Transthyretin amyloid polyneuropathy in France: A cross-sectional study with 413 patients and real-world tafamidis meglumine use (2009-2019).

OBJECTIVE: We aimed to describe characteristics of patients with ATTR variant polyneuropathy (ATTRv-PN) and ATTRv-mixed and assess the real-world use and safety profile of tafamidis meglumine 20mg. METHODS: Thirty-eight French hospitals were invited. Patient files were reviewed to identify clinical manifestations, diagnostic methods, and treatment compliance. RESULTS: Four hundred and thirteen patients (296 ATTRv-PN, 117 ATTRv-mixed) were analyzed. Patients were predominantly male (68.0%) with a mean age of 57.2±17.2 years. Interval between first symptom(s) and diagnosis was 3.4±4.3 years. First symptoms included sensory complaints (85.9%), dysautonomia (38.5%), motor deficits (26.4%), carpal tunnel syndrome (31.5%), shortness of breath (13.3%), and unexplained weight loss (16.0%). Mini-invasive accessory salivary gland or punch skin and nerve biopsies were most common, with a performance of 78.8-100%. TTR genetic sequencing, performed in all patients, revealed 31 TTR variants. Tafamidis meglumine was initiated in 156/214 (72.9%) ATTRv-PN patients at an early disease stage. Median treatment duration was 6.00 years in ATTRv-PN and 3.42 years in ATTRv-mixed patients. Tafamidis was well tolerated, with 20 adverse events likely related to study drug among the 336 patients. CONCLUSION: In France, ATTRv patients are usually identified early thanks to the national network and the help of diagnosis combining genetic testing and mini-invasive biopsies.

Measurement of interatrial dyssynchrony using tissue Doppler imaging predicts functional capacity and cardiac involvement in systemic sclerosis.

OBJECTIVES: We aimed to assess the prevalence of interatrial electromechanical dyssynchrony in systemic sclerosis (SSc) patients, and to study the correlation between interatrial delay and standard follow-up parameters. METHODS: Forty consecutive patients with SSc were studied. Classical echocardiographic measurements were obtained, including indices of left ventricular (LV) systolic and diastolic function, right ventricular function, and pulmonary artery pressure (PAP). Left atrial (LA) function was studied using volume measurements. The interatrial mechanical (IAMD) delay was obtained by measuring the time delay between the peak atrial velocities at the lateral tricuspid and mitral annuli using tissue Doppler imaging. A cut-off value of 35 ms was chosen to define the presence of a significant interatrial delay. The IAMD was compared to NYHA class, six-minute walking test (6MWT), NT proBNP levels, and the carbon monoxide diffusion capacity over alveolar volume ratio (DLCO/VA), as well as to classical echocardiographic parameters. RESULTS: Forty percent of patients were found to have significant interatrial dyssynchrony with an IAMD of 35 ms or more. Patients with interatrial dyssynchrony were more symptomatic, had a shorter 6MWT, higher NT proBNP levels, and a lower DLCO/VA compared with those without dyssynchrony. Regarding conventional echocardiographic parameters, increased IAMD was associated with more pronounced LV diastolic dysfunction, LA enlargement and dysfunction, altered RV function, and higher PAP. CONCLUSIONS: IAMD correlated with all of the standard follow-up parameters in SSc, and is probably a sensitive marker of LA involvement. This easy to measure parameter should be added to the routine echocardiographic assessment of these patients.

Severe cardiomyopathy revealing antineutrophil cytoplasmic antibodies-negative eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of systemic vasculitis in which cardiac involvement is frequent and severe, and accounts for half of EGPA-related deaths. ANCA-positive EGPA differs from ANCA-negative EGPA in that the former is significantly associated with renal involvement, peripheral neuropathy and biopsy proven vasculitis, whereas the latter is associated with cardiac involvement. Herein, we report a case of EGPA with myocarditis in a woman, who was successfully treated with steroids and cyclophosphamide. This report highlights the importance of diagnosing cardiac involvement in EGPA early, especially in ANCA-negative patients.

[Transthyretin cardiac amyloidosis]. / L'amylose cardiaque à transthyrétine.

