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Many of the patients undergoing chemotherapy or radiotherapy for cancer are at increased risk of developing cardiovascular diseases. Recent evidence suggests that cardiac dysfunction and subsequent heart failure are mainly due to vascular toxicity rather than only to due to myocyte toxicity. However, not all of the vascular toxicity of cancer therapies can be explained by epicardial coronary artery disease. In fact, in the last decades, it has been found that myocardial ischemia may occur as a consequence of structural or functional dysfunction of the complex network of vessels, which cannot be seen by a coronary angiography: the coronary microcirculation. Nowadays many diagnostic and therapeutic options are available both in coronary microvascular dysfunction and cardio-oncology. Aim of this review is to suggest future theranostic implications of the relationship between cardiotoxicity in oncology and coronary microvascular dysfunction, showing common pathophysiologic mechanisms, proposing new diagnostic approaches and therapeutic options for cardioprotection.

Cardiovascular magnetic resonance (CMR) has evolved from a pioneering research tool to an established noninvasive imaging method for detecting inducible myocardial perfusion deficits. In this consensus document, experts of different imaging techniques summarize the existing body of evidence regarding CMR perfusion as a viable complement to other established noninvasive tools for the assessment of perfusion and discuss the advantages and pitfalls of the technique. A rapid, standardized CMR perfusion protocol is described, which is safe, clinically feasible, and cost-effective for centers with contemporary magnetic resonance equipment. CMR perfusion can be recommended as a routine diagnostic tool to identify inducible myocardial ischemia.

Heart rate plays a major role in myocardial ischemia. A high heart rate increases myocardial performance and oxygen demand and reduces diastolic time. Ivabradine reduces heart rate by inhibiting the If current of sinoatrial-node cells. In contrast to beta-blockers, ivabradine has no negative inotropic and lusitropic effect for a comparable heart rate reduction. Consequently, diastolic duration is increased with ivabradine compared to beta-blockers. This has potential consequences on coronary blood flow since compression of the vasculature by the surrounding myocardium during systole impedes flow and coronary blood flow is mainly diastolic. Moreover, ivabradine does not unmask alpha-adrenergic vasoconstriction and, unlike beta-blockers, maintains coronary dilation during exercise. In comparison with beta-blockers, ivabradine increases coronary flow reserve and collateral perfusion promoting the development of coronary collaterals. Ivabradine attenuates myocardial ischemia and its consequences even in the absence of heart rate reduction, possibly through reduced formation of reactive oxygen species. In conclusion, ivabradine differs from other anti-anginal agents by improving coronary blood flow and by additional pleiotropic effects. These properties make ivabradine an effective anti-anginal and anti-ischemic agent for the treatment of patients with coronary artery disease.

Objective To assess the prevalence, characteristics and prognostic value of pulmonary hypertension (PH) and right ventricular dysfunction (RVD) in hospitalised, non-intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). Methods This single-centre, observational, cross-sectional study included 211 patients with COVID-19 admitted to non-ICU departments who underwent a single transthoracic echocardiography (TTE). Patients with poor acoustic window (n=11) were excluded. Clinical, imaging, laboratory and TTE findings were compared in patients with versus without PH (estimated systolic pulmonary artery pressure >35 mm Hg) and with versus without RVD (tricuspid annular plane systolic excursion

© 2018 Elsevier B.V. All rights reserved., Background:The cornerstone of the treatment of patients affected by stable angina is based on drugs administration classified as first (beta-blockers, calcium channel blockers, short acting nitrates) or second line treatment (long-acting nitrates, ivabradine, nicorandil, ranolazine and trimetazidine). However, few data on comparison between different classes of drugs justify that one class of drugs is superior to another.Methods:We performed a systematic review of the literature following PRISMA guidelines. Inclusion criteria:i) paper published in English; ii) diagnosis of stable coronary disease; iii) randomized clinical trial; iv) comparison of two anti-angina drugs; v) a sample size N 100 patients; vi) a follow-up lasting at least 2 weeks; vii) paper published after 1999, when a meta-analysis of trials comparing beta-blockers, calcium antagonists, and nitratesfor stable angina of Heidenreich et al. was published. Outcome: to establish whether the categorization in first and second line anti-anginal treatment is scientifically supported.Results:Eleven trials fulfilled inclusion criteria. The results show that there is a paucity of data comparing the efficacy of anti-anginal agents. The little data available show that there are not compounds superior to others in terms of improvement in exercise test duration, frequency of anginal attacks, need for sub-lingual nitroglycerin.Conclusion:The categorization of anti-anginal drug in first and second line is not confirmed.

