Neuropeptides and peptide hormones in syncope and orthostatic intolerance

Syncope and orthostatic intolerance (OI) are common clinical syndromes often requiring medical attention. The former is defined as transient loss of consciousness and postural tone due to self-limited cerebral hypoperfusion, while the latter consists of inappropriate cardiovascular responses to upright posture such as occur with orthostatic hypotension (OH) or postural orthostatic tachycardia syndrome. The most frequent causes of syncope and OI are conditions that temporarily disrupt essential moment-to-moment interaction between the autonomic nervous system and cardiovascular system. In this regard, many neuropeptides (NPs) or peptide hormones (PH) exert cardioactive effects that might contribute to the pathophysiology of certain forms of syncope or OI. To date, the principal peptides that have been studied in this context are: atrial and B-type-neuropeptides, adrenomedullin, endothelin-1 (ET-1), galanin, and vasopressin. While definitive conclusions cannot yet be drawn, the intrinsic vasoconstrictor ET-1 appears to be elevated in OH, presumably to compensate for vasodilation and hypotension of other etiologies. As such elevated ET-1 may become a marker for OH. Further, elevated NT-proBNP may play a role in causing vasodilation and hypotension in some forms of OH of previously unknown cause, and may be a marker in other patients of a cardiovascular cause of syncope and OI. In the end, the study of the role of NPs and PHs in syncope and OI syndromes is at an early stage, and considerable further future effort is needed

Percutaneous Left Atrial Appendage Occlusion Therapy: Past, Present, and Future

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is increasing in incidence and prevalence worldwide. AF significantly increases the risk of intracardiac thrombus formation and, if left untreated, ischemic stroke. In patients with nonvalvular AF (NVAF), the left atrial appendage (LAA) has been determined to be the source of thrombus development in 91% to 99% of cases. In this regard, oral anticoagulants (OACs) have become the standard treatment for stroke prevention in most patients with AF; however, OACs are associated with a risk of bleeding complications, and their efficacy depends on optimal patient compliance. Among alternative approaches to embolic stroke prevention, surgical LAA excision for stroke prevention for valvular AF was attempted as early as the late 1940s. LAA excision remains recommended in surgical guidelines for patients with NVAF requiring open-heart coronary bypass or valvular replacement/repair surgeries. However, owing to the traumatic/invasive nature and suboptimal outcomes of conventional surgical LAA intervention, clinical application of this approach is limited in current cardiology practice. Percutaneous LAA occlusion (LAAO) is increasingly being performed as an alternative to OAC for stroke prevention, particularly in patients with elevated bleeding risk. Substantial progress has been made in percutaneous LAAO therapy since its inception approximately 20 years ago. This article systematically reviews the literature leading to the development of LAAO and the evidence-based clinical experience supporting the application of this treatment strategy for NVAF, with a focus on recently published critical evaluations of US FDA and CE mark approved LAAO devices. Future perspectives regarding knowledge and technology gaps are also discussed, recognizing the many ongoing clinical trials that are likely to be transformative and the critical unanswered questions regarding LAAO therapy

Variability of cardioinhibition in vasovagal syncope:differences between subgroups during cardioinhibition and beyond

Purpose: We compared hemodynamic parameters between subjects with marked, intermediate and minimal cardioinhibition during vasovagal syncope.Methods: The study included subjects with a decrease in heart rate while experiencing a complete vasovagal syncope during tilt-table testing. The subjects were classified as having marked, intermediate or minimal cardioinhibition, based on tertile values of the decrease in heart rate. Hemodynamic parameters between these groups were compared before tilt in the supine position, shortly after tilt and during cardioinhibition. Results:A total of 149 subjects with a median age of 43 (interquartile range 24–60) years were included in the study. Among the three groups with different levels of cardioinhibition, the highest heart rate was observed in subjects with marked cardioinhibition both before and shortly after tilt and at the start of cardioinhibition. The heart rate decrease in these subjects was both larger and faster compared to subjects with minimal and intermediate cardioinhibition. Conclusion: Subjects with marked cardioinhibition have both a larger and faster decrease in heart rate compared to subjects with intermediate and minimal cardioinhibition, as early as from the start of cardioinhibition. Marked cardioinhibition is related to differences in hemodynamic profiles already present well before the start of cardioinhibition.</p

