Pierre Ambrosi

Risk of Embolism and Death in Infective Endocarditis: Prognostic Value of Echocardiography. A Prospective Multicenter Study

Background—The incidence of embolic events (EE) and death is still high in patients with infective endocarditis (IE), and data about predictors of these 2 major complications are conflicting. Moreover, the exact role of echocardiography in risk stratification is not well defined. Methods and Results—In a multicenter prospective European study, including 384 consecutive patients (aged 57±17 years) with definite IE according to Duke University criteria, we tested clinical, microbiological, and echocardiographic data as potential predictors of EE and 1-year mortality. Transesophageal echocardiography was performed in all patients. Embolism occurred before or after IE diagnosis (total-EE) in 131 patients (34.1%) and after initiation of antibiotic therapy (new-EE) in 28 patients (7.3%). Staphylococcus aureus and Streptococcus bovis were independently associated with total-EE, whereas vegetation length >10 mm and severe vegetation mobility were predictors of new-EE, even after adjustment for S aureus and S bovis. One-year mortality was 20.6%. In multivariable analysis, independently of the other predictors of death (age, female sex, creatinine serum >2 mg/L, moderate or severe congestive heart failure, and S aureus) and comorbidity, vegetation length >15 mm was a predictor of 1-year mortality (adjusted relative risk=1.8; 95% CI, 1.10 to 2.82; P=0.02). Conclusions—In IE, vegetation length is a strong predictor of new-EE and mortality. In combination with clinical and microbiological findings, echocardiography may identify high-risk patients who will need a more aggressive therapeutic strategy.

Human Serum Albumin in the Clinical Syndrome of Heart Failure

Hypoalbuminemia is common in patients with heart failure, and this condition becomes more prevalent with increasing age and illness. Hypoalbuminemia is thought to result mainly from malnutrition, inflammation and cachexia. Other causal factors include hemodilution, liver dysfunction, protein-losing enteropathy, increased transcapillary escape rate, and nephrotic syndrome. According to Starlings law, low plasma oncotic pressure related to hypoalbuminemia induces a fluid shift from the intravascular to the interstitial space, and there is now clinical evidence that hypoalbuminemia facilitates the onset of cardiogenic pulmonary edema. Hypoalbuminemia has emerged as an independent predictor of incident heart failure in end-stage renal disease and elderly patients. Recent data also suggest that hypoalbuminemia provides prognostic information incremental to the usual clinical and biochemical variables in patients with heart failure regardless of clinical presentation. The presence of hypoalbuminemia in patients with heart failure may have potential therapeutic consequence in clinical practice. If present, subclinical excess of fluid must be removed. A dietary survey should also be performed, and renutrition may be indicated. It is unknown whether targeted nutritional intervention and albumin administration confer benefits to hypoalbuminemic patients with heart failure, and further research is warranted in this setting.

Comparison of clinical and echocardiographic characteristics of Streptococcus bovis endocarditis with that caused by other pathogens

The aim of our study was to compare the clinical, echographic, and prognostic features of Streptococcus bovis (S. bovis) endocarditis with those caused by other streptococci and pathogens in a large sample of patients with definite endocarditis by Duke criteria, using transesophageal echocardiography. Two hundred six patients (149 men, mean age 57 +/- 15 years) with a diagnosis of infective endocarditis formed the study population. All patients underwent multiplane transesophageal echocardiography and blood cultures. Cerebral, thoracoabdominal computed tomographic scan was performed in almost all patients (95%). All patients with S. bovis endocarditis underwent colonoscopy. Incidence of S. bovis endocarditis in our sample was 19%. Patients with S. bovis endocarditis were older than other groups. Multiple valve involvement, native valves, and large vegetations (>10 mm) were more frequent in patients with S. bovis. There was a significantly higher occurrence of embolism in the S. bovis group. Splenic embolism and multiple embolisms were significantly more frequent in patients with S. bovis. Gastrointestinal lesions, anemia, and spondylitis were observed more frequently with S. bovis endocarditis. In addition to the requirement for gastrointestinal examination for S. bovis endocarditis, our study underlines the need for systematic screening for vertebral and splenic localizations, and suggests the use of early surgery to prevent the high risk of embolism in these patients.

