Future Adverse Events Research Articles

Rheumatic heart disease presenting with paracentral acute middle maculopathy (PAMM): A case report from rural India

A 38-year-old gentleman presented to us with disturbance in his superior field of view for 3 days. His visual acuity in both eyes was 6/6, N6. The macula of the left eye had a hypopigmented band. OCT demonstrated hyperreflectivity of the inner plexiform, inner nuclear, and outer plexiform layers of the retina, and perimetry showed a corresponding visual field defect. The patient revealed a history of heart surgery 26 years ago, and an echocardiogram revealed mitral valve abnormalities. The history and findings led to a diagnosis of paracentral acute middle maculopathy (PAMM) secondary to rheumatic heart disease. The patient was referred to a cardiologist and started on anti-platelet medications. Thus, we report an unusual case of PAMM due to chronic rheumatic heart disease in a young male from remote rural India. In our case, we made sure to start the patient on anti-platelet medications to prevent future adverse events.

Relationship between serum iron level and physical function in heart failure patients is lost by presence of diabetes.

Iron deficiency (ID) is common in patients with heart failure (HF) and is reportedly associated with exercise intolerance and impaired quality of life. Iron supplementation therapy in HF patients with ID improves exercise capacity. Conversely, protective roles of iron depletion in the development of diabetes mellitus (DM) and its complications have been proposed. This study aimed to determine the impact of ID on physical function in HF patients with and without DM. We enrolled consecutive patients who were admitted to our institute for HF diagnosis and management. The short physical performance battery (SPPB) was used to evaluate physical function, and low physical function was defined as an SPPB score of <10 points as individuals with SPPB scores of <10 points are most likely to be classified as frail and are at high risk for disability and future adverse events, including death. ID was defined as serum ferritin<100 or 100-299ng/mL when transferrin saturation (TSAT) was <20% according to the HF guidelines. Among the 562 HF patients (72±14years old; 56% male), 329 patients (58%) and 191 patients (34%) had ID and low physical function, respectively. Multivariate logistic regression analysis showed that TSAT as a continuous variable, but not ID, was a predictor of low physical function (odds ratio: 0.980, P=0.024). Subgroup analysis showed that a significant association between low TSAT and low physical function was lost in HF patients with DM (P for interaction<0.001). A spline dose-response curve for the relationship between TSAT and risk of low physical function with adjustments for covariates associated with low physical function in non-DM patients was almost linear with an increase in the risk of low physical function as the TSAT increased, but such a relationship was not found in the analyses of DM patients. A lack of close TSAT-SPPB relationship in HF patients with DM was confirmed also in a propensity-score-matched cohort. TSAT as a continuous variable, but not ID, was independently associated with physical function in HF patients, and a significant association was lost in patients with HF and DM, suggesting a limited impact of iron supplementation therapy in HF patients with DM.

‘Super Rehab’: can we achieve coronary artery disease regression? A feasibility study protocol

IntroductionPatients diagnosed with coronary artery disease (CAD) are currently treated with medications and lifestyle advice to reduce the likelihood of disease progression and risk of future major adverse cardiovascular events...

Longitudinal clustering of Life's Essential 8 health metrics: application of a novel unsupervised learning method in the CARDIA study.

Changes in cardiovascular health (CVH) during the life course are associated with future cardiovascular disease (CVD). Longitudinal clustering analysis using subgraph augmented non-negative matrix factorization (SANMF) could create phenotypic risk profiles of clustered CVH metrics. Life's Essential 8 (LE8) variables, demographics, and CVD events were queried over 15ears in 5060 CARDIA participants with 18years of subsequent follow-up. LE8 subgraphs were mined and a SANMF algorithm was applied to cluster frequently occurring subgraphs. K-fold cross-validation and diagnostics were performed to determine cluster assignment. Cox proportional hazard models were fit for future CV event risk and logistic regression was performed for cluster phenotyping. The cohort (54.6% female, 48.7% White) produced 3 clusters of CVH metrics: Healthy & Late Obesity (HLO) (29.0%), Healthy & Intermediate Sleep (HIS) (43.2%), and Unhealthy (27.8%). HLO had 5 ideal LE8 metrics between ages 18 and 39years, until BMI increased at 40. HIS had 7 ideal LE8 metrics, except sleep. Unhealthy had poor levels of sleep, smoking, and diet but ideal glucose. Race and employment were significantly different by cluster (P < .001) but not sex (P = .734). For 301 incident CV events, multivariable hazard ratios (HRs) for HIS and Unhealthy were 0.73 (0.53-1.00, P = .052) and 2.00 (1.50-2.68, P < .001), respectively versus HLO. A 15-year event survival was 97.0% (HIS), 96.3% (HLO), and 90.4% (Unhealthy, P < .001). SANMF of LE8 metrics identified 3 unique clusters of CVH behavior patterns. Clustering of longitudinal LE8 variables via SANMF is a robust tool for phenotypic risk assessment for future adverse cardiovascular events.

