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Hypertrophic Cardiomyopathy (HCM) is the most common cause of sudden cardiac death (SCD) in young people. The implantable cardioverter-defibrillator (ICD) has been shown to be a safe and effective therapeutic intervention in patients with HCM, both for primary and secondary prevention of SCD. We reviewed ICD data of patients with HCM to determine the indications for, efficacy, safety and complications of the device. Out of 828 patients currently being reviewed in ICD clinic, Royal Victoria Hospital, Belfast 28 patients (4%) had HCM as primary diagnosis. Twenty four (85%) ICDs were inserted for primary prevention and 4 (15%) for secondary prevention of SCD. Pre ICD insertion the following risk factors for SCD were identified; 13 (46%) had a family history of SCD, 6 (21%) had a history of syncope, 5 (17%) had nonsustained ventricular tachycardia, 4 (14%) had ventricular tachycardia, 4 (14%) had frequent ventricular premature complex, 2 (7%) had atrial fibrillation and 2 (7%) had supraventricular tachycardia on holter monitor prior ICD insertion, 2 (7%) had an inappropriate blood pressure response to exercise and 2 (7%) had a raised left ventricular outflow tract velocity. The mean septal diameter was 22±6mm. The mean age of ICD insertion was 49.6±17years. During a mean follow up period of 32months, 9 appropriate shocks were delivered in 6 patients (21%) and 3 inappropriate shocks were delivered in 3 (10%) patients. Four patients who had appropriate shock delivered were on oral amiodarone and one patient on sotalol. Complications identified included one patients requiring ICD box replacement and one patient required lead replacement due to insulation defect of the leads. The high rate of appropriate ICD shocks in our study is similar to published data. Risk assessment for SCD should be performed in every HCM patient and ICD should be considered in high risk patients. [ABSTRACT FROM AUTHOR]

Introduction: Hypercholesterolemia is a major risk factor for coronary artery disease. Revised Joint British Society Guidelines 2005 (JBS-2) have recommended tighter lipid targets for both primary and secondary prevention. We reviewed trends in fasting lipid levels of patients admitted with Myocardial Infarction (MI) to our centre and assessed compliance with these guidelines. Methods: Fasting lipid profiles were analysed on patients admitted with an MI from January 2000 to December 2006 (n=1346). For patients admitted in 2005 lipid profile values were re-evaluated at least 6 months after admission to determine if JBS-2 target lipid values had been achieved. Results: Average Total Cholesterol decreased from 5.26 mmol/L in 2000 to 4.73 mmol/L in 2006 (p=0.026), LDL Cholesterol from 3.14 mmol/L in 2000 to 2.57 mmol/L in 2006 (p<0.001) and HDL Cholesterol rose from 1.11 mmol/L in 2000 to 1.58 mmol/L in 2002 (p=0.013) but declined to 1.33 mmol/L in 2006 (p=0.423). ST elevation Myocardial Infarction (STEMI) patients had significantly higher Total Cholesterol (5.11 Vs 4.78; p<0.001), LDL (2.97 Vs 2.69; p<0.001) and lower HDL (1.28 Vs 1.39: p=0.399) when compared with those admitted with Non ST-elevation Myocardial Infarction (NSTEMI). In 2005, 69% had achieved Total Cholesterol, 74% LDL and 71% HDL cholesterol targets 6 months after their admission. Conclusion: Our study reveals reduction in lipid profile values on admission from 2000 to 2006. We also noted that patients admitted with STEMI had a higher Total Cholesterol, LDL and lower HDL than NSTEMI. Current guidelines for primary and secondary prevention of coronary heart disease has led to more fastidious use of anti-lipid medications and has had a significant impact on the reduction of cholesterol. [ABSTRACT FROM AUTHOR]

Background: Excimer laser atherectomy (ELCA) is an established adjunctive technique to facilitate acute success in percutaneous coronary intervention (PCI). Despite this there are a lack of contemporary outcome data, particulary longer-term, forpatients treated with ELCA PCI., Aims: To evaluate the contemporary use ofELCA in PCI, the frequency of periprocedural complications and the longer-term outcomes associated with ELCA PCI., Methods: This was a retrospective study that included all patients undergoing PCI (with or without ELCA) between April 2005 and May 2021. Relevant features from all cases were downloaded from the patient record and matched to hospital data on mortality on November 22, 2022. Kaplan