Circulating Endothelial Cell Count as a Diagnostic Marker for Non–ST-Elevation Acute Coronary Syndromes

Background—Shedding of endothelial cells from damaged endothelium into the blood occurs in a variety of vascular disorders. The purpose of this study was to evaluate the utility of circulating endothelial cell (CEC) count as a diagnostic marker of non–ST-elevation acute coronary syndromes (ACSs). Methods and Results—CEC counts were determined immediately (H0), 4 hours (H4), and 8 hours (H8) after admission in 60 patients with documented non–ST-elevation ACS and 40 control patients with no evidence of coronary artery disease. A total of 32 patients in the ACS group had elevated CEC counts (>3 cells/mL) in relation to early admission and single-episode chest pain. Patients from the control group had normal CEC counts. The interval between the chest pain episode and elevation was significantly shorter for CEC than troponin I. No correlation was found between the 2 markers. Interestingly, a subgroup of ACS patients with initially normal troponin I levels had high CEC counts, thus allowing early diagnosis in 30% more cases. At H0, the mean area under the receiver operating characteristic curve was significantly higher with the CEC count than with the troponin I level. At H4 and H8, the combined use of CEC and troponin was significantly better as a marker of ACS than CEC alone or troponin I alone. Conclusions—This study demonstrates that CEC count can be used as an early, specific, independent diagnostic marker for non–ST-elevation ACS. A combined strategy using CEC count and troponin I level could provide an effective diagnostic tool.

Hypoalbuminemia in elderly patients with acute diastolic heart failure

OBJECTIVES This study evaluated the relative contribution of serum colloid osmotic pressure (COP) lowering and pulmonary artery wedge pressure (PAWP) elevation in the pathogenesis of pulmonary edema in patients with systolic or isolated diastolic heart failure (DHF). BACKGROUND The role of hypoalbuminemia and the resulting low COP have been shown in some patients with acute systolic heart failure (SHF). Colloid osmotic pressure and PAWP were determined in 100 patients with acute heart failure (HF) (56 with DHF and 44 with SHF; mean age, 78 +/- 12 years), in 35 patients with acute dyspnea from pulmonary origin, and in 15 normal controls. Pulmonary artery wedge pressure was estimated using transthoracic Doppler echocardiography. RESULTS Colloid osmotic pressure was significantly lower in the DHF group (20.5 +/- 5 mm Hg) than in the SHF group (24.2 +/- 3.7 mm Hg, p < 0.001), pulmonary disease group (25.1 +/- 4.2 mm Hg, p < 0.001), or normal control group (24.7 +/- 3 mm Hg). Low COP resulted from hypoalbuminemia due to age, malnutrition, and sepsis. Pulmonary artery wedge pressure was significantly higher in patients with SHF (26 +/- 6.3 mm Hg) than in the patients with DHF (20.3 +/- 7 mm Hg, p < 0.001) and was significantly higher in the patients with DHF than in the patients with pulmonary disease (13 +/- 4.2 mm Hg, p < 0.001). The COP-PAWP gradient was similar in patients with SHF (-1.6 +/- 7.1 mm Hg) and patients with DHF (0.7 +/- 6 mm Hg). CONCLUSIONS Frequent hypoalbuminemia resulting in low COP facilitates the onset of pulmonary edema in patients with DHF who usually have lower PAWP than patients with SHF.

