ABSTRACT
Objective:To investigate the relationship between double mutations of myosin heavy chain gene (MYH6) p.Gly743Arg and p.Glu1389Lys and the cardiac phenotype.Methods:Patients carrying double mutations in the MYH6 gene p.Gly743Arg and p.Glu1389Lys were screened from 52 unrelated left ventricular hypertrophy (LVH) who were admitted to the Second Hospital of Chongqing Medical University from 2015 to 2020, and the genetic testing of peripheral blood of patients by second-generation whole-exome sequencing assay technology and genomic DNA of their family members Sanger sequencing was performed to validate the genomic DNA of the family members. The cardiac phenotype was evaluated by electrocardiogram, coronary computed tomography angiography (CTA), echocardiography, and cardiac magnetic resonance imaging (MRI) as adjuncts.Results:All whole-exome gene were detected in 52 unrelated patients with LVH, of which 1 patient (1.9%) had double mutations in MYH6 gene p.Gly743Arg and p.Glu1389Lys (proband). Two members of the maternal line of this patient carried p.Glu1389Lys mutation, but there was no obvious clinical phenotype. Two members of the paternal line carried p.Gly743Arg mutation and had obvious clinical phenotype of bradycardia, but there was no LVH. The male proband, aged 21 years old, presented with LVH and sinus bradycardia but no coronary artery stenosis on CTA before treatment, MRI showed that the left ventricular end diastolic diameter was 58 mm. After treatment with angiotensin receptor-enkephalinase inhibitor (ARNI), electrocardiogram showed that the heart rate increased significantly (from 43 bpm to 72 bpm). Echocardiography showed that the left ventricular end diastolic diameter decreased significantly (from 60 mm to 49 mm).Conclusions:The p.Glu1389Lys mutation of the MYH6 gene may not manifest the phenotype of heart disease. MYH6 gene p.Gly743Arg mutation may be manifested asymptomatic sinus bradycardia, but there is no LVH phenotype. The cardiac disease phenotype caused by the double mutations of p.Gly743Arg and p.Glu1389Lys in the MYH6 gene is more obvious. Asymptomatic LVH and sinus bradycardia can appear in adolescence, but the LVH phenotype can be reversed in a short period of time after ARNI treatment.
ABSTRACT
OBJECTIVE：To analyze the situation of inpatients with heart failure taking sacubitril-valsartan. METHODS ：The data of heart failture inpatients using sacubitril-valsartan in our hospital were collected during Oct. 2019 to Mar. 2020，including basic information of patients such as gender ，age，inpatient department ，length of stay ；the application of sacubitril-valsartan ， including indications ，contraindications，usage and dosage ，course of medication ；conversion with angiotensin converting enzyme inhibitor（ACEI）/angiotensin Ⅱ receptor antagonist （ARB）and adverse drug reactions ，were summarized. RESULTS ：A total of 252 cases were collected ，including 172 males（68.25％）and 80 females（31.75％）. The average age of the patients was （67.02± 14.23）years old ，and 85 cases were 75 years or older （33.73％）. Average hospitalization time was （12.03±8.19）d，the average left ventricular ejection fraction （LVEF）before medication was （38.69±10.45）％，the average blood potassium was （4.16±0.65） mmol/L，and the average estimated value of glomerular filtration （eGFR）was（69.14±32.01）mL/（min·1.73 m2）. The main distri- bution departments were cardiology department （59.14％），followed by nephrology department （8.73％），respiration department （7.14％），cardiac surgery department （5.95％），geriatrics department （5.56％），emergency medicine department （3.57％）and neurology department （3.17％）. All patients had indications ，but 25 cases（9.92％）had contraindications ，6 cases（2.38％）had blood potassium ＞5.4 mmol/L，19 cases（7.54％）had eGFR ＜15 mL/（min·1.73 m2）. The usage and dosage was 50 mg/bid （45.24％）；39 cases（15.47％）were given medicine once a day ，which was unreasonable. Average treatment course was （7.80± 5.86）d. 7 patients（2.78％）converted to ACEI ，and 3 patients（42.86％）had a conversion interval less than 36 h；20 patients （7.93％） were converted to ARB ，and there was no obvious inappropriate conversion. Hypotension occurred in 14 patients （5.56％）. Blood pressure returned to the normal range in 2 patients after drug withdrawal and 12 patients after dose reduction. No patient had adverse reactions such as involuntary muscle tremor and arrhythmia. CONCLUSIONS ： All the inpatients wit h heart failure in our hospital have indications and good safety. Only a few patients have blood pressure intolerance. However ，there were problems such as low dosage ，inappropriate frequency of administration ，drug use against contraindications，and inappropriate timing of drug conversion. Clinical pharmacists can carry out the knowledge propaganda of rational drug use ，strengthen the pharmaceutical care of patients ，timely detect the situation of irrational drug use and monitor adverse drug reactions ，and actively intervene to ensure the rationality and safety of patients ’medication.
ABSTRACT
OBJECTIVE： To investigate the clinical application of angiotensin receptor enkephalinase inhibitor sacubitril valsartan in patients with heart failure， and to provide reference for its standardized use. METHODS： The electronic medical records of inpatients with heart failure using sacubitril valsartan in cardiovascular medicine department of the First Affiliated Hospital of Soochow University were collected from hospital information system during Oct. 2017 to Jun. 2018. Those medical records were analyzed statistically in respects of indication， contraindications， usage and dosage， conversion with angiotensin converting enzyme inhibitor （ACEI） or angiotensin Ⅱ receptor antagonist （ARB）， ADR and standard-reaching rate of target dose， etc. RESULTS： A total of 61 patients were given sacubitril valsartan， among which there were 7 cases （11.48％） without indication and 5 cases （8.20％） with contraindications. There were 34 cases （55.74％） with unreasonable initial dose， 4 cases （6.56％） with unreasonable frequency， 7 cases （11.48％） with unreasonable conversion with ACEI， 2 cases （3.28％） with unreasonable conversion with ARB. 9 cases （14.75％） suffered from ADR. All patients did not reach the target dose， but 27 patients （44.26％） met the target blood pressure. CONCLUSIONS： There is still a certain gap between clinical application of sacubitril valsartan and 2016 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure and 2017 Guideline for the Management of Heart Failure， mainly involving indication， contraindications， usage and dosage， drug conversion， etc. Specially the initial dosage is generally low. It is suggested that its clinical application should be further standardized by means of real-time checking and regular evaluation.