Meier curves were used to compare mortality between the ELCA PCI and non-ELCA PCI cohorts with a landmark at 1 year. Multivariable Cox regression was performed to assess whether ELCA PCI was independently associated with long-term mortality., Result: There were 21,256 patients in this analysis, of which 448 (2.1%) were treated with ELCA PCI. ELCA PCI was associated with a higher frequency of any periprocedural complication. Median follow-up was 2812 days (IQR, 1577-4245 days) with higher mortality in ELCA PCI (38.2% vs. 29.0%, p < 0.001). However, on multivariable analysis, ELCA PCI was not independently associated with long-term mortality. The TVR frequency in ELCA PCI was 16.7% but TVR was significantly higher for cases of in-stent restenosis (ISR) (29.5%)., Conclusion: Despite ELCA PCI being used in higher risk populations with complex coronary artery disease there was no long-term increased mortality associated with the use of this device. ELCA PCI for ISR is highly effective and safe although TVR in this cohort remains high in long-term follow-up., (© 2024 Wiley Periodicals LLC.)

Introduction: Stent under-expansion due to calcification is associated with a less durable result. The development of intravascular lithotripsy (IVL) has provided clinicians with a readily available, simple-to-use treatment option for coronary calcification, but the use of IVL within a previously stented segment is currently off-license. There are, however, developing data suggesting that the use of IVL can be an effective treatment option for patients with calcific stent under-expansion., Method: This was a single-center study of all patients treated with IVL for calcific stent under-expansion between January 2019 and June 2021. The impact of IVL on quantitative coronary angiography (QCA) stenosis and on the minimal stent area (MSA) derived from intracoronary imaging were recorded. The presence of periprocedural complications and adverse cardiovascular events was obtained from the clinical record during the study timeframe., Results: Thirty-nine patients underwent IVL for calcific stent under-expansion during the study time frame with one patient treated with more than one lesion in the same session. In all lesions, there was an improvement in the QCA stenosis with 37 (92.5%) having a residual stenosis of ≤30%. The mean QCA stenosis pre-IVL was 68 ± 21% and following IVL the mean QCA was 18 ± 9% (p < 0.001). In all lesions, there was an improvement in the MSA, with 26 (92.9%) achieving an MSA of more than 4.5 mm 2 . The mean MSA pre-IVL was 3.88 ± 1.51 mm 2 and following IVL the mean MSA was 7.41 ± 2.34 mm 2 (p < 0.001). There were no major procedural complications. Over a mean follow-up of 506 ± 277 days, one patient died from ventricular arrhythmia but there were no other major adverse cardiovascular events., Conclusion: This single-center study demonstrates that IVL is a safe and effective treatment for calcific stent under-expansion with good medium-term results., (© 2022 Wiley Periodicals LLC.)

The menopausal transition period in aging women is strongly associated with weight gain. Evidence shows that weight changes during menopause increases the risk of developing cardiovascular disease (CVD) in postmenopausal women. However, the potential mechanisms that cause weight gain and adverse changes to body composition specifically during the menopausal transition period remain to be elucidated. In this contemporary review, we examined recent evidence for adverse changes in body composition at midlife during the menopausal transition and the link to increased CVD risk and described factors that may contribute to these changes, including normal chronological aging, hormonal factors (decreased estrogen, etc.), behavioral factors (changes in diet, physical activity), or other emerging factors ( e.g. , sleep). This review focused on identifying factors that make the menopausal transition period a critical window for prevention of CVD. Future study is needed to decipher the extent to which hormonal changes, age-related factors, and behavioral factors interact with and contribute to increased CVD risk in women undergoing menopause. Understanding the causes of weight gain during the menopausal transition may help to inform strategies to mitigate adverse CVD outcomes for women transitioning through menopause., Competing Interests: No competing financial interests exist., (© Varna Kodoth et al., 2022; Published by Mary Ann Liebert, Inc.)

