Challenges and Opportunities in Myocardial Infarction
Angel Martin Castellanos
Abstract
Despite the impact of the COVID‑19 pandemic, myocardial infarction remains the leading cause of cardiovascular deaths in Europe. Body mass index (BMI)-defined obesity is a major risk factor for myocardial infarction. However, in the association of anthropometrics and myocardial infarction, the lack of balance between the simple body measurements when comparing healthy and unhealthy cases has demonstrated that affects the outcome. Thus, regardless of association strength of anthropometrics, other criteria to judge the biological causality must be investigated.
We aim to assess different studies worldwide to understand the key concepts to demonstrate association biases for anthropometrics when predicting myocardial infarction risk. In this approach, natural mathematical inequalities between simple measurements in healthy subjects were investigated. Weight, height, height/2, waist circumference and hip circumference mathematically represent absolute values that do not express mathematically equality for the true risk. That way, the mathematical concept of fraction or ratio in anthropometrics such as BMI, waist-to-hip ratio (WHR) or waist-to-height ratio (WHtR) plays an important role. Thus, some anthropometrics may be seen as confounding variables when measuring high-risk body composition. Weight is a confounding factor without indicating a high-risk body composition, meaning that BMI is not fully predictive. WHR is a confounding variable concerning waist and WHtR due to imbalances between the mean hip–waist and hip–height, respectively, which indicates a protective overestimation for hip concerning waist and height. Waist measure may be a confounding variable concerning WHtR due to an imbalance in the mean waist–height. This occurs if, and only if, WHtR risk cut-off is >0.5 and if height is ignored as volume factor, therefore creating an overestimation of risk for waist circumference in the tallest people and underestimation in the shortest. Mathematically/anthropometrically, only WHtR-associated risk above BMI, waist and WHR holds true while considering it as a relative risk volume linked to a causal pathway of higher cardiometabolic risk.
In conclusion, WHtR is the only metric that is directly associated to a risk volume and having more biological plausibility. It should be used to assess the anthropometrically-measured myocardial infarction risk, once the imbalances between measurements and association biases are recognised.
ngel Martin Castellanos
Abstract
Cardiovascular diseases, mainly myocardial infarction and stroke, are the leading cause of death globally. Therefore, epidemiological research seems necessary to prevent cardiovascular events and mortality. However, real-world data from obesity metrics has intrinsic limitations for the assessment of causality. Despite of historical studies showing that the body mass index (BMI), the waist-to-hip ratio (WHR) and the waist circumference (WC) have been associated with increased risk of myocardial infarction, they might not be accurate from a causal inference.
Our aim was to summarize historical and novel findings about obesity metrics and myocardial infarction to evidence causal association biases. Method: an epidemiological review study was conducted while being original research when adding new anthropometrics in study design. Mathematical inequalities between the simple body measurements in anthropometrically healthy adults were described. Mean values and cut-offs for classic and several newer anthropometric variables were established. Classic metrics, ratios between the means of the simple measurements, a modulus |x| as a result of subtracting some measurement means from others (e.g., mean fat free mass minus fat mass) and somatotype ratings were collated. Mathematically, a non-zero difference for each modulus |x| in any population study would indicate an unbalanced distribution of the measurements between groups being compared, and therefore, the risk exposure levels differing. Thus, when between-groups the high-risk body compositions and somatotype ratings differ, any metric-associated risk is biased from a causal inference. After investigating large epidemiological studies, the historical omission of key anthropometric variables is stated, and as being uncontrolled confounding factors distorted causal inferences. Therefore, a protective overestimate of fat free mass and hip circumference over fat mass and WC, respectively, always occurred. Similarly, when the waist-to-height ratio values of >0.5 are associated; a protective underestimate of height over WC occurs. Any metric-associated risk is biased if prediction is made from WC or technologically measured body compositions without accounting for relative risk volume measures. In conclusion, summarizing the historical and novel findings regarding risk prediction, BMI, WHR and WC alone show evidence of causal association biases because of high-risk body compositions and risk exposure levels always differ between the groups being compared.
False Positive Results on Dobutamine Stress Echocardiography: A New Marker of Risk for Ischemic Events
Lisa Ferraz, Andreia Fernandes, Ana Faustino, Simão Carvalho, Adriana Pacheco & Ana Neves
Abstract
Background: Although dobutamine stress echocardiography (DSE) has a high specificity, there is still a subset of patients with false positive tests (FP); whether these results have prognostic value remains unclear.
Aims: To identify the clinical and echocardiographic predictors of FP on DSE and to evaluate the prognostic impact of FP on DSE.
