Predictors and outcomes of pacemaker implantation in patients with cardiac amyloidosis.

OBJECTIVE: We sought to investigate prevalence, incidence and prognostic implications of permanent pacemaker (PPM) implantation in patients with cardiac amyloidosis (CA), thereby identifying the predictors of time to PPM implantation. METHODS: Seven hundred eighty-seven patients with CA (602 men, median age 74 years, 571 transthyretin amyloidosis (ATTR), 216 light-chain amyloidosis (AL)) evaluated at two European referral centres were retrospectively included. Clinical, laboratory and instrumental data were analysed. The associations between PPM implantation and mortality, heart failure (HF) or a composite endpoint of mortality, cardiac transplantation and HF were analysed. RESULTS: 81 (10.3%) patients had a PPM before initial evaluation. Over a median follow-up time of 21.7 months (IQR 9.6-45.2), 81 (10.3%) additional patients (18 with AL (22.2%) and 63 with ATTR (77.8%)) underwent PPM implantation with a median time to implantation of 15.6 months (IQR 4.2-40), complete atrioventricular block was the most common indication (49.4%). Independent predictors of PPM implantation were QRS duration (HR 1.03, 95% CI 1.02 to 1.03, p<0.001) and interventricular septum (IVS) thickness (HR 1.1, 95% CI 1.03 to 1.17, p=0.003). The model to estimate the probability of PPM at 12 months and containing both factors showed a C-statistic of 0.71 and a calibration of slope of 0.98. CONCLUSIONS: Conduction system disease requiring PPM is a common complication in CA that affects up to 20.6% of patients. QRS duration and IVS thickness are independently associated with PPM implantation. A PPM implantation at 12 months model was devised and validated to identify patients with CA at higher risk of requiring a PPM and who require closer follow-up.

Ivabradine for controlling heart rate in permanent atrial fibrillation: A translational clinical trial.

BACKGROUND: Pharmacological options for rate control in atrial fibrillation are scarce. Ivabradine was postulated to reduce the ventricular rate in this setting. OBJECTIVES: The objectives of this study were to evaluate the mechanism of inhibition of atrioventricular conduction produced by ivabradine and to determine its efficacy and safety in atrial fibrillation. METHODS: The effects of ivabradine on atrioventricular node and ventricular cells were studied by in vitro whole-cell patch-clamp experiments and mathematical simulation of human action potentials. In parallel, a multicenter, randomized, open-label, phase III clinical trial compared ivabradine with digoxin for uncontrolled permanent atrial fibrillation despite ß-blocker or calcium channel blocker treatment. RESULTS: Ivabradine 1 µM inhibited "funny" current and rapidly activating delayed rectifier potassium channel current by 28.9% and 22.8%, respectively (P < .05). The sodium channel current and L-type calcium channel current were reduced only at 10 µM. Ivabradine slowed the firing frequency of a modeled human atrioventricular node action potential by 10.6% and induced a minimal prolongation of ventricular action potential. Thirty-five (51.5%) patients were randomized to ivabradine and 33 (49.5%) to digoxin. The mean daytime heart rate decreased by 11.6 beats/min (-11.5%) in the ivabradine arm (P = .02) vs 19.6 (-20.6%) in the digoxin arm (P < .001), although the noninferiority margin of efficacy was not met (Z = -1.95; P = .97). The primary safety end point occurred in 3 patients (8.6%) on ivabradine and in 8 (24.2%) on digoxin (P = .10). CONCLUSION: Ivabradine produced a moderate rate reduction in patients with permanent atrial fibrillation. The inhibition of funny current in the atrioventricular node seems to be the main mechanism responsible for this reduction. Compared with digoxin, ivabradine was less effective, was better tolerated, and had a similar rate of serious adverse events.

Cryoballoon Ablation for Persistent and Paroxysmal Atrial Fibrillation: Procedural Differences and Results from the Spanish Registry (RECABA).

