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.

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.

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.

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.