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.