Endothelial ILK induces cardioprotection by preventing coronary microvascular dysfunction and endothelial-to-mesenchymal transition.

Endothelial dysfunction is an early event in coronary microvascular disease. Integrin-linked kinase (ILK) prevents endothelial nitric oxide synthase (eNOS) uncoupling and, thus, endothelial dysfunction. However, the specific role of endothelial ILK in cardiac function remains to be fully elucidated. We hypothesised that endothelial ILK plays a crucial role in maintaining coronary microvascular function and contractile performance in the heart. We generated an endothelial cell-specific ILK conditional knock-out mouse (ecILK cKO) and investigated cardiovascular function. Coronary endothelial ILK deletion significantly impaired cardiac function: ejection fraction, fractional shortening and cardiac output decreased, whilst left ventricle diastolic internal diameter decreased and E/A and E/E' ratios increased, indicating not only systolic but also diastolic dysfunction. The functional data correlated with extensive extracellular matrix remodelling and perivascular fibrosis, indicative of adverse cardiac remodelling. Mice with endothelial ILK deletion suffered early ischaemic-like events with ST elevation and transient increases in cardiac troponins, which correlated with fibrotic remodelling. In addition, ecILK cKO mice exhibited many features of coronary microvascular disease: reduced cardiac perfusion, impaired coronary flow reserve and arterial remodelling with patent epicardial coronary arteries. Moreover, endothelial ILK deletion induced a moderate increase in blood pressure, but the antihypertensive drug Losartan did not affect microvascular remodelling whilst only partially ameliorated fibrotic remodelling. The plasma miRNA profile reveals endothelial-to-mesenchymal transition (endMT) as an upregulated pathway in endothelial ILK conditional KO mice. Our results show that endothelial cells in the microvasculature in endothelial ILK conditional KO mice underwent endMT. Moreover, endothelial cells isolated from these mice and ILK-silenced human microvascular endothelial cells underwent endMT, indicating that decreased endothelial ILK contributes directly to this endothelial phenotype shift. Our results identify ILK as a crucial regulator of microvascular endothelial homeostasis. Endothelial ILK prevents microvascular dysfunction and cardiac remodelling, contributing to the maintenance of the endothelial cell phenotype.

Statins and psoriasis: Position statement by the Psoriasis Task Force of the European Academy of Dermatology and Venerology.

BACKGROUND: Psoriasis is associated with an increased mortality risk, with cardiovascular disease being the leading excess cause (in a dose-response manner with psoriasis severity). Statins have demonstrated a reduction in all-cause mortality with no excess of adverse events among the general population. The underuse of interventions in cardiovascular prevention, such as statins, for patients with psoriasis may be the result of an insufficient evaluation. OBJECTIVES: To provide the dermatologist with a tool for systematizing the treatment of dyslipidemia in psoriasis, which generally escapes the scope of dermatological practice, and to facilitate decision-making about the referral and treatment of patients. METHODS: The Psoriasis Task Force of the European Academy of Dermatology and Venereology performed this two-phase study to achieve a consensus and create recommendations on the use of statin therapy in patients with psoriasis. The first phase included a systematic review to identify a list of outline concepts and recommendations according to guidelines. The second phase consisted in a two-round Delphi study to evaluate those recommendations not literally taken from guidelines. RESULTS: A list of 47 concepts and recommendations to be followed by dermatologists involved in the treatment of patients with moderate-severe psoriasis was created. It included six main concepts about cardiovascular risk and psoriasis, six items related with the role of low-density lipoprotein cholesterol (LDL-c) and the benefits of statin treatment in psoriasis patients, eight recommendations about how cardiovascular risk should be assessed, three on the role of non-invasive cardiovascular imaging, three on LDL-c thresholds, eight key points related to statin prescription, 10 on statin treatment follow-up and three on patient referral to another specialist. CONCLUSIONS: The application of this position statement (close final list of concepts and recommendations) will help dermatologists to manage dyslipidemia and help psoriasis patients to reduce their cardiovascular risk.

Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations.

Cancer and cardiovascular (CV) disease are the most prevalent diseases in the developed world. Evidence increasingly shows that these conditions are interlinked through common risk factors, coincident in an ageing population, and are connected biologically through some deleterious effects of anticancer treatment on CV health. Anticancer therapies can cause a wide spectrum of short- and long-term cardiotoxic effects. An explosion of novel cancer therapies has revolutionised this field and dramatically altered cancer prognosis. Nevertheless, these new therapies have introduced unexpected CV complications beyond heart failure. Common CV toxicities related to cancer therapy are defined, along with suggested strategies for prevention, detection and treatment. This ESMO consensus article proposes to define CV toxicities related to cancer or its therapies and provide guidance regarding prevention, screening, monitoring and treatment of CV toxicity. The majority of anticancer therapies are associated with some CV toxicity, ranging from asymptomatic and transient to more clinically significant and long-lasting cardiac events. It is critical however, that concerns about potential CV damage resulting from anticancer therapies should be weighed against the potential benefits of cancer therapy, including benefits in overall survival. CV disease in patients with cancer is complex and treatment needs to be individualised. The scope of cardio-oncology is wide and includes prevention, detection, monitoring and treatment of CV toxicity related to cancer therapy, and also ensuring the safe development of future novel cancer treatments that minimise the impact on CV health. It is anticipated that the management strategies discussed herein will be suitable for the majority of patients. Nonetheless, the clinical judgment of physicians remains extremely important; hence, when using these best clinical practices to inform treatment options and decisions, practitioners should also consider the individual circumstances of their patients on a case-by-case basis.

Oral anticoagulation and left atrial appendage closure: a new strategy for recurrent cardioembolic stroke.

BACKGROUND AND PURPOSE: There are no recommendations regarding how to treat cardioembolic recurrent strokes when patients are well anticoagulated. We evaluated the safety and efficacy of combining oral anticoagulation (OAC) with percutaneous left atrial appendage closure (LAAC) in patients with well-anticoagulated atrial fibrillation (AF) with recurrent strokes. METHODS: In an explorative, prospective, observational study, LAAC was performed in patients with AF with at least two ischaemic strokes in the previous year, despite good anticoagulation using the Amplatzer Cardiac Plug (St Jude Medical, St Paul, MN, USA) or Amulet Abbot device (Abbot Vascular, Santa Clara, CA, USA). We recorded age, type of AF, CHA2 DS2 -VASC and HAS-BLED scores, types of OAC and risk factors. After closure, treatment with aspirin (100 mg/day) was continued for 3 months in combination with indefinite OAC. Clinical status, recurrent embolisms and bleeding complications were recorded during follow-up. RESULTS: A total of 19 patients were included (mean age, 72.1 ± 9.6 years; mean CHA2 DS2 -VASC score, 5.3 ± 1.48; mean number of previous strokes, 2.78 ± 1.15). Thirteen had spontaneous echocardiographic contrast and all had dilatation of the left atrium. Eighteen patients had a multilobulated left atrial appendage, 17 with 'chicken-wing' morphology and one patient had a left atrial appendage thrombus. There were no complications during the procedure. Only one patient had a transient ischaemic attack and no major bleeding occurred during a mean follow-up of 17.4 ± 11.5 months. CONCLUSION: Combination therapy with indefinite OAC plus LAAC in patients with AF with recurrent strokes despite good anticoagulation should be considered in order to prevent a new stroke.

Recommendations for transoesophageal echocardiography: update 2010.

Transoesophageal echocardiography (TOE) is a standard and indispensable technique in clinical practice. The present recommendations represent an update and extension of the recommendations published in 2001 by the Working Group on Echocardiography of the European Society of Cardiology. New developments covered include technical advances such as 3D transoesophageal echo as well as developing applications such as transoesophageal echo in aortic valve repair and in valvular interventions, as well as a full section on perioperative TOE.

