Lack of Correlations between Electrophysiological and Anatomical-Mechanical Atrial Remodeling in Patients with Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) progressively leads to electrical remodeling (ER) and anatomical-mechanical remodeling (AR), whose relationships in humans remain poorly known. METHODS: ER and AR were compared in patients undergoing percutaneous radiofrequency (RF) ablation for AF. ER was defined by right and left appendage activation rates as a surrogate for atrial refractory periods. AR was approached by left atrial (LA) diameters and area and left atrial appendage (LAA) area and contractile function (mean emptying flow velocity) (LAAFV) before RF ablation. Mean duration between successive LAA contractions was considered as LAA mechanical rate. RESULTS: Forty-one patients (31 men, age: 64 ± 9 years) with paroxysmal (27%), persistent (61%), or long-persistent AF (12%) were prospectively included (ejection fraction: 44 ± 16%). Parameters exploring AR were highly correlated to each other: LA area (28 ± 7 cm(2) ), LAA area (5.7 ± 2.25 cm(2) ), LA transverse (49 ± 7 mm), and anteroposterior diameter (59 ± 13 mm) or LAAFV (29 ± 13 cm/s; P < 0.05 for each comparison). Parameters exploring ER were also highly correlated: right atrial appendage (RAA; 181 ± 39 ms) and LAA (176 ± 33 ms) activation rates (P < 0.0001). There was no significant correlation between any ER and AR parameter. Only LAA mechanical rate (174 ± 36 ms) was correlated to LAA or RAA activations rates (P ≤ 0.01). CONCLUSION: ER and AR are not mutually related, atrial activation rate being not correlated to LA or LAA size or function. Thus, the mechanisms leading to AF-induced atrial remodeling may differ for anatomical and electrophysiological aspects.

Prediction of all-cause mortality from gated-SPECT global myocardial wall thickening: comparison with ejection fraction and global longitudinal 2D-strain.

BACKGROUND: The aim of this study was to assess the correlation between global wall thickening (GWT) obtained by gated-single photon emission computed tomography (SPECT) and echocardiographic measures [ejection fraction (EF), global longitudinal strain (GLS), and strain rate (GLSR)] and to compare their prognostic value for all-cause mortality. METHODS AND RESULTS: Seventy-four patients with referral for dipyridamole myocardial perfusion SPECT were prospectively included and underwent transthoracic echocardiography to measure left ventricular EF, GLS, and GLSR. The strongest correlation with GWT was for EF (R = 0.63, P < .001), followed by GLSR (R = -0.57, P < .001) and GLS (R = -0.53, P < .001). There were ten deaths over a period of 14.6 ± 5.7 months. Using the multivariate Cox analysis, summed stress score (HR 1.108; P = .023), EF (HR 1.01, P = .031), GLS (HR 1.593, P = .001), and GWT (HR 0.898, P = .034) remained independent predictors of mortality. Mean survival rate evaluated by Kaplan-Meier analysis was longer in patients with GWT ≥ 24% (21.9 ± 0.6 months) than those with GWT < 24% (13.6 ± 2.7 months; P < .001). CONCLUSIONS: GWT assessed is a highly sensitive tool to detect early myocardial systolic dysfunction and may bring additional prognostic information.

[Obesity and the prognosis of heart failure: the obesity paradox, myth or reality?]. / Obésité et Pronostic de l'insuffisance cardiaque: le paradoxe de l'obésité, mythe ou réalité?

Obesity has now reached epidemic proportions worldwide. Obesity is associated with numerous comorbidities, including hypertension, lipid disorders and type II diabetes, and is also a major cause of cardiovascular disease, coronary disease, heart failure, atrial fibrillation, and sudden death. Obesity is the main cause of heart failure in respectively 11% and 14% of cases in men and women. The Framingham study showed that, after correction for other risk factors, each point increase in the body mass index raises the risk of heart failure by 5% in men and 7% in women. Obesity increases the heart workload, causes left ventricular hypertrophy, and impairs both diastolic and systolic function. The most common form of heart failure is diastolic dysfunction, and heart failure in obese individuals is associated with preserved systolic function. Despite these comorbidities and the severity of heart failure, numerous studies have revealed an "obesity paradox" in which overweight and obese individuals with heart failure appear to have a better prognosis than non overweight subjects. This review summarizes the adverse cardiac effects of this nutritional disease, the results of some studies supporting the obesity paradox, the better survival rate of obese patients with heart failure. Potential explanations for these surprising data include the possibility that a number of obese patients may simply not have heart failure, as well as methodological bias, and protective effects of adipose tissue. Further studies of large populations are needed to determine how obesity may improve the prognosis of heart failure.

