Pascal de Groote

Right ventricular ejection fraction is an independent predictor of survival in patients with moderate heart failure

OBJECTIVES We sought to study the relationship between survival and right ventricular ejection fraction (RVEF) in a subgroup of patients with moderate congestive heart failure (CHF). BACKGROUND It has been demonstrated that RVEF is an independent predictor of survival in patients with advanced CHF. METHODS Cardiopulmonary exercise testing and radionuclide angiography (to determine right and left ventricular ejection fraction) were prospectively performed in 205 consecutive patients with moderate CHF (140 patients in New York Heart Association [NYHA] class II, 65 in class III). RESULTS Left ventricular ejection fraction was 29.3%+/-10.1%, RVEF was 37.5%+/-14.6% and peak oxygen consumption (VO2) was 16.2+/-5.4 ml/min/kg (60.2%+/-19% of maximal predicted VO2). After a median follow-up period of 755 days, there were 44 cardiac-related deaths, 3 deaths from noncardiac causes and 15 transplantations of whom 2 were urgent; 1 patient was lost to follow-up. Multivariate analysis showed that three variables-NYHA classification, percent of maximal predicted VO2 and RVEF-were independent predictors of both survival and event-free cardiac survival. Left ventricular ejection fraction and peak VO2 normalized to body weight had no predictive value. The event-free survival rates from cardiovascular mortality and urgent transplantation at 1 year were 80%, 90% and 95% in patients with an RVEF <25%, with a RVEF > or =25% and <35% and with a RVEF > or =35%, respectively. At 2 years, survival rates were 59%, 77% and 93% in the same subgroups, respectively. CONCLUSIONS In addition to the NYHA classification and to the percent of maximal predicted VO2, RVEF is an independent predictor of survival in patients with moderate CHF.

Circulating Long Noncoding RNA, LIPCAR, Predicts Survival in Patients With Heart Failure

Rationale: Long noncoding RNAs represent a novel class of molecules regulating gene expression. Long noncoding RNAs are present in body fluids, but their potential as biomarkers was never investigated in cardiovascular disease. Objective: To study the role of long noncoding RNAs as potential biomarkers in heart disease. Methods and Results: Global transcriptomic analyses were done in plasma RNA from patients with or without left ventricular remodeling after myocardial infarction. Regulated candidates were validated in 3 independent patient cohorts developing cardiac remodeling and heart failure (788 patients). The mitochondrial long noncoding RNA uc022bqs.1 (LIPCAR) was downregulated early after myocardial infarction but upregulated during later stages. LIPCAR levels identified patients developing cardiac remodeling and were independently to other risk markers associated with future cardiovascular deaths. Conclusions: LIPCAR is a novel biomarker of cardiac remodeling and predicts future death in patients with heart failure.Rationale: Long non-coding RNAs (lncRNAs) represent a novel class of molecules regulating gene expression. LncRNAs are present in body fluids, but their potential as biomarkers was never investigated in cardiovascular disease. Objective: Role of lncRNAs as potential biomarkers in heart disease. Methods and Results: Global transcriptomic analyses were done in plasma RNA from patients with/without left ventricular (LV)-remodeling after myocardial infarction. Regulated candidates were validated in three independent patient cohorts developing cardiac remodeling and heart failure (788 patients). The mitochondrial lncRNA uc022bqs.1 ( LIPCAR ) was down-regulated early after MI but up-regulated during later stages. LIPCAR levels identified patients developing cardiac remodeling and were independently to other risk markers associated with future cardiovascular deaths. Conclusions: LIPCAR is a novel biomarker of cardiac remodeling and predicts future death in heart failure patients.

Screening for pulmonary arterial hypertension in patients with systemic sclerosis: clinical characteristics at diagnosis and long-term survival.

