Clinical Interpretation of Serum Troponin in the Era of High-Sensitivity Testing.

Cardiac troponin (Tn) plays a central role in the evaluation of patients with angina presenting with acute coronary syndrome. The advent of high-sensitivity assays has improved the analytic sensitivity and precision of serum Tn measurement, but this advancement has come at the cost of poorer specificity. The role of clinical judgment is of heightened importance because, more so than ever, the interpretation of serum Tn elevation hinges on the careful integration of findings from electrocardiographic, echocardiographic, physical exam, interview, and other imaging and laboratory data to formulate a weighted differential diagnosis. A thorough understanding of the epidemiology, mechanisms, and prognostic implications of Tn elevations in each cardiac and non-cardiac etiology allows the clinician to better distinguish between presentations of myocardial ischemia and myocardial injury-an important discernment to make, as the treatment of acute coronary syndrome is vastly different from the workup and management of myocardial injury and should be directed at the underlying cause.

Shorter Dual Antiplatelet Therapy for Older Adults After Percutaneous Coronary Intervention: A Systematic Review and Network Meta-Analysis.

Importance: The optimal duration of dual antiplatelet therapy (DAPT) for older adults after percutaneous coronary intervention (PCI) is uncertain because they are simultaneously at higher risk for both ischemic and bleeding events. Objective: To investigate the association of abbreviated DAPT with adverse clinical events among older adults after PCI. Data Sources: The Cochrane Library, Google Scholar, Embase, MEDLINE, PubMed, Scopus, and Web of Science were searched from inception to August 9, 2023. Study Selection: Randomized clinical trials comparing any 2 of 1, 3, 6, and 12 months of DAPT were included if they reported results for adults aged 65 years or older or 75 years or older. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline was used to abstract data and assess data quality. Risk ratios for each duration of DAPT were calculated with alternation of the reference group. Main Outcomes and Measures: The primary outcome of interest was net adverse clinical events (NACE). Secondary outcomes were major adverse cardiovascular events (MACE) and bleeding. Results: In 14 randomized clinical trials comprising 19 102 older adults, no differences were observed in the risks of NACE or MACE for 1, 3, 6, and 12 months of DAPT. However, 3 months of DAPT was associated with a lower risk of bleeding compared with 6 months of DAPT (relative risk [RR], 0.50 [95% CI, 0.29-0.84]) and 12 months of DAPT (RR, 0.57 [95% CI, 0.45-0.71]) among older adults. One month of DAPT was also associated with a lower risk of bleeding compared with 6 months of DAPT (RR, 0.68 [95% CI, 0.54-0.86]). Conclusions and Relevance: In this systematic review and meta-analysis of different durations of DAPT for older adults after PCI, an abbreviated DAPT duration was associated with a lower risk of bleeding without any concomitant increase in the risk of MACE or NACE despite the concern for higher-risk coronary anatomy and comorbidities among older adults. This study, which represents the first network meta-analysis of this shortened treatment for older adults, suggests that clinicians may consider abbreviating DAPT for older adults.

Clinical Biochemistry of Serum Troponin.

Accurate measurement and interpretation of serum levels of troponin (Tn) is a central part of the clinical workup of a patient presenting with chest pain suspicious for acute coronary syndrome (ACS). Knowledge of the molecular characteristics of the troponin complex and test characteristics of troponin measurement assays allows for a deeper understanding of causes of false positive and false negative test results in myocardial injury. In this review, we discuss the molecular structure and functions of the constituent proteins of the troponin complex (TnT, TnC, and TnI); review the different isoforms of Tn and where they are from; survey the evolution of clinical Tn assays, ranging from first-generation to high-sensitivity (hs); provide a primer on statistical interpretation of assay results based on different clinical settings; and discuss potential causes of false results. We also summarize the advances in technologies that may lead to the development of future Tn assays, including the development of point of care assays and wearable Tn sensors for real-time continuous measurement.

Sepsis increases the risk of in-hospital cardiac arrest: a population-based analysis.

