Prognostic value of hemoglobin decline over the GRACE score in patients hospitalized for an acute coronary syndrome.

In this work, we analyzed the prognostic significance of changes in hemoglobin during intensive care unit (ICU) stay in patients with acute coronary syndromes (ACS). We prospectively enrolled 591 patients (62 ± 14 years old, 73% male, 48% ST elevated myocardial infarction) free of blood cell transfusion or bleeding events. Changes in hemoglobin between admission and ICU discharge were obtained. The primary endpoint was death or hospitalization for MI within 6 months. Hemoglobin decreased from 13.65 ± 1.77 to 13.17 ± 1.74 g/dl, p < 0.0001 in the whole population. The end point was reached in 43 patients at a mean follow-up of 180 (range 2-180 days). A decrease in hemoglobin ≥0.9 g/dl (32% of the population) was associated with adverse clinical outcomes (HR 2.37, 95% CI (1.30-4.35), p = 0.005, respectively). In multivariate analysis, age >77 year-old (p = 0.0016), Killip class ≥2 (p = 0.009), anemia (p = 0.0064), decreased estimated glomerular filtration rate (p = 0.003), and hemoglobin decline ≥0.9 g/dl (p < 0.0001) were independently associated with outcome. Hemoglobin decline and anemia both provided additional prognostic information on top of the GRACE score, as demonstrated by a systematic improvement in model global fit, discrimination, and calibration. Hemoglobin decline is frequent during ICU stay in non-bleeding ACS patients. A decline in hemoglobin ≥0.9 g/dl identifies high-risk patients. Identification of these patients refines the prognostic value of the GRACE score.

Addition of B-type natriuretic peptide to the GRACE score to predict outcome in acute coronary syndrome: a retrospective (development) and prospective (validation) cohort-based study.

AIMS: The present study was designed to build and validate a composite score based on the Global Registry of Acute Coronary Events (GRACE) score and B-type natriuretic peptide (BNP) concentrations to predict outcome in patients with acute coronary syndromes (ACS). METHODS: The GRACE risk score and BNP concentrations were obtained in a retrospective and a prospective cohort. A composite score including the GRACE score and BNP concentrations was first developed in a retrospective cohort of 248 patients with ACS and then validated in a prospective cohort of 575 patients. The primary outcome was 6-month death or myocardial infarction. RESULTS: End points were reached in 34 patients in the retrospective cohort and in 68 patients in the prospective cohort. Both higher BNP concentration and GRACE score were independently associated with outcome in the retrospective cohort (p=0.003 and p<0.0001). The composite score could be obtained as follows: GRACE+BNP/60. The use of the composite score increased the accuracy of the GRACE score, with an increase in the C statistic from 0.810 (0.727 to 0.892) to 0.822 (0.745 to 0.902) in the retrospective cohort and from 0.724 (0.657 to 0.791) to 0.750 (0.686 to 0.813) in the prospective cohort. Finally, 7% of patients in the prospective study population were reclassified from low to high risk or from high to low risk using this composite score. CONCLUSIONS: Plasma BNP levels refine the accuracy of the GRACE score. A comprehensive risk score, which includes BNP concentration and the GRACE risk score, might improve ACS risk stratification in clinical practice.

Functional mitral regurgitation: a link to pulmonary hypertension in heart failure with preserved ejection fraction.

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) may present with Pulmonary hypertension (PH) and functional mitral regurgitation (MR). Whether PH is linked to the presence of functional MR has not been investigated in HFpEF patients. METHODS AND RESULTS: Systolic pulmonary artery pressure (sPAP) and functional MR were assessed by 2-dimensional Doppler echocardiography in 70 ambulatory HFpEF patients and 70 hypertensive control subjects free of organic mitral valve lesions, significant valve disease, and comorbid conditions associated with PH. Whereas none of control subjects had more than trivial MR, 21 patients with HFpEF had functional MR (mean mitral effective regurgitant orifice, regurgitant volume, and regurgitant fraction 7 ± 3 mm,(2) 15 ± 8 mL, and 28 ± 14%, respectively). Pulmonary hypertension (sPAP >35 mm Hg) was significantly more prevalent in HFpEF patients with functional MR than in HFpEF patients without functional MR (62 vs 22%; P = .002). Functional MR remained an independent predictor of PH in HFpEF patients (P = .004) after adjustment on mitral E wave to e' mitral annulus velocity ratio (E/e'; P = .022) and left atrial volume index (P = .025). Systolic PAP and E/e' were greater in HFpEF patients than in control subjects (35 ± 9 vs 29 ± 8 mm Hg [P < .0001] and 13 ± 6 vs 11 ± 5 [P = .018], respectively). Systolic PAP remained greater in HFpEF patients than in control subjects after adjusting for E/e' (P = .002). CONCLUSIONS: Pulmonary hypertension appears to be linked to the presence of functional MR in HFpEF patients.

Renal resistance index and its prognostic significance in patients with heart failure with preserved ejection fraction.

BACKGROUND: Functional renal impairment is a common feature of heart failure with preserved ejection fraction (HFpEF). The link between functional renal impairment and HFpEF remains incompletely understood. With hypertension and diabetes as frequent co-morbidities, patients with HFpEF are at risk of developing intra-renal vascular hemodynamic alterations that may lead to functional renal impairment and impact on prognosis. METHODS: Renal resistive index (RRI) was non-invasively determined by Doppler ultrasonic examination in 90 HFpEF patients and 90 age- and sex-matched hypertensive patients without evidence of heart failure (HF) who served as controls. Clinical, laboratory and cardiac echocardiography data were obtained in HFpEF patients and controls. To investigate its possible clinical relevance, RRI was evaluated as a prognostic index of all-cause mortality and hospitalization for HF. RESULTS: Mean RRI was substantially greater in HFpEF patients than in controls (P < 0.0001), while mean blood pressure, glomerular filtration rate, hemoglobin and serum protein levels were significantly lower in HFpEF patients than in controls. On multivariable analysis, mean RRI was independently associated with HFpEF. In addition, increased mean RRI was an independent predictor of poor outcome [hazard ratio = 1.06 95% confidence interval (1.01-1.10), P = 0.007] and remained significantly associated with the outcome after adjustment for univariate predictors that included low mean blood pressure, low hemoglobin concentration and low glomerular filtration rate. Conclusion. Patients with HFpEF exhibit intra-renal vascular hemodynamic alterations. The severity of intra-renal vascular hemodynamic alterations correlates with a poor outcome.

Prognostic importance of comorbidities in heart failure with preserved left ventricular ejection fraction.

The relative impact of comorbidities and parameters of left ventricular diastolic function on clinical outcome has not been thoroughly investigated in patients who are hospitalized for heart failure decompensation and found to have preserved ejection fraction. We identified 98 HFpEF patients among 1452 patients admitted with acute heart failure. Clinical characteristics, hemoglobin levels, estimated glomerular filtration rate (eGFR), B-type natriuretic peptide (BNP) and Doppler-echocardiographic parameters were analyzed. The primary end point of the study combined death and rehospitalization for decompensated heart failure after the index hospitalization. Mean age was 76 ± 9 years. LV ejection fraction, E/E (a) ratio, and estimated systolic pulmonary artery pressure were 61 (55-67)%, 12.9 (9.4-15.1), 40 (32-46) mmHg, respectively. BNP values, hemoglobin and eGFR were 287 (164-562) pg/mL, 11.3 (10.4-12.4) g/dL and 45 (37-74) mL/min/m(2), respectively. During a mean follow-up of 17 ± 11 months, 56% reached the primary endpoint of the study: 31 died and 24 were re-hospitalised for heart failure. Diabetes [HR = 1.76 (1.03-3.00), P = 0.039], lower systolic blood pressure [HR = 0.99 (0.97-0.99), P = 0.016], hemoglobin [HR = 0.62 (0.49-0.76), P < 0.0001], and eGFR [HR = 0.98 (0.97-0.99), P = 0.004] were associated with a poor outcome. Neither BNP nor echocardiographic parameters were correlated with outcome. Comorbidities primarily correlate with outcome in patients with HFpEF.

