Impaired cerebral autoregulation in Fabry disease: A case-control study.

BACKGROUND AND PURPOSE: Cerebral small vessel disease is a common manifestation among patients with Fabry disease (FD). As a biomarker of cerebral small vessel disease, the prevalence of impaired cerebral autoregulation as assessed by transcranial Doppler (TCD) ultrasonography was evaluated in FD patients and healthy controls. METHODS: TCD was performed to assess pulsatility index (PI) and vasomotor reactivity expressed by breath-holding index (BHI) for the middle cerebral arteries of included FD patients and healthy controls. Prevalence of increased PI (>1.2) and decreased BHI (<0.69) and ultrasound indices of cerebral autoregulation were compared in FD patients and controls. The potential association of ultrasound indices of impaired cerebral autoregulation with white matter lesions and leukoencephalopathy on brain MRI in FD patients was also evaluated. RESULTS: Demographics and vascular risk factors were similar in 23 FD patients (43% women, mean age: 51 ± 13 years) and 46 healthy controls (43% women, mean age: 51 ± 13 years). The prevalence of increased PI (39%; 95% confidence interval [CI]: 20%-61%), decreased BHI (39%; 95% CI: 20%-61%), and the combination of increased PI and/or decreased BHI (61%; 95% CI: 39%-80%) was significantly (p < .001) higher in FD patients compared to healthy controls (2% [95% CI: 0.1%-12%], 2% [95% CI: 0.1%-12%], and 4% [95% CI: 0.1%-15%], respectively). However, indices of abnormal cerebral autoregulation were not associated independently with white matter hyperintensities and presented a low-to-moderate predictive ability for the discrimination of FD patients with and without white matter hyperintensities. CONCLUSIONS: Impaired cerebral autoregulation as assessed by TCD appears to be highly more prevalent among FD patients compared to healthy controls.

D313Y Variant in Fabry Disease: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: There is accumulating evidence in the literature indicating a strong correlation between Fabry disease (FD) phenotypes and specific sequence variations in the Galactosidase Alpha (GLA) gene. Among them, the potential pathogenicity and clinical relevance of D313Y variation in patients with FD remain debated. METHODS: We performed a systematic review and meta-analysis of studies reporting D313Y as single occurring variant in the GLA gene and sought to evaluate (1) the prevalence of D313Y variation in different populations with or without clinical manifestations of FD, (2) the clinical FD phenotype in D313Y-positive patients, and (3) the proportion of D313Y-positive patients presenting abnormal laboratory findings (alpha-galactosidase-A deficiency or globotriaosylceramide accumulation). RESULTS: Forty cohorts comprising 211 individuals with D313Y variation among 42,723 participants with available GLA gene-sequencing data were included. Patients highly suspected for FD had a higher prevalence of D313Y variation (4.9%, 95% CI 1.6%-9.9%; I2 = 95.5%) compared with the general population (0%, 95% CI 0%-0.1%; I2 = 1.9%; p = 0.004). The prevalence of D313Y variation was 0.6% (95% CI 0.3%-1%; I2 = 74.1%), 0.4% (95% CI 0.2%-0.7%; I2 = 0%), and 0.3% (95% CI 0.2%-0.4%; I2 = 0%) in patients presenting with neurologic, cardiac, or renal manifestations, respectively. D313Y was associated with a milder, late-onset FD phenotype, as indicated by the mean patient age of 51 years (95% CI 44-59; I2 = 94%) and the evidence of alpha-galactosidase A deficiency and globotriaosylceramide accumulation in 26.7% (95% CI 15.3%-40%; I2 = 34%) and 16.2% (95% CI 8%-26.4%; I2 = 35%) of cases, respectively. D313Y-positive patients displayed predominantly neurologic FD manifestations (58.1%, 95% CI 37.7%-77.1%; I2 = 78%), with central and peripheral nervous system (CNS/PNS) involvement noted in 28.2% (95% CI 15.4%-43.2%; I2 = 51%) and 28.5% (95% CI 17.8%-40.5%; I2 = 61%) of cases, respectively. DISCUSSION: D313Y variation seems to correlate with an atypical, mild late-onset phenotype with predominantly neurologic FD manifestations. Monitoring for CNS/PNS involvement is thus paramount to identify D313Y-positive patients with latent or early-FD pathology, which may qualify for enzyme-replacement therapy or chaperone treatment.

HEllenic Registry on Myocarditis SyndromES on behalf of Hellenic Heart Failure Association: The HERMES-HF Registry.

