Long-term outcomes of cardioneuroablation with and without extra-cardiac vagal stimulation confirmation in severe cardioinhibitory neurocardiogenic syncope.

BACKGROUND: Cardioneuroablation (CNA) is a novel therapeutic approach for functional bradyarrhythmias, specifically neurocardiogenic syncope or atrial fibrillation, achieved through endocardial radiofrequency catheter ablation of vagal innervation, obviating the need for pacemaker implantation. Originating in the nineties, the first series of CNA procedures was published in 2005. Extra-cardiac vagal stimulation (ECVS) is employed as a direct method for stepwise denervation control during CNA. OBJECTIVE: This study aimed to compare the long-term follow-up outcomes of patients with severe cardioinhibitory syncope undergoing CNA with and without denervation confirmation via ECVS. METHOD: A cohort of 48 patients, predominantly female (56.3%), suffering from recurrent syncope (5.1 ± 2.5 episodes annually) that remained unresponsive to clinical and pharmacological interventions, underwent CNA, divided into two groups: ECVS and NoECVS, consisting of 34 and 14 cases, respectively. ECVS procedures were conducted with and without atrial pacing. RESULTS: Demographic characteristics, left atrial size, and ejection fraction displayed no statistically significant differences between the groups. Follow-up duration was comparable, with 29.1 ± 15 months for the ECVS group and 31.9 ± 20 months for the NoECVS group (p = .24). Notably, syncope recurrence was significantly lower in the ECVS group (two cases vs. four cases, Log Rank p = .04). Moreover, the Hazard ratio revealed a fivefold higher risk of syncope recurrence in the NoECVS group. CONCLUSION: This study demonstrates that concluding CNA with denervation confirmation via ECVS yields a higher success rate and a substantially reduced risk of syncope recurrence compared to procedures without ECVS confirmation.

Treatment of Symptomatic Functional Atrioventricular Block by Cardioneuroablation as an Alternative to Pacemaker Implantation.

A woman with recurrent presyncope caused by a functional atrioventricular (AV) block after meals, with limiting symptoms, underwent cardioneuroablation and AV node vagal denervation without pacemaker implantation. Normal AV conduction was recovered with complete abolishment of symptoms. (Level of Difficulty: Advanced.).

Treatment of symptomatic functional atrioventricular block by cardioneuroablation as an alternative to pacemaker implantation

ABSTRACT: A woman with recurrent presyncope caused by a functional atrioventricular (AV) block after meals, with limiting symptoms, underwent cardioneuroablation and AV node vagal denervation without pacemaker implantation. Normal AV conduction was recovered with complete abolishment of symptoms.

Long-Term Evaluation of the Vagal Denervation by Cardioneuroablation using Holter and Heart Rate Variability

ABSTRACT: Several disorders present reflex or persistent increase in vagal tone that may cause refractory symptoms even in a normal heart patient. Cardioneuroablation (CNA), the vagal denervation by RF ablation of the neuromyocardial interface, was developed to treat these conditions without pacemaker implantation. A theoretical limitation could be the reinnervation, that naturally grows in the first year, that could recover the vagal hyperactivity. This study aims to verify the vagal denervation degree in the chronic phase after CNA. Additionally, it intends to investigate the arrhythmias behavior after CNA. METHODS - prospective longitudinal study with intra-patient comparison of 83 very symptomatic cases without significant cardiopathy, submitted to CNA, 49(59%) male, 47.3±17 years-old, having vagal paroxysmal atrial fibrillation 58(70%) or neurocardiogenic syncope 25(30%), NYHA Class < II and absence of significant comorbidities. CNA was performed in both atria by interatrial septum puncture, with irrigated conventional catheter and electroanatomic reconstruction. Ablation targeted the neuromiocardial interface by fragmentation mapping (AFNests) using the Velocity Fractionation software, conventional recording and anatomical localization of the ganglionated plexi. There were compared the time and frequency domain of the heart rate variability (HRV) and arrhythmias in 24h Holter pre-, 1-year-post- and 2-year-postCNA. Clinical outpatient follow-up and serial Holter showed 80% asymptomatic cases at 40 months. RESULTS - Time and frequency domain HRV demonstrated significant decrease in all autonomic parameters, showing an important parasympathetic and sympathetic activity reduction at 2 yearspost-CNA (p0.05) suggesting that the reinnervation has halted. There was also an important reduction in all brady- and tachyarrhythmias pre- vs. post-CNA, (p<0.01). CONCLUSIONS ­ There is an important and significant vagal and sympathetic denervation after 2 years of CAN with a significant reduction in brady and tachyarrhythmia in the whole group. There were no complications.

