Objective 1: To calculate the proportion of families who did not show up for the first stage of cardiac screening (basic evaluation), we analyzed 1992 families: 1662 with CMs and 330 with channelopathies. In the first group, there were 1087 families (65.4%) with HCM, 434 (26.1%) with DCM, and 141 (8.5%) with ACM. In the second group, there were 238 families (72.1%) with Brugada syndrome and 92 (27.9%) with LQTS.

Objective 2: To calculate the proportion of patients who did not show up for cardiac MRI, we studied 1539 patients (mean±standard deviation [SD] age, 47±7 years; 48% women) in whom this test was considered advisable after an electrocardiogram and an echocardiogram. The family condition was HCM in 889 cases (57.8%), DCM in 406 (26.4%), and ACM in 244 (15.8%). We then interviewed 102 patients (52 women and 50 men) who did attend an appointment to determine their reasons. To calculate the proportion of patients who did not undergo the pharmacological challenge, we studied 837 patients (mean±SD age, 38.7±16 years, 54% men) for whom provocative testing with a sodium channel blocker or adrenaline had been requested. In this case, the family condition was Brugada syndrome in 741 cases (88.5%) and LQTS in 96 (11.5%). To investigate reasons for refusal, we interviewed 92 patients (49 women and 43 men).

Objective 3: For objective 3, we selected high-risk patients with an indication for ICD implantation (n=395) or long-term anticoagulation (n=402) from a group of 2372 patients with a definitive diagnosis of a CM or a channelopathy (43% HCM, 18% DCM, 7% ACM, 10% Brugada syndrome, 4% LQTS, 18% other). We then calculated the proportion of patients who refused these treatments and investigated complications associated with this decision.

The statistical analysis was performed in SPSS (version 20.0). The data were analyzed using basic descriptive statistics, with qualitative variables expressed as percentages and quantitative variables as mean±SD.

To analyze demographic and clinical predictors of refusal to follow medical recommendations, we studied the following variables: type of IHD (CM, channelopathy, and subtypes), age, sex, family history of SCD, presence of symptoms or arrhythmias, proband status, genetic study (yes/no), a positive genetic test result, and confirmation of IHD in the family.

Dichotomous qualitative variables were compared using Pearson's χ2 test and quantitative variables using the t test for equality of variances. Logistic regression analysis with backward elimination was used to evaluate associations between individual variables and refusal of diagnostic tests, without adjustment for potential confounders. In all cases, differences were considered significant for a P value of less than .05.

A total of 472 families with a CM (28.4%) did not undergo cardiac screening after the initial evaluation of the proband and family tree. There were 287 families (26.4%) with HCM, 151 (34.8%) with DCM, and 34 (24.1%) with ACM. There were significant differences in refusal rates between DCM and HCM (P=.001) and between DCM and ACM (P=.018). Refusal was highest in families with DCM.

Seventy-eight families with a channelopathy (23.6%) did not participate in the cardiac screening program: 51 (21.4%) with Brugada syndrome and 27 (29.3%) with LQTS. No significant differences were found between families with Brugada syndrome and those with LQTS (P=.129).

We did, however, observe significant differences between families with and without a history of SCD (21.0% vs 29.7%, P<.005). Refusal rates were lower in families with multiple cases of SCD (10.3% vs 29.7%, P<.0001).

The main reason listed for failure to attend the basic screening evaluation was “unknown/did not show up” (324 families [58.9%]). Other reasons were “administrative problems” (149 families [27.1%]), “residence in another region or country” (45 families [8.2%]), “direct refusal with no explanation” (14 families [2.5%]), and”wants to postpone appointment” (11 families [2.0%]).

Just 215 (14.9%) of the 1442 families who participated in the screening program had a confirmed diagnosis of IHD before screening. This number increased to 574 (39.8%) after screening (figure 1).

Figure 1.

Prevalence of different forms of IHD before and after family screening at an inherited heart disease unit. ACM, arrhythmogenic cardiomyopathy; BS, Brugada syndrome; DCM, dilated cardiomyopathy; HCM, hypertrophic cardiomyopathy; IHD, inherited heart disease; LQTS, long QT syndrome.

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Significant differences for a confirmed diagnosis were observed between CMs and channelopathies (42.4% vs 27.8%, P<.0005). There were no differences between the different subtypes of CMs or channelopathies.

Slightly over a quarter of the families studied chose not to participate in the IHD screening program. This means that only 1 patient—the proband—was evaluated in these families. Following evaluation of the family tree, all first-degree relatives are offered a screening appointment, but the necessary tests are not done. Refusal of screening was significantly more common in families with DCM (35%), possibly because of a lack of information or a lower awareness among healthcare providers about the hereditary nature of DCM (vs HCM and ACM). Participation in screening programs is higher in families with a history of SCD, possibly because of a greater sense of fear. Having moved to another region or country also accounts for a significant portion of reasons for nonparticipation in familial screening. This should not be an insurmountable problem in Spain, as these tests can be performed in another region and the Spanish Ministry of Health has a national system that provides coverage to patients at an accredited referral hospital or unit irrespective of their place of residence.

Our findings confirm that active cardiac screening results in more families being diagnosed with IHD than questioning of probands only. The program we analyzed confirmed a diagnosis of IHD in 42% of families with a CM and in 30% of those with a channelopathy. These figures are consistent with previous reports.1.6 The net increase in diagnosis lies around 25%.

A considerable proportion (1 in every 5) of cardiac MRIs ordered were not performed. Regardless of the reasons, failure to perform these tests poses a considerable problem in terms of managing the resources of the IHD unit and the hospital. Administrative problems were listed as the reason for not attending an MRI appointment for over half the cases. Other reasons mentioned by the patients interviewed were fear, claustrophobia, and accessibility.

It has been proposed that it is difficult to determine the true prevalence of inherited channelopathies, as this requires asymptomatic relatives to undergo a pharmacological challenge, and over 40% refuse to do this. This high refusal rate could explain the low penetrance and varying prevalence rates reported for inherited channelopathies (e.g., 15%-37% for Brugada syndrome).6,8,9 We were pleased to observe that over 80% of patients advised to undergo a pharmacological challenges in our study agreed to do so. Several predictors of refusal were identified, including a history of arrhythmias (mainly atrial fibrillation) and others factors linked to a lack of prior information. Higher participation was associated with a positive genetic test result and a history of SCD in the family.

Our questioning of patients on why they did not undergo a pharmacological challenge also showed that a considerable percentage of individuals did not do so because they were afraid (46%) or did not consider it necessary (25%).

Our findings show that only a minority of high-risk patients with a CM or a channelopathy refused to undergo IAD implantation (5%) or receive anticoagulation therapy (<3%). This rate is significantly lower than rates observed for the diagnostic tests, although it is not surprising as all the individuals in this sample had been diagnosed with an IHD. We did not detect any clear predictors of refusal to follow medical advice in terms of age, sex, or type of IHD. We did, however, find that a high percentage (almost 5%) of patients who refused ICD implantation died of SCD. By contrast, none of the patients who refused oral anticoagulation developed any complications as a result.

Our findings may be affected by selection bias in relation to referral of patients considered to be at highest risk or to have more complex conditions to the IHD unit. In addition, participation by relatives in the screening program is voluntary and therefore the study of certain families may be incomplete. A family study was considered to have been performed when at least 2 relatives were evaluated. We also chose different subpopulations to meet each of our objectives, and this could complicate interpretation of our results. Our choice of second-line tests (cardiac MRI and pharmacological challenge) and treatments (IAD implantation and anticoagulation therapy) to meet objectives 2 and 3, respectively, was arbitrary. In addition, the small number of cases in certain subgroups and the relatively short follow-up time may have limited the statistical power of these analyses.

The design of the telephone survey did not allow for further investigation of the administrative problems mentioned by the patients who did not undergo second-line tests. Probable reasons include a lack of information on the test, scheduling delays, and problems establishing contact to arrange appointments.