New concept of myocardial longitudinal strain reserve assessed by a dipyridamole infusion using 2D-strain echocardiography: the impact of diabetes and age, and the prognostic value.

AIMS: Although dipyridamole is a widely used pharmacological stress agent, the direct effects on myocardium are not entirely known. Diabetic cardiomyopathy can be investigated by 2D-strain echocardiography. The aim of this study was to assess myocardial functional reserve after dipyridamole infusion using speckle-tracking echocardiography. METHODS: Seventy-five patients referred for dipyridamole stress myocardial perfusion gated SPECT (MPGS) were examined by echocardiography to assess a new concept of longitudinal strain reserve (LSR) and longitudinal strain rate reserve (LSRR) respectively defined by the differences of global longitudinal strain (GLS) and longitudinal strain rate between peak stress after dipyridamole and rest. Twelve patients with myocardial ischemia were excluded on the basis of MPGS as gold standard. RESULTS: Mean LSR was -2.28±2.19% and was more important in the 28 (44%) diabetic patients (-3.27±1.93%; p=0.001). After multivariate analyses, only diabetes improved LSR (p=0.011) after dipyridamole infusion and was not associated with glycaemic control (p=0.21), insulin therapy (p=0.46) or duration of the disease (p=0.80). Conversely, age (p=0.002) remained associated with a decrease in LSR. LSSR was also correlated to age (p=0.005). Patients with a LSR<0% have a better survival after 15 months (log-rank p=0.0012). CONCLUSION: LSR explored by 2D speckle-tracking echocardiography after dipyridamole infusion is a simple and new concept that provides new insights into the impact of diabetes and age on the myocardium with a potential prognostic value.

Transseptal implantation of a left ventricular pacing lead for an ectopic location of the coronary sinus ostium in the left atrium.

Congenital abnormalities of the coronary sinus (CS) are rare but can be responsible for unsuccessful implantation of a cardiac resynchronization therapy device. We report the case of an ectopic drainage of the CS in the left atrium. A left ventricular lead was implanted by the transseptal route.

[Stress cardiomyopathy, a topical cardiac disorder]. / Les cardiomyopathies de stress, une pathologie cardiaque d'actualité.

Stress cardiomyopathy (Tako-Tsubo, Broken Heart syndrome, or apical ballooning syndrome) was recently recognized as a distinct clinical entity. The aims of this review are to define this acute and reversible cardiomyopathy and to list its major clinical, biological and angiographic features. We performed a Medline scan for all relevant case series. The studies thus identified suggest that the apical ballooning syndrome accounts for 2% of ST-elevation infarcts, mainly affects women, and occurs after major emotional or physical stress. Most patients present with chest pain and dyspnoea, cardiogenic shock and (or?) ventricular fibrillation. ST segment modifications and mildly elevated cardiac enzyme levels are reported in 81% of patients. Left ventricular dysfunction occurs in the absence of epicardial coronary artery obstruction and typically consists of a hyperkinetic basal region and an akinetic apical half of the ventricle. The in-hospital mortality rate is about 1.2%. Most patients recover fully after a few weeks. Norepinephrine concentrations are elevated in three-quarters of patients. This syndrome should be considered among the differential diagnoses in patients presenting with chest pain, and especially in post-menopausal women with a recent history of stress. In its broadest sense, this phenomenon may encompass a range of disorders, including left ventricular dysfunction following central nervous system injury. It should also be considered in women with acute coronary syndromes.

Real-time 3D transoesophageal echocardiography for guiding Amplatzer septal occluder device deployment in an adult patient with atrial septal defect.

A 32-year-old male with secundum atrial septal defect underwent percutaneous transcatheter occlusion. The procedure was performed under general anaesthesia and guided by real-time 3D transoesophageal echocardiography (TEE) (i.e. 33, matrix probe 2-7 MHz). The device delivery system was advanced through a femoral vein catheter and placed in the left upper pulmonary vein. A 3D left atrial view was instantaneously obtained. The size of the septal occluder was chosen according to the balloon catheter method. A 12 mm Amplatzer device was deployed under real-time 3D TEE without fluoroscopy. The 3D views depicted the progression of the left-side disc from the left atrial cavity towards the septum. Left and right atrial views demonstrated the perfect application of the device to the atrial septum. Keeping a steady traction on the delivery rod, the right-side disc of the device was then deployed on the right atrial side of the defect. A pushing and pulling of the delivery cable ensured that the device was in a secure and stable position. Absence of peri prosthetic residual shunt was assessed by 2D colour Doppler TEE before release. Transthoracic echocardiography performed the day after ensured the right position of the device. Real-time 3D TEE is a very recent technology allowing on-line guidance of atrial septal occluder device deployment; such imaging should increase delivery safety and decrease fluoroscopy time.