Clinical and echocardiographic correlates of plasma B-type natriuretic peptide levels in patients with aortic valve stenosis and normal left ventricular ejection fraction.

BACKGROUND: Several studies suggest that BNP testing may help define the timing of aortic valve surgery in patients with aortic valve stenosis (AVS) prior onset of overt LV systolic dysfunction. The aim of this study was to identify clinical and echocardiographic correlates of plasma BNP levels in a large cohort of patients with AVS and preserved LV ejection fraction. METHOD AND RESULTS: One hundred thirty-five consecutive patients were prospectively included in the present study (Mean age 73 ± 13 years old, 66 (49%) male). Eighty-nine patients (66%) had severe AVS (aortic valve area <0.6 cm(2) /m(2) BSA). Plasma BNP levels, clinical and comprehensive Doppler echocardiography evaluation was performed in all patients. Independent clinical correlates of plasma BNP levels (R(2) = 0.19) were older age (P < 0.0001) and presence of AVS symptoms (P = 0.004). Independent echocardiographic correlates of plasma BNP levels (R(2) = 0.38) were E/Ea ratio (P = 0.01), LV mass index (P = 0.018), left atrial surface (P < 0.0001) and systolic pulmonary artery pressure (sPAP; P = 0.004). Overall, independent correlates of plasma BNP levels (R(2) = 0.47) were older age (P = 0.001), known coronary artery disease (P = 0.047), increased LV mass index (P = 0.001), left atrial enlargement (P = 0.002), and increased sPAP (P = 0.003). CONCLUSIONS: In patients with AVS and normal LV ejection fraction, plasma BNP predominantly reflects the clinical and echocardiographic consequences of afterload burden imposed on the left ventricle rather than the severity of valve stenosis, per se.

Atrial septal defect associated with dilated cardiomyopathy in the setting of acute cardiac failure: importance of comprehensive bedside echocardiography in ICU.

The current report describes two patients with severe heart failure due to dilated cardiomyopathy in whom discrepancy between thermodilution cardiac output and clinical status was due to left-to-right shunt. Misdiagnosis of shunting was harmful in the early management of the first case. Secundum type atrial septal defect was confirmed by pathology in both cases. Blood samples for oxymetry should be routinely drawn during right heart catheterization for screening for intracardiac shunts. Using bedside echocardiography pulmonary-to-systemic flow ratio should also be systematically evaluated in the setting of right ventricular dilation.

Exercise-induced functional mitral regurgitation in heart failure and preserved ejection fraction: a new entity.

We report here the worsening of functional mitral regurgitation (MR) during dynamic exercise Doppler echocardiography in four female patients with heart failure and preserved ejection fraction. MR worsened concomitantly to an increase in systolic mitral tenting area and in E/E(a) ratio, whereas local left ventricular (LV) remodelling was not substantially aggravated by exercise. We accordingly suggest that exercise-induced increase in LV filling or left atrial pressure that in turn leads to increase in mitral tenting area worsens functional MR during exercise.

Clinical significance of unsuspected rise in cardiac troponin in the setting of falls in older people.

OBJECTIVES: To assess the clinical significance of unsuspected rise in cardiac troponin I (cTnI) levels in elderly patients who have fallen. DESIGN: Monocentre prospective observational pilot study. PARTICIPANTS: Consecutive elderly patients (age >65 years) referred to the emergency department after being immobilised on the ground after a fall. MEASUREMENTS: Clinical, laboratory and Doppler echocardiography data were collected on admission to assess the cardiac correlates of increased cTnI. The survival endpoint was a composite of death or cardiovascular event. RESULTS: 60 patients were included in this study. Mean age was 81+/-8 years. Cardiac TnI was > or =0.05 ng/ml in at least one blood sample in 40 patients (67%). New diagnosis of cardiac disease was performed in 14 patients, 13 of them had cTnI > or =0.05 ng/ml. Transient apical ballooning was diagnosed in six patients. During a median follow-up of 92 (49-131) days death occurred in six patients, myocardial infarction in three, stroke in one and acute heart failure in five. Cardiac TnI > or =0.05 ng/ml was a predictor of these events (p=0.034). CONCLUSION: An unsuspected rise in cTnI correlates with new diagnosis of cardiac disease and is a potential marker of stress induced cardiomyopathy in elderly patients who fall. Cardiac TnI might be a strong predictor of outcome in these patients.

