Embolic strokes of undetermined source: a clinical consensus statement of the ESC Council on Stroke, the European Association of Cardiovascular Imaging and the European Heart Rhythm Association of the ESC.

One in six ischaemic stroke patients has an embolic stroke of undetermined source (ESUS), defined as a stroke with unclear aetiology despite recommended diagnostic evaluation. The overall cardiovascular risk of ESUS is high and it is important to optimize strategies to prevent recurrent stroke and other cardiovascular events. The aim of clinicians when confronted with a patient not only with ESUS but also with any other medical condition of unclear aetiology is to identify the actual cause amongst a list of potential differential diagnoses, in order to optimize secondary prevention. However, specifically in ESUS, this may be challenging as multiple potential thromboembolic sources frequently coexist. Also, it can be delusively reassuring because despite the implementation of specific treatments for the individual pathology presumed to be the actual thromboembolic source, patients can still be vulnerable to stroke and other cardiovascular events caused by other pathologies already identified during the index diagnostic evaluation but whose thromboembolic potential was underestimated. Therefore, rather than trying to presume which particular mechanism is the actual embolic source in an ESUS patient, it is important to assess the overall thromboembolic risk of the patient through synthesis of the individual risks linked to all pathologies present, regardless if presumed causally associated or not. In this paper, a multi-disciplinary panel of clinicians/researchers from various backgrounds of expertise and specialties (cardiology, internal medicine, neurology, radiology and vascular surgery) proposes a comprehensive multi-dimensional assessment of the overall thromboembolic risk in ESUS patients through the composition of individual risks associated with all prevalent pathologies.

PSYChosomatic Medicine in ONcologIc and Cardiac Disease (PSYCHONIC) Study-A Retrospective and Prospective Observational Research Protocol.

Psychosocial factors play an important role in non-communicable diseases (NCDs). This observational study is primarily aimed at assessing the relationship of psychological characteristics of patients with the outcomes of different NCDs, and to assess short-term psychotherapy (STP) efficacy in the real world. Methods: One hundred and forty patients with recent acute myocardial infarction, Takotsubo syndrome, or non-metastatic breast cancer and a control group of 140 age and sex-matched healthy subjects, will be enrolled. All subjects will be administered psychometric tests, quality of life tests, a specific body perception questionnaire, a dream questionnaire, and a projective test, the Six Drawing test at baseline and follow-up. All subjects with medical conditions will be asked to freely choose between an ontopsychological STP along with standard medical therapy and, whenever indicated, rehabilitation therapy or medical therapy plus rehabilitation alone. The study endpoints will be to evaluate: the relationship of the psychological characteristics of enrolled subjects with the outcomes of different NCDs, predictors of the choice of psychotherapy, and the efficacy of ontopsychological intervention on psychological and medical outcomes. Conclusion: This study will generate data on distinctive psychological characteristics of patients suffering from different CDs and their relationship with medical outcomes, as well as explore the efficacy of ontopsychological STP in these patients in the real world. (Number of registration: NCT03437642).

Insertable cardiac monitor detection of silent atrial fibrillation in candidates for percutaneous patent foramen ovale closure.

AIM: An underlying atrial vulnerability or a preexisting misdiagnosed atrial fibrillation in some patients who are candidates for patent foramen ovale (PFO) closure may lead to an unnecessary percutaneous intervention. The aim of this work was to define paroxysmal atrial fibrillation rate, through a 6-month insertable loop-recorder monitoring, in patients over 55 years old with cryptogenic stroke and PFO. METHODS: PFO closure criteria: significant right-to-left shunt and at least one high-risk feature (permanent right-to-left shunt, atrial septal aneurysm, prominent Eustachian valve, recurrent brain ischemia, previous deep vein thrombosis, thrombophilia). Insertable cardiac monitoring criteria: previous cryptogenic stroke, more than 55 years and at least one atrial fibrillation risk factor (heart failure, hypertension, age older than 65 years, diabetes, atrial runs, left atrium dilatation, left ventricle hypertrophy, pulmonary disease, thyroid disease, obesity). Atrial fibrillation detection threshold: arrhythmia duration longer than 5 min. RESULTS: From January 2008 to March 2017, 195 patients underwent to loop-recorder monitoring. A total of 70 (36%) patients were candidates for PFO closure. The 6-month silent atrial fibrillation rate was 11.4%. In the arrhythmia-free cohort, 28 patients (45.2%) underwent percutaneous foramen ovale closure (group A) and 34 (54.8%) were medically treated (group B). Atrial fibrillation detection rate was 14.3% in group A and 0% in group B. The 36-month atrial fibrillation-free survival was 76%. CONCLUSION: An occult preexisting atrial fibrillation may lead to unnecessary percutaneous foramen ovale closure in a significant proportion of patients. A 6-month loop-recorder monitoring may improve the patient oriented decision-making.