Increased mean aliphatic lipid chain length in left ventricular hypertrophy secondary to arterial hypertension: A cross-sectional study.

About 77.9 million (1 in 4) American adults have high blood pressure. High blood pressure is the primary cause of left ventricular hypertrophy (LVH), which represents a strong predictor of future heart failure and cardiovascular mortality. Previous studies have shown an altered metabolic profile in hypertensive patients with LVH. The goal of this study was to identify blood metabolomic LVH biomarkers by H NMR to provide novel diagnostic tools for rapid LVH detection in populations of hypertensive individuals. This cross-sectional study included 48 hypertensive patients with LVH matched with 48 hypertensive patients with normal LV size, and 24 healthy controls. Two-dimensional targeted M-mode echocardiography was performed to measure left ventricular mass index. Partial least squares discriminant analysis was used for the multivariate analysis of the H NMR spectral data. From the H NMR-based metabolomic profiling, signals coming from methylene (-CH2-) and methyl (-CH3) moieties of aliphatic chains from plasma lipids were identified as discriminant variables. The -CH2-/-CH3 ratio, an indicator of the mean length of the aliphatic lipid chains, was significantly higher (P < 0.001) in the LVH group than in the hypertensive group without LVH and controls. Receiver operating characteristic curve showed that a cutoff of 2.34 provided a 52.08% sensitivity and 85.42% specificity for discriminating LVH (AUC = 0.703, P-value < 0.001). We propose the -CH2-/-CH3 ratio from plasma aliphatic lipid chains as a biomarker for the diagnosis of left ventricular remodeling in hypertension.

QT dynamicity: a prognostic factor for sudden cardiac death in chronic heart failure.

INTRODUCTION: The aim of this study was to determine whether impaired adaptation of the QT interval to changes in heart rate predicts sudden death in patients with chronic heart failure (CHF). METHODS: We prospectively included 175 CHF patients in sinus rhythm. QT dynamicity was evaluated by analyzing 24-h Holter recordings. The linear regression slope of QT interval measured to the apex and to the end of T wave plotted against RR intervals was calculated using a dedicated Holter algorithm. RESULTS: Mean follow-up was 29.9+/-17.9 months. There were 48 deaths, of which 21 were sudden. The actuarial 3-year mortality rates were 38.4% for overall mortality and 14.1% for sudden death. Of all the parameters, an increased QTe/RR slope (>0.28) was the strongest independent predictor of sudden death (relative risk 3.47, 95% confidence interval 1.43-8.40, p=0.006). CONCLUSION: Increased 24-h QTe dynamicity is independently predictive of sudden death among patients with heart failure. This simple parameter may help to stratify risk and select patients who may benefit from antiarrhythmic prophylaxis.

Uncomplicated human obesity is associated with a specific cardiac transcriptome: involvement of the Wnt pathway.

A dramatic increase in obesity prevalence and cardiovascular morbidity is expected for the coming years. However, with relevance to the heart, little is known about the specific contribution of obesity on associated morbidity. Consequently, global analysis of gene regulations in human heart was undertaken to monitor molecular regulations related to obesity or to obesity-related hypertension. Transcriptome analysis using cDNA arrays was performed in right appendage biopsies from obese patients (n=5), from patients with arterial hypertension with (n=5) or without obesity (n=5), and from 5 leans. All biopsies came from patients that had cardiac surgery and coronary bypass. Statistical analysis of the data revealed 2686 differentially expressed genes out of 11,500 when compared with lean tissues. Differential expression was verified by real-time PCR in 84% of 50 randomly chosen genes. Among genes encountered, 397 were specifically regulated in obese, 1,299 in non-obese hypertensive, and 355 in obese hypertensive patients, respectively, whereas an additional set of 153 genes was differentially expressed in all these situations. Ontology analysis, hierarchical clustering, and molecular pathway analysis indicated that the heart molecular picture of obesity differs clearly from that observed for obesity-related hypertension or arterial hypertension. Clearly, the Wnt pathway known to be involved in cardiac hypertrophy mechanisms, showed opposite regulation in obese heart compared with hypertensive heart and potentially prevented the development of cardiac remodeling in obese patients. All over, this work shows that uncomplicated obesity has a strong impact on cardiac gene expression, which could be considered as precursor signs for future cardiac disease and also demonstrates that obesity-related hypertension generates a heart-molecular-distinct phenotype that cannot be predicted by a simple sum of the impact of obesity and arterial hypertension on gene expression.

