Digoxin is frequently used for rate control of atrial fibrillation (AF). It has, however, been associated with increased mortality. It remains unclear whether digoxin itself is responsible for the increased mortality (toxic drug effect) or whether it is prescribed to sicker patients with inherently higher mortality due to comorbidities. The goal of our study was to determine the relationship between digoxin and mortality in patients with AF. The association between digoxin and mortality was assessed in patients enrolled in the AF Follow-Up Investigation of Rhythm Management (AFFIRM) trial using multivariate Cox proportional hazards models. Analyses were conducted in all patients and in subsets according to the presence or absence of heart failure (HF), as defined by a history of HF and/or an ejection fraction <40%. Digoxin was associated with an increase in all-cause mortality [estimated hazard ratio (EHR) 1.41, 95% confidence interval (CI) 1.19–1.67, P < 0.001], cardiovascular mortality (EHR 1.35, 95% CI 1.06–1.71, P = 0.016), and arrhythmic mortality (EHR 1.61, 95% CI 1.12–2.30, P = 0.009). The all-cause mortality was increased with digoxin in patients without or with HF (EHR 1.37, 95% CI 1.05–1.79, P = 0.019 and EHR 1.41, 95% CI 1.09–1.84, P = 0.010, respectively). There was no significant digoxin–gender interaction for all-cause (P = 0.70) or cardiovascular (P = 0.95) mortality. Digoxin was associated with a significant increase in all-cause mortality in patients with AF after correcting for clinical characteristics and comorbidities, regardless of gender or of the presence or absence of HF. These findings call into question the widespread use of digoxin in patients with AF.
Optimal cryoballoon ablation parameters for pulmonary vein (PV) isolation remain to be defined. We conducted a randomized preclinical trial to compare 2- versus 4-minute ablation lesions and assess the safety of active (forced) cryoballoon deflation.Thirty-two dogs underwent PV isolation with a second-generation 23 mm cryoballoon catheter. The left superior (LSPV) and inferior (LIPV) PVs were randomized in a factorial design to (1) a single 2- versus 4-minute cryoapplication, and (2) passive versus active cryoballoon deflation. Animals were survived for 30 days, after which histopathologic analysis was performed. Acute PV isolation was attained in 89.8% of PVs after a single application (93.8% LSPV, 85.2% LIPV; P = 0.2823). Mean time to PV isolation was 29.5 ± 18.5 seconds. Although 4-minute lesions were associated with a thicker neointima than 2-minute lesions (223.8 μm versus 135.6 μm; P = 0.007), no differences were observed in procedural characteristics (freezing temperature, rewarming time), rates of acute PV isolation, or the achievement of complete circumferentially transmural lesions at 30 days (78.7% overall; 86.2% for 2 minutes vs 70.0% for 4 minutes; P = 0.285). Active deflation was associated with faster balloon rewarming but not with significant differences in mean or maximum neointimal thickness.A single application with the second-generation cryoballoon catheter results in a high rate of PV isolation. The degree of vascular injury was not increased by active balloon deflation and no differences in acute efficacy or mature transmural circumferential lesions were observed with 2- versus 4-minute applications.
Introduction: Cardiac Resynchronization Therapy (CRT) with simultaneous biventricular pacing (BiVP) is recommended for patients with heart failure and wide QRS, however up to a third of patients do not respond. GREATER-EARTH has demonstrated similar benefits with BiVP or LV pacing (LVP). Herein, we evaluate the effects of these two CRT modes on cardiac remodeling, evaluated by echocardiography and circulating biomarkers. Methods: 121 patients (LVEF≤35% and QRS≥120ms) referred for defibrillator implantation were randomized to BiVP or LVP for consecutive 6-month periods with cross-over. The primary endpoint was the change in LV end-systolic volume (LVESV) between patients with BiVP vs LVP from baseline to 6 months. Secondary endpoints included changes in LVEF, mitral regurgitation, RV and diastolic function. Changes in levels of markers of cardiac remodeling were also compared. Results: Both CRT pacing modes led to remodeling benefits after 6-months of therapy: LVESV decreased from 162±57mL at baseline to 130±63mL with BiVP vs 130±60 mL with LVP (p=0.68 between CRTs), with a positive response (≥15% LVESV reduction) being observed in 49% of patients with BiVP and 33% of LVP, p=0.09. Similarly, RV remodeling (dimension and RV-MPI) was equally improved with both pacing strategies (p=0.69 and p=0.38 respectively, between CRTs). Interestingly, estimated systolic PAP (from 43±14 to 37±10 and 41±14, p=0.008), selected indices of LV diastolic function such as indexed LA volume (p=0.045) and diastolic dysfunction grade (p=0.019), as well as changes in MR grade (p=0.004) were significantly improved only with BiVP. In parallel, there was a non-statistically significant decrease in NT-proBNP, from 2559±3296 to 1554±2092 and 1630±1950 ng/L, with BiVP and LVP respectively (p=0.093) as well as a trend in decreasing PIIINP levels, from 8.3±3.0 to 7.5±2.7 and 7.6±2.3 with BiVP and LVP respectively, p=0.097. Conclusions: In this prospective, multicenter, randomized, double-blind study, both BiVP and LVP resulted in improvements in LV remodelling assessed by echocardiography, while more patients responded to BiVP. BiVP may be superior to LVP to improve multiple aspects of myocardial remodeling and should remain the preferred mode of CRT in patients with advanced HF.
