Arrhythmogenic right ventricular cardiomyopathy: an update on pathophysiology, genetics, diagnosis, and risk stratification.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy accounting for life-threatening ventricular tachyarrhythmias and sudden death in young individuals and athletes. Over the past years, mutations in desmosomal genes have been identified as disease-causative. However, genetic heterogeneity and variable phenotypic expression alongside with diverse disease progression still render the evaluation of its prognostic implication difficult. ARVC was initially entered into the canon of cardiomyopathies of the World Health Organization in 1995, and international efforts have resulted in the 2010 modified diagnostic criteria for ARVC. Despite all additional insights into pathophysiology, clinical management, and modern risk stratification, under-/misdiagnosing of ARVC remains a problem and hampers reliable statements on the incidence, prevalence, and natural course of the disease.This review provides a comprehensive overview of the current literature on the pathogenesis, diagnosis, treatment, and prognosis of ARVC and sheds some light on potential new developments in these areas.

[Acute coronary syndrome: peri-interventional antithrombotic therapy]. / Akutes Koronarsyndrom. Peri-interventionelle antithrombotische Therapie.

In patients with acute coronary syndrome (ACS), the periinterventional antithrombotic treatment has become increasingly important for the choice of reperfusion strategy and as an adjunct pharmacological treatment prior, during and after percutaneous coronary interventions (PCI). In NSTE-ACS and early invasive strategy (<48 h), treatment with ASA, clopidogrel and heparin - unfractionated heparin (UFH) preferred - should be initiated as soon as possible. Direct thrombin inhibitors are an alternative to heparin, particularly in the setting of increased risk of bleeding and heparin-induced thrombocytopenia. In highrisk patients, an so-called upstream therapy with glycoprotein IIb/IIIa inhibitors (tirofiban, eptifibatide) is recommended as an adjunct to PCI. In STEMI, primary PCI is the reperfusion therapy of choice and should be supported by early adjunct treatment with ASA, clopidogrel, UFH and glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide). "Facilitated" PCI with thrombolytics is not recommended because of increased mortality and complication rates.

Aminoterminal B-type pro-natriuretic peptide as a marker of recovery after high-risk coronary artery bypass grafting in patients with ischemic heart disease and severe impaired left ventricular function.

BACKGROUND: Aminoterminal B-type pro-natriuretic peptide (NT-proBNP) is a reliable indicator of heart failure severity. Levels of NT-proBNP are markedly increased in patients with coronary artery disease (CAD) and severely impaired left ventricular (LV) function. The aim of our study was to assess the impact of NT-proBNP levels after high-risk coronary artery bypass grafting (CABG) with regard to recovery potential. METHODS: Between 1998 and 2004, 121 patients with CAD and severely impaired LV function, who were undergoing CABG, were investigated. Their mean age was 64 +/- 11 years. All patients were in New York Heart Association (NYHA) Class III/IV status; LV ejection fraction (EF) was 20 +/- 6%. All survivors underwent follow-up (59 +/- 34 months) spiroergometric, electrocardiographic (ECG) and echocardiographic assessment and were tested for routine blood controls and NT-proBNP levels (Roche, Mannheim, Germany). RESULTS: The survival rate after 8 years was 70%. All survivors received follow-up assessment. Among survivors the median NT-proBNP level at follow-up was 896 (521 to 1,687) pg/ml. The maximum oxygen uptake was 14.6 +/- 4.9 ml/min/kg, and EF increased to 42% at follow-up among all survivors. On dichotomizing survivors into two groups with NT-proBNP levels above and below the median, the post-operative body mass index was significantly higher in the high NT-proBNP group (p = 0.036). EF (p = 0.028) and NYHA classification (p < 0.05) improved significantly in both groups, with a tendency toward higher EF in the low NT-proBNP group. CONCLUSIONS: Patients undergoing a high-risk CABG procedure have a survival rate comparable to heart transplantation patients and show a potential for clinical and myocardial recovery. NT-proBNP use a useful marker for recovery after a high-risk CABG procedure, with significant correlation with clinical parameters.

