Percutaneous balloon aortic valvuloplasty in the era of transcatheter aortic valve implantation: a narrative review

The role of percutaneous balloon aortic valvuloplasty (BAV) in the management of severe symptomatic aortic stenosis has come under the spotlight following the development of the transcatheter aortic valve implantation (TAVI) technique. Previous indications for BAV were limited to symptom palliation and as a bridge to definitive therapy for patients undergoing conventional surgical aortic valve replacement (AVR). In the TAVI era, BAV may also be undertaken to assess the ‘therapeutic response’ of a reduction in aortic gradient in borderline patients often with multiple comorbidities, to assess symptomatic improvement prior to consideration of definitive TAVI intervention. This narrative review aims to update the reader on the current indications and practical techniques involved in undertaking a BAV procedure. In addition, a summary of the haemodynamic and clinical outcomes, as well as the frequently encountered procedural complications is presented for BAV procedures conducted during both the pre-TAVI and post-TAVI era

Influence of artificial aging and ZrO2 nanoparticle-reinforced repair resin on the denture repair strength

Background: The purpose of this study was to evaluate the effect of aging process on the tensile strength (TS) of repaired acrylic denture base using ZrO2 nanoparticles (nano-ZrO2)-reinforced autopolymerized resin. Material and Methods: A total of 240 heat-polymerized acrylic resin specimens (n=10) were prepared and sectioned creating 2 mm-repair-gap. Autopolymerized acrylic resin, pure and modified with 2.5, 5, and 7.5wt% nano-ZrO2were used for specimens repair. TS of repaired specimens were measured using the universal testing machine af-ter water immersion at 37oC for 2, 7 and 30 days. At each time interval, half the immersed specimens underwent thermo-cycling aging process (5000 cycles at 5/55°C) before TS testing. One-way ANOVA and Tukey-Kramer multiple-comparison tests were used for data analysis at ?=0.05. Results: Aging process for all groups showed significant differences in TS between unreinforced and nano-ZrO2reinforced groups (p<0.05). Within immersed nano-ZrO2-reinforced specimens, 5% group immersed for 30-days showed the highest significant TS value (p<0.05). With regards to thermocycling, 5% group showed the highest TS values after 2-days and 30-days groups while after 7-days, significant differences were found between 2.5% group and 5% and 7.5% groups (p?0.05). SEM images analysis displayed the ductile fracture type for nano-ZrO2reinforced groups.Conclusions: In summary, 5.0%-nano-ZrO2 addition to repair resin showed an improvement in tensile strength of repaired acrylic resin with different aging processes

Toll-Like Receptor Signalling Pathways Regulate Hypoxic Stress Induced Fibroblast Growth Factor but Not Vascular Endothelial Growth Factor-A in Human Microvascular Endothelial Cells

Retinal diseases are the leading causes of irreversible blindness worldwide. The role of toll-like receptor (TLR) signalling mechanisms (MyD88 and TRIF) in the production of pro-angiogenic growth factors from human microvascular endothelial cells (HMEC-1) under hypoxic stress remains unexplored. HMEC-1 was incubated under normoxic (5% CO2 at 37 °C) and hypoxic (1% O2, 5% CO2, and 94% N2; at 37 °C) conditions for 2, 6, 24, and 48 h, respectively. For TLR pathway analysis, HMEC-1 was pre-treated with pharmacological inhibitors (Pepinh-MyD88 and Pepinh-TRIF) and subjected to normoxia and hypoxia conditions. Gene and protein expressions of vascular endothelial growth factor-A (VEGF-A), fibroblast growth factor (FGF-2), hypoxia inducible factor 1-alpha (HIF1-α) were performed using quantitative polymerase chain reaction (qPCR), ELISA, and Western blot methodologies. Levels of TLR3 and TLR4 were analysed by flow cytometry. Under hypoxia, levels of VEGF-A and FGF-2 were elevated in a time-dependent fashion. Inhibition of MyD88 and TRIF signalling pathways decreased FGF-2 levels but failed to modulate the secretion of VEGF-A from HMEC-1. Blocking a known regulator, endothelin receptor (ETR), also had no effect on VEGF-A secretion from HMEC-1. Overall, this study provides the proof-of-concept to target TLR signalling pathways for the management of blinding retinal diseases

