Severity of congenital long QT syndrome disease manifestation and risk of depression, anxiety, and mortality: a nationwide study.

AIMS: We examined if a congenital long QT syndrome (cLQTS) diagnosis and severity of cLQTS disease manifestation was associated with increased risk of depression, anxiety, and all-cause mortality. METHODS AND RESULTS: All patients with known cLQTS in Denmark were identified using nationwide registries and specialized inherited cardiac disease clinics (1994-2016) and followed for up to 3 years after their cLQTS diagnosis. Risk factors for depression, anxiety, and all-cause mortality were determined using multivariable Cox proportional-hazards regression. An age- and sex-matched control population was identified (matching 1:4). Overall, 589 patients with cLQTS were identified of which 119/589 (20.2%) developed depression or anxiety during follow-up compared with 302/2356 (12.8%) from the control population (P < 0.001). Severity of cLQTS disease manifestation was identified for 324/589 (55%) of patients with cLQTS; 162 were asymptomatic, 119 had ventricular tachycardia (VT)/syncope, and 43 had aborted sudden cardiac death (aSCD). In multivariable models, patients with aSCD, VT/syncope, or unspecified cLQTS disease manifestation had a higher risk of developing depression or anxiety compared with the control population (hazard ratio [HR]=2.4, 95% confidence interval [CI]: 1.1-5.1; HR = 1.9, 95% CI: 1.2-3.0; HR = 1.6, 95% CI: 1.1-2.3, respectively). Asymptomatic patients had similar risk of developing depression or anxiety as the control population (HR = 1.2, 95% CI: 0.8-1.9). During follow-up, 10/589 (1.7%) patients with cLQTS died compared with 27/2356 (1.1%) from the control population (P = 0.5). Furthermore, 4/10 who died had developed depression or anxiety. CONCLUSION: A severe cLQTS disease manifestation was associated with a greater risk of depression or anxiety. All-cause mortality for patients with cLQTS was low.

Long-term proarrhythmic pharmacotherapy among patients with congenital long QT syndrome and risk of arrhythmia and mortality.

AIMS: It is Class I recommendation that congenital long QT syndrome (cLQTS) patients should avoid drugs that can cause torsades de pointes (TdP). We determined use of TdP risk drugs after cLQTS diagnosis and associated risk of ventricular arrhythmia and all-cause mortality. METHODS AND RESULTS: Congenital long QT syndrome patients (1995-2015) were identified from four inherited cardiac disease clinics in Denmark. Individual-level linkage of nation-wide registries was performed to determine TdP risk drugs usage (www.crediblemeds.org) and associated risk of ventricular arrhythmias and all-cause mortality. Risk analyses were performed using Cox-hazards analyses. During follow-up, 167/279 (60%) cLQTS patients were treated with a TdP risk drug after diagnosis. Most common TdP risk drugs were antibiotics (34.1%), proton-pump inhibitors (15.0%), antidepressants (12.0%), and antifungals (10.2%). Treatment with a TdP risk drug decreased 1 year after diagnosis compared with 1 year before (28.4% and 23.2%, respectively, P < 0.001). Five years after diagnosis, 33.5% were in treatment (P < 0.001). Risk factors for TdP risk drug treatment were age at diagnosis (5-year increment) [hazard ratio (HR) = 1.07, confidence interval (CI) 1.03-1.11] and previous TdP risk drug treatment (HR = 2.57, CI 1.83-3.61). During follow-up, nine patients were admitted with ventricular arrhythmia (three were in treatment with a TdP risk drug). Eight patients died (four were in treatment with a TdP risk drug). No significant association between TdP risk drug use and ventricular arrhythmias or all-cause mortality was found (P = 0.53 and P = 0.93, respectively), but events were few. CONCLUSION: Torsades de pointes risk drug usage was common among cLQTS patients after time of diagnosis and increased over time. A critical need for more awareness in prescribing patterns for this high-risk patient group is needed.

Hypercholesterolaemia treated with inclisiran.

In this case report, a 31-year-old woman with heterozygous familial hypercholesterolaemia (FH) underwent treatment with statins and PCSK9 inhibitor but had to discontinue due to elevated creatine kinase levels and neurological and muscular side effects. In 2021, the patient received inclisiran therapy, the first known instance of its application in Denmark. No side effects were reported, and LDL cholesterol levels were significantly reduced. This case report highlights the potential of inclisiran as an effective and well-tolerated treatment for individuals with heterozygous FH.

Self-reported health and adverse outcomes among women living with symptoms of angina or unspecific chest pain but no diagnosis of obstructive coronary artery disease-findings from the DenHeart study.

AIMS: The objectives were to describe differences in self-reported health at discharge between women diagnosed with angina or unspecific chest pain and investigate the association between self-reported health and adverse outcomes within 3 years. METHODS AND RESULTS: Data from a national cohort study were used, including data from the DenHeart survey combined with 3 years of register-based follow-up. The population included two groups of women with symptoms of angina but no diagnosis of obstructive coronary artery disease at discharge (women with angina and women with unspecific chest pain). Self-reported health measured with validated instruments was combined with register-based follow-up on adverse outcomes (a composite of unplanned cardiac readmissions, revascularization, or all-cause mortality). Associations between self-reported health and time to first adverse outcomes were investigated with Cox proportional hazard models, reported as hazards ratios with 95% confidence intervals. In total, 1770 women completed the questionnaire (49%). Women with angina (n = 931) reported significantly worse self-reported health on several outcomes compared to women with unspecific chest pain (n = 839). Within the 3 years follow-up, women with angina were more often readmitted (29 vs. 23%, P = 0.011) and more underwent revascularization (10 vs. 1%, P < 0.001), whereas mortality rates were similar (4 vs. 4%, P = 0.750). Self-reported health (physical and mental) was associated with adverse outcomes between both groups (on most instruments). CONCLUSION: Women with angina reported significantly worse self-reported health on most instruments compared to women with unspecific chest pain. Adverse outcomes varied between groups, with women diagnosed with angina experiencing more events. REGISTRATION: ClinicalTrials.gov (NCT01926145).