Long-Term Evaluation of the Vagal Denervation by Cardioneuroablation Using Holter and Heart Rate Variability.

BACKGROUND: Several disorders present reflex or persistent increase in vagal tone that may cause refractory symptoms even in a normal heart patient. Cardioneuroablation, the vagal denervation by radiofrequency ablation of the neuromyocardial interface, was developed to treat these conditions without pacemaker implantation. A theoretical limitation could be the reinnervation, that naturally grows in the first year, that could recover the vagal hyperactivity. This study aims to verify the vagal denervation degree in the chronic phase after cardioneuroablation. Additionally, it intends to investigate the arrhythmias behavior after cardioneuroablation. METHODS: Prospective longitudinal study with intrapatient comparison of 83 very symptomatic cases without significant cardiopathy, submitted to cardioneuroablation, 49 (59%) male, 47.3±17 years old, having vagal paroxysmal atrial fibrillation 58 (70%) or neurocardiogenic syncope 25 (30%), New York Heart Association class0.05) suggesting that the reinnervation has halted. There was also an important reduction in all bradyarrhythmias and tachyarrhythmias pre-cardioneuroablation versus post-cardioneuroablation (P<0.01). CONCLUSIONS: There is an important and significant vagal and sympathetic denervation after 2 years of cardioneuroablation with a significant reduction in bradyarrhythmia and tachyarrhythmia in the whole group. There were no complications.

Ablation of "Background Tachycardia" in Long Standing Atrial Fibrillation: Improving the Outcomes by Unmasking a Residual Atrial Fibrillation Perpetuator.

BACKGROUND: Catheter ablation of long-standing persistent AF (LSAF) remains challenging. Since AF-Nest (AFN) description, we have observed that a stable, protected, fast source firing, namely "Background Tachycardia"(BT), could be hidden beneath the chaotic AF. Following pulmonary vein isolation (PVI)+AFN ablation one or more BT may arise or be induced in 30-40% of patients, which could be the culprit forAF maintenance and ablation recurrences. METHODS AND RESULTS: We studied 114 patients, from 322 sequential LSAF regular ablations, having spontaneous or induced residual BT after EGM-guided PVI+AFN ablation of LSAF; 55.6±11y/o, 97males (85.1%), EF=65.5±8%, LA=42.8±6.7mm. Macroreentrant tachycardias were excluded. Pre-ablationAF 12-leads ECG Digital processing(DP) and spectral analysis(SA) was performed searching for BT before AF ablation and its correlation with BT during ablation.After PVI, 38.1±9 AFN sites/patient and 135 sustained BTs (1-3, 1.2±0.5/patient) were ablated. BT cycle length(CL) was 246.3±37.3ms. In 79 patients presenting suitable DP for SA, the BT-CL was 241.6±34.3ms with intra procedure BT-CL correlation r=0.83/p<0.01. Following BT ablation, AF could not be induced. During FU of 13→60 months(22.8±12m), AF freedom for BT RF(+) vs. BT RF(-) groups were 77.9% vs. 56.4% (p=0.009), respectively. There was no significant complication. CONCLUSION: BT ablation following PVI and AFN ablation improved long-term outcomes ofLSAF ablation. BT is likely due to sustained microreentry, protected during AF by entry block. BT can be suspected by spectral analysis of the pre-ablation ECG and is likely one important AF perpetuator by causing electrical resonance of the AFN. This ablation strategy warrants randomized, multicenter investigation.

Simplified Method for Vagal Effect Evaluation in Cardiac Ablation and Electrophysiological Procedures.

