RNA-seq profiling reveals different pathways between remodeled vessels and myocardium in hypertrophic cardiomyopathy.

Objective: Coronary microvascular dysfunction (CMD) is a key pathophysiological feature of hypertrophic cardiomyopathy (HCM), contributing to myocardial ischemia and representing a critical determinant of patients' adverse outcome. The molecular mechanisms underlying the morphological and functional changes of CMD are still unknown. Aim of this study was to obtain insights on the molecular pathways associated with microvessel remodeling in HCM.

Myosins and MyomiR Network in Patients with Obstructive Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy. The molecular mechanisms determining HCM phenotypes are incompletely understood. Myocardial biopsies were obtained from a group of patients with obstructive HCM (n = 23) selected for surgical myectomy and from 9 unused donor hearts (controls).

Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy: An Expert Consensus Document.

Myocarditis is an inflammatory disease of the heart that may occur because of infections, immune system activation, or exposure to drugs. The diagnosis of myocarditis has changed due to the introduction of cardiac magnetic resonance imaging. We present an expert consensus document aimed to summarize the common terminology related to myocarditis meanwhile highlighting some areas of controversies and uncertainties and the unmet clinical needs.

Extent and characteristics of carotid plaques and brain parenchymal loss in asymptomatic patients with no indication for revascularization.

Background And Aims: Extent of subclinical atherosclerosis has been associated with brain parenchymal loss in community-dwelling aged subjects. Identification of patient-related and plaque-related markers could identify subjects at higher risk of brain atrophy, independent of cerebrovascular accidents. Aim of the study was to investigate the relation between extent and characteristics of carotid plaques and brain atrophy in asymptomatic patients with no indication for revascularization.

Mitochondrial Energetics and Ca2-Activated ATPase in Obstructive Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common genetic disease of the myocardium associated to mutations in sarcomeric genes, but the link between genotype and phenotype remains poorly understood. Magnetic resonance spectroscopy studies have demonstrated impaired cardiac energetics in patients with HCM, and altered mitochondria were described in biopsies, but little is known about possible perturbations of mitochondrial function and adenosine triphosphate (ATP) production/consumption. The aim of this study was to investigate possible abnormalities in mitochondrial enzymes generating/scavenging reactive oxygen species, and changes in the Ca-activated ATPases in myocardial tissue from patients with obstructive HCM undergoing surgical myectomy compared to unused donor hearts (CTRL).

Progression of brain white matter hyperintensities in asymptomatic patients with carotid atherosclerotic plaques and no indication for revascularization.

Background And Aims: Brain white matter hyperintensities (WMHs) have been associated with an increased risk of ischemic stroke and considered as markers of brain ischemia. Progression of WMHs in asymptomatic patients with non-hemodynamically significant carotid plaque could represent a putative marker of plaque vulnerability. We prospectively evaluate progression and determinants of WMHs in this population.

Carotid artery plaque uptake of C-PK11195 inversely correlates with circulating monocytes and classical CD14CD16 monocytes expressing HLA-DR.

Background: We explored the relation between blood concentrations of monocyte/lymphocyte subsets and carotid artery plaque macrophage content, measured by positron emission tomography (PET) with C-PK11195.

Methods And Results: In 9 patients with carotid plaques we performed C-PK11195-PET/computed tomography angiography imaging and measurement of absolute concentrations and frequencies of circulating monocytes and T-cell subsets. Plaque standardized uptake value (SUV) for C-PK11195 was negatively correlated with concentrations of total monocytes (r = -0.

Relation between characteristics of carotid atherosclerotic plaques and brain white matter hyperintensities in asymptomatic patients.

White matter hyperintensities (WMH) can be incidentally found in patients with carotid atherosclerosis on brain magnetic resonance imaging (MRI). We investigated the relationship between WMH and characteristics of carotid plaques in asymptomatic patients without indication for carotid revascularization. We prospectively screened 235 consecutive patients with carotid stenosis <70%.

Determinants of outcome in patients with chronic ischemic left ventricular dysfunction undergone percutaneous coronary interventions.

Background: Percutaneous coronary interventions (PCI) in patients with ischemic systolic left ventricular dysfunction (SLVD) are routinely performed although their impact on prognosis remains unclear.

