Major limb amputation during the COVID-19 pandemic-Have we seen a change in practice?

Introduction: There have been significant changes in The delivery of Health care as a consequence of The COVID-19 pandemic. Standard operating procedures have been re-defined to minimise harm from The reduction in access to services, whilst at The same time protecting hospitals (and in particular critical care units) from admissions. We have explored major limb amputation (MLA) practice and compared this with a historical series. Method(s): Retrospective review of major limb amputations (March 2019 to October 2021). Historical datasets have also been scrutinised (2008-2010). Specific variables of interest included The annual number of major limb amputations, primary versus secondary amputation and ratio of transtibial (TTA) to transfemoral (TFA) amputations. Result(s): A complete dataset was available for 282 patients during The COVID period. Patient demographics were as anticipated-206 (73%) male, mean age 63-years (range 23 to 90-years). Peripheral arterial disease (190) and diabetes mellitus (149) were common. These demographics were comparable to The historical data. The annual number of MLA has not changed over The COVID period. The ratio of primary to secondary MLA was 1:1.3 in The historical series and 1:1 during The COVID period. The ratio of TTA to TFA was 3:1.8 in The historical series and 2:1 during The COVID period. Conclusion(s): The trends suggest that practice has not changed significantly during The COVID period. There has been a slight change in The ratio of transtibial to transfemoral amputation, which may reflect patients presenting with later stage disease.

Role of adenosine receptors in cardiovascular disorders and novel corona virus infection

Objective: To assess the importance of adenosine signaling in cardiovascular disorders (thrombosis, ischemia) and novel corona virus infection. Methodology: A specified web search was done to gather the relevant information using different scientific research forums and databases like WHO database, Pubmed and Google Scholar etc. Results: Adenosine receptors are P1 type of purinergic receptors and belong to G protein-coupled receptors (GPCRs), which is the largest family of integral membrane bound proteins receptors. Adenosine receptors are further classified into four subclasses known as A1, A2A, A2B, and A3. All four subclasses are being mediated by extracellular adenosine and perform a key role in a wide range of physiological functions such as immune system modulation, angiogenesis and sleep regulation. Adenosine receptors are thought to play a significant role in many pathophysiological conditions including cardiovascular disorders such as ischemia and thrombosis and novel corona virus infection making it a key target against these disorders. Conclusion: We suggest that modulation of adenosine receptor activity could increase the regenerative phase in these disorders by increasing the proliferation and differentiation rates of damaged tissue.

Current lipid-lowering approach and LDL target achievement in very high-risk patients: in-hospital results of a high-volume primary percutaneous coronary intervention tertiary center

Background: Low-density lipoprotein-cholesterol (LDL-C) is a well-accepted causal risk factor for atherothrombotic cardiovascular disease. Several randomized controlled trials and meta-analyses have shown that lipid-lowering therapies reduce cardiovascular events and have a positive effect in reducing vulnerable plaques. In particular, the recommended target for LDL-C has become more and more stringent, moving to 1.4 mmol/l (55 mg/dl) for very high-risk patients. According to the 2019 ESC/EAS Guidelines, the current paradigm for lipid management favors a stepwise approach consisting of early initiation of high-intensity statin, followed by subsequent addition of ezetimibe, and ultimately a consideration of PCSK9 inhibitor treatment if LDL-C levels remain elevated. Methods: We recruited 307 patients admitted for acute coronary syndrome (ACS) during the COVID-19 pandemic from March 2020 to December 2020. Baseline LDL-C concentration and prescribed hypolipemiant treatment at hospital admission and discharge were registered. Therefore, we included all consecutive patients identified as very-high cardiovascular risk, according to 2019 ESC guidelines. We stratified our population through variables independently associated with non-attainment of LDL-cholesterol such as hypertension, diabetes, peripheral arterial disease, clinical manifestations of ACS, number of main vessels treated, and complexity of the atherosclerotic disease. Results: 274 patients were included. Mean age was 69,9 years (SD 11,4), 20,8%were women, 23,7%had diabetes, 16,4%had PAD and 32,1 % suffered from valvular disease, mainly with mitral regurgitation or aortic stenosis no more than mild or moderate. Of 25.1% with a previous history of acute myocardial infarction, the 33,3% of whom didn't have statin therapy pre-ACS index (p =0,001). At admission, medium cholesterol levels of patients that underwent previous coronary revascularization (25,5% of the total population) were 84,21 ± 31,2 mg/dL, not in range according to both 2016 and 2019 ESC guidelines. At discharge, 77,37 % of all the patients included received only statin therapy VS 22,63% with statin plus ezetimibe. In the subpopulation of patients with recurring ACS events with LDL pre-admission > 100 mg/dL,despite high dose statin, only 25% of this population were discharged adding ezetimibe (VS 75% who kept on the treatment of high dose statin without up-titration). Conclusions: Management of dyslipidemia is frequently suboptimal and the gap between guidelines and clinical practice for lipid management across Europe has been exacerbated by the 2019 guidelines. A greater utilization of non-statin lipid-lowering therapies is likely needed to reach the LDL-C optimal target. A correct stratification of the risk class would help to identify, in a personalized perspective of treatment, patients at very high risk that would take advantage of more aggressive therapy to reach the lowest target of LDL-C ('the lower is better'). (Figure Presented).

