Multiple Cardiac Biomarker Testing Among Patients With Acute Dyspnea From the ICON-RELOADED Study.

BACKGROUND: Among patients with acute dyspnea, concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T, and insulin-like growth factor binding protein-7 predict cardiovascular outcomes and death. Understanding the optimal means to interpret these elevated biomarkers in patients presenting with acute dyspnea remains unknown. METHODS AND RESULTS: Concentrations of NT-proBNP, high-sensitivity cardiac troponin T, and insulin-like growth factor binding protein-7 were analyzed in 1448 patients presenting with acute dyspnea from the prospective, multicenter International Collaborative of NT-proBNP-Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department (ICON-RELOADED) Study. Eight biogroups were derived based upon patterns in biomarker elevation at presentation and compared for differences in baseline characteristics. Of 441 patients with elevations in all 3 biomarkers, 218 (49.4%) were diagnosed with acute heart failure (HF). The frequency of acute HF diagnosis in this biogroup was higher than those with elevations in 2 biomarkers (18.8%, 44 of 234), 1 biomarker (3.8%, 10 of 260), or no elevated biomarkers (0.4%, 2 of 513). The absolute number of elevated biomarkers on admission was prognostic of the composite end point of mortality and HF rehospitalization. In adjusted models, patients with one, 2, and 3 elevated biomarkers had 3.74 (95% confidence interval [CI], 1.26-11.1, P = .017), 12.3 (95% CI, 4.60-32.9, P < .001), and 12.6 (95% CI, 4.54-35.0, P < .001) fold increased risk of 180-day mortality or HF rehospitalization. CONCLUSIONS: A multimarker panel of NT-proBNP, hsTnT, and IGBFP7 provides unique clinical, diagnostic, and prognostic information in patients presenting with acute dyspnea. Differences in the number of elevated biomarkers at presentation may allow for more efficient clinical risk stratification of short-term mortality and HF rehospitalization.

Cardiovascular Risk in Men with Prostate Cancer: Insights from the RADICAL PC Study.

PURPOSE: We describe the cardiovascular risk profile in a representative cohort of patients with prostate cancer treated with or without androgen deprivation therapy. MATERIALS AND METHODS: We prospectively characterized in detail 2,492 consecutive men (mean age 68 years) with prostate cancer (newly diagnosed or with a plan to prescribe androgen deprivation therapy for the first time) from 16 Canadian sites. Cardiovascular risk was estimated by calculating Framingham risk scores. RESULTS: Most men (92%) had new prostate cancer (intermediate risk 41%, high risk 50%). The highest level of education achieved was primary school in 12%. Most (58%) were current or former smokers, 22% had known cardiovascular disease, 16% diabetes, 45% hypertension, 31% body mass index 30 kg/m2 or greater, 24% low levels of physical activity, mean handgrip strength was 37.3 kg and 69% had a Framingham risk score consistent with high cardiovascular risk. Participants in whom androgen deprivation therapy was planned had higher Framingham risk scores than those not intending to receive androgen deprivation therapy, and this risk was abolished after adjustment for confounders. CONCLUSIONS: Two-thirds of men with prostate cancer are at high cardiovascular risk. There is a positive association between a plan to use androgen deprivation therapy and baseline cardiovascular risk factors. However, this association is explained by confounding factors.

Rationale and design of the ICON-RELOADED study: International Collaborative of N-terminal pro-B-type Natriuretic Peptide Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department.