The hippocampus is essential for consolidating transient experiences into long-lasting memories. Memory consolidation is facilitated by postlearning sleep, although the underlying cellular mechanisms are largely unknown. We took an unbiased approach to this question by using a mouse model of hippocampally mediated, sleep-dependent memory consolidation (contextual fear memory). Because synaptic plasticity is associated with changes to both neuronal cell membranes (e.g., receptors) and cytosol (e.g., cytoskeletal elements), we characterized how these cell compartments are affected by learning and subsequent sleep or sleep deprivation (SD). Translating ribosome affinity purification was used to profile ribosome-associated RNAs in different subcellular compartments (cytosol and membrane) and in different cell populations (whole hippocampus, Camk2a+ neurons, or highly active neurons with phosphorylated ribosomal subunit S6 [pS6+]). We examined how transcript profiles change as a function of sleep versus SD and prior learning (contextual fear conditioning; CFC). While sleep loss altered many cytosolic ribosomal transcripts, CFC altered almost none, and CFC-driven changes were occluded by subsequent SD. In striking contrast, SD altered few transcripts on membrane-bound (MB) ribosomes, while learning altered many more (including long non-coding RNAs [lncRNAs]). The cellular pathways most affected by CFC were involved in structural remodeling. Comparisons of post-CFC MB transcript profiles between sleeping and SD mice implicated changes in cellular metabolism in Camk2a+ neurons and protein synthesis in highly active pS6+ (putative "engram") neurons as biological processes disrupted by SD. These findings provide insights into how learning affects hippocampal neurons and suggest that the effects of SD on memory consolidation are cell type and subcellular compartment specific., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Sleep loss disrupts consolidation of hippocampus-dependent memory. To characterize effects of learning and sleep loss, we quantified activity-dependent phosphorylation of ribosomal protein S6 (pS6) across the dorsal hippocampus of mice. We find that pS6 is enhanced in dentate gyrus (DG) following single-trial contextual fear conditioning (CFC) but is reduced throughout the hippocampus after brief sleep deprivation (SD; which disrupts contextual fear memory [CFM] consolidation). To characterize neuronal populations affected by SD, we used translating ribosome affinity purification sequencing to identify cell type-specific transcripts on pS6 ribosomes (pS6-TRAP). Cell type-specific enrichment analysis revealed that SD selectively activated hippocampal somatostatin-expressing (Sst+) interneurons and cholinergic and orexinergic hippocampal inputs. To understand the functional consequences of SD-elevated Sst+ interneuron activity, we used pharmacogenetics to activate or inhibit hippocampal Sst+ interneurons or cholinergic input from the medial septum. The activation of either cell population was sufficient to disrupt sleep-dependent CFM consolidation by gating activity in granule cells. The inhibition of either cell population during sleep promoted CFM consolidation and increased S6 phosphorylation among DG granule cells, suggesting their disinhibition by these manipulations. The inhibition of either population across post-CFC SD was insufficient to fully rescue CFM deficits, suggesting that additional features of sleeping brain activity are required for consolidation. Together, our data suggest that state-dependent gating of DG activity may be mediated by cholinergic input and local Sst+ interneurons. This mechanism could act as a sleep loss-driven inhibitory gate on hippocampal information processing., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Background/purpose: Calcified coronary artery stenosis remains a challenge for Percutaneous Coronary Intervention (PCI). Calcium modification is facilitated by rotablation and is used in 1-3% of cases. Data on rotablation in patients ≥80 years is limited and perceived to be high risk. We compared PCI with rotablation and outcomes between patients ≥80 years and those <80 years., Methods/materials: Retrospective analysis was performed of consecutive patients who underwent rotablation and PCI from 3 United Kingdom (UK) PCI Centres (2014-2017). In-hospital outcomes (composite of stroke, myocardial infarction, death, emergency coronary artery bypass graft surgery, vascular damage, coronary perforation, advanced AV-block, bleeding and renal impairment) and 30 day mortality risk score was compared between groups., Results: 213 patients were included. 