16th INASH AbstractT Book

The proceedings contain 45 papers. The topics discussed include: neuropeptide levels effect on blood pressure in chronic kidney disease patients with hypertension;dry weight gain and incidence of intradialytic hypertension: a cross-sectional study in rural hospital;why they don't take the pill: a qualitative study of antihypertensive medication nonadherence in East Borneo primary health care;antihypertensive effect of nigella sativa (Habbatus Sauda) supplementation in population with cardiometabolic risk factors: a systematic review and meta-analysis of randomized controlled trials;risk factors of peripheral artery disease in the hypertensive chronic kidney disease patients on hemodialysis;impact of day-to-day blood pressure variability to in-hospital mortality in patients with COVID-19 and efficacy of antihypertensive agents;and systolic blood pressure as risk factor associated with persisting proteinuria after delivery in women with preeclampsia.

A physiotherapist-led, home-based walking intervention for peripheral arterial disease: MOtivating Structured walking Activity for Intermittent Claudication (MOSAIC) randomised controlled trial

Keywords: Peripheral arterial disease;Exercise;Behaviour change Purpose: Walking is recommended for adults with peripheral arterial disease. However, provision of supervised walking programmes is variable and adherence to self-directed walking tends to be low. MOtivating Structured walking Activity for Intermittent Claudication (MOSAIC) is a physiotherapist-led, structured, home-based intervention that incorporates motivational interviewing and behaviour change principles to increase participants’ motivation and commitment to walking. This trial investigated whether MOSAIC improved walking performance compared to usual care in adults with peripheral arterial disease. Methods: This multicentre, parallel group, two-arm, randomised, controlled superiority trial enrolled participants from six NHS Trusts between January 2018 and March 2020. Inclusion criteria comprised: aged ≥50 years with established peripheral arterial disease and intermittent claudication. Exclusion criteria included: unstable disease;walking >90 min/week;contraindications to exercise or completed/offered any medically supervised exercise in previous/upcoming six-months. The primary outcome was six-minute walk distance (6MWD, metres (m)) at three-months (clinically meaningful change: ≥8 m). Secondary outcomes included pain-free walking distance measured during six-minute walk test (PFWD, seconds), self-reported walking limitation (Walking Estimated-Limitation Calculated by History, WELCH, range 0–100;self-reported maximum walking distance, SR-MWD (m)), activities of daily living (Nottingham Extended Activities of Daily Living Questionnaire, NEADL, range 0–66), and quality of life (Vascular Quality of Life Questionnaire-6, VASuQoL-6, range 6–24). All measures were collected at baseline and three-months by an assessor masked to participant allocation. The self-reported outcomes were also collected at six-months. Consenting participants were randomly assigned (by King's Clinical Trials Unit remote computer-generated randomisation system) to receive either MOSAIC (two face-to-face and two telephone consultations delivered over three-months by trained physiotherapists, a pedometer and a bespoke manual) or usual care. Participants and physiotherapists were not masked to group allocation. Participant recruitment and collection of primary outcome data at three-months was ceased early due to COVID-19 restrictions. All self-reported six-month outcomes were collected as per protocol. Outcomes were evaluated on an intention-to-treat basis using multiple regression with baseline value and stratification factors as covariates. Results: 190 participants (mean age (Standard Deviation) 68 (9) years, 57 (30%) female, 150 (79%) White) were recruited (95/group). At three-months, participants receiving MOSAIC had greater mean 6MWD compared to participants receiving usual care (adjusted mean difference (95% confidence interval (95%CI): 16.4 m (3.8, 29.1)). Secondary outcomes also indicated greater improvement for those receiving MOSAIC than usual care (adjusted mean differences (95% CI): PFWD (31.2 s (6.3, 56.0));WELCH (10.2 points (5.6, 14.8));SR-MWD (251 s (11.0;194.9));NEADL (2.8 points (0.1;5.4));VASuQoL-6 (0.6 points (−0.2;1.4)). At six months, there was a sustained improvement in WELCH in participants receiving MOSAIC compared to usual care (adjusted mean difference (95% CI): 7.4 points (2.5, 1.3)). Results for the other secondary outcomes were inconclusive (SR-MWD (309.9 s (−17.8;637.6)), NEADL (−1.6 points (−4.6, 1.5)), VASuQoL-6 (0.6 points (−0.4;1.6)). Thirty-seven adverse events (25 MOSAIC, 12 usual care) were reported. Conclusion(s): MOSAIC is an effective treatment for the management of peripheral arterial disease and could be integrated into physiotherapy practice to support walking behaviour change. Impact: MOSAIC is an effective treatment for the management of peripheral arterial disease and could be integrated into physiotherapy practice to support walking behaviour change. Funding acknowledgements: This work was suppor ed by The Dunhill Medical Trust [grant number: [R477/0516].

