The BE-ALIVE score: assessing 30-day mortality risk in patients presenting with acute coronary syndromes

AIM: To create and validate a simple scoring system for predicting 30-day mortality in patients presenting with acute coronary syndromes (ACS) at their moment of admission. METHODS AND RESULTS: 2407 consecutive patients presenting to Harefield Hospital with measured arterial blood gases, from January 2011 to December 2020, were studied to build the training set. 30-day mortality in this group was 17.2%. A scoring algorithm that was built using binary logistic regression of variables available on admission was then converted to an additive risk score. The resultant scoring system is the BE-ALIVE score, which incorporates the following factors:Base Excess (1 point for <-2 mmol/L), Age (<65 years: 0 points, 65-74: 1 point, 75-84: 2 points, ≥85: 3 points), Lactate (<2 mmol/L: 0 points, 2-4.9: 1 point, 5-9.9: 3 points, ≥10: 6 points), Intubated (2 points), Left Ventricular function (mildly impaired or better: -1 point, moderately impaired: 1 point, severely impaired: 3 points) and External/out of hospital cardiac arrest 2 points).The scoring system was validated using a testing set of 515 patients presenting to Harefield Hospital in 2021. The validation metrics were excellent with a c-statistic of 0.9, Brier's score 0.06 vs a naïve classifier of 0.15, Spiegelhalter's z-statistic probability of 0.267 and a calibration slope of 1.08. CONCLUSION: The BE-ALIVE score is a simple and accurate scoring system to predict 30-day mortality in patients presenting with ACS. Appreciating this mortality risk can allow prompt involvement of appropriate care such as the shock team

Complete revascularization is associated with higher mortality in patients with ST-elevation myocardial infarction, multi-vessel disease and shock defined by hyperlactataemia: results from the Harefield Shock Registry incorporating explainable machine learning

Aims Revascularization strategy for patients with ST-elevation myocardial infarction (STEMI) and multi-vessel disease varies according to the patient’s cardiogenic shock status, but assessing shock acutely can be difficult. This article examines the link between cardiogenic shock defined solely by a lactate of ≥2 mmol/L and mortality from complete vs. culprit-only revascularization in this cohort. Methods and results Patients presenting with STEMI, multi-vessel disease without severe left main stem stenosis and a lactate ≥2 mmol/L between 2011 and 2021 were included. The primary endpoint was mortality at 30 days by revascularization strategy for shocked patients. Secondary endpoints were mortality at 1 year and over a median follow-up of 30 months. Four hundred and eight patients presented in shock. Mortality in the shock cohort was 27.5% at 30 days. Complete revascularization (CR) was associated with higher mortality at 30 days [odds ratio (OR) 2.1 (1.02–4.2), P = 0.043], 1 year [OR 2.4 (1.2–4.9), P = 0.01], and over 30 months follow-up [hazard ratio (HR) 2.2 (1.4–3.4), P < 0.001] compared with culprit lesion-only percutaneous coronary intervention (CLOP). Mortality was again higher in the CR group after propensity matching (P = 0.018) and inverse probability treatment weighting [HR 2.0 (1.3–3.0), P = 0.001]. Furthermore, explainable machine learning demonstrated that CR was behind only blood gas parameters and creatinine levels in importance for predicting 30-day mortality. Conclusion In patients presenting with STEMI and multi-vessel disease in shock defined solely by a lactate of ≥2 mmol/L, CR is associated with higher mortality than CLOP.British Heart Foundation (FS/19/73/34690 to I.C.)

Coronary heart disease in Indian Asians.

The Indian Asian population accounts for a fifth of all global deaths from coronary heart disease (CHD). CHD deaths on the Indian subcontinent have doubled since 1990, and are predicted to rise a further 50% by 2030. Reasons underlying the increased CHD mortality among Indian Asians remain unknown. Although conventional cardiovascular risk factors contribute to CHD in Indian Asians as in other populations, these do not account for their increased risk. Type-2 diabetes, insulin resistance and related metabolic disturbances are more prevalent amongst Indian Asians than Europeans, and have been proposed as major determinants of higher CHD risk among Indian Asians. However, this view is not supported by prospective data. Genome-wide association studies have not identified differences in allele frequencies or effect sizes in known loci to explain the increased CHD risk in Indian Asians. Limited knowledge of mechanisms underlying higher CHD risk amongst Indian Asians presents a major obstacle to reducing the burden of CHD in this population. Systems biology approaches such as genomics, epigenomics, metabolomics and transcriptomics, provide a non-biased approach for discovery of novel biomarkers and disease pathways underlying CHD. Incorporation of these omic approaches in prospective Indian Asian cohorts such as the London Life Sciences Population Study (LOLIPOP) provide an exciting opportunity for the identification of new risk factors underlying CHD in this high risk population

