Prognostic value of left ventricular longitudinal strain in patients with aortic stenosis

Left ventricular (LV) hypertrophy in patients with aortic stenosis (AS) is an adaptive mechanism that tries to maintain left ventricular systolic function despite obstruction.1 The appearance of myocardial fibrosis (MF) is a turning point from adaptive hypertrophy to maladaptation, that changes ventricular function and represents the basis for development of ventricular arrhythmias. There are two types of MF: reversible interstitial MF in early stage, and irreversible replacement MF in the later stage of disease. MF occupies LV midwall, usually in LV posterobasal part. Cardiac magnetic resonance (CMR) by late gadolinium enhancement (LGE) is the „gold standard“ in diagnosis of replacement MF. Positive LGE results indicate significantly greater risk of adverse outcome than it is in patients without MF. Echocardiography suggests the presence of MF with significant reliability, because global longitudinal strain (GLS) shows good correlation with results of CMR. Consequently, GLS can serve as a surrogate marker of MF and an indicator of adverse events in AS.2-4 MF mostly influences LV longitudinal function, while circumferential and radial deformation are less modified. In severe compensated AS circumferential deformation and apical rotation (ApR) are increased, what is likely a compensative mechanism for keeping cardiac output. The increased ApR is also associated with worse survival. With disease progression these compensative changes disappear. Mechanical dispersion (MD) is an indicator of contractile heterogeneity caused by fibrosis. Increased MD demonstrates significant association with mortality and can serve as an additional prognostic parameter. Along with more extensive MF the risk for sudden cardiac death increases what raises the question of the benefit of cardioverter-defibrillator. In conclusion, impaired GLS suggests MF, what must be confirmed by CMR. MF classifies the patients with severe asymptomatic AS into the group with increased risk of adverse outcome. Therefore, it is to be expected that these new facts will result in new guidelines for treatment of severe asymptomatic AS

Hepatopulmonary syndrome – commonly unrecognized complication in liver cirrhosis

Cilj: Hepatopulmonalni sindrom (HPS) kao plućnu komplikaciju uznapredovale bolesti jetre karakterizira trijas: jetrena bolest, arterijska hipoksemija i dilatacija plućnog krvožilja. Prevalencija iznosi i do 47 %, no u kliničkoj praksi rijetko se prepoznaje i dijagnosti cira, stoga je cilj ovoga prikaza upozoriti na često postojanje HPS-a u bolesnika s cirozom jetre i respiratornom simptomatologijom, te istaknuti dijagnosti čke postupke i adekvatno liječenje. Prikaz slučaja: Bolesnik je 54-godišnjak s cirozom jetre (Child-Pugh C 10) i dispnejom. Kliničkim pregledom (dispneja) i laboratorijskim nalazima (arterijska hipoksemija, ortodeoksija) postavljena je sumnja na HPS. Primjenom kontrastne ehokardiografi ije, višeslojne računalne tomografije (MSCT) pluća i CT plućne angiografije, potvrđena je radna dijagnoza. Rasprava i zaključak: U bolesnika s cirozom jetre i respiratornim tegobama treba posumnjati na HPS i potvrditi ga odgovarajućim dijagnostičkim metodama. Dijagnostika ovog sindroma obuhvaća detaljnu anamnezu i fizikalni pregled, analizu plinova u arterijskoj krvi, preglednu snimku grudnih organa, kontrastnu ehokardiografi ju, MSCT pluća, scinti grafi ju makroagregati ma albumina obilježenih tehnecijem i, u dvojbenim slučajevima, plućnu angiografiju. Provedena su brojna istraživanja o učinkovitosti različitih lijekova, ali niti jedan se nije pokazao dovoljno učinkovitim u liječenju ovog sindroma. Jedina potencijalno kurati vna metoda danas je ortotopna transplantacija jetre (OTJ).Aim: Hepatopulmonary syndrome (HPS), a pulmonary complicati on of liver cirrhosis, is the triad of liver disease, arterial hypoxemia and intrapulmonary vascular dilatation. Prevalence may be up to 47%, but in clinical practi ce it is rarely recognized and diagnosed. We present the case of HPS in a pati ent with liver cirrhosis and respiratory simptomatology and emphasise the importance of early recogniti on of HPS because of timely and adequate therapy approach. Case report: The pati ent was a 54-year-old male with liver cirrhosis (Child Pugh C 10) and dyspnea. Clinically (dyspnea) and biochemically (arterial hypoxemia, ortodeoxia) our presumpti ve diagnosis was HPS. Early diagnosis was established by applying contrast echocardiography, lung MSCT and CT pulmonary angiography. Discussion and conclusion: It is necessary to recognize HPS as a complication in liver cirrhosis and to verify it by using proper diagnostic methods. Diagnostics of HPS include detailed anamnesis and physical examination, blood gas analysis, chest x-ray, contrast echocardiography, lung MSCT, lung perfusion scinti graphy (99m-Tc macro aggregated albumin lung perfusion scan) and CT pulmonary angiography in doubtful cases. Various trials evaluating drug effi ciency have been performed, but no medicati on has been found suitable for HPS treatment. Orthotopic liver transplantati on (OLT) is the only potential curative method

