Predictors Of Left Ventricular Dysfunction Research Articles

Abdominal adiposity, general obesity, and subclinical systolic dysfunction in the elderly: A population-based cohort study.

General obesity, measured by body mass index (BMI), and abdominal adiposity, measured as waist circumference (WC) and waist-to-hip ratio (WHR), are associated with heart failure and cardiovascular events. However, the relationship of general and abdominal obesity with subclinical left ventricular (LV) dysfunction is unknown. We assessed the association of general and abdominal obesity with subclinical LV systolic dysfunction in a population-based elderly cohort. Participants from the Cardiovascular Abnormalities and Brain Lesions study underwent measurement of BMI, WC, and WHR. Left ventricular systolic function was assessed by two-dimensional echocardiographic LV ejection fraction (LVEF) and speckle-tracking global longitudinal strain (GLS). The study population included 729 participants (mean age 71 ± 9 years, 60% women). In multivariate analysis, higher BMI (but not WC and WHR) was associated with higher LVEF (β = 0.11, P = 0.003). Higher WC (β = 0.08, P = 0.038) and higher WHR (β = 0.15, P < 0.001) were associated with lower GLS, whereas BMI was not (P = 0.720). Compared with normal WHR, high WHR was associated with lower GLS in all BMI categories (normal, overweight, and obese), and was associated with subclinical LV dysfunction by GLS both in participants without [adjusted odds ratio (OR) 2.0, 95% confidence interval (CI) 1.1-3.6, P = 0.020] and with general obesity (adjusted OR 5.4, 95% CI 1.1-25.9, P = 0.034). WHR was incremental to BMI and risk factors in predicting LV dysfunction. Abdominal adiposity was independently associated with subclinical LV systolic dysfunction by GLS in all BMI categories. BMI was not associated with LV dysfunction. Increased abdominal adiposity may be a risk factor for LV dysfunction regardless of the presence of general obesity.

Predictive Implication of Initial Electrocardiogram and Creatine Kinase for Left Ventricular Ejection Fraction in Patients with Acute ST-Elevation Myocardial Infarction

Aim: Our aim was to determine the clinical, electrocardiographic (ECG) and biochemical predictors of left ventricular dysfunction in patients with acute ST elevation myocardial infarction (STEMI). Methods: Patients with STEMI admitted in Loghman Hakim hospital were studied. The ECG variables were: ECG rate, ECG rhythm, QRS duration, sum of absolute ST deviation (in all, inferior and anterior leads), number of leads with ST elevation, maximum ST elevation, presence of pathological Q waves and location of the infarct. The primary outcome measure was LVEF ≤ 40%. Results: A total of 124 patients (91 male, 33 female) were studied. Mean age of the patients was 59.1 years (SD=12.6). Of these, 52 patients (44.4%) had an LVEF ≤ 40% and angiography was recommended to 68 patients (54.8%) at the time of discharge. The multivariate analysis showed an association of LVEF ≤ 40% with prior MI, diabetes, maximum creatine kinase (CK) levels, the sum of absolute ST deviation in all and inferior leads. Conclusions: The initial ECG and CK levels in patients with STEMI may contain valuable information for risk stratification, determination of prognosis and the subsequent management plan. The results of this study warrant further studies to define patients who benefit most from invasive and sophisticated interventions.

Serum levels of N-terminal-pro B-type natriuretic peptide as a diagnostic marker for left ventricular dysfunction in children with end-stage renal disease on hemodialysis.

The objective of this study was to determine the diagnostic cutoff value of N-terminal-pro B-type natriuretic peptide (NT-pro BNP) as a marker of left ventricular (LV) dysfunction in children with end-stage renal disease (ESRD) on regular hemodialysis (HD). The study was carried out on thirty children with ESRD on regular HD and thirty healthy controls. Echocardiographic studies were done, including a conventional mode for ejection fraction, fractional shortening, tissue Doppler imaging, and longitudinal global strain by speckle tracking. Serum levels of NT-pro BNP were measured in venous blood samples before and about 30 min after HD by ELISA. Volume status was assessed by calculating interdialytic weight gain %. There were significant higher serum NT-pro BNP levels before HD (mean: 702.3 ± 274.3 ng/L) compared to controls (mean: 365.55 ± 76.5 ng/L) (P <0.001) and these levels decreased significantly after the HD session (mean: 625.1 ± 117.69 ng/L) (P = 0.031). Echocardiographic studies showed a significant impairment of LV function of the patients compared to controls. Patients with LV dysfunction had significant higher serum concentrations of NT-pro BNP compared to patients without dysfunction both before (P = 0.003) and after dialysis (P <0.001). Receiver operating curve demonstrated better prediction of LV dysfunction by NT-pro BNP levels after HD compared to its levels before HD (area under the curve was 0.9 and 0.73, respectively). Using a cutoff value of 630 ng/L, serum NT-pro BNP levels after dialysis were a diagnostic predictor of LV dysfunction with a sensitivity of 86.6%, specificity of 93.3%, positive predictive value of 92.8%, and negative predictive value of 87.5%. Serum NT-pro BNP levels were strongly correlated with the parameters of LV dysfunction in children with ESRD on regular HD. A postdialysis cutoff value of 630 ng/L could serve as a biochemical marker of LV dysfunction in those children regardless of chronic fluid overload.

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

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

Impact of HbA1c on Outcomes of Acute Coronary Syndrome in Non-Diabetic Patients

Background : Elevated glucose levels have been previously shown to be associated with adverse outcomes in patients of acute coronary syndrome. However, admission glucose levels are affected by various factors like meals, circadian cycle and also the stress response. HbA1c is a better marker of long- term glucose status. The value of HbA1c as a predictor of prognosis in acute coronary syndrome has not been extensively studied. Objective : To study the relationship between admission HbA1c levels and short-term outcome in non-diabetic patients admitted with acute coronary syndrome. Material and Methods : This open-label, hospital based, cohort study was conducted on 200 patients without previously known diabetes admitted with acute coronary syndrome. A detailed history and clinical examination were carried out. Admission plasma glucose, fasting glucose and HbA1c levels were recorded. Those presenting with fasting plasma glucose of >126 mg% or HbA1c >6.5% were labeled as “Undiagnosed Diabetic Patients”. Outcome was measured mainly by assessing the left ventricular systolic function. Data were analysed using chi square test, student t-test, ANOVA and partial correlation regression, wherever applicable. Results : Mean age of patients was 56.38 years. Average BMI was 25.1±3.5 kg/m2. Mean HbA1c was 6.3±1.5%. 79 (39.5%) patients had HbA1c between 6 and 6.5. There was a linear correlation between ejection fraction and HbA1c (p value =0.019). Conclusion : HbA1c is a strong predictor of left ventricular dysfunction in non-diabetic patients presenting with acute coronary syndrome, therefore, measurement of HbA1c levels may improve risk assessment in patients presenting with acute coronary syndrome.

Abstract 12081: Glycemic Variability as Determined by a Continuous Glucose Monitoring System Predicts Left Ventricular Dysfunction in Patients With a First ST-Segment Elevation Myocardial Infarction

Background: Glycemic Variability (GV) may play an important role in development of cardiovascular disease however the clinical significance of GV is not fully understood in patients with ST-segment elevation myocardial infarction (STEMI). We explored the clinical utility of GV using continuous glucose monitoring system (CGMS; iPro2, Medtronic, USA). Methods: Seventy-four patients (66 males, 63±12 years) with a first STEMI were enrolled. STEMI was de[[Unable to Display Character: &amp;#64257;]]ned as chest pain lasting for at least 30 minutes accompanied by ST-segment elevation and an increase in the serum peak-creatine phosphokinase (CPK) level to more than twice the upper limit of normal. All patients were equipped with a CGMS 1 week after admission and GV was assessed by measuring the Mean Amplitude of Glycemic Excursion (MAGE) during 24 hours with 3 regular meals. At 7 month, all patients underwent conventional 2D echocardiography and blood sampling (BNP; brain natriuretic peptide) to explore the effect of GV to their cardiac function. Results: On univariate analysis male, culprit left anterior descending artery (LAD), peak CK-MB and MAGE were predictors of decreased left ventricular ejection fraction (LVEF). On multivariate analysis higher MAGE level was an independent predictor of decreased LVEF. Higher MAGE level was also an independent predictor of higher BNP level at 7 month. Conclusions: GV was an independent predictor of left ventricular dysfunction in patients with a first STEMI.