[Right ventricular tachyarrhythmias--diagnostics and therapy]. / Rechtsventrikuläre Tachyarrhythmien--Diagnostik und Therapie.

Ventricular tachyarrhythmias originating from the right ventricle frequently occur in young, apparently healthy patients with rare underlying cardiac diseases. Among these are arrhythmogenic right ventricular cardiomyopathy (ARVC), idiopathic right ventricular outflow-tract tachycardia (RVOVT), and Brugada syndrome (BrS). All harbor the risk of sudden cardiac death, whereas they differ substantially as to diagnosis, therapy and prognosis. This is the reason why detailed investigations are an essential prerequisite for further efficient individualized management strategies which are mainly directed to prevent sudden cardiac death and to minimize the risk of arrhythmia recurrences in affected patients, respectively. Both antiarrhythmic drug therapy, catheter ablation, and the implantation of an automatic cardioverter defibrillator may, therefore, be a first-line therapeutic option in tailored treatment regimens. This review is a summary of the available literature on pathogenesis, diagnosis, treatment, and prognosis of such diseases associated with right ventricular tachyarrhythmias.

Cardiothoracic surgery after heart and heart-lung transplantation.

OBJECTIVE: We sought to examine our management and the outcomes of cardiothoracic procedures after heart and heart lung transplantation. METHODS: We performed a retrospective review of cardiothoracic surgical procedures carried out between 1990 and 2004 in patients who had previously undergone heart or heart-lung transplantation at our institution. RESULTS: Twenty-one out of 340 patients (6.2 %) were identified. Cardiothoracic surgery was performed 44.4 +/- 33 months (range 1 - 115 months) after transplantation. Predominant types of surgery were coronary artery bypass grafting due to allograft vasculopathy (n = 5), aortic surgery due to acute dissection (n = 3), biventricular assist device implantation due to acute rejection (n = 1), tricuspid valve repair (n = 1), multiple cardiac surgical procedures including coronary artery bypass grafting, retransplantation, and tricuspid valve replacement (n = 2), explantation of a functionless heterotopic transplanted heart (n = 1). Lung surgery was performed in six patients due to pneumonia (n = 2), primary lung carcinoma (n = 3), lung torsion following heart-lung transplantation (n = 1). All patients underwent either lobectomy or segmental lung resection. Single lung retransplantation (n = 2) after prior heart-lung transplantation due to bronchiolitis obliterans was performed. In one patient a pneumonectomy (n = 1) due to severe chronic rejection of the contralateral lung was performed. Six subsequent deaths after cardiothoracic procedures were recorded after 1, 4, 78, 163, 205, and 730 days, respectively. Causes of death were advanced carcinoma (n = 1), multi-organ failure due to sepsis (n = 2), sudden heart death (n = 2), and advanced heart failure (n = 1). Fifteen out of 21 patients having undergone cardiothoracic procedures (71.4 %) survived the observation period of 56.6 +/- 34 months (range 1 - 114). CONCLUSIONS: Reasons for cardiothoracic procedures after prior heart or heart-lung transplantation were allograft vasculopathy, aortic dissections years after transplantation, chronic rejection, and either lung infections or malignancies. Surgical repair can be performed with an acceptable operative risk and good long-term survival rates.

Stroke volume and mitral annular velocities. Insights from tissue Doppler imaging.