The South Asian genome

Genetics of disease Microarrays Variant genotypes Population genetics Sequence alignment AllelesThe genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.Whole genome sequencing to discover genetic variants underlying type-2 diabetes, coronary heart disease and related phenotypes amongst Indian Asians. Imperial College Healthcare NHS Trust cBRC 2011-13 (JS Kooner [PI], JC Chambers)

Inconsistency in aortic stenosis severity between CT and echocardiography: Prevalence and insights into mechanistic differences using computational fluid dynamics

© 2019 Author(s). Objectives The aims of this study were to evaluate the inconsistency of aortic stenosis (AS) severity between CT aortic valve area (CT-AVA) and echocardiographic Doppler parameters, and to investigate potential underlying mechanisms using computational fluid dynamics (CFD). Methods A total of 450 consecutive eligible patients undergoing transcatheter AV implantation assessment underwent CT cardiac angiography (CTCA) following echocardiography. CT-AVA derived by direct planimetry and echocardiographic parameters were used to assess severity. CFD simulation was performed in 46 CTCA cases to evaluate velocity profiles. Results A CT-AVA>1 cm 2 was present in 23% of patients with echocardiographic peak velocity≥4 m/s (r=-0.33) and in 15% patients with mean Doppler gradient≥40 mm Hg (r=-0.39). Patients with inconsistent severity grading between CT and echocardiography had higher stroke volume index (43 vs 38 mL/m 2, p1 cm 2 in up to a quarter of patients. CFD demonstrates that haemodynamic severity may be exaggerated on Doppler analysis due to high LVOT flow rates, with or without skewed velocity profiles, across the valve orifice. These factors should be considered before making a firm diagnosis of severe AS and evaluation with CT can be helpful

Initial experience of a large, self-expanding, and fully recapturable transcatheter aortic valve: The UK & Ireland Implanters' registry.

OBJECTIVES: The UK & Ireland Implanters' registry is a multicenter registry which reports on real-world experience with novel transcatheter heart valves. BACKGROUND: The 34 mm Evolut R transcatheter aortic valve is a self-expanding and fully recapturable transcatheter aortic valve, designed to treat patients with a large aortic annulus. METHODS: Between January 2017 and April 2018, clinical, procedural and 30-day outcome data were prospectively collected from all patients receiving the 34 mm Evolut R valve across 17 participating centers in the United Kingdom and Ireland. The primary efficacy outcome was the Valve Academic Research Consortium-2(VARC-2)-defined endpoint of device success. The primary safety outcome was the VARC-2-defined composite endpoint of early safety at 30 days. RESULTS: A total of 217 patients underwent attempted implant. Mean age was 79.5 ± 8.8 years and Society of Thoracic Surgeons Predicted Risk of Mortality Score 5.2% ± 3.4%. Iliofemoral access was used in 91.2% of patients. Device success was 79.7%. Mean gradient was 7.0 ± 4.6 mmHg and effective orifice area 2.0 ± 0.6 cm2 . Paravalvular regurgitation was more than mild in 7.2%. A new permanent pacemaker was implanted in 15.7%. Early safety was demonstrated in 91.2%. At 30 days, all-cause mortality was 3.2%, stroke 3.7%, and major vascular complication 2.3%. CONCLUSIONS: Real-world experience of the 34 mm Evolut R transcatheter aortic valve demonstrated acceptable procedural success, safety, valve function, and incidence of new permanent pacemaker implantation

Sedentary behaviour is associated with increased long-term cardiovascular risk in patients with rheumatoid arthritis independently of moderate-to-vigorous physical activity