OBJECTIVE Pulmonary arterial hypertension (PAH) is a severe, life-limiting complication of systemic sclerosis (SSc). Guidelines recommend early detection and management of SSc-PAH. However, little is known about the impact of detection programs on patients with SSc-PAH. This study was undertaken to assess the clinical characteristics of patients with SSc-PAH at diagnosis and their long-term outcomes. METHODS Two incident cohorts of patients with SSc-PAH from the same management era (2002/2003) were studied. The first cohort (designated the routine practice cohort) included consecutive adult patients with symptomatic SSc in whom a diagnosis of PAH was made by right-sided heart catheterization (RHC) at the time of recruitment into the French PAH Registry. The second cohort (designated the detection cohort) comprised consecutive patients with SSc who entered a systematic PAH detection program and were subsequently found to have PAH on RHC. Clinical characteristics at diagnosis of PAH and subsequent 8-year mortality were compared between the cohorts. RESULTS There were 16 patients in each cohort. At the time of PAH diagnosis, patients in the detection cohort had less advanced pulmonary vascular disease compared with patients in the routine practice cohort, as evidenced by more patients being in New York Heart Association class I and class II, a lower mean pulmonary artery pressure and pulmonary vascular resistance index, and a higher cardiac output. Patients in the detection cohort were less likely to receive diuretics and warfarin, but there was no difference in exposure to PAH-specific therapies between the cohorts. The 1-, 3-, 5-, and 8-year survival rates were 75%, 31%, 25%, and 17%, respectively, in the routine practice cohort compared with 100%, 81%, 73%, and 64%, respectively, in the detection cohort (P = 0.0037). CONCLUSION Compared with patients in routine clinical practice, PAH detection programs in SSc are able to identify patients with milder forms of the disease, allowing earlier management.

Influence of diabetes mellitus on heart failure risk and outcome

Our aim is to summarize and discuss the recent literature linking diabetes mellitus with heart failure, and to address the issue of the optimal treatment for diabetic patients with heart failure.The studies linking diabetes mellitus (DM) with heart failure (HF)The prevalence of diabetes mellitus in heart failure populations is close to 20% compared with 4 to 6% in control populations. Epidemiological studies have demonstrated an increased risk of heart failure in diabetics; moreover, in diabetic populations, poor glycemic control has been associated with an increased risk of heart failure. Various mechanisms may link diabetes mellitus to heart failure: firstly, associated comorbidities such as hypertension may play a role; secondly, diabetes accelerates the development of coronary atherosclerosis; thirdly, experimental and clinical studies support the existence of a specific diabetic cardiomyopathy related to microangiopathy, metabolic factors or myocardial fibrosis. Subgroup analyses of randomized trials demonstrate that diabetes is also an important prognostic factor in heart failure. In addition, it has been suggested that the deleterious impact of diabetes may be especially marked in patients with ischemic cardiomyopathy.Treatment of heart failure in diabetic patientsThe knowledge of the diabetic status may help to define the optimal therapeutic strategy for heart failure patients. Cornerstone treatments such as ACE inhibitors or beta-blockers appear to be uniformly beneficial in diabetic and non diabetic populations. However, in ischemic cardiomyopathy, the choice of the revascularization technique may differ according to diabetic status. Finally, clinical studies are needed to determine whether improved metabolic control might favorably influence the outcome of diabetic heart failure patients.

The three-year incidence of pulmonary arterial hypertension associated with systemic sclerosis in a multicenter nationwide longitudinal study in France.

