In the late eighties of the last century, the concept of an “open coronary artery” in the treatment of acute myocardial infarction (AMI) moved from phamaco-coagulation laboratory to the invasive cardiology laboratory. (1, 2) Since 1997 our principle invasive cardiology institution, University Hospital Sestre milosrdnice in Zagreb initiated primary percutaneous coronary intervention (pPCI) in acute myocardial infarction with ST-segment elevation (STEMI) (3). In late 2000 this center also started with continuous preparedness of invasive cardiologists for STEMI (24 hours/7 days). (4) This concept was also extended in early 2001 to the laboratories in University Hospital Zagreb and University Hospital Dubrava in Zagreb (5) whereas the entire Zagreb region was gradually covered. The profession is simultaneously evolving in Rijeka, where the first pPCI was performed already in 1998.

Since 2004, upon the initiative of the members of the Croatian Cardiac Society the Croatian pPCI network was established and after that it started extending to some other territories since 2005, from Zagreb and Rijeka to some new invasive cardiology laboratories, covering major part of the Croatian territory, recording fascinating results. (6) The network resulted in a greater availability and reduced differences in the treatment of AMI for our citizens, both in terms of territorial allegiance and by age and gender. (7) However there are certain “grey zones of our territory” where the network did not include all of its population and all of its patients, partly because of a lack of understanding by local hospital principals till the mid of 2013 (Slavonski Brod), partly because of a lack of skilled invasive cardiologists till the end of 2012 (Dubrovnik).

The invasive cardiac laboratory of Dubrovnik General Hospital was established in 2009 and in the next few years it worked on certain occasions, in summer and at weekends, when colleagues from Zagreb would come to this hospital. Since the transport to Split within a reasonable time was almost impossible (only the journey takes 3-4 hours), including 210 km partly along the “mountain road” from Ploce to Vrgorac and two border crossings, the reperfusion therapy in Dubrovnik mainly included fibrinolysis prior to the 1st of January 2013. Since that date a continuous operation of the laboratory and constant preparedness for acute coronary syndrome (ACS) (24/7) started with one invasive cardiologist in the first half of the year and another colleague after she fulfilled some conditions. (7) The laboratory is integrated with the coronary unit into Department for acute cardiac care and interventional cardiology, and the results of the first year of operation are descriptively presented in this article.

During the year 2013, the Dubrovnik General Hospital received 227 patients with ACS, of whom 151 patients (66.5%) with AMI and 76 patients (33.5%) with unstable angina pectoris (UAP). Among the patients with AMI there were 89 patients (39.2% ACS) with acute myocardial infarction without ST-segment elevation (NSTEMI) and 62 patients (27.2% ACS) with STEMI (Table 1).

In the first year of operation, the invasive cardiac workup was performed in a total of 361 patients, of whom two-thirds of patients were admitted in an emergency department (241 patients, 66.8%), and one third as ordered patients (120 patients; 33.2%). The average age of patients was 65.5 (range 25-89 years of age). Women were on average slightly older (67.4) and there were fewer of them (33.2%) than men (Table 2).

Coronary angiographies were performed in 215 of emergency coronary patients (94.7%), in all 76 patients with UAP (100%), in the majority of patients with AMI (92%) and in 61 of 62 patients with STEMI (98,4%). Among 120 patients ordered for invasive workup, 80 of them had indication for stable angina pectoris, and the same diagnosis was made in 7 emergency patients, received for some other reason, while the workup and preparation was done mostly for non-cardiac surgery. The workup was done in 30 ordered patients for valvular diseases and cardiomyopathy. Almost the same number of patients underwent the invasive workup for valvular disease and cardiomyopathy after being admitted from the emergency department (28 patients). Transradial access was done in a total of 192 procedures, 53.2% (Table 1).

The workup of 361 patients found 570 significant stenosis /occlusions, 1.6 per patient. We found 31 (5.4%) stenosis of the left main coronary artery (LM) and a half of them on the large arteries, almost one third of them (27.4%) on the left anterior descending artery (LAD) and one fourth of them (23.9%) on the right coronary artery (RCA) (Table 3). Percutaneous coronary interventions were performed in 167 patients, accounting for 46.3% of all invasive procedures and also on one third of all found significant stenosis/occlusions (34%). The average age of patients who underwent PCI was 65 years (range 36-87), women were older, on average 67.7 years, and there were fewer of them, 27.6% (Table 2).