Environmental Exposures: Impact on Male Fertility

It is recognised that male health has a significant impact on male reproductive capacity. These health-related associations may begin before birth. For instance, a man’s sperm count is negatively impacted if his mother smoked during pregnancy, and health trajectories through childhood and adolescence into adulthood may influence male reproductive capacity in later life. Further, other factors such as the age of man at the time of conception may influence the health of their offspring. Of further relevance is the fact that studies have shown a relationship between adult reproductive function and longer-term health outcomes. For instance, adverse associations have been demonstrated between most semen parameters, and other markers of testicular function, with the presence of metabolic syndrome. It has further been shown that there exist an association between erectile dysfunction and future adverse cardiovascular events.

Impact of acute kidney injury on major adverse cardiovascular events in intensive care survivors

BackgroundAcute kidney injury commonly occurs in patients admitted to ICU. After acute kidney injury, kidney function may not completely recover leading to increased risk of future cardiovascular events. We sought to ascertain the rates of cardiovascular events in ICU survivors and if these rates were affected by the presence of acute kidney injury whilst in ICU. MethodsThis retrospective observational cohort study utilised routinely collected data to identify patients who had survived an admission to one of two ICUs between July 2015 and June 2018. Baseline serum creatinine and subsequent values were used to identify acute kidney injury. Major adverse cardiovascular events described were myocardial injury, coronary artery intervention, or radiological evidence of stroke. ResultsOf the 3994 ICU survivors, major adverse cardiovascular events were identified in 385 patients (9.6%; 95% confidence interval [CI] 8.8–10.6%). Presence of acute kidney injury whilst in ICU was significantly associated with future major adverse cardiovascular events (hazard ratio=1.38; 95% CI 1.12–1.70; P-value=0.003) and future biochemical myocardial injury (hazard ratio=1.48; 95% CI 1.16–1.89; P-value=0.001). Acute kidney injury did not have a statistically significant association with future coronary artery interventions or future cerebrovascular events. ConclusionsOne in 10 ICU survivors experiences a major adverse cardiovascular event after discharge. Acute kidney injury whilst in ICU was associated with an increased risk of major adverse cardiovascular events and specifically myocardial injury. Further research is warranted on whether ICU survivors with acute kidney injury merit enhanced strategies for cardiovascular protection.

MINOCA: A Working Diagnosis.

Cases of patients presenting with myocardial infarction (MI) without angiographic obstructive CAD are not trivial and have significant prevalence. "The Fourth Universal Definition of MI" (4UDMI) published in 2018 introduced MI with non-obstructive coronary arteries (MINOCA).The new section was of great importance as it validated the diagnosis by defining its criteria and recognizing its presence in the community and the need for further investigation. Given the nature of the diagnosis of MINOCA, coronary angiography provides limited information about prognosis and risk stratification for future major adverse cardiovascular events (MACE). Thus, additional imaging to understand the underlying etiology of MINOCA in conjunction with a better understanding of prognostic factors is necessary to expand on the current guidelines and aid in screening for possible complications, risk of MACE, and all-cause mortality. Discerning the etiology of the presentation is crucial, and physiologic studies, as well as additional imaging, are an important part of this evaluation. These modalities includeintravascular studies such as optical coherence tomography (OCT), intravascular ultrasound (IVUS), fractional flow reserve (FFR), and imaging in the form of cardiac CT (CCT) and cardiac MRI (CMR). This step is essential to target treatment regimens more efficiently. The purpose of promoting multiple imaging modalities beyond traditional angiography is to address the working MINOCA diagnosis, with the finality of identifying the specific ischemic pathophysiology. MINOCA has multiple causative mechanisms, making it a heterogeneous collection of etiologies, resulting in acute MI: atherosclerotic, and non-atherosclerotic. This literature revision demonstrates that MINOCA prevalence and mortality are not trivial, and the diagnosis affects quality of life. MINOCA presents a definitive risk of MACE without proper stratification and targeted medical therapy. Several prognostic factors of morbidity and mortality in MI-CAD patients have been identified to correlate with MINOCA patients, especially inflammatory markers. MINOCA is not an exclusion diagnosis but a working diagnosis for which further imaging studies should be performed.