Methods: Retrospective study of 355 consecutive patients who underwent DSE for ischemia assessment over a one-year period: 134 (37,7%) women, 70,3 ± 0,57 years. Demographics, risk factors, clinical and laboratorial parameters and DSE variables were evaluated. Patients were divided into 2 groups regarding the presence (FP+) or the absence (FP0) of a FP result on DSE and a comparative analysis was performed to characterize the groups and identify potencial predictors of FP results. Patients were followed for 2 years to assess acute myocardial infarction, hospitalization for acute heart failure (HF) and mortality.
Results: The FP rate was 4,5%. Comparing to FP0, patients in group FP+ were younger, baseline wall motion abnormalities were more frequent, had higher mean blood pressure values at rest and at peak stage and more often hypertensive response. There were no significant differences regarding previous coronary artery disease, medication or complete left bundle branch block. By multivariate analysis, only mean blood pressure values at rest (OR 0,01; 95%CI 0,005-0,02; p=0,003) and at peak stage (OR 0,02; 95%CI 0,000-0,004; p=0,003) were independent predictors of FP. During follow-up was observed: acute myocardial infarction (FP+: 12,5% vs FP0: 1,8%, p=0,046), HF (FP+: 6,3% vs FP0: 11,5%, p=0,44) and mortality (FP+: 6,3% vs FP0: 6,2%, p=0,65). After adjustment for age, sex and comorbidities, there were no diferences between the groups regarding HF and mortality, but the group FP+ mantained a higher rate of acute myocardial infarction (OR 0,21; 95%CI 0,065-0,354; p=0,005).
Conclusion: A FP result on DSE was associated with higher mean blood pressure values during the test and with higher rates of acute myocardial infarction during follow-up. This result on DSE should therefore be faced as a risk marker for ischemic events and can identify patients that may benefit from aggressive risk factor control and careful clinical follow-up.
Angel Martin Castellanos
Abstract
Among the components of Life’s Essential 8, body mass index is the anthropometric used in the scoring algorithm of cardiovascular health. Concerning myocardial infarction, the waist-to-hip ratio may show more predictive value than body mass index, waist circumference, and waist-to-height ratio, and has showed a greater excess risk of myocardial infarction in women than in men. However, bias has occurred in global research because of inadequate comparisons with the high-risk body composition. Hence, cardiology may have been confused for a long time because bias-related errors were always overlooked. This situation occurred when risk association was distorted by over- or under-estimating some simple measurements over others. Our aim was to determine whether the historical risk associated with some anthropometrics might provide a bias in causal inferences. Our study design was a review on data of the body of literature. We created new anthropometric variables, which were always omitted in previous large studies. In most studies, mathematical inequalities between the simple measurements in anthropometrically healthy subjects were overlooked, including disparities between lean and fat masses. That way, in omitting the difference in means between the simple measurements of length and body mass components, association findings and causality cannot be assumed. No anthropometric will be equivalent for estimating the same high-risk body composition if the difference in means between the simple measurements present an unbalanced distribution, and besides, being associated as confounding factors. Therefore, after describing new anthropometric variables termed as “x” and demonstrating that the simple measurements showed means of differences differentially distributed between healthy and unhealthy cases worldwide, association biases for the body mass index, waist-to-hip ratio or waist circumference alone may be endorsed, indicating the importance of these results. From a new anthropometric perspective, the waist-to-height ratio may indicate the concrete volume of an abdominal three-dimensional disc in direct-inverse relationship with waist-body height without showing association biases. This index may represent a new construct by defining a risk abdominal volume and avoiding potential confounding factors. In a paradigm shift, only the waist-to-height ratio meets causality criteria as the optimal index to predict myocardial infarction risk and to promote cardiovascular health.
Akira T Kawaguchi
Tatsuhide Tanaka, PhD & Mariko Yamano, PhD
Hideaki Sumiyoshi, PhD, Yoshiyuki Yamada, MD, PhD & Gen T Kawaguchi, MD
Hiroaki Kitagishi, PhD
Jacob Bergsland, MD, PhD
Abstract
Objective: Effects of PEGylated-carboxyhemoglobin bovine (SG) infusion and carbon monoxide (CO) inhalation were compared in a rat model of myocardial infarction (MI).
Methods: Lewis rats with induced MI received either 10 mL/kg of SG or of saline (SL), or 400 ppm CO inhalation (CO) daily for 3 days, 4 doses in total. On the fourth day, all animals had left ventricular (LV) functions studied by pressure-volume relationship analyses or in-situ myocardial gene expression by polymerase-chain reaction (PCR).