Obstructive disease of the epicardial coronary arteries is the main cause of angina. However, a number of patients with anginal symptoms have normal coronaries or non-obstructive coronary artery disease (CAD) despite electrocardiographic evidence of ischaemia during stress testing. In addition to limited microvascular vasodilator capacity, the coronary microcirculation of these patients is particularly sensitive to vasoconstrictor stimuli, in a condition known as microvascular angina. This review briefly summarizes the determinants and control of coronary blood flow (CBF) and myocardial perfusion. It subsequently analyses the mechanisms responsible for transient myocardial ischaemia: obstructive CAD, coronary spasm and coronary microvascular dysfunction in the absence of epicardial coronary lesions, and variable combinations of structural anomalies, impaired endothelium-dependent and/or -independent vasodilation, and enhanced perception of pain. Lastly, we exemplify mechanism of angina during tachycardia. Distal to a coronary stenosis, coronary dilator reserve is already recruited and can be nearly exhausted at rest distal to a severe stenosis. Increased heart rate reduces the duration of diastole and thus CBF when metabolic vasodilation is no longer able to increase CBF. The increase in myocardial oxygen consumption and resulting metabolic vasodilation in adjacent myocardium without stenotic coronary arteries further acts to divert blood flow away from the post-stenotic coronary vascular bed through collaterals.

Persistence or recurrence of angina after a percutaneous coronary intervention (PCI) may affect about 20–40% of patients during short–medium-term follow-up. This appears to be true even when PCI is ‘optimized’ using physiology-guided approaches and drug-eluting stents. Importantly, persistent or recurrent angina post-PCI is associated with a significant economic burden. Healthcare costs may be almost two-fold higher among patients with persistent or recurrent angina post-PCI vs. those who become symptom-free. However, practice guideline recommendations regarding the management of patients with angina post-PCI are unclear. Gaps in evidence into the mechanisms of post-PCI angina are relevant, and more research seems warranted. The purpose of this document is to review potential mechanisms for the persistence or recurrence of angina post-PCI, propose a practical diagnostic algorithm, and summarize current knowledge gaps.

Atherosclerosis is one of the leading causes of death and disability worldwide. It is a complex disease characterized by lipid accumulation within the arterial wall, inflammation, local neoangiogenesis, and apoptosis. Innate immune effectors, in particular monocytes and macrophages, play a pivotal role in atherosclerosis initiation and progression. Although most of available evidence on the role of monocytes and macrophages in atherosclerosis is derived from animal studies, a growing body of evidence elucidating the role of these mononuclear cell subtypes in human atherosclerosis is currently accumulating. A novel pathogenic role of monocytes and macrophages in terms of atherosclerosis initiation and progression, in particular concerning the role of these cell subsets in neovascularization, has been discovered. The aim of the present article is to review currently available evidence on the role of monocytes and macrophages in human atherosclerosis and in relation to plaque characteristics, such as plaque neoangiogenesis, and patients’ prognosis and their potential role as biomarkers.