Short-TErm Psychotherapy IN Acute Myocardial Infarction (STEP-IN-AMI) Trial: Final Results.

PURPOSE: The purpose of this research was to assess whether short-term psychotherapy enhances long-term clinical outcomes in patients with a recent acute myocardial infarction (AMI). METHODS: Patients ≤70 years old were randomized within 1 week of their AMI to short-term ontopsychological psychotherapy plus routine medical therapy vs routine medical therapy only. The primary composite outcome was defined as the combined incidence of new cardiovascular events (re-infarction, death, stroke, revascularization, life-threatening ventricular arrhythmias, and the recurrence of clinically significant angina) and clinically significant new comorbidities. Secondary outcome measures were: rates for individual components of the primary composite outcome; the rate of re-hospitalization for cardiovascular problems; and New York Heart Association functional class. RESULTS: Ninety-four patients were analyzed, translating into 425 patient-years. The 2 treatment groups were similar across baseline characteristics. At 5-year follow-up, psychotherapy patients had a lower incidence of primary outcome, relative to controls (77/223 vs 98/202 patient-years, respectively; P = .035; absolute risk reduction = 19%, number needed to treat = 8); this benefit was attributable to the lower incidence of new comorbidities and clinically significant angina in the psychotherapy group. Gains in the primary outcome, relative to controls, among psychotherapy patients occurred in the first year and subsequently remained stable over the following 4 years. CONCLUSIONS: Adding short-term ontopsychological psychotherapy to routine secondary prevention of myocardial infarction improves clinical outcomes overall up to 5 years post AMI. Studying time trends may aid in better targeting of psychological interventions during follow-up. Larger studies remain necessary to confirm these results. TRIAL REGISTRATION: www.ClinicalTrial.gov NCT00769366.

Residual SYNTAX score following coronary artery bypass grafting.

Objectives: To quantify residual coronary artery disease measured using the SYNTAX score (SS) and its relation to outcomes after coronary artery bypass grafting (CABG). Methods: We conducted a retrospective analysis on a consecutive series of 1608 patients [mean age 68 years, standard deviation (SD): 7, F:M, 242:1366] undergoing first-time isolated CABG from 2004 to 2015. The baseline SS was retrospectively determined from preoperative angiograms, and the residual SS (rSS) was measured during assessment of the actual operative report for each patient after CABG. Patients were then stratified according to tercile cut points of low (rSS low 0-11, N = 537), intermediate (rSS mid >11-18.5, N = 539) and high residual SS (rSS high >18.5, N = 532). The Cox regression model was used to investigate the impact of rSS on major adverse cardiac and cerebrovascular events (MACCE) at 1 year. Results: The mean preoperative SS was 26.6 (SD: 9.4) (range 10.1-53), and the residual SS after CABG was 15.3 (SD: 8.4) (range 0-34) ( P < 0.001 versus preoperative). At 1 year, cumulative incidence of MACCE in the low rSS was 1.5% ( N = 8/537), 4.5% ( N = 24/539) in the intermediate and 8.8% ( N = 47/532) in the high rSS group. Kaplan-Meier analysis showed a statistically significant difference of MACCE-free survival between the three groups (log-rank test, P < 0.001). The estimated MACCE-free survival rate at 1 year was 98.1% [standard error (SE): 1.6] for the rSS low , 95.5% (SE: 1.9) for the rSS mid , and 90.5% (SE: 1.3) for the rSS high group, respectively. After multivariable adjustment, the rSS high group was independently associated with a higher incidence of MACCE at 1 year (hazard ratio 1.92, 95% confidence interval 1.21-3.23) compared to the rSS low group. Conclusions: These unanticipated findings suggest that a residual SS may be a useful tool for risk stratification of patients undergoing isolated first-time CABG. Our study may set the stage for further investigations addressing this important clinical question.

