Re-Appraisal of Echocardiographic Assessment in Patients with Pulmonary Embolism: Prospective Blinded Long-Term Follow-Up.

BACKGROUND: Acute pulmonary embolism (PE) is considered to be one of the most common cardiovascular diseases with considerable mortality. Conflicting data imply possible role for echocardiography in assessing this disease. OBJECTIVES: To determine which of the echo parameters best predicts short-term and long-term mortality in patients with PE. METHODS: We prospectively enrolled 235 patients who underwent computed tomography of pulmonary arteries (CTPA) and transthoracic Echocardiography (TTE) within < 24 hours. TTE included a prospectively designed detailed evaluation of the right heart including right ventricular (RV) myocardial performance index (RIMP), RV end diastolic and end systolic area, RV fractional area change, acceleration time (AT) of pulmonary flow and visual estimation. Interpretation and performance of TTE were blinded to the CTPA results. RESULTS: Although multiple TTE parameters were associated with PE, all had low discriminative capacity (AUC < 0.7). Parameters associated with 30-day mortality in univariate analysis were acceleration time (AT) < 81 msec (P = 0.04), stroke volume < 44 cc (P = 0.005), and RIMP > 0.42 (P = 0.05). The only RV independent echo parameter associated with poor long-term prognosis (adjusted for significant clinical, and routine echo associates of mortality) was RIMP (hazard ratio 3.0, P = 0.04). The only independent RV echo parameters associated with mortality in PE patients were RIMP (P = 0.05) and AT (P = 0.05). Addition of RIMP to nested models eliminated the significance of all other parameters assessing RV function. CONCLUSIONS: Doppler-based parameters like pulmonary flow AT, RIMP, and stroke volume, have additive value in addition to visual RV estimation to assess prognosis in patients with PE.

Elevated Neutrophil Gelatinase-Associated Lipocalin for the Assessment of Structural versus Functional Renal Damage among ST-Segment Elevation Myocardial Infarction Patients.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of renal tubular damage. We investigated the incidence and possible implications of elevated NGAL levels (suggesting renal damage) compared to both functional and damage markers (manifested as serum creatinine [sCr] elevation) and no NGAL/sCr change, among -ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). METHODS: We included 131 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn 24 h following PCI. We used the terms NGAL(-) or NGAL(+) with levels ≥100 ng/mL suggesting renal tubular damage and the terms. sCr(-) or sCr(+) to consensus diagnostic increases in sCr defining acute kidney injury. Patients were also assessed for in hospital-adverse outcomes. RESULTS: Of the study patients, 56 (42%) were NGAL(-)/sCr(-), 58 (44%) NGAL(+)/sCr(-), and 18 (14%) were both NGAL(+)/sCr(+). According to the 3 study groups, there was a stepwise increase in the proportion of left ventricular ejection fraction ≤45% (43 vs. 60. vs. 72%; p = 0.04), in-hospital adverse outcomes (9 vs. 14 vs. 56%; p < 0.001) and their combination. Specifically, more NGAL(+)/sCr(-) patients developed the composite endpoint when compared to NGAL(-)/sCr(-) patients (64 vs. 46%; OR 2.1, [95% CI 1.1-4.5], p = 0.05). A similar and consistent increase was observed in peak sCr, length of hospital stay, and C-reactive protein levels. CONCLUSIONS: Elevated NGAL levels suggesting renal tubular damage, increased inflammation, or both are common among STEMI patients and are associated with adverse outcomes even in the absence of diagnostic increase in sCr.

Quantitative assessment of effective regurgitant orifice: impact on risk stratification, and cut-off for severe and torrential tricuspid regurgitation grade.