Introduction: Cryoballoon ablation (CBA) has become a standard treatment for paroxysmal atrial fibrillation (PaAF) but limited data is available for outcomes in patients with persistent atrial fibrillation (PeAF). Methods: We analyzed the first 944 patients included in the Spanish Prospective Multi-center Observation Post-market Registry to compare characteristics and outcomes of patients undergoing CBA for PeAF versus PaAF. Results: A total of 944 patients (57.8 ± 10.4 years; 70.1% male) with AF (27.9% persistent) were prospectively included from 25 centers. PeAF patients were more likely to have structural heart disease (67.7 vs. 11.4%; p < 0.001) and left atrium dilation (72.6 vs. 43.3%; p < 0.001). CBA of PeAF was less likely to be performed under general anesthesia (10.7 vs. 22.2%; p < 0.001), with an arterial line (32.2 vs. 44.6%; p < 0.001) and assisted transeptal puncture (11.9 vs. 17.9%; p = 0.025). During an application, PeAF patients had a longer time to −30 °C (35.91 ± 14.20 vs. 34.93 ± 12.87 s; p = 0.021) and a colder balloon nadir temperature during vein isolation (−35.04 ± 9.58 vs. −33.61 ± 10.32 °C; p = 0.004), but received fewer bonus freeze applications (30.7 vs. 41.1%; p < 0.001). There were no differences in acute pulmonary vein isolation and procedure-related complications. Overall, 76.7% of patients were free from AF recurrences at 15-month follow-up (78.9% in PaAF vs. 70.9% in PeAF; p = 0.09). Conclusions: Patients with PeAF have a more diseased substrate, and CBA procedures performed in such patients were more simplified, although longer/colder freeze applications were often applied. The acute efficacy/safety profile of CBA was similar between PaAF and PeAF patients, but long-term results were better in PaAF patients.

Trapped p waves causing loss of physiological left bundle branch pacing.

We present the case of a 75-year-old woman with severe aortic stenosis and moderate left ventricular dysfunction, who underwent elective transcatheter aortic valve replacement. After the procedure, the patient developed a left bundle branch block and a long PR interval. For this reason, a dual chamber pacemaker with pacing in the left bundle branch area was implanted. On device interrogation, we confirmed the presence of functional atrial undersensing causing loss of ventricular electric resynchronization. This case highlights the importance of recognizing this problem and, by means of device reprogramming and pharmacological intervention, suggests a stepwise approach to solve it.

Zfhx3 Transcription Factor Represses the Expression of SCN5A Gene and Decreases Sodium Current Density (INa).

The ZFHX3 and SCN5A genes encode the zinc finger homeobox 3 (Zfhx3) transcription factor (TF) and the human cardiac Na+ channel (Nav1.5), respectively. The effects of Zfhx3 on the expression of the Nav1.5 channel, and in cardiac excitability, are currently unknown. Additionally, we identified three Zfhx3 variants in probands diagnosed with familial atrial fibrillation (p.M1260T) and Brugada Syndrome (p.V949I and p.Q2564R). Here, we analyzed the effects of native (WT) and mutated Zfhx3 on Na+ current (INa) recorded in HL-1 cardiomyocytes. ZFHX3 mRNA can be detected in human atrial and ventricular samples. In HL-1 cardiomyocytes, transfection of Zfhx3 strongly reduced peak INa density, while the silencing of endogenous expression augmented it (from -65.9 ± 8.9 to -104.6 ± 10.8 pA/pF; n ≥ 8, p < 0.05). Zfhx3 significantly reduced the transcriptional activity of human SCN5A, PITX2, TBX5, and NKX25 minimal promoters. Consequently, the mRNA and/or protein expression levels of Nav1.5 and Tbx5 were diminished (n ≥ 6, p < 0.05). Zfhx3 also increased the expression of Nedd4-2 ubiquitin-protein ligase, enhancing Nav1.5 proteasomal degradation. p.V949I, p.M1260T, and p.Q2564R Zfhx3 produced similar effects on INa density and time- and voltage-dependent properties in WT. WT Zfhx3 inhibits INa as a result of a direct repressor effect on the SCN5A promoter, the modulation of Tbx5 increasing on the INa, and the increased expression of Nedd4-2. We propose that this TF participates in the control of cardiac excitability in human adult cardiac tissue.