PCI has resulted in more than one half of interventions in coronary patients (54.4%, 165/303), and the proportion of PCI in patients with ACS was higher, 62%. 140 patients underwent PCI on one, and 27 patients on two or more arteries (16.2%). 223 stents were implanted, 1.33 per intervention, of which 52 of them were drug-eluting stents (DES), with a penetration of 25.6%. 15 patients (9%) underwent percutaneous transluminal coronary angioplasty, without stent implantation.

A half of the 156 significant stenosis /occlusions on the LAD was treated with PCI (48.7%), which is 45.5% of all interventions, and out of 136 lesions on the RCA 41.2% was treated with PCI, which is 33.5% of all PCIs. The remaining 21% of PCI was performed in circumflex coronary artery (CCA) (12.9%) and on the smaller vessels, somewhat more on marginal (OM) branches (10.8%) than on the diagonal (D) and posterodescending (PD) branch (a total of 7.7%) (Table 3). Untreated lesions remained in patients who were recommended to undergo surgical cardiac revascularization (CABG), non-recanalized chronic total occlusions, patients with staged PCI (mainly after STEMI) and in two patients who were referred to a tertiary center with cardiosurgical support, University Hospital Dubrava (one PCI of the left main and one PCI on the only residual vessel, total 1.2%). Transradial access was performed in a total of 95 PCIs (56.5%).

Out of 61 patients invasively processed for STEMI, 55 of them underwent PCI, one patient had Takotsubo cardiomyopathy and did not need an intervention, 3 of them were recommended to undergo urgent CABG without prior PCI, and 3 patients underwent PCI and were recommended to undergo CABG for their findings in other vessels. In 2 patients no vessel flow was achieved (TIMI 0 flow) (Table 2 and 5) and two patients had final TIMI 2 flow. 93.4% of patients with STEMI had a total TIMI 3 flow (Table 5).

Cardiac surgery, elective or direct transfer was recommended in 69 patients (19.1% of totally worked up). There were no urgent or helicopter transported patients. Among the patients worked up for coronary heart disease, 43 patients (14.2%) received the recommendation for CABG, and among the patients treated for valvular disease or cardiomyopathy there were 26 of them who were recommended to undergo valvular surgery with or without CABG (44.8%).

Finally, of all coronary patients about 30% remained on medical therapy, with approximately 55% who underwent PCI and 15% of them were recommended to undergo cardiac surgery.

The city of Dubrovnik is a major tourist destination and the Dubrovnik-Neretva County is visited by more than one million tourists each year. Although no data on the demographic structure of guests is available yet, we can say that in 2013 some 25 foreign citizens underwent invasive treatment and PCI was performed in 15 of them (60%). PCI was per formed in two of four patients with UAP, four of 10 patients with NSTEMI and all 9 patients with STEMI (Table 4).

Of course, there were some adverse events we faced (Table 5). Non-standardized in-hospital lethality of patients with AMI was 2.61% (4/153), all of them were women, mean age 81.2 (range 76-88), in three of the four with anterior wall AMI, in two with unsuccessful PCI on the LAD and in one after unsuccessful treatment with fibrinolysis during malfunction of the appliance. In-hospital lethality of patients with STEMI was 4.8%. There were no deaths in patients with UAP and stable angina pectoris. During the year there were 2.4% of acute and subacute stent thrombosis (4/168), all of them in patients with ACS and all of them in men, in three cases on the RCA and one in Acx. One patient had clinically guided rePCI for restenosis after 3 months. There were three peripheral complications that required surgical treatment (0.8%), two in patients with ACS and one in a patient who was ordered (Table 5).

The consumption of major supplies in 2013 can be seen in Table 6. Based on consumption in 2013, we planned to spend 900 diagnostic and 280 guiding catheters in 2014. Finally, according to the national tender, 200 diagnostic catheters and no guiding catheters (sic!) were approved to us. We planned to implant 300 bare-metal stents (BMS) and 45 drug-eluting stents, however only 130 BMS were approved to us.

