Cardiac amyloidosis and left atrial appendage closure. The CAMYLAAC study.

INTRODUCTION AND OBJECTIVES: Transthyretin cardiac amyloidosis (ATTR-CA) patients often have atrial fibrillation and increased bleeding/thrombogenic risks. We aimed to evaluate outcomes of left atrial appendage closure (LAAC) compared with patients without a known diagnosis of CA. METHODS: Comparison at long-term of patients diagnosed with ATTR-CA who underwent LAAC between 2009 and 2020 and those without a known diagnosis of CA. RESULTS: We studied a total of 1159 patients. Forty patients (3.5%) were diagnosed with ATTR-CA; these patients were older and had more comorbidities, higher HAS-BLED and CHA2DS2-VASc scores, and lower left ventricular function. Successful LAAC was achieved in 1137 patients (98.1%) with no differences between groups. Regarding in-hospital and follow-up complications, there were no differences between the groups in ischemic stroke (5% vs 2.5% in those without a known diagnosis of CA; P=.283), hemorrhagic stroke (2.5% and 0.8% in the control group; P=.284), major or minor bleeding. At the 2-year follow-up, there were no significant differences in mortality (ATTR-CA: 20% vs those without known CA: 13.6%, 0.248); however, the at 5-year follow-up, ATTR-CA patients had higher mortality (40% vs 19.2%; P <.001) but this difference was unrelated to hemorrhagic complications or ischemic stroke. CONCLUSIONS: LAAC could reduce the risk of bleeding complications and ischemic cerebrovascular events without increasing the rate of early or mid-term complications. Although long-term survival was impaired in ATTR-CA patients, it was comparable to that of patients without a known diagnosis of CA at the 2-year follow-up, suggesting that LAAC for patients with ATTR-CA might not be futile.

A Fibrosis Biomarker Early Predicts Cardiotoxicity Due to Anthracycline-Based Breast Cancer Chemotherapy.

Anthracycline-based cancer chemotherapy (ACC) causes myocardial fibrosis, a lesion contributing to left ventricular dysfunction (LVD). We investigated whether the procollagen-derived type-I C-terminal-propeptide (PICP): (1) associates with subclinical LVD (sLVD) at 3-months after ACC (3m-post-ACC); (2) predicts cardiotoxicity 1-year after ACC (12m-post-ACC) in breast cancer patients (BC-patients); and (3) associates with LVD in ACC-induced heart failure patients (ACC-HF-patients). Echocardiography, serum PICP and biomarkers of cardiomyocyte damage were assessed in two independent cohorts of BC-patients: CUN (n = 87) at baseline, post-ACC, and 3m and 12m (n = 65)-post-ACC; and HULAFE (n = 70) at baseline, 3m and 12m-post-ACC. Thirty-seven ACC-HF-patients were also studied. Global longitudinal strain (GLS)-based sLVD (3m-post-ACC) and LV ejection fraction (LVEF)-based cardiotoxicity (12m-post-ACC) were defined according to guidelines. BC-patients: all biomarkers increased at 3m-post-ACC versus baseline. PICP was particularly increased in patients with sLVD (interaction-p < 0.001) and was associated with GLS (p < 0.001). PICP increase at 3m-post-ACC predicted cardiotoxicity at 12m-post-ACC (odds-ratio ≥ 2.95 per doubling PICP, p ≤ 0.025) in both BC-cohorts, adding prognostic value to the early assessment of GLS and LVEF. ACC-HF-patients: PICP was inversely associated with LVEF (p = 0.004). In ACC-treated BC-patients, an early increase in PICP is associated with early sLVD and predicts cardiotoxicity 1 year after ACC. PICP is also associated with LVD in ACC-HF-patients.

Differences in scar lesion formation between radiofrequency and cryoballoon in atrial fibrillation ablation: a comparison study using ultra-high-density mapping.