Penetrance of Hypertrophic Cardiomyopathy in Sarcomere Protein Mutation Carriers

[Abstract] Background. Predictive genetic screening of relatives of patients with hypertrophic cardiomyopathy (HCM) caused by sarcomere protein (SP) gene mutations is current standard of care, but there are few data on long-term outcomes in mutation carriers without HCM. Objectives. The aim of this study was to determine the incidence of new HCM diagnosis in SP mutation carriers. Methods. This was a retrospective analysis of adult and pediatric SP mutation carriers identified during family screening who did not fulfill diagnostic criteria for HCM at first evaluation. Results. The authors evaluated 285 individuals from 156 families (median age 14.2 years [interquartile range: 6.8 to 31.6 years], 141 [49.5%] male individuals); 145 (50.9%) underwent cardiac magnetic resonance (CMR). Frequency of causal genes was as follows: MYBPC3 n = 123 (43.2%), MYH7 n = 69 (24.2%), TNNI3 n = 39 (13.7%), TNNT2 n = 34 (11.9%), TPM1 n = 9 (3.2%), MYL2 n = 6 (2.1%), ACTC1 n = 1 (0.4%), multiple mutations n = 4 (1.4%). Median follow-up was 8.0 years (interquartile range: 4.0 to 13.3 years) and 86 (30.2%) patients developed HCM; 16 of 50 (32.0%) fulfilled diagnostic criteria on CMR but not echocardiography. Estimated HCM penetrance at 15 years of follow-up was 46% (95% confidence interval [CI]: 38% to 54%). In a multivariable model adjusted for age and stratified for CMR, independent predictors of HCM development were male sex (hazard ratio [HR]: 2.91; 95% CI: 1.82 to 4.65) and abnormal electrocardiogram (ECG) (HR: 4.02; 95% CI: 2.51 to 6.44); TNNI3 variants had the lowest risk (HR: 0.19; 95% CI: 0.07 to 0.55, compared to MYBPC3). Conclusions. Following a first negative screening, approximately 50% of SP mutation carriers develop HCM over 15 years of follow-up. Male sex and an abnormal ECG are associated with a higher risk of developing HCM. Regular CMR should be considered in long-term screening

Ultrasensitive in-vitro monitoring of monoamine neurotransmitters from dopaminergic cells

The design of biosensing assay of monoamine neurotransmitters (MANTs) such as epinephrine (Ep), norepinephrine (NE), and dopamine (DA), as well as the monitoring of these MANTs released from dopaminergic cells, are of particular interest. Electrochemical sensors based on the novel construction of nickel oxides (NiO) were fabricated and employed for electrochemical screening of MANTs. A novel NiO-lacy flower-like (NLF) geometrical structure with semi-spherical head surfaces connected with a trunk as an arm was achieved. The designed semi-spherical head associated with abundant and the well-dispersed tubular branches with needle-like open ends might lead to the creation of vascular vessels for facile diffusion and suitable accommodation of the released MANTs throughout active and wide-surface-area coverage, multi-diffusive pores, and caves with connective open macro-/meso-windows along the entire top-view nanoneedles of lacy flower head and trunk. These electrode surfaces possess high-index catalytic site facets associated with the formation of ridges/defects on {110}-top-cover surface dominants for strong binding, fast response, and signaling of MANTs. The NLF- modified electrode enabled high sensitivity for MANTs and a low limit of detection of 6 nM. Ultrasensitive in-vitro monitoring of DA released from dopaminergic cells (such as PC12) was realized. The NLF electrode was used to detect MANTs from its sources (PC12), and it could be used for clinical diagnosis

The impact of the COVID-19 pandemic on the delivery of primary percutaneous coronary intervention in STEMI

Objectives: The clinical environment has been forced to adapt to meet the unprecedented challenges posed by the COVID-19 pandemic. Intensive care facilities were expanded in anticipation of the pandemic where the consequences include severe delays in elective procedures. Emergent procedures such as Percutaneous Coronary Intervention (PCI) in acute myocardial infarction (AMI) in which delays in timely delivery have well established adverse prognostic effects must also be explored in the context of changes in procedure and public behaviour associated with the COVID-19 pandemic. The aim for this single centre retrospective cohort study is to determine if door-to-balloon (D2B) times in PCI for ST Elevation Myocardial Infarction (STEMI) during the United Kingdom’s first wave of the COVID-19 pandemic differed from pre-COVID-19 populations. Methods: Data was extracted from our single centre PCI database for all patients that underwent pPCI for STEMI. The reference (Pre-COVID-19) cohort was collected over the period 01-03-2019 to 31-05-2019 and the exposure group (COVID-19) over the period 01-03-2020 to 31-05-2020. Baseline patient characteristics for both populations were extracted. The primary outcome measurement was D2B times. Secondary outcome measurements included: time of symptom onset to call for help, transfer time to first hospital, transfer time from non-PCI to PCI centre, time from call-to-help to PCI centre, time to table and onset of symptoms to balloon time. Categorical and continuous variables were assessed with Chi squared and Mann-Whitney U analysis respectively. Procedural times were calculated and compared in the context of heterogeneity findings. Results: 4 baseline patient characteristics were unbalanced between populations with statistical significance (P<0.05). The pre-covid-19 cohort was more likely to have suffered out of hospital cardiac arrest (OHCA) and had left circumflex disease, whereas the 1st wave cohort were more likely to have been investigated with left ventriculography and be of Afro-Caribbean origin. No statistically significant difference in in-hospital procedural times was found with D2B, C2B, O2B times comparable between groups. Pre-hospital delays were the greatest contributors in missed target times: the 1st wave group had significantly longer delayed time of symptom onset to call for help (Control: 31 mins; IQR [82.5] vs 1st wave: 60 mins; IQR [90.0], P=0.001) and time taken from call for help to arrival at the PCI hospital (control: 72 mins; IQR [23] vs 1st wave: 80 mins; IQR [66.5], P=0.042). Conclusion: Enhanced infection prevention and control procedures considering the COVID-19 pandemic did not impede the delivery of pPCI in our single centre cohort. The public health impact of the pandemic has been demonstrated with times being significantly impacted by patient related delays. The recovery of public engagement in emergency medical services must become the focus for public health initiatives as we emerge from the height of COVID-19 disease burden in the UK.Publisher PDFPeer reviewe

