[Saw tooth cardiomyopathy: How to better diagnose?] / Saw tooth cardiomyopathy : comment mieux faire le diagnostic ?

With the increasing use of cardiac MRI, several cases were described as "sawtooth cardiomyopathy" or "tiger heart". The pathological aspects of these rare forms of myocardial dysplasia, frequently assimilated to non-compaction of the left ventricle, and its prognostic implications remain unclear. We present a case of "sawtooth cardiomyopathy" in a patient with a transient ischemic attack. This article aims to determine, with the other clinical cases in the literature, the MRI and echocardiography criteria for the diagnosis of this cardiomyopathy. Sawtooth cardiomyopathy is probably under diagnosed and deserves to be better known.

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.

[NT-proBNP in practice: from chemistry to medicine]. / NT-proBNP en pratique "de la biologie à la clinique".

Since introduction of routine assay for natriuretic peptides, there are a growing number of clinical applications for those new tests. Numerous studies have defined analytical characteristics and clinical interest of NT-proBNP assay. Originally limited to acute heart failure diagnosis in the emergency room, NT-proBNP assay has now a wide number of applications. This review presents the "state of art" of this marker, detailing NT-proBNP physiological recent knowledge and its recognized or investigated clinical applications.

Membrane water for probing neuronal membrane potentials and ionic fluxes at the single cell level.

Neurons communicate through electrochemical signaling within a complex network. These signals are composed of changes in membrane potentials and are traditionally measured with the aid of (toxic) fluorescent labels or invasive electrical probes. Here, we demonstrate an improvement in label-free second harmonic neuroimaging sensitivity by ~3 orders of magnitude using a wide-field medium repetition rate illumination. We perform a side-by-side patch-clamp and second harmonic imaging comparison to demonstrate the theoretically predicted linear correlation between whole neuron membrane potential changes and the square root of the second harmonic intensity. We assign the ion induced changes to the second harmonic intensity to changes in the orientation of membrane interfacial water, which is used to image spatiotemporal changes in the membrane potential and K+ ion flux. We observe a non-uniform spatial distribution and temporal activity of ion channels in mouse brain neurons.

Dual action of L-Lactate on the activity of NR2B-containing NMDA receptors: from potentiation to neuroprotection.

L-Lactate is a positive modulator of NMDAR-mediated signaling resulting in plasticity gene induction and memory consolidation. However, L-Lactate is also able to protect neurons against excito-toxic NMDAR activity, an indication of a mitigating action of L-Lactate on NMDA signaling. In this study, we provide experimental evidence that resolves this apparent paradox. Transient co-application of glutamate/glycine (1 µM/100 µM; 2 min) in primary cultures of mouse cortical neurons triggers a NMDA-dependent Ca2+ signal positively modulated by L-Lactate (10 mM) or DTT (1 mM) but decreased by Pyruvate (10 mM). This L-Lactate and DTT-induced potentiation is blocked by Ifenprodil (2 µM), a specific blocker of NMDARs containing NR2B sub-units. In contrast, co-application of glutamate/glycine (1 mM/100 µM; 2 min) elicits a NMDAR-dependent excitotoxic death in 49% of neurons. L-Lactate and Pyruvate significantly reduce this rate of cell death processes (respectively to 23% and 9%) while DTT has no effect (54% of neuronal death). This L-Lactate-induced neuroprotection is blocked by carbenoxolone and glibenclamide, respectively blockers of pannexins and KATP. In conclusion, our results show that L-Lactate is involved in two distinct and independent pathways defined as NMDAR-mediated potentiation pathway (or NADH pathway) and a neuroprotective pathway (or Pyruvate/ATP pathway), the prevalence of each one depending on the strength of the glutamatergic stimulus.

[Therapeutic education for heart failure: a necessity in 2007]. / Education thérapeutique pour l'insuffisance cardiaque: une nécessité en 2007.

Heart failure is a severe illness, marked with a still too high morbidity and mortality. Therapeutic education, fundamental for any chronic pathology, is taking a more and more important place in heart failure. Its value has been proved, and its importance in the multidisciplinary management of heart failure patients has been confirmed in terms of improving the prescription of medical treatment and allowing a better quality of life. France was late to recognise this technique, but the successful development of the I-CARE programme should contribute to improving both the quality of care for patients and the understanding of this pathology.