The presence of myocardial noncompaction (NC), regardless of the criterion used, does not identify cardiomyopathy per se. The distinction between a morphological variant and the presence of an NC cardiomyopathy is challenging. However, thanks to larger cohorts of patients and longer periods of follow-up, better clinical characterization and prognostic evaluation are becoming available. Indeed, the physician is required to integrate the evidence of NC with the clinical history of the patient, which is supplemented by necessary advanced instrumental investigations before a definite diagnosis of NC cardiomyopathy can be made. Therefore, we extensively revised the current literature in order to help the clinicians to identify clinical features which are pivotal supporting diagnostic element for the correct recognition of Left ventricular noncompaction cardiomyopathy and thus highlighting the difference between a form of cardiomyopathy and a mere intraventricular hypertrabeculation.

Purpose: The advent of hybrid positron emission tomography/magnetic resonance (PET/MR) systems has opened the gate to integrated multiparametric evaluation of patients with suspected cardiac sarcoidosis. The aim of the present paper is to systematically review all available literature to define the role of hybrid PET/MR in patients with confirmed or suspected cardiac sarcoidosis. Methods: The review strategy was developed following the PRISMA 2009 statement. An electronic database (Medline, Google Scholar, Clinical Trials.gov) search was conducted to identify articles on hybrid PET/MR in cardiac sarcoidosis. Only reports on hybrid PET/MR systems were considered. All PET tracers were considered. No date limitation was applied. Following duplicate removal, abstracts or full articles in case of case reports were screened for inclusion criteria. The full text of the remaining studies was reviewed. Results: Eleven studies were found, including seven case reports, two case series, and two diagnostic accuracy studies. All studies reported feasibility and interpretability of cardiac 18F-FDG PET/MR in cardiac sarcoidosis. The two case series demonstrated non-inferiority of PET/MR compared to PET/CT and, in fact, suggested greater sensitivity. Diagnostic accuracy studies showed satisfactory sensitivity and specificity of PET/MR to diagnose cardiac sarcoidosis. Two reports also showed the usefulness of cardiac PET/MR to assess response to treatment. Conclusion: Hybrid cardiac PET/MR is a valuable tool for the diagnosis of cardiac sarcoidosis. Moreover, as it offers activity and tissue characterisation, it can be used to tailor and monitor treatment.

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. Methods: This prospective study included 51 asymptomatic patients with carotid stenosis

Atherosclerotic disease of the epicardial coronary arteries has been accepted as the cause of angina pectoris for more than two hundred years while sudden, thrombotic occlusion of an epicardial coronary artery has been well established as the cause of myocardial infarction for more than one hundred years. However, the epicardial arteries, also known as conductance vessels, are only one segment of the arterial coronary circulation. These vessels give rise to smaller arteries and arterioles which in turn feed the capillaries and constitute the coronary microcirculation, the main site of regulation of myocardial blood flow. In the past two decades, a number of studies have demonstrated that abnormalities in the function and structure of the coronary microcirculation occur in many clinical conditions. In some instances these abnormalities represent epiphenomena, whereas in others they represent important markers of risk or may even contribute to the pathogenesis of myocardial ischaemia, thus becoming therapeutic targets.

Possible ethnic differences in clinical characteristics and long-term prognosis of contemporary patients with vasospastic angina (VSA) remain to be elucidated.The Japanese Coronary Spasm Association (JCSA) conducted an international, prospective, and multicenter registry study for VSA patients. A total of 1457 VSA patients (Japanese/Caucasians, 1339/118) were enrolled based on the same diagnostic criteria. Compared with Caucasian patients, Japanese patients were characterized by higher proportions of males (68 vs. 51%) and smoking history (60 vs. 49%). Japanese patients more often had angina especially during the night and early morning hours, compared with Caucasians. Ninety-five percent of Japanese and 84% of Caucasian patients underwent pharmacological provocation test. Importantly, no significant differences in the patterns of coronary spasm were apparent, with diffuse spasm most frequently noted in both ethnicities. The prescription rate of calcium-channel blockers was higher in Japanese (96 vs. 86%), whereas the uses of nitrates (46 vs. 59%), statins (43 vs. 65%), renin-angiotensin-system inhibitors (27 vs. 51%), and β-blockers (10 vs. 24%) were more common in Caucasian patients. Survival rate free from major adverse cardiac events (MACE) was slightly but significantly higher in Japanese than in Caucasians (86.7 vs. 76.6% at 5 years, P 0.001). Notably, multivariable analysis revealed that the JCSA risk score correlated with MACE rates not only in Japanese but also in Caucasian patients.These results indicate that there are ethnic differences in clinical profiles and long-term prognosis of contemporary VSA patients.