Sepsis patients have a high risk of developing in-hospital cardiac arrest (IHCA), which portends poor survival. However, little is known about whether the increased incidence of IHCA is due to sepsis itself or to comorbidities harbored by sepsis patients. We conducted a retrospective population-based cohort study comprising 20,022 patients admitted with sepsis to hospitals in Taiwan using the National Health Insurance Research Database (NHIRD). We constructed three non-sepsis comparison cohorts using risk set sampling and propensity score (PS) matching. We used univariate conditional logistic regression to evaluate the risk of IHCA and associated mortality. We identified 12,790 inpatients without infection (matched cohort 1), 12,789 inpatients with infection but without sepsis (matched cohort 2), and 10,536 inpatients with end-organ dysfunction but without sepsis (matched cohort 3). In the three PS-matched cohorts, the odds ratios (OR) for developing ICHA were 21.17 (95% CI 17.19, 26.06), 18.96 (95% CI: 15.56, 23.10), and 1.23 (95% CI: 1.13, 1.33), respectively (p < 0.001 for all ORs). In conclusion, in our study of inpatients across Taiwan, sepsis was independently associated with an increased risk of IHCA. Further studies should focus on identifying the proxy causes of IHCA using real-time monitoring data to further reduce the incidence of cardiopulmonary insufficiency in patients with sepsis.

The Brain-Heart Axis: Neuroinflammatory Interactions in Cardiovascular Disease.

PURPOSE OF REVIEW: The role of neuroimmune modulation and inflammation in cardiovascular disease has been historically underappreciated. Physiological connections between the heart and brain, termed the heart-brain axis (HBA), are bidirectional, occur through a complex network of autonomic nerves/hormones and cytokines, and play important roles in common disorders. RECENT FINDINGS: At the molecular level, advances in the past two decades reveal complex crosstalk mediated by the sympathetic and parasympathetic nervous systems, the renin-angiotensin aldosterone and hypothalamus-pituitary axes, microRNA, and cytokines. Afferent pathways amplify proinflammatory signals via the hypothalamus and brainstem to the periphery, promoting neurogenic inflammation. At the organ level, while stress-mediated cardiomyopathy is the prototypical disorder of the HBA, cardiac dysfunction can result from a myriad of neurologic insults including stroke and spinal injury. Atrial fibrillation is not necessarily a causative factor for cardioembolic stroke, but a manifestation of an abnormal atrial substrate, which can lead to the development of stroke independent of AF. Central and peripheral neurogenic proinflammatory factors have major roles in the HBA, manifesting as complex bi-directional relationships in common conditions such as stroke, arrhythmia, and cardiomyopathy.

Orthostatic Hypotension, Hypertension Treatment, and Cardiovascular Disease: An Individual Participant Meta-Analysis.

Importance: There are ongoing concerns about the benefits of intensive vs standard blood pressure (BP) treatment among adults with orthostatic hypotension or standing hypotension. Objective: To determine the effect of a lower BP treatment goal or active therapy vs a standard BP treatment goal or placebo on cardiovascular disease (CVD) or all-cause mortality in strata of baseline orthostatic hypotension or baseline standing hypotension. Data Sources: Individual participant data meta-analysis based on a systematic review of MEDLINE, EMBASE, and CENTRAL databases through May 13, 2022. Study Selection: Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) with orthostatic hypotension assessments. Data Extraction and Synthesis: Individual participant data meta-analysis extracted following PRISMA guidelines. Effects were determined using Cox proportional hazard models using a single-stage approach. Main Outcomes and Measures: Main outcomes were CVD or all-cause mortality. Orthostatic hypotension was defined as a decrease in systolic BP of at least 20 mm Hg and/or diastolic BP of at least 10 mm Hg after changing position from sitting to standing. Standing hypotension was defined as a standing systolic BP of 110 mm Hg or less or standing diastolic BP of 60 mm Hg or less. Results: The 9 trials included 29 235 participants followed up for a median of 4 years (mean age, 69.0 [SD, 10.9] years; 48% women). There were 9% with orthostatic hypotension and 5% with standing hypotension at baseline. More intensive BP treatment or active therapy lowered risk of CVD or all-cause mortality among those without baseline orthostatic hypotension (hazard ratio [HR], 0.81; 95% CI, 0.76-0.86) similarly to those with baseline orthostatic hypotension (HR, 0.83; 95% CI, 0.70-1.00; P = .68 for interaction of treatment with baseline orthostatic hypotension). More intensive BP treatment or active therapy lowered risk of CVD or all-cause mortality among those without baseline standing hypotension (HR, 0.80; 95% CI, 0.75-0.85), and nonsignificantly among those with baseline standing hypotension (HR, 0.94; 95% CI, 0.75-1.18). Effects did not differ by baseline standing hypotension (P = .16 for interaction of treatment with baseline standing hypotension). Conclusions and Relevance: In this population of hypertension trial participants, intensive therapy reduced risk of CVD or all-cause mortality regardless of orthostatic hypotension without evidence for different effects among those with standing hypotension.