Methods: We retrospectively evaluated 385 consecutive patients (76 % male, 66 ± 9 years) with SLVD (left ventricular ejection fraction [LVEF] ≤40 %) due to chronic coronary artery disease, who underwent PCI between 1999 and 2009, and explored clinical factors associated with higher risk of death or of a composite of death and hospitalization for acute decompensated heart failure (ADHF).

Results: The median follow-up was 28 months (inter-quartile range 14-46 months).

Non-invasive imaging of vascular inflammation.

In large-vessel vasculitides, inflammatory infiltrates may cause thickening of the involved arterial vessel wall leading to progressive stenosis and occlusion. Dilatation, aneurysm formation, and thrombosis may also ensue. Activated macrophages and T lymphocytes are fundamental elements in vascular inflammation.

Inflammation and microvascular dysfunction in cardiac syndrome X patients without conventional risk factors for coronary artery disease.

Objectives: The aim of this study was to ascertain whether coronary microvascular dysfunction (CMD) and inflammation are related in cardiac syndrome X (CSX).

Background: CMD can lead to CSX, defined as typical angina and transient myocardial ischemia despite normal coronary arteriograms. Inflammation has been suggested to play a role in the pathogenesis of myocardial ischemia in CSX.

Myocardial oxygenation in coronary artery disease: insights from blood oxygen level-dependent magnetic resonance imaging at 3 tesla.

Objectives: The purpose of this study was to assess the diagnostic accuracy of blood oxygen-level dependent (BOLD) MRI in suspected coronary artery disease (CAD).

Background: By exploiting the paramagnetic properties of deoxyhemoglobin, BOLD magnetic resonance imaging can detect myocardial ischemia. We applied BOLD imaging and first-pass perfusion techniques to: 1) examine the pathophysiological relationship between coronary stenosis, perfusion, ventricular scar, and myocardial oxygenation; and 2) evaluate the diagnostic performance of BOLD imaging in the clinical setting.

Non-invasive anatomic and functional imaging of vascular inflammation and unstable plaque.

Over the last several decades, basic cardiovascular research has significantly enhanced our understanding of pathobiological processes leading to formation, progression, and complications of atherosclerotic plaques. By harnessing these advances in cardiovascular biology, imaging has advanced beyond its traditional anatomical domains to a tool that permits probing of particular molecular structures to image cellular behaviour and metabolic pathways involved in atherosclerosis. From the nascent atherosclerotic plaque to the death of inflammatory cells, several potential molecular and micro-anatomical targets for imaging with particular selective imaging probes and with a variety of imaging modalities have emerged from preclinical and animal investigations.

[Revascularization of the hibernated myocardium: a clinical problem still unsolved].

The mid- and long-term outcome of revascularization procedures is still uncertain in patients with chronic left ventricular systolic dysfunction due to coronary artery disease. The identification of dysfunctional myocardial segments with residual viability that can improve after revascularization is pivotal for further patient management. Hibernating myocardium (chronically dysfunctional but still viable tissue) can be identified by positron emission tomography and cardiac magnetic resonance and its presence and extent can predict functional recovery after revascularization.

Imaging intraplaque inflammation in carotid atherosclerosis with 11C-PK11195 positron emission tomography/computed tomography.

Aims: We sought to determine whether intraplaque inflammation could be measured with positron emission tomography/computed tomography angiography (PET/CTA) using (11)C-PK11195, a selective ligand of the translocator protein (18 kDa) (TSPO) which is highly expressed by activated macrophages.

Methods And Results: Patients (n = 32; mean age 70 ± 9 years) with carotid stenoses (n = 36; 9 symptomatic and 27 asymptomatic) underwent (11)C-PK11195 PET/CTA imaging. (11)C-PK11195 uptake into carotid plaques was measured using target-to-background ratios (TBR).

The coronary circulation and blood flow in left ventricular hypertrophy.

