Imbalanced Angiogenesis in Peripartum Cardiomyopathy　- Diagnostic Value of Placenta Growth Factor.

BACKGROUND: Concentrations of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) are altered in peripartum cardiomyopathy (PPCM). In this study we investigated changes in the angiogenesis balance in PPCM.Methods and Results:Plasma concentrations of sFlt-1 and the pro-angiogenic placenta growth factor (PlGF) were determined in patients with PPCM during the post-partum phase (n=83), in healthy women at delivery (n=30), and in patients with acute heart failure (AHF; n=65). Women with cardiac failure prepartum or associated with any form of hypertension, including pre-eclampsia, were excluded. Compared with non-pregnant women, in women with AHF and PPCM, median PlGF concentrations were greater (19 [IQR 16-22] and 98 [IQR 78-126] ng/mL, respectively; P<0.001) and the sFlt-1/PlGF ratio was lower (9.8 [6.6-11.3] and 1.2 [0.9-2.8], respectively; P<0.001). The sFlt-1/PlGF ratio was lower in PPCM than in normal deliveries (1.2 [0.9-2.8] vs. 94.8 [68.8-194.1], respectively; P<0.0001). The area under the curve for PlGF (cut-off value: 50ng/mL) and/or the sFlt-1/PlGF ratio (cut-off value: 4) to distinguish PPCM from either normal delivery or AHF was >0.94. Median plasma concentrations of the anti-angiogenic factor relaxin-2 were lower in PPCM and AHF (0.3 [IQR 0.3-1.7] and 0.3 [IQR 0.3-1] ng/mL, respectively) compared with normal deliveries (1,807 [IQR 1,101-4,050] ng/mL; P<0.001). CONCLUSIONS: Plasma of PPCM patients shows imbalanced angiogenesis. High PlGF and/or low sFlt-1/PlGF may be used to diagnose PPCM.

[Shall we Follow the Guidelines for Isosorbide Dinitrate in Acute Pulmonary Edema?]. / Y a-t-il une place pour le dinitrate d'isosorbide dans l'œdème aigu pulmonaire ?

PURPOSE: Prospective evaluation of short (dyspnoea) and mid-term outcomes in 47 consecutive patients admitted in the intensive care unit for acute pulmonary edema treated on a liberal basis. RESULTS: Patients were elderly (83 year-old) and 60% had preserved left ventricular ejection fraction (>50%). Dyspnoea assessed by visual analogue score was weakly associated with treatment posology. Despite low use of inotropes (6%) and intubation (9%), hospital and D90 mortality was high (19% and 32% respectively). Higher mortality was noticed in patients receiving no isosorbide dinitrate (p = 0.04). In the multivariate analysis, only age and delta brain natriuretic peptide (difference between BNP on D1 and D0) remained significantly associated with mortality on D90 (OR 1.13; p = 0.03 and OR 1.004; p = 0.04 respectively). CONCLUSION: Acute pulmonary edema carried a dramatic in-hospital and mid-term mortality in our elderly patients. Isosorbide dinitrate was associated with decreased D90 mortality but not in the multivariate analysis.

Electrocardiographic abnormalities in centenarians and octogenarians: a case-matched study.