Regional anaesthesia for infra-inguinal revascularisation in patients with symptomatic peripheral arterial disease

Introduction: General anaesthesia is considered to be an aerosol generating procedure. The global Covid-19 pandemic has resulted in review of practice to reduce risk to both patients and health care workers. The outcome of regional anaesthesia (RA) for infra-inguinal arterial reconstruction in patients with symptomatic occlusive atherosclerotic has been explored and compared with patients managed with general anaesthesia (GA). Methods: Patients undergoing infra-inguinal revascularisation between 2019-2020 were identified from a prospectively maintained administrative theatre dataset. Case-linkage was used to complete the dataset. Specific end points included to critical care admission and peri-operative mortality. Results: There were 204 patients identified (46 RA and 158 GA). The mean age of patients in both groups was 67-years and procedures were commonly performed in male patients (although the male:female ratio was higher in the RA group 2.8:1 than in the GA group 1.4:1). More patients in the RA had intervention for chronic limb threatening ischaemia (80% versus 59%). The interventions performed were comparable in both groups. The mean length of procedure was less in the RA group (142-minutes versus 160-minutes). No patients in the RA required admission to critical care (10 patients managed with GA required admission to critical care). The 30-day mortality was comparable in the RA and GA groups (2.2% and 1.9% respectively). Conclusions: Regional anaesthesia would appear to be feasible for patients undergoing infra-inguinal arterial reconstruction with a reduction in operating time and critical care admission without increased peri-operative risk.

Acute peripheral arterial thrombosis and Takotsubo cardiomyopathy in a patient with CoViD-19 infection

Background: The most frequent clinical manifestations of CoViD- 19 are related to the respiratory tract. However variable clinical manifestations are often observed ranging from asymptomatic cases to the most serious complications. We report a case showing that the patient's genetic predisposition and comorbidities are likely strong influencer of the severity of CoViD-19 extra-pulmonary manifestations. Description of the case: We report a case of Takotsubo cadiomyopathy in a 81-year old woman affected by CoViD-19 without a pre-existing cardiac condition. After 25 days of hospitalization, the patient experimented fever, respiratory insufficiency and acute right lower limb ischaemia requiring urgent amputation. 4 days later, electrocardiogram and ultrasound showed myocardial suffering and kinetics alterations respectively, suggestive for Takotsubo cardiomyopathy. Despite a gradual recovery of ventricular function, patient's lung function worsened, death occurred at day 34. Conclusions: The patient experimented acute lower limb ischaemia as a vascular complication of virus infection, although it was treated with enoxaparin. We demonstrated that there was a prothrombotic predisposition: levels of homocysteine and anticoagulation proteins C and S were reduced. This case highlights a link between prothrombotic predisposition and CoViD-19-associated peripheral arterial disease.

Predictors of left ventricular ejection fraction recovery after transcatheter aortic valve replacement (TAVR)