AIMS: Asses the added value of quantitative evaluation of tricuspid regurgitation (TR), the proper cut-off value for severe TR and 'torrential TR' based on outcome data. The added value of quantitative evaluation of TR, and the cut-off values associated with increased mortality are unknown. METHODS AND RESULTS: In patients with all-cause TR assessed both qualitatively and quantitatively by proximal iso-velocity surface area method, long-term and 1-year outcome analysis was conducted. Thresholds for excess mortality were assessed using spline curves, receiver-operating characteristic curves, and minimum P-value analysis. The study involved 676 patients with all-cause TR (age 73.9 ± 14 years, male 45%, ejection fraction 52.9 ± 14%). Effective regurgitant orifice (ERO) was strongly associated with decreased survival in unadjusted [hazard ratio (HR) 2.38 (1.79-3.01), P < 0.0001 per 0.1 cm2 increment] and adjusted [2.6 (1.25-5.0), P = 0.01] analyses. Quantitative grading was superior to qualitative grading in prediction of outcome (P < 0.01). The optimal cut-off value for the best separation in survival between groups of patients with severe vs. lesser degree of TR was 0.35 cm2 [P < 0.0001, HR =2.0 (1.5-2.7)]. ERO negatively impacted survival, even when including only the subgroup of patients with severe TR [HR 1.5 (1.01-2.3); P = 0.04]. The optimal threshold corresponding for the best separation for survival between groups of patients with severe vs. 'torrential' TR was 0.7 cm2 [P = 0.005, HR =2.6 (1.2-5.1)]. CONCLUSION: TR can be severe and even 'torrential' and is associated with excess mortality. Quantitative assessment of TR by ERO measurement is a powerful independent predictor of outcome, superior to standard qualitative assessment. The optimal cut-off above which mortality is increased is 0.35 cm2, similar albeit slightly lower than suggested in recent guidelines. Torrential TR >0.7 cm2 is associated with poorer survival compared to patients with severe TR (ERO > 0.4 cm2 and <0.7 cm2).

Assessment of Respiratory Distress by the Roth Score.

INTRODUCTION: Health care demand is increasing due to greater longevity of patients with chronic comorbidities. This increasing demand is occurring in a setting of resource scarcity. To address these changes, high-value care initiatives, such as telemedicine, are valuable resource-preservation strategies. This study introduces the Roth score as a telemedicine tool that uses patient counting times to accurately risk-stratify dyspnea severity in terms of hypoxia. HYPOTHESIS: The Roth score has correlation with dyspnea severity. METHODS: This is a prospective, controlled-cohort study. Roth score index is measured by having the patient count from 1 to 30 in their native language, in a single breath, as rapidly as possible. The primary result of the Roth score is the duration of time and the highest number reached. RESULTS: There was a strongly positive correlation between pulse oximetry and both maximal count achieved in 1 breath (r = 0.67; P < 0.001) and counting time (r = 0.59; P < 0.001). For oxygen saturation <95%, the maximal count number area under the curve is 0.828 and counting time area under the curve is 0.764. Counting time >8 seconds had a sensitivity of 78% and specificity of 73% for pulse oximetry <95%. CONCLUSIONS: The Roth score has strong correlation with dyspnea severity as determined by hypoxia. This tool is reproducible, low resource-utilization, and amenable to telemedicine. It is not intended to replace full clinical workup and diagnosis of respiratory distress, but it is useful in risk-stratifying severity of dyspnea that warrants further clinical evaluation.

Serial Echocardiographic Assessment of Left Ventricular Filling Pressure and Remodeling among ST-Segment Elevation Myocardial Infarction Patients Treated by Primary Percutaneous Intervention.

