Diagnosis and management of heart failure from hospital admission to discharge: A practical expert guidance.

Heart failure (HF) has high event rates, mortality, and is challenging to manage in clinical practice. Clinical management is complicated by complex therapeutic strategies in a population with a high prevalence of comorbidity and general frailty. In the last four years, an abundance of research has become available to support multidisciplinary management of heart failure from within the hospital through to discharge and primary care as well as supporting diagnosis and comorbidity management. Within the hospital setting, recent evidence supports sacubitril-valsartan combination in frail, deteriorating or de novo patients with LVEF≤40%. Furthermore, new strategies such as SGLT2 inhibitors and vericiguat provide further benefit for patients with decompensating HF. Studies with tafamidis report major clinical benefits specifically for patients with ATTR cardiac amyloidosis, a remaining underdiagnosed and undertreated disease. New evidence for medical interventions supports his bundle pacing to reduce QRS width and improve haemodynamics as well as ICD defibrillation for non-ischemic cardiomyopathy. The Mitraclip reduces hospitalisations and mortality in patients with symptomatic, secondary mitral regurgitation and ablation reduces mortality and hospitalisations in patients with paroxysmal and persistent atrial fibrillation. In end-stage HF, the 2018 French Heart Allocation policy should improve access to heart transplants for stable, ambulatory patients and, mechanical circulatory support should be considered to avoid deteriorating on the waiting list. In the community, new evidence supports that improving discharge education, treatment and patient support improves outcomes. The authors believe that this review fills the gap between the guidelines and clinical practice and provides practical recommendations to improve HF management.

[ST elevation myocardial infarction in young adults: Is there an interest for thrombophilia screening?] / Syndrome coronarien aigu avec sus-décalage du segment ST chez les jeunes adultes : le bilan de thrombophilie a-t-il un intérêt ?

BACKGROUND: Coronary lesions characteristics as well as patient thrombogenicity can explain coronary events manifestation. In young patient, local conditions are usually less important and thrombogenicity could play a significant role. Assessing thrombophilia could be justified in young patients and may induce an adapted therapeutic management. PURPOSE: We aimed to assess the prevalence of thrombophilia and therapeutic modification in young adults aged≤55 years admitted in our department for ST elevation myocardial infarction (STEMI). METHODS: From January 2013 to January 2017, data on all patients aged≤55 years with STEMI admitted in emergency were retrospectively retrieved from our database. Thrombophilia investigation was made regarding clinical (with or without cardiovascular risk factors [CVRF]), biological and/or angiographic evaluation. RESULTS: A total of 133 patients aged≤55 years with STEMI were included. Cardiac arrest occurred in 15 patients (11%). One or less CVRF were found in 47 patients (35%). Smoking was reported in 93 patients (70%) and drug addiction (cannabis, cocaine) in 19 patients (14%). A subset of 51 patients (38%) were screened for thrombophilia. Patients with thrombophilia assessment were younger, less active smokers and presented less CVRF than patients without investigation (P<0.001). Single vessel diseased was found in 88 patients (66%). No differences regarding coronary procedural characteristic were found between the two groups. The most frequently encountered aetiology, found in 122 patients (92%), was de novo intra-arterial thrombosis related to atherosclerosis. In patients with thrombophilia assessment (n=51), one or more abnormal biological results was found in 22 patients (43%) and a therapeutic adjustment was made in 6 patients (12%). CONCLUSION: Thrombophilia screening in young STEMI adults showed an abnormality in 43% of cases. Antithrombotic treatment can be modified after its demonstration.

Inflammation versus mechanical stretch biomarkers over time in acutely decompensated heart failure with reduced ejection fraction.

Heart failure can be associated with inflammation but it is unclear if inflammation is directly related to hemodynamic worsening or is an independent pathway. Our aim was to investigate inflammation and mechanical stress using serial measurements of biomarkers in acute and chronic heart failure with reduced ejection fraction (AHF and CHF). METHOD: The following biomarkers were measured on admission, at discharge and one month after discharge: B-type natriuretic peptide (BNP), high-sensitivity C-Reactive protein (hsCRP), Tumour Necrosis Factor alpha (TNFα), interleukin 6 (IL6), myeloperoxidase (MPO), suppression of tumorigenicity 2 (ST2), mid-regional pro-adrenomedullin (MR-proADM), galectin 3 (Gal3), Growth differentiating factor 15 (GDF15) and procalcitonin (PCT). RESULTS: In control CHF group (n=20, 69±11y, NYHA 1-2), most biomarker levels were low and stable over time. In AHF (n=55, 71±14y), BNP, ST2 and GDF15 levels were highly increased on admission and then decreased rapidly with clinical improvement; BNP, ST2 and GDF15 levels were statistically correlated (r=0.64, 0.46 and 0.39; p<0.001 for both). Both hsCRP, MPO, TNFα and Gal3 levels were increased in most AHF patients (70, 56, 83 and 98% respectively) with poor change over time. HsCRP, MPO and TNFα levels were correlated. IL6, MR-proADM and PCT levels were slightly increased, without change over time. Highest quartiles of BNP and ST2 were associated with death or readmission at one year (HR 2.33 [95CI 1.13-4.80] and 2.42 [1.27-4.60]). CONCLUSION: AHF is associated with systemic inflammation. This inflammatory response continued up to one month after discharge despite normalisation of mechanical stress-related markers.

