Percutaneous left atrial appendage occlusion: impact on left atrial deformation indices.

BACKGROUND: Percutaneous left atrial appendage occlusion (LAAO) is an accepted alternative to thromboprophylaxis in patients with atrial fibrillation (AF) who are: (i) intolerant to oral anticoagulation (OAC) (e.g. life-threatening haemorrhage), (ii) non-adherent to OAC, or (iii) at a high bleeding risk with OAC. Improvement in LA mechanics was shown post-LAAO in the LAFIT-LARIAT study, using the Lariat device. No significant change was seen in LA mechanics after LAAO with the Watchman device in the LAFIT-Watchman study. The impact of LAAO with the Amplatzer or Amulet device on LA deformation mechanics has not been investigated. PURPOSE: To evaluate the impact of LAAO with the Amplatzer or Amulet device on echocardiographic LA deformation indices. METHODS: All patients undergoing percutaneous LAAO from 2013 to 2021 at a single centre were included from an ongoing clinical registry. LA reservoir (εreservoir), conduit (εconduit) and contractile strain (εcontractile) and strain rate (SRreservoir, SRconduit, SRcontractile) were assessed with two-dimensional speckle tracking echocardiography from an apical four-chamber view. Conduit and contractile strain and strain rates were only recorded for patients without AF at the time of echocardiography. Changes in LA deformation indices over time were compared with a linear mixed model. RESULTS: 28 LAAO recipients (mean age 73 ± 12 years, 68% male) were analysed. 5 (18%) patients had AF pre- or post-procedure. After a mean follow-up of 1.6 ± 1.4 months, the mean LA εreservoir increased from 10.15 ± 6.44% to 10.18 ± 8.72% (p = 0.985), the mean LA εconduit increased from 5.12 ± 5.48% to 5.31 ± 6.11% (p = 0.891) and the mean LA εcontractile decreased from 5.14 ± 4.32% to 4.95 ± 5.30% (p = 0.898). During the same time interval, the mean LA SRreservoir decreased from + 0.54 ± 0.23.s- 1 to + 0.48 ± 0.43.s- 1 (p = 0.566), the mean LA SRconduit remained stable: -0.47 ± 0.41.s- 1 to -0.47 ± 0.32.s- 1 (p = 0.997) and the mean LA SRcontractile decreased from - 0.66 ± 0.50.s- 1 to -0.55 ± 0.46.s- 1 (p = 0.660). CONCLUSION: No significant improvement in LA mechanical function was seen after LAAO with the Amplatzer or Amulet device. Different LAAO devices therefore appear to have divergent effects on LA deformation, the clinical implications of which may warrant further study.

Mutation location and IKs regulation in the arrhythmic risk of long QT syndrome type 1: the importance of the KCNQ1 S6 region.

AIMS: Mutation type, location, dominant-negative IKs reduction, and possibly loss of cyclic adenosine monophosphate (cAMP)-dependent IKs stimulation via protein kinase A (PKA) influence the clinical severity of long QT syndrome type 1 (LQT1). Given the malignancy of KCNQ1-p.A341V, we assessed whether mutations neighbouring p.A341V in the S6 channel segment could also increase arrhythmic risk. METHODS AND RESULTS: Clinical and genetic data were obtained from 1316 LQT1 patients [450 families, 166 unique KCNQ1 mutations, including 277 p.A341V-positive subjects, 139 patients with p.A341-neighbouring mutations (91 missense, 48 non-missense), and 900 other LQT1 subjects]. A first cardiac event represented the primary endpoint. S6 segment missense variant characteristics, particularly cAMP stimulation responses, were analysed by cellular electrophysiology. p.A341-neighbouring mutation carriers had a QTc shorter than p.A341V carriers (477 ± 33 vs. 490 ± 44 ms) but longer than the remaining LQT1 patient population (467 ± 41 ms) (P < 0.05 for both). Similarly, the frequency of symptomatic subjects in the p.A341-neighbouring subgroup was intermediate between the other two groups (43% vs. 73% vs. 20%; P < 0.001). These differences in clinical severity can be explained, for p.A341V vs. p.A341-neighbouring mutations, by the p.A341V-specific impairment of IKs regulation. The differences between the p.A341-neighbouring subgroup and the rest of LQT1 mutations may be explained by the functional importance of the S6 segment for channel activation. CONCLUSION: KCNQ1 S6 segment mutations surrounding p.A341 increase arrhythmic risk. p.A341V-specific loss of PKA-dependent IKs enhancement correlates with its phenotypic severity. Cellular studies providing further insights into IKs-channel regulation and knowledge of structure-function relationships could improve risk stratification. These findings impact on clinical management.

Renal Denervation in High-risk Patients with Hypertension.

Hypertension is a common health problem, which leads to a substantial mortality and morbidity burden, globally. The management of patients with high-risk and treatment-resistant hypertension remains a major clinical challenge to the treating physician. Renal denervation (RD) is an emerging technique, comprising modification of the renal sympathetic nerve supply which courses around the renal arteries. Endovascular access is obtained to the renal arteries, followed by delivery of heat energy to the peri-renal sympathetic nerves. This leads to the reduction of blood pressure with or without the addition of anti-hypertensive pharmacotherapy. Earlier trials led to clinical equipoise, but more recent trials (e.g. SPYRAL HTN-OFF MED, SPYRAL HTN-ON MED and RADIANCE-HTN SOLO), which were designed to overcome the limitations of the initial studies, have provided support for the efficacy of RD in hypertension management. Evidence (from randomised, non-randomised, sham-controlled and non-sham-controlled trials) for the use of RD in the treatment of hypertension is reviewed in this article. Finally, the current clinical role, gaps in evidence, and the expected future evolution of RD are discussed.

Does pregnancy increase cardiac risk for LQT1 patients with the KCNQ1-A341V mutation?

OBJECTIVES: The purpose of this study was to assess the pregnancy-related cardiovascular risk in LQT1 patients. BACKGROUND: Only 1 study addressed this issue in genotyped patients and reported that the highest risk is for LQT2 patients. METHODS: This case-control study, performed in a cohort of patients from 22 families affected by LQT1 and all sharing the common KCNQ1-A341V mutation, involved 36 mutation carriers and 24 of their unaffected sisters for a total of 182 pregnancies. RESULTS: There were 3 (2.6%) cardiac events (2 cardiac arrests) in the 115 LQT1 pregnancies. Because they occurred only among the 27 mothers with previous symptoms, all off-therapy, the risk for symptomatic patients is 11%, but decreases to 0 in symptomatic patients treated with beta-blockers. Carriers and control subjects did not differ for the incidence of miscarriage (10% vs. 15%). Cesarean sections (C-sections), elective or owing to fetal distress, were performed more often in carriers than in non-carriers (27% vs. 14%). Beta-blocker therapy did not influence the prevalence of fetal distress. Among the infants born to carriers, all those with fetal distress were carriers of the A341V mutation (10 of 10, 100%). Among the offspring of the carriers, 48 of 92 (52%) were mutation carriers, and of those, 15% died suddenly at age 14 +/- 6 years. CONCLUSIONS: Women affected by the common KCNQ1-A341V mutation are at low risk for cardiac events during pregnancy and without excess risk of miscarriage; their infants delivered by C-section because of fetal distress are extremely likely to also be mutation carriers. Beta-blockers remain recommended. These conclusions likely apply to most LQT1 patients.