Single-centre experience on transthyretin familial amyloid polyneuropathy : case series and literature review

Familial amyloid polyneuropathy (FAP) is a most often length-dependent axonal neuropathy, often part of a multisystem disorder also affecting other organs, such as cardiac, gastrointestinal, genitourinary, renal, meningeal and eye tissue. It is most frequently the result of a mutation in the TTR gene, most commonly a p.Val50Met mutation. TTR-FAP is a rare autosomal dominant heritable disabling, heterogeneous disease in which early diagnosis is of pivotal importance when attempting treatment. This paper discusses the course of four Belgian FAP patients with different TTR mutations (p.Val48Met; p.Val52Ala; p.Ala59Val; p.Val50Met). We also review the diagnosis and differential diagnosis of TTR-FAP, diagnostic studies, follow-up, its current treatment and those in development, prognosis and the importance of genetic counseling. At first, TTR-FAP is often misdiagnosed as a chronic inflammatory demyelinating polyneuropathy or chronic idiopathic axonal polyneuropathy. Genetic testing is obligatory to confirm the diagnosis of TTR-FAP, except in familial cases. Biopsy samples are an asset in diagnosing TTR-FAP but can be falsely negative. At the moment, tafamidis meglumine is considered as first-line treatment in stage I neurological disease. Patients eligible for liver transplantation should be carefully selected when first-line therapy fails

Percutaneous closure of PFO in patients with reduced oxygen saturation at rest and during exercise : short- and long-term results

Background. A patent foramen ovale (PFO) is a rare cause of hypoxemia and clinical symptoms of dyspnea. Due to a right-to-left shunt, desaturated blood enters the systemic circulation in a subset of patients resulting in dyspnea and a subsequent reduction in quality of life (QoL). Percutaneous closure of PFO is the treatment of choice. Objectives. This retrospective multicentre study evaluates short- and long-term results of percutaneous closure of PFO in patients with dyspnea and/or reduced oxygen saturation. Methods. Patients with respiratory symptoms were selected from databases containing all patients percutaneously closed between January 2000 and September 2018. Improvement in dyspnea, oxygenation, and QoL was investigated using pre- and postprocedural lung function parameters and two postprocedural questionnaires (SF-36 and PFSDQ-M). Results. The average follow-up period was 36 [12-43] months, ranging from 0 months to 14 years. Percutaneous closure was successful in 15 of the 16 patients. All patients reported subjective improvement in dyspnea immediately after device deployment, consistent with their improvement in oxygen saturation (from 90 +/- 6% to 94 [92-97%] on room air and in upright position) (p<0.05). Both questionnaires also indicated an improvement of dyspnea and QoL after closure. The two early and two late deaths were unrelated to the procedure. Conclusion. PFO-related dyspnea and/or hypoxemia can be treated successfully with a percutaneous intervention with long-lasting benefits on oxygen saturation, dyspnea, and QoL

Electron photodetachment dissociation of DNA anions with covalently or noncovalently bound chromophores

Double stranded DNA multiply charged anions coupled to chromophores were subjected to UV-Vis photoactivation. in a quadrupole ion trap mass spectrometer. The chromophores included noncovalently bound minor groove binders (activated in the near UV), noncovalently bound intercalators (activated with visible light), and covalently linked fluorophores and quenchers (activated at their maximum absorption wavelength). We found that the activation of only chromophores having long fluorescence lifetimes did result in efficient electron photodetachment from the DNA complexes. In the case of ethidium-dsDNA complex excited at 500 nm, photodetachment is a multiphoton process. The MS3 fragmentation of radicals produced by photodetachment at lambda = 260 nm (DNA excitation) and by photodetachment at lambda > 300 nm (chromophore excitation) were compared. The radicals keep no memory of the way they were produced. A weakly bound noncovalent ligand (m-amsacrine) allowed probing experimentally that a fraction of the electronic internal energy was converted into vibrational internal energy. This fragmentation channel was used to demonstrate that excitation of the quencher DABSYL resulted in internal conversion, unlike the fluorophore 6-FAM. Altogether, photodetachment of the DNA complexes upon chromophore excitation can be interpreted by the following mechanism: (1) ligands with sufficiently long excited-state lifetime undergo resonant two-photon excitation to reach the level of the DNA excited states, then (2) the excited-state must be coupled to the DNA excited states for photodetachment to occur. Our experiments also pave the way towards photodissociation probes of biomolecule conformation in the gas-phase by Forster resonance energy transfer (FRET)