OBJECTIVES: The objectives were to reassess use of amino-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations for diagnosis and prognosis of acute heart failure (HF) in patients with acute dyspnea. BACKGROUND: NT-proBNP facilitates diagnosis, prognosis, and treatment in patients with suspected or proven acute HF. As demographics of such patients are changing, previous diagnostic NT-proBNP thresholds may need updating. Additionally, value of in-hospital NT-proBNP prognostic monitoring for HF is less understood. METHODS: In a prospective, multicenter study in the United States and Canada, patients presenting to emergency departments with acute dyspnea were enrolled, with demographic, medication, imaging, and clinical course information collected. NT-proBNP analysis will be performed using the Roche Diagnostics Elecsys proBNPII immunoassay in blood samples obtained at baseline and at discharge (if hospitalized). Primary end points include positive predictive value of previously established age-stratified NT-proBNP thresholds for the adjudicated diagnosis of acute HF and its negative predictive value to exclude acute HF. Secondary end points include sensitivity, specificity, and positive and negative likelihood ratios for acute HF and, among those with HF, the prognostic value of baseline and predischarge NT-proBNP for adjudicated clinical end points (including all-cause death and hospitalization) at 30 and 180days. RESULTS: A total of 1,461 dyspneic subjects have been enrolled and are eligible for analysis. Follow-up for clinical outcome is ongoing. CONCLUSIONS: The International Collaborative of N-terminal pro-B-type Natriuretic Peptide Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department study offers a contemporary opportunity to understand best diagnostic cutoff points for NT-proBNP in acute HF and validate in-hospital monitoring of HF using NT-proBNP.

Antithrombotic Management and Outcomes of Anterior ST-Elevation Myocardial Infarction With New-Onset Wall Motion Abnormalities in Men and Women.

Background: In patients with anterior ST-elevation myocardial infarction (STEMI) and new-onset antero-apical wall motion abnormalities (WMAs), whether the rate of prophylaxis against left ventricular thrombus and outcomes differ between men and women is unknown. Methods: A multicentre retrospective cohort study of patients with STEMI and new-onset antero-apical WMAs treated with primary percutaneous coronary intervention was conducted. Patients with an established indication of oral anticoagulation (OAC) were excluded. The rates of triple therapy (double antiplatelet therapy + OAC) at discharge were compared for women vs men. The rates of net adverse clinical events, a composite of mortality, myocardial infarction, stroke or transient ischemic attack, systemic thromboembolism or Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding at 6 months were compared across sex using a multivariate logistic regression model. Results: A total of 1664 patients were included in the primary analysis, of whom 402 (24.2%) were women and 1262 (75.8%) were men. A total of 138 women (34.3%) and 489 men (38.7%) received a triple therapy prescription at discharge (P = 0.11). At 6 months, 33 women (8.2%) and 96 men (7.6%) experienced a net adverse clinical event (adjusted odds ratio 0.82; 95% confidence interval 0.49-1.37). No difference occurred in the risk of bleeding events and ischemic events between men and women, when these were analyzed separately. Conclusions: The rates of OAC prescription for left ventricular thrombus prophylaxis and clinical outcomes at 6 months were similar in women and men following anterior STEMI with new-onset antero-apical WMAs.

Contexte: On ignore si le taux de prophylaxie contre le thrombus ventriculaire gauche et les résultats thérapeutiques diffèrent entre les hommes et les femmes qui ont subi un infarctus du myocarde avec élévation du segment ST (STEMI) antérieur et ont des anomalies du mouvement pariétal (AMP) antéroapical d'apparition récente. Méthodes: Nous avons mené une étude de cohorte rétrospective multicentrique auprès de patients qui ont subi un STEMI et ont des AMP d'apparition récente traitées par une intervention coronarienne percutanée primaire. Nous avons exclu les patients chez lesquels il existait une indication établie à l'anticoagulation orale (ACO). Nous avons comparé les taux de trithérapie (bithérapie antiplaquettaire + ACO) à la sortie de l'hôpital entre les femmes et les hommes. Nous avons comparé les taux d'événements indésirables cliniques nets, le critère composite de mortalité, d'infarctus du myocarde, d'accident vasculaire cérébral ou d'accident ischémique transitoire, la thromboembolie systémique ou l'hémorragie de type 3 ou 5 selon le Bleeding Academic Research Consortium (BARC) après 6 mois entre les sexes au moyen du modèle de régression logistique multivariée. Résultats: Au sein des 1 664 patients de l'analyse principale, 402 (24,2 %) étaient des femmes et 1262 (75,8 %) étaient des hommes. Un total de 138 femmes (34,3 %) et de 489 hommes (38,7 %) ont reçu une ordonnance de trithérapie à la sortie de l'hôpital (P = 0,11). Après 6 mois, 33 femmes (8,2 %) et 96 hommes (7,6 %) ont subi un événement indésirable net (rapport de cotes ajusté 0,82 ; intervalle de confiance à 95 % 0,49-1,37). Aucune différence n'a été notée dans le risque d'événements hémorragiques et d'événements ischémiques entre les hommes et les femmes lorsque ces événements étaient analysés séparément. Conclusions: Les taux d'ordonnances d'ACO en prophylaxie du thrombus ventriculaire gauche et les résultats cliniques après 6 mois étaient similaires entre les femmes et les hommes à la suite du STEMI antérieur et des AMP antéroapicale d'apparition récente.