[Perception and understanding chronic heart failure by the patient. The impact of therapeutic education on the level of knowledge of patients. About 350 cases]. / Perception et compréhension de l'insuffisance cardiaque chronique par le patient. Impact d'une formation éducative sur les connaissances des patients. Etude médico-infirmière à propos de 35 cas.

UNLABELLED: Heart failure is a severe disease with a poor prognosis despite major therapeutic progresses achieved recently. A key factor is the high number of hospitalizations for heart failure, considered as being avoidable, since they are related to a lack of adequate management of the patients. Several therapeutic education programs focused on heart failure are in progress. Even though these programs aim at making patients an active agent managing the disease, data on patient's level of knowledge and experience regarding heart failure are scarce. The aim of our study was to analyze the patient's perception of the disease and his/her practices about this disease, as well as the treatments used. METHODS: we included 350 consecutive patients and analyzed their level of knowledge and experience using a questionnaire, as well as interviews performed by nurses and physicians. This initial assessment was followed by a second assessment after an 8-hours course in 2 days, made by the multidisciplinary education team of R. Dubos hospital (including physicians, nurses, physiotherapists, dietician). RESULTS: in contrast to tests assessing the knowledge on the disease, which were in overall satisfactory, the results on the level of knowledge on treatments and heart failure pathways were poor. The courses improve significantly the level of knowledge in all domains, whatever would the age and the level of patient's demand for information be. The analysis of the patient's conception of his/her own disease reveals the lack of knowledge on the severity of heart failure. Frequently, the effect of treatments is considered as poorly efficient, and a substantial fraction of these patients have underlying depressive moods. CONCLUSION: the understanding of the level of knowledge and the perception of the patient regarding his/her disease is primordial for setting educational structures and programs. However, the patient's conception of the disease is different from care providers. It is therefore essential to assess the patient's conception by an educational diagnosis prior to implement adapted education programs, in order to improve durably the patient's knowledge, at every age.

Management of heart failure in the elderly: recommendations from the French Society of Cardiology (SFC) and the French Society of Gerontology and Geriatrics (SFGG).

Heart failure, a frequent disease in the elderly, has a pejorative prognosis. Clinical diagnosis is complicated by atypical or difficult-to-interpret symptoms and by the concomitant presence of other diseases, particularly cognitive impairment, neurological disorders and diseases of the musculoskeletal system. Among the additional investigations, echocardiography remains underused. Impairment of diastolic left ventricular function is frequent. The usual laboratory tests must include calculation of the creatinine clearance, which is indispensable for dosage adjustment of certain drugs (ACE inhibitors, digoxin, spironolactone). The value of plasma natriuretic peptide assays as diagnostic tools has not been determined in elderly or very elderly populations and the plasma B-type natriuretic peptide increases with age. Comprehensive geriatric assessment is essential in order to screen for concomitant diseases and determine the patient's degree of dependence. The general objectives of treatment remain applicable to the elderly subject: improvement in the quality of life, reduction of mortality and the number and duration of hospitalisations, and slowing disease progression. In the frail elderly subject, symptom alleviation is to be the primary objective. In the absence of specific studies on elderly or very elderly subjects, most of the recommendations have been extrapolated from the data based on the evidence generated in younger populations. The dietary rules are to be more flexible than those used for younger subjects, particularly in order to prevent the risk of denutrition induced by strict salt-free diets. Special precautions for the use of heart failure drugs are due to comorbidities and the pharmacokinetic and pharmacodynamic changes related to aging. Drugs dosage increase is to be cautious and carefully monitored for adverse reactions. The therapeutic programmes in which multidisciplinary teams are involved reduce the number and duration of hospitalisations and the costs generated by the disease.

[Secondary prevention in the elderly or very elderly patient: indications, limitations and...perspectives]. / Prévention secondaire chez le patient âgé, voire très âgé: indications, limites et...perspectives.

