Journal: Eur Heart J

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Abstract

Benefits of surgery in obstructive hypertrophic cardiomyopathy: bring septal myectomy back for European patients.

Maron BJ, Yacoub M, Dearani JA
Hypertrophic cardiomyopathy (HCM), a heterogeneous genetic heart disease with global distribution, is an important cause of heart failure disability at any age. For 50 years, surgical septal myectomy has been the preferred and primary treatment strategy for most HCM patients with progressive, drug refractory functional limitation due to left ventricular (LV) outflow tract obstruction. With very low surgical mortality at experienced centres, septal myectomy reliably abolishes impedance to LV outflow and heart failure-related symptoms, restores quality of life, and importantly is associated with long-term survival similar to that in the general population. Nevertheless, alternatives to surgical management are necessary for selected HCM patients. For example, after a brief flirtation with dual-chamber pacing 20 years ago, percutaneous alcohol septal ablation has garnered a large measure of enthusiasm and a dedicated following in the interventional cardiology community, achieving benefits for patients, paradoxically, by virtue of producing a transmural myocardial infarct. However, an unintended consequence has been the virtual obliteration of the surgical option for HCM patients in Europe, where several robust myectomy programmes once existed. Therefore, clear differences are now evident internationally regarding management strategies for symptomatic obstructive HCM. The surgical option is now unavailable to many patients based solely on geography, including some who would likely benefit more substantially from surgical myectomy than from catheter-based alcohol ablation. It is our aspiration that this discussion will generate reconsideration and resurgence of interest in surgical septal myectomy as a treatment option for severely symptomatic obstructive HCM patients within Europe.

Eur Heart J: 17 Feb 2011; epub ahead of print
Maron BJ, Yacoub M, Dearani JA
Eur Heart J: 17 Feb 2011; epub ahead of print | PMID: 21324934
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Abstract

Factors influencing underutilization of evidence-based therapies in women.

Bugiardini R, Yan AT, Yan RT, Fitchett D, ... Goodman SG, on behalf of the Canadian Acute Coronary Syndrome Registry I and II Investigators
Aims Previous studies have reported differences in the use of cardiovascular medications for acute coronary syndromes (ACSs) according to the sex of the patient. We analysed which clinical factors are associated with underutilization of evidence-based therapies in women. Methods and results From the Canadian Registry of ACS I and II, 6558 patients (4471 men and 2087 women) with a final diagnosis of ACS were selected for the current analysis. Covariates were chosen using the approach described by Blackstone. The final selected model included 23 patient clinical variables. Women were less likely than men to receive beta-blockers (75.76 vs. 79.24%; P < 0.01), lipid-modifying agents (56.37 vs. 65.44%; P < 0.0001), and angiotensin-converting enzyme (ACE)-inhibitors (55.52 vs. 59.99%; P < 0.01). Female sex and clinical decision not to investigate with cardiac catheterization were the strongest independent predictors for not receiving lipid-modifying agents and ACE-inhibitors. Age, Killip class 2, and Killip class 3/4 were significant independent predictors of underutilization of beta-blocker use. Women were older (69 ± 12 vs. 64 ± 12; P < 0.01) with a higher prevalence of Killip class ≥ 2 (19.95 vs. 15.54%; P < 0.068), and they were less likely to be referred for cardiac catheterization (41.9 vs. 49.6 %; P < 0.001). Conclusions The current findings demonstrate that underutilization of evidence-based therapies in women with ACS compared with men is associated with multiple factors related to the patient (age), the consequences of the disease (congestive heart failure), and the physician\'s assessment of patient risk (decision to catheterize). Female gender remains associated with underutilization of lipid-modifying agents and ACE-inhibitors despite adjustment for these confounders.

Eur Heart J: 08 Mar 2011; epub ahead of print
Bugiardini R, Yan AT, Yan RT, Fitchett D, ... Goodman SG, on behalf of the Canadian Acute Coronary Syndrome Registry I and II Investigators
Eur Heart J: 08 Mar 2011; epub ahead of print | PMID: 21383003
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Abstract

Intrinsic cardiac origin of human cardiosphere-derived cells.

White AJ, Smith RR, Matsushita S, Chakravarty T, ... Marbán E, Makkar R
Aims Cardiosphere-derived cells (CDCs) are in clinical development as a regenerative cell product which can be expanded ex vivo from patient cardiac biopsies. Cardiosphere-derived cells are clonogenic, exhibit multilineage differentiation, and exert functional benefits in preclinical models of heart failure. The origin of CDCs remains unclear: are these cells endogenous to the heart, or do they arise from cells that populate the heart via blood-borne seeding? Methods and results Right ventricular endomyocardial biopsies were obtained from cardiac transplant recipients (n = 10, age 57 ± 15 years), and CDCs expanded from each biopsy. Donor-recipient mismatches were used to probe the origin of CDCs in three complementary ways. First, DNA analysis of short-tandem nucleotide repeats (STRs) was performed on genomic DNA from donor and recipient, then compared with the STR pattern of CDCs. Second, in two cases where the donor was male and the recipient female, CDCs were examined for the presence of X and Y chromosomes by fluorescence in situ hybridization. Finally, in two cases, quantitative PCR (qPCR) was performed for individual-specific polymorphisms of a major histocompatability locus to quantify the contribution of recipient cells to CDCs. In no case was recipient DNA detectable in the CDCs by STR analysis. In the two cases in which a female patient had received a male heart, all CDCs examined had an X and Y chromosome, similarly indicating exclusively donor origin. Likewise, qPCR on CDCs did not detect any recipient DNA. Conclusion Cardiosphere-derived cells are of endogenous cardiac origin, with no detectable contribution from extra-cardiac seeding.

Eur Heart J: 10 Jun 2011; epub ahead of print
White AJ, Smith RR, Matsushita S, Chakravarty T, ... Marbán E, Makkar R
Eur Heart J: 10 Jun 2011; epub ahead of print | PMID: 21659438
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Abstract

Clinical course and predictive value of congestion during hospitalization in patients admitted for worsening signs and symptoms of heart failure with reduced ejection fraction: findings from the EVEREST trial.

Ambrosy AP, Pang PS, Khan S, Konstam MA, ... Gheorghiade M, on behalf of the EVEREST trial investigators
AimsSigns and symptoms of congestion are the most common cause for hospitalization for heart failure (HHF). The clinical course and prognostic value of congestion during HHF has not been systemically characterized.Methods and resultsA post hoc analysis was performed of the placebo group (n = 2061) of the EVEREST trial, which enrolled patients within 48 h of admission (median ∼24 h) for worsening HF with an EF ≤40% and two or more signs or symptoms of fluid overload [dyspnoea, oedema, or jugular venous distension (JVD)] for a median follow-up of 9.9 months. Clinician-investigators assessed patients daily for dyspnoea, orthopnoea, fatigue, rales, pedal oedema, and JVD and rated signs and symptoms on a standardized 4-point scale ranging from 0 to 3. A modified composite congestion score (CCS) was calculated by summing the individual scores for orthopnoea, JVD, and pedal oedema. Endpoints were HHF, all-cause mortality (ACM), and ACM + HHF. Multivariable Cox regression models were used to evaluate the risk of CCS at discharge on outcomes at 30 days and for the entire follow-up period. The mean CCS obtained after initial therapy decreased from the mean ± SD of 4.07 ± 1.84 and the median (25th, 75th) of 4 (3, 5) at baseline to 1.11 ± 1.42 and 1 (0, 2) at discharge. At discharge, nearly three-quarters of study participants had a CCS of 0 or 1 and fewer than 10% of patients had a CCS >3. B-type natriuretic peptide (BNP) and amino terminal-proBNP, respectively, decreased from 734 (313, 1523) pg/mL and 4857 (2251, 9642) pg/mL at baseline to 477 (199, 1079) pg/mL, and 2834 (1218, 6075) pg/mL at discharge/Day 7. A CCS at discharge was associated with increased risk (HR/point CCS, 95% CI) for a subset of endpoints at 30 days (HHF: 1.06, 0.95-1.19; ACM: 1.34, 1.14-1.58; and ACM + HHF: 1.13, 1.03-1.25) and all outcomes for the overall study period (HHF: 1.07, 1.01-1.14; ACM: 1.16, 1.09-1.24; and ACM + HHF 1.11, 1.06-1.17). Patients with a CCS of 0 at discharge experienced HHF of 26.2% and ACM of 19.1% during the follow-up.ConclusionAmong patients admitted for worsening signs and symptoms of HF and reduced EF, congestion improves substantially during hospitalization in response to standard therapy alone. However, patients with absent or minimal resting signs and symptoms at discharge still experienced a high mortality and readmission rate.

Eur Heart J: 06 Jan 2013; epub ahead of print
Ambrosy AP, Pang PS, Khan S, Konstam MA, ... Gheorghiade M, on behalf of the EVEREST trial investigators
Eur Heart J: 06 Jan 2013; epub ahead of print | PMID: 23293303
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Abstract

Identification of a novel loss-of-function calcium channel gene mutation in short QT syndrome.

Templin C, Ghadri JR, Rougier JS, Baumer A, ... Abriel H, Duru F
Aims Short QT syndrome (SQTS) is a genetically determined ion-channel disorder, which may cause malignant tachyarrhythmias and sudden cardiac death. Thus far, mutations in five different genes encoding potassium and calcium channel subunits have been reported. We present, for the first time, a novel loss-of-function mutation coding for an L-type calcium channel subunit. Methods and results The electrocardiogram of the affected member of a single family revealed a QT interval of 317 ms (QTc 329 ms) with tall, narrow, and symmetrical T-waves. Invasive electrophysiological testing showed short ventricular refractory periods and increased vulnerability to induce ventricular fibrillation. DNA screening of the patient identified no mutation in previously known SQTS genes; however, a new variant at a heterozygous state was identified in the CACNA2D1 gene (nucleotide c.2264G > C; amino acid p.Ser755Thr), coding for the Ca(v)α(2)δ-1 subunit of the L-type calcium channel. The pathogenic role of the p.Ser755Thr variant of the CACNA2D1 gene was analysed by using co-expression of the two other L-type calcium channel subunits, Ca(v)1.2α1 and Ca(v)β(2b), in HEK-293 cells. Barium currents (I(Ba)) were recorded in these cells under voltage-clamp conditions using the whole-cell configuration. Co-expression of the p.Ser755Thr Ca(v)α(2)δ-1 subunit strongly reduced the I(Ba) by more than 70% when compared with the co-expression of the wild-type (WT) variant. Protein expression of the three subunits was verified by performing western blots of total lysates and cell membrane fractions of HEK-293 cells. The p.Ser755Thr variant of the Ca(v)α(2)δ-1 subunit was expressed at a similar level compared with the WT subunit in both fractions. Since the mutant Ca(v)α(2)δ-1 subunit did not modify the expression of the pore-forming subunit of the L-type calcium channel, Ca(v)1.2α1, it suggests that single channel biophysical properties of the L-type channel are altered by this variant. Conclusion In the present study, we report the first pathogenic mutation in the CACNA2D1 gene in humans, which causes a new variant of SQTS. It remains to be determined whether mutations in this gene lead to other manifestations of the J-wave syndrome.

Eur Heart J: 08 Mar 2011; epub ahead of print
Templin C, Ghadri JR, Rougier JS, Baumer A, ... Abriel H, Duru F
Eur Heart J: 08 Mar 2011; epub ahead of print | PMID: 21383000
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Abstract

Testosterone: a hormone preventing cardiovascular disease or a therapy increasing cardiovascular events?

Gencer B, Mach F
Decreasing testosterone levels with ageing is a well-known condition in older men named \'low T\', \'manopause\', or hypogonadism. Observational studies suggested an association between low endogenous testosterone levels and a high cardio-metabolic profile (increased blood pressure, dyslipidaemia, insulin resistance, atherosclerosis, thrombosis), as well as a modest increase in total and cardiovascular (CV) mortality. Controversies persist regarding the need for screening \'low T\' in older men, as well as what precisely should be the indication(s) for testosterone replacement therapy. So far, no data have shown that normalization of testosterone levels reduce CV events. Although testosterone replacement therapy seems to have beneficial effects on male quality of life or physical condition, some data suggest serious adverse events, such as CV events. In addition, there is a lack of consensus on the threshold for treatment indication in men with non-specific symptoms or borderline levels of testosterone. Available data from clinical practice setting suggest an increase in testosterone prescription over time and possible overtreatment. In recent years, pharmaceutical companies have promoted \'low T\' as a treatable disease, suggesting that testosterone replacement may help restore energy, positive mood and sexuality, and despite ageing. Currently, well-designed, adequately powered randomized controlled trials are needed to assess the impact of testosterone replacement therapy on CV clinically relevant CV outcomes within age-specific ranges to strengthen the evidence for clinical practice guidelines.

Eur Heart J: 04 Dec 2015; epub ahead of print
Gencer B, Mach F
Eur Heart J: 04 Dec 2015; epub ahead of print | PMID: 26637832
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Abstract

Novel mechanisms in the pathogenesis of atrial fibrillation: practical applications.

Lau DH, Schotten U, Mahajan R, Antic NA, ... Kalman JM, Sanders P
Intensive research over the last few decades has seen significant advances in our understanding of the complex mechanisms underlying atrial fibrillation (AF). The epidemic of AF and related hospitalizations has been described as a \'rising tide\' with estimates of the global AF burden showing no sign of retreat. There is urgency for effective translational programs in this field to facilitate more individualized and targeted therapy to modify the abnormal atrial substrate responsible for the perpetuation of this arrhythmia. In this review, we chose to focus on several novel aspects of AF pathogenesis whereby practical applications in clinical practice are currently available or potentially not too far away. Specifically, we explored the contribution of atrial fibrosis, epicardial adipose tissue, autonomic nervous system, hyper-coagulability, and focal drivers to adverse atrial remodelling and AF persistence. We also highlighted the potential practical means of monitoring and targeting these factors to achieve better outcomes in patients suffering from this debilitating illness. Emerging data also support a new paradigm for targeting AF substrate with aggressive risk factor management. Finally, multi-disciplinary integrated care approach has shown great promise in improving cardiovascular outcomes of patients with AF along with potential cost savings.

Eur Heart J: 17 Nov 2015; epub ahead of print
Lau DH, Schotten U, Mahajan R, Antic NA, ... Kalman JM, Sanders P
Eur Heart J: 17 Nov 2015; epub ahead of print | PMID: 26578197
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Abstract

Pregnancy outcome in women with congenital heart disease and residual haemodynamic lesions of the right ventricular outflow tract.

Greutmann M, Von Klemperer K, Brooks R, Peebles D, O\'Brien P, Walker F
Aims To determine pregnancy outcome and risk factors for adverse events in women with congenital heart disease (CHD) and residual haemodynamic right ventricular (RV) outflow tract (RVOT) lesions. Methods and results Pregnancy outcome data for women with CHD and residual RVOT lesions have been recorded since 2001. There were 76 pregnancies in 47 women that continued beyond 24 weeks gestation. At conception 20% had RVOT obstruction, 32% had pulmonary regurgitation (PR) and 49% had mixed RVOT obstruction and PR. Moderate-to-severe PR was present in 30 (39%) and RVOT obstruction >/=30 mmHg in 12 (16%) of pregnancies. Seven pregnancies (9%) were complicated by right heart failure (RHF). No arrhythmias were documented. Predictors for RHF were moderate-to-severe PR in combination with at least one additional risk factor (twin pregnancy, branch pulmonary artery stenosis, RV systolic dysfunction, RV hypertrophy). All patients responded to diuretic treatment and had a good pregnancy outcome without foetal complications. Conclusion In patients with CHD and residual RVOT lesions, the outcome of pregnancy is good. Patients with moderate-to-severe PR were at risk for symptomatic RHF only if additional risk factors were present. When treated by a multidisciplinary team, maternal and foetal outcome was good. The general recommendation that pulmonary valve replacement should be undertaken prior to pregnancy in patients with moderate-to-severe PR and RV dilatation needs to be reconsidered.

Eur Heart J: 31 May 2010; epub ahead of print
Greutmann M, Von Klemperer K, Brooks R, Peebles D, O'Brien P, Walker F
Eur Heart J: 31 May 2010; epub ahead of print | PMID: 20511325
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Abstract

Prevalence and clinical correlates of QT prolongation in patients with hypertrophic cardiomyopathy.

Johnson JN, Grifoni C, Bos JM, Saber-Ayad M, ... Olivotto I, Ackerman MJ
Aims Congenital or acquired QT prolongation is a risk factor for life-threatening arrhythmias. In patients with hypertrophic cardiomyopathy (HCM), the QT interval may be intrinsically prolonged. However, the prevalence, cause, and significance of QT prolongation among patients with HCM are unknown. Methods and results After exclusion of patients on QT-prolonging drugs, a blinded, retrospective analysis of electrocardiograms, echocardiograms, and genotype status in 479 unrelated patients with HCM [201 females, age at diagnosis 41 ± 18 years, maximal left ventricular wall thickness (MLVWT) 22 ± 6 mm] from two independent centres was performed. The mean QTc was 440 ± 28 ms. The QTc exceeded 480 ms in 13% of patients. Age, gender, family history of HCM or sudden cardiac arrest, and genotype status had no association with QTc. Patients with a QTc over 480 ms were more symptomatic at diagnosis (P < 0.001), had a higher MLVWT (P = 0.03), were more obstructive (P < 0.001), and were more likely to have undergone septal reduction therapy (P = 0.02). There was a weak but significant direct linear relationship between QTc and peak outflow gradient (r(2) = 0.05, P < 0.0001). Conclusions Compared with <1 in 200 otherwise healthy adults, QT prolongation (QTc > 480 ms) was present in 1 out of 8 patients with HCM. The QTc was partly reflective of the degree of cardiac hypertrophy and left ventricular outflow tract obstruction. Because of its pro-arrhythmic potential and its potential relevance to management and risk stratification, routine QTc assessment should be performed in patients with HCM, particularly when concomitant use of QT-prolonging medications is considered.

Eur Heart J: 24 Feb 2011; epub ahead of print
Johnson JN, Grifoni C, Bos JM, Saber-Ayad M, ... Olivotto I, Ackerman MJ
Eur Heart J: 24 Feb 2011; epub ahead of print | PMID: 21345853
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Abstract

EuroHeart score for the evaluation of in-hospital mortality in patients undergoing percutaneous coronary intervention.

de Mulder M, Gitt A, van Domburg R, Hochadel M, ... Hamm C, Boersma E
Aims The applicability of currently available risk prediction models for patients undergoing percutaneous coronary interventions (PCIs) is limited. We aimed to develop a model for the prediction of in-hospital mortality after PCI that is based on contemporary and representative data from a European perspective. Methods and results Our analyses are based on the Euro Heart Survey of PCIs, which contains information on 46 064 consecutive patients who underwent PCI for different indications in 176 participating European centres during 2005-08. Patients were randomly divided into a training (n = 23 032) and a validation (n = 23 032) set with similar characteristics. In these sets, 339 (1.5%) and 305 (1.3%) patients died during hospitalization, respectively. On the basis of the training set, a logistic model was constructed that related 16 independent patient or lesion characteristics with mortality, including PCI indication, advanced age, haemodynamic instability, multivessel disease, and proximal LAD disease. In both the training and validation data sets, the model had a good performance in terms of discrimination (C-index 0.91 and 0.90, respectively) and calibration (Hosmer-Lemeshow P-value 0.39 and 0.18, respectively). Conclusion In-hospital mortality in PCI patients was well predicted by a risk score that contains 16 factors. The score has strong applicability for European practices.