Purpose: Transcatheter closure of peri-membranous ventricular septal defects (pmVSDs) has been associated with a significant risk of complete heart block, leading most groups to abandon the technique. We describe the initial world experience of pmVSD closure with a newly designed occluder. Methods: Patients with pmVSD underwent catheter closure using the Amplatzer® Membranous VSD Occluder 2 (St. Jude Medical, MN, USA). Results: Nineteen patients from the 4 centers initially involved worldwide were prospectively included and followed for a 12±3 months. Patients ranged in age from 1.4 to 62 years (median 6 years) and in weight from 9.3 to 96 kg (median26 kg). The Qp/Qs ratio was (mean ± SD) 1.9±1.6. The size of the defect on left ventricular side was (mean ± SD) 9.9±3.5 mm (range 4.6 – 16 mm) and the orifice on right ventricularside was 8.1±2.8 mm (range 3.9 – 14 mm) by echocardiography. Mean device size was 9.4±2.4 mm (range 5 – 14 mm). An eccentric device was used in 9 patients (47%) and a concentric device in 10 (53%). A device was successfully implanted in 18 patients (95%). Procedural time was 122±39 min (range 60 – 207 min). There were no significant procedural complications. Mild (0-2 mm) residual shunt was initially observed in 14 patients (78%). At last follow-up, mild residual shunt was still observed in only 3 patients (17%). There was no significant increase of aortic or tricuspid regurgitation, compared to pre-catheterization levels. No patient showed conduction abnormalities on the ECG, and 17 out of 18 had a Holter evaluation, which was normal in all. Conclusions: Transcatheter closure of pmVSD with the Amplatzer pmVSD Occluder 2 is safe and effective. No conduction abnormalities or any other complications were observed on short and one-year follow of this initial human series.
Key Teaching Points•When a pacemaker fails to record a ventricular high-rate (VHR) event, true vs functional undersensing should be considered.•True undersensing refers to failure to detect a VHR event owing to small-amplitude intrinsic signals or the nature of the sensing algorithm.•Functional undersensing occurs if the episode fails to meet the definition of a VHR or is not detected as a result of the way in which refractory or blanking periods are programmed.•Functional undersensing of sustained ventricular tachycardia can occur with Biotronik pacemakers if the ventricular rate exceeds 240 beats per minute owing to the fact that the ventricular refractory period is nominally set to 250 ms and that sensed beats that fall within this refractory period do not increase the VHR counter. •When a pacemaker fails to record a ventricular high-rate (VHR) event, true vs functional undersensing should be considered.•True undersensing refers to failure to detect a VHR event owing to small-amplitude intrinsic signals or the nature of the sensing algorithm.•Functional undersensing occurs if the episode fails to meet the definition of a VHR or is not detected as a result of the way in which refractory or blanking periods are programmed.•Functional undersensing of sustained ventricular tachycardia can occur with Biotronik pacemakers if the ventricular rate exceeds 240 beats per minute owing to the fact that the ventricular refractory period is nominally set to 250 ms and that sensed beats that fall within this refractory period do not increase the VHR counter.
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Introduction: Late complications after tetralogy of Fallot repair (rTOF) often arise from chronic pulmonary regurgitation (PR). Prospective studies of outcomes in those with rTOF and significant PR are lacking. Hypothesis: We hypothesized that cardiovascular magnetic resonance imaging (CMR) imaging measurements would be associated with poor outcomes in an “at risk” population with rTOF and ≥moderate PR. Methods: This was a prospective, international study (North America, Europe and Asia) of children and adults. Inclusion criteria were rTOF in childhood, age ≥12 years, ≥moderate PR, and CMR within 18 months of enrollment. All CMR analysis occurred in a central core laboratory. Patient reported outcomes were collected using standardized tools. The primary clinical outcome was death or sustained (>30 seconds) ventricular tachycardia (VT) recorded at 3 year follow-up. Results: We enrolled 629 patients (55% male) at 29±14 years (2013-2017). Primary rTOF was done at 1.6 years (IQR 0.6,4.2) with a transannular patch in 55%. By standardized symptom assessment, 78% were asymptomatic (NYHA 1). Baseline CMR findings included PR fraction 38±14%, right ventricular (RV) end-diastolic volume indexed (EDVi) 155±41mL/m2, RV ejection fraction (EF) 44±7%, RV mass indexed 59±16 g/m2, left ventricular (LV) EDVi 85±18mL/m2, LVEF 55±7% and LV mass indexed 88±27 g/m2. Outcomes at 3 years were recorded (available in n=101). During follow-up, surgical pulmonary valve replacement (PVR) occurred in 38 patients (38%). In the PVR group compared with the non-PVR group, baseline RVEDVi was larger (189 vs. 152 mL/m2, p<0.0001) and RV mass was higher (65 vs. 58 g/m2, p=0.04); RVEF, LVEF and LV mass did not differ between groups. At 3 year follow-up, 4 patients (4%) had an outcome (n=2 deaths, n=2 VT) and half of these patients (n=2) had PVR. Those with outcomes had higher baseline RV mass and LV mass as compared to those without outcomes (73±12 vs. 59±13g/m2, p=0.04 and 132±32 vs. 89±28g/m2, p=0.01); volumes and function did not differ between groups. Conclusions: Despite significant PR, most patients with rTOF were asymptomatic. At 3 year follow-up, PVR occurred in more than one third of patients. Death or VT was observed in a small number of patients who had higher RV and LV mass on baseline CMR.