The Role of Osteopontin in Atherosclerosis and Its Clinical Manifestations (Atherosclerotic Cardiovascular Diseases)-A Narrative Review.

Atherosclerotic cardiovascular diseases (ASCVDs) are the most common and severe public health problem nowadays. Osteopontin (OPN) is a multifunctional glycoprotein highly expressed at atherosclerotic plaque, which has emerged as a potential biomarker of ASCVDs. OPN may act as an inflammatory mediator and/or a vascular calcification (VC) mediator, contributing to atherosclerosis progression and eventual plaque destabilization. In this article, we discuss the complex role of OPN in ASCVD pathophysiology, since many in vitro and in vivo experimental data indicate that OPN contributes to macrophage activation and differentiation, monocyte infiltration, vascular smooth muscle cell (VSMC) migration and proliferation and lipid core formation within atherosclerotic plaques. Most but not all studies reported that OPN may inhibit atherosclerotic plaque calcification, making it "vulnerable". Regarding clinical evidence, serum OPN levels may become a biomarker of coronary artery disease (CAD) presence and severity. Significantly higher OPN levels have been found in patients with acute coronary syndromes than those with stable CAD. In limited studies of patients with peripheral artery disease, circulating OPN concentrations may be predictive of future major adverse cardiovascular events. Overall, the current literature search suggests the contribution of OPN to atherosclerosis development and progression, but more robust evidence is required.

Right ventricular myocardial fibrosis evaluated by extracellular volume fraction by magnetic resonance imaging in patients with repaired tetralogy of Fallot: a meta-analysis.

The objective of this meta-analysis was to assess the clinical utility of anomalous discoveries on cardiac magnetic resonance, particularly the right ventricular extracellular volume (RV-ECV), among individuals who underwent surgical repair for Tetralogy of Fallot (rTOF). We conducted a systematic search of electronic databases including PubMed, Web of Science Core Collection, Cochrane advanced search, and EMBASE. Our analysis involved a comparison of ECV levels between rTOF patients and controls, as well as an evaluation of the predictive value of ECV for future adverse events. We identified 16 eligible studies that encompassed 856 rTOF patients and 283 controls. Our meta-analysis showed a significant increase in LV-ECV among rTOF patients compared to control subjects (MD = 2.63, 95%CI: 1.35 to 3.90, p < 0.0001, I2 = 86%, p for heterogeneity < 0.00001). Moreover, RV-ECV was found to be substantially higher in patients compared to LV-ECV. Our meta-analysis also revealed a significant association between RV-ECV and adverse events (HR = 1.15, 95% CI: 1.04 to 1.27, p = 0.005, I2 = 0%, p for heterogeneity = 0.62), while LV-ECV did not show any significant association with adverse events (HR = 1.12, 95% CI: 0.92 to 1.36, p = 0.16, I2 = 0%, p for heterogeneity = 0.46). The results of this meta-analysis on RV-ECV confirmed the presence of RV fibrosis as one of the prognostic factors in rTOF patients.

