Profiling and validation of circulating microRNAs for cardiovascular events in patients presenting with ST-segment elevation myocardial infarction.

AIMS: MicroRNAs (miRNA) are important non-coding modulators controlling patterns of gene expression. However, profiling and validation of circulating miRNA levels related to adverse cardiovascular outcome has not been performed in patients with an acute coronary syndrome (ACS). METHODS AND RESULTS: In a multicentre, prospective ACS cohort, 1002 out of 2168 patients presented with ST-segment elevation myocardial infarction (STEMI). Sixty-three STEMI patients experienced an adjudicated major cardiovascular event (MACE, defined as cardiac death or recurrent myocardial infarction) within 1 year of follow-up. From a miRNA profiling in a matched derivation case-control cohort, 14 miRNAs were selected for validation. Comparing 63 cases vs. 126 controls, 3 miRNAs were significantly differentially abundant. In patients with MACE, miR-26b-5p levels (P = 0.038) were decreased, whereas miR-320a (P = 0.047) and miR-660-5p (P = 0.01) levels were increased. MiR-26b-5p has been suggested to prevent adverse cardiomyocyte hypertrophy, whereas miR-320a promotes cardiomyocyte death and apoptosis, and miR-660-5p has been related to active platelet production. This suggests that miR-26b-5p, miR-320a, and miR-660-5p may reflect alterations of different pathophysiological pathways involved in clinical outcome after ACS. Consistently, these three miRNAs reliably discriminated cases from controls [area under the receiver-operating characteristic curve (AUC) in age- and sex-adjusted Cox regression for miR-26b-5p = 0.707, miR-660-5p = 0.683, and miR-320a =0.672]. Combination of the three miRNAs further increased AUC to 0.718. Importantly, addition of the three miRNAs to both, the Global Registry of Acute Coronary Events (GRACE) score and a clinical model increased AUC from 0.679 to 0.720 and 0.722 to 0.732, respectively, with a net reclassification improvement of 0.20 in both cases. CONCLUSION: This is the first study performing profiling and validation of miRNAs that are associated with adverse cardiovascular outcome in patients with STEMI. MiR-26b-5p, miR-320a, and miR-660-5p discriminated for MACE and increased risk prediction when added to the GRACE score and a clinical model. These findings suggest that the release of specific miRNAs into circulation may reflect the activation of molecular pathways that impact on clinical outcome after STEMI.

[Cardiology update 2017]. / Cardiologie.

As usual, numerous papers published in 2017 contributed to optimize the management of patients in all clinical cardiologic fields. It is of course impossible to summarize them all in such an article. Subjects and papers were thus selected if they were thought to be particularly important for non-cardiologist physicians, especially general practitioners. The authors would also like to take the opportunity of this article to honor the memory of Pr Daniel Wagner who unfortunately passed away after less than six months at the head of our Cardiology Department. He was well recognized for his generosity as well as his clinical and scientific competence. This article is dedicated to him.

Comme à l'accoutumée, l'année 2017 a été marquée par la publication de nombreux travaux permettant d'optimaliser la prise en charge de nos patients dans tous les domaines de la cardiologie et il est évidemment impossible de les synthétiser ici de façon exhaustive. Nous avons donc sélectionné les sujets et les travaux qui nous ont paru les plus saillants et surtout les plus utiles pour nos collègues non cardiologues et particulièrement pour nos collègues médecins de premier recours. Cette revue de l'année 2017 ne serait toutefois pas complète sans un hommage au Pr Daniel Wagner qui a débuté son activité de chef du service de cardiologie du CHUV au 1er janvier et nous a quittés après seulement quelques mois passés parmi nous. Daniel fut un chef de service apprécié tant pour ses qualités humaines que pour ses compétences scientifiques et cliniques. Cet article lui est donc dédié.

[Cardiology update in 2016]. / Cardiologie.