Endothelial progenitor cells predict long-term prognosis in patients with stable angina treated with percutaneous coronary intervention: five-year follow-up of the PROCREATION study.

BACKGROUND: The association between endothelial progenitor cells (EPCs) at the time of percutaneous coronary intervention (PCI) and the subsequent long-term clinical outcome remains undefined. To address this issue, a pre-specified analysis of the PROgenitor Cells role in Restenosis and progression of coronary ATherosclerosis after percutaneous coronary intervention (PROCREATION) study was done. METHODS AND RESULTS: A total of 155 patients with stable angina treated with PCI had flow cytometry before PCI. Patients had a 5-year follow-up. Primary outcome was the composite of major adverse cardiac or cerebrovascular events (MACCE), that is, death, stroke, myocardial infarction, and revascularization. During follow-up, MACCE occurred in 65 of 155 patients (42%). There were no significant differences in clinical and angiographic variables between patients with or without MACCE, apart from a different extent of coronary atherosclerosis. The incidence of MACCE increased significantly over tertiles of CD34+/KDR+/CD45- cells and CD133+/KDR+/CD45- cells, with rates of 25%, 39%, and 69% (P=0.0001), and 26%, 44%, and 59% (P=0.003), respectively. On multivariate analysis it was estimated that the increase in CD34+/KDR+/CD45- cells was associated with a 35% higher risk for MACCE (hazard ratio [HR], 1.75; 95% confidence interval [CI]: 1.07-1.99; P=0.001), and the increase in CD133+/KDR+/CD45- cells was associated with a 25% higher risk for MACCE (HR, 1.35; 95% CI: 1.01-1.74; P=0.03). CONCLUSIONS: Assessment of subpopulations of circulating EPCs in patients with stable angina treated with PCI can improve characterization of long-term prognosis (ClinicalTrials.gov: NCT01575431).

[Secondary cardiovascular prevention after acute coronary syndrome in clinical practice]. / Prevenzione cardiovascolare secondaria dopo sindrome coronarica acuta nella pratica clinica.

Secondary prevention after acute coronary syndromes should be aimed at reducing the risk of further adverse cardiovascular events, thereby improving quality of life, and lengthening survival. Despite compelling evidence from large randomized controlled trials, secondary prevention is not fully implemented in most cases after hospitalization for acute coronary syndrome. The Lazio Region (Italy) has about 5.3 million inhabitants (9% of the entire Italian population). Every year about 11 000 patients are admitted for acute coronary syndrome in hospitals of the Lazio Region. Most of these patients receive state-of-the art acute medical and interventional care during hospitalization. However, observational data suggest that after discharge acute coronary syndrome patients are neither properly followed nor receive all evidence-based treatments. This consensus document has been developed by 11 Scientific Societies of Cardiovascular and Internal Medicine in order develop a sustainable and effective clinical approach for secondary cardiovascular prevention after acute coronary syndrome in the local scenario of the Lazio Region. An evidence-based simplified decalogue for secondary cardiovascular prevention is proposed as the cornerstone of clinical intervention, taking into account regional laws and relative shortage of resources. The following appropriate interventions should be consistently applied: smoking cessation, blood pressure control (blood pressure < 130/80 mmHg), optimal lipid management (LDL cholesterol < 80 mmHg), weight and diabetes management, promotion of physical activity and rehabilitation, correct use of antiplatelet agents, beta-blockers, renin-angiotensin-aldosterone system blockers.

Recovery of distal coronary flow reserve in LAD and LCx after Y-Graft intervention assessed by transthoracic echocardiography.

