[Diagnostic value of a two-dimensional echocardiographic score for left ventricular hypertrophy validated by the Imatron CT scan in familial hypertrophic cardiomyopathy]. / Valeur diagnostique d'un score echocardiographique bidimensionnel d'hypertrophie du ventricule gauche validé par scanner Imatron dans la cardiomyopathie hypertrophique familiale.

The aim of this study was to validate a two-dimensional echocardiographic score for left ventricular hypertrophy in familial hypertrophic cardiomyopathy (HCM) by fast CT scan and to study the diagnostic value by an indexed threshold value in affected and genotyped families in comparison with the classical diagnostic method of maximal wall thickness (E max). The study was performed successively in two patient groups with HCM. The echo/CT scan population comprised 26 patients. They underwent echocardiography and Imatron CT scanning. The E max and 2D echo score (sum of the thickness of 4 segments) were measured by echocardiography and compared to the left ventricular mass obtained by the CT method. The 2D echo score was closely correlated to the CT left ventricular mass (r = 0.85) with a higher correlation coefficient than the E max (r = 0.78). The echo/generic population comprised 109 genotyped adults with an identified mutation. The E max and 2D echo score were measured. The genotype was the reference for diagnosis. A theoretical value of the 2D echo score was determined in healthy individuals by a multiple linear regression model of ages, sex and body surface area. A threshold value for abnormality was established after analysis of the ROC. The sensitivity and specificity were 63% and 100% respectively for E max and 73% and 96% respectively for the indexed 2D echo score. The improvement in sensitivity was marked in young adults (< 50 years) with 69% for the indexed 2D echo score versus 54% for E max, p < 0.04. The authors conclude that the indexed 2D score has been validated as an index of hypertrophy by the Imatron CT and has a better diagnostic value than E max, especially in young adults. This echocardiographic criterion could be proposed as an alternative diagnostic sign for screening families.

[Coronary angioplasty in the acute phase of a myocardial infarction on a myocardial bridge]. / Angioplastie coronaire à la phase aiguë d'un infarctus du myocarde sur pont myocardique.

A myocardial bridge is usually asymptomatic but can cause myocardial ischemia, myocardial infarction or sudden death. Two occurrences of coronary angioplasty in the acute phase of an anterior myocardial infarction on a myocardial bridge are reported. The first case was first treated only with a balloon, and then with a stent 12 h later after a relapse of angina pectoris and the recurrence of a severe compression. The second case immediately benefited from a stent. A systematic control at six months has shown the absence of restenosis in the first case and an asymptomatic occlusion of the stent in the second case. Its deocclusion has revealed a myocardial bridge downstream of the stent. Myocardial stunning might have caused a decreased systolic compression by the bridge in the first case, and an underestimation of its actual length in the second case. Its regression is held responsible for these two relapses. A long active stent installed at high pressure could be used to treat myocardial bridges during myocardial infarctions.

[Myoblast transplantation for heart failure: where are we heading?]. / Thérapie cellulaire en cardiologie: rêve ou réalité?

Cell therapy in cardiology is already a reality, as evidenced by the number of ongoing clinical trials. These studies entail administration of either skeletal myoblasts in patients with severe ischemic left ventricular dysfunction or of bone marrow-derived cells in patients with acute myocardial infarction and in whom cell therapy is an adjunct to a percutaneous revascularization procedure. The techniques of preparation, expansion and storage of myoblasts are now quite effective. The problem is simpler for bone marrow cells as in most studies, the procedure is limited to an iliac crest biopsy followed by reinjection of the crude, unfractionated bone marrow, as routinely done in clinical haematology since many years. The results of these studies are not yet fully available. Some of them have been enthusiastically reported to be positive but should be interpreted cautiously because of the usually small sample sizes and the common lack of randomisation and double-blind assessment of outcomes. Thus, the fact that cell therapy has now become a reality should not lead to underscore the yet unsettled fundamental issue, i.e., the ability of this novel mode of therapy to truly regenerate areas of necrotic myocardium and restore function in once akinetic territories. From this standpoint, cell therapy is still a dream. Since the beginning, it has been clear that myoblasts were exclusively committed to differentiate into myotubes, without any evidence for a phenotypic conversion into cardiomyocytes. Although the debate is more controversial for bone marrow cells, the reliance on accurate genetic methods of cell tracking has led to increasingly challenge the purported plasticity of these cells. This by no means implies that cell therapy does not exert beneficial effects that could be mediated by alternate mechanisms like limitation of remodelling of paracrine effects. The basic point is that neither skeletal myoblasts nor bone marrow cells fulfill the major criteria required for a true cardiac regeneration: a coupling of the grafted cells with those of the recipient myocardium and the subsequent generation of a contractile force. It is therefore critical to go on exploring other paths, among which embryonic stem cells are particularly attractive.