One of few successfully implemented national programs in the last decade, not only in health care, is the program of the Croatian network of primary PCI. (6) At the initiative of the Leadership of the Croatian Cardiac Society, which monitored the integrated development of the pPCI network in other countries as in the Czech Republic, invasive and non-invasive cardiologists, emergency physicians and family physicians along with already established Croatian laboratories for pPCI have successfully, with the help of then Ministry of Health organized the Croatian network for primary PCI in 2005. At the beginning of interventional cardiology, before the Network was organized, the Croatian citizens were discriminated against in the treatment of ACS, both by gender and by age and by territorial affiliation. It was lost after the introduction of the Network and start of unison procedures according to the European Society of Cardiology guidelines. (7-9) However, seven years after the introduction of the Network, the entire territory of the country was not yet fully covered, for example in the regions of Dubrovnik-Neretva County and the region of Western Slavonia. Owing to the colleagues’ enthusiasm and despite the latest published schemes in which these areas are designated as those that provide this service only during normal working hours (10), the pPCI service has been available in the General Hospital Dubrovnik 24 hours/7 days since early 2013, and in General Hospital Slavonski Brod since early 2014. (11) By including new pPCI centers now we have 11 of them in Croatia, while 391,000 inhabitants gravitate to one center. This is an excellent result at the European level and only the following European countries have a better availability to pPCI: Austria, Belgium, France, Germany, Italy and Switzerland. (12) How reasonable it is at this point remains the task for our experts for Health Economics to evaluate the costs benefit analysis for pPCI in Croatia. (8) The Swedish analysis shows that in their environment the final results of treatment with pPCI are better and that the total cost of treatment is lower compared to fibrinolysis. (13)

Dubrovnik-Neretva County has 122,500 inhabitants, of whom 70% (86,000) are mainly treated in General Hospital Dubrovnik. However, when the visits by over one million tourists a year are added, we can roughly speak about the population of approximately 100,000 inhabitants that gravitate towards our hospital. In 2013, about 230 patients with ACS were admitted, of whom 27% for STEMI, which is a proportion similar to the one in the American registry (29%), (14) although the GRACE registry suggests the proportion of 38% of patients with STEMI. (15) Since 2010, the figures of the Croatian Institute for Health Insurance have been finally available to us, so now we know that some 7,300 patients with acute myocardial infarction (170/100.000) and 2,552 with unstable angina (26% ACS), that is, 9,852 patients with ACS (229/100.000) were hospitalized in Croatia in that year. It is necessary to establish the Croatian national registry for ACS and PCI for better classification and follow-up of some groups of patients and achieving success in the therapy. In 2013, 62 patients with STEMI were admitted to the General Hospital Dubrovnik, with a similar frequency as in the Swedish registry (66/ 100.000), while the rate of 89 NSTEMI patients was lower than in other registries (120-130). (16) European Society of Cardiology expects the European average of 190 patients with AMI per 100,000 population, (12) while our figure of 151 patients is better than the expected EU average, but also the Croatian average of 170 patients. However, the question remains how many of our patients with NSTEMI have not even contacted a doctor, for reasons of not being properly informed, and also because an increase in troponin level was not registered in one portion of patients with unstable angina for reasons of cost saving and they were not classified as NSTEMI patients.

According to the ESC guidelines, patients with ACS whose choice of treatment should not be PCI, at least within 72 hours are rare. Among the patients with ACS, 94% of them underwent invasive workup in General Hospital Dubrovnik, and 62% were finally treated by the PCI, whereas CABG was recommended to 13.7% of patients. A third of all performed PCI were primary PCI (33%), which is above the Croatian average in 2007 (22%), while the proportion in Europe ranges from 9-39%. (12) Among the patients with STEMI, 98.4% underwent the invasive workup and 90.2% underwent pPCI, which is a further step towards reaching the ideal goal that all patients with STEMI are treated by pPCI. 43% of patients with NSTEMI and 65% of patients with STEMI underwent invasive treatment in the United States of America in 2005. (17)

There were 3,600 STEMI (82/100.000) patients in Croatia in 2007, more than in our county and 1,150 pPCI (22.5/100.000), significantly less than now in our county. (12) The comparison of results suggests our focusing on interventional treatment of emergency patients and ACS, which accounted for about 2/3 of all interventions performed, and placing a less emphasis on stable angina pectoris and ordered patients. To be fair, even doctors’ strike in 2013 had an impact on a smaller number of orders for coronary angiography. This fact also affected the failure to achieve our plan to perform at least 200 PCI per year, which is needed to classify a single PCI center into the medium-sized center without cardiac support, and which according to American standards it would be able to function independently. (9)

