Rapid Plaque Progression Is Independently Associated With Hyperglycemia and Low HDL Cholesterol in Patients With Stable Coronary Artery Disease: A PARADIGM Study.

BACKGROUND: We assessed whether combinations of cardiometabolic risk factors independently predict coronary plaque progression (PP) and major adverse cardiovascular events in patients with stable coronary artery disease. METHODS: Patients with known or suspected stable coronary artery disease (60.9±9.3 years, 55.4% male) undergoing serial coronary computed tomography angiographies (≥2 years apart), with clinical characterization and follow-up (N=1200), were analyzed from the PARADIGM study (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging). Plaque volumes measured in coronary segments (≥2 mm in diameter) were summed to provide whole heart plaque volume (mm3) and percent atheroma volume (plaque volume/vessel volume×100; %) per patient at baseline and follow-up. Rapid PP was defined as a percent atheroma volume increase of ≥1.0%/y. Major adverse cardiovascular events included nonfatal myocardial infarction, death, and unplanned coronary revascularization. RESULTS: In an interscan period of 3.2 years (interquartile range, 1.9), rapid PP occurred in 341 patients (28%). At multivariable analysis, the combination of cardiometabolic risk factors defined as metabolic syndrome predicted rapid PP (odds ratio, 1.51 [95% CI, 1.12-2.03]; P=0.007) together with older age, smoking habits, and baseline percent atheroma volume. Among single cardiometabolic variables, high fasting plasma glucose (diabetes or fasting plasma glucose >100 mg/dL) and low HDL-C (high-density lipoprotein cholesterol; <40 mg/dL in males and <50 mg/dL in females) were independently associated with rapid PP, in particular when combined (odds ratio, 2.37 [95% CI, 1.56-3.61]; P<0.001). In a follow-up of 8.23 years (interquartile range, 5.92-9.53), major adverse cardiovascular events occurred in 201 patients (17%). At multivariable Cox analysis, the combination of high fasting plasma glucose with high systemic blood pressure (treated hypertension or systemic blood pressure >130/85 mm Hg) was an independent predictor of events (hazard ratio, 1.79 [95% CI, 1.10-2.90]; P=0.018) together with family history, baseline percent atheroma volume, and rapid PP. CONCLUSIONS: In patients with stable coronary artery disease, the combination of hyperglycemia with low HDL-C is associated with rapid PP independently of other risk factors, baseline plaque burden, and treatment. The combination of hyperglycemia with high systemic blood pressure independently predicts the worse outcome beyond PP. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02803411.

Appropriateness criteria for the use of cardiac computed tomography, SIC-SIRM part 2: acute chest pain evaluation; stent and coronary artery bypass graft patency evaluation; planning of coronary revascularization and transcatheter valve procedures; cardiomyopathies, electrophysiological applications, cardiac masses, cardio-oncology and pericardial diseases evaluation.

In the past 20 years, cardiac computed tomography (CCT) has become a pivotal technique for the noninvasive diagnostic workup of coronary and cardiac diseases. Continuous technical and methodological improvements, combined with fast growing scientific evidence, have progressively expanded the clinical role of CCT. Randomized clinical trials documented the value of CCT in increasing the cost-effectiveness of the management of patients with acute chest pain presenting in the emergency department, also during the pandemic. Beyond the evaluation of stents and surgical graft patency, the anatomical and functional coronary imaging have the potential to guide treatment decision-making and planning for complex left main and three-vessel coronary disease. Furthermore, there has been an increasing demand to use CCT for preinterventional planning in minimally invasive procedures, such as transcatheter valve implantation and mitral valve repair. Yet, the use of CCT as a roadmap for tailored electrophysiological procedures has gained increasing importance to assure maximum success. In the meantime, innovations and advanced postprocessing tools have generated new potential applications of CCT from the simple coronary anatomy to the complete assessment of structural, functional and pathophysiological biomarkers of cardiac disease. In this complex and revolutionary scenario, it is urgently needed to provide an updated guide for the appropriate use of CCT in different clinical settings. This manuscript, endorsed by the Italian Society of Cardiology (SIC) and the Italian Society of Medical and Interventional Radiology (SIRM), represents the second of two consensus documents collecting the expert opinion of cardiologists and radiologists about current appropriate use of CCT.