The Promise and Illusion of Continuous, Cuffless Blood Pressure Monitoring.

PURPOSE OF REVIEW: Blood pressure (BP) fluctuations outside of clinic are increasingly recognized for their role in the development of cardiovascular disease, syncope, and premature death and as a promising target for tailored hypertension treatment. However, current cuff-based BP devices, including home and ambulatory devices, are unable to capture the breadth of BP variability across human activities, experiences, and contexts. RECENT FINDINGS: Cuffless, wearable BP devices offer the promise of beat-to-beat, continuous, noninvasive measurement of BP during both awake and sleep periods with minimal patient inconvenience. Importantly, cuffless BP devices can characterize BP variability, allowing for the identification of patient-specific triggers of BP surges in the home environment. Unfortunately, the pace of evidence, regulation, and validation testing has lagged behind the pace of innovation and direct consumer marketing. We provide an overview of the available technologies and devices for cuffless BP monitoring, considerations for the calibration and validation of these devices, and the promise and pitfalls of the cuffless BP paradigm.

Trends and Inhospital Outcomes of Intravascular Imaging on Single-Vessel Coronary Chronic Total Occlusion Treated With Percutaneous Coronary Intervention.

Intravascular imaging (IVI), including intravascular ultrasound (IVUS) and optical coherence tomography (OCT), improves outcomes of percutaneous coronary intervention (PCI) for chronic total occlusions (CTOs). We sought to quantify temporal trends in the uptake of IVI for CTO-PCI in the United States. We identified adults who underwent single-vessel PCI for CTO between 2008 and 2020. We quantified yearly trends in the number of IVUS-guided and OCT-guided single-vessel CTO-PCIs by Cochran-Armitage and linear regression tests. We also examined the rates of inhospital mortality and other prespecified inhospital outcomes in patients who underwent CTO-PCIs with and without IVI, using logistic regression. Our study included a total of 151,998 PCIs on single-vessel CTOs, with the absolute number of CTO-PCIs decreasing from 12,345 in 2008 to 8,525 in 2020 (p trend <0.001). IVUS use has increased dramatically from 6% in 2008 to 18% in 2020 for single-vessel CTO-PCIs (p trend <0.001). Rates of OCT use have increased as well, from 0% in 2008 to 7% in 2020 (p trend <0.001). There was no difference in inhospital mortality between patients who underwent CTO-PCI with and without IVI (p logistic = 0.60). In the largest national analysis of single-vessel CTO-PCI trends to date, we found that the use of IVUS has increased substantially accompanied by a similar but lesser increase in the use of OCT. There were no differences in rates of inhospital mortality between patients who underwent single-vessel CTO-PCIs with and without IVI.

Sequencing Quadruple Therapy for Heart Failure with Reduced Ejection Fraction: Does It Really Matter?

The conventional sequence of guideline-directed medical therapy (GDMT) initiation in heart failure with reduced ejection fraction (HFrEF) assumes that the effectiveness and tolerability of GDMT agents mirror their order of discovery, which is not true. In this review, the authors discuss flexible GDMT sequencing that should be permitted in special populations, such as patients with bradycardia, chronic kidney disease, or atrial fibrillation. Moreover, the initiation of certain GDMT medications may enable tolerance of other GDMT medications. Most importantly, the achievement of partial doses of all four pillars of GDMT is better than achievement of target dosing of only a couple.