Introduction: Transcatheter aortic valve replacement (TAVR) has proven benefits in patients with reduced left ventricular ejection fraction (LVEF). A significant proportion of them shows recovery of systolic function Objective: To analyse the main baseline, electrocardiographic and echocardiographic characteristics that may predict LVEF recovery after TAVR. Methods: A cohort study was conducted. Consecutive patients undergoing TAVR in our center from January 2012 to December 2020 were included. Baseline clinical profile, electrocardiographic (EKG), echocardiographic (ECH) parameters were recorded, as well as MACE during followup (major adverse cardiovascular events including: all-cause mortality, myocardial infarction, cerebrovascular accident and heart failure hospitalization). Reduced systolic function was defined as LVEF <50%. We considered recovery of systolic function as LVEF ≥50% at follow-up. Results: A total of 292 patients were included. 48% were women and the median age was 81.07 years (77.63-86.22). 22.6% (66 patients) had reduced LVEF at baseline. Half of them showed recovered systolic function during follow-up. Patients who did not recovered LVEF had a higher prevalence of dyslipidemia and peripheral artery disease. History of cardiac surgery was more frequently found in this group, and they showed a higher surgical risk estimated by EuroScore II. They had lower LVEF and aortic valve mean gradient, and more frequently presented non-synus rhythm (NSR), left bundle branch block and right ventricular dysfunction (RVD). These characteristics are shown in figure 1. In univariate analysis lower Euroscore II, presence of synus rhythm, absence of LBBB and RVD, as well as higher aortic valve mean gradient were predictors of LVEF recovery. In multivariate analysis RVD and mean aortic gradient were independent predictors. Among all patients included in our study, those presenting with RV dysfunction were significantly associated with lower LVEF mean values (46,0% vs 57,2%;p<0,01) After a median follow-up of 21.3 (8.52-38.94) months, MACE were lower in recovered LVEF group (HR 0.25 95% CI: 0.05-1.21). There were no statistically significant differences in all-cause mortality, nevertheless there was a trend towards a higher non-cardiovascular mortality in this group, essentially at the expense of deaths from malignant neoplasms and SARS-COV- 2 infections. Survival curves for MACE are represented in figure 2. Conclusion: In our study, half of the patients with impaired ventricular function undergoing TAVR showed recovery of ejection fraction. Right ventricular function and aortic valve mean gradient at baseline were independent predictors of recovery. Identifying predictors of LVEF recovery is fundamental in the evaluation of potential candidates for TAVR, and can help clinicians assess risks and benefits, as well as long-term prognosis of these patients.

Meta-Analysis of COVID-19 treatments on patients with a previous diagnosis of cardiovascular disease

Background: The COVID-19 pandemic has spread globally, infecting and killing millions. Those subjects with cardiovascular disease (CVD) are at higher risk of severe COVID-19 morbidity and mortality following SARSCoV- 2 infection. Purpose: To investigate the response to different treatments against COVID-19 in patients with a pre-existing CVD. Methods: We conducted a systematic review and meta-analysis following Cochrane, PRISMA and MOOSE guidelines (PROSPERO ref:CRD42020183057). Eligible articles reported in-hospital mortality rate in COVID-19 patients with CVD after testing specific treatments. Statistical concordance was performed by Cohen's kappa coefficient. The primary outcome was in-hospital mortality rate, secondary outcome was the length of hospital stay (LOS). The analysis utilised a random-effects model. Categorical variables were expressed as risk ratio (RR) and continuous variable with weighted mean difference (WMD) and standard deviation with 95% confidence interval (CI). I2 and Chi-tests were used to assess studies' heterogeneity. Publication bias was visualised by L'Abbe' plot and funnel plot with Egger's test. Subgroup analysis (pooling analysis) was also performed to compare the three groups' mortality differences: 'CVD treated' vs.'CVD untreated' vs.'no-CVD (treated and untreated)'. Meta-regression models were used to determine the effects of specific treatments and risk factors on the primary outcomes. R-studio used for analysis. Results: Of 1,673 articles retrieved, 46 studies included CVD patients from which 11 included control group, finally five were comparative studies and were included in the quantitative analysis. From those studies, the sample size was 130 (mean age 63.9±2.7 years;55.3% male). There was 100% concordance between reviewers equating to a Cohen's kappa coefficient of κ=1. The most frequent CV risk factor (CVRF) was hypertension (60%) followed by diabetes (28.5%). The most frequent CVD seen in patients was coronary artery disease at 9.09% and peripheral arterial disease at 5.4%. Mortality rate was significant higher in the CVD treated group (RR:1.52;95% CI [1.05,2.21], CVD treated vs overall population p=0.03). Meta-regression showed that no treatment was significant associated to mortality and systemic hypertension, but an independent risk factor for mortality. Pooled single analysis showed no difference between treated vs untreated CVD patients. There was certain degree of heterogeneity (I2 50%) across the studies. L'Abbe and funnel plot visualized not significant dispersion (Egger test, p=0.71). There was no difference in terms of LOS [0,79, 95% CI (-0.48, 2,05);p-value 0.22]. Conclusions: This quantitative analysis showed that CVD patients despite specific treatments were exposed to significant higher mortality when compared to the overall population. These results remark the clinical relevance to reduce CVD risk factors and ameliorate specific COVID-19 treatments to lower the risk of mortality in this group.