This study assessed the incidence of long-term adverse outcomes in patients with Takotsubo syndrome (TTS).The long-term prognosis of TTS is controversial. It is also unclear whether presenting characteristics are associated with the subsequent long-term prognosis.We searched the PubMed, Embase, and Cochrane databases and reviewed cited references up to March 31, 2018, to identify studies with6 months of follow-up data.Overall, we selected 54 studies that included a total of 4,679 patients (4,077 women and 602 men). Death during admission occurred in 112 patients (2.4%), yielding a frequency of 1.8% (95% confidence interval [CI]: 1.2% to 2.5%), with significant heterogeneity (IOur update analysis of patients discharged alive after TTS showed that long-term rates of overall mortality and recurrence were not trivial, and that some presenting features (older age, physical stressor, and atypical ballooning) were significantly associated with an unfavorable long-term prognosis.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018., Chronic stable angina is the most prevalent symptom of ischaemic heart disease and its management is a priority. Current guidelines recommend pharmacological therapy with drugs classified as being first line (beta blockers, calcium channel blockers, short acting nitrates) or second line (long-acting nitrates, ivabradine, nicorandil, ranolazine, and trimetazidine). Second line drugs are indicated for patients who have contraindications to first line agents, do not tolerate them or remain symptomatic. Evidence that one drug is superior to another has been questioned. Between January and March 2018, we performed a systematic review of articles written in English over the past 50 years English-written articles in Medline and Embase following preferred reporting items and the Cochrane collaboration approach. We included double blind randomized studies comparing parallel groups on treatment of angina in patients with stable coronary artery disease, with a sample size of, at least, 100 patients (50 patients per group), with a minimum follow-up of 1 week and an outcome measured on exercise testing, duration of exercise being the preferred outcome. Thirteen studies fulfilled our criteria. Nine studies involved between 100 and 300 patients, (2818 in total) and a further four enrolled greater than 300 patients. Evidence of equivalence was demonstrated for the use of beta-blockers (atenolol), calcium antagonists (amlodipine, nifedipine), and channel inhibitor (ivabradine) in three of these studies. Taken all together, in none of the studies was there evidence that one drug was superior to another in the treatment of angina or to prolong total exercise duration. There is a paucity of data comparing the efficacy of anti-anginal agents. The little available evidence shows that no anti-anginal drug is superior to another and equivalence has been shown only for three classes of drugs. Guidelines draw conclusions not from evidence but from clinical beliefs.

Background: There is controversy about the outcome of patients with acute myocarditis (AM), and data are lacking on how patients admitted with suspected AM are managed. We report characteristics, in-hospital management, and long-term outcome of patients with AM based on a retrospective multicenter registry from 19 Italian hospitals. Methods: A total of 684 patients with suspected AM and recent onset of symptoms (70 years of age and those >50 years of age without coronary angiography were excluded. The final study population comprised 443 patients (median age, 34 years; 19.4% female) with AM diagnosed by either endomyocardial biopsy or increased troponin plus edema and late gadolinium enhancement at cardiac magnetic resonance. Results: At presentation, 118 patients (26.6%) had left ventricular ejection fraction P P P =0.18). After a median time of 196 days, 200 patients had follow-up cardiac magnetic resonance, and 8 of 55 (14.5%) with complications at presentation had left ventricular ejection fraction Conclusions: In this contemporary study, overall serious adverse events after AM were lower than previously reported. However, patients with left ventricular ejection fraction

The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology

Coronary artery diseases and particularly acute myocardial infarction are the leading causes of mortality and morbidity in western countries. Despite the achievements of the last decades with the advent of double antiplatelet therapy, new antithrombotics and reperfusion strategies (either pharmacological or mechanical), many patients still have adverse cardiovascular events after ST-segment elevation acute myocardial infarction; at least some of these adverse events are related to the no reflow phenomenon that occurs after primary percutaneous coronary intervention. In our review we will discuss the various aspects of this phenomenon.