Aortic valve replacement due to granulomatosis with polyangiitis : a case series

Background Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is a systemic inflammatory process predominantly affecting upper and lower respiratory tract and kidneys. Valvular heart disease is a rare manifestation of GPA. Case summary We report two cases of acute valvular heart disease mimicking acute endocarditis caused by GPA. Both patients were middle-aged females with acute aortic valve regurgitation suggestive of possible infective endocarditis. In their recent medical history, atypical otitis and sinusitis were noted. The first patient was admitted with heart failure and the second patient because of persisting fever. Echocardiogram revealed severe aortic regurgitation with an additional structure on two cusps, suggestive of infective endocarditis in both patients. Urgent surgical replacement was performed; however, intraoperative findings did not show infective endocarditis, but severe inflammatory changes of the valve and surrounding tissue. In both patients, the valve was replaced by a prosthetic valve. Microscopic examination of the valve/myocardial biopsy showed diffuse acute and chronic inflammation with necrosis and necrotizing granulomas, compatible with GPA after infectious causes were excluded. Disease remission was obtained in both patients, in one patient with Rituximab and in the other with Glucocorticoids and Cyclophosphamide. Both had an uneventful follow-up. Discussion Granulomatosis with polyangiitis can be a rare cause of acute aortic valve regurgitation mimicking infective endocarditis with the need for surgical valve replacement. Atypical ear, nose, and throat symptoms can be a first sign of GPA. Symptom recognition is important for early diagnosis and appropriate treatment to prevent further progression of the disease

Summary of 2020 ESC guidelines on non-STE ACS, adult congenital heart disease, sports cardiology and atrial fibrillation.

peer reviewedDuring the ESC congress in September 2020, the new ESC guidelines were presented and are available on the ESC website. The new guidelines describe management recommendations on following cardiovascular diseases: non-STE ACS, adult congenital heart disease, sports cardiology and atrial fibrillation. The present document gives a summary of these guidelines and highlights the most important recommendations and changes in the management of these diseases. It will help to increase awareness about the new guidelines and may stimulate to consult the full document for specific items. Ultimately, the authors hope that this document will enhance implementation of new ESC guidelines in daily clinical practice

Preinfarction angina protects against out-of-hospital ventricular fibrillation in patients with acute occlusion of the left coronary artery

AbstractOBJECTIVESThe goal of this study was to evaluate the effect of preconditioning on out-of-hospital ventricular fibrillation (VF) in patients with acute myocardial infarction (AMI).BACKGROUNDMore than half of the deaths associated with AMI occur out of the hospital and within 1 h of symptom onset. In humans, preinfarction angina (PA), which can serve as a surrogate marker for preconditioning, reduces infarct size, but the protective effect against out-of-hospital VF has not been investigated.METHODSPreinfarction angina status and acute coronary angiographic findings of 72 consecutive patients with AMI complicated by out-of-hospital VF were compared with 144 matched controls without this complication.RESULTSPreinfarction angina is associated with a lower risk for VF (odds ratio [OR]: 0.40, 95% confidence interval [CI]: 0.18 to 0.88). In patients with acute occlusion of the left coronary artery (LCA) (n = 136), the risk reduction is pronounced (OR: 0.25, 95% CI: 0.10 to 0.66), whereas, in patients with acute occlusion of the right coronary artery (RCA) (n = 67), the protective effect of PA on VF was not observed (OR: 2.25, 95% CI: 0.45 to 11.22). Subgroup and multivariate analyses show that the protective effect is independent of cardiovascular risk factors, preinfarction treatment with beta-adrenergic blocking agents or aspirin, the presence of collaterals or residual antegrade flow or the extent of coronary artery disease.CONCLUSIONSPreinfarction angina protects against out-of-hospital VF in patients with acute occlusion of the LCA. This protection is independent of risk factors or coronary anatomy. A larger study is needed to examine the apparently different effect in patients with acute occlusion of the RCA