Endothelial dysfunction as predictor of atherosclerosis during a translatitudinal sea voyage in the Arctic: prospective study

INTRODUCTION. Human labor activity in the Arctic takes place in severe climatic conditions associated with cooling, atmospheric pressure drops, high humidity, photoperiodicity, low oxygen content in the air. Endothelial dysfunction is an early pathophysiological sign and an independent predictor of poor prognosis in most cardiovascular diseases.&#x0D; OBJECTIVE.Тo analyze the dynamics of the level of metalloproteinase-9 and thrombin activity as predictors of the development of atherosclerosis in sailors during a translatitudinal sea voyage in the Arctic.&#x0D; MATERIALS AND METHODS. A prospective clinical and laboratory study of crew members was performed during the integrated marine research expedition “Transarctic-2019”. A clinical and laboratory study of the level of metalloprotease-9 (enzyme-linked immunosorbent assay), coagulation analysis of the parameters of the thrombin generation test, as well as ultrasonic dopplerography of the thickness of the intima-media complex were carried out. Statistical data processing was carried out using the methods of descriptive and analytical statistics in the StataCorp Stata 14.2 program. The study protocol was approved by the local ethical committee of the SSMU (protocol No. 03/5 dated May 27, 2015) and supported by the state task reg. No. NIOKTR 121030300111-7.&#x0D; RESULTS. A statistically significant increase in the level of MMP-9 in sailors after the expedition was noted, the relationship between the level of MMP-9, indicators of the thrombin generation test (lag time, min (p=0.0190), tPeak (p=0.0177), Peak (p= 0.0217) and KIM thickening.&#x0D; DISCUSSION. MMP-9 levels may be a predictor of early atherosclerosis and atherosclerotic plaque instability, as well as a risk factor for future adverse cardiovascular events. The relationship of MMP-9 with the kinetics of thrombin (one of the regulators of the antithrombotic state of the endothelium) during a translatitudinal voyage in sailors indicates the formation of readiness for prothrombotic events.&#x0D; CONCLUSION. Thus, in Arctic conditions, under conditions of chronic oxidative stress, which contribute to the progression of the development of endothelial dysfunction in the presence of external risk factors, the likelihood of progression of atherosclerotic vascular lesions increases, and, as a result, the development of vascular events.

Severity of obstructive sleep apnea is associated with left ventricular abnormality in patients with hypertension in the young

Abstract Background Hypertension in the young is defined as the presence of hypertension in individuals with an age of onset before 35 years. A previous study found that obstructive sleep apnea (OSA) may be a contributing factor of hypertension in the young up to 90% if other causes of secondary hypertension were excluded. Left ventricular (LV) abnormality is a marker of future cardiovascular consequences. There is limited data on risk factors of LV abnormality in patients with hypertension in the young with OSA. Objectives We aim to evaluate risk factors of LV abnormality in patients with hypertension in the young. Methods This study was a retrospective study. The eligible patients were adult patients who diagnosed as hypertension at age before 35 years and evaluated for echocardiogram. Those with causes of secondary hypertension or pregnant women were excluded. The study period was between October 2017 and January 2021. OSA was categorized as mild, moderate, and severe by an apnea-hypopnea index of 5-14.9, 15-29.9, and 30 or over times/hour. LV abnormality defined by relative wall thickness (RWT) over 0.42 mm. by a Doppler echocardiography. Other echocardiographic findings were also reported including left ventricular mass (LVM), left ventricular mass index (LVMI), and ejection fraction (EF). Differences of variables among severities of OSA were computed by a one-way ANOVA, while differences of proportions between groups were calculated by Chi square test. Multivariable analyses, linear and logistic regressions were performed to find the association between OSA and LV abnormality. Results There were 52 patients who met the study criteria. Mild OSA group had lower LVM, LVMI, and RWT than moderate OSA and severe OSA group (172.98 vs 232.16 vs 177.78 g; p 0.036 for LVMI; 83.03 vs 107.87 vs 84.99 g/m2; p 0.013 for LVMI; and 0.38 vs 0.45 vs 0.47 mm; p 0.010 for RWT). There was no significant difference in EF among the three groups. Severe OSA was found have an increased association with the presence of LV abnormality compared to patients with mild to moderate OSA (OR 3.28, 95% CI 0.96-12.5), however this was not statistically significant (p-value 0.07) Patients with severe OSA was found to have a correlation with RWT measurements of greater than 0.42 (correlation co-efficient 0.2, 95% CI 0.01-0.39, p-value 0.04). Conclusion Hypertensive patients under the age of 35 with severe OSA have a higher proportion of LV abnormality compared to mild and moderate OSA. Severe OSA was found to be correlated to RWT measurements of greater than 0.42. This finding might be one of prognostic indicators of the future adverse cardiovascular events and be required proper management. However, this relationship should be needed further study.