OBJECTIVES: The aim of this study is to show a simplified reversible approach to investigate and confirm vagal denervation at any time during the ablation procedure without autonomic residual effect. BACKGROUND: Parasympathetic denervation has been increasingly applied in ablation procedures such as in vagal-related atrial fibrillation and cardioneuroablation. This method proposes an easy way to study the vagal effect and to confirm its elimination following parasympathetic denervation through vagal stimulation (VS) by an electrophysiological catheter placed in the internal jugular vein. METHODS: A prospective controlled study including 64 patients without significant cardiopathy (48 male [75.0%], age 46.4 ± 16.4 years) who had a well-defined RF ablation indication for symptomatic arrhythmias, comprising a "denervation group" (DG), with indication for ablation with parasympathetic denervation (vagal-related atrial fibrillation or severe cardioinhibitory syncope) and a "control group" (CG), with ablation indication without parasympathetic denervation (accessory pathway or ventricular arrhythmia). By using a neurostimulator, both groups underwent non simultaneous bilateral VS (8 to 12 s, frequency: 30 Hz, pulse width: 50 µs, amplitude: 0.5 to 1 V/kg up to 70 V) through the internal jugular vein pre- and post-ablation. RESULTS: Significant cardioinhibition was achieved pre-ablation in all cases (pause of 11.5 ± 1.9 s in DG vs. 11.4 ± 2.1 s in CG; p = 0.79). Eight patients (12.5%) presented catheter progression difficulty in 1 jugular vein (2 right, 6 left); however, the contralateral VS was adequate for cardioinhibition. After ablation, the cardioinhibition was reproduced only in CG (pause of 11.2 ± 2.2 s) as in DG it was entirely eliminated. There was no significant difference between pre- and post-ablation cardioinhibition in CG (p = 0.84). There was no complication (follow-up 8.8 ± 5 months). CONCLUSIONS: The vagal stimulation was feasible, easy, and reliable, and showed no complications. It may be repeated during the procedure to control the denervation degree without residual effect. It could be a suitable tool for vagal denervation confirmation or autonomic tests during electrophysiological studies. Ablation without parasympathetic denervation did not change the vagal response.

Herencia autosómica recesiva en paciente no sindrómico con múltiples dientes supernumerarios / Autosomal recessive inheritance in a non-syndromic patient with multiple supernumerary teeth

La hiperdoncia es una condición caracterizada por la presencia de un número de dientes superior al normal en el arco dentario. Su etiología es incierta, aunque factores genéticos y ambientales así como varias teorías han sido propuestas para explicarlo. Describir las características clínicas y radiográficas presentes en un paciente no sindrómico con múltiples supernumerarios, heredados de manera autosómica recesiva. Se presenta el caso de un hombre de 27 años de edad que acudió a consulta para evaluación odontológica. Al examen físico y extrabucal no reveló deformidades, retardo mental ni presencia de ningún síndrome. Al examen intrabucal se evidenció la presencia de irritantes locales y maloclusión dentaria, ocasionada por el aumento del número dientes en los arcos dentarios. Radiográficamente se observaron múltiples imágenes radiopacas compatibles con 9 unidades dentarias incluidas y 2 erupcionadas. Los exámenes de laboratorio no revelaron alteraciones ni relación con algún síndrome. Se solicitaron radiografías panorámicas a los padres, hermanos e hija del paciente, para descartar la presencia de dientes supernumerarios, encontrándose 9 dientes supernumerarios incluidos en un hermano varón, determinándose la trasmisión del rasgo de manera autosómica recesiva. El hallazgo de la trasmisión de manera autosómica recesiva de múltiples supernumerarios en un paciente no sindrómico encontrado en este caso, no es común, lo cual indica que el examen clínico y estudio de cada paciente debe ser llevado a cabo de manera exhaustiva, para determinar este tipo de trastorno o cualquier otro sin evidencias o manifestaciones clínicas.

Hyperdontia is a condition characterized by the presence of a higher number of teeth than normal in the dental arch. Even though genetic and environmental factors as well as a series of theories have been proposed to explain hyperdontia, its etiology is uncertain. To describe clinical and radiographical characteristics found in a non-syndromic patient with multiple supernumerary teeth by autosomal recessive inheritance. A 27-year-old male referred for dental assessment. Physical and extraoral examinations did not reveal deformities, mental retardation or the presence of syndromes. Intraoral examination evidenced the presence of local irritants and dental malocclusion produced by the increased number of teeth in both dental arches. Radiographs revealed multiple radiopaque images compatible with 9 unerupted and 2 erupted teeth. Laboratory tests did not show alterations or a connection to any syndromes. Panoramic radiographs were requested from parents, siblings and daughter of the patient to rule out the presence of supernumerary teeth. Nine supernumerary unerupted teeth were found in one brother, which determined the transmission of characteristics by autosomal recessive inheritance. The incidental finding of the autosomal recessive transmission of multiple supernumerary teeth in a non-syndromic patient observed in this case is not a common result, indicating that clinical examinations and the study of each patient must be carried out thoroughly in order to determine this or any other type of disorders without evidence or clinical manifestations.

Effect of physical training on lipids, lipoproteins, apolipoproteins, lipases, and endogenous sex hormones in men with premature myocardial infarction.