BACKGROUND: Y- graft (Y-G) is a graft formed by the Left Internal Mammary Artery (LIMA) connected to the Left Anterior Descending Artery (LAD) and by a free Right Internal Mammary Artery (RIMA) connected to LIMA and to a Marginal artery of Left Circumflex Artery (LCx). Aim of the work was to study the flow of this graft during a six months follow-up to assess whether the graft was able to meet the request of all the left coronary circulation, and to assess whether it could be done by evaluation of coronary flow reserve (CFR). METHODS: In 13 consecutive patients submitted to Y-G (13 men), CFR was measured in distal LAD and in distal LCx from 1 week after , every two months, up to six months after operation (a total of 8 tests for each patient) by means of transthoracic echocardiography (TTE) and Adenosine infusion (140 mcg/kg/min for 3-6 min). A Sequoia 256, Acuson-Siemens, was used. Contrast was used when necessary (Levovist 300 mg/ml solution at a rate of 0,5-1 ml/min). Max coronary flow diastolic velocity post-/pre-test > or =2 was considered normal CFR. RESULTS: Coronary arteriography revealed patency of both branches of Y-G after six months. Accuracy of TTE was 100% for LAD and 85% for LCx. Feasibility was 100% for LAD and 85% for LCx. CFR improved from baseline in LAD (2.21 +/- 0.5 to 2.6 +/- 0.5, p = 0.03) and in LCx (1.7 +/- 1 to 2.12 +/- 1, p = 0.05). CFR was under normal at baseline in 30% of patients vs 8% after six months in LAD (p = 0.027), and in 69% of patients vs 30% after six months in LCx (p = 0.066). CONCLUSION: CFR in Y-G is sometimes reduced in both left territories postoperatively but it improves at six months follow-up. A follow-up can be done non-invasively by TTE and CFR evaluation.

Endothelial progenitor cells in patients with coronary artery disease and left ventricular dysfunction.

OBJECTIVES: Endothelial progenitor cells (EPCs) play a key role in maintenance of endothelial integrity and postnatal neovascularization. We verified whether the number of subpopulations of EPCs is different in patients with coronary artery disease (CAD) and normal or impaired left ventricular (LV) function. METHODS: Sixty-eight consecutive patients (37 men, age 60+/-18 years) with CAD were studied. All patients underwent quantitative coronary angiography and flow cytometric analysis. RESULTS: Patients with LV ejection fraction <45% (n=22) were compared with those with normal function (n=46). The two groups had similar age, sex, cardiovascular risk factors, medical therapy, LV dimension, and number of diseased vessels. Patients with LV dysfunction, by study design, were more symptomatic and had a lower LV ejection fraction. The two groups had similar white cell count and mononuclear cells. The absolute number of CD34 and CD133 cells was significantly (P<0.05) higher in patients with LV dysfunction as compared with patients with normal function or healthy participants. In contrast, CD14 cells were significantly (P=0.005) lower in the former patients than in the latter, whereas no significant difference was noted in the number of cells positive for CD105 among groups. CONCLUSION: Subpopulations of EPCs have a discordant behavior in CAD patients with or without LV dysfunction, with cells positive for the endothelial markers CD34 and CD133 being increased and cells that promote vasculogenesis and microvascular development being significantly reduced.

Distal left circumflex coronary artery flow reserve recorded by transthoracic Doppler echocardiography: a comparison with Doppler-wire.

BACKGROUND: Coronary flow reserve (CFR) recording by means of transthoracic echocardiography (TTDE) in all the main distal coronary arteries is a challenge for advanced echocardiography. Validation studies of TTDE versus Doppler-wire (DW) recordings are available for Left Anterior Descending artery (LAD) and the Posterior Descending coronary artery (PD), but lacking for the more technically challenging Left Circumflex coronary artery (LCx). AIM: To evaluate the reliability of TTDE in assessing CFR in LCx when compared to the intracoronary Doppler flow-wire gold standard. METHODS: we evaluated 5 patients (age = 60 +/- 9 years, 5 males) on LCx by TTDE and invasive CFR assessment. TTDE recording was performed using a low-frequency probe, with a four-chamber as a guiding 2D view. The 2 tests were performed on different days and in random order within 48 hours in a blind fashion. Vasodilator stimulus was adenosine, intravenously (140 gamma/kg/min x 3-6 min) for TTDE and intracoronary (40 gamma bolus) for DW recordings. RESULTS: CFR values on LCx ranged from 1.9 to 2.8 for DW, and from 2.0 to 3.0 for TTDE, with an overall correlation of R = 0,85 (p = 0,06); normal (CFR > 2.5) or abnormal (CFR < 2.5) value was concordantly identified by the 2 techniques in 4 out 5 cases (80%). CONCLUSION: CFR of LCx artery can be obtained noninvasively with TTDE.

Virulent strains of Helicobacter pylori and vascular diseases: a meta-analysis.

