Electrical storm in an acquired short QT syndrome successfully treated with quinidine.

Short QT syndrome (SQTS) is a malignant heart disorder defined by the presence of ventricular arrhythmias causing syncope and sudden cardiac arrest. The prevalence in the pediatric population is 0.05%. Quinidine is an established agent for pharmacological prophylaxis in SQTS patients, but can also terminate an electrical storm.

Novel approaches for the treatment of ventricular tachycardia.

Ventricular tachycardia (VT) is a crucial cause of sudden cardiac death (SCD) and a primary cause of mortality and morbidity in patients with structural cardiac disease. VT includes clinical disorders varying from benign to life-threatening. Most life-threatening episodes are correlated with coronary artery disease, but the risk of SCD varies in certain populations, with various underlying heart conditions, specific family history, and genetic variants. The targets of VT management are symptom alleviation, improved quality of life, reduced implantable cardioverter defibrillator shocks, prevention of reduction of left ventricular function, reduced risk of SCD, and improved overall survival. Antiarrhythmic drug therapy and endocardial catheter ablation remains the cornerstone of guideline-endorsed VT treatment strategies in patients with structural cardiac abnormalities. Novel strategies such as epicardial ablation, surgical cryoablation, transcoronary alcohol ablation, pre-procedural imaging, and stereotactic ablative radiotherapy are an appealing area of research. In this review, we gathered all recent advances in innovative therapies as well as experimental evidence focusing on different aspects of VT treatment that could be significant for future favorable clinical applications.

Management of Coronary Artery Disease and Conduction Abnormalities in Transcatheter Aortic Valve Implantation.

OPINION STATEMENT: Transcatheter aortic valve replacement (TAVR) is an expanding, catheter-based technology that allows the implantation of a prosthetic valve without requiring open heart surgery for the treatment of severe aortic stenosis (AS). The frequency of coronary artery disease (CAD) in patients (pts) with severe AS undergoing surgical treatment ranges from 30 to 50 %. This tends to be higher in pts undergoing TAVR with a prevalence of 49-76 % and is more prevalent with older age and the fact that TAVR is commonly performed in high-risk groups with more advanced cardiovascular disease. The overall influence of CAD on TAVR procedural outcomes remains controversial, and the management of concomitant artery disease is still under discussion. There are three major issues that must be addressed: the impact of CAD, optimal timing of percutaneous coronary intervention (PCI) and TAVR, and extent of revascularization. Today, TAVR is commonly performed as a stand-alone procedure with variable degrees of concomitant CAD tolerated without intervention. One of the major potential complications with TAVR is the damage to the conduction system. The requirement of permanent pacemaker (PM) implantation ranges from 9 to 49 % of cases with a mean of ~20 %, whereas surgical aortic valve replacement (sAVR) is associated with a complete heart block that requires permanent PM in 3-12 % of cases. Reports have demonstrated an increased incidence of conduction damage in patients undergoing TAVR with the CoreValve (Medtronic Minneapolis, MN, USA) prosthesis (mean 20.8 %, range 9.3-30.0 %) compared with the Edwards SAPIEN (Edwards Lifesciences LLC; Irvine, CA, USA) prosthesis (mean 5.4 %, range 0-10.1 %). Factors predicting PM implantation include preexisting bundle branch block (BB) or conduction abnormalities. The prognostic significance of new left bundle branch block (LBBB) after TAVR is unclear. In the future, new valve designs may improve the incidence of permanent PM implantation after TAVR.

A case-matched comparative study of surgical radiofrequency (RF) ablation for patients with persistent or long-standing atrial fibrillation undergoing concomitant heart surgery.

