Corrigendum to: 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases.

Corrigendum to: 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases [Eur Heart Journal (2014) 35, 2873­2926,doi:10.1093/eurheartj/ehu281]. In Table 3, the radiation for MRI is "0" and not "-". The corrected table is shown below.

Genetics of sudden cardiac death in the young.

Sudden cardiac death (SCD) has an enormous impact on those who are left behind, evoking strong feelings of anxiety and incomprehension because such a dramatic event was not anticipated. Moreover, over the last decade a prominent genetic contribution to the pathogenesis of SCD has been unveiled. As many inherited cardiac diseases show an autosomal dominant pattern of inheritance, the risk of carrying the same inherited predisposition is a real concern for the relatives. In this article, we discuss the major causes of primary electrical disorders, cardiomyopathies and thoracic aortic dissection and address issues in genotype-phenotype correlation, personalized management and cardiogenetic counselling.

Impaired coronary flow reserve after a recent myocardial infarction: correlation with infarct size and extent of microvascular obstruction.

BACKGROUND: The exact relationship between the coronary flow reserve (CFR) and infarct size remains unknown. In this prospective study the relationship between the CFR both in the infarcted and remote myocardium and infarct size was investigated. Furthermore, the diagnostic value of the CFR to predict the extent of microvascular obstruction (MO) was evaluated. METHODS: In thirty patients the CFR was measured with a Doppler guide wire 6 ± 3 days after a first myocardial infarction (MI) in the infarct related and in a reference coronary artery. MO and infarct size were determined with magnetic resonance imaging. RESULTS: The CFR was inversely related to infarct size in the infarcted and remote myocardium (respectively, r=-0.60, p<0.01 and r=-0.62, p<0.01). In the infarcted myocardium the extent of MO was strongly related to the infarct size and was in a multivariate analysis the single significant determinant of the CFR and the hyperaemic flow. In the remote myocardium no relationship was present between infarct size and hyperaemic flow, but the baseline flow increased as the infarct size became larger (r=0.58, p<0.01). In a receiver operator characteristic (ROC) analysis, a CFR value ≤ 2 in the infarct related coronary artery offered the best sensitivity (65%) and specificity (71%) to detect the presence of MO (p<0.05). CONCLUSIONS: After MI, the CFR both in the infarcted and remote myocardium is inversely related to infarct size. In the infarcted myocardium, a CFR value ≤ 2 predicts the presence of MO with moderate sensitivity and specificity.

Severe stomatitis complicating immune-suppressive switch after cardiac transplantation.

Everolimus is a recently developed immunosuppressive drug for patients following solid organ transplantation. Its mechanism of action, independent of calcineurin, is different from that of ciclosporin and tacrolimus and because of its lack of nephrotoxicity, it is a good alternative for calcineurin inhibitors in patients with renal dysfunction. In this paper we describe the case report of a 66-year-old caucasian female who underwent heart transplantation in December 2006. After induction with rabbit anti-thymocytic globulin, her immunosuppressive therapy comprised the combination of tacrolimus, mycophenolate mofetil (MMF) and steroids. Because of renal dysfunction, tacrolimus was changed for everolimus after 6 months. Unfortunately our patient developed severe stomatitis with aphthous ulcerations, shortly after the switch. Despite oral therapy (local anaesthetics), severe pain and malnourishment prompted interruption of everolimus and MMF and therapy was changed to ciclosporin and azathioprine. In addition, thalidomide was added. During the following weeks, there was progressive healing of the ulcerations. MMF was re-introduced and thalidomide was stopped after 6 weeks, without recurrent lesions after 4 months of follow-up.

Molecular aspects of the congenital and acquired Long QT Syndrome: clinical implications.

