature data. Trastuzumab-related cardiotoxicity is manifested by an asymptomatic decrease in the LVEF and less commonly by clinical heart failure. Most instances are transient, asymptomatic and reversible.

Myocardial strain imaging: how useful is it in clinical decision making?

Myocardial strain is a principle for quantification of left ventricular (LV) function which is now feasible with speckle-tracking echocardiography. The best evaluated strain parameter is global longitudinal strain (GLS) which is more sensitive than left ventricular ejection fraction (LVEF) as a measure of systolic function, and may be used to identify sub-clinical LV dysfunction in cardiomyopathies. Furthermore, GLS is recommended as routine measurement in patients undergoing chemotherapy to detect reduction in LV function prior to fall in LVEF. Intersegmental variability in timing of peak myocardial strain has been proposed as predictor of risk of ventricular arrhythmias. Strain imaging may be applied to guide placement of the LV pacing lead in patients receiving cardiac resynchronization therapy. Strain may also be used to diagnose myocardial ischaemia, but the technology is not sufficiently standardized to be recommended as a general tool for this purpose. Peak systolic left atrial strain is a promising supplementary index of LV filling pressure. The strain imaging methodology is still undergoing development, and further clinical trials are needed to determine if clinical decisions based on strain imaging result in better outcome. With this important limitation in mind, strain may be applied clinically as a supplementary diagnostic method.

Trastuzumab-induced cardiotoxicity in Uruguayan HER2-positive breast cancer patients.

143 Background: To evaluate the incidence, severity and outcome of Trastuzumab-induced cardiotoxicity in HER2 positive Uruguayan breast cancer (BC) patients. Methods: Retrospective observational analysis of HER2 positive BC patients who were treated with Trastuzumab (TTZ) from January 2007 to December 2013 at two Uruguayan centers. Cardiac monitoring included physical examination and assessment of left ventricular ejection fraction (LVEF) by echocardiography that was evaluated before TTZ administration and every 12 weeks thereafter during the duration of therapy. Cardiovascular risk factors analyzed were: obesity (BMI ≥ 30 kg/m2), hypertension, diabetes, sedentary lifestyle and high cholesterol. Results: Sixty nine female patients were found in the databases of our institutions. Median age was 48 years (range: 27-73). Stage at diagnosis was as detailed: 19 % EI, 46 % EII, 29 % EIII and 4 % EIV. Eighty nine percent of patients received adjuvant TTZ , 4 % neoadjuvant TTZ and 7 % received it as a palliative therapy. Thirty patients (43, 5%) had at least one cardiovascular risk factors: 26% hypertension, 16% obesity, 9% sedentary lifestyle, and 4% high cholesterol. Median number of TTZ cycles was 15. Cycles were administered every 3 weeks at standard dose. Nineteen patients (27%) developed cardiotoxicity, of whom 12 had a transient suspension because of a reversible fall in LVEF, 2 had a irreversible reduction in LVEF, and 5 had a symptomatic heart failure. Eighty-nine percent of our patients (62 patients) completed treatment and the rest had a definitive suspension due to a irreversible reduction in LVEF or symptomatic heart failure. Most patients that developed cardiotoxicity (15 out of 19) had cardiovascular risk factors and also most of them (16 out of 19) had received anthracyclines before TTZ. Conclusions: Cardiotoxicity incidence was similar to the incidence reported in the literature and when it was present, in most cases was transient, asymptomatic, and reversible.

How Does the Brain Talk to the Arteries and Heart?

In many hypertension (Htn) models, myogenic tone (MT) in isolated small arteries is increased. MT is regulated mainly by Ca2+ transporters. Arterial transporter expression is “reprogrammed” in many Htn models: e.g., Na/Ca exchanger (NCX) and SR Ca2+ pumps (SERCA2) are increased; this enhances constriction and MT. In heart failure (HF), cardiac Ca2+ transporter “reprogramming” impairs contraction: e.g., NCX1 is increased, and SERCA2 expression or function is reduced. Do these cardiovascular (CV) changes in Htn and HF have a common trigger? The brain RAAS is activated in both Htn and HF. Central Ang II infusion increases BP, circulating endogenous ouabain (EO), and arterial NCX and SERCA2 expression; brain RAAS blockade prevents all effects (Hamlyn et al., PloS one 9: e108916, 2014). Here we induced Htn in rats (mean BP = 124 vs Control = 99 mm Hg) and mice (139 vs C = 110 mm Hg) with sc low dose Ang II (150‐350 ng/kg/min) and a high (2‐6%) salt diet. Also, in mice, coronary artery ligation caused ~45% LV myocardial infarction (MI) and HF: a 38±4% fall in LV ejection fraction at 8 wks post‐MI. In both Htn and HF, plasma EO increased (1.31‐2.59 nM vs C = 0.07‐0.53 nM) as did expression of arterial NCX (1.7‐1.8xC) and SERCA2 (2.0‐2.3xC) and cardiac NCX (1.7‐1.9xC), but cardiac SERCA2 expression declined (0.58‐0.74xC). In vitro 48‐72 hr treatment with 50‐100 nM ouabain, but not digoxin, increased NCX and SERCA2 protein in primary cultured arterial myocytes (published), and NCX (1.3‐1.7xC) in cardiomyocytes.Conclusionplasma EO is the signal from the brain that triggers Ca2+ transporter reprogramming in both Htn and HF. The novel slow brain RAAS‐plasma EO‐CV system modifies responses to the rapid RAAS‐activated sympathetic nerve pathway, and both modulate CV function in Htn and HF.

Paradoxically, iron overload does not potentiate doxorubicin-induced cardiotoxicity in vitro in cardiomyocytes and in vivo in mice

Doxorubicin (DOX) is known to induce serious cardiotoxicity, which is believed to be mediated by oxidative stress and complex interactions with iron. However, the relationship between iron and DOX-induced cardiotoxicity remains controversial and the role of iron chelation therapy to prevent cardiotoxicity is called into question.Firstly, we evaluated in vitro the effects of DOX in combination with dextran–iron on cell viability in cultured H9c2 cardiomyocytes and EMT-6 cancer cells. Secondly, we used an in vivo murine model of iron overloading (IO) in which male C57BL/6 mice received a daily intra-peritoneal injection of dextran–iron (15mg/kg) for 3weeks (D0–D20) and then (D21) a single sub-lethal intra-peritoneal injection of 6mg/kg of DOX.While DOX significantly decreased cell viability in EMT-6 and H9c2, pretreatment with dextran–iron (125–1000μg/mL) in combination with DOX, paradoxically limited cytotoxicity in H9c2 and increased it in EMT-6. In mice, IO alone resulted in cardiac hypertrophy (+22%) and up-regulation of brain natriuretic peptide and β-myosin heavy-chain (β-MHC) expression, as well as an increase in cardiac nitro-oxidative stress revealed by electron spin resonance spectroscopy. In DOX-treated mice, there was a significant decrease in left-ventricular ejection fraction (LVEF) and an up-regulation of cardiac β-MHC and atrial natriuretic peptide (ANP) expression. However, prior IO did not exacerbate the DOX-induced fall in LVEF and there was no increase in ANP expression.IO did not impair the capacity of DOX to decrease cancer cell viability and could even prevent some aspects of DOX cardiotoxicity in cardiomyocytes and in mice.