Withdrawal of drug therapy in responders to cardiac resynchronization therapy: rationale and design of the REMOVE trial.

INTRODUCTION AND OBJECTIVES: Cardiac resynchronization therapy (CRT) is an effective treatment for patients with nonischemic dilated cardiomyopathy associated with left bundle branch block (LBBB). In these patients, the device can normalize left ventricular ejection fraction (LVEF). Nevertheless, it remains unclear whether CRT responders still require neurohormonal blockers. The aim of this study is to determine the long-term safety of withdrawing drug therapy in these patients. METHODS: The REMOVE trial is a prospective, multicenter, open-label and randomized 1:1 study designed to assess the effect of withdrawing neurohormonal blockers in patients with nonischemic dilated cardiomyopathy associated with left bundle branch block who recovered LVEF after CRT. The study will include a 12-month follow-up with the option to continue into the follow-up extension phase for up to 24 months. The primary endpoint is the recurrence of cardiomyopathy defined as any of the following criteria: a) a reduction in LVEF >10% (provided the LVEF is <50%); b) a reduction in LVEF >10% accompanied by an increase >15% in the indexed end-systolic volume relative to the previous value and in a range higher than the normal values, or c) decompensated heart failure requiring intravenous diuretic administration. In patients meeting the primary endpoint, drug therapy will be restarted. CONCLUSIONS: The results of this study will help to enhance our understanding of CRT superresponders, a specific group of patients. Registred at ClinicalTrials.gov (Identifier: NCT05151861).

Searching for genetic modulators of the phenotypic heterogeneity in Brugada syndrome.

In Brugada syndrome, even within the same family where all affected individuals share the same mutation, phenotypic variation is prominent, with variable penetrance and expressivity, presenting different degrees of involvement. It is difficult to establish a direct correlation between genotype and phenotype to predict prognosis in complications and risk of sudden death. The factors that modulate this inter- and intra-familial phenotypic variability remain to be determined. With the intention of testing whether other genetic factors, in addition to the causal mutation in SCN5A, may have a modulating effect on the Brugada phenotype and the risk of sudden death, we have studied 8 families with a causal variant in SCN5A with at least two affected individuals, one of whom has suffered cardiac arrest or sudden death. Whole exome sequencing was performed looking for additional variants that modify the phenotype and allow us to predict a better or worse prognosis for the evolution of the disease. The results did not show any clear genetic modifier; nevertheless, highlight the possible implication of the cholesterol and fibrosis pathways, as well as the circadian rhythm, as possible modulators of Brugada syndrome phenotype.

Emergency department attendance and reasons for consultation after cryoballoon ablation for pulmonary vein isolation of atrial fibrillation.

INTRODUCTION AND OBJECTIVES: There are few data on emergency visits after cryoballoon-based pulmonary vein isolation. The aim of this study was to quantify emergency department visits during the first 3 months after the procedure and to identify the reasons for consultation, final diagnoses, and the therapeutic approach. METHODS: Observational, retrospective study of 330 consecutive patients undergoing a first cryoballoon-based ablation procedure. Patients were followed up for 90 days after the procedure. We recorded emergency visits, symptoms, electrocardiographic data, and the therapeutic approach. Final diagnoses were classified as rhythm disorder, confirmed complication, possible complication, and unrelated to the procedure or to the arrhythmic disorder. RESULTS: A total of 112 (34%) patients attended the emergency department, 50 (44.6%) for palpitations. Sustained atrial arrhythmias were documented in 44 (39.3%) patients. Among the 29 (25.9%) visits for complications potentially related to the procedure, 5 were confirmed inguinal puncture complications and 10 were classified as unconfirmed possible complications. Forty-one visits were unrelated to the procedure or to the arrhythmic disorder. A total of 21.4% of the visits were due to palpitations requiring no therapeutic action. CONCLUSIONS: A third of the patients attended the emergency department at least once, with the most frequent reason being arrhythmia-related symptoms. Late complications were rare and generally mild. Up to 20% of emergency visits could potentially be avoided by the availability of a teleconsulting system with remote electrocardiogram transmission.

Medium- and long-term outcome after a single second-generation cryoballoon ablation in patients with paroxysmal and persistent atrial fibrillation.

