Effect of colchicine on progression of known coronary atherosclerosis in patients with STable CoROnary artery disease CoMpared to placebo (EKSTROM) trial-rationale and design.

BACKGROUND: Cardiovascular disease is the major cause of mortality in the United States. Despite lifestyle modification and traditional risk factor control residual inflammatory risk remains an untreated concern. Colchicine is an oral, medication that has been used for gout, mediterranean fever and pericarditis for decades. In recent trials, colchicine has been shown to reduce major adverse cardiovascular events, however the mechanism of benefit remains unclear. The objective of the randomized, double-blind, placebo controlled EKSTROM trial is to evaluate the effects of colchicine 0.5mg/day on atherosclerotic plaque. METHODS: Eighty-four participants will be enrolled after obtaining informed consent and followed for 12 months. Eligible patients will be randomly assigned to colchicine 0.5mg/day or placebo in a 1:1 fashion as add-on to their standard of care. All participants will undergo coronary computed tomography angiography (CCTA) at baseline and at 12 months. RESULTS: As of November 2023, the study is 100% enrolled with an expected end of study by the second quarter of 2024. The primary endpoint is change in low attenuation plaque volume as measured by CCTA. Secondary endpoints include change in volume of different plaque types (including total atheroma volume, noncalcified plaque volume, dense calcified plaque volume, remodeling index), change in inflammatory markers (IL-6, IL-1ß, IL-18, hs-CRP), change in pericoronary adipose tissue attenuation, change in epicardial adipose tissue volume and attenuation and change in brachial flow mediated dilation. CONCLUSION: EKSTROM is the first randomized study to assess the effects of colchicine on plaque progression, pericoronary and epicardial fat. EKSTROM will provide important information on the mechanistic effects of colchicine on the cardiovascular system. TRIAL REGISTRATION: Registry: clinicaltrials.gov, Registration Number: NCT06342609 url: https://www. CLINICALTRIALS: gov/study/NCT06342609?term=EKSTROM&rank=1.

Prognostic value of coronary artery calcium score for the prediction of atherosclerotic cardiovascular disease in participants with suspected nonalcoholic hepatic steatosis: Results from the multi-ethnic study of atherosclerosis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) events; thus, a diagnostic approach to help identify NAFLD patients at high risk is needed. In this study, we hypothesized that coronary artery calcium (CAC) screening could help stratify the risk of ASCVD events in participants with suspected nonalcoholic hepatic steatosis. METHODS: A total of 713 participants with suspected nonalcoholic hepatic steatosis without previous cardiovascular events from the Multi-Ethnic Study of Atherosclerosis (MESA) were followed for the occurrence of incident ASCVD. Nonalcoholic hepatic steatosis was defined using nonenhanced computed tomography and liver/spleen attenuation ratio <1. Cox proportional hazards regression models were used to estimate hazard ratios (HR). C-statistics and areas under the time-dependent receiver operating characteristic curves (tAUC) were used to compare incremental contributions of CAC score when added to the clinical risk factors. RESULTS: In multivariable analyses, CAC score was found to be independently associated with incident ASCVD (HR = 1.33, 95% CI = 1.22-1.44, P < .001). The addition of CAC score to clinical risk factors increased the C-statistic from 0.677 to 0.739 (P < .001) and tAUC at 10 years from 0.668 to 0.771, respectively. In subgroup analyses, the incremental prognostic value of CAC score was more significant in participants with low/borderline- (<7.5%) and intermediate- (7.5%-20%) 10-year ASCVD risk scores. CONCLUSIONS: The inclusion of CAC score in global risk assessment was found to significantly improve the classification of incident ASCVD events in participants with suspected nonalcoholic hepatic steatosis, indicating a potential role for CAC screening in risk assessment.

Psychiatric Illness in Takotsubo (Stress) Cardiomyopathy: A Review.