The aim of this study was to assess the impact of stroke volume (SV) on mitral annular velocities derived from tissue Doppler imaging (TDI). To this end, conventional echocardiographic variables and TDI derived mitral annular velocities (S', E', A') were obtained in 14 patients (pts) with increased SV (due to primary mitral (n=12) (ISV group)), in 41 pts with reduced SV (due to ischemic (n=27) or dilated cardiomyopathy (n=9) or hypertensive heart disease (n=5) (RSV group)) and 29 asymptomatic controls with normal SV (CON group). Systolic (S') and early diastolic (E') mitral annular velocities were elevated in the ISV group in the comparison to the CON group, but were significantly reduced in the RSV group. Late diastolic annular velocities (A') did not differ between the ISV and the CON group, but were lowest in the RSV group. On simple linear regression analysis, SV was significantly related to S' (r=0.74, p<0.001), to E' (r=0.74, p<0.001) and to A' (r=0.43, p<0.01). On multiple regression analysis, SV was a stronger independent predictor of S' and E' than conventional systolic or diastolic echocardiographic variables. Thus, stroke volume has a significant impact on TDI derived systolic (S') and early diastolic (E') mitral annular velocities. This should be considered, when TDI is used in the evaluation of LV performance or in the estimation of filling pressures.

[Right ventricular arrhythmias]. / Arrhythmien aus dem rechten Ventrikel.

Right ventricular arrhythmias predominantly occur in young patients with rare cardiac diseases. Underlying cardiac conditions include idiopathic right ventricular outflow-tract tachycardia (RVOT-VT), arrhythmogenic right ventricular cardiomyopathy (ARVC), Brugada syndrome, and postoperative congenital heart disease (i.e. tetralogy of Fallot). According to the underlying cardiac disease, there are significant differences in the diagnostic and therapeutic management and prognosis which is mainly determined by life-threatening ventricular arrhythmia recurrences and sudden cardiac death. To provide optimal treatment for affected patients, a detailed diagnostic evaluation and risk stratification is mandatory. Tailored treatment strategies aim at the suppression or effective termination of recurrent ventricular tachyarrhythmias and prevention of sudden death by antiarrhythmic drug therapy, catheter ablation, and the implantation of cardioverter-defibrillators. This review summarizes the current knowledge on pathogenesis, diagnosis, treatment and prognosis of those conditions that are associated with arrhythmias originating from the right ventricle.

Arterial hypertension and ischaemic stroke.

OBJECTIVES: Arterial hypertension is, besides age, the number one risk factor for ischaemic stroke. Patients with arterial hypertension frequently present with additional coexisting vascular risk factors interacting in a complex way. MATERIAL AND METHODS: This paper reviews the benefit of antihypertensive treatment, as well as different treatment options of arterial hypertension and their side-effects. RESULTS: Patients with definite arterial hypertension, but also patients with so-called normal or high-normal blood pressure are at increased risk to develop stroke and other cardiovascular complications. Vascular remodelling of small and large vessels provoked by arterial hypertension is the initial step in the development of atherosclerosis and lipohyalinosis. Vascular remodelling can be improved or even normalized by antihypertensive treatment with angiotensin-converting-enzyme inhibitors and angiotensin-I-receptor antagonists showing the most convincing effects. Angiotensin-converting-enzyme inhibitors and angiotensin-I-receptor antagonists have the lowest rate of side-effects, however, economic restraints hinder their general application. Statins are needed to treat dyslipidaemia. They also lower blood pressure and have a synergistic effect with the above two antihypertensive components in lowering blood pressure. In hypertensive patients, risk of stroke and other cardiovascular complications is determined by the blood pressure level and the presence or absence of target organ damage and the interaction with other risk factors, such as cigarette smoking, dyslipidaemia, and diabetes. These high-risk patients should be treated even more aggressively than usual. CONCLUSIONS: In the vast majority of patients and healthy individuals, target blood pressure should be as high as or below 120/80 mmHg to minimize the occurrence of stroke and other cardiovascular complications.

[Aneurysm of the subclavian artery after operatively corrected coarctation of the aorta: 20 years of follow-up and review of the current literature]. / Aneurysma der Arteria subclavia nach Korrektur einer Aortenisthmusstenose. 20-jähriger Langzeitverlauf und Literaturübersicht.