INTRODUCTION AND OBJECTIVES: To report medium- and long-term results following a single second-generation cryoballoon (CB2)-based ablation procedure in patients with paroxysmal (PAF) and persistent (PeAF) atrial fibrillation. METHODS: A retrospective study was performed of consecutive patients undergoing a first CB2-based ablation procedure in a tertiary center. Cryoenergy was applied for 3 min if a time to effect <60 s was documented or 4 min otherwise, with a bonus application in cases of late isolation or suboptimal temperature. Follow-up was obtained from the regional health electronic records system and by telephone or personal interviews. Recurrence was defined as any atrial arrhythmia >30 s beyond a three-month blanking period. The clinical impact of recurrences was classified using a severity score. RESULTS: A total of 172 patients (134 PAF and 38 PeAF) were included, of whom 25 (14.5%) had structural heart disease and 120 (69.7%) had a normal or mildly dilated left atrium. Acute success was achieved in 167 (97.1%). After a median follow-up of 27 (14-41) months, 100 patients (58.1%) remained free of atrial arrhythmias (64.2% for PAF and 36.8% for PeAF, p=0.006). Left atrial size (p=0.05) and clinical presentation as PeAF (p=0.006) were predictors of recurrence. Of patients with recurrences, 11.1% did not require further therapies and an additional 16.7% had good control with antiarrhythmic drugs. CONCLUSIONS: A single CB2 procedure resulted in 58.1% of patients remaining free of atrial arrhythmias at 27-month follow-up. Conservative management was useful in 27.8% of patients with recurrences.

Value of the "Standing Test" in the Diagnosis and Evaluation of Beta-blocker Therapy Response in Long QT Syndrome.

INTRODUCTION AND OBJECTIVES: Patients with congenital long QT syndrome (LQTS) have an abnormal QT adaptation to sudden changes in heart rate provoked by standing. The present study sought to evaluate the standing test in a cohort of LQTS patients and to assess if this QT maladaptation phenomenon is ameliorated by beta-blocker therapy. METHODS: Electrographic assessments were performed at baseline and immediately after standing in 36 LQTS patients (6 LQT1 [17%], 20 LQT2 [56%], 3 LQT7 [8%], 7 unidentified-genotype patients [19%]) and 41 controls. The corrected QT interval (QTc) was measured at baseline (QTcsupine) and immediately after standing (QTcstanding); the QTc change from baseline (ΔQTc) was calculated as QTcstanding - QTcsupine. The test was repeated in 26 patients receiving beta-blocker therapy. RESULTS: Both QTcstanding and ΔQTc were significantly higher in the LQTS group than in controls (QTcstanding, 528 ± 46ms vs 420 ± 15ms, P < .0001; ΔQTc, 78 ± 40ms vs 8 ± 13ms, P < .0001). No significant differences were noted between LQT1 and LQT2 patients. Typical ST-T wave patterns appeared after standing in LQTS patients. Receiver operating characteristic curves of QTcstanding and ΔQTc showed a significant increase in diagnostic value compared with the QTcsupine (area under the curve for both, 0.99 vs 0.85; P < .001). Beta-blockers attenuated the response to standing in LQTS patients (QTcstanding, 440 ± 32ms, P < .0001; ΔQTc, 14 ± 16ms, P < .0001). CONCLUSIONS: Evaluation of the QTc after the simple maneuver of standing shows a high diagnostic performance and could be important for monitoring the effects of beta-blocker therapy in LQTS patients.

Heterogeneous Phenotype of Long QT Syndrome Caused by the KCNH2-H562R Mutation: Importance of Familial Genetic Testing.

INTRODUCTION AND OBJECTIVES: Long QT syndrome is an inherited ion channelopathy that leads to syncope and sudden death. Because of the heterogeneous phenotype of this disease, genetic testing is fundamental to detect individuals with concealed long QT syndrome. In this study, we determined the features of a family with 13 carriers of the KCNH2-H562R missense mutation, which affects the pore region of the HERG channel. METHODS: We identified the KCNH2-H562R mutation in a 65-year-old man with a prolonged QTc interval who had experienced an episode of torsade de pointes. Subsequently, a total of 13 mutation carriers were identified in the family. Carriers (age 48 [26] years; 46% males) underwent clinical evaluation, electrocardiography and echocardiography. RESULTS: The mean (standard deviation) QTc in carriers was 493 (42) ms (3 [23%] showed normal QTc); 6 (46%) had symptoms (4, syncope; 1, sudden death; 1, aborted sudden death [proband]). While under treatment with beta-blockers, 11 of 12 carriers (92%) remained asymptomatic at 5 years of follow-up (1 patient required left cardiac sympathectomy). The QTc shortening with beta-blockers was 50 (37) ms. There was 1 sudden death in a patient who refused treatment. CONCLUSIONS: Family study is essential in the interpretation of a genetic testing result. This article describes the heterogeneous and variable phenotype of a large family with the KCNH2-H562R mutation and highlights the role of genetic study for the appropriate identification of at-risk individuals who would benefit from treatment.

Narrow irregular QRS tachycardia with AV dissociation: what is the mechanism?

