Inpatient detection of cardiac-inherited disease: the impact of improving family history taking (original) (raw)
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Penetrance and Risk Profile in Inherited Cardiac Diseases Studied in a Dedicated Screening Clinic
The American Journal of Cardiology, 2009
Genetically transmitted cardiomyopathies can affect several members in a family. Identification of high-risk patients could lead to a preventive treatment. We report the results of a 5-year experience of a dedicated clinic. Family screening was offered to 493 consecutive unrelated patients; 2,328 subjects (40 ؎ 19 years old, 52% men) were evaluated (mean 4.4 relatives/family). Electrocardiography and echocardiography were performed in all cases; additional tests were indicated depending on the disease. Familial study was recommended because of a proband with hypertrophic cardiomyopathy (HC) in 57%, idiopathic dilated cardiomyopathy (IDC) in 14%, arrhythmogenic right ventricular cardiomyopathy (ARVC) in 2%, left ventricular noncompaction in 2%, Brugada syndrome (BS) in 15%, long QT syndrome (LQTS) in 3%, and other conditions in 6%. Familial disease was confirmed in 164 (39%); 43% with HC, 47% with IDC, 25% with ARVC, 33% with left ventricular noncompaction, 28% with BS, and 30% with LQTS. Two hundred twenty-two (44 ؎ 20 years old, 60% men) affected relatives were identified (129 of whom were newly diagnosed). Sixtyfour patients were newly diagnosed with HC, 40 with IDC, 2 with ARVC, 5 with left ventricular noncompaction, 14 with BS, and 2 with LQTS, in whom appropriate risk stratification and medication, if needed, were initiated (specific medication in 40, 31.0%). Cardioverter-defibrillator implantation was indicated in 4 relatives for primary prevention. Ninety-two (18.7%) had a family history of sudden death (FHSCD). Consanguinity was rare but significantly associated to a higher percentage of family disease (75.0% vs 38.3%, p ؍ 0.003) and family history of sudden death (42.1% vs 17.8, p <0.001). In conclusion, the prevalence of familial disease in inherited cardiac conditions is high. Systematic familial study identified many asymptomatic affected patients who could benefit from early treatment to prevent complications. Dedicated clinics and multidisciplinary teams are needed for proper screening programs.
American Journal of Medical Genetics Part A, 2010
In potentially inherited cardiac diseases, the family history is of great importance. We looked at the way cardiologists take a family history in patients with idiopathic dilated cardiomyopathy (DCM) or long QT syndrome (LQTS) and whether this led to screening of relatives or other follow-up. We performed retrospective cross-sectional analyses of adult index patients with DCM or LQTS in a general hospital (GH) or a University Medical Center (UMC). We identified 82 index patients with DCM (34 GH; 48 UMC) and 20 with LQTS (all UMC) between 1996 and 2005. Mean follow-up was 58 months. A family history was recorded in 90% of both LQTS and DCM patients most of the cases restricted to first-degree family members. The genetic aspects, counseling and screening of family members was discussed significantly more often with LQTS than DCM patients (all P < 0.05). Also follow-up (screening of family members, DNA analysis and referral) was performed significantly more often in LQTS than DCM patients. Cardiologists in the UMC referred DCM index patients for genetic counseling more often than those in the GH (25% vs. 6%; P < 0.05). Only a few index patients with DCM were referred to a clinical genetics department. One-third of DCM cases and nearly all LQTS cases are familial. Since early recognition and treatment may reduce morbidity and mortality we recommend cardiologists take a more thorough family history and always consider referring to a clinical genetics department in such index patients.