BACKGROUND: Centenarians have been proposed as a model of successful aging but recent studies suggest a high prevalence of cardiovascular diseases. Some findings on their electrocardiograms (ECGs) are simply age-related and others mirror underlying diseases. We aimed to identify ECG features truly associated with extreme age. METHODS: Retrospective analysis of 55 centenarians hospitalized between January 2000 and June 2010. Each centenarian was matched with three octogenarians according to gender, presence of hypertension, aortic stenosis, heart failure, and ischemic heart disease. RESULTS: A history of hypertension was present in 32 (58%) centenarians, aortic stenosis in 6 (11%), heart failure in 8 (15%), and ischemic heart disease in 6 (11%). Centenarians had a higher heart rate than octogenarians (81 ± 15 bpm vs. 72 ± 15 bpm, respectively, P < 0.001) but were less frequently on beta-blockers (7% vs. 36%, respectively, P < 0.001). Centenarians displayed more frequently atrial premature beats than octogenarians (18% vs. 3%, respectively, P < 0.001) but tended to have less atrial fibrillation (15% vs. 22% respectively, P = 0.21). Centenarians had more frequently left QRS axis deviation (48% vs. 28%, P = 0.009) and Q waves (14% vs. 1%, P = 0.02). QT interval was more prolonged in centenarians (446 ± 42 ms vs. 429 ± 39 ms, P = 0.008). Two centenarians (4%) and 24 (15%) octogenarians had a strictly normal ECG (P = 0.02). CONCLUSIONS: Abnormal ECG is a common finding in centenarians, with different characteristics than in younger elderly individuals. These differences are unrelated to the presence of cardiac diseases.

Impact analysis of heart failure across European countries: an ESC-HFA position paper.

Heart failure (HF) is a long-term clinical syndrome, with increasing prevalence and considerable healthcare costs that are further expected to increase dramatically. Despite significant advances in therapy and prevention, mortality and morbidity remain high and quality of life poor. Epidemiological data, that is, prevalence, incidence, mortality, and morbidity, show geographical variations across the European countries, depending on differences in aetiology, clinical characteristics, and treatment. However, data on the prevalence of the disease are scarce, as are those on quality of life. For these reasons, the ESC-HFA has developed a position paper to comprehensively assess our understanding of the burden of HF in Europe, in order to guide future policies for this syndrome. This manuscript will discuss the available epidemiological data on HF prevalence, outcomes, and human costs-in terms of quality of life-in European countries.

Heart rate per se impacts cardiac function in patients with systolic heart failure and pacing: a pilot study.

AIMS: This study was designed to compare the specific effects of two heart rates (HR), 55 and 75 b.p.m., in patients with heart failure (HF). METHODS AND RESULTS: Patients with chronic HF, left ventricular ejection fraction (LVEF) 90% of paced QRS, were included in a randomized cross-over trial of two 3-month periods where pacing rate was set at either 55 or 75 b.p.m. At the end of each period, patients were examined and radionuclide ventriculography, echocardiography, and blood sampling were performed for centralized and blinded analysis. Two patients did not complete the study because of early worsening while paced at 75 b.p.m. Twelve patients completed the study. Compared with 75 b.p.m., pacing at 55 b.p.m. was associated with a higher LVEF [+4.7% (2.6-6.7), P < 0.001], lower B-type natriuretic peptide levels [-91 pg/mL (-148 to -33), P < 0.01], lower systolic pulmonary artery pressure (41 +/- 10 vs. 47 +/- 10 mmHg, P = 0.02) and lower NYHA (New York Heart Association) class (2.2 +/- 0.6 vs. 2.6 +/- 0.5, P = 0.03). The baseline pacing rate prior to inclusion had no effect on results. CONCLUSION: HR per se may impact cardiac function and low HR might be beneficial in patients with systolic HF compared with intermediate HR.

[Not Available]. / Comment évaluer et traiter l'insuffisance cardiaque à fraction d'éjection préservée.

The concept of heart failure with preserved left ventricular ejection fraction has replaced that of diastolic heart failure. It is today the most frequent presentation of heart failure because of the progressive aging of the population. Its prognosis appears to be similar to that of heart failure with reduced systolic function. B type natriuretic peptide dosing as well as doppler-echocardiography are useful for the diagnosis. Today, no treatment has revealed effective but clinical trials have been scarce. Renin-angiotensin system antagonists have promising properties but haven't shown efficacy. This article reviews the epidemiologic, diagnostic, pathophysiologic and therapeutic aspects of the disease.

French Society of Cardiology guidelines on exercise tests (part 2): Indications for exercise tests in cardiac diseases.

