Mitral annular disjunction in idiopathic ventricular fibrillation patients: just a bystander or a potential cause?

AIMS: Previously, we demonstrated that inferolateral mitral annular disjunction (MAD) is more prevalent in patients with idiopathic ventricular fibrillation (IVF) than in healthy controls. In the present study, we advanced the insights into the prevalence and ventricular arrhythmogenicity by inferolateral MAD in an even larger IVF cohort. METHODS AND RESULTS: This retrospective multi-centre study included 185 IVF patients [median age 39 (27, 52) years, 40% female]. Cardiac magnetic resonance images were analyzed for mitral valve and annular abnormalities and late gadolinium enhancement. Clinical characteristics were compared between patients with and without MAD. MAD in any of the 4 locations was present in 112 (61%) IVF patients and inferolateral MAD was identified in 24 (13%) IVF patients. Mitral valve prolapse (MVP) was found in 13 (7%) IVF patients. MVP was more prevalent in patients with inferolateral MAD compared with patients without inferolateral MAD (42 vs. 2%, P < 0.001). Pro-arrhythmic characteristics in terms of a high burden of premature ventricular complexes (PVCs) and non-sustained ventricular tachycardia (VT) were more prevalent in patients with inferolateral MAD compared to patients without inferolateral MAD (67 vs. 23%, P < 0.001 and 63 vs. 41%, P = 0.046, respectively). Appropriate implantable cardioverter defibrillator therapy during follow-up was comparable for IVF patients with or without inferolateral MAD (13 vs. 18%, P = 0.579). CONCLUSION: A high prevalence of inferolateral MAD and MVP is a consistent finding in this large IVF cohort. The presence of inferolateral MAD is associated with a higher PVC burden and non-sustained VTs. Further research is needed to explain this potential interplay.

2-year outcomes of phased radiofrequency ablation for atrial fibrillation with the second-generation PVAC Gold ablation catheter.

PURPOSE: The second-generation multi-electrode catheter, PVAC Gold, was designed to improve the safe delivery of phased radiofrequency energy using a "single shot" approach for pulmonary vein isolation (PVI), while retaining efficacy. This large registry presents long-term performance in a daily practice setting. METHODS: A total of 1011 patients undergoing first time ablation for atrial fibrillation (AF) using PVAC Gold were included, 639 patients with PVI for paroxysmal AF (PAF PVI) and 372 patients with persistent or long-standing persistent AF, divided into 175 patients receiving PVI only (PersAF PVI) and 197 patients receiving PVI with additional substrate ablation (PersAF PVI +). RESULTS: At 24-month follow-up, single procedure freedom from atrial tachyarrhythmia (ATA) was 58% (368/639) in the PAF PVI group, 44% (77/175) in the PersAF PVI group, and 29% (57/197) in the PersAF PVI + group. Allowing one repeat procedure in 33% of patients, 76%, 65%, and 54% were free from ATA at 24 months, respectively. Pulmonary vein reconnection was observed in 98% of patients with recurrent arrhythmia after PVI. CONCLUSIONS: Although phased RF ablation with PVAC Gold is quick and safe, the efficacy outcomes are modest compared to current mainstream ablation strategies.

Initial experience with AcQMap catheter for treatment of persistent atrial fibrillation and atypical atrial flutter.

INTRODUCTION: The AcQMap High Resolution Imaging and Mapping System was recently introduced. This system provides 3D maps of electrical activation across an ultrasound-acquired atrial surface. METHODS: We evaluated the feasibility and the acute and short-term efficacy and safety of this novel system for ablation of persistent atrial fibrillation (AF) and atypical atrial flutter. RESULTS: A total of 21 consecutive patients (age (mean ± standard deviation) 62 ± 8 years, 23% female) underwent catheter ablation with the use of the AcQMap System. Fourteen patients (67%) were treated for persistent AF and 7 patients (33%) for atypical atrial flutter. Eighteen patients (86%) had undergone at least one prior ablation procedure. Acute success, defined as sinus rhythm without the ability to provoke the clinical arrhythmia, was achieved in 17 patients (81%). At 12 months, 4 patients treated for persistent AF (29%) and 4 patients treated for atypical flutter (57%) remained in sinus rhythm. Complications included hemiparesis, for which intra-arterial thrombolysis was given with subsequent good clinical outcome (n = 1), and complete atrioventricular block, for which a permanent pacemaker was implanted (n = 2). No major complications attributable to the mapping system occurred. CONCLUSION: The AcQMap System is able to provide fast, high-resolution activation maps of persistent AF and atypical atrial flutter. Despite a high acute success rate, the recurrence rate of persistent AF was relatively high. This may be due to the selection of the patients with therapy-resistant arrhythmias and limited experience in the optimal use of this mapping system that is still under development.