Cardiovascular diseases are the principal cause of death in the developed countries. This is particularly true in the elderly despite the medical advances in the diagnosis and management of coronary artery disease. Although secondary prevention is a keystone in the management of young patients, this is too often absent in the elderly. However, the elderly may benefit at least as much as the younger patient population with respect to the correction of major risk factors such as dyslipidaemia, smoking and hypertension. Similarly, physical exercise, if possible, which is usually the case, should be proposed and encouraged. Patient education is an important factor in the management of autonomous elderly patients. The tolerance and observance of treatment must be systematic and regularly assessed. A multidisciplinary approach associating the cardiologist, general practitioner, geriatrician if possible and also nursing personnel, is probably one of the conditions for optimal management of secondary prevention of our elderly patients.

[Importance of therapeutic education in the multidisciplinary management of heart failure]. / Importance de l'education thérapeutique dans la prise en charge multidisciplinaire de l'insuffisance cardiaque.

Heart failure is a severe disease with high morbidity and mortality rates. The interest for multidisciplinary heart failure patient management is increasing in order to improve prescription of medical therapies and to allow a better quality of life. Proofs of reduction in morbi-mortality exist and some models of management have been assessed. The most important point remains the major role of therapeutic education. Training of health care professionals is needed. Tools for therapeutic education have been created and can be associated with complementary informative means. All these elements allow that a new approach of heart failure takes in place in France.

L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade.

Converging experimental data indicate a neuroprotective action of L-Lactate. Using Digital Holographic Microscopy, we observe that transient application of glutamate (100 µM; 2 min) elicits a NMDA-dependent death in 65% of mouse cortical neurons in culture. In the presence of L-Lactate (or Pyruvate), the percentage of neuronal death decreases to 32%. UK5099, a blocker of the Mitochondrial Pyruvate Carrier, fully prevents L-Lactate-mediated neuroprotection. In addition, L-Lactate-induced neuroprotection is not only inhibited by probenicid and carbenoxolone, two blockers of ATP channel pannexins, but also abolished by apyrase, an enzyme degrading ATP, suggesting that ATP produced by the Lactate/Pyruvate pathway is released to act on purinergic receptors in an autocrine/paracrine manner. Finally, pharmacological approaches support the involvement of the P2Y receptors associated to the PI3-kinase pathway, leading to activation of KATP channels. This set of results indicates that L-Lactate acts as a signalling molecule for neuroprotection against excitotoxicity through coordinated cellular pathways involving ATP production, release and activation of a P2Y/KATP cascade.

[Therapeutic education for cardiac failure patients: the I-care programme]. / Education thérapeutique des patients insuffisants cardiaques: le programme I-care.

Therapeutic education is becoming increasingly important in the management of chronic diseases including cardiac failure. The I-CARE programme consists of an evaluation of the role of therapeutic education in France, creating standardised tools and setting up training sessions for therapeutic education in the context of cardiac failure. Approximately two thirds of the French centres contacted perform therapeutic education with their available means. The lack of personnel, space, and training tools represent obstacles to the development of therapeutic education. The tools developed in the programme fall into 5 areas: diagnosis education, understanding the illness, diet, physical activity/daily life, and treatment. Training sessions were organised for the teams, consisting of at least one cardiologist and nurse. The I-CARE programme should allow the expansion of therapeutic education for cardiac failure and improve the multidisciplinary management of this disease which increasingly affects often elderly subjects.

[BNP and dyspnea: proposition of a diagnostic strategy based on two cut-off]. / BNP et dyspnée: proposition d'une stratégie diagnostique basée sur deux seuils décisionnels de BNP.

The purpose of this study was to evaluate the cut-off value of brain natriuretic peptide (BNP) assayed with AxSYM BNP assay (Abbott). 86 patients have been included (mean age of 66 years). The clinical sensibility was 100% at 100 ng/L versus 80% at 250 ng/L. The clinical specificity was 66% at 100 ng/L versus 92% at 250 ng/L. The positive predictive value was 80% at 100 ng/L versus 92% at 250 ng/L. The negative predictive value was 100% at 100 ng/L versus 88% at 250 ng/L. The double cut-off strategy is more suitable to diagnose a dyspnea of cardiac origin than the usual strategy based on a single cut-off.value. With such a strategy, the two cut-off strategy improve the diagnosis of 9% in the total population.

