Aims
Atrial fibrillation (AF) worsens the prognosis of patients with heart failure (HF). Successful treatments are still very scarce for those with permanent AF and preserved (HFpEF) or mildly ...reduced (HFmrEF) ejection fraction. In this study, the long‐term benefits and safety profile of heart rate regularization through left‐bundle branch pacing (LBBP) and atrioventricular node ablation (AVNA) will be explored in comparison with pharmacological rate‐control strategy.
Methods and results
The PACE‐FIB trial is a multicentre, prospective, open‐label, randomized (1:1) clinical study that will take place between March 2022 and February 2027. A total of 334 patients with HFpEF/HFmrEF and permanent AF will receive either LBBP followed by AVNA (intervention arm) or optimal pharmacological treatment for heart rate control according to European guideline recommendations (control arm). All patients will be followed up for a minimum of 36 months. The primary outcome measure will be the composite of all‐cause mortality, HF hospitalization, and worsening HF at 36 months. Other secondary efficacy and safety outcome measures such as echocardiographic parameters, functional status, and treatment‐related adverse events, among others, will be analysed too.
Conclusion
LBBP is a promising stimulation mode that may foster the clinical benefit of heart rate regularization through AV node ablation compared with pharmacological rate control. This is the first randomized trial specifically addressing the long‐term efficacy and safety of this pace‐and‐ablate strategy in patients with HFpEF/HFmrEF and permanent AF.
Compatibility of DiamondTemp (DT) radiofrequency (RF) catheter with the Rhythmia mapping system has not been manufacturer-reported nor its tracking accuracy reported.
Consecutive patients undergoing ...macroreentrant atrial tachycardia ablation guided by Rhythmia and ablated using DT were prospectively enrolled. Following catheter configuration, ablation lines were performed and remapped to measure the RF tag to effective-ablation-line-center (RFT-ALC) distance.
Among 20 consecutive patients (54 maps), 40 ablation lines were evaluated. Overall, the RFT-ALC distance was 3.88 ± 2.95 mm, and the operator assessment of accuracy was high. No complications occurred.
The use of DT catheter guided by the Rhythmia mapping system is feasible and accurate.
The coronavirus 2019 disease (COVID‐19) pandemic threatened the Spanish health‐care system. Patients with demanding conditions such as precapillary pulmonary hypertension (PH) faced a potentially ...severe infection, while their usual access to medical care was restricted. This prospective, unicentric study assessed the impact of COVID‐19 on PH patients' outcomes and the operational changes in the PH network. Sixty‐three PH patients (41 pulmonary arterial hypertension PAH; 22 chronic thromboembolic pulmonary hypertension CTEPH) experienced COVID‐19. Overall mortality was 9.5% without differences when stratifying by hemodynamics or PAH‐risk score. Patients who died were older (73.6 ± 5 vs. 52.2 ± 15.4; p = 0.001), with more comorbidities (higher Charlson index: 4.17 ± 2.48 vs. 1.14 ± 1.67; p = 0.0002). Referrals to the PH expert center decreased compared to the previous 3 years (123 vs. 160; p = 0.002). The outpatient activity shifted toward greater use of telemedicine. Balloon pulmonary angioplasty activity could be maintained after the first pandemic wave and lockdown while pulmonary thromboendarterectomy procedures decreased (19 vs. 36; p = 0.017). Pulmonary transplantation activity remained similar. The COVID‐19 mortality in PAH/CTEPH patients was not related to hemodynamic severity or risk stratification, but to comorbidities. The pandemic imposed structural changes but a planned organization and resource reallocation made it possible to maintain PH patients' care.
The
and
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 (I
) recorded in HL-1 cardiomyocytes.
mRNA can be detected in human atrial and ventricular samples. In HL-1 cardiomyocytes, transfection of Zfhx3 strongly reduced peak I
density, while the silencing of endogenous expression augmented it (from -65.9 ± 8.9 to -104.6 ± 10.8 pA/pF;
≥ 8,
< 0.05). Zfhx3 significantly reduced the transcriptional activity of human
,
,
, and
minimal promoters. Consequently, the mRNA and/or protein expression levels of Nav1.5 and Tbx5 were diminished (
≥ 6,
< 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 I
density and time- and voltage-dependent properties in WT. WT Zfhx3 inhibits I
as a result of a direct repressor effect on the
promoter, the modulation of Tbx5 increasing on the I
, and the increased expression of Nedd4-2. We propose that this TF participates in the control of cardiac excitability in human adult cardiac tissue.
Chronic kidney disease (CKD) is associated with increased propensity for arrhythmias. In this context, ventricular repolarization alterations have been shown to predispose to fatal arrhythmias and ...sudden cardiac death. Between mineral bone disturbances in CKD patients, increased fibroblast growth factor (FGF) 23 and decreased Klotho are emerging as important effectors of cardiovascular disease. However, the relationship between imbalanced FGF23-Klotho axis and the development of cardiac arrhythmias in CKD remains unknown.
