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Ventricular Arrhythmic Storm after Initiating Sacubitril/Valsartan.
Vicent, L, Juárez, M, Martín, I, García, J, González-Saldívar, H, Bruña, V, Devesa, C, Sousa-Casasnovas, I, Fernández-Avilés, F, Martínez-Sellés, M
Cardiology. 2018;(2):119-123
Abstract
OBJECTIVES Sacubitril/valsartan was approved recently for the treatment of patients with heart failure and reduced ejection fraction. We present 6 cases of ventricular arrhythmia, that occurred shortly after sacubitril/valsartan initiation, that required drug withdrawal. Other potential triggering factors of electrical storm were ruled out and, from the arrhythmic perspective, all of the patients were stable in the previous year. Our aim is to describe the possible association of sacubitril/valsartan with arrhythmic storm. METHODS This was an observational monocentric study performed in the first 7 months of sacubitril/valsartan commercialization in Spain (October 2016). All patients were included in the SUMA (Sacubitril/Varsartan Usado Ambulatoriamente en Madrid [Sacubitril/Valsartan Used in Outpatients in Madrid]) registry. Patients were consecutively enrolled on the day they started the drug. Ventricular arrhythmic storm was defined as ≥2 episodes of sustained ventricular arrhythmia or defibrillator therapy application in 24 h. RESULTS From 108 patients who received the drug, 6 presented with ventricular arrhythmic storm (5.6%). Baseline characteristics were similar in the patients with and without ventricular arrhythmic storm. The total number of days that sacubitril/valsartan was administered to each patient was 5, 6, 44 (8 since titration), 84, 93, and 136 (105 since titration), respectively. CONCLUSIONS Our data are not enough to infer a cause-and-effect relationship. Further investigations regarding a potential proarrhythmic effect of sacubitril/valsartan are probably needed.
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Cardiac arrhythmia and late-onset muscle weakness caused by a myofibrillar myopathy with unusual histopathological features due to a novel missense mutation in FLNC.
Avila-Smirnow, D, Gueneau, L, Batonnet-Pichon, S, Delort, F, Bécane, HM, Claeys, K, Beuvin, M, Goudeau, B, Jais, JP, Nelson, I, et al
Revue neurologique. 2016;(10):594-606
Abstract
Myofibrillar myopathies (MFM) are mostly adult-onset diseases characterized by progressive morphological alterations of the muscle fibers beginning in the Z-disk and the presence of protein aggregates in the sarcoplasm. They are mostly caused by mutations in different genes that encode Z-disk proteins, including DES, CRYAB, LDB3, MYOT, FLNC and BAG3. A large family of French origin, presenting an autosomal dominant pattern, characterized by cardiac arrhythmia associated to late-onset muscle weakness, was evaluated to clarify clinical, morphological and genetic diagnosis. Muscle weakness began during adult life (over 30 years of age), and had a proximal distribution. Histology showed clear signs of a myofibrillar myopathy, but with unusual, large inclusions. Subsequently, genetic testing was performed in MFM genes available for screening at the time of clinical/histological diagnosis, and desmin (DES), αB-crystallin (CRYAB), myotilin (MYOT) and ZASP (LDB3), were excluded. LMNA gene screening found the p.R296C variant which did not co-segregate with the disease. Genome wide scan revealed linkage to 7q.32, containing the FLNC gene. FLNC direct sequencing revealed a heterozygous c.3646T>A p.Tyr1216Asn change, co-segregating with the disease, in a highly conserved amino acid of the protein. Normal filamin C levels were detected by Western-blot analysis in patient muscle biopsies and expression of the mutant protein in NIH3T3 showed filamin C aggregates. This is an original FLNC mutation in a MFM family with an atypical clinical and histopathological presentation, given the presence of significantly focal lesions and prominent sarcoplasmic masses in muscle biopsies and the constant heart involvement preceding significantly the onset of the myopathy. Though a rare etiology, FLNC gene should not be excluded in early-onset arrhythmia, even in the absence of myopathy, which occurs later in the disease course.
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Compound heterozygous mutations in the SCN5A-encoded Nav1.5 cardiac sodium channel resulting in atrial standstill and His-Purkinje system disease.
Baskar, S, Ackerman, MJ, Clements, D, Mayuga, KA, Aziz, PF
The Journal of pediatrics. 2014;(5):1050-2
Abstract
An 11-year-old girl on evaluation for syncope was found to have progressive sinus node dysfunction and His-Purkinje system disease with atrial standstill. Genetic analysis revealed compound heterozygous mutations of the SCN5A gene in a novel combination.
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Muscle weakness, palpitations and a small chin: the Andersen-Tawil syndrome.