[Medico-economic impact of an innovative management of CHF by HF unit]. / Analyse médico-économique de l'impact d'une prise en charge de l'insuffisance cardiaque chronique en unité thérapeutique d'insuffisance cardiaque versus prise en charge habituelle de ville.

Chronic heart failure remains a frequent, severe and costly disease. Despite encouraging data from different countries, heart failure clinics are scarce in France. We have analyzed the impact of a heart failure clinic (UTIC of Pontoise) in terms of reduction of rehospitalizations and in hospitalization costs in 4855 consecutive patients. In our study, heart failure clinic management dramatically reduces HF related hospitalizations (RRR: -28 %, P=0.001) and HF related costs (55% reduction, P<0.001) regardless of comorbidities or disease severity. HF clinics have to be developed in France in order to optimize management of CHF and reduce the HF related costs.

Bedside B-type natriuretic peptide and functional capacity in chronic heart failure.

OBJECTIVES: To determine if B-type natriuretic peptide (BNP) measurement could be useful in determination of functional capacity in patients suffering from chronic heart failure. BACKGROUND: Evaluating functional capacity is a crucial factor in the follow-up of patients with chronic heart failure. There are numerous methods for measuring functional capacity and their relative merits remain under discussion. Clinical classifications are very subjective and other methods are difficult to use in clinical practice. METHODS: We evaluated functional capacity in 151 consecutive patients using the 6-min walk test. All patients were clinically classified using the New York Heart Association (NYHA) classification. We measured BNP plasma levels using a bedside BNP test. RESULTS: Six minute walk test performance decreased through NYHA classes 1 to 4 (469+/-87, 411+/-82, 325+/-83 and 196+/-63 m, respectively, P<0.01) and BNP levels increased through NYHA classes 1 to 4 (26.3+/-7.2, 73+/-13, 401+/-74 and 924+/-84 pg/ml, respectively, P<0.001). There was a significant correlation between 6-min walk test performance and BNP plasma levels (R=0.69 P<0.001) and a weaker correlation between BNP and left ventricular ejection fraction (R=0.45 P<0.04). In some patients there was a mismatch between NYHA classification and 6-min walk test performance. In all cases BNP could correct the clinical estimation of functional capacity. When we divided the patients into three sub-groups within each NYHA class, we showed that using BNP could better define functional capacity in patients suffering from chronic heart failure in NYHA classes I to III. CONCLUSION: The measurement of BNP levels thus usefully supplements the clinical examination. The existence of bedside BNP testing methods facilitates its use in routine clinical practice. It also permits easier follow-up of patients with chronic heart failure.

Short-term effects of sinus rhythm restoration in patients with lone atrial fibrillation: a hormonal study.

It is well known that atrial fibrillation can lead to heart failure, and is attributed to rapid ventricular rate (tachycardia-induced cardiomyopathy). Some recent studies suggest the possible existence of an intrinsic left-ventricular factor related to atrial fibrillation, irrespective of other elements. In order to demonstrate the implication of this factor, we measured B-type Natriuretic Peptide, known as a functional marker of left-ventricular dysfunction, in 40 consecutive patients with chronic non-valvular atrial fibrillation, with low ventricular rate and absence of clinical heart failure or echocardiographic left-ventricular dysfunction. In all patients, Brain Natriuretic Peptide (BNP) plasma level was high and dramatically decreased 24 h after external electrical cardioversion (61.4 pg/ml before cardioversion, 23.5 pg/ml 1 day after cardioversion, P<0.002). Our study demonstrates that atrial fibrillation, in absence of high ventricular rate, induces an asymptomatic cardiac alteration that is not detectable by echocardiography.

Myocardial contractile reserve under low doses of dobutamine and improvement of left ventricular ejection fraction with treatment by carvedilol.