33.3% (n = 71) were ≥80 years. Baseline and angiographic characteristics were similar in the two groups. Older patients were more likely to present with acute coronary syndrome (ACS) (≥80 years 53.5% vs. 33.8% in <80 years, p = 0.006) and had increased hospital stay (≥80 years 2.8 days (±6.0) vs. 1.3 days (±1.9) <80 years, p = 0.009). Majority of PCI were performed through radial access (≥80 years 91.5% vs. 88.0% <80 years, p = 0.43). In-hospital composite outcomes were similar between the groups (≥80 years 5.6% vs. 4.9% <80 years, p = 1.0). The 30-day mortality risk score demonstrated a higher average risk of 2.5% in ≥80 years versus under 1% risk in <80 years (p < 0.001)., Conclusion: This study demonstrates that outcomes after rotablation in the very elderly are similar to younger patients despite being high risk and presenting with ACS., Competing Interests: Declaration of competing interest No disclosures., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Background Impaired microcirculatory reperfusion worsens prognosis following acute ST-segment-elevation myocardial infarction. In the T-TIME (A Trial of Low-Dose Adjunctive Alteplase During Primary PCI) trial, microvascular obstruction on cardiovascular magnetic resonance imaging did not differ with adjunctive, low-dose, intracoronary alteplase (10 or 20 mg) versus placebo during primary percutaneous coronary intervention. We evaluated the effects of intracoronary alteplase, during primary percutaneous coronary intervention, on the index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio. Methods and Results A prespecified physiology substudy of the T-TIME trial. From 2016 to 2017, patients with ST-segment-elevation myocardial infarction ≤6 hours from symptom onset were randomized in a double-blind study to receive alteplase 20 mg, alteplase 10 mg, or placebo infused into the culprit artery postreperfusion, but prestenting. Index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio were measured after percutaneous coronary intervention. Cardiovascular magnetic resonance was performed at 2 to 7 days and 3 months. Analyses in relation to ischemic time (<2, 2-4, and ≥4 hours) were prespecified. One hundred forty-four patients (mean age, 59±11 years; 80% male) were prospectively enrolled, representing 33% of the overall population (n=440). Overall, index of microcirculatory resistance (median, 29.5; interquartile range, 17.0-55.0), coronary flow reserve(1.4 [1.1-2.0]), and resistive reserve ratio (1.7 [1.3-2.3]) at the end of percutaneous coronary intervention did not differ between treatment groups. Interactions were observed between ischemic time and alteplase for coronary flow reserve ( P =0.013), resistive reserve ratio ( P =0.026), and microvascular obstruction ( P =0.022), but not index of microcirculatory resistance. Conclusions In ST-segment-elevation myocardial infarction with ischemic time ≤6 hours, there was overall no difference in microvascular function with alteplase versus placebo. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02257294.

Sleep loss affects many aspects of cognition, and memory consolidation processes occurring in the hippocampus seem particularly vulnerable to sleep loss. The immediate-early gene Arc plays an essential role in both synaptic plasticity and memory formation, and its expression is altered by sleep. Here, using a variety of techniques, we have characterized the effects of brief (3-h) periods of sleep vs. sleep deprivation (SD) on the expression of Arc mRNA and Arc protein in the mouse hippocampus and cortex. By comparing the relative abundance of mature Arc mRNA with unspliced pre-mRNA, we see evidence that during SD, increases in Arc across the cortex, but not hippocampus, reflect de novo transcription. Arc increases in the hippocampus during SD are not accompanied by changes in pre-mRNA levels, suggesting that increases in mRNA stability, not transcription, drives this change. Using in situ hybridization (together with behavioral observation to quantify sleep amounts), we find that in the dorsal hippocampus, SD minimally affects Arc mRNA expression, and decreases the number of dentate gyrus (DG) granule cells expressing Arc. This is in