Michel Slama

American College of Chest Physicians/La Société de Réanimation de Langue Française Statement on Competence in Critical Care Ultrasonography

OBJECTIVE To define competence in critical care ultrasonography (CCUS). DESIGN The statement is sponsored by the Critical Care NetWork of the American College of Chest Physicians (ACCP) in partnership with La Société de Réanimation de Langue Française (SRLF). The ACCP and the SRLF selected a panel of experts to review the field of CCUS and to develop a consensus statement on competence in CCUS. RESULTS CCUS may be divided into general CCUS (thoracic, abdominal, and vascular), and echocardiography (basic and advanced). For each component part, the panel defined the specific skills that the intensivist should have to be competent in that aspect of CCUS. CONCLUSION In defining a reasonable minimum standard for CCUS, the statement serves as a guide for the intensivist to follow in achieving proficiency in the field.

Results of percutaneous mitral commissurotomy in 200 patients

To assess the feasibility and efficacy of percutaneous mitral commissurotomy (PMC), the procedure was attempted in 200 patients with severe mitral stenosis. There were 154 women and 46 men, their mean age was 43 +/- 16 years (range 13 to 79) and 15 were older than 70 years of age. Forty-four had had previous surgical commissurotomy. Forty were in New York Heart Association class II, 152 in class III and 8 in class IV. In regard to valvular anatomy, 67 had calcified valves, 58 had pliable valves and only mild subvalvular disease, and 75 had flexible valves but extensive subvalvular disease. Grade 1+ mitral regurgitation was present in 62 and grade 2+ in 2. In 11 patients the procedure was discontinued because of complications in 3 and technical failure in 8. Six of the 8 technical failures occurred during the first 15 attempts. Effective PMC was performed in 189 patients using 1 balloon in 23 and 2 balloons in 166. After PMC, there was a significant improvement in mean left atrial pressure (21 +/- 7 to 12 +/- 5 mm Hg, p less than 0.0001), mean mitral gradient (16 +/- 6 to 6 +/- 2 mm Hg, p less than 0.0001), cardiac index (2.6 +/- 0.8 to 3.1 +/- 0.8 liters/min/m2, p less than 0.001) and valve area assessed by hemodynamics (1.1 +/- 0.3 to 2.2 +/- 0.5 cm2, p less than 0.0001) and 2-dimensional echocardiography (1 +/- 0.3 to 1.9 +/- 0.4 cm2, p less than 0.0001). No patient died. Embolism occurred in 8 (4%), with no further sequelae. Sixteen (8%) had atrial septal defect detected by oxymetry.(ABSTRACT TRUNCATED AT 250 WORDS)

Low-Gradient, Low-Flow Severe Aortic Stenosis With Preserved Left Ventricular Ejection Fraction: Characteristics, Outcome, and Implications for Surgery

BACKGROUND Severe low-gradient, low-flow (LG/LF) aortic stenosis with preserved left ventricular ejection fraction (EF) has been described as a more advanced form of aortic stenosis. However, the natural history and need for surgery in patients with LG/LF aortic stenosis remain subjects of intense debate. OBJECTIVES We sought to investigate the outcome of LG/LF aortic stenosis in comparison with moderate aortic stenosis and with high-gradient (HG) aortic stenosis in a real-world study, in the context of routine practice. METHODS This analysis included 809 patients (ages 75 ± 12 years) diagnosed with aortic stenosis and preserved EF (≥50%). Patients were divided into 4 groups: mild-to-moderate aortic stenosis; HG aortic stenosis; LG/LF aortic stenosis; and low-gradient, normal-flow (LG/NF) aortic stenosis. RESULTS Compared with mild-to-moderate aortic stenosis patients, LG/LF aortic stenosis patients had smaller valve areas and stroke volumes, higher mean gradients, and comparable degrees of ventricular hypertrophy. Under medical management (22.8 months; range 7 to 53 months), compared with mild-to-moderate aortic stenosis patients, HG aortic stenosis patients were at higher risk of death (adjusted hazard ratio [HR]: 1.47; 95% confidence interval [CI]: 1.03 to 2.07), whereas LG/LF aortic stenosis patients did not have an excess mortality risk (adjusted HR: 0.88; 95% CI: 0.53 to 1.48). During the entire (39.0 months; range 11 to 69 months) follow-up (with medical and surgical management), the mortality risk associated with LG/LF aortic stenosis was close to that of mild-to-moderate aortic stenosis (adjusted HR: 0.96; 95% CI: 0.58 to 1.53), whereas the excess risk of death associated with HG aortic stenosis was confirmed (adjusted HR: 1.74; 95% CI: 1.27 to 2.39). The benefit associated with aortic valve replacement was confined to the HG aortic stenosis group (adjusted HR: 0.29; 95% CI: 0.18 to 0.46) and was not observed for LG/LF aortic stenosis (adjusted HR: 0.75; 95% CI: 0.14 to 4.05). CONCLUSIONS In this study, the outcome of severe LG/LF aortic stenosis with preserved EF was similar to that of mild-to-moderate aortic stenosis and was not favorably influenced by aortic surgery. Further research is needed to better understand the natural history and the progression of LG/LF aortic stenosis.