To examine the ability of myocardial contractile reserve (MCR) assessment to predict the improvement of left ventricular ejection fraction with treatment by carvedilol, a prospective study was undertaken in 85 patients with chronic heart failure and left ventricular ejection fraction < 45%. Low dose dobutamine echocardiography (DSE), a 6-min walk test and measured brain natriuretic peptide (BNP) were assessed in all the patients. Patients were separated into two groups. Group A were patients without any myocardial reserve and group B patients with a myocardial contractile reserve defined as an increment of more than 20% of the resting left ventricular ejection fraction during dobutamine infusion. The two groups differed for percentage of ischemic cardiomyopathy (67.8 in group A vs. 29.7% in group B P = 0.028), 6-min walk test performance (respectively, 343 vs. 415 meters P < 0.05) and BNP plasma levels (respectively, 184.5 vs. 70.1 P < 0.02) but not for left ventricular ejection fraction or NYHA class. During DSE, MCR and heart rate variation was higher in group B than in group A. At the end of the follow up, LVEF increased and NYHA class decreased in group B but not in group A. In multivariate analysis the existence of MCR could predict the improvement of LVEF with treatment by carvedilol. In our study, studying MCR could help to predict patients who will improve their LVEF with carvedilol prior to the administration of the treatment.

Electrophysiological studies of oxytocin neurons in organotypic slice cultures.

We have developed organotypic slice cultures derived from postnatal rat hypothalamus which contain well-differentiated oxytocin neurons. Intracellular recordings of identified neurons show that these cultured oxytocin cells exhibit basal electrical properties closely similar to those of magnocellular cells recorded in vivo and in acute in vitro preparations from adult animals. The cultures also include GABAergic and glutamatergic neurons making connections with the oxytocin cells, which strongly suggests that the rich GABAergic and glutamatergic innervations of adult oxytocin neurons in vivo derive largely from local hypothalamic sources. Pharmacological manipulations indicate that the cultured oxytocin neurons present functional GABAA (but not GABAB) receptors, and ionotropic non-NMDA and NMDA receptors, but no metabotropic receptors for glutamate. These synaptic inputs control to a great extent the electrical activity of oxytocin neurons. Of particular interest is our observation that the cultured oxytocin neurons display a recurrent bursting activity which does not appear to result from an endogenous regenerative activity, but from a patterned glutamatergic input. Our preliminary data show that oxytocin plays a facilitatory role in this bursting activity and suggest that such activity is generated within an hypothalamic circuitry.

[Paralysing hypokalemic thyrotoxicosis]. / Thyrotoxicose hypokaliémique paralysante.

Thyrotoxicosis is a rare cause of hypokalaemia. The clinical presentation associates signs of thyrotoxicosis which may be discrete, with severe hypokalaemia and peripheral muscular weakness with paralysis of the lower limbs. It is important not to miss this diagnosis because of the therapeutic implications. Treatment of this form of hypokalaemia is that of hyperthyroidism.

[Bartonella quintana endocarditis. Aortic localization and mitral valve abscess]. / Endocardite à Bartonella quintana. Localisation aortique et abcès mitral.

Bartonella Quintana is an exceptionally rare cause of endocarditis. The frequency of this condition is increasing and is probably underestimated because of the difficulty in diagnosing. The clinical context is that of socially deprived classes, the agent of transmission of the germ being body lice. The commonest valve affected is the aortic valve. This infection may also give rise to a mitral annulus abscess, as in this particular case. The diagnosis should be suspected in all cases of endocarditis with negative blood cultures in socially deprived patients as special diagnostic methods are required. Bartonellosis serology and drainage of effusions to perform a Gimenez stain to show intra-cellular bacteria and a polymerase chain reaction to sequence the nucleic acids, will give an accurate diagnosis. Similarly, the operative specimens should be sent to a specialised department for the culture of these bacteria (in France, the Marseille Ricketsioses Institute). The treatment of Bartonella endocarditis is very controversial. The usual recommendations are an association of betalactamines and an aminoside for one month and macrolides or tetracyclines. There is lack of consensus about follow-up. It would seem prudent to perform a clinical examination to search for a relapse of the infection and monthly serologies until they return to normal values.