Delirium in older adults after percutaneous coronary intervention: Prevalence, risks, and clinical phenotypes.

INTRODUCTION: In-hospital delirium is more common among older adults and is associated with increased mortality and adverse health-related outcomes. We aim to establish the contemporary prevalence of delirium among older adults undergoing percutaneous coronary intervention (PCI) and the impact of delirium on in-hospital complications. METHODS: We identified older adults aged ≥75 years in the National Inpatient Sample who underwent inpatient PCI for any reason from 2016 to 2020 and stratified them into those with and without delirium. The primary outcome was in-hospital mortality, and secondary outcomes encompassed post-procedural complications. RESULTS: Delirium occurred in 14,130 (2.6 %) hospitalizations in which PCI was performed. Patients who developed delirium were older and had more comorbidities. Patients with in-hospital delirium had higher odds of in-hospital mortality (adjusted odds ratio [aOR] 1.27, p = 0.002) and non-home discharge (aOR 3.17, p < 0.001). Delirium was also associated with higher odds of intracranial hemorrhage (aOR 2.49, p < 0.001), gastrointestinal hemorrhage (aOR 1.25, p = 0.030), need for blood transfusion (aOR 1.52, p < 0.001), acute kidney injury (aOR 1.62, p < 0.001), and fall in hospital (aOR 1.97, p < 0.001). CONCLUSION: Delirium among older adults undergoing PCI is relatively common and associated with higher odds of in-hospital mortality and adverse events. This highlights the importance of vigilant delirium prevention and early recognition in the peri-procedural setting, especially for older adults.

Fever with atypical lymphocytosis: pearls and pitfalls in Epstein-Barr virus serology.

The heterophile antibody (also known as the Monospot) test is a useful screening tool for infectious mononucleosis (IM) resulting from primary Epstein-Barr virus (EBV) infection. However, up to 10% of patients with IM are heterophile negative. Heterophile-negative patients who have lymphocytosis or atypical lymphocytes on peripheral blood smear should be further tested for EBV serologies, which include testing for specific IgM and IgG antibodies against viral capsid antigens, early antigens and EBV nuclear antigen proteins. A diagnostic dilemma arises when the patient has clinical and laboratory features of IM, but is both heterophile negative and seronegative for IM, as illustrated in this case presentation. To avoid missed diagnoses of IM, misdiagnosis of mononucleosis-like illnesses and unnecessary testing, knowledge of test characteristics and the evolving course of EBV serologies is important to assure and inform both the physician and the patient.

A Case of Fulminant Right Heart Failure Owing to Tumoral Pulmonary Hypertension.

Tumoral pulmonary hypertension is a rare cause of pulmonary hypertension. We report a patient who was thought to have idiopathic pulmonary arterial hypertension, but later developed fulminant right heart failure ultimately leading to death. Autopsy revealed substantial pulmonary tumor embolism burden originating from liver adenocarcinoma. (Level of Difficulty: Advanced.).

Validating cuffless continuous blood pressure monitoring devices.

Cuff-based home blood pressure (BP) devices, which have been the standard for BP monitoring for decades, are limited by physical discomfort, convenience, and their ability to capture BP variability and patterns between intermittent readings. In recent years, cuffless BP devices, which do not require cuff inflation around a limb, have entered the market, offering the promise of continuous beat-to-beat measurement of BP. These devices take advantage of a variety of principles to determine BP, including (1) pulse arrival time, (2) pulse transit time, (3) pulse wave analysis, (4) volume clamping, and (5) applanation tonometry. Because BP is calculated indirectly, these devices require calibration with cuff-based devices at regular intervals. Unfortunately, the pace of regulation of these devices has failed to match the speed of innovation and direct availability to patient consumers. There is an urgent need to develop a consensus on standards by which cuffless BP devices can be tested for accuracy. In this narrative review, we describe the landscape of cuffless BP devices, summarize the current status of validation protocols, and provide recommendations for an ideal validation process for these devices.

Association of Perceived Health Competence With Cardiac Rehabilitation Initiation.

