Complications following transcatheter edge-to-edge mitral valve repair: Personal experience and review of the literature

Mitral valve dysfunction affects around 2% of the population and its incidence is still increasing, making it the second most common valvular heart disease, after aortic stenosis. Depending on the etiology of the disease, it can be classified into primary or secondary mitral regurgitation. The first line of treatment is optimal medical therapy. If ineffective, mitral valve intervention can be considered. For patients disqualified from surgical treatment, transcatheter edge-to-edge repair with the use of MitraClip may be considered. Over 100,000 MitraClip procedures have been performed which makes this the most established transcatheter technique for the treatment of severe mitral regurgitation. The aim of this review is to discuss the technical details of the MitraClip procedure, clinical evidence regarding the efficacy of MitraClip, complications related to the clip implantation alongside with acute complications based on the currently available evidence and clinical experience

Subadventitial stenting around occluded stents: A bailout technique to recanalize in-stent chronic total occlusions

To evaluate the outcomes of subadventitial stenting (SS) around occluded stents for recanalizing in-stent chronic total occlusions (IS-CTOs).There is little evidence on the outcomes of SS for IS-CTO.We examined the outcomes of SS for IS-CTO PCI at 14 centers between July 2011 and June 2017, and compared them to historical controls recanalized using within-stent stenting (WSS). Target-vessel failure (TVF) on follow-up was the endpoint of this study, and was defined as a composite of cardiac death, target-vessel myocardial infarction, and target-vessel revascularization.During study period, 422 IS-CTO PCIs were performed, of which 32 (7.6%) were recanalized with SS, usually when conventional approaches failed. The most frequent CTO vessel was the right coronary artery (72%). Mean J-CTO score was 3.1 ± 0.9. SS was antegrade in 53%, and retrograde in 47%. Part of the occluded stent was crushed in 37%, while the whole stent was crushed in 63%. Intravascular imaging was used in 59%. One patient (3.1%) suffered tamponade. Angiographic follow-up was performed in 10/32 patients: stents were patent in six cases, one had mild neointimal hyperplasia, and three had severe restenosis at the SS site. Clinical follow-up was available for 29/32 patients for a mean of 388 ± 303 days. The 24-month incidence of TVF was 13.8%, which was similar to historical controls treated with WSS (19.5%, P = 0.49).SS is rarely performed, usually as last resort, to recanalize complex IS-CTOs. It is associated with favorable acute and mid-term outcomes, but given the small sample size of our study additional research is warranted

Late onset of new conduction disturbances requiring permanent pacemaker implantation following TAVI

Background: The timing of onset and associated predictors of late new conduction disturbances (CDs) leading to permanent pacemaker implantation (PPI) following transcatheter aortic valve implantation (TAVI) are still unknown, however, essential for an early and safe discharge. This study aimed to investigate the timing of onset and associated predictors of late onset CDs in patients requiring PPI (LCP) following TAVI. Methods and results: We performed retrospective analysis of prospectively collected data from five large volume centres in Europe. Post-TAVI electrocardiograms and telemetry data were evaluated in patients with a PPI post-TAVI to identify the onset of new advanced CDs. Early onset CDs were defined as within 48 hours after procedure, and late onset CDs as after 48 hours. A total of 2804 patients were included for analysis. The PPI rate was 12%, of which 18% was due to late onset CDs (>48 hours). Independent predictors for LCP were pre-existing non-specific intraventricular conduction delay, pre-existing right bundle branch block, self-expandable valves and predilation. At least one of these risk factors was present in 98% of patients with LCP. Patients with a balloon-expandable valve without predilation did not develop CDs requiring PPI after 48 hours. Conclusions: Safe early discharge might be feasible in patients without CDs in the first 48 hours after TAVI if no risk factors for LCP are present

Outcome and Predictors for Mortality in Patients with Cardiogenic Shock:A Dutch Nationwide Registry-Based Study of 75,407 Patients with Acute Coronary Syndrome Treated by PCI