Comparison of thrombolysis followed by broad use of percutaneous coronary intervention with primary percutaneous coronary intervention for ST-segment-elevation acute myocardial infarction: data from the french registry on acute ST-elevation myocardial infarction (FAST-MI).

BACKGROUND: Intravenous thrombolysis remains a widely used treatment for ST-elevation myocardial infarction; however, it carries a higher risk of reinfarction than primary PCI (PPCI). There are few data comparing PPCI with thrombolysis followed by routine angiography and PCI. The purpose of the present study was to assess contemporary outcomes in ST-elevation myocardial infarction patients, with specific emphasis on comparing a pharmacoinvasive strategy (thrombolysis followed by routine angiography) with PPCI. METHODS AND RESULTS: This nationwide registry in France included 223 centers and 1714 patients over a 1-month period at the end of 2005, with 1-year follow-up. Sixty percent of the patients underwent reperfusion therapy, 33% with PPCI and 29% with intravenous thrombolysis (18% prehospital). At baseline, the Global Registry of Acute Coronary Events score was similar in thrombolysis and PPCI patients. Time to initiation of reperfusion therapy was significantly shorter in thrombolysis than in PPCI (median 130 versus 300 minutes). After thrombolysis, 96% of patients had coronary angiography, and 84% had subsequent PCI (58% within 24 hours). In-hospital mortality was 4.3% for thrombolysis and 5.0% for PPCI. In patients with thrombolysis, 30-day mortality was 9.2% when PCI was not used and 3.9% when PCI was subsequently performed (4.0% if PCI was performed in the same hospital and 3.3% if performed after transfer to another facility). One-year survival was 94% for thrombolysis and 92% for PPCI (P=0.31). After propensity score matching, 1-year survival was 94% and 93%, respectively. CONCLUSIONS: When used early after the onset of symptoms, a pharmacoinvasive strategy that combines thrombolysis with a liberal use of PCI yields early and 1-year survival rates that are comparable to those of PPCI.

Pivotal role of bedside Doppler echocardiography in the assessment of patients with acute heart failure and mitral regurgitation.

Patients presenting with mitral regurgitation and acute heart failure remain a challenge for the clinicians. Bedside echocardiography ascertains the functional or primary nature of mitral regurgitation, thereby allowing to focus therapy on the left ventricle and mitral valve apparatus in patients with functional mitral regurgitation and to hasten mitral valve repair or replacement when acute heart failure results from primary mitral regurgitation. This short article reviews the evaluation by bedside echocardiography to guide management of these patients.

Exercise does not enhance the prognostic value of Doppler echocardiography in patients with left ventricular systolic dysfunction and functional mitral regurgitation at rest.

BACKGROUND: Functional mitral regurgitation (MR) is a powerful predictor of poor prognosis in patients with chronic heart failure (CHF) due to left ventricular systolic dysfunction (LVSD). However, severity of MR varies with dynamic exercise. Accordingly, we sought to assess the prognostic value of exercise-induced changes in functional MR in patients with LVSD and functional MR at rest. METHODS: One hundred four patients with chronic heart failure due to LVSD (ejection fraction [EF] < 45%) and functional MR at rest underwent conventional continuous 2-dimensional Doppler echocardiography at rest and during maximal symptom-limited exercise. The primary end point of the study was all-cause mortality. The median follow-up period was 20 months. RESULTS: Fifty-six patients (54%) had ischemic cardiomyopathy. When feasible, all 56 patients with ischemic cardiomyopathy had undergone revascularization procedures before enrollment into the study. In the whole patient cohort, resting LV end-diastolic volume was 205 +/- 76 mL and EF was 26% +/- 9%. Univariate predictors of death were functional class (New York Heart Association), LV EF, LV end-diastolic volume, resting mitral effective regurgitant orifice, mitral E deceleration time, tricuspid annular plane systolic excursion < or = 14 mm, systolic blood pressure, LV EF, and trans-tricuspid pressure gradient response to exercise. Exercise-induced change in mitral effective regurgitant orifice did not predict survival (HR 0.99, 95% CI 0.94-1.04, P = .63). By Cox multivariate analysis, resting LV end-diastolic volume and tricuspid annular plane systolic excursion < or = 14 mm were the independent predictors of death. CONCLUSIONS: Exercise Doppler echocardiography does not refine the predictive value of resting Doppler echocardiography in patients with LVSD and functional MR at rest.