Classification of PCI by treated vessels is similar to the one in other registries of patients with ACS, and focusing on emergency patients shows the proportion of PCI on large vessels, mostly on LAD on which 45.5% of all procedures were performed. (5) This explained the DES penetration of 25.6%, which for the European level was minimal, but actually realistic. Among 58 patients with STEMI whose treatment of choice was pPCI, final TIMI 3 flow was achieved in 93.4% of patients, which is a better result than the European average of 85%. Although this data is one on the small group of patients together with intra-hospital lethality of AMI of 2.61% and 4.8% of STEMI certainly does not suggest the poor, but rather outstanding quality of work even when we compare it with mortality in Europe, regarding AMI from 5-14% and regarding STEMI from 4.2 to 13.5% and in the U.S. (in 2005) 9.7% for STEMI and 9.5% for NSTEMI. (12, 17) In 2007, mortality in STEMI patients was 10% in Croatia, (12) and the data from the neighboring Split-Dalmatia County shows that the mortality of AMI significantly dropped by introducing PCI, from 15% to 10% in 2005, the first year of work of their laboratory. (18) Mortality from AMI dropped to 4% in Split over the next five years, (18) while the mortality from STEMI was 6.3%. (19) The available data for the University Hospital Dubrava in 2003 shows intra-hospital lethality of STEMI 6.2%, while in 2005, intra-hospital lethality of STEMI was 13.9% and 9.6% of NSTEMI in University Hospital Zagreb. (5, 20)

In addition to TIMI flow and mortality, the incidence of complications is also a measure of quality of work. The incidence of acute and subacute stent thrombosis of 2.4% among all patients and 3.6% among patients with STEMI was still higher than in the general registries, ranging from 0.5-2%. (21) This complication is not shown in analysis of Split, and at one meeting in Croatia higher incidence was shown, namely, up to 13.3% in patients with STEMI. (22) All our patients with stent thrombosis underwent the required dual antiaggregation therapy with clopidogrel, as in the registries (prasugrel and ticagrelor might have better results) and it will be necessary to continue to monitor this complication and look for its causes in order to reach the European results. However, the necessary assistance in this matter will have to be provided to us by introducing new intravascular imaging methods (IVUS and/or OCT), which will check some postPCI results, which angiographically look great, but will later result in thrombosis. Fortunately, all those patients were managed by reintervention, without further complications. Peripheral complications were present in 1.2% in case of femoral access and 0.5% in case of radial access, and we had one extremely rare radial artery pseudoaneurysm, with a total need for surgical treatment in 0.8% of patients. Global registries report that with modern pharmacotherapy local complications in femoral access occur in 5.5 to 7.4% of patients, with the need for surgical treatment in 1.3% patients. (23-25) There were 1.6% of such complications in the neighboring county, in Split. (19)

Covering the rest of Croatia by the Network, namely our population of 100,000 inhabitants, but mentioning 210 km half poorly built roads, two EU border crossings and more than a million of tourists a year as well as the lack of laboratories in the border regions of the neighboring countries, we believe that there was a reasonable need to establish the Center for Interventional Cardiology in Dubrovnik-Neretva County, and the scope of work only with emergency patients in 2013 almost confirms it. Dubrovnik which generates considerable revenues from cruise ships must render an integral high quality acute medical care as an accompanying service, and finally there are almost 15% (9/61) foreign nationals of all pPCI for STEMI. It is nice to be paid compliments by foreign cardiologists regarding our interventions, when patients with the CD intervention findings come back to the USA (26), United Kingdom, France and Spain, which certainly increased the reputation of our country as a safe tourist destination. However, our primary task in the Dubrovnik-Neretva County and General Hospital Dubrovnik in the next year was conceived as to increase the proportion of hospitalizations in the coronary care unit, separate other non-cardiac patients by establishing a general internal intensive care, and in the segment of interventions we are about to increase the volume of work in the field of ordered patients (by the end of the year, 80 patients were in the waiting list), present the pPCI service to some neighboring countries, new equipment purchase, injector, IVUS and FFR. As the laboratory was not functioning at the time of initiating the national tender for supplies in interventional cardiology, we were not recognized as a permanent interventional center at the beginning. After we made an analysis on 2013, we forecasted the supplies for the next year, but were warned that we had to reduce the quantity of forecasted supplies, and in early 2014, we received the decision in which we noticed that the approved quantity of supplies was half the size of the one we had already reduced (Table 6). We faced an incredible fact that we have been approved catheters for only 90-100 diagnostic procedures, that we have not been approved a single catheter for interventions, which I suppose should not be performed by us, but then we wondered what the purpose of 130 approved stents was? