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.

Minor psychiatric disorders and syncope: the role of psychopathology in the expression of vasovagal reflex.

BACKGROUND: A high prevalence of minor psychiatric disorders (MPDs) has been reported in patients with vasovagal syncope (VVS). However, the relationship between the psychiatric substrate and syncope remains unclear. METHODS: In order to test the hypothesis that MPDs may predispose to VVS, we assessed the prevalence of syncope, the response to head-up tilt test (HUTT) and the efficacy of psychiatric drug treatment in reducing syncopal episodes, in patients with recently diagnosed MPDs. The response to HUTT was compared with that in an equal number of matched (a) patients with VVS and (b) healthy controls. RESULTS: A high rate of patients with MPDs (58%) had a positive HUTT. Additionally, 45% had a history of syncope; among them, the rate of positive HUTT was identical to that in the VVS group (83%). Following psychiatric drug treatment, the number of patients with syncope decreased in the MPD group (6/67 from 30/67, p < 0.01). Psychiatric symptoms and quality of life were also improved. The number of syncopal spells decreased equally in the MPD and VVS groups (0.6 +/- 0.5 from 2.5 +/- 1.4, p < 0.01, and 0.7 +/- 0.5 from 2.7 +/- 1.3, p < 0.01, respectively). CONCLUSION: A high proportion of patients with MPDs experience syncope, associated with a high rate of positive HUTT, comparable to that observed in VVS. Psychiatric treatment results in the improvement of syncopal and psychiatric symptoms. These findings suggest involvement of co-occurring MPDs in the pathogenesis of VVS. Therefore, the diagnosis and treatment of MPDs, when present, may be crucial for the effective therapy of vasovagal syndrome.

The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy.

AIMS: To investigate whether genetic variants of the histidine-rich calcium (HRC)-binding protein are associated with idiopathic dilated cardiomyopathy (DCM) and its progression. METHODS AND RESULTS: We screened 123 idiopathic DCM patients and 96 healthy individuals by single-strand conformation polymorphism analysis and direct sequencing for genetic variants in HRC. Six polymorphisms were detected: Leu35Leu (A/G), Ser43Asn (G/A), Ser96Ala (T/G), Glu202_Glu203insGlu (-/GAG), Asp261del (GAT/-), and an in-frame insertion of 51 amino acids at His321. The analysis of their frequencies did not reveal any significant correlation with DCM development. However, the Ser96Ala polymorphism exhibited a statistically significant correlation with the occurrence of life-threatening ventricular arrhythmias. During a follow-up of 4.02 +/- 2.4 years, the risk for ventricular arrhythmias was higher (HR, 9.620; 95% CI, 2.183-42.394; P = 0.003) in the Ala/Ala patients, compared with Ser/Ser homozygous patients. On multivariable Cox regression analysis, the Ser96Ala polymorphism was the only significant genetic arrythmogenesis predictor in DCM patients (HR, 4.191; 95% CI, 0.838-20.967; P = 0.018). CONCLUSION: The Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias in idiopathic DCM and may serve as an independent predictor of susceptibility to arrhythmogenesis in the setting of DCM.

The ischemia-modified albumin in relation to pacemaker and defibrillator implantation.

BACKGROUND: Ischemia-modified albumin (IMA) is considered a marker of myocardial ischemia whereas cardiac enzymes are released when cardiac necrosis occurs. It has previously been shown that permanent pacemaker-defibrillator insertion is associated with myocardial injury expressed as cardiac enzyme rise. OBJECTIVE: We assessed whether pacemaker-defibrillator implantation also induces changes in IMA plasma levels and whether, therefore, myocardial ischemia precedes necrosis. METHODS: We studied 64 consecutive patients undergoing pacemaker or defibrillator implantation; 43 were men and 21 women and their age was 70 +/- 11 years (range 23-84 years). Blood samples were collected at baseline, six hours and 48 hours following the procedure. IMA measured by the albumin cobalt binding test (ACB, Integra 800 analyzer), as well as creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB) and cardiac troponin I (Tn-I) were evaluated. RESULTS: Data analysis showed that compared to baseline measurements, IMA increased at six hours (P = 0.015) and at 48 hours (P = 0.003)[97.6 +/- 10.2 vs 101.4 +/- 10.7 vs 102.1 +/- 9.2 U/mL at baseline, six hours and 48 hours, respectively]; similarly, CK increased at six hours (P = 0.0001) and remained high at 48 hours (P = 0.0001) [74.9 +/- 49.9 vs 136.1+/-186.7 vs 115.2 +/- 63.9 mIU/mL], while CK-MB increased at six hours (P = 0.0001), but returned to baseline values at 48 hours (P = 0.05) [0.90 +/- 0.89 vs 1.27 +/- 134 vs 0.71 +/- 0.63 ng/mL] and Tn-I increased at six hours (P = 0.0001) and returned to baseline levels at 48 hours (P = 0.32) [0.057 +/- 0.23 vs 0.16 +/- 0.36 vs 0.03 +/- 0.045 ng/mL]. CONCLUSION: Permanent pacemaker-defibrillator insertion is associated with myocardial ischemia and necrosis.