Kinetic analysis of cardiac transcriptome regulation during chronic high-fat diet in dogs.

In the present study, we investigated, using custom dog cDNA arrays, the time course of transcriptional changes in the left ventricle of dogs fed a normal diet or a high-fat diet (HFD) for 9-24 wk. Array hybridizations were performed with complex probes representing mRNAs expressed in left ventricles from obese hypertensive and lean control dogs. We identified 63 differentially expressed genes, and expression of 17 of 20 randomly chosen genes was confirmed by real-time PCR. Transcripts were categorized into groups involved in metabolism, cell signaling, tissue remodeling, ionic regulation, cell proliferation, and protein synthesis. Hierarchical clustering indicated that the pattern of coregulated genes depends on duration of the HFD, suggesting that HFD-induced obesity hypertension is associated with continuous cardiac transcriptome adaptation despite stability of both body weight and blood pressure. GenMAPP analysis of the data pointed out the crucial importance of the ventricle TGF-beta pathway. Our results suggest that this system may be involved in molecular remodeling during HFD and in changes observed in the transcription profile, reflecting functional and morphological abnormalities that arise during prolonged HFD. These results also suggest some novel regulatory pathways for cardiac adaptation to obesity.

[Heart failure with preserved left ventricular function: clinical, echocardiographic, and clinical course features. Prognostic factors]. / L'insuffisance cardiaque à fonction ventriculaire systolique préservée: aspects cliniques, échocardiographiques et évolutifs. Facteurs du pronostic.

Heart failure is clinically associated with inadequate myocardial contraction, a significant reduction of left ventricular systolic function and ejection fraction and a cardiac enlargement. Some studies have reported that patients with symptomatic heart failure may have an impaired left ventricular filling with a normal or preserved left ventricular systolic function and an ejection fraction > 45%. These patients have a "diastolic heart failure" often neglected or misdiagnosed. The aims of our study is to describe clinical, echocardiographic and hemodynamic characteristics of 64 patients hospitalized for symptomatic heart failure, to determine possible variables with prognosis relevance, and for evaluating the severity of this diastolic left ventricular dysfunction. All patients were assessed by physical and radiographic examination, 12 leads electrocardiogram, and usual laboratory tests. The internal diameter of left atrium and left ventricular end diastolic and tele-systolic diameter were measured following the recommendations of the American Society of Echocardiography, Ejection fraction was determined following Simpson's method. Left ventricular filling patterns were evaluated by pulsed Doppler mitral or venous pulmonary flow. The following parameters were assessed: maximum velocity of E and A waves, E/A ratio, E wave deceleration time and isovolumic relaxation time. The patients were studied following Appleton's classification. 45 patients were submitted to left heart catheterization and coronary angiography. All subjects were routinely followed by cardiologic examinations and the mean follow up is 18 +/- 4, 5 months. 29 women (45.3%) and 35 men with a mean age of 72.5 +/- 3.2 years were included in this study. Left ventricular ejection fraction was in mean 48.5 +/- 4.2%. 65% of patients had ischemic cardiomyopathy with severe coronary stenosis > 50%, often associated with hypertension. 52% of patients had hypertensive heart disease and 38% were diabetics. 34 patients were re-hospitalized for recurrent heart failure despite medical treatment with diuretics, ACE inhibitors (90% of patients), beta-blockers, (37%) or nitrates (36%). 24 patients have been treated by coronary angioplasty. In hospital mortality was 6.2% and during the follow up at 18 months the mortality reaches 18.7%. The factors of poor prognosis are age > 75 years, left ventricular restrictive pattern at doppler diastolic trans mitral flow evaluation, (p < 0.001), history of myocardial infarction, and renal insufficiency defined by creatinemia > 150 micromoles (p = 0.002). In conclusion heart failure with preserved left systolic ventricular function is frequent in women with hypertensive heart disease. The prognosis at mean term is better that prognosis of patients with systolic dysfunction but despite medical treatment there is a high morbidity with numerous re hospitalizations. Restrictive left ventricular filling pattern is significantly related to the occurrence of events and mortality.