We report of long-term follow-up of a combined fusiform aneurysm of the right subclavian artery extending to the thyreocervical trunk (3.2 x 2.8 x 2.2 cm (width x height x depth)) in a 33-year old patient. As a newborn, the clinical diagnosis of an aortic isthmus stenosis was made without need for intervention at this stage. Further development of the child remained unremarkable until the age of eleven years when he experienced dizziness after sporting activities. Due to clinically proven progress, cardiac catheterization was performed and confirmed the initial diagnosis of a juxtaductale stenosis of the aortic isthmus, which was operated thereafter with an end-to-end anastomosis. Furthermore, an aneurysm of the right subclavian artery was revealed. Since then, non-invasive routine follow-up showed no significant worsening of this aneurysm, which extends to the thyreocervical trunk. The patient has been event free and completely asymptomatic. This case report illustrates the more than twenty years of follow-up of an asymptomatic combined fusiform aneurysm of the subclavian artery and thyreocervical trunk and provides a review of the literature on this topic.

Radioligands for imaging myocardial alpha- and beta-adrenoceptors.

Alpha- and beta-adrenoceptors play an important role in the control of heart function. According to their molecular, biological, and pharmacological characteristics, they are subdivided into alpha(1)-, alpha(2)- and beta(1)-, beta(2)-, beta(3)-, beta(4)-adrenoceptors. In cardiac disease, there is often a selective downregulation of beta(1)-adrenoceptors associated with a relative increase in beta(2)- and alpha(1)-adrenoceptors. Functional imaging techniques like single-photon emission tomography (SPECT) and positron emission tomography (PET) provide the unique capability for non-invasive assessment of cardiac adrenoceptors. Radioligands with high specific binding to cardiac alpha- and beta-adrenoceptors suitable for radiolabelling are required for clinical studies. The non-selective beta-adrenoceptor antagonist [(11)C]CGP-12177 was used to quantify beta-adrenoceptor density using PET in patients with heart disease. New non-selective ligands (e. g. [(11)C]CGP-12388, [(18)F]CGP-12388, [(11)C]carazolol and [(18)F]fluorocarazolol) are currently evaluated; beta(1)-selective radioligands (e. g. [(11)C]CGP-26505, [(11)C]bisoprolol, [(11)C]HX-CH 44) and beta(2)-selective radioligands (e. g. [(11)C]formoterol, [(11)C]ICI-118551) were assessed in animals. None of them turned out as suitable for cardiac PET. Potential radioligands for imaging cardiac alpha(1)-adrenoceptors are based on prazosin. Whereas [(11)C]prazosin shows low specific binding to myocardium, its derivative [(11)C]GB67 looks more promising. The putative alpha(2)-adrenoceptor radioligand [(11)C]MK-912 shows high uptake in rodent myocardium but has not yet been evaluated in man. A number of radioligands were evaluated for assessing cardiac adrenoceptors using PET. New radioligands are needed to provide more insight into cardiac pathophysiology which may influence the therapeutic management of patients with cardiovascular disease.

Genetics of arrhythmogenic right ventricular cardiomyopathy--status quo and future perspectives.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary myocardial disorder of unknown origin. In recent years, the disease has been recognized as a major cause of ventricular tachyarrhythmias and sudden cardiac death in young patients with apparently normal hearts. Although characteristic structural, imaging and electrocardiographic features are included in a proposed catalogue of diagnostic criteria, the correct diagnosis of ARVC often remains difficult. Much effort has been undertaken to enlarge the knowledge on pathophysiological mechanisms of the disease. The role of molecular genetics for the pathogenesis of ARVC is discussed in the following review. On the basis of linkage analyses in large families affected by ARVC, there is growing evidence for genetic alterations in ARVC, which, in the majority of chromosomal loci (seven) reported so far, follow a Mendelian autosomal-dominant pattern of inheritance with variable penetrance and polymorphic phenotype. Besides this, two autosomal-recessive forms of ARVC are known. These can be differentiated from the autosomal-dominant forms not only in terms of the mode of inheritance but also as to their specific phenotype: patients with Naxos disease exhibit characteristic hair and skin abnormalities and experience a more severe course of disease. Patients with another autosomal-recessive form display the typical but milder signs of ARVC together with opacifications of the crystalline lens. So far, two mutations in cardiac genes responsible for the development of ARVC have been reported. A homozygous two base pair deletion in the gene encoding for the cytoskeletal protein plakoglobin seems to account for the evolution of Naxos disease. The second mutation affecting the cardiac ryanodine receptor gene was found in patients with ARVC-2. Routine genetic testing of patients or relatives with a suspected diagnosis of ARVC is not available at present but may become the future gold standard with potential implications for a better understanding of the pathogenesis and management of the disease.