Abstract 17285: Impact of Baseline Yellow Plaque Assessed by Coronary Angioscopy on 11-month Vascular Response After Stent Implantation

Background: In-stent yellow plaque (YP) evaluated by coronary angioscopy (CAS) 1 year after stent implantation is associated with the future adverse cardiac event. However, the impact of baseline YP on vascular response has not been fully investigated. Methods: This was a sub-analysis of the Collaboraiton-1 study (multicenter, retrospective, observational study). A total of 88 lesions from 80 patients with chronic coronary syndrome who underwent percutaneous coronary intervention with polymer-free biolimus A9-coated stent or durable-polymer everolimus-eluting stent implantation were analyzed. Optical coherence tomography (OCT) and CAS were serially performed immediately and 11 months after stent implantation. YP was defined as the stented segment with yellow or intensive yellow color assessed by CAS. Neoatherosclerosis was defined as a lipid or calcified neointima assessed by OCT. Neointimal coverage (NIC) over the stent was classified into 4 grades by CAS: grade 0, stent struts fully visible; grade 1, stent struts bulging into the lumen, although covered; grade 2, stent struts embedded in the neointima, but translucently visible; and grade 3, stent struts fully embedded and invisible. OCT and CAS findings at 11 months were compared between the lesions with baseline YP (YP group) and those without YP (Non-YP group). Results: Baseline YP was detected in 37 lesions (42%). OCT findings at 11 months showed that the incidence of neoatherosclerosis was significantly higher in YP than Non-YP groups (11% versus 0%, P=0.028) and mean neointimal thickness tended to be lower (104±43 μm versus 120±48 μm, P=0.098). CAS finding at 11 months demonstrated that dominant and minimum NIC grades were significantly lower (Figure) and maximum yellow color grade was significantly higher in YP than Non-YP groups. Conclusions: Baseline YP affected the incidence of neoatherosclerosis as well as poor neointimal coverage at 11 months after stent implantation.

Abstract 12263: Inflammation and Cholesterol as Predictors of Cardiovascular Events and Risk Reduction With Bempedoic Acid Among Statin Intolerant Patients: An Analysis of the CLEAR Outcomes Trial

Introduction: Among contemporary statin-treated patients, residual inflammatory risk assessed by high-sensitivity C-reactive protein (hsCRP) is a stronger predictor of future cardiovascular (CV) events and all-cause mortality than residual cholesterol risk assessed by low density lipoprotein cholesterol (LDLC). Whether these relationships are present among statin-intolerant patients is unknown but has implications for the choice of preventive therapies including bempedoic acid, an agent that reduces both LDLC and hsCRP. Methods: In the multi-national CLEAR-Outcomes trial, 13,970 statin-intolerant patients were randomly allocated 1:1 to 180 mg oral bempedoic acid daily or matching placebo and followed for incident myocardial infarction (MI), stroke, coronary revascularization, CV death, and all-cause mortality. Quartiles of increasing baseline hsCRP and LDLC were assessed as predictors of future adverse CV events after adjustment for traditional risk factors and treatment (bempedoic acid vs. placebo). Results: Baseline hsCRP was significantly associated with incident composite endpoint of MI, stroke, coronary revascularization, and CV death (highest vs lowest hsCRP quartile, HR=1.43, 95% CI 1.24-1.65), CV mortality (HR=2.00, 95% CI 1.53-2.61), and all-cause mortality (HR=2.21, 95% CI 1.79-2.73). By contrast, the relationship of baseline LDLC quartile (highest vs. lowest) to future CV events was smaller for the composite endpoint (HR=1.19, 95% CI 1.04-1.37) and neutral for CV mortality (HR 0.90, 95% CI 0.70-1.17) and all-cause mortality (HR 0.95, 95% CI 0.78-1.16) such that risks were high for those with elevated hsCRP irrespective of LDLC level. Compared to placebo, bempedoic acid reduced median hsCRP by 21.6% and mean LDLC levels by 21.1% at 6 months and demonstrated similar efficacy in reducing major adverse CV events across all levels of hsCRP and LDLC. Interpretation: Among contemporary statin-intolerant patients, inflammation assessed by hsCRP was a stronger predictor of risk for future CV events and death than was hyperlipidemia assessed by LDLC. Compared to placebo, bempedoic acid had similar efficacy for reducing CV risk across hsCRP and LDLC strata.