BACKGROUND: Takotsubo cardiomyopathy (TC), also known as stress-induced cardiomyopathy, has been increasingly described in relation to psychiatric illness. METHODS: We performed a literature review to identify the key findings related to psychiatric illness in TC that may be relevant to the practice of mental health and other health care providers. RESULTS: The association of psychiatric illness with TC in addition to the spectrum of psychiatric illness found in TC, the role of exacerbation or treatment of psychiatric illness in triggering TC, different modes of presentation, prognostic implications, and long-term management of psychiatric illness in TC are discussed. Additionally, we review the limitations of the pre-existing literature and suggest areas of future research. CONCLUSIONS: There is a strong association between pre-existing psychiatric illness, particularly anxiety and mood spectrum disorders, and TC. Acute exacerbation of psychiatric illness, rapid uptitration or overdose of certain psychotropic agents, and electroconvulsive therapy may trigger TC. Further studies are needed to better evaluate the prognostic significance and long-term management of psychiatric illness in TC.

Neurosurgical referral service using smartphone client WhatsApp: preliminary study at a tertiary referral neurosurgical unit.

BACKGROUND: Smartphone-based clients are being increasingly used in a medical world for individual as well as group communications. The authors report the use of WhatsApp, a common social media smartphone client for neurosurgical referral service in their Institution. They extend the use of WhatsApp application from a purely intra-departmental informal communication to a formal tertiary referral service for Neurosurgical referrals. The pros and cons of deploying such system are discussed and important concerns are highlighted. METHODS: Over a period of one year, the authors record 1412 referrals to the Neurosurgical service at a tertiary referral centre using WhatsApp application. All the data gathered through WhatsApp referrals was subsequently validated and analysed for any errors. They identify eight incidences where the system did not accurately convey the intended information. They highlight the potential issues related to data accuracy and confidentiality encountered in using such a system. OBSERVATIONS: In this preliminary study, the authors consider WhatsApp application as an important tool for Neurosurgical referrals. It is safe, cheap, reliable and user-friendly application allowing seamless transfer of data including clinical videos and scan images to the on call neurosurgical team. Loss of data quality, concerns surrounding patient confidentiality, errors caused by inter-operator variability in capturing data and default prohibition of use of such social media applications in many institutions are important disadvantages in regularly using such service. CONCLUSIONS: Smartphone-based social media clients such as WhatsApp provide a promising future for faster, reliable communication of clinical and radiological data, which can be used for on-call neurosurgical referrals. Integration with PACs applications and facial recognition may facilitate increasing use of such applications in future addressing many of the concerns that currently prohibit their universal use.

Left Ventricular Septolateral Mechanical Delay Is Associated with Reduced Long-Term Survival in Systolic Heart Failure with Narrow QRS Duration: Nine-Year Outcome in 109 Patients.

BACKGROUND: The long-term prognostic importance of left ventricular (LV) dyssynchrony in patients with systolic heart failure is not known. We investigated this question in 109 consecutive patients with systolic heart failure with an LV ejection fraction (EF) ≤35% and QRS duration <130 ms. METHODS: The cohort is a prospective series of 109 patients with EF ≤35% and QRS duration <130 ms who did not receive a defibrillator. Onset to onset septolateral and anteroposterior mechanical delays were computed from tissue Doppler velocity signals of the four quadrants of the mitral annulus and related to mortality. RESULTS: Patient characteristics included age 53 ± 12 years, 73% male, 23% with coronary artery disease, LVEF 24 ± 7%, LV end-diastolic dimension 64 ± 9 mm, LV end-systolic dimension 55 ± 9 mm, QRS duration 107 ± 30 ms, and 92 with QRS duration <120 ms. Over a follow-up of 9 years, there were 51 deaths. Univariate predictors of mortality included LV septolateral delay (HR 1.01 per ms, P < 0.0001), anteroposterior delay (P = 0.003), and age (P = 0.005), but not EF, LV size, or QRS duration. Using Cox regression analysis, LV septolateral delay was an independent predictor of higher mortality (P = 0.0005) after adjusting for age, gender, EF, LV size, QRS duration, coronary artery disease, diabetes mellitus, and use of beta blockers or angiotensin-converting enzyme inhibitors. CONCLUSION: In patients with heart failure, LVEF ≤35% and QRSd < 130 ms, LV mechanical dyssynchrony is a strong and independent predictor of long-term mortality.