The exercise test is performed routinely in cardiology; its main indication is the diagnosis of myocardial ischemia, evaluated along with the subject's pretest probability and cardiovascular risk level. Other criteria, such as analysis of repolarization, must be taken into consideration during the interpretation of an exercise test, to improve its predictive value. An exercise test is also indicated for many other cardiac diseases (e.g. rhythm and conduction disorders, severe asymptomatic aortic stenosis, hypertrophic cardiomyopathy, peripheral artery disease, hypertension). Moreover, an exercise test may be indicated for specific populations (women, the elderly, patients with diabetes mellitus, patients in a preoperative context, asymptomatic patients and patients with congenital heart defects). Some cardiac diseases (such as chronic heart failure or arterial pulmonary hypertension) require a cardiopulmonary exercise test. Finally, an exercise test or a cardiopulmonary exercise test is indicated to prescribe a cardiac rehabilitation programme, adapted to the patient.

Safety, Tolerability and efficacy of Rapid Optimization, helped by NT-proBNP and GDF-15, of Heart Failure therapies (STRONG-HF): rationale and design for a multicentre, randomized, parallel-group study.

AIMS: Patients admitted for acute heart failure (HF) are at high risk of readmission and death, especially in the 90 days following discharge. We aimed to assess the safety and efficacy of early optimization of oral HF therapy with beta-blockers (BB), angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) or angiotensin receptor-neprilysin inhibitors (ARNi), and mineralocorticoid receptor antagonists (MRA) on 90-day clinical outcomes in patients admitted for acute HF. METHODS: In a multicentre, randomized, open-label, parallel-group study, a total of 900 patients will be randomized in a 1:1 ratio to either 'usual care' or 'high-intensity care'. Patients enrolled in the usual care arm will be discharged and managed according to usual clinical practice at the site. In the high-intensity care arm, doses of oral HF medications - including a BB, ACEi or ARB, and MRA - will be up-titrated to 50% of recommended doses before discharge and to 100% of recommended doses within 2 weeks of discharge. Up-titration will be delayed if the patients develop worsening symptoms and signs of congestion, hyperkalaemia, hypotension, bradycardia, worsening of renal function or significant increase in N-terminal pro-B-type natriuretic peptide between visits. The primary endpoint is 90-day all-cause mortality or HF readmission. CONCLUSIONS: STRONG-HF is the first study to assess whether rapid up-titration of evidence-based guideline-recommended therapies with close follow-up in a large cohort of patients discharged from an acute HF admission is safe and can affect adverse outcomes during the first 90 days after discharge. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03412201.

French Society of Cardiology guidelines on exercise tests (part 1): Methods and interpretation.

The exercise test is still a key examination in cardiology, used for the diagnosis of myocardial ischemia, as well as for the clinical evaluation of other heart diseases. The cardiopulmonary exercise test can further define functional capacity and prognosis for any given cardiac pathology. These new guidelines focus on methods, interpretation and indications for an exercise test or cardiopulmonary exercise test, as summarized below. The safety rules associated with the exercise test must be strictly observed. Interpretation of exercise tests and cardiopulmonary exercise tests must be multivariable. Functional capacity is a strong predictor of all-cause mortality and cardiovascular events. Chest pain, ST-segment changes and an abnormal ST/heart rate index constitute the first findings in favor of myocardial ischemia, mostly related to significant coronary artery disease. Chronotropic incompetence, abnormal heart rate recovery, QRS changes (such as enlargement or axial deviations) and the use of scores (based on the presence of various risk factors) must also be considered in exercise test interpretation for a coronary artery disease diagnosis. Arrhythmias or conduction disorders arising during the exercise test must be considered in the assessment of prognosis, in addition to a decrease or low increase in blood pressure during the exercise phase. When performing a cardiopulmonary exercise test, peak oxygen uptake and the volume of expired gas/carbon dioxide output slope are the two main variables used to evaluate prognosis.

Biomarker-based strategy for screening right ventricular dysfunction in patients with non-massive pulmonary embolism.