Eur Heart J: 24 Feb 2011; epub ahead of print
de Mulder M, Gitt A, van Domburg R, Hochadel M, ... Hamm C, Boersma E
Eur Heart J: 24 Feb 2011; epub ahead of print | PMID: 21345854
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Abstract

Gene therapy for the treatment of heart failure: promise postponed.

Hulot JS, Ishikawa K, Hajjar RJ
Gene therapy has emerged as a powerful tool in targeting the molecular mechanisms implicated in heart failure. Refinements in vector technology, including the development of recombinant adeno-associated vectors, have allowed for safe, long-term, and efficient gene transfer to the myocardium. These advancements, coupled with evolving delivery techniques, have placed gene therapy as a viable therapeutic option for patients with heart failure. However, after much promise in early-phase clinical trials, the more recent larger clinical trials have shown disappointing results, thus forcing the field to re-evaluate current vectors, delivery systems, targets, and endpoints. We provide here an updated review of current cardiac gene therapy programmes that have been or are being translated into clinical trials.

Eur Heart J: 27 Feb 2016; epub ahead of print
Hulot JS, Ishikawa K, Hajjar RJ
Eur Heart J: 27 Feb 2016; epub ahead of print | PMID: 26922809
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Abstract

Intracoronary imaging of coronary atherosclerosis: validation for diagnosis, prognosis and treatment.

Koskinas KC, Ughi GJ, Windecker S, Tearney GJ, Räber L
While coronary atherosclerosis is a leading cause of mortality, evaluation of coronary lesions was previously limited to either indirect angiographic assessment of the lumen silhouette or post mortem investigations. Intracoronary (IC) imaging modalities have been developed that allow for visualization and characterization of coronary atheroma in living patients. Used alone or in combination, these modalities have enhanced our understanding of pathobiological mechanisms of atherosclerosis, identified factors responsible for disease progression, and documented the ability of various medications to reverse the processes of plaque growth and destabilization. These methodologies have established a link between in vivo plaque characteristics and subsequent coronary events, thereby improving individual risk stratification, paving the way for risk-tailored systemic therapies and raising the option for pre-emptive interventions. Moreover, IC imaging is increasingly used during coronary interventions to support therapeutic decision-making in angiographically inconclusive disease, guide and optimize procedural results in selected lesion and patient subsets, and unravel mechanisms underlying stent failure. This review aims to summarize current evidence regarding the role of IC imaging for diagnosis and risk stratification of coronary atherosclerosis, and to describe its clinical role for guiding percutaneous coronary interventions. Future perspectives for in-depth plaque characterization using novel techniques and multimodality imaging approaches are also discussed.

Eur Heart J: 13 Dec 2015; epub ahead of print
Koskinas KC, Ughi GJ, Windecker S, Tearney GJ, Räber L
Eur Heart J: 13 Dec 2015; epub ahead of print | PMID: 26655874
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Abstract

Biomarkers of renal injury and function: diagnostic, prognostic and therapeutic implications in heart failure.

van Veldhuisen DJ, Ruilope LM, Maisel AS, Damman K
Heart failure guidelines suggest evaluating renal function as a routine work-up in every patient with heart failure. Specifically, it is advised to calculate glomerular filtration rate and determine blood urea nitrogen. The reason for this is that renal impairment and worsening renal function (WRF) are common in heart failure, and strongly associate with poor outcome. Renal function, however, consists of more than glomerular filtration alone, and includes tubulointerstitial damage and albuminuria. For each of these renal entities, different biomarkers exist that have been investigated in heart failure. Hypothetically, and in parallel to data in nephrology, these markers may aid in the diagnosis of renal dysfunction, or for risk stratification, or could help in therapeutic decision-making. However, as reviewed in the present manuscript, while these markers may carry prognostic information (although not always additive to established markers of renal function), their role in predicting WRF is limited at best. More importantly, none of these markers have been evaluated as a therapeutic target nor have their serial values been used to guide therapy. The evidence is most compelling for the oldest-serum creatinine (in combination with glomerular filtration rate)-but even for this biomarker, evidence to guide therapy to improve outcome is circumstantial at best. Although many new renal biomarkers have emerged at the horizon, they have only limited usefulness in clinical practice until thoroughly and prospectively studied. For now, routine measurement of (novel) renal biomarkers can help to determine cardiovascular risk, but there is no role for these biomarkers to change therapy to improve clinical outcome in heart failure.

Eur Heart J: 05 Nov 2015; epub ahead of print
van Veldhuisen DJ, Ruilope LM, Maisel AS, Damman K
Eur Heart J: 05 Nov 2015; epub ahead of print | PMID: 26543046
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Abstract

Prognostic utility of neopterin and risk of heart failure hospitalization after an acute coronary syndrome.

Nazer B, Ray KK, Sloan S, Scirica B, ... Cannon CP, Braunwald E
Aims There is increasing evidence that immune mechanisms are involved in the pathogenesis of heart failure (HF). The relationship between neopterin and the risk of HF has yet to be investigated on a large scale. We assessed the relationship between neopterin, a novel marker of monocyte activation, and risk of hospitalization for HF. Methods and results Among the subjects of Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 trial, 3946 had neopterin levels measured at study entry, on average 7 days after acute coronary syndrome (ACS). We assessed the relationship between neopterin and hospitalization for HF, and for death or HF over 2 years mean follow-up in a post hoc analysis using Cox regression models. Unadjusted hospitalization rates for HF increased across quartiles of neopterin, from 0.66 to 3.97 per 100 person-years. Per 1SD increment in log (neopterin), the adjusted risk of HF increased by 34% [hazard ratio (HR) 1.34, CI 1.10-1.64; P = 0.004]. Even after excluding individuals with a prior history of HF or recurrent ischaemic events, the relationship between neopterin and HF hospitalization remained significant. When added to a multivariable Cox model of HF-risk containing traditional risk factors, C-reactive protein and brain natriuretic protein (BNP), the further addition of neopterin significantly improved the HF-risk prediction model by likelihood ratio test analysis (P = 0.005), C-statistic (increasing from 0.743 to 0.773; P = 0.027), integrated discrimination improvement (IDI) analysis (P = 0.001), but not net reclassification improvement (NRI) analysis (P = 0.406). Similar results were obtained for the endpoint of death or HF. Conclusion Neopterin levels are an independent predictor of HF hospitalization, and improve risk prediction over and above conventional biomarkers. http://www.clinicaltrials.gov/ registration number NCT00382460.

Eur Heart J: 24 Feb 2011; epub ahead of print
Nazer B, Ray KK, Sloan S, Scirica B, ... Cannon CP, Braunwald E
Eur Heart J: 24 Feb 2011; epub ahead of print | PMID: 21345849
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Abstract

Pathophysiology of ST-segment elevation myocardial infarction: novel mechanisms and treatments.

Montecucco F, Carbone F, Schindler TH
Despite major advances in mechanical and pharmacological reperfusion strategies to improve acute myocardial infarction (MI) injury, substantial mortality, morbidity, and socioeconomic burden still exists. To further reduce infarct size and thus ameliorate clinical outcome, the focus has also shifted towards early detection of MI with high-sensitive troponin assays, imaging, cardioprotection against pathophysiological targets of myocardial reperfusion injury with mechanical (ischaemic post-conditioning, remote ischaemic pre-conditioning, therapeutic hypothermia, and hypoxemia) and newer pharmacological interventions (atrial natriuretic peptide, cyclosporine A, and exenatide). Evidence from animal models of myocardial ischaemia and reperfusion also demonstrated promising results on more selective anti-inflammatory compounds that require additional validation in humans. Cardiac stem cell treatment also hold promise to reduce infarct size and negative remodelling of the left ventricle that may further improves symptoms and prognosis in these patients. This review focuses on the pathophysiology, detection, and reperfusion strategies of ST-segment elevation MI as well as current and future challenges to reduce ischaemia/reperfusion injury and infarct size that may result in a further improved outcome in these patients.

Eur Heart J: 05 Nov 2015; epub ahead of print
Montecucco F, Carbone F, Schindler TH
Eur Heart J: 05 Nov 2015; epub ahead of print | PMID: 26543047
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Abstract

Prognostic implication of stress echocardiography in 6214 hypertensive and 5328 normotensive patients.

Cortigiani L, Bigi R, Landi P, Bovenzi F, Picano E, Sicari R
Aims To compare the prognostic implication of stress echocardiography (SE) in a large cohort of hypertensive and normotensive patients with known or suspected coronary artery disease (CAD). The relative prognostic meaning of the SE result in hypertensive and normotensive patients remains to be addressed. Methods and results The study group was formed by 11 542 patients (6214 hypertensive patients; 5328 normotensive patients) who underwent exercise (n= 686), dobutamine (n= 2524), or dipyridamole (n= 8332) SE for evaluation of known (n= 4563) or suspected (n= 6979) CAD. Patients were followed up for a median of 25 months (1st quartile, 7; 3rd quartile, 57). Ischaemia on SE (new wall motion abnormality) was detected in 3209 (28%) patients. During follow-up, 1587 events (924 deaths, 663 non-fatal infarctions) occurred. Patients (n= 2764) undergoing revascularization were censored. The annual event rate was 7.0% in hypertensive and 5.7% in normotensive patients (P = 0.02) with known CAD, and 3.7% in hypertensive and 2.4% in normotensive patients (P< 0.0001) with suspected CAD. Ischaemia on stress echo, resting wall motion abnormality (RWMA), age, male sex, and diabetes mellitus were multivariable prognostic predictors in both patient groups. Analysing data according to the interaction of prognostically important echocardiographic covariates, such as ischaemia on SE and RWMA, an effective risk assessment was obtained in hypertensive as well as normotensive patients. The annual event rate was markedly higher in hypertensive than in normotensive patients with no ischaemia and no RWMA (2.5 and 1.7%, P = 0.0001). Finally, the incremental prognostic value of inducible ischaemia over clinical evaluation and resting left ventricular function was greater in hypertensive than in normotensive patients both with known and suspected CAD. Conclusion The SE result allows an effective prognostication in hypertensive and normotensive patients. However, a non-ischaemic test predicts better survival in normotensive than in hypertensive patients with no RWMA.

Eur Heart J: 17 Mar 2011; epub ahead of print
Cortigiani L, Bigi R, Landi P, Bovenzi F, Picano E, Sicari R
Eur Heart J: 17 Mar 2011; epub ahead of print | PMID: 21411815
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Abstract

Taxonomy of segmental myocardial systolic dysfunction.

McDiarmid AK, Pellicori P, Cleland JG, Plein S
The terms used to describe different states of myocardial health and disease are poorly defined. Imprecision and inconsistency in nomenclature can lead to difficulty in interpreting and applying trial outcomes to clinical practice. In particular, the terms \'viable\' and \'hibernating\' are commonly applied interchangeably and incorrectly to myocardium that exhibits chronic contractile dysfunction in patients with ischaemic heart disease. The range of inherent differences amongst imaging modalities used to define myocardial health and disease add further challenges to consistent definitions. The results of several large trials have led to renewed discussion about the classification of dysfunctional myocardial segments. This article aims to describe the diverse myocardial pathologies that may affect the myocardium in ischaemic heart disease and cardiomyopathy, and how they may be assessed with non-invasive imaging techniques in order to provide a taxonomy of myocardial dysfunction.

Eur Heart J: 04 May 2016; epub ahead of print
McDiarmid AK, Pellicori P, Cleland JG, Plein S
Eur Heart J: 04 May 2016; epub ahead of print | PMID: 27147609
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The management of myocarditis.

Schultheiss HP, Kühl U, Cooper LT
Despite considerable advances in our understanding of myocarditis pathogenesis, the clinical management of myocarditis has changed relatively little in the last few years. This review aims to help bridge the widening gap between recent mechanistic insights, which are largely derived from animal models, and their potential impact on disease burden. We illustrate the pathogenenic mechanisms that are prime targets for novel therapeutic interventions. Pathway and pathogen-specific molecular diagnostic tests have expanded the role for endomyocardial biopsy. State of the art cardiac magnetic resonance imaging can now provide non-invasive tissue characterization and localize inflammatory infiltrates but imaging techniques are misleading if infectious agents are involved. We emphasize the gaps in our current clinical knowledge, particularly with respect to aetiology-based therapy, and suggest opportunities for high impact, translational investigations.

Eur Heart J: 27 Jun 2011; epub ahead of print
Schultheiss HP, Kühl U, Cooper LT
Eur Heart J: 27 Jun 2011; epub ahead of print | PMID: 21705357
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Abstract

Recommendations for cardiovascular magnetic resonance in adults with congenital heart disease from the respective working groups of the European Society of Cardiology.

Kilner PJ, Geva T, Kaemmerer H, Trindade PT, Schwitter J, Webb GD
This paper aims to provide information and explanations regarding the clinically relevant options, strengths, and limitations of cardiovascular magnetic resonance (CMR) in relation to adults with congenital heart disease (CHD). Cardiovascular magnetic resonance can provide assessments of anatomical connections, biventricular function, myocardial viability, measurements of flow, angiography, and more, without ionizing radiation. It should be regarded as a necessary facility in a centre specializing in the care of adults with CHD. Also, those using CMR to investigate acquired heart disease should be able to recognize and evaluate previously unsuspected CHD such as septal defects, anomalously connected pulmonary veins, or double-chambered right ventricle. To realize its full potential and to avoid pitfalls, however, CMR of CHD requires training and experience. Appropriate pathophysiological understanding is needed to evaluate cardiovascular function after surgery for tetralogy of Fallot, transposition of the great arteries, and after Fontan operations. For these and other complex CHD, CMR should be undertaken by specialists committed to long-term collaboration with the clinicians and surgeons managing the patients. We provide a table of CMR acquisition protocols in relation to CHD categories as a guide towards appropriate use of this uniquely versatile imaging modality.

Eur Heart J: 13 Jan 2010; epub ahead of print
Kilner PJ, Geva T, Kaemmerer H, Trindade PT, Schwitter J, Webb GD
Eur Heart J: 13 Jan 2010; epub ahead of print | PMID: 20067914
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Abstract

Sodium-glucose cotransporter-2 inhibition for the reduction of cardiovascular events in high-risk patients with diabetes mellitus.

Marx N, McGuire DK
Patients with type 2 diabetes mellitus (T2D) exhibit an increased risk for cardiovascular (CV) events. Hyperglycaemia itself contributes to the pathogenesis of atherosclerosis and heart failure (HF) in these patients, but glucose-lowering strategies studied to date have had little to no impact on reducing CV risk, especially in patients with a long duration of T2D and prevalent CV disease (CVD). Sodium glucose cotransporter-2 (SGLT2) inhibitors are a novel class of anti-hyperglycaemic medications that increase urinary glucose excretion, thus improving glycaemic control independent of insulin. The recently published CV outcome trial, EMPA-REG OUTCOME, demonstrated in 7020 patients with T2D and prevalent CVD that the SGLT2-inhibitor empagliflozin significantly reduced the combined CV endpoint of CV death, non-fatal myocardial infarction, and non-fatal stroke vs. placebo in a population of patients with T2D and prevalent atherosclerotic CVD. In addition and quite unexpectedly, empagliflozin significantly and robustly reduced the individual endpoints of CV death, overall mortality, and hospitalization for HF in this high-risk population. Various factors beyond glucose control such as weight loss, blood pressure lowering and sodium depletion, renal haemodynamic effects, effects on myocardial energetics, and/or neurohormonal effects, among others may contribute to these beneficial effects of SGLT2-inhibition. The present review summarizes known and postulated effects of SGLT2-inhibition on the CV system and discusses the role of SGLT2-inhibition for the treatment of high-risk patients with T2D and CVD.

Eur Heart J: 06 May 2016; epub ahead of print
Marx N, McGuire DK
Eur Heart J: 06 May 2016; epub ahead of print | PMID: 27153861
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Abstract

Primary percutaneous coronary intervention by magnetic navigation compared with conventional wire technique.

Patterson MS, Dirksen MT, Ijsselmuiden AJ, Amoroso G, ... Serruys PW, Kiemeneij F
Aims Comparison of magnetic guidewire navigation in percutaneous coronary intervention (MPCI) vs. conventional percutaneous coronary intervention (CPCI) for the treatment of acute myocardial infarction. Methods and results We compared 65 sequential patients (mean age 61 +/- 15 years) undergoing primary MPCI with those of 405 patients undergoing CPCI (mean age 61 +/- 13 years). The major endpoint was contrast media use. Technical success and procedural outcomes were evaluated. Clinical demographics and angiographic characteristics of the two groups were similar, except for fewer patients with previous coronary artery bypass grafting (CABG) and hypertension in the CPCI group and fewer patients with diabetes in the MPCI group. The technical success rate was high in both the MPCI and CPCI groups (95.4 vs. 98%). There was significantly less contrast media usage in the MPCI compared with the CPCI group, median reduction of contrast media of 30 mL with an OR = 0.41 (0.21-0.81). Fluoroscopy times were significantly reduced for MPCI compared with CPCI, median reduction of 7.2 min with an OR = 0.42 (0.20-0.79). Conclusion This comparison indicates the feasibility and non-inferiority of magnetic navigation in performing primary PCI and suggests the possibility of reductions in contrast media use and fluoroscopy time compared with CPCI.

Eur Heart J: 06 Jan 2010; epub ahead of print
Patterson MS, Dirksen MT, Ijsselmuiden AJ, Amoroso G, ... Serruys PW, Kiemeneij F
Eur Heart J: 06 Jan 2010; epub ahead of print | PMID: 20051425
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Abstract

Updated European Heart Rhythm Association practical guide on the use of non-vitamin-K antagonist anticoagulants in patients with non-valvular atrial fibrillation: Executive summary-Revision 1.