Acute and critically ill peripartum cardiomyopathy and 'bridge to' therapeutic options: a single center experience with intra-aortic balloon pump, extra corporeal membrane oxygenation and continuous-flow left ventricular assist devices

Introduction: Peripartum cardiomyopathy (PPCM) patients refractory to medical therapy and intra-aortic balloon pump (IABP) counterpulsation or in whom weaning from these therapies is impossible, are candidates for a left ventricular assist device (LVAD) as a bridge to recovery or transplant. Continuous-flow LVADs are smaller, have a better long-term durability and are associated with better outcomes. Extra corporeal membrane oxygenation (ECMO) can be used as a temporary support in patients with refractory cardiogenic shock. The aim of this study was to evaluate the efficacy and safety of mechanical support in acute and critically ill PPCM patients. Methods: This was a retrospective search of the patient database of the Ghent University hospital (2000 to 2010). Results: Six PPCM-patients were treated with mechanical support. Three patients presented in the postpartum period and three patients at the end of pregnancy. All were treated with IABP, the duration of IABP support ranged from 1 to 13 days. An ECMO was inserted in one patient who presented with cardiogenic shock, multiple organ dysfunction syndrome and a stillborn baby. Two patients showed partial recovery and could be weaned off the IABP. Four patients were implanted with a continuous-flow LVAD (HeartMate II(R), Thoratec Inc.), including the ECMO-patient. Three LVAD patients were successfully transplanted 78, 126 and 360 days after LVAD implant; one patient is still on the transplant waiting list. We observed one peripheral thrombotic complication due to IABP and five early bleeding complications in three LVAD patients. One patient died suddenly two years after transplantation. Conclusions: In PPCM with refractory heart failure IABP was safe and efficient as a bridge to recovery or as a bridge to LVAD. ECMO provided temporary support as a bridge to LVAD, while the newer continuous-flow LVADs offered a safe bridge to transplant

Lifestyle behaviour and risk factor control in coronary patients : Belgian results from the cross-sectional EUROASPIRE surveys

Objective: The aim of this study was to assess lifestyle behaviour as well as risk factor management across Belgian coronary patients who participated in the cross-sectional European Action on Secondary Prevention through Intervention to Reduce Events (EUROASPIRE) surveys. Methods: Analyses are based on a series of coronary patients by combining data from the Belgian participants in the EUROASPIRE III (328 patients; in 2006-2007) and EUROASPIRE IV (343 patients; in 2012-2013) surveys. Four hospitals located in the Ghent area participated in the surveys. Patients included in the analyses were >= 18 years old and had been hospitalised for a coronary event. Information on cardiovascular risk factors, lifestyle behaviour and medical treatment were obtained. Results: Overall, the proportion of smokers was 11% with 40% persistent smokers. Adequate physical activity levels were reported by 17%, 28% of patients were obese, 47% was central obese and known diabetes was prevalent in 21% of patients. Hypertension was observed in 46% of patients and 20% had a total cholesterol >= 5 mmol/L. About 80% had participated in a cardiac rehabilitation programme and the majority of patients were treated with blood pressure (92%) or lipid-lowering drugs (92%). Anxiety and depressive symptoms were reported by 30% and 24%, respectively. Differences between EUROASPIRE III and IV were limited. Conclusions: Compared to the overall EUROASPIRE results in Europe, Belgian CHD patients seem to do slightly better. However, tackling obesity, physical inactivity, hypertension and psychosocial distress remains an important challenge in the management of coronary patients