Glycated Hemoglobin vs Fasting Plasma Glucose as a Predictor of Left Ventricular Dysfunction After ST-Elevation Myocardial Infarction

BackgroundThe World Health Organization and the American Diabetes Association recommend a level of glycated hemoglobin (HbA1c) ≥ 6.5% as diagnostic for diabetes. However, concordance between fasting plasma glucose (FPG) and HbA1c levels in acutely unwell patients is unknown. Furthermore, the prognostic value of HbA1c for left ventricular (LV) dysfunction is unclear. This study aimed to evaluate the concordance between HbA1c levels and FPG in consecutive patients with acute ST-elevation MI (STEMI) and compare their prognostic value in predicting LV dysfunction and elevated filling pressures on echocardiography. MethodsA total of 142 patients with a first incidence of STEMI were prospectively recruited. LV diastolic function was defined as mean septal and lateral early diastolic velocities (average e’); filling pressure was the ratio of transmitral E velocity to average e’ (average E/e’). ResultsMean FPG and HbA1c levels were 7.7 ± 2.8 mmol/L and 6.5% ± 1.6%, respectively. Of 109 patients without previous diabetes, HbA1c levels identified an additional 18 patients (16.5%) as having diabetes, and the concordance with FPG was poor. Between diabetic and nondiabetic patients, there were no differences in LV end-diastolic volume (116 ± 37 vs 118 ± 43 mL; P = 0.78), end-systolic volume (69 ± 33 vs 68 ± 35 mL; P = 0.93), and ejection fraction (42 ± 12 vs 44 ± 11%; P = 0.49). On multivariable analyses, average e’ was independently associated with HbA1c (β = −0.161; P = 0.045) but not FPG (P = 0.82). Similarly, average E/e’ was independently associated with HbA1c (β = 0.168; P = 0.04) but not FPG (P = 0.32). Receiver operating characteristic curve analysis showed that an HbA1c cutoff of 6.4% (area under the curve, 0.68; P = 0.002) was associated with an elevated LV filling pressure. ConclusionsOnly HbA1c was independently associated with impaired LV diastolic function and increased filling pressures after STEMI.

Long noncoding RNAs in patients with acute myocardial infarction.

Long noncoding RNAs (lncRNAs) constitute a novel class of noncoding RNAs that regulate gene expression. Although recent data suggest that lncRNAs may be associated with cardiac disease, little is known about lncRNAs in the setting of myocardial ischemia. To measure lncRNAs in patients with myocardial infarction (MI). We enrolled 414 patients with acute MI treated by primary percutaneous coronary intervention. Blood samples were harvested at the time of reperfusion. Expression levels of 5 lncRNAs were measured in peripheral blood cells by quantitative polymerase chain reaction: hypoxia inducible factor 1A antisense RNA 2, cyclin-dependent kinase inhibitor 2B antisense RNA 1 (ANRIL), potassium voltage-gated channel, KQT-like subfamily, member 1 opposite strand/antisense transcript 1 (KCNQ1OT1), myocardial infarction-associated transcript, and metastasis-associated lung adenocarcinoma transcript 1. Levels of hypoxia inducible factor 1A antisense RNA 2, KCNQ1OT1, and metastasis-associated lung adenocarcinoma transcript 1 were higher in patients with MI than in healthy volunteers (P<0.01), and levels of ANRIL were lower in patients with MI (P=0.003). Patients with ST-segment-elevation MI had lower levels of ANRIL (P<0.001), KCNQ1OT1 (P<0.001), myocardial infarction-associated transcript (P<0.001), and metastasis-associated lung adenocarcinoma transcript 1 (P=0.005) when compared with patients with non-ST-segment-elevation MI. Levels of ANRIL were associated with age, diabetes mellitus, and hypertension. Patients presenting within 3 hours of chest pain onset had elevated levels of hypoxia inducible factor 1A antisense RNA 2 when compared with patients presenting later on. ANRIL, KCNQ1OT1, myocardial infarction-associated transcript, and metastasis-associated lung adenocarcinoma transcript 1 were significant univariable predictors of left ventricular dysfunction as assessed by an ejection fraction ≤40% at 4-month follow-up. In multivariable and reclassification analyses, ANRIL and KCNQ1OT1 improved the prediction of left ventricular dysfunction by a model, including demographic features, clinical parameters, and cardiac biomarkers. Levels of lncRNAs in blood cells are regulated after MI and may help in prediction of outcome. This motivates further investigation of the role of lncRNAs after MI.