Mitral valve surgery in patients with poor left ventricular function.

BACKGROUND: Mitral valve surgery for the correction of secondary mitral valve regurgitation (MR) in cardiomyopathy is associated with a poor outcome. Numerous studies have identified a severe left ventricular dysfunction as an indicator for a poor prognosis. The aim of the study was to asses the follow-up after mitral valve surgery and severe left ventricular dysfunction. METHODS: Between 1994 and 2000, 31 patients with mitral regurgitation and a left ventricular ejection fraction of below thirty percent undergoing isolated repair (n = 16) or replacement (n = 15) were investigated. All patients received maximal drug therapy. Twenty-one patients were New York Heart Association (NYHA) class III and 10 were class IV. Follow-up with echocardiography, ECG, and chest x-ray was performed in 87 % of the survivors. The mean duration of follow-up was 39 +/- 16 months. RESULTS: The mean duration of ICU and hospital stay was 3.6 +/- 2.1 days and 8.1 +/- 5.4 days, respectively. The 1-, 2-, and 5-year survival rates were 91 %, 84 %, and 77 %, respectively. NYHA class improved from 3.3 +/- 0.8 to 2.1 +/- 0.7 at follow-up (p < 0.01). The ejection fraction improved from 23.1 +/- 6.6 % to 36 +/- 6.8 % at follow-up (p < 0.02). Freedom from readmission for heart failure was 85 %, 79 %, and 68 % at 1-, 2-, and 5 years, respectively. CONCLUSIONS: Mitral valve surgery improves left ventricular function and reduces heart failure severity in patients with MR and cardiomyopathy. High-risk mitral valve surgery may be an alternative to heart transplantation in selected patients.

Electrophysiologic investigation in Brugada syndrome; yield of programmed ventricular stimulation at two ventricular sites with up to three premature beats.

INTRODUCTION: Numerous reports on the inducibility of ventricular tachyarrhythmias (VT) in patients with atypical right bundle branch block and right precordial ST-elevation (Brugada syndrome) are based on multicentre studies that have used different stimulation protocols. Therefore, we prospectively investigated the inducibility of VT in these patients using a uniform protocol. METHODS: In 41 consecutive patients (29 males) showing a pattern of right bundle branch block and ST-elevation, programmed ventricular stimulation was performed in the right ventricular apex with up to three premature stimuli at sinus rhythm and at four different paced cycle lengths (500, 430, 370, and 330 ms) until refractoriness was reached or reproducible induction of a sustained (>30s) VT occurred. If a VT was not reproducibly inducible, the same protocol was repeated in the right ventricular outflow tract. RESULTS: A history of life-threatening events defined as syncope (n=17) or aborted sudden cardiac death (n=13) was present in 30 patients (73%); 11 individuals were asymptomatic. Inducibility (68%) was similar between symptomatic (n=21, 70%) and asymptomatic patients (n=7, 64%). In 16 (39%) patients, VT were reproducibly inducible. If patients were only stimulated in the right ventricular apex, inducibility rate decreased to 39%. If only two premature beats at two sites were used it was as low as 32%. The mean coupling intervals of the second and third premature stimuli inducing sustained VT were short: 189+/-21 ms vs 186+/-22 ms, respectively. Forty-four percent of all patients (i.e. 64% of the inducible patients) had inducible VT only with coupling intervals shorter than 200 ms. CONCLUSIONS: The stimulation protocol markedly influences the extent of inducibility of VT in patients with right bundle branch block and ST-segment elevation. These findings question the significance of previous multicentre studies using different stimulation protocols and should have implications for further studies.