Genetic Characteristics of Latvian Patients with Familial Hypercholesterolemia: The First Analysis from Genome-Wide Sequencing.

BACKGROUND: There is limited data on the genetic characteristics of patients with familial hypercholesterolemia (FH) in Latvia. We aim to describe monogenic variants in patients from the Latvian Registry of FH (LRFH). METHODS: Whole genome sequencing with 30× coverage was performed in unrelated index cases from the LRFH and the Genome Database of Latvian Population. LDLR, APOB, PCSK9, LDLRAP1, ABCG5, ABCG8, LIPA, LPA, CYP27A1, and APOE genes were analyzed. Only variants annotated as pathogenic (P) or likely pathogenic (LP) using the FH Variant Curation Expert Panel guidelines for LDLR and adaptations for APOB and PCSK9 were reported. RESULTS: Among 163 patients, the mean highest documented LDL-cholesterol level was 7.47 ± 1.60 mmol/L, and 79.1% of patients had LDL-cholesterol ≥6.50 mmol/L. A total of 15 P/LP variants were found in 34 patients (diagnostic yield: 20.9%): 14 in the LDLR gene and 1 in the APOB gene. Additionally, 24, 54, and 13 VUS were detected in LDLR, APOB, and PCSK9, respectively. No P/LP variants were identified in the other tested genes. CONCLUSIONS: Despite the high clinical likelihood of FH, confirmed P/LP variants were detected in only 20.9% of patients in the Latvian cohort when assessed with genome-wide next generation sequencing.

A case report of pulmonary vein isolation performed in a patient with polysplenia and interrupted inferior vena cava.

BACKGROUND: Pulmonary vein isolation (PVI) has entrenched itself as one of the main approaches for the treatment of paroxysmal symptomatic atrial fibrillation (AF). Pulmonary vein isolation prevents focal triggers from pulmonary veins from initiating AF paroxysms. As standard-PVI is performed through the inferior vena cava (IVC) approach, through the femoral vein. However, there are conditions when this approach is not appropriate or is not available. CASE SUMMARY: We report a case of a 53-year-old male who was referred to Pauls Stradins Clinical University Hospital for PVI due to worsening AF. Due to the rare anatomical variant of the venous system, the standard approach to PVI could not be applied. Interrupted cava inferior did not allow for femoral vein and IVC access. We had to figure out a different path-a combination of internal jugular and subclavian veins was used. Transseptal puncture was performed under transoesophageal echocardiography (TOE) control with a puncture needle stiletto. Pulmonary veins were isolated successfully, no complications were observed, and the patient was discharged in sinus rhythm. DISCUSSION: In some patients, PVI cannot be done through the standard IVC approach. In such cases, a different venous access must be chosen. Our patient had a rare variant of interrupted IVC and we had to use superior vena cava approach for the procedure. The difficulty of this approach is that procedure instruments are not designed for non-standard venous access; however, a combined use of TOE, general anaesthesia, and contact force-guided ablation has succeeded in isolating patients' pulmonary veins.

Lead-Related Infective Endocarditis in Latvia: A Single Centre Experience.

Background and Objectives: Over the last five decades cardiac implantable electronic devices (CIED) have become established as the mainstay for the treatment of permanent bradycardias, chronic heart failure and dangerous heart rhythm disturbances. These devices improve survival and quality of life in many patients. However, infections associated with CIED implantation, particularly lead-related infective endocarditis (LRIE), can offset all benefits and make more harm than good for the patient. To date, there are no other studies in Latvia, addressing patients with lead-related infective endocarditis. The objective of this study was to identify the most common pathogens associated with LRIE and their antimicrobial resistance and to identify possible risk factors of patients who present with LRIE. Materials and Methods: The study was performed retrospectively at Pauls Stradins Clinical University Hospital (PSCUH). The study included patients who were referred to PSCUH due to LRIE for lead extraction. Patients were identified from procedural journals. Information about isolated microorganisms, patient comorbidities and visual diagnostics data was taken from patient records. Results: Forty-nine patients with CIED related infective endocarditis were included in the study, 34 (69.4%) were male, median age of all patients was 65.0 (50.5-73.0) years, median hospital stay was 15.5 (22.0-30.5) days. Successful and complete lead extraction was achieved in all patients. Thirty-two (65.3%) had received antibiotics prior to blood sample. Only in 31 (63.3%) positive culture results were seen. The most common isolated pathogens were Staphylococcus aureus (23.5%) and coagulase negative staphylococci (23.5%). Other bacteria were isolated considerably less often. The atrial lead was most common location for lead vegetations, seen in 50.0% of cases. Five (10.2%) patients have died due to the disease. Conclusions: Lead-related infective endocarditis is a major complication of cardiac implantable electronic devices with considerable morbidity and mortality, which in our study was as high as 10.2%.

Latvian registry of familial hypercholesterolemia: The first report of three-year results.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) was rarely diagnosed in Latvia before 2015, when the Latvian Registry of FH (LRFH) was established. Here, we report the first experience of the LRFH over three years (2015-2017). METHODS: The LRFH is an ongoing nationwide, dynamic, long-term prospective cohort. The diagnosis of FH was assessed using the Dutch Lipid Clinic Network (DLCN) criteria. Cascade screening of first-degree relatives using age- and sex-specific percentiles of low-density lipoprotein cholesterol (LDL-C) was performed in relatives of patients with definite and probable FH. RESULTS: Among the 416 individuals included in the LRFH, 181 patients were diagnosed with FH (140 index cases and 41 relatives) and 151 with possible FH (not analysed in this report). The mean age was 51.3 ±â€¯14.1 years, 38.1% (n = 69) were men and 35.4% (n = 64) had a history of premature coronary heart disease. Only 54.1% (n = 98) of patients were on any lipid-lowering therapy before inclusion in the LRFH. The maximal statin dose was used by 23.2% (n = 42), and only 4.4% (n = 8) had their LDL-C levels below the goal. The initial mean total and LDL-C levels were 7.7 ±â€¯2.2 and 5.5 ±â€¯2.1 mmol/L, respectively. In a subgroup of patients (n = 49) with follow-up, LDL-C levels were reduced from 6.1 ±â€¯2.1 to 3.6 ±â€¯1.7 mmol/L (p < 0.001). CONCLUSIONS: An estimated 2.3% of FH patients in Latvia were diagnosed within three years. The vast majority of FH patients were under-recognized and poorly treated before their inclusion in the LRFH. Specialized care of FH patients within the frames of the registry substantially improved the management of this high-risk group.