Predicting in-hospital mortality among patients admitted with a diagnosis of heart failure: a machine learning approach.

Existing risk prediction models for hospitalized heart failure patients are limited. We identified patients hospitalized with a diagnosis of heart failure between 7 May 2013 and 26 April 2022 from a large academic, quaternary care medical centre (training cohort). Demographics, medical comorbidities, vitals, and labs were collected and were used to construct random forest machine learning models to predict in-hospital mortality. Models were compared with logistic regression, and to commonly used heart failure risk scores. The models were subsequently validated in patients hospitalized with a diagnosis of heart failure from a second academic, community medical centre (validation cohort). The entire cohort comprised 21 802 patients, of which 14 539 were in the training cohort and 7263 were in the validation cohort. The median age (25th-75th percentile) was 70 (58-82) for the entire cohort, 43.2% were female, and 6.7% experienced inpatient mortality. In the overall cohort, 7621 (35.0%) patients had heart failure with reduced ejection fraction (EF ≤ 40%), 1271 (5.8%) had heart failure with mildly reduced EF (EF 41-49%), and 12 910 (59.2%) had heart failure with preserved EF (EF ≥ 50%). Random forest models in the validation cohort demonstrated a c-statistic (95% confidence interval) of 0.96 (0.95-0.97), sensitivity (SN) of 87.3%, and specificity (SP) of 90.6% for the prediction of in-hospital mortality. Models for those with HFrEF demonstrated a c-statistic of 0.96 (0.94-0.98), SN 88.2%, and SP 91.0%, and those for patients with HFpEF showed a c-statistic of 0.95 (0.93-0.97), SN 87.4%, and SP 89.5% for predicting in-hospital mortality. The random forest model significantly outperformed logistic regression (c-statistic 0.87, SN 75.9%, and SP 86.9%), and current existing risk scores including the Acute Decompensated Heart Failure National Registry risk score (c-statistic of 0.70, SN 69%, and SP 62%), and the Get With the Guidelines-Heart Failure risk score (c-statistic 0.69, SN 67%, and SP 63%); P < 0.001 for comparison. Machine learning models built from commonly recorded patient information can accurately predict in-hospital mortality among patients hospitalized with a diagnosis of heart failure.

Testosterone therapy and the risk of cardiovascular disease in older, hypogonadal men.

The debate over the cardiovascular (CV) implications of testosterone therapy (TT) have resulted in diverging safety recommendations and clinical guidelines worldwide. This narrative review synthesizes and critically evaluates long-term studies examining the effects of TT within the context of aging, obesity, and endogenous sex hormones on CV disease (CVD) risk to support informed clinical decision-making. Observational studies have variably linked low endogenous testosterone with increased CVD risk, while randomized controlled trials (RCTs) demonstrate that TT yields cardiometabolic benefits without increasing short-term CV risk. The TRAVERSE trial, as the first RCT powered to assess CVD events, did not show increased major adverse cardiac events (MACE) incidence; however, its limitations - specifically the maintenance of testosterone at low-normal levels, a high participant discontinuation rate, and short follow-up - warrant a careful interpretation of its results. Furthermore, findings from the TTrials cardiovascular sub-study, which showed an increase in non-calcified plaque, indicate the need for ongoing research into the long-term CV impact of TT. The decision to initiate TT should consider the current evidence gaps, particularly for older men with known CVD. The CV effects of maintaining physiological testosterone levels through exogenous means remain to be fully explored. Until more definitive evidence is available, clinical practice should prioritize individualized care and informed discussions on the potential CV implications of TT.

Colchicine and plaque: A focus on atherosclerosis imaging.

