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BACKGROUND: Current guidelines recommend that relatives of index patients with hypertrophic cardiomyopathy (HCM) are offered clinical investigations to identify individuals at risk of adverse disease complications and sudden cardiac death. However, the value of family screening in relatives of index patients with a normal genetic investigation of recognized HCM genes is largely unknown. OBJECTIVES: The purpose of this study was to perform family screening among relatives of HCM index patients with a normal genetic investigation to establish the frequency of familial disease and the clinical characteristics of affected individuals. METHODS: Clinical and genetic investigations were performed in consecutive and unrelated HCM index patients. Relatives of index patients who did not carry pathogenic/likely pathogenic variants in recognized HCM genes were invited for clinical investigations. RESULTS: In total, 60% (270 of 453) of HCM index patients had a normal genetic investigation. A total of 80% of their relatives (751 of 938, median age 44 years) participated in the study. Of these, 5% (34 of 751) were diagnosed with HCM at baseline, whereas 0.3% (2 of 717 [751-34]) developed the condition during 5 years of follow-up. Their median age at diagnosis was 57 years (IQR: 51-70 years). Two-thirds (22 of 36) were diagnosed following family screening, whereas one-third (14 of 36) had been diagnosed previously because of cardiac symptoms, a murmur, or an abnormal electrocardiogram. None of the affected relatives experienced adverse disease complications. The risk of SCD was low. CONCLUSIONS: Systematic family screening of index patients with HCM and normal genetic investigations was associated with a low frequency of affected relatives who appeared to have a favorable prognosis.
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Cardiomiopatía Hipertrófica , Pruebas Genéticas , Humanos , Adulto , Persona de Mediana Edad , Anciano , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/epidemiología , Cardiomiopatía Hipertrófica/genética , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , PronósticoRESUMEN
Background: Little evidence is available on the disease expression in relatives of index patients with hypertrophic cardiomyopathy (HCM). This information has important implications for family screening programs, genetic counseling, and management of affected families. Objectives: The purpose of this study was to investigate the disease expression and penetrance in relatives of index patients carrying pathogenic/likely pathogenic (P/LP) variants in recognized HCM genes. Methods: A total of 453 consecutive and unrelated HCM index patients underwent clinical and genetic investigations. A total of 903 relatives of genotype-positive index patients were invited for clinical investigations and genetic testing. Penetrance, disease expression, and incidence rates of major adverse cardiac events (MACEs) were investigated in individuals carrying P/LP variants. Results: Forty percent (183/453) of index patients carried a P/LP variant. Eighty-four percent (757/903) of all relatives of index patients with P/LP variants were available for the investigation, of whom 54% (407/757) carried a P/LP variant. The penetrance of HCM among relatives was 39% (160/407). Relatives with HCM and index patients were diagnosed at a similar age (43 ± 18 years vs 46 ± 15 years; P = 0.11). There were no differences in clinical characteristics or incidence rates of MACE during 8 years of follow-up. Conclusions: The disease expression of HCM among index patients and affected relatives carrying P/LP variants in recognized disease genes was similar, with an equal risk of experiencing MACE. These findings provide evidence to support family screening and follow-up of genotype-positive HCM families to improve management and diminish the number of adverse disease complications among relatives.
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INTRODUCTION: Numerous studies have shown that lowering of low-density lipoprotein-cholesterol (LDL-C) reduces the risk of cardiovascular disease (CVD). To optimise treatment, some patients are referred to a lipid clinic. The reduction in LDL-C achieved in a lipid clinic in contemporary practice is, however, not well described. The aim of the present study was to assess the LDL-C lowering effect among very high-risk patients with or without statin-associated muscle symptoms (SAMS) after treatment at a specialised lipid clinic endorsing European guidelines. METHODS: Medical records from 653 patients referred to our Lipid Clinic from 1 January 2013 to 1 May 2017 were examined retrospectively. Very high-risk patients were defined as either having CVD or diabetes mellitus Type 2 who were active smokers and/or had hypertension. The reduction in LDL-C and the number of patients reaching the LDL-C treatment target were investigated by comparing baseline data with the most recent values recorded. RESULTS: We identified 208 patients at a very high-risk for CVD. They obtained an LDL-C reduction of 23% corresponding to a reduction in LDL-C of 0.7 mmol/l (p less than 0.001). The percentage of patients reaching their LDL-C goal increased from 13% to 32%. In patients who had experienced SAMS, LDL-C was reduced by 26% corresponding to a reduction in LDL-C of 0.9 mmol/l (p less than 0.001), and the percentage of patients reaching their LDL-C goal increased from 8% to 23%. CONCLUSIONS: Very high-risk patients with or without SAMS obtained a clinically meaningful reduction in LDL-C of approximately 25% owing to their Lipid Clinic treatment. FUNDING: none. TRIAL REGISTRATION: not relevant.