High-density versus low-density mapping in ablation of atypical atrial flutter.

PURPOSE: Ablation of atypical atrial flutter (AAFL) can be challenging. High-density (HD) mapping of ablation targets may potentially increase procedural success and freedom from recurrent AAFL. The objective of the present study was to explore whether employing HD mapping leads to a more favorable outcome in ablation of AAFL. METHODS: We compared baseline and procedural characteristics, procedural success, safety and outcome of mapping and ablation of atypical flutter in three groups. (1) HD Grid catheter + the high-density electroanatomical mapping (EAM) system EnSite Precision; (2) standard 10-pole circular mapping catheter (CMC) + EnSite Precision; (3) CMC + the low-density EnSite Velocity EAM. Voltage and propagation maps were constructed. RESULTS: Mapping of 142 AAFL in 82 patients was performed. Acute ablation success was 78%, 68%, and 51% in groups 1, 2, and 3 (p = 0.037 between group 1 and 3, non-significant between groups otherwise). Moreover, 8%, 27%, and 36% of flutters were unmappable in groups 1, 2, and 3, respectively (p < 0.05 between group 1 and both groups 2 and 3). AAFL recurrence at 1-year FU was 26%, 36%, and 62% in groups 1, 2, and 3 (p = 0.007 between groups 1 and 3, p = 0.05 between groups 2 and 3). AAFL-free survival was significantly higher in patients mapped with Precision than with Velocity (p = 0.011). No strokes or mortality occurred within 30 days. CONCLUSIONS: Acute procedural success of ablation of atypical atrial flutter is higher and the number of unmappable flutters is lower using the HD Grid mapping catheter in combination with the high-density EnSite Precision system, as compared to a decapolar circular mapping catheter and the low-density EnSite Velocity EAM system. This may lead to increased freedom from recurrent AAFL at 1 year. HD mapping is safe.

Acute success and safety of the second-generation PVAC GOLD phased RF ablation catheter for atrial fibrillation.

PURPOSE: The second-generation multi-electrode catheter, pulmonary vein ablation catheter (PVAC) GOLD, was designed to improve the delivery of phased radiofrequency energy and reduce procedure times using a 'single-shot' approach for pulmonary vein isolation (PVI), while retaining efficacy and safety. This large registry presents acute success rates and safety outcomes in a daily practice setting. METHODS: A total of 1017 patients undergoing first-time ablation for atrial fibrillation (AF) using PVAC GOLD were included, 644 patients with paroxysmal AF and 373 patients with non-paroxysmal AF, divided into 175 patients receiving PVI only and 198 patients receiving PVI with additional substrate modification. RESULTS: High and comparable percentages of successful PVI could be achieved in all groups (98%, 95% and 99%; p = 0.108). The median total procedure time for all groups was 90 min [70-100]. As expected, the total procedure, ablation and fluoroscopy time were significantly longer in the PVI + substrate modification group compared with the PVI-only cases (all p < 0.001), but not between the PVI-only groups (p = 0.306, p = 0.088, p = 0.233, respectively). A total of 44 complications were observed in 43 patients (4.2%). Major complications were seen in 19 patients (1.87%) and non-major procedure-related complications were seen in 25 patients (2.46%). Complications leaving permanent sequelae were rare and occurred in only four patients (0.39%). Complications did not differ between groups (p = 0.199, p = 0.438, p = 0.240 and p = 0.465 respectively). CONCLUSION: PVAC GOLD performs successful PVI, while reducing procedure times and retaining safety for paroxysmal, persistent and long-standing persistent AF. Safety was unaffected by additional substrate modification.

