Neuroscientific therapies for atrial fibrillation.

The cardiac autonomic nervous system (ANS) plays an integral role in normal cardiac physiology as well as in disease states that cause cardiac arrhythmias. The cardiac ANS, comprised of a complex neural hierarchy in a nested series of interacting feedback loops, regulates atrial electrophysiology and is itself susceptible to remodelling by atrial rhythm. In light of the challenges of treating atrial fibrillation (AF) with conventional pharmacologic and myoablative techniques, increasingly interest has begun to focus on targeting the cardiac neuraxis for AF. Strong evidence from animal models and clinical patients demonstrates that parasympathetic and sympathetic activity within this neuraxis may trigger AF, and the ANS may either induce atrial remodelling or undergo remodelling itself to serve as a substrate for AF. Multiple nexus points within the cardiac neuraxis are therapeutic targets, and neuroablative and neuromodulatory therapies for AF include ganglionated plexus ablation, epicardial botulinum toxin injection, vagal nerve (tragus) stimulation, renal denervation, stellate ganglion block/resection, baroreceptor activation therapy, and spinal cord stimulation. Pre-clinical and clinical studies on these modalities have had promising results and are reviewed here.

Conceptual Considerations for Device-Based Therapy in Acute Decompensated Heart Failure: DRI2P2S.

Acute decompensated heart failure remains the most common cause of hospitalization in older adults, and studies of pharmacological therapies have yielded limited progress in improving outcomes for these patients. This has prompted the development of novel device-based interventions, classified mechanistically based on the way in which they intend to improve central hemodynamics, increase renal perfusion, remove salt and water from the body, and result in clinically meaningful degrees of decongestion. In this review, we provide an overview of the pathophysiology of acute decompensated heart failure, current management strategies, and failed pharmacological therapies. We provide an in depth description of seven investigational device classes designed to target one or more of the pathophysiologic derangements in acute decompensated heart failure, denoted by the acronym DRI2P2S. Dilators decrease central pressures by increasing venous capacitance through splanchnic nerve modulation. Removers remove excess fluid through peritoneal dialysis, aquaphoresis, or hemodialysis. Inotropes directly modulate the cardiac nerve plexus to enhance ventricular contractility. Interstitial devices enhance volume removal through lymphatic duct decompression. Pushers are novel descending aorta rotary pumps that directly increase renal artery pressure. Pullers reduce central venous pressures or renal venous pressures to increase renal perfusion. Selective intrarenal artery catheters facilitate direct delivery of short acting vasodilator therapy. We also discuss challenges posed in clinical trial design for these novel device-based strategies including optimal patient selection and appropriate end points to establish efficacy.

New therapies for arterial hypertension.

Arterial hypertension is the most common chronic disease in developed countries and it is the leading risk factor for stroke, ischemic heart disease, congestive heart failure, chronic renal failure and peripheral artery disease. Its prevalence appears to be about 30-45% of the general population. Recent European guidelines estimate that up to 15-20% of the hypertensive patients are not controlled on a dual antihypertensive combination and they require three or more different antihypertensive drug classes to achieve adequate blood pressure control. The guidelines confirmed that diuretics, beta-blockers, calcium-channel blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are suitable for the initiation and maintenance of antihypertensive treatment, either as monotherapy or in combination therapy. Very few antihypertensive agents have reached the market over the last few years, but no new therapeutic class has really emerged. The long-term adherence to cardiovascular drugs is still low in both primary and secondary prevention of cardiovascular diseases. In particular, the issue of compliance is persistently high in hypertension, despite the fixed-dose combination therapy. As a consequence, a cohort of high-risk hypertensive population, represented by patients affected by refractory and resistant hypertension, can be identified. Therefore, the need of controlling BP in high-risk patients may be addressed, in part, by the development of new drugs, devices and procedures that are designed to treat hypertension and comorbidities. In this review we will comprehensively discuss the current literature on recent therapeutic advances in hypertension, including both medical therapy and interventional procedures.

Permanent sinus dysfunction after pulmonary vein isolation ablation: observations and potential mechanisms.