The growing discoveries coming from clinical and basic research during the past decades have revolutionized our knowledge regarding pathophysiologic mechanisms underlying the atherosclerotic process and its thrombotic complications.The traditional view focusing on the severity of stenosis of atherosclerotic plaque has given way to the evidence that the clinical complications of atherosclerotic vascular disease, particularly the propensity to develop thrombotic complications, are determined mainly by the biological composition of the plaque.This paradigm shift has reinforced the need to move from the sole anatomical assessment toward combined anatomic and functional imaging modalities enabling the molecular and cellular characterization of the disease on top of its structural properties.Together, the progress to identify molecular targets related to plaque vulnerability and the improvement of imaging techniques for the detection of such molecular targets have allowed us to obtain new important pathophysiological information.This might allow better patient stratification for the identification of subjects at high risk to develop premature atherosclerosis who might need an aggressive therapeutic approach.Nuclear techniques, magnetic resonance imaging, computed tomography angiography, and contrast-enhanced ultrasound represent the currently available non-invasive imaging modalities for molecular imaging which can provide different and complementary insights into the biological features of the atherosclerotic process. This clinical review will discuss the evidence and potential translational applications of the individual imaging techniques particularly concerning their ability to detect the main atherosclerotic features related to plaque vulnerability, such as plaque inflammation and intertwined neovascularization.

Alteration of circulating T-cell subpopulations may reflect the local immune process in plaques [(1)][1], providing insights on atherosclerosis pathogenesis. Only limited knowledge concerning the relationship between circulating lymphocytes and features of atherosclerotic lesions is available [(2

The European Union defines a rare disease as a condition that affects less than 5 in 10,000 of the general population. By this definition, there are between 6000 and 8000 known rare disorders that together affect 1 in 17 Europeans. For this reason, rare disorders are the subject of intense scrutiny by governments and healthcare organisations that are developing new systems for clinical care, research and patient involvement.

Unraveling the mechanisms underlying Takotsubo (TTS) leads to question the current inclusion of the condition within the spectrum of cardiomyopathies. Indeed, the clinical presentation and pathophysiology of TTS clearly differ from cardiomyopathies, i.e. diseases of heart muscle unexplained by abnormal loading conditions or coronary artery disease, which cannot recover spontaneously and may cause sudden death often in minimally symptomatic individuals or result in a gradual deterioration in ventricular function and end-stage heart failure. Furthermore, the term ‘cardiomyopathy’ can no longer be applied when functional or morphologic abnormalities of the coronary arteries leading to acute myocardial ischemia are deemed responsible for left ventricular (LV) systolic dysfunction. After 27 years of investigation, time has come to recognize that patients with TTS do suffer from severe myocardial ischemia and fulfill all criteria of acute coronary syndromes, i.e. acute chest pain, typical electrocardiographic changes, cardiac troponin rise, as well as LV wall motion abnormalities. Accordingly, we propose that TTS should be labeled as an acute ‘syndrome’ to be included more appropriately within the spectrum of ischemic heart disease. With regard to the term ‘stress’ it may imply that the catecholamine surge is essential to produce the typical transient myocardial injury. Thus, the terminology ‘Takotsubo (stress) syndrome’ would more accurately reflect recent advances in the pathophysiology.