Two distinct types of left ventricular hypertrophy (LVH) have been described: the so called "physiologic" hypertrophy, which is normally found in professional athletes, and "pathologic" LVH which is found in patients with inherited heart muscle disease such as hypertrophic cardiomyopathy (HCM) or patients with cardiac and systemic diseases characterized by pressure or volume overload. Patients with pathologic LVH have often symptoms and signs suggestive of myocardial ischemia despite normal coronary angiograms. Under these circumstances ischemia is due to coronary microvascular dysfunction (CMD).

Is there evidence supporting coronary revascularization in patients with left ventricular systolic dysfunction?

The mid- and long-term outcomes of revascularization procedures in patients with chronic left ventricular (LV) systolic dysfunction due to coronary artery disease (CAD) in the presence or absence of heart failure (HF) symptoms are still uncertain. The identification of dysfunctional myocardial segments with residual viability that can improve after revascularization is pivotal for further patient management. Hibernating myocardium (ie, chronically dysfunctional but still viable tissue) can be identified by positron emission tomography (PET) and cardiac magnetic resonance (CMR) and its presence and extent can predict functional recovery after revascularization.

Detection and quantification of large-vessel inflammation with 11C-(R)-PK11195 PET/CT.

Unlabelled: We investigated whether PET/CT angiography using 11C-(R)-PK11195, a selective ligand for the translocator protein (18 kDa) expressed in activated macrophages, could allow imaging and quantification of arterial wall inflammation in patients with large-vessel vasculitis.

Methods: Seven patients with systemic inflammatory disorders (3 symptomatic patients with clinical suspicion of active vasculitis and 4 asymptomatic patients) underwent PET with 11C-(R)-PK11195 and CT angiography to colocalize arterial wall uptake of 11C-(R)-PK11195. Tissue regions of interest were defined in bone marrow, lung parenchyma, wall of the ascending aorta, aortic arch, and descending aorta.

Assessment of myocardial ischaemia and viability: role of positron emission tomography.

In developed countries, coronary artery disease (CAD) continues to be a major cause of death and disability. Over the past two decades, positron emission tomography (PET) imaging has become more widely accessible for the management of ischemic heart disease. Positron emission tomography has also emerged as an important alternative perfusion imaging modality in the context of recent shortages of molybdenum-99/technetium-99m ((99m)Tc).

Imaging of vascular inflammation with [11C]-PK11195 and positron emission tomography/computed tomography angiography.

Objectives: We sought to investigate whether positron emission tomography/computed tomography (CT) angiography using [11C]-PK11195, a selective ligand for peripheral benzodiazepine receptors expressed in activated macrophages, can be used to image vascular inflammation.

Background: Activated macrophages and T lymphocytes are fundamental elements in the pathogenesis of large-vessel vasculitides.

Methods: Fifteen patients (age 52+/-16 years) with systemic inflammatory disorders (6 consecutive symptomatic patients with clinical suspicion of active vasculitis and 9 asymptomatic control patients) underwent positron emission tomography with [11C]-PK11195 and CT angiography.

Myocardial beta-adrenoceptor down-regulation early after infarction is associated with long-term incidence of congestive heart failure.

Aims: Adverse left ventricular (LV) remodelling after myocardial infarction (MI) frequently leads to congestive heart failure (CHF). We have previously shown that myocardial beta-adrenoceptor density (beta-ARD) is reduced soon after acute MI and correlates with LV dilatation in the short term. The aim of the present study was to determine whether myocardial beta-ARD measured early after MI was associated with progression to CHF in the long term.

Relationship between regional myocardial oxygenation and perfusion in patients with coronary artery disease: insights from cardiovascular magnetic resonance and positron emission tomography.

Background: It is recognized that the interplay between myocardial ischemia, perfusion, and oxygenation in the setting of coronary artery disease (CAD) is complex and that myocardial oxygenation and perfusion may become dissociated. Blood oxygen level-dependent (BOLD) cardiovascular magnetic resonance (CMR) has the potential to noninvasively measure myocardial oxygenation, whereas positron emission tomography (PET) with oxygen-15 labeled water is the gold standard technique for myocardial blood flow quantification. Thus, we sought to apply BOLD CMR at 3 T and oxygen-15-labeled water PET in patients with CAD and normal volunteers to better understand the relationship between regional myocardial oxygenation and blood flow during vasodilator stress.