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Enfermedades Cardiovasculares , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Instituciones de Atención Ambulatoria , Enfermedades Cardiovasculares/prevención & control , LDL-Colesterol , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
AIM: To investigate the added value of myocardial perfusion scintigraphy imaging (MPI) in consecutive patients with suspected coronary artery disease (CAD) and a recent, normal exercise electrocardiography (ECG). METHODS: This study was a retrospective analysis of consecutive patients referred for MPI during a 2-year period from 2006-2007 at one clinic. All eligible patients were suspected of suffering from CAD, and had performed a satisfactory bicycle exercise test (i.e., peak heart rate > 85% of the expected, age-predicted maximum) within 6 mo of referral, their exercise ECG was had no signs of ischemia, there was no exercise-limiting angina, and no cardiac events occurred between the exercise test and referral. The patients subsequently underwent a standard 2-d, stress-rest exercise MPI. Ischemia was defined based on visual scoring supported by quantitative segmental analysis (i.e., sum of stress score > 3). The results of cardiac catheterization were analyzed, and clinical follow up was performed by review of electronic medical files. RESULTS: A total of 56 patients fulfilled the eligibility criteria. Most patients had a low or intermediate ATPIII pre-test risk of CAD (6 patients had a high pre-test risk). The referral exercise test showed a mean Duke score of 5 (range: 2 to 11), which translated to a low post-exercise risk in 66% and intermediate risk in 34%. A total of seven patients were reported with ischemia by MPI. Three of these patients had high ATPIII pre-test risk scores. Six of these seven patients underwent cardiac catheterization, which showed significant stenosis in one patient with a high pre-test risk of CAD, and indeterminate lesions in three patients (two of whom had high pre-test risk scores). With MPI as a gate keeper for catheterization, no significant, epicardial stenosis was observed in any of the 50 patients (0%, 95% confidence interval 0.0 to 7.1) with low to intermediate pre-test risk of CAD and a negative exercise test. No cardiac events occurred in any patients within a median follow up period of > 1200 d. CONCLUSION: The added diagnostic value of MPI in patients with low or intermediate risk of CAD and a recent, normal exercise test is marginal.
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OBJECTIVES: The aim of this study was to evaluate the potential utility of genetic diagnosis in clinical management of families with hypertrophic cardiomyopathy (HCM) caused by mutations in the gene for cardiac troponin I (TNNI3). BACKGROUND: Knowledge about the clinical disease expression of sarcomeric gene mutations in HCM has predominantly been obtained by investigations of single individuals (probands) or selected families. To establish the role of genetic diagnosis in HCM families, systematic investigations of probands and their relatives are needed. METHODS: Cardiac troponin I was investigated by direct sequencing and fluorescent (F)-SSCP analysis in 748 consecutive HCM families. Relatives of HCM probands with TNNI3 mutations were invited for cardiovascular and genetic assessment. RESULTS: The prevalence of TNNI3 mutations was 3.1%. Mutations appeared to cluster in exons 7 and 8. A total of 100 mutation carriers were identified in 23 families with 13 different mutations (6 novel). Disease penetrance was 48%. Patients were diagnosed from the second to eighth decade of life. The morphologic spectrum observed represented a wide range of HCM. Two offspring of clinically unaffected mutation carriers were resuscitated from cardiac arrest, and an additional four individuals died suddenly as their initial presentation. Six individuals experienced other disease-related deaths. CONCLUSIONS: The clinical expression of TNNI3 mutations was very heterogeneous and varied both within and between families with no apparent mutation- or gene-specific disease pattern. The data suggest that disease development may be monitored by regular assessment of cardiac symptoms and electrocardiographic abnormalities. Genetic diagnosis of TNNI3 is valuable in identifying clinically unaffected mutation carriers at risk of disease development and facilitates accurate management and counseling.