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.

High Lipoprotein(a) May Explain One-Quarter of Clinical Familial Hypercholesterolemia Diagnoses in Danish Lipid Clinics.

CONTEXT: Cholesterol carried in lipoprotein(a) adds to measured low-density lipoprotein cholesterol (LDL-C) and may therefore drive some diagnoses of clinical familial hypercholesterolemia (FH). OBJECTIVE: We investigated plasma lipoprotein(a) in individuals referred to Danish lipid clinics and evaluated the effect of plasma lipoprotein(a) on a diagnosis of FH. METHODS: Individuals referred to 15 Danish lipid clinics who were suspected of having FH according to nationwide referral criteria were recruited between September 1, 2020 and November 30, 2021. All individuals were classified according to the Dutch Lipid Clinical Network criteria for FH before and after LDL-C was adjusted for 30% cholesterol content in lipoprotein(a). We calculated the fraction of individuals fulfilling a clinical diagnosis of FH partly due to elevated lipoprotein(a). RESULTS: We included a total of 1166 individuals for analysis, of whom 206 fulfilled a clinical diagnosis of FH. Median lipoprotein(a) was 15 mg/dL (29 nmol/L) in those referred and 28% had lipoprotein(a) greater than or equal to 50 mg/dL (105 nmol/L), while 2% had levels greater than or equal to 180 mg/dL (389 nmol/L). We found that in 27% (55/206) of those fulfilling a clinical diagnosis of FH, this was partly due to high lipoprotein(a). CONCLUSION: Elevated lipoprotein(a) was common in individuals referred to Danish lipid clinics and in one-quarter of individuals who fulfilled a clinical diagnosis of FH, this was partly due to elevated lipoprotein(a). These findings support the notion that the LPA gene should be considered an important causative gene in patients with clinical FH and further support the importance of measuring lipoprotein(a) when diagnosing FH as well as for stratification of cardiovascular risk.

Genetic testing increases the likelihood of a diagnosis of familial hypercholesterolaemia among people referred to lipid clinics: Danish national study.

BACKGROUND AND AIMS: It is unclear to what extent genetic testing improves the ability to diagnose familial hypercholesterolaemia (FH). We investigated the percentage with FH among individuals referred to Danish lipid clinics, and evaluated the impact of genetic testing for a diagnosis of FH. METHODS: From September 2020 through November 2021, all patients referred for possible FH to one of the 15 Danish lipid clinics were invited for study participation and >97% (n = 1488) accepted. The Dutch Lipid Clinical Network criteria were used to diagnose clinical FH. The decision of genetic testing for FH was based on local practice. RESULTS: A total of 1243 individuals were referred, of whom 25.9% were diagnosed with genetic and/or clinical FH. In individuals genetically tested (n = 705), 21.7% had probable or definite clinical FH before testing, a percentage that increased to 36.9% after genetic testing. In individuals with unlikely and possible FH before genetic testing, 24.4% and 19.0%, respectively, had a causative pathogenic variant. CONCLUSIONS: In a Danish nationwide study, genetic testing increased a diagnosis of FH from 22% to 37% in patients referred with hypercholesterolaemia suspected of having FH. Importantly, approximately 20% with unlikely or possible FH, who without genetic testing would not have been considered having FH (and family screening would not have been undertaken), had a pathogenic FH variant. We therefore recommend a more widespread use of genetic testing for evaluation of a possible FH diagnosis and potential cascade screening.

A Large Pericardial Cyst in the Left Cardiophrenic Causing Persistent Chest Pain and Cough: A Case Report.