Severe conduction defects requiring permanent pacemaker implantation in patients with a new-onset left bundle branch block after transcatheter aortic valve implantation.

AIMS: Transcatheter aortic valve implantation (TAVI) is frequently associated with cardiac conduction defects (CCD) requiring permanent pacemaker implantation (PPI). Although new-onset left bundle branch block (LBBB) is often seen, the rate of progression to severe CCD is unclear. We aimed to find clinical and electrocardiographic (ECG) parameters associated with severe CCD requiring PPI in patients with a new-onset LBBB after TAVI and assess its effect on clinical outcome. METHODS AND RESULTS: All consecutive patients undergoing TAVI who developed a new-onset LBBB were retrospectively analysed. We excluded patients with pre-existing bundle branch block or pacemaker. Patients were divided into two groups: with or without PPI after TAVI. We included 155 patients (50% female, 80 ± 7 years), of which 37 (24%) developed CCD requiring PPI, mainly due to a total atrioventricular block (n = 17; 46%). Cardiac conduction defects requiring PPI were associated with the following pre-existing parameters: atrial fibrillation (AF), the use of digoxin, CoreValve implantation, and left heart axis. Furthermore, it was associated with the following post-procedural parameters: left heart axis, lower mean heart rate, and prolonged PQ and QRS times. During follow-up, patients with PPI showed a lower mortality rate (11 vs. 29%, P = 0.03). In patients without PPI, mortality was lower in those with narrower QRS complex and transient LBBB. CONCLUSION: The severity and persistence of a new-onset LBBB after TAVI is associated with mortality. Cardiac conduction defects requiring PPI are associated with prior AF, the use of digoxin, CoreValve implantation, and a left heart axis. In these patients, PPI portends a better prognosis than no PPI.

Predictors of outcome after alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy. Special interest for the septal coronary anatomy.

BACKGROUND: Alcohol septal ablation (ASA) provides symptomatic relief in most but not all patients with hypertrophic obstructive cardiomyopathy (HOCM). Therefore we investigated predictors of outcome after ASA. METHODS: Clinical, echocardiographic, angiographic and procedural characteristics were analysed in 113 consecutive patients. Successful ASA was defined as NYHA ≤ 2 with improvement of at least 1 class combined with a resting gradient < 30 mmHg and provoked gradient < 50 mmHg at 4-month follow-up. RESULTS: In 37 patients ASA was not successful. In multivariate analysis, baseline gradient (OR 1.06 (1.01-1.11) per 5 mmHg, p = 0.024) and distance to the ablated septal branch (OR 1.09 (1.03-1.16) per mm, p = 0.004) were predictors of unsuccessful outcome. The combined presence of a non-ablated septal branch and a distance ≥ 19 mm to the ablated branch was a predictor of unsuccessful outcome (OR 5.88 (2.06-16.7), p < 0.001). CONCLUSIONS: Baseline gradient and a greater distance from the origin of the left anterior descending artery to the ablated septal branch combined with a non-ablated proximal septal branch are associated with an unsuccessful outcome after ASA.

Conduction recovery in patients with recurrent atrial fibrillation after pulmonary vein isolation using multi-electrode duty cycled radiofrequency ablation.

