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Az Európai Kardiológus Társaság (ESC) az akut és krónikus szívelégtelenség (SzE) diagnosztikájával és kezelésével kapcsolatos ajánlása 2021. augusztus 27-én került publikálásra. A korábbi (2016) ajánláshoz képest, a közleményben 41 új és 15 megújított ajánlás szerepel. A SzE-ben szenvedő betegek kezelésének célja változatlanul a klinikai státusz, a funkcionális kapacitás és az életminőség javítása, a hospitalizáció megelőzése és a mortalitás csökkentése. A korábban is I A-indikációval javasolt szerek ajánlásában nincsen lényegi változás, a neurohormonális antagonisták (ACE-gátlók [ACEI], mineralokortikoid-receptor-antagonisták [MRA] és béta-blokkolók [BB]) bizonyítottan javítják a túlélést HFrEF-ben, ennélfogva kontraindikáció vagy intolerancia hiányában alkalmazásuk minden HFrEF-beteg esetében javasolt. Lényegi változás, hogy az új evidenciák alapján a nátrium-glükóz-kotranszporter-2 (SGLT2) inhibitorok is első vonalban, I A-szintű evidenciával alkalmazandók. Az új ajánlás talán legfontosabb változtatása, hogy az I A-indikációval alkalmazandó szerek hierarchikus, több lépcsőben való alkalmazási javaslatát megszünteti. Az útmutatóban megváltozott a HFmrEF elnevezése („mildly reduced” – mérsékelten csökkent) és ajánlások fogalmazódtak meg a betegcsoport kezelése tekintetében. Említést érdemel még a szolubilis guanilát-cikláz-receptor-stimulátor vericiguát és az angiotenzinreceptor neprilizin-inhibitor (ARNI) sacubitril/valsartan kibővített indikációja is. Jelen közleményben a krónikus szívelégtelenség kezelésének rövid ismertetése mellett az SGLT2-gátlók I A-indikációjú ajánlásának evidenciáit és alkalmazásának lehetőségeit is áttekintjük.

A szívamyloidosis egy súlyos, progresszív, infiltratív betegség, amelyet amiloidfibrillumok szívizomban való lerakódása okoz. Hátterében általában hematológiai, krónikus gyulladásos betegségek, illetve genetikai eltérések állhatnak, de az időskorban jellemző forma esetében a pontos ok ismeretlen. Az utóbbi években a modern képalkotó eljárásoknak és a noninvazív diagnosztika lehetőségének, valamint az egyre több, hatásos betegség specifikus terápiának köszönhetően növekszik a diagnosztizált esetek száma, így feltételezhetően a kórkép a korábban gondolthoz képest gyakoribb eltérés lehet. Sorra jelentek meg a diagnosztikus és terápiás algoritmusok a közelmúltban, így 2021-ben az ESC Myocardial and Pericardial Diseases Munkacsoportja egy áttekintő közleményt adott ki a jelenleg alkalmazandó irányelvekről.

Háttér: A hipertrófiás cardiomyopathia (HCM) a myocardium primer betegsége, amelyet típusosan a sarcomerfehérjéket kódoló gének mutációi okoznak. A hipertrófiás cardiomyopathiát utánzó HCM-fenokópiák, pl. a Fabry-betegség kardiális manifesztációjának elkülönítése, adott esetben jelentős differenciáldiagnosztikai nehézséget okozhat. Esetismertetés: Munkánkban egy HCM kardiális fenotípusával rendelkező nőbeteg részletes genetikai analízisét végeztük el. Az első észlelésekor a 49 éves nőbeteg szinte állandóan fennálló mellkasi fájdalom, fulladás és igen alacsony terhelhetőség miatt került észlelésre. Panaszai hátterében hipertrófiás cardiomyopathia igazolódott, amely főként az anterior septumot érintette (maximális balkamra-falvastagság: 27 mm), azonban kiáramlási pálya obstrukciót nem okozott. Gondozása során a beállított terápia mellett panaszai változatlan jellegűek voltak, de kardiálisan kompenzált volt. NT-proBNP-érték 244 pg/ml volt, diasztolés funkciót jellemző paraméterek relaxációs zavarra utaltak. Szív-MRI-vizsgálat is igazolta a megnövekedett végdiasztolés bal kamrai izomtömeget (LVM: 169 g, LVMi: 76,9 g/m2 ), és a főként az anterior septum basalis-középső szegmentumát érintő hipertrófiát. Polyneuropathiát véleményező elektroneurográfia vizsgálata és proteinuria alapján Fabry-betegséget nem lehetett kizárni, amely miatt Fabry-kór irányában genetikai vizsgálat történt. Utóbbi a GLA-gén c.376A>G (p.Ser126Gly) mutációját igazolta, ismételten is normális lysoGb3-szintek (≤1,8 ng/ml) mellett. A Fabry-kór kardiális érintettségének egyértelmű igazolására szívizom-biopszia történt, amelynek szövettani elemzése Fabry-kórra jellemző eltéréseket nem talált, HCM-nek megfelelő képet mutatott. Sarcomer-génmutáció detektálása céljából kiterjesztett, új generációs szekvenálással végzett, 103 cardiomyopathia gént érintő genetikai vizsgálatot végeztünk, amely a MYBPC3-gén p.Ala1056fs, feltehetően kóroki mutációját igazolta. Következtetések: Fentiek alapján a betegben észlelt HCM kardiális fenotípusát a MYBPC3-gén p.Ala1056fs sarcomer génmutáció okozta, s az nem a Fabry-kór kardiális manifesztációjának következménye.

