Excessive Weight Favours Skin Physiology - Up to a Point: Another Expression of the Obesity Paradox.

BACKGROUND/AIMS: Recently classified as an epidemic by the WHO, obesity (as well as the state of being overweight) clearly affects significant populations across all ages. The relationship between obesity and some diseases (e.g. cardiovascular ones) is known, although many paradoxes remain to be explained. Very little information is available, however, regarding its impact on skin physiology and skin disease. This study aims to examine the influence of excessive weight on epidermal hydration and transepidermal water loss, key variables of skin water balance and skin biomechanics. METHODS: A convenience sample of 89 healthy female volunteers was selected and divided into 4 groups, according to their BMI (body mass index), as normal (control), overweight, obese (I and II), and morbid. Skin physiology was quantitatively assessed in all individuals in 4 anatomical areas using non-invasive biometrical analysis by reference instrumentation. Descriptive and comparative statistics were applied, adopting a confidence level of 95%. RESULTS: A non-linear alteration for all variables was detected as a function of BMI. CONCLUSION: Results suggest that excessive weight might favour skin performance within certain limits, reflecting a particular adaptation of the skin to the weight gain and body contour.

Speech-induced atrial tachycardia: A narrative review of putative mechanisms implicating the autonomic nervous system.

Despite being uncommon, speech-induced atrial tachycardias carry significant morbidity and affect predominantly healthy individuals. Little is known about their mechanism, treatment, and prognosis. In this review, we seek to identify the underlying connections and pathophysiology between speech and arrhythmias while providing an informed approach to evaluation and management.

Acute and Long-Term Scar Characterization of Venous Ethanol Ablation in the Left Ventricular Summit.

BACKGROUND: Venous ethanol ablation (VEA) can be effective for ventricular arrhythmias from the left ventricular summit (LVS); however, there are concerns about excessive ablation by VEA. OBJECTIVES: The purpose of this study was to delineate and quantify the location, extent, and evolution of ablated tissue after VEA as an intramural ablation technique in the LVS. METHODS: VEA was performed in 59 patients with LVS ventricular arrhythmias. Targeted intramural veins were selected by electrograms from a 2F octapolar catheter or by guide-wire unipolar signals. Median ethanol delivered was 4 mL (IQR: 4-7 mL). Ablated areas were estimated intraprocedurally as increased echogenicity on intracardiac echocardiography (ICE) and incorporated into 3-dimensional maps. In 44 patients, late gadolinium enhancement cardiac magnetic resonance (CMR) imaged VEA scar and its evolution. RESULTS: ICE-demonstrated increased intramural echogenicity (median volume of 2 mL; IQR: 1.7-4.3) at the targeted region of the 3-dimensional maps. Post-ethanol CMR showed intramural scar of 2.5 mL (IQR: 2.1-3.5 mL). Early (within 48 hours after VEA) CMR showed microvascular obstruction (MVO) in 30 of 31 patients. Follow-up CMR after a median of 51 (IQR: 41-170) days showed evolution of MVO to scar. ICE echogenicity and CMR scar volumes correlated with each other and with ethanol volume. Ventricular function and interventricular septum remained intact. CONCLUSIONS: VEA leads to intramural ablation that can be tracked intraprocedurally by ICE and creates regions of MVO that are chronically replaced by myocardial scar. VEA scar volume does not compromise septal integrity or ventricular function.

Thermally responsive hydrogel for atrial fibrillation related stroke prevention.

Atrial fibrillation induced stroke accounts for up to 15% of all strokes. These strokes are caused approximately 90% of the time by clot formation in the left atrial appendage (LAA). To prevent these clots, the most common approach is to administer blood thinners. However, contraindications prevent some people from being able to have blood thinners. Devices have been developed to seal the LAA to prevent clot formation in these patients. Current devices, such as the LARIAT® tie off the LAA theoretically preventing blood from entering the LAA. These have had limited clinical success mainly due to failure to completely close the LAA leaving holes and orifices for thrombi to form. To overcome this lack of complete closure, many surgeons use off-label approaches, classically filling the LAA filamentous coils, to cover these holes. Although this usually helps largely cover the holes, placement is challenging, the coils can migrate, the holes are not fully closed as there is space within and around the coils that don't fully mold to the LAA geometry. Furthermore, the coils can develop device related thrombi defeating their purpose. Therefore, these are not fully sufficient to complement the closure techniques in closing the LAA. To address limitation of the closure devices and coil sealing of remaining holes, we developed a thermally responsive hydrogel (Thermogel) that solidifies once injected into the LAA to uniformly and fully close off the LAA thus preventing clot formation and device related thrombi. This Thermogel consists of three portions: 1) a structural component composed of thiolated Pluronic F127 for gel to solid transition following injection, 2) Heparin for anticoagulation, and 3) Dopamine for adhesion to the surrounding endothelium in the turbulent flow encountered in cardiovascular applications. Here we have demonstrated that Thermogel, in conjunction with the LARIAT®, is capable of filling the defects in small and large animals through catheter injection. Thermogel was biocompatible and led to atrophy of the LAA at 5 weeks in a large animal model. Given the advantages of this Thermogel for sealing this defect and ability to be delivered through an endovascular approach, Thermogel presents a viable adjuvant to current occlusion-based treatments for sealing cardiovascular defects.