PURPOSE: Cardiac rehabilitation (CR), a program of supervised exercise and cardiovascular risk management, is widely underutilized. Psychological factors such as perceived health competence, or belief in one's ability to achieve health-related goals, may play a role in CR initiation. The aim of this study was to evaluate the association of perceived health competence with CR initiation among patients hospitalized for acute coronary syndrome (ACS) after adjusting for demographic, clinical, and psychosocial characteristics. METHODS: The Vanderbilt Inpatient Cohort Study (VICS) characterized the effect of psychosocial characteristics on post-discharge outcomes in ACS inpatients hospitalized from 2011 to 2015. The primary outcome for this analysis was participation in an outpatient CR program. The primary predictor was the two-item Perceived Health Competence Scale (PHCS-2), which yields a score from 2 to 10 (higher scores indicate greater perceived health competence). Multiple logistic regression was used to evaluate the relationship between the PHCS-2 and CR initiation. RESULTS: A total of 1809 VICS participants (median age: 61 yr, 39% female) with ACS were studied, of whom 294 (16%) initiated CR. The PHCS-2 was associated with a higher odds of CR initiation (OR = 1.15/point increase: 95% CI, 1.06-1.26, P = .001) after adjusting for covariates. Participants with comorbid heart failure had a lower odds of CR initiation (OR = 0.31: 95% CI, 0.16-0.60, P < .001) as did current smokers (OR = 0.64: 95% CI, 0.43-0.96, P = .030). CONCLUSION: Perceived health competence is associated with outpatient CR initiation in patients hospitalized with ACS. Interventions designed to support perceived health competence may be useful for improving CR participation.

Readmission and In-Hospital Outcomes After Transcatheter Aortic Valve Replacement in Patients With Dementia.

BACKGROUND/PURPOSE: The prevalence of dementia and aortic stenosis (AS) increases with each decade of age. Transcatheter aortic valve replacement (TAVR) is a definitive treatment for AS, but there are scarce data on morbidity, mortality, and readmission risk after TAVR in patients with dementia. METHODS/MATERIALS: We identified all admissions for TAVR in patients with AS in the National Readmissions Database in 2017-2018 and stratified them according to the presence or absence of a secondary diagnosis of dementia. Inpatient outcomes were compared using logistic regression. Cox proportional-hazards models were used to compare 30-, 60-, and 90-day readmissions. RESULTS: A total of 48,923 index hospitalizations for TAVR were identified, of which 2192 (4.5 %) had a secondary diagnosis of dementia. Presence of dementia was associated with higher odds of delirium, pacemaker placement, acute kidney injury, and fall in hospital. The hazard of 30-day readmission was not significantly different between patients with and without dementia, but patients with dementia experienced a higher hazard of 60-day readmission (HR 1.15, 95 % CI 1.03-1.26, p = 0.011) in the unadjusted model and higher hazard of 90-day readmission in both unadjusted (HR 1.18, 95 % CI 1.08-1.30, p < 0.001) and adjusted models (aHR 1.14, 95 % CI 1.04-1.25, p = 0.004). CONCLUSIONS: Patients with dementia who undergo TAVR are at higher risk of in-hospital adverse outcomes and 60- and 90-day readmissions compared with patients without dementia. These estimates should be integrated into shared decision-making discussions with patients and families.

Readmission and adverse outcomes after percutaneous coronary intervention in patients with dementia.