In 2016 the European Society of Cardiology (ESC) published new guidelines. These documents update the knowledge in various fields such as atrial fibrillation, heart failure, cardiovascular prevention and dyslipidemia. Of course it is impossible to summarize these guidelines in detail. Nevertheless, we decided to highlight the major modifications, and to emphasize some key points that are especially useful for the primary care physician.

L'année 2016 en cardiologie a été marquée par la publication de nouvelles recommandations, par la Société européenne de cardiologie (ESC). Ces documents actualisent les connaissances dans des domaines variés que sont la fibrillation auriculaire, l'insuffisance cardiaque, la prévention cardiovasculaire et les dyslipidémies. Il est bien entendu impossible de synthétiser ces recommandations de façon exhaustive. Néanmoins, il nous a paru important de résumer les nouveautés majeures, mais également de rappeler certains points essentiels et surtout utiles pour le médecin de premier recours.

Prevalence and management of familial hypercholesterolaemia in patients with acute coronary syndromes.

AIMS: We aimed to assess the prevalence and management of clinical familial hypercholesterolaemia (FH) among patients with acute coronary syndrome (ACS). METHODS AND RESULTS: We studied 4778 patients with ACS from a multi-centre cohort study in Switzerland. Based on personal and familial history of premature cardiovascular disease and LDL-cholesterol levels, two validated algorithms for diagnosis of clinical FH were used: the Dutch Lipid Clinic Network algorithm to assess possible (score 3-5 points) or probable/definite FH (>5 points), and the Simon Broome Register algorithm to assess possible FH. At the time of hospitalization for ACS, 1.6% had probable/definite FH [95% confidence interval (CI) 1.3-2.0%, n = 78] and 17.8% possible FH (95% CI 16.8-18.9%, n = 852), respectively, according to the Dutch Lipid Clinic algorithm. The Simon Broome algorithm identified 5.4% (95% CI 4.8-6.1%, n = 259) patients with possible FH. Among 1451 young patients with premature ACS, the Dutch Lipid Clinic algorithm identified 70 (4.8%, 95% CI 3.8-6.1%) patients with probable/definite FH, and 684 (47.1%, 95% CI 44.6-49.7%) patients had possible FH. Excluding patients with secondary causes of dyslipidaemia such as alcohol consumption, acute renal failure, or hyperglycaemia did not change prevalence. One year after ACS, among 69 survivors with probable/definite FH and available follow-up information, 64.7% were using high-dose statins, 69.0% had decreased LDL-cholesterol from at least 50, and 4.6% had LDL-cholesterol ≤1.8 mmol/L. CONCLUSION: A phenotypic diagnosis of possible FH is common in patients hospitalized with ACS, particularly among those with premature ACS. Optimizing long-term lipid treatment of patients with FH after ACS is required.

[Approach to chronic mitral regurgitation in 2016]. / L' insuffisance mitrale: mise au point en 2016.

Mitral regurgitation (MR) is the most frequent valvular disease in industrialised countries. MR is classified as primary (mostly degenerative with valve prolapse) or secondary (mainly due to underlying ischemic heart disease resulting in deformation of the valve structure). Surgical repair represents the optimal treatment for severe primary MR, whereas the benefits of surgical correction of secondary MR are controversial. Over the past few years, transcatheter techniques have been developed to treat MR, such as the percutaneous edge-to-edge procedure (MitraClip). These approaches represent a novel therapeutic choice for patients judged inoperable by the "heart team". This review article aims to summarize the principles of MR assessment and discuss current therapeutic options for severe MR, taking into account the latest advances in the field.

[Cardiology update in 2015]. / Cardiologie.

The present review provides a selected choice of clinical trials and therapeutic advances in the field of cardiology in 2015. A new treatment option in heart failure will become available this year in Switzerland. In interventional cardiology, new trials have been published on the duration of dual antiplatelet therapy, the new stents with bioresorbable scaffold and the long-term results of TAVR in patients who are not surgical candidates or at high surgical risk. RegardingAF the BRIDGE trial provides new evidences to guide the management of patients during warfarin interruption for surgery. Recent publications are changing the paradigm of AF treatment by showing a major impact of the management of cardiometabolic risk factors. Finally, refined criteria for ECG interpretation in athletes have been recently proposed to reduce the burden of false-positive screening.