Rajakulendran, S, Tan, SV, Hanna, MG
Practical neurology. 2010;(4):227-31
Abstract
'Ion channelopathies' have emerged in the past decade as a new cause of several neurological diseases. These Mendelian disorders are caused by mutations in genes that encode ion channel subunits and are often characterised by paroxysmal attacks of brain or muscle dysfunction, interspersed with periods of clinical normality. Andersen-Tawil syndrome is one of the rarest and is characterised clinically by the triad of periodic paralysis, cardiac dysrhythmias and skeletal abnormalities. Mutations in a potassium channel gene, KCNJ2 which encodes the potassium channel, Kir2.1, underlie the disorder. Here, the authors describe a patient and review the clinical spectrum and genetic features of the disorder.
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Dolasetron overdose resulting in prolonged QTc interval and severe hypotension: a case report and literature review.
Rochford, M, Kiernan, TJ, Aziz, A
Emergency medicine journal : EMJ. 2007;(7):515-7
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Abstract
Dolasetron (Anzemet) overdose is uncommon, and, to our knowledge, this is the only case report of an intentional overdose. Dolasetron (dolasetron mesylate) is a selective 5-hydroxytryptamine 3 antagonist derived from pseudopelletierine, and is used in the prevention and treatment of nausea and vomiting. Transient and asymptomatic ECG changes, including QRS widening and PR and QTc prolongation, have been reported in therapeutic doses. The case of a 21-year-old woman who presented after an intentional overdose of 10x200 mg dolasetron tablets resulting in prolongation of the QTc interval and severe hypotension is reported here. Management of hypotension included intravenous fluid resuscitation and norepinephrine infusion with invasive monitoring in a high dependency unit. Sodium cardiac channel block contributes to cardiotoxicity observed in dolasetron overdose. Sodium bicarbonate was used in an attempt to reduce cardiac sodium channel block, although we observed no apparent benefit. As dolasetron becomes more commonly used in the outpatient setting, both doctors and patients need to be aware of the dangers of dolasetron in toxic doses. The pharmacology and toxicology of dolasetron are discussed.
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Discrimination of Brugada syndrome patients from individuals with the saddle-back type ST-segment elevation using a marker of the standard 12-lead electrocardiography.
Nakazawa, K, Sakurai, T, Kishi, R, Takagi, A, Osada, K, Ryu, S, Fujita, S, Matsuda, H, Ishikawa, Y, Miyake, F
Circulation journal : official journal of the Japanese Circulation Society. 2007;(4):546-9
Abstract
BACKGROUND In the clinical situation, the saddle-back (S-B) type is more frequently detected than the coved type. In the present study, the discrimination of Brugada syndrome from the S-B type individuals using a marker of the standard 12-lead electrocardiography (ECG) was attempted. METHODS AND RESULTS The study group consisted of 55 individuals with the S-B type in whom pilsicainide provocation test (PLC test) was carried out. The time from the onset of the QRS wave in lead V(2) (IV (2)) to the peak of the late R-like wave in the QRS wave (PV(2)), and the time from IV(2) to the offset of the QRS wave in lead V(5) (EV(5)) were measured. The coved type was induced by the PLC test in 29 cases (N-C group), but not in the remaining 26 cases (N-N group). The (IV(2) -PV(2)) - (IV(2) - EV(5)) value before the PLS test was greater in the N-C group than in the N-N group. The negative predictive value of ;(IV(2) - PV(2)) - (IV(2) - EV(5)) > or =0' was 76.4% for the prediction of a positive PLC test. CONCLUSIONS A ;(IV(2) - PV(2)) - (IV(2) - EV(5)) > or =0' is a useful ECG marker for the discrimination of Brugada syndrome in the S-B type individuals.
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Complex drug-drug-disease interactions between amiodarone, warfarin, and the thyroid gland.
Kurnik, D, Loebstein, R, Farfel, Z, Ezra, D, Halkin, H, Olchovsky, D
Medicine. 2004;(2):107-113
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Abstract
Many patients with cardiac arrhythmias require concomitant therapy with warfarin and amiodarone. Beyond the predictable pharmacokinetic drug-drug interaction requiring a significant warfarin dose reduction, the iodine-rich amiodarone affects the thyroid gland, causing overt hypothyroidism or thyrotoxicosis in 14%-18% of cases. In turn, thyroid disorders may affect warfarin sensitivity, with hypothyroidism and thyrotoxicosis resulting in increased or decreased warfarin requirements, respectively. We describe 3 patients on concomitant amiodarone and warfarin who developed amiodarone-induced thyrotoxicosis heralded by a significant decrease in warfarin requirements. We review the literature on the mechanisms of the complex drug-drug and drug-disease interactions within the thyroid gland, warfarin, and amiodarone triad. Given that significant thyroid disorders may be only mildly symptomatic and thus may escape clinical detection, we suggest that thyroid function should be tested in any patient with otherwise unexplained changes in warfarin dose requirements, particularly if concomitantly treated with amiodarone.