INTRODUCTION: The pulmonary vein ablation catheter (PVAC) is designed for pulmonary vein isolation (PVI). Electrical reconnection of pulmonary veins is believed to result in AF recurrence. The purpose of this study was to establish the location and extent of PV reconnection after PVI with the PVAC catheter. METHODS AND RESULTS: Eighty-two patients (79 % male, age 60 ± 9 years) that underwent a redo procedure for recurrent AF after PVAC ablation were assessed for prevalence and location of reconnection. The number of reconnected PV's was 0, 1, 2, 3, or 4 in 2 (2.4 %), 14 (17 %), 23 (28 %), 28 (34 %), and 15 (18 %) patients, respectively. Reconnection of left superior, left inferior, left common, right superior, and right inferior PV's was found in 66, 63, 83, 57, and 67 %, respectively (p = 0.48). In the left PV's, reconnection was located significantly more anterior than posterior; LSPV anterior 32/70 vs posterior 13/70 (p < 0.01), LIPV anterior 26/70 vs posterior 9/70 (p < 0.01). In the right PV's reconnection was distributed equally in all quadrants. Different modes of RF delivery during PVAC ablation (bipolar/unipolar 2:1 [n = 35] vs. 4:1 [n = 47]) yielded comparable rates of PV reconnection. During follow-up (median 296 days) no AF/AT was documented in 57 patients (70 %). CONCLUSION: Almost all patients (98 %) with AF after PVAC ablation show reconnection of at least one PV. All PV's are equally likely to show reconnection. In the left PV's, reconnection was found more often anteriorly than posteriorly. During pulmonary vein isolation with the PVAC catheter, prevalent sites of reconnection deserve close attention to increase success.

A patient with dizziness, tachycardia and a DDDR pacemaker.

An 84-year-old female patient presented to the coronary care unit with dizziness. A DDD-R minute ventilation sensor pacemaker had been implanted eight years previously. The ECG showed an atrial and ventricular paced rhythm of 140 beats/min. After disconnecting the patient from the cardiac monitor the pacemaker rate dropped gradually to 90 beats/min. The cardiac rhythm monitoring system applies low-amplitude electrical pulses in order to measure respiration rate by transthoracic impedance (TTI) measurement. The minute ventilation pacemaker sensor is driven by the same TTI measurement for rate response. Inappropriate interference between these two systems caused a sensor-driven high pacemaker rate. The dizziness was not related to the sensor-driven high rate.

AT(1)-receptor blockade and sympathetic neurotransmission in cardiovascular disease.

1. The present survey is dealing with the interactions between the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system (SNS) in various organs and tissues, with an emphasis on the angiotensin AT-receptors located at the sympathetic nerve endings. 2. Angiotensin II, the main effector of the RAAS is known to stimulate sympathetic nerve traffic and its sequelae in numerous organs and tissues, such as the central nervous system, the adrenal medulla, the sympathetic ganglia and the sympathetic nerve endings. These stimulatory effects are mediated by AT(1)-receptors and counteracted by AT(1)-receptor antagonists. 3. Sympatho-inhibition at the level of the sympathetic nerve ending appears to be a class effect of the AT(1)-receptor blockers, mediated by presynaptic AT(1)-receptors. With respect to the ratio pre-/postsynaptic AT(1)-receptor antagonism important quantitative differences between the various compounds were found. 4. Both the pre- and postjunctional receptors at the sympathetic nerve endings belong to the AT(1)-receptor population. However, the presynaptic receptors belong to the AT(1B)-subtype, whereas the postjunctional receptors probably belong to a different AT(1)-receptor subpopulation. 5. Sympatho-inhibition is a class effect of the AT(1)-receptor antagonists. In conditions in which the SNS plays a pathophysiological role, such as hypertension and congestive heart failure, this property may well be of therapeutic relevance.

Vasomotor effects of arg-gly-asp (RGD) peptides are limited and not related to endothelium-derived hyperpolarizing factor-mediated relaxation in rat mesenteric arteries.