SIRM-SIC appropriateness criteria for the use of Cardiac Computed Tomography. Part 1: Congenital heart diseases, primary prevention, risk assessment before surgery, suspected CAD in symptomatic patients, plaque and epicardial adipose tissue characterization, and functional assessment of stenosis.

In the past 20 years, Cardiac Computed Tomography (CCT) has become a pivotal technique for the noninvasive diagnostic work-up of coronary and cardiac diseases. Continuous technical and methodological improvements, combined with fast growing scientific evidence, have progressively expanded the clinical role of CCT. Recent large multicenter randomized clinical trials documented the high prognostic value of CCT and its capability to increase the cost-effectiveness of the management of patients with suspected CAD. In the meantime, CCT, initially perceived as a simple non-invasive technique for studying coronary anatomy, has transformed into a multiparametric "one-stop-shop" approach able to investigate the heart in a comprehensive way, including functional, structural and pathophysiological biomarkers. In this complex and revolutionary scenario, it is urgently needed to provide an updated guide for the appropriate use of CCT in different clinical settings. This manuscript, endorsed by the Italian Society of Medical and Interventional Radiology (SIRM) and by the Italian Society of Cardiology (SIC), represents the first of two consensus documents collecting the expert opinion of Radiologists and Cardiologists about current appropriate use of CCT.

PCSK9 and atherosclerosis: Looking beyond LDL regulation.

Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) is involved in cholesterol homeostasis. After binding to the complex low-density lipoprotein (LDL)-receptor, PCSK9 induces its intracellular degradation, thus reducing serum LDL clearance. In addition to the well-known activity on the hepatic LDL receptor-mediated pathway, PCSK9 has been, however, associated with vascular inflammation in atherogenesis. Indeed, PCSK9 is expressed by various cell types that are involved in atherosclerosis (e.g. endothelial cells, smooth muscle cells and macrophages) and is detected inside human atherosclerotic plaques. We here analyse the biology of PCSK9 and its possible involvement in molecular processes involved in atherosclerosis, beyond the regulation of circulating LDL cholesterol levels.

Variability of radiation doses of cardiac diagnostic imaging tests: the RADIO-EVINCI study (RADIationdOse subproject of the EVINCI study).

BACKGROUND: Patients with coronary artery disease can accumulate significant radiation dose through repeated exposures to coronary computed tomographic angiography, myocardial perfusion imaging with single photon emission computed tomography or positron emission tomography, and to invasive coronary angiography. Aim of the study was to audit radiation doses of coronary computed tomographic angiography, single photon emission computed tomography, positron emission tomography and invasive coronary angiography in patients enrolled in the prospective, randomized, multi-centre European study-EVINCI (Evaluation of Integrated Cardiac Imaging for the Detection and Characterization of Ischemic Heart Disease). METHODS: We reviewed 1070 tests (476 coronary computed tomographic angiographies, 85 positron emission tomographies, 310 single photon emission computed tomographies, 199 invasive coronary angiographies) performed in 476 patients (mean age 60 ± 9 years, 60% males) enrolled in 12 centers of the EVINCI. The effective doses were calculated in milli-Sievert (mSv) as median, interquartile range (IQR) and coefficient of variation of the mean. RESULTS: Coronary computed tomographic angiography (476 exams in 12 centers) median effective dose was 9.6 mSv (IQR = 13.2 mSv); single photon emission computed tomography (310 exams in 9 centers) effective dose was 9.3 (IQR = 2.8); positron emission tomography (85 in 3 centers) effective dose 1.8 (IQR = 1.6) and invasive coronary angiography (199 in 9 centers) effective dose 7.4 (IQR = 7.3). Inter-institutional variability was highest for invasive coronary angiography (100%) and coronary computed tomographic angiography (54%) and lowest for single photon emission computed tomography (20%). Intra-institutional variability was highest for invasive coronary angiography (121%) and coronary computed tomographic angiography (115%) and lowest for single photon emission computed tomography (14%). CONCLUSION: Coronary computed tomographic angiography and invasive coronary angiography doses vary substantially between and within centers. The variability in nuclear medicine procedures is substantially lower. The findings highlight the need to audit doses, to track cumulative exposures and to standardize doses for imaging techniques. TRIAL REGISTRATION: The study protocol is available at https://www.clinicaltrials.gov/ (ClinicalTrials.gov Identifier: NCT00979199 ). Information provided on September 16, 2009.