Ablation of atrial tachycardias with radiofrequency current after surgical repair of complex congenital heart defects.

INTRODUCTION: Atrial tachycardias are a common problem following the surgical repair of complex congenital heart defects (CHD) and have a poor response to medication. The aim of this study was to describe the results of the treatment of such tachycardias with radiofrequency ablation in our hospital. METHODS: A retrospective study was performed of the medical records and electronically stored data from electrophysiological studies (EPS) and ablation procedures in patients with atrial tachycardias following the surgical repair of CHD. Established electrophysiological techniques were used in all patients, while newer three-dimensional imaging methods were also employed in some cases. Ablation was carried out using a radiofrequency generator and catheters with a 4-10 mm terminal electrode. RESULTS: Twenty-two patients aged 11-45 years (30.6 +/- 10.8), including 9 women, underwent an EPS and ablation of atrial tachycardias after the surgical repair of CHD. All had recurrent tachycardias refractory to antiarrhythmic medication. The anatomical diagnoses were tetralogy of Fallot (8), transposition of the great arteries (6), single ventricle (3), and other (5). Most patients had typical atrial flutter and/or incisional atrial reentrant tachycardia. The initial success rate of ablation for all arrhythmias was 88% in patients with tetralogy of Fallot, 83% for transposition of the great arteries, 66% for single ventricle, and 80% for the other diagnoses. Three-dimensional imaging was of significant assistance in mapping and ablation and in reducing the duration of fluoroscopy. Two vascular complications (femoral arteriovenous fistulae) were observed. The tachycardia recurrence rate was 54%. After repeated procedures, 59% of patients were free of arrhythmias and antiarrhythmic medications. No patient with a single ventricle remained free of arrhythmias during follow up, while in the other groups the arrhythmia/drug-free rate was 66-75%. Two patients with unsuccessful ablation died, one from heart failure and the other because of the tachycardia. CONCLUSIONS: Atrial tachycardias in patients with surgically treated CHD are associated with increased morbidity and mortality. Radiofrequency ablation has satisfactory results. In spite of the high relapse rate, a significant number of patients can become free of arrhythmias after repeat procedures.

Neurocardiogenic mechanisms of unexplained syncope in idiopathic dilated cardiomyopathy.

Syncope in patients with advanced heart failure is a sign of poor prognosis. The cause of syncope in patients with dilated cardiomyopathy (DC) is not fully recognized and may remain elusive even after standardized evaluation. The purpose of the present study was to examine the implication of neurally mediated mechanisms in the pathophysiology of syncopal episodes in patients with DC. Twenty-six patients (21 men, 5 women; mean age 59 +/- 2 years, range 38 to 79) with DC and left ventricular ejection fractions

Ischaemia modified albumin in radiofrequency catheter ablation.

UNLABELLED: Aim Ischaemia modified albumin (IMA) is considered a marker of myocardial ischaemia, in contrast to the biomarkers of myocardial injury [creatine kinase (CK), the MB isoenzyme of CK, and cardiac troponin I (Tn-I)] that are released when cardiac necrosis occurs. Ischaemia modified albumin has been reported to increase following percutaneous coronary intervention and in acute coronary syndromes. We sought to determine whether IMA increases following radiofrequency (RF) ablation. METHODS AND RESULTS: We studied 40 consecutive patients who underwent RF catheter ablation; 20 were men and 20 women and their age was 47 +/- 16 (16-77) years. All patients underwent electrophysiological study and subsequent RF ablation. Peripheral venous samples were collected before the procedure (baseline), immediately after the procedure, 2 h post-procedure and the following day (20 h post-procedure) and assayed for CK, the MB isoenzyme of CK, cardiac Tn-I and IMA. Ischaemia-modified albumin plasma levels did not differ significantly at all four time points, baseline, and following ablation (P = 0.5974), whereas CK, CK-MB, and Tn-I increased significantly at all time points compared with baseline (P < 0.0001). Post-ablation, all but three 3 CK measurements were in the normal range; 14 patients had CK-MB plasma levels above the upper limit of normal; all but one patient had Tn-I elevated. CONCLUSION: The IMA plasma levels do not change significantly following RF ablation, unlike biomarkers of myocardial injury, implying that myocardial necrosis occurs without preceding ischaemia.

Ischemia-modified albumin in relation to exercise stress testing.