Filamin C variants are associated with a distinctive clinical and immunohistochemical arrhythmogenic cardiomyopathy phenotype

Background: Pathogenic variants in the filamin C (FLNC) gene are associated with inherited cardiomyopathies including dilated cardiomyopathy with an arrhythmogenic phenotype. We evaluated FLNC variants in arrhythmogenic cardiomyopathy (ACM) and investigated the disease mechanism at a molecular level. Methods: 120 gene-elusive ACM patients who fulfilled diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC) were screened by whole exome sequencing. Fixed cardiac tissue from FLNC variant carriers who had died suddenly was investigated by histology and immunohistochemistry. Results: Novel or rare FLNC variants, four null and five variants of unknown significance, were identified in nine ACM probands (7.5%). In FLNC null variant carriers (including family members, n = 16) Task Force diagnostic electrocardiogram repolarization/depolarization abnormalities were uncommon (19%), echocardiography was normal in 69%, while 56% had >500 ventricular ectopics/24 h or ventricular tachycardia on Holter and 67% had late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMRI). Ten gene positive individuals (63%) had abnormalities on ECG or CMRI that are not included in the current diagnostic criteria for ARVC. Immunohistochemistry showed altered key protein distribution, distinctive from that observed in ARVC, predominantly in the left ventricle. Conclusions: ACM associated with FLNC variants presents with a distinctive phenotype characterized by Holter arrhythmia and LGE on CMRI with unremarkable ECG and echocardiographic findings. Clinical presentation in asymptomatic mutation carriers at risk of sudden death may include abnormalities which are currently non-diagnostic for ARVC. At the molecular level, the pathogenic mechanism related to FLNC appears different to classic forms of ARVC caused by desmosomal mutations. Keywords: ARVC; Arrhythmogenic cardiomyopathy; Filamin C variants; Immunohistochemistry; Late gadolinium enhancement

Effectiveness of the 2014 European Society of Cardiology guideline on sudden cardiac death in hypertrophic cardiomyopathy: a systematic review and meta-analysis.

Objective In 2014, the European Society of Cardiology (ESC) recommended the use of a novel risk prediction model (HCM Risk-SCD) to guide use of implantable cardioverter defibrillators (ICD) for the primary prevention of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). We sought to determine the performance of HCM Risk-SCD by conducting a systematic review and meta-analysis of articles reporting on the prevalence of SCD within 5 years of evaluation in low, intermediate and high-risk patients as defined by the 2014 guidelines (predicted risk <4%, 4%–<6% and ≥6%, respectively). Methods The protocol was registered with PROSPERO (registration number: CRD42017064203). MEDLINE and manual searches for papers published from October 2014 to December 2017 were performed. Longitudinal, observational cohorts of unselected adult patients, without history of cardiac arrest were considered. The original HCM Risk-SCD development study was included a priori. Data were pooled using a random effects model. Results Six (0.9%) out of 653 independent publications identified by the initial search were included. The calculated 5-year risk of SCD was reported in 7291 individuals (70% low, 15% intermediate; 15% high risk) with 184 (2.5%) SCD endpoints within 5 years of baseline evaluation. Most SCD endpoints (68%) occurred in patients with an estimated 5-year risk of ≥4% who formed 30% of the total study cohort. Using the random effects method, the pooled prevalence of SCD endpoints was 1.01% (95% CI 0.52 to 1.61) in low-risk patients, 2.43% (95% CI 1.23 to 3.92) in intermediate and 8.4% (95% CI 6.68 to 10.25) in high-risk patients. Conclusions This meta-analysis demonstrates that HCM Risk-SCD provides accurate risk estimations that can be used to guide ICD therapy in accordance with the 2014 ESC guidelines. Registration number PROSPERO CRD42017064203;Pre-results.pre-print379 K