Relation of Serum Sodium Level to Long-Term Outcome After a First Hospitalization for Heart Failure With Preserved Ejection Fraction

Hyponatremia is a predictor of adverse short-term outcomes in patients with acute heart failure (HF). The impact of hyponatremia on long-term survival in patients with HF with preserved ejection fraction (HFPEF) has not been evaluated. Our aim was to prospectively assess the impact of baseline natremia and changes in sodium level during hospitalization on 7-year outcome in 358 patients surviving a first hospitalization for HFPEF. On admission, hyponatremia (sodium <136 mEq/L) was diagnosed in 91 patients (25.4%). Baseline hyponatremia was associated with an increased risk of overall (hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.50 to 2.61) and cardiovascular mortality (HR 1.92, 95% CI 1.36 to 2.73). After adjustment for covariates, the relations remained significant. Seven-year relative survival (observed/expected survival) of hyponatremic patients was lower than that of patients with normal baseline natremia (31% vs 63%). The association of sodium and risk of death appeared linear across quartiles of baseline natremia and slightly stronger at the lowest of sodium values. At discharge, 45 patients with low baseline sodium had normal natremia (49%) and 46 had persistent hyponatremia (51%). Patients with normalized natremia at discharge had excess 7-year overall mortality compared with the normonatremic group (HR 1.50, 95% CI 1.03 to 2.19). Patients with persistent hyponatremia had the lowest 7-year survival (HR 2.67, 95% CI 1.89 to 3.78). After adjustment for covariates, patients with persistent hyponatremia had an impressive increase in relative risk of overall mortality compared with patients with normal baseline natremia. In conclusion, hyponatremia is a powerful predictor of long-term mortality in patients with HFPEF. Patients with HFPEF and persistent hyponatremia are at high risk of adverse outcomes.

Effects of phosphate on vascular function under normal conditions and influence of the uraemic state.

AIMS Increased serum phosphorus levels are associated with cardiovascular disease in patients with chronic kidney disease (CKD) and in the general population. High phosphate levels may play a direct role in vascular dysfunction. We investigated here the effects of phosphate loading and of the phosphate binder sevelamer-HCl on vascular function. METHODS AND RESULTS CKD and non-CKD C57/BL6 mice were used to study the effects of CKD, phosphate, and sevelamer-HCl on vascular function and structure. In vitro, phosphate exhibited a direct vasoconstrictor effect on aortic rings. This effect was smaller in vessels from CKD than non-CKD mice and it was abolished by reactive oxygen species inhibitor dimethylthiourea. A high-phosphate diet (1.3%) increased phenylephrine-induced contraction and lowered acetylcholine-induced relaxation of aortic rings ex vivo, both in non-CKD and CKD mice. It also induced endothelial cell detachment. Sevelamer-HCl exposure in vitro normalized the endothelial dysfunction induced by 3.0 mM phosphate and restored endothelial integrity. Sevelamer-HCl treatment of CKD mice under normal diet (0.65% phosphate) improved the endothelial dysfunction, aortic systolic expansion rate, and pulse wave velocity, and it reduced the endothelial expression of adhesion molecules. CONCLUSION Changes in extracellular phosphorus concentrations may directly modulate vascular function and thereby modulate the vascular smooth muscle response to physiological or pathological stimuli in normal and CKD mice. Whether serum phosphorus lowering and/or dietary phosphate restriction can improve arterial function in humans remains to be established.