Heidbuchel H, Verhamme P, Alings M, Antz M, ... Kirchhof P, Advisors:
In 2013, the European Heart Rhythm Association (EHRA) published a Practical Guide on the use of non-VKA oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) (Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P, European Heart Rhythm A. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625-651; Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P. EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J 2013; 34: :2094-2106). The document received widespread interest, not only from cardiologists but also from neurologists, geriatricians, and general practitioners, as became evident from the distribution of >350 000 copies of its pocket version (the EHRA Key Message Booklet) world-wide. Since 2013, numerous new studies have appeared on different aspects of NOAC therapy in AF patients. Therefore, EHRA updated the Practical Guide, including new information but also providing balanced guiding in the many areas where prospective data are still lacking. The outline of the original guide that addressed 15 clinical scenarios has been preserved, but all chapters have been rewritten. Main changes in the Update comprise a discussion on the definition of \'non-valvular AF\' and eligibility for NOAC therapy, inclusion of finalized information on the recently approved edoxaban, tailored dosing information dependent on concomitant drugs, and/or clinical characteristics, an expanded chapter on neurologic scenarios (ischaemic stroke or intracranial haemorrhage under NOAC), an updated anticoagulation card and more specifics on start-up and follow-up issues. There are also many new flow charts, like on appropriate switching between anticoagulants (VKA to NOAC or vice versa), default scenarios for acute management of coronary interventions, step-down schemes for long-term combined antiplatelet-anticoagulant management in coronary heart disease, management of bleeding, and cardioversion under NOAC therapy. The Updated Guide is available in full in EP Europace (Heidbuchel H, Verhamme P, Alings M, Antz M, Diener HC, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P, Advisors. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015; 17: :1467-1507), while additional resources can be found at the related ESC/EHRA website (www.NOACforAF.eu).

Eur Heart J: 09 Jun 2016; epub ahead of print
Heidbuchel H, Verhamme P, Alings M, Antz M, ... Kirchhof P, Advisors:
Eur Heart J: 09 Jun 2016; epub ahead of print | PMID: 27282612
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Abstract

Ischaemic postconditioning revisited: lack of effects on infarct size following primary percutaneous coronary intervention.

Freixa X, Bellera N, Ortiz-Pérez JT, Jiménez M, ... Betriu A, Masotti M
Aims To assess the short- and long-term effects of postconditioning (p-cond) on infarct size, extent of myocardial salvage, and left ventricular ejection fraction (LVEF) in a series of patients presenting with evolving ST-elevation myocardial infarction (STEMI). Previous studies have shown that p-cond during primary percutaneous coronary intervention (PCI) confers protection against ischaemia-reperfusion injury and thus might reduce myocardial infarct size. Methods and results Seventy-nine patients undergoing PCI for a first STEMI with TIMI grade flow 0-1 and no collaterals were randomized to p-cond (n= 39) or controls (n= 40). Postconditioning was performed by applying four consecutive cycles of 1 min balloon inflation, each followed by 1 min deflation. Infarct size, myocardial salvage, and LVEF were assessed by cardiac-MRI 1 week and 6 months after MI. Postconditioning was associated with lower myocardial salvage (4.1 ± 7.2 vs. 9.1 ± 5.8% in controls; P= 0.004) and lower myocardial salvage index (18.9 ± 27.4 vs. 30.9 ± 20.5% in controls; P= 0.038). No significant differences in infarct size and LVEF were found between the groups at 1 week and 6 months after MI. Conclusion This randomized study suggests that p-cond during primary PCI does not reduce infarct size or improve myocardial function recovery at both short- and long-term follow-up and might have a potential harmful effect.

Eur Heart J: 17 Aug 2011; epub ahead of print
Freixa X, Bellera N, Ortiz-Pérez JT, Jiménez M, ... Betriu A, Masotti M
Eur Heart J: 17 Aug 2011; epub ahead of print | PMID: 21846677
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Abstract

Impaired myocardial perfusion reserve and fibrosis in Friedreich ataxia: a mitochondrial cardiomyopathy with metabolic syndrome.

Raman SV, Phatak K, Hoyle JC, Pennell ML, ... Kissel JT, Al-Dahhak R
Aims Cardiomyopathy produces significant mortality in patients with Friedreich ataxia (FA), a genetic disorder that produces intra-mitochondrial iron accumulation. We sought to test the hypothesis that abnormal myocardial perfusion reserve and fibrosis represent early manifestations of cardiomyopathy. Methods and results Twenty-six patients with genetically proven FA ages 36 ± 12 years without cardiomyopathy and eight controls underwent cardiac magnetic resonance with adenosine. Precontrast imaging for myocardial iron estimation was performed. Myocardial perfusion reserve index (MPRI) was quantified using the normalized upslope of myocardial enhancement during vasodilator stress vs. rest. Left ventricular (LV) mass and volumes were computed from short-axis cine images. Serologies included lipids, and platelets were isolated for iron quantification using inductively coupled plasma mass spectrometry. Left ventricular ejection fraction and mass averaged 64.1 ± 8.3% and 62.7 ± 16.7 g/m(2), respectively, indicating preserved systolic function and absence of significant hypertrophy. Myocardial perfusion reserve index quantification revealed significantly lower endocardial-to-epicardial perfusion reserve in patients vs. controls (0.80 ± 0.18 vs. 1.22 ± 0.36, P = 0.01). Lower MPRI was predicted by increased number of metabolic syndrome (met-S) features (P < 0.01). Worse concentric remodelling occurred with increased GAA repeat length (r = 0.64, P < 0.001). Peripheral platelet iron measurement showed no distinction between patients and controls (5.4 ± 8.5 × 10(-7) vs. 5.5 ± 2.9 × 10(-7) ng/platelet, P = 0.88), nor did myocardial T2* measures. Conclusions Patients with FA have abnormal myocardial perfusion reserve that parallels met-S severity. Impaired perfusion reserve and fibrosis occur in the absence of significant hypertrophy and prior to clinical heart failure, providing potential therapeutic targets for stage B cardiomyopathy in FA and related myocardial diseases.

Eur Heart J: 15 Dec 2010; epub ahead of print
Raman SV, Phatak K, Hoyle JC, Pennell ML, ... Kissel JT, Al-Dahhak R
Eur Heart J: 15 Dec 2010; epub ahead of print | PMID: 21156720
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Abstract

Cardiac resynchronization therapy in patients undergoing atrioventricular junction ablation for permanent atrial fibrillation: a randomized trial.

Brignole M, Botto G, Mont L, Iacopino S, ... Navazio A, Menozzi C
Aims On the basis of the current knowledge, cardiac resynchronization therapy (CRT) cannot be recommended as a first-line treatment for patients with severely symptomatic permanent atrial fibrillation undergoing atrioventricular (AV) junction ablation. We examined whether CRT was superior to conventional right ventricular (RV) pacing in reducing heart failure (HF) events. Methods and results In this prospective, multi-centre study, we randomly assigned 186 patients, in whom AV junction ablation and CRT device implantation had been successfully performed, to receive optimized echo-guided CRT (97 patients) or RV apical pacing (89 patients). The data were analysed according to the intention-to-treat principle. During a median follow-up of 20 months (interquartile range 11-24), the primary composite endpoint of death from HF, hospitalization due to HF, or worsening HF occurred in 11 (11%) patients in the CRT group and 23 (26%) patients in the RV group [CRT vs. RV group: sub-hazard ratio (SHR) 0.37 ( 95% CI 0.18-0.73), P = 0.005]. In the CRT group, compared with the RV group, fewer patients had worsening HF [SHR 0.27 (95% CI 0.12-0.58), P = 0.001] and hospitalizations for HF [SHR 0.20 (95% CI 0.06-0.72), P = 0.013]. Total mortality was similar in both groups [hazard ratio (HR) 1.57 (95% CI 0.58-4.27), P = 0.372]. The beneficial effects of CRT were consistent in patients who had ejection fraction ≤35%, New York Heart Association Class ≥III and QRS width ≥120 and in those who did not. At multi-variable Cox regression, only CRT mode remained an independent predictor of absence of clinical failure during the follow-up [HR = 0.23 (95% CI 0.08-0.66), P = 0.007]. Conclusions In patients undergoing \'Ablate and Pace\' therapy for severely symptomatic permanent atrial fibrillation, CRT is superior to RV apical pacing in reducing the clinical manifestations of HF. (ClinicalTrials.gov number: NCT00111527).

Eur Heart J: 24 May 2011; epub ahead of print
Brignole M, Botto G, Mont L, Iacopino S, ... Navazio A, Menozzi C
Eur Heart J: 24 May 2011; epub ahead of print | PMID: 21606084
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Abstract

Systemic inflammation and arrhythmic risk: lessons from rheumatoid arthritis.

Lazzerini PE, Capecchi PL, Laghi-Pasini F
Rheumatoid arthritis (RA) is a chronic immuno-mediated disease primarily affecting the joints, characterized by persistent high-grade systemic inflammation. Cardiovascular morbidity and mortality are significantly increased in RA, with >50% of premature deaths attributable to cardiovascular disease. In particular, RA patients were twice as likely to experience sudden cardiac death compared with non-RA subjects, pointing to an increased propensity to develop malignant ventricular arrhythmias. Indeed, ventricular repolarization (QT interval) abnormalities and cardiovascular autonomic nervous system dysfunction, representing two well-recognized risk factors for life-threatening ventricular arrhythmias in the general population, are commonly observed in RA. Moreover, large population-based studies seem to indicate that also the prevalence of atrial fibrillation is significantly higher in RA subjects than in the general population, thus suggesting that these patients are characterized by an abnormal diffuse myocardial electrical instability. Although the underlying mechanisms accounting for the pro-arrhythmogenic substrate in RA are probably intricate, the leading role seems to be played by chronic systemic inflammatory activation, able to promote arrhythmias both indirectly, by accelerating the development of ischaemic heart disease and congestive heart failure, and directly, by affecting cardiac electrophysiology. In this integrated mechanistic view, lowering the inflammatory burden through an increasingly tight control of disease activity may represent the most effective intervention to reduce arrhythmic risk in these patients. Intriguingly, these considerations could be more generally applicable to all the diseases characterized by chronic systemic inflammation, and could help elucidate the link between low-grade chronic inflammation and arrhythmic risk in the general population.

Eur Heart J: 01 Jun 2016; epub ahead of print
Lazzerini PE, Capecchi PL, Laghi-Pasini F
Eur Heart J: 01 Jun 2016; epub ahead of print | PMID: 27252448
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The gene expression profile of patients with new-onset heart failure reveals important gender-specific differences.

Heidecker B, Lamirault G, Kasper EK, Wittstein IS, ... Baughman KL, Hare JM
Aims We sought to test the hypothesis that inherent biological factors contribute to gender differences in disease pathophysiology of new-onset heart failure (HF), which can be detected from the transcriptome of a single endomyocardial biopsy (EMB). Methods and results We analysed samples from male (n = 29) and female patients (n = 14) with idiopathic dilated cardiomyopathy (IDCM) and new-onset HF with U133 Plus 2.0 microarrays (Affymetrix) and significance analysis of microarrays (SAM). There were 35 overexpressed and 16 downregulated transcripts in men vs. women [q < 5%, fold change (FC) > 1.2]. In addition to overexpression of Y-chromosome-related transcripts (n = 18), such as USP9Y (FC > 13.1), DDX3Y (FC > 11.3), RPS4Y1 (FC > 9.9), and EIF1AY (FC > 11.8) in males, there was overexpression of CD24 (FC > 5.6) and KCNK1 (FC > 1.5). In females, XIST was highly overexpressed (FC > 28.9), together with X-linked zinc finger proteins (FC > 1.9) and autosomal genes GATAD1 (FC > 1.6), SLC2A12 (FC > 2.9), and PDE6B (FC > 1.5). Analysis of a public data set of end-stage IDCM (n = 15) resulted in approximately 85% overlap with our findings. Conclusion This is the first study that identified gender-specific transcriptomic differences in new-onset HF. Our findings may offer novel insights into fundamental biological differences in the pathophysiology of HF between sexes and provide a platform for personalized medicine.

Eur Heart J: 24 Dec 2009; epub ahead of print
Heidecker B, Lamirault G, Kasper EK, Wittstein IS, ... Baughman KL, Hare JM
Eur Heart J: 24 Dec 2009; epub ahead of print | PMID: 20031959
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Abstract

Antithrombotic therapy in heart failure patients with and without atrial fibrillation: update and future challenges.

Ferreira JP, Girerd N, Alshalash S, Konstam MA, Zannad F
Atrial fibrillation (AF) and heart failure (HF) often coexist, and patients with AF and HF have a higher risk of thromboembolic events and overall mortality compared with those with AF without HF. Additionally, the prevalence of AF increases with the severity of HF. The use of vitamin K antagonists is more unstable in patients with concomitant AF and HF, which is an independent risk factor for reduced time under therapeutic range. More recently, non-vitamin K antagonists oral anticoagulants (NOACs) have emerged as therapeutic alternatives for stroke prevention in patients with non-valvular AF, as they have been shown to be at least as efficacious and safe, with less intracranial bleeding events, compared with vitamin K antagonists. The subgroup analyses of the NOAC trials in patients with AF and HF show that the efficacy and safety of these agents are likely to be similar to those observed in patients with AF and no HF. However, many gaps in evidence exist, since HF has not been consistently defined nor used as an endpoint in these trials. In patients with HF and sinus rhythm, the risk of stroke and other thrombotic events is high, and the use of warfarin has not, to date, been shown to confer outcome benefit. The benefit of the NOAC, rivaroxaban, is being investigated in HF without AF in the ongoing COMMANDER-HF trial. This review aims to provide an insightful perspective on the use of antithrombotic treatments in patients with both AF and HF, and in patients with HF and sinus rhythm, with particular attention to the NOACs, and provides background for therapeutic, outcome and trial improvement.

Eur Heart J: 01 Jun 2016; epub ahead of print
Ferreira JP, Girerd N, Alshalash S, Konstam MA, Zannad F
Eur Heart J: 01 Jun 2016; epub ahead of print | PMID: 27252452
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Abstract

Liver microRNAs: potential mediators and biomarkers for metabolic and cardiovascular disease?

Willeit P, Skroblin P, Kiechl S, Fernández-Hernando C, Mayr M
Recent discoveries have revealed that microRNAs (miRNAs) play a key role in the regulation of gene expression. In this review, we summarize the rapidly evolving knowledge about liver miRNAs (including miR-33, -33*, miR-223, -30c, -144, -148a, -24, -29, and -122) and their link to hepatic lipid metabolism, atherosclerosis and cardiovascular disease, non-alcoholic fatty liver disease, metabolic syndrome, and type-2 diabetes. With regards to its biomarker potential, the main focus is on miR-122 as the most abundant liver miRNA with exquisite tissue specificity. MiR-122 has been proposed to play a central role in the maintenance of lipid and glucose homeostasis and is consistently detectable in serum and plasma. This miRNA may therefore constitute a novel biomarker for cardiovascular and metabolic diseases.

Eur Heart J: 20 Apr 2016; epub ahead of print
Willeit P, Skroblin P, Kiechl S, Fernández-Hernando C, Mayr M
Eur Heart J: 20 Apr 2016; epub ahead of print | PMID: 27099265
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Abstract

When are pro-inflammatory cytokines SAFE in heart failure?

Lecour S, James RW
The cytokine hypothesis presently suggests that an excessive production of pro-inflammatory cytokines, such as tumour necrosis factor alpha (TNF) and interleukin 6 (IL6), contributes to the pathogenesis of heart failure. The concept, successfully proved in genetically modified animal models, failed to translate to humans. Recently, accumulation of apparently paradoxical experimental data demonstrates that, under certain conditions, production of pro-inflammatory cytokines can initiate the activation of a pro-survival cardioprotective signalling pathway. This novel path that involves the activation of a transcription factor, signal transducer and activator of transcription 3 (STAT3), has been termed the survival activating factor enhancement (SAFE) pathway. In this review, we will discuss whether targeting the SAFE pathway may be considered as a preventive and/or therapeutic measure for the treatment of heart failure.

Eur Heart J: 09 Feb 2011; epub ahead of print
Lecour S, James RW
Eur Heart J: 09 Feb 2011; epub ahead of print | PMID: 21303780
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Abstract

Cyclooxygenase-2 inhibitors and cardiovascular risk in a nation-wide cohort study after the withdrawal of rofecoxib.

Bäck M, Yin L, Ingelsson E
AimsThe use of selective cyclooxygenase (COX)-2 inhibitors (coxibs) has been associated with an increased cardiovascular risk. The aim of the present study was to evaluate the association of coxib use and future risk of cardiovascular events in a population-based cohort followed after the warnings concerning the cardiovascular safety of this class of drugs were issued.Methods and resultsA nation-wide, population-based cohort of 7 million subjects, integrating data from the Prescribed Drug, Patient, Cause of Death, Income, Educational and Emigration Registers, was followed from 1 July 2005 to 31 December 2008. Analyses were performed for different cardiovascular outcomes in the whole population after exclusion of individuals with prior cardiovascular diagnosis (incident primary cardiovascular events; sample size, n = 6 991 645). Cox proportional hazard ratios (HRs) revealed no significant association of coxib use with risk for myocardial infarction, ischaemic stroke, or heart failure. In contrast to these findings, coxib use was associated with an increased risk for a first episode of atrial fibrillation [HR 1.16; 95% confidence interval (CI) 1.05-1.29]. A post hoc analysis for different coxibs revealed a significant association with incident atrial fibrillation for etoricoxib (HR 1.35; 95% CI 1.19-1.54) but not for celecoxib (HR 0.94; 95% CI 0.79-1.11).ConclusionWhereas safety measures appear to have limited serious cardiovascular consequences of COX-2 inhibitors, the risk of developing atrial fibrillation may have been overlooked and may necessitate consideration and precautions.

Eur Heart J: 23 Nov 2011; epub ahead of print
Bäck M, Yin L, Ingelsson E
Eur Heart J: 23 Nov 2011; epub ahead of print | PMID: 22108833
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Abstract

Ultrasound of extravascular lung water: a new standard for pulmonary congestion.

Picano E, Pellikka PA
Extravascular lung water (EVLW) is a key variable in heart failure management and prognosis, but its objective assessment remains elusive. Lung imaging has been traditionally considered off-limits for ultrasound techniques due to the acoustic barrier of high-impedance air wall. In pulmonary congestion however, the presence of both air and water creates a peculiar echo fingerprint. Lung ultrasound shows B-lines, comet-like signals arising from a hyper-echoic pleural line with a to-and-fro movement synchronized with respiration. Increasing EVLW accumulation changes the normal, no-echo signal (black lung, no EVLW) into a black-and-white pattern (interstitial sub-pleural oedema with multiple B-lines) or a white lung pattern (alveolar pulmonary oedema) with coalescing B-lines. The number and spatial extent of B-lines on the antero-lateral chest allows a semi-quantitative estimation of EVLW (from absent, ≤5, to severe pulmonary oedema, >30 B-lines). Wet B-lines are made by water and decreased by diuretics, which cannot modify dry B-lines made by connective tissue. B-lines can be evaluated anywhere (including extreme environmental conditions with pocket size instruments to detect high-altitude pulmonary oedema), anytime (during dialysis to titrate intervention), by anyone (even a novice sonographer after 1 h training), and on anybody (since the chest acoustic window usually remains patent when echocardiography is not feasible). Cardiologists can achieve much diagnostic gain with little investment of technology, training, and time. B-lines represent \'the shape of lung water\'. They allow non-invasive detection, in real time, of even sub-clinical forms of pulmonary oedema with a low cost, radiation-free approach.

