Paced P-wave morphology templates to guide atrial tachycardia localization: A derivation and validation study.

BACKGROUND: Surface ECG is a useful tool to guide mapping of focal atrial tachycardia (AT). OBJECTIVES: We aimed to construct 12-lead ECG templates for P-wave morphology (PWM) during endocardial pacing from different sites in both atria in patients with no apparent structural heart disease (derivation cohort), with the goal of creating a localization algorithm, which could subsequently be validated in a cohort of patients undergoing catheter ablation of focal AT (validation cohort). METHODS: We prospectively enrolled consecutive patients who underwent electrophysiology study, had no structural heart disease and no atrial enlargement. Atrial pacing, at twice diastolic threshold, was carried out at different anatomical sites in both atria. Paced PWM and duration were assessed. An algorithm was generated from the constructed templates of each pacing site. The algorithm was applied on a retrospective series of successfully ablated AT patients. Overall and site-specific accuracy were determined. RESULTS: Derivation cohort included 65 patients (25 men, age 37 ± 13 years). Atrial pacing was performed in 1025 sites in 61 patients (95%) in RA and in 15 patients (23%) in LA. The validation cohort included 71 patients (28 men, age 52 ± 19 years). AT were right atrial in 66.2%. The algorithm successfully predicted AT origin in 91.5% of patients (100% in LA and 87.2% in RA). It was off by one adjacent segment in the remaining 8.5%. CONCLUSIONS: A simple ECG algorithm based on paced PWM templates was highly accurate in localizing site of origin of focal AT in patients with structurally normal hearts.

Correlation of echocardiographic parameters in prone and supine positions in normal adults using a novel approach.

BACKGROUND: Transthoracic echocardiography (TTE) in prone position is challenging. Innovative use of transesophageal echocardiography (TEE) probe to perform TTE for such patients has been described; but reproducibility and correlation of the TTE measurements by this technique with those obtained by the standard supine TTE study are still unknown. METHODS: We enrolled 30 non-COVID-19 individuals, with a mean (SD) age 35 (10.9) years and 11 females, to study the agreement between the transthoracic measurements of the left ventricular (LV), left atrial (LA), aortic dimensions, and ejection fraction (EF) obtained in prone position using an external TEE probe versus the standard supine position using the conventional TTE probe. RESULTS: There were no significant differences between LV end-diastolic and end-systolic diameters, septal wall thickness, posterior wall thickness, and aortic root dimensions in the prone versus the supine positions, while the mean EF (60.3% vs 63.1%, P = .014) and mean LA dimensions (1.8 vs 1.9 cm/m2 , P < .001) were significantly lower in the prone position. The mean time of scans was significantly longer in the prone as compared to the supine position (12.5 vs 4.5 minutes, P < .001). All supine studies had good quality while in the prone position four studies were of poor quality, and one was nondiagnostic. CONCLUSIONS: Assessment of cardiac dimensions and systolic function in the prone position using transthoracic TEE probe was feasible. LV and aortic dimensions agreed well with the standard TTE in supine position; however, LA dimensions and EF were lower in the prone position.

Nourin-Dependent miR-137 and miR-106b: Novel Biomarkers for Early Diagnosis of Myocardial Ischemia in Coronary Artery Disease Patients.