The synthetic pentasaccharide fondaparinux prevents coronary microvascular injury and myocardial dysfunction in the ischemic heart.

Fondaparinux is a synthetic pentasaccharide with powerful anticoagulant properties, which may also reduce ischemia-reperfusion (I/R) injury in vivo. However, the relative contributions of the anticoagulant and anti-inflammatory activities of fondaparinux to the observed protection are unknown. To address this issue, a crystalloid-perfused heart model was used to assess potential effects of fondaparinux on IR-induced heart injury in the absence of blood. Fondaparinux protects the ischemic myocardium independently of its haemostasis effects. Fondaparinux improved post ischemic myocardial contractile performance and tissue damage. These beneficial effects of fondaparinux may be related to the observed reduction in IR-induced oxidative stress and endothelial activation. In addition, fondaparinux altered NADPH oxidase activity and phosphorylated extracellular signal-regulated kinase (ERK) 1/2, suggesting activation of survival signaling pathways. The present study provides novel information by demonstrating that fondaparinux can attenuate inflammatory responses and oxidative stress in connection with IR heart injury. These findings could represent a potential therapeutic strategy for the prevention of myocardial dysfunction.

Left ventricular abnormal response during dynamic exercise in patients with heart failure and preserved left ventricular ejection fraction at rest.

BACKGROUND: The mechanisms that contribute to limit functional capacity are incompletely understood in patients with preserved resting ejection fraction (HFpREF). We assessed left ventricular (LV) systolic response to dynamic exercise in patients with HFpREF and in patients with similar comorbidities to HFpREF patients but without history or evidence of heart failure. METHODS AND RESULTS: Twenty-five HFpREF patients in steady-state clinical condition without significant coronary artery disease and 25 hypertensive controls underwent exercise echocardiography. At rest, systolic pulmonary artery pressure, left atrial area, E/A and E/e' ratios were greater in patients with HFpREF than in control patients, whereas peak systolic mitral annular velocity was lower in HFpREF patients. The exercise-induced changes in LVEF, forward stroke volume, and cardiac output were significantly lower in HFpREF compared with control patients (-4 +/- 8 vs. +6 +/- 6 %, P = .001; -4 +/- 9 vs. +10 +/- 10 mL, P < .0001, and 1.6 +/- 1.2 vs. 3.5 +/- 1.8 L/min, P < .0001, respectively). Exercise-induced changes in effective arterial elastance significantly differed in HFpREF and control patients (0.5 +/- 0.6 vs. -0.2 +/- 0.5 mm Hg/mL, P < .0001). In addition, 7 of the 25 HFpREF patients developed functional mitral regurgitation during exercise and none in controls. CONCLUSIONS: When compared with patients with similar comorbidities but without history or evidence of heart failure, patients with HFpREF experience greater arterial stiffening and thereby a deterioration of global LV systolic performance during dynamic exercise.

Pathology of inverted Takotsubo cardiomyopathy.

Myocardial dysfunction without coronary involvement may occur in acute cerebral diseases. The inverted Takotsubo pattern has been recently recognized as a novel heart neurologic stress-related syndrome. We report on the case of a 40-year-old woman presenting with massive subarachnoid hemorrhage and brain death. Echocardiography revealed an extensive left ventricular circumferential akinesis except at the apex. Histologic analysis of the heart confirmed the absence of myocardial infarction and revealed only sparse foci of myocyte necrosis with contraction bands in the akinetic areas.