[Prediction of intolerance to beta blocker therapy in chronic heart failure patients using BNP]. / Prédiction du risque d'intolérance du traitement bêtabloquant chez l'insuffisant cardiaque chronique par le dosage du BNP.

Beta-blocker therapy is actually recommended as first line therapy for systolic heart failure. However, beta-blocker have a low prescription rate comparatively to ACEI. Beta-blocker potential side effects as bradycardia, hypotension and especially acute decompensation could explain this under prescription. Clinical data could easily identify high-risk patients for hypotension or bradycardia but not high-risk patients for induced decompensation linked to beta-blocker therapy. BNP could identify these patients with a high sensitivity. Patients with BNP above 1000 pg/ml had a 40% risk of acute decompensation after introduction or increase of beta-blocker therapy. As a conclusion, clinicians must be very cautious for introducing or increasing Carvedilol therapy in patients with high BNP levels.

In vivo induction of endothelial apoptosis leads to vessel thrombosis and endothelial denudation: a clue to the understanding of the mechanisms of thrombotic plaque erosion.

BACKGROUND: The mechanisms of thrombosis on plaque erosion are poorly understood. We examined the potential role of endothelial apoptosis in endothelial erosion and vessel thrombosis. METHODS AND RESULTS: Segments of New Zealand White rabbit femoral arteries were temporarily isolated in vivo. One artery was incubated with staurosporin for 30 minutes, whereas the contralateral artery was incubated with saline and served as control. Three days later, thrombosis was evaluated angiographically and histologically. TUNEL score in the endothelial layer was significantly increased in staurosporin-treated arteries compared with controls (2.43+/-0.30 versus 0.93+/-0.44, respectively; P=0.001). Large areas of endothelial denudation were detectable in staurosporin-treated vessels, whereas endothelium integrity was almost preserved in the saline group. Vessel thrombosis occurred in 58% of staurosporin-treated arteries (7 of 12) but in only 8% of saline-treated segments (P<0.01). Immunoreactivities for tissue factor, platelets, and fibrin were detectable within the thrombus. Addition of ZVAD-fmk (0.1 mmol/L) significantly reduced the occurrence of thrombosis (1 of 7 arteries or 14%, P=0.04). These results were confirmed in balloon-injured atheromatous arteries. CONCLUSIONS: In vivo induction of endothelial apoptosis leads to both vessel thrombosis and endothelial denudation. Endothelial apoptosis may be a critical step in the transition from a stable endothelialized plaque to plaque erosion and thrombosis.

Accuracy of European diagnostic criteria for familial hypertrophic cardiomyopathy in a genotyped population.

BACKGROUND: Since the sensitivity of conventional diagnostic criteria for familial hypertrophic cardiomyopathy (HCM) is low, new diagnostic criteria were proposed by a European collaboration. However, their diagnostic value remains unknown. The aim of the study was to evaluate the accuracy of these new criteria, using the genetic status as the criterion of reference. METHODS: We studied 109 genotyped adults (54 genetically affected, 55 unaffected) from 7 families (mutations in 3 genes). Major European echographic criteria were a maximal wall thickness >or=13 mm or >or=15 mm according to the segment involved, or the presence of SAM. Major European ECG criteria were abnormal Q waves, left ventricular hypertrophy, or marked ST-T changes. Combined major/minor European criteria were also evaluated. RESULTS: Sensitivity and specificity of major European criteria (72 and 92%, respectively) were similar to those of major conventional criteria (70 and 94%) and were not improved by combined major/minor European criteria (72 and 90%). When all the minor European criteria were considered, sensitivity increased to 87% but specificity dramatically decreased to 51%. However, one of these minor ECG criteria, deep S V2, was of interest and when added to major European criteria, sensitivity increased to 76% and specificity remained good (90%). CONCLUSIONS: The diagnostic value of new European criteria for HCM was evaluated for the first time. We found that it was not different from that of conventional criteria, with a good specificity but a low sensitivity. Additional criteria should be studied to improve the early identification of HCM.

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.

[Brain natriuretic peptide, heart failure and elderly patients]. / BNP, insuffisance cardiaque et sujet âgé.

Natriuretic Peptides like BNP or NT Pro BNP are diagnostic and prognostic makers largely used in clinical practice. Ageing may increase these peptides, especially in case of comorbidities like renal failure or hypertension and require adjustment for age. Diagnostic value of natriuretic peptides seems however preserved in elderly people.

[Educating patients about heart failure in community hospitals: it is possible...]. / Education des patients concernant l'insuffisance cardiaque en centre hospitalier général: c'est possible....

Prognosis for heart failure is linked to patient's compliance. Compliance is also dependent from patient education about his disease and treatment. Therapeutic education could be done in a community hospital but needs a lot of time. However, therapeutic education for heart failure patients becomes more and more essential in clinical practice and improves patient knowledge and implication and hospitalization duration.