BACKGROUND Pericardial cyst is a rare benign mass of the mediastinum. More than two-thirds of pericardial cysts are located in the right cardiophrenic angle and less than one-third in the left cardiophrenic angle. Most cases are asymptomatic and discovered incidentally during to thoracic imaging such as chest X-ray, CT scans, and transthoracic echocardiograms. When pericardial cysts present with symptoms, they are often persistent and non-specific and include chest pain, dyspnea, and persistent cough. The optimal management of pericardial cysts is unclear, and no large studies regarding safety, efficacy, and long-term follow-up exist. Management strategies include cyst resection with sternotomy, thoracotomy or video-assisted thoracic surgery, cyst aspiration, and sclerosis after aspiration. The optimal mode of follow-up for asymptomatic cases is also unclear. Here, we present a case of a large pericardial cyst in the left cardiophrenic angle in a middle-aged Danish woman with persistent and unresolved dyspnea and chest pain. CASE REPORT A 57-year-old woman was referred for transthoracic echocardiography because of year-long cough and left-sided chest pain, which were exacerbated in the supine position. The echocardiography revealed a large cyst-like structure over the left ventricle. A cardiac CT scan and MRI scan were performed, confirming the presence of a large pericardial cyst with no communication with the pericardium. The cyst was surgically removed via thoracotomy. CONCLUSIONS Pericardial cysts should be considered as a rare differential diagnosis, giving rise to common cardio-pulmonary symptoms such as chest pain, dyspnea, and cough.

Prognostic value of myocardial perfusion imaging after first-line coronary computed tomography angiography: A multi-center cohort study.

PURPOSE: Further diagnostic testing may be required after a coronary computed tomography angiography (CTA) showing suspected coronary stenosis. Whether myocardial perfusion imaging (MPI) provides further prognostic information post-CTA remains debated. We evaluated the prognosis for patients completing CTA stratified for post-CTA diagnostic work-up using real-world data. METHODS: We identified all patients in our uptake area with angina symptoms undergoing first-time CTA over a 10-year period. Follow-up time was a median of 3.7 years [1.9-5.8]. The primary endpoint was a composite of myocardial infarction or death. The secondary endpoint was late revascularization. RESULTS: During the study period 53,351 patients underwent CTA. Of these, 24% were referred for further down-stream testing, 3,547 (7%) to MPI and 9,135 (17%) to invasive coronary angiography (ICA). The primary and secondary endpoints occurred in 2,026 (3.8%) and 954 (1.8%) patients. Patient-characteristic-adjusted hazard ratios for the primary and secondary endpoint using patients with a normal CTA as reference were 1.37 (1.21-1.55) and 2.50 (1.93-3.23) for patient treated medically, 1.68 (1.39-2.03) and 6.13 (4.58-8.21) for patients referred to MPI and 1.94 (1.69-2.23) and 9.18 (7.16-11.78) for patients referred for ICA, respectively. Adjusted analysis with stratification for disease severity at CTA showed similar hazard ratios for patients treated medically after CTA and patients referred for MPI and treated medically after the MPI. CONCLUSION: In patients completing coronary CTA, second-line MPI testing seems to identify patients at low risk of future events. MPI seems to have the potential to act as gatekeeper for ICA after coronary CTA.

Implementation of coronary computed tomography angiography as nationally recommended first-line test in patients with suspected chronic coronary syndrome: impact on the use of invasive coronary angiography and revascularization.

AIMS: To investigate the impact of applying coronary computed tomography angiography (CCTA), as the recommended first-line diagnostic test in patients with suspected chronic coronary syndrome (CCS) on the use of invasive coronary angiography (ICA) and revascularization practice. METHODS AND RESULTS: We included all patients undergoing a first-time CCTA (n = 53555) and first-time ICA (n = 41451) from 2008 to 2017 due to suspected CCS in Western Denmark (3.3 million inhabitants). The number of CCTA procedures increased from 352 (2008) to 7739 (2017) (2098%), ICA examinations declined from 4538 to 3766 (17%). The average proportion of no- or non-obstructive coronary artery disease by CCTA was 77.5%. Referral to ICA after CCTA occurred in 16.9% of patients in 2008-10 vs. 13.9% in 2014-17 (P < 0.0001). Revascularization in patients referred to ICA after CCTA increased from 33.8% in 2008-10 vs. 44.4% in 2014-17 (P < 0.0001). The revascularization proportion in patients undergoing ICA with no preceding CCTA was 32.3% in 2008-10 vs. 33.3% in (2014-17) (P = 0.1063). Stratified by age, the overall revascularization proportion increased in the younger age groups and was unchanged or decreased in older age groups: <50 years: 60% increase, 50-59 years: 33% increase, 60-69 years: 0%, and >70 years: 9.5% decrease. CONCLUSION: The introduction of CCTA as a first-line diagnostic test in patients with suspected CCS does not associate with increased use of invasive angiography and seems to have facilitated a more appropriate revascularization practice.