Sleep Apnea and Atrial Fibrillation: Role of the Cardiac Autonomic Nervous System.

Sleep apnea is highly associated with atrial fibrillation (AF), and both diseases are highly prevalent in the United States. The mechanistic underpinnings that contribute to their association remain uncertain, but numerous possible mechanisms have been proposed, including dysfunction of the cardiac autonomic nervous system (ANS). Studies have reported that apnea induces hyperactivity of the ANS, leading to increases in AF susceptibility. This review compiles the latest evidence on the role of the ANS in sleep-apnea-induced AF.

Alcohol Ablation for Ventricular Tachycardia.

Catheter-based radiofrequency (RF) ablation is an effective, well-established therapy for ventricular tachycardia (VT). However, a large number of patients still have recurrences, particularly those with substrates arising from intramural locations that are inaccessible through endo- or epicardial catheter approaches. Several unconventional ablation techniques have been proposed to treat RF-refractory VT, including transarterial coronary ethanol ablation and retrograde coronary venous ethanol ablation. We review the evidence regarding the mechanisms, procedural aspects, and alcohol ablation outcomes for ventricular arrhythmias.

Venous anatomy of the left ventricular summit: Therapeutic implications for ethanol infusion.

BACKGROUND: Venous ethanol ablation (VEA) is effective for treatment of left ventricular (LV) summit (LVS) arrhythmias. The LVS venous anatomy is poorly understood and has inconsistent nomenclature. OBJECTIVE: The purpose of this study was to delineate the LVS venous anatomy by selective venography and 3-dimensional (3D) mapping during VEA and by venous-phase coronary computed tomographic angiography (vCTA). METHODS: We analyzed (1) LVS venograms and 3D maps of 53 patients undergoing VEA; and (2) 3D reconstructions of 52 vCTAs, tracing LVS veins. RESULTS: Angiography identified the following LVS veins: (1) LV annular branch of the great cardiac vein (GCV) (19/53); (2) septal (rightward) branches of the anterior ventricular vein (AIV) (53/53); and (3) diagonal branches of the AIV (51/53). Collateral connections between LVS veins and outflow, conus, and retroaortic veins were common. VEA was delivered to target arrhythmias in 38 of 53 septal, 6 of 53 annular, and 2 of 53 diagonal veins. vCTA identified LVS veins (range 1-5) in a similar distribution. GCV-AIV transition could either form an angle close to the left main artery bifurcation (n = 16; 88° ± 13°) or cut diagonally (n = 36; 133°±12°) (P ≤.001). Twenty-one patients had LV annular vein. In 28 patients only septal LVS veins were visualized in vCTA, in 2 patients only diagonal veins and in 22 patients both septal and diagonal veins were seen. In 39 patients the LVS veins reached the outflow tracts and their vicinity. CONCLUSION: We provide a systematic atlas and nomenclature of LVS veins related to arrhythmogenic substrates. vCTA can be useful for noninvasive evaluation of LVS veins before ethanol ablation.

Neuromodulatory Approaches for Atrial Fibrillation Ablation.

In this review, the authors describe evolving alternative strategies for the management of AF, focusing on non-invasive and percutaneous autonomic modulation. This modulation can be achieved - among other approaches - via tragus stimulation, renal denervation, cardiac afferent denervation, alcohol injection in the vein of Marshall, baroreceptor activation therapy and endocardial ganglionated plexi ablation. Although promising, these therapies are currently under investigation but could play a role in the treatment of AF in combination with conventional pulmonary vein isolation in the near future.

Double-balloon technique for retrograde venous ethanol ablation of ventricular arrhythmias in the absence of suitable intramural veins.