Comprehensive multi-modality imaging approach in arrhythmogenic cardiomyopathy-an expert consensus document of the European Association of Cardiovascular Imaging.

Arrhythmogenic cardiomyopathy (AC) is a progressive disease with high risk of life-threatening ventricular arrhythmias. A genetic mutation is found in up to 50-60% of probands, mostly affecting desmosomal genes. Diagnosis of AC is made by a combination of data from different modalities including imaging, electrocardiogram, Holter monitoring, family history, genetic testing, and tissue properties. Being a progressive cardiomyopathy, repeated cardiac imaging is needed in AC patients. Repeated imaging is important also for risk assessment of ventricular arrhythmias. This expert consensus document gives clinical recommendations for how to use multi-modality imaging in the different aspects of AC disease, including diagnosis, family screening, follow-up, risk assessment, and differential diagnosis.

HDL cholesterol, leptin and interleukin-6 predict high risk coronary anatomy assessed by CT angiography in patients with stable chest pain.

OBJECTIVES: Coronary computed tomography angiography (CTA) describes several features of coronary plaques, i.e. location, severity, and composition. Integrated CTA scores are able to identify individual patterns of higher risk. We sought to test whether circulating biomarkers related with metabolism and inflammation could predict high risk coronary anatomy at CTA in patients with stable chest pain. METHODS: We evaluated a panel of 17 biomarkers in 429 patients (60.3 ± 0.4 years, 268 males) with stable chest pain who underwent coronary CTA having been enrolled in the Evaluation of Integrated Cardiac Imaging (EVINCI) study. The individual CTA risk score was calculated combining plaque extent, severity, composition, and location. The presence and distribution of non-calcified, mixed and calcified plaques were analyzed in each patient. RESULTS: After adjustment for age, sex and medical treatment, high-density lipoprotein (HDL) cholesterol, leptin, and interleukin-6 (IL-6) were independent predictors of CTA risk score at multivariate analysis (P = 0.050, 0.002, and 0.007, respectively). Integrating these biomarkers with common clinical variables, a model was developed which showed a better discriminating ability than the Framingham Risk Score and the Euro-SCORE in identifying the patients with higher CTA risk score (area under the receiver-operating characteristics curve = 0.81, 0.63 and 0.71, respectively, P < 0.001). These three biomarkers were significantly altered in patients with mixed or non-calcified plaques. CONCLUSIONS: In patients with stable chest pain, low HDL cholesterol, low leptin and high IL-6 are independent predictors of high risk coronary anatomy as defined by an integrated CTA risk score.

Partial deletion of eNOS gene causes hyperinsulinemic state, unbalance of cardiac insulin signaling pathways and coronary dysfunction independently of high fat diet.

