Nova generacija CT uređaja za oslikavanje koronarne bolesti srca – implikacije za buduće pružanje usluga

The European Society of Cardiology (ESC) published guidelines for the diagnosis and management of chronic coronary syndromes in 2019 that included new recommendations for coronary computed tomography angiography (CCTA). The new ESC guidelines promoted CCTA as a Class I examination, which means that CCTA or non-invasive functional imaging is recommended or indicated for myocardial ischemia as the initial test for diagnosing CAD in symptomatic patients in whom obstructive CAD cannot be excluded by clinical assessment alone. Patients who are difficult to scan, such as those with extensive coronary calcifications (>400 Agatston Units), increased (>65 bpm) or irregular heart rate, or those who are obese (body mass index >30) and unable to hold their breath, have been already identified by the National Institute for Health and Care Excellence (NICE) in earlier scanner generations. For these patients, NICE recommends the new generation of scanners or even particular scanner models, as opposed to the ESC guidelines which do not recommend CCTA. In spite of differences between ESC and NICE recommendations, an experienced clinical team consisting of a radiographer, radiologist, and cardiologist can obtain good image quality from new-generation CT scanners, even from patients who are difficult to scan. Considering the burden of risk factors and the 2019 ESC guidelines, referrals to CCTA are expected to rise at the national level, as they have in other countries with a similar cardiovascular burden, although clinical practice may vary. Numerous public hospitals have purchased scanners that fulfil SCCT technical guidelines, but these are neither cardiac-dedicated nor recommended for patients who are difficult to scan. CT scanners for these patients should feature dual-source technology with two powerful current generators in order to provide good temporal resolution; they should also have a long z-detector array in order to ensure high spatial resolution and volume coverage. Good image quality requires appropriate patient preparation and the adjustment of scan protocols to individual patient characteristics. This is the only way patients can benefit from this high-tech radiological procedure, according to recent clinical guidelines.Europsko kardiološko društvo (ESC) izdalo je 2019. godine Smjernice za dijagnostiku i liječenje kroničnoga koronarnog sindroma, koje uključuju nove preporuke za MSCT koronarografiju. Nove ESC smjernice promaknule su MSCT koronarografiju u pretragu klase I., što podrazumijeva da je MSCT koronarografija ili neinvazivno funkcionalno oslikavanje preporučena pretraga za ishemiju miokarda i prvi test kojim se dijagnosticira koronarna bolest srca (CAD) u simptomatskih bolesnika u kojih se opstruktivna CAD ne može isključiti na temelju kliničke procjene. Bolesnike zahtjevne za snimanje, kao što su primjerice oni s opsežnim koronarnim kalcifikacijama (>400 Agatstonovih jedinica), povišenom (>65/min) ili nepravilnom frekvencijom srca, pretili i oni koji ne mogu zadržati dah, već je prije prepoznao Nacionalni institut za izvrsnost zdravlja i skrbi (NICE) na starijim generacijama uređaja. U takvih pacijenata NICE, za razliku od ESC smjernica preporučuje uporabu uređaja nove generacije ili čak neke specifične modele. Usprkos razlikama u preporukama NICE-a i ESC-a iskusan klinički tim sastavljen od inženjera radiologije, radiologa i kardiologa i u bolesnika zahtjevnih za snimanje na CT uređajima nove generacije može dobiti dobru kvalitetu slike. Kada se uzme u obzir opterećenje čimbenicima kardiovaskularnog rizika i Smjernice ESC-a iz 2019. godine, možemo očekivati porast upućivanja bolesnika na MSCT koronarografiju na nacionalnoj razini, što je slučaj i u drugim zemljama sa sličnim kardiovaskularnim opterećenjem usprkos opaženim varijacijama u kliničkoj praksi. Brojne javne bolnice kupile su uređaje koji ispunjavaju tehničke smjernice Društva za kardiovaskularnu kompjutoriziranu tomografiju (SCCT), međutim, oni nisu namijenjeni za kardiovaskularno oslikavanje niti preporučeni za bolesnike zahtjevne za snimanje. Za takve bolesnike CT uređaji trebali bi sadržavati tehnologiju s dvjema rendgenskim cijevima s dvama snažnim strujnim generatorima koji osiguravaju dobru temporalnu rezoluciju i dugačak niz detektora u z-smjeru kako bi se osigurale visoka prostorna razlučivost i volumska pokrivenost. Za dobru kvalitetu slika potrebno je pripremiti bolesnika i prilagoditi protokol snimanja prema njegovim obilježjima. Samo na takav način, u skladu s nedavnim kliničkim smjernicama, bolesnici mogu imati dobrobit od ove radiološke pretrage visoke tehnološke razine