BACKGROUND: Venous ethanol infusion via an occlusive balloon has been used as a bailout approach to treat ablation-refractory ventricular arrhythmias (VAs). Unfavorable venous anatomy (lack of intramural veins at the targeted site or collateral vein-ethanol shunting) limits its efficacy. Blocking collateral flow with a second balloon may optimize myocardial ethanol delivery. OBJECTIVE: The purpose of this study was to validate the "double-balloon" approach to enhance ethanol delivery in cases of unfavorable venous anatomy. METHODS: Eight patients referred after failed ablations (3 left ventricular [LV] summit, 5 scar-related ventricular tachycardia) underwent endocardial mapping and additional radiofrequency ablation without VA resolution. Coronary veins were mapped using a multipolar catheter or wire, and selective venograms were obtained. The double balloon was used when (1) distal collateral branches shunted flow away from the targeted region; (2) the target vein had optimal signals only proximally; or (3) a large vein was targeted that had multiple branches for a large area of interest. RESULTS: Acute successful ethanol infusion myocardial delivery and resolution of VA was accomplished using the posterolateral LV veins (n = 2 patients, 3 procedures), lateral LV vein (n = 1), apical anterior interventricular vein (AIV; n = 1), middle cardiac vein (n = 1), and septal branches of the AIV (n = 3). At median follow-up of 313.5 days, 2 patients experienced recurrence. CONCLUSION: The double-balloon technique can enhance ethanol delivery to target isolated vein segments, block collateral flow, or target extensive areas, and can expand the utility of venous ethanol for treatment of VAs.

Intramural Venous Ethanol Infusion for Refractory Ventricular Arrhythmias: Outcomes of a Multicenter Experience.

OBJECTIVES: The aim of this study was to assess the long-term efficacy and outcomes of retrograde venous ethanol ablation in treating ventricular arrhythmias (VAs). BACKGROUND: Retrograde coronary venous ethanol ablation (RCVEA) can be effective for radiofrequency ablation (RFA)-refractory VAs, particularly those arising in the LV summit (LVS). METHODS: Patients with drug and RFA-refractory VAs were considered for RCVEA after RF failure attempts. Intramural coronary veins (tributaries of the great cardiac, anterior interventricular, lateral cardiac, posterolateral, and middle cardiac) were mapped using an angioplasty wire. Ethanol infusion was delivered in veins with appropriate signals. RESULTS: Of 63 patients (age 63 ± 14 years; 60% men) with VAs (71% extrasystole, 29% ventricular tachycardia, 76% LVS origin), RCVEA was performed in 56 patients who had suitable vein branches. These were defined as those amenable to cannulation and with intramural signals that preceded those mapped in the epicardium or endocardium and had better matching pace maps or entrainment responses. Seven patients had no suitable veins and underwent RFA. In 38 of 56 (68%) patients, the VAs were successfully terminated exclusively with ethanol infusion. In 17 of 56 (30%) patients, successful ablation was achieved using ethanol with adjunctive RFA in the vicinity of the infused vein due to acute recurrence or ethanol-induced change in VA morphology. Overall, isolated or adjuvant RCVEA was successful in 55 of 56 (98%) patients. At 1-year follow-up, 77% of patients were free of recurrent arrhythmias. Procedural complications included 2 venous dissections that led to pericardial effusions. CONCLUSIONS: RCVEA offers a significant long-term effective treatment for patients with drug and RF-refractory VAs.

NS5806 Induces Electromechanically Discordant Alternans and Arrhythmogenic Voltage-Calcium Dynamics in the Isolated Intact Rabbit Heart.

Background: NS5806 activates the transient outward potassium current I to, and has been claimed to reproduce Brugada Syndrome (BrS) in ventricular wedge preparations. I to modulates excitation-contraction coupling, which is critical in alternans dynamics. We explored NS5806-arrhythmogenic effects in the intact whole heart and its impact on alternans. Methods: Langendorff-perfused rabbit hearts (n = 20) underwent optical AP and Ca mapping during pacing at decremental cycle lengths (CL). Spontaneous arrhythmias and pacing-induced alternans was characterized at baseline (BL), after perfusing with NS5806, before and after adding verapamil (VP), and SEA0400 (SEA, n = 5 each), to modulate Ca-current and Na-Ca exchange, the main AP-Ca coupling mechanisms. Results: NS5806 induced BrS-like ECG features in 6 out of 20 hearts. NS5806 prolonged steady-state (3 Hz) action potential duration (APD) by 16.8%, Ca decay constant by 34%, and decreased conduction velocity (CV) by 52.6%. After NS5806 infusion, spontaneous ventricular ectopy (VE) and AP/Ca alternans occurred. Pacing-induced alternans during NS5806 infusion occurred at longer CL and were AP/Ca discordant from its onset. Spatially discordant alternans after NS5806 infusion had non-propagation-driven nodal line distribution. No spontaneous phase-2 reentry occurred. Under NS5806 + VP, alternans became AP/Ca concordant and only induced in two out of five; NS5806 + SEA did not affect alternans but suppressed spontaneous ectopy. Conclusions: NS5806 disrupts AP-Ca coupling and leads to Ca-driven, AP/Ca-discordant alternans and VE. Despite BrS-like ECG features, no spontaneous sustained arrhythmias or phase-2 reentry occurred. NS5806 does not fully reproduce BrS in the intact rabbit heart.