Results: Both SG infusion and CO inhalation increased the arterial carboxyhemoglobin fraction to 10%, which decreased the total O2 content by 10% for 3 hours before returning to control level, except for the plasma hemoglobin (Hb) over 200 mg/dL 24 hours later, in SG rats. Four days after MI, the SL and CO rats had enhanced cardiac contraction and relaxation, while the SG rats had LV end-systolic pressure, and the isovolumic contraction as well as relaxation remained suppressed at the post-MI levels. PCR showed significant reductions in in-situ antioxidant transcriptional master regulator (Nrf2), its down-stream antioxidant response genes (Nqo-1), hypoxic signal transduction in SG compared to SL or CO rats with enhanced pro-inflammatory, pro-apoptotic genes, and myocardial damage. These cardiac indices were reversed 4 weeks after MI, when SG had less LV dilatation, dysfunction, and myoglobin loss than those with SL or CO.
Conclusion: The results suggest that repeated SG infusion, but not CO inhalation, generates less oxidative stress, reduces hypoxic responses, supports early hemodynamics, and alleviates cardiac compensation early after MI, resulting in attenuated LV dilatation, dysfunction, and myoglobin loss late after MI in this rat model.
Siddhartha Mani, MD(Medicine), DM(Cardiology)
Sujata Sen, DNB(Emergency Medicine)
Kaushik Nag, MD(Community Medicine)
Prof. Sobhan Biswas, MD(Medicine)
Abstract
Background: The occurrence of arrhythmias among acute coronary syndrome patients is very common. However, their diagnosis is not considered in contemporary acute coronary syndrome patients. This study investigates the incidence and types of arrhythsmias among acute coronary syndrome patients presenting to the emergency department, as well as their association with various factors and patient outcomes.
Methods: The current prospective observational study was conducted at a tertiary care center in Kolkata, India. Data were collected from 76 acute coronary syndrome patients admitted between October 2020 and May 2021 to the emergency department. Information was gathered through semi-structured interviews and relevant investigations.
Results: The majority of the patients were aged 61-70 years, with three fourth of the study population being male. The incidence of arrhythmia was diagnosed in 77.6% of the patients. The most common arrhythmias were sinus tachycardia, ventricular premature complex, atrial fibrillation, sinus bradycardia, and complete heart block. Arrhythmias were more prevalent among ST-elevation myocardial infarction (62.7%) and unstable angina (8.5%) patients. Patients with Left Ventricular Ejection Fraction ≤ 40% had a higher incidence of arrhythmias (93.5%). The mortality rate during hospital stay was 11.9% among acute coronary syndrome patients with arrhythmias, while all acute coronary syndrome patients without arrhythmia had a 100% survival rate.
Conclusion: This study highlights the incidence and types of arrhythmias in acute coronary syndrome patients presenting to the emergency department. It reveals a higher prevalence of arrhythmias in specific subgroups, such as patients with ST-elevation myocardial infarction and those with a reduction in left ventricular function. These findings contribute to our understanding of arrhythmias in acute coronary syndrome and their association with patient outcomes, emphasizing the importance of appropriate management and monitoring in this population.
Arthur J. Siegel, M.D.
Abstract
The COVID-19 pandemic has decreased life-expectancy in the United States in 2021, causing over one million deaths especially in elderly persons with medical co-morbidities. While now waning, this epidemic continues to cause more than 500 fatalities per week mostly in individuals over70 years of age who are unvaccinated. Since viral epidemics have been shown to increase mortality due to atherosclerotic coronary heart disease and low-dose aspirin has been shown to reduce first myocardial infarctions by 44%, we recommend consideration of expanding the use of aspirin for primary cardiovascular prevention to reduce the cardiac morbidity and excess mortality associated with COVID-19 infections. Such aspirin use may be seen as especially appropriate for vulnerable elderly persons who qualify for treatment with Paxlovid (ritonavir-boosted nirmatrelvir) but are currently excluded for such in primary prevention guidelines of subspecialty societies. The rationale for this approach is further supported by recent proof of concept that vaccination, an alternative intervention for primary cardiovascular prevention, reduces the excess mortality associated with COVID-19 infection.
Can greater use of aspirin for primary cardiovascular prevention mitigate the excess cardiac mortality associated with COVID-19 as shown with prior viral epidemics 1-3? Recommendations from the 2019 ACC/AHA and 2021 ESC guidelines currently advise limited aspirin use for primary prevention except in persons aged 40 to 59 years with elevated ASCVD risk scores (10-year risk ≥10%) and for those aged 60 to 69 years only with risk ≥20% in the context of no excess risk of bleeding (Figure 1) 4,5. These guidelines have been endorsed by the United States Preventive Services Task Force, which acknowledge that low-dose aspirin in the primary prevention setting reduces the risk of major atherosclerotic cardiovascular events including myocardial infarction and ischemic stroke offset by an increased risk of gastrointestinal bleeding 7,8. Currently endorsed guidelines specifically recommend against aspirin use in individuals at age 70 and beyond.