OBJECTIVES: We examined whether ischemia-modified albumin (IMA) plasma levels change during exercise stress testing (EST) in patients with known coronary artery disease and whether the induced changes differ between positive and negative exercise tests. BACKGROUND: Ischemia modified albumin is considered a marker of myocardial ischemia and increases after coronary angioplasty and in acute coronary syndromes. METHODS: We studied 40 consecutive patients with established coronary artery disease who underwent EST. Venous samples, for IMA measurement, were collected before the stress test (baseline), at peak exercise, and 60 min after the completion of the exercise test. RESULTS: There was significant difference in the IMA values at the 3 prespecified time points (p = 0.012), whereas there was no interaction between the IMA changes and the result of the stress test, whether positive or negative (p for the interaction term = 0.94). Baseline, peak EST, and post-EST IMA levels were similar in patients with positive and negative exercise tests (p = 0.61). The IMA significantly decreased at peak exercise compared with baseline values in positive (p < 0.0001) and in negative EST (p = 0.012). Moreover, IMA concentration increased 60 min after EST compared with peak-EST values in positive (p < 0.0001) and in negative tests (p = 0.003), returning to pre-EST levels in both groups. CONCLUSIONS: The IMA plasma levels change significantly during exercise testing in patients with coronary artery disease, but there is no difference between positive and negative stress tests; this possibly implies that the observed changes do not reflect myocardial ischemia.

Primary stenting of an unprotected left main coronary artery total occlusion in a patient with acute myocardial infraction and cardiogenic shock.

Acute total occlusion of the left main coronary artery (LMCA) is a rare angiographic finding with very poor prognosis. We report a case of a 39-year-old man who presented with pulmonary edema and cardiogenic shock due to an acute anterior myocardial infarction. Coronary angiography, which was performed under the support of an intra-aortic balloon pump, revealed total occlusion of the LMCA. Prompt and successful percutaneous transluminal coronary angioplasty with sirolimus-stent deployment in the LMCA allowed for an uneventful recovery and discharge of the patient.

Antiinflammatory effects of cardiac resynchronization therapy in patients with chronic heart failure.

BACKGROUND: Cardiac resynchronization therapy (CRT) pacing has been proposed as an additional treatment to medical therapy to improve heart failure patients with left ventricular asynchrony. The aim of this study was to evaluate the influence of CRT treatment on proinflammatory cytokines in patients with heart failure. METHODS: Twenty patients, with a mean age 64 +/- 2 years, with severe chronic heart failure NYHA class II-IV (mean ejection fraction 25 +/- 2%), were included in the study. Patients were treated with CRT pacing, after failure of optimal therapy. Blood samples were taken at baseline, 3 months after pacing therapy, and after a subsequent 3-month period of no pacing for the assessment of proinflammatory cytokines TNF-alpha and its receptors (sTNFR-I, sTNFR-II), IL-6, adhesion molecules sICAM-1 and sVCAM-1, and the apoptotic indices sFas and sFas-Ligand. RESULTS: Levels of TNF-alpha, sTNFR-I, and sTNFR-II were reduced at the end of 3 months of CRT therapy and further reduced at the end of the no pacing period (P < 0.05, compared to baseline). Levels of IL-6 also declined after 3 months of CRT pacing (from 8.9 +/- 2.5 pg/mL to 4.7 +/- 1.3 pg/mL, P < 0.05) and this was maintained during the no pacing period (3.9 +/- 1.1 pg/mL P < 0.05 compared to baseline). The adhesion molecule sICAM-1 levels also reduced (from 265 +/- 17 ng/mL to 235 +/- 12, P < 0.05) after 3 months of CRT pacing and remained unchanged at the end of the no pacing period (219 +/- 12 ng/mL, P < 0.05 compared to baseline values). CONCLUSION: Major proinflammatory cytokines and the adhesion molecule sICAM-1 are reduced with CRT therapy and this effect is maintained for at least 3 months after discontinuation of pacing.

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.

The effects of 5-HT4 receptor blockade and stimulation, during six hours of atrial fibrillation.

AIMS: Stimulation of atrial 5-HT4 receptors is associated with arrhythmias. Their blockade prolongs atrial effective refractory period (ERP), following short runs of atrial fibrillation (AF). The role of 5-HT4 receptors during longer periods of AF is unknown. In this study, we investigated the effects of the selective 5-HT4 receptor stimulation and blockade on porcine atria, during 6 h of AF. METHODS: Atrial ERP, monophasic action potential (MAP) duration, time to sinus rhythm restoration (TSRR) and ERP/MAP ratio were assessed in 27 pigs, at baseline and every hour, during 6 h of AF, induced by rapid atrial pacing. Ten animals were used as controls, 10 were administered the selective 5-HT4 antagonist SB203186 and seven were administered the selective 5-HT4 agonist RS67333. RESULTS: During the first few hours of fibrillation, ERP, MAP and TSRR were preserved in SB203186-treated pigs, while they were shortened in controls and RS67333-treated animals. After 6 h of arrhythmia, ERP and MAP were shortened in all three groups, but the decrease was less in SB203186-treated pigs. ERP/MAP ratio increased in controls and RS67333-treated animals, while it remained unchanged in SB203186-treated pigs. Towards the end of the AF period, four of the SB203186-treated pigs developed sustained atrial tachycardia. CONCLUSION: Following short periods of AF, 5-HT4 receptors' blockade protects the porcine atria against ERP and MAP shortening, while their stimulation has the opposite result. This beneficial effect, though, is gradually diminished following longer periods of AF and atrial tachycardia may develop.

