Concomitant Left Atrial Appendage Occlusion and Transcatheter Aortic Valve Replacement Among Patients With Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is common in patients undergoing transcatheter aortic valve replacement (TAVR) and is associated with increased risk of bleeding and stroke. While left atrial appendage occlusion (LAAO) is approved as an alternative to anticoagulants for stroke prevention in patients with AF, placement of these devices in patients with severe aortic stenosis, or when performed at the same time as TAVR, has not been extensively studied. METHODS: WATCH-TAVR (WATCHMAN for Patients with AF Undergoing TAVR) was a multicenter, randomized trial evaluating the safety and effectiveness of concomitant TAVR and LAAO with WATCHMAN in AF patients. Patients were randomized 1:1 to TAVR + LAAO or TAVR + medical therapy. WATCHMAN patients received anticoagulation for 45 days followed by dual antiplatelet therapy until 6 months. Anticoagulation was per treating physician preference for patients randomized to TAVR + medical therapy. The primary noninferiority end point was all-cause mortality, stroke, and major bleeding at 2 years between the 2 strategies. RESULTS: The study enrolled 349 patients (177 TAVR + LAAO and 172 TAVR + medical therapy) between December 2017 and November 2020 at 34 US centers. The mean age of patients was 81 years, and the mean scores for CHA2DS2-VASc and HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol concomitantly) were 4.9 and 3.0, respectively. At baseline, 85.4% of patients were taking anticoagulants and 71.3% patients were on antiplatelet therapy. The cohorts were well-balanced for baseline characteristics. The incremental LAAO procedure time was 38 minutes, and the median contrast volume used for combined procedures was 119 mL versus 70 mL with TAVR alone. At the 24-month follow-up, 82.5% compared with 50.8% of patients were on any antiplatelet therapy, and 13.9% compared with 66.7% of patients were on any anticoagulation therapy in TAVR + LAAO compared with TAVR + medical therapy group, respectively. For the composite primary end point, TAVR + LAAO was noninferior to TAVR + medical therapy (22.7 versus 27.3 events per 100 patient-years for TAVR + LAAO and TAVR + medical therapy, respectively; hazard ratio, 0.86 [95% CI, 0.60-1.22]; Pnoninferiority<0.001). CONCLUSIONS: Concomitant WATCHMAN LAAO and TAVR is noninferior to TAVR with medical therapy in severe aortic stenosis patients with AF. The increased complexity and risks of the combined procedure should be considered when concomitant LAAO is viewed as an alternative to medical therapy for patients with AF undergoing TAVR. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03173534.

The REDUCE HTN: REINFORCE: Randomized, Sham-Controlled Trial of Bipolar Radiofrequency Renal Denervation for the Treatment of Hypertension.

OBJECTIVES: The aim of this study was to investigate bipolar radiofrequency renal denervation in patients with hypertension not receiving medications at baseline. BACKGROUND: A blood pressure-reducing effect of renal denervation has been difficult to isolate in clinical investigations. METHODS: REDUCE HTN: REINFORCE (Renal Denervation Using the Vessix Renal Denervation System for the Treatment of Hypertension) was a randomized, sham-controlled multicenter trial. Patients with office systolic blood pressure (SBP) of 150 to 180 mm Hg and average 24-h ambulatory SBP of 135 to 170 mm Hg after medication washout underwent bipolar radiofrequency renal denervation or a sham procedure. The planned outcome was 8-week change in 24-h ambulatory SBP. Enrollment was terminated for apparent futility before a sufficient sample for powered efficacy comparisons was enrolled. Safety assessments included all-cause death, renal failure, severe hypotension or syncope, hypertensive crisis, and renal artery stenosis. RESULTS: Baseline 24-h blood pressure was 148.3 ± 10.9/85.7 ± 9.1 mm Hg for the denervation group (n = 34, mean age 58.5 ± 10.1 years, 47% women) and 149.1 ± 7.2/86.4 ± 9.8 mm Hg for the control group (n = 17, mean age 58.2 ± 9.8 years, 24% women). At 8 weeks, mean 24-h SBP reductions for the renal denervation and control groups were -5.3 mm Hg (95% confidence interval [CI]: -8.8 to -1.8 mm Hg) and -8.5 mm Hg (95% CI: -13.3 to -3.8 mm Hg), respectively (difference 3.3 mm Hg; 95% CI: -2.8 to 9.3 mm Hg; p = 0.30). Antihypertensive medications could then be added. By 6 months, decreases in SBP were greater for the denervation group, yielding between-group differences of -7.2 mm Hg (95% CI: -15.2 to 0.8 mm Hg; p = 0.08), -9.7 mm Hg (95% CI: -17.7 to -1.7 mm Hg; p = 0.02), and -11.4 mm Hg (95% CI: -19.2 to -3.7 mm Hg; p < 0.01) for 24-h, daytime ambulatory, and office measurements, respectively. Through 12 months, 1 patient (renal denervation group) had a hypertensive urgency requiring immediate management, and 1 experienced progression of renal artery stenosis. CONCLUSIONS: Future studies of radiofrequency renal denervation must anticipate delayed treatment effects. (Renal Denervation Using the Vessix Renal Denervation System for the Treatment of Hypertension [REDUCE HTN: REINFORCE]; NCT02392351).