State of play and future direction with NOACs: An expert consensus.

Atrial fibrillation (AF) and venous thromboembolism (VTE) are cardiovascular conditions significant in contemporary practice. In both, the use of anticoagulation with vitamin K antagonists (VKAs) has been traditionally used to prevent adverse events. However, VKA therapy is associated with challenges relating to dose maintenance, the need to monitor anticoagulation, and bleeding risks. The non-vitamin K oral anticoagulants (NOACs) are becoming accepted as a clear alternative to VKA therapy for both AF and VTE management. The aim of this paper was to review contemporary evidence on the safety of NOACs in both conditions. A comprehensive literature review was conducted to explore key safety issues and expert consensus was achieved from eight professionals specialised in AF and VTE care. Consensus-based statements were formulated where available evidence was weak or contradictory. The expert statements in this paper form a key overview of the safety of NOACs compared with VKA therapy, and the comparative safety of different NOACs. It is apparent that a detailed patient work-up is required in order to identify and manage individual risk factors for bleeding and thrombosis prior to NOAC therapy. Additional measures, such as dose reductions, may also be used to maintain the safety of NOACs in practice.

Role of echocardiography in the assessment of mechanical dyssynchrony.

The aim of this paper is to summarize the current scientific evidence regarding the prognostic implications of mechanical asynchrony, the benefits of identifying mechanical asynchrony prior to cardiac resynchronization therapy by means of echocardiography to predict response to cardiac resynchronization therapy and the different described parameters for dyssynchrony evaluation and measurement.

Recommendations on managing lenvatinib and everolimus in patients with advanced or metastatic renal cell carcinoma.

INTRODUCTION: There are several second-line treatment options for patients with renal cell carcinoma after first-line failure of a tyrosine kinase inhibitor, especially with the recent approvals of cabozantinib, nivolumab, and the lenvatinib plus everolimus combination. A lack of reliable biomarkers and an overall lack of prospective head-to-head comparisons make it a challenge to choose a second-line treatment in the clinic. Areas covered: In this review/meta-opinion, we describe the safety profile of the lenvatinib plus everolimus combination in renal cell carcinoma. The combination of lenvatinib plus everolimus has achieved the highest rates of objective responses and the longest progression free and overall survival in cross-comparison trials. At the same time, the safety profile of this combination, including the rate of total and severe adverse events, the percentage of dose reductions required, and the rate of treatment discontinuation, was less favorable compared with available monotherapy options, suggesting that better management could help to maximize the activity of this combination while protecting patients from undue harm. Expert opinion: Herein, we aim to postulate multidisciplinary recommendations on the advice to offer to patients and caregivers before starting treatment and how to manage the combination from the perspective of daily clinical practice.

Identifying the needs for competency-based education in Europe: a needs assessment of cardiologists across 52 countries.

Objective: This international needs assessment was mandated by the European Society of Cardiology (ESC) to obtain an in-depth understanding of the current gaps and challenges of European cardiology professionals, with the aim to provide evidence for the development of needs-driven educational and professional development activities. Methods: This ethics-approved needs assessment was conducted among cardiologists from all sub-specialties across 56 countries of Europe and the Mediterranean basin. A mixed-methods research approach was used, combining qualitative in-depth interviews and focus groups with a quantitative survey. Results: Seventy-four (74) cardiologists participated in the qualitative phase and 866 completed the survey. Respondents represented 52 of the 56 targeted countries. Three themes were identified: 1) Challenges in the clinical decision-making process, 2) Challenges in establishing the patient-physician relationship, and 3) Sub-optimal team communication and collaboration. Specific gaps and causalities related to each challenge were found. Although most of the gaps were common across countries and sub-specialties, some significant differences were noted. Conclusion: The findings of this needs assessment indicate gaps and challenges in clinical practice across countries and across sub-specialities. Taking cardiology as an example, this study identifies clear areas of focus, especially around issues of collaboration and communication, for targeted competency-based education in Europe.