INTRODUCTION: Recent guidelines from the European Society of Cardiology suggest that surgical ablation should be considered in patients with atrial fibrillation (AF) who present for concomitant surgically correctable disease. This is a case-matched study of radiofrequency ablation during concomitant cardiac surgery versus lone surgery on patients with persistent and long-standing permanent AF. METHODS: Surgical ablation was performed in 21 patients, 14 with persistent and 7 with long-standing permanent AF. Patients with paroxysmal AF, recent onset persistent AF (<6 months), duration >6 years or left atrial diameter >8 cm were excluded. The study patients were matched 1-2 for age, sex, type of operation, type and duration of atrial fibrillation with 42 patients operated during the same period in the same department without ablation. The catheters used deliver continuously monitored radiofrequency energy, creating linear lesions on the inside of the arrested left and/or right atrial wall. Follow up was with regular outpatients' appointments and 24-hour ECG recordings at 6 and 12 months. RESULTS: Sinus rhythm maintenance rate at discharge and 12-month follow up was significantly higher in the ablation group (12 months: 71% vs. 5%, p<0.01). The ablation group had significantly longer operative times. Mean ablation duration was 15.5 minutes (CI: 12-20). There were no deaths. There were no statistically significant differences in postoperative in-hospital stay, NYHA class, left atrial size, or left ventricular ejection fraction. All patients who maintained sinus rhythm during the ablation had echocardiographically confirmed left atrial systole at follow up. CONCLUSION: Epicardial radiofrequency ablation in patients with persistent and long lasting permanent AF, who are being operated for concomitant cardiac surgical disease, is a safe, reproducible method with acceptable sustainability of sinus rhythm at medium-term follow up.

Disorders of the autonomic nervous system in patients with Brugada syndrome: a pilot study.

INTRODUCTION: The aim of this study was to examine autonomic disorders in patients with Brugada syndrome by performing a cardiac sympathetic innervation evaluation, a head-up tilt-test (HUT) and heart rate variability (HRV) analysis. METHODS AND RESULTS: We enrolled 20 patients with Brugada syndrome (mean age 42.5 +/- 8.8 years), 9 with spontaneous and 11 with an induced type 1 electrocardiogram (ECG) in the setting of symptoms and 20 age-matched controls. All subjects underwent a HUT with parallel measurements of plasma catecholamines and cortisol, a (123)I-metaiodobenzylguanidine single photon emission tomography, and HRV evaluation. Ten control subjects participated in the innervation portion of the study. The tilt-test with clomipramine challenge was positive in 15 of 20 (75%) patients (7 spontaneous, 8 induced) and in 1 in controls (P < 0.01). A sympathoadrenal imbalance was shown in positive tests. The pattern of innervation in all groups was heterogenic and similar to controls with a trend towards lower measurements in patients with a spontaneous type 1 ECG and a positive HUT. HRV analysis did not reveal any significant differences during day and night. Four patients (20%) had sustained ventricular arrhythmias during a follow-up of 31.1 +/- 8.6 months, but no correlations with innervation or response to tilting were found. CONCLUSION: A high susceptibility to vasovagal syncope was observed in patients with Brugada syndrome, which could be disease-related symptoms. Conversely, sympathetic innervation was observed to follow a physiological, heterogenic pattern; however, these factors did not have prognostic value for life-threatening arrhythmias.

Patents in the diagnosis and therapy of neurocardiogenic syncope.

Neurocardiogenic syncope is one of the most common types of syncope, characterized by arterial vasodilatation with or without bradycardia. The regulation of blood pressure and heart rate is the result of a complex reaction between the central and peripheral nervous system with the circulatory system. Multiple therapies, pharmaceutical and interventional, have been applied without any proven effect. The initial positive reports on pacing were not demonstrated in enough number of controlled studies. Neurocardiogenic syncope continues to remain a clinical problem in terms of understanding its underlying mechanisms and therapy needs to be enlightened by future studies. This article provides a background of diagnosis and therapy of neurocardiogenic syncope and reviews some related patents.

Contribution of electroanatomical mapping to the diagnosis of arrhythmogenic right ventricular cardiomyopathy in a patient with sustained ventricular tachycardia.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary cardiomyopathy, characterized mainly by anatomic and functional defects of the right ventricle. In many cases its diagnosis is quite difficult in spite of the existence of defined diagnostic criteria for the disease. We describe an interesting case of a patient with sustained ventricular tachycardia derived from the right ventricular outflow tract, in whom the diagnosis of ARVC was made with the contribution of electrophysiologic study and electroanatomical mapping, as the use of all other diagnostic tests and laboratory methods had left many unanswered questions. Based on our case, but also on other studies and case reports in the literature, we conclude that electroanatomical mapping is useful for the documentation of the diagnosis of ARVC, whenever this is not clear from the use of available diagnostic tests according to the defined criteria of the disease.

Fluoxetine vs. propranolol in the treatment of vasovagal syncope: a prospective, randomized, placebo-controlled study.

