A proof of principle study of atomoxetine for the prevention of vasovagal syncope: the Prevention of Syncope Trial VI.

AIMS: There are few effective therapies for vasovagal syncope (VVS). Pharmacological norepinephrine transporter (NET) inhibition increases sympathetic tone and decreases tilt-induced syncope in healthy subjects. Atomoxetine is a potent and highly selective NET inhibitor. We tested the hypothesis that atomoxetine prevents tilt-induced syncope. METHODS AND RESULTS: Vasovagal syncope patients were given two doses of study drug [randomized to atomoxetine 40 mg (n = 27) or matched placebo (n = 29)] 12 h apart, followed by a 60-min drug-free head-up tilt table test. Beat-to-beat heart rate (HR), blood pressure (BP), and cardiac haemodynamics were recorded using non-invasive techniques and stroke volume modelling. Patients were 35 ± 14 years (73% female) with medians of 12 lifetime and 3 prior year faints. Fewer subjects fainted with atomoxetine than with placebo [10/29 vs. 19/27; P = 0.003; risk ratio 0.49 (confidence interval 0.28-0.86)], but equal numbers of patients developed presyncope or syncope (23/29 vs. 21/27). Of patients who developed only presyncope, 87% (13/15) had received atomoxetine. Patients with syncope had lower nadir mean arterial pressure than subjects with only presyncope (39 ± 18 vs. 69 ± 18 mmHg, P < 0.0001), and this was due to lower trough HRs in subjects with syncope (67 ± 30 vs. 103 ± 32 b.p.m., P = 0.006) and insignificantly lower cardiac index (2.20 ± 1.36 vs. 2.84 ± 1.05 L/min/m2, P = 0.075). There were no significant differences in stroke volume index (32 ± 6 vs. 35 ± 5 mL/m2, P = 0.29) or systemic vascular resistance index (2156 ± 602 vs. 1790 ± 793 dynes*s/cm5*m2, P = 0.72). CONCLUSION: Norepinephrine transporter inhibition significantly decreased the risk of tilt-induced syncope in VVS subjects, mainly by blunting reflex bradycardia, thereby preventing final falls in cardiac index and BP.

Multidetector cardiac tomography: a useful tool before cardiac resynchronization therapy.

BACKGROUND: Left ventricular lead placement in a suitable coronary vein is a key determi-nant of responsiveness to cardiac resynchronization therapy (CRT). Multidetector cardiac tomography (MDCT) is a non-invasive alternative to depict cardiac venous anatomy although coronary sinus (CS) retrograde venography (RV) is the gold standard. The aim of this study was to evaluate the accuracy of MDCT to determine the presence of CS tributaries before CRT. METHODS: A retrospective analysis of 41 consecutive patients eligible to CRT was performed. MDCT was assessed in all patients before CRT and RV was achieved in 39 patients. Both methods evaluated the presence of the inferior interventricular vein (IIV), posterior vein (PV) and lateral main vein (LMV). CS ostium diameter and distance between the CS ostium and right atrium (RA) lateral wall were also measured. RESULTS: The IIV was identified in 100% of MDCT and in 43.6% of RV. In comparison to RV, the MDCT's sensitivity to identify PV and LMV was 100% for both, kappa coefficient of 0.792 (CI 95% 0.46-0.93) and 0.69 (CI 95% 0.46-0.91), respectively. There was no significant difference between ischemic and non-ischemic patients regarding the presence of PV or LMV. Median CS antero-posterior diameter was 10.3 mm (IQR 7.5-13) and supero-inferior was 14.1 mm (IQR 11.5-17) (p < 0.01). A positive correlation (p < 0.001) between echocardiographic RA area and the distance from CS ostium to the RA lateral wall in the MDCT was observed. CONCLUSIONS: MDCT is as accurate as RV to depict CS and its tributaries (IIV, PV, LMV), and it could be useful as a non-invasive technique before CRT.