Several heart muscle diseases can cause heart failure, the etiological diagnosis of which may serve the basis of targeted, tailored, effective personalized therapy. Such a heart muscle disease is transthyretin amyloidosis (ATTR) which is an infiltrative disorder affecting most frequently the heart and peripheral nerves, due to the accumulation of transthyretin protein. Deposition of mutant transthyretin, due to mutations in the TTR gene encoding for transthyretin, occurs in the familial form of the disease (hATTR), while in senile amyloidosis, wild-type transthyretin accumulates (wtATTR). We report on a 79-years-old male patient who presented 9 years before because of novel onset atrial fibrillation. Echocardiography at that time showed severe concentric left ventricular hypertrophy which progressed through the years. Laboratory values displayed increased liver enzymes and troponin T levels. He was hospitalized several times because of left- and later right-sided heart failure, with increasing tendency towards hypotension. At last admission he was admitted to us after suffering syncope at home necessitating cardiopulmonary resuscitation. Transthoracic echocardiography showed severe, concentric biventricular hypertrophy (LV wall thickness 22 mm, RV wall thickness 12 mm), with depressed LV and RV function, apical sparing, and low cardiac output. Taking low voltage, seen on ECG, and other anamnestic data into consideration, the suspicion of ATTR amyloidosis was raised. The patient died after a short observational period due to intractable heart failure. Autopsy and histology revealed systemic amyloidosis, affecting predominantly the heart which was interpreted as wtATTR according to immunohistochemistry, negative TTR gene sequencing and the lack of monoclonal gammopathy. Our case illustrates the importance of the diagnostic delay which is very frequently encountered in TTR amyloidosis. Features of ATTR which includes the multidisciplinary nature of assessment, specialized diagnostic modalities and unique therapy call for the need of specialized diagnostic centers.

Background B-lines detected by lung ultrasound (LUS) during exercise stress echocardiography (ESE), indicating pulmonary congestion, have not been systematically evaluated in patients with hypertrophic cardiomyopathy (HCM). Aim To assess the clinical, anatomical and functional correlates of pulmonary congestion elicited by exercise in HCM. Methods We enrolled 128 HCM patients (age 52 +/- 15 years, 72 males) consecutively referred for ESE (treadmill in 46, bicycle in 82 patients) in 10 quality-controlled centers from 7 countries (Belgium, Brazil, Bulgaria, Hungary, Italy, Serbia, Spain). ESE assessment at rest and peak stress included: mitral regurgitation (MR, score from 0 to 3); E/e'; systolic pulmonary arterial pressure (SPAP) and end-diastolic volume (EDV). Change from rest to stress was calculated for each variable. Reduced preload reserve was defined by a decrease in EDV during exercise. B-lines at rest and at peak exercise were assessed by lung ultrasound with the 4-site simplified scan. B-lines positivity was considered if the sum of detected B-lines was >= 2. Results LUS was feasible in all subjects. B-lines were present in 13 patients at rest and in 38 during stress (10 vs 30%, p < 0.0001). When compared to patients without stress B-lines (n = 90), patients with B-lines (n = 38) had higher resting E/e' (14 +/- 6 vs. 11 +/- 4, p = 0.016) and SPAP (33 +/- 10 vs. 27 +/- 7 mm Hg p = 0.002). At peak exercise, patients with B-lines had higher peak E/e' (17 +/- 6 vs. 13 +/- 5 p = 0.003) and stress SPAP (55 +/- 18 vs. 40 +/- 12 mm Hg p < 0.0001), reduced preload reserve (68 vs. 30%, p = 0.001) and an increase in MR (42 vs. 17%, p = 0.013) compared to patients without congestion. Among baseline parameters, the number of B-lines and SPAP were the only independent predictors of exercise pulmonary congestion. Conclusions Two-thirds of HCM patients who develop pulmonary congestion on exercise had no evidence of B-lines at rest. Diastolic impairment and mitral regurgitation were key determinants of pulmonary congestion during ESE. These findings underscore the importance of evaluating hemodynamic stability by physiological stress in HCM, particularly in the presence of unexplained symptoms and functional limitation.

Background B-lines detected by lung ultrasound (LUS) indicate pulmonary congestion during exercise stress echo (ESE). Aim To assess B-lines during ESE in hypertrophic cardiomyopathy (HCM). Methods We enrolled 110 HCM patients (age 52±16 years, 74 males) referred for ESE (treadmill in 39, semi-supine bicycle in 71 patients) in 10 quality-controlled centers from 8 countries (Belgium, Brazil, Bulgaria, Hungary, Italy, Portugal, Serbia, Spain). ESE assessment included: left ventricular outflow tract gradient (LVOTG); mitral regurgitation (MR, score from 0 to 3); E/e'; systolic pulmonary arterial pressure (SPAP, from tricuspid regurgitant jet velocity); end-diastolic volume (EDV); left atrial volume (LAV). B-lines were assessed by LUS with the 4-site simplified scan, each site scored from 0 (normal A-lines) to 10 (coalescing B-lines). The positivity criterion was a B-line score stress ≥2 points. Results LUS was feasible in all subjects, with additional scanning and analysis time Conclusion B-lines are found in about 1 of 10 HCM patients at rest and in 1 of 3 during ESE. Acute backward heart failure during exercise can recognize multiple mechanisms in HCM, and ESE can help to capture this heterogeneity. Funding Acknowledgement Type of funding sources: None. Functional correlates of stress B-lines