contrast to neighboring cortical areas, which show large increases in neuronal Arc expression after SD. Using immunohistochemistry, we find that Arc protein expression is also differentially affected in the cortex and DG with SD - while larger numbers of cortical neurons are Arc+, fewer DG granule cells are Arc+, relative to the same regions in sleeping mice. These data suggest that with regard to expression of plasticity-regulating genes, sleep (and SD) can have differential effects in hippocampal and cortical areas. This may provide a clue regarding the susceptibility of performance on hippocampus-dependent tasks to deficits following even brief periods of sleep loss., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

A wireless powered implantable atrial defibrillator consisting of a battery driven hand-held radio frequency (RF) power transmitter (ex vivo) and a passive (battery free) implantable power receiver (in vivo) that enables measurement of the intracardiac impedance (ICI) during internal atrial defibrillation is reported. The architecture is designed to operate in two modes: Cardiac sense mode (power-up, measure the impedance of the cardiac substrate and communicate data to the ex vivo power transmitter) and cardiac shock mode (delivery of a synchronised very low tilt rectilinear electrical shock waveform). An initial prototype was implemented and tested. In low-power (sense) mode, >5 W was delivered across a 2.5 cm air-skin gap to facilitate measurement of the impedance of the cardiac substrate. In high-power (shock) mode, >180 W (delivered as a 12 ms monophasic very-low-tilt-rectilinear (M-VLTR) or as a 12 ms biphasic very-low-tilt-rectilinear (B-VLTR) chronosymmetric (6ms/6ms) amplitude asymmetric (negative phase at 50% magnitude) shock was reliably and repeatedly delivered across the same interface; with >47% DC-to-DC (direct current to direct current) power transfer efficiency at a switching frequency of 185 kHz achieved. In an initial trial of the RF architecture developed, 30 patients with AF were randomised to therapy with an RF generated M-VLTR or B-VLTR shock using a step-up voltage protocol (50-300 V). Mean energy for successful cardioversion was 8.51 J ± 3.16 J. Subsequent analysis revealed that all patients who cardioverted exhibited a significant decrease in ICI between the first and third shocks (5.00 Ω (SD(σ) = 1.62 Ω), p < 0.01) while spectral analysis across frequency also revealed a significant variation in the impedance-amplitude-spectrum-area (IAMSA) within the same patient group (|∆(IAMSAS1-IAMSAS3)[1 Hz - 20 kHz] = 20.82 Ω-Hz (SD(σ) = 10.77 Ω-Hz), p < 0.01); both trends being absent in all patients that failed to cardiovert. Efficient transcutaneous power transfer and sensing of ICI during cardioversion are evidenced as key to the advancement of low-energy atrial defibrillation.

Unlabelled: With the introduction of transcatheter aortic valve implantation (TAVI), the precise role of balloon aortic valvuloplasty (BAV) remains to be established., Methods: Between August 2008 and November 2010, consecutive patients undergoing BAV for severe aortic stenosis (AS) in our center were enrolled. The primary endpoint was survival to hospital discharge. Secondary endpoints were 30-day survival and progression to aortic valve replacement (AVR)., Results: Enrolled were 64 patients (age, 82 ± 8 years; 45% male). Treatment objectives were: symptom palliation (69%); potential AVR (23%); and facilitation of withdrawal of ventilation or non-cardiac surgery (8%). At baseline, patients had logistic EuroSCORE of 35.7 ± 19.5, NT-proBNP of 11,195 ± 11,694 ng/L, aortic valve area of 0.53 ± 0.17 cm², and peak transaortic gradient (PG) of 75.2 ± 25.3 mm Hg. The primary endpoint of survival to hospital discharge was reached by 97% patients. The secondary endpoint of 30-day mortality occurred in 8 patients (13%). Overall, 12 patients showed clinical improvement within 1 month of BAV. Of these, 8 patients underwent AVR (TAVI in 3/8 [38%]). After multivariate adjustment, the strongest correlates for 30-day survival and progression to AVR pre-BAV were: New York Heart Association ≤II, SBP ≥90 mm Hg, estimated glomular filtration rate ≥45 mL min-1, left ventricular ejection fraction ≥45% and transaortic PG <80 mm Hg., Conclusion: In patients with severe AS and high operative risk, BAV has the potential to facilitate progression to TAVI in those who are technically suitable.