[Albuminuria and cardiovascular risk: basal results of the KORAL-CARDIO study]. / Albuminuria y riesgo cardiovascular. Estudio KORAL-CARDIO.

BACKGROUND AND OBJECTIVES: Albuminuria is a marker of higher cardiovascular and renal risk in hypertension; it also indicates the need of a tighter control of blood pressure with drugs blocking the renin-angiotensin system. The objective of the KORAL-CARDIO study was to assess the clinical picture and management of patients with hypertension and cardiac disease and albuminuria not previously treated with angiotensin inhibitors. METHODS: A total of 2711 hypertensive patients (44% female) with ischemic or hypertensive cardiopathy or atrial fibrillation and with a positive screening test for albuminuria was included. Type 2 diabetes was also present in 42%. RESULTS: Macroalbuminuria was present in 7.2% of non diabetic and 12.7% of diabetic patients, respectively. Associated complications were: 25% and 35% body mass index over 30 kg/m2; 22% and 39% ischemic heart disease; 4% and 8% stroke; 19% and 22% atrial fibrillation; 42% and 53% high cholesterol levels; 8% and 8% grade 3 hypertension, for non-diabetics and diabetics respectively. Antihypertensive monotherapy was used in 66% of non-diabetics and in 63% of diabetics; only 7% of patients in both groups were treated with triple antihypertensive therapy. CONCLUSIONS: Cardiovascular complications are very frequently associated to albuminuria in patients with hypertension and heart disease not previously treated with angiotensin inhibitors. Blood pressure control was clearly inadequate in this group.

Transesophageal echocardiography in right-sided endocarditis.

OBJECTIVES: Our aim was to determine the diagnostic value of transesophageal echocardiography in right-sided endocarditis. BACKGROUND: Recent studies have demonstrated that transesophageal echocardiography is superior to transthoracic echocardiography in the detection of vegetations associated with left-sided endocarditis. Its diagnostic value in right-sided endocarditis has not been established. METHODS: Transthoracic and transesophageal echocardiography were prospectively performed in 48 patients who met specific criteria for the suspicion of right-sided endocarditis. All were intravenous drug abusers. RESULTS: Vegetations were found in 22 of 48 patients by both transthoracic and transesophageal echocardiography. The vegetations were more precisely characterized by transesophageal echocardiography in 14 (63%) of 22 patients. In the remaining 26 patients, no vegetations were found by either transthoracic or transesophageal echocardiography. No statistically significant differences were found between the two techniques in the assessment of tricuspid regurgitation, which was detected in 21 (44%) of 48 patients. CONCLUSIONS: We conclude that transesophageal echocardiography does not improve the diagnostic accuracy of transthoracic echocardiography in the detection of vegetations associated with right-sided endocarditis in intravenous drug abusers. Transesophageal echocardiography may not be indicated as a routine procedure in patients suspected of having right-sided endocarditis.

[Effect of the use of echoenhancers on interobserver variability in dobutamine stress echocardiography]. / Influencia de la administración de ecopotenciadores sobre la variabilidad interobservador en la ecocardiografía de estrés con dobutamina.

INTRODUCTION: Dobutamine stress echocardiography is an accurate technique for the noninvasive diagnosis of coronary artery disease. However, interobserver variability is an important limitation of stress echocardiography. Image quality and echocardiographer experience have been described to influence interobserver agreement. AIM: The aim of this study was to determine whether use of contrast agents during dobutamine stress echocardiography improves the agreement between an experienced and a unexperienced observer, and if learning period would be influenced by the use of contrast. METHODS: Two blind observers interpreted all the studies: one experienced echocardiographer (A) and one unexperienced observer (B) in this technique. The contrast agent Levovist/Levograf 2.5 g was administered by two bolus (at rest and at peak stress). In all cases, second harmonic imaging and stress digitalisation packs were used. The kappa test was used to determine interobserver agreement. RESULTS: Fifty-two unselected consecutive studies in 51 patients were analyzed. Twenty-two studies were performed with contrast. The agreement between the experienced and the unexperienced observer was Kappa 0.58 and 0.52, with and without the use of contrast, with no statistically significant difference being archived. CONCLUSIONS: The routine use of contrast provides better although not significant, interobserver agreement. However, this improvement is not sufficient to substitute specific training.