Factores predictores de aparición de fibrilación auricular en pacientes con miocardiopatía dilatada / Predicting factors of atrial fibrillation in patients with dilated cardiomyopathy

Resumen Introducción El uso de terapia anticoagulante en pacientes con miocardiopatía dilatada es controvertido. El riesgo hemorrágico hace que habitualmente no se use en pacientes en ritmo sinusal. Objetivo Analizar los factores predictores de fibrilación auricular (FA) en pacientes con miocardiopatía dilatada y fracción de eyección del ventrículo izquierdo (FEVI) < 40. Método: Se estudiaron los pacientes incluidos en el registro multicéntrico UMBRELLA a quienes se había implantado un desfibrilador (DAI) bicameral o tricameral y que presentaban miocardiopatía dilatada isquémica o no isquémica y FEVI < 40%. Se definió FA como cualquier episodio > 30 segundos de duración y una frecuencia auricular > 175 latidos por minuto. Resultados Se incluyeron 684 enfermos. La mediana de edad fue de 70 años (rango intercuartílico [RIQ]: 62-77). El 79.1% eran varones. La FEVI fue < 30% en el 76.3%. El 87.3% presentaban insuficiencia cardiaca (ICC) clínica. Se implantó un DAI resincronizador en el 59.5%. El 51.2% tenían bloqueo de rama izquierda del haz de His y el 7.1% de rama derecha (BRDHH). Se documentó FA en el 49% de los enfermos con una mediana de seguimiento de 29.93 meses (RIQ: 14.78-45.63). Las variables que se relacionaron con la aparición de FA fueron la presencia de ICC (hazard ratio [HR]: 2; intervalo de confianza del 95% [IC 95%]: 1.31-3.04; p = 0.001), el BRDHH (HR: 1.48; IC 95%: 1-2-18; p = 0.045), el ictus previo (HR: 2.11; IC 95%: 1.4-3.19; p < 0.001) y la edad > 75 años (HR: 1.21; IC 95%: 1.05-1.40; p = 0.008). Conclusiones La edad > 75 años, el BRDHH, la ICC y el ictus previo predicen la aparición de FA en la población con miocardiopatía dilatada y FEVI < 40%.

Abstract Introduction Anticoagulant treatment in patients with dilated cardiomyopathy and sinus rhythm is controversial due to haemorrhage risk. Objective To analyze the factors predicting atrial fibrillation (AF) in patients with dilated cardiomyopathy and ejection fraction (LVEF) < 40%. Method All patients included in UMBRELLA multicentre registry without AF, who had a dual or three-chamber implantable cardiac defibrillator (ICD), dilated cardiomyopathy and LVEF < 40% were included. AF was defined as any episode > 30 seconds of duration and atrial frequency > 175 bpm. Results 684 patients were included. Median age was 70 years (IQR 62-77); 79.1% were male. LVEF was < 30% in 76.3% of cases; 87.3% presented clinical heart failure (CHF). A CRT-D was implanted in 59.5%; 51.2% of patients presented Left Bundle Branch Block (LBBB) and 7.1% presented Right Bundle Branch Block (RBBB). AF was documented in 49% of patients, with a median follow-up of 29.93 months (IQR: 14.78-45.63). The presence of CHF (HR: 2; 95% CI: 1.31-3.04; p = 0.001), RBBB (HR: 1.48; 95% CI: 1-2-18; p = 0.045), previous stroke (HR: 2.11; 95% CI: 1.4-3.19; p < 0.001) and age > 75 years (HR: 1.21; 95% CI: 1.05-1.40; p = 0.008) were associated with diagnosis of AF. Conclusions Age > 75 years, RBBB, CHF and previous stroke are predictors of AF development in the population with dilated cardiomyopathy and LVEF < 40%.

Primary results of the Spanish Cryoballoon Ablation Registry: acute and long-term outcomes of the RECABA study.