[Heart failure with preserved ejection fraction: a systemic disorder?]. / L'insuffisance cardiaque à fraction d'éjection préservée : une maladie de système ?

When the syndrome of heart failure (HF) is due to left ventricular (LV) systolic dysfunction the clinical manifestations and natural history of the syndrome depend primarily on the severity of LV systolic dysfunction. In contrast, when the syndrome is attributed to LV diastolic dysfunction multiple comorbidities are responsible for the clinical manifestations and the natural history of the syndrome. The present review underscores the multifactorial pathogenesis of the syndrome of HF associated with LV diastolic dysfunction that nowadays is more properly referred to as HF with preserved LV ejection fraction (HFpEF) than to diastolic HF. The prognosis is similarly poor whether HF is due to systolic dysfunction or associated with diastolic dysfunction. The cause of death that is commonly non-cardiovascular in HFpEF supports the pathogenic importance of comorbidities in this condition. Hypertension, chronic kidney disease (CKD), diabetes, obesity and sleep disorder breathing are among the most frequent comorbidities in HFpEF. These comorbidities account for the multiple clinical presentations of the syndrome of HFpEF. Limited functional capacity is in HFpEF largely related to the downward spiral between CKD mediated fluid accumulation and LV stiffness as well as altered ventricular-vascular coupling. The diagnosis of HFpEF currently relies on 2D-Doppler echocardiography findings of impaired LV relaxation and increased LV stiffness and to a lesser extent on biomarkers. Owing to both lack of stringent inclusion and exclusion enrollment criteria and mistaken therapeutic target, placebo-controlled randomized therapeutic trials have been so far negative in HFpEF.

Prognostic value of plasma B-type natriuretic peptide in patients with severe cardiotoxic drug poisoning.

BACKGROUND/OBJECTIVES: Cardiotoxic drug poisoning can lead to severe cardiac shock (CS) and death. B-type natriuretic peptide (BNP) is a well-established diagnostic and prognostic marker in heart failure but has never been assessed in patients with cardiotoxic drug poisoning. The aim of the study was to determine whether BNP could be useful for early stratification of patients admitted to intensive care unit. METHODS: 30 consecutive patients experiencing shock and cardiotoxic drug exposure were enrolled in a prospective monocentric study and underwent at least two BNP measurements within the first 24 h after admission. RESULTS: While BNP values on admission were poorly informative, subsequent BNP measurements (11 ± 6 h after admission) were significantly increased in patients with CS compared to those with non-CS (756; [364-1130] versus 24; [15-65] pg/ml respectively; P = 0.008). This second BNP level was also significantly increased in non-survivor patients compared to survivor patients (784; [654-1028] versus 29; [15-104] pg/ml respectively; P = 0.05): BNP levels above 360 pg/ml predicted in-hospital mortality (sensitivity = 100%, specificity = 92%). In a multivariate analysis, BNP, SAPS II score and lactate blood level were associated with death. CONCLUSIONS: Serial BNP measurements after admission for cardiotoxic drug poisoning are useful to identify patients at the highest risk of CS as well as in-hospital death.

[Advantages of vasodilating beta-blockers in congestive heart failure]. / Intérêt des bêtabloquants vasodilatateurs dans l'insuffisance cardiaque.

Beta-blockers play a pivotal role in the treatment of chronic systolic heart failure. However, the pharmacological family of beta-blockers is inhomogeneous regarding their pharmacological properties and their clinical effects can differ substantially according to different pharmacological properties. Because of vasodilator effects, the third generation of beta-blockers has additional potential across the cardiovascular diseases, from hypertension to heart failure. Nebivololol has both high selectivity for beta1-adrenergic receptors, no intrinsic sympathetic activity and ability to stimulate endothelial nitric oxide production. Such properties result in specific hemodynamic effects compared with others beta-blockers. Such properties also result in both high tolerability and positive metabolic effects which are crucial in high-risk groups. In the SENIORS trial, nebivolol demonstrated its efficacy and high tolerability in elderly patients with chronic heart failure irrespective of the left ventricular ejection fraction. More clinical trials would be useful to exhibit specific benefits of nebivolol in other high-risk groups of patients.

