Troponin elevation in patients with heart failure: on behalf of the third Universal Definition of Myocardial Infarction Global Task Force: Heart Failure Section

Cardiac troponin testing is commonly performed in patients with heart failure (HF). Despite being strongly linked to spontaneous (Type I) acute myocardial infarction (MI)-a common cause of acute HF syndromes-it is well recognized that concentrations of circulating troponins above the 99th percentile of a normal population in the context of both acute and chronic HF are highly prevalent, and frequently unrelated to Type I MI. Other mechanism(s) leading to troponin elevation in HF syndromes remain elusive in many cases but prominently includes supply-demand inequity (Type II MI), which may be associated with coronary artery obstruction and endothelial dysfunction, or may occur in the absence of coronary obstruction due to increased oxygen demand related to increased wall tension, anaemia, or other factors provoking subendocardial injury. Non-coronary triggers, such as cellular necrosis, apoptosis, or autophagy in the context of wall stress may explain the troponin release in HF, as can toxic effects of circulating neurohormones, toxins, inflammation, and infiltrative processes, among others. Nonetheless, across a wide spectrum of HF syndromes, when troponin elevation occurs, independent of mechanism, it is strongly predictive of an adverse outcome. Clinicians should be aware of the high frequency of troponin elevation when measuring the marker in patients with HF, should keep in mind the possible causes of this phenomenon, and, independent of a diagnosis of 'acute MI', should recognize the considerable ramifications of troponin elevation in this setting.     

Study of lipoprotein(a) and its impact on atherosclerotic cardiovascular disease: Design and rationale of the Mass General Brigham Lp(a) Registry

Lipoprotein(a) [Lp(a)] is independently associated with atherosclerotic cardiovascular disease and calcific aortic valve stenosis. Elevated Lp(a) affects approximately one in five individuals and meaningfully contributes to the residual cardiovascular risk in individuals with otherwise well-controlled risk factors. With targeted therapies in the therapeutic pipeline, there is a need to further characterize the clinical phenotypes and outcomes of individuals with elevated levels of this unique biomarker. The Mass General Brigham Lp(a) Registry will be built from the longitudinal electronic health record of two large academic medical centers in Boston, Massachusetts, to develop a detailed cohort of patients who have had their Lp(a) measured. In combination with structured data sources, clinical documentation will be analyzed using natural language processing techniques to accurately characterize baseline characteristics. Important outcome measures including all-cause mortality, cardiovascular mortality, and cardiovascular events will be available for analysis. Approximately 30 000 patients who have had their Lp(a) tested within the Mass General Brigham system from January 2000 to July 2019 will be included in the registry. This large Lp(a) cohort will provide meaningful observational data regarding the differential risk associated with Lp(a) values and cardiovascular disease. With a new frontier of targeted Lp(a) therapies on the horizon, the Mass General Brigham Lp(a) Registry will help provide a deeper understanding of Lp(a)'s role in long term cardiovascular outcomes.     

Management of low blood pressure in ambulatory heart failure with reduced ejection fraction patients

Low blood pressure is common in patients with heart failure and reduced ejection fraction (HFrEF). While spontaneous hypotension predicts risk in HFrEF, there is only limited evidence regarding the relationship between hypotension observed during heart failure (HF) drug titration and outcome. Nevertheless, hypotension (especially orthostatic hypotension) is an important factor limiting the titration of HFrEF treatments in routine practice. In patients with signs of shock and/or severe congestion, hospitalization is advised. However, in the very frequent cases of non‐severe and asymptomatic hypotension observed while taking drugs with a class I indication in HFrEF, European and US guidelines recommend maintaining the same drug dosage. In instances of symptomatic or severe persistent hypotension (systolic blood pressure < 90 mmHg), it is recommended to first decrease blood pressure reducing drugs not indicated in HFrEF as well as the loop diuretic dose in the absence of associated signs of congestion. Unless the management of hypotension appears urgent, a HF specialist should then be sought rather than stopping or decreasing drugs with a class I indication in HFrEF. If symptoms or severe hypotension persist, no recommendations exist. Our HF group reviewed available evidence and proposes certain steps to follow in such situations in order to improve the pharmacological management of these patients.     

Natriuretic Peptide testing for predicting adverse events following heart failure hospitalization

Concentrations of both B-type natriuretic peptide (BNP) and amino-terminal pro-BNP (NT-proBNP) are useful for diagnostic evaluation of patients with acute decompensated heart failure (ADHF), providing important information regarding presence and severity of heart failure. In addition, levels of both BNP and NT-proBNP are strongly prognostic for adverse outcomes in this setting. While values for BNP and NT-proBNP at hospital admission predict impending risk for adverse outcome, their measurement following HF treatment provides incremental prognostic information, even more accurately identifying patients at highest risk for death or rehospitalization in the short term. Thus, changes in BNP or NT-proBNP following treatment should be considered an important part of the pre-discharge decision making for patients hospitalized with ADHF. ?2012 Wiley Periodicals, Inc.     

Moving troponin testing into the 21st century: will greater sensitivity be met with greater sensibility?