Metabonomics analysis of plasma reveals the lactate to cholesterol ratio as an independent prognostic factor of short-term mortality in acute heart failure.

OBJECTIVE: Mortality in heart failure (AHF) remains high, especially during the first days of hospitalization. New prognostic biomarkers may help to optimize treatment. The aim of the study was to determine metabolites that have a high prognostic value. METHODS: We conducted a prospective study on a training cohort of AHF patients (n = 126) admitted in the cardiac intensive care unit and assessed survival at 30 days. Venous plasmas collected at admission were used for (1)H NMR--based metabonomics analysis. Differences between plasma metabolite profiles allow determination of discriminating metabolites. A cohort of AHF patients was subsequently constituted (n = 74) to validate the findings. RESULTS: Lactate and cholesterol were the major discriminating metabolites predicting 30-day mortality. Mortality was increased in patients with high lactate and low total cholesterol concentrations at admission. Accuracies of lactate, cholesterol concentration and lactate to cholesterol (Lact/Chol) ratio to predict 30-day mortality were evaluated using ROC analysis. The Lact/Chol ratio provided the best accuracy with an AUC of 0.82 (P < 0.0001). The acute physiology and chronic health evaluation (APACHE) II scoring system provided an AUC of 0.76 for predicting 30-day mortality. APACHE II score, Cardiogenic shock (CS) state and Lact/Chol ratio ≥ 0.4 (cutoff value with 82% sensitivity and 64% specificity) were significant independent predictors of 30-day mortality with hazard ratios (HR) of 1.11, 4.77 and 3.59, respectively. In CS patients, the HR of 30-day mortality risk for plasma Lact/Chol ratio ≥ 0.4 was 3.26 compared to a Lact/Chol ratio of < 0.4 (P = 0.018). The predictive power of the Lact/Chol ratio for 30-day mortality outcome was confirmed with the independent validation cohort. CONCLUSION: This study identifies the plasma Lact/Chol ratio as a useful objective and simple parameter to evaluate short term prognostic and could be integrated into quantitative guidance for decision making in heart failure care.

Relation between left ventricular outflow tract obstruction and left ventricular shape in patients with hypertrophic cardiomyopathy: a cardiac magnetic resonance imaging study.

BACKGROUND: Hypertrophic cardiomyopathies (HCM) are often associated with left ventricular (LV) outflow tract obstruction, which can explain symptoms and impact prognosis. AIMS: To better understand the mechanisms that link obstruction and LV shape in HCM. METHODS: Patients with HCM who underwent cardiac magnetic resonance (CMR) imaging were included retrospectively. Obstructive HCM was defined as LV outflow gradient more than 30 mm Hg at rest by transthoracic echocardiography. The LV shape and mitral angle were assessed by CMR. Results were compared with control subjects. RESULTS: Mean LV-mitral angle was smaller in patients with obstructive HCM (n=29) than in patients with non-obstructive HCM (n=15) or control subjects (n=15) (80 ± 5° vs 87 ± 7° [P=0.0002] and 89 ± 2° [P<0.0001]). Mean mitral papillary muscles angle was greater in patients with non-obstructive HCM than in patients with obstructive HCM or control subjects (136 ± 17° vs 123 ± 16° [P=0.007] and 118 ± 10° [P=0.002]). Patients with non-obstructive HCM had a greater mean LV-aortic root angle than patients with obstructive HCM or control subjects (139 ± 6° vs 135 ± 7° [P=0.04] and 133 ± 7° [P=0.03]). CONCLUSION: There is a relation between morphological and functional parameters in HCM within which the mitral valve is probably part of pathophysiogenesis.

[Management of aortic dissection. Stent grafts for who?]. / Dissections aortiques aiguës non compliquées. Des stent-grafts pour qui?

Acute aortic syndrome (AAS) describes several life threatening aortic pathologies. Acute aortic syndrome include intramural haematoma, penetrating aortic ulcer and acute aortic dissection. Advances in both imaging and endovascular treatment has led to an increase in diagnosis and improved management of these often catastrophic pathologies. The current place of stent-grafts for the AAS management is defined on the basis of the most recent literature.

ST-segment changes after direct current external cardioversion for atrial fibrillation. Incidence, characteristics and predictive factors.