The Long QT Syndrome (LQTS) is a complex and multi-factorial disorder that predisposes to life-threatening ventricular arrhythmias. Both hereditary and acquired subforms have been identified over the years. Recently, it has become clear that the interaction of multiple acquired and genetic aetiologic factors (e.g. disease modifiers) play an important role in differentiating genotype into a continuous spectrum of clinical or subclinical phenotypes. The genotype-phenotype correlation thereby remains very unpredictable in asymptomatic patients, raising important concerns for clinical practice and also for drug development. Therefore, this review aims at providing a comprehensive overview on LQTS highlighting the molecular mechanisms of arrhythmogenesis involved in both the hereditary and the acquired subtypes of the disorder. From this perspective this manuscript then focuses on how the genotype translates into phenotype. A logical overview is provided with the multitude of hereditary and acquired factors that are involved and of the complexity of the interactions that ultimately result in the heterogeneous expressivity and the unpredictability of the phenotype. Based on recent basic and clinical data this review further aims at providing an update on the clinical properties and management of LQT patients including diagnostic work-up and therapy.

Coronary microvascular dysfunction after myocardial infarction: increased coronary zero flow pressure both in the infarcted and in the remote myocardium is mainly related to left ventricular filling pressure.

OBJECTIVE: To investigate the underlying mechanisms of a decreased coronary flow reserve after myocardial infarction (MI) by analysing the characteristics of the diastolic hyperaemic coronary pressure-flow relationship. DESIGN: Prospective study. SETTING: Tertiary care hospital. PATIENTS: 68 patients with a recent MI and 27 patients with stable angina pectoris (AP; control group). MAIN OUTCOME MEASURES: The intercept with the pressure axis (the zero flow pressure or Pzf) and slope index of the pressure-flow relationship (SIPF) were calculated from the simultaneously recorded hyperaemic intracoronary blood flow velocity and aortic pressure after successful coronary stenting. RESULTS: A stepwise increase in Pzf from AP (14.6 (8.0) mm Hg), over non-Q-wave MI (22.5 (9.1) mm Hg), to Q-wave MI (37.1 (12.9) mm Hg; p<0.001) was observed. Similar changes in Pzf were found in a reference artery perfusing the non-infarcted myocardium. Multivariate analysis showed that in both regions the left ventricular end-diastolic pressure (LVEDP) was the most important determinant of the Pzf. The SIPF was not statistically different in the treated vessel between patients with MI and AP, but was increased in MI patients with a markedly increased LVEDP. CONCLUSIONS: After an MI, the coronary pressure-flow relationship is shifted to the right both in the infarcted and in the non-infarcted remote myocardium, as shown by the increased Pzf. The correlation with Pzf suggests that elevated left ventricular filling pressures contribute to the impediment of myocardial perfusion in patients with infarction.

Mianserin and ventricular tachycardia: case report and review of the literature.

Mianserin is a drug frequently used to treat depression and sleep disturbances. Despite documented effects on various cardiac tissues in animal studies, mianserin has a very safe clinical profile. Only one case of ventricular arrhythmias in a patient treated with mianserin has been reported. This patient had a severe cardiac history. Our case is to our knowledge the first report on ventricular arrhythmias in a patient treated with mianserin without previous or present cardiac disease. After discontinuation of mianserin the arrhythmias disappeared within days. The literature on mianserin toxicity is reviewed.

Myocardial ischemia/reperfusion-injury, a clinical view on a complex pathophysiological process.

Myocardial infarction is the major cause of death in the world. Over the last two decades, coronary reperfusion therapy has become established for the management of acute myocardial infarction (AMI). However, restoration of blood flow to previously ischemic myocardium results in the so-called ischemia/reperfusion (IR)-injury. The different clinical manifestations of this injury include myocardial necrosis, arrhythmia, myocardial stunning and endothelial- and microvascular dysfunction including the no-reflow phenomenon. The pathogenesis of ischemia/reperfusion injury consists of many mechanisms. Recently, there's increasing evidence for an important role in IR-injury on hypercontracture induced by high levels of cytosolic calcium or by low concentrations of ATP. In the last years, many studies on experimental models were investigated, but the clinical trials confirming these effects remain spare. Recently, the beneficial effect of Na(+)/H(+)-exchange inhibitor cariporide and of the oxygen-derived free radical (ODFR) scavenger vitamin E on coronary bypass surgery-induced IR-injury were demonstrated. Also recently, the beneficial effect of allopurinol on the recovery of left ventricular function after rescue balloon-dilatation was demonstrated. The beneficial effect of magnesium and trimetazidine on IR-injury remains controversial. The beneficial effect of adenosine remains to be further confirmed. There's also increasing interest in agentia combining the property of upregulating NO-synthase (e.g. L-arginine) and restoring the balance between NO and free radicals (e.g. tetrahydrobiopterin). One of such agents could be folic acid. In this review article the authors give an overview of the recent insights concerning pathogenesis and therapeutic possibilities to prevent IR-induced injury.