[Multiple coronary aneurysms in a young man. A diagnostic approach via different technics]. / Aneurismas coronarios múltiples en un varón joven. Aproximación diagnóstica mediante diferentes técnicas.

Coronary aneurysms are uncommon. The most frequent etiologies are atherosclerotic and congenital, although there are several other rare causes. Myocardial infarction and sudden death may be the initial manifestations which are usually a consequence of aneurysm complications such as rupture or distal embolization. Although coronariography is the gold standard diagnostic technique, coronary aneurysm may also be detected by non-invasive methods such as ultrasonography and nuclear magnetic resonance. We report the case of a young male with hypercholesterolemia who presented cardiac arrest as the first clinical manifestation. Ultrasonography and MRI revealed the presence of multiple coronary aneurysm. This case illustrates the usefulness of non-invasive techniques for the diagnosis of coronary aneurysm.

[Intramyocardial dissection of the posterior wall of the left ventricle with shunt to coronary sinus after myocardial infarction]. / Disección intramiocárdica postinfarto de la pared posterior del ventrículo izquierdo con comunicación con el seno coronario.

A 83 year old diabetic woman was admitted to our hospital with the diagnosis of subacute inferoposterior myocardial infarction. Four days later physical examination revealed a new systolic murmur at the left sternal border and apex. Transthoracic echocardiogram showed inferoposterior akinesis and a dissection tract in the posterior wall of the left ventricle arising from the distal to mid-segment with an entrance tear of 7 mm. Doppler color showed a systolic jet with a mosaic flow pattern inside the right atrium which appeared to originate in the coronary sinus. Transesophageal echocardiogram confirmed the intramyocardial dissection of the posterior wall and its communication with the coronary sinus, and identified the latter as the origin of the mosaic flow inside the right atrium. Medical treatment was initiated and the patient has been followed up for two years. The diameter of the entrance tear remains unchanged although the dissection tract and coronary sinus have enlarged, no significant enlargement has been observed in the right chamber on follow up.

[The evaluation of the mechanism of mitral bioprosthesis malfunction by transesophageal echocardiography]. / Valoración del mecanismo de disfunción de las bioprótesis mitrales mediante ecocardiografía transesofágica.

OBJECTIVES: The aim of this study was to assess the usefulness of transesophageal echocardiography for detection of the mechanism of dysfunction in bioprosthetic valves in the mitral position. METHODS: Transthoracic and transesophageal echocardiograms were performed in 40 patients (mean age 61 +/- 12 years) with a dysfunctional bioprosthetic mitral valve. Echocardiographic results were compared to surgical findings in all except 1 patient. RESULTS: All 9 patients with stenotic degenerated bioprosthesis were diagnosed by transthoracic and transesophageal echocardiography. Mechanism of dysfunction in the remaining patients were as follows: cusp tear or rupture in 18, dehiscence in 4 and endocarditis in 6. Transthoracic and transesophageal echocardiography visualized respectively: 8 (44%) and 15 (83%; p < 0.05) with cusp tears or ruptures; 3 (75%) and 3 (75%) with dehiscence; 3 (50%) and 6 (100%; p < 0.1) with endocarditis. One patient with pannus formation and 1 of 2 bioprosthetic thrombosis were not correctly identified by either echocardiographic technique. CONCLUSIONS: Transesophageal echocardiography is suited for the assessment of mechanism of mitral regurgitation and for the diagnosis of vegetations in most of patients with bioprosthetic mitral valves. Transesophageal echocardiography adds little information to the transthoracic study in the evaluation of patients with stenotic bioprosthetic mitral valves, particularly in calcified degeneration.