First-degree atrioventricular block may not be that benign after all

I n this issue of the Journal, Uhm et al. [1] report a study from Korea, which indicates that first-degree atrioventricular block (AVB) is associated with an increased risk of advanced AVB, atrial fibrillation and left ventricular dysfunction in patients with hypertension. First-degree AVB is a result of conduction delay occurring in the right atrium, AV node, His bundle or Purkinje network. Potential underlying mechanisms suggested by the authors include atherosclerosis of the coronary arteries, atrial fibrosis, dilated cardiomyopathy, infiltrative cardiomyopathies, left ventricular dysfunction, neuromuscular disease and insufficient blood pressure control causing left ventricular hypertrophy. Therefore, first-degree AVB may be a marker of underlying heart disease, rather than being an independent predictor of left ventricular dysfunction. The current study by Uhm et al. [1] retrospectively examined 3816 hypertensive middle-aged participants with sinus rhythm on baseline ECG and no cardiac implantable electronic devices, baseline left ventricular dysfunction, ventricular preexcitation or advanced AVB. The 544 (14.3%) participants with first-degree AVB were older, used more nondihydropyridine calcium channel blockers, had more left ventricular hypertrophy and longer QRS duration at baseline. In Cox multivariate analyses, baseline firstdegree AVB was associated with subsequent development of atrial fibrillation, left ventricular dysfunction and advanced AVB. In earlier studies, first-degree AVB was not associated with higher morbidity and mortality and has previously been considered a benign finding of no adverse prognostic significance [2,3]. More recently, a growing body of literature has emerged that first-degree AVB might be an ominous sign compared with patients with normal AV conduction [4,5]. In the Heart and Soul Study, including 938 patients with stable coronary artery disease, first-degree

Can left ventricular function be assessed on non-ECG-gated CT?

To evaluate whether non-gated computed tomography (CT) can assess left ventricular (LV) function, 101 patients with both CT and echocardiography were selected, with ejection fraction <50% on echocardiography used as a reference standard. CTs were blindly reevaluated, and qualitative assessment of LV dysfunction on CT correlated with echocardiographic dysfunction, odds ratio of 21.0 (95% confidence interval=6.55–71.0), specificity of 86% (56/65). Systolic and diastolic images were identified on CT, and the ratio of systolic to diastolic LV internal diameters and ratio of LV to RV internal diameter were determined, both showing correlation with LV dysfunction on echocardiography (P<.0001). Non-gated CT can be used to predict LV dysfunction.