Abnormalities in eNOS gene, possibly interacting with high fat diet (HFD), affect peripheral vascular function and glucose metabolism. The relative role of eNOS gene, HFD and metabolic derangement on coronary function has not been fully elucidated. We test whether eNOS gene deficiency per se or in association with HFD modulates coronary function through mechanisms involving molecular pathways related to insulin signaling. Wild type (WT), eNOS-/- and eNOS+/- mice were studied. WT and eNOS+/- mice were fed with either standard or HF diet for 16 weeks and compared with standard diet fed eNOS-/-. Glucose and insulin tolerance tests were performed during the last week of diet. Coronary resistance (CR) was measured at baseline and during infusions of acetylcholine (Ach) or sodium-nitroprusside (SNP) to evaluate endothelium-dependent or independent vasodilation, in the Langendorff isolated hearts. Cardiac expression of Akt and ERK genes as evaluation of two major insulin-regulated signaling pathways involved in the control of vascular tone were assessed by western blot. HFD-fed mice developed an overt diabetic state. Conversely, chow-fed genetically modified mice (in particular eNOS-/-) showed a metabolic pattern characterized by normoglycemia and hyperinsulinemia with a limited degree of insulin resistance. CR was significantly higher in animals with eNOS gene deletions than in WT, independently of diet. Percent decrease in CR, during Ach infusion, was significantly lower in both eNOS-/- and eNOS+/- mice than in WT, independently of diet. SNP reduced CR in all groups except eNOS-/-. The cardiac ERK1-2/Akt ratio, increased in animals with eNOS gene deletions compared with WT, independently of diet. These results suggest that the eNOS genetic deficiency, associated or not with HFD, has a relevant effect on coronary vascular function, possibly mediated by increase in blood insulin levels and unbalance in insulin-dependent signaling in coronary vessels, consistent with a shift towards a vasoconstrictive pattern.

Effects of amlodipine and adenosine on coronary haemodynamics: in vivo study and numerical simulation.

Amlodipine (AMLO) is a calcium channel blocker with vasodilating properties, in which the specific effects on the coronary circulation are not fully known. Coronary flow velocity-pressure (F/P) curves were obtained at rest and during administration of AMLO (10 mg to 20 mg iv) or adenosine (ADO, 1 mg ic) in 10 normal subjects (six women, age 48 ± 14 years). F/P curves were reproduced in a numerical simulator of systemic and coronary circulations (CARDIOSIM(©)) by adjustment of coronary resistance ( > or < 100 µm diameter vessels) and extravascular resistance applied to smaller vessels at endocardial (ENDO), middle and epicardial (EPI) myocardial layers. Best matching of in silico to in vivo curves was achieved by trial and error approach. ADO induced 170% and 250% increase in coronary flow velocity CFV and F/P diastolic slope as compared to 80% and 25-30% increase induced by AMLO, respectively. In the cardiovascular model, AMLO effects were predicted by progressive reduction of>100 µm vessels resistance from EPI to ENDO. ADO effects were mimicked by reducing resistance of both>100 µm and < 100 µm vessels, progressively from EPI to ENDO in the latter. Additional reduction in extravascular resistance avoided to impose a transmural gradient of vasodilating effect for both drugs. Numerical simulation predicts vasodilating effects of AMLO mainly on larger arteries and of ADO on both>and < 100 µm vessels. In vivo F/P loops could be completely reproduced in silico by adding extravascular resistance reduction for both drugs. Numerical simulator is useful tool for exploring the coronary effects of cardioactive drugs.

Insulin resistance is a major determinant of myocardial blood flow impairment in anginal patients.

PURPOSE: In patients with chest pain, stress-induced myocardial perfusion abnormalities are often the result of depressed myocardial blood flow (MBF) reserve. We investigated the relative contribution of cardiovascular risk factors and coronary atherosclerosis to MBF abnormalities in anginal patients. METHODS: We studied 167 patients with typical (n = 100) or atypical (n = 67) chest pain who underwent quantitative evaluation of MBF by PET at rest and after dipyridamole infusion, and quantitative coronary angiography (invasive or by 64-slice CT). Patients with left ventricular (LV) dysfunction (ejection fraction <45 %) were excluded. Coronary atherosclerosis of ≥50 % was defined as obstructive. RESULTS: At rest median MBF was 0.60 ml min-1 g-1, and after dipyridamole infusion median MBF was 1.22 ml min-1 g-1. MBF reserve was <2 in 77 of 167 patients (46 %). Coronary atherosclerosis was present in 67 patients (40 %), 26 with obstructive disease. In a univariate analysis several variables were associated with reduced MBF at rest, including male gender, coronary atherosclerosis and elevated LV end-diastolic diameter, and during hyperaemia, including male gender, insulin resistance (IR), smoking habit, LV ejection fraction and end-diastolic diameter. In a multivariate analysis, after adjustment for LV function and for pharmacological treatments, male gender was the only independent predictor of reduced MBF at rest (P < 0.001), while male gender (P = 0.003), IR (P = 0.033) and coronary atherosclerosis (P < 0.001) remained the only independent predictors of reduced hyperaemic MBF. IR (P = 0.043) and coronary atherosclerosis (P = 0.005) were the only predictors of depressed MBF reserve. Coronary atherosclerosis, male gender and IR showed additive effects on hyperaemic MBF. CONCLUSION: In patients with chest pain and normal LV systolic function, IR, male gender and coronary atherosclerosis are independent and additive determinants of impaired hyperaemic MBF.