Imprecision of high-sensitivity cardiac troponin assays at the female 99th-percentile.

BACKGROUND: An analytical benchmark for high-sensitivity cardiac troponin (hs-cTn) assays is to achieve a coefficient of variation (CV) of ≤ 10.0 % at the 99th percentile upper reference limit (URL) used for the diagnosis of myocardial infarction. Few prospective multicenter studies have evaluated assay imprecision and none have determined precision at the female URL which is lower than the male URL for all cardiac troponin assays. METHODS: Human serum and plasma matrix samples were constructed to yield hs-cTn concentrations near the female URLs for the Abbott, Beckman, Roche, and Siemens hs-cTn assays. These materials were sent (on dry ice) to 35 Canadian hospital laboratories (n = 64 instruments evaluated) participating in a larger clinical trial, with instructions for storage, handling, and monthly testing over one year. The mean concentration, standard deviation, and CV for each instrument type and an overall pooled CV for each manufacturer were calculated. RESULTS: The CVs for all individual instruments and overall were ≤ 10.0 % for two manufacturers (Abbott CVpooled = 6.3 % and Beckman CVpooled = 7.0 %). One of four Siemens Atellica instruments yielded a CV > 10.0 % (CVpooled = 7.7 %), whereas 15 of 41 Roche instruments yielded CVs > 10.0 % at the female URL of 9 ng/L used worldwide (6 cobas e411, 1 cobas e601, 4 cobas e602, and 4 cobas e801) (CVpooled = 11.7 %). Four Roche instruments also yielded CVs > 10.0 % near the female URL of 14 ng/L used in the United States (CVpooled = 8.5 %). CONCLUSIONS: The number of instruments achieving a CV ≤ 10.0 % at the female 99th-percentile URL varies by manufacturer and by instrument. Monitoring assay precision at the female URL is necessary for some assays to ensure optimal use of this threshold in clinical practice.

Contemporary incidence and predictors of left ventricular thrombus in patients with anterior acute myocardial infarction.

BACKGROUND: The incidence of left ventricular thrombus (LVT) after anterior acute myocardial infarction (AMI) has not been well established in the era of primary percutaneous coronary intervention (pPCI) and potent dual antiplatelet therapy. The objective of this study is to establish the contemporary incidence of LVT in this population, to identify their risk factors, and to examine their association with clinical outcomes. METHODS: A multicenter retrospective cohort study including AMI patients with new-onset antero-apical wall motion abnormalities treated with pPCI between 2009 and 2017 was conducted. The primary outcome was LVT during the index hospitalization. Predictors of LVT were identified using multivariate logistic regression. Net adverse clinical events (NACE), a composite of mortality, myocardial infarction, stroke or transient ischemic attack, systemic thromboembolism or BARC type 3 or 5 bleeding at 6 months were compared between the LVT and no LVT groups. RESULTS: Among the 2136 patients included, 83 (3.9%) patients developed a LVT during index hospitalization. A lower left ventricular ejection fraction (LVEF) [adjusted odds ratio (aOR) 0.97; 95% confidence intervals (CI) 0.94-0.99] and the degree of worse anterior WMA (aOR 4.34; 95% CI 2.24-8.40) were independent predictors of LVT. A NACE occurred in 5 (5.72 per 100 patient-year) patients in the LVT group and in 127 (6.71 per 100 patient-year) patients in the no LVT group at 6 months [adjusted hazard ratio (aHR): 0.87; 95% CI 0.35-2.14]. CONCLUSIONS: The risk of LVT after anterior AMI with new-onset wall motion abnormalities is low, but this complication remains present in the contemporary era of timely pPCI and potent dual antiplatelet therapy .

Oral Anticoagulation for the Prevention of Thromboembolic Events in Patients With Anterior ST-Segment Elevation Myocardial Infarction.

