Michel Slama

Assessing fluid responsiveness in critically ill patients: False-positive pulse pressure variation is detected by Doppler echocardiographic evaluation of the right ventricle

Objectives:To determine whether peak systolic velocity of tricuspid annular motion assessed by tissue Doppler echocardiography (Sta), a right ventricular function parameter, can discriminate patients with true- and false-positive pulse pressure variation. Pulse pressure variation is used to predict fluid responsiveness in mechanically ventilated patients. However, this parameter has been reported to be falsely positive, especially in patients with right ventricular dysfunction. Design:A prospective study. Setting:Medical and surgical intensive care unit of a university hospital. Patients:Thirty- five mechanically ventilated patients hospitalized for >24 hrs with a pulse pressure variation of >12%. Interventions:Doppler echocardiography (including measurement of Sta and stroke volume) was performed before and after infusion of 500 mL of colloid solution. Patients were classified into two groups according to their response to fluid infusion: responders (at least 15% increase in stroke volume) and nonresponders. Measurements and Main Results:Twenty-three patients (66%) were responders (true-positive group) and 12 (34%) were nonresponders (false-positive group). Before volume expansion, Sta was statistically lower in the nonresponder group (0.13 [0.04] vs. 0.20 [0.05], p = .0004). The area under the curve of the receiver operating characteristic curve was 0.87 (95% confidence interval, 0.74-1). In patients with pulse pressure variation of >12%, a Sta cutoff value of 0.15 m/s discriminated between responders and nonresponders with a sensitivity of 91% (80-100) and a specificity of 83% (62-100). Conclusions:A Sta value of <0.15 m/s seems to be an accurate parameter to detect false-positive pulse pressure variation. Echocardiography should therefore be performed before fluid infusion in patients with pulse pressure variation of >12%.

Diastolic dysfunction in hypertension.

Heart failure is one of the most common causes of cardiovascular morbidity and mortality, and hypertension is the most common cause of cardiac failure. Recent studies have shown that isolated diastolic dysfunction very often accompanies hypertensive heart disease. Ventricular diastolic function may be divided into an active relaxation phase and a passive compliance period. These two components have been investigated invasively, and they remain the gold standards for the study of diastolic function. However, in the routine clinical setting, echocardiographic and Doppler techniques are most useful for evaluating ventricular filling. Thus, analysis of E and A waves of mitral flow have provided important and useful information. Unfortunately, these indices depend on too many factors. Newer indices obtained from ventricular time intervals, tissue Doppler imaging, and color M-mode echocardiography have enhanced the means to assess diastolic function. In addition, new methods including MRI and cine CT have also provided better understanding of left ventricular filling in hypertension. Using these techniques, diastolic dysfunction has been found to be common in patients with hypertension, even before left ventricular hypertrophy is demonstrable and before hypertension in young, normotensive male offspring of hypertensive parents has developed. Furthermore, it has been made clear recently that myocardial ischemia and fibrosis are two important factors associated with diastolic dysfunction in hypertension.

Relation between cardiovascular risk factors and nonrheumatic severe calcific aortic stenosis among patients with a three-cuspid aortic valve