Association of mild hyperhomocysteinemia with cardiac graft vascular disease

In non-transplant patients mild hyperhomocysteinemia is an independent risk factor for vascular disease. The aim of this study was to determine whether hyperhomocysteinemia is associated with graft vascular disease. Fasting total plasma homocysteine was assessed in 18 patients with graft vasculopathy and 18 transplanted patients without graft vasculopathy matched for age, sex and the time since transplant. All were on cyclosporin. Graft vasculopathy was defined at coronary angiography as stenoses > or = 25%, or aneurysms. We found that hyperhomocysteinemia ( > or = 15 micromol/l) is common among transplanted heart recipients and significantly more frequent in the patients with graft vasculopathy (17/18 versus 11/18). Accordingly, the mean homocysteinemia was significantly higher in the group with graft vasculopathy (23.6+/-7.8 versus 16.9+/-7.1 micromol/l, P=0.01). The elevation of homocysteine plasma levels in the heart transplant recipients has probably multiple causes. The main cause seems to be renal failure. Additional causes could be azathioprine treatment or genetic polymorphisms. These results suggest that besides the immunological factors, homocysteine can play an additional role in the pathogenesis of graft vascular disease.

Effects of folate supplementation in hyperhomocysteinemic pigs.

OBJECTIVES The aim of this study was to evaluate the therapeutic effects of folic acid in the pig model of hyperhomocysteinemia. BACKGROUND We have previously shown that pigs fed a methionine-rich diet develop hyperhomocysteinemia, arterial lesions and thrombotic events. Elevated homocysteine level is an independent risk factor for atherosclerosis that can be markedly lowered with daily folic acid administration. However, it is not known whether this treatment can prevent arterial lesions. METHODS Three groups of pigs were studied: 8 control subjects received a standard diet; 8 received a methionine-rich diet for four months; 8 received a methionine-rich diet for 1 month and then the methionine-rich diet + 5 mg/day folic acid for 3 months. At month 4 after hemodynamic investigation, all the pigs were sacrificed. RESULTS Control animals developed few usual vascular streaks. All the pigs fed a methionine-rich diet without folic acid treatment developed hyperhomocysteinemia (10.3+/-1.3 micromol/liter at basal state, 18.2+/-2.5 micromol/liter at one month and 14.6+/-3.8 micromol/liter at four months), hemodynamic abnormalities and diffuse arterial lesions with smooth muscle cell hyperplasia, endothelial alterations and elastic lamina dislocation. In this group, one pig died of venous thromboembolism and one of myocardial infarction. The pigs fed a methionine-rich diet + folic acid displayed similar arterial lesions and two had thrombotic events (one myocardial infarction and one pulmonary embolism), despite normalization of homocysteine levels (10.9+/-1.3 micromol/liter at basal state, 19.5+/-2.5 micromol/liter at one month and 11.4+/-3.8 micromol/liter at four months). CONCLUSIONS In the pig model of hyperhomocysteinemia, 5 mg/day folic acid did not prevent arterial lesions or thrombotic events.

Usefulness of serum albumin and serum total cholesterol in the prediction of hospital death in older patients with severe, acute heart failure

BACKGROUND Acute heart failure (HF) carries high hospital mortality rates in older patients; a multimarker strategy may help identify patients at high risk. AIMS To investigate prospectively the prognostic relevance of serum albumin and serum total cholesterol (TC) in older patients with severe, acute HF. METHODS Usual prognostic variables were collected on admission in 207 consecutive patients aged>70 years with severe, acute HF. Serum albumin and serum TC were obtained soon after clinical improvement. RESULTS Hospital mortality rate was 19%. Patients who died were similar to patients who survived in terms of age, sex, heart rate, serum haemoglobin and left ventricular ejection fraction. Patients who died had higher concentrations of B-type natriuretic peptide (BNP), blood urea nitrogen, serum creatinine, C-reactive protein and serum troponin I, lower systolic blood pressure, and lower concentrations of serum albumin and serum TC than patients who survived (P<0.01 for all). Serum albumin was the best independent predictor of hospital death (odds ratio 0.82 [0.74-0.90], P<0.001), with blood urea nitrogen (P=0.02) and log (BNP) (P=0.02). A simple risk score based on serum albumin (<3g/dL; 2 points), BNP (>840pg/mL; 1 point) and blood urea nitrogen (>15.3mmol/L; 1 point) discriminated patients without (score 0 to 1, hospital death 4%) from patients with (score 2 to 4, hospital death 35%, P<0.001) a high risk of death. CONCLUSION Hypoalbuminaemia offers powerful additional prognostic information to usual prognostic variables in older patients with severe, acute HF, and deserves further attention in multimarker strategies.