Mysterious atrial mass mimicking severe mitral stenosis

Introduction: The differential diagnosis of an intracardiac mass include benign and malignant primary heart tumors, metastatic tumors and thrombi. Primary tumors of the heart consist mainly of myxomas, with an incidence of less than 0.5%. Clinical manifestations are consequence of embolic phenomena, intracardiac obstruction or constitutional symptoms. In rare instances, myxomas can cause a mass effect, resulting in mitral valve obstruction1. Case report: 68-year-old male with a history of ulcerative colitis complained to his gastroenterologist about having exercise intolerance. Undergoing regular colitis evaluation, CT thorax and abdomen scan was performed incidentally revealing a large intracardiac mass. Echocardiogram ordered by the consulting cardiologist demonstrated a large ellipsoid left atrial cyst (50×31 mm), occupying nearly the entire left atrium (Figure 1). The mass was protruding across the mitral valve orifice in diastole causing functional stenosis with an elevated mean diastolic gradient of 10,9 mmHg. Mitral valve area calculated by pressure half-time was 1.0 cm2. Doppler showed moderate tricuspid regurgitation with a systolic pulmonary artery pressure of 50 mmHg. The systolic function was preserved with an estimated left ventricular ejection fraction of 58%. Transesophageal echocardiography described a cavitating lesion (measuring 15,1 cm2, attached to interatrial septum with 24 mm base), having characteristics consistent with a hemorrhagic cyst (Figure 2). Preoperative coronary angiography displayed coronary artery disease and a rare condition of dual coronary artery supply with left circumflex artery (LCx) providing two (Figure 3) and right coronary artery (RCA) one tumor branch (Figure 4) producing a characteric "tumor blush". CT showed large intracardiac mass (Figure 5 and Figure 6). Patient underwent cardiothoracic surgery with successful excision of the tumor (4,5x3x2 cm), the pathohistology confirmed myxoma. Postoperative course was uneventful, exercise intolerance symptoms improved, and echocardiographic follow up showed no intracardiac mass. Conclusion: We described a rare case of cystic-appearance cardiac myxoma with dual coronary supply mimicking mitral valve stenosis. There are not many patients reported with left atrial myxoma being vascularized from both RCA and LCx as seen in our case2. Although more than half of atrial myxomas show obstructive symptoms, severe mitral valve obstruction is rare1. Early echocardiographic examination of patients presenting with exertional dyspnea is advised, as myxomas have an excellent prognosis following surgical excision, preventing complications and improving quality of life

Thyroid hormone levels are associated with metabolic components:A cross-sectional study

Aim: To analyze the association of thyroid function and hormone levels with metabolic syndrome (MetS) and its components. Methods: This cross-sectional population-based study involved 2183 Croatian individuals with no history of thyroid disease, hypertension, diabetes, and hyperlipidemia. MetS was diagnosed according to the National Cholesterol Education Program’s Adult Treatment Panel III criteria. Results: We found no association between thyroid function groups and the prevalence of MetS and its components. Clinically hypothyroid participants showed significantly higher triceps skinfold measurements than subclinically hypothyroid and euthyroid participants. Furthermore, clinically hypothyroid participants had higher abdominal skinfold thickness than subclinically hypothyroid participants. Otherwise, suprailiac and abdominal skinfold measurements were higher in the subclinically and clinically hyperthyroid group of participants compared with euthyroid and subclinically hypothyroid participants. A strong positive association of thyroid-stimulating hormone (TSH) and strong negative association of free triiodothyronine (fT3) and free thyroxine (fT4) levels with HOMA-IR and cholesterol levels were found. Furthermore, the fT4 level also showed a strong negative association with HDL and triceps skinfold thickness. Conclusions: This study supports the standing that TSH, fT3, and fT4 levels are important variables to determine the association of thyroid function with MetS

Genome-Wide Association Analysis and Genomic Prediction of Thyroglobulin Plasma Levels

Thyroglobulin (Tg) is an iodoglycoprotein produced by thyroid follicular cells which acts as an essential substrate for thyroid hormone synthesis. To date, only one genome-wide association study (GWAS) of plasma Tg levels has been performed by our research group. Utilizing recent advancements in computation and modeling, we apply a Bayesian approach to the probabilistic inference of the genetic architecture of Tg. We fitted a Bayesian sparse linear mixed model (BSLMM) and a frequentist linear mixed model (LMM) of 7,289,083 variants in 1096 healthy European-ancestry participants of the Croatian Biobank. Meta-analysis with two independent cohorts (total n = 2109) identified 83 genome-wide significant single nucleotide polymorphisms (SNPs) within the ST6GAL1 gene ([Formula: see text]). BSLMM revealed additional association signals on chromosomes 1, 8, 10, and 14. For ST6GAL1 and the newly uncovered genes, we provide physiological and pathophysiological explanations of how their expression could be associated with variations in plasma Tg levels. We found that the SNP-heritability of Tg is 17% and that 52% of this variation is due to a small number of 16 variants that have a major effect on Tg levels. Our results suggest that the genetic architecture of plasma Tg is not polygenic, but influenced by a few genes with major effects