Obilježja vulnerabilnog plaka na višeslojnoj kompjutoriziranoj tomografiji koronarnih arterija

SUMMARY: According to morbidity and mortality indicators, cardiovascular diseases are the leading public health issue in the Republic of Croatia and the European Union. Although mortality rates from ischemic disease have been reduced, Croatia is still categorized among countries with high cardiovascular risk. The guidelines of the European Society of Cardiology from 2020 for acute coronary syndrome (ACS) in patients with low to intermediate risk of coronary atherosclerotic heart disease (CHD) recommend coronary computed tomography angiography (CCTA) as an alternative to invasive coronarography. In most patients with suspicion of CHD, CCTA leads to the diagnosis of non-obstructive diseases, which causes the majority of ACS cases. Multi-slice Computed Tomography scanners of the newest generation employ low doses of radiation and low contrast volume to reliably show the characteristics of vulnerable plaque: (i) positive remodeling, (ii) low attenuation plaque, (iii) spotty calcification, and the (iv) napkin-ring sign. Due to positive remodeling, these plaques are often non-obstructive, and according to the CAD-RADS 2.0 guidelines from 2022 all their characteristics should be specifically emphasized in CCTA findings. Based on the assessment of the prognostic value of vulnerable plaque characteristics for adverse cardiac events, CCTA has been shown to be equally valid as other invasive diagnostic methods. Additionally, it was shown to be useful in indicating the optimal medication therapy and monitoring its effects. The results of large international randomized trials indicate the direction of the treatment approach for vulnerable plaque.SAŽETAK: Kardiovaskularne su bolesti, prema pokazateljima morbiditeta i mortaliteta, vodeći javnozdravstveni problem u Republici Hrvatskoj i Europskoj uniji. Premda stope smrtnosti od ishemijske bolesti srca padaju, Hrvatska se još uvijek ubraja u države visokog kardiovaskularnog rizika. Smjernice Europskoga kardiološkog društva iz 2020. godine za akutni koronarni sindrom (AKS) u bolesnika s niskim do srednjim rizikom od koronarne aterosklerotske bolesti srca (KBS) preporučuju MSCT koronarografiju kao alternativu invazivnoj koronarografiji. U većine bolesnika sa sumnjom na KBS nakon MSCT koronarografije postavi se dijagnoza neopstruktivne bolesti koja uzrokuje većinu slučajeva AKS-a. MSCT uređaji najnovije generacije uz nisku dozu zračenja i mali volumen kontrasta pouzdano prikazuju obilježja vulnerabilnog plaka: (i) pozitivno remodeliranje, (ii) plak niske atenuacije, (iii) točkastu kalcifikaciju i (iv) znak prstena za salvete. Ti su plakovi zbog pozitivnog remodeliranja često neopstruktivni, a prema smjernicama CAD-RADS 2.0 iz 2022. godine, sva njihova obilježja potrebno je na MSCT nalazima posebno naglasiti. Pri procjeni prognostičke vrijednosti obilježja vulnerabilnog plaka za neželjene kardijalne događaje MSCT se pokazao podjednako valjan kao i druge invazivne dijagnostičke metode. Isto tako, kod vulnerabilnih plakova pokazao se korisnim pri indiciranju optimalne medikamentne terapije kao i u praćenju njezina učinka. Rezultati velikih međunarodnih randomiziranih istraživanja upućuju na smjer terapijskog pristupa vulnerabilnom plaku

The Association of ABO and RhD Blood Groups with COVID-19 Mortality of Patients Hospitalized in the COVID Ward at General Hospital Karlovac

Cilj: Cilj ovog istraživanja je ispitati povezanost krvnih grupa ABO i RhD sa smrtnošću od bolesti COVID-19 u pacijenata hospitaliziranih na COVID odjelu Opće bolnice Karlovac. Ispitanici i metode: U istraživanje je uključeno 778 pacijenata oboljelih od bolesti COVID-19 hospitaliziranih na COVID odjelu Opće bolnice Karlovac od 1. ožujka 2020. do 31. prosinca 2021. Za istraživanje su prikupljeni podatci iz bolničkog informacijskog sustava hospitaliziranih bolesnika o dobi, spolu, krvnim grupama i RhD statusu, komorbiditetima, primjeni kisika i respiratora, cijepljenju, tijeku i ishodu bolesti. Nadalje, ispitana je povezanost ABO i RhD krvnih grupa s brojem dana u bolnici i stopom mortaliteta. Rezultati: Najzastupljenija krvna grupa bila je O s 283 bolesnika (36,4 %), dok je krvna grupa A bila druga po zastupljenosti (35,8 %). Krvna grupa AB bila je najmanje zastupljena sa 7,6 %. U trenutku hospitalizacije procijepljenost je iznosila svega 8,1 %. Ukupna smrtnost povezana s COVID-om iznosila je 25,9 %. Stopa smrtnosti u osoba krvne grupe A bila je 39,7 %, krvne grupe B 24,2 %, krvne grupe AB 23,7 % i krvne grupe O 23,7 % (P = 0,588). Stopa smrtnosti od bolesti COVID-19 bila je veća u RhD-pozitivnih osoba (26,4 %) u odnosu na RhD-negativne osobe (23,7 %). Najveći udio bolesnika liječenih na respiratoru (16,5 %) imao je krvnu grupu A. Zaključak: U istraživanju nije pronađena značajna povezanost između ABO i RhD sustava krvnih grupa i težine i smrtnosti od bolesti COVID-19 među bolesnicima hospitaliziranim na COVID odjelu Opće bolnice Karlovac.Aim: This study aimed to examine the association of ABO and RhD blood groups with COVID-19 mortality of patients hospitalized in the COVID ward at General Hospital Karlovac. Participants and methods: The study included data about 778 patients with COVID-19 hospitalized in the COVID ward at General Hospital Karlovac from March 2020 to the end of December 2021. Data about the hospitalized patients’ age, sex, blood groups, RhD status, comorbidities, oxygen, respirator use, vaccination, and disease course and outcome were obtained from the Hospital Management System. Furthermore, the association of ABO and RhD blood groups with the number of days in the hospital and the mortality rate was examined. Results: The prevalent blood group was O, with 283 patients (36.4%), while the A blood group was the second most common (35.8%). The least common blood group was AB (7.6%). At the time of hospitalization, a small number of patients had been vaccinated, only 8.1%. The overall COVID-19-associated mortality of 25.9% was observed. The mortality rate was 39.7% in blood group A, 24.2% in group B, 23.7% in group AB and 23.7% in group O (P = 0.588). The mortality rate from the COVID-19 disease was higher in RhD-positive (26.4%) compared to RhD-negative individuals (23.7%). The largest number of patients on a respirator (16.5%) were A blood group. Conclusion: The study did not find a significant association between the ABO and RhD blood group and the COVID-19 severity and mortality among patients hospitalized in the COVID ward at General Hospital Karlovac

Performance of WHO Angina Questionnaire in Measuring Burden of Coronary Heart Disease in Human Isolate Populations

Isolated human populations represent good candidates for studying genetic and environmental causes of common complex diseases because of their decreased genetic and environmental diversity. The possibility of inexpensive and reliable detection of disease prevalence in such populations is therefore of considerable importance, as comprehensive routine health data and disease registries are rarely available in these populations. In this study, we validated the performance of the WHO Rose Angina Questionnaire (RQ) in measuring the burden of coronary heart disease (CHD) in 9 settlements in these Croatian Adriatic islands. CHD was defined as myocardial infarction (MI) diagnosed by a specialist in the local general hospital, or angina pectoris (AP) by a local general practitioner (GP). The »true« prevalence of CHD in 1,001 adult persons was 10.5%. The results of the RQ screening based on the first 3, 5 and 6 questions were compared with medical record of CHD. Increasing the number of RQ questions from 3 to 6 resulted in decreasing test sensitivity (from 59.0% to 30.5%) and increasing test specificity (from 86.3% to 93.0%) in the prediction of true CHD status. CHD prevalence was overestimated by 76% when subset of the first 3 questions of RQ was used and by 25% when the first 5 questions were used. However, it was underestimated by 10% when the first 6 questions were used. We conclude that RQ is a useful screening method for measuring burden of CHD in isolate human populations, and that the result based on the first 6 questions is a good approximation of the true CHD prevalence in the population, although it should be considered a slight underestimate

Strategy for Mapping Quantitative Trait Loci (QTL) by Using Human Metapopulations

Aim: To present a novel strategy for mapping quantitative trait loci (QTL), using human metapopulations. The strategy is based on the expectation that in geographic clusters of small and distinct human isolates, a combination of founder effect and genetic drift can dramatically increase population frequency of rare QTL variants with large effect. In such cases, the distribution of QT measurements in an “affected” isolate is expected to deviate from that observed in neighboring isolates. Methods: We tested this hypothesis in 9 villages from a larger Croatian isolate resource, where 7 Mendelian disorders have been previously reported. The values of 10 physiological and biochemical QTs were measured in a random sample of 1001 individuals (100 inhabitants of each of 9 villages and 101 immigrant controls). Results: Significant over- or under- representation of individuals from specific villages in extreme ends of standardized QT measurement distribution was found 10 times more frequently than expected by chance. The large majority of such clusters of individuals with extreme QT values (34/36, 94.4%) originated from the 6 villages with the most pronounced geographic isolation and endogamy. Conclusion: Early epidemiological assessment supports the feasibility of the proposed strategy. Clusters of individuals with extreme QT values responsible for over-representation of single villages can usually be linked to a larger pedigree and may be useful for further QTL mapping, using linkage analysis

An Analysis of the Work of Croatian Invasive Cardiologic Laboratories between 2010 and 2014

Uz napredak intervencijske kardiologije u Republici Hrvatskoj unatrag dva i pol desetljeća svrha je ovog rada bila analizirati broj i složenost perkutanih koronarnih intervencija (PCI) u pojedinim centrima. Od 2010. do 2014. u ukupno 13 centara prosječno su učinjena 9 494 PCI-ja godišnje. Sedam centara svrstavamo u velike, Kliniku Magdalena s najvećim brojem PCI-ja svake godine i prosječnim godišnjim rastom od 6,2 % (s 1545 na 1941 PCI-ja), slijedi Klinički bolnički centar (KBC) Zagreb u kojem se bilježi prosječno godišnje smanjenje od 1,8 % (s 1474 na 1308), KBC Rijeka s prosječnim rastom od 15,8 % (s 1013 na 1632), Klinička bolnica (KB) Dubrava s najvećim prosječnim godišnjim smanjenjem od 5,7 % (s 1153 na 905) i KBC Sestre milosrdnice s prosječnim porastom od 2,3 % ali znatnim sniženjem broja PCI-ja u zadnjoj promatranoj godini (s 1082 na 815). Slijede KBC Split s prosječnim godišnjim porastom od 6,7 % (sa 662 na 821) i KBC Osijek s porastom od 12,4 % (sa 677 na 905). Pet centara svrstavamo u srednje velike: KB Merkur s prosječnim godišnjim smanjenjem od 3,7 % (sa 670 na 506), dok se u ostalim centrima bilježi prosječni porast, u Općoj bolnici (OB) Slavonski Brod za 29,1 % (sa 264 na 660), KB Sveti Duh za 7,5 % (s 306 na 382), u OB Zadar za čak 70,5 % (sa 105 na 430), a u OB Dubrovnik za 32,4 % (s 84 na 232). Udio složenih zahvata na dvjema ili više žila u RH bio je 9,7 %. Najviši je bio u KBC-u Rijeka (18,2 %) i KB-u Dubrava (17,1 %), a slijede OB Zadar (15,3 %), KBC Split (11 %) i Klinika Magdalena (10,4 %). KBC Zagreb imao je udio sličan prosjeku (10,1 %), kao i OB Dubrovnik (8,6 %). Niže su udjele složenih zahvata imale KB Sveti Duh (7,9 %), KBC Sestara milosrdnica (6,9 %) i OB Slavonski Brod (6,3 %), a najniže KBC Osijek (3,5 %) i KB Merkur (1,7 %). Uz takav napredak intervencijske kardiologije i nakon što se uvede registar koronarnih intervencija i certificira centre i osoblje, sljedeći korak u RH trebalo bi biti uvođenje niza novih zahvata u bolesnika sa stečenim strukturnim i kongenitalnim bolestima srca koji su za sada još nedostatno razvijeni.With the advancements in interventional cardiology in the Republic of Croatia over the last two and a half decades, the goal of this study was to analyze the number and complexity of percutaneous coronary intervention (PCI) procedures in individual centers. Between 2010 and 2014, an average of 9,494 PCI procedures was performed annually in a total of 13 centers. Seven centers are classified as high-volume centers: the Magdalena Clinic with the highest number of PCI procedures performed annually, with an average annual increase of 6.2% (1545 to 1941 PCI over analyzed period), the University Hospital Centre (UHC) Zagreb with an average annual decrease of 1.8% in procedure numbers (1474 to 1308), UHC Rijeka with an average annual increase of 15.8% (1013 to 1632), University Hospital (UH) Dubrava with an average annual decrease of 5.7% (1153 to 905), and the UHC “Sestre milosrdnice” with an average annual increase of 2.3%; however this hospital experienced a decrease of procedures in the last year of period (1082 to 815). These are followed by the UHC Split with an average annual increase of 6.7% (662 to 821) and the UHC Osijek with an increase of 12.4% (677 to 905). Five centers are classified as medium-volume centers: the UH Merkur with an average annual decrease in PCI procedures of 3.7% (670 to 506), whereas the number of procedures increased in the rest of the medium-sized centers: in General Hospital (GH) Slavonski Brod by 29.1% annually (264 to 660), UH “Sveti Duh” by 7.5% annually (306 to 382), in the GH Zadar by as much as 70.5% annually (105 to 430), and in the GH Dubrovnik by 32.4% annually (84 to 232). In Croatia overall, the percentage of complex procedures on two or more vessels was 9.7%. It was highest in the UHC Rijeka (18.2%) and UH Dubrava (17.1%), followed by the GH Zadar (15.3%), UHC Split (11.0%), and the Magdalena Clinic (10.4%). The UHC Zagreb had a value similar to the national average (10.1%), as did the GH Dubrovnik (8.6%). Lower percentages of complex procedures were present in the UH “Sveti Duh” (7.9%), UHC “Sestre milosrdnice” (6.9%), and the GH Slavonski Brod (6.3%), whereas the lowest rate of complex procedures was found in the UHC Osijek (3.5%) and the UH Merkur (1.7%). With such advancements in coronary interventions and once the introduction of a registry of coronary interventions and certificates for centers and staff is completed, the next step in Croatia should be the introduction of a plethora of new procedures in patients with acquired or congenital structural heart diseases that are currently underdeveloped

The Evaluation of the Stroke Unit in Croatia at the University Hospital »Sestre milosrdnice«, Zagreb: 1995–2006 Experience

This study evaluate the effects of the Stroke Unit (SU) in Croatia by comparing the in-hospital case fatality rate in the period before (1995–2000) and after (2001–2006) the implementation of SU and to compare the prevalence of risk factors, such as hypertension, diabetes mellitus (DM), atrial fibrillation (AF) and ischemic heart disease (IHD) among the patients who died. The study was conducted in twelve-year period during which 10 901 stroke patients were admitted to hospital and 1 818 of them died. The endpoints were in-hospital case fatality rate and prevalence of risk factors among the patients who died. Before the SU period the case fatality rate was 20.1%, whereas afterwards it decreased significantly to 12.8% (p<0.001). The relative risk (RR) was 1.57, while the estimate of the odds ratio (OR) showed a 71% increase in chances of death in the pre-SU period. The prevalence of DM, IHD and AF increased significantly, while hypertension was the only risk factor which significantly decreased (p<0.001). The results showed that the implementation of SU care is associated with a significant reduction of in-hospital case fatality rate of acute stroke patients which strongly suggests that development of the SU network in Croatia should be given priority in the health management

The Evaluation of the Stroke Unit in Croatia at the University Hospital »Sestre milosrdnice«, Zagreb: 1995–2006 Experience

This study evaluate the effects of the Stroke Unit (SU) in Croatia by comparing the in-hospital case fatality rate in the period before (1995–2000) and after (2001–2006) the implementation of SU and to compare the prevalence of risk factors, such as hypertension, diabetes mellitus (DM), atrial fibrillation (AF) and ischemic heart disease (IHD) among the patients who died. The study was conducted in twelve-year period during which 10 901 stroke patients were admitted to hospital and 1 818 of them died. The endpoints were in-hospital case fatality rate and prevalence of risk factors among the patients who died. Before the SU period the case fatality rate was 20.1%, whereas afterwards it decreased significantly to 12.8% (p<0.001). The relative risk (RR) was 1.57, while the estimate of the odds ratio (OR) showed a 71% increase in chances of death in the pre-SU period. The prevalence of DM, IHD and AF increased significantly, while hypertension was the only risk factor which significantly decreased (p<0.001). The results showed that the implementation of SU care is associated with a significant reduction of in-hospital case fatality rate of acute stroke patients which strongly suggests that development of the SU network in Croatia should be given priority in the health management

Genome-wide association study identifies _FUT8_ and _ESR2_ as co-regulators of a bi-antennary N-linked glycan A2 (GlcNAc~2~Man~3~GlcNAc~2~) in human plasma proteins

HPLC analysis of N-glycans quantified levels of the biantennary glycan (A2) in plasma proteins of 924 individuals. Subsequent genome-wide association study (GWAS) using 317,503 single nucleotide polymorphysms (SNP) identified two genetic loci influencing variation in A2: FUT 8 and ESR2. We demonstrate that human glycans are amenable to GWAS and their genetic regulation shows sex-specific effects with _FUT 8_ variants explaining 17.3% of the variance in pre-menopausal women, while _ESR2_ variants explained 6.0% of the variance in post-menopausal women