Journal of the American College of Cardiology, 1998
Objectives. This study sought to determine whether early disease is identifiable in asymptomatic relatives of patients with dilated cardiomyopathy (DCM) by means of noninvasive cardiologic assessment. Background. DCM is diagnosed on the basis of advanced heart failure, where cardiac dilation and impaired contractility are recognized in the absence of a recognized etiology (World Health Organization criteria). However, initial clinical presentation may be with severe complications: thromboembolism, arrhythmia or sudden death. DCM has recently been recognized to be familial, with autosomal dominant inheritance in many cases. Familial disease is present in 9% to 20% of patients with DCM, and the ability to identify early disease in such people may improve patient management and aid in the understanding of pathogenesis. Method. We prospectively assessed 408 asymptomatic relatives (mean [؎SD] age 35 ؎ 15 years, 193 men) of 110 consecutive patients with DCM by means of history and physical examination, two-dimensional echocardiography, 12-lead and signal-averaged electrocardiography and metabolic exercise testing. We hypothesized that signs of lesser cardiac dysfunction in such relatives might indicate early disease. Results. Twenty-nine percent of relatives had abnormal results on the echocardiogram. Twenty percent (n ؍ 45) had left ventricular enlargement (LVE), defined as LV end-diastolic diameter (LVEDD) > ؊ 112% predicted; 6% (n ؍ 13) had depressed fractional shortening (dFS), defined as FS < ؊ 25%; and 3% (n ؍ 7) had frank DCM, defined as LV dilation, impaired contractile performance and LVEDD > ؊ 112% plus FS < ؊ 25%. Other abnormalities of cardiac function were identified in relatives with LVE or dFS: A greater number with LVE had an abnormal metabolic exercise test result than normal relatives (9% vs. 1%, p < 0.05). Relatives with LVE and abnormal maximal oxygen consumption (VO 2 max) (defined as VO 2 max <80% predicted) had a lower absolute VO 2 max than normal relatives (30 ؎ 8 vs. 43 ؎ 9 ml/min per kg, p ؍ 0.01). The QRS duration (at the 25-Hz filter) on the signalaveraged electrocardiogram was prolonged in relatives with LVE (103 ؎ 13 ms) and dFS (102 ؎ 12 ms) compared with that of normal relatives (97 ؎ 12 ms, p < 0.05). Over a mean 39-month follow-up period, 12 relatives with LVE (27%) and none with dFS developed symptomatic DCM (p < 0.0001). One relative with LVE died suddenly, and another underwent heart transplantation. Conclusions. Nearly one-third of asymptomatic relatives (29%) have echocardiographic abnormalities, and 27% of such relatives progress to development of overt DCM. Early identification of such people would permit appropriate intervention that might influence the serious complications and mortality of this disease.
Familial occurrence of isolated non-compaction cardiomyopathy
European Journal of Heart Failure, 2006
Background and aims: Isolated left ventricular non-compaction cardiomyopathy (LVNC) may have an autosomal dominant or X-linked recessive inheritance. We focus on the familial occurrence of LVNC after misdiagnosing this disorder in symptomatic patients in two families. After identification of the index patient we studied the families more intensively in order to unmask affected family members. Methods and results: LVNC was defined as an end-systolic non-compacted subendocardial layer of the left ventricular wall of at least twice the thickness of the subepicardial compacted layer (2D echocardiogram and MRI). This was studied in 13 patients in 2 families (A and B). LVNC was found in 3 out of 11 patients in family A. The grandmother was asymptomatic. Her daughter suffered from recurrent syncope and heart failure. Her daughter received a cardiac transplant because of progressive heart failure at the age of 14 years. In family B, LVNC was found in 2 patients, a father and his son and presumed in a brother and a sister of the father who died suddenly at the age of 17 and 21 years, respectively. Conclusions: In all symptomatic patients, proven LVNC was previously misdiagnosed as hypertrophic or dilated cardiomyopathy. Misdiagnosis may lead to insufficient treatment and will misdirect targeted molecular genetic analysis. LVNC was identified in seven patients in two families. Family screening may unmask affected family members for primary prevention including anti-coagulation and ICD-therapy.
Prospective Familial Assessment in Dilated Cardiomyopathy
Circulation, 2006
Background— In autoimmune disorders, circulating autoantibodies identify healthy relatives at risk years before clinical presentation. Healthy relatives of patients with dilated cardiomyopathy (DCM) who have echocardiographic changes, including left ventricular enlargement or depressed fractional shortening at baseline, have increased medium-term risk for DCM development. Approximately one third of relatives have serum anti-heart autoantibodies (AHAs) at baseline; we intended to assess their potential role in predicting DCM development. Methods and Results— Baseline evaluation, including electrocardiography, echocardiography, and AHA, was performed in 592 asymptomatic relatives of 169 consecutive DCM patients (291 males and 301 females; mean age 36±16 years). Relatives were classified in accordance with published echocardiographic criteria; those who did not have DCM were followed up (median of 58 months). DCM among relatives was diagnosed by echocardiography at follow-up. Of the 59...