We carried out a translational approach to study the relationship between the FGF23-Klotho signaling axis and acquired long QT syndrome in CKD-associated uremia. FGF23 levels and cardiac repolarization dynamics were analyzed in patients with dialysis-dependent CKD and in uremic mouse models of 5/6 nephrectomy (Nfx) and Klotho deficiency (hypomorphism), which show very high systemic FGF23 levels.
Patients in the top quartile of FGF23 levels had a higher occurrence of very long QT intervals (> 490 ms) than peers in the lowest quartile. Experimentally, FGF23 induced QT prolongation in healthy mice. Similarly, alterations in cardiac repolarization and QT prolongation were observed in Nfx mice and in Klotho hypomorphic mice. QT prolongation in Nfx mice was explained by a significant decrease in the fast transient outward potassium (K
) current (I
), caused by the downregulation of K
channel 4.2 subunit (Kv4.2) expression. Kv4.2 expression was also significantly reduced in ventricular cardiomyocytes exposed to FGF23. Enhancing Klotho availability prevented both long QT prolongation and reduced I
current. Likewise, administration of recombinant Klotho blocked the downregulation of Kv4.2 expression in Nfx mice and in FGF23-exposed cardiomyocytes.
The FGF23-Klotho axis emerges as a new therapeutic target to prevent acquired long QT syndrome in uremia by minimizing the predisposition to potentially fatal ventricular arrhythmias and sudden cardiac death in patients with CKD.
Objective: To report the case of a successful pregnancy outcome in a severely symptomatic woman affected by catecholaminergic polymorphic ventricular tachycardia (CPVT) carrier of a novel variant in ...ryanodine receptor 2 (RYR2) followed by a review of the current literature. Case(s): A 27-year-old primigravida affected by CPVT was referred to our tertiary care hospital after an implantable cardioverter defibrillator (ICD) shock. The patient also received medical treatment with metoprolol and flecainide. A healthy baby was born by Cesarean section at 31 weeks after the onset of preterm labor and premature rupture of membranes. CPVT is a rare inherited cardiac condition characterized by episodic polymorphic ventricular arrhythmias with a structurally normal heart. These are usually triggered by exercise or emotional stress and can lead to syncope or even sudden cardiac death. Treatment of this condition comprises betablockers in isolation or in addition to other antiarrhythmics, left cardiac sympathetic denervation and/or ICD. Conclusion: This case illustrates the importance of a multidisciplinary approach in this clinical scenario and the benefits of an optimization of the medical treatment, and demonstrates that, even in severely affected patients, a successful pregnancy is possible under close control. However, the risk of arrhythmic events and the course of pregnancy remain largely unknown in patients with CPVT, and further investigation is needed.
Aims
Women may have different management patterns than men in specialised care. Our aim was to assess potential sex differences in referral, management and outcomes of patients attending outpatient ...cardiac consultations.
Methods and results
Retrospective observational analysis of patients ≥18 years referred for the first time from primary care to a tertiary hospital cardiology clinic in 2017–2018, comparing reasons for referral, decisions and post-visit outcomes by sex.
A total of 5,974 patients, 2,452 (41.0%) men aged 59.2 ± 18.6 years and 3,522 (59.0%) women aged 64.5 ± 17.9 years (
P
< 0.001) were referred for a first cardiology consultation. The age-related referral rates were higher in women. The most common reasons for consultation were palpitations in women (
n
= 676; 19.2%) and ECG abnormalities in men (
n
= 570; 23.2%). Delays to cardiology visits and additional tests were similar. During 24 months of follow-up, women had fewer cardiology hospitalisations (204; 5.8% vs. 229; 9.3%;
P
= 0.003) and lower mortality (65; 1.8% vs. 66; 2.7%;
P
= 0.028), but those aged <65 years had more emergency department visits (756; 48.5% vs. 560; 39.9%,
P
< 0.001) than men.
Conclusion
There are substantial sex differences in primary care cardiology referral patterns, including causes, rates, decisions and outcomes, which are only partially explained by age differences. Further research is needed to understand the reasons for these differences.
Telemonitoring through multiple variables measured on cardiac devices has the potential to improve the follow-up of patients with heart failure. The HeartLogic algorithm (Boston Scientific), ...implemented in some implantable cardiac defibrillators and cardiac resynchronisation therapy, allows monitoring of the nocturnal heart rate, respiratory movements, thoracic impedance, physical activity and the intensity of heart tones, with the aim of predicting major clinical events. Although HeartLogic has demonstrated high sensitivity for the detection of heart failure decompensations, its effects on hospitalisation and mortality in randomised clinical trials has not yet been corroborated. This review details how the HeartLogic algorithm works, compiles available evidence from clinical studies, and discusses its application in daily clinical practice.
PDF