Eur Heart J: 12 May 2016; epub ahead of print
Picano E, Pellikka PA
Eur Heart J: 12 May 2016; epub ahead of print | PMID: 27174289
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Abstract

Biomechanical stress in coronary atherosclerosis: emerging insights from computational modelling.

Thondapu V, Bourantas CV, Foin N, Jang IK, Serruys PW, Barlis P
Coronary plaque rupture is the most common cause of vessel thrombosis and acute coronary syndrome. The accurate early detection of plaques prone to rupture may allow prospective, preventative treatment; however, current diagnostic methods remain inadequate to detect these lesions. Established imaging features indicating vulnerability do not confer adequate specificity for symptomatic rupture. Similarly, even though experimental and computational studies have underscored the importance of endothelial shear stress in progressive atherosclerosis, the ability of shear stress to predict plaque progression remains incremental. This review examines recent advances in image-based computational modelling that have elucidated possible mechanisms of plaque progression and rupture, and potentially novel features of plaques most prone to symptomatic rupture. With further study and clinical validation, these markers and techniques may improve the specificity of future culprit plaque detection.

Eur Heart J: 22 Feb 2016; epub ahead of print
Thondapu V, Bourantas CV, Foin N, Jang IK, Serruys PW, Barlis P
Eur Heart J: 22 Feb 2016; epub ahead of print | PMID: 26903533
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Abstract

Cardiac manifestations of sarcoidosis: diagnosis and management.

Birnie DH, Kandolin R, Nery PB, Kupari M
Approximately 5% of patients with sarcoidosis will have clinically manifest cardiac involvement presenting with one or more of ventricular arrhythmias, conduction abnormalities, and heart failure. Cardiac presentations can be the first (and/or an unrecognized) manifestation of sarcoidosis in a variety of circumstances. Cardiac symptoms are usually dominant over extra-cardiac as most patients with clinically manifest disease have minimal extra-cardiac disease and up to two-thirds have isolated cardiac sarcoidosis (CS). It is estimated that another 20-25% of pulmonary/systemic sarcoidosis patients have asymptomatic cardiac involvement (clinically silent disease). The extent of left ventricular dysfunction seems to be the most important predictor of prognosis among patients with clinically manifest CS. In addition, the extent of myocardial late gadolinium enhancement is emerging as an important prognostic factor. The literature shows some controversy regarding outcomes for patients with clinically silent CS and larger studies are needed. Immunosuppression therapy (usually with corticosteroids) has been suggested for the treatment of clinically manifest CS despite minimal data supporting it. Fluorodeoxyglucose Positron Emission Tomography imaging is often used to detect active disease and guide immunosuppression. Patients with clinically manifest disease often need device therapy, typically with implantable cardioverter defibrillators.

Eur Heart J: 28 Jul 2016; epub ahead of print
Birnie DH, Kandolin R, Nery PB, Kupari M
Eur Heart J: 28 Jul 2016; epub ahead of print | PMID: 27469375
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Left ventricular systolic and diastolic function assessed by tissue Doppler imaging and outcome in asymptomatic aortic stenosis.

Stewart RA, Kerr AJ, Whalley GA, Legget ME, ... White HD, for the New Zealand Heart Valve Study Investigators
Aims Left ventricular (LV) hypertrophy and abnormal non-invasive measures of LV diastolic function are common in patients with severe aortic stenosis (AS) but their prognostic importance is uncertain. This study aimed to determine whether tissue Doppler measures of LV systolic and/or diastolic function or echocardiographic LV hypertrophy are useful for risk stratifying asymptomatic patients with severe calcific AS. Methods and results One hundred and eighty-three initially asymptomatic patients with moderate or severe AS (valve area mean 0.96 +/- SD 0.3 cm(2)) and a normal LV ejection fraction were followed for median 31 (IQR 14-40) months. Peak systolic (S\') and diastolic (E\') mitral annular velocities and LV mass were measured by echocardiography at baseline and during follow-up. During follow-up 106 (58%) patients suffered symptomatic deterioration, including three sudden deaths and one resuscitated cardiac arrest. Peak aortic velocity (for 0.5 m/s increase HR = 1.43, 95% CI 1.25, 1.64, P < 0.0001) and aortic valve area (-0.1 cm(2)/m(2) HR = 1.23, 95% CI 1.12, 1.35, P = 0.004) at baseline were most strongly associated with symptomatic deterioration. After peak aortic velocity adjustment neither LV mass index nor any measure of LV systolic or diastolic function was associated with symptomatic deterioration (P > 0.2 for all). Conclusion In patients with calcific AS who have a normal LV ejection fraction the severity of stenosis is the most important correlate of symptomatic deterioration. Tissue Doppler measures of LV systolic and diastolic function and LV mass provide limited predictive information after accounting for the severity of stenosis.

Eur Heart J: 01 Jun 2010; epub ahead of print
Stewart RA, Kerr AJ, Whalley GA, Legget ME, ... White HD, for the New Zealand Heart Valve Study Investigators
Eur Heart J: 01 Jun 2010; epub ahead of print | PMID: 20513730
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Abstract

Obesity and cardiovascular disease: friend or foe?

Kim SH, Després JP, Koh KK
Obesity is currently one of the greatest public health issues worldwide. However, despite its known deleterious effects on the cardiovascular system and its association with numerous cardiovascular diseases (CVD), recent findings leading to the development of concepts such as metabolically healthy obesity, the obesity paradox, and protective subcutaneous fat depots have raised a lively debate on the disparate effects of obesity on health outcomes. Regarding the concept of metabolically healthy obesity, by presumably labelling a subset of obese people as metabolically healthy, physicians may not feel pressed to curb the current obesity epidemic and prevent the next generation of people from becoming obese. Another issue is that the most commonly used anthropometric index to define obesity, the body mass index, is at the core of the controversy because of its limitations including its inability to discriminate between fat mass and muscle mass. Many recent epidemiological and metabolic studies have used other indices such as waist-hip ratio, waist circumference, and imaging (computed tomography or magnetic resonance imaging) measurements of visceral adiposity and of ectopic fat depots. In addition, emerging evidence supports the importance of cardiorespiratory fitness, skeletal muscle mass and strength in patients with obesity as useful variables to predict CVD risk beyond adiposity. In this review, we will discuss the complex and disparate effects of obesity on CVD, particularly focusing on whether, under given circumstances, it could be harmful, potentially harmless or neutral, or even possibly protective.

Eur Heart J: 20 Dec 2015; epub ahead of print
Kim SH, Després JP, Koh KK
Eur Heart J: 20 Dec 2015; epub ahead of print | PMID: 26685971
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Abstract

Tissue coverage of a hydrophilic polymer-coated zotarolimus-eluting stent vs. a fluoropolymer-coated everolimus-eluting stent at 13-month follow-up: an optical coherence tomography substudy from the RESOLUTE All Comers trial.

Gutiérrez-Chico JL, van Geuns RJ, Regar E, van der Giessen WJ, ... Windecker S, Serruys PW
Aims To compare the tissue coverage of a hydrophilic polymer-coated zotarolimus-eluting stent (ZES) vs. a fluoropolymer-coated everolimus-eluting stent (EES) at 13 months, using optical coherence tomography (OCT) in an \'all-comers\' population of patients, in order to clarify the mechanism of eventual differences in the biocompatibility and thrombogenicity of the devices. Methods and results Patients randomized to angiographic follow-up in the RESOLUTE All Comers trial (NCT00617084) at pre-specified OCT sites underwent OCT follow-up at 13 months. Tissue coverage and apposition were assessed strut by strut, and the results in both treatment groups were compared using multilevel logistic or linear regression, as appropriate, with clustering at three different levels: patient, lesion, and stent. Fifty-eight patients (30 ZES and 28 EES), 72 lesions, 107 stents, and 23 197 struts were analysed. Eight hundred and eighty-seven and 654 uncovered struts (7.4 and 5.8%, P= 0.378), and 216 and 161 malapposed struts (1.8 and 1.4%, P= 0.569) were found in the ZES and EES groups, respectively. The mean thickness of coverage was 116 ± 99 µm in ZES and 142 ± 113 µm in EES (P= 0.466). No differences in per cent neointimal volume obstruction (12.5 ± 7.9 vs. 15.0 ± 10.7%) or other areas-volumetric parameters were found between ZES and EES, respectively. Conclusion No significant differences in tissue coverage, malapposition, or lumen/stent areas and volumes were detected by OCT between the hydrophilic polymer-coated ZES and the fluoropolymer-coated EES at 13-month follow-up.

Eur Heart J: 10 Jun 2011; epub ahead of print
Gutiérrez-Chico JL, van Geuns RJ, Regar E, van der Giessen WJ, ... Windecker S, Serruys PW
Eur Heart J: 10 Jun 2011; epub ahead of print | PMID: 21659439
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Abstract

Low-gradient aortic stenosis.

Clavel MA, Magne J, Pibarot P
An important proportion of patients with aortic stenosis (AS) have a \'low-gradient\' AS, i.e. a small aortic valve area (AVA <1.0 cm(2)) consistent with severe AS but a low mean transvalvular gradient (<40 mmHg) consistent with non-severe AS. The management of this subset of patients is particularly challenging because the AVA-gradient discrepancy raises uncertainty about the actual stenosis severity and thus about the indication for aortic valve replacement (AVR) if the patient has symptoms and/or left ventricular (LV) systolic dysfunction. The most frequent cause of low-gradient (LG) AS is the presence of a low LV outflow state, which may occur with reduced left ventricular ejection fraction (LVEF), i.e. classical low-flow, low-gradient (LF-LG), or preserved LVEF, i.e. paradoxical LF-LG. Furthermore, a substantial proportion of patients with AS may have a normal-flow, low-gradient (NF-LG) AS: i.e. a small AVA-low-gradient combination but with a normal flow. One of the most important clinical challenges in these three categories of patients with LG AS (classical LF-LG, paradoxical LF-LG, and NF-LG) is to differentiate a true-severe AS that generally benefits from AVR vs. a pseudo-severe AS that should be managed conservatively. A low-dose dobutamine stress echocardiography may be used for this purpose in patients with classical LF-LG AS, whereas aortic valve calcium scoring by multi-detector computed tomography is the preferred modality in those with paradoxical LF-LG or NF-LG AS. Although patients with LF-LG severe AS have worse outcomes than those with high-gradient AS following AVR, they nonetheless display an important survival benefit with this intervention. Some studies suggest that transcatheter AVR may be superior to surgical AVR in patients with LF-LG AS.

Eur Heart J: 17 May 2016; epub ahead of print
Clavel MA, Magne J, Pibarot P
Eur Heart J: 17 May 2016; epub ahead of print | PMID: 27190103
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Abstract

Environmental stressors and cardio-metabolic disease: part I-epidemiologic evidence supporting a role for noise and air pollution and effects of mitigation strategies.

Münzel T, Sørensen M, Gori T, Schmidt FP, ... Brook RD, Rajagopalan S
Traffic noise and air pollution together represent the two most important environmental risk factors in urbanized societies. The first of this two-part review discusses the epidemiologic evidence in support of the existence of an association between these risk factors with cardiovascular and metabolic disease. While independent effects of these risk factors have now clearly been shown, recent studies also suggest that the two exposures may interact with each other and with traditional risk factors such as hypertension and type 2 diabetes. From a societal and policy perspective, the health effects of both air pollution and traffic noise are observed for exposures well below the thresholds currently accepted as being safe. Current gaps in knowledge, effects of intervention and their impact on cardiovascular disease, will be discussed in the last section of this review. Increased awareness of the societal burden posed by these novel risk factors and acknowledgement in traditional risk factor guidelines may intensify the efforts required for effective legislation to reduce air pollution and noise.

Eur Heart J: 26 Jul 2016; epub ahead of print
Münzel T, Sørensen M, Gori T, Schmidt FP, ... Brook RD, Rajagopalan S
Eur Heart J: 26 Jul 2016; epub ahead of print | PMID: 27460892
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Abstract

Coronary microvascular dysfunction in chronic inflammatory rheumatoid diseases.

Faccini A, Kaski JC, Camici PG
Chronic inflammatory rheumatoid diseases (CIRD) such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis are an important risk factor for the development of ischaemic heart disease and a source of high cardiovascular morbidity and mortality. In patients affected by CIRD, inflammation can affect coronary microvascular function and contribute to the development of myocardial ischemia and cardiovascular events, even in the absence of obstructive epicardial coronary artery disease. Understanding the molecular aspects that underlie the development of coronary microvascular dysfunction (CMD) in CIRD is of fundamental importance to identify specific therapeutic targets. In this article, we review the pathogenic mechanisms leading to CMD in CIRD, including the controversial results obtained with the use of different therapeutic strategies. We also propose that a practical diagnostic algorithm as the identification of CMD in patients with CIRD may lead to effective measures to prevent the development of angina pectoris and reduce the risk of rapid disease progression.

Eur Heart J: 24 Feb 2016; epub ahead of print
Faccini A, Kaski JC, Camici PG
Eur Heart J: 24 Feb 2016; epub ahead of print | PMID: 26912605
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Abstract

Interventional cardiology, where real life and science do not necessarily meet.

Meier B
Evidence-based diagnosis, decision-making, and therapy appear a must these days. Generating and publishing evidence is a tedious job according to ever new and tightened research practice regulations. Rules will never prevent the typical human behaviour from showing the new thing to be shinier and the old thing dustier than they really are. The medical community is solicited to concoct a meal that is gullible for patients, authorities, and third-party payers out of the available evidence (after applying some conversion factors correcting the common bias of the researchers), anticipation of what will be the evidence tomorrow, common sense, and digested experience. Examples of misguidance by poorly produced or misinterpreted evidence are plentiful in interventional cardiology as they are in other disciplines. Coronary stents, for instance, were first underestimated due to the fact that they were generally used in bailout situations where the outcome remained rather dismal in spite of the salvaging potential of stents. Then they were overused quite uncritically rather to the detriment of the patient. Now with the high quality of the modern drug-eluting stents (DESs), the overuse persists but is no longer a concern. However, the enhanced potential of DESs compared with bare-metal stents was poorly exploited for >10 years because of reports that slipped through the meshes of good review and publication practice to convey the untenable message that bare-metal stents were preferable in many situations. As other examples, use of the fractional flow reserve (FFR) for decision-making has to be questioned despite prominently published reports recommending it. Fixing a lesion is today easier and hardly more complication prone than assessing it with the FFR. Closure of the patent foramen ovale may never be properly applied, because the collection of the understandably requested evidence takes decades, a follow-up duration that makes research unattractive to physicians and financiers. Transarterial aortic valve replacement, finally, is certain to eventually supplant surgical aortic valve replacement. However, this should have already been accomplished as a logical progress. The adoption of this remarkable breakthrough technology is slowed down by the quest for providing randomized evidence in patients, for whom the evidence should rather be derived from already existing studies, and by the quest to triage all these patients in a heart team, meaning to also keep the surgeons happy, although these patients do not really need them.

Eur Heart J: 04 Jul 2016; epub ahead of print
Meier B
Eur Heart J: 04 Jul 2016; epub ahead of print | PMID: 27378604
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Abstract

A review of sex-specific benefits and risks of antithrombotic therapy in acute coronary syndrome.

Wang WT, James SK, Wang TY
Over the past decade, more men than women have shown improved outcomes from antithrombotic therapies after acute coronary syndrome (ACS), which raises the question of whether there are sex-specific differences in treatment patterns and response to therapy. Differences in presenting clinical characteristics, pathophysiologic profile, and disparities in treatment may contribute to this outcomes discrepancy. Analyses of large trials and registry data suggest that male and female ACS patients experience similar benefits from antithrombotic therapy without significant difference in treatment utilization rates, yet women are consistently at higher risk of bleeding than men. Bleeding may result in antithrombotic treatment disruption, which increases the risk of long-term thrombotic events. Additionally, female ACS patients are more likely to receive suboptimal medication dosing and have lower rates of long-term medication adherence. These differences have significant clinical implications for women, indicating the need for strategies that will optimize initial treatment and long-term management attuned to these recognized sex-specific gaps.

Eur Heart J: 03 Feb 2016; epub ahead of print
Wang WT, James SK, Wang TY
Eur Heart J: 03 Feb 2016; epub ahead of print | PMID: 26843278
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Abstract

Right ventricular mechanical dispersion is related to malignant arrhythmias: a study of patients with arrhythmogenic right ventricular cardiomyopathy and subclinical right ventricular dysfunction.

Sarvari SI, Haugaa KH, Anfinsen OG, Leren TP, ... Amlie JP, Edvardsen T
Aims We evaluated if right ventricular (RV) mechanical dispersion by strain was related to ventricular arrhythmias (VT/VF) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and if mechanical dispersion was increased in so far asymptomatic mutation carriers. Methods and results We included 69 patients, 42 had symptomatic ARVC and 27 were mutation positive asymptomatic family members. Forty healthy individuals served as controls. Myocardial strain was assessed in 6 RV and 16 left ventricular (LV) segments. Contraction duration (CD) in 6 RV and 16 LV segments were measured as the time from onset R on electrocardiogram to maximum myocardial shortening in each segment. The standard deviation of CD was defined as mechanical dispersion. Mechanical dispersion was more pronounced in ARVC patients with arrhythmias compared with asymptomatic mutation carriers and healthy individuals in RV [52(41,63) vs. 35(23,47) vs. 13(9,19)ms, P < 0.001]. Mechanical dispersion was more pronounced in asymptomatic mutation carriers compared with healthy individuals (P < 0.001). Right ventricular mechanical dispersion predicted VT/VF in a multivariate logistic regression analysis [odds ratio (OR), 1.66 (95% confidence interval (CI) 1.06-2.58), P < 0.03]. Right ventricular and LV function by strain were reduced in symptomatic ARVC patients and correlated significantly (R = 0.81, P < 0.001). Right ventricular and LV strain were reduced in asymptomatic mutation carriers compared with healthy individuals (P < 0.001). Conclusion Right ventricular mechanical dispersion was pronounced in patients with ARVC with VT/VF. Right ventricular mechanical dispersion was present in asymptomatic mutation carriers and may be helpful in risk stratification. Right ventricular and LV function correlated in ARVC patients implying that ARVC is a biventricular disease.

Eur Heart J: 16 Mar 2011; epub ahead of print
Sarvari SI, Haugaa KH, Anfinsen OG, Leren TP, ... Amlie JP, Edvardsen T
Eur Heart J: 16 Mar 2011; epub ahead of print | PMID: 21406439
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Abstract

Mineralocorticoid receptor antagonism: therapeutic potential in acute heart failure syndromes.