Transthyretin (TTR) cardiac amyloidosis results from the dissociation of the tetrameric, liver-synthetized transport protein, either because of a mutation (hereditary CA), or spontaneously due to ageing (wild type CA). Monomers self-associate into amyloid fibrils within the myocardium, causing heart failure, arrhythmias and conduction defects. This overlooked disease must be recognized in case of unexplained increased thickness of the myocardium, particularly in subjects of African descent, in patients with heart failure and preserved ejection fraction, and in those with aortic stenosis. Some extra-cardiac symptoms must also be considered as red flags: carpal tunnel syndrome, lumbar canal stenosis, recent deafness, peripheral neuropathy, or dysautonomia. Medical assessment includes an electrocardiogram, biological assessment including troponin, natriuretic peptide and monoclonal protein assay, echocardiography with 2-D strain study, MRI and bone scintigraphy. Once the diagnosis established, cardiologic management must avoid beta-blockers and other rate-slowing drugs, which are deleterious in restrictive cardiomyopathy, and restrain the use of renin-angiotensin system inhibitors, of little use and often poorly tolerated. Congestion must be treated with diuretics. Anticoagulants are often necessary due to the risk of arrhythmias and stroke. Pacemaker or defibrillator implantation should be determined in patients with high risk of sudden death. Until now, etiologic treatments were liver and/or heart transplantation in some rare cases. Tafamidis, a TTR stabilizer has recently been approved, and new therapeutic approaches targeting TTR at the transcriptional level are under investigation.

Low-frequency electromyostimulation and chronic heart failure.

Low-frequency electromyostimulation (EMS) acts on the skeletal muscle abnormalities that aggravate intolerance to effort in patients with chronic heart failure (CHF). It improves the oxidative capacity of muscles and thus enhances aerobic performance and physical capacity to almost the same degree, as does conventional physical training. No local or hemodynamic intolerance has been reported, even in cases of severe CHF. However, the presence of a pacemaker is one of the relative contra-indications (prior evaluation of tolerance is required), while that of an implanted defibrillator is one of the absolute contra-indications. EMS is an alternative to physical effort training when the latter is impossible due to a high degree of deconditioning or because there is a contra-indication, which may be temporary, due to the risk of acute decompensation and/or rhythm troubles. EMS can also be used in patients waiting for a heart transplant or in CHF patients who are unwilling to engage in physical activities. As EMS is not expensive and easy to set up, its use is likely to develop in the future.

[Acute heart failure and preserved systolic function: can we explain all only by the diastolic dysfunction? A prospective study on 145 patients hospitalized for acute pulmonary edema]. / Insuffisance cardiaque aiguë et fonction systolique préservée: peut-on tout expliquer par la seule dysfonction diastolique? Etude prospective sur 145 patients hospitalisés pour OAP.

INTRODUCTION: Heart failure with conserved systolic function is frequent and attributed to the diastolic dysfunction. The diagnosis of diastolic heart failure requires the association of clinical signs of heart failure, a conserved left ventricular systolic function and a diastolic dysfunction. OBJECTIVE: To determine the proportion of cases of isolated diastolic heart failure among patients hospitalized for acute pulmonary edema. METHODS: The left ventricular ejection fraction (LVEF), the diastolic function and levels of NT-proBNP have been assessed at admission of 145 patients hospitalized for acute pulmonary edema. RESULTS: 49% of patients included were older than 80 years (mean age 78.6 + 0.9 years). Among the 83 patients with conserved LVEF, 25% had an ischemic heart disease, 24% a severe valvular disease, 22% an atrial fibrillation, 5% a severe bradycardia, 2% a severe hypertrophic obstructive cardiomyopathy. Only 15 patients presented an isolated diastolic heart failure. The level of NT-proBNP was correlated to LVEF but was not able to identify those with isolated diastolic heart failure in the group with "conserved systolic function". CONCLUSION: Among patients hospitalized for acute pulmonary edema, the prevalence of heart failure with conserved systolic function is high, but only 10% of them presented an isolated diastolic heart failure. The NT-proBNP levels do not permit to identify them.

Possible association of thrombotic, nonbacterial vegetations of the mitral ring-mitral annular calcium and stroke.

Although numerous studies have shown an increased risk of stroke associated with mitral annular calcification, a direct link has rarely been demonstrated. We report the occurrence of long, pedunculated thrombi attached to the calcified mitral annulus in 3 patients who suffered from stroke, with resolution after anticoagulant and antithrombotic therapy.