BACKGROUND: Acute myocardial infarction and remodeling of the left ventricle is associated with significant changes in systolic and diastolic echocardiographic derived indices. The investigators have tried to determine whether persistence of increased ratio of transmitral flow velocity (E) to early mitral annulus velocity (e'), signifying increased cardiac filling pressure, is associated with left ventricular (LV) remodeling and increased chamber size among patients presenting with ST-segment elevation myocardial infarction, who underwent successful reperfusion with primary percutaneous coronary intervention. METHODS: Fifty-two patients (76% men; mean age, 61 ± 10 years) with first ST-segment elevation myocardial infarctions who underwent primary percutaneous coronary intervention were retrospectively studied. Echocardiography was performed at baseline (days 1-3) and after 178 ± 62 days. Patients were stratified according to E/septal e' ratio >15 and ≤15 in both examinations. All patients received optimal medical therapy according to guidelines and local practice. RESULTS: Patients with maintained or worsened E/septal e' ratios to >15 demonstrated on the second examination worse LV ejection fractions (mean, 45 ± 12% vs 52 ± 8%; P = .03) and higher indexed LV end-diastolic volumes (mean, 81.3 ± 22.9 vs 69.2 ± 13.4 mL/m(2); P = .01) and end-systolic volumes (mean, 33.0 ± 12.2 vs 23.7 ± 13.4 mL/m(2); P = .02) compared with the first examination, representing LV remodeling. Patients with E/septal e' ratios > 15 on the second examination demonstrated a positive correlation between the change in E/septal e' ratio and the change in indexed LV end-diastolic volume (linear R(2) = 0.344, P = .03). CONCLUSIONS: Among patients with ST-segment elevation myocardial infarctions undergoing primary percutaneous coronary intervention, early and persistent elevation of the E/septal e' ratio may be associated with LV remodeling.

Added value of pulmonary venous flow Doppler assessment in patients with preserved ejection fraction and its contribution to the diastolic grading paradigm.

AIMS: To evaluate the prognostic role of pulmonary venous flow parameters and their role in patients with preserved ejection fraction (EF). METHODS AND RESULTS: Pulmonary venous flow parameters were measured in 365 patients in sinus rhythm, without significant mitral disease, and EF >50% (age 64.9 ± 19; 52% female) by a single sonographer. Survival, time to re-admission for heart failure, and to a combined cardiac end point (cardiac death, heart failure, and atrial fibrillation) were retrospectively analysed and correlated to echo parameters. Systolic (S) and diastolic (D) pulmonary vein flow were obtainable in 73% of patients and Ar in 65%. The lower peak S/D ratio and higher ΔAr-A time were associated with higher rate of heart failure readmission (P = 0.03 for both). The S/D integral ratio was the best pulmonary vein flow predictor of heart failure readmissions (P = 0.0009), better than the peak S/D ratio, or ΔA-Ar time (P < 0.01 for both), and independently predicted worse outcome even when adjusted for diastolic grading (using recent guidelines), left ventricle mass index, E/e', and left atrial volume index (P < 0.05 for all). The addition S/D ratio to diastolic grading recognized patients with pseudo-normal filling pattern and S/D ratio >1 with similar clinical outcomes to grade I (P > 0.5), but worse clinical outcomes than in the pseudo-normal patients with lower S/D ratio (P < 0.01). CONCLUSIONS: PVFP are obtainable in most patients, add prognostic information on top of routine diastolic parameters, and define an early stage of diastolic dysfunction resembling the pseudo-normal pattern in which S/D ratio is >1, and outcome is excellent.

Gender-related mortality and in-hospital complications following ST-segment elevation myocardial infarction: data from a primary percutaneous coronary intervention cohort.