Low statin use in adults hospitalized with acute coronary syndrome.

OBJECTIVE: To assess recommended and actual use of statins in primary prevention of cardiovascular disease (CVD) based on clinical prediction scores in adults who develop their first acute coronary syndrome (ACS). METHOD: Cross-sectional study of 3172 adults without previous CVD hospitalized with ACS at 4 university centers in Switzerland. The number of participants eligible for statins before hospitalization was estimated based on the European Society of Cardiology (ESC) guidelines and compared to the observed number of participants on statins at hospital entry. RESULTS: Overall, 1171 (37%) participants were classified as high-risk (10-year risk of cardiovascular mortality ≥5% or diabetes); 1025 (32%) as intermediate risk (10-year risk <5% but ≥1%); and 976 (31%) as low risk (10-year risk <1%). Before hospitalization, 516 (16%) were on statins; among high-risk participants, only 236 of 1171 (20%) were on statins. If ESC primary prevention guidelines had been fully implemented, an additional 845 high-risk adults (27% of the whole sample) would have been eligible for statins before hospitalization. CONCLUSION: Although statins are recommended for primary prevention in high-risk adults, only one-fifth of them are on statins when hospitalized for a first ACS.

[Cardiology update in 2014]. / Cardiologie.

Important clinical trials and therapeutic advances in the field of cardiology have been presented in 2014. New evidences on the management of acute myocardial infarction and the duration of dual antiplatelet therapy after coronary stent implantation have been published. A new class of therapeutic agents seems to offer promising perspectives for patients with heart failure and reduced ejection fraction. The new generation of subcutaneous or MRI-compatible implantable defibrillators is a major technological breakthrough. Finally, the European Society of Cardiology published new recommendations for the management of patients with cardiovascular diseases. This selective review of the literature summarizes the most important studies in the field of interventional cardiology, rhythmology, heart failure and cardiac imaging.

[Geriatric assessment in old patients candidate to transcatheter aortic implantation]. / Evaluation gériatrique des patients agés candidats a un remplacement valvulaire aortique percutané.

Aortic stenosis mostly occurs among old-old patients. Once symptoms appear, prognosis is guarded, with 2-year mortality as high as 50%. Transcatheter Aortic Valve Implantation (TAVI) is a new therapeutic option in patients at very high surgical risk, who are mostly older persons. However, TAVI is associated with some complications, and patient selection remains a challenge. Comprehensive geriatric assessment (CGA) identifies patients with medical and functional problems likely to affect the TAVI post-operative course. Collaboration between cardiologists and geriatricians will likely become a standard approach to enhance the assessment of these frail patients and identify those most likely to benefit from TAVI.

Circadian variations of ischemic burden among patients with myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: Several parameters of cardiovascular physiology and pathophysiology exhibit circadian rhythms. Recently, a relation between infarct size and the time of day at which it occurs has been suggested in experimental models of myocardial infarction. The aim of this study is to investigate whether circadian rhythms could cause differences in ischemic burden in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). METHODS: In 353 consecutive patients with STEMI treated by PPCI, time of symptom onset, peak creatine kinase (CK), and follow-up at 30 days were obtained. We divided 24 hours into 4 time groups based on time of symptom onset (00:00-05:59, 06:00-11:59, 12:00-17:59, and 18:00-23:59). RESULTS: There was no difference between the groups regarding baseline patients and management's characteristics. At multivariable analysis, there was a statistically significant difference between peak CK levels among patients with symptom onset between 00:00 and 05:59 when compared with peak CK levels of patients with symptom onset in any other time group (mean increase 38.4%, P < .05). Thirty-day mortality for STEMI patients with symptom onset occurring between 00:00 and 05:59 was significantly higher than any other time group (P < .05). CONCLUSION: This study demonstrates an independent correlation between the infarct size of STEMI patients treated by PPCI and the time of the day at which symptoms occurred. These results suggest that time of the day should be a critical issue to look at when assessing prognosis of patients with myocardial infarction.