Preoperative echocardiographic measures as predictors of left ventricular dysfunction after mitral valve repair

Preoperative echocardiographic measures as predictors of left ventricular dysfunction after mitral valve repair

Role of tissue Doppler imaging in predicting left ventricular dysfunction after myocardial infarction

Left ventricular (LV) dysfunction is a well known complication following ST-segment elevation myocardial infarction (STEMI). Tissue Doppler imaging (TDI) is used as a non-invasive method to assess LV diastolic function. Measurements obtained from TDI augment the prognostic information of clinical risk score.In this study, we are trying to use TDI to predict the development of LV dysfunction (LVEF% <50%) in patients presenting with first attack of STEMI.We randomly selected 40 patients with acute STEMI, followed-up for 6 months. Two groups of patients were included according to the presence or absence of LV dysfunction.Of 40 stable post-STEMI patients, 14 (35%) developed LV dysfunction during 6-month follow-up. Along the lateral and septal mitral annulus, the e′-wave velocity and E/e′ ratio showed a significant correlation with LV dysfunction following STEMI (p-value <0.001). A baseline cutoff value of E/e′ ratio at the lateral mitral annulus >8.0 showed high sensitivity and specificity, 93% and 89%, respectively. Also, a baseline cutoff value of E/e′ ratio at the septal mitral annulus >10.0 had a sensitivity of 79% and specificity of 88%.In conclusion, selected TDI parameters (e′-wave and E/e′ along the septal and lateral mitral annulus) could guide post-STEMI risk stratification, and thus predicting LV dysfunction.

Utility of Transmural Myocardial Strain Profile for Prediction of Early Left Ventricular Dysfunction in Patients With Duchenne Muscular Dystrophy

Myocardial damage in Duchenne muscular dystrophy (DMD) has lethal outcomes, making early detection of myocardial changes in patients with DMD vital, because early treatment can help prevent the development of myocardial fibrosis. The aim of the present study was, therefore, to test the hypothesis that transmural strain profile (TMSP) analysis can predict future left ventricular (LV) dysfunction in patients with DMD with preserved ejection fraction. We studied 82 consecutive patients with DMD without LV wall motion abnormality, with an ejection fraction of 60 ± 5% (all ≥55%) and age 11 ± 3 years. Echocardiography was performed at baseline and 1 year of follow-up. TMSP in the posterior wall was evaluated from the mid-LV short-axis view. A normal TMSP pattern (1 peak in the endocardium, group 1) was seen in 44 patients, and TMSP with a notch (2 peaks in the endocardium, group 2) in the remaining 38 (46%). Wall motion abnormality in the posterior wall was observed in 16 patients (42%) in group 2 at 1 year of follow-up but in none of the patients in group 1 (42% vs 0%; p <0.001). Importantly, multivariate analysis showed that only TMSP with a notch (odds ratios 1.524, p <0.001) was an independent determinant of the presence of LV posterior wall motion abnormality at 1 year of follow-up. In conclusion, subclinical LV dysfunction can be detected by evaluation of TMSP in patients with DMD who do not have wall motion abnormalities by conventional echocardiography. TMSP with a notch proved effective for evaluating subtle early changes in patients with DMD and might be useful for predicting LV dysfunction.

Prediction of Anthracycline-Induced Left Ventricular Dysfunction by Cardiac Troponins

Evidence suggests prognostic utility of troponin (Tn) serum concentrations for a variety of conditions. We sought to determine whether elevated concentrations early after anthracycline chemotherapy predict the development of left ventricular systolic dysfunction in adult patients with cancer. PubMed/MEDLINE searches identified original reports that assessed cardiac TnI or TnT within 5 days of anthracycline chemotherapy and evaluated left ventricular systolic function after treatment for review. Ten reports qualified for review. Four studies indicated a significant relation between elevated Tn and subsequent left ventricular systolic dysfunction. One study that enrolled patients actively receiving anthracyclines and others who had previously received anthracyclines also demonstrated a significant relation. The remaining five reports identified no such relation. Heterogeneity in experimental methods, sampling times, and handling of confounders was significant between positive and negative studies. The present evidence is insufficient to suggest that Tns are reliable predictors of left ventricular dysfunction in patients with cancer. These data suggest, however, that larger prospective studies using frequent scheduled Tn measurement with adjustment for confounding factors could determine the predictive value of Tns in this setting.