Abstract 17493: Racial/Ethnic Under-Representation in Early Phase Clinical Trials

Introduction: There is severe underrepresentation of racial and ethnic groups in many cardiovascular clinical trials. Early-phase clinical trials examine the action and safety limits of treatment and thus, underrepresentation may have particularly deleterious effects. Hypothesis: Ethnic and Racial groups are underrepresented in early-phase trials. Methods: Using the clinicaltrials.gov database, we examined the racial and ethnic representation in Phases 1, 2, 3, and 4 in completed heart failure clinical trials (N=89) with reported results from 2016-2021. We examined the proportion of trials with a representation equal or greater than % U.S. Census population (12% for African American (AA), 19% for Hispanic/Latino (HL), and 7% for Asian (AN)) and determined the median trial representation percentage for AA, HL, and AN groups. Using Chi-square analysis we compared the percent representation across the trial phases. Results: We found that 49%, 91%, and 87% Phase 1 and 2 trials have a lower AA, HL, and AN representation, respectively, compared to that in the U.S. Population (Table 1). HL and AN representation in Phase 1 and 2 trials is particularly low. There is significant variation in AA, HL, and AN representation across all trial phases(p&lt;0.001). Conclusions: Significant underrepresentation of racial and ethnic groups persist in contemporary Phase 1 and 2 trials. Efforts to create a standard for collecting and reporting demographics along with increasing racial and ethnic group representation closer to US population may reduce the risk of future adverse events.

Inflammation and Cholesterol as Predictors of Cardiovascular Events Among 13 970 Contemporary High-Risk Patients With Statin Intolerance.

Among patients treated with statin therapy to guideline-recommended cholesterol levels, residual inflammatory risk assessed by high-sensitivity C-reactive protein (hsCRP) is at least as strong a predictor of future cardiovascular events as is residual risk assessed by low-density lipoprotein cholesterol (LDLC). Whether these relationships are present among statin-intolerant patients with higher LDLC levels is uncertain but has implications for the choice of preventive therapies, including bempedoic acid, an agent that reduces both LDLC and hsCRP. The multinational CLEAR-Outcomes trial (Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen Outcomes Trial) randomly allocated 13 970 statin-intolerant patients to 180 mg of oral bempedoic acid daily or matching placebo and followed them for a 4-component composite of incident myocardial infarction, stroke, coronary revascularization, or cardiovascular death, and for all-cause mortality. Quartiles of increasing baseline hsCRP and LDLC were assessed as predictors of future adverse events after adjustment for traditional risk factors and randomized treatment assignment. Compared with placebo, bempedoic acid reduced median hsCRP by 21.6% and mean LDLC levels by 21.1% at 6 months. Baseline hsCRP was significantly associated with the primary composite end point of major cardiovascular events (highest versus lowest hsCRP quartile; hazard ratio [HR], 1.43 [95% CI, 1.24-1.65]), cardiovascular mortality (HR, 2.00 [95% CI, 1.53-2.61]), and all-cause mortality (HR, 2.21 [95% CI, 1.79-2.73]). By contrast, the relationship of baseline LDLC quartile (highest versus lowest) to future events was smaller in magnitude for the primary composite cardiovascular end point (HR, 1.19 [95% CI, 1.04-1.37]) and neutral for cardiovascular mortality (HR, 0.90 [95% CI, 0.70-1.17]) and all-cause mortality (HR, 0.95 [95% CI, 0.78-1.16]). Risks were high for those with elevated hsCRP irrespective of LDLC level. Bempedoic acid demonstrated similar efficacy in reducing cardiovascular events across all levels of hsCRP and LDLC. Among contemporary statin-intolerant patients, inflammation assessed by hsCRP predicted risk for future cardiovascular events and death more strongly than hyperlipidemia assessed by LDLC. Compared with placebo, bempedoic acid had similar efficacy for reducing cardiovascular risk across hsCRP and LDLC strata. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02993406.