1. In the present study we tested the effect of arg-gly-asp (RGD) peptides on vasomotor responses in rat isolated mesenteric arteries. More specifically, the hypothesis was tested that RGD interaction with integrins mediates relaxation attributed to endothelium-derived hyperpolarizing factor (EDHF). 2. The presence of the beta3 integrin subunit was shown by western blot analysis. To study its functional role, arteries (355 +/- 11 microm; n = 50) were mounted in a wire myograph set-up to measure isometric force generation. After blockade of nitric oxide synthesis with N(G)-nitro-L-arginine (0.1 mmol/L) and prostaglandin synthesis with indomethacin (10 micromol/L), methacholine (10 micromol/L) induced a transient relaxation within 1 min of 72 +/- 4.0% (as percentage of precontraction with phenylephrine; n = 27). 3. These responses were inhibited by a 60 mmol/L potassium buffer (18 +/- 6.0%; n = 6) or endothelium denudation (12 +/- 3.2%; n = 7), consistent with EDHF. 4. A function-blocking monoclonal antibody against the integrin beta3 chain did not affect relaxation. 5. The RGD peptides gly-arg-gly-asp-thr-pro (GRGDTP), gly-arg-gly-asp-ser (GRGDS) and cyclic RGD, ligands for the RGD binding site of integrins, also did not affect relaxation induced by methacholine. 6. Cyclic RGD increased contraction from 91 +/- 3 to 98 +/- 3% (as percentage of 120 mmol/L potassium). 7. In conclusion, these data show that vasomotor responses related to integrins are small and not involved in hyperpolarization attributed to EDHF in rat mesenteric artery.

Inhibition of facilitation of sympathetic neurotransmission and angiotensin II-induced pressor effects in the pithed rat: comparison between valsartan, candesartan, eprosartan and embusartan.

BACKGROUND: In the pithed rat model, endogenously generated angiotensin (Ang) II can enhance sympathetic neurotransmission by acting on Ang II type 1 (AT1) receptors that are located on sympathetic nerve terminals. OBJECTIVE: To compare the inhibitory potency of candesartan, valsartan, eprosartan and embusartan in blocking presynaptically and postsynaptically located AT1 receptors. DESIGN: To investigate blockade of presynaptic AT1 receptors, we studied the effect of AT1 receptor blockade on the sequelae of electrical stimulation of the thoracolumbar sympathetic outflow (0.25-8 Hz). To investigate the interaction between postsynaptic AT1 blockers and alpha-adrenoceptors, the effects of these compounds on pressor responses to exogenous noradrenaline were determined. To investigate blockade of postsynaptic AT1 receptors, we studied the effect of the AT1 antagonists on dose-response curves elicited by exogenous Ang II. RESULTS: The stimulation-induced increase in diastolic blood pressure (DBP) and the Ang II-elicited DBP response were dose-dependently reduced by all AT1 receptor blockers. Interestingly, the greatest doses of the AT1 antagonists caused less than maximal reduction in the stimulation-induced increase in DBP, resulting in a U-shaped dose-response relationship. To compare sympathoinhibitory potencies, the doses that, at 2 Hz, reduced the change in DBP by 20 mmHg (ED20 values, expressed as -log mol/kg) were calculated; they were 5.50 +/- 0.12, 5.77 +/- 0.10, 6.32 +/- 0.12 and 5.62 +/- 0.13 for valsartan, candesartan, eprosartan and embusartan, respectively. The order of potency, therefore, was eprosartan> valsartan = candesartan = embusartan (where > signifies P < 0.05). To compare the order of potency for inhibition of the Ang II-induced increase in DBP, we calculated pA2 values (the X intercept in Schild regression). They were 7.20 +/- 0.17, 8.01 +/- 0.01, 7.20 +/- 0.03 and 7.25 +/- 0.16, for valsartan, candesartan, eprosartan and embusartan, respectively. Accordingly, the order of potency for inhibition of the direct pressor effects of Ang II was candesartan> valsartan = eprosartan = embusartan (where > signifies P < 0.05). CONCLUSION: In the pithed rat, the effects on DBP of stimulation of the thoracolumbar spinal cord are partly dependent on endogenously formed Ang II. These effects can be counteracted by blockade of presynaptically located AT1 receptors. No interaction was found between postsynaptically located AT1 receptors and alpha-adrenoceptors. The order of potency of the agents tested for sympathoinhibition clearly differed from that for inhibition of the direct pressor effects of Ang II. These findings suggest considerable differences in affinity of the various AT1 blockers for pre- and postsynaptic AT1 receptors.