Diseases affecting the brain contribute to a substantial proportion of morbidity and mortality in the general population. Conditions such as stroke, dementia and cognitive impairment have a prominent impact on global public health. Despite the heterogeneous clinical manifestations of these conditions and their diverse prognostic implications, current evidence supports a role for cardiovascular disease as a common pathophysiological ground. Brain white matter hyperintensities (WMH) are patchy white matter signal hyperintensity on T2-weighted magnetic resonance imaging sequences commonly found in elderly individuals. WMH appear to have a vascular pathogenesis and have been shown to confer an increased risk of stroke and cognitive decline. Indeed, they were proposed as a marker for central nervous system frailty. Cardiovascular diseases seem to play a key role in the etiology of WMH. Carotid atherosclerosis and atrial fibrillation were shown to be associated with higher WMH burden, while adequate blood pressure control has been reported reducing WMH progression. Aim of the present work is to review the available evidence linking WMH to cardiovascular disease, highlighting the complex interplay between cerebral and cardiovascular health.

Background and Aim Patients with Systemic Lupus Erythematosus (SLE) present increased cardiovascular mortality compared to the general population. Few studies have assessed the long-term development and progression of carotid atherosclerotic plaque in SLE patients. Our aim was to investigate the association of clinical and laboratory markers of disease activity and classical cardiovascular risk factors (CVRF) with carotid atherosclerosis development in SLE patients in a prospective 5-year study. Methods and results Clinical history and information on principal CVRFs were collected at baseline and after 5 years in 40 SLE patients (36 women, mean age 42 ± 9 years; 14.4 ± 7 years of mean disease duration) and 50 age-matched controls. Carotid Doppler ultrasonography was employed to quantify the atherosclerotic burden at baseline and at follow up. Clinimetrics were applied to assess SLE activity over time (SLEDAI). The association between basal circulating T cell subsets (including CD4+CCR5+; CD4+CXCR3+; CD4+HLADR+; CD4+CD45RA+RO−, CD4+CD45RO+RA− and their subsets) and atherosclerosis development was evaluated. During the 5-year follow up, 32% of SLE patients, developed carotid atherosclerosis compared to 4% of controls. Furthermore, considering SLEDAI changes over time, patients within the highest tertile were those with increased incidence of carotid atherosclerosis independently of CVRF. In addition, increased levels of CD4+CCR5+ T cells were independently associated with the development of carotid atherosclerosis in SLE patients. Conclusion Serial clinical evaluations over time, rather than a single point estimation of disease activity or CVRF burden, are required to define the risk of carotid atherosclerosis development in SLE patients. Specific T cell subsets are associated with long-term atherosclerotic progression and may further be of help in predicting vascular disease progression.

Background and aims Plaque border irregularity is a known imaging characteristic of vulnerable plaques, but its evaluation heavily relies on subjective evaluation and operator expertise. Aim of the present work is to propose a novel fractal-analysis based method for the quantification of atherosclerotic plaque border irregularity and assess its relation with cardiovascular risk factors. Methods and results Forty-two asymptomatic subjects with carotid stenosis underwent ultrasound evaluation and assessment of cardiovascular risk factors. Total, low-density lipoprotein (LDL), high-density lipoprotein (HDL) plasma cholesterol and triglycerides concentrations were measured for each subject. Fractal analysis was performed in all the carotid segments affected by atherosclerosis, i.e. 147 segments. The resulting fractal dimension (FD) is a measure of irregularity of plaque profile on long axis view of the plaque. FD in the severest stenosis (main plaque FD,mFD) was 1.136±0.039. Average FD per patient (global FD,gFD) was 1.145±0.039. FD was independent of other plaque characteristics. mFD significantly correlated with plasma HDL (r = -0.367,p = 0.02) and triglycerides-to-HDL ratio (r = 0.480,p = 0.002). Conclusions Fractal analysis is a novel, readily available, reproducible and inexpensive technique for the quantitative measurement of plaque irregularity. The correlation between low HDL levels and plaque FD suggests a role for HDL in the acquisition of morphologic features of plaque instability. Further studies are needed to validate the prognostic value of fractal analysis in carotid plaques evaluation.