Medical students’ experiences, perceptions, and management of second victim: an interview study

BackgroundThe term second victim describes a healthcare professional who has been involved in an adverse event and feels wounded by the event. The effects of this experience differ. It can present as second victim syndrome, describing a wide range and degree of emotional and behavioural responses. Studies show that medical students can also experience second victim. The aim of this study was to elucidate medical students’ experiences, perceptions, and management of second victim and second victim syndrome and to describe possible learning needs around these issues.MethodsThirteen medical students and two recent medical graduates participated in semi-structured focus group interviews. The interviews lasted 1.5–2 h and were audiotaped, transcribed, and analysed using Braun and Clarke’s six-step approach for thematic analysis.ResultsFour main themes were identified: contributing factors; current coping strategies; perception of own requirements and learning needs; wishes for the future healthcare system. Students’ behavioural and emotional response to dilemmas were affected by stakeholders and practices embedded in the healthcare system. Students described patient-injury and unexpected events as triggers for second victim, but also harmful interactions with individuals and feelings of self-blame. Students’ coping centred around their network, formal offers, and separation of personal- and work-life. Students sought a clear definition of second victim and a desire for role-models. Students' wished to learn how to handle feeling like a burden to others, managing waiting time after patient complaints, and learning how to help second victims recover. Students emphasized the importance of the healthcare organisation understanding students’ needs and providing them relevant support. ConclusionStudents experience second victim as described in the literature. Students’ emotional responses were caused by classical second victim triggers, but also other triggers in the educational environment: harmful interactions and self-blame. Although some triggers differ from the second victim definition, these different triggers should be considered equally serious and acknowledged. We must aim to prepare students for future adverse events and emotional responses. The health organisation and healthcare professionals must support students’ mental well-being and contribute to ideal conditions for students' professional development and management of second victim as future physicians.

Cardiac decompensation of patients before transcatheter aortic valve implantation-clinical presentation, responsiveness to associated medication, and prognosis.

Cardiac decompensation (CD) in patients with aortic stenosis is a "red flag" for future adverse events. We classified patients undergoing transcatheter aortic valve implantation (TAVI) into those with acute, prior, or no prior CD at the timepoint of TAVI and compared their clinical presentation, prognosis, and effects of the prescribed medication during follow-up. Retrospective analysis of patients of one center fulfilling the criteria of 30-day device success after transfemoral TAVI. From those patients with no CD (n = 1,985) ranging to those with prior CD (n = 497) and to those with acute CD (n = 87), we observed a stepwise increase in the proportion of patients in poor clinical condition, NYHA class III/IV, low psoas muscle area, fluid overload (rales, oedema, pleural effusion), reduced ejection fraction, renal insufficiency, and anemia. More diuretics but less renin-angiotensin system inhibitors (ACEI/ARB) were prescribed for patients with acute CD compared to other groups. Prior CD (hazard ratio and 95% CI 1.40; 1.02-1.91) and acute CD (1.72; 1.01-2.91), a reduced general condition (1.53; 1.06-2.20), fluid overload (1.54;1.14-2.08), atrial fibrillation (1.76; 1.32-2.33), and anemia (1.43;1.08-1.89) emerged as strong independent predictors of one-year mortality. In all three classes of CD, prescribing of ACEI/ARB was associated with a substantial improvement of survival. The clinical presentation of (acute or prior) cardiac decompensation in patients with AS overlapped substantially with that of patients with classical signs of heart failure. Our results may support an early treatment strategy in patients with left ventricular dysfuntion before clinical signs of congestion are manifest. Moreover, these patients require intensive medical attention after TAVI.

Diagnosis and Prognostic Value of the Underlying Cause of Acute Coronary Syndrome in Optical Coherence Tomography-Guided Emergency Percutaneous Coronary Intervention.