[Cell-based regenerative therapy in cardiology: the future at present]. / Thérapie cellulaire régénérative en cardiologie: le futur au présent?

Cell-based regenerative therapy treatment of cardiovascular diseases considered as irreversible, as acute myocardial infarction, chronic ischemic heart failure, non-ischemic dilated cardiomyopathy and refractory angina pectoris. Large randomized clinical trials with hard clinical endpoints are still necessary before considering cell-based regenerative therapy as a valuable alternative therapeutic option in cardiology.

Reduced atrial emptying after orthotopic heart transplantation masquerading as restrictive transmitral Doppler flow pattern?*.

BACKGROUND: An elevated early (E) to late (A) diastolic filling velocities ratio, typically seen in advanced diastolic dysfunction, has also been observed after cardioversion of atrial fibrillation as a consequence of the depressed left atrial (LA) contractility. We hypothesized that the impaired LA contractile function demonstrated after orthotopic cardiac transplantation (OCT) could also lead to this "pseudorestrictive" pattern. METHOD: E/A ratio related to the tissue Doppler early mitral annular velocity (Ea) as preload-independent index of LV relaxation was evaluated in all consecutive OCT patients between 2005 and 2007. RESULTS: The study population comprised 48 patients 97 ± 77 months after OCT. Thirty-two patients (67%) had an E/A ratio > 2. LV systolic function and myocardial relaxation assessed by the Ea velocity were similar compared to patients with normal ratio (61 ± 6% vs. 60 ± 12%, P = 0.854 and 15 ± 4 cm/s vs. 14 ± 3 cm/s, r = 0.15, P = 0.323, respectively). On the other hand, the proportion of the recipient and donor LA cuffs as estimated by the recipient/global LA area ratio and the LA emptying fraction significantly correlated with the E/A ratio (r = 0.40, P = 0.005 and r =-0.33, P = 0.022, respectively). CONCLUSION: Our study shows that there is a high prevalence of elevated E/A ratio after standard OCT which seems mainly related to reduced LA contractility. Recognition of this "pseudorestrictive" pattern may avoid misdiagnosis of diastolic dysfunction.

[A Swiss multicentric project to improve the prevention of cardiovascular event recurrence after acute coronary syndromes]. / Un projet multicentrique suisse pour améliorer la prévention et la récidive après un syndrome coronarien aigu.

Recurrence of cardiovascular events and mortality remain high after acute coronary syndromes. A Swiss multicentric study, "Inflammation and acute coronary syndromes (ACS)--Novel strategies for prevention and clinical managements", is currently underway with the support of the Swiss National Science Foundation. The study includes a clinical research subproject of which the aim is to assess the impact of the ELIPS program (multi-dimEnsionaL prevention Program after acute coronary Syndrome) on the recurrence of cardiovascular events after an ACS. The basic research sub-projects aim to investigate novel cardiovascular risk biomarkers and genetic determinants of recurrence and to study the role of stem cells after an ACS. Another sub-project will evaluate intracoronary imaging techniques and the efficacy of different types of stents.

Long-Term Quality of Prescription for ST-Segment Elevation Myocardial Infarction (STEMI) Patients: A Real World 1-Year Follow-Up Study.