Non-Hodgkin's lymphoma of the heart in patients infected with human immunodeficiency virus.

A case of HIV-associated cardiac non-Hodgkin's lymphoma (NHL) is described, and the epidemiologic and clinicopathologic features of 21 cases previously reported in the literature are analyzed. All patients were homosexual males, and the cardiac NHL was the first acquired immune deficiency syndrome-defining condition in the majority. Patients were referred with nonspecific clinical findings including dyspnea and tachycardia, but rapid progression of cardiac dysfunction was frequent after symptoms appeared. Echocardiography constitutes the most useful noninvasive procedure in the diagnosis of cardiac NHL. Most of the patients had disseminated diseased at initial presentation; pathologically, the lymphomas were of B lymphocyte origin and of high-grade subtypes. Prognosis of HIV-associated cardiac NHL is generally poor, although clinical remission has been observed with combination chemotherapy. Cardiac lymphomas in HIV-associated patients are typically high-grade and often disseminate early. Although the prognosis is poor, patients in whom dissemination has not occurred could have longer survival under systemic chemotherapy.

Prevention of apoptosis by deferoxamine during 4 hours of cold cardioplegia and reperfusion: in vitro study of isolated working rat heart model.

INTRODUCTION: Heart transplantation is often accompanied by multiple functional alterations, especially in reperfusion period. These are probably related to the reactive oxygen species (ROS) formation catalyzed by transition metals such as iron and copper, and thus the preservation time of the donor hearts is limited. Metabolic protection of the heart grafts is a permanent objective of numerous experiments. Recently, an iron chelator deferoxamine (DFX) was proposed as antioxidant agent for storage solutions in heart grafts. Oxidative stress is also known to mediate the apoptotic cell death in different tissues during ischemia-reperfusion. METHODS: The aim of this study was to evaluate a possible role of DFX in prevention of apoptosis using in vitro model of isolated working rat heart and cold cardioplegia. Two groups of rats were evaluated: (a) group 'DFX 50 &mgr;M' (n=8) and (b) group 'controls' (n=8). Isolated rat hearts were perfused by Krebs-Henseleit buffer (KHB) for 30 min, arrested by cardioplegic solution and stored for 4 h in B21 solution at 4 degrees C. Then, the hearts were reperfused by KHB for 45 min. DFX was added to the cardioplegic and storage solutions and in KHB in reperfusion. Basic functional parameters were evaluated: coronary, aortic, cardiac outputs and heart rate. At the end of reperfusion period a tissue samples were taken from left ventricle and in situ detection of apoptotic cells was performed using an ApopTag kit. RESULTS: DFX significantly reduced the occurrence of apoptotic cells in myocardium (*P<0.05). Hearts treated by 50 &mgr;M of DFX showed also a better recovery of the cardiac output (***P<0.001). The presence of DFX in KHB, cardioplegic and storage solution reduced also the incidence of postischemic arrhythmias and fibrillation's but without statistical significance. CONCLUSIONS: Our results give evidence of the protective potential of DFX during cold ischemia and reperfusion, presumably due to its antioxidant properties. The significant decrease of apoptosis in hearts treated by DFX could be considered as an existence of close link between oxidative stress and apoptotic death promotion in ischemia-reperfusion injury.

Melatonin protects against ischemia-reperfusion injury and inhibits apoptosis in isolated working rat heart.