224–232. 2. Leclerq C, Kass DA. Retiming the failing heart: principles and current clinical status of cardiac resynchronization. J Am Coll Cardiol 2002;39:194–202. 3. Waggoner AD, Bierig SM. Tissue Doppler imaging. A useful echocardiographic method for the cardiac sonographer to assess systolic and diastolic ventricular function. J Am Soc Echocardiogr 2001;14:1143–1152. 4. Yu C, Chau E, Sanderson JE, Fan K, Tang MO, Fung WH, Lin H, Kong SL, Lam YM, Hill MR, Lau CP. Tissue Doppler echocardiographic evidence of reverse remodeling and improved synchronicity by simultaneously delaying regional contraction after biventricular pacing therapy in heart failure. Circulation 2002;105:438–445. 5. Garrigue S, Jais P, Espil M, Labeque J, Jais P, Hocini M, Shah DC, Haissaguerre M, Clementy J. Comparison of chronic biventricular pacing between epicardial and endocardial left ventricular stimulation using Doppler tissue imaging in patients with heart failure. Am J Cardiol 2001;88:858–862. 6. Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E, Kocovic DZ, Packer M, Clavell AL, Haves DL, et al. Cardiac resynchronization in heart failure. N Engl J Med 2002;346:1845–1853. 7. Bax JJ, Poldermans D, Elhendy A, Cornel JH, Boersma E, Rambaldi R, Roelandt JR, Fioretti PM. Improvement of left ventricular ejection fraction, heart failure symptoms and prognosis after revascularization in patients with chronic coronary artery disease and viable myocardium detected by dobutamine stress echocardiography. J Am Coll Cardiol 1999;34:163–169. 8. Gulati VK, Katz WE, Follansbee WP, Gorcsan J. Mitral annular descent velocity by tissue Doppler echocardiography as an index of global left ventricular function. Am J Cardiol 1996;77:979–984.

International consensus statement on training standards for advanced critical care echocardiography

Endorsed by the European Society of Intensive Care Medicine (ESICM), American College of Chest Physicians (ACCP), American Thoracic Society (ATS), Société de Réanimation de Langue Française (SRLF), Asia Pacific Association of Critical Care Medicine, Canadian Critical Care Society, College of Intensive Care Medicine of Australia and New Zealand, Hong Kong College of Anaesthesiologists, Hong Kong Society of Critical Care Medicine. All authors certify that they endorse all parts of the published manuscript. The expert round table participants and the authors as a group are listed in the Appendix.

Prevention of hypertension

Hypertension is a major risk factor for many cardiovascular diseases including stroke, coronary heart disease, cardiac failure, and endstage renal disease. Therefore, prevention of hypertension becomes an important goal in overall efforts to control blood pressure and reduce the incidence of hypertension-related cardiovascular and renal complications and outcomes. Many risk factors underlying hypertension have been identified including nonmodifiable factors such as age, gender, genetic factors, and race, as well as modifiable factors including overweight, high sodium intake, low potassium intake, alcohol consumption, and reduced physical activity. A number of studies have demonstrated that interventions aimed at changing these modifiable factors might decrease blood pressure and even prevent the development of hypertension. Thus, present national recommendations and guidelines include lifestyle modifications ranging from weight loss in case of obesity, engagement in regular isotonic physical activity, reduced sodium diet (<100 mmol/d), supplementation of potassium, and alcohol moderation (<1 ounce of ethanol or its equivalent per day).

Hypertension in the intensive care unit

Purpose of review The severity of hypertensive crises is determined by the presence of target organ damage rather than the level of blood pressure. Hypertensive urgencies with no signs of organ dysfunction can therefore be distinguished from hypertensive emergencies in which the presence of severe end-organ damage requires prompt therapy. Hypertensive emergencies include acute aortic dissection, hypertensive encephalopathy, acute myocardial ischaemia, severe pulmonary oedema, eclampsia, and acute renal failure. Recent developments Malignant hypertension is a severe form of hypertensive emergency demanding special consideration because of the risks of permanent blindness and renal failure. Catecholamine excess and postoperative hypertension may also sometimes require urgent treatment. The management of patients with hypertensive emergencies must be ensured in an intensive care unit, and must include the parenteral administration of antihypertensive drugs and accurate blood pressure monitoring. Summary Except for acute aortic dissection, the recommended goals of treatment are a reduction of mean arterial pressure by no more than 20% during the first few hours, because an abrupt fall in blood pressure in patients with preexisting hypertension may induce severe ischaemic injury in major organs as a result of the chronic adaptation of autoregulation mechanisms. Hypertension in the context of acute stroke should be treated only rarely and cautiously because of the presence of impaired autoregulation.