BACKGROUND: Although cardiovascular imaging techniques are widely used to diagnose myocardial ischemia in patients with suspected stable coronary artery disease (CAD), they have limitations related to lack of specificity, sensitivity and "late" diagnosis. Additionally, the absence of a simple laboratory test that can detect myocardial ischemia in CAD patients, has led to many patients being first diagnosed at the time of the development of myocardial infarction. Nourin is an early blood-based biomarker rapidly released within five minutes by "reversible" ischemic myocardium before progressing to necrosis. Recently, we demonstrated that the Nourin-dependent miR-137 (marker of cell damage) and miR-106b-5p (marker of inflammation) can diagnose myocardial ischemia in patients with unstable angina (UA) and also stratify severity of ischemia, with higher expression in acute ST-segment elevation myocardial infarction (STEMI) patients compared to UA patients. Minimal baseline-gene expression levels of Nourin miRNAs were detected in healthy subjects. OBJECTIVES: To determine: (1) whether Nourin miRNAs are elevated in chest pain patients with myocardial ischemia suspected of CAD, who also underwent dobutamine stress echocardiography (DSE) or ECG/Treadmill stress test, and (2) whether the elevated levels of serum Nourin miRNAs correlate with results of ECHO/ECG stress test in diagnosing CAD patients. METHODS: Serum gene expression levels of miR-137, miR-106b-5p and their corresponding molecular pathway network were measured blindly in 70 enrolled subjects using quantitative real time PCR (qPCR). Blood samples were collected from: (1) patients with chest pain suspected of myocardial ischemia (n = 38) both immediately "pre-stress test" and "post-stress test" 30 min. after test termination; (2) patients with acute STEMI (n = 16) functioned as our positive control; and (3) healthy volunteers (n = 16) who, also, exercised on ECG/Treadmill stress test for Nourin baseline-gene expression levels. RESULTS: (1) strong correlation was observed between Nourin miRNAs serum expression levels and results obtained from ECHO/ECG stress test in diagnosing myocardial ischemia in CAD patients; (2) positive "post-stress test" patients with CAD diagnosis showed upregulation of miR-137 by 572-fold and miR-106b-5p by 122-fold, when compared to negative "post-stress test" patients (p < 0.001); (3) similarly, positive "pre-stress test" CAD patients showed upregulation of miR-137 by 1198-fold and miR-106b-5p by 114-fold, when compared to negative "pre-stress test" patients (p < 0.001); and (4) healthy subjects had minimal baseline-gene expressions of Nourin miRNAs. CONCLUSIONS: Nourin-dependent miR-137 and miR-106b-5p are promising novel blood-based biomarkers for early diagnosis of myocardial ischemia in chest pain patients suspected of CAD in outpatient clinics. Early identification of CAD patients, while patients are in the stable state before progressing to infarction, is key to providing crucial diagnostic steps and therapy to limit adverse cardiac events, improve patients' health outcome and save lives.

Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as independent predictors of outcome in infective endocarditis (IE).

BACKGROUND: Early and accurate risk assessment is an important clinical demand in patients with infective endocarditis (IE). The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are independent predictors of prognosis in many infectious and cardiovascular diseases. Very limited studies have been conducted to evaluate the prognostic role of these markers in IE. RESULTS: We analyzed clinical, laboratory, and echocardiographic data and outcomes throughout the whole period of hospitalization for a total of 142 consecutive patients with definitive IE. The overall in-hospital mortality was 21%. Major complications defined as central nervous system embolization, fulminant sepsis, acute heart failure, acute renal failure, and major artery embolization occurred in 38 (27%), 34 (24%), 32 (22.5%), 40 (28%), and 90 (63.4%) patients, respectively. The NLR, total leucocyte count (TLC), neutrophil percentage, creatinine, and C-reactive protein (CRP) level obtained upon admission were significantly higher in the mortality group [p ≤ 0.001, p = 0.008, p = 0.001, p = 0.004, and p = 0.036, respectively]. A higher NLR was significantly associated with fulminant sepsis and major arterial embolization [p = 0.001 and p = 0.028, respectively]. The receiver operating characteristic (ROC) curve of the NLR for predicting in-hospital mortality showed that an NLR > 8.085 had a 60% sensitivity and an 84.8% specificity for an association with in-hospital mortality [area under the curve = 0.729, 95% confidence interval (CI) 0.616-0.841; p = 0.001]. The ROC curve of the NLR for predicting severe sepsis showed that an NLR > 5.035 had a 71.8% sensitivity and a 68.5% specificity for predicting severe sepsis [area under the curve 0.685, 95% CI 0.582-0.733; p = 0.001]. The PLR showed no significant association with in-hospital mortality or in-hospital complications. CONCLUSION: A higher NLR, TLC, neutrophil percentage, creatinine level, and CRP level upon admission were associated with increased in-hospital mortality and morbidity in IE patients. Furthermore, a lower lymphocyte count/percentage and platelet count were strong indicators of in-hospital mortality among IE patients. Calculation of the NLR directly from a CBC upon admission may assist in early risk stratification of patients with IE.