BACKGROUND: Incidence, characteristics and predictive factors of transient ST-segment changes after DC shock are poorly known. METHODS: 91 consecutive pts referred for external cardioversion of atrial fibrillation (AF) (61 men, 69±10 yo) were prospectively included. The presence of ST elevation or depression was assessed on 12 lead-ECG immediately after the first DC shock. Correlations with DC shock characteristics (monophasic/biphasic and energy), clinical variables, echocardiographic parameters, biological parameters, medications, anaesthetic drugs as well with morphological features were made. RESULTS: 18 and 20 pts underwent 200 J or 300 J monophasic and 53 pts 200 J biphasic DC shocks. We found an incidence of 48% for ST-segment changes: 35% for ST elevation and 13% for ST depression. ST changes did not induce significant cardiac events or alter AF recurrences. ST changes were not related to energy but ST elevation was significantly more often induced by monophasic (76% vs 6%, p<0.0001) and ST depression by biphasic DC shocks (26% vs 3%, p=0.01). Using multivariate analysis, independent predictors for ST elevation were the use of monophasic DC shocks, of propofol and increased CRP, while a low ejection fraction and use of biphasic DC shocks were independent predictors of ST depression. CONCLUSION: ST-segment changes after external cardioversion with DC shock are common, short living and do not carry clinical significance. They are related to the monophasic or biphasic configuration of DC shock, to the use of propofol, to the ejection fraction and to an increased CRP.

Blood signature of pre-heart failure: a microarrays study.

BACKGROUND: The preclinical stage of systolic heart failure (HF), known as asymptomatic left ventricular dysfunction (ALVD), is diagnosed only by echocardiography, frequent in the general population and leads to a high risk of developing severe HF. Large scale screening for ALVD is a difficult task and represents a major unmet clinical challenge that requires the determination of ALVD biomarkers. METHODOLOGY/PRINCIPAL FINDINGS: 294 individuals were screened by echocardiography. We identified 9 ALVD cases out of 128 subjects with cardiovascular risk factors. White blood cell gene expression profiling was performed using pangenomic microarrays. Data were analyzed using principal component analysis (PCA) and Significant Analysis of Microarrays (SAM). To build an ALVD classifier model, we used the nearest centroid classification method (NCCM) with the ClaNC software package. Classification performance was determined using the leave-one-out cross-validation method. Blood transcriptome analysis provided a specific molecular signature for ALVD which defined a model based on 7 genes capable of discriminating ALVD cases. Analysis of an ALVD patients validation group demonstrated that these genes are accurate diagnostic predictors for ALVD with 87% accuracy and 100% precision. Furthermore, Receiver Operating Characteristic curves of expression levels confirmed that 6 out of 7 genes discriminate for left ventricular dysfunction classification. CONCLUSIONS/SIGNIFICANCE: These targets could serve to enhance the ability to efficiently detect ALVD by general care practitioners to facilitate preemptive initiation of medical treatment preventing the development of HF.

ApoO, a novel apolipoprotein, is an original glycoprotein up-regulated by diabetes in human heart.

Obesity is an independent risk factor for cardiac failure. Obesity promotes excessive deposition of fat in adipose and nonadipose tissues. Intramyocardial lipid overload is a relatively common finding in nonischemic heart failure, especially in obese and diabetic patients, and promotes lipoapoptosis that contributes to the alteration of cardiac function. Lipoprotein production has been proposed as a heart-protective mechanism through the unloading of surplus cellular lipids. We previously analyzed the heart transcriptome in a dog nutritional model of obesity, and we identified a new apolipoprotein, regulated by obesity in heart, which is the subject of this study. We detected this new protein in the following lipoproteins: high density lipoprotein, low density lipoprotein, and very low density lipoprotein. We designated it apolipoprotein O. Apolipoprotein O is a 198-amino acid protein that contains a 23-amino acidlong signal peptide. The apolipoprotein O gene is expressed in a set of human tissues. Confocal immunofluorescence microscopy colocalized apolipoprotein O and perilipins, a cellular marker of the lipid droplet. Chondroitinase ABC deglycosylation analysis or cell incubation with p-nitrophenyl-beta-d-xyloside indicated that apolipoprotein O belongs to the proteoglycan family. Naringenin or CP-346086 treatments indicated that apolipoprotein O secretion requires microsomal triglyceride transfer protein activity. Apolipoprotein O gene expression is up-regulated in the human diabetic heart. Apolipoprotein O promoted cholesterol efflux from macrophage cells. To our knowledge, apolipoprotein O is the first chondroitin sulfate chain containing apolipoprotein. Apolipoprotein O may be involved in myocardium-protective mechanisms against lipid accumulation, or it may have specific properties mediated by its unique glycosylation pattern.