Standard Orthotopic Heart Transplantation Versus Total Orthotopic Heart Transplantation A Transesophageal Echocardiography Study of the Incidence of Left Atrial Thrombosis

BACKGROUND After standard orthotopic heart transplantation (Sd HT), the enlarged resultant atria may promote atrial thrombosis. The purpose of this study was to compare the incidence of spontaneous echo contrast and left atrial thrombosis after Sd HT and total orthotopic (Tot HT) heart transplantation. METHODS AND RESULTS Transesophageal echocardiography (TEE) was performed in 75 patients with Sd HT and in 20 patients with Tot HT. Despite the use of antiplatelet therapy, an acute arterial embolism occurred in 11 (15%) of the 75 patients with Sd HT but in none of the 20 Tot HT patients. All patients were in sinus rhythm. Left ventricular ejection fraction was similar in Sd HT and Tot HT patients. Left atrial diameter was smaller in Tot HT patients than in Sd HT patients (41 +/- 4 versus 58 +/- 6 mm, P < .001). In Sd HT patients, spontaneous echo contrast was present in 43 patients (57%) and was associated with left atrial thrombus in 20 patients (on the left atrial appendage in 12 patients, on the posterior wall in 6, and on the suture in 2). No thrombus was detected by transthoracic echocardiography; all thrombi were detected by TEE. On the other hand, no left atrial thrombus was observed in Tot HT patients, and only 1 patient had spontaneous echo contrast. Of the 11 Sd HT patients who experienced an arterial embolism, 5 had both spontaneous echo contrast and left atrial thrombus and 5 had only spontaneous echo contrast. CONCLUSIONS This study demonstrates a high rate of left atrial thrombus after Sd HT and emphasizes the role of TEE in the follow-up of these patients. The therapeutic implications are the need for a preventive anticoagulant therapy in the high-risk population receiving Sd HT diagnosed with TEE and the consideration of Tot HT as a better surgical approach as far as thrombotic complications are concerned.

Accuracy of tissue Doppler echocardiography in the emergency diagnosis of decompensated heart failure with preserved left ventricular systolic function: comparison with B-type natriuretic peptide measurement.

Background: Tissue Doppler echocardiography provides a reliable noninvasive estimation of left ventricular (LV) filling pressures irrespective of LV ejection fraction. However, the diagnostic accuracy of E/Ea ratio has not been adequately determined in patients with suspected heart failure (HF) with preserved LV systolic function in the acute care setting. Objective: To investigate the accuracy of E/Ea ratio in the emergency diagnosis of decompensated HF with preserved LV systolic function. Methods: Seventy patients with a LV ejection fraction ≥45%, 32 with decompensated HF (77 ± 12 years of age), and 38 with noncardiac cause of acute dyspnea (74 ± 12) were enrolled. B‐type natriuretic peptide (BNP) was measured on admission; lateral, septal and average E/Ea ratios were calculated within 24 hours. Results: Using receiver‐operating characteristic curves to evaluate diagnostic performance, BNP (AUC of 0.875, P < 0.0001) and E/Ea ratios (AUC of 0.90–0.92, P < 0.0001) provided similar accuracy for predicting decompensated HF. Optimal cutoffs were 146 pg/ml for BNP (sensitivity and specificity of 90.6% and 76.3%), 9.8 for lateral E/Ea (83.3% and 88.9%), 12.7 for septal E/Ea (76.7% and 91.4%), and 11.5 for average E/Ea ratio (80% and 94.3%). On multivariate logistic regression analysis, average E/Ea ratio yielded independent additional information to a model based on the clinical judgment and BNP level according to the standard cutoff of 100 pg/ml. Conclusions: Tissue Doppler echocardiography is accurate for predicting decompensated HF with preserved LV systolic function and may be used as a diagnostic complement to inconclusive BNP level in this setting.