Background and Objectives: Cancer therapy containing anthracyclines is associated with cancer-treatment-related cardiac dysfunction and heart failure (HF). Conventional cardioprotective medications can be frequently complicated by their blood-pressure-lowering effect. Recently, elevated resting heart rate was shown to independently predict mortality in patients with cancer. As a heart rate-lowering drug without affecting blood pressure, ivabradine could present an alternative management of anthracyclines-induced cardiotoxicity. Materials and Methods: This study aimed to investigate the probable protective effects of ivabradine in cancer patients with elevated heart rate (>75 beats per minute) undergoing anthracycline chemotherapy. Patients referred by oncologists for baseline cardiovascular risk stratification before anthracycline chemotherapy who met the inclusion criteria and had no exclusion criteria were randomly assigned to one of two strategies: ivabradine 5 mg twice a day (intervention group) or controls. Electrocardiogram, transthoracic echocardiogram with global longitudinal strain (GLS), troponin I (Tn I), and N-terminal natriuretic pro-peptide (NT-proBNP) were performed at baseline, after two and four cycles of chemotherapy and at six months of follow-up. The primary endpoint was the prevention of a >15% reduction in GLS. Secondary endpoints were effects of ivabradine on Tn I, NT-proBNP, left ventricular (LV) systolic and diastolic dysfunction, right ventricle dysfunction, and myocardial work indices. Results: A total of 48 patients were enrolled in the study; 21 were randomly assigned to the ivabradine group and 27 to the control group. Reduced GLS was detected 2.9 times less often in patients receiving ivabradine than in the control group, but this change was non-significant (OR [95% CI] = 2.9 [0.544, 16.274], p = 0.208). The incidence of troponin I elevation was four times higher in the control group (OR [95% CI] = 4.0 [1.136, 14.085], p = 0.031). There was no significant change in NT-proBNP between groups, but the increase in NT-proBNP was almost 12% higher in the control group (OR [95% CI] = 1.117 [0.347, 3.594], p = 0.853). LV diastolic dysfunction was found 2.7 times more frequently in the controls (OR [95% CI] = 2.71 [0.49, 15.10], p = 0.254). Patients in the ivabradine group were less likely to be diagnosed with mild asymptomatic CTRCD during the study (p = 0.045). No differences in right ventricle function were noted. A significant difference was found between the groups in global constructive work and global work index at six months in favour of the ivabradine group (p = 0.014 and p = 0.025). Ivabradine had no adverse effects on intracardiac conduction, ventricular repolarization, or blood pressure. However, visual side effects (phosphenes) were reported in 14.3% of patients. Conclusions: Ivabradine is a safe, well-tolerated drug that has shown possible cardioprotective properties reducing the incidence of mild asymptomatic cancer-therapy-induced cardiac dysfunction, characterised by a new rise in troponin concentrations and diminished myocardial performance in anthracycline-treated women with breast cancer and increased heart rate. However, more extensive multicentre trials are needed to provide more robust evidence.

The study was designed to evaluate whether the preserved coronary flow reserve (CFR) 72 hours after reperfused acute myocardial infarction (AMI) is associated with less microvascular dysfunction and is predictive of left ventricular (LV) functional recovery and the final infarct size at follow-up.

Background and Objectives: Hereditary transthyretin amyloidosis (ATTRv) is a rare disease caused by pathogenic variants in the transthyretin (TTR) gene. More than 140 different disease-causing variants in TTR have been reported. Only a few individuals with a rare TTR variant, c.302C>T, p.(Ala101Val) (historically known as p.(Ala81Val)), primarily associated with cardiac ATTRv, have been described. Therefore, our aim was to analyze the clinical characteristics of individuals with the identified c.302C>T TTR variant at our center. Materials and Methods: We analyzed data from individuals with ATTRv who were diagnosed and treated at Vilnius University Hospital Santaros Klinikos. ATTRv was confirmed by negative hematological analysis for monoclonal protein, positive tissue biopsy or bone scintigraphy and a pathogenic TTR variant. Results: During 2018-2021, the TTR NM_000371.3:c.302C>T, NP_000362.1:p.(Ala101Val) variant was found in one individual in a homozygous state and in three individuals in a heterozygous state. The age of onset of symptoms ranged from 44 to 74 years. The earliest onset of symptoms was in the individual with the homozygous variant. A history of carpal tunnel syndrome was identified in two individuals. On ECG, three individuals had low QRS voltage in limb leads. All individuals had elevated NT-proBNP and hsTroponine I levels on baseline laboratory tests and concentric left ventricular hypertrophy on transthoracic echocardiography. The individual with the homozygous c.302C>T TTR variant had the most pronounced polyneuropathy with tetraparesis. Other patients with the heterozygous variant had more significant amyloid cardiomyopathy. When screening family members, the c.302C>T TTR variant was identified in two phenotypically negative relatives at the ages of 33 and 47 years. Conclusions: c.302C>T is a rare TTR variant associated with ATTRv cardiomyopathy. The homozygous state of this variant was not reported before, and is associated with earlier disease onset and neurological involvement compared to the heterozygote state.