AIMS: Atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) is usually associated to conduction gaps in pulmonary veins (PVs). Our objective was to characterize gaps in patients with recurrences after a first radiofrequency (RF) or cryoballoon (CB) PVI procedure, using a high-density mapping (HDM) system. METHODS AND RESULTS: Fifty patients with AF recurrence after a first PVI procedure (pre-RF 25 patients; pre-CB 25 patients) were included at two centres. Activation map (AM) and voltage map (VM) of the left atrium and PVs were built using the HDM Rhythmia® system. Superior PVs were reconnected more frequently in both groups. Right PVs were reconnected more frequently in pre-RF patients. Pre-RF patients had more reconnected veins than pre-CB patients (mean ± standard deviation: 3.00 ± 0.96 vs. 1.88 ± 1.13; P < 0.001) and more gaps (4.84 ± 2.06 vs. 2.16 ± 1.49; P < 0.001). Gaps in the VM were wider in pre-CB patients (16.5 ± 9.5 mm vs. 12.1 ± 4.8 mm; P = 0.006). There was a gap in 179 of the 800 PV segments analysed (22%); 52% were identified in both AM and VM maps; 39% only in the AM and 8% only in the VM. The highest sensitivity and specificity for gap detection was obtained with VM in pre-CB patients and with AM in pre-RF patients. CONCLUSION: In conclusion, HDM seems to be a useful and precise tool to detect conduction gaps after a first PVI procedure. The anatomical pattern and location of gaps depends on the technique used previously, usually being multiple, smaller, and better detected by AM after RF, and fewer, wider, and better detected by VM after CB.

Identification of pulmonary vein reconnection gaps with high-density mapping in redo atrial fibrillation ablation procedures.

Aims: Maps obtained by means of electroanatomic high-density mapping (HDM) systems have shown their use in the identification of conduction gaps in experimental atrial linear lesion models. The objective of this study was to assess the use of HDM in the recognition of reconnection gaps in pulmonary veins (PV) in redo atrial fibrillation (AF) ablation procedures. Methods and results: One hundred and eight patients were included in a non-randomized study that assessed the recognition of reconnection gaps in PV by means of HDM compared to a control group that received conventional non-fluoroscopic guidance with a circular multipolar catheter (CMC). Among the HDM group, adequate recognition of reconnection gaps was obtained in 60.99% of the reconnected PVs (86 of 141), a figure significantly higher than that achieved with analysis of CMC recorded signals (39.66%, 48 of 121; P = 0.001). The number of applications and total radiofrequency time were also significantly lower in the HDM group (12.46 ± 6.1 vs. 15.63 ± 7.7 and 7.61 ± 3 vs. 9.29 ± 5; P = 0.02, and P = 0.03, respectively). At the 6-month follow-up, no statistically significant differences were found in recurrence of AF or any other atrial tachycardia between the HDM group (8 patients, 14.8%) and the control group in (16 patients, 29.6%; P = 0.104). Conclusion: An analysis of the high-density activation maps allows greater precision in the identification of reconnection gaps in PV, which results in lower radiofrequency time for the new isolation.

Atrial Fibrillation Ablation Guided by a Novel Nonfluoroscopic Navigation System.

INTRODUCTION AND OBJECTIVES: Rhythmia is a new nonfluoroscopic navigation system that is able to create high-density electroanatomic maps. The aim of this study was to describe the acute outcomes of atrial fibrillation (AF) ablation guided by this system, to analyze the volume provided by its electroanatomic map, and to describe its ability to locate pulmonary vein (PV) reconnection gaps in redo procedures. METHODS: This observational study included 62 patients who underwent AF ablation with Rhythmia compared with a retrospective cohort who underwent AF ablation with a conventional nonfluoroscopic navigation system (Ensite Velocity). RESULTS: The number of surface electrograms per map was significantly higher in Rhythmia procedures (12 125 ± 2826 vs 133 ± 21 with Velocity; P < .001), with no significant differences in the total procedure time. The Orion catheter was placed for mapping in 99.5% of PV (95.61% in the control group with a conventional circular mapping catheter; P = .04). There were no significant differences in the percentage of PV isolation between the 2 groups. In redo procedures, an ablation gap could be identified on the activation map in 67% of the reconnected PV (40% in the control group; P = .042). The measured left atrial volume was lower than that calculated by computed tomography (109.3 v 15.2 and 129.9 ± 13.2 mL, respectively; P < .001). There were no significant differences in the number of complications. CONCLUSIONS: The Rhythmia system is effective for AF ablation procedures, with procedure times and safety profiles similar to conventional nonfluoroscopic navigation systems. In redo procedures, it appears to be more effective in identifying reconnected PV conduction gaps.

Mediguide-Assisted Transseptal Puncture without Echocardiographic Guidance.

BACKGROUND: First description of a technique for left atrium transseptal puncture (TSP) with minimal radiation exposure by using the nonfluoroscopic MediGuide™ tracking system (MG; St. Jude Medical, St. Paul, MN, USA) without the assistance of intracardiac echocardiography. METHODS: This study included 31 consecutive patients with atrial fibrillation undergoing an MG-assisted percutaneous catheter ablation procedure. A Brockenbrough transseptal needle (BRK) is connected to a standard pressure transducer through a two-input valve. Then, an MG-enabled guidewire is inserted so that its tip exactly matches the BRK's distal tip. After the acquisition of two short radioscopic cine-loops we are able to trace the needle tip on the MG screen, performing the usual TSP maneuver but without fluoroscopy. Successful left atrium access is confirmed by noticing the change in the pressure curve and by advancing the guidewire into the left pulmonary veins. As a control group, 31 matched patients who underwent atrial fibrillation ablation with fluoroscopically guided, pressure-monitored TSP were included. RESULTS: Sixty-two MG-assisted TSP attempts were performed; all but two were successfully accomplished without changing to the conventional technique (96.7%). The mean total fluoroscopy time, until the double transseptal access was performed, was 26.65 ± 37.97 seconds in the MG group and 129.13 ± 37.77 seconds in the conventional-TSP group (P < 0.001). No major complications occurred during any of the procedures. CONCLUSION: This new technique for TSP using MG is feasible and can be performed with minimal radiation exposure without the need for additional imaging techniques, achieving a significant reduction of fluoroscopy time.

Comparative Evaluation of Four Risk Scores for Predicting Mortality in Patients With Implantable Cardioverter-defibrillator for Primary Prevention.

INTRODUCTION AND OBJECTIVES: Several clinical risk scores have been developed to identify patients at high risk of all-cause mortality despite implantation of an implantable cardioverter-defibrillator. We aimed to examine and compare the predictive capacity of 4 simple scoring systems (MADIT-II, FADES, PACE and SHOCKED) for predicting mortality after defibrillator implantation for primary prevention of sudden cardiac death in a Mediterranean country. METHODS: A multicenter retrospective study was performed in 15 Spanish hospitals. Consecutive patients referred for defibrillator implantation between January 2010 and December 2011 were included. RESULTS: A total of 916 patients with ischemic and nonischemic heart disease were included (mean age, 62 ± 11 years, 81.4% male). Over 33.4 ± 12.9 months, 113 (12.3%) patients died (cardiovascular origin in 86 [9.4%] patients). At 12, 24, 36, and 48 months, mortality rates were 4.5%, 7.6%, 10.8%, and 12.3% respectively. All the risk scores showed a stepwise increase in the risk of death throughout the scoring system of each of the scores and all 4 scores identified patients at greater risk of mortality. The scores were significantly associated with all-cause mortality throughout the follow-up period. PACE displayed the lowest c-index value regardless of whether the population had heart disease of ischemic (c-statistic = 0.61) or nonischemic origin (c-statistic = 0.61), whereas MADIT-II (c-statistic = 0.67 and 0.65 in ischemic and nonischemic cardiomyopathy, respectively), SHOCKED (c-statistic = 0.68 and 0.66, respectively), and FADES (c-statistic = 0.66 and 0.60) provided similar c-statistic values (P ≥ .09). CONCLUSIONS: In this nontrial-based cohort of Mediterranean patients, the 4 evaluated risk scores showed a significant stepwise increase in the risk of death. Among the currently available risk scores, MADIT-II, FADES, and SHOCKED provide slightly better performance than PACE.

La ablación de fibrilación auricular en España

Introducción: la ablación de la fibrilación auricular es uno de los procedimientos más frecuentemente realizados en las unidades de arritmias. La información de los resultados proviene de estudios prospectivos, registros multicéntricos y registros nacionales. Objetivo: evaluar la situación de la ablación de la fibrilación auricular en España a través de los datos recogidos en el Registro Español de Ablación, auspiciado por la Sección de Electrofisiología y Arritmias de la Sociedad Española de Cardiología. Métodos: los datos analizados provienen de los formularios remitidos, de forma voluntaria y anónima, por los diferentes centros hospitalarios, tanto de financiación pública como privada, durante el período 2008-2013. Cada centro fue analizado, año a año, de forma independiente. Analizamos los recursos humanos y materiales de los centros que realizaron procedimientos de ablación de fibrilación auricular durante ese período de tiempo. Asimismo, analizamos la técnica utilizada, el tipo de energía, complicaciones, etcétera. Comparamos todas las variables de forma evolutiva, año a año. Dividimos a los centros en función del número de procedimientos de ablación realizados cada año: 1-49, grupo A; 50-99, grupo B, y 100 o más, grupo C. Resultados: trescientos noventa y un centros (n=391) y 8.926 procedimientos de ablación fueron analizados. Año a año ha aumentado el número de centros que realizan ablación de fibrilación auricular y el número de procedimientos que realiza cada centro. El porcentaje de complicaciones se ha mantenido estable reduciéndose ligeramente la mortalidad. Los centros con mayor volumen tienen mayor dotación de recursos humanos y materiales. Realizan ablación de fibrilación auricular persistente con mayor frecuencia y realizan crioablación con menor frecuencia. Asimismo, estos centros tienen una menor incidencia de complicaciones. Conclusiones: la ablación de fibrilación auricular en España ha aumentado en los últimos años y presenta resultados similares a los recogidos en otros registros nacionales y multinacionales.