OBJECTIVE An algorithm for the detection of pulmonary arterial hypertension (PAH), based on the presence of dyspnea and the findings of Doppler echocardiographic evaluation of the velocity of tricuspid regurgitation (VTR) and right-sided heart catheterization (RHC), which was applied in a large multicenter systemic sclerosis (SSc) population, estimated the prevalence of PAH to be 7.85%. The aim of this observational study was to investigate the incidence of PAH and pulmonary hypertension (PH) during a 3-year followup of patients from the same cohort (the ItinérAIR-Sclérodermie Study). METHODS Patients with SSc and without evidence of PAH underwent evaluation for dyspnea and VTR at study entry and during subsequent visits. Patients in whom PAH was suspected because of a VTR of 2.8-3.0 meters/second and unexplained dyspnea or a VTR of >3.0 meters/second underwent RHC to confirm the diagnosis. RESULTS A total of 384 patients were followed up for a mean+/-SD of 41.03+/-5.66 months (median 40.92 months). At baseline, 86.7% of the patients were women, and the mean+/-SD age of the patients was 53.1+/-12.0 years. The mean+/-SD duration of SSc at study entry was 8.7+/-7.6 years. After RHC, PAH was diagnosed in 8 patients, postcapillary PH in 8 patients, and PH associated with severe pulmonary fibrosis in 2 patients. The incidence of PAH was estimated to be 0.61 cases per 100 patient-years. Two patients who exhibited a mean pulmonary artery pressure of 20-25 mm Hg at baseline subsequently developed PAH. CONCLUSION The estimated incidence of PAH among patients with SSc was 0.61 cases per 100 patient-years. The high incidence of postcapillary PH highlights the value of RHC in investigating suspected PAH.

Association between beta-1 and beta-2 adrenergic receptor gene polymorphisms and the response to beta-blockade in patients with stable congestive heart failure.

Previous studies have clearly demonstrated the beneficial effect of &bgr;-blockers in patients with stable congestive heart failure (CHF). &bgr;-blockers improve left ventricular ejection fraction (LVEF) and reduce cardiac mortality. However, there is an interindividual variability in the response to these agents. Two studies have suggested a possible impact of some functional &bgr;AR gene polymorphisms on the effects of &bgr;-blockade. The objective of the study is to analyse the association between genetic variations in the &bgr;1 or the &bgr;2 adrenoreceptor (AR) gene and the effects of &bgr;-blockade in patients with stable CHF. We studied 199 consecutive patients with stable CHF not treated with &bgr;-blockers. Before introduction of &bgr;-blockers and 3 months after the maximal tolerated dose was reached, patients underwent an echocardiography and a radionuclide angiography. The &bgr;1ARGly389Arg, &bgr;1ARSer49Gly, &bgr;2ARGly16Arg, &bgr;2ARGln27Glu and &bgr;2ARThr164Ile polymorphisms were determined: &bgr;-blockade resulted in a significant decrease in heart rate, a significant increase in LVEF (from 30±10% to 40±13%, P<0.0001). There was no association between the five polymorphisms and heart rate or LVEF, either before or after &bgr;-blockade. Heart rate and LVEF responses to &bgr;-blockade were not associated with the &bgr;1AR or the &bgr;2AR polymorphisms. &bgr;AR polymorphisms did not explain the interindividual variability in the response to &bgr;-blockers.

Kinetics of oxygen consumption during and after exercise in patients with dilated cardiomyopathy. New markers of exercise intolerance with clinical implications.

OBJECTIVES This study analyzed the kinetics of oxygen consumption during and after a maximal cardiopulmonary exercise test in patients with dilated cardiomyopathy. The prognostic information derived from indexes of recovery was also studied. BACKGROUND Previous studies have examined the kinetics of oxygen consumption during a short recovery period in a limited number of patients. To our knowledge, no study has examined the prognostic information derived from indexes of recovery. METHODS We studied 153 patients and 55 control subjects. We calculated the ratio between total oxygen consumption during exercise and recovery, the half-recovery time of peak oxygen consumption, the time constant of recovery, the recovery time and the ratio between duration of exercise and recovery time. RESULTS Recovery of oxygen consumption was significantly delayed in patients, and this delay was related to the degree of exercise intolerance. After a median follow-up period of 439 days, for the total study group, percent of predicted peak oxygen consumption (p = 0.003) and ejection fraction (p = 0.03) were independent predictors of survival. In a subgroup of patients with moderate exercise intolerance (percent peak oxygen consumption > 40%), the ratio between total oxygen consumption during exercise and recovery (p = 0.013) and the ejection fraction (p = 0.013) were independent predictors of survival. CONCLUSIONS The kinetics of oxygen consumption during recovery was delayed in patients with dilated cardiomyopathy. Although indexes of recovery were not prognostic markers in the total study group, the ratio between total oxygen consumption during exercise and recovery was an independent prognostic marker in patients with moderate exercise intolerance.