Background: Variant transthyretin amyloidosis (ATTRv) is an autosomal dominant inherited disease, where the mutation of the transthyretin gene (TTR) results in the deposition of pathogenic protein fibrils in various tissues. The mutation type influences the clinical course. Until now, no data were available on the genotype, phenotype, and prevalence of Hungarian ATTRv patients. The aim of our study was to assess the prevalence, regional distribution, genotypes, and phenotypes of Hungarian patients with ATTRv. Methods: With the collaboration of Hungarian regional and university centers, we identified patients diagnosed with ATTRv. We also searched prior publications for case studies of Hungarian ATTRv patients. Results: 40 individuals in 23 families with ATTRv were identified within the borders of Hungary. At the time of the diagnosis, 24 of them were symptomatic. The two most common mutations were ATTRHis88Arg (nine families) and ATTRIle107Val (8 families). ATTRVal30Met was demonstrated in 2 families, and ATTRVal122del, ATTRPhe33Leu, ATTRIle84Ser, and ATTRAsp18Gly in one family each. The median age of the symptomatic patients at the time of clinical diagnosis was 65 years. The most common clinically significant organ involvement was restrictive cardiomyopathy, found in 24 patients. Polyneuropathy was diagnosed in 20 patients. A total of 19 patients showed a mixed phenotype. The leading symptom was heart failure in 8 cases (3 of them had only cardiac symptoms), polyneuropathy in 11 cases (all of them also had cardiac symptoms), and equally severe cardiac and neuropathy symptoms were present in 3 cases. Out of 24 symptomatic patients, 10 received targeted pharmacological therapy. The follow-up period ranged from 1 to 195 months. At the time of the retrospective analysis, 12 patients had already died, and 1 patient underwent heart transplantation. Conclusions: As TTR genotype influences the phenotype and clinical course of ATTRv, it is important to know the regional data. In Hungary, ATTRHis88Arg and ATTRIle107Val are the most common mutations in ATTRv, both presenting with mixed phenotype, but the median age at the time of the diagnosis is 9 years lower in patients with ATTRHis88Arg than in patients with ATTRIle107Val.

Funding Acknowledgements Type of funding sources: None. Background Blunted heart rate reserve (HRR) during exercise is associated with cardiac autonomic dysfunction and poor outcome. Purpose To evaluate the anatomical, functional and prognostic correlates of HRR during exercise stress echocardiography (ESE) in hypertrophic cardiomyopathy (HCM). Methods We prospectively recruited a consecutive sample of 121 HCM patients [age 47 ± 13 years, 67 males; NYHA class 1.7 ± 0.7; left ventricular (LV) ejection fraction 71 ± 9 %; LV maximal wall thickness 24 ± 5 mm; 58 (48%) with LV outflow tract obstruction (LVOTO, gradient ≥ 50 mmHg) at rest] who underwent semi-supine bicycle ESE from January 2006 to September 2019. HRR was calculated as the peak/rest heart rate (HR) ratio. All patients were followed-up for a median of 7.5 years. Results HR was 68 ± 11 bpm at rest and 105 ± 19 bpm at peak stress. Receiver-operating characteristic analysis was used to determine the best cut-off value of HRR (≤ 1.48, blunted) to predict all-cause death. A blunted HRR was present in 52 patients (43 %, Group 1). Patients with blunted HRR had more frequently hypertension (Group 1= 41/52 vs Group 2= 40/69, 79 vs 58 %, p = 0.019), resting systolic anterior motion of the mitral valve [(SAM) , Group 1= 41/52 vs Group 2= 40/69, 79 vs 58 %, p = 0.019] and rest LVOTO (Group 1= 31/52 vs Group 2= 27/69, 60 vs 39 %, p = 0.029). Patients in Group 1 had larger left atrial diameter (48.8 ± 6.5 vs 46.5 ± 7.6, p = 0.076), lower LV end-diastolic [(EDD) , 44.8 ± 4.6 vs 46.7 ± 4.6 mm p = 0.02] and LV end-systolic diameter [(ESD), 25.2 ± 5.3 vs 27.6 ± 5.5 mm p = 0.02] at rest. Patients in Group 1 had higher NYHA class (1.9 ± 0.6 vs 1.6 ± 0.7, p = 0.009), resting HR (71.5 ± 11.4 vs 64.6 ± 10.6 bpm p During the follow-up, 13 patients died. All-cause death was observed in 10/52 patients of Group 1 and 3/69 patients of Group 2 (19 vs 4 %, p Conclusion HRR is a simple non-imaging biomarker of cardiac autonomic function and is frequently abnormal in HCM. The blunted increase in frequency is associated with NYHA functional class, exercise time, rest HR, rest LVOTO, SAM, LV EDD and ESD. HRR independently predicts survival in HCM. The lower the HRR, the worse the outcome. Abstract Figure.

Aims Subunit interactions at the cytoplasmic domain interface (CD-I) have recently been shown to control gating in inward rectifier potassium channels. Here we report the novel KCNJ2 variant p.Glu293Lys that has been found in a patient with Andersen-Tawil Syndrome type 1 (ATS1), causing amino acid substitution at the CD-I of the inward rectifier potassium channel subunit Kir2.1. Neither has the role of Glu293 in gating control been investigated, nor has a pathogenic variant been described at this position. This study aimed to assess the involvement of Glu293 in CD-I subunit interactions and to establish the pathogenic role of the p.Glu293Lys variant in ATS1. Methods and results The p.Glu293Lys variant produced no current in homomeric form and showed dominant negative effect over wild type (WT) subunits. Immunocytochemical labelling showed the p.Glu293Lys subunits to distribute in the subsarcolemmal space. Salt bridge prediction indicated the presence of an intersubunit salt bridge network at the CD-I of Kir2.1, with the involvement of Glu293. Subunit interactions were studied by the NanoBiT split reporter assay. Reporter constructs carrying NanoBiT tags on the intracellular termini produced no bioluminescent signal above background with the p.Glu293Lys variant in homomeric configuration and significantly reduced signals in cells co-expressing WT and p.Glu293Lys subunits simultaneously. Extracellularly presented reporter tags, however, generated comparable bioluminescent signals with heteromeric WT and p.Glu293Lys subunits and with homomeric WT channels. Conclusions Loss of function and dominant negative effect confirm the causative role of p.Glu293Lys in ATS1. Co-assembly of Kir2.1 subunits is impaired in homomeric channels consisting of p.Glu293Lys subunits and is partially rescued in heteromeric complexes of WT and p.Glu293Lys Kir2.1 variants. These data point to an important role of Glu293 in mediating subunit assembly, as well as in gating of Kir2.1 channels. Translational perspective Andersen-Tawil Syndrome (ATS) is a rare genetic disorder characterized by the triad of periodic paralysis, dysmorphic features and ventricular arrhythmias. Symptoms can be mild and atypical, therefore, genetic screening of affected families is pivotal. This study describes the p.Glu293Lys variant of KCNJ2 encoding the Kir2.1 ion channel subunit as pathogenic, thereby aiding genetic testing of ATS. The study also identifies disturbed interactions between the cytoplasmic domains of Kir2.1 subunits as the molecular mechanism of loss-of-function in the p.Glu293Lys variant. Targeting cytoplasmic domain interactions may represent a promising strategy for the development of Kir2.1 agonists.