Colchicine is an anti-inflammatory medication, classically used to treat a wide spectrum of autoimmune diseases. More recently, colchicine has proven itself a key pharmacotherapy in cardiovascular disease (CVD) management, atherosclerotic plaque modification, and coronary artery disease (CAD) treatment. Colchicine acts on many anti-inflammatory pathways, which translates to cardiovascular event reduction, plaque transformation, and plaque reduction. With the FDA's 2023 approval of colchicine for reducing cardiovascular events, a novel clinical pathway opens. This advancement paves the route for CVD management that synergistically merges lipid lowering approaches with inflammation inhibition modalities. This pioneering moment spurs the need for this manuscript's comprehensive review. Hence, this paper synthesizes and surveys colchicine's new role as an atherosclerotic plaque modifier, to provide a framework for physicians in the clinical setting. We aim to improve understanding (and thereby application) of colchicine alongside existing mechanisms for CVD event reduction. This paper examines colchicine's anti-inflammatory mechanism, and reviews large cohort studies that evidence colchicine's blossoming role within CAD management. This paper also outlines imaging modalities for atherosclerotic analysis, reviews colchicine's mechanistic effect upon plaque transformation itself, and synthesizes trials which assess colchicine's nuanced effect upon atherosclerotic transformation.

Slow rate of progression of grade 1 and 2+ aortic regurgitation.

BACKGROUND AND AIM OF THE STUDY: Although the progression of aortic stenosis has been well studied, the rate of progression of aortic regurgitation (AR) has not been definitively established. Further data would be valuable for clinical decision-making in patients with milder degrees of AR undergoing non-aortic valve cardiac surgery. Hence, this point was investigated in a large cohort of patients with grade 1 or 2+ AR. METHODS: The authors' echocardiographic database acquired between 1993 and 2007 was screened for patients with grade 1 or 2+ AR who had undergone follow up echocardiography at least one year later. The AR severity was graded as 1 to 4+, and any annual changes in AR grade were monitored. RESULTS: Among a total of 4,128 patients identified, 3,266 had grade 1+ AR and 862 had grade 2+ AR on the initial echocardiogram: the mean age was 67 +/- 15 years, and the duration of follow up was 4.2 +/- 2.7 years. Of those patients initially with grade 1+ AR, 95% showed no change in AR over a mean interval of 4.2 years, with an annual average increase in AR grade of 0.04. Of those patients initially with grade 2+ AR, 90% showed no change over this period, with an annual average increase in grade of 0.07. In the entire cohort, the AR progression correlated positively with age (p = 0.03), ventricular septal thickness (p < 0.0001), stroke distance (the time velocity integral of flow in the left ventricular outflow tract) (p = 0.0003), the presence of any degree of aortic stenosis (p = 0.01), and initial AR severity (p < 0.0001). CONCLUSION: The rate of AR progression is extremely slow, and prophylactic aortic valve replacement during non-aortic surgery may not be indicated in patients with grade 1 or 2+ AR in the absence of any higher risk for progression, such as grade 2+ AR combined with any degree of aortic stenosis and advanced age.

Head Over Wheels: Traumatic Head and Neck Injuries Secondary to Mountain Biking.

OBJECTIVES: The popularity of mountain biking (MTB) in the United States has risen in recent years. We sought to identify the prevalence and distribution of MTB associated head and neck injuries presenting to emergency departments across the U.S. and identify risk factors for hospital admission in this patient population. METHODS: The National Electronic Injury Surveillance System (NEISS) was queried for MTB related injuries of the head and neck from 2009 to 2018, with analysis for incidence, age, gender, anatomic site, and diagnoses. RESULTS: A total of 486 cases were identified, corresponding to an estimated 18 952 head and neck MTB related ED visits. Patients were predominantly male (80.7%) and white (69.8%) with a median age of 35 years (interquartile range, 21-46 years). A majority (88.4%) of patients were released from the ED, but a significant proportion of patients were admitted (9.2%) or transferred (1.2%). The most common facial fractures were facial/not specified (35%), nasal bone (29%), mandible (15%), orbit (12%), and zygomaxillary complex (9%). The greatest predictors of hospital admission/transfer were injury to the mouth or neck and avulsion-type injury (P < .001). CONCLUSIONS: MTB results in a significant number of traumatic head and neck injuries nationwide. Patients are primarily adult, white males. The majority of injuries result in discharge from the ED, however a small amount of these patients experience significant morbidity necessitating hospital admission. Understanding the distribution of MTB head and neck injuries may aid in the clinical evaluation of these patients. LEVEL OF EVIDENCE: 4.