Effects of sevelamer treatment on cardiovascular abnormalities in mice with chronic renal failure

Elevated serum phosphate and fibroblast growth factor 23 (FGF23) levels are associated with cardiovascular disease (CVD) in patients with chronic renal failure (CRF). The phosphate-binder sevelamer has been shown to decrease both phosphate and FGF23, but limited data indicate that sevelamer improves CRF-related CVD, such as diastolic dysfunction, left ventricular hypertrophy (LVH), and aortic stiffness. To gain additional information, we measured the effects of sevelamer on CVD in a murine model of CRF. Groups of CRF and sham-operated mice received regular chow or 3% sevelamer-HCl in the chow for 14 weeks, starting 6 weeks after the initiation of CRF or sham operation. After the first 8 weeks of sevelamer treatment, CRF mice had decreased serum phosphate levels and an improved aortic systolic expansion rate, pulse-wave velocity, and diastolic function, although LVH remained unchanged. Following an additional 6-week course of sevelamer, LVH had not progressed. The FGF23 serum level was not reduced by sevelamer until after 14 weeks of treatment. In multiple regression analysis, serum phosphate, but not FGF23, was independently correlated with LV diastolic function and mass. Thus, sevelamer first improved aortic stiffness and diastolic dysfunction and secondarily prevented LVH in mice with CRF. The phosphate-lowering, rather than FGF23-lowering, effect appears to be responsible for the observed cardiovascular improvement.

Prevalence and clinical phenotype of hereditary transthyretin amyloid cardiomyopathy in patients with increased left ventricular wall thickness

AIMS Increased left ventricular wall thickness (LVWT) is a common finding in cardiology. It is not known how often hereditary transthyretin-related familial amyloid cardiomyopathy (mTTR-FAC) is responsible for LVWT. Several therapeutic modalities for mTTR-FAC are currently in clinical trials; thus, it is important to establish the prevalence of TTR mutations (mTTR) and the clinical characteristics of the patients with mTTR-FAC. METHODS AND RESULTS In a prospective multicentre, cross-sectional study, the TTR gene was sequenced in 298 consecutive patients diagnosed with increased LVWT in primary cardiology clinics in France. Among the included patients, median (25-75th percentiles) age was 62 [50;74]; 74% were men; 23% were of African origin; and 36% were in NYHA Class III-IV. Median LVWT was 18 (16-21) mm. Seventeen (5.7%; 95% confidence interval [CI]: [3.4;9.0]) patients had mTTR of whom 15 (5.0%; 95% CI [2.9;8.2]) had mTTR-FAC. The most frequent mutations were V142I (n = 8), V50M (n = 2), and I127V (n = 2). All mTTR-FAC patients were older than 63 years with a median age of 74 [69;79]. Of the 15 patients with mTTR-FAC, 8 were of African descent while 7 were of European descent. In the African descendants, mTTR-FAC median age was 74 [72;79] vs. 55 [46;65] years in non-mTTR-FAC (P < 0.001). In an adjusted multivariate model, African origin, neuropathy, carpal tunnel syndrome, electrocardiogram (ECG) low voltage, and late gadolinium enhancement (LGE) at cardiac-magnetic resonance imaging were all independently associated with mTTR-FAC. CONCLUSION Five per cent of patients diagnosed with hypertrophic cardiomyopathy have mTTR-FAC. Mutated transthyretin genetic screening is warranted in elderly subjects with increased LVWT, particularly, those of African descent with neuropathy, carpal tunnel syndrome, ECG low voltage, or LGE.