Introduction Data about the efficacy of palliative double stenting for malignant duodenal and biliary obstruction are limited. Methods A systematic literature search was performed to assess the feasibility and optimal method of double stenting for malignant duodenobiliary obstruction compared with surgical double bypass in terms of technical and clinical success, adverse events, reinterventions, and survival. Event rates with 95% confidence intervals were calculated. Results Seventy-two retrospective and 8 prospective studies published until July 2018 were included. Technical and clinical success rates of double stenting were 97% (95%-99%) and 92% (89%-95%), respectively. Clinical success of endoscopic biliary stenting was higher than that of surgery (97% [94%-99%] vs 86% [78%-92%]). Double stenting was associated with less adverse events (13% [8%-19%] vs 28% [19%-38%]) but more frequent need for reintervention (21% [16%-27%] vs 10% [4%-19%]) than double bypass. No significant difference was found between technical and clinical success and reintervention rate of endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic drainage, and endoscopic ultrasound-guided biliary drainage. ERCP was associated with the least adverse events (3% [1%-6%]), followed by percutaneous transhepatic drainage (10% [0%-37%]) and endoscopic ultrasound-guided biliary drainage (23% [15%-33%]). Discussion Substantially high technical and clinical success can be achieved with double stenting. Based on the adverse event profile, ERCP can be recommended as the first choice for biliary stenting as part of double stenting, if feasible. Prospective comparative studies with well-defined outcomes and cohorts are needed.

Introduction: While cardiac amyloidosis (CA) is a rare systemic disease characterized by extracellular deposition of protein-derived fibrils, hypertrophic cardiomyopathy (HCM) is histopathologically characterized by myocyte hypertrophy and disarray, interstitial fibrosis, and small intramural coronary arteriole dysplasia. The aim of the present study was to compare left atrial (LA) volumetric and functional characteristics between light-chain (AL) CA and HCM by three-dimensional (3D) speckle-tracking echocardiography (STE). Methods: The AL-CA group initially consisted of 17 patients with AL-CA, but one patient was excluded due to inadequate image quality, and so the study population consisted of 16 patients (mean age: 64.0±9.6 years, five men). Their results were compared with data on 20 age-matched HCM patients (mean age: 59.8±5.2 years, 10 men) and on 16 age-matched healthy controls (mean age: 58.2±7.2 years, six men). Complete two-dimensional Doppler echocardiography and 3D-STE were performed in all cases. Results: Significantly increased LA volumes were observed in both AL-CA and HCM compared with the control group. Only active atrial emptying fraction was found to be significantly reduced in AL-CA patients compared to controls. Peak global and mean segmental circumferential, longitudinal and area strains showed significant reductions in AL-CA patients compared with controls, but only peak mean segmental longitudinal strain differed significantly between HCM patients and controls. While no differences were demonstrated in global and mean segmental strain at atrial contraction between HCM patients and controls, AL-CA patients showed reductions in certain strain parameters compared to controls and HCM patients. Conclusions: Different patterns of LA functional characteristics were demonstrated in AL-CA and HCM patients by 3D-STE. Resumo: Introdução: A amiloidose cardíaca (CA) é uma doença sistémica rara, caracterizada pela deposição extracelular de fibrilhas derivadas das proteínas; por outro lado, a miocardiopatia hipertrófica (HCM) é caracterizada do ponto de vista histopatológico por hipertrofia e desorganização dos miócitos, fibrose intersticial e displasia das pequenas arteríolas coronárias intramurais. No presente estudo fomos comparar as características volumétricas e funcionais da aurícula esquerda (AE) entre a CA de cadeias leves (AL) e a HCM com ecocardiografia speckle-tracking tridimensional (3DSTE). Métodos: A população do estudo foi constituída por 17 doentes com AL-CA, foi excluído um doente por deficiente qualidade de imagem. Desse modo, o grupo final de AL-CA consistiu em 16 doentes (média de 64,0 ± 9,6 anos, cinco homens). Os resultados desse grupo foram comparados com os de 20 doentes com HCM emparelhados por idade (idade média: 59,8 ± 5,2 anos, 10 homens) e com 16 controlos saudáveis igualmente emparelhados por idade média: 58,2 ± 7,2 anos, seis homens). Em todos os doentes foi feito ecocardiograma Doppler bidimensional e 3DSTE. Resultados: Os volumes da AE foram significativamente maiores nos doentes com AL-CA e com HCM comparados com o grupo controlo. Apenas a fração de esvaziamento auricular ativo foi significativamente mais baixa nos doentes com AL-CA em comparação com o grupo de controlo. Apesar de os strains de pico e médio segmentares, circunferenciais, longitudinais e em área serem significativamente mais baixos nos doentes com AL-CA por comparação com o grupo controlo, apenas o strain longitudinal segmentar médio de pico foi significativamente diferente entre os doentes com HCM e os do grupo de controlo. Apesar de não ter sido possível demonstrar diferenças no strain segmentar global e médio entre os doentes com HCM e o grupo de controlo, no caso dos doentes com AL-CA observou-se redução em alguns parâmetros de strain por comparação quer com o grupo de doentes com HCM quer com o grupo de controlo. Conclusão: Foi possível demonstrar a presença de diferentes padrões funcionais da AE por 3DSTE em doentes com amiloidose cardíaca e miocardiopatia hipertrófica. Keywords: Echocardiography, Function, Left atrium, Three-dimensional, Speckle-tracking, Hypertrophic cardiomyopathy, Cardiac amyloidosis, Palavras-chave: Ecocardiografia, Função, Aurícula esquerda, Tridimensional, Speckle-tracking, Miocardiopatia hipertrófica, Amiloidose cardíaca