Coronary circulation and interventional cardiology.

Cardiovascular disease has long been the leading cause of death in developed countries and it is rapidly becoming the number one killer in developing countries. Sudden heart attacks remain the primary cause of death in the United States: over 1.4 million attacks are suffered every year, more than half of which prove fatal. Interventional Cardiology is aimed to alleviate symptoms of cardiac pains and poor coronary circulation, and reduce the risk of death and nonfatal myocardial infarction. Our understanding of the coronary circulation has improved several folds due to the introduction of advance technologies. Yet, the microcirculatory flow needs future investigation.

Importance of methodology in determination of Chlamydia pneumoniae seropositivity in healthy subjects and in patients with coronary atherosclerosis.

Enzyme immunoassays (EIAs) for the detection of Chlamydia pneumoniae antibodies were compared to the microimmunofluorescence (MIF) test, the reference method. Furthermore, we assessed the hypothesis that a possible relationship between Chlamydia pneumoniae immunoglobulin G (IgG) antibodies and coronary artery disease is dependent on the type of EIA. Sera from 112 healthy men (mean age, 50.1 years) were tested for antibodies against Chlamydia pneumoniae by five commercial test kits: Focus Chlamydia MIF IgG test, Labsystems Chlamydia pneumoniae IgG EIA (LS EIA), R-Biopharm Elegance Chlamydia pneumoniae IgG EIA (RB EIA), Medac Chlamydia pneumoniae IgG sandwich enzyme-linked immunosorbent assay ELISA (MCp sELISA) and Medac Chlamydia IgG recombinant enzyme-linked immunosorbent assay ELISA (MC rELISA). Sera from 106 consecutive male patients (mean age, 63.6 years) undergoing diagnostic coronary angiography were also examined using the Focus MIF, LS EIA, MCp sELISA, and MC rELISA techniques. The agreement between LS EIA (65 to 83% [controls-patients]) or MC rELISA (49 to 61%) and Focus MIF (78 to 83%) was average to fair (kappa = 0.597 and 0.234, respectively). MCp sELISA and RB EIA showed good agreement with MIF (kappa = 0.686 and 0.665, respectively), with 80 to 89 and 79% of individuals reacting positively. A significant difference in seroprevalence between patients and healthy subjects was observed with the LS EIA, while seropositivities in the two study groups appeared equal when the Focus MIF assay was applied. The MC rELISA and MCp sELISA gave statistically significant differences in antibody seroprevalence in patients with two-vessel disease or when the patient group combined individuals with a two- or a three-vessel disease, respectively. The concordance between MIF and other commonly used serological assays for C. pneumoniae IgG antibody detection is good to fair. The choice of serological assay has important implications for C. pneumoniae antibody seroprevalence, as well as for the relationship between C. pneumoniae seropositivity and coronary artery disease.

Chlamydia pneumoniae and atherosclerosis.

Chlamydia pneumoniae, a human respiratory pathogen, has been linked to atherosclerotic disease based on sero-epidemiologic studies, direct detection of the organism in atherosclerotic lesions, animal experiments and tissue culture. In this review paper we propose to interpret results in line with the biology of Chlamydia with persistence of Chlamydia pneumoniae antigens in the pathogenesis of atherosclerosis rather than viable bacteriae.

Combined endurance/resistance training reduces plasma TNF-alpha receptor levels in patients with chronic heart failure and coronary artery disease.