A hereditary moyamoya syndrome with multisystemic manifestations.

OBJECTIVE: We report a detailed description of a family affected by a hereditary multisystem disorder associated with moyamoya syndrome. METHODS: In this family case report, we evaluated 9 members of the same family originating from Algeria. Investigations included neuroimaging, cardiologic and ophthalmologic evaluation, hormonal testing, hemoglobin electrophoresis, chromosomal karyotyping, muscle biopsy for morphology, immunohistochemistry and enzyme assays, mtDNA mutation screening, and haplotype analysis of 2 loci previously linked to moyamoya, on chromosomes 10 (ACTA2) and 17. RESULTS: Five males related through a maternal lineage were affected, suggesting an X-linked inheritance. Four of them had symptomatic moyamoya syndrome with an onset of acute neurologic manifestations between 4 and 32 years. Hypergonadotropic hypogonadism, azoospermia, short stature of postnatal onset (-2 to -4 SD in adulthood), premature graying of hair, and dysmorphism were present in all patients. The other features of the disease included early cataract in 4, dilated cardiomyopathy in 3, and partial growth hormone deficiency in 2 members. Muscle biopsy data did not reveal signs of a mitochondrial disorder. All conditions known to be associated with moyamoya syndrome such as Down syndrome, neurofibromatosis, and sickle cell disease were excluded. We also excluded linkage to the 2 loci previously reported to be involved in autosomal dominant syndromic and nonsyndromic moyamoya. Carrier females had normal phenotype and clinical history. CONCLUSIONS: These data strongly suggest that this family is affected by a hereditary moyamoya multisystem disorder with X-linked recessive pattern of inheritance.

[Diabetes and heart failure, a fatal association]. / Diabète et insuffisance cardiaque, une association morbide.

The prevalence of heart failure and diabetes are both increasing: 25 to 30% of patients with heart failure suffer from diabetes, and the latter aggravates heart failure. The presence of macro- or micro-angiopathy, cardiac neuropathy or renal failure worsens the clinical pattern and disturbs treatment strategies. Doppler-echocardiography and the dosage of BNP can probably help to detect and consequently to treat prematurely heart failure in the diabetic patient. The usual treatments in heart failure have similar or lower efficacy in the diabetic patient, and treatment intolerance is frequent. Treatments used for diabetes can be handled with difficulty in case of heart failure (metformin, glitazones). In the future, it is therefore extremely important: 1--to prevent the occurrence of diabetes in patients with glucose intolerance; 2--in diabetic patients, to prematurely detect cardiac dysfunction and optimally control diabetes, in order to avoid its occurrence; 3--and finally, in diabetic patients with heart failure, to optimize the medical treatment, in order that these patients have similar benefits compared to non-diabetic patients with heart failure. The ACE-inhibitors and angiotensin-2 antagonists seem to have an important role. Treatments breaking the glycation bridges, as well as statins, appear as interesting therapeutic options. Finally, the exact role of myocardial revascularization, either by angioplasty or surgery, might probably be important.

[Rotational coronary angiography]. / Angiographie coronaire rotationnelle.

CONTEXT: Rotational angiography (RA) is a radiological technique that provides multiple views of a vessel for a single injection of contrast. Its significance in the field of coronary angiography is poorly known at present. This study aimed to compare the radiation dose as well as the volume of contrast used during RA compared to standard angiography (SA), and to evaluate its diagnostic precision. METHOD: 78 patients sent for diagnostic coronary angiography were explored using the radial approach. The patients were randomised between RA (3 acquisitions for the left coronary and 1 for the right coronary) or SA. Once a decision to undertake angioplasty had been made following the angiography (RA or SA), the initial study was complemented using the alternative technique (SA or RA) before the angioplasty procedure was performed at a later stage. The severity of the lesions as shown by RA and SA was compared by four experienced coronary angiography operators. RESULTS: 65 patients (mean age 61+/-10 years--mean BMI 26+/-4 Kg/m2) underwent complete RA+SA investigation. The total x-ray dose used during ciné-angiography, the dose received by the patient, and the volume of contrast were significantly reduced in the RA group compared to the SA group (-25%; -36%; -33% respectively). An evaluation of the severity of the stenoses was performed on 168 arterial segments. There was a significant correlation between the two techniques (R=0.95--p<0.001) and the intra-observer variability was non significant (3.7+/-6.8%--p=NS). CONCLUSIONS: Rotational angiography allows the radiation dose and the volume of contrast to be reduced, while retaining a diagnostic precision similar to that of standard angiography.