AIMS: To compare the therapeutic efficacy of placebo, propranolol, and fluoxetine in patients with vasovagal syncope (VVS). METHODS AND RESULTS: Ninety-six consecutive patients with VVS were randomized to treatment with placebo, propranolol, or fluoxetine and followed-up for 6 months. Before and during treatment, they reported their syncopal and presyncopal episodes and graded their well-being, expressed as the general evaluation of life, general activities, and everyday activities (each scaled from 1 = very good to 5 = very bad). Two patients refused follow-up. Among the remaining 94, no difference between groups was observed regarding the distribution of time of vasovagal events (syncopes or presyncopes) during follow-up (log-rank test). No difference was also observed when syncopes and presyncopes were assessed separately. Eighteen patients discontinued therapy. Among the remaining 76 ('on-treatment' analysis), the mean time to a vasovagal episode (syncope or presyncope) was significantly longer in the fluoxetine group when compared with the two other groups (log-rank test, P < 0.05). A significant difference in favour of fluoxetine was also observed regarding presyncopes. The difference between groups regarding the syncope-free period was not significant. During therapy, patients' well-being was improved (decreased) only in the fluoxetine-group (13.4 +/- 0.7 vs. 15.4 +/- 0.9 before treatment, P < 0.01). CONCLUSION: Fluoxetine seems to be equivalent to propranolol and placebo in the treatment of VVS. However, it improves patients' well-being and might be more effective in reducing presyncopes and total vasovagal events in some patients with recurrent VVS.

Growth hormone-induced reduction of soluble apoptosis mediators is associated with reverse cardiac remodelling and improvement of exercise capacity in patients with idiopathic dilated cardiomyopathy.

OBJECTIVE: Recent experimental and clinical data indicate that abnormal inflammatory and apoptotic processes contribute to the progression of chronic heart failure (CHF). We sought to study the effects of growth hormone (GH) on circulating soluble apoptosis mediators, and to investigate whether these GH-induced anti-apoptotic effects are associated with the reduction of left ventricular (LV) volumes and attenuation of exercise intolerance in idiopathic dilated cardiomyopathy (IDC) patients. METHODS: Plasma tumour necrosis factor-alpha (TNF-alpha), its soluble receptors sTNFRI and sTNFRII, and plasma apoptosis mediators soluble Fas (sFas) and sFas Ligand (sFAsL) were measured (enzyme-linked immunosorbent assay) in 12 IDC patients (NYHA III; LVEF: 24+/-2%) before and after a 3-month subcutaneous administration of GH 4 IU every other day (randomized, crossover design). Peak oxygen uptake (VO2max), as well as LV volume indices, wall thickness, and end-systolic wall stress (ESWS) were also determined at the same period. RESULTS: Treatment with GH produced a significant reduction in plasma TNF-alpha (7.8+/-1.1 versus 5.5+/-0.9 pg/ml, P<0.02), sTNFRI (4.0+/-0.4 versus 3.3+/-0.3 ng/ml, P<0.05), sTNFRII (2.8+/-0.3 versus 2.4+/-0.2 ng/ml, P<0.05), sFas (4.7+/-0.7 versus 3.3+/-0.5 ng/ml, P<0.05) and sFasL (33.5+/-9.7 versus 20.2+/-6.2 pg/ml, P<0.01). A significant reduction in ESWS (841+/-62 versus 634+/-48 g/cm, P<0.01), LV end-systolic volume index (LVESVI, 128+/-12 versus 102+/-12 ml/m, P<0.001) and LV end-diastolic volume index (LVEDVI, 228+/-16 versus 200+/-18 ml/m, P<0.01) as well as a significant increase in VO2max (15.3+/-0.7 versus 17.1+/-0.9 ml/kg per min, P<0.01) were also observed in the patient population after GH administration. Significant correlations were found between the GH-induced decrease of sTNFRII and sFasL and respective reduction of LVESVI. CONCLUSION: Growth hormone administration reduces circulating TNF system and soluble apoptosis mediators in patients with IDC. These GH-induced anti-apoptotic effects may be associated with the improvement in exercise capacity as well as with the reverse of LV remodelling in patients with CHF and IDC.

Situational syncope: response to head-up tilt testing and follow-up: comparison with vasovagal syncope.

Among sequential patients with neurally-mediated syncope, we studied the response to head-up tilt test (HUTT) in patients with situational syncope (SS) and their follow-up. Our findings were compared to those in patients with vasovagal syncope (VVS). The response to HUTT in patients with SS has not to date been fully investigated. Additionally, the prognosis of SS patients has not been systematically studied. We studied 162 consecutive patients with recurrent SS or VVS, all free of structural heart disease. Before study inclusion, they underwent an HUTT and were followed up for 12 months. Patients with SS were advised to avoid the trigger event. Patients with VVS were treated with propranolol or fluoxetine. For each patient we compared the number of syncopal spells during the last 12 months before study inclusion with that during follow-up. Among the 162 patients, 36 had SS and 126 had VVS. The response to HUTT and the number of syncopes before and during follow-up were similar in both groups. Among patients with SS, 10 (28%) had also experienced occasional episodes of VVS; however, they had a similar response to HUTT and prognosis to the remaining 26 SS patients without VVS attacks. Patients with SS have a similar response to HUTT and similarly benign clinical course to patients with VVS. The coexistence of occasional VVS episodes in patients with SS is not associated with a higher rate of positive HUTT or worse prognosis.

Effects of growth hormone on circulating cytokine network, and left ventricular contractile performance and geometry in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Recent experimental and clinical data indicate that abnormal central and peripheral immune reactions contribute to the progression of chronic heart failure, and that immunomodulation may be an important therapeutic approach in this syndrome. Aims We sought to study the effects of growth hormone (GH) administration on circulating pro-inflammatory/anti-inflammatory cytokine balance, and to investigate whether these GH-induced immunomodulatory effects are associated with the improvement of left ventricular (LV) contractile performance in idiopathic dilated cardiomyopathy (DCM) patients. METHODS: Plasma pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF) and its soluble receptor (sGM-CSFR), chemotactic cytokine macrophage chemoattractant protein-1 (MCP-1), soluble adhesion molecules intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1), and, finally, anti-inflammatory cytokines interleukin-10 (IL-10) and transforming growth factor-beta2 (TGF-beta2) were measured (ELISA method) in 12 patients with DCM (NYHA class III; LV ejection fraction: 23.6+/-1.7%) before and after a 3-month subcutaneous administration of GH 4IU every other day (randomized crossover design). Peak oxygen uptake (VO2 max), LV dimensions, LV mass index, end-systolic wall stress (ESWS), mean velocity of circumferential fibre shortening (Vcfc), and contractile reserve (change of ratio Vcfc/ESWS after dobutamine administration) were also determined at the same period. RESULTS: Treatment with GH produced a significant reduction in plasma TNF-alpha (7.8+/-1.1 vs 5.5+/-0.9pg/ml, P=0.013), IL-6 (5.7+/-0.5 vs 4.7+/-0.4pg/ml, P=0.043), GM-CSF (27.3+/-1.7 vs 23.3+/-1.8pg/ml, P=0.042), sGM-CSFR (4.0+/-0.4 vs 3.2+/-0.4ng/ml, P=0.039), MCP-1 (199+/-5 vs 184+/-6pg/ml, P=0.048), sICAM-1 (324+/-34 vs 274+/-27ng/ml, P=0.008) and sVCAM-1 (1238+/-89 vs 1043+/-77ng/ml, P=0.002) in DCM patients. A significant increase in ratios IL-10/TNF-alpha (1.9+/-0.3 vs 3.5+/-0.9, P=0.049), IL-10/IL-6(2.6+/-0.6 vs 3.2+/-0.5, P=0.044) and TGF-beta2/TNF-alpha (3.1+/-0.6 vs 4.4+/-0.6, P=0.05) was alsofound with GH therapy. A significant reduction in ESWS (841+/-62 vs 634+/-48gr/cm(2), P=0.0026) and LV end-systolic volume index (LVESVI, 128+/-12 vs 102+/-12ml, P=0.035) as well as a significant increase in posterior wall thickness (PWTH, 9.2+/-0.5 vs 10.3+/-0.6mm, P=0.034), contractile reserve (0.00029+/-0.0001 vs 0.00054+/-0.0001circ*cm(2)/gr*s, P=0.00028) and VO2max (15.3+/-0.7 vs 17.1+/-0.9ml/kg/min, P=0.002) were observed after GH administration. Good correlations were found between GH-induced increase in contractile reserve and the increases in VO2max (r=0.63, P=0.028), IL-10/TNF-alpha (r=0.69, P=0.011) and TGF-beta2/TNF-alpha (r=0.58, P=0.046) ratios, as well as the reduction in plasma TNF-alpha levels (r=-0.86, P=0.0004). CONCLUSIONS: GH administration modulates beneficially circulating cytokine network and soluble adhesion molecules in patients with DCM, whilst enhancing contractile reserve and diminishing LV volumes. These GH-induced anti-inflammatory effects may be associated with the improvement in LV contractile performance and exercise capacity as well as with the reverse of LV remodelling of patients with DCM.