A 39-year-old woman with no structural heart disease and frequent episodes of sudden onset palpitations was referred for the electrophysiological study. During the study, a slightly irregular narrow QRS tachycardia with AV dissociation was repeatedly induced and spontaneously terminated. Apparently, irregular cycles and termination of the tachycardia were related to the dissociated sinus rhythm: atrial depolarizations timed when the AV junction was refractory were able to reset the tachycardia, while early atrial depolarizations caused its termination. This observation was enough to diagnose the tachycardia mechanism in our case.

Multiple interatrial electrical connection after heart transplantation.

A 62-year-old woman who underwent heart transplantation 6 years later presented a regular atrial tachycardia. Electrophysiologic evaluation showed an atrial arrhythmia in the recipient atrium with 2:1 conduction to the donor atrium, with a confusing electroanatomical map. With the suspect of alternant conduction through two different breakthroughs, the map was split in two concordant maps, corresponding to two connections that were successfully ablated. Later on, a third connection was detected and therefore ablated.

[Phrenic nerve identification with cardiac multidetector computed tomography]. / Identificación del nervio frénico con tomografía computarizada cardiaca multidetector.

Cryoballoon ablation of the pulmonary veins is a new technique that has proven useful in preventing paroxysmal and persistent atrial fibrillation recurrence. One of the most serious complications of this method is right phrenic nerve palsy. The usefulness of multidetector computed tomography to locate the right phrenic nerve and artery and predict the risk of phrenic nerve palsy during cryoablation according to the distance between the right phrenic neurovascular bundle and the right superior pulmonary vein ostium has recently been described. Fifty-five consecutive patients with paroxysmal atrial fibrillation (52 ± 12 years) underwent balloon cryoablation, following multidetector computed tomography to measure the pulmonary veins. We were able to identify segments of the right pericardiacophrenic artery (mean length 25 mm [range 7-68 mm]) in only 10 patients (20%).

Premature ventricular complexes as a trigger for ventricular fibrillation.

INTRODUCTION AND OBJECTIVES: The mechanisms that trigger ventricular fibrillation (VF) are poorly understood. The aim of this study was to analyze the initiation of VF in electrograms stored in implantable cardioverter-defibrillators (ICDs). METHODS: We analyzed ICD electrograms from patients who had suffered at least one episode of VF. RESULTS: Of 250 patients with ICDs, 13 (10 male and 3 female, age 49+/-22 years) had at least one episode of VF. The diagnoses were Brugada syndrome (n=4), ischemic heart disease (n=3), dilated cardiomyopathy (n=2), hypertrophic cardiomyopathy (n=1), short-coupled variant of torsades de pointes (n=1), endocardial fibroelastosis (n=1) and idiopathic VF (n=1). In 7 patients, VF was the reason for ICD implantation. Overall, 31 episodes of VF were recorded, including three episodes of arrhythmic storm. In the 7 patients who had more than one episode of VF (within minutes or up to 3 years apart), all episodes started with premature ventricular complexes (PVCs) that had the same morphology and similar coupling intervals. A short-long-short cycle was observed in 2 patients. In 21 episodes, PVCs that did not trigger VF were observed during sinus rhythm. There was no significant difference between them and PVCs that did trigger VF in terms of morphology, coupling interval (409+/-121 ms vs. 411+/-123 ms) or the preceding sinus rhythm RR interval (801+/-233 ms vs. 793+/-230 ms). CONCLUSIONS: Spontaneous VF in the form of an arrhythmic storm or an isolated episode were triggered by PVCs. On occasions, PVCs preceded VF without triggering it.

Same morphology of ventricular premature complexes triggering repeated ventricular fibrillation.

BACKGROUND: Episodes ventricular fibrillation (VF) initiated by ventricular premature complexes (VPCs) of a single morphology have been reported. However, the characteristics of the VPCs over long periods of time are unknown. OBJECTIVES: To compare the morphologies and coupling intervals of VPCs that initiate episodes of VF that occur at different time periods. METHODS: The database of the follow-up of the International Classification of Diseases (ICD) unit was reviewed and patients having at least two spontaneous VF episodes with available recorded EGMs in unipolar and bipolar configuration were included in the study. The coupling interval and morphology of the initiating beat were analyzed. RESULTS: Nine out of 300 patients with ICD had two or more spontaneous VF episodes. The time interval between episodes ranged from seconds (arrhythmic storm) to 3 years. The fibrillatory VPCs presented the same morphology in both recordings in all episodes of each patient. The coupling intervals of VPCs initiating VF were close for the episodes that occurred during a single arrhythmic storm and were more variable when the time intervals between episodes of VF were longer. CONCLUSION: VPCs triggering VF that occur at different times in the same patient have similar morphologies suggesting similar sites of origin for the initial VPC of VF in each patient.

ICD proarrhythmia as a consequence of an interaction with an algorithm to prevent atrial arrhythmias.