Effect of the AT1-receptor antagonists losartan, irbesartan, and telmisartan on angiotensin II-induced facilitation of sympathetic neurotransmission in the rat mesenteric artery.

SUMMARY: The effect of the AT1-receptor antagonists losartan, irbesartan, and telmisartan on angiotensin II (Ang II)-induced facilitation of noradrenergic neurotransmission was investigated in the isolated rat mesenteric artery under isometric conditions. Electrical field stimulation (2, 4, and 8 Hz) caused a frequency-dependent increase of contractile force. At stimulation frequencies of 2, 4, and 8 Hz, Ang 11 (10 nM) increased the stimulation-induced vasoconstrictor responses by a factor 4.8 +/- 0.9, 2.9 +/- 0.7, and 1.3 +/- 0.1, respectively (p < 0.05 compared with control for all frequencies). The enhancement could be concentration-dependently antagonized by losartan (1 nM-1 microM), irbesartan (0.1 nM-0.1 microM), and telmisartan (0.01 nM-0.01 microM). At a stimulation frequency of 2 Hz, the relation between stimulation-induced vasoconstrictor responses (in presence of Ang II 10 nM) and the concentration of the AT1-antagonists used could be described by linear regression. The order of potency concerning sympathoinhibition was telmisartan > irbesartan > losartan (p < 0.05 between linear regression lines). Contractile responses to exogenous noradrenaline were unaltered in the presence of Ang II 10 nM. We conclude that the facilitating effect of Ang II on noradrenergic neurotransmission is mediated by presynaptically located AT1-receptors. Conversely, this facilitating effect can be dose-dependently counteracted by blockade of these receptors. Sympathoinhibitory properties are likely to contribute to the therapeutic effect of AT1-blockers, in particular in conditions in which the sympathetic nervous system is activated, such as congestive heart failure and hypertension.

Inhibition of angiotensin II-induced facilitation of sympathetic neurotransmission in the pithed rat: a comparison between losartan, irbesartan, telmisartan, and captopril.

OBJECTIVE: Numerous studies have shown that angiotensin II enhances sympathetic nervous transmission. The objective of the present study was to quantify the inhibitory effect of the angiotensin II type 1 (AT1) receptor blockers losartan, irbesartan and telmisartan and the angiotensin converting enzyme (ACE) inhibitor captopril on sympathetic neurotransmission and to compare the potency of these agents both at the presynaptic and the postsynaptic levels. DESIGN: In the male, normotensive pithed rat model, we studied the effect of losartan (1, 3, 10 and 30 mg/kg), irbesartan (3, 10, 30 and 60 mg/kg), telmisartan (0.3, 1, 3 and 10 mg/kg) and captopril (1.5, 5, 15 and 45 mg/kg) on electrical stimulation of the thoraco-lumbar spinal cord. To investigate the interaction between postsynaptic AT1-receptors and alpha-adrenoceptors, the effects of these compounds on pressor responses to exogenous noradrenaline were studied. RESULTS: Stimulation of the thoracolumbar spinal cord caused a stimulation-frequency dependent rise in diastolic blood pressure (DBP) that could be dose-dependently reduced by both AT1 receptor blockade and ACE inhibition. Interestingly, the highest doses of the AT1 antagonists caused less than maximal reduction in the rise in DBP. This phenomenon was not observed after ACE inhibition by captopril. In experiments with exogenous noradrenaline, no effect of AT1 blockade or ACE inhibition on alpha-adrenoceptor-mediated blood pressure responses was seen. CONCLUSION: We conclude that, in the pithed rat model, the effects of stimulation of the thoraco-lumbar spinal cord on DBP are counteracted by blockade of presynaptically located AT1 receptors. The order of potency concerning sympatico-inhibition is telmisartan > losartan > irbesartan. Regarding the inhibition of angiotensin II-induced facilitation of sympathetic neurotransmission, marked differences were observed between selective AT1 blockade and ACE inhibition. The finding that all three AT1 blockers cause less than maximal inhibition in their highest doses, as opposed to captopril, suggests that this is a class effect of the AT1 antagonists.