Abstract
Background: Although pancreaticoduodenectomy (PD) is safe when performed in high-volume hospitals, many patients in low-income countries cannot access these hospitals. Barbados is a small island that does not have a high-volume pancreatic center. We sought to document peri-operative outcomes when PD was performed in Barbados.
Methods: We carried out a retrospective cohort study of all consecutive patients who underwent PDs over from August 1, 2016 to October 30, 2022. Therapeutic outcomes, post-operative morbidity and mortality were evaluated. Statistical analyses were performed using SPSS ver 16.0.
Results: Six patients at a mean age of 54.8 years underwent PD (mean annual case volume of 1). Two patients underwent planned vein resections and reconstruction. In this subset, the mean operating time was 325 minutes (Range 300-250; Median 325; SD ±35.4), mean estimated blood loss was 825mls (Range 750-900; Median 825; SD±106.1), and the mean transfusion requirement was 1 unit of packed cells (Range 0-2; Median 1; SD±1.41).
In the four patients without vein resection, mean operating time was 308 minutes (Range 280-350; Median 300; SD±24.01), median blood loss was 575 ml (Range 150-900; Median 700; SD±320.6) and mean transfusion requirements were 0.5 units of packed cells (Range 0-2; Median 0; SD ±0.84).
The mean ICU stay was 2.17 days (Range 1-3; Median 2.5; SD±0.98), and the mean duration of hospitalization was 9.3 days (Range 7-11; Median 9.5; SD±1.37). There were no recorded peri-operative deaths, but there was 1 (17%) minor complication (delayed gastric emptying) and 1 (17%) major complication (myocardial infarction).
Conclusion: In Barbados, there are good peri-operative outcomes after PD despite the low volume and challenging healthcare environment. We believe that (1) surgeon experience (2) continuous adaptive hospital learning and (3) regular audit of hospital data are better indicators of PD quality than volume data alone.
Abstract
Coronary artery disease (CAD) is the number cause of death in the world. It is estimated that 50% of Americans will experience a cardiac event in their lifetime. The underlying pathology leading to coronary artery disease and its clinical manifestations, such as angina, myocardial infarction, and sudden death is coronary atherosclerosis. While the disease is not usually manifested clinically until the sixth or seventh decade, the underlying pathology is initiated as early as the second or third decade. Numerous randomized clinical trials have shown cardiac morbidity and mortality can be prevented by lowering the risk of known conventional risk factors for CAD such as decreasing plasma cholesterol or controlling hypertension. Secondary prevention of these conventional risk factors has been very effective; however, primary prevention has been shown to be even more effective. A major barrier to primary prevention is the lack of markers to detect among young asymptomatic individuals those at risk for CAD. The conventional risk factors are often not present until the sixth or seventh decade which could be late for primary prevention. Genetic predisposition accounts for 50% of the risk for CAD. Recently over 200 genetic risk variants predisposing to CAD have been discovered. Based on these variants, one can express the genetic risk for CAD in a single number referred to as the Polygenic Risk Score (PRS). The PRS has been evaluated in over one million individuals and shown that those with high genetic risk have the highest incidence of heart disease and can be reduced by 40-50%, utilizing drugs (statins and PCSK9 inhibitors) or lifestyle changes (favorable diet and increased exercise). The genetic risk for CAD is determined at conception and thus can be predicted anytime from birth onward. The PRS detection of young asymptomatic individuals based on the PRS enables one to implement early primary prevention. Adoption of the PRS to risk stratify for CAD could represent a paradigm shift in the prevention of this pandemic disease.
John T. Braggio
Abstract
The success of remote sensing methodology to accurately estimate ambient particulate matter (PM) on the earth’s surface has resulted in the increased use of aerosol optical depth (AOD) AOD-PM10, AOD-PM2.5, and AOD-PM1 concentration level fused surfaces in cardiovascular epidemiologic and hypothesis-testing of inflammatory physiologic studies. AOD-PM fused surfaces have served as proxies for ambient PM monitor measurements in economically developed and developing counties as well as in urban and rural areas. Since 2012, 45 published studies have evaluated the association between increased AOD-PM concentration level readings and adverse cardiovascular outcomes. Fifteen surveillance studies used inflammation as a descriptive physiologic mechanism and another 20 investigations used the inflammatory physiologic mechanism to explain how AOD-PM exposure changes the cardiovascular system. Among the remaining ten studies, nine mentioned another description and one referred to another explanation. Analyses of the published studies showed: 1) There was 81% agreement between AOD-PM2.5 readings and ambient PM2.5 monitor measurements. 2) Developing countries had higher AOD-PM2.5 readings than developed countries. 3) Descriptive physiologic inflammatory studies found positive associations between higher AOD-PM readings and more acute myocardial infarction, cardiovascular disease, and heart failure outcomes. 4) Higher AOD-PM readings were associated with abnormal blood glucose, c-reactive protein and lipids in studies that cited the inflammatory physiologic mechanism as an explanation. 5) The percentage of specific outcomes increased as the number of identified risk factors also went up only if the AOD-PM2.5 readings were higher and decreased if the AOD-PM2.5 readings were lower. 6) The inflammation description AOD-PM2.5 readings mean (43.4 μg/m3) did not differ from the inflammation explanation AOD-PM2.5 mean (32.0 μg/m3). Study results were used to update the physiologic inflammatory mechanism as a mediator of the effects of AOD-PM exposure on the cardiovascular system. The full extent of the adverse effects of AOD-PM exposure on the cardiovascular system only becomes evident when cardiovascular and other pathophysiological changes are also considered and evaluated. This review paper aims to demonstrate why AOD-PM and cardiovascular system studies are a new and useful source of information about how ambient PM exposure adversely impacts the cardiovascular system in diverse populations in different countries.