Repeated exercise stress testing identifies early and late preconditioning.

BACKGROUND: The warm-up phenomenon has been considered to trigger preconditioning. We investigated whether repeated exercise treadmill tests in humans are capable of inducing adaptation to ischemia by triggering both the early and late phase of preconditioning. METHODS: In 25 consecutive patients with stable coronary artery disease, four repeated treadmill tests were performed. Thirty minutes following the first test (T1) a second one was performed (T2), followed 6 h later by a third test (T3). Twenty-four hours later all patients were subjected to a fourth exercise test (T4). In every fifth patient, simultaneous echocardiographic examination was performed at the time of the exercise tests in an attempt to reveal ischemic abnormalities. RESULTS: At baseline there was no difference between the variables. At ST segment depression >1.5 mm, the rate-pressure product (RPP) was higher in T2 and T4 (231.3+/-17.9 and 232.6+/-15.8 mm Hg s 10(2)) than in T1 and T3 (210+/-17 and 210.2+/-16.7 mm Hg s 10(2)), p<0.001. Additionally, time to the onset of chest pain was longer in T2 and T4 (430.8+/-60.5 and 438+/-47 s) than in T1 and T3 (345.6+/-69 and 345.6+/-58 s), p<0.001. At peak exercise, the RPP was higher in T2 and T4 (278.6+/-21.6 and 278.3+/-19.6 mm Hg s 10(2)) than in T1 and T3 (255.6+/-23.1 and 256.6+/-23 mm Hg s 10(2)), p<0.001. The wall motion score index was higher in T1 and T3 (1.65+/-0.17 and 1.53+/-0.16) than in T2 and T4 (1.3+/-0.07 and 1.37+/-0.1), p<0.001. CONCLUSION: By using repeated exercise treadmill tests both the early and late phase of protection can be obtained.

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.

Superior vena cava syndrome and syncope in an implantable cardioverter defibrillator recipient.

We describe the case of a recipient of an implantable cardioverter defibrillator with multiple syncopal episodes due both to superior vena cava obstruction and electrical instability. These complications occurred in the presence of two transvenous implantable cardioverter defibrillator leads. The patient has been managed conservatively with anticoagulants and new antiarrhythmic drugs with improvement in both his clinical problems.

Effect of biventricular pacing on heart rate variability in patients with chronic heart failure.

BACKGROUND: Biventricular pacing is emerging as a long-term therapy for symptomatic heart failure. Analysis of heart rate variability (HRV) has become an important predictive tool in this syndrome. AIM OF THE STUDY: To assess whether chronic resynchronization therapy can affect HRV in patients with heart failure. METHODS AND RESULTS: Thirteen patients with heart failure were studied (mean age+/-1 S.E. 65+/-2.2 years, QRS 195+/-5.3 ms, NYHA class 3.2+/-0.1, LVEF 21+/-1.7%). The protocol included a preliminary no pacing period for 1 month following device implantation. Twenty-four hour Holter ECG recordings were performed at the end of this period (baseline) and after 3 months of biventricular stimulation (VDD mode). Prior to and following pacing patients underwent NYHA class evaluation, 6-min walk test, Quality of Life Assessment and a cardiopulmonary exercise test. Biventricular pacing improved functional class (P<0.0001) and Quality of life (P<0.0001), increased 6-min walk distance, (P=0.008) and exercise duration (P<0.0001) but had no significant effect on peak exercise VO(2). Resynchronization therapy increased mean 24-h RR (922+/-58 vs. 809+/-41 ms at baseline, P=0.006), SDNN (111+/-11 vs. 83+/-8 ms, P=0.003), SDNN-I (56+/-10 vs. 40+/-5 ms, P=0.02), rMSSD (66+/-14 vs. 41+/-8 ms, P=0.003), Total Power (5724+/-1875 vs. 2074+/-553 ms(2), P=0.03), Ultra Low Frequency Power (1969+/-789 vs. 653+/-405 ms(2), P=0.03) and Very Low Frequency Power (2407+/-561 vs. 902+/-155 ms(2), P=0.004). CONCLUSION: Biventricular pacing in heart failure improves autonomic function by increasing HRV. This may have important prognostic implications.

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.