BACKGROUND: As the population ages, clinicians increasingly encounter ischemic heart disease in patients with underlying dementia. Therefore, we quantified differences in inhospital adverse events and 30-day readmission rates among patients with and without dementia undergoing percutaneous coronary intervention (PCI). METHODS: Using the National Readmissions Database 2017-2018, we identified 755,406 index hospitalizations in which PCI was performed, of which 17,309 (2.3%) had a diagnosis of dementia. After propensity score matching patients with and without dementia, we assessed 30-day readmission and inhospital adverse events by Cox proportional hazards and logistic regression modeling and compared them with those of other common cardiac (pacemaker placement [PP]) and noncardiac (hip replacement surgery [HRS]) procedures. RESULTS: Thirty-day readmission was significantly higher in patients with dementia than patients without dementia (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.60-1.74). Patients with dementia also experienced higher odds of delirium (odds ratio [OR] 4.37, CI 3.69-5.16), inhospital mortality (OR 1.15, CI 1.01-1.30), cardiac arrest (OR 1.19, CI 1.01-1.39), acute kidney injury (OR 1.30, CI 1.21-1.39), and fall (OR 2.51, CI 2.06-3.07). On multivariable Cox modeling, dementia independently predicted 30-day readmission (HR 1.14, CI 1.07-1.20). The higher readmission risk with PCI (11%) among those with dementia was similar to that of patients undergoing PP (10%), but lower than in those undergoing HRS (41%). CONCLUSION: Patients with dementia who undergo PCI experience significantly increased rates of inhospital delirium, mortality, kidney injury, falls, and 30-day readmission. These adverse outcomes should be considered during shared decision-making with patients and their families.

Using the HER2/CEP17 FISH Ratio to Predict Pathologic Complete Response Following Neoadjuvant Anti-HER2 Doublet Therapy in HER2+ Breast Cancer.

BACKGROUND: Clinical trials of HER2-directed therapy that omit neoadjuvant conventional chemotherapy for HER+ breast cancer demonstrate that a subset of patients still obtains a pCR. Identifying tumor characteristics which predict pCR may help select patients for de-escalated neoadjuvant dual HER2-targeted treatment without chemotherapy. This is the first study evaluating the HER2/CEP17 ratio by FISH as a biomarker to predict pCR among patients who received neoadjuvant anti-HER2 regimens without chemotherapy. PATIENTS AND METHODS: Data from patients with locally advanced HER2+ breast cancer who received neoadjuvant dual HER2-targeted therapy without conventional chemotherapy from a single center was retrospectively reviewed. All patients were enrolled in one of 3 clinical trials evaluating chemotherapy de-escalation. Logistic regression modeling assessed for a relationship between the HER2/CEP17 FISH ratio obtained from baseline tissue biopsy and pCR based on pathology at the time of definitive breast surgery following neoadjuvant treatment. RESULTS: Following neoadjuvant treatment with dual HER2-targeted therapies in 56 patients, the probability of pCR was 73% among patients with a HER2 ratio of 13.1 compared to a probability of 38% among patients with HER2 ratio of 5.5 (OR 4.14, 95% CI 1.44-11.89; P = .012). This positive association persisted after controlling for different treatment regimens administered (OR 2.87, 95% CI 0.9-9.18, P = .020). CONCLUSIONS: These data found a positive association between the HER2/CEP17 FISH ratio and pCR following neoadjuvant dual HER2-targeted therapy without chemotherapy. Larger prospective studies are needed to validate the HER2 ratio as a biomarker to select patients for neoadjuvant dual anti-HER2 therapy without chemotherapy.

Spontaneous Adrenal Hemorrhage with Mild Hypoadrenalism in a Patient Anticoagulated with Apixaban for Antiphospholipid Syndrome: A Case Report and Literature Review.

Background: Adrenal hemorrhage (AH) is a serious endocrine complication of antiphospholipid syndrome (APLS). Case Presentation. We report a 45-year-old man who presented with several deep venous thromboses and was initially treated with apixaban, who later developed bilateral AH. Laboratory findings were consistent with cortisol deficiency yet preserved aldosterone physiology. He was diagnosed with APLS and treated with warfarin. After 8 months of follow-up, he remained on cortisol replacement with no evidence of recovery. We reviewed PubMed/MEDLINE indexed articles from 1950 to 2022 for cases of AH in APLS patients on anticoagulation. Six cases of patients on direct oral anticoagulants (DOACs) were reported. Discussion. The unique vasculature of the adrenal glands creates a "functional vascular dam" in the zona reticularis, which is susceptible to thrombosis in situ and hemorrhage. DOACs may further increase the risk of AH. Conclusion: Depending on the degree of adrenal involvement in AH, patients can present with partial or complete primary adrenal insufficiency. More data are needed to characterize adrenal function after AH, and the safety of DOAC versus warfarin in patients with APLS warrants further studies.