Activated protein C improves lipopolysaccharide-induced cardiovascular dysfunction by decreasing tissular inflammation and oxidative stress

Background:Recombinant human activated Protein C (APC) is used as an adjunctive therapeutic treatment in septic shock. APC seemingly acts on coagulation-inflammation interaction but also by decreasing proinflammatory gene activity, thus inhibiting subsequent production of proinflammatory cytokines, NO and NO-induced mediators, reactive oxygen species production and leukocyte-endothelium interaction. The hemodynamic effects of APC on arterial pressure and cardiac function are now well established in animal models. However, the specific effects of APC on heart and vessels have never been studied. Objectives:To investigate the potential protective properties of therapeutic ranges of APC on a rat endotoxic shock model in terms of anti-inflammatory and cytoprotective pathways. Design:Laboratory investigation. Setting:University medical center research laboratory. Interventions:Rats were exposed to lipopolysaccharide (LPS) (10 mg/Kg intravenous). Endotoxic shock was treated with infusion of saline with or without APC (33 &mgr;g/kg/h) during 4 hrs. Hemodynamic parameters were continuously assessed and measurements of muscle oxygen partial pressures, NO and superoxide anion (O2−) by spin trapping, of NF-&kgr;B, metalloproteinase-9 (MMP-9) and inducible NO synthase (iNOS) by Western blotting, as well as leukocyte infiltration and MMP-9 activity were performed at both the heart and aorta level (tissue). Main Results:APC partially prevented the reduction of blood pressure induced by LPS and improved both vascular hyporeactivity and myocardial performance. This was associated with a decreased up-regulation of NF-&kgr;B, iNOS and MMP-9. LPS-induced tissue increases in NO and O2− production were decreased by APC. Furthermore, APC decreased tissue leukocyte infiltration/activation as assessed by a decrease in myeloperoxydase and matrix metalloproteinase 9 activity. Conclusions:These data suggest that APC improves cardiovascular function: 1) by modulating the endotoxin induced-proinflammatory/prooxydant state, 2) by decreasing endothelial/leukocyte interaction and 3) by favoring stabilization of the extracellular matrix.

Prognostic value of Doppler-derived myocardial performance index in patients with left ventricular systolic dysfunction

S studies have attempted to identify the prognostic factors of patients with heart failure and left ventricular (LV) systolic dysfunction.1–4 In this population, echocardiographic parameters have been described to predict a poor outcome including LV enlargement, low LV ejection fraction or fractional shortening, high mitral flow E/A ratio, and short deceleration time of mitral E flow.1–4 Early reports have shown that isovolumic intervals can be used to analyze cardiac dysfunction in patients with heart failure.5–11 Recently, a Doppler-derived interval index including systolic and diastolic performance of the left ventricle was reported to be a useful, sensitive, and reproducible parameter to detect myocardial dysfunction in many clinical situations.12–14 This index, which is easy to obtain, was defined as the ratio of the summation of isovolumic contraction and relaxation time to ejection time. However, the prognostic value of this index in patients with heart failure and LV systolic dysfunction remains unclear and has not been previously prospectively studied. Therefore, we decided to record, in a prospective study, this index in patients with LV systolic dysfunction to analyze its prognostic value. • • • Between February 1996 and February 1998, we prospectively included 100 consecutive patients (79 men and 21 women, aged 65 11 years) in sinus rhythm, hospitalized with clinical congestive heart failure and LV ejection fraction 40% at echocardiographic examination, and without any valvular heart disease. Patients were clinically stable for at least 3 weeks. All echocardiographic measurements were analyzed without knowledge of clinical data. The entire echocardiography and Doppler examination was completed for each patient (Sonos 2000 or 5500, Philips Ultrasound System, probe 2.5 MHz, Andover, Massachusetts) including measurements of LV diastolic and systolic diameters, diastolic and systolic volumes using Simpson’s method,15 and right ventricular end-diastolic diameter. LV ejection fraction and shortening fraction were calculated. On mitral flow, we measured maximum velocity of E and A waves and the deceleration time of the E wave, and we calculated E/A ratio. The myocardial performance index (MPI) was calculated as previously described by Tei et al.14 Briefly, using pulsed Doppler, we recorded mitral and aortic flow from 4 and 5 apical chamber views, with a 1-mm sample placed at the level of mitral tips during diastole and at the level of the aortic annulus during systole. Ejection time b was measured from the opening to the closure of the aortic valve on the LV outflow velocity profile. The interval a was obtained from mitral flow recordings from the cessation to the onset of mitral inflow, which was equal to the sum of isovolumic relaxation and contraction time and ejection time. Thus, a b represented the sum of isovolumic relaxation and contraction time. Therefore, the MPI was calculated as: MPI (a b)/b . Tricuspid regurgitation was recorded and pulmonary systolic artery pressure was calculated. All reported parameters are the average of 5 measurements. Follow-up information was obtained from the family physician or by direct-mail questionnaires or interviews. Results are presented as mean SD. A 2-sample t test was performed to compare continuous variables. The chi-square test was used to compare categorical variables. A p value 0.05 was considered statistically significant. The Kaplan-Meier method was used for cumulative survival analysis, with the log-rank test for assessing statistical differences between curves. Univariate analysis was applied to define differences between survivors and deaths. Multivariate Cox proportional-hazards regression (toward stepwise procedure) was used to investigate whether the variables identified with a p value 0.10 in the univariate analysis were independent predictors of mortality. The previously mentioned variables were treated as dichotomous variables. Analysis was done with STATVIEW computer version 5 software (Abacus Concepts, Inc., Berkeley, California). • • • Most patients were men (79%), in New York Heart Association (NYHA) functional class III to IV (77%). Etiology of heart failure was coronary artery disease in 65% and idiopathic-dilated cardiomyopathy in 35%. The baseline clinical and echocardiographic characteristics of patients are listed in Table 1. Mean LV ejection fraction was 33 6% and mean MPI was 0.69 0.30 (range 0.10 to 1.70). There was a significant correlation between the index and the ejection fraction (r 0.35, p 0.0043), the shortening fraction (r 0.34, p 0.006), LV end-diastolic (r 0.40, p 0.0008) and end-systolic (r 0.42, p 0.0005) diameters, and LV end-diastolic (r 0.31, p 0.013) From the Department of Cardiology and the UPRES Unit, South Hospital, University of Picardie, Amiens, France; and the Division of Cardiovascular and Internal Medicine, Mayo Clinic, Rochester, Minnesota. Dr. Slama’s address is: Unite de reanimation, Service de Nephrologie, Hopital Sud, 80054 Amiens Cedex 1, France. E-mail: MSlama0508@aol.com. Manuscript received May 14, 2002; revised manuscript received and accepted July 29, 2002.

High rate of ventricular septal defects in WKY rats.

In 1979, we first reported occurrence of biventricular hypertrophy in the original normotensive Wistar-Kyoto (WKY) strain obtained from the National Heart, Lung, and Blood Institute, which was derived directly from the Kyoto laboratory of Okamoto. At that time, we recommended that both ventricles be weighted when WKY are studied so that invalid conclusions are not made. Because no paper confirmed these findings for almost 20 years, heart weights were reported in only a few WKY studies, and the cause of this biventricular hypertrophy remained unknown, we re-evaluated this problem in commercially available rats. We, therefore, investigated WKY rats using transthoracic echocardiography to define the congenital heart defect. Up to 28% of commercially available WKY rats demonstrated severe congenital cardiac abnormalities associated with biventricular hypertrophy. Ventricular septal defect with pulmonary regurgitation was the most commonly encountered cardiac defect; other abnormalities included patent ductus arteriosus, and valvular defects. Pathologic and invasive hemodynamic studies confirmed these echocardiographic findings. Because this defect occurs in a large number of WKY rats obtained commercially from 2 different sources, investigators using this strain must carefully measure both ventricular weights to be certain that inappropriate and invalid conclusions are not derived therefrom.

Pearls and pitfalls in comprehensive critical care echocardiography

Critical care echocardiography is developing rapidly with an increasing number of specialists now performing comprehensive studies using Doppler and other advanced techniques. However, this imaging can be challenging, interpretation is far from simple in the complex critically ill patient and mistakes can be easy to make. We aim to address clinically relevant areas where potential errors may occur and suggest methods to hopefully improve accuracy of imaging and interpretation.