Background Rheumatoid Arthritis (RA) is associated with an increased risk of cardiovascular disease (CVD). The physical dysfunction symptomatic of RA means people living with this disease spend large periods of the day sedentary, which may further elevate their risk of CVD. The primary aim of this study was to investigate relationships between objectively assessed sedentary behaviour patterns and light physical activity (LPA) with 10-year risk of CVD. Secondary aims were to explore the role of sedentary behaviour patterns and LPA for individual CVD risk factors and functional disability in RA. The extent to which associations were independent of moderate-to-vigorous physical activity (MVPA) engagement was also examined. Methods Baseline data from a subsample of participants recruited to the Physical Activity in Rheumatoid Arthritis (PARA) study were used to answer current research questions. Sixty-one patients with RA (mean age (± SD) = 54.92 ± 12.39 years) provided a fasted blood sample and underwent physical assessments to evaluate factors associated with their cardiovascular health. Sedentary behaviour patterns (sedentary time, sedentary bouts, sedentary breaks), LPA and MVPA were measured via 7-days of accelerometry. Ten-year CVD risk was computed (Q-risk-score2), and functional disability determined via questionnaire. Results Regressions revealed significant positive associations between sedentary time and the number of sedentary bouts per day ≥20 min with 10-year CVD risk, with the reverse true for LPA participation. Associations were independent of MVPA engagement. Conclusions Promoting LPA participation and restricting sedentary bouts to <20 min may attenuate long-term CVD risk in RA, independent of MVPA engagement

Factors associated with parasympathetic activation following exercise in patients with rheumatoid arthritis: a cross-sectional study

Background Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease (CVD) with poor parasympathetic function being implicated as an underlying factor. Factors related to parasympathetic function, commonly assessed by heart rate recovery (HRR) following maximal exercise, are currently not known in RA. We aimed to explore the association between HRR with CVD risk factors, inflammatory markers, and wellbeing in patients with RA. Methods Ninety-six RA patients (54.4 ± 12.6 years, 68 % women) completed a treadmill exercise test, during which heart rate (HR) was monitored. HRR1 and HRR2 were defined as the absolute change from HR peak to HRR 1 min post HR peak and 2 min post HR peak, respectively. Cardiorespiratory fitness, CVD risk factors, and serological markers of inflammation were measured in all patients. The Framingham Risk Score (FRS) was used as an assessment of global risk for CVD events, and wellbeing was assessed by questionnaires. Results Mean HRR1 and HRR2 were 29.1 ± 13.2 bpm and 46.4 ± 15.3 bpm, respectively. CVD risk factors as well as most inflammatory markers and measures of wellbeing were inversely correlated with HRR1 and HRR2. Multivariate regression analyses revealed that 27.9 % of the variance in HRR1 and 37.9 % of the variance in HRR2 was explained collectively by CVD risk factors, measures of inflammation, and wellbeing (p = 0.009, p = 0.001 respectively), however no individual measure was independently associated with HRR1 or HRR2. Conclusion Parasympathetic activation was associated with overall CVD risk, arthritis-related burden and wellbeing in patients with RA

Mini aortic valve replacement versus transcatheter aortic valve implantation: a propensity-matched study

Background: Total sternotomy for aortic valve replacement has been superseded by less invasive approaches such as mini sternotomy or transcatheter procedures. There has been an exponential uptake in transcatheter aortic valve implantation (TAVI) in younger and lower risk patients following recent randomized trials. This study aims to compare the outcomes of patients with aortic stenosis treated with minimally invasive approaches: mini sternotomy for aortic valve replacement (mini AVR) and TAVI implantation. Methods: Between January 2015 and December 2021, a total of 1437 TAVI and 176 mini AVR patients from 2 tertiary centers fulfilled the criteria and were included in the propensity matching model. Results: A total of 256 TAVIs and 146 mini AVR were included in the matched cohort. There was no significant difference in 30-day mortality in the two groups (TAVI vs. mini AVR 2.7% vs. 2.8%, p=0.935). TAVI confers slightly lower gradients in the follow-up echo when compared with mini AVR (peak gradient 20±8.7mmHg vs 24.5±10mmHg, p <0.001; mean gradient 10.9±5.6mmHg vs 13.2±5.7mmHg, p<0.001). On the other hand, mini AVR exhibits remarkably lower rates of paravalvular leak (mild leak 8% vs 41.5%, p<0.001; moderate leak 2.8% vs 0%, p<0.001), and of need for permanent pacemaker implantation (2% vs 12.2%, p<0.001). Unsurprisingly, TAVI has lower in hospital stay 3 (2 to 6) days vs. 10 (8 to 13) days, p<0.001). Conclusions: For eligible aortic stenosis patients in the 7th decade of life, mini AVR remains an excellent therapeutic option