Estado actual de la terapia de resincronización cardiaca / Current status of cardiac resynchronization therapy

Se revisa el estado actual de la terapia de resincronización cardiaca en sus diferentes aspectos: mecanismos de acción, indicaciones actuales y técnica de implante.

The present document reviews various aspects of the current status of cardiac resynchronization therapy: mechanisms of action, current indications and implantation technique.

Cardiac resynchronization therapy-induced left ventricular reverse remodelling is associated with reduced plasma annexin A5.

AIMS: Cardiac resynchronization therapy (CRT) diminishes cardiac apoptosis and improves systolic function in heart failure (HF) patients with ventricular dyssynchrony. Plasma annexin A5 (AnxA5), a protein related to cellular damage, is associated with systolic dysfunction. We investigated whether the response to CRT is associated with plasma AnxA5. We also studied AnxA5 overexpression effects in HL-1 cardiomyocytes. METHODS AND RESULTS: AnxA5 ELISA was performed in plasma from 57 patients with HF and ventricular dyssynchrony at baseline and after 1 year of CRT. Patients were categorized as responders if they presented both a reduction in left ventricular (LV) end-systolic volume index (LVESVi) >10% and an increase in LV ejection fraction (LVEF) >10%. HL-1 cells were transfected with human AnxA5 cDNA, and AnxA5, PKC, Akt, p38MAPK, Bcl-2, mitochondrial integrity, caspase-3, and ATP were assessed. At baseline, an increased plasma AnxA5 level was associated with decreased LVEF and increased LVEDVi values (P < 0.05). No differences in baseline AnxA5 were observed between responders and non-responders. After CRT, AnxA5 decreased (P = 0.001) in responders but remained unchanged in non-responders. Final values of AnxA5 were independently associated with LVEF (r = -0.387, P = 0.003) and LVESVi (r = 0.403, P = 0.004) in all patients. Compared with control cells, AnxA5-transfected cells exhibited AnxA5 overexpression, decreased PKC and Akt and increased p38MAPK and Bcl-2 phosphorylation, loss of mitochondrial integrity, caspase-3 activation, and decreased ATP. CONCLUSION: CRT-induced LV reverse remodelling is associated with reduction in plasma AnxA5. The excess of AnxA5 is detrimental for HL-1 cardiomyocytes. Collectively, these data suggest that the beneficial effects of CRT might be related to an AnxA5 decrease.

Cardiac resynchronization therapy and valvular cardiomyopathy after corrective surgery.

Cardiac resynchronization therapy (CRT) has been shown to have clinical benefits in certain groups of patients with advanced heart failure (HF). However, patients with valvular cardiomyopathy are underrepresented in randomized clinical studies. The aim of this study was to assess the medium-term (i.e., at 6 months) effects of CRT in patients with HF exclusively due to valvular disease. The study included 40 consecutive patients who underwent CRT device implantation. At 6 months, there were improvements in functional class, left ventricular remodeling, and intraventricular dyssynchrony parameters in treated patients. In this particular subgroup of patients, the benefits of CRT were similar to those observed in patients with HF due to other etiologies.

Fatal left internal mammary artery graft to subclavian vein fistula complicating dual-chamber pacemaker implantation.

We describe the case of a 75-year-old woman with an iatrogenic fistula between a left internal mammary artery graft to the left anterior descending coronary artery and the left subclavian vein that developed after implantation of a dual-chamber pacemaker.

Cardiac resynchronization therapy: predictive factors of unsuccessful left ventricular lead implant.

AIMS: Cardiac resynchronization therapy is an established therapy for advanced heart failure. However, coronary sinus access and pacing is not achieved in about 5-10% of patients. The aim of this study was to identify predictive factors for failure of left ventricular (LV) lead transvenous implant. METHODS AND RESULTS: We evaluated 212 consecutive patients who received a cardiac resynchronization system. In 26 patients (12.3%), the attempt to pace the LV was unsuccessful. At univariate analysis, in patients with an unsuccessful implant a higher proportion of permanent atrial fibrillation (AF), valvular heart disease, and previous heart surgery were observed. Anteroposterior, longitudinal, and transversal left atrium diameters (LAD) were also larger among patients with an unsuccessful implant. The anteroposterior LAD (APLAD) with an optimal value to predict implant failure was 48.5 mm. At logistic regression analysis, the presence of permanent AF and APLAD were independent predictors of failed implant (OR 7.7, 95% CI 2.5-23.9, P=0.002 and OR 11.7, 95% CI 3.1-37.6, P<0.001, respectively). CONCLUSION: The presence of permanent AF and APLAD are factors that predict unsuccessful pacing from the LV.