Cardiac Afferent Denervation Abolishes Ganglionated Plexi and Sympathetic Responses to Apnea: Implications for Atrial Fibrillation.

Background The autonomic nervous system response to apnea and its mechanistic connection to atrial fibrillation (AF) are unclear. We hypothesize that sensory neurons within the ganglionated plexi (GP) play a role. We aimed to delineate the autonomic response to apnea and to test the effects of ablation of cardiac sensory neurons with resiniferatoxin (RTX), a neurotoxic TRPV1 (transient receptor potential vanilloid 1) agonist. Methods Sixteen dogs were anesthetized and ventilated. Apnea was induced by stopping ventilation until oxygen saturations decreased to 80%. Nerve recordings from bilateral vagal nerves, left stellate ganglion, and anterior right GP were obtained before and during apnea, before and after RTX injection in the anterior right GP (protocol 1, n=7). Atrial effective refractory period and AF inducibility on single extrastimulation were assessed before and during apnea, and before and after intrapericardial RTX administration (protocol 2, n=9). GPs underwent immunohistochemical staining for TRPV1. Results Apnea increased anterior right GP activity, followed by clustered crescendo vagal bursts synchronized with heart rate and blood pressure oscillations. On further oxygen desaturation, a tonic increase in stellate ganglion activity and blood pressure ensued. Apnea-induced effective refractory period shortening from 110.20±31.3 ms to 90.6±29.1 ms ( P<0.001), and AF induction in 9/9 dogs versus 0/9 at baseline. After RTX administration, increases in GP and stellate ganglion activity and blood pressure during apnea were abolished, effective refractory period increased to 126.7±26.9 ms ( P=0.0001), and AF was not induced. Vagal bursts remained unchanged. GP cells showed cytoplasmic microvacuolization and apoptosis. Conclusions Apnea increases GP activity, followed by vagal bursts and tonic stellate ganglion firing. RTX decreases sympathetic and GP nerve activity, abolishes apnea's electrophysiological response, and AF inducibility. Sensory neurons play a role in apnea-induced AF.

Assessment of cardiovascular risk and social framework of Cape Verdean university students studying in Portugal.

INTRODUCTION: The migration of African populations to Europe poses problems of adaptation that may increase the risk of cardiovascular disease. We assessed the cardiovascular risk of Cape Verdean university students studying in Portugal (CV-PT) compared to Cape Verdean university students in Cape Verde (CV-CV) and to Caucasian university students in Portugal (PT-PT). METHODS: A cross-sectional study was performed comparing three university populations, 54-62% female, aged 19-28 years: CV-PT (n=104), CV-CV (n=100) and PT-PT (n=100). Anthropometric data, blood pressure (BP), pulse wave velocity (PWV), albuminuria and estimated 24-h urinary sodium excretion (UNa+) using the Kawasaki formula were measured. RESULTS: The CV-PT group had higher body mass index and sodium intake (UNa+: CV-PT 235±91, CV-CV 197±85, PT-PT 194±90 mmol/24h; p<0.001), more sedentary lifestyles and worse socioeconomic, integration and adaptation indices compared to CV-CV and PT-PT. CV-PT and CV-CV also had higher systolic BP (CV-PT 119±12mmHg, CV-CV 121±15mmHg, PT-PT 107±14mmHg; p<0.001), PWV (CV-PT 8.7±1.1, CV-CV 8.8±1.8, PT-PT 8.0±1.2 m/s; p<0.04), and albuminuria (CV-PT 13.0±34.1, CV-CV 9.2±21.2, PT-PT 5.7±6.4µg/mg creatinine; p<0.04). CONCLUSION: Cape Verdean university students in Portugal (CV-PT) have higher albuminuria, BP and PWV values than PT-PT and CV-CV students, associated with less healthy lifestyles, higher cardiovascular risk and worse socioeconomic conditions. The higher cardiovascular risk in these African immigrants means that it is important to implement measures to address modifiable risk factors, to improve integration and to promote healthy lifestyles.