Albaghdadi M, Gheorghiade M, Pitt B
Acute heart failure syndromes (AHFS) are a heterogeneous group of commonly encountered and difficult to manage clinical syndromes associated with high morbidity and mortality. Dyspnoea, pulmonary, and systemic congestion often characterize AHFS due to acutely elevated intracardiac filling pressures and fluid overload. Diuresis, respiratory support, vasodilator therapy, and gradual attenuation of the activation of renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS) are the keystones of AHFS management. Despite available therapies, post-discharge mortality and re-hospitalization rates remain unacceptably high in AHFS. Neurohumoral-mediated cardiorenal dysfunction and congestion may contribute to these high event rates. Mineralocorticoid receptor antagonists (MRAs) serve a dual therapeutic role by enhancing diuresis and attenuating the pathological effects of RAAS and SNS activation. Although these agents are indicated in patients with chronic, severe heart failure with reduced ejection fraction (HF/REF) and in patients with HF/REF post-myocardial infarction (MI), they have not been systematically studied in patients with AHFS. The purpose of this review is to explore the potential efficacy and safety of MRAs in AHFS.

Eur Heart J: 15 Jun 2011; epub ahead of print
Albaghdadi M, Gheorghiade M, Pitt B
Eur Heart J: 15 Jun 2011; epub ahead of print | PMID: 21672933
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Abstract

Familial ventricular aneurysms and septal defects map to chromosome 10p15.

Tremblay N, Yang SW, Hitz MP, Asselin G, ... Radford D, Andelfinger G
Aims Although ventricular septal defects (VSD) are the most common congenital heart lesion, familial clustering has been described only in rare instances. The aim of this study was to identify genetic factors and chromosomal regions contributing to VSD. Methods and results A unique, large kindred segregating various forms of septal pathologies-including VSD, ventricular septal aneurysms, and atrial septal defects (ASD)-was ascertained and characterized clinically and genetically. Eighteen family members in three generations could be studied, out of whom 10 are affected (2 ASD, 3 septal aneurysm, 4 VSD, and 1 tetralogy of Fallot). Parametric multipoint LOD scores reach significance on chromosome 10p15.3-10p15.2 (max. 3.29). The LOD score support interval is in a gene-poor region where deletions have been reported to associate with septal defects, but that is distinct from the DiGeorge syndrome 2 region on 10p. Multiple linkage analysis scenarios suggest that tetralogy of Fallot is a phenocopy and genetically distinct from the autosomal dominant form of septal pathologies observed in this family. Conclusion This study maps a rare familial form of VSD/septal aneurysms to chromosome 10p15 and extends the spectrum of the genetic heterogeneity of septal pathologies. Fine mapping, haplotype construction, and resequencing will provide a unique opportunity to study the pathogenesis of septal defects and shed light on molecular mechanisms of septal development.

Eur Heart J: 20 Dec 2010; epub ahead of print
Tremblay N, Yang SW, Hitz MP, Asselin G, ... Radford D, Andelfinger G
Eur Heart J: 20 Dec 2010; epub ahead of print | PMID: 21169613
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Abstract

Computed tomography stress myocardial perfusion imaging in patients considered for revascularization: a comparison with fractional flow reserve.

Ko BS, Cameron JD, Meredith IT, Leung M, ... Defrance T, Seneviratne SK
Aims Adenosine stress computed tomography myocardial perfusion imaging (CTP) is an emerging non-invasive method for detecting myocardial ischaemia. Its value when compared with fractional flow reserve (FFR), a highly accurate index of ischaemia, is unknown. Our aim was to determine the diagnostic accuracy of CTP and its incremental value when used with computed tomography coronary angiography (CTA) for detecting ischaemia compared with FFR. Methods and results Forty-two patients (126 vessel territories), who had at least one ≥50% angiographic stenosis on invasive angiography considered for non-urgent revascularization, were included and underwent FFR and CT assessment, including CTP, delayed contrast enhancement scan and CTA all acquired using 320-detector row CT, and prospective ECG gating. Fractional flow reserve was determined in 86 territories subtended by vessels with ≥50% stenosis upon visual assessment. Fractional flow reserve ≤0.8 was considered to indicate significant ischaemia. Computed tomography myocardial perfusion imaging correctly identified 31/41 (76%) ischaemic territories and 38/45 (84%) non-ischaemic territories. Per-vessel territory sensitivity, specificity, positive, and negative predictive values of CTP were 76, 84, 82, and 79%, respectively. The combination of a ≥50% stenosis on CTA and perfusion defect on CTP was 98% specific for ischaemia, while the presence of <50% stenosis on CTA and normal perfusion on CTP was 100% specific for exclusion of ischaemia. Mean radiation for CTP and combined CT was 5.3 and 11.3 mSv, respectively. Conclusion Computed tomography myocardial perfusion imaging is moderately accurate in identifying perfusion defects associated with ischaemia as assessed by FFR in patients considered for revascularization. In territories, where CTA and CTP are concordant, CTA/CTP is highly accurate in the detection and exclusion of ischaemia. This is achievable with acceptable radiation exposure using 320-detector row CT and prospective ECG gating.

Eur Heart J: 03 Aug 2011; epub ahead of print
Ko BS, Cameron JD, Meredith IT, Leung M, ... Defrance T, Seneviratne SK
Eur Heart J: 03 Aug 2011; epub ahead of print | PMID: 21810860
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Abstract

Early diagnosis of acute myocardial infarction in the elderly using more sensitive cardiac troponin assays.

Reiter M, Twerenbold R, Reichlin T, Haaf P, ... Gea J, Mueller C
Aims To examine the diagnostic accuracy of sensitive cardiac troponin (cTn) assays in elderly patients, since elevated levels with sensitive cTn assays were reported in 20% of elderly patients without acute myocardial infarction (AMI). Methods and results In this multi-centre study, we included 1098 consecutive patients presenting with symptoms suggestive of AMI, 406 (37%) were >70 years old. Measurement of three investigational sensitive cTn assays [Roche high-sensitive cTnT (hs-cTnT), Siemens cTnI-Ultra, and Abbott-Architect cTnI) and the standard assay (Roche cTnT) was performed in a blinded fashion. The final diagnosis was adjudicated by two independent cardiologists. Acute myocardial infarction was the adjudicated final diagnosis in 24% of elderly patients. Among elderly patients without AMI, baseline cTn levels were elevated above the 99th percentile in 51% with Roche hs-cTnT, in 17% with Siemens TnI-Ultra, and 13% with Abbott-Architect cTnI. The diagnostic accuracy as quantified by the area under the receiver operating characteristic (ROC) curve (AUC) was significantly greater for the sensitive cTn assays compared with the standard assay (AUC for Roche hs-cTnT, 0.94; Siemens cTnI-Ultra, 0.95; and Abbott-Architect cTnI, 0.95 vs. AUC for the standard assay, 0.90; P < 0.05 for comparisons). The best cut-offs for the sensitive cTn-assays determined by the ROC-curve in elderly patients differed clearly from those in younger patients. Furthermore, the prognostic value regarding 90-day mortality varied among the sensitive cTn assays. Conclusion Sensitive cTn assays have high diagnostic accuracy also in the elderly. Mild elevations are common in elderly non-AMI patients, therefore the optimal cut-off levels are substantially higher in elderly as compared with younger patients. Furthermore, sensitive cTn assays yielded different prognostic value (ClinicalTrials.gov number, NCT00470587).

Eur Heart J: 02 Mar 2011; epub ahead of print
Reiter M, Twerenbold R, Reichlin T, Haaf P, ... Gea J, Mueller C
Eur Heart J: 02 Mar 2011; epub ahead of print | PMID: 21362702
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Abstract

Both cultured and freshly isolated adipose tissue-derived stem cells enhance cardiac function after acute myocardial infarction.

Bai X, Yan Y, Song YH, Seidensticker M, ... Vykoukal D, Alt E
Aims We assessed whether freshly isolated human adipose tissue-derived cells (fhADCs) or cultured human adipose tissue-derived stem cells (hASCs) have beneficial effects on cardiac function after myocardial infarction (MI), whether the injected cells can survive long term, and whether their effects result from direct differentiation or paracrine mechanisms. Methods and results Myocardial infarction was experimentally induced in severe combined immunodeficient mice, and either fhADCs, cultured hASCs, or phosphate-buffered saline was injected into the peri-infarct region. Myocardial function improved significantly in mice treated with hASCs or fhADCs 4 weeks after MI. Immunofluorescence revealed that grafted hASCs and fhADCs underwent cardiomyogenic differentiation pathway, as indicated by expression of connexin 43 and troponin I in a fusion-independent manner. Some of the injected cells integrated with host cardiomyocytes through connexin 43, and others were incorporated into newly formed vessels. Human adipose tissue-derived stem cells survived in injured hearts up to 4 months, as detected by luciferase-based bioluminescence imaging. Vascular density was significantly increased, and fewer apoptotic cells were present in the peri-infarct region of cell-injected mice. Conclusion This is the first study to systematically compare the effects of fhADCs and hASCs on myocardial regeneration. Both cell types engraft into infarcted myocardium, survive, and improve myocardial function, suggesting that fhADCs, like hASCs, are a promising alternative cell source for myocardial repair after MI.

Eur Heart J: 28 Dec 2009; epub ahead of print
Bai X, Yan Y, Song YH, Seidensticker M, ... Vykoukal D, Alt E
Eur Heart J: 28 Dec 2009; epub ahead of print | PMID: 20037143
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Abstract

Catheter ablation in patients with persistent atrial fibrillation.

Kirchhof P, Calkins H
Catheter ablation is increasingly offered to patients who suffer from symptoms due to atrial fibrillation (AF), based on a growing body of evidence illustrating its efficacy compared with antiarrhythmic drug therapy. Approximately one-third of AF ablation procedures are currently performed in patients with persistent or long-standing persistent AF. Here, we review the available information to guide catheter ablation in these more chronic forms of AF. We identify the following principles: Our clinical ability to discriminate paroxysmal and persistent AF is limited. Pulmonary vein isolation is a reasonable and effective first approach for catheter ablation of persistent AF. Other ablation strategies are being developed and need to be properly evaluated in controlled, multicentre trials. Treatment of concomitant conditions promoting recurrent AF by life style interventions and medical therapy should be a routine adjunct to catheter ablation of persistent AF. Early rhythm control therapy has a biological rationale and trials evaluating its value are underway. There is a clear need to generate more evidence for the best approach to ablation of persistent AF beyond pulmonary vein isolation in the form of adequately powered controlled multi-centre trials.

Eur Heart J: 07 Jul 2016; epub ahead of print
Kirchhof P, Calkins H
Eur Heart J: 07 Jul 2016; epub ahead of print | PMID: 27389907
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Abstract

The 200th anniversary of the stethoscope: Can this low-tech device survive in the high-tech 21st century?

Bank I, Vliegen HW, Bruschke AV
In 1816, Laennec discovered that auscultation of the heart and lungs could effectively be performed by placing a hollow cylinder (initially made of a roll of paper) between the chest of the patient and the ear of the examiner. This was the first step in the development of the stethoscope, which was a breakthrough in the diagnosis and management of cardiac and pulmonary patients. Technical improvements of the stethoscope followed and in cardiac patients auscultation soon became a major diagnostic tool. In the second half of the 20th century, new powerful non-invasive diagnostic modalities were developed and the interest in auscultation declined. As a result, the auscultatory skills of students and physicians at all levels of training decreased to a disappointingly low level. We now must decide whether we should stimulate the use of and proficiency in auscultation or if we should accept the further decline and eventual abolishment of this component of the physical examination. Reviewing the literature and taking into consideration the setting in which the patients are presented, including the availability of advanced diagnostic facilities, we conclude that the time-honoured stethoscope, in spite of its limitations, still has potential as a patient-friendly, effective, and economical instrument in medical practice. However, new initiatives are required to train students, physicians and allied health professionals in cardiac auscultation to avoid misinterpretations that may harm the patients and generate extra costs. To be successful such programs will require wide support from the medical community.

Eur Heart J: 23 Feb 2016; epub ahead of print
Bank I, Vliegen HW, Bruschke AV
Eur Heart J: 23 Feb 2016; epub ahead of print | PMID: 26908946
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Abstract

Imaging atherosclerosis with positron emission tomography.

Joseph P, Tawakol A
Positron emission tomography (PET) provides a non-invasive method to measure biological processes that are relevant to atherosclerosis, including arterial inflammation and calcification. The vast majority of studies imaging atherosclerosis with PET have utilized the tracer (18)F-fluorodeoxyglucose (FDG) to better understand how inflammation contributes to atherosclerosis development, and to test the efficacy of therapeutic interventions aimed at reducing its progression. Additional tracers such as (18)F-sodium fluoride ((18)F-NaF) provide additional avenues for characterizing atherosclerosis development. This review examines the emerging uses of PET arterial imaging as a marker of vascular inflammation and atherosclerosis, as a prognostic tool, and as a clinical research tool. In addition, we examine emerging methods that should advance arterial imaging with PET.

Eur Heart J: 28 Apr 2016; epub ahead of print
Joseph P, Tawakol A
Eur Heart J: 28 Apr 2016; epub ahead of print | PMID: 27125951
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Abstract

Highly sensitive troponin and coronary computed tomography angiography in the evaluation of suspected acute coronary syndrome in the emergency department.

Ferencik M, Hoffmann U, Bamberg F, Januzzi JL
The evaluation of patients presenting to the emergency department with suspected acute coronary syndrome (ACS) remains a clinical challenge. The traditional assessment includes clinical risk assessment based on cardiovascular risk factors with serial electrocardiograms and cardiac troponin measurements, often followed by advanced cardiac testing as inpatient or outpatient (i.e. stress testing, imaging). Despite this costly and lengthy work-up, there is a non-negligible rate of missed ACS with an increased risk of death. There is a clinical need for diagnostic strategies that will lead to rapid and reliable triage of patients with suspected ACS. We provide an overview of the evidence for the role of highly sensitive troponin (hsTn) in the rapid and efficient evaluation of suspected ACS. Results of recent research studies have led to the introduction of hsTn with rapid rule-in and rule-out protocols into the guidelines. Highly sensitive troponin increases the sensitivity for the detection of myocardial infarction and decreases time to diagnosis; however, it may decrease the specificity, especially when used as a dichotomous variable, rather than continuous variable as recommended by guidelines; this may increase clinician uncertainty. We summarize the evidence for the use of coronary computed tomography angiography (CTA) as the rapid diagnostic tool in this population when used with conventional troponin assays. Coronary CTA significantly decreases time to diagnosis and discharge in patients with suspected ACS, while being safe. However, it may lead to increase in invasive procedures and includes radiation exposure. Finally, we outline the opportunities for the combined use of hsTn and coronary CTA that may result in increased efficiency, decreased need for imaging, lower cost, and decreased radiation dose.

Eur Heart J: 03 Feb 2016; epub ahead of print
Ferencik M, Hoffmann U, Bamberg F, Januzzi JL
Eur Heart J: 03 Feb 2016; epub ahead of print | PMID: 26843275
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Abstract

Coronary microcirculatory pathophysiology: can we afford it to remain a black box?

Pries AR, Reglin B
Coronary microvascular networks play the key role in determining blood flow distribution in the heart. Matching local blood supply to tissue metabolic demand entails continuous adaptation of coronary vessels via regulation of smooth muscle tone and structural dilated vessel diameter. The importance of coronary microcirculation for relevant pathological conditions including angina in patients with normal or near-normal coronary angiograms [microvascular angina (MVA)] and heart failure with preserved ejection fraction (HFpEF) is increasingly recognized. For MVA, clinical studies have shown a prevalence of up to 40% in patients with suspected coronary artery disease and a relevant impact on adverse cardiovascular events including cardiac death, stroke, and heart failure. Despite a continuously increasing number of corresponding clinical studies, the knowledge on pathophysiological cause-effect relations involving coronary microcirculation is, however, still very limited. A number of pathophysiological hypotheses for MVA and HFpEF have been suggested but are not established to a degree, which would allow definition of nosological entities, stratification of affected patients, or development of effective therapeutic strategies. This may be related to a steep decline in experimental (animal) pathophysiological studies in this area during the last 15 years. Since technology to experimentally investigate microvascular pathophysiology in the beating heart is increasingly, in principle, available, a concerted effort to build \'coronary microcirculatory observatories\' to close this gap and to accelerate clinical progress in this area is suggested.

Eur Heart J: 03 Feb 2016; epub ahead of print
Pries AR, Reglin B
Eur Heart J: 03 Feb 2016; epub ahead of print | PMID: 26843279
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Abstract

Environmental stressors and cardio-metabolic disease: part II-mechanistic insights.

Münzel T, Sørensen M, Gori T, Schmidt FP, ... Brook RD, Rajagopalan S
Environmental factors can act as facilitators of chronic non-communicable diseases. Ambient noise and air pollution collectively outrank all other environmental risk factors in importance, contributing to over 75% of the disease and disability burden associated with known environmental risk factors. In the first part of this review, we discussed the global burden and epidemiologic evidence supporting the importance of these novel risk factors as facilitators of cardiometabolic disease. In this part, we will discuss pathophysiological mechanisms responsible for noise and air pollution-mediated effects. Akin to traditional cardiovascular risk factors, a considerable body of evidence suggests that these environmental agents induce low-grade inflammation, oxidative stress, vascular dysfunction, and autonomic nervous system imbalance, thereby facilitating the development of diseases such as hypertension and diabetes. Through their impact on traditional risk factors and via additional novel mechanisms, environmental risk factors may have much larger impact on cardiovascular events than currently appreciated. In the second part of this review, we discuss deficiencies and gaps in knowledge and opportunities for new research.

Eur Heart J: 26 Jul 2016; epub ahead of print
Münzel T, Sørensen M, Gori T, Schmidt FP, ... Brook RD, Rajagopalan S
Eur Heart J: 26 Jul 2016; epub ahead of print | PMID: 27460891
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Abstract

Hypertrophic obstructive cardiomyopathy: alcohol septal ablation.

Fifer MA, Sigwart U
Alcohol septal ablation (ASA) was introduced in 1994 as an alternative to septal myectomy for patients with hypertrophic obstructive cardiomyopathy and symptoms refractory to medical therapy. This procedure alleviates symptoms by producing a targeted, limited infarction of the upper interventricular septum, resulting in an increase in left ventricular outflow tract (LVOT) diameter, a decrease in LVOT gradient, and regression of the component of LV hypertrophy that is due to pressure overload. Clinical success, with improvement in symptoms and reduction in gradient, is achieved in the great majority of patients with either resting or provocable LVOT obstruction. The principal morbidity of the procedure is complete heart block, resulting in some patients in the requirement for a permanent pacemaker. The introduction of myocardial contrast echocardiography as a component of the ASA procedure has contributed to the induction of smaller myocardial infarctions with lower dosages of alcohol and, in turn, fewer complications. Non-randomized comparisons of septal ablation and septal myectomy have shown similar mortality rates and post-procedure New York Heart Association class for the two procedures.