Background The prognostic impact of optical coherence tomography-diagnosed culprit lesion morphology in acute coronary syndrome (ACS) has not been systematically examined in real-world settings. Methods and Results This investigator-initiated, prospective, multicenter, observational study was conducted at 22 Japanese hospitals to identify the prevalence of underlying ACS causes (plaque rupture [PR], plaque erosion [PE], and calcified nodules [CN]) and their impact on clinical outcomes. Patients with ACS diagnosed within 24 hours of symptom onset undergoing emergency percutaneous coronary intervention were enrolled. Optical coherence tomography-guided percutaneous coronary intervention recipients were assessed for underlying ACS causes and followed up for major adverse cardiac events (cardiovascular death, myocardial infarction, heart failure, or ischemia-driven revascularization) at 1 year. Of 1702 patients with ACS, 702 (40.7%) underwent optical coherence tomography-guided percutaneous coronary intervention for analysis. PR, PE, and CN prevalence was 59.1%, 25.6%, and 4.0%, respectively. One-year major adverse cardiac events occurred most frequently in patients with CN (32.1%), followed by PR (12.4%) and PE (6.2%) (log-rank P<0.0001), primarily driven by increased cardiovascular death (CN, 25.0%; PR, 0.7%; PE, 1.1%; log-rank P<0.0001) and heart failure trend (CN, 7.1%; PR, 6.8%; PE, 2.2%; log-rank P<0.075). On multivariate Cox regression analysis, the underlying ACS cause was associated with 1-year major adverse cardiac events (CN [hazard ratio (HR), 4.49 [95% CI, 1.35-14.89], P=0.014]; PR (HR, 2.18 [95% CI, 1.05-4.53], P=0.036]; PE as reference). Conclusions Despite being the least common, CN was a clinically significant underlying ACS cause, associated with the highest future major adverse cardiac events risk, followed by PR and PE. Future studies should evaluate the possibility of ACS underlying cause-based optical coherence tomography-guided optimization.

Clinical research stakeholders’ experiences of clinical research during COVID-19: a qualitative study

BackgroundThe COVID-19 pandemic created a complex high-risk clinical research environment with clinical research activities significantly impacted. Clinical research stakeholders adapted rapidly to new clinical practices; PPE, infection control policies, all while engaging with a more unwell patient demographic. The aim of this study is to explore the experiences of conducting clinical research during COVID-19 with clinical research stakeholders.MethodsThis qualitative study of semi-structured interviews conducted with clinical research stakeholders in an acute Hospital setting across a variety of disciplines; Consultant Geriatrician, Clinical Research Nurse, Occupational Therapy, Physiotherapy. Interviews were fully transcribed prior to reflexive thematic analysis. NVivo software was used to support data management and analysis.ResultsThree main themes were produced; (1) The challenging COVID-19 clinical research landscape, (2) COVID-19 clinical research communication barriers, and (3) Adaptations and learnings from clinical research during COVID-19.ConclusionsThis study explored the experiences of conducting clinical research during COVID-19 with clinical research stakeholders examining challenges faced and adaptations required. The findings inform, equip and support clinical research stakeholders in the event of future adverse public health events.

Associations between Differential Aging and Lifestyle, Environment, Current, and Future Health Conditions: Findings from Canadian Longitudinal Study on Aging

Introduction: An aging population will bring a pressing challenge for the healthcare system. Insights into promoting healthy longevity can be gained by quantifying the biological aging process and understanding the roles of modifiable lifestyle and environmental factors, and chronic disease conditions. Methods: We developed a biological age (BioAge) index by applying multiple state-of-art machine learning models based on easily accessible blood test data from the Canadian Longitudinal Study of Aging (CLSA). The BioAge gap, which is the difference between BioAge index and chronological age, was used to quantify the differential aging, i.e., the difference between biological and chronological age, of the CLSA participants. We further investigated the associations between the BioAge gap and lifestyle, environmental factors, and current and future health conditions. Results: BioAge gap had strong associations with existing adverse health conditions (e.g., cancers, cardiovascular diseases, diabetes, and kidney diseases) and future disease onset (e.g., Parkinson’s disease, diabetes, and kidney diseases). We identified that frequent consumption of processed meat, pork, beef, and chicken, poor outcomes in nutritional risk screening, cigarette smoking, exposure to passive smoking are associated with positive BioAge gap (“older” BioAge than expected). We also identified several modifiable factors, including eating fruits, legumes, vegetables, related to negative BioAge gap (“younger” BioAge than expected). Conclusions: Our study shows that a BioAge index based on easily accessible blood tests has the potential to quantify the differential biological aging process that can be associated with current and future adverse health events. The identified risk and protective factors for differential aging indicated by BioAge gap are informative for future research and guidelines to promote healthy longevity.