Abstract: Telemedicine is a young science that integrates innovations of information-technology and telecommunications into medical science. A successful telemedicine procedure should guarantee reduced workload of the healthcare system with well secured and cost-effective processes. Our goal was to collect the development phases of telemedicine projects through existing telecardiology solutions. Subsequent to reviewing international publications we analyzed the past and present situation of blood pressure monitoring, remote diagnostics of electrocardiography, implantable cardioverter defibrillator monitoring and pocket ultrasound devices. In case of new solutions (a) several internationally accepted, confidently reproducible “good practices” are needed for creating (b) guidelines and recommendations of international medical associations. They have to ensure (c) cost-effective work, with well-designed sustainability and (d) patient confidentiality. Improving (e) education for professionals and patients is essential. We recommend to telemedicine developers to use our standards in order to introduce their products more effectively into clinical practice. It is encouraging that current possibilities of telecardiology partly or fully meet the aforementioned criteria. Further development of the topic can contribute to financial sustainability of our healthcare and might be able to resolve limitations of human resources. Orv Hetil. 2017; 158(44): 1741–1746.

The most important molecular determinant of heart rate regulation in sino-atrial pacemaker cells includes hyperpolarization-activated, cyclic nucleotide-gated ion channels, the major isoform of which is encoded by the HCN4 gene. Mutations affecting the HCN4 gene are associated primarily with sick sinus syndrome.A novel c.1737+1 GT 'splice-site' HCN4 mutation was identified in a large family with familial bradycardia which co-segregated with the disease providing a two-point LOD score of 4.87. Twelve out of the 22 investigated family members [4 males, 8 females average age 36 (SD 6) years] were considered as clinically affected (heart rate60/min on resting ECG). Minimum [36 (SD 7) vs. 47 (SD 5) bpm, p=0.0087) and average heart rates [62 (SD 8) vs. 73 (SD 8) bpm, p=0.0168) were significantly lower in carriers on 24-hour Holter recordings. Under maximum exercise test carriers achieved significantly lower heart rates than non-carrier family members, and percent heart rate reserve and percent corrected heart rate reserve were significantly lower in carriers. Applying rigorous criteria for chronotropic incompetence a higher number of carriers exhibited chronotropic incompetence. Parameters, characterizing short-term variability of heart rate (i.e. rMSSD and pNN50%) were increased in carrier family members, even after normalization for heart rate, in the 24-hour ECG recordings with the same relative increase in 5-minute recordings.The identified novel 'splice site' HCN4 gene mutation, c.1737+1 GT, causes familial bradycardia and leads to reduced heart rate response, impaired chronotropic competence and increased short-term heart rate variability in the mutation carriers.

Abstract: Heart failure is associated with a poor prognosis despite significant advances in the pharmacological and device therapy and incurs very high cost because of frequent hospitalizations. Therefore, professional high-quality care is essential for both patients and the healthcare system. The best way to evaluate the quality of care for a particular disease is the use of disease-specific registries. Until now, there has not been a registry evaluating characteristics and management of heart failure patients in Hungary. For that reason, the Hungarian Society of Cardiology initiated the set-up of the Hungarian Heart Failure Registry. The Aim of this paper is to present the goals, methods and first year results of the Hungarian Heart Failure Registry. The goal of the Registry is to create a modern, web-based database that summarizes the data of large number of patients who are currently or were previously admitted to hospital or who are currently or were previously patients in an outpatient department due to severe heart failure (NYHA III–IV). Currently 17 cardiology departments participate in the development of the Registry. The planned number of patients is 2000. Initially follow-up was planned for one year (pilot study). After the evaluation of the relevant experiences of the pilot study, long-term follow-up is planned. The Registry collects information about the type of heart failure (heart failure with reduced – LVEF≤45% – vs. preserved – LVEF>45% – ejection fraction), etiology, co-morbidities, diagnostic methods, treatment as well as morbidity and mortality. After the first year, assessing the baseline parameters of 698 patients enrolled in the Registry we found that the majority of patients (87.8%) has heart failure with reduced ejection fraction and in 39.8% of the patients heart failure has an ischaemic origin. The most frequent co-morbidity was hypertension followed by diabetes, renal insufficiency and COPD. The patients were treated with ACE inhibitors or ARBs in 94.4%, with beta blockers in 95.9%, and mineralocorticoid receptor antagonists in 73.9%. The mean dose of neurohormonal antagonists was higher than half of the target dose defined by current guidelines. The use of cardiac resynchronisation therapy was 11.7% and implantable cardioverter defibrillator was 25.8%. The pharmacological and device therapy of patients who were enrolled in the Registry until now was fit the current guidelines’ recommendations. This, however, does not mean that the management of heart failure is without problems in our country but that high quality patient care is available with adequate heart failure treatment in cardiology departments dedicated to heart failure care. Orv. Hetil., 2017, 158(3), 94–100.

Fabry disease (FD) is an X-linked inherited lysosomal storage disorder caused by mutations in the GLA gene, encoding for the enzyme α-galactosidase A. Although hundreds of mutations in the GLA gene have been described, many of them are variants of unknown significance. Here we report a novel GLA mutation, p.Ile239Met, identified in a large Hungarian three-generation family with FD. A 69 year-old female index patient with a clinical history of renal failure, hypertrophic cardiomyopathy, and 2nd degree AV block was screened for mutation in the GLA gene. Genetic screening identified a previously unreported heterozygous mutation in exon 5 of the GLA gene (c.717A>G; p.Ile239Met). Family screening indicated that altogether 6 family members carried the mutation (5 females, 1 male, average age: 55 ± 16 years). Three family members, including the index patient, manifested the cardiac phenotype of hypertrophic cardiomyopathy, while two other family members were diagnosed with left ventricular hypertrophy. Taking affection status as the presence of hypertrophic cardiomyopathy, left ventricular hypertrophy or elevated lyso-Gb3 levels, all affected family members carried the mutation. Linkage analysis of the family gave a two-point LOD score of 2.01 between the affection status and the p.Ile239Met GLA mutation. Lyso-Gb3 levels were elevated in all carrier family members (range: 2.4-13.8 ng/mL; upper limit of normal +2STD: ≤ 1.8 ng/mL). The GLA enzyme level was markedly reduced in the affected male family member (< 0.2 µmol/L/hour; upper limit of normal ± 2STD: ≥ 2.6 µmol/L/hour). We conclude that the p. Ile239Met GLA mutation is a pathogenic mutation for FD associated with predominant cardiac phenotype.

Abstract: The Szeged cardiomyopathy and ion channel diseases registry aims to establish a representative disease-specific registry based on the recruitment of patients with different cardiomyopathies and ion channel diseases followed at the Cardiology Center, University of Szeged. The registry collects patient data on the main forms of primary cardiomyopathies (hypertrophic, dilated, restrictive, arrhythmogenic right ventricular, left ventricular non-compact, tako-tsubo cardiomyopathy) and ion channel diseases (long QT syndrome, short QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia). Patients with hypertrophic cardiomyopathy (388 patients) make up the largest group of patients in the registry. Patients with dilated cardiomyopathy (310 patients) and patients with the long QT syndrome (111 patients) form two other sizable groups. Analyzed data of the group of patients with hypertrophic cardiomyopathy indicate similar figures with regard to disease related mortality and morbidity and clinical parameters. Orv. Hetil., 2017, 158(3), 101–105.

We assessed the cardiovascular safety of long-term direct-acting oral anticoagulant (DOAC) treatment. A search of the medical literature was performed from inception until May 31, 2019. Inclusion criteria were (1) randomized trial that assessed the clinical efficacy and/or safety of 1 or more DOAC, (2) control group including oral anticoagulation and/or antiplatelet and/or placebo treatment, and (3) the incidence of acute coronary syndrome during follow-up was reported. Fixed-effect and random-effects models were applied. The analyzed outcomes were myocardial infarction (MI), major bleeding, and mortality. Twenty-eight randomized clinical trials (196 761 patients) were included. Rivaroxaban was associated with a 21% reduction in the relative risk of MI when compared to placebo (relative risk [RR]: 0.79 [95% credible interval, CrI: 0.65-0.94]) and a 31% reduction (RR: 0.70 [95% CrI: 0.53-0.89]) when compared to dabigatran. Apixaban resulted in 24% (RR: 0.76 [95% CrI: 0.58-0.99]) and vitamin K antagonists anticoagulation resulted in 19% (RR: 0.81 [95% CrI: 0.65-0.98]) risk reduction compared to dabigatran. The computed probability of being the first best choice of treatment was 61.8% for rivaroxaban. Cardiovascular safety shows considerable heterogeneity among oral anticoagulants. Treatment with rivaroxaban is associated with reduced rate of MI.

In pediatric burns the use of systemic antibiotic prophylaxis is a standard procedure in some burn centers, though its beneficial effect on the infectious complications is debated. The present meta-analysis aimed at determining whether systemic antibiotic prophylaxis prevents infectious complications in pediatric patients with burn injuries. We searched the PubMed, EMBASE, and Cochrane Library databases from inception to August 2019. We included 6 studies, in which event rates of infectious complications were reported in children with burn injuries receiving or not receiving systemic antibiotic prophylaxis. We found that the overall odds ratio (OR) of developing an infection (including local and systemic) was not different between the groups (OR = 1.35; 95% CI, 0.44, 4.18). The chances for systemic infectious complications alone were also not different between antibiotic-treated and non-treated patients (OR = 0.74; 95% CI, 0.38, 1.45). Based on the age, affected total body surface area, and country income level, we did not find any subgroup that benefited from the prophylaxis. Our findings provide quantitative evidence for the inefficacy of systemic antibiotic prophylaxis in preventing infections in pediatric burns. To validate our conclusion, multinational, randomized trials in a diverse population of children with burn injuries are warranted.

IntroductionSandblasting is one of the oldest implant surface modifications to enhance osseointegration. Regarding its superiority over machined surface controversies still exist. Our objective was to compare implant failures (IF) and marginal bone level (MBL) changes between sandblasted and machined dental implants by a meta-analysis utilizing the available data. The PROSPERO registration number of the meta-analysis is CRD42018084190.MethodsThe systematic search was performed in Cochrane, Embase and Pubmed. Inclusion criteria included participants with neither systemic diseases, nor excessive alcohol consumption, nor heavy smoking. We calculated pooled Risk Ratio (RRs) with confidence intervals of 95% (CIs) for dichotomous outcomes (implant failure) and weighted mean difference (WMD) CIs of 95% for continuous outcomes (marginal bone level change). We applied the random effect model with DerSimonian-Laird estimation. I2 and chi2 tests were used to quantify statistical heterogeneity and gain probability-values, respectively.ResultsLiterature search revealed 130 records without duplicates. Out of these, seven studies met the inclusion criteria and all were included in data synthesis, involving 362 sand-blasted and 360 machined implants. The results indicate that there is an 80% (RR = 0.2 95% CI:0.06-0.67; I2 = 0.0% p = 0.986) lower among sandblasted compared to machined implants after one year of use and 74% (RR = 0.26 95% CI:0.09-0.74; I2 = 0.0% p = 0.968) five years of use, respectively. In contrast, there is no significant difference in MBL (WMD:-0.10mm, 95% CI:-0.20, 0.01; p>0.05; I2 = 0.0%, p = 0.560 and WMD:-0.01mm, 95% CI:-0.12, 0.09; p>0.05; I2 = 26.2%, p = 0.258) between the two implant surfaces after one and five years of use.ConclusionsThis meta-analysis reveals that sandblasting is superior over machined surface in implant failure but not in marginal bone level in healthy subjects. It also points out the need for further randomized clinical trials with large sample size for objective determination of the clinical benefits of certain implant surface modifications.

Telemedicine is a young science that integrates innovations of information-technology and telecommunications into medical science. A successful telemedicine procedure should guarantee reduced workload of the healthcare system with well secured and cost-effective processes. Our goal was to collect the development phases of telemedicine projects through existing telecardiology solutions. Subsequent to reviewing international publications we analyzed the past and present situation of blood pressure monitoring, remote diagnostics of electrocardiography, implantable cardioverter defibrillator monitoring and pocket ultrasound devices. In case of new solutions (a) several internationally accepted, confidently reproducible "good practices" are needed for creating (b) guidelines and recommendations of international medical associations. They have to ensure (c) cost-effective work, with well-designed sustainability and (d) patient confidentiality. Improving (e) education for professionals and patients is essential. We recommend to telemedicine developers to use our standards in order to introduce their products more effectively into clinical practice. It is encouraging that current possibilities of telecardiology partly or fully meet the aforementioned criteria. Further development of the topic can contribute to financial sustainability of our healthcare and might be able to resolve limitations of human resources. Orv Hetil. 2017; 158(44): 1741-1746.

Fabry disease (FD) is an X-linked inherited lysosomal storage disorder caused by mutations in the GLA gene, encoding for the enzyme α-galactosidase A. Although hundreds of mutations in the GLA gene have been described, many of them are variants of unknown significance. Here we report a novel GLA mutation, p.Ile239Met, identified in a large Hungarian three-generation family with FD. A 69 year-old female index patient with a clinical history of renal failure, hypertrophic cardiomyopathy, and 2nd degree AV block was screened for mutation in the GLA gene. Genetic screening identified a previously unreported heterozygous mutation in exon 5 of the GLA gene (c.717AG; p.Ile239Met). Family screening indicated that altogether 6 family members carried the mutation (5 females, 1 male, average age: 55 ± 16 years). Three family members, including the index patient, manifested the cardiac phenotype of hypertrophic cardiomyopathy, while two other family members were diagnosed with left ventricular hypertrophy. Taking affection status as the presence of hypertrophic cardiomyopathy, left ventricular hypertrophy or elevated lyso-Gb3 levels, all affected family members carried the mutation. Linkage analysis of the family gave a two-point LOD score of 2.01 between the affection status and the p.Ile239Met GLA mutation. Lyso-Gb3 levels were elevated in all carrier family members (range: 2.4-13.8 ng/mL; upper limit of normal +2STD: ≤ 1.8 ng/mL). The GLA enzyme level was markedly reduced in the affected male family member (0.2 µmol/L/hour; upper limit of normal ± 2STD: ≥ 2.6 µmol/L/hour). We conclude that the p. Ile239Met GLA mutation is a pathogenic mutation for FD associated with predominant cardiac phenotype.

Heart failure is associated with a poor prognosis despite significant advances in the pharmacological and device therapy and incurs very high cost because of frequent hospitalizations. Therefore, professional high-quality care is essential for both patients and the healthcare system. The best way to evaluate the quality of care for a particular disease is the use of disease-specific registries. Until now, there has not been a registry evaluating characteristics and management of heart failure patients in Hungary. For that reason, the Hungarian Society of Cardiology initiated the set-up of the Hungarian Heart Failure Registry. The Aim of this paper is to present the goals, methods and first year results of the Hungarian Heart Failure Registry. The goal of the Registry is to create a modern, web-based database that summarizes the data of large number of patients who are currently or were previously admitted to hospital or who are currently or were previously patients in an outpatient department due to severe heart failure (NYHA III-IV). Currently 17 cardiology departments participate in the development of the Registry. The planned number of patients is 2000. Initially follow-up was planned for one year (pilot study). After the evaluation of the relevant experiences of the pilot study, long-term follow-up is planned. The Registry collects information about the type of heart failure (heart failure with reduced - LVEF≤45% - vs. preserved - LVEF45% - ejection fraction), etiology, co-morbidities, diagnostic methods, treatment as well as morbidity and mortality. After the first year, assessing the baseline parameters of 698 patients enrolled in the Registry we found that the majority of patients (87.8%) has heart failure with reduced ejection fraction and in 39.8% of the patients heart failure has an ischaemic origin. The most frequent co-morbidity was hypertension followed by diabetes, renal insufficiency and COPD. The patients were treated with ACE inhibitors or ARBs in 94.4%, with beta blockers in 95.9%, and mineralocorticoid receptor antagonists in 73.9%. The mean dose of neurohormonal antagonists was higher than half of the target dose defined by current guidelines. The use of cardiac resynchronisation therapy was 11.7% and implantable cardioverter defibrillator was 25.8%. The pharmacological and device therapy of patients who were enrolled in the Registry until now was fit the current guidelines' recommendations. This, however, does not mean that the management of heart failure is without problems in our country but that high quality patient care is available with adequate heart failure treatment in cardiology departments dedicated to heart failure care. Orv. Hetil., 2017, 158(3), 94-100.

The Szeged cardiomyopathy and ion channel diseases registry aims to establish a representative disease-specific registry based on the recruitment of patients with different cardiomyopathies and ion channel diseases followed at the Cardiology Center, University of Szeged. The registry collects patient data on the main forms of primary cardiomyopathies (hypertrophic, dilated, restrictive, arrhythmogenic right ventricular, left ventricular non-compact, tako-tsubo cardiomyopathy) and ion channel diseases (long QT syndrome, short QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia). Patients with hypertrophic cardiomyopathy (388 patients) make up the largest group of patients in the registry. Patients with dilated cardiomyopathy (310 patients) and patients with the long QT syndrome (111 patients) form two other sizable groups. Analyzed data of the group of patients with hypertrophic cardiomyopathy indicate similar figures with regard to disease related mortality and morbidity and clinical parameters. Orv. Hetil., 2017, 158(3), 101-105.