OBJECTIVES: The objective is to assess the comparative effectiveness and safety of dual-antiplatelet therapy (DAPT) vs triple therapy (TT) with DAPT + oral anticoagulant (OAC) in patients with anterior ST-segment elevation myocardial infarction (STEMI) and with new-onset anterior/apical wall-motion abnormalities (WMAs) treated with primary percutaneous coronary intervention (PCI). BACKGROUND: Patients with STEMI and new-onset anterior/apical WMA may benefit from the addition of OAC to prevent left ventricular thrombus and cardioembolic events. METHODS: A multicenter, retrospective cohort study was conducted. Patients with a concomitant indication for OAC were excluded. Patients discharged on TT were compared with patients discharged on DAPT using adjusted Cox proportional hazards analysis and inverse probability of treatment weighting. The primary endpoint was the net adverse clinical event (NACE) rate at 6 months (composite of all-cause mortality, non-fatal MI, stroke, or transient ischemic attack, systemic thromboembolism or type 3 or 5 Bleeding Academic Research Consortium [BARC] bleeding). RESULTS: A total of 1666 patients were included, among which 627 were treated with TT and 1039 were treated with DAPT. A NACE occurred in 55 patients (6.03 per 100 patient-years) in the TT group and in 74 patients (7.18 per 100 patient-years) in the DAPT group (adjusted hazard ratio, 0.86; 95% confidence interval, 0.55-1.32). Adjusted risk of the individual components of the primary endpoint, ischemic events, and bleeding events were similar between both groups (P>.05 for all). CONCLUSIONS: The addition of OAC to DAPT in anterior STEMI patients with new-onset WMA treated with PCI was not associated with a significant reduction in NACE.

Muscle Mass and Direct Oral Anticoagulant Activity in Older Adults With Atrial Fibrillation.

BACKGROUND: Direct oral anticoagulants (DOAC) are hydrophilic drugs with plasma levels inversely proportional to lean body mass. Sarcopenic patients with low muscle mass may be at risk for supra-therapeutic DOAC levels and bleeding complications. We therefore sought to examine the influence of lean body mass on DOAC levels in older adults with atrial fibrillation (AF). METHODS: A prospective cohort study was conducted with patients 65 years of age or more receiving rivaroxaban or apixaban for AF. Appendicular lean mass (ALM) was measured using a bioimpedance device and a dual X-ray absorptiometry scanner. DOAC levels were measured using a standardized anti-Xa assay 4 hours after (peak) and 1 hour before (trough) ingestion. RESULTS: The cohort consisted of 62 patients (47% female, 77.0 ± 6.1 years). The prescribed DOACs were apixaban 2.5 mg (21%), apixaban 5 mg (53%), and rivaroxaban 20 mg (26%). Overall, 16% had supra-therapeutic DOAC levels at trough and 25% at peak. In the multivariable logistic regression model, lower ALM was independently associated with supra-therapeutic DOAC levels at trough (odds ratio per ↓ 1-kg 1.23, 95% confidence interval 1.02 to 1.49) and peak (odds ratio per ↓ 1-kg 1.18, 95% confidence interval 1.02 to 1.37). Addition of ALM to a model consisting of age, total body weight, and renal function resulted in improved discrimination for supra-therapeutic DOAC levels. CONCLUSION: Our proof-of-concept study has identified an association between ALM and DOAC levels in older adults with AF. Further research is needed to determine the impact of ALM on bleeding complications and the potential role of ALM-guided dosing for sarcopenic patients.

A Patient-Led Referral Strategy for Cardiovascular Screening of Family and Household Members at the Time of Cardiac Intensive Care Unit Admission.