OBJECTIVE: To evaluate the usefulness of B-type natriuretic peptide and troponin I measurements in predicting right ventricular dysfunction (RVD) in non-massive pulmonary embolism. DESIGN: Prospective observational study. SETTING: University-affiliated emergency unit, cardiology and pneumology departments. PATIENTS: Sixty-seven patients admitted because of acute pulmonary embolism, without shock on admission, completed the study. INTERVENTIONS: Blood samples and echocardiography were obtained on admission for subsequent and independent assessment of B-type natriuretic peptide (BNP) and troponin I levels as well as RVD. MEASUREMENTS AND RESULTS: Echocardiographic RVD was diagnosed in 36 patients and was severe in 13 on admission. BNP and troponin I levels were higher in patients with RVD than in those with no RVD [62 (27-105) vs. 431 (289-556) pg/ml for BNP, p<0.001; 0.01 (0-0.09) vs. 0.16 (0.03-0.32) microg/l for troponin I, p=0.005]. The area under the receiving operating characteristic curve (AUC) for diagnosing RVD was 0.93 for BNP and 0.72 for troponin I. The troponin I level increased further when RVD was severe, compared with moderate, and the AUC was 0.91 for identifying severe RVD. Diagnoses of RVD and severe RVD were ruled out by BNP100 pg/ml and troponin I >0.10 microg/l. CONCLUSION: In hemodynamically stable pulmonary embolism, BNP/troponin I measurement is helpful on admission, especially for ruling out RVD, i.e. patients with in-hospital high-risk.

Comparative effect of aspirin and clopidogrel on arterial function in CHF.

BACKGROUND: By inhibiting prostaglandins, aspirin may be deleterious in congestive heart failure (CHF) and/or partially counteract the efficacy of angiotensin-converting enzyme inhibitors (ACEI). Conversely, clopidogrel has no effect on prostaglandin metabolism. The aim of this study was to prospectively investigate the effect of aspirin and clopidogrel on arterial functional properties in CHF patients treated with ACEI. METHODS: Forty-five patients with stable NYHA class II-IV CHF (64.0+/-15.5 years), ejection fraction <40%, were included in this prospective double-blind study and randomized to receive aspirin 325 mg/day or clopidogrel 75 mg/day for 14 days. Reflected wave assessed by radial applanation tonometry and pulse wave velocity (PWV) were measured at day 0 and day 14. RESULTS: Aspirin resulted in an increase in the augmentation index of the reflected wave (Delta=+3.5+/-5.2%, p=0.005) and the height above the shoulder of the reflected wave (Delta=+1.7+/-3.1 mm Hg, p=0.023), without statistically variation in PWV. Conversely, clopidogrel had no effect on the same parameters (p=0.512, p=0.677 and 0.801, respectively). Overall, variations in the augmentation index of reflected wave significantly differed when compared aspirin with clopidogrel (p=0.0261). CONCLUSION: This study demonstrates the existence of a negative effect of aspirin 325 mg/day when compared to clopidogrel 75 mg/day on arterial functional properties in CHF patients treated with ACEI.

Predischarge B-type natriuretic peptide assay for identifying patients at high risk of re-admission after decompensated heart failure.