Surgical correction of left coronary artery origin from the right coronary artery.

We describe the case of a patient with limiting angina pectoris and anomalous origin of the left coronary artery from the right coronary artery, with a retroaortic course. Myocardial ischemia in the left anterior descending territory was documented by positron emission tomography, confirmed by fractional flow reserve, and relieved by surgical coronary reimplantation. This patient did not have coronary atherosclerosis or any other significant anatomic abnormality, such as myocardial bridging or compression between the aorta and the pulmonary artery. We attempt to describe the mechanisms of myocardial ischemia that contributed to the clinical manifestations in our patient.

Hybrid image visualization tool for 3D integration of CT coronary anatomy and quantitative myocardial perfusion PET.

PURPOSE: Multimodal cardiac imaging by CTA and quantitative PET enables acquisition of patient-specific coronary anatomy and absolute myocardial perfusion at rest and during stress. In the clinical setting, integration of this information is performed visually or using coronary arteries distribution models. We developed a new tool for CTA and quantitative PET integrated 3D visualization, exploiting XML and DICOM clinical standards. METHODS: The hybrid image tool (HIT) developed in the present study included four main modules: (1) volumetric registration for spatial matching of CTA and PET data sets, (2) an interface to PET quantitative analysis software, (3) a derived DICOM generator able to build DICOM data set from quantitative polar maps, and (4) a 3D visualization tool of integrated anatomical and quantitative flow information. The four modules incorporated in the HIT tool communicate by defined standard XML files: XML-transformation and XML MIST standards. RESULTS: The HIT tool implements a 3D representation of CTA showing real coronary anatomy fused to PET-derived quantitative myocardial blood flow distribution. The technique was validated on 16 data sets from EVINCI study population. The validation of the method confirmed the high matching between "original" and derived data sets as well as the accuracy of the registration procedure. CONCLUSIONS: Three-dimensional integration of patient- specific coronary artery anatomy provided by CTA and quantitative myocardial blood flow obtained from PET imaging can improve cardiac disease assessment. The HIT tool introduced in this paper may represent a significant advancement in the clinical use of this multimodal approach.

Placental stem cells pre-treated with a hyaluronan mixed ester of butyric and retinoic acid to cure infarcted pig hearts: a multimodal study.

AIMS: Pre-treating placenta-derived human mesenchymal stem cells (FMhMSCs) with a hyaluronan mixed ester of butyric and retinoic acid (HBR) potentiates their reparative capacity in rodent hearts. Our aim was to test FMhMSCs in a large-animal model by employing a novel combination of in vivo and ex vivo analyses. METHODS AND RESULTS: Matched regional quantifications of myocardial function and viability were performed by magnetic resonance imaging (MRI) and positron emission tomography (PET) 4 weeks after myocardial infarction combined with intramyocardial injection of FMhMSCs (n = 7), or HBR-pre-treated FMhMSCs (HBR-FMhMSCs, n = 6), or saline solution (PBS, n = 7). Sham-operated pigs (n = 4) were used as control animals. Despite no differences in the ejection fraction and haemodynamics, regional MRI revealed, in pigs treated with HBR-FMhMSCs compared with the other infarcted groups, a 40% smaller infarct scar size and a significant improvement of the end-systolic wall thickening and circumferential shortening of the infarct border zone. Consistently, PET showed that myocardial perfusion and glucose uptake were, respectively, 35 and 23% higher in the border zone of pigs treated with HBR-FMhMSCs compared with the other infarcted groups. Histology supported in vivo imaging; the delivery of HBR-FMhMSCs significantly enhanced capillary density and decreased fibrous tissue by approximately 68%. Moreover, proteomic analysis of the border zone in the HBR-FMhMSCs group and the FMhMSCs group indicated, respectively, 45 and 30% phenotypic homology with healthy tissue, while this homology was only 26% in the border zone of the PBS group. CONCLUSION: Our results support a more pronounced reparative potential of HBR-pre-treated FMhMSCs in a clinically relevant animal model of infarction and highlight the necessity of using combined diagnostic imaging to avoid underestimations of stem cell therapeutic effects in the heart.