Baroreflexes in vasovagal syncope: two types of abnormal response.

Heart rate changes to hypotensive stimuli (baroreceptor sensitivity [BRS]) and forearm blood flow (FBF) reduction during head-up tilt are mediated by arterial and cardiopulmonary baroreceptors. Regarding baroreflexes in neurocardiogenic syncope (NCS), an apparent variation exists in findings reported in the literature. This may be due to the existence of different types of response. This study included 39 patients with NCS and positive tilt test and 26 normal subjects with negative test. Patients were grouped according to the type of tilt test response (mixed, cardioinhibitory, vasodepressor). BRS was noninvasively assessed in the supine position as an estimate of arterial baroreceptor sensitivity. As an estimate of cardiopulmonary baroreceptor reactivity, FBF was measured by venous occlusion plethysmography in the supine position and every 2.5 minutes during the first 15 minutes of tilt. BRS was related to percent of FBF changes. BRS was impaired in syncopal patients relative to controls (7.2 +/- 0.9 vs 10.4 +/- 0.3 ms/mmHg, P = 0.01), especially in vasodepressive type (4.9 +/- 1.0 ms/mmHg, P = 0.0001). FBF changes during tilt were subnormal in NCS, ascribed to two different patterns: one, characterized by impaired vasoconstriction (FBF during tilt showing < 10% mean reduction relative to baseline, especially in vasodepressive type) and another, characterized by a great variability across time (unstable response, especially in cardioinhibitory type). In controls, BRS was related to the percent of FBF changes after 2.5, 5, and 10 minutes of tilt (P values 0.0001, 0.004, and 0.008). In patients, BRS was uncoupled from FBF changes. In conclusion, baroreflexes in NCS are impaired, unstable, and disorganized. Impairment predominates in the vasodepressive type and instability in the cardioinhibitory. The results of this study are indicative of more than one baroreflex-mediated response types.

Vasovagal syncope: a prospective, randomized, crossover evaluation of the effect of propranolol, nadolol and placebo on syncope recurrence and patients' well-being.

OBJECTIVES: We sought to assess the relative therapeutic efficacy of propranolol, nadolol and placebo in recurrent vasovagal syncope (VVS). BACKGROUND: Central and peripheral mechanisms have been implicated in the pathogenesis of VVS. Propranolol, nadolol and placebo have different sites of action on central and/or peripheral mechanisms. It has not yet been clarified whether one of the aforementioned treatments is more efficient than the others in reducing clinical episodes and exerting a beneficial effect on patients' well-being. METHODS: We studied 30 consecutive patients with recurrent VVS and a positive head-up tilt test. All were serially and randomly assigned to propranolol, nadolol or placebo. Therapy with each drug lasted three months. On the day of drug crossover, patients reported the total number of syncopal and presyncopal attacks during the previous period. They also gave a general assessment of their quality of life, taking into account: 1) symptom recurrence; 2) drug side effects; and 3) their personal well-being during therapy (scale 0 to 4: 0 = very bad/discontinuation; 1 = bad; 2 = good; 3 = very good; 4 = excellent). At the end of the nine-month follow-up period, they reported whether they preferred a specific treatment over the others. RESULTS: Spontaneous syncopal and presyncopal episode recurrence during each three-month follow-up period was reduced by all drugs tested (analysis of variance [ANOVA]: chi-square = 67.4, p < 0.0001 for syncopal attacks; chi-square = 60.1, p < 0.0001 for presyncopal attacks) No differences were observed in the recurrence of syncope and presyncope among the three drugs. All drugs improved the patients' well-being (ANOVA: chi-square = 61.9, p < 0.0001). CONCLUSIONS: Propranolol, nadolol and placebo are equally effective treatments in VVS, as demonstrated by a reduction in the recurrence of syncope and presyncope, as well as an improvement in the patients' well-being.