OBJECTIVES: The aim of this study was to determine the value of serial B-type natriuretic peptide (BNP) assay for predicting post-discharge outcome of patients admitted for decompensated congestive heart failure (CHF). BACKGROUND: Patients hospitalized for decompensated CHF are frequently re-admitted. Thus, identification of high-risk patients before their discharge is a major issue that remains challenging. B-type natriuretic peptide measurement could be useful. METHODS: Serial BNP measurements were performed from admission to discharge in two samples of consecutive patients. Survivors were monitored for six months; the main end point combined death or first re-admission for CHF. RESULTS: Among the 105 survivors of the derivation study, all serial BNP values, percentage change in BNP levels, and predischarge Doppler mitral pattern correlated with the outcome. In contrast, clinical variables and left ventricular ejection fraction were poorly predictive. The predischarge BNP assay had the best discriminative power (area under the receiver operating characteristic [ROC] curve = 0.80) and remained the lone significant variable in multivariate analysis (hazard ratio [HR] = 1.14 [95% confidence interval [CI], 1.02 to 1.28], p = 0.027). Among the 97 survivors of the validation study, the predischarge BNP assay was also the most predictive parameter (area under the ROC curve = 0.83). The risk of death or re-admission increased in stepwise fashion across increasing predischarge BNP ranges (p < 0.0001). After adjustment for baseline covariables, the HRs were 5.1 [95% CI 2.8 to 9.1] for BNP levels between 350 and 700 ng/l and 15.2 [95% CI 8.5 to 27] for BNP levels >700 ng/l, compared with BNP <350 ng/l. CONCLUSIONS: High predischarge BNP assay is a strong, independent marker of death or re-admission after decompensated CHF, more relevant than common clinical or echocardiographic parameters and more relevant than changes in BNP levels during acute cares.

Comparative value of Doppler echocardiography and B-type natriuretic peptide assay in the etiologic diagnosis of acute dyspnea.

OBJECTIVES: We compared the accuracy of B-type natriuretic peptide (BNP) assay with Doppler echocardiography for the diagnosis of decompensated congestive left-heart failure (CHF) in patients with acute dyspnea. BACKGROUND: Both BNP and Doppler echocardiography have been described as relevant diagnostic tests for heart failure. METHODS: One hundred sixty-three consecutive patients with severe dyspnea underwent BNP assay and Doppler echocardiogram on admission. The accuracy of the two methods for etiologic diagnosis was compared on the basis of the final diagnoses established by physicians who were blinded to the BNP and Doppler findings. RESULTS: The final etiologic diagnosis was CHF in 115 patients. Twenty-four patients (15%) were misdiagnosed at admission. The BNP concentration was 1,022 +/- 742 pg/ml in the CHF subgroup and 187 +/- 158 pg/ml in the other patients (p < 0.01). A BNP cutoff of 300 pg/ml correctly classified 88% of the patients (odds ratio [OR] 85 [19 to 376], p < 0.0001), but a high negative predictive value (90%) was only obtained when the cutoff was lowered to 80 pg/ml. The etiologic value of BNP was low in patients with values between 80 and 300 pg/ml (OR 1.85 [0.4 to 7.8], p = 0.4) and also in patients who were studied very soon after onset of acute dyspnea. Among the 138 patients with assessable Doppler findings, a "restrictive" mitral inflow pattern had a diagnostic accuracy for CHF of 91% (OR 482 [77 to 3,011], p < 0.0001), regardless of the BNP level. CONCLUSIONS: Bedside BNP measurement and Doppler echocardiography are both useful for establishing the cause of acute dyspnea. However, Doppler analysis of the mitral inflow pattern was more accurate, particularly in patients with intermediate BNP levels or "flash" pulmonary edema.

Circulating microRNAs and Outcome in Patients with Acute Heart Failure.

BACKGROUND: The biomarker value of circulating microRNAs (miRNAs) has been extensively addressed in patients with acute coronary syndrome. However, prognostic performances of miRNAs in patients with acute heart failure (AHF) has received less attention. METHODS: A test cohort of 294 patients with acute dyspnea (236 AHF and 58 non-AHF) and 44 patients with stable chronic heart failure (CHF), and an independent validation cohort of 711 AHF patients, were used. Admission levels of miR-1/-21/-23/-126/-423-5p were assessed in plasma samples. RESULTS: In the test cohort, admission levels of miR-1 were lower in AHF and stable CHF patients compared to non-AHF patients (p = 0.0016). Levels of miR-126 and miR-423-5p were lower in AHF and in non-AHF patients compared to stable CHF patients (both p<0.001). Interestingly, admission levels of miR-423-5p were lower in patients who were re-admitted to the hospital in the year following the index hospitalization compared to patients who were not (p = 0.0001). Adjusted odds ratio [95% confidence interval] for one-year readmission was 0.70 [0.53-0.93] for miR-423-5p (p = 0.01). In the validation cohort, admission levels of miR-423-5p predicted 1-year mortality with an adjusted odds ratio [95% confidence interval] of 0.54 [0.36-0.82], p = 0.004. Patients within the lowest quartile of miR-423-5p were at high risk of long-term mortality (p = 0.02). CONCLUSIONS: In AHF patients, low circulating levels of miR-423-5p at presentation are associated with a poor long-term outcome. This study supports the value of miR-423-5p as a prognostic biomarker of AHF.