Intramural myocardial hemorrhagic rupture in a patient with metastatic cancer and myocardial infarction.

A 77-year-old man with anterior ST-elevated myocardial infarction and lateral myocardial rupture underwent successful percutaneous revascularization. Cardiac magnetic resonance imaging (MRI) and positron emission tomography (PET) unveiled a disseminated metastatic cancer, likely responsible not only for a prothrombotic paraneoplastic syndrome but also for ventricular metastasis and myocardial rupture. The patient unfortunately died because of noncardiovascular complications of cancer.

[The mysterious case of an intracardiac mass]. / Il caso di una massa intra-cardiaca.

The authors describe the case of a 73-year old patient, with multiple cardiovascular risk factors and severe renal insufficiency, presenting with an intracardiac mass, as shown at echocardiography. Differential diagnosis and use of different imaging tests are discussed.

Coronary flow reserve in severe aortic valve stenosis: a positron emission tomography study.

OBJECTIVES: The purpose was to test whether, in patients with severe aortic stenosis, impaired myocardial blood flow reserve is dependent on myocardial hypertrophy and may improve after valve replacement. METHODS: Fifteen patients with severe aortic stenosis, normal coronary arteries and normal left ventricular systolic function (ejection fraction>50%) underwent a resting/dipyridamole (0.56 mg/kg over 4 min) N-NH3 flow positron emission tomography study and a resting 2D echocardiogram before and 12 months after (eight patients) surgery. Myocardial blood flow reserve was defined as dipyridamole/resting mean myocardial blood flow ratio. RESULTS: Before surgery, the transvalvular maximal pressure gradient was 86+/-19 mmHg, valve area 0.82+/-0.24 cm and left ventricular mass index 185+/-37 g/m. As compared with a positron emission tomography population of normal subjects, patients had a normal resting myocardial blood flow (1.02+/-0.34 vs. 1.04+/-0.22, not significant), a depressed dipyridamole myocardial blood flow (1.58+/-0.69 vs. 3.67+/-0.86, P<0.001) and myocardial blood flow reserve (1.54+/-0.39 vs. 3.63+/-0.97, P<0.001). After surgery, left ventricular mass index decreased (172+/-47 to 118+/-40, P<0.01) but no change was found in resting myocardial blood flow, dipyridamole myocardial blood flow and myocardial blood flow reserve. There was no correlation between flow values and pressure gradient or left ventricular mass index, before or after valve replacement and in pooled data from the two studies. CONCLUSION: In severe aortic stenosis, myocardial blood flow reserve is depressed independent of myocardial hypertrophy and transvalvular pressure gradient. Removal of pressure overload by valve replacement is not able to improve myocardial perfusion.

Beneficial effect of heme oxygenase-1 expression on myocardial ischemia-reperfusion involves an increase in adiponectin in mildly diabetic rats.