Septic pseudo-aneurysm of the left main trunk in a dialysis patient.

This case report relating the association between a septic pseudo-aneurysm of the left trunk and myocardial infarction underscores the importance of early non-invasive imaging when acute myocardial infarction is associated with frank clinical or biological signs of systemic sepsis.

Prognostic importance of tissue Doppler-derived diastolic function in patients presenting with acute coronary syndrome: a bedside echocardiographic study.

AIMS: We sought to evaluate the prognostic value of bedside tissue Doppler derived diastolic function in patients presenting with acute coronary syndrome (ACS) on top of major clinical predictors of mortality and routine laboratory testings. METHODS AND RESULTS: Bedside Doppler echocardiography and laboratory tests were prospectively performed in 239 consecutive patients (mean age 62 +/- 14, 69% men) admitted for ACS. Ratio of early transmitral flow (E) to early mitral annulus velocities (e') was calculated. The study endpoint was cardiac death. The median follow-up period was 2 years. E/e' was >15 in 39 patients. Multivariate predictors of E/e' > 15 were older age, diabetes, non-ST-segment elevation ACS, and decreased LV ejection fraction (LVEF). Survival free from cardiac death was lower in patients with E/e' ratio >15 (P = 0.01). History of coronary artery disease, lower creatinine clearance, higher glycemia on admission, decreased LVEF, and E/e' >15 were independent predictors of cardiac death. CONCLUSION: Bedside Doppler echocardiography provides prognostic information on top of major clinical predictors of mortality and routine laboratory testings in patients presenting with ACS.

Steady endothelial nitric oxide synthase expression in heart failure.

BACKGROUND: Vascular nitric oxide (NO)-mediated vasodilation is reduced in the limb vasculature of patients with chronic heart failure. Depressed gene expression of vascular endothelial NO synthase has been reported in experimental models of heart failure. We sought to investigate endothelial NO synthase (eNOS) mRNA expression in the skeletal muscle vasculature of patients with chronic heart failure (CHF) and in controls. METHODS AND RESULTS: Transcript levels for eNOS were measured and normalized to von Willebrand factor gene expression level, in samples of skeletal muscle from patients with CHF (n = 20) and healthy subjects (n = 7). CHF was not associated with a decrease in eNOS expression. There was a trend towards an increased expression in NYHA class IV patients. Similar results were found when normalized to GAPDH mRNA levels. CONCLUSION: Vascular endothelial dysfunction that is observed in patients with severe heart failure does not appear to be related to a specific decrease in the expression of the gene encoding for endothelial NOS.

Acute coronary syndromes associated with thrombus in the sinus of valsalva and normal coronary arteriography: the pivotal role of transesophageal echocardiography in the intensive care unit.

We describe 4 patients with thrombus in nonaneurysmal sinus of Valsalva. The diagnosis was made with transesophageal echocardiography performed in the Intensive care unit, in the setting of acute coronary syndromes. Coronary arterlography showed normal coronary arteries in each patient. In 3 patients, conservative medical therapy resulted in full recovery. Two patients had previously undergone aortic valve surgery.

[What is the place of beta-adrenergic blockade therapy in coronary syndromes in the modern management era?]. / Bêta-bloquants et syndromes coronariens: les réponses d'hier s'appliquent-elles aux stratégies d'aujourd'hui?

This paper shows the eventual benefits of treatment with beta-blockers in post-myocardial infarction. An overview of main clinical trials that have been conducted to test this therapeutic in acute coronary syndrome. In patients presenting with acute myocardial infarction, the early use of intravenous beta-blockers had shown a modest and non significant reduction in mortality. Substantial reductions in mortality and reinfarction have been demonstrated when beta-blockers have been used soon after an acute myocardial infarction and continued long-term. However, these benefits were observed in randomised clinical trials conducted in the 1970s and 1980s, prior to the widespread use of reperfusion therapies and antiplatelet agents. It appears obvious that the long-term use of beta-blockers may be questionable after any acute coronary syndrome especially if complete reperfusion has been achieved and left ventricular function is preserved.