Prognostic Impact of Angiotensin-Converting Enzyme Inhibitor Therapy in Diastolic Heart Failure

The angiotensin-converting enzyme (ACE) inhibitor has a well defined place in the treatment of systolic heart failure (HF). Evidence for routine prescription of an ACE inhibitor in patients with diastolic HF (DHF) is inconsistent. Therefore, our aim was to evaluate the prognostic impact of ACE inhibitor in patients with DHF. The present prospective study included patients with normal or slightly impaired ejection fraction (> or =50%) surviving a first hospitalization for HF. We assessed the long-term prognosis of these patients according to prescription of an ACE inhibitor at discharge. ACE inhibitor therapy prescribed at discharge in 46% (n = 165) of the 358 included patients was associated with a 30% relative decrease in the risk of 5-year mortality (hazard ratio 0.70, 95% confidence interval 0.53 to 0.93, p = 0.013). On multivariable Cox analysis, the relation between ACE inhibitor prescription and mortality remained significant (hazard ratio 0.73, 95% confidence interval 0.54 to 0.99, p = 0.045). Using propensity score analysis, 120 patients receiving an ACE inhibitor were matched with 120 patients not receiving this medication. In the postmatch group, prescription of ACE inhibitor was associated with a significant decrease in the risk of 5-year mortality (hazard ratio 0.61, 95% confidence interval 0.43 to 0.87, p = 0.006). Five-year relative survival (observed/expected survival) of the ACE inhibitor group was better than that of the no-ACE inhibitor group (65% vs 57%). In conclusion, we demonstrate that in this cohort of patients with DHF, prescription of ACE inhibitor was associated with a significant decrease in long-term mortality.

Residents learning ultrasound-guided catheterization are not sufficiently skilled to use landmarks

IntroductionUltrasound-guided (UG) technique is the recommended procedure for central venous catheterization (CVC). However, as ultrasound may not be available in emergency situations, guidelines also propose that physicians remain skilled in landmark (LM) placement. We conducted this prospective observational study to determine the learning curve of the LM technique in residents only learning the UG technique.MethodsDuring the first three months of their rotation in our ICU, residents inexperienced in CVC used only the real-time UG technique. During the following three months, residents were allowed to place CVC by means of the LM technique when authorized by the attending physician.ResultsA total of 172 procedures (84 UG and 88 LM) were performed by the inexperienced residents during the study. The success rate was lower (72% versus 84%; P = 0.05) and the complication rate was higher (22% versus 10%; P = 0.04) for LM compared to UG procedures. Comparison between the five last UG procedures and the first five LM procedures performed demonstrated that the transition between the two techniques was associated with a marked decrease of the success rate (65% versus 93%; P = 0.01) and an increase of the complication rate (33% versus 8%; P = 0.01). After 10 LM procedures, residents achieved a success rate and a complication rate of 81% and 6%, respectively.ConclusionsResidents who only learn the UG technique will not be immediately able to perform the LM technique, but require specific training based on at least 10 LM procedures. The question of whether or not the LM technique should still be taught when an ultrasound device is not available must therefore be addressed.

Prognostic Implication of Plasma Osteopontin Levels in Patients with Chronic Kidney Disease

Aims: To assess (a) plasma osteopontin (pOPN) in a cohort of chronic kidney disease (CKD) patients; (b) the relationship between pOPN and aortic calcification and stiffness, and (c) the association between pOPN and the overall and cardiovascular mortality risk. Methods: pOPN, the abdominal aortic calcification score and pulse wave velocity (PWV) were determined in 94 CKD patients (68 ± 13 years; 60% males; 31% at CKD stages 2–3, 31% at stages 4–5, 38% at stage 5D), prospectively followed for mortality. Results: pOPN was higher in CKD patients than in controls. Interleukin (IL)-6 (r2 = 0.086; p = 0.004), CRP (r2 = 0.046; p = 0.038), iPTH (r2 = 0.065; p = 0.014), albumin (r2 = 0.210; p < 0.0001) and statin use (r2 = 0.038; p = 0.059) were associated with pOPN. There was no association between pOPN and the aortic calcification score or PWV. During follow-up (969 ± 405 days), 32 patients died. In crude analysis, pOPN >167 ng/ml predicted overall and cardiovascular mortality (p = 0.02 and 0.01, respectively), but this effect was lost after adjustment for albumin or IL-6. Conclusions: pOPN is elevated from the early stages of CKD onward. We found no associations between pOPN and the aortic calcification score or the PWV. The positive association between pOPN and clinical outcomes was dependent of the patients’ inflammatory status.