With its superior sensitivity and specificity, cardiac troponin has gradually replaced other cardiac enzymes, and is now the biomarker of choice in making the critical diagnosis of an acute coronary syndrome (ACS). The early stratification of risk from unstable angina to non-ST segment elevation myocardial infarction (NSTEMI), is crucial in the timing and treatment of the ACS. Troponin elevations have also been shown to be powerfully prognostic in a variety of clinical settings and because of this predictive value, may be useful in determining benefit of various clinical interventions. However, inherent in this improved sensitivity and specificity of the measurement tools is the inclusion of non-ACS patients with abnormal troponin measurements. Increased understanding of the alternative diagnoses associated with elevated troponins as well as assays which allow more rapid and accurate diagnosis of ACS, are needed to further improve patient care. Clinical trials of risk stratification controlling for concomitant associated diagnoses including renal insufficiency, pulmonary embolism, atrial fibrillation and congestive heart failure will provide data to optimize this tool.     

Utility of B-type natriuretic peptide for the evaluation of intensive care unit shock

OBJECTIVES: Among patients with congestive heart failure, B-type natriuretic peptide measurement is useful to estimate filling pressures and to prognosticate adverse outcome. However, among critically ill intensive care unit patients with shock, the utility of B-type natriuretic peptide to assess cardiac hemodynamics or prognosis has not been explored. DESIGN: Clinical investigation. SETTING: Hospital. PATIENTS: Forty-nine patients with shock and indication for pulmonary artery catheterization. INTERVENTIONS: Analysis for B-type natriuretic peptide was performed on blood obtained at the time of catheter placement. MEASUREMENTS AND MAIN RESULTS: Correlations between B-type natriuretic peptide and pulmonary artery occlusion pressure as well as cardiac index were calculated using Spearman analysis. Mortality at the time of study completion was correlated with B-type natriuretic peptide values and Acute Physiology and Chronic Health Evaluation II scores, and logistic regression identified independent predictors of mortality. A wide range of B-type natriuretic peptide concentrations was seen in intensive care unit patients (<5 to >5000 pg/mL); only eight patients (16%) had normal B-type natriuretic peptide concentrations. Log-transformed B-type natriuretic peptide concentrations did not correlate with interpatient cardiac index or pulmonary artery occlusion pressure (all p = not significant); however, a B-type natriuretic peptide <350 pg/mL had a negative predictive value of 95% for the diagnosis of cardiogenic shock. Median B-type natriuretic peptide concentrations were higher in those who died than those who survived (943 pg/mL vs. 378 pg/mL, p <.001). In multivariable analysis, a B-type natriuretic peptide concentration in the highest log-quartile was the strongest predictor of mortality (odds ratio = 4.50, 95% confidence interval = 1.87-99.0, p <.001). CONCLUSION: B-type natriuretic peptide concentrations are frequently elevated among critically ill patients in the intensive care unit and cannot be used as a surrogate for pulmonary artery catheterization. B-type natriuretic peptide concentrations in intensive care unit shock may provide powerful information for use in mortality prediction.     

High-sensitivity troponin T and C-reactive protein to identify patients without cardiac structural and functional abnormalities as assessed by cardiac CT and SPECT imaging: can biomarkers predict cardiac health?

While high-sensitivity troponin-T (hsTnT) and C-reactive protein (hsCRP) are associated with structural heart disease, we thought to determine whether biomarkers can predict which heart is healthy based on multimodality imaging. Patients from the emergency department with acute chest pain suggestive of acute coronary syndrome undergoing contrast enhanced cardiac CT and stress single photon emission computed tomography (SPECT) myocardial perfusion imaging were included. HsTnT and hsCRP were assessed at time of CT. Imaging data were assessed for coronary atherosclerosis, left ventricular hypertrophy/dysfunction and myocardial perfusion abnormalities. Patients were stratified into those with or without any cardiac findings, who were considered as cardiac healthy. For biomarkers, low cut-off corresponding to good specificity and high cut-off corresponding to good sensitivity for cardiac health were derived. Among 117 patients (52 years, 55 % male), 42 (36 %) were cardiac healthy based on cardiac CT and SPECT imaging. These patients had significantly lower hsTnT and hsCRP levels as compared to those with functional or structural abnormalities (3.58 vs. 5.63 ng/L, p = 0.002; 0.82 vs. 1.93 mg/L, p = 0.0005; respectively). Patients with both low hsTnT (<3.00 ng/L) and hsCRP (<0.45 mg/L) had a probability of 85 % for being cardiac healthy. In contrast, patients with high hsTnT (>7.00 ng/L) and hsCRP (>2.00 mg/L) had 8 % probability for being cardiac healthy. Discriminative capacity of a dual-biomarker strategy was significantly improved as compared to hsTnT or hsCRP alone or to Framingham Risk score (AUC: 0.781 vs. 0.691; vs. 0.678; vs. 0.649; all p ≤ 0.02, respectively). A dual-biomarker strategy of hsTnT and hsCRP is highly discriminative for patients with normal cardiac structure and function and provides incremental value beyond the Framingham risk score.