Timothy syndrome 1 (TS1) is a rare genetic disorder characterized by multisystem abnormalities including QT prolongation, congenital heart defects, facial dysmorphism, episodic hypoglycemia, and neurological symptoms. A morphological hallmark of TS1 is syndactyly, present in all cases. TS1 is caused by the canonical p.Gly406Arg mutation in the alternatively spliced exon 8A in the CACNA1C gene, encoding for the main cardiac L-type calcium channel. A variant case of TS1 is reported. The proband had intermittent fetal bradycardia with heart rate of 72 bpm. On the first day of life bradycardia due to 2:1 atrioventricular (AV) block and marked QTc prolongation of 600 ms was noted. On medical therapy with propranolol and mexiletine 1:1 AV conduction returned with QTc prolongation of 470-580 ms. The patient lacked other extracardiac manifestations, most importantly syndactyly, neurological complications or autism. On genetic analysis, the canonical TS1 causing mutation, p.Gly406Arg in exon 8A of the CACNA1C gene was detected. The CACNA1C p.Gly406Arg variant was not present in the parents, but was detected in different DNA samples of the index patient. Our case highlight further phenotypic variability in TS. Most importantly, it underlines that the lack of syndactyly does not exclude the presence of a TS1 genotype. (c) 2017 Wiley Periodicals, Inc.

Cardiac amyloidosis (CA) is an infiltrative disease primarily caused by extracellular tissue deposition of amyloid fibrils in the myocardial interstitium. The aim of the present study was to examine left ventricular (LV) rotational mechanics in biopsy-proven CA by three-dimensional (3D) speckle-tracking echocardiography (STE). Ten patients (65.3±11.5 years, 6 males) with CA entered the study. The mean basal LV rotations were 0.3±3.8°, while mean apical LV rotations proved to be 7.0±3.3°. LV basal and apical rotations were in the same counterclockwise direction in 6 out of 10 CA patients demonstrating near absence of LV twist [LV rigid body rotation (RBR)]. Apico-basal difference was near 3 or less degrees in three patients with LV-RBR, and 6−10 degrees in the other three subjects with LV-RBR. One another patient showed normal rotational mechanics, while two patients had significant hyporotations and one had significant hyperrotations in normal directions. To conclude with, different patterns of LV rotational mechanics could be demonstrated in CA. LV RBR, the near absence of LV twist seems to be a frequent phenomenon in CA.

Objective: Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease and defined by the presence of unexplained left ventricular hypertrophy (LVH). Vascular alterations are frequently associated with HCM including microvascular and/or peripherial endothelial dysfunction. This study was designed to evaluate echocardiographic ascending aortic elastic properties and arteriograph-derived pulse-wave velocity (PWV) and augmentation index (Aix) in HCM. Methods: This study comprised 38 patients with typical features of HCM. Their results were compared to 20 hypertensive patients with LVH and 23 controls. Systolic and diastolic ascending aortic diameters were recorded in M-mode at a level of 3 cm above the aortic valve from a parasternal long-axis view. The following echocardiographic aortic elastic properties were measured from aortic data and forearm blood pressure values: aortic strain, distensibility, and stiffness index. Arteriograph-derived PWV and AIx were also measured. Results: Aortic stiffness index (18.4 ± 17.6 vs. 6.88 ± 3.63, P < 0.05), PWV (9.44 ± 4.08 vs. 7.97 ± 1.20 m/sec, P < 0.05) and Aix (-24.9 ± 32.6 vs. –41.4 ± 24.3, P < 0.05) were increased, while aortic strain (0.061 ± 0.053 vs. 0.100 ± 0.059, P < 0.05) and aortic distensibility (1.94 ± 1.68 cm2/dynes 10−6 vs. 3.08 ± 1.77 cm2/dynes 10−6, P < 0.05) were decreased in HCM patients compared to controls. Aortic elastic properties of hypertensive patients with LVH showed similar alterations to HCM patients. Conclusions: Abnormal echocardiographic aortic elastic properties and arteriograph-derived PWV and Aix could be demonstrated in HCM patients compared to matched controls. (Echocardiography 2011;28:848-852)

Percutaneous coronary intervention (PCI) via radial approach has been shown to be an alternative to femoral approach in emergency cases; however, its feasibility has been questioned. This single-center study was performed to compare the outcomes and complication rates between transradial (TR) and transfemoral (TF) PCI in ST-segment-elevation myocardial infarction (STEMI).The clinical and angiographic data of 582 consecutive STEMI patients treated with PCI between 2001 and 2006 were evaluated in a retrospective study. Forty-three patients were excluded from the present study due to cardiogenic shock or rescue PCI. Patients (n=539) were categorized into the TR group (n=167) or the TF group (n=372), and several parameters were evaluated to assess the advantages and drawbacks of TR access: access-site crossover, rate of access-site complications, procedure time, fluoroscopy time, X-ray area dose, major adverse cardiac events (MACE) at 1 month, and consumption of angioplasty equipment.In the TR group, the crossover rate to femoral access was 5%, while in the TF group, it was 0.8% (P.05). There was a significant difference, in both major and minor access-site complications, between the TR group and the TF group (0% vs. 5%, P.05, and 4% vs. 9%, P.05, respectively). Consumption of angioplasty equipment proved to be the same for the two groups. The MACE rate was 4% in the TR group and 11% in the TF group (P.05).Our results suggest that the TR approach is a safe and effective way to treat STEMI; furthermore, site-related complications are less common with this approach.