Ashish Vasudev, BSc (Hons), MBchB
Abdus Samee Wasim, BSc (Hons), MBBS, MRSC
Akash Sharma, FRCS(Tr&Orth)
Yuvraj Agrawal, FRCS(Tr&Orth)
Abstract
Hip and knee arthroplasty is an extremely successful and cost-effective procedure that is widely performed to restore function and alleviate pain. The arrival of the SARS-CoV-2 virus (COVID-19) brought significant disruptions to delivery of surgery worldwide, including lower limb arthroplasty. Three years on from the start of the pandemic the effects of the virus are still present. This literature review aims to explore current data published from our single specialty orthopaedic centre and data collected nationally and internationally, on the impact of the COVID-19 pandemic on lower limb arthroplasty.
Elective hip and knee arthroplasty in the UK fell by approximately 40% and 50% respectively (2020 vs 2019) and by the end of 2021 the number of procedures completed still remained below pre-pandemic levels. As a result, elective waiting times are longer than ever before, with more patients suffering worse health states and a significant impact on quality of life. The UK National Hip Fracture Database showed an active COVID-19 infection was associated with a three-fold greater risk of 30-day mortality post lower limb arthroplasty. Several reports have also correlated peri-operative COVID-19 infection with increased risk of systemic complications with the virus such as pneumonia, deep vein thrombosis, pulmonary embolisms, acute kidney injury and myocardial infarction to name a few.
NHS England provided guidelines for safe recommencement for elective operating. Upon adoption of these recommendations, several orthopaedic units found similar rates of post-operative complications and mortality to pre-pandemic levels, demonstrating that safe elective care can be delivered even during an emergency pandemic setting. The development of rapid testing, use of personal protective equipment and introduction of pre- and post-operative isolation protocols were effective measures to allow elective surgery to restart. For infected individuals awaiting surgery, delays of at least seven weeks are recommended to reduce complication rates. There is limited literature discussing the impact of the vaccine on post-operative complications and mortality. Early reports however have suggested vaccinated individuals benefit from a reduced mortality risk in emergency cases of hip fracture surgery, but this is an area which would benefit from further research.
Ovidiu Vasile Jimborean, Daniela Tatiana Sala, Cristian Borz, Marton Denes, Mara Andreea Vultur, Gabriela Jimborean & Radu Mircea Neagoe
Abstract
We analized the early and late postoperative complications that occurred after 693 bypass operations (574 anatomic and 119 extra-anatomic) performed in 10 consecutive years (1997-2006). The bypass graft failures (infection + thrombosis) treatment and the subsequent evolution of the patients were detected by analyzing patients’ readmissions made to solve these major post-bypass complications. The follow-up period extended up to 12 years after the primary arterial bypass reconstruction. In this period we registered: 89 secondary arterial reconstructions for early and late graft thrombosis; 8 healings after removal of the infected prostheses, followed by extraanatomic bypass operations (7 obturator bypass + 1 axillo-bifemoral bypass). The most frequent vascular prosthesis infection sites were the Scarpa triangle and the thoraco-abdominal subcutaneous segment of the axillo(bi)-femoral graft. Major amputations after extraanatomic bypass operations: at 4 years postoperatively for axillo(bi)-femoral operations the amputation rate was 17.6%, while for crossover operations it was 7.5%. Perioperatory mortality after anatomic bypass operations = 2 intraoperatory and 8 postoperatory (1.38%/574 operations); perioperatory mortality after extraanatomic bypass operations: 2 postoperatory deaths (1.68%/119 operations), 1 after axillo-femoral prosthesis infection and 1 after acute myocardial infarction. In order to reduce the graft major complication rate after extraanatomic bypass operations we took the following measures: 1. When there are arterial occlusive lesions distal to the femoral tripod we ensured an adequate outflow which favores the long-term patency of the extraanatomic graft; this goal was obtained by 2 methods: by enlargement profundoplasty and/or by performing an additional distal bypass towards the popliteal artery or towards the subgenicular arteries. The distal subgenicular anastomosis was made between a venous graft and the distal outflow artery for reducing the intimal hyperplasia. 2. For crossover bypass operations we often used autologous vein grafts; 3. In crossover ilio-femoral bypass operation with venous graft we avoid the graft compression in its path through abdominal wall by passing the graft through a stable caliber hole made in a polypropylene closure mesh of the abdominal wall. 4. We promote the tunneling of the axillo-femoral prosthesis through the subaponeurotic muscular tissue because this tissue better protects the prosthetic graft against infection. 5. In order to reduce the groin prosthesis infections, we prefer performing ilio-femoral crossover bypass instead of femoro-femoral one. 6. The obturator bypass remains a valuable tratment for groin infected prosthesis.