Although transient sinus arrest has been reported during pulmonary vein isolation (PVI), the long-term impairment of sinus node after PVI has not been described. In this report, we present a case of sinus node dysfunction necessitating a permanent pacemaker, caused during PVI. Clinical data, intracardiac electrograms, and cardiac imaging were incompatible with previous sinus node dysfunction, sinus node artery occlusion, or an ectopic atrial rhythm from the pulmonary veins. Impairment of the neural pathways connecting the ganglionated plexi of the right superior pulmonary veins with the sinus node is a possible underlying mechanism.

Efficacy of cardiac autonomic denervation for atrial fibrillation: a meta-analysis.

INTRODUCTION: Adjunctive complex fractionated atrial electrograms (CFAE) ablation or ganglionated plexi (GP) ablation have been proposed as new strategies to increase the elimination of AF, but the difference between CFAE/GP ablation and pulmonary vein isolation (PVI), as well as the combined effect of CFAE/GP plus PVI ablation were unclear. This meta-analysis was designed to determine whether adjunctive cardiac autonomic denervation (CAD) was effective for the elimination of AF, and whether CAD alone was superior to PVI in AF patients. METHODS: A systemic literature search in MEDLINE, EMBASE, and Cochrane Controlled Trials Register (CCRT) was performed and controlled trials comparing the effect of PVI plus CFAE/GP ablation with PVI, as well as CFAE/GP ablation with PVI were collected. RESULTS: A total of 15 trials including 1,147 patients with AF were qualified for this meta-analysis. CAD plus PVI significantly increased the freedom from AF/ATs (OR 1.85, 95% CI: 1.33-2.59, P = 0.29). Subgroup analysis showed that additional CAD increased the ratio of sinus rhythm maintenance in both paroxysmal AF (OR 1.69; 95% CI: 1.09-2.62, P = 0.41) and nonparoxysmal AF (OR 2.11, 95% CI: 1.14-3.90, P = 0.14). Besides, when compared respectively, adjunctive CAD was not superior to PVI (OR 0.31; 95% CI: 0.11-0.86, P = 0.002). CONCLUSION: This study suggested that CAD plus PVI significantly increase the freedom from recurrence of AF both in paroxysmal and nonparoxysmal patients. However, when compared alone, the benefit of CAD was not superior to PVI.

New therapeutic approaches for resistant hypertension.

In the past few years, 2 new procedures have been developed for the treatment of resistant hypertension: electrical stimulation of carotid baroreceptors and catheter-based renal denervation. Both of these procedures have a solid pathophysiological background, which is based on the evidence that carotid baroreceptors and renal nerves are involved in the pathogenesis of different forms of experimental hypertension, potentiating sympathetic cardiovascular influence and thus promoting the development and progression of elevated blood pressure values. This paper will review the results of the clinical trials performed so far making use of each of the 2 above-mentioned approaches. The pros and cons of each intervention as well as the questions that remain to be addressed in the future will also be discussed.

Inflammation abnormalities and inducibility of atrial fibrillation after epicardial ganglionated plexi ablation.

BACKGROUND: Epicardial ganglionated plexi (GP) ablation can prevent atrial fibrillation inducibility. However, the long-term effects of GP ablation on atrial fibrillation have not been elucidated. METHODS: Thirteen adult dogs of either sex, weighing 13-17kg, were randomly assigned to a sham-operated group (n=6) or a GP ablation group (n=7). After right thoracotomy, the atrial effective refractory period (AERP) was measured and atrial fibrillation was induced by right atrial rapid burst pacing. Atrial fibrillation and AERP were remeasured after anterior right and inferior right GP ablation in the GP ablation group. The animals were allowed to recover for 8 weeks, after which atrial fibrillation and AERP were measured again. Concentrations of C-reactive protein, tumour necrosis factor-alpha (TNF-α) and interleukin-6 were measured in the blood and atrial tissues. RESULTS: After 8 weeks, atrial fibrillation was induced in all animals in the GP ablation group. AERP and dispersion of AERP (dAERP; maximum AERP minus minimum AERP) were increased after GP ablation but AERP recovered after 8 weeks. There were no significant differences in the concentrations of C-reactive protein, TNF-α or interleukin-6 in venous blood between the two groups and the concentration of C-reactive protein in the atrium did not change before and after GP ablation. However, the concentrations of TNF-α and interleukin-6 in the atrium increased significantly 8 weeks after GP ablation (P<0.05). CONCLUSION: Increased concentrations of TNF-α and interleukin-6 in the atrium after GP ablation provide a new causative factor in terms of atrial fibrillation vulnerability.