[Has the obligation to inform patients changed our mode of practice?]. / L'information du patient a-t-elle modifié notre comportement?

From January 2000, the Council of State has harmonised the jurisprudence with the Court of Appeal, changing the responsibility of medical practitioners by requiring them to provide proof that information was both given and understood by their patients. This obligation to inform patients raises several questions: who should give the information? to whom should the information be addressed? how can proof of this information be provided? what should the information be? The authors sent a questionnaire to practicing cardiologists by the internet site of the French Society of Cardiology from the 1st December 2002 to 15th January 2003. Three hundred and thirty-two replies were received of which 305 could be exploited. The activities of the cardiologists who replied were mainly in public hospitals (51.8%), private (18.2%) or mixed (30%). Patient information was mainly performed before invasive procedures, especially coronary angiography (90%) or cardiac pacing (77.3%). On the other hand, it was less commonly undertaken before exercise stress tests (63.2%) or transoesophageal echocardiography (61.4%), although these percentages are much higher than those recorded during previous enquiries in 2000 and 2001. The information given was, in the large majority of cases, that proposed by the French Society of Cardiology and it was usually the practitioner who ordered the investigation who informed the patient (45.4%). In 2002, the role of the nurse was much greater as the nurse informed the patient in 27.2% of cases. The patient was generally given the information the day before the procedure was carried out (74.1%) with complementary information (90.7%), and less than 1% of patients declined the investigation under these conditions. In order to provide proof of patient information, the practitioner usually required the patient's signature (58.3% of cases); less commonly, the referring physician was informed by letter (13.9% of cases) or a note was made in the patient's file (33.9% of cases). The new requirements for patient information have changed medical practice in nearly 53.5% of cases. Finally, although patient information is considered to be part of the normal patient-doctor relationship in most cases (42.7%), doctors thought that patients interpreted this procedure as a cover for the medical team in 18.2% of cases. The information bases most commonly used to determine the methods of informing patients and the nature of the information to be provided were medical reviews (38.9%) or the internet (30.5%). The authors conclude that patient information is carried out before complementary cardiological investigations. The new laws of the Code of Public Health are not well known. Finally, the proof of patient information is not easily provided and the majority of cardiologists request written patient consent, which is not a legal requirement.

[Value of type B natriuretic peptide in the emergency management of patients with suspected cardiac failure. Report of 125 cases]. / Apports du peptide natriurétique de type B dans la prise en charge aux urgences des patients suspects d'insuffisance cardiaque. A propos de 125 patients.

Shortness of breath is a common cause of consultation in the emergency unit. Therefore, it is essential to diagnose cases of cardiac failure. This may be difficult in some cases. The authors set out to assess the value of measuring brain natiuretic peptide in this context. Brain natiuretic peptide (BNP) was measured by an ultrafast method (Biosite/BMD) on arrival of 125 patients to the emergency unit. The results were then compared with the diagnoses made in the emergency unit and those of the hospital discharge summary. Nearly 18% of patients were wrongly classified in the emergency room; 1/3 were falsely diagnosed as cardiac failure and 2/3 were not recognised initially as having cardiac failure. In 90% of patients, in particular in the group wrongly considered as not having cardiac failure, BNP measurement could have helped correct the mistake. The optimal threshold value of BNP for diagnosis of cardiac failure in this study was 300 pg/mL, with positive and negative predictive values of 92.4 and 90.2%, respectively.

[Biochemical markers of myocardial ischemia and necrosis]. / Marqueurs biochimiques d'ischémie et de nécrose myocardique.

The biochemical markers of myocardial ischaemia have to be interpreted according to their kinetics; their interests depend on the clinical presentation. They are helpful to orient to a myocardial ischaemia in front of undefined chest pain, to stratify the outcome of acute coronary syndrome without ST segment elevation, to evaluate the amount of myocardial damage following infarction, to detect the failure of thrombolysis therapy and probably to stratify the post percutaneous coronary intervention outcome.

Genetic testing and genetic counselling in hypertrophic cardiomyopathy: the French experience.