AIMS: Despite the existence of many studies, there are still limited data about the characteristics of myocarditis in Greece. This led to the creation of the Greek Myocarditis Registry aiming to document the different symptoms and treatment of myocarditis, assess possible prognostic factors, and find similarities and differences to what is already published in literature. This paper is a preliminary descriptive analysis of this Registry. METHODS AND RESULTS: We analysed data for the hospitalization period of all patients included in the Registry from December 2015 until November 2017. Statistics are reported as frequency (%) or median and inter-quartile range (IQR) as appropriate. In total, 146 patients were included; 83.3% of the patients reported an infection during the last 3 months. The most common symptom, regardless of the underlying infection, was chest pain (82.2%) followed by dyspnoea (18.5%), while the most common finding in clinical examination was tachycardia (26.7%). Presentation was more frequent in the winter months. ECG findings were not specific, with the repolarization abnormalities being the most frequent (60.3%). Atrial fibrillation was observed in two patients, both of whom presented with a reduced ventricular systolic function. Left ventricular ejection fraction changed significantly during the hospitalization [55% (IQR: 50-60%) on admission vs. 60% (IQR: 55-60%) on discharge, P = 0.0026]. Cardiac magnetic resonance was performed in 88 patients (61%), revealing mainly subepicardial and midcardial involvement of the lateral wall. Late gadolinium enhancement was present in all patients, while oedema was found in 39 of them. Only 11 patients underwent endomyocardial biopsy. Discharge medication consisted mainly of beta-blockers (71.9%) and angiotensin-converting enzyme inhibitors (41.8%), while 39.7% of the patients were prescribed both. CONCLUSIONS: This preliminary analysis describes the typical presentation of myocarditis patients in Greece. It is a first step in developing a better prognostic model for the course of the disease, which will be completed after the incorporation of the patients' follow-up data.

The Role of Colchicine in Treating Postoperative and Post-catheter Ablation Atrial Fibrillation.

PURPOSE: The goal of this review was to summarize, analyze, and compare trials studying the efficacy of colchicine in the prevention of atrial fibrillation (AF) post-operatively (POAF) and post-catheter ablation. Ongoing studies and current guidelines are also presented and reviewed. METHODS: Published studies on the field were identified through a literature search of the PubMed and clinicaltrials.gov databases. FINDINGS: Four original studies regarding POAF, two original studies regarding post-catheter ablation AF, and six meta-analyses were identified. In addition, the 3 most recent guidelines/expert consensus documents were scrutinized. IMPLICATIONS: AF occurs frequently after cardiac surgery (POAF) and catheter pulmonary vein isolation (postablation AF) and is associated with increased cardiovascular morbidity. A number of trials over the last few years have investigated the role of colchicine in the prevention of POAF and postablation AF targeting the local and systemic inflammatory process that leads to initiation and maintenance of AF. Available data imply that colchicine may have a preventive role in POAF and/or postablation AF. However, certain limitations of these studies underline the need for further investigation.

Colchicine Pharmacokinetics and Mechanism of Action.

Colchicine is a tricyclic, lipid-soluble alkaloid derived from the plant of the Lily family Colchicum autumnale, sometimes called the "autumn crocus". It is predominantly metabolized in the gastrointestinal tract. Two proteins, P-glycoprotein (P-gp) and CYP3A4 seem to play a pivotal role, governing its pharmacokinetic. The commonest side effects are gastrointestinal (nausea, vomiting and particularly dose-related-diarrhea) occurring in 5-10% of patients. Colchicine exerts its unique action mainly through inhibition of microtubule polymerization. Microtubule polymerization affects a variety of cellular processes including maintenance of shape, signaling, division, migration, and cellular transport. Colchicine interferes with several inflammatory pathways including adhesion and recruitment of neutrophils, superoxide production, inflammasome activation, the RhoA/Rho effector kinase (ROCK) pathway and the tumor necrosis factor alpha (TNF-α) -induced nuclear factor κΒ (NF-κΒ) pathway attenuating the inflammatory response. This concise paper attempts to give a brief review of its pharmacokinetic properties and its main mechanisms of action.

Rapid normalization of vasculitis-induced left ventricular dysfunction related with multiple cardiac thrombi.

We present a young female patient admitted in the emergency department with pulmonary edema, severely impaired left ventricular function, and simultaneous intracardiac thrombi in left and right ventricle as well as in right atrium, at echocardiography. A magnetic resonance tomography showed excess myocardial tissue edema and diffuse gadolinium enhancement. Blood analysis showed an elevated eosinophils count. The patient showed a rapid normalization of left ventricular function as well as resolution of intracardiac thrombi and myocardial tissue edema 3 months after proper treatment with cyclophosphamide and steroids for Churg-Strauss syndrome.

Cardiac plasmacytoma: a rare clinical entity.

Primary malignant cardiac tumors are rare. Among these tumors, cardiac plasmacytoma is extremely rare and is the subject of few case reports. We present the case of a 73-year-old man who had isolated cardiac plasmacytoma 26 years after successful treatment of an axillary plasmacytoma. Multiple imaging methods-including echocardiography, cardiac magnetic resonance, and positron-emission tomography/computed tomography-were valuable and complementary to each other in this patient's diagnosis and optimal management. His case illustrates the use of these techniques in the successful diagnosis and treatment of a rare clinical entity, cardiac plasmacytoma.