Refractory hypertensive emergency associated with complete heart block resolved after permanent pacemaker implantation: A case report.

Severe hypertension sometimes improves with treatment of bradycardia but this phenomenon is under-reported. Here, an elderly gentleman with complete heart block and a hypertensive emergency was refractory to medical therapies and blood pressure only improved following pacemaker implantation. We discuss the possible mechanisms relating to heart rate and artificial pacing.

Optimal ablation strategy for arrhythmia recurrence following persistent atrial fibrillation ablation; anatomy or electrophysiology?

The optimal strategy for ablation of persistent atrial fibrillation (PsAF) remains to be defined. Established substrate-based ablation techniques, particularly techniques targeting complex electrograms, with complementary linear ablation for organized atrial tachycardias, have been associated with modest success rates. Recently, the development of VoM ethanol ablation (Et-VoM) has facilitated ablation of previously inaccessible arrhythmogenic substrate. This has allowed comparison of a standardized anatomically-guided protocol with Et-VOM to a traditional electrophysiology-guided approach for PsAF ablation.

UBLED AF (Uninterrupted BLackpool EDoxaban vs Warfarin vs Rivaroxaban in Atrial Fibrillation/Flutter ablation) Study.

AIM: Catheter ablation in patients with atrial fibrillation (AF)/atrial flutter carries a risk of thromboembolism and major bleeding. In light of recent prospective trial data on the safety and efficacy of uninterrupted edoxaban in patients undergoing AF/flutter ablation, real-world Data was aimed for validation. METHODS: A total of 228 patients who underwent AF/atrial flutter ablation over 14 months at our centre were retrospectively analyzed. All patients received uninterrupted oral anticoagulation for at least 4 weeks prior to ablation and 3 months post-ablation. Both bleeding and thromboembolic events were assessed at 24 hours comparing patients on warfarin, rivaroxaban and edoxaban. RESULTS: Mean age of patients were 68.5 +/- 8 years in the warfarin group ( N =86), 63.4 +/- 10.6 years; in the edoxaban group ( N =63) and 62.3 +/- 11.6 years in the rivaroxaban group ( N =79). CHADSVASc scores were 2.43 +/- 1.34, 1.68 +/- 1.34 and 1.64 +/- 1.38 respectively. The mean left atrial sizes were 42.7 +/- 6.8 mm, 42.0 +/- 6 mm and 41.1 +/- 6.5 mm respectively. The study endpoint was death, acute thromboembolism or major bleeding. There was 1 pericardial effusion (1.2%) in the warfarin group, 1 pericardial effusion and 1 transient ischaemic attack (2.5%) in the rivaroxaban group and 1 pericardial effusion needing drainage (1.6%) in the edoxaban group. There were no significant differences in the study endpoints between groups. CONCLUSION: This real-world study demonstrated no significant difference in safety and efficacy between uninterrupted edoxaban, warfarin and rivaroxaban in patients undergoing AF/flutter ablation.

Silencing miR-370-3p rescues funny current and sinus node function in heart failure.

Bradyarrhythmias are an important cause of mortality in heart failure and previous studies indicate a mechanistic role for electrical remodelling of the key pacemaking ion channel HCN4 in this process. Here we show that, in a mouse model of heart failure in which there is sinus bradycardia, there is upregulation of a microRNA (miR-370-3p), downregulation of the pacemaker ion channel, HCN4, and downregulation of the corresponding ionic current, If, in the sinus node. In vitro, exogenous miR-370-3p inhibits HCN4 mRNA and causes downregulation of HCN4 protein, downregulation of If, and bradycardia in the isolated sinus node. In vivo, intraperitoneal injection of an antimiR to miR-370-3p into heart failure mice silences miR-370-3p and restores HCN4 mRNA and protein and If in the sinus node and blunts the sinus bradycardia. In addition, it partially restores ventricular function and reduces mortality. This represents a novel approach to heart failure treatment.

Biology of the Sinus Node and its Disease.

The sinoatrial node (SAN) is the normal pacemaker of the heart and SAN dysfunction (SND) is common, but until recently the pathophysiology was incompletely understood. It was usually attributed to idiopathic age-related fibrosis and cell atrophy or ischaemia. It is now evident that changes in the electrophysiology of the SAN, known as electrical remodelling, is an important process that has been demonstrated in SND associated with heart failure, ageing, diabetes, atrial fibrillation and endurance exercise. Furthermore, familial SND has been identified and mutations have been characterised in key pacemaker genes of the SAN. This review summarises the current evidence regarding SAN function and the pathophysiology of SND.

Characterization of a right atrial subsidiary pacemaker and acceleration of the pacing rate by HCN over-expression.

AIMS: Although the right atrium (RA contains subsidiary atrial pacemaker (SAP) tissue that can take over from the sinoatrial node (SAN) in sick sinus syndrome (SSS), SAP tissue is bradycardic. Little is known about SAP tissue and one aim of the study was to characterize ion channel expression to obtain insight into SAP pacemaker mechanisms. A second aim was to determine whether HCN over-expression (a 'biopacemaker'-like strategy) can accelerate the pacemaker rate producing a pacemaker that is similar in nature to the SAN. METHODS AND RESULTS: SAP tissue was isolated from the rat and the leading pacemaker site was characterized. Cell size at the leading pacemaker site in the SAP was smaller than in the RA and comparable to that in the SAN. mRNA levels showed the SAP to be similar to, but distinct from, the SAN. For example, in the SAN and SAP, expression of Tbx3 and HCN1 was higher and Nav1.5 and Cx43 lower than in the RA. Organ-cultured SAP tissue beat spontaneously, but at a slower rate than the SAN. Adenovirus-mediated gene transfer of HCN2 and the chimeric protein HCN212 significantly increased the pacemaker rate of the SAP close to that of the native SAN, but HCN4 was ineffective. CONCLUSION: SAP tissue near the inferior vena cava is bradycardic, but shares characteristics with the SAN. Pacing can be accelerated by the over-expression of HCN2 or HCN212. This provides proof of concept for the use of SAP tissue as a substrate for biopacemaking in the treatment of SSS.