Pentoxifylline in heart failure: a meta-analysis of clinical trials.

BACKGROUND: Pentoxifylline possess antiinflammatory and rheological properties and has been tested in heart failure (HF). METHODS: A comprehensive search was performed from 1980 until July 2013 in PubMed, to identify randomized controlled trials evaluating pentoxifylline versus placebo in HF, to determine impact on mortality. Search strategy is as follows: "Pentoxifylline" AND "heart" AND "trial". Study selection of six randomized controlled trials evaluating mortality as outcome. Then, we conducted a meta-analysis of randomized controlled trials versus placebo in HF. Determination of Mantel-Haenszel fixed effect and random-effect pooled odds ratios for all-cause mortality and corresponding 95% confidence intervals. RESULTS: Data from a total of 221 patients with LVEF ≤40% from six randomized controlled trials were included in this analysis. Pentoxifylline 1200 mg per day was administered during 6 months, except in one study (administered during 1 month for severe acute HF). The use of pentoxifylline was not significantly associated with a reduction in mortality in HF in individual studies. The pooled data including 221 patients showed a nearly fourfold reduction in mortality (5.4% vs. 18.3%; OR 0.29; CI 0.12-0.74; P < 0.01) with homogenous results (I² 0%). CONCLUSION: A meta-analysis evaluating pentoxifylline versus placebo in HF suggested a significant nearly fourfold decrease in all-cause mortality in the pentoxifylline group.

Influence of systolic blood pressure on clinical outcomes in elderly heart failure patients treated with nebivolol: data from the SENIORS trial.

AIMS: There is limited information about the effects of beta-blockers in heart failure (HF) stratified by blood pressure, especially in the elderly and those with preserved EF. We evaluate the effects of nebivolol on outcomes in elderly patients with HF stratified by baseline systolic blood pressure (SBP) and EF. METHODS AND RESULTS: The SENIORS trial evaluated the effects of nebivolol and enrolled 2128 patients ≥ 70 years of age with HF. Patients were divided into three baseline pre-treatment SBP categories (<110, 110-130, and >130 mmHg). In addition, we evaluated the influence of SBP (≤ 130 and > 130 mmHg) on patients with LVEF <40% vs. ≥ 40%. Low baseline SBP was associated with worse clinical outcomes irrespective of treatment group, both in patients with reduced EF and in those with preserved EF. Nebivolol had similar benefits irrespective of baseline SBP: the hazard ratio (HR) for primary outcome of all-cause mortality or cardiovascular hospitalization in the three SBP categories for nebivolol vs. placebo was 0.85 [95% confidence interval (CI) 0.50-1.45], 0.79 (95% CI 0.61-1.01), and 0.88 (95% CI 0.72-1.07), respectively (P for interaction = 0.61). Similar results were obtained for the secondary endpoint of all-cause mortality. There was no significant interaction for the effects of nebivolol by baseline SBP stratified by LVEF. CONCLUSIONS: Elderly HF patients with lower SBP have a worse outcome than those with higher SBP, but nebivolol appears to be safe and well tolerated, with similar benefits on the composite outcome of death or cardiovascular hospital admission irrespective of baseline SBP and LVEF.