GENETICS in MEDICINE
Purpose: Hypertrophic cardiomyopathy (HCM) is considered a hereditary autosomal dominant condition, but genetic testing is positive in only half of patients. In patients with negative genetic tests, the inheritance pattern and utility of family screening are unclear. Methods: Subjects with HCM were prospectively enrolled in a registry. A survey at a median follow-up of 4 years determined the yield of family screening. Results: The outcome of cardiac screening on 267 family members was reported by 120 survey respondents. Subjects with positive genetic test or family history (n = 74, 62%) reported an HCM diagnosis in 34 of 203 first-degree relatives who were screened (17%). Affected family members were diagnosed at a mean age of 30-39 years, and 22 of 34 experienced HCM-related adverse events (65%). Gene test-negative subjects with no prior family history of HCM (n = 46, 38%) reported an HCM diagnosis in only 2 of 64 first-degree relatives who were screened (3%, po0.001). These two individuals were diagnosed at age > 40 years without HCM-related adverse events. Conclusion: Hypertrophic cardiomyopathy is a heterogeneous disorder, only half of which tracks with a Mendelian inheritance pattern. Negative genetic testing and family history indicates a more complex genetic basis corresponding to low risk for family members.
Heart Rhythm, 2013
BACKGROUND It has been reported that cardiological screening and genetic evaluation in relatives of families with sudden unexplained death syndrome and unexplained cardiac arrest (UCA) may uncover a heritable etiology in a significant proportion of families. OBJECTIVE To evaluate the yield of a comprehensive evaluation protocol of a large unselected cohort of consecutive families with autopsy-negative sudden unexplained death syndrome (termed sudden arrhythmic death syndrome [SADS]) and UCA. METHODS We studied (1) 109 consecutive families (411 relatives) referred with 1 or more sudden deaths in the family and (2) 52 consecutive probands with UCA (91 relatives) referred by cardiologists between January 2007 and December 2012. A comprehensive cardiological screening was performed followed by targeted genetic evaluation if a clinical phenotype was proven or suspected. Diagnosis was made by a multidisciplinary team using published clinical criteria. RESULTS A diagnosis was made in 19 of 109 families with SADS (yield 18%), with the majority having long QT syndrome (LQTS). Diagnosis varied according to proband age, with LQTS most common in the very young (r20 years) and Brugada syndrome in the older age probands (Z40 years) (P ¼ .03). In contrast, a diagnosis was made in 32 of 52 families with UCA (yield 62%), the majority of which had LQTS and Brugada syndrome. No clinical or circumstantial factors increased the likelihood of diagnosis in families with either SADS or UCA. CONCLUSIONS In contrast to previously published series, a comprehensive strategy of cardiological evaluation and targeted genetic testing in more than 100 families with SADS was found to have a lower diagnostic yield (18%). Diagnostic yield in families with UCA was approximately 4 times higher (62%), which is consistent with the published literature. KEYWORDS Sudden arrhythmic death syndrome; Sudden unexplained death syndrome; Unexplained cardiac arrest; Long QT syndrome; Brugada syndrome; Cardiological screening; Genetic testing ABBREVIATIONS ARVC ¼ arrhythmogenic right ventricular cardiomyopathy; BrS ¼ Brugada syndrome; CPVT ¼ catecholaminergic polymorphic ventricular tachycardia; ECG ¼ electrocardiography/ electrocardiogram; ER ¼ early repolarization; EST ¼ exercise stress test; HCM ¼ hypertrophic cardiomyopathy; LQTS ¼ long QT syndrome; MRI ¼ magnetic resonance imaging; SADS ¼ sudden arrhythmic death syndrome; SQT ¼ short QT syndrome; SUDS ¼ sudden unexplained death syndrome; UCA ¼ unexplained cardiac arrest