It is important to gain more insight into the cardiogenic shock (CS) population, as currently, little is known on how to improve outcomes. Therefore, we assessed clinical outcome in acute coronary syndrome (ACS) patients treated by percutaneous coronary intervention (PCI) with and without CS at admission. Furthermore, the incidence of CS and predictors for mortality in CS patients were evaluated. The Netherlands Heart Registration (NHR) is a nationwide registry on all cardiac interventions. We used NHR data of ACS patients treated with PCI between 2015 and 2019. Among 75,407 ACS patients treated with PCI, 3028 patients (4.1%) were identified with CS, respectively 4.3%, 3.9%, 3.5%, and 4.3% per year. Factors associated with mortality in CS were age (HR 1.02, 95%CI 1.02-1.03), eGFR (HR 0.98, 95%CI 0.98-0.99), diabetes mellitus (DM) (HR 1.25, 95%CI 1.08-1.45), multivessel disease (HR 1.22, 95%CI 1.06-1.39), prior myocardial infarction (MI) (HR 1.24, 95%CI 1.06-1.45), and out-of-hospital cardiac arrest (OHCA) (HR 1.71, 95%CI 1.50-1.94). In conclusion, in this Dutch nationwide registry-based study of ACS patients treated by PCI, the incidence of CS was 4.1% over the 4-year study period. Predictors for mortality in CS were higher age, renal insufficiency, presence of DM, multivessel disease, prior MI, and OHCA

Characteristics, Treatment Strategies and Outcome in Cardiogenic Shock Complicating Acute Myocardial Infarction:A Contemporary Dutch Cohort

Cardiogenic shock (CS) complicating acute myocardial infarction (AMI) is associated with high morbidity and mortality. Our study aimed to gain insights into patient characteristics, outcomes and treatment strategies in CS patients. Patients with CS who underwent percutaneous coronary intervention (PCI) between 2017 and 2021 were identified in a nationwide registry. Data on medical history, laboratory values, angiographic features and outcomes were retrospectively assessed. A total of 2328 patients with a mean age of 66 years and of whom 73% were male, were included. Mortality at 30 days was 39% for the entire cohort. Non-survivors presented with a lower mean blood pressure and increased heart rate, blood lactate and blood glucose levels (p-value for all &lt;0.001). Also, an increased prevalence of diabetes, multivessel coronary artery disease and a prior coronary event were found. Of all patients, 24% received mechanical circulatory support, of which the majority was via intra-aortic balloon pumps (IABPs). Furthermore, 79% of patients were treated with at least one vasoactive agent, and multivessel PCI was performed in 28%. In conclusion, a large set of hemodynamic, biochemical and patient-related characteristics was identified to be associated with mortality. Interestingly, multivessel PCI and IABPs were frequently applied despite a lack of evidence.</p

Quaking promotes monocyte differentiation into pro-atherogenic macrophages by controlling pre-mRNA splicing and gene expression

A hallmark of inflammatory diseases is the excessive recruitment and influx of monocytes to sites of tissue damage and their ensuing differentiation into macrophages. Numerous stimuli are known to induce transcriptional changes associated with macrophage phenotype, but posttranscriptional control of human macrophage differentiation is less well understood. Here we show that expression levels of the RNA-binding protein Quaking (QKI) are low in monocytes and early human atherosclerotic lesions, but are abundant in macrophages of advanced plaques. Depletion of QKI protein impairs monocyte adhesion, migration, differentiation into macrophages and foam cell formation in vitro and in vivo. RNA-seq and microarray analysis of human monocyte and macrophage transcriptomes, including those of a unique QKI haploinsufficient patient, reveal striking changes in QKI-dependent messenger RNA levels and splicing of RNA transcripts. The biological importance of these transcripts and requirement for QKI during differentiation illustrates a central role for QKI in posttranscriptionally guiding macrophage identity and function.No sponso

Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease : An Individual-Level Meta-Analysis

Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD.Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed.Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98-1.05 and rs7672915, HR: 0.97, 95% CI 0.94-1.00; rs3755863, HR: 1.02, 95% CI 0.99-1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intron 2) and the primary outcome among 1) individuals aged >= 65, 2) individuals with renal impairment, and 3) antiplatelet users.Conclusion: We found no clear associations between polymorphisms in the PPARGC1A gene and subsequent CHD events in patients with established CHD at baseline.Peer reviewe

Association of Factor V Leiden with Subsequent Atherothrombotic Events:A GENIUS-CHD Study of Individual Participant Data

BACKGROUND: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD. METHODS: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality. RESULTS: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16]; I2=28%; P-heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality were also close to identity. CONCLUSIONS: Factor V Leiden was not associated with increased risk of subsequent atherothrombotic events and mortality in high-risk participants with established and treated CHD. Routine assessment of factor V Leiden status is unlikely to improve atherothrombotic events risk stratification in this population