In 17 men, aged 27 to 54 years, with myocardial infarction 2 to 10 months before the current exercise study, we aimed to determine whether 3 months of exercise training, at a level designed to elevate high-density lipoprotein cholesterol (HDLC), would be associated with changes in endogenous sex steroid hormones and postheparin lipoprotein and hepatic lipases, and whether the changes in sex hormones, lipids, lipoproteins, apolipoproteins, and physical activity were interrelated. Supervised bicycle ergometry, 30 minutes, 3 days per week, eliciting 75% of maximum heart rate, produced a significant training effect, with a 26% increase in the duration of the exercise test at a standardized, submaximal workload (P less than or equal to .001), and a reduction in heart rate measured at a standardized submaximal workload, P = .08. After 3 months' training, mean HDLC increased 23% (30 to 37 mg/dL), P less than or equal to .001, mean apo A2 increased 19% (43 to 51 mg/dL), P less than or equal to .001, and the ratio of total cholesterol (TC) to HDLC decreased 26% (P less than or equal to .01), while estradiol (E2) levels decreased 45% (50.1 to 27.8 pg/mL), P less than or equal to .0001. After 1 and 2 months' exercise, TC (12% [P less than or equal to .001], 11% [P less than or equal to .01]), and low-density lipoprotein cholesterol (LDLC) (13% [P less than or equal to .01], 12% [P less than or equal to .01]) were reduced. Hepatic lipase decreased 16% (P less than or equal to .01) and 16% (P less than or equal to .05) after 1 and 3 months' exercise. There were no significant changes in apo A1, lipoprotein lipase, testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), or weight. By stepwise regression analysis, after 3 months' training, 66% (P = .0025) of the variance for the increase in HDLC from baseline to day 90 was accounted for independently by a decrease in triglyceride (F = 13.2, P = .003), by reduced heart rate on a fixed submaximal load (F = 12.7, P = .0035), and by a decrease in hepatic lipase (F = 5.5, P = .036). A modest, achievable exercise program can have significant cardiovascular benefit for men after myocardial infarction by ameliorating their hyperestrogenemia, reducing TC and LDLC, improving the TC to HDLC ratio, and elevating HDLC and apo A2. The increment in HDLC was related independently to improved capacity to sustain submaximal exercise and to exercise-induced reductions in triglyceride and postheparin hepatic lipase.

Sex hormones, lipids, lipoprotein cholesterols, and apolipoproteins in normal and obese subjects: atherogenic relationships.

Our aim in the current study of 20 normal controls, 28 overweight, and 26 severely overweight (obese) subjects was to assess interrelationships of obesity, endogenous estradiol (E2) and testosterone (T), and the E2/T ratio with major independent explanatory variables for coronary heart disease (CHD), including lipids, lipoproteins, and apolipoproteins. Most of the lipid and lipoprotein variables (total, high-, low-, and very-low-density lipoprotein cholesterols) as well as apolipoproteins A1, A2, and B did not vary significantly with the presence of obesity. With increasing relative ponderosity, there were, however, increasing levels of total triglycerides and VLDL triglyceride. Levels of FSH, LH, prolactin, and testosterone did not differ significantly with obesity. The obese subjects had the highest E2 and E2/T levels; overweight subjects had intermediate levels which were also significantly higher than in the controls. Using multiple regression analyses, in obese subjects increasing T was associated with increasing apo B, and increasing E2 was correlated with decreasing apo A1. Opposite relationships were found in the normal controls where increasing T and increasing Quetelet indices were associated with diminished apo B and increasing E2 was associated with increasing A1. Obesity's association with increased CHD risk may be mediated through increasing E2 and apo B and reducing apo A1. Since obese subjects have higher E2 levels and often have lower T, they are likely to have a pattern of endogenous sex hormones (higher E2, lower T, higher E2/T ratios) similar to those observed in young men with premature myocardial infarction.

Estradiol, testosterone, apolipoproteins, lipoprotein cholesterol, and lipolytic enzymes in men with premature myocardial infarction and angiographically assessed coronary occlusion.