AIM: American and European associations of cardiology published specific guidelines about recommended drugs for secondary prevention in ST-segment elevation myocardial infarction (STEMI) patients. Our aim was to assess whether drug prescription for STEMI patients was in accordance with the guidelines at discharge and after 1 year. METHOD: We used data of 361 patients admitted for STEMI in a tertiary hospital in Switzerland from 2014 to 2016. We assessed the adequacy of prescription of recommended drugs at two time points: discharge and after 1 year. Medications assessed were aspirin, P2Y12 inhibitors, statin, angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) and ß-blockers. We took into account several criteria like statin dosage (low versus high intensity) and presence of contraindication for consideration of optimal therapy. Predictors of incomplete prescription of guideline medications were then assessed with multivariate logistic regression models. RESULTS: From discharge (n = 358) to 1-year follow-up (n = 303), rate of optimal prescription was reduced from 98.6 to 91.7% for aspirin, from 93.9 to 79.1% for P2Y12 inhibitors, from 83.8 to 65.7% for statins, from 98.6 to 95.6% for ACEIs/ARBs, and from 97.1 to 96.9% for ß-blockers. Predictors of incomplete prescription of guideline medications at discharge were female sex (odds ratio [OR] 2.54, p = 0.007), active or former smoker status (OR 2.29, p = 0.017), multivessel disease (OR 2.07, p = 0.022), left ventricular ejection fraction < 40% (OR 2.49, p = 0.008), and transfer to cardiac surgery (OR 9.66, p = 0.018). At 1 year, age > 65 (OR 1.92, p = 0.036) remained the only significant predictor. CONCLUSION: The present study showed a high prescription rate of guideline-recommended medications in a referral center for primary percutaneous coronary intervention. At discharge, women and co-morbid patients were at the highest risk of incomplete prescription of guideline medications, whereas long-term prescription was suboptimal for elderly. A drug lacking at time of discharge was rarely introduced within the year, which underscores the paramount importance of optimal prescription at time of discharge. Strategies like implementing a standardized prescription could reduce the proportion of suboptimal prescription. It could therefore be one way to improve the long-term quality of care of our patients to the highest level. This study used local data from AMIS Plus-National Registry of Acute Myocardial Infarction in Switzerland (NCT01305785).

Ventricular arrhythmia in coronary artery disease: limits of a risk stratification strategy based on the ejection fraction alone and impact of infarct localization.

AIMS: Estimates of the left ventricular ejection fraction (LVEF) in patients with life-threatening ventricular arrhythmias related to coronary artery disease (CAD) have rarely been reported despite it has become the basis for determining patient's eligibility for prophylactic defibrillator. We aimed to determine the extent and distribution of reduced LVEF in patients with sustained ventricular tachycardia or ventricular fibrillation. METHODS AND RESULTS: 252 patients admitted for ventricular arrhythmia related to CAD were included: 149 had acute myocardial infarction (MI) (Group I, 59%), 54 had significant chronic obstructive CAD suggestive of an ischaemic arrhythmic trigger (Group II, 21%) and 49 patients had an old MI without residual ischaemia (Group III, 19%). 34% of the patients with scar-related arrhythmias had an LVEF > or =40%. Based on pre-event LVEF evaluation, it can be estimated that less than one quarter of the whole study population had a known chronic MI with severely reduced LVEF. In Group III, the proportion of inferior MI was significantly higher than anterior MI (81 vs. 19%; absolute difference, -62; 95% confidence interval, -45 to -79; P < or = 0.0001), though median LVEF was higher in inferior MI (0.37 +/- 10 vs. 0.29 +/- 10; P = 0.0499). CONCLUSION: Patients included in defibrillator trials represent only a minority of the patients at risk of sudden cardiac death. By applying the current risk stratification strategy based on LVEF, more than one third of the patients with old MI would not have qualified for a prophylactic defibrillator. Our study also suggests that inferior scars may be more prone to ventricular arrhythmia compared to anterior scars.

[Cardiology]. / Cardiologie.

This article reviews: 1) some of the results of drug eluting stents (SYNTAX and FAME); 2) the questionnable benefit of physical training in heart failure patients (HF-ACTION); 3) the benefit on cardiac remodelling of cardiac resynchronisation in heart failure patients (REVERSE study) and 4) the role of rate over rhythm control in patients with atrial fibrillation and heart failure (AF-CHF study); this article also reports the encouraging evolution of new technology allowing percutaneous implantation of stents-valves. Finally, this article address the screening of athletes for cardiac diseases.