The use of ranolazine to facilitate electrical cardioversion in cardioversion-resistant patients: a case series.

BACKGROUND: Occasionally atrial fibrillation (AF) is resistant to electrical cardioversion (EC). Ranolazine (RZ) is an antianginal agent, which inhibits abnormal late Na(+) channel currents in cardiomyocytes and decreases Na(+) /Ca(++) overload. RZ is a potent inhibitor of after-depolarizations and triggered activity and prolongs atrial refractory periods. We postulated RZ could facilitate EC in patients resistant to EC. METHODS: Over a 3-year period, we identified 25 EC-resistant patients who had been administered oral RZ shortly after failing attempted EC. The anterior-posterior cardioversion approach was used and each patient had failed to be restored to sinus rhythm despite using up to the maximum output of a biphasic cardioversion device. Repeat EC was performed 3.5-4 hours after administration of 2 g of oral RZ using the same device, sedation, and lead placement. RESULTS: Sinus rhythm was successfully restored in 19 (76%) of 25 EC-resistant patients. Three patients spontaneously converted before the second attempt at EC within 4 hours of the RZ dose. Of the 22 patients undergoing another attempt at EC, 16 were successfully converted to sinus rhythm. Five of the six patients who were refractory to repeat EC despite RZ had AF of unknown duration and each is now in permanent AF. No adverse effects were noted. CONCLUSION: RZ shows promise as a safe and convenient agent to facilitate EC in EC-resistant patients. It appears to be most effective in patients whose AF duration is known to be less than 3 months.

Electrophysiological Changes of the Atrium in Patients with Lone Paroxysmal Atrial Fibrillation.

BACKGROUND: The "Pill-in-Pocket" (PIP) is an approach to atrial fibrillation (AF) where oral anti-arrhythmics at 75% to 100% of the normal daily dose, given as a single dose, is used to convert recent-onset AF. Pro-arrhythmic risk has limited this approach to patients without structural heart disease (SHD). Ranolazine is an anti-anginal agent, which inhibits the abnormal late Na+ channel current resulting in decreased Na+/Ca++ overload. This inhibits after-depolarizations and reduces pulmonary vein firing, which have been implicated in the initiation and propagation of AF. Ranolazine increases atrial refractoriness and has no known pro-arrhythmic affects. Ranolazine is routinely given to patients with SHD. The ability of Ranolazine to terminate AF in man has not been described but if useful could be a safer PIP agent with application in the presence or absence of SHD. We describe our experience using oral Ranolazine to convert new or recurrent AF. METHOD: 2000 mg of ranolazine was administered to 35 patients with new (16 patients) or recurrent (19 patients) AF of at least 3 but not greater than 48 hours duration. Clinical features, echocardiographic data, and SHD were noted. Success was defined as restoring sinus rhythm within 6 hours of Ranolazine. RESULTS: All but 4 patients had some form of SHD. Twenty-five patients were in the hospital, 5 were in the office, and 5 were at home at the time Ranolazine was administered. Twenty-five of 35 patients converted to sinus rhythm. No pro-arrhythmic effects, hemodynamic instability, adverse rate effects, or perceived intolerance were noted. The 71% conversion rate was comparable to other reported PIP protocols and much higher than reported placebo conversion rates. CONCLUSIONS: High dose oral Ranolazine shows utility as a possible safe agent to convert new or recurrent AF. Larger placebo-controlled studies would appear to be warranted.