BACKGROUND: The increased mortality related to female gender in ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI) has been reported from various patient cohorts and treatment strategies with controversial results. In the present work, we evaluated the impact of female gender on mortality and in-hospital complications among a specific subset of consecutive STEMI patients managed solely by PPCI. HYPOTHESIS: Female gender is not an independent predicor for mortality among STEMI patients. METHODS: We performed a retrospective, single-center observational study that included 1346 consecutive STEMI patients undergoing PPCI, of which 1075 (80%) were male. Patient's records were evaluated for 30-day mortality, in-hospital complications, and long-term mortality over a mean period of 2.7 ± 1.6 years. RESULTS: Compared with males, females were older (69 ± 13 vs 60 ± 13 years, P < 0.001), had a significantly higher rate of baseline risk factors, and had prolonged symptom duration (460 ± 815 minutes vs 367 ± 596 minutes, P = 0.03). Females suffered from more in-hospital complications and had higher 30-day mortality (5% vs 2%, P = 0.008) as well as higher overall mortality (12.5% vs 6%, P < 0.001). In spite of the significant mortality risk in unadjusted models, a multivariate adjusted Cox regression model did not demonstrate that female gender was an independent predictor for mortality among STEMI patients. CONCLUSIONS: Among patients with STEMI treated by PPCI, female gender is associated with a higher 30-day mortality and complications rates compared to males. Following multivariate analysis, female gender was not a significant predictor of long-term death following STEMI.

Comparative analysis of methods for assessment of circulating endothelial progenitor cells.

The number and properties of endothelial progenitor cells (EPC) in disease states is of considerable interest due to the importance attributed to this distinct cell population. However, there has been no study comparing each of the methods employed in the same sampled individuals. Herein, we performed an analysis of several methods used for circulating EPC assessment and correlated them with humoral factors known to influence their numbers. Thirty-eight individuals (mean age of 34 +/- 9 years) were tested. Peripheral blood mononuclear cells were obtained and stained for FACS analysis with antibodies to CD34, CD45, CD133, and KDR and the remaining cells grown under endothelial cell conditions for assessment of colony-forming unit (CFU) numbers and adhesive properties. Levels of circulating vascular endothelial growth factor (VEGF), erythropoietin (EPO), and C-reactive protein (CRP) were determined and correlated with each of the EPC markers. CFU numbers did not correlate with CD34/KDR or CD34/CD133/KDR and negatively correlated with CD34/ CD133 numbers. CD34/KDR numbers correlated with CD34/CD133/KDR, but not with CD34/ CD133. Only CD34/KDR and CD34/CD133/KDR correlated with VEGF serum levels. The number of EPC adhering to fibronectin and endothelial cells correlated with CFU numbers and not with either of the EPC membrane markers. Current methods for quantitatively assessing numbers of circulating EPC are not correlated. VEGF serum levels are associated only with CD34/KDR and CD34/ CD133/KDR, whereas CFU numbers correlate with EPC functional properties. These findings may suggest that CD34/KDR is more appropriate for the definition of circulating EPC, whereas CFU numbers are more likely to reflect their ability to proliferate.

Usefulness of anti-oxidized LDL antibody determination for assessment of clinical control in patients with heart failure.

BACKGROUND: It has been suggested that oxidative stress may play a role in the pathogenesis of heart failure, this may have potential implications for therapeutic strategies. However, measures of oxidative stress are subject to confounding inaccuracies. IgG antibodies to oxidized LDL reflect exposure to the lipoprotein over an extended period and may thus mirror oxidative stress over a prolonged time frame. Therefore, we tested the hypothesis that anti-oxLDL antibodies correlate with the control of heart failure (HF), as manifested by hospital admissions for cardiac dysfunction. METHODS: One hundred and two consecutive patients attending the HF clinic with either systolic or diastolic HF were enrolled and the quality of clinical control was evaluated by assessing hospital admissions over the year prior to index determination of the oxidative stress marker. Antibodies to oxLDL were determined by ELISA and pro-BNP levels were also measured. RESULTS: Most patients (mean age 71.5 years) had systolic HF; mean NYHA functional class was 2.7 and mean left ventricular ejection fraction was 39.7%. Anti-oxLDL antibodies, but not pro-BNP, correlated significantly with mean NYHA score (averaged from all clinic visits in the year prior to blood testing), and with hospital admissions over the year prior to blood testing. Mean IgG anti-oxLDL antibody levels in patients with hospital admissions were 3.4 times higher than those in subjects not hospitalized over the previous year. CONCLUSION: IgG anti-oxLDL antibody levels correlate with the severity of HF.