Correction: Aspergillus endocarditis: Diagnostic criteria and predictors of outcome, A retrospective cohort study.

[This corrects the article DOI: 10.1371/journal.pone.0201459.].

Aspergillus endocarditis: Diagnostic criteria and predictors of outcome, A retrospective cohort study.

BACKGROUND: Fungal Endocarditis (FE), a relatively rare disease, has a high rate of mortality and is associated with multiple morbidities. Aspergillus endocarditis (AE) is severe form of FE. Incidence of AE has increased and is expected to rise due to an increased frequency of invasive procedures, cardiac devices and prosthetic valves together with increased use of immune system suppressors. AE lacks most of the clinical criteria used to diagnose infective endocarditis (IE), where blood culture is almost always negative, and fever may be absent. Diagnosis is usually late and in many cases is made post-mortem. Late or mistaken diagnosis of AE contribute to delayed and incorrect management of patients. In the current study we aimed to describe the clinical, laboratory and imaging characteristics of AE, to identify predictors of early diagnosis of this serious infection. METHODS: Patients with definite/possible IE, as diagnosed by the Kasr Al-Ainy IE Working Group from February 2005 through June 2016, were reviewed in this study. We compared the demographic, clinical, laboratory and imaging criteria of AE patients to non-fungal IE patients. RESULTS: This study included 374 patients with IE in which FE accounted for 43 cases. Aspergillus was the most common fungus (31 patients; 8.3%) in the patient group. Lack of fever and acute limb ischemia at presentation were significantly associated with AE (p < 0.001, p = 0.014, respectively). Health care associated endocarditis (HAE) and prosthetic valve endocarditis (PVE) were the only significant risk factors associated with AE (p < 0.001 for each). Mitral, non-valvular, and aortotomy site vegetations, as well as aortic abscess/pseudoaneurysm, were significantly associated with AE (p = 0.022, p = 0.004, p < 0.001, and p < 0.001, respectively). Through multivariate regression analysis, HAE, PVE, aortic abscess/pseudoaneurysm, and lack of fever were strongly linked to AE. The probability of an IE patient having AE with HAE, PVE, and aortic abscess/pseudoaneurysm, but no fever, was 0.92. In contrast, the probability of an IE patient having AE with fever, native valve IE, but no health-care associated IE and no abscess/pseudoaneurysm, was 0.003. Severe sepsis and mortality in the Aspergillus group were higher as compared to the non-fungal group (p = 0.098 and 0.097, respectively). Thirteen AE patients died during hospitalization. PVE, the use of single versus dual antifungal agents, severe heart failure, and severe sepsis were significant predictors of mortality (p = 0.008, 0.012, 0.003, and 0.01, respectively). CONCLUSION: To our knowledge, this is the first study to address diagnostic criteria for AE. Through multivariate regression analysis, absence of fever, HAE, PVE, and aortic abscess/pseudoaneurysm were strong predictors of AE. Use of these criteria my lead to earlier diagnoses of AE. Early treatment of AE patients with voriconazole in combination with other antifungal agents may be possible based on the previously mentioned criteria, which may facilitate better patient outcomes.

Correction: Aspergillus endocarditis: Diagnostic criteria and predictors of outcome, A retrospective cohort study.

[This corrects the article DOI: 10.1371/journal.pone.0201459.].

Segmental peri-coronary epicardial adipose tissue volume and coronary plaque characteristics.