Pericardioscopy in the Etiologic Diagnosis of Pericardial Effusion in 141 Consecutive Patients

BACKGROUND Although previous small series have documented the utility of pericardioscopy for accurate etiologic diagnosis of pericardial effusion, this technique remains underused. The aim of our study was to assess the benefits and risks of surgical pericardioscopy in a large prospective series. METHODS AND RESULTS One hundred forty-one consecutive patients with unexplained pericardial effusion underwent 142 pericardioscopies with a rigid mediastinoscope. For each patient, the etiologic data obtained by pericardioscopy (visualization of pericardium, guided biopsies, subxiphoid window biopsy, and fluid analysis) were compared with the results that would have been obtained with only conventional surgical drainage and biopsy (subxiphoid window biopsy and fluid analysis). After complete workup, a specific cause was found in 69 cases (48.6%); the other 73 cases were considered idiopathic effusions (51.4%). Procedural and in-hospital mortality was 8 of 141 patients (5.6%). No death was directly attributable to pericardioscopy. During long-term follow-up (median duration, 24 months; range, 6 to 96), a previously unrecognized cause was discovered in 6 patients (4%). By comparing the areas under the receiver-operating characteristic curves, the diagnostic advantage of pericardioscopy was significant for the whole series (pericardioscopy, 0.98 +/- 0.011; conventional surgical drainage, 0.89 +/- 0.029; P < .001). The increase in sensitivity was more marked for some types such as neoplastic (21%), radiation-induced (100%), or purulent (83%) effusions. CONCLUSIONS Our data demonstrate that pericardioscopy increases the diagnostic sensitivity of surgical pericardial drainage and biopsy without specific risk.

Left Ventricular Response to Exercise in Aortic Stenosis: An Exercise Echocardiographic Study

Background: While normal at rest, left ventricular (LV) systolic function may become abnormal during exercise in patients with aortic stenosis. Once contraindicated in patients with aortic stenosis, exercise testing is now recommended in asymptomatic patients with aortic stenosis to elicit symptoms and thereby ascertain the need for aortic valve replacement. However, the clinical significance of an abnormal LV response to exercise in asymptomatic patients with aortic stenosis remains unknown. Objective: The aim of this study was to evaluate the clinical implications of an abnormal LV response during exercise in the setting of aortic stenosis. Methods: We monitored the LV response to exercise by 2D‐Doppler echocardiography during a symptom limited semirecumbent bicycle exercise in 50 patients with tight aortic stenosis (aortic valve area ≤ 1.0 cm2) and a normal LV systolic function (LV ejection fraction, EF ≥ 50%) and followed them for an average of 11 months. Results: Twenty patients had an abnormal LV response to exercise with a mean decrease in LV EF from 64 ± 10 to 53 ± 12% while 30 patients had a normal LV response to exercise with a mean increase in LV EF from 62 ± 7 to 70 ± 8%. Patients with an abnormal LV response during exercise were more likely to develop symptoms during exercise than patients with a normal LV response: 80% versus 27% (P < 0.0001). The survival free of cardiac events was significantly lower in patients with abnormal LV response to exercise than in patients with a normal response (P = 0.03). Conclusion: Exercise echocardiography provides objective data that facilitate interpretation of exercise elicited symptoms in asymptomatic patients with severe aortic stenosis. In addition, an abnormal LV response to exercise may predict a poor outcome.

Current aspects of the spectrum of acute heart failure syndromes in a real-life setting: the OFICA study.

To improve knowledge of epidemiological data, management, and clinical outcome of acute heart failure (AHF) in a real‐life setting in France.