INTRODUCTION: Melatonin (MEL), a pineal hormone, is well known as a potent antioxidant in a variety of ischemia-reperfusion models. Recent studies have assumed a pivotal role of reactive oxygen species (ROS) in the development of apoptosis. There are few pieces of information concerning a possible protective role of MEL against apoptosis in ischemia-reperfusion injury of myocardium. METHODS: We conducted an in vitro experiment: (1) to study the effect of MEL in the model of isolated and perfused working rat heart; (2) to evaluate the antioxidant capacity of MEL by a simple fluorescence test; and (3) to analyze the extent of apoptosis inhibition by MEL. Four groups of male Wistar rat were used: (a) group 'MEL 50 muM' (n=8); (b) group 'ischemia 30 min' (n=8); (c) group 'controls' (n=8); and (d) group 'controls+MEL 50 muM' (n=8). The perfusion medium was an oxygenated Krebs-Henseleit buffer (KHB). Hearts in groups (a) and (b) underwent 30 min of global normothermic ischemia and 45 min of reperfusion; 3 min before ischemia the hearts of group (a) received KHB with MEL 50 muM (and MEL 50 muM was also present in KHB solution during reperfusion). Hearts of group (c) were only perfused by KHB, and hearts of group (d) perfused by KHB+MEL 50 muM throughout the experiment. Registered were basic hemodynamic parameters: coronary, aortic, cardiac output and heart rate. At the end of each experiment, a left ventricle samples were taken for in situ detection of apoptosis using a TUNEL in-situ detection kit (POD) and quantitative analysis was performed. Malonedialdehyde concentrations were evaluated from heart homogenate to determine the severity of oxidative damage. To study the antioxidant capacity of MEL, a fluorescence test with allophycocyanin as an indicator was performed. A peroxyl radical generator, 2,2'-azobis(2-amidinopropan)-4-hydrochloride (AAPH) was used, and the antioxidant effect of MEL was expressed in oxygen-radical absorbing capacity (ORAC) units. RESULTS: Treatment by MEL resulted in a significant improvement of hemodynamic parameters and reduction of postischemic arrhythmias during reperfusion. All hearts in group 'ischemia 30 min' developed fatal ventricular fibrillations. MEL significantly reduced the incidence of apoptotic cells (14+/-4.3%; **P<0.01) vs. group 'ischemia 30 min' (58+/-2.1%). No apoptotic cells were detected in both control groups (c) and (d). In the fluorescence test, MEL exhibited a significant dose-dependent protective effect against peroxyl radical; MEL also reduced significantly the level of lipoperoxidation (MDA; *P<0.05). Analysis of hemodynamic parameters in both control groups (c) and (d) did not show any significant differences; the presence of MEL 50 muM in KHB solution did not have any important influence on cardiac performance in this type of experiment. CONCLUSION: We confirmed the previously reported beneficial effects of MEL against ischemia-reperfusion injury, presumably via its antioxidant properties. A significant suppression of apoptosis and the peroxyl radical scavenging properties of MEL in our study could contribute to the hypothesis of a close link between oxidative stress and apoptosis promotion.

[Valvuloplasty of a tricuspid bioprosthesis by the Inoue's technique]. / Valvuloplastie d'une bioprothèse en position tricuspide par la technique d'Inoue.

The authors report the case of a patient who had undergone tricuspid valve replacement with a bioprosthesis in 1985 after infectious endocarditis complicated by paradoxical embolism. The appearance of signs of right heart failure eight years later led to the diagnosis of stenotic degeneration of the bioprosthesis. Inoue balloon valvuloplasty was performed with no complications leading to significant improvement in the patient's condition.

[What are the indications for digitalis glycosides in the current treatment of cardiac insufficiency?]. / Que reste-t-il des indications des digitaliques dans le traitement actuel de l'insuffisance cardiaque?

Digitalis was discovered over two centuries ago and has been in everyday use for 100 years: however nowadays it is not considered to be the almost exclusive treatment of heart failure as it used to be with diuretic therapy. In the last decade, our understanding of the physiopathology of heart failure and the body's mechanisms of adaptation have improved and this has lead to the use of new molecules and a different approach to the problem of left ventricular failure. The classical contra-indications and precautions of use of digitalis have been studied in detail. The use of digitalis is contested especially in patients in sinus rhythm or with ischemic heart disease and it is used less often in adult cardiac emergencies. The competition between digitalis and vasodilator therapy is now very apparent in some situations; however, the choice between these two groups of drugs (as treatment of first intention or in association) has to be carefully considered in each individual case. The future of digitalis therapy lies without doubt in pediatric cardiology where it remains irreplaceable.

[Long-term follow-up of anatomic heart transplantation. Apropos of 60 patients with a mean follow-up of 36 months]. / Suivi à long terme de la transplantation cardiaque anatomique. A propos de 60 patients dont le suivi moyen est de 36 mois.