BACKGROUND: Cytotoxin-associated gene A (CagA)-positive strains of Helicobacter pylori are an etiological factor for peptic ulcer and gastric cancer. Studies on the role of these virulent strains in vascular diseases yield conflicting results. METHODS: We searched the MEDLINE database for relevant studies. Meta-analysis was performed using the random effects method. RESULTS: We found 10 retrospective case-control studies (with 1527 case patients and 1661 control subjects) and 3 prospective cohort studies (with 701 case patients and 1439 control subjects) on CagA status and ischemic heart disease and 4 retrospective case-control studies (with 513 case patients and 590 control subjects) on CagA status and cerebral ischemia. In the case-control studies, an association of ischemic heart disease with CagA-positive strains (OR 1.87, 95% CI 1.46-2.40) but no significant association with CagA-negative strains (OR 1.15, 95% CI 0.83-1.60) has been found; in the 3 prospective studies, association with ischemic heart disease was weaker but still significant (OR 1.26, 95% CI 1.05-1.51). In the 4 case-control studies, CagA-positive strains were significantly associated with cerebral ischemia (OR 2.43, 95% CI 1.89-3.13), again with no association for CagA-negative strains. CONCLUSIONS: We found a small but significant association between vascular diseases and virulent CagA-positive strains of H. pylori. The lack of association with CagA-negative strains further supports the hypothesis of an independent relationship between virulent strains of H. pylori and vascular diseases. The magnitude of the association with cerebral ischemia needs to be confirmed by prospective studies.

New insights into molecular mechanisms of diffuse coronary ectasiae: a possible role for VEGF.

BACKGROUND: Diffuse coronary artery ectasiae (DCE) are occasionally found at necropsy or at angiography. Pathogenetic mechanisms of DCE are still poorly known. Matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs) and vascular endothelial growth factor (VEGF) are involved in vascular remodeling and may play a role in DCE. METHODS: A total of 1280 consecutive coronary angiograms performed in a single institution in 1 year were screened. DCE were found in 15 patients. Diagnosis at hospital admission was acute coronary syndromes in all of them. Two patients died during initial admission and 1 refused blood sampling; the remaining 12 patients were enrolled in the study. No patient with DCE exhibited coronary stenoses. Plasma levels of VEGF, MMP-2, TIMP-1, TIMP-2 and C-reactive protein (CRP) were measured in these 12 patients 12 months after discharge during a silent clinical phase, in 12 age- and sex-matched patients with stable angina (SA) and coronary artery disease, and in 12 age- and sex-matched patients with normal coronary arteries (NCA). RESULTS: VEGF levels were higher in patients with DCE than in SA or NCA (151.6 pg/ml [36.2-252.9] vs. 66.6 pg/ml [36.4-93.3] and 54.8 pg/ml [14.5-87.1], respectively, p = 0.012]. TIMP-2 levels were lower in DCE and SA than in NCA (5.9 ng/ml [0-33.6] and 5.0 [0-17.4] vs. 139.3 ng/ml [114.4-237.4], respectively, p < 0.001). TIMP-1 and MMP-2 plasma levels were similar in all groups (p = NS), and CRP levels were within normal limits (< 3 mg/L) in most patients, irrespective of their coronary anatomy (75% for DCE, 66% for SA, and 84% for NCA [p = NS]). CONCLUSIONS: Symptomatic patients with DCE typically present with an acute coronary syndrome and exhibit lack of obstructive stenosis at angiography, decreased plasma levels of TIMP-2 and raised plasma levels of VEGF. The simultaneous occurrence of reduced MMPs inhibition and increased angiogenetic activity suggests an accelerated and persistent extracellular matrix remodeling process favouring arterial remodeling and aneurysms formation which is likely to enhance the risk of thrombosis because of low shear stress.

A uncommon cause of angina during upper limb exercise.

Subclavian artery stenosis or occlusion may be a cause of myocardial ischemia in patients treated using an internal mammary artery graft. Subclavian stenosis may cause myocardial ischemia during arm exercise by a coronary-subclavian steal phenomenon, with flow inversion in the graft from the coronary tree to the left subclavian artery. We here describe a case of a patient developing left subclavian occlusion after coronary artery bypass grafting with the left internal mammary artery. The lesion was successfully treated with a carotid-subclavian bypass. The article underscores the importance of an early diagnosis (possibly before bypass surgery) and discusses possible treatments. Percutaneous interventions with stent implantation appear the treatment of choice, but surgery has an important role in case of total occlusion.