[Cardiomyopathy and cardiac magnetic resonance]. / Rôle de l'IRM cardiaque dans le dépistage des cardiomyopathies de l'adulte.

Cardiovascular magnetic resonance (CMR) is a rapidly emerging non-invasive imaging technique free of X-Ray and offers higher spatial resolution than alternative forms of cardiac imaging for the assessment of left ventricular (LV) anatomy, function, and viability due to the unique capability of myocardial tissue characterization after gadolinium-chelates contrast administration. This imaging technique has clinical utility over a broad spectrum of heart diseases: ranging from ischaemic to non ischaemic aetiologies. Cardiomyopathies (CMP) are a heterogeneous group of diseases of the myocardium associated with architectural abnormalities and mechanical dysfunction. CMR can help excluding coronary artery disease and can provide positive diagnostic features for several CMP resulted in better diagnosis and management, Leading to improvements in mortality.

[Microvascular dysfunction and myocardial ischemia]. / Dysfonction microvasculaire et ischémie du myocarde.

Functional or structural lesions in intramural arterioles influence the ischemic threshold of the myocardium. Microvascular dysfonction is evidenced by a decrease in coronary blood flow during maximum hyperemia in the presence of angiographically normal or near-normal coronary arteries. Microvascular dysfonction may reflect endothelial dysfonction in diabetic or hyperlipidemic patients, as well as structural and functional changes in patients with hypertrophic cardiomyopathy, aortic stenosis or hypertension. Assessing microvascular fonction after thrombolysis or primary angioplasty for acute myocardial infarction allows to estimate the quality of myocardial reperfusion. Assessing microvascular fonction is a major component of the evaluation of myocardial ischemia in the absence of coronary artery stenoses.

Long-Term Incremental Prognostic Value of Cardiovascular Magnetic Resonance After ST-Segment Elevation Myocardial Infarction: A Study of the Collaborative Registry on CMR in STEMI.

OBJECTIVES: This study sought to investigate whether early post-infarction cardiac magnetic resonance (CMR) parameters provide additional long-term prognostic value beyond traditional outcome predictors in ST-segment elevation myocardial infarction (STEMI) patients. BACKGROUND: Long-term prognostic significance of CMR in STEMI patients has not been assessed yet. METHODS: This was a longitudinal study from a multicenter registry that prospectively included STEMI patients undergoing CMR after infarction. Between May 2003 and August 2015, 810 revascularized STEMI patients were included. CMR was performed at a median of 4 days after STEMI. Infarct size, microvascular obstruction (MVO), and left ventricular (LV) volumes and function were measured. Primary endpoint was a composite of all death and decompensated heart failure (HF). RESULTS: During median follow-up of 5.5 years (range 1.0 to 13.1 years), primary endpoint occurred in 99 patients (39 deaths and 60 HF hospitalization). MVO was a strong predictor of the composite endpoint after correction for important clinical, CMR, and angiographic parameters, including age, LV systolic function, and infarct size. The independent prognostic value of MVO was confirmed in all multivariate models irrespective of whether it was included as a dichotomous (presence of MVO, hazard ratio [HR]: 1.985 to 1.995), continuous (MVO extent as % LV, HR: 1.095 to 1.097), or optimal cutoff value (MVO extent ≥2.6% of LV; HR: 3.185 to 3.199; p < 0.05 for all). MVO extent ≥2.6% of LV was a strong independent predictor of all death (HR: 2.055; 95% confidence interval: 1.076 to 3.925; p = 0.029) and HF hospitalization (HR: 5.999; 95% confidence interval: 3.251 to 11.069; p < 0.001). Finally, MVO extent ≥2.6% of LV provided incremental prognostic value over traditional outcome predictors (net reclassification improvement index: 0.16 to 0.30; p < 0.05 for all models). CONCLUSIONS: Early post-infarction CMR-based MVO is a strong independent prognosticator in revascularized STEMI patients. Remarkably, MVO extent ≥2.6% of LV improved long-term risk stratification over traditional outcome predictors.