Eur Heart J: 30 Mar 2011; epub ahead of print
Fifer MA, Sigwart U
Eur Heart J: 30 Mar 2011; epub ahead of print | PMID: 21447511
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Abstract

Indications and use of the wearable cardiac defibrillator.

Sharma PS, Bordachar P, Ellenbogen KA
The implantable cardiac defibrillator (ICD) has been an effective tool for prevention of sudden cardiac death (SCD) in populations at high risk for life-threatening sustained ventricular tachycardia (VT) and ventricular fibrillation (VF). However, ICD implantation is dependent on defining ventricular substrate, evaluating the future risk of SCD and estimation of the patient\'s overall survival. The ability to predict risk of SCD is often difficult. If ventricular dysfunction (a surrogate marker for the risk of SCD) improves, ICD therapy may not be indicated. The wearable cardiac defibrillator (WCD) provides an option for protection during this vulnerable period when the risk of SCD is unclear. It combines an electrocardiogram-monitoring system with an external automatic defibrillator. The WCD can be a safe and effective tool for prevention of VT/VF related SCD events and is used in a variety of clinical situations where the risk of SCD is changing. Such situations include the early phase after acute myocardial infarction with poor left ventricular function (≤35%), after acute coronary revascularization procedures and reduced left ventricular ejection fraction (≤35%), acute heart failure and non-ischemic cardiomyopathy of uncertain duration and prior to medical therapy initiation. The WCD also has a role in patients waiting for heart transplantation or who need a ventricular-assist device and those who have an acute contra-indication to implantation such as active infection. This review discusses the technical aspects of the WCD, its potential clinical application and summarizes the currently available data on the WCD in different populations and future directions.

Eur Heart J: 26 Aug 2016; epub ahead of print
Sharma PS, Bordachar P, Ellenbogen KA
Eur Heart J: 26 Aug 2016; epub ahead of print | PMID: 27566663
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Abstract

Stroke mortality and trends from 1990 to 2006 in 39 countries from Europe and Central Asia: implications for control of high blood pressure.

Redon J, Olsen MH, Cooper RS, Zurriaga O, ... Coca A, Mancia G
Aims The aim of the present study was to extend our understanding of international trends in stroke and major sequelae in Europe and countries peripheral to Europe by assessing: (1) current mortality rates, (2) the most recent 15-year prevalence trends, and (3) the relationship between systolic blood pressure in community surveys and national stroke mortality. Methods and results Data were obtained from the World Health Organization (WHO www.who.int/whosis/database/mort/table.cfm), and represent national vital statistics as reported by 39 countries (European and Central Asian countries) using a standard format and population-based cardiovascular surveys. Total numbers of deaths by stroke (International Classification of Diseases 430-438, 444) and the age, sex-adjusted incidence rates were obtained and grouped according to three standard demographic categories: A, B, and C (WHO). A Bayesian linear mixed effect model was fitted to the annual mortality rates. Higher rates of stroke mortality were observed for B and C group countries as compared with those countries belonging to Group A (e.g. Bulgaria 273.9 and 281.1; Israel 37.7 and 45.4 per 100 000 men and women, respectively). Even though the mortality rates within the country groupings were relatively similar, countries with marked deviation from the average were observed, mainly in Groups B and C. Stroke mortality decreased sharply in Group A during the period of study; conversely it had increased substantially in Group B and to a lesser extent in Group C. For both sexes markedly higher rates were noted moving from west to east, with some exceptions. Conclusion We have entered a period of rapidly increasing international inequality in stroke risk, where countries with low adult mortality in the latter 20th century extended their downward trend and countries with moderate as well as high mortality have on average seen unprecedented increases in death rates from stroke.

Eur Heart J: 13 Apr 2011; epub ahead of print
Redon J, Olsen MH, Cooper RS, Zurriaga O, ... Coca A, Mancia G
Eur Heart J: 13 Apr 2011; epub ahead of print | PMID: 21487117
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Abstract

Inflammatory cytokines in atherosclerosis: current therapeutic approaches.

Tousoulis D, Oikonomou E, Economou EK, Crea F, Kaski JC
The notion of atherosclerosis as a chronic inflammatory disease has intensified research on the role of cytokines and the way these molecules act and interact to initiate and sustain inflammation in the microenvironment of an atherosclerotic plaque. Cytokines are expressed by all types of cells involved in the pathogenesis of atherosclerosis, act on a variety of targets exerting multiple effects, and are largely responsible for the crosstalk among endothelial, smooth muscle cells, leucocytes, and other vascular residing cells. It is now understood that widely used drugs such as statins, aspirin, methotrexate, and colchicine act in an immunomodulatory way that may beneficially affect atherogenesis and/or cardiovascular disease progression. Moreover, advancement in pharmaceutical design has enabled the production of highly specific antibodies against key molecules involved in the perpetuation of the inflammatory cascade, raising hope for advances in the treatment of atherosclerosis. This review describes the actions and effects of these agents, their potential clinical significance, and future prospects.

Eur Heart J: 03 Feb 2016; epub ahead of print
Tousoulis D, Oikonomou E, Economou EK, Crea F, Kaski JC
Eur Heart J: 03 Feb 2016; epub ahead of print | PMID: 26843277
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Abstract

Roles of exosomes in cardioprotection.

Barile L, Moccetti T, Marbán E, Vassalli G
Exosomes are extracellular vesicles of endosomal origin which have emerged as key mediators of intercellular communication. All major cardiac cell types-including cardiomyocytes, endothelial cells, and fibroblasts-release exosomes that modulate cellular functions. Exosomes released from human cardiac progenitor cells (CPCs) are cardioprotective and improve cardiac function after myocardial infarction to an extent comparable with that achieved by their parent cells. Cardiac progenitor cell-derived exosomes are enriched in cardioprotective microRNAs, particularly miR-146a-3p. Circulating exosomes mediate remote ischaemic preconditioning. Moreover, they currently are being investigated as diagnostic markers. The discovery that cell-derived extracellular signalling organelles mediate the paracrine effects of stem cells suggests that cell-free strategies could supplant cell transplantation. This review discusses emerging roles of exosomes in cardiovascular physiology, with a focus on cardioprotective activities of CPC-derived exosomes.

Eur Heart J: 21 Jul 2016; epub ahead of print
Barile L, Moccetti T, Marbán E, Vassalli G
Eur Heart J: 21 Jul 2016; epub ahead of print | PMID: 27443883
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Abstract

microRNAs in heart disease: putative novel therapeutic targets?

Condorelli G, Latronico MV, Dorn GW
microRNAs (miRs) are short, approximately 22-nucleotide-long non-coding RNAs involved in the control of gene expression. They guide ribonucleoprotein complexes that effect translational repression or messenger RNA degradation to targeted messenger RNAs. miRs were initially thought to be peculiar to the developmental regulation of the nematode worm, in which they were first described in 1993. Since then, hundreds of different miRs have been reported in diverse organisms, and many have been implicated in the regulation of physiological processes of adult animals. Of importance, misexpression of miRs has been uncovered as a pathogenic mechanism in several diseases. Here, we first outline the biogenesis and mechanism of action of miRs, and then discuss their relevance to heart biology, pathology, and medicine.

Eur Heart J: 01 Feb 2010; epub ahead of print
Condorelli G, Latronico MV, Dorn GW
Eur Heart J: 01 Feb 2010; epub ahead of print | PMID: 20118173
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Abstract

Loss of Akt activity increases circulating soluble endoglin release in preeclampsia: identification of inter-dependency between Akt-1 and heme oxygenase-1.

Cudmore MJ, Ahmad S, Sissaoui S, Ramma W, ... Egginton S, Ahmed A
Aims Endothelial dysfunction is a hallmark of preeclampsia. Desensitization of the phosphoinositide 3-kinase (PI3K)/Akt pathway underlies endothelial dysfunction and haeme oxygenase-1 (HO-1) is decreased in preeclampsia. To identify therapeutic targets, we sought to assess whether these two regulators act to suppress soluble endoglin (sEng), an antagonist of transforming growth factor-β (TGF-β) signalling, which is known to be elevated in preeclampsia. Methods and results Vascular endothelial growth factor-A (VEGF-A), fibroblast growth factor (FGF-2), angiopoietin-1 (Ang-1), and insulin, which all activate the PI3K/Akt pathway, inhibited the release of sEng from endothelial cells. Inhibition of the PI3K/Akt pathway, by overexpression of phosphatase and tensin homolog (PTEN) or a dominant-negative isoform of Akt (Akt(dn)) induced sEng release from endothelial cells and prevented the inhibitory effect of VEGF-A. Conversely, overexpression of a constitutively active Akt (Akt(myr)) inhibited PTEN and cytokine-induced sEng release. Systemic delivery of Akt(myr) to mice significantly reduced circulating sEng, whereas Akt(dn) promoted sEng release. Phosphorylation of Akt was reduced in preeclamptic placenta and this correlated with the elevated level of circulating sEng. Knock-down of Akt using siRNA prevented HO-1-mediated inhibition of sEng release and reduced HO-1 expression. Furthermore, HO-1 null mice have reduced phosphorylated Akt in their organs and overexpression of Akt(myr) failed to suppress the elevated levels of sEng detected in HO-1 null mice, indicating that HO-1 is required for the Akt-mediated inhibition of sEng. Conclusion The loss of PI3K/Akt and/or HO-1 activity promotes sEng release and positive manipulation of these pathways offers a strategy to circumvent endothelial dysfunction.

Eur Heart J: 17 Mar 2011; epub ahead of print
Cudmore MJ, Ahmad S, Sissaoui S, Ramma W, ... Egginton S, Ahmed A
Eur Heart J: 17 Mar 2011; epub ahead of print | PMID: 21411816
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Abstract

23S rDNA real-time polymerase chain reaction of heart valves: a decisive tool in the diagnosis of infective endocarditis.

Vollmer T, Piper C, Horstkotte D, Körfer R, Kleesiek K, Dreier J
Aims A new diagnostic strategy to improve the detection of pathogens in heart valves (HVs) from patients with infective endocarditis (IE) was evaluated. Methods and results Three hundred and fifty seven HVs surgically removed from 326 patients with proven IE or suspicious intra-operative findings, examined by 16S rDNA polymerase chain reaction (PCR) and culture were retrospectively analysed according to the predictive value of various PCR methods. Patients were classified into four categories: active IE, IE with ambiguous infective status, healed IE, and valve diseases but no IE. Retained samples of 200 HVs were analysed by real-time PCR targeting bacterial 23S rDNA, fungal 28S rDNA, and mycoplasmal tuf gene. 16S rDNA PCR revealed 80.6% sensitivity, 100% specificity, 100% positive predictive value, and 71% negative predictive value (NPV), compared with cultivation with 33.4, 96.6, 95.5, and 40.9%, respectively. The use of real-time PCR increased diagnostic sensitivity to 96.4%, and NPV to 92.5%. Bacterial load, C-reactive protein, and white blood cell counts (WBCs) decreased during antibiotic treatment. Bacterial load showed no correlation to C-reactive protein or WBCs, whereas C-reactive protein and WBCs were significantly correlated. Conclusion 23S rDNA real-time PCR of surgically removed HVs improves the diagnosis of IE. Polymerase chain reaction analysis of explanted HVs allow the optimization of the antimicrobial therapy, especially in patients with culture-negative IE.

Eur Heart J: 22 Jan 2010; epub ahead of print
Vollmer T, Piper C, Horstkotte D, Körfer R, Kleesiek K, Dreier J
Eur Heart J: 22 Jan 2010; epub ahead of print | PMID: 20093256
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Abstract

Anticoagulation in coronary intervention.

Zeymer U, Rao SV, Montalescot G
Percutaneous coronary intervention (PCI) induces thrombin generation and is associated with the risk of acute, subacute, or long-term ischaemic events. Therefore, intravenous anticoagulation is recommended to minimize thrombotic complications. The intensity and duration of anticoagulation needed are dependent on the clinical presentation (elective PCI for stable coronary artery disease, PCI for non-ST elevation acute coronary syndromes, or primary PCI for ST-segment elevation myocardial infarction) and procedural features. As both ischaemic and periprocedural bleeding complications are associated with acute and long-term mortality, the optimal level of anticoagulation and the best agents are a matter of debate. Despite a number of limitations and the lack of large randomized clinical trials, unfractionated heparin (UFH) is still been used in the majority of interventions. Intravenous enoxaparin, a low-molecular-weight heparin, leads to a more predictable level of anticoagulation and has been compared with UFH in patients with elective PCI and primary PCI with favourable results. The direct thrombin inhibitor bivalirudin has been studied in numerous trials and consistently shown to reduce bleeding complications when compared with UFH with or without glycoprotein IIb/IIIa inhibitors. This review will summarize the current status of anticoagulation for PCI and the results of most recent trials and give recommendations for different clinical scenarios.

Eur Heart J: 05 Mar 2016; epub ahead of print
Zeymer U, Rao SV, Montalescot G
Eur Heart J: 05 Mar 2016; epub ahead of print | PMID: 26946415
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Abstract

Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 1.

Diener HC, Aisenberg J, Ansell J, Atar D, ... Veltkamp R, Lip GY
Patients with atrial fibrillation (AF) have a high risk of stroke and mortality, which can be considerably reduced by oral anticoagulants (OAC). Recently, four non-vitamin-K oral anticoagulants (NOACs) were compared with warfarin in large randomized trials for the prevention of stroke and systemic embolism. Today\'s clinician is faced with the difficult task of selecting a suitable OAC for a patient with a particular clinical profile or a particular pattern of risk factors and concomitant diseases. We reviewed analyses of subgroups of patients from trials of vitamin K antagonists vs. NOACs for stroke prevention in AF with the aim to identify patient groups who might benefit from a particular OAC more than from another. In the first of a two-part review, we discuss the choice of NOAC for stroke prevention in the following subgroups of patients with AF: (i) stable coronary artery disease or peripheral artery disease, including percutaneous coronary intervention with stenting and triple therapy; (ii) cardioversion, ablation and anti-arrhythmic drug therapy; (iii) mechanical valves and rheumatic valve disease, (iv) patients with time in therapeutic range of >70% on warfarin; (v) patients with a single stroke risk factor (CHA2DS2VASc score of 1 in males, 2 in females); and (vi) patients with a single first episode of paroxysmal AF. Although there are no major differences in terms of efficacy and safety between the NOACs for some clinical scenarios, in others we are able to suggest that particular drugs and/or doses be prioritized for anticoagulation.

Eur Heart J: 04 Feb 2016; epub ahead of print
Diener HC, Aisenberg J, Ansell J, Atar D, ... Veltkamp R, Lip GY
Eur Heart J: 04 Feb 2016; epub ahead of print | PMID: 26848149
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Abstract

Statins, fibrates, and venous thromboembolism: a meta-analysis.

Squizzato A, Galli M, Romualdi E, Dentali F, ... Venco A, Ageno W
Aims The aim is to make a systematic review of the literature to assess the effect of lipid-lowering drugs on venous thromboembolism (VTE) occurrence. Methods and results MEDLINE and EMBASE databases were searched to identify studies that evaluated the effect of lipid-lowering drugs, in particular statins and fibrates, on VTE risk until April 2009. A scoring system was used to divide studies into two quality categories. Odds ratios (ORs) and 95% confidence intervals (CIs) were then calculated and pooled using a fixed and a random-effects model. Statistical heterogeneity was evaluated through the use of I(2) statistics. Three randomized controlled trials (RCTs), three cohort, and eight case-control studies were included in our systematic review, for a total of 863 805 patients. Statins use significantly reduced VTE risk [OR, 0.81; 95% CI, 0.66-0.99, random-effect model)]. There was a very high heterogeneity among the studies (I(2) > 80%). The use of fibrates was associated with a significant increase in the risk of VTE (OR, 1.58; 95% CI, 1.23-2.02), without heterogeneity (I(2) = 0%). Data on other lipid-lowering drugs were lacking. Conclusion This meta-analysis of available literature suggests that statins may lower the risk of VTE, whereas fibrates may increase this risk. Due to several methodological limitations, this conclusion should be considered with caution, and additional, specifically designed RCTs are warranted.

Eur Heart J: 24 Dec 2009; epub ahead of print
Squizzato A, Galli M, Romualdi E, Dentali F, ... Venco A, Ageno W
Eur Heart J: 24 Dec 2009; epub ahead of print | PMID: 20031958
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Abstract

The relationship between ventricular electrical delay and left ventricular remodelling with cardiac resynchronization therapy.

Gold MR, Birgersdotter-Green U, Singh JP, Ellenbogen KA, ... Seth M, Tchou PJ
AimsThe aim of the present study was to evaluate the relationship between left ventricular (LV) electrical delay, as measured by the QLV interval, and outcomes in a prospectively designed substudy of the SMART-AV Trial.Methods and resultsThis was a multicentre study of patients with advanced heart failure undergoing cardiac resynchronization therapy (CRT) defibrillator implantation. In 426 subjects, QLV was measured as the interval from the onset of the QRS from the surface ECG to the first large peak of the LV electrogram. Left ventricular volumes were measured by echocardiography at baseline and after 6 months of CRT by a blinded core laboratory. Quality of life (QOL) was assessed by a standardized questionnaire. When separated by quartiles based on QLV duration, reverse remodelling response rates (>15% reduction in LV end systolic volume) increased progressively from 38.7 to 68.4% and QOL response rate (>10 points reduction) increased from 50 to 72%. Patients in the highest quartile of QLV had a 3.21-fold increase (1.58-6.50, P = 0.001) in their odds of a reverse remodelling response after correcting for QRS duration, bundle branch block type, and clinical characteristics by multivariate logistic regression analysis.ConclusionElectrical dyssynchrony, as measured by QLV, was strongly and independently associated with reverse remodelling and QOL with CRT. Acute measurements of QLV may be useful to guide LV lead placement.

Eur Heart J: 30 Aug 2011; epub ahead of print
Gold MR, Birgersdotter-Green U, Singh JP, Ellenbogen KA, ... Seth M, Tchou PJ
Eur Heart J: 30 Aug 2011; epub ahead of print | PMID: 21875862
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Abstract

Pre-treatment with P2Y12 inhibitors in ACS patients: who, when, why, and which agent?