The aim of this study was to collect different problems seen in long-term evolution of patients who had anatomical cardiac transplantation and to compare with those seen in patients with standard transplantation. During the mean follow-up of 36 months, we analysed different data of 60 patients mean aged 51, who underwent anatomical cardiac transplantation. Six patients (10%) died within the 30 days after surgery. No patient needed the use of permanent pacemaker. Echocardiographic examination found normal atrial shape. One month after surgery, echocardiography described 16 tricuspid regurgitations (22.66%) and 8 mitral regurgitations (13.33%), 1 year later, there was respectively 13.33 and 6.66% tricuspid and mitral regurgitation. We had 8 late deaths: 1 sudden death, 2 chronic rejections, 1 pancreatitis and 4 cancers. The survival analysis pointed out 84% at 1 year, 80 at 2 years, 78 at 3 years and 73 at 5 years. Six months after surgery, 80% of patients were treated for high blood pressure; 85% had serum creatinine level equal or superior to 13 mg/L, with mean serum ciclosporin at 130 ng/mL. At the 3rd month, 6 endomyocardial biopsies were equal or superior to grade 2 rejection (International Society for Heart Transplantation). Between the 3rd and 12th month, 3 endomyocardial biopsies were equal or superior to grade 2 rejection, and the same between the 12th and 24th month. The infections rate was 0.8 episode per patient. Long term follow-up of anatomical cardiac transplantation faces the same problems as in standard cardiac transplantation. It is better to perform anatomical cardiac transplantation because of its early postsurgical advantages. Long term care is the same as in standard cardiac transplantation.

["Spontaneous" rupture of the left iliac vein complicating Cockett's syndrome]. / Rupture "spontanée" de la veine iliaque gauche compliquant un syndrome de Cockett.

The case history reported concerns a female patient aged 42 years for whom the clinical picture was that of a blue phlebitis (phlegmatia caerulea dolens), associated with a state of shock evoking a severe pulmonary embolus. The absence of echocardiographic dilatation of the right cavities, and the appearance of a left iliac fossa mass, steered the diagnosis towards internal haemorrhage. Emergency laparotomy allowed diagnosis and treatment of a so-called spontaneous rupture of the left iliac vein, a rare condition for which 20 cases have been reported in the literature. Re-operation performed 24 hours afterwards for the absence of venous return allowed the discovery of Cockett's syndrome with ascending thrombosis, requiring cross-venous bypass associated with the creation of an arterio-venous fistula in order to maintain permeability. One year afterwards the appearance of signs of cardiac insufficiency led to the closure of this fistula.

[Randomized comparison of 4F and 6F catheters for diagnostic coronary angiographies via the femoral approach]. / Comparaison randomisée des cathéters 4 F versus 6 F pour la réalisation des coronarographies diagnostiques par voie fémorale.

The use of 6F catheters has been validated for coronary angiography. The use of small-caliber catheters is a more recent development. The aim of this study was to assess the feasibility, the cost and complications of coronary angiography using the femoral approach with 4F catheters. The authors undertook a randomized prospective study of 4F Care Infiniti catheters (N = 100) and 6F Spertorque Plus catheters (N = 100) in hospitalised patients. Criteria of non-inclusion were valvular pathology, acute myocardial infarction, aorto-coronary bypass or aorto-femoral bypass procedures. No statistical difference was observed between the two groups with respect to feasibility, to duration of the procedure, or of irradiation or to cost. The quality of the angiograms was good except in one patient in the 4F group; 4 patients in the 6F group required a 4F catheter to complete their examination. Left ventricular catheterisation was more difficult with 4F catheters (p = 0.016). Use of 4F catheters was associated with injection of significantly less contrast (p = 0.00007), reduced the duration of compression (p < 10(-6)) and its complications (p = 0.004). The authors conclude that 4F catheters are safe and well tolerated. They are associated with less patient morbidity, without any loss in quality of the angiogrammes. Other studies in valvular heart disease and after coronary bypass surgery should lead to the generalisation of their use in all coronary patients.

[Unexplained pulmonary edema: demonstration of obstruction to pulmonary venous return by transesophageal echocardiography. Apropos of 4 cases]. / Oedèmes pulmonaires inexpliqués: mise en évidence d'une gêne au retour veineux pulmonaire par échocardiographie transoesophagienne. A propos de quatre observations.