Periannular complications in infective endocarditis involving prosthetic aortic valves.

The periannular extension of infection in prosthetic valve endocarditis (PVE) is a serious complication of infective endocarditis associated with high mortality. Periannular lesions in PVE occasionally rupture into adjacent cardiac chambers, leading to aortocavitary fistulae and intracardiac shunting. It is unknown whether the prognosis of patients with aortocavitary fistulae is worse than that of those with nonruptured abscesses. The aims of this study were to determine the distinctive clinical characteristics of patients with PVE and either aortocavitary fistulization or nonruptured abscesses. In a retrospective multicenter study of >872 PVE episodes, 150 patients (17%) with periannular complications in PVE in the aortic position were identified (29 with aortocavitary fistulization and 121 with nonruptured abscesses). Early-onset PVE was present in 73 patients (49%). Rates of heart failure (p = 0.09), ventricular septal defect (p <0.01), and third-degree atrioventricular block (p = 0.07) were higher in patients with fistulization. Surgical treatment was undertaken in 128 patients (83%). In-hospital mortality in the overall population was 39%. Multivariate analysis identified heart failure (odds ratio [OR] 3.3, 95% confidence interval [CI] 1.6 to 6.8), renal failure (OR 2.5, 95% CI 1.2 to 5.2), and co-morbidity (OR 2.4, 95% CI 1.1 to 5.1) as independent risk factors for death. Fistulous tract formation was not associated with increased in-hospital mortality (OR 1.6, 95% CI 0.7 to 3.7). The actuarial 5-year survival rate in surgical survivors was 100% in patients with fistulae and 78% in patients with nonruptured abscesses (log-rank p = 0.14). In conclusion, aortocavitary fistulous tract formation in PVE complicated with periannular complications is associated with higher rates of heart failure, ventricular septal defect, and atrioventricular block than nonruptured abscesses. Despite the frequent complications, fistulous tract formation in the current era of infective endocarditis is not an independent risk factor for mortality.

Aorto-cavitary fistulous tract formation in infective endocarditis: clinical and echocardiographic features of 76 cases and risk factors for mortality.

AIMS: To investigate the clinical features, echocardiographic characteristics, management, and prognostic factors of mortality of aorto-cavitary fistulization (ACF) in infective endocarditis (IE). Extension of infection in aortic valve IE beyond valvular structures may result in peri-annular complications with resulting necrosis and rupture, and subsequent development of ACF. Aorto-cavitary communications create intra-cardiac shunts, which may result in further clinical deterioration and haemodynamic instability. METHODS AND RESULTS: In a retrospective multi-centre study over 4681 episodes of IE, a total of 76 patients with ACF [1.6%, confidence interval (CI) 95%: 1.2-2.0%] diagnosed by echocardiography or during surgery were identified. Fistulae were found in 1.8% of cases of native valve IE and in 3.5% of cases of prosthetic valve IE from the general population and in 0.4% of drug abusers. PVE was present in 31 (41%) cases of ACF. Transthoracic and transoesophageal echocardiography detected the fistulous tracts in 53 and 97% of cases, respectively. Peri-annular abscesses were detected in 78% of cases, fistulae originated in similar rates from the three sinuses of Valsalva, and the four cardiac chambers were equally involved in the fistulous tracts. Heart failure (HF) developed in 62% of cases and surgery was performed in 66 (87% CI 95% 77-93%) patients with a mortality of 41% (95% CI 30-53%) in the overall population. Multivariate analysis identified HF (OR 3.4, CI 95% 1.0-11.5), prosthetic IE (OR 4.6, CI 95% 1.4-15.4) and urgent or emergency surgical treatment (OR 4.3, CI 95% 1.3-16.6) as variables significantly associated with an increased risk of death. Major complications during follow-up (death, re-operation, or re-admission for HF) among the five operative survivors with residual fistulae occurred in 20 and 100% of patients at 1 and 2 years, respectively. CONCLUSION: Aorto-cavitary fistulous tract formation is an uncommon but extremely serious complication of IE. In-hospital mortality was exceptionally high despite aggressive management with surgical intervention in the majority of patients. Prosthetic IE, urgent surgery, and the development of HF identify the subgroup of patients with IE and ACF that have significantly increased risk of in-hospital death.