Lawrence Baruch
Kirtipal Bhatia, MD& Persio David Lopez, MD
Olga Sherman, PharmD
Abstract
Direct oral anticoagulants are recommended as first line therapy for patients with atrial fibrillation and venous thromboembolic disease. Measurement of drug levels or pharmacodynamic effect is not recommended during treatment. Dose adjustments are based on age, weight, kidney function and drug-drug interactions. These adjustments are generally based on an estimate of their effect on drug concentration. DOAC dosing recommendations differ across the world. These differences in prescribing recommendations result in different levels of DOAC exposure in patients with identical clinical characteristics. Additionally, data from clinical trials has shown that drug levels may vary significantly in individual patients with identical clinical characteristics despite taking the same prescribed dose. More concerning is that current prescribing recommendations provide cut points for dose adjustments, as an example age 80 or greater in the case of apixaban in atrial fibrillation, which may result in dramatically higher drug concentrations in patients with significantly higher bleeding risk.
Data from outcome trials in both atrial fibrillation and venous thromboembolism have provided mean-median drug concentrations for each of the DOACs. These trial results appear to demonstrate that once a threshold DOAC plasma concentration is reached, higher concentrations fail to provide significant added ischemic stroke reduction while at the same time add an increased risk of bleeding. Bleeding remains a significant problem with DOACs and is associated with an increase in short and long-term mortality, ischemic stroke, myocardial infarction, cost, and drug interruption and discontinuation.
Over the past years, our clinic has been assessing DOAC concentration in patients at risk for under or over exposure. Based on our experience, clinical characteristics alone appear to be insufficient, as a significant number of patients with characteristics suggesting high exposure would be under-dosed using a purely clinical approach and an even greater number, who are at elevated risk of bleeding would have had excessive levels, if prescribing were based strictly on the established dose reduction criteria. We propose, and provide our supporting clinical experience, that measuring DOAC levels in select patients will increase the margin of safety of these medications without compromising efficacy.
Abstract
There have been significant improvement in the care of acute ischemic stroke (AIS) resulting in reducing death and improving outcomes. Numerous groundbreaking positive randomized controlled trials have demonstrated that strokes with large vessel occlusion (LVO) treated with endovascular mechanical thrombectomy (EVMT) with standard treatment are associated with much better outcomes compared to those treated only with standard therapy. Additional evidence also revealed that the positive outcomes continue to persists for stroke patients with large vessels occlusion if they are treated with 24 hours of symptoms including those with wake-up stroke. The evidence suggests that for every two-patient treated with EVMT, one patient can be saved, which is the highest evidence in the medicine surpassing acute myocardial infarction and other acute lifesaving therapies. Based on these evidence, the local, National and International organizations have updated the guidelines in the treatment of AIS which have remarkably strengthen the process, pathways and standards for acute ischemic stroke management in the developed countries. However, not much progresses have made in the developing and third-world countries for stroke therapies, because of cost, affordability and there are no third-party payers. Most recent trials have further discovered that stroke patient with LVO and a large core volume treated with endovascular perfusion therapy in conjunction with standard treatment do significantly better comparted to standard treatment alone. New trials have also demonstrated that stroke patients undergoing EVMT with or without thrombolytic have equal functional outcome. Additional evidence suggests that non-disabling stroke patients treated with dual antiplatelet have equal functional outcome with less bleeding risk compared to intravenous thrombolysis. These evolving evidences have provided us with the opportunities to simplify the algorithm and treatment of acute ischemic stroke, which not only will cutdown time by eliminating unnecessary steps and redundant therapies, but also will reduce the healthcare cost and improving global access, specially, countries where patients bear the costs. In this review, author presents real life stroke patients treated based on recent evidence and provides with a simple and swift algorithm, that will reduce time to perfusion therapy and will make treatment affordable globally.
Abhinav Shrivastava
Department of Cardiology, Maharaja Agrasen Hospital, New Delhi, India.