BACKGROUND: Screening relatives of patients with ischemic heart disease can identify over half of the population with poorly controlled cardiovascular (CV) risk factors. Family or household members (FMs) may be highly motivated to undergo CV primary prevention screening at the time of their relative's admission to the Cardiovascular Intensive Care Unit (CICU). METHODS: Patients aged ≤ 70 years admitted to a tertiary CICU for an acute coronary event were given a letter to refer FMs for CV screening. Interested FMs underwent CV risk-factor assessment and primary prevention counselling. The objectives were to identify FMs with an intermediate or high modified 10-year Framingham risk score (FRS) and to evaluate whether a family-oriented primary prevention strategy improved CV risk. RESULTS: There were 51 CV probands who referred 101 FMs (62 family, 39 household; mean age: 44.8 ± 15.3; 65 (64.4%) female) for screening. One-third of FMs aged ≥ 30 years (n = 28 of 84; 32.1%) had a new diagnosis of either hypertension, diabetes, or dyslipidemia. Nearly half of FMs (n = 38; 45.2%) had an intermediate or high modified Framingham 10-year CV risk. In FMs aged ≥ 30 years attending the 6-month follow-up (51 of 84; 60.7%), the mean FRS decreased by 4.6% (from 13.2% ± 12.7 to 8.6% ± 10.0, P < 0.001), and 30.4% (7 of 23) of FMs had a low FRS who had initially had an intermediate or high FRS. CONCLUSIONS: A patient-led referral strategy at the time of CICU admission led to a high rate of identification of previously undiagnosed CV risk factors in FMs. Implementing a similar referral program on a larger scale could identify a considerable burden of CV risk.

CONTEXTE: Le dépistage des parents proches de patients atteints de cardiopathie ischémique permet d'identifier plus de la moitié de la population présentant des facteurs de risques cardiovasculaires (CV) mal contrôlés. Les membres de la famille ou du ménage (MF) peuvent se révéler très motivés à se soumettre à un dépistage de prévention CV primaire au moment de l'admission de leur parent proche à l'unité de soins intensifs cardiovasculaires (USCV). MÉTHODES: Les patients âgés de ≤ 70 ans admis dans une USCV tertiaire pour un événement coronarien aigu ont reçu une lettre les invitant à envoyer des MF pour un dépistage CV. Les MF intéressés ont subi une évaluation des facteurs de risques CV et ont reçu des conseils de prévention primaire. Les objectifs étaient d'identifier les MF présentant un score de risque de Framingham (SRF) modifié intermédiaire ou élevé sur 10 ans et d'évaluer si une stratégie de prévention primaire axée sur le lien familial diminuait le risque CV. RÉSULTATS: Cinquante et un (51) sujets ayant des troubles CV ont référé 101 MF (62 membres de la famille, 39 membres du ménage; âge moyen : 44,8 ± 15,3 ans; 65 (64,4 %) femmes) à un dépistage. Un tiers des MF âgés de ≥ 30 ans (n = 28 sur 84; 32,1 %) ont reçu un nouveau diagnostic d'hypertension, de diabète ou de dyslipidémie. Près de la moitié des MF (n = 38; 45,2 %) présentaient un score de risques CV à 10 ans intermédiaire ou élevé, sur l'échelle du score de risque de Framingham (SRF) modifié. Parmi les MF âgés de ≥ 30 ans ayant participé au suivi sur 6 mois (51 sur 84; 60,7 %), le SRF moyen a diminué de 4,6 % (de 13,2 % ± 12,7 à 8,6 % ± 10,0, p < 0,001), et 30,4 % (7 sur 23) des MF avaient un SRF faible après avoir initialement eu un SRF intermédiaire ou élevé. CONCLUSIONS: Une stratégie d'orientation effectuée au moment de l'admission du patient à l'USCV a conduit à un taux élevé d'identification de facteurs de risques CV non diagnostiqués auparavant parmi les MF. La mise en œuvre d'un programme d'orientation similaire à plus grande échelle pourrait permettre d'identifier un nombre considérable de personnes à risques CV.

Diagnostic and Prognostic Utilities of Insulin-Like Growth Factor Binding Protein-7 in Patients With Dyspnea.

OBJECTIVES: This study examined whether insulin-like growth factor binding protein-7 (IGFBP7) would aid in the diagnosis and prognosis of acute heart failure (HF) beyond N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration. BACKGROUND: IGFBP7 is associated with impaired ventricular relaxation and worse prognosis. METHODS: The ICON-RELOADED (International Collaborative of NT-proBNP-Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department) study was a prospective, multicenter clinical trial that enrolled subjects presenting with dyspnea. Six-month prognosis for death or repeat hospitalization was obtained. RESULTS: Among 1,449 patients, 274 (18.9%) were diagnosed with acute HF. Those with IGFBP7 concentrations in the highest quartile were older, male, had hypertension and HF, had lower estimated glomerular filtration rate (eGFR) and lowest ejection fraction (41 ± 20%; all p < 0.001). Independent predictors of IGFBP7 were age, male sex, history of diabetes, history of HF, and eGFR. Median concentrations of NT-proBNP (2,844 ng/ml vs. 99 ng/ml) and IGFBP7 (146.1 ng/ml vs. 86.1 ng/ml) were higher in those with acute HF (both; p < 0.001). Addition of IGFBP7 to NT-proBNP concentrations improved discrimination, therefore increasing the area under the receiver operating curve for diagnosis of acute HF (from 0.91 to 0.94; p < 0.001 for differences). Addition of IGFBP7 to a complete model of independent predictors of acute HF improved model calibration. IGFBP7 significantly reclassified acute HF diagnosis beyond NT-proBNP (net reclassification index: +0.25). Higher log2-IGFBP7 concentrations in patients with acute HF predicted death or rehospitalization at 6 months (hazard ratio: 1.84 per log2-SD; 95% confidence interval: 1.30 to 2.61; p = 0.001). In Kaplan-Meier analyses, supramedian concentrations of IGFBP7 were associated with shorter event-free survival (log-rank: p < 0.001). CONCLUSIONS: Among patients with acute dyspnea, concentrations of IGFBP7 add to NT-proBNP for diagnosis of acute HF and provide added prognostic utility for short-term risk.

Echocardiographic assessment of insulin-like growth factor binding protein-7 and early identification of acute heart failure.

AIMS: Concentrations of insulin-like growth factor binding protein-7 (IGFBP7) have been linked to abnormal cardiac structure and function in patients with chronic heart failure (HF), but cardiovascular correlates of the biomarker in patients with more acute presentations are lacking. We aimed to determine the relationship between IGFBP7 concentrations and cardiac structure and to evaluate the impact of IGFBP7 on the diagnosis of acute HF among patients with acute dyspnoea. METHODS AND RESULTS: In this pre-specified subgroup analysis of the International Collaborative of N-terminal pro-B-type Natriuretic Peptide Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department (ICON-RELOADED) study, we included 271 patients with and without acute HF. All patients presented to an emergency department with acute dyspnoea, had blood samples for IGFBP7 measurement, and detailed echocardiographic evaluation. Higher IGFBP7 concentrations were associated with numerous cardiac abnormalities, including increased left atrial volume index (LAVi; r = 0.49, P < 0.001), lower left ventricular ejection fraction (r = -0.27, P < 0.001), lower right ventricular fractional area change (r = -0.31, P < 0.001), and higher tissue Doppler E/e' ratio (r = 0.44, P < 0.001). In multivariable linear regression analyses, increased LAVi (P = 0.01), lower estimated glomerular filtration rate (P = 0.008), higher body mass index (P = 0.001), diabetes (P = 0.009), and higher concentrations of amino-terminal pro-B-type natriuretic peptide (NT-proBNP, P = 0.02) were independently associated with higher IGFBP7 concentrations regardless of other variables. Furthermore, IGFBP7 (odds ratio = 12.08, 95% confidence interval 2.42-60.15, P = 0.02) was found to be independently associated with the diagnosis of acute HF in the multivariable logistic regression analysis. CONCLUSIONS: Among acute dyspnoeic patients with and without acute HF, increased IGFBP7 concentrations are associated with a range of cardiac structure and function abnormalities. Independent association with increased LAVi suggests elevated left ventricular filling pressure is an important trigger for IGFBP7 expression and release. IGFBP7 may enhance the diagnosis of acute HF.

Association between troponin T and impaired left ventricular relaxation in patients with acute decompensated heart failure with preserved systolic function.

AIMS: To examine relationships between cardiac troponin T (cTnT) and parameters of left ventricular (LV) structure and function in patients with acute destabilized heart failure (HF) with preserved LV ejection fraction. METHODS AND RESULTS: In 44 patients with acute heart failure (HF) with preserved left ventricular (LV) ejection fraction, parameters of LV structure and function were assessed via comprehensive two-dimensional Doppler echocardiography. There was no correlation between cTnT and LV wall thickness, left atrial volume index, or transmitral E wave velocity or deceleration time. There were associations between cTnT and LV end-diastolic dimension (r = -0.34, P = 0.02) and LV mass index (r = 0.32; P = .04). A lower tissue Doppler Ea wave peak velocity was associated with higher cTnT concentrations (r = -0.90, P < 0.001). In multivariate analyses, only LV end-diastolic dimension (t = 2.2; P = 0.04), LV mass index (t = 2.3; P = .03), and tissue Doppler Ea wave peak velocity (t = -4.7; P < .001) emerged as significant predictors of cTnT. CONCLUSION: In patients with HF with preserved LV ejection fraction, cTnT is strongly associated with the extent of LV relaxation abnormalities and LV mass.

Amino-terminal pro-B-type natriuretic peptide testing for the diagnosis or exclusion of heart failure in patients with acute symptoms.

When used for the evaluation of patients with acute symptoms in the emergency department setting, amino-terminal pro-B-type natriuretic peptide (NT-proBNP) testing is highly sensitive and specific for the diagnosis or exclusion of acute destabilized heart failure (HF), with results comparable to those reported for B-type natriuretic peptide (BNP) testing. When used for the diagnostic evaluation of the patient with possible HF, NT-proBNP testing returns information that may be superior to clinical judgment. However, the optimal application of NT-proBNP is in concert with history and physical examination, adjunctive testing, and with the knowledge of the differential diagnosis of an elevated NT-proBNP level. Studies indicate a dual use for NT-proBNP, both to exclude acute HF (where NT-proBNP concentrations <300 ng/L have a 98% negative predictive value), as well as to identify the diagnosis. To identify acute HF in patients with dyspnea, an age-independent NT-proBNP cut point of 900 ng/L has a similar value as that reported for a BNP value of 100 ng/L. However, age stratification of NT-proBNP using cut points of 450, 900, and 1,800 ng/L (for age groups of <50, 50-75, and >75 years) reduces false-negative findings in younger patients, reduces false-positive findings in older patients, and improves the overall positive predictive value of the marker without a change in overall sensitivity or specificity. Clinically validated, cost-effective algorithms for the use of NT-proBNP testing exist. Therefore, the logical use of NT-proBNP for the evaluation of the patient with suspected acute HF is useful, cost-effective, and may reduce adverse outcomes compared with standard clinical evaluation without natriuretic peptide testing.

Use of tissue Doppler to distinguish discrete upper ventricular septal hypertrophy from obstructive hypertrophic cardiomyopathy.

Discrete upper septal hypertrophy (DUSH) is a well-recognized but poorly understood echocardiographic finding that may indicate localized remodeling modulated by pressure loading or a forme fruste variant of obstructive hypertrophic cardiomyopathy (HC). It was hypothesized that (1) a comparison of tissue Doppler indexes of myocardial function in normal patients and those with DUSH or aortic stenosis (AS) could provide insight into the clinical significance of DUSH and (2) these indexes could distinguish between DUSH and obstructive HC. A retrospective analysis was performed on patients aged 50 to 80 years who underwent routine echocardiography and who could be classified into normal, DUSH, AS, and HC groups (n = 25, 33, 23, and 34, respectively) on the basis of clinical and echocardiographic criteria. Early diastolic mitral annular velocities (Ea) in the DUSH (7.1 +/- 1.8 cm/s) and AS (7.1 +/- 1.7 cm/s) groups were lower compared with those in the normal group (9.3 +/- 1.9 cm/s) and higher compared with those in the HC group (5.4 +/- 1.3 cm/s), whereas the E/Ea ratio was higher in the DUSH and AS groups (10.0 +/- 3.1 and 11.3 +/- 2.8, respectively) compared with the normal group (7.1 +/- 1.6) and lower compared with the HC group (18.8 +/- 7.5). These differences remained significant after adjusting for age and the use of beta blockers and calcium channel blockers. E/Ea > or =13 distinguished between patients with HC and those with DUSH (sensitivity 78%, specificity 90%, positive predictive value 90%, negative predictive value 81%). In conclusion, abnormal Ea and E/Ea in patients with DUSH, with values similar to those in patients with AS, suggest that DUSH may represent a variant hypertrophic response to chronic pressure loading. Simple echocardiographic indexes may be helpful in distinguishing between patients with DUSH and those with obstructive HC.

Phase Angle as a Biomarker for Frailty and Postoperative Mortality: The BICS Study.

Background Phase angle (PA) is a bioimpedance measurement that is determined lean body mass and hydration status. Patients with low PA values are more likely to be frail, sarcopenic, or malnourished. Previous work has shown that low PA predicts adverse outcomes after cardiac surgery, but the effect of PA on survival has not previously been assessed in this setting. Methods and Results The BICS (Bioimpedance in Cardiac Surgery) study recruited 277 patients undergoing major cardiac surgery at 2 university-affiliated hospitals in Montreal, QC, Canada. Bioimpedance measurements as well as frailty and nutritional assessments were performed preoperatively. The primary outcome was all-cause mortality. Secondary outcomes were 30-day mortality, postoperative morbidity, and hospital length of stay. There were 10 deaths at 1 month of follow-up and 16 deaths at 12 months of follow-up. PA was associated with age, sex, body mass index, comorbidities, and frailty, as measured by the Short Physical Performance Battery and Fried scales. After adjusting for Society of Thoracic Surgeons-predicted mortality, lower PA was associated with higher mortality at 1 month (adjusted odds ratio, 3.57 per 1° decrease in PA ; 95% confidence interval, 1.35-9.47) and at 12 months (adjusted odds ratio, 3.03 per 1° decrease in PA ; 95% confidence interval, 1.30-7.09), a higher risk of overall morbidity (adjusted hazard ratio, 2.51 per 1° decrease in PA ; 95% confidence interval, 1.32-4.75), and a longer hospital length of stay (adjusted ß, 4.8 days per 1° decrease in PA ; 95% confidence interval, 1.3-8.2 days). Conclusions Low PA is associated with frailty and is predictive of mortality, morbidity, and length of stay after major cardiac surgery. Further work is needed to determine the responsiveness of PA to interventions aimed at reversing frailty.

N-Terminal Pro-B-Type Natriuretic Peptide in the Emergency Department: The ICON-RELOADED Study.

BACKGROUND: Contemporary reconsideration of diagnostic N-terminal pro-B-type natriuretic peptide (NT-proBNP) cutoffs for diagnosis of heart failure (HF) is needed. OBJECTIVES: This study sought to evaluate the diagnostic performance of NT-proBNP for acute HF in patients with dyspnea in the emergency department (ED) setting. METHODS: Dyspneic patients presenting to 19 EDs in North America were enrolled and had blood drawn for subsequent NT-proBNP measurement. Primary endpoints were positive predictive values of age-stratified cutoffs (450, 900, and 1,800 pg/ml) for diagnosis of acute HF and negative predictive value of the rule-out cutoff to exclude acute HF. Secondary endpoints included sensitivity, specificity, and positive (+) and negative (-) likelihood ratios (LRs) for acute HF. RESULTS: Of 1,461 subjects, 277 (19%) were adjudicated as having acute HF. The area under the receiver-operating characteristic curve for diagnosis of acute HF was 0.91 (95% confidence interval [CI]: 0.90 to 0.93; p < 0.001). Sensitivity for age stratified cutoffs of 450, 900, and 1,800 pg/ml was 85.7%, 79.3%, and 75.9%, respectively; specificity was 93.9%, 84.0%, and 75.0%, respectively. Positive predictive values were 53.6%, 58.4%, and 62.0%, respectively. Overall LR+ across age-dependent cutoffs was 5.99 (95% CI: 5.05 to 6.93); individual LR+ for age-dependent cutoffs was 14.08, 4.95, and 3.03, respectively. The sensitivity and negative predictive value for the rule-out cutoff of 300 pg/ml were 93.9% and 98.0%, respectively; LR- was 0.09 (95% CI: 0.05 to 0.13). CONCLUSIONS: In acutely dyspneic patients seen in the ED setting, age-stratified NT-proBNP cutpoints may aid in the diagnosis of acute HF. An NT-proBNP <300 pg/ml strongly excludes the presence of acute HF.