The use of oral ranolazine to convert new or paroxysmal atrial fibrillation: a review of experience with implications for possible "pill in the pocket" approach to atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia requiring treatment. High dose oral anti-arrhythmics may cardiovert some paroxysmal AF. This "pill in pocket" approach has allowed patients to treat themselves on an as needed basis. Pro-arrhythmic concerns have limited the usefulness of this approach to patients without structural heart disease. Ranolazine is an anti-anginal agent, which inhibits abnormal late Na+ channel currents in cardiomyocytes and decreases sodium-calcium overload. Ranolazine is a potent inhibitor of after-depolarizations, which have been implicated in the initiation and propagation of AF. Because ranolazine has no known pro-arrhythmic effects, it could be useful as a safe "pill in the pocket" agent if it were effective in converting AF. We describe our experience using oral ranolazine to convert new or paroxysmal AF. METHODS: 2000 mg of ranolazine were administered to 18 patients with new (11 patients) or paroxysmal (7 patients) AF of at least 3, but not greater than 48 hours duration. Most patients (14) were in the hospital at the time ranolazine was administered. Age, sex, echocardiographic data, associated health conditions and structural heart disease were recorded. Successful conversion was defined as restoring sinus rhythm within 6 hours of ranolazine administration. RESULTS: All but 1 patient had some form of structural heart disease and all but 2 patients had left atrial enlargement. Thirteen of 18 patients converted to sinus rhythm. No pro-arrhythmic effects, hemodynamic instability, adverse rate effects, or perceived intolerance (other than constipation) were noted. The 72% conversion rate was comparable to other reported "pill in the pocket" protocols. CONCLUSIONS: High dose oral ranolazine shows utility as a possible safe agent to convert new or paroxysmal AF. Lack of blinded controls and small numbers limits the power of this observation.

Effects of glucose-insulin-potassium solution on myocardial salvage and left ventricular function after primary angioplasty.

OBJECTIVE: To evaluate the effects of glucose-insulin-potassium (GIK) therapy on infarct size and left ventricular function when used as an adjuvant therapy to primary angioplasty. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Cardiac intensive care unit at a university hospital. PATIENTS: Thirty-seven patients with acute myocardial infarction for whom primary angioplasty was indicated. INTERVENTIONS: Eligible patients were randomized by a blinded pharmacist to GIK solution (30% glucose in water with insulin 50 U/L, and KCl 40 mM/L) vs. placebo at 1.5 mL/kg/hr for 24 hrs. MEASUREMENTS AND MAIN RESULTS: Tc 99m sestamibi myocardial scintigraphy was performed at admission and at 3 months. Primary end points were the changes in left ventricular ejection fraction (LVEF) and the size of salvaged myocardium. Baseline clinical characteristics were similar in both groups. At the 3-month follow-up, a significant overall decrease in infarct size (37 +/- 16% vs. 12 +/- 10%, p <.005) and an increase in LVEF (34 +/- 13% vs. 49 +/- 9%, p =.005) were observed. Patients randomized to GIK solution experienced a significant increase in their LVEF at 3 months (39 +/- 12 to 51 +/- 13, p =.002). Patients who received placebo had no significant differences between baseline and 3-month measurements (44 +/- 13 vs. 49 +/- 14, p = NS). There was a trend toward an increase in myocardial salvage in the GIK group, which did not reach statistical significance. When patients from both groups were compared directly, differences in LVEF improvement were no longer significant. CONCLUSIONS: GIK solution did not improve LVEF or decrease the infarct size among patients undergoing primary angioplasty.

Función ventricular segmentaria en valvulopatías / Segmental ventricular function in patients with valvular heart disease

La frecuencia con que existen alteraciones segmentarias de la función ventricular (FVS) en las valvulopatías y su relación con la función sistólica global, son poco conocidas. Con el fin de aclarar este punto estudiamos 110 pacientes con patología valvular pura (22 estenosis aórtica, 24 estenosis mitral, 34 insuf. aórtica y 30 insuficiencia mitral) que tenían ventriculografía de contraste de buena calidad técnica, comparándolos con 19 normales (estudio invasivo por dolor torácico que resultó normal). Todos los pacientes sobre 45 años tenían coronariografía normal. Estudiamos el % de cambio de área segmentaria (% AS) en la región anterobasal (AB), anterolateral (AL), apical (AP), inferior (IN) e inferobasal (IB). Usamos la relación entre % AS y el % de cambio de área global. Definimos como alteración segmentaria a un índice menor a dos desviaciones estándar del promedio de los normales, para cada segmento. De los 550 segmentos analizados, existieron 14 anormales en AB, 37 en AL, 23 en AP, 11 en IN y 8 en IB (p<0.001). En conclusión: las alteraciones de la FVS son frecuentes en las valvulopatías, tienen mayor incidencia en los segmentos AL y AP y coexisten más frecuentemente con disfunción global del ventrículo izquierdo

Predicción del diámetro del tronco de la coronaria izquierda a partir del diámetro de sus ramas / Diameter of left main coronary artery by estimating the diameter of its branches

Una de las limitaciones del análisis angiográfico de las coronarias es la determinación de la magnitud de las lesiones del tronco común. Una situación especialmente compleja se presenta frente a la coexistencia de tronco corto y una lesión difusa de este mismo vaso. En esta situación es muy difícil definir el grado de estenosis, en ausencia de un lumen sano con el cual comparar. El propósito de este trabajo fue validar angiográficamente formas que permitieran predecir el diámetro del tronco común a partir de sus ramas. Con este fin elaboramos una fórmula partiendo de la hipótesis de que el área del tronco es igual a la suma del área de la descendente anterior (DA) y de la circunfleja (C), corregida por un factor de progresión distal del área. La expresión matemática de esta suposición, despejando el diámetro calculado del tronco (DTc), es la siguiente: DTc=2*rad.DA+rad.C+FC.(FC=factor de progresión de área). Comparamos esta fórmula con otra derivada del postulado de que el cubo del diámetro de un vaso es igual a la suma del cubo de sus ramas (DTc=d3 DA + d3 Cx). Evaluamos estas fórmulas midiendo los diámetros de estos vasos en 27 coronariografías definidas previamente como libres de enfermedad coronaria. Se efectuó análisis de regresión y correlación entre el diámetro calculado del tronco (DTc) y el medido según la fórmula (DTm). La ecuación de regresión fue: DTc=1.04 DTm+0.01 mm; Error St Estim.= 0.81; r= 0.92; p<0.0001, para la fórmula basada en la igualdad de las áreas de sección, siendo el FC despreciable por su pequeña magnitud. Para la Fórmula basada en la igualdad de los volúmenes la ecuación de regresión fue:DTc=0.92 DTm+0.03 mm; Error St Estim. +0.73;r= 0.92; p<0.0001. En conclusión, hemos validado fórmulas capaces de predecir el diámetro del tronco a partir de los diámetros de DA y C., siendo de esperar aproximadamente un 10% de variación en la predicción, probablemente por error de medición

Estructura de morbilidad de adolescentes consultantes en el sector oriente de Santiago / Structure of morbidity of adolescent out patients in the eastern sector of Santiago

El conocimiento de las necesidades de salud del adolescente es primordial para organizar la atención y planificar la asignación de recursos. La recolección de esta información se hace difícil dado que la atención de este grupo etario está hoy fragmentada entre los programas infantil y del adulto, por lo que los estudios tienen gran variabilidad según cual sea la fuente de información utilizada. En el Area Oriente de Santiago se han organizado diferentes modalidades de atención de salud del adolescente en el nivel primario: por ejemplo, en el consultorio La Faena existe una unidad de adolescencia que atiende adolescentes de ambos sexos entre los 10 y 19 años a cargo de un especialista y en el Centro de Adolescencia de Las Condes se realiza una atención integral por un equipo multidisciplinario. En este trabajo se describen las características sociodemográficas de esta población adolescente, su morbilidad, hábitos de vida y de consumo de sustancias químicas, comparando los hallazgos en ambos tipos de establecimientos. Los resultados muestran adolescentes de edad promedio de 15,75 años y escolaridad de 8- Año Básico, insertos en familias numerosas (5,2 personas por familia) que en proporción de 75% perciben problemas familiares. El principal grupo de motivos de consulta corresponden en descendente al grupo de mentales, gíneco-obstétrico, endocrinos, nutrición. El Centro de Las Condes concentra mayor consulta de patología mental que el de La Faena. El consumo de sustancias es semejante al de los estudios de población infantil: 4 y 13% de consumo frecuente de alcohol y 5 y 9% de uso frecuente de marihuana. En la discusión se comenta la utilidad de la recolección sistemática de información, y también como la exploración conjunta de los problemas biológicos con los problemas psicosociales permiten reconocer las verdaderas necesidades de salud de este grupo etario

Caracteristicas de los consultantes en el centro del adolescente "Las Condes" / Characteristics of patients in the Adolescent Center \"Las Condes\"

Se trata de la única publicación hecha en Chile que describe las características de los consultantes de un Centro de Atención Integral con problemas de salud propios del adolescente, en una Comuna de Santiago. Estas características según diagnóstico, edad y sexo, son relacionadas con los problemas familiares y escolares que denunciaron los consultantes, con la evolución clínica de los casos y con la frecuencia del consumo de sustancias psicotrópicas. 250 adolescentes ingresados en los primeros 10 meses de trabajo fueron diagnosticados como desadaptación el 59,8% y como ansiedad y angustia el 10,8%. 45 jóvenes, 18%, consumían excesivamente bebidas alcohólicas y drogas. 21 casos de consumo de marihuana y otras drogas eran en su mayoría consumo social u ocasional. Fuera de un 6,4% de casos de depresión los demás desórdenes mentales fueron escasos. Los cuadros más graves: retardo mental, esquizofrenia y psicopatías, concentraron más varones que niñas; la mayoría con graves problemas familiares. Los casos de agresividad e hiperkinesia se dieron en varones. Los consultantes denunciaron más problemas graves familiares que escolares, los esquizofrénicos y psicópatas en el hogar y los hiperkinéticos en el colegio. La ecuacón sano-mejoró, vesus desertó indica un buen rendimiento terapéutico