Preetika Maurya
Department of cardiology, Base Hospital Delhi Cantt, New Delhi, India.
Sunny Pathania
Army Institute of Cardiothoracic Sciences (AICTS), Pune, Maharashtra, India.
Sugam K Singh
Army Institute of Cardiothoracic Sciences (AICTS), Pune, Maharashtra, India.
Sanya Chhikara
Jacobi Medical Center, Bronx, New York, USA.
Ashwin Mahesh
Department of Cardiology UPMC Harrisburg Pennsylvania, USA.
Balwinder Singh
Army Institute of Cardiothoracic Sciences (AICTS), Pune, Maharashtra, India.
Navreet Singh
Army Institute of Cardiothoracic Sciences (AICTS), Pune, Maharashtra, India.
Ranjit Kumar Nath
Department of Cardiology, Dr RML Hospital & ABVIMS, New Delhi, India.
Nalin Kumar Mahesh
St. Gregorios Medical Mission Hospital, Parumala, Kerala, India.
Nitin Bajaj
Army Institute of Cardiothoracic Sciences (AICTS), Pune, Maharashtra, India.
Prafull Sharma
Department of Cardiology, Army Hospital Research and Referral, New Delhi, India.
Prashant Panda
Department of Cardiology, Advanced Cardiac Centre, PGIMER, Chandigarh, India.
Jaskaran S Dugal
Deapartment of Cardiology, Jehangir Hospital, Pune, India.
Ankush Gupta, MD, DM, FACC
Professor of Medicine and Interventional Cardiologist, Army Institute of Cardiothoracic Sciences (AICTS), Pune, India.
Abstract
Introduction: Contemporary evidence suggest the comparable performance of biodegradable polymer sirolimus eluting stents (BPSES) with that of second generation durable polymer drug eluting stents. This study was done to evaluate the performance of BPSES in all comer patients undergoing percutaneous intervention (PCI) in real world setting over a period of three years.
Materials & Methods: This was a prospective observational study, wherein all comer consecutive patients undergoing PCI with BPSES (Yukon Choice Elite stent by Translumina Therapeutics, India) were enrolled and followed up for 3 years. The study’s primary endpoint was the Device Oriented Composite Endpoint (DOCE), which included cardiac death, target vessel myocardial infarction (MI), and clinically driven target lesion revascularization (TLR); the co-primary endpoint was the Patient-Oriented Composite Endpoint (POCE), which included all-cause mortality, any MI , and any repeat revascularization and the secondary endpoint was definite or probable stent thrombosis (DST & PST).
Results: 301 patients with 502 lesions were treated with 485 BP-SES. Mean age of the study cohort was 61.6± 9.3 yrs and males were 79.1%. 18.6% patients were diabetic, 29.6% had ejection fraction less than 40% and 73.1% patients presented with acute coronary syndrome (ACS). Majority of the patient had triple vessel disease (TVD) (51.8%), multivessel PCI was done in 15.6% and complex PCI in 26.2% patients. A mean of 1.6 ±0.8 stents per patient with mean diameter 3.0 ± 0.3 mm and mean length of 27.2 ± 0.8 mm were placed. DOCE & POCE occurred in 7.9% (cardiac death-4.8%, TLR-2.6% & target vessel MI-0.4%) and 12.8% (All deaths-9.7%, any MI- 0.4% and any revascularisation-2.6%) patients respectively at three years follow-up. DST & PST rate was 0.9% and 0.4% respectively in the study cohort. All the cases of stent thrombosis occurred within 30 days. Kaplan Meier analysis revealed that diabetes mellitus, low ejection fraction (EF), acute coronary syndrome (ACS), long stents and complex intervention had no impact on occurrence of DOCE & POCE while using BP-SES in all-comer patient population.
Conclusion: Present study showed favourable long term safety and efficacy profile of BP-SES for all-comer patients undergoing PCI.
Aynur Ozge, MD, PhD
Department of Neurology, Mersin University School of Medicine, Mersin, Türkiye
Reza Ghouri
Department of Neurology, Brain 360 Integrative Center, İstanbul, Türkiye
Derya Uludüz
Department of Neurology, Brain 360 Integrative Center, İstanbul, Türkiye; Department of Neurology, Cerrahpaşa University Medical Faculty, İstanbul, Türkiye
Abstract
This comprehensive review examines the impact of vascular risk factors on the phenotypic expression of migraine in the elderly population. Migraine, particularly migraine with aura, has been established as a risk factor for ischemic lesions of the brain, stroke, and other cardiovascular diseases. The association between migraine and specific vascular events, such as stroke, myocardial infarction, and angina pectoris, underscores the need for a comprehensive understanding of the interplay between migraine and cardiovascular diseases. The challenges in differentiating migraine from vascular insults, especially in the elderly population, highlight the need for improved diagnostic and treatment strategies to address the complexities of managing migraine in this demographic. Patient education and treatment of modifiable risk factors may decrease future vascular events, emphasizing the importance of addressing vascular risk factors in migraine management. The potential impact of prevention and treatment of unfavorable arterial hemodynamics on neurocognitive outcomes underscores the broader implications of addressing vascular risk factors in migraine management. The clinical and public health relevance of understanding the modifiability of vascular risk factors in elderly migraine patients extends to addressing challenges in cancer survivorship, radiological emergency response, and rational person behavior, emphasizing the diverse applications of addressing vascular risk factors in healthcare and public health. Ultimately, the clinical and public health relevance of understanding the impact of vascular risk factors on the phenotypic expression of elderly migraine underscores the need for continued research and clinical vigilance in addressing the complex interplay between migraine and vascular risk factors in the elderly population.