Despite improvements in the treatment of acute myocardial infarction (MI), both long-term morbidity and mortality remain significant. It is therefore important to stratify patients’ prognosis in order to identify those at higher risk. Historically ST-segment resolution (STR) has been taken as a marker of effective reperfusion, especially in the era of thrombolysis. Thereafter angiographic criteria based on thrombolysis in myocardial infarction (TIMI) frame count and myocardial blush grade (MBG), have been introduced and are still the most common methods of assessment at the end of percutaneous revascularization procedures. Nowadays cardiac magnetic resonance (CMR) criteria have been developed and validated and represent the most sensitive and specific tool for the detection of microvascular obstruction (MVO) after MI. There is evidence that the prognostic value of CMR-based criteria offer superior sensitivity compared to those based on angiographic criteria.

We thank Drs Jin-shan and Xue-bin for their interest in our work. We cannot provide evidence-based answers to all their queries, and our replies reflect personal opinions or impressions based on our clinical practice. First, we believe that the larger proportion of females with fulminant myocarditis (FM) could be attributable to the presence of autoimmune disorders that are more frequently reported in women, and could contribute to more intense lymphocytic response to triggers (ie, transient viral infections). With regard to potential predictors of fulminant forms, …

Background The late sodium current inhibitor ranolazine reverses the main electrophysiological and mechanical abnormalities of human hypertrophic cardiomyopathy (HCM) cardiomyocytes in vitro, suggesting potential clinical benefit. We aimed to assess the effect of ranolazine on functional capacity, symptomatic status, diastolic function, and arrhythmias in HCM. Methods and Results In this multicenter, double-blind, phase 2 study, 80 adult patients with nonobstructive HCM (age 53±14 years, 34 women) were randomly assigned to placebo (n=40) or ranolazine 1000 mg bid (n=40) for 5 months. The primary end point was change in peak VO 2 compared with baseline using cardiopulmonary exercise test. Echocardiographic lateral and septal E/E′ ratio, prohormone brain natriuretic peptide levels, 24-hour Holter arrhythmic profile, and quality of life were assessed. Ranolazine was safe and well tolerated. Overall, there was no significant difference in VO 2 peak change at 5 months in the ranolazine versus placebo group (delta 0.15±3.96 versus −0.02±4.25 mL/kg per minute; P =0.832). Ranolazine treatment was associated with a reduction in 24-hour burden of premature ventricular complexes compared with placebo (>50% reduction versus baseline in 61% versus 31%, respectively; P =0.042). However, changes in prohormone brain natriuretic peptide levels did not differ in the ranolazine compared with the placebo group (geometric mean median [interquartile range], −3 pg/mL [−107, 142 pg/mL] versus 78 pg/mL [−71, 242 pg/mL]; P =0.251). Furthermore, E/E′ ratio and quality of life scores showed no significant difference. Conclusions In patients with nonobstructive HCM, ranolazine showed no overall effect on exercise performance, plasma prohormone brain natriuretic peptide levels, diastolic function, or quality of life. The drug showed an excellent safety profile and was associated with reduced premature ventricular complex burden. Late sodium current inhibition does not seem to improve functional capacity in HCM. Clinical Trial Registration: URL: https://www.clinicaltrialsregister.eu . Unique identifier: 2011-004507-20

Summary Far from being merely a passive cholesterol accumulation within the arterial wall, the development of atherosclerosis is currently known to imply both inflammation and immune effector mechanisms. Adaptive immunity has been implicated in the process of disease initiation and progression interwined with traditional cardiovascular risk factors. Although the body of knowledge regarding the correlation between atherosclerosis and immunity in humans is growing rapidly, a relevant proportion of it derives from studies carried out in animal models of cardiovascular disease (CVD). However, while the mouse is a well-suited model, the results obtained therein are not fully transferrable to the human setting due to intrinsic genomic and environmental differences. In the present review, we will discuss mainly human findings, obtained either by examination of post-mortem and surgical atherosclerotic material or through the analysis of the immunological profile of peripheral blood cells. In particular, we will discuss the findings supporting a pro-atherogenic role of T cell subsets, such as effector memory T cells or the potential protective function of regulatory T cells. Recent studies suggest that traditional T cell-driven B2 cell responses appear to be atherogenic, while innate B1 cells appear to exert a protective action through the secretion of naturally occurring antibodies. The insights into the immune pathogenesis of atherosclerosis can provide new targets in the quest for novel therapeutic targets to abate CVD morbidity and mortality.

Background: Neovascularization is a marker of plaque vulnerability that can be assessed noninvasively using contrast-enhanced ultrasound (CEUS). The presence and extent of plaque neovascularization and their relation to cardiovascular risk factors and treatments were assessed in asymptomatic patients with carotid stenosis of intermediate severity and no indication for revascularization. Methods: Sixty-six patients aged 69 ± 8 years (59% men) were prospectively enrolled. Plaque neovascularization was assessed using CEUS with sulfur hexafluoride contrast in each of the four carotid segments bilaterally (a total of 528 segments). In each plaque, the presence or absence of contrast enhancement was assessed semiquantitatively as CEUS grade 1 (no signal or signal confined to the adventitia and/or shoulder of the plaque) or CEUS grade 2 (signal within the plaque). Results: Plaques were detectable in 289 of 528 carotid segments (54.7%). CEUS grade 2 was present in at least one plaque in 48 of 66 patients (72.7%) and was not influenced by stenosis severity or morphology. The highest CEUS grade 2 prevalence was observed in patients with diabetes and the lowest in those treated with angiotensin-converting enzyme inhibitors and statins, especially when low-density lipoprotein cholesterol was

We wish to thank Drs Mewton and Croisille for their interest in our study1 and for their proactive comments. In our study, among the 31 patients with angiographic no reflow that represented 36% of the overall population, 18 had impaired thrombolysis in myocardial infarction flow …

Eosinophilic myocarditis (EM) is an acute life-threatening inflammatory disease of the heart. Neither large case series nor clinical trials on this specific myocarditis have been reported.Based on a systematic revision of all published histologically proven cases, this study aimed to describe the clinical presentation, treatment, and outcome of EM.The study screened 443 manuscripts in MEDLINE and EMBASE on cases of EM published until June 2017. The authors identified 264 patients and included in the main analysis 179 patients admitted to hospital with histologically proven EM.Median age was 41 years (interquartile range: 27 to 53 years) with similar prevalence in both sexes; pediatric cases (≤16 years of age) accounted for 10.1%. The main symptom at presentation was dyspnea (59.4%), with peripheral eosinophilia observed in 75.9%. Median left ventricular ejection fraction at presentation was 35% (interquartile range: 25% to 50%). The disorders most frequently associated with EM were hypersensitivity and eosinophilic granulomatosis with polyangiitis, which accounted for 34.1% and 12.8% of cases, respectively, whereas idiopathic or undefined forms accounted for 35.7% of cases. Steroids were administered in 77.7% of patients. A temporary mechanical circulatory support (n = 30) was instituted in 16.8% of patients. In-hospital death was 22.3% (n = 40), with the highest occurrence in the hypersensitivity form (36.1%; p = 0.026).EM has a poor prognosis during the acute phase, despite a publication bias that could have led to an overestimation of mortality. Associated conditions are identified in approximately 65% of cases. Specific trials and multicenter registries are needed to provide evidence-based treatments to improve in-hospital outcome.

A detailed questionnaire with instructions and examples was mailed to the presidents or designated delegates of the national societies of cardiology represented in the European Society of Cardiology. They distributed a copy of the questionnaire to all institutions performing diagnostic or interventional cardiac catheterizations in their respective countries. Upon completion the questionnaires were returned to the representatives to be compiled in a national summary data sheet. The summary data sheets were entered into a central database and subsequently analysed. No data were received from Cyprus and Ireland until entry closure. Sufficiently complete surveys were available from 29 countries representing more than 550 million people in Europe. The definitions of diseases and procedures were used according to previously published reports.