Cryoablation is safe and effective for the treatment of atrial fibrillation (AF) in controlled clinical trials, but contemporary real-world usage and outcomes are limited. The Report of the Spanish Cryoballoon Ablation Registry (RECABA) was designed to evaluate acute and 12-month outcomes of cryoballoon ablation for the treatment of AF in Spain. Patients from 27 Spanish centers were prospectively enrolled. Patients were treated with cryoballoon ablation and managed according to standard of care protocols at each center. The primary endpoint was ≥ 30 s freedom from AF at 12-month after a 3-month blanking period. Secondary endpoints included a description of patient characteristics, cryoablation procedural strategy and safety, and predictors of efficacy. In total, 1742 patients (71.4% PAF, 68.8% male, mean age 58.02 ± 10.40 years, 76.1% overweight or obese, CHA2DS2-VASc index 1.40 ± 1.28) were enrolled. Patients received 7.2 ± 2.67 cryo-applications. PV potentials could be detected in 61% of the PVs during ablation, with a mean time to block of 52.9 ± 37.02 s. Acute PVI was observed in 97% of PVs with 75.8% isolated with the first cryo-application. Mean procedural time was 113 ± 41 min. Acute complications occurred in 4.4% of the cases. With follow-up in 1628 patients, AF-free survival was 78.5% (PAF: 80.6% vs PersAF 73.3%; p < 0.001). Left atrium enlargement, female sex, non-PAF, and early recurrence were independent predictors of AF recurrence (p < 0.05). RECABA provides detailed insight into current dosing practices and demonstrates cryoablation is safe and effective in real-world use.ClinicalTrials.gov number: NCT02785991.

Revascularization of coronary chronic total occlusions in an infarct-related artery and recurrence of ventricular arrhythmias among patients with secondary prevention implantable cardioverter defibrillator.

OBJECTIVES: To evaluate whether the revascularization of a coronary chronic total occlusion in an infarct-related artery (IRACTO) may be associated with lower recurrence of ventricular arrhythmias (VA) among patients with a secondary prevention implantable cardioverter defibrillator (ICD). BACKGROUND: IRACTO is increasingly recognized as an independent predictor of VA. It is unknown whether IRACTO revascularization can reduce the burden of VA. METHODS: Multicenter observational cohort study that included consecutive patients with prior myocardial infarction and secondary prevention ICD. The primary endpoint was any appropriate ICD therapy. RESULTS: Among the 460 patients included, 269 (58%) had at least one IRACTO at the coronary angiogram performed before ICD implantation; of these, 20 (7%) had their IRACTO successfully revascularized (IRACTO-R) afterwards. During a median follow-up of 48 months, 229 patients (49%) had at least one appropriate ICD therapy. Patients with IRACTO not revascularized (IRACTO-NR) had the highest incidence of ICD therapies (65%) while patients with IRACTO-R had the lowest (10%, p < .001). In the entire cohort, IRACTO-NR was an independent predictor of appropriate ICD therapies (HR 2.85, p < .001) and appropriate ICD shocks (HR 2.94, p < .001). Among patients with IRACTO at baseline, IRACTO-R was independently associated with a marked reduction of appropriate ICD therapies (HR 0.12, p = .002) and appropriate ICD shocks (HR 0.21, p = .03). CONCLUSIONS: In patients with prior myocardial infarction and secondary prevention ICD, IRACTO revascularization was independently associated with a markedly lower incidence of appropriate ICD therapies and shocks. These results should be corroborated by larger prospective studies.

Clinical characteristics and determinants of the phenotype in TMEM43 arrhythmogenic right ventricular cardiomyopathy type 5.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy type V (ARVC-5) is the most aggressive heterozygous form of ARVC. It is predominantly caused by a fully penetrant mutation (p.S358L) in the nondesmosomal gene TMEM43-endemic to Newfoundland, Canada. To date, all familial cases reported worldwide share a common ancestral haplotype. It is unknown whether the p.S358L mutation by itself causes ARVC-5 or whether the disease is influenced by genetic or environmental factors. OBJECTIVE: The purpose of this study was to examine the phenotype, clinical course, and the impact of exercise on patients with p.S358L ARVC-5 without the Newfoundland genetic background. METHODS: We studied 62 affected individuals and 73 noncarriers from 3 TMEM43-p.S358L Spanish families. The impact of physical activity on the phenotype was also evaluated. RESULTS: Haplotype analysis revealed that the 3 Spanish families were unrelated to patients with ARVC-5 with the Newfoundland genetic background. Two families shared 10 microsatellite markers in a 4.9 cM region surrounding TMEM43; the third family had a distinct haplotype. The affected individuals showed a 38.7% incidence of sudden cardiac death, which was higher in men. Left ventricular involvement was common, with 40% of mutation carriers showing a left ventricular ejection fraction of <50%. Compared with noncarriers, the R-wave voltage in lead V3 was lower (3.2 ± 2.8 mV vs 7.5 ± 3.6 mV; P < .001) and QRS complex in right precordial leads wider (104.7 ± 24.0 ms vs 88.2 ± 7.7 ms; P = .001). A history of vigorous exercise showed a trend toward more ventricular arrhythmias only in women (P = .053). CONCLUSION: ARVC-5 is associated with a high risk of sudden cardiac death and characteristic clinical and electrocardiographic features irrespective of geographical origin and genetic background. Our data suggest that, as in desmosomal ARVC, vigorous physical activity could aggravate the phenotype of TMEM43 mutation carriers.

Dizziness in a patient with a permanent VVI pacemaker.

A 83-year-old woman with a single-chamber pacemaker implanted 15 years earlier was brought to the ED due to symptomatic bradycardia. ECG continuous monitoring allowed the diagnosis of atrial fibrillation with complete atrioventricular block in the setting of a complete failure to capture. The differing timing cycles of pacing outputs can confirm that sensing is preserved in the absence of a pacemaker programmer.

Marcapasos sin cables debido a estenosis subclavia bilateral / Leadless pacemaker due to bilateral subclavian stenosis

No disponible

Necesidades de los pacientes ingresados en la Unidad de Cuidados Intensivos / Needs of patients hospitalized at the intensive care unit

OBJETIVO: describir las necesidades que reconocen tener los pacientes durante su estancia en la Unidad de Cuidados Intensivos (UCI) y analizar los factores ambientales estresantes percibidos por ellos. METODOLOGÍA: revisión narrativa de la literatura. Las bases de datos utilizadas fueron Cuiden Plus, PubMed, CINAHL, SciELO, i-cercador, IME y Cochrane. Los criterios de inclusión de los artículos fueron: publicados en castellano o inglés, entre 2005 y 2014, pacientes adultos y puntuación de la escala metodológica The SQUIRE ≥ 10 puntos. Se excluyeron la literatura gris y los estudios que evaluaran las necesidades de la familia. RESULTADOS: se incluyeron 13 artículos. Las necesidades más detectadas han sido: estar informados sobre su proceso y poder decidir sobre él, poder comunicarse con su familia y los profesionales, tener un buen descanso disminuyendo los despertares frecuentes y mantenerse en contacto con su familia debido a la gran soledad que sienten. CONCLUSIONES: la estancia en la UCI genera un alto grado de estrés para los pacientes. Las necesidades que el paciente manifiesta como no cubiertas son sentirse informados, tomar decisiones, descansar y sentirse seguro por la soledad, preocupación y sensación de muerte inminente que padecen. Los propios pacientes y sus familiares reclaman pasar el mayor tiempo juntos, afirmando que sería muy beneficioso para promocionar el bienestar y el confort de ambos en la UCI

OBJECTIVE: to describe the needs reported by patients during their stay at the Intensive Care Unit (ICU), and to analyze the environmental stressors they perceived. METHODOLOGY: a narrative review of literature. The databases used were: Cuiden Plus, PubMed, CINAHL, SciELO, i-cercador, IME and Cochrane. The inclusion criteria for the articles were: published in Spanish or English, between 2005 and 2014, about adult patients, and with a score in the methodological scale The SQUIRE ≥ 10 scores. Grey literature was excluded, as well as those studies assessing the needs of the family. RESULTS: thirteen (13) articles were included. The most common needs detected were: being informed about their process and being able to make decisions about it, being able to communicate with their family and the professionals, being able to rest well without frequent awakenings, and staying in contact with their family, due to the high level of loneliness they felt. CONCLUSIONS: ICU stays generate a high level of stress for patients. The unmet needs reported by patients were: feeling informed, making decisions, resting, and feeling safe, due to the loneliness, concern and feeling of imminent death experienced. Patients and their relatives demanded being together as long as possible, and claimed that this would be very beneficial in order to promote their wellbeing and comfort in the ICU

Genome-wide linkage analysis of congenital heart defects using MOD score analysis identifies two novel loci.

BACKGROUND: Congenital heart defects (CHD) is the most common cause of death from a congenital structure abnormality in newborns and is often associated with fetal loss. There are many types of CHD. Human genetic studies have identified genes that are responsible for the inheritance of a particular type of CHD and for some types of CHD previously thought to be sporadic. However, occasionally different members of the same family might have anatomically distinct defects - for instance, one member with atrial septal defect, one with tetralogy of Fallot, and one with ventricular septal defect. Our objective is to identify susceptibility loci for CHD in families affected by distinct defects. The occurrence of these apparently discordant clinical phenotypes within one family might hint at a genetic framework common to most types of CHD. RESULTS: We performed a genome-wide linkage analysis using MOD score analysis in families with diverse CHD. Significant linkage was obtained in two regions, at chromosome 15 (15q26.3, P(empirical) = 0.0004) and at chromosome 18 (18q21.2, P(empirical) = 0.0005). CONCLUSIONS: In these two novel regions four candidate genes are located: SELS, SNRPA1, and PCSK6 on 15q26.3, and TCF4 on 18q21.2. The new loci reported here have not previously been described in connection with CHD. Although further studies in other cohorts are needed to confirm these findings, the results presented here together with recent insight into how the heart normally develops will improve the understanding of CHD.

Cardiac resynchronization therapy in patients with permanent atrial fibrillation. Is it mandatory to ablate the atrioventricular junction to obtain a good response?

AIM: Current guidelines recommend atrioventricular junction (AVJ) ablation in patients with atrial fibrillation (AF) treated with cardiac resynchronization therapy (CRT). Our study compared the CRT response of patients in sinus rhythm (SR) vs. AF. METHODS AND RESULTS: In this observational, prospective, multicentre study, patients were grouped by intrinsic rhythm. For the first 2 months, the negative chronotropic drug was optimized in the AF group. If ventricular pacing was ≤85%, AVJ ablation was recommended. Responders were defined as patients who survived without requiring heart transplant and had a ≥ 10% reduction in left ventricular end-systolic volume (LVESV) at 12 months after implantation. Of 202 patients included, 156 (77%) were in SR and 46 (23%) had AF. After drug optimization, only 13/46 (28%) of the AF patients required AVJ ablation (AF + AVJ). The percentage of responders was 83/156 (53%) for SR vs. 22/46 (48%) AF (P = 0.4). Among AF patients the response was 16/33 (48%) for AF with non-AVJ ablation vs. 6/13 (46%) AF + AVJ, P = 0.56. The LVESV decreased in all three groups: -30 ± 39 mL, -24 ± 43 mL, and -22 ± 36 mL, respectively (P = 0.75). Mortality was higher in patients with AF compared with SR: 10/46 (21%) vs. 9/156 (5.7%), log rank 10.6, P <0.05. CONCLUSION: Although only 28% of the patients in AF had the AVJ ablated, there were no differences in the percentage of response and echo improvement between patients in SR and AF. However, mortality was higher in patients with AF compared with patients in SR.

Evaluation of a telemedicine service for the secondary prevention of coronary artery disease.

PURPOSE: Efficient ways are needed to implement the secondary prevention (SP) of coronary heart disease. Because few studies have investigated Web-based SP programs, our aim was to determine the usefulness of a new Web-based telemonitoring system, connecting patients provided with self-measurement devices and care managers via mobile phone text messages, as a tool for SP. METHODS: A single-blind, randomized controlled, clinical trial of 203 acute coronary syndrome (ACS) survivors, was conducted at a hospital in Madrid, Spain. All patients received lifestyle counseling and usual-care treatment. Patients in the telemonitoring group (TMG) sent, through mobile phones, weight, heart rate, and blood pressure (BP) weekly, and capillary plasma lipid profile and glucose monthly. A cardiologist accessed these data through a Web interface and sent recommendations via short message service. Main outcome measures were BP, body mass index (BMI), smoking status, low-density lipoprotein-cholesterol (LDL-c), and glycated hemoglobin A1c (HbA1c). RESULTS: At 12-month followup, TMG patients were more likely (RR = 1.4; 95% CI = 1.1-1.7) to experience improvement in cardiovascular risk factors profile than control patients (69.6% vs 50.5%, P = .010). More TMG patients achieved treatment goals for BP (62.1% vs 42.9%, P = .012) and HbA1c (86.4% vs 54.2%, P = .018), with no differences in smoking cessation or LDL-c. Body mass index was significantly lower in TMG (-0.77 kg/m² vs +0.29 kg/m², P = .005). CONCLUSIONS: A telemonitoring program, via mobile phone messages, appears to be useful for improving the risk profile in ACS survivors and can be an effective tool for secondary prevention, especially for overweight patients.