AIMS: Physical reconditioning of patients with chronic heart failure (CHF) improves exercise capacity and restores endothelial function and skeletal muscle changes. The effects of 4 months combined endurance/resistance exercise training on cytokines and cytokine receptors in patients with CHF were studied. In addition, changes in submaximal and maximal exercise performance were addressed. METHODS AND RESULTS: Twenty-three patients with stable CHF due to coronary artery disease (CAD, n=12) or idiopathic dilated cardiomyopathy (IDCM, n=11) were trained for 4 months. Blood sampling for measurement of plasma concentrations (ELISA) of interleukin (IL)-6, tumour necrosis factor (TNF)-alpha, soluble TNF receptor 1 (sTNFR1) and 2 (sTNFR2), as well as cardiopulmonary exercise testing were performed at baseline and after 4 months. Training induced a significant decrease in sTNFR1 (P=0.02) for the total population, and in both sTNFR1 (P=0.01) and sTNFR2 (P=0.02) concentrations for the CAD group only. IL-6 and TNF-alpha levels were not altered. Cytokine concentrations remained unchanged in an untrained age- and sex-matched control group. NYHA functional class, submaximal and maximal workrate were significantly improved in both patient groups. Oxygen uptake at the anaerobic threshold (P=0.002) and at peak exercise increased in the CAD patients only (P=0.008). CONCLUSION: Besides an overall beneficial effect on exercise capacity, combined endurance/resistance exercise training has an anti-inflammatory effect in patients with CHD and CAD.

Comparison of antiplatelet effect of loading dose of clopidogrel versus abciximab during coronary intervention.

Randomized clinical trials have evidently shown that the addition of thienopyridines or abciximab to standard aspirin results in a significant reduction of ischaemic complications after coronary stent implantation. A head-to-head comparison of these antithrombotic drug regimens during coronary intervention is, however, lacking, and this was the main aim of the present study. Thirty-nine patients with angina pectoris who were scheduled for coronary stent implantation were assigned to either group 1 (160 mg aspirin + 500 mg ticlopidine post-stent), group 2 (160 mg aspirin + abciximab + 500 mg ticlopidine post-stent) or group 3 (160 mg aspirin + loading dose (375/450 mg) clopidogrel pre-stent and 75 mg clopidogrel post-stent). A loading dose of 450 mg clopidogrel was found to be more effective than the standard loading dose of 375 mg. Platelet aggregation induced by 4 micromol/l adenosine diphosphate (ADP) was assessed in samples collected before intervention and 10 min, 4 h and 20 h after intervention. Before intervention, a moderate antiplatelet effect because of aspirin intake was observed (ADP aggregation level, +/- 50%) in all study groups. After intervention, platelet aggregation tended to be enhanced in group 1 while it was strongly inhibited in the groups pre-treated with clopidogrel or abciximab: ADP induced an aggregation level early after intervention of 60 +/- 12% in group 1 (ticlopidine post-stenting) versus 30 +/- 10% in group 3 (loading dose clopidogrel) versus 3 +/- 6% in group 2 (abciximab). Abciximab achieved a more complete inhibition of aggregation than clopidogrel (P = 0.007). The overall complication rate was low with only one major bleeding and one death due to side-branch occlusion with re-infarction occurring, both in the abciximab group. Platelet aggregation during coronary intervention is strongly inhibited by both abciximab and by high loading dose of clopidogrel. Although abciximab showed a stronger antiplatelet effect than clopidogrel, it remains to be established whether this ex vivo superiority of abciximab also translates into an overall clinical benefit in patients with elective stent implantation.

Reliability of fractional flow reserve measurements in patients with associated microvascular dysfunction: importance of flow on translesional pressure gradient.