[Massive pulmonary embolism and stroke due to thrombus across the foramen ovale]. / Thrombus enclavé dans le foramen ovale responsable d'embolie pulmonaire et d'accident vasculaire cérébral.

We report the case of a man admitted for massive pulmonary embolism. Transthoracic echocardiography showed a serpentine thrombus in the right atrium across the foramen oval. Because of an acute worsening of the circulatory insufficiency, an intravenous thrombolysis was prescribed and the patient recovered progressively. An early control echocardiography showed the disappearing of the intracardiac thrombus and no evidence of abnormality of interatrial septum. While there was no evidence of venous thrombosis in legs, a renal cancer was diagnosed by echography. Silent stroke were highlighted at the scanner. This clinical case leads to discuss the origin of thrombus (in situ formation or thrombus migration) as well as the treatment (heparinotherapy, thrombolysis, surgical embolectomy, definitive closure of the foramen oval).

Cardiac resynchronisation therapy reduces functional mitral regurgitation during dynamic exercise in patients with chronic heart failure: an acute echocardiographic study.

OBJECTIVES: To assess non-invasively the acute effects of cardiac resynchronisation therapy (CRT) on functional mitral regurgitation (MR) at rest and during dynamic exercise. METHODS: 21 patients with left ventricular (LV) systolic dysfunction and functional MR at rest, treated with CRT, were studied. Each patient performed a symptom-limited maximal exercise with continuous two dimensional Doppler echocardiography twice. The first exercise was performed with CRT; the second exercise was performed without CRT. Mitral regurgitant flow volume (RV), effective regurgitant orifice area (ERO) and LV dP/dt were measured at rest and at peak exercise. RESULTS: CRT mildly reduced resting mitral ERO (mean 8 (SEM 2) v 11 (2) mm(2) without CRT, p = 0.02) and RV (13 (3) v 18 (3) ml without CRT, p = 0.03). CRT attenuated the spontaneous increase in mitral ERO and RV during exercise (1 (1) v 9 (2) mm(2), p = 0.004 and 1 (1) v 8 (2) ml, p = 0.004, respectively). CRT also significantly increased exercise-induced changes in LV dP/dt (140 (46) v 479 (112) mm Hg/s, p < 0.001). CONCLUSION: Attenuation of functional MR, induced by an increase in LV contractility during dynamic exercise, may contribute to the beneficial clinical outcome of CRT in patients with chronic heart failure and LV asynchrony.

Interaction between pulse wave velocity, augmentation index, pulse pressure and left ventricular function in chronic heart failure.

Pulse wave velocity (PWV), the carotid augmentation index (AIx), and pulse pressure (PP) may be prognostic factors in heart failure, but the possible influence of the ejection fraction (EF) and other simple haemodynamic variables on them has not been investigated in this setting. Noninvasive methods were used to measure carotid-radial (CR), carotid-femoral (CF) PWV and AIx, and brachial PP, in 135 consecutive patients with stable symptomatic chronic heart failure. The patients were divided into two groups, with preserved (>or=40%) or reduced (<40%) EF. CF-PWV, AIx and PP were lower in the decreased EF group (8.85+/-2.77 versus 10.60+/-2.75 m/s, P<0.001; 121+/-21 versus 132+/-24, P=0.009 and 41+/-19 versus 67+/-17 mmHg, P<0.001), but CR-PWV values were similar regardless of the EF status. These results were not modified after adjustment for age and sex. Multiple regression analysis showed that AIx and PP were systematically related to time domain parameters (heart rate or ejection duration) and EF, whatever the group. CF-PWV was weakly related to time domain values and unrelated to mean blood pressure (BP) or EF in the preserved EF group, whereas it was related to both mean BP and EF in the low EF group. In conclusion, whatever the EF level, PP and AIx were strongly modulated in the time domain, by pressure and by the EF level. The same relationships were found with CF-PWV, but only in the reduced EF group. Whether CF-PWV is the best prognostic factor in patients with 'diastolic' heart failure must be confirmed in a prospective study.

[Heart failure and cachexia]. / Insuffisance cardiaque et cachexie.