A series of thirty-three Venezuelan men with premature myocardial infarction (mean age (M +/- SEM) 45 +/- 1.5 yrs) and with greater than 50% occlusion of at least 2 coronary arteries, and 19 weight matched control men (age 44 +/- 2 yrs) with normal coronary arteries on coronary angiography were studied. The percentages of significantly abnormal (greater than +/- 2 S.D. of controls) serum or plasma concentrations of various measurements (in decreasing order) were: estradiol (33%), total apolipoprotein (apo)B (24%), estradiol/testosterone ratio (21%), low density lipoprotein (LDL) apo B (19%), apo AI (17%), apo AI/total plasma apo B ratio (17%), total cholesterol (17%), and LDL-cholesterol (LDL-C) (11%). In addition, a multivariate discriminant function analysis showed that only estradiol, apo AI, LDL-C, estradiol/testosterone ratio and total cholesterol were statistically significant independent markers of myocardial infarction with occlusive coronary disease in these patients. Both serum estradiol and estradiol/testosterone ratio correlated positively with plasma apo B and LDL apo B, and inversely with apo AI; serum testosterone correlated inversely with plasma apo B (p less than 0.05). The data suggest that circulating sex hormones (estrogens, testosterone) are not only independent markers of coronary disease but may be pathogenetically linked to apo B and apo AI metabolism.

Plasma lipids and lipoprotein lipase activating property in women on three different combinations of estrogens and progestins.

PIP: 71 healthy women aged 20-35, nonobese and who had received 1 of 3 different combinations of ethinyl estradiol and D-norgestrel for more than 6 months were studied to observe the influence of the drugs on the plasma lipids and lipoprotein lipase. The 3 combinations were: 1) 30 mcg ethinyl estradiol and 250 mcg D-norgestrel; 2) 50 mcg ethinyl estradiol and 250 mcg D-norgestrel; and 3) 50 mcg ethinyl estradiol and 500 mcg D-norgestrel. Results were compared to data from a similar study on 24 normal females who were not on OC. Patients in groups 1 and 2 had significantly elevated total plasma cholesterol and LDL-C (high density lipoprotein cholesterol) as compared to the controls. In group 2 total plasma LPL (lipoprotein lipase) activator property was significantly lower than in controls, but total plasma triglycerides level was significantly higher. Patients in group 3 has significantly lower total plasma triglycerides but high LPL activating property than women in group 2. These results show that OC may affect plasma triglycerides through the influence of apolipoproteins that modulate lipoprotein lipase activity.^ieng

Lipids and lipoproteins in 13--18-year-old Venezuelan and American school children. Within- and cross-cultural comparisons.

Plasma lipids, lipoproteins, and anthropometric measurements were assessed in 996 Venezuelan school children (ages 13--18 years) (441 in private, 555 in public schools, Merida, Venezuela) with cross-cultural comparisons to 419 13--18-year-old American school children from suburban Cincinnati, Ohio. Although there were no systematic differences in plasma cholesterol and triglyceride between public and private Venezuelan school children, low density lipoprotein cholesterol (LDL-C) levels were higher and high density lipoprotein cholesterol (HDL-C) levels lower in public than private school children. Within Venezuelan schools, and between sex, female children had consistently higher total plasma cholesterol, marginally higher HDL-C, and appreciably higher LDL-C than males. There were no consistent cross-sectional changes in lipids and lipoproteins in Venezuelan school children with age. Within sex, cross-cultural comparisons with Cincinnati school children revealed 2 major, consistent differences; Venezuelan children had higher fasting plasma triglyceride and lower HDL-C levels, not attributable to systematic differences in Quetelet index, laboratory methodology, subject selection, or sampling technique. Total plasma cholesterol and HDL-C were similar for Venezuelan and Cincinnati school children. Maintenance of comparable LDL-C but lower HDL-C levels by Venezuelan children into adulthood might, speculatively, be associated with augmented risk for coronary heart disease.

Lipids and lipoproteins in subjects at 1,000 and 3,500 meter altitudes.

To assess the relationship between altitude, atherogenic, and anti-atherogenic lipoprotein cholesterols (low- [C-LDL] and high [C-HDL] density lipoprotein cholesterols, respectively), 136 and 94 Venezuelan Mestizos living at 1,000 and 3,500 in elevation were studied. The two groups did not differ in regard to height, weight, ethnic origin, social or economic status, nutritional patterns, age, or occupation. Both groups had a high level of daily physical exertion, an imperative in their subsistence rural agricultural economy. Due to the mountainous terrain, high altitude residents were thought to have increased levels of physical activity. Males and females at high altitude had significantly lower plasma total cholesterol and C-LDL levels, and slightly lower C-HDL levels than those at low altitudes. It is speculated that reduced coronary heart disease event rates at high altitude might be related to lower levels of the atherogenic lipoprotein cholesterol, C-LDL.