AIMS: Epicardial adipose tissue (EAT) has been proposed to modulate underlying coronary plaque features. The study aimed to determine the relation between segmental EAT (sEAT) volume, assessed by cardiac magnetic resonance (CMR), and underlying coronary plaque characteristics, as estimated by multidetector computed tomography (CT) (MDCT). METHODS AND RESULTS: The study included 32 male patients with stable angina pectoris and 11 age-matched healthy controls. For each CAD patient, sEAT volume around 8 coronary segments (3 in left anterior descending artery, 3 in right coronary artery, and 2 in left circumflex artery) was quantified by CMR. By MDCT, plaques in each coronary segment were characterized in terms of plaque volume, type, CT attenuation, and severity of luminal stenosis. Serum levels of adipokines were measured. Total EAT volume was significantly higher in CAD patients than in control group. Serum resistin showed significant correlation with EAT volume (r = 0.69, P < 0.001). Analysis of 256 coronary segments showed larger sEAT volume with increasing luminal stenosis of the corresponding segment (mild: 8.2 cm(3); moderate: 11 cm(3); severe: 11.8 cm(3), P < 0.001). sEAT volume was larger in segments with mixed than those with calcified or non-calcified plaques (12.1 vs. 10.2 vs. 9.5 cm(3), respectively, P = 0.015). sEAT volume was larger in segments with low CT attenuation non-calcified plaques compared with non-calcified plaques with CT attenuation >30 HU (10.5 vs. 8.2 mm(3), P < 0.001). CONCLUSION: Peri-coronary epicardial adipose tissue volume is significantly associated with the extent and severity of coronary atherosclerosis and may be a determinant of plaque vulnerability.

Impact of serology and molecular methods on improving the microbiologic diagnosis of infective endocarditis in Egypt.

BACKGROUND: Conventional diagnosis of infective endocarditis (IE) is based mainly on culture-dependent methods that may fail because of antibiotic therapy or fastidious microorganisms. OBJECTIVES: We aimed to evaluate the added values of serological and molecular methods for diagnosis of infective endocarditis. PATIENTS AND METHODS: One hundred and fifty-six cases of suspected endocarditis were enrolled in the study. For each patient, three sets of blood culture were withdrawn and serum sample was collected for Brucella, Bartonella and Coxiella burnetii antibody testing. Galactomannan antigen was added if fungal endocarditis was suspected. Broad range PCR targeting bacterial and fungal pathogens were done on blood culture bottles followed by sequencing. Culture and molecular studies were done on excised valve tissue when available. RESULTS: One hundred and thirty-two cases were diagnosed as definite IE. Causative organisms were detected by blood cultures in 40 (30.3 %) of cases. Blood culture-negative endocarditis (BCNE) represented 69.7 %. Of these cases, PCR followed by sequencing on blood and valvular tissue could diagnose five cases of Aspergillus flavus. Eleven patients with BCNE (8.3 %) were diagnosed as zoonotic endocarditis by serology and PCR including five cases of Brucella spp, four cases of Bartonella spp and two cases of Coxiella burnetii. PCR detected three cases of Brucella spp and two cases of Bartonella spp, while cases of Coxiella burnetii were PCR negative. The results of all diagnostic tools decreased the percentage of non-identified cases of BCNE from 69.7 to 49.2 %. CONCLUSION: Our data underline the role of serologic and molecular tools for the diagnosis of blood culture-negative endocarditis.

Association between surgical indications, operative risk, and clinical outcome in infective endocarditis: a prospective study from the International Collaboration on Endocarditis.

BACKGROUND: Use of surgery for the treatment of infective endocarditis (IE) as related to surgical indications and operative risk for mortality has not been well defined. METHODS AND RESULTS: The International Collaboration on Endocarditis-PLUS (ICE-PLUS) is a prospective cohort of consecutively enrolled patients with definite IE from 29 centers in 16 countries. We included patients from ICE-PLUS with definite left-sided, non-cardiac device-related IE who were enrolled between September 1, 2008, and December 31, 2012. A total of 1296 patients with left-sided IE were included. Surgical treatment was performed in 57% of the overall cohort and in 76% of patients with a surgical indication. Reasons for nonsurgical treatment included poor prognosis (33.7%), hemodynamic instability (19.8%), death before surgery (23.3%), stroke (22.7%), and sepsis (21%). Among patients with a surgical indication, surgical treatment was independently associated with the presence of severe aortic regurgitation, abscess, embolization before surgical treatment, and transfer from an outside hospital. Variables associated with nonsurgical treatment were a history of moderate/severe liver disease, stroke before surgical decision, and Staphyloccus aureus etiology. The integration of surgical indication, Society of Thoracic Surgeons IE score, and use of surgery was associated with 6-month survival in IE. CONCLUSIONS: Surgical decision making in IE is largely consistent with established guidelines, although nearly one quarter of patients with surgical indications do not undergo surgery. Operative risk assessment by Society of Thoracic Surgeons IE score provides prognostic information for survival beyond the operative period. S aureus IE was significantly associated with nonsurgical management.

Evaluation of broad-range 16S rRNA PCR for the diagnosis of bloodstream infections: two years of experience.

INTRODUCTION: Diagnosis of bloodstream infections using bacteriological cultures suffers from low sensitivity and reporting delay. Advanced molecular techniques introduced in many laboratories provide rapid results and may show improvements in patient outcomes. This study aimed to evaluate the usefulness of a molecular technique, broad-range 16S rRNA PCR followed by sequencing for the diagnosis of bloodstream infections, compared to blood culture in different patient groups. METHODOLOGY: Conventional PCR was performed, using broad-range 16S rRNA primers, on blood cultures collected from different patients with suspected bloodstream infections; results were compared with those of blood culture. RESULTS: Though blood culture is regarded as the gold standard, PCR evaluation showed sensitivity of 86.25%, specificity of 91.25%, positive predictive value of 76.67%, negative predictive value of 95.22%, and accuracy of 88.8%. CONCLUSIONS: Molecular assays seem not to be sufficient to replace microbial cultures in the diagnosis of bloodstream infections, but they can offer a rapid, good negative test to rule out infection due to their high negative predictive value.

In-hospital and 1-year mortality in patients undergoing early surgery for prosthetic valve endocarditis.

IMPORTANCE: There are limited prospective, controlled data evaluating survival in patients receiving early surgery vs medical therapy for prosthetic valve endocarditis (PVE). OBJECTIVE: To determine the in-hospital and 1-year mortality in patients with PVE who undergo valve replacement during index hospitalization compared with patients who receive medical therapy alone, after controlling for survival and treatment selection bias. DESIGN, SETTING, AND PARTICIPANTS: Participants were enrolled between June 2000 and December 2006 in the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS), a prospective, multinational, observational cohort of patients with infective endocarditis. Patients hospitalized with definite right- or left-sided PVE were included in the analysis. We evaluated the effect of treatment assignment on mortality, after adjusting for biases using a Cox proportional hazards model that included inverse probability of treatment weighting and surgery as a time-dependent covariate. The cohort was stratified by probability (propensity) for surgery, and outcomes were compared between the treatment groups within each stratum. INTERVENTIONS: Valve replacement during index hospitalization (early surgery) vs medical therapy. MAIN OUTCOMES AND MEASURES: In-hospital and 1-year mortality. RESULTS: Of the 1025 patients with PVE, 490 patients (47.8%) underwent early surgery and 535 individuals (52.2%) received medical therapy alone. Compared with medical therapy, early surgery was associated with lower in-hospital mortality in the unadjusted analysis and after controlling for treatment selection bias (in-hospital mortality: hazard ratio [HR], 0.44 [95% CI, 0.38-0.52] and lower 1-year mortality: HR, 0.57 [95% CI, 0.49-0.67]). The lower mortality associated with surgery did not persist after adjustment for survivor bias (in-hospital mortality: HR, 0.90 [95% CI, 0.76-1.07] and 1-year mortality: HR, 1.04 [95% CI, 0.89-1.23]). Subgroup analysis indicated a lower in-hospital mortality with early surgery in the highest surgical propensity quintile (21.2% vs 37.5%; P = .03). At 1-year follow-up, the reduced mortality with surgery was observed in the fourth (24.8% vs 42.9%; P = .007) and fifth (27.9% vs 50.0%; P = .007) quintiles of surgical propensity. CONCLUSIONS AND RELEVANCE: Prosthetic valve endocarditis remains associated with a high 1-year mortality rate. After adjustment for differences in clinical characteristics and survival bias, early valve replacement was not associated with lower mortality compared with medical therapy in the overall cohort. Further studies are needed to define the effect and timing of surgery in patients with PVE who have indications for surgery.