Background: Fabry disease (FD) is a rare X-linked inherited lysosomal storage disorder caused by α-galactosidase A deficiency leading to intracellular glycosphingolipid accumulation. FD manifestation is multisystem, and can differ depending on disease-related genetic variants. Currently, more than 700 different FD-causing mutations have been identified in the human GLA gene. We identified a novel mutation in a Lithuanian family with classical manifestations of Fabry disease, revealing severe effects to the cardiovascular systems of heterozygous women. Case presentation: A 49-year-old woman underwent echocardiography due to progressive dyspnea that lasted seven years, reduced physical activity, and periodic cardiac arrhythmia. Echocardiography revealed left ventricular hypertrophy with normal diastolic function. The patient had experienced acroparesthesia in her upper limbs and abdominal pain since childhood, and in the last decade had experienced mild proteinuria without renal failure. Her renal biopsy was typical for Fabry disease. The patient’s brain magnetic resonance imaging (MRI) (T2 flair) showed white matter hyperintensities lesions. DNA sequencing of the proband, her mother and one of her sons showed a novel GLA gene exon 2 mutation, c.270C>G (p.Cys90Trp). All three patients had decreased α-galactosidase A activity and specific FD manifestations. Conclusions: A novel GLA mutation, c.270C>G (p.Cys90Trp), was found in a Lithuanian family with a classical form of Fabry disease in heterozygous women with predominant cardiac involvement. However, the exact manifestation of this mutation is still unclear as it is newly reported and further research must be done.

Background/Objectives: Hypertrophic cardiomyopathy (HCM) is an inherited disease with genetic and phenotypic variability and an unclear genotype–clinical course relationship. The aim of our study was to assess the phenotypic and molecular characteristics of patients with HCM. Methods: Clinical and genetic data from adult HCM patients treated at a university hospital between 2005 and 2024 were analysed. A comparative analysis of probands with a single pathogenic/likely pathogenic (P/LP) variant and without a P/LP variant was performed. Results: The analysis involved 214 individuals with HCM, 42.1% being females. The median age at HCM diagnosis was 52 (38–62) years. P/LP variants were identified in 92 (43.0%) individuals. Compared to patients without an identified genetic cause, individuals with P/LP variants had a significantly earlier HCM diagnosis (43.5 (32.3–58.0) vs. 54.0 (45.8–65.0) years, p < 0.001) and higher maximal thickness on cardiac imaging (17.5 (15.0–21.0) vs. 17.0 (15.0–19.0) mm, p = 0.009 on transthoracic echocardiography and 21.0 (18.0–23.0) vs. 18.0 (16.0–20.0) mm, p < 0.001 on cardiac magnetic resonance imaging). During the median follow-up of 4.2 (1.6–6.8) years, individuals with P/LP HCM variants had earlier onset of atrial fibrillation (p = 0.021), ventricular tachycardia (p = 0.004), heart failure composite (p = 0.006), and overall composite outcome (p = 0.002). No difference between the groups was observed when hazard ratios for clinical outcomes were adjusted by age at HCM diagnosis and gender. Conclusions: Genotype influences HCM phenotype, as patients with P/LP variants experience earlier onset and more pronounced hypertrophy. However, once diagnosed, genotype may not predict the outcomes of HCM.