Determinants of thyroid volume in healthy young adults of Dalmatia

Background and purpose: The aim of this study was to investigate thyroid volume (TV) and its determinants in healthy young adults without present or previous thyroid disease. Materials and methods: The study was performed in a sample of 145 healthy young participants aged 19-29 years, living in an iodine-sufficient area of Dalmatia. Dimensions of the thyroid gland were obtained by ultrasound and used to determine TV. Anthropometric data was collected, and measurements of serum TSH, fT4, Tg, TgAb, and TPOAb levels were determined. Correlations between TV and other continuous variables were determined using the Pearson correlation test, while multivariate linear regression analysis was used to determine the associations of the potential predictors for the TV. Results: TV in men was larger than in women (p=3.53x10-8) and was positively correlated with anthropometric measurements, with the highest correlation coefficient for height (r=0.53, p=6.36x10-12), then body surface area, BSA (r=0.48, p=1.68x10-9), weight (r=0.43, p=8.28x10-8) and body mass index, BMI (r=0.17, p=0.04). Age and cigarette smoking did not appear to be significantly associated with TV (p=0.13 and p=0.95, respectively). Univariate analysis showed TV correlated with fT4 plasma levels (r=0.35, 1.73x10-5), while multivariate analysis showed height and fT4 levels to be important parameters with a significant role in TV. Conclusions: We confirmed previously observed association of TV with sex and anthropometric parameters and reported a significant correlation between TV and fT4 levels. Furthermore, fT4 levels and height were found to be the important parameters for predicting TV.</p

The heart in Fabry’s disease

Introduction: Fabry disease is rare X-linked, recessive lysosomal storage disorder expressed as deficiency in enzyme α-galactosidase A that leads to progressive accumulation of globotriaosylceramide and related glycosphingolipids in various tissues. In cardiac tissues, progressive globotriaosylceramide accumulation leads to irreversible cardiac damage.1,2 Males are primarily affected by Fabry disease, but female heterozygotes may also have symptoms.3 Case report: Our patient is 47-years-old who has been suffering from chronic kidney disease since he was 23 years old. Only twelve years later he developed end-stage renal disease and has been undergoing regular haemodialysis in Dialysis Centre Prijedor (Bosnia and Herzegovina). He started his journey towards kidney transplantation in 2014 in University Hospital Centre Rijeka, which was performed in May 2018. In 2014, during pretransplantation workup, echocardiography was performed revealing concentric cardiac hypertrophy without left ventricle outflow tract obstruction (Figure 1 and Figure 2) associated with contractility and diastolic filling impairment. Following suspicion on Fabry disease, diagnosis was made by measuring α-galactosidase enzyme activity in leukocytes and molecular genetic testing of GLA gene mutation. Enzyme replacement therapy was started with intravenous infusion of recombinant α-galactosidase A (agalsidase beta). Conclusion: Renal disease and echocardiographic features of hypertrophic cardiomyopathy combined with electrocardiographic and clinical criteria should be considered as “red flags” for Fabry disease

Dietary Factors Associated with Plasma Thyroid Peroxidase and Thyroglobulin Antibodies

The knowledge about dietary habits and their influence in the development of autoimmune thyroid disease is insufficient. The aim of this study was to analyse the association of dietary factors and plasma thyroid peroxidase antibodies (TPO-Ab) and/or thyroglobulin antibodies (Tg-Ab). The study enrolled 1887 participants originating from the South Croatia. Participants with elevated plasma TPO-Ab and/or Tg-Ab were defined as cases (n = 462) and those with TPO-Ab and/or Tg-Ab within referent values were defined as controls (n = 1425). Dietary intake was evaluated according to a food frequency questionnaire containing 58 food items. Principal component analysis was used to group food items into dietary groups. We used logistic regression analysis to examine dietary groups associated with positive plasma TPO-Ab and/or Tg-Ab. The results indicate that the dietary group with frequent consumption of animal fats and butter is associated with positive plasma TPO-Ab and/or Tg-Ab (p = 0.01). The dietary group with frequent consumption of vegetables as well as the dietary group with high consumption of dried fruit, nuts, and muesli are associated with negative findings of TPO-Ab and/or Tg-Ab (p = 0.048 and p = 0.02, respectively). We showed that the anti-inflammatory dietary groups are associated with the negative findings of plasma TPO-Ab and/or Tg-Ab