Echocardiographic Predictors of Left Ventricular Dysfunction after Aortic Valve Surgery in Children with Chronic Aortic Regurgitation

Postoperative left ventricular dysfunction is associated with poor prognosis in adults with severe chronic aortic regurgitation and published practice guidelines aim to minimize this risk. However, only limited information exists in pediatrics. The goal of this study was to define preoperative risk factors for postoperative left ventricular dysfunction in children with chronic aortic regurgitation. Patients fulfilling the following criteria were included in this study: (1) age at preoperative echocardiogram ≤18 years; (2) ≥moderate aortic regurgitation; (3) ≤mild aortic valve stenosis; (4) no additional valve disease/shunt; (5) underwent aortic valve surgery for aortic regurgitation; and (6) available preoperative and ≥6-month postoperative echocardiograms with adequate information. Primary outcome was postoperative left ventricular dysfunction defined as ejection fraction z-score < -2. Median ages at diagnosis and surgery of the 53 eligible patients were 6.9 (0.04-17.2) and 13 years (1.2-22.4), respectively. Compared with patients whose postoperative left ventricular ejection fraction was normal, those with left ventricular ejection fraction z-score < -2 (n = 10) had significantly higher preoperative left ventricular end-diastolic and systolic volumes and dimensions and lower indices of systolic function. Preoperative left ventricular ejection fraction z-score < -1 was the most sensitive (89%; confidence interval [CI] 52, 100) but least specific (58%; CI 41, 73), whereas left ventricular end-systolic diameter z-score ≥ 5 was the most specific (95%; CI 84, 99) but least sensitive (60%; CI 26, 88) outcome identifier. A combination of shortening fraction z-score < -1 or end-systolic diameter z-score ≥ 5 best identified postoperative left ventricular dysfunction with an area of 0.819 under the receiver-operator characteristic curve. Lower indices of left ventricular systolic function and severity of dilation identify children at risk for postoperative left ventricular dysfunction after aortic valve surgery. These identifiers are similar to predictors defined in adult patients albeit with different threshold values.

Recent advances in natriuretic peptide family genes and cardiovas-cular diseases

Natriuretic peptide family consists of several hormones produced by cardiomyocyte, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). They possess similar gene structures and protective effects of cardiovascular physiology, such as anti-hypertrophy, anti-fibrosis, myocardial relaxation and blood pressure regulation. The corresponding natriuretic peptide receptor A, B and C mediate multiple effects of natriuretic peptides to maintain cardiovascular homeostasis. Specially, natriuretic peptide receptor-A preferentially binds ANP and BNP, while natriuretic peptide receptor-B is more selective for C-type natriuretic peptides. Natriuretic peptide receptor-C(NPR-C), binding all kinds of natriuretic peptides, clears natriuretic peptides from the circulation through receptor-mediated internalization and degradation. BNP levels were reported to be a good predictor of left ventricular dysfunction and decompensated heart failure from a clinical standpoint. BNP infusion is an effective treatment for acute heart failure. Investigations on natriuretic peptides' single nucleotide polymorphisms and biological function suggested that they could be associated with several cardiovascular diseases, such as atrial fibrillation, cardiomyopathy, heart failure and so on. Transgenic mice with natriuretic peptides and their receptors gene deletion display myocardial hypertrophy and fibrosis, which are associated with the development of hypertension, cardiomyopathy and heart failure. Certain stimuli triggering cardiac hypertrophy and ischemic injuries may be involved in regulating gene expression of natriuretic peptides and their receptors. Therefore, advances in understanding of natriuretic peptide family genes and their regulatory mechanisms will lead to greater insight into the pathogenesis of cardiovascular diseases and blaze a new trail in clinical treatment.