Sibbing D, Kastrati A, Berger PB
Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor is the mainstay of treatment for acute coronary syndrome (ACS) patients, whether they undergo a percutaneous coronary intervention (PCI) or are managed medically. In recent years, the most appropriate timing for initiation and duration of P2Y12 receptor inhibition has been a focus of great interest. Many observational studies and a single prospective trial (CREDO) utilizing clopidogrel had focused on whether pre-treatment with clopidogrel, i.e. its administration upstream of coronary angiography and PCI, is beneficial. Although the rationale for pre-treatment is obvious, large-scale randomized trials supporting a pre-treatment strategy with clopidogrel or with the newer P2Y12 inhibitors prasugrel and ticagrelor did not exist. Proponents of a pre-treatment strategy had to rely on their best guess, on non-randomized studies, or on negative studies in which a trend for a benefit had been demonstrated. Recently, however, two randomized trials directly evaluated the value of pre-treatment-one in patients with a non-STE elevation myocardial infarction (NSTEMI)-the Comparison of Prasugrel at the Time of Percutaneous Coronary Intervention or as Pretreatment at the Time of Diagnosis in Patients with Non-ST Elevation Myocardial Infarction (ACCOAST) trial, and a second trial evaluating the use of ticagrelor in ST-elevation myocardial infarction (STEMI) patients, the Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST-elevation myocardial Infarction to open the Coronary artery (ATLANTIC) trial. Neither of the two trials, however, answered all the questions clinicians have about pre-treatment. And given the recent approval of the intravenous and rapidly acting P2Y12 inhibitor cangrelor, the choice of who should receive treatment with a P2Y12 inhibitor, which one should be used, and when it should be administered, should be carefully re-evaluated for all patients. This clinical review aims at evaluating the available evidence regarding the value of pre-treatment with the now four available oral and intravenous P2Y12 inhibitors that can be administered to patients in whom coronary angiography followed by a possible PCI is planned.

Eur Heart J: 28 Dec 2015; epub ahead of print
Sibbing D, Kastrati A, Berger PB
Eur Heart J: 28 Dec 2015; epub ahead of print | PMID: 26712838
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Abstract

Avoiding non-responders to cardiac resynchronization therapy: a practical guide.

Daubert C, Behar N, Martins RP, Mabo P, Leclercq C
Over two decades after the introduction of cardiac resynchronization therapy (CRT) into clinical practice, ∼30% of candidates continue to fail to respond to this highly effective treatment of drug-refractory heart failure (HF). Since the causes of this non-response (NR) are multifactorial, it will require multidisciplinary efforts to overcome. Progress has, thus far, been slowed by several factors, ranging from a lack of consensus regarding the definition of NR and technological limitations to the delivery of therapy. We critically review the various endpoints that have been used in landmark clinical trials of CRT, and the variability in response rates that has been observed as a result of these different investigational designs, different sample populations enrolled and different means of therapy delivered, including new means of multisite and left ventricular endocardial simulation. Precise recommendations are offered regarding the optimal device programming, use of telemonitoring and optimization of management of HF. Potentially reversible causes of NR to CRT are reviewed, with emphasis on loss of biventricular stimulation due to competing arrhythmias. The prevention of NR to CRT is essential to improve the overall performance of this treatment and lower its risk-benefit ratio. These objectives require collaborative efforts by the HF team, the electrophysiologists and the cardiac imaging experts.

Eur Heart J: 01 Jul 2016; epub ahead of print
Daubert C, Behar N, Martins RP, Mabo P, Leclercq C
Eur Heart J: 01 Jul 2016; epub ahead of print | PMID: 27371720
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Abstract

The dream of near-zero X-rays ablation comes true.

Gaita F, Guerra PG, Battaglia A, Anselmino M
While radiation exposure related to natural sources plays a minor role, medicine-related exposure, represents, to date, a major exposure source. Within this exposure interventional electrophysiology is a relevant contributor. Unfortunately, no safe dose in radioprotection exists, the negative acute and long-term effects of radiological exposure may emerge at any radiation exposure dose. For this reason, patients and physicians should be aware of the risk of radiation exposure and the benefits of the imaging/procedure balanced by the required radiation exposure. Given this, performing a near to zero X-rays transcatheter ablation procedure should therefore represent an aim for all electrophysiological lab. Fortunately, the introduction of electroanatomic mapping systems, have provided the possibility to perform simple and complex electrophysiological procedures avoiding, or at least, limiting the use of radiations. The present review summarizes state of the art of feasibility and safety of the near to zero approach for the main electrophysiological procedures, highlighting the potential health benefits.

Eur Heart J: 28 Jun 2016; epub ahead of print
Gaita F, Guerra PG, Battaglia A, Anselmino M
Eur Heart J: 28 Jun 2016; epub ahead of print | PMID: 27354053
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Abstract

Disordered haematopoiesis and athero-thrombosis.

Murphy AJ, Tall AR
Atherosclerosis, the major underlying cause of cardiovascular disease, is characterized by a lipid-driven infiltration of inflammatory cells in large and medium arteries. Increased production and activation of monocytes, neutrophils, and platelets, driven by hypercholesterolaemia and defective high-density lipoproteins-mediated cholesterol efflux, tissue necrosis and cytokine production after myocardial infarction, or metabolic abnormalities associated with diabetes, contribute to atherogenesis and athero-thrombosis. This suggests that in addition to traditional approaches of low-density lipoproteins lowering and anti-platelet drugs, therapies directed at abnormal haematopoiesis, including anti-inflammatory agents, drugs that suppress myelopoiesis, and excessive platelet production, rHDL infusions and anti-obesity and anti-diabetic agents, may help to prevent athero-thrombosis.

Eur Heart J: 11 Feb 2016; epub ahead of print
Murphy AJ, Tall AR
Eur Heart J: 11 Feb 2016; epub ahead of print | PMID: 26869607
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Abstract

Rising adiposity curbing decline in the incidence of myocardial infarction: 20-year follow-up of British men and women in the Whitehall II cohort.

Hardoon SL, Morris RW, Whincup PH, Shipley MJ, ... Singh-Manoux A, Brunner EJ
Aims To estimate the contribution of risk factor trends to 20-year declines in myocardial infarction (MI) incidence in British men and women. Methods and results From 1985 to 2004, 6379 men and 3074 women in the Whitehall II cohort were followed for incident MI and risk factor trends. Over 20 years, the age-sex-adjusted hazard of MI fell by 74% (95% confidence interval 48-87%), corresponding to an average annual decline of 6.5% (3.2-9.7%). Thirty-four per cent (20-76%) of the decline in MI hazard could be statistically explained by declining non-HDL cholesterol levels, followed by increased HDL cholesterol (17%, 10-32%), reduced systolic blood pressure (13%, 7-24%), and reduced cigarette smoking prevalence (6%, 2-14%). Increased fruit and vegetable consumption made a non-significant contribution of 7% (-1-20%). In combination, these five risk factors explained 56% (34-112%). Rising body mass index (BMI) was counterproductive, reducing the scale of the decline by 11% (5-23%) in isolation. The MI decline and the impact of the risk factors appeared similar for men and women. Conclusion In men and women, over half of the decline in MI risk could be accounted for by favourable risk factor time trends. The adverse role of BMI emphasizes the importance of addressing the rising population BMI.

Eur Heart J: 09 Jun 2011; epub ahead of print
Hardoon SL, Morris RW, Whincup PH, Shipley MJ, ... Singh-Manoux A, Brunner EJ
Eur Heart J: 09 Jun 2011; epub ahead of print | PMID: 21653562
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Abstract

Prevention of sudden death in hypertrophic cardiomyopathy: bridging the gaps in knowledge.

Weissler-Snir A, Adler A, Williams L, Gruner C, Rakowski H
Sudden cardiac death (SCD) is the most devastating complication of hypertrophic cardiomyopathy (HCM). Although the annual rate of SCD in the general HCM population is <1% per year according to contemporary series, there is still a small subset of patients who are at increased risk of SCD. The greatest challenge in the management of HCM is identifying those at increased risk as an implantable cardioverter defibrillator is a potentially life-saving therapy. In this review, we sought to summarize the available data on SCD in HCM and provide a clinical perspective on the current differing and somewhat conflicting European and American recommendations on risk stratification, with balanced guidance with regards to rational clinical decision making. Additionally, we sought to learn more on the actual implementation of the guidelines by HCM experts worldwide.

Eur Heart J: 01 Jul 2016; epub ahead of print
Weissler-Snir A, Adler A, Williams L, Gruner C, Rakowski H
Eur Heart J: 01 Jul 2016; epub ahead of print | PMID: 27371714
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Abstract

Optimal duration of dual antiplatelet therapy after drug-eluting stent implantation: conceptual evolution based on emerging evidence.

Palmerini T, Stone GW
The objective of this article is to review the contemporary literature on optimal dual antiplatelet therapy (DAPT) duration after drug-eluting stent (DES) implantation. Relevant studies were searched through MEDLINE, the Cochrane database, and the EMBASE database. Of the 6852 publications retrieved, 23 were considered relevant, including 11 randomized controlled trials (RCTs) and 12 meta-analyses. Initially prescribed for 3-6 months after first-generation DES, the recommended duration of DAPT was subsequently prolonged to at least 1 year, a response to reports of late stent thrombosis after DAPT discontinuation. Seven RCTs subsequently suggested that 1-year DAPT may not be necessary after DES implantation, and that a 6-month or even a 3-month course of DAPT may be as effective and safer. In contrast, four RCTs examining the benefit of DAPT beyond 1 year reached conflicting conclusions. In the DAPT trial, 30-month compared with 12-month DAPT after DES resulted in reduced rates of stent thrombosis and major adverse cardiovascular events, but greater rates of major bleeding with increased non-cardiac mortality. Several meta-analyses have subsequently been performed collectively demonstrating increased rates of all-cause mortality with prolonged DAPT compared with shorter DAPT after DES, due to greater non-cardiovascular mortality with prolonged DAPT not offset by a concomitant reduction in cardiac mortality. The benefit-risk ratio of prolonged DAPT appears to be better in patients with myocardial infarction (MI) than in those without prior MI. On the basis of these findings, a personalized approach is advisable when deciding upon the optimal duration of DAPT after DES, wherein the individualized risks of ischaemic vs. bleeding events are carefully considered for each patient.

Eur Heart J: 21 Jan 2016; 37:353-64
Palmerini T, Stone GW
Eur Heart J: 21 Jan 2016; 37:353-64 | PMID: 26795933
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Abstract

Position Paper of the European Society of Cardiology Working Group Cellular Biology of the Heart: cell-based therapies for myocardial repair and regeneration in ischemic heart disease and heart failure.

Madonna R, Van Laake LW, Davidson SM, Engel FB, ... Ferdinandy P, Sluijter JP
Despite improvements in modern cardiovascular therapy, the morbidity and mortality of ischaemic heart disease (IHD) and heart failure (HF) remain significant in Europe and worldwide. Patients with IHD may benefit from therapies that would accelerate natural processes of postnatal collateral vessel formation and/or muscle regeneration. Here, we discuss the use of cells in the context of heart repair, and the most relevant results and current limitations from clinical trials using cell-based therapies to treat IHD and HF. We identify and discuss promising potential new therapeutic strategies that includeex vivocell-mediated gene therapy, the use of biomaterials and cell-free therapies aimed at increasing the success rates of therapy for IHD and HF. The overall aim of this Position Paper of the ESC Working Group Cellular Biology of the Heart is to provide recommendations on how to improve the therapeutic application of cell-based therapies for cardiac regeneration and repair.

Eur Heart J: 07 Apr 2016; epub ahead of print
Madonna R, Van Laake LW, Davidson SM, Engel FB, ... Ferdinandy P, Sluijter JP
Eur Heart J: 07 Apr 2016; epub ahead of print | PMID: 27055812
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Abstract

Hybrid intravascular imaging: recent advances, technical considerations, and current applications in the study of plaque pathophysiology.

Bourantas CV, Jaffer FA, Gijsen FJ, van Soest G, ... Tearney GJ, Serruys PW
Cumulative evidence from histology-based studies demonstrate that the currently available intravascular imaging techniques have fundamental limitations that do not allow complete and detailed evaluation of plaque morphology and pathobiology, limiting the ability to accurately identify high-risk plaques. To overcome these drawbacks, new efforts are developing for data fusion methodologies and the design of hybrid, dual-probe catheters to enable accurate assessment of plaque characteristics, and reliable identification of high-risk lesions. Today several dual-probe catheters have been introduced including combined near infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), that is already commercially available, IVUS-optical coherence tomography (OCT), the OCT-NIRS, the OCT-near infrared fluorescence (NIRF) molecular imaging, IVUS-NIRF, IVUS intravascular photoacoustic imaging and combined fluorescence lifetime-IVUS imaging. These multimodal approaches appear able to overcome limitations of standalone imaging and provide comprehensive visualization of plaque composition and plaque biology. The aim of this review article is to summarize the advances in hybrid intravascular imaging, discuss the technical challenges that should be addressed in order to have a use in the clinical arena, and present the evidence from their first applications aiming to highlight their potential value in the study of atherosclerosis.

Eur Heart J: 26 Apr 2016; epub ahead of print
Bourantas CV, Jaffer FA, Gijsen FJ, van Soest G, ... Tearney GJ, Serruys PW
Eur Heart J: 26 Apr 2016; epub ahead of print | PMID: 27118197
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Abstract

Agents with vasodilator properties in acute heart failure.

Singh A, Laribi S, Teerlink JR, Mebazaa A
Millions of patients worldwide are admitted for acute heart failure (AHF) each year and physicians caring for these patients are confronted with the short-term challenges of reducing symptoms while preventing end organ dysfunction without causing additional harm, and the intermediate-term challenges of improving clinical outcomes such as hospital readmission and survival. There are limited data demonstrating the efficacy of any currently available therapies for AHF to meet these goals. After diuretics, vasodilators are the most common intravenous therapy for AHF, but neither nitrates, nitroprusside, nor nesiritide have robust evidence supporting their ability to provide meaningful effects on clinical outcomes, except perhaps early symptom improvement. Recently, a number of novel agents with vasodilating properties have been developed for the treatment of AHF. These agents include serelaxin, natriuretic peptides (ularitide, cenderitide), β-arrestin-biased angiotensin II type 1 receptor ligands (TRV120027), nitroxyl donors (CXL-1020, CXL-1427), soluble guanylate cyclase modulators (cinaciguat, vericiguat), short-acting calcium channel blockers (clevidipine), and potassium channel activators (nicorandil). These development programmes range from the stage of early dose-finding studies (e.g. TRV120027, CXL-1427) to large, multicentre mortality trials (e.g. serelaxin, ularitide). There is an urgent need for agents with vasodilating properties that will improve both in-hospital and post-discharge clinical outcomes, and these novel approaches may provide opportunities to address this need.

Eur Heart J: 05 Feb 2016; epub ahead of print
Singh A, Laribi S, Teerlink JR, Mebazaa A
Eur Heart J: 05 Feb 2016; epub ahead of print | PMID: 26850077
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Abstract

The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: a continual challenge.

Heusch G, Gersh BJ
The incidence of ST segment elevation myocardial infarction (STEMI) has decreased over the last two decades in developed countries, but mortality from STEMI despite widespread access to reperfusion therapy is still substantial as is the development of heart failure, particularly among an expanding older population. In developing countries, the incidence of STEMI is increasing and interventional reperfusion is often not available. We here review the pathophysiology of acute myocardial infarction and reperfusion, notably the temporal and spatial evolution of ischaemic and reperfusion injury, the different modes of cell death, and the resulting coronary microvascular dysfunction. We then go on to briefly characterize the cardioprotective phenomena of ischaemic preconditioning, ischaemic postconditioning, and remote ischaemic conditioning and their underlying signal transduction pathways. We discuss in detail the attempts to translate conditioning strategies and drug therapy into the clinical setting. Most attempts have failed so far to reduce infarct size and improve clinical outcomes in STEMI patients, and we discuss potential reasons for such failure. Currently, it appears that remote ischaemic conditioning and a few drugs (atrial natriuretic peptide, exenatide, metoprolol, and esmolol) reduce infarct size, but studies with clinical outcome as primary endpoint are still underway.

Eur Heart J: 28 Jun 2016; epub ahead of print
Heusch G, Gersh BJ
Eur Heart J: 28 Jun 2016; epub ahead of print | PMID: 27354052
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The prevalence, distribution, and clinical outcomes of electrocardiographic repolarization patterns in male athletes of African/Afro-Caribbean origin.

Papadakis M, Carre F, Kervio G, Rawlins J, ... Fonseca T, Sharma S
Aims Athletic training in male black athletes (BAs) is associated with marked ECG repolarization changes that overlap with hypertrophic cardiomyopathy (HCM). Differentiating between the two entities is prudent since BAs exhibit a higher prevalence of exercise-related sudden death from HCM compared with white athletes (WAs). Methods and results Between 1996 and 2010, 904 BAs underwent serial cardiac evaluations including ECG and echocardiography. Athletes exhibiting T-wave inversions were investigated further for HCM. Results were compared with 1819 WAs, 119 black controls (BCs), and 52 black HCM patients. Athletes were followed up for 69.7 ± 29.6 months. T-wave inversions were present in 82.7% HCM patients, 22.8% BAs, 10.1% BCs, and 3.7% WAs. In athletes, the major determinant of T-wave inversions was black ethnicity. T-wave inversions in BAs (12.7%) were predominantly confined to contiguous anterior leads (V1-V4). Only 4.1% of BAs exhibited T-wave inversions in the lateral leads. In contrast, both BCs and HCM patients exhibited lower prevalence of T-wave inversions in leads V1-V4 (4.2 and 3.8%, respectively) with most T-wave inversions in HCM patients (76.9%) involving the lateral leads. During follow-up one BA survived cardiac arrest and two athletes (one BA, one WA) were diagnosed with HCM. All three exhibited T-wave inversions in the lateral leads. Conclusions T-wave inversions in leads V1-V4 appear to represent an ethnic variant of \'athlete\'s heart\'. Conversely, T-wave inversions in the lateral leads may represent the initial expression of underlying cardiomyopathy and merit further evaluation and regular surveillance.

Eur Heart J: 26 May 2011; epub ahead of print
Papadakis M, Carre F, Kervio G, Rawlins J, ... Fonseca T, Sharma S
Eur Heart J: 26 May 2011; epub ahead of print | PMID: 21613263
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Abstract

Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events.

Jespersen L, Hvelplund A, Abildstrøm SZ, Pedersen F, ... Kelbæk H, Prescott E
AimsPatients with chest pain and no obstructive coronary artery disease (CAD) are considered at low risk for cardiovascular events but evidence supporting this is scarce. We investigated the prognostic implications of stable angina pectoris in relation to the presence and degree of CAD with no obstructive CAD in focus.Methods and resultsWe identified 11 223 patients referred for coronary angiography (CAG) in 1998-2009 with stable angina pectoris as indication and 5705 participants from the Copenhagen City Heart Study for comparison. Main outcome measures were major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, stroke or heart failure, and all-cause mortality. Significantly more women (65%) than men (32%) had no obstructive CAD (P< 0.001). In Cox\'s models adjusted for age, body mass index, diabetes, smoking, and use of lipid-lowering or antihypertensive medication, hazard ratios (HRs) associated with no obstructive CAD were similar in men and women. In the pooled analysis, the risk of MACE increased with increasing degrees of CAD with multivariable-adjusted HRs of 1.52 (95% confidence interval, 1.27-1.83) for patients with normal coronary arteries and 1.85 (1.51-2.28) for patients with diffuse non-obstructive CAD compared with the reference population. For all-cause mortality, normal coronary arteries and diffuse non-obstructive CAD were associated with HRs of 1.29 (1.07-1.56) and 1.52 (1.24-1.88), respectively.ConclusionPatients with stable angina and normal coronary arteries or diffuse non-obstructive CAD have elevated risks of MACE and all-cause mortality compared with a reference population without ischaemic heart disease.