The usual causes of pulmonary edema are left ventricular dysfunction, mitral valve disease or left atrial myxoma. Obstruction to pulmonary venous drainage is a rare and unrecognised diagnosis which should be considered when the usual investigations are unproductive. The authors report four cases in which transesophageal echocardiography showed pulmonary edema to be due to compression of one or more pulmonary veins by a mediastinal mass (2 cases), by the false lumen of dissection of the aorta (1 case) and postoperative stenosis of the pulmonary veins (1 case). These cases underline the diagnostic value of this technique which rapidly provides diagnostic information with privileged visualisation of the pulmonary veins and abnormalities of acceleration of blood velocities in the Doppler mode due to obstruction.

[Transesophageal echocardiography in cardiac and paracardiac tumors. A multicenter study]. / Apport de l'échocardiographie transoesophagienne au cours des tumeurs cardiaques et paracardiaques. Etude multicentrique.

A multicentre study was undertaken to determine the diagnostic value of transoesophageal echocardiography (TOE) in tumours of the heart and pericardium. Forty-five cases were recensed: 24 myxomas, 1 fibroma, 1 hydatid cyst, 2 lymphomas, 3 sarcomas, 1 pleuropericardial cyst, 1 branchogenic cyst and 12 cardiac metastases. The diagnosis was made in all 45 cases by TOE but only in 35 cases by conventional transthoracic echocardiography which failed to recognise 2 myxomas, 1 hydatid cyst, 1 sarcoma, 2 paracardiac cysts and 4 cardiac metastases. The site of the tumour was identified 45 times by TOE compared with only 12 times by transthoracic echocardiography. However, the anatomical investigation of mediastinal tumours requires complementary computerised tomography. Moreover, TOE, like all other imaging techniques, is unable to predict the benign or malignant nature of the tumour, 1 leiomyosarcoma having been confused with a myxoma.

[Valve ring abscesses: apropos of 59 cases. A multicenter study]. / Les abcès para-annulaires; à propos de 59 cas. Etude multicentrique.

The authors report the results of a multicenter study which recensed 59 cases (46 men, 13 women, average age 59.8 +/- 14 years) of valve ring abscesses defined by echocardiographic criteria alone (20 cases) or by echocardiographic and/or operative criteria (39 cases). The site of abscess was aortic (53 cases), mitral (5 cases) and tricuspid (1 case). The abscess complicated a prosthetic valve in 34 cases, occurred with a non-pathological valve in 11 cases or a pathological valve in 14 cases. Taking the 39 operated patients as a reference, the diagnostic sensitivity of transthoracic echocardiography was 25% and that of transoesophageal echocardiography: 88%. Bacterial vegetations were diagnosed with a sensitivity of 55% for transthoracic and 88% for transoesophageal echocardiography. The mediocre results of transthoracic echocardiography make transoesophageal echocardiography mandatory when there is a clinical suspicion of abscess: transoesophageal echocardiography should be systematic in prosthetic valve endocarditis and widely employed in native aortic valve endocarditis. The clinical outcome of these cases was: 39 cases were operated: global mortality of 23%, and 18 cases were treated medically, surgery having been declined for various reasons: old age (2 patients), operative risk (1 patient), patient refusal (4 patients), general condition considered to be too good to justify surgery (11 cases, including 6 sterilised abscesses diagnosed some time after the acute infectious phase). The outcome of these 18 patients, who form the biggest non-operated series of valve ring abscesses to date, was studied in detail: 4 died (18% mortality), 1 was operated secondarily for progressive valve dehiscence and 13 had a favourable outcome with an average follow-up period of 2 years.(ABSTRACT TRUNCATED AT 250 WORDS)

[Angiosarcoma of the pericardium. Apropos of a case]. / Angiosarcome du péricarde. A propos d'un cas.

Malignant primary cardio-pericardial tumours are rare and difficult to diagnose because of the diversity of their clinical expression. The authors report a case of pericardial angiosarcoma and review the literature, underlining the value of new non-invasive imaging techniques in the diagnosis and surgical approach to obtaining histological confirmation. Magnetic resonance imaging is a valuable tool in this context as it allows scanning of the tumoral extension in all spatial planes and the visualisation of the haemorrhagic signs of malignancy the pericardial effusion related to this pathology.