Relationship of Paroxysmal Atrial Tachyarrhythmias to Volume Overload

BACKGROUND: Clinical experience suggests that atrial tachyarrhythmias (ATs) are a frequent comorbidity in heart failure patients with left ventricular systolic dysfunction and that volume overload may increase AT susceptibility. However, substantiating this apparent relationship in free-living patients is difficult. Recently, certain implantable cardioverter-defibrillators provide, by measuring transpulmonary electric bioimpedance, an index of intrathoracic fluid status (OptiVol index [OI]). The goal of this study was to determine whether periods of greater intrathoracic fluid congestion (as detected by OI) correspond with increased AT event frequency. METHODS AND RESULTS: This analysis retrospectively assessed the relation between AT events and OI estimate of volume overload in patients with left ventricular systolic dysfunction and OI-capable implantable cardioverter-defibrillators. OI values were stratified into 3 levels: group 1, \u3c40; group 2, 40 to 60; and group 3, \u3e60. An OI threshold-crossing event was defined as OI \u3e or = 60, a value previously associated with clinically significant volume overload. Findings in 59 patients (mean left ventricular ejection fraction, 24%) with 225 follow-up visits (mean, 3.8 visits per patient) were evaluated. AT prevalence was 73%. AT frequency (percent of patients visits with at least 1 episode of AT since previous device interrogation) was greater in group 3 versus group 1 (P=0.0342). Finally, in terms of temporal sequence, AT episodes preceded OI threshold-crossing event in 43% of incidences, followed threshold-crossing event in 29%, and was simultaneous or indeterminate in the remainder. CONCLUSIONS: These findings not only support the view that worsening pulmonary congestion is associated with increased AT frequency in patients with left ventricular dysfunction but also suggest that AT events may be responsible for triggering episodic pulmonary congestion more often than previously suspected

Isolated Atrial Segment Pacing An Alternative to His Bundle Pacing After Atrioventricular Junctional Ablation

ObjectivesThis study was designed to investigate a practical alternative to His bundle pacing after atrioventricular (AV) junctional ablation by pacing a small area of isolated atrial tissue surrounding the AV node.BackgroundHis bundle pacing is preferred after AV junctional ablation in patients with refractory atrial fibrillation. However, it is technically difficult and not clinically useful at the present time.MethodsThis study was conducted in an isolated working swine heart model (n = 5), with real-time imaging capabilities. A small area of atrial tissue surrounding the AV node and the His bundle was isolated using sequential radiofrequency ablation lesions.ResultsComplete AV block created by segmental atrial isolation was achieved in 5 of 5 experiments. The isolated atrial segment was bordered by the ablation lines, the tricuspid annulus, and the AV node–His bundle. The AV conduction was characterized using a pacing electrode implanted into the isolated atrial segment. Pacing from the atria, the ventricles, and the isolated atrial segment at different rates confirmed complete bidirectional block between the atria and isolated area, whereas antegrade and retrograde AV nodal conduction between the isolated atrial segment and the ventricles remained intact. Pacing from the isolated area produced minimal changes in systolic left ventricular pressure compared with baseline sinus rhythm (mean −2 mm Hg).ConclusionsIsolation of a small area of atrial tissue surrounding the AV node is feasible by transcatheter radiofrequency ablation. This procedure may be a useful alternative to conventional AV junctional ablation because it can create complete AV block, while in effect permitting the equivalent of His bundle pacing after AV junctional ablation

Percutaneous Left Atrial Appendage Occlusion Therapy: Evolution and Growing Evidence

Atrial fibrillation (AF) is the most common cardiac arrhythmia and if untreated, significantly increases both the risk of intracardiac thrombus formation and ischemic stroke. In patients with nonvalvular AF (NVAF), the left atrial appendage (LAA) has been estimated to be the source of thrombus development in 91% to 99% of cases. Consequently, oral anticoagulation (OAC) to provide stroke prevention has become the standard of care for most AF patients; however, OACs are associated with a risk of bleeding and their efficacy depends on optimal patient compliance. In terms of alternative approaches to preventing embolic events, surgical LAA excision was attempted as early as in the late 1940s in patients with valvular AF; LAA excision remains a recommendation in surgical guidelines for NVAF patients who need open-heart coronary bypass or valvular replacement/repair surgeries. However, due to its invasive nature surgical LAA intervention has limited clinical application in present cardiology practice. Percutaneous LAA occlusion (LAAO) is increasingly being performed as an alternative to OAC for stroke prevention; this is particularly the case in patients at increased bleeding risk. Substantial progress has been made in percutaneous LAAO therapy since its inception some twenty years ago. Herein we systematically review both the critical literature that led to the development of LAAO, and the increasing clinical evidence supporting the application of this treatment strategy in NVAF. To this end we focus on recently published critical evaluations of United States Food and Drug Administration (US FDA) and Conformité Européenne (Commercial Sale of Licensed Product in the EU) (CE-Mark) approved LAAO devices, summarize the current status of LAAO therapy, and discuss the future perspectives regarding the knowledge and technology gaps in this area by recognizing the potential contributions of many ongoing but likely transformative clinical trials