Fractional flow reserve (FFR) has been applied with success as a lesion-specific functional indicator of stenosis severity, at least in patients with normal microcirculation. This study sought to assess the reliability of FFR calculations in patients with associated microvascular dysfunction (e.g., post myocardial infarction, or post-MI). First, the effect of coronary flow changes on translesional pressure gradient was assessed. Therefore, intracoronary pressure and flow was recorded simultaneously across 19 non-infarct-related lesions (both pre- and postinterventional lesions with a mean diameter stenosis of 47% +/- 12%). Measurements were performed by means of a pressure and Doppler wire during maximal hyperemia and also during submaximal hyperemia induced by low-dose adenosine. The drop of coronary flow from 48 +/- 23 ml/min during maximal hyperemia to 36 +/- 18 ml/min during submaximal hyperemia was associated with a small decrease in translesional pressure gradient (from 22 +/- 12 mm Hg to 19 +/- 12 mm Hg; P = 0.02) and a small increase in the mean distal/arterial pressure ratio (Pd/Pa) going from 77% +/- 11% to 81% +/- 11% (P = 0.003). Then, intracoronary pressure and flow measurements were compared across 21 non-infarct-related lesions vs. 22 matched infarct-related lesions. For a similar angiographic stenosis severity (% DS = +/- 44%), maximal flow was 48 +/- 22 ml/min in the non-infarct arteries and 37 +/- 26 ml/min in the infarct arteries (P = 0.03), confirming the presence of severe microvascular dysfunction in infarct regions. Similar to the earlier findings, this hyperemic flow reduction in MI patients was associated with a small increase of FFR (= Pd/Pa): 79% +/- 12% in no MI vs. 83% +/- 12% in MI patients (P = 0.3). A reduction of hyperemic flow by +25%, [correction] such as can be found in patients with severely impaired microvascular function, has a limited effect on FFR calculations (+ 5%). This finding allows the application of standard FFR calculations in a more general population of ischemic heart disease, including patients with recent MI.

Screening for solid organ malignancies prior to heart transplantation.

BACKGROUND: Prognosis of solid organ cancer in immunosuppressed hosts is generally dismal. Therefore, every effort to identify patients with asymptomatic carcinomas before transplantation should be encouraged. METHODS: Sixty-seven patients referred for heart transplantation were examined adhering to the scheme proposed at the 24th Bethesda Conference. To increase the sensitivity of this work-up, the following items were added: tumor marker assays (prostate-specific antigen in males, carcino embryogenic antigen), abdominal ultrasound, CT scan of the abdomen and the thorax, mammography/echography of the breasts, PAP smear, colonoscopy if carcino embryogenic antigen abnormal or occult blood in stool, prostate echography if prostate-specific antigen abnormal or prostate hypertrophy. RESULTS: Carcinoma was detected in 10 of the 67 patients; for 8 patients of this cancer group, transplantation was denied. Importantly, 9 of the 10 malignancies were detected by means of the diagnostic items that were added to the standard screening protocol. There were no significant differences between the cancer and the non-cancer group regarding mean age, sex, etiology of heart failure, and smoking history. Stratifying patients in younger (i.e., < or =54 years) and older (i.e., > or =55 years) age groups showed a significantly greater proportion of older patients in the cancer group (8/10=80%) compared to the non-cancer group (25/57=44%), P=0.04. After a mean follow-up of 34 months, 5 of the 36 transplanted patients developed a malignancy (4 skin carcinomas, 1 non-Hodgkin lymphoma). There have been no malignancy-related deaths until now. CONCLUSION: The importance of a thorough screening program in the triage of candidates with preexisting malignancies, especially in an older patient population, is illustrated in this report.

Successful recovery after ventricular fibrillation in a patient with Kawasaki disease.

Kawasaki disease (KD) is an uncommon cause of sudden death in young adults in Europe. Angiographically, the disease is characterized by coronary artery aneurysms which can be fully obstructed by acute thrombosis or by progression of the disease. If diagnosis of KD is made, immediate investigation should be made to determine whether ischemia is occurring and if so, to establish optimal time for revascularisation or cardiac transplantation. We describe an 18-year-old Caucasian male who was not previously known to have KD and who suffered from an acute myocardial infarction complicated by ventricular fibrillation, caused by acute thrombosis of a coronary artery aneurysm.