Relationship between hematologic parameters and left ventricular systolic dysfunction in stable patients with multi-vessel coronary artery disease

Multi-vessel coronary artery disease (MVCAD) has long been recognized as an important predictor of adverse outcomes in patients with chronic stable angina. The aim of this study is to investigate the relationship between hematologic parameters and impairment of left ventricular systolic functions in patients with stable MVCAD. Patients (n=202) with stable angina and MVCAD were included in this study. According to the left ventricle ejection fraction (LVEF) determined by echocardiography, patients were divided into two groups as the preserved group (LVEF >50%) and the impaired group (LVEF <50%). The preserved group consisted of 106 patients and the impaired group consisted of 96 patients. The frequency of diabetes mellitus was significantly higher in the impaired group compared to the preserved group (respectively, 50% vs. 33%, p=0.01). High sensitivity C-reactive protein (hs-CRP) levels and, neutrophil/lymphocyte ratio (N/L ratio) were significantly higher in the impaired group than in the preserved group (3.9±2.4 vs. 7.9±3.8, p<0.001; 2.7±0.7 vs. 3.9±1.2, p<0.001, respectively). There was a significant correlation between LVEF, N/L ratio and hs-CRP; hs-CRP and N/L ratio were positively correlated (r=0.584; p<0.001), and LVEF was negatively correlated with both hs-CRP and N/L ratio (r=-0.48, p<0.001 and r=-0.43, p<0.001, respectively). A N/L ratio >3.0 had 77% sensitivity and 68% specificity in predicting left ventricular dysfunction in patients with stable MVCAD. In multivariate analysis, N/L ratio (OR: 2.456, <95% Cl 2.056-4.166; p<0.001) was an independent predictor of left ventricular dysfunction in stable patients with MVCAD. N/L ratio and hs-CRP, which is inexpensive and easily measurable in the laboratory, is independently associated with impaired LV systolic functions in patients with stable MVCAD.

OT1-02-12: Early Detection of Cardiotoxicity by Advanced Cardiac Imaging and a Novel Biomarker in Breast Cancer Patients Undergoing Chemotherapy.

Abstract Background The survival rate of breast cancer patients has increased due to improvements in cancer treatment. However, many survivors develop irreversible or reversible cardiotoxicity associated with anthracycline or trastuzumab therapy, respectively. To detect cardiac damage, the currently accepted method is to measure left ventricular ejection fraction (LVEF) by echocardiography, which lacks the sensitivity to predict early cardiac dysfunction. Early identification of cardiotoxicity is essential to cancer survivors, as development of cardiomyopathy carries a worse outcome independent of cancer prognosis. Currently, there are no accepted guidelines for the early detection of myocardial injury. The use of cardiac biomarkers and more sensitive echocardiographic techniques have expanded options for monitoring, but have yet to reach a consensus. Hence, our study will evaluate the potential predictive value of novel cardiac biomarkers and advanced echocardiographic and cardiac magnetic resonance imaging (CMR) techniques to detect subclinical myocardial damage. Our findings may be applicable for monitoring new antineoplastic agents during food and drug administration (FDA) clinical trials. Trial Design Prospective cohort study with internal control of 20 patients newly diagnosed with breast cancer. The trial will assess endpoints at baseline, 2 weeks after initiation of therapy, and 2 weeks and 6 months after chemotherapy completion. 1. Primary Endpoint a. Decline in left ventricular ejection fraction assessed by CMR and 3D-echo not detected by conventional methods b. Presence of either myocardial fibrosis or edema detected by CMR c. Changes in myocardial deformation detected by echo or CMR strain d. Increase in cardiac biomarkers (Serum caspase-3 p17 peptide, Troponin I, B-type natriuretic peptide) and possible correlation with imaging parameters 2. Secondary Endpoint a. Development New York Heart Association class 1 to 4 symptoms b. Decrease in LVEF of ≥5% to ≤50% with or without symptoms Eligibility Criteria Inclusion Criteria: 1. Newly diagnosed stage I, II, or III breast cancer 2. Age between 18 and 75 years old. 3. Treatment with trastuzumab or anthracycline-based chemotherapy Exclusion Criteria: 1. History of cardiovascular disease 2. Pacemaker 3. History of mediastinal radiotherapy 4. Creatinine clearance &amp;lt;30 ml/min 5. Serum bilirubin &amp;gt;2.0 mg/dl, ALT and AST &amp;gt; 100 U/1) 6. Hypertension, uncontrolled &amp;gt;140/90 7. LVEF &amp;lt;55% per 2-D echocardiogram 8. Claustrophobia Specific Aims 1. Detect early myocardial injury. 2. Evaluate early predictors of left ventricular dysfunction. 3. Evaluate timing of monitoring during or post treatment Statistical Method This is a pilot study and 20 patients are required to reach statistical significance with 85% power. All values will be analyzed as mean±SD or n (%). Categorical indicators will be analyzed using nonparametric statistics such as Cochran's Q. Changes in imaging and biomarker parameters will be assessed using analysis of variance, while correlation between the two will be assessed using mixed models appropriate for binary outcome. Significance will be accepted at p ≤0.05 for all tests. Present accrual and target accrual Nine subjects are enrolled with a goal of 20. Contact for people interested in trial: 1. Dr. Erick Avelar, eavelar@uchc.edu 2. Dr. Susan Tannenbaum, stannenbaum@uchc.edu Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-02-12.