Cachexia is related to a malnutrition state related to hypercatabolism. Initially described in cancer, it is also related to several chronic diseases including heart failure. Defined by an unintentional weight loss exceeding 7.5% of body mass during more than 6 months, it is presented by the association of nutritional deficiencies, digestive and/or urinary losses as well as metabolic abnormalities causing fat and lean mass loss and is associated to a poor prognosis. The pathophysiology of cachexia and heart failure presented some similarities associating especially neuro-hormonal activation, a cortisol/DHEA ratio imbalance, as well as pro-inflammatory cytokines activation. Currently the treatment of cachexia is mainly preventive, based on ACE-inhibitors and beta-blockers therapy and physical reconditioning. The benefits of hormonal and nutritional substitutes remains to be evidenced.

[Medical treatment of acute heart failure]. / Traitement médical de l'insuffisance cardiaque aiguë décompensée.

Medical treatment of acute decompensated heart failure has little changed in the last years, except with the advent of non-invasive ventilation. Doppler-echocardiography and BNP dosing have simplified the diagnostic approach and limited the need for invasion evaluation. Vasodilators remain probably underused whereas some doubts have emergency regarding the safety of positive inotropes. Analysis of the hemodynamic profile is mandatory for an optimal management of these patients. The next decade will be that of morbimortality trials in this common form of heart failure with severe prognosis.

[Ultra-rapid measurement of brain natriuretic peptide]. / Dosage ultrarapide du brain natriuretic peptide.

B-type natriuretic peptide (BNP) is secreted by overloaded ventricles. Emerging of bedside dosages cause an increasing interest for this peptide as marker in various clinical situations with heart failure. At first, BNP dosage is a potential tool for detecting heart failure and left ventricular dysfunction. BNP has also a powerful and well-established prognosis value in chronic heart failure. In the emergency setting, and mainly about acute dyspnea, low blood BNP level could eliminate diagnosis of congestive heart failure. Moreover, serial measurement of BNP could allow non-invasive hemodynamic monitoring during decompensated heart failure and could also lead cares as need for intensifying treatment. Nevertheless, its daily use in various clinical situations require that cut-off values are refined.

Myocardial gene therapy.

Myocardial gene therapy was born at the beginning of the 90's from the marriage of well-defined pathophysiological mechanisms with recombinant adenovirus technology. Together with the development of relatively simple vector delivery procedures during the last few years, this made it possible to consider the possibility of treating diseases such as ischemic cardiomyopathies by the delivery of angiogenic factors and to bring the first proof, in rats, that myocardial gene therapy for experimental heart failure can improve cardiac performance and prolong life duration of the animals. It is now conceivable that such an approach will be applied to human heart failure within the next years. In contrast, regarding familial cardiomyopathies and channelopathies, because of the specificity of each disease type and complexity of the pathophysiology of each mutation, it is likely that much more time will be necessary. However, a number of barriers still exist before myocardial gene therapy can spread to the field of routine clinical cardiology, including finding a safe vector allowing good transduction efficiency rates to cardiac myocytes when delivered through coronary arteries. In contrast, it is conceivable that in the open chest setting, myocardial gene therapy will rapidly be used by surgeons, by itself or in association with the injection of "wild" cells or cells transfected with various types of genes. It can now be assumed that such biotherapies will soon offer patients suffering from myocardial diseases (and especially heart failure) the perspective of major therapeutic progresses.

A non-invasively determined surrogate of cardiac power ('circulatory power') at peak exercise is a powerful prognostic factor in chronic heart failure.

OBJECTIVES: This study was designed to assess the prognostic value of a new variable derived from a cardiopulmonary exercise test, the circulatory power, a surrogate of cardiac power, at peak exercise, in patients with chronic heart failure. BACKGROUND: Peak exercise cardiac power and stroke work are invasive parameters with recently proven prognostic value. It is unclear whether these variables have better prognostic value than peak oxygen uptake (VO(2)). METHODS: The study population comprised 175 patients with chronic heart failure (ejection fraction <45%) who underwent a cardiopulmonary exercise test. Circulatory power and circulatory stroke work were defined as the product of systolic arterial pressure and VO(2) and oxygen pulse, respectively. Prognostic value was assessed by survival curves (Kaplan-Meier method) and uni- and multivariate Cox analyses. RESULTS: With a mean follow-up of 25+/-10 months, ejection fraction, heart rate, systolic arterial pressure, peak VO(2), VCO(2), the anaerobic threshold, minute ventilation, the ventilatory equivalents of oxygen and carbon dioxide, the half times of VO(2) and VCO(2) recoveries, and the circulatory stroke work and power predicted outcome. Multivariate analysis demonstrated that the peak circulatory power (chi-square=19.9, P<0.001) (but not peak circulatory stroke work) was the only variable predictive of prognosis. CONCLUSION: The prognostic value of cardiopulmonary exercise tests in heart failure patients can be improved by assessing a new variable, the circulatory power - a surrogate of cardiac power - at peak exercise.