AIMS: A major breakthrough in the molecular genetics of hypertrophic cardiomyopathy (HCM) has made genetic testing now available in clinical practice, raising new questions about its implications, potential benefits, and the organisation of the procedure. The aim of this work was (1) to discuss the different questions related to genetic testing in HCM, and propose guidelines for the different situations, (2) to report our preliminary experience with a specific procedure. METHODS AND RESULTS: The main questions asked by patients and relatives concern presymptomatic diagnosis and prenatal counselling/diagnosis, while clinicians sometimes discuss diagnostic and prognostic testing. To take into account the complex medical and psychological implications of this new approach, we developed a specific, multidisciplinary, and multiple step procedure, including a cardiologist, a geneticist, and a psychologist. Seventy subjects were examined, including (1) 29 adults for presymptomatic diagnosis (of whom 10 left the procedure after the first visit and 19 continued, among whom six had a mutation and two experienced negative psychological impact, observed during follow up), (2) nine couples of parents for presymptomatic diagnosis in their children (the procedure was stopped after the first visit in eight and continued in one), (3) 22 couples for prenatal counselling (no prenatal genetic testing was asked for after the first visit), and (4) 10 subjects for diagnostic testing. We decided to perform no prognostic testing. CONCLUSION: Our preliminary experience confirms the complexity of the situation and suggests the necessity for a specific procedure to ensure good practice in genetic testing of HCM.

Relation between QT duration and maximal wall thickness in familial hypertrophic cardiomyopathy.

BACKGROUND: QT abnormalities have been reported in left ventricular hypertrophy and hypertrophic cardiomyopathy. OBJECTIVE: To determine the relation between left ventricular hypertrophy and increased QT interval in familial hypertrophic cardiomyopathy. METHODS: The QT interval was measured in 206 genotyped adult subjects with familial hypertrophic cardiomyopathy from 15 unrelated families carrying mutations in the beta myosin heavy chain (beta-MHC) gene (five families, n = 68) or the cardiac myosin binding protein C (MyBPC) gene (10 families, n = 138). Subjects were classified as genetically unaffected (controls, n = 112), affected with left ventricular hypertrophy (penetrants, n = 58), or affected without left ventricular hypertrophy (non-penetrants, n = 36). RESULTS: There was a significant increase in QTmax and QTmin from controls to non-penetrants and penetrants for both the MyBPC group (p < or = 0.001 and p < or = 0.001, respectively) and the beta-MHC group (p < or = 0.001 and p < or = 0.001, respectively). In the MyBPC group, the increase in the QT interval could be explained by increased left ventricular hypertrophy. In the beta-MHC group, non-penetrants had a significantly longer QTmax than controls despite the absence of left ventricular hypertrophy, and a similar QT interval to penetrants despite a lesser degree of left ventricular hypertrophy. CONCLUSIONS: In familial hypertrophic cardiomyopathy, genetically affected subjects without left ventricular hypertrophy may have a prolonged QT duration, which depends not only on the degree of left ventricular hypertrophy, when present, but also on the causative mutation.

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.

[Familial hypertrophic cardiomyopathy. French study of the duration and outcome of pregnancy]. / Cardiomyopathie hypertrophique familiale. Etude française du déroulement des grossesses et des accouchements.

Hypertrophic cardiomyopathy (HCM) is a rare, often familial condition, which may be complicated by syncope, atrial or ventricular arrhythmias and episodes of cardiac failure. This genetic disease affects young people and may be observed in women wishing for a pregnancy. The duration and outcome of such pregnancies has not been extensively studied. The authors undertook a retrospective study by questionnaire to compare the pregnancies of 41 women with HCM, a total of 150 pregnancies, with those of 39 unaffected women from the same families: a total of 132 pregnancies. None of the women died, there were no hospital admission for cardiac causes and there was no aggravation of functional status (31% of women with HCM had symptoms before pregnancy compared with 27% during pregnancy). The foetal prognosis was good with no increase in prematurity or neonatal crises. Only the women with symptoms before pregnancy had an increased risk of foetal prematurity compared with healthy women (18% versus 5%). These results indicate the good tolerance of pregnancy of women with HCM and should lead to a revision of systematic medical contra-indication of pregnancy in these patients.

[Stress ultrasonography under low doses of dobutamine, contractile reserve and dilated cardiomyopathy]. / Echographie de stress sous faibles doses de dobutamine, réserve contractile et cardiomyopathies dilatées.

The demonstration of a myocardial contractile reserve with low dose dobutamine is an emerging imaging technique in patients with dilated cardiomyopathy. This contractile reserve is correlated with a better prognosis and enables identification of subgroups of patients who could increase their left ventricular ejection fractions under carvedilol. A review of the published literature shows that the method does not expose patients to major risk, providing patients are selected and carefully monitored during the procedure. Complementary studies of larger numbers of patients are required to confirm its value as a prognostic and therapeutic marker in patients with dilated cardiomyopathy.

[Heart failure clinics. Concept, organization, results]. / Unités d'insuffisance cardiaque. Concept, organisation, résultats.

Chronic heart failure is linked to high rate of death and hospitalization. Some studies have highlighted the beneficial effect of heart failure clinics on morbidity and mortality. We have developed this type of structure at CHR Dubos since 3 years and we have recently created an heart failure clinic (10 beds). It's based on a concept including an experienced medical and nurse team, patient's and patient's family education and evaluation of the structure.