Usefulness of NT-Pro-BNP and Echocardiography in the Diagnosis of Subclinical Clozapine-Related Cardiotoxicity

Available information regarding clozapine-related cardiomyopathy is limited to reports of severe left ventricular dysfunction not rarely with fatal clinical evolution. A subclinical cardiotoxic effect might be diagnosed using echocardiography and N-terminal pro-B-type natriuretic peptide assay. Thirty-eight patients with psychotic disorder in chronic therapy with clozapine (24 male and 14 female subjects; mean age, 38.4 years) were enrolled. Left ventricular ejection fraction (LVEF) was measured by area-length method (average of 5 measurements). Twelve patients showed a mild depression of left ventricular function (LVEF between 50% and 55%), 2 LVEF less than 50% and 1 less than 30%. The area under the receiver operating characteristic curve for N-terminal pro-B-type natriuretic peptide as a predictor of left ventricular dysfunction was 0.87. A subclinical left ventricular dysfunction was found in 3 of 38 patients, whereas a mild impairment of the left ventricular systolic function occurred in 1 of 3 of young, previously healthy, clozapine-treated patients A prospective study in clozapine-naive patients may be useful to better understand cardiotoxic effects of clozapine.

Predicting left ventricular dysfunction after valve repair for mitral regurgitation due to leaflet prolapse: additive value of left ventricular end-systolic dimension to ejection fraction

Left ventricular (LV) dysfunction is the first cause of late mortality after mitral valve surgery. In this retrospective analysis, we studied the association between preoperative echocardiographic LV measures and occurrence of LV dysfunction after mitral valve repair (MVR). Between 1991 and 2009, 335 consecutive patients underwent MVR for severe mitral regurgitation due to leaflet prolapse in our institution. Echocardiography was performed preoperatively and at 10.8 (9.1-12.0) months after surgery in 303 patients who represented the study population. Cardiac events were recorded during follow-up. LV ejection fraction (EF) decreased from 68 ± 9% before surgery to 59 ± 9% post-operatively (P < 0.001). Preoperative EF <64% and LV end-systolic diameter (ESD) ≥ 37 mm were the best cut-off values for the prediction of post-operative LV dysfunction (EF < 50%). On the basis of a combined analysis, the occurrence of post-operative LV dysfunction was 9% when EF was ≥ 64% and LVESD < 37 mm, 21% with EF < 64% or LVESD ≥ 37 mm, and 33% with EF < 64% and LVESD ≥ 37 mm (P for trend < 0.001). The combined variable EF < 64% and LVESD ≥ 37 mm added incremental prognostic value to the multivariable regression model (P = 0.001). Simple preoperative echocardiography measures allow the prediction of LV dysfunction after MVR in patients with leaflet prolapse. Patients with preoperative EF ≥ 64% and LVESD < 37 mm incur relatively low risk of post-operative LV dysfunction.