Eur Heart J: 13 Sep 2011; epub ahead of print
Jespersen L, Hvelplund A, Abildstrøm SZ, Pedersen F, ... Kelbæk H, Prescott E
Eur Heart J: 13 Sep 2011; epub ahead of print | PMID: 21911339
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Abstract

Molecular mechanism of endothelial and vascular aging: implications for cardiovascular disease.

Camici GG, Savarese G, Akhmedov A, Lüscher TF
Western societies are aging due to an increasing life span, decreased birth rates, and improving social and health conditions. On the other hand, the prevalence of cardiovascular (CV) and cerebrovascular (CBV) diseases rises with age. Thus, in view of the ongoing aging pandemic, it is appropriate to better understand the molecular pathways of aging as well as age-associated CV and CBV diseases. Oxidative stress contributes to aging of organs and the whole body by an accumulation of reactive oxygen species promoting oxidative damage. Indeed, increased oxidative stress produced in the mitochondria and cytosol of heart and brain is a common denominator to almost all CV and CBV diseases. The mitochondrial adaptor protein p66(Shc) and the family of deacetylase enzymes, the sirtuins, regulate the aging process, determine lifespan of many species and are involved in CV diseases. GDF11, a member of TGFβ superfamily with homology to myostatin also retards the aging process via yet unknown mechanisms. Recent evidence points towards a promising role of this novel \'rejuvenation\' factor in reducing age-related heart disease. Finally, telomere length is also involved in aging and the development of age-related CV dysfunction. This review focuses on the latest scientific advances in understanding age-related changes of the CV and CBV system, as well as delineating potential novel therapeutic targets derived from aging research for CV and CBV diseases.

Eur Heart J: 05 Nov 2015; epub ahead of print
Camici GG, Savarese G, Akhmedov A, Lüscher TF
Eur Heart J: 05 Nov 2015; epub ahead of print | PMID: 26543043
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Abstract

Antidepressant medication use and future risk of cardiovascular disease: the Scottish Health Survey.

Hamer M, David Batty G, Seldenrijk A, Kivimaki M
Aims The association between antidepressant use and risk of cardiovascular disease (CVD) remains controversial, particularly in initially healthy samples. Given that antidepressants such as selective serotonin reuptake inhibitors (SSRIs) are now prescribed not only for depression, but also for a wide range of conditions, this issue has relevance to the general population. We assessed the association between antidepressant medication use and future risk of CVD in a representative sample of community-dwelling adults without known CVD. Methods and results A prospective cohort study of 14 784 adults (aged 52.4 ± 11.9 years, 43.9% males) without a known history of CVD was drawn from the Scottish Health Surveys. Of these study participants, 4.9% reported the use of antidepressant medication. Incident CVD events (comprising CVD death, non-fatal myocardial infarction, coronary surgical procedures, stroke, and heart failure) over 8-year follow-up were ascertained by a linkage to national registers; a total of 1434 events were recorded. The use of tricyclic antidepressants (TCAs) was associated with elevated risk of CVD [multivariate-adjusted hazard ratio (HR) = 1.35, 95% confidence interval (CI), 1.03-1.77] after accounting for a range of covariates. There was a non-significant association between TCA use and coronary heart disease events (969 events, multivariate-adjusted HR = 1.24, 95% CI, 0.87-1.75). The use of SSRIs was not associated with CVD. Neither class of drug was associated with all-cause mortality risk. Conclusion Although replication is required, the increased risk of CVD in men and women taking TCAs was not explained by existing mental illness, which suggests that this medication is associated with an excess disease burden.

Eur Heart J: 01 Dec 2010; epub ahead of print
Hamer M, David Batty G, Seldenrijk A, Kivimaki M
Eur Heart J: 01 Dec 2010; epub ahead of print | PMID: 21118851
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Abstract

Living history of medicine: vascular scaffolding, from dream to reality.

Sigwart U
Following the launch of balloon angioplasty in 1977, its deficiencies-abrupt occlusion requiring emergency bypass surgery in one in twenty attempts and recurrence in one in three cases-became soon apparent. The attempts to eliminate the element of chance from this otherwise highly attractive technique resulted in the concept of intra-vascular scaffolding. Following the inception of self-expanding mesh stents made from stainless steel and extensive bench testing and animal experiments, the first clinical data were obtained in Switzerland almost 30 years ago in 1986 with promising, albeit not undisputed results. Technical improvements including potent platelet inhibitors have made the technique a cornerstone of catheter-treatment of vascular disease. This paper gives an account of the sometimes difficult beginnings of coronary and non-coronary stenting at the University of Lausanne in Switzerland.

Eur Heart J: 20 Jan 2016; epub ahead of print
Sigwart U
Eur Heart J: 20 Jan 2016; epub ahead of print | PMID: 26792876
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Abstract

TAVI or No TAVI: identifying patients unlikely to benefit from transcatheter aortic valve implantation.

Puri R, Iung B, Cohen DJ, Rodés-Cabau J
Transcatheter aortic valve implantation (TAVI) has spawned the evolution of novel catheter-based therapies for a variety of cardiovascular conditions. Newer device iterations are delivering lower peri- and early post-procedural complication rates in patients with aortic stenosis, who were otherwise deemed too high risk for conventional surgical valve replacement. Yet beyond the post-procedural period, a considerable portion of current TAVI recipients fail to derive a benefit from TAVI, either dying or displaying a lack of clinical and functional improvement. Considerable interest now lies in better identifying factors likely to predict futility post-TAVI. Implicit in this are the critical roles of frailty, disability, and a multimorbidity patient assessment. In this review, we outline the roles that a variety of medical comorbidities play in determining futile post-TAVI outcomes, including the critical role of frailty underlying the identification of patients unlikely to benefit from TAVI. We discuss various TAVI risk scores, and further propose that by combining such scores along with frailty parameters and the presence of specific organ failure, a more accurate and holistic assessment of potential TAVI-related futility could be achieved.

Eur Heart J: 27 Jan 2016; epub ahead of print
Puri R, Iung B, Cohen DJ, Rodés-Cabau J
Eur Heart J: 27 Jan 2016; epub ahead of print | PMID: 26819226
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Abstract

Statins and renovascular disease in the elderly: a population-based cohort study.

Hackam DG, Wu F, Li P, Austin PC, ... Mamdani MM, Garg AX
Aims More than 90% of cases of renovascular disease (RVD) are caused by atherosclerosis; thus patients with this condition are at high risk for vascular events. We examined the association of statins with prognosis in patients with RVD. Methods and results We performed a population-based cohort study in 4040 patients with RVD older than 65 years using province-wide health data in Ontario, Canada. The primary outcome was time to first cardiorenal event, specifically myocardial infarction, stroke, heart failure, acute renal failure, dialysis or death; the primary analysis used a time-dependent covariate for statin exposure. Despite having a greater burden of cardiovascular and renal comorbidity, the risk of the primary outcome was significantly lower in statin users than in non-users [unadjusted hazard ratio (HR) 0.51, 95% confidence interval (CI) 0.47-0.57; P < 0.0001]. This association was materially unchanged after adjusting for demographic characteristics, cardiovascular risk factors, other comorbidities, measures of health-care utilization, screening, and concomitant medications (adjusted HR 0.51, 95% CI 0.46-0.57). An analysis using the same endpoint in a propensity-matched cohort without time-dependent statin exposure revealed a lower risk of the primary outcome in statin-treated patients but with a substantially more conservative point estimate (HR 0.82, 95% CI 0.71-0.95). Conclusion These data suggest that statins are associated with improved prognosis in elderly patients with RVD.

Eur Heart J: 15 Dec 2010; epub ahead of print
Hackam DG, Wu F, Li P, Austin PC, ... Mamdani MM, Garg AX
Eur Heart J: 15 Dec 2010; epub ahead of print | PMID: 21156722
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Abstract

Deficiency of type 1 cannabinoid receptors worsens acute heart failure induced by pressure overload in mice.

Liao Y, Bin J, Asakura M, Xuan W, ... Takashima S, Kitakaze M
Aims We investigated the influence of type one cannabinoid receptor (CB1) deficiency on acute heart failure (AHF) and the underlying mechanism. Acute heart failure syndrome is an important clinical problem because of its high morbidity and mortality rates. Activation of CB1 induces vascular dilation and reinforces the properties of morphine, long-standing therapies for AHF syndrome, but the effect of endogenous CB1 activation on AHF is largely unknown. Methods and results Acute heart failure mouse model characterized by hypertension and pulmonary oedema was created by using transverse aortic constriction (TAC). Mortality, echocardiography, haemodynamic, morphology, and circulatory catecholamine levels in response to TAC were evaluated in CB1 knockout (KO) and wild-type mice. Type one cannabinoid receptor KO mice had a much higher mortality rate at 1 week after TAC attributable to AHF (65 vs. 11%, P< 0.001). One hour after TAC, CB1 KO mice had significant larger lung weight to body weight ratio (LW/BW, 14.53 + 1.09 mg/g in KO vs. 10.42 + 0.36 mg/g in WT, P < 0.01) and higher plasma epinephrine levels (9720 + 1226 pg/mL vs. 6378 + 832 pg/mL, P < 0.05). Pharmacological activation of CB1 reduced LW/BW in wild-type mice. Administration of epinephrine to wild-type TAC mice significantly increased left ventricular end-diastolic pressure and LW/BW, while CB1 agonists reduced the LW/BW and the plasma levels of catecholamine and increased myocardial activity of AMP-activated protein kinase. Conclusion Endogenous activation of CB1 in mice has cardiac protection in AHF, which is attributable to the inhibition of excessive sympathetic activation.

Eur Heart J: 25 Jul 2011; epub ahead of print
Liao Y, Bin J, Asakura M, Xuan W, ... Takashima S, Kitakaze M
Eur Heart J: 25 Jul 2011; epub ahead of print | PMID: 21785110
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Abstract

Standing at the crossroads between new and historically prevalent heart disease: effects of migration and socio-economic factors in the Heart of Soweto cohort study.

Stewart S, Carrington M, Pretorius S, Methusi P, Sliwa K
Aims Migration, urbanization, and change in socio-economic factors have potentially profound effects on heart disease in low-to-middle income countries. Methods and results Chris Hani Baragwanath Hospital in Soweto, South Africa, provides health care to >1 million Africans. We systematically captured data from all de novo presentations of suspected heart disease (focusing on \'new\' vs. historically prevalent forms) during 2006-2008. There were 3168 female (52 ± 18 years) vs. 2160 male (53 ± 17 years) cases. Overall, 999 (19%) presented with uncomplicated hypertension (n = 988) or type II diabetes, 1862 cases (35%) \'new\' heart disease (1146 and 581 cases of hypertensive heart failure and coronary artery disease), and 2092 cases (39%) of historically prevalent heart disease (including 724 with primary valve disease and 502 idiopathic dilated cardiomyopathies). Level of education and non-communicable risk factors were important correlates of advanced disease. The rate of historically prevalent cases was higher in those aged 20-49 years (19-60 cases/100 000 population/annum) whilst being higher for "new" heart disease in those aged >50 years (155-343 cases/population/annum). Historically prevalent heart disease cases were younger [adjusted odds ratio (OR) 0.98, 95% 0.97-0.99 per year], more likely to be African (OR 4.59, 95% 2.76-7.60) while being less likely to originate from Soweto (OR 0.87, 95% 0.75-1.00) and be female (OR 0.67, 95% 0.49-0.92). Conclusion Dynamic socio-economic and lifestyle factors characteristic of epidemiological transition appear to have positioned the urban, mainly African community of Soweto at the crossroads between historically prevalent and \'new\' forms of heart disease.

Eur Heart J: 17 Dec 2010; epub ahead of print
Stewart S, Carrington M, Pretorius S, Methusi P, Sliwa K
Eur Heart J: 17 Dec 2010; epub ahead of print | PMID: 21163850
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Prognostic predictors in arrhythmogenic right ventricular cardiomyopathy: results from a 10-year registry.

Pinamonti B, Dragos AM, Pyxaras SA, Merlo M, ... Mestroni L, Sinagra G
Aims We sought to examine the clinical presentation and natural history and to identify long-term prognostic predictors in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) as information concerning the natural history and risk stratification of ARVC is still incomplete. Methods and results A cohort of 96 ARVC patients (68% males, 35 ± 15 years) was enrolled and underwent structured diagnostic protocol and follow-up. Primary study endpoints were death and heart transplantation (HTx). Clinical and echo-Doppler data were assessed as prognostic indicators. Sixty-five per cent of patients had right ventricular (RV) systolic dysfunction (RV fractional area change < 33%) and 24% had left ventricular (LV) systolic dysfunction (LV ejection fraction <50%). During a mean follow-up of 128 ± 92 months, 20 patients (21%) experienced cardiac death or underwent HTx. At multivariate analysis (Model 1), RV dysfunction [hazard ratio (HR): 4.12; 95% confidence interval (CI): 1.01-18.0; P = 0.05], significant tricuspid regurgitation (HR: 7.6; 95% CI: 2.6-22.0; P < 0.001), and amiodarone treatment (HR: 3.4; 95% CI: 1.3-8.8; P = 0.01) resulted as predictors of death/HTx. When inserting in the model, the \'ordinal dysfunction\' (Model 2), which considers the presence of both RV and LV dysfunctions, this variable emerged as an independent prognostic predictor (HR: 6.3; 95% CI: 2.17-17.45; P < 0.001). At the receiver operating characteristic analysis, Model 2 was significantly more accurate in predicting long-term outcome compared with Model 1 (area under the curve 0.84 vs. 0.78, respectively; P = 0.04). Conclusion In our tertiary referral centre ARVC population, the presence of LV dysfunction at diagnosis has an incremental power in predicting adverse outcome compared with RV dysfunction alone.

Eur Heart J: 02 Mar 2011; epub ahead of print
Pinamonti B, Dragos AM, Pyxaras SA, Merlo M, ... Mestroni L, Sinagra G
Eur Heart J: 02 Mar 2011; epub ahead of print | PMID: 21362707
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Abstract

Invasive coronary imaging: any role in primary and secondary prevention?

Di Mario C, Moreno PR
This review discusses the possibilities offered by new modalities of non-invasive and invasive coronary imaging in an effort to optimize risk stratification for coronary artery disease, and identify subgroups at high risk that may benefit from an aggressive, personalized approach, with access to a growing number of novel drugs and interventions. Special emphasis is placed on the progress of novel invasive imaging techniques such as near infrared spectroscopy and optical coherence tomography that can reliably identify thin-capped fibroatheromas. Multiple trials are exploring the feasibility of these techniques to guide modulation of risk factor control and treatment of non-flow limiting lesions at high risk of destabilization and progression in patients undergoing clinically mandated angioplasty of angiographically critical lesions. Asymptomatic patients at high risk of cardiovascular ischaemic events may also benefit, with the intermediate step of a wider application of calcium score and angiography with multi-slice computed tomography, by a selective use of invasive imaging.

Eur Heart J: 21 Mar 2016; epub ahead of print
Di Mario C, Moreno PR
Eur Heart J: 21 Mar 2016; epub ahead of print | PMID: 27002121
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Randomized comparison of everolimus- and paclitaxel-eluting stents: pooled analysis of the 2-year clinical follow-up from the SPIRIT II and III trials.

Onuma Y, Serruys PW, Kukreja N, Veldhof S, ... Stone GW, on behalf of the SPIRIT II and III Investigators
Aims To investigate the clinical impact of the following observations in the randomized SPIRIT II and III trials: an incremental increase in in-stent neointima between 1 and 2 years with the everolimus-eluting stent (EES) but not with the paclitaxel-eluting stent (PES) in SPIRIT II; a tendency of lower stent thrombosis in EES than in PES among those who first discontinued a thienopyridine after 6 months. Methods and results A pooled analysis was performed using the 2-year clinical data from the SPIRIT II and III trials randomizing a total of 1302 patients with de novo coronary artery lesions either to EES or to PES. Inclusion and exclusion criteria were comparable between two trials. Major adverse cardiac event (MACE) was defined as cardiac death, myocardial infarction, or ischaemia-driven target lesion revascularization (TLR). At 2 years, MACE rates were 7.1% in EES vs. 12.3% in PES, respectively (log-rank P = 0.0014), without late increase in TLR. Among those who first discontinued a thienopyridine after 6 months, Academic Research Consortium (ARC) definite or probable stent thrombosis was 1.1% in EES vs. 1.3% in PES (P = 1.00). Conclusion The benefits of EES in reducing TLR were robust between 6 months and 2 years. No significant difference in the thrombosis rate among those who first stopped a thienopyridine after 6 months was observed.

Eur Heart J: 01 Feb 2010; epub ahead of print
Onuma Y, Serruys PW, Kukreja N, Veldhof S, ... Stone GW, on behalf of the SPIRIT II and III Investigators
Eur Heart J: 01 Feb 2010; epub ahead of print | PMID: 20118171
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Abstract

Imaging and atrial fibrillation: the role of multimodality imaging in patient evaluation and management of atrial fibrillation.

Tops LF, Schalij MJ, Bax JJ
Atrial fibrillation (AF) is the most common cardiac arrhythmia, and is associated with an increased risk of cardiac morbidity and mortality. In this review, the role of multimodality imaging in the evaluation and treatment of AF is discussed in two main parts. First, an overview of the initial assessment of an AF patient is provided, including the role of different imaging techniques. Conditions that are associated with AF (coronary artery disease, heart failure, valvular heart disease, and left ventricular hypertrophy), and the assessment with various imaging modalities, will be reviewed. Furthermore, left atrial size assessment and the screening for thrombus formation are addressed. Secondly, the role of imaging in the invasive treatment of AF with catheter ablation is reviewed. Issues that should be considered before the procedure including contra-indications and pulmonary vein and left atrial anatomy will be discussed. Furthermore, the integration of different imaging modalities during catheter ablation is explored. Finally, an overview of the role of imaging in the follow-up of patients treated with catheter ablation will be provided.

Eur Heart J: 03 Feb 2010; epub ahead of print
Tops LF, Schalij MJ, Bax JJ
Eur Heart J: 03 Feb 2010; epub ahead of print | PMID: 20124284
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This program is still in alpha version.