Pancreaticoduodenectomies in a Low Volume, Small Island Eastern Caribbean State: A Retrospective Cohort Study
Abstract
Background: Although pancreaticoduodenectomy (PD) is safe when performed in high-volume hospitals, many patients in low-income countries cannot access these hospitals. Barbados is a small island that does not have a high-volume pancreatic center. We sought to document peri-operative outcomes when PD was performed in Barbados.
Methods: We carried out a retrospective cohort study of all consecutive patients who underwent PDs over from August 1, 2016 to October 30, 2022. Therapeutic outcomes, post-operative morbidity and mortality were evaluated. Statistical analyses were performed using SPSS ver 16.0.
Results: Six patients at a mean age of 54.8 years underwent PD (mean annual case volume of 1). Two patients underwent planned vein resections and reconstruction. In this subset, the mean operating time was 325 minutes (Range 300-250; Median 325; SD ±35.4), mean estimated blood loss was 825mls (Range 750-900; Median 825; SD±106.1), and the mean transfusion requirement was 1 unit of packed cells (Range 0-2; Median 1; SD±1.41).
In the four patients without vein resection, mean operating time was 308 minutes (Range 280-350; Median 300; SD±24.01), median blood loss was 575 ml (Range 150-900; Median 700; SD±320.6) and mean transfusion requirements were 0.5 units of packed cells (Range 0-2; Median 0; SD ±0.84).
The mean ICU stay was 2.17 days (Range 1-3; Median 2.5; SD±0.98), and the mean duration of hospitalization was 9.3 days (Range 7-11; Median 9.5; SD±1.37). There were no recorded peri-operative deaths, but there was 1 (17%) minor complication (delayed gastric emptying) and 1 (17%) major complication (myocardial infarction).
Conclusion: In Barbados, there are good peri-operative outcomes after PD despite the low volume and challenging healthcare environment. We believe that (1) surgeon experience (2) continuous adaptive hospital learning and (3) regular audit of hospital data are better indicators of PD quality than volume data alone.
Jacques Fair
Bachelors of Science, USA
Esperanza Acuna
Bachelors of Science in Physiology, USA
Robert Roberts
Executive Director of the Heart and Vascular Institute, St. Joseph’s Hospital and Medical Center in Phoenix, USA
Abstract
Coronary artery disease (CAD) is the number cause of death in the world. It is estimated that 50% of Americans will experience a cardiac event in their lifetime. The underlying pathology leading to coronary artery disease and its clinical manifestations, such as angina, myocardial infarction, and sudden death is coronary atherosclerosis. While the disease is not usually manifested clinically until the sixth or seventh decade, the underlying pathology is initiated as early as the second or third decade. Numerous randomized clinical trials have shown cardiac morbidity and mortality can be prevented by lowering the risk of known conventional risk factors for CAD such as decreasing plasma cholesterol or controlling hypertension. Secondary prevention of these conventional risk factors has been very effective; however, primary prevention has been shown to be even more effective. A major barrier to primary prevention is the lack of markers to detect among young asymptomatic individuals those at risk for CAD. The conventional risk factors are often not present until the sixth or seventh decade which could be late for primary prevention. Genetic predisposition accounts for 50% of the risk for CAD. Recently over 200 genetic risk variants predisposing to CAD have been discovered. Based on these variants, one can express the genetic risk for CAD in a single number referred to as the Polygenic Risk Score (PRS). The PRS has been evaluated in over one million individuals and shown that those with high genetic risk have the highest incidence of heart disease and can be reduced by 40-50%, utilizing drugs (statins and PCSK9 inhibitors) or lifestyle changes (favorable diet and increased exercise). The genetic risk for CAD is determined at conception and thus can be predicted anytime from birth onward. The PRS detection of young asymptomatic individuals based on the PRS enables one to implement early primary prevention. Adoption of the PRS to risk stratify for CAD could represent a paradigm shift in the prevention of this pandemic disease.