Transient reduction in coronary perfusion pressure in the isolated mouse heart increases microvascular resistance (paradoxical vasoconstriction) by an endothelium-mediated mechanism. To assess the presence and extent of paradoxical vasoconstriction in hearts from normal and diabetic rats and to determine whether increased heme oxygenase (HO)-1 expression and HO activity, using cobalt protoporphyrin (CoPP), attenuates coronary microvascular response, male Wistar rats were rendered diabetic with nicotinamide/streptozotocin for 2 wk and either CoPP or vehicle was administered by intraperitoneal injection weekly for 3 wk (0.5 mg/100 g body wt). The isolated beating nonworking heart was submitted to transient low perfusion pressure (20 mmHg), and coronary resistance (CR) was measured. During low perfusion pressure, CR increased and was associated with increased lactate release. In diabetic rats, CR was higher, HO-1 expression and endothelial nitric oxide synthase were downregulated, and inducible nitric oxide synthase and O(2)(-) were upregulated. After 3 wk of CoPP treatment, HO activity was significantly increased in the heart. Upregulation of HO-1 expression and HO activity by CoPP resulted in the abolition of paradoxical vasoconstriction and a reduction in oxidative ischemic damage. In addition, there was a marked increase in serum adiponectin. Elevated HO-1 expression was associated with increased expression of cardiac endothelial nitric oxide synthase, B-cell leukemia/lymphoma extra long, and phospho activator protein kinase levels and decreased levels of inducible nitric oxide synthase and malondialdehyde. These results suggest a critical role for HO-1 in microvascular tone control and myocardial protection during ischemia in both normal and mildly diabetic rats through the modulation of constitutive and inducible nitric oxide synthase expression and activity, and an increase in serum adiponectin.

Circulating heat shock proteins and inflammatory markers in patients with idiopathic left ventricular dysfunction: their relationships with myocardial and microvascular impairment.

Little information is available on peripheral levels of Hsp72, Hsp60, and anti-Hsp60 antibodies in patients with left ventricular (LV) dysfunction due to non-atherosclerotic cardiac disease. In this study, serum Hsp72, Hsp60 and anti-Hsp60 antibodies, IL-6, and C-reactive protein (CRP) were measured in 44 healthy controls and in 82 patients with angiographically normal coronary arteries (LV ejection fraction [EF] > or = 50%, n=22; -35% to <50%, n=32; <35%, n=28). Patients with more severe disease (more depressed myocardial blood flow at rest and during dipyridamole, indicative of coronary microvascular impairment) showed more elevated circulating Hsp60 and auto-antibodies, Hsp72, and CRP levels. IL-6 was increased progressively as a function of severity of LV dysfunction. Anti-Hsp60 antibodies, Hsp72, and IL-6 were significantly correlated with brain natriuretic peptide (BNP) levels and LV end-diastolic dimensions (LVEDD) values. IL-6 tended to be related with Hsp72 in particular in patients with more severe disease (r = 0.45, P = 0.021). Hsp60 and Hsp72 activation and inflammatory markers were correlated with the extent of cardiac and microvascular dysfunction in patients with angiographycally normal coronary arteries. These results suggest a pathogenic role of infective-metabolic insult and inflammatory reaction in the development of vascular and myocardial damage in patients with heart failure even in the absence of overt coronary artery disease.

Increased levels of C-type natriuretic peptide in patients with idiopathic left ventricular dysfunction.

C-type natriuretic peptide (CNP) is expressed in the vascular endothelium. It is not known whether CNP is specifically increased in patients with idiopathic left ventricular systolic dysfunction (ILVDys) with or without overt heart failure, and whether in these patients it is related with indicators of myocardial and/or endothelial/microvascular impairment. We determined plasma CNP levels in 51 ILVDys and in 60 controls. We observed a significant increase in patients with (7.0+/-0.9 pg/ml) or without (6.1+/-0.53 pg/ml) overt heart failure (p<0.001) in respect to controls (2.5+/-0.12 pg/ml). CNP was significantly correlated with LVEF (p<0.001), end-diastolic dimension (p<0.05), ANP (p<0.001) and BNP (p<0.001), interleukin-6 (p<0.001), total cholesterol (p<0.05), low-density lipoprotein (p=0.05), ratio total cholesterol/ high-density lipoprotein (p=0.05) and, in a subgroup of patients, with abnormal vasodilating capacity of the coronary microcirculation. In conclusion, CNP is activated in patients with LV dysfunction but without coronary artery disease, independently of the presence of overt heart failure and in tune with the extent of myocardial functional involvement. In these patients CNP is also related with both systemic and coronary indicators of endothelial/microvascular damage.