An episode of device-related proarrhythmia is reported. Ventricular tachycardia was induced by ventricular pacing in a dual-chamber implantable cardioverter-defibrillator due to an inappropriate interaction of programmed device settings with the atrial preference pacing, an automatic algorithm designed to prevent atrial tachyarrhythmias.

[Influence of gender on the clinical characteristics and prognosis of patients hospitalized for heart failure]. / Influencia del sexo en el perfil clínico y pronóstico de la insuficiencia cardiaca tras el alta hospitalaria.

BACKGROUND AND OBJECTIVES: The natural history of heart failure (HF) may be different in women due to their clinical characteristics, treatment and prognosis being distinct. Our aim was to describe the differential characteristics of women hospitalized with HF. METHODS: We prospectively studied consecutive patients who were discharged with a diagnosis of HF (n=412). Clinical, laboratory, echocardiographic, and therapeutic variables were recorded at discharge. During follow-up (16 [9] months), all-cause mortality and the need for rehospitalization were recorded. RESULTS: Compared with men, women (n=157, 38%) were older (75 [12] years vs. 71 [18] years, P< .001), had a higher prevalence of arterial hypertension (71% vs. 51%, P< .001), had more frequently been previously hospitalized for HF (36% vs. 25%, P=.02), had a higher prevalence of HF with a preserved left ventricular ejection fraction (LVEF) (44% vs. 21%, P<001), had less coronary disease (34% vs. 49%, P=.007), had more hypertensive cardiomyopathy (17% vs. 8%, P=.006), had worse renal function (52 [25] vs. 58 [25] mL/min per 1.73m2, P=.002), and had lower hemoglobin levels (12.1 [1.7] vs. 12.9 [1.9] g/dL, P< .001). This clinical profile resulted in less use of coronary angiography (22% vs. 37%, P=.001), antiplatelet drugs (45% vs. 62%, P=.001), and beta-blockers (39% vs. 50%, P=.03). In addition, women received statin treatment less often (31% vs. 45%, P=.003). Nevertheless, mortality (23% vs. 18%, P=.26) and the rehospitalization rate (44% vs. 46%, P=.81) were similar. In women, age (hazard ratio [HR] = 1.05, 95% confidence interval [CI] 1.01-1.09; P=.036) and anemia (HR = 2.43, 95% CI 1.16-5.12; P=.015) were independent predictors of death. CONCLUSIONS: Women hospitalized for HF had a distinct clinical profile: their LVEF was greater and they more frequently had comorbid conditions. This led to different treatment, though prognosis was similar to that in men.

[Clinical determinants and prognostic value of hemoglobin in hospitalized patients with systolic heart failure]. / Determinantes clínicos y valor pronóstico de la hemoglobina en pacientes hospitalizados con insuficiencia cardiaca sistólica.

INTRODUCTION AND OBJECTIVES: Anemia is a common finding in outpatients with heart failure (HF) and is associated with increased mortality. The aims of this study were to identify determinants of the hemoglobin level in a large group of hospitalized patients with systolic HF and to investigate the medium-term prognostic value of the hemoglobin level. METHODS: The study included 460 consecutive patients (age 68.3 [12.3] years, 74% male) who were hospitalized with a diagnosis of HF and left ventricular systolic dysfunction (i.e., a left ventricular ejection fraction <45%). At hospital discharge, biochemical and hematological parameters were measured and clinical and echocardiographic variables were recorded. Patients were followed up for 16.8[9.7] months. RESULTS: Anemia, as defined by World Health Organization criteria, was present in 189 (41.1%) patients. The following independent determinants of the hemoglobin level were identified: age (relative risk [RR]=1.035, 95% CI, 1.011-1.060; P=.004), female sex (RR=1.843, 95% CI, 1.083-3.135; P=.024), diabetes mellitus (RR=1.413, 95% CI, 1.087-1.838; P=.010), plasma urea level (RR=1.013, 95% CI, 1.005-1.022; P=.001), and loop diuretic use (RR=2.801, 95% CI, 1.463-5.364; P=.002). A decrease in hemoglobin level was associated with increased risks of death (RR per g/dL=1.232, 95% CI, 1.103-1.375; P<.001) and death or HF readmission (RR per g/dL=1.152, 95% CI, 1.058-1.255; P<.001), but not with readmission for non-fatal HF (RR per g/dL=1.081, 95% CI, 0.962-1.215; P=.265). Blood transfusion during hospitalization did not alter the increased risk of death (RR=2.19, 95% CI 1.40-3.41; P=.001). CONCLUSIONS: In hospitalized patients with systolic HF, the hemoglobin level at hospital discharge was an independent predictor of death in the medium term, but not of readmission for non-fatal HF. The main determinants of the hemoglobin level were age, sex, renal function, diabetes, and the need for diuretics.