Bladder-sparing treatment in MIBC: where do we stand?

INTRODUCTION: The gold-standard treatment of muscle-invasive bladder cancer is radical cystectomy (RC), but this can be associated with morbidity and perioperative risks. Patients may not be fit for RC or choose to preserve their bladders. There are evolving bladder-sparing treatments that are often delivered in a multimodal approach. Here, we aim to review recent advances in bladder-sparing treatments. EVIDENCE ACQUISITION: We undertook a narrative review informed by a Medline/PubMed literature search using a combination of terms for recent (5 years) articles in English. Relevant studies from authors' bibliographies were retrieved. EVIDENCE SYNTHESIS: Bladder-sparing treatment consists of transurethral resection of bladder tumour (TURBT), radiotherapy and chemotherapy. Experimental approaches with immunotherapy and using gene signatures for radiation therapy and chemotherapy response are being explored. CONCLUSIONS: Bladder-sparing treatment is an option for patients with bladder cancer. Those who may benefit most are those with solitary invasive cancers, those with good bladder capacity and compliance, those who choose to preserve their bladder and sexual function and who are not fit for RC. Multimodal bladder-sparing approaches may have comparable oncological outcomes to RC and so appear an attractive alternative in suitable patients.

Cross-Modal Health State Estimation.

Individuals create and consume more diverse data about themselves today than any time in history. Sources of this data include wearable devices, images, social media, geo-spatial information and more. A tremendous opportunity rests within cross-modal data analysis that leverages existing domain knowledge methods to understand and guide human health. Especially in chronic diseases, current medical practice uses a combination of sparse hospital based biological metrics (blood tests, expensive imaging, etc.) to understand the evolving health status of an individual. Future health systems must integrate data created at the individual level to better understand health status perpetually, especially in a cybernetic framework. In this work we fuse multiple user created and open source data streams along with established biomedical domain knowledge to give two types of quantitative state estimates of cardiovascular health. First, we use wearable devices to calculate cardiorespiratory fitness (CRF), a known quantitative leading predictor of heart disease which is not routinely collected in clinical settings. Second, we estimate inherent genetic traits, living environmental risks, circadian rhythm, and biological metrics from a diverse dataset. Our experimental results on 24 subjects demonstrate how multi-modal data can provide personalized health insight. Understanding the dynamic nature of health status will pave the way for better health based recommendation engines, better clinical decision making and positive lifestyle changes.

Temporal Pattern and Prognostic Significance of Hypokalemia in Patients Undergoing Targeted Temperature Management Following Cardiac Arrest.

Hypokalemia has been consistently reported as a common occurrence during targeted temperature management (TTM) in comatose survivors of cardiac arrest. We sought to better describe changes in serum potassium throughout the different stages of TTM and to assess for any prognostic significance. We analyzed a prospectively collected cohort of 240 patients treated with TTM following cardiac arrest at a tertiary care hospital between 2007 and 2014. The primary outcome was poor neurologic outcome at hospital discharge, defined as a Cerebral Performance Category score >2. Secondary outcomes included death and recurrent ventricular arrhythmia before hospital discharge. Multivariable logistic regression was used to assess for association of hypokalemia and hyperkalemia with the designated outcomes. During all phases of TTM, hypokalemia and hyperkalemia occurred in 207 (86%) and 77 (32%) of patients, respectively. Hypokalemia occurred in 203 (85%) patients at target temperature, and 25 (10%) patients were hyperkalemic following normothermia. In multivariable logistic regression, hypokalemia was not associated with poor neurologic outcomes or recurrent ventricular arrhythmia. Hypokalemia was associated with reduced odds of death before hospital discharge (odds ratio = 0.36, 95% confidence interval 0.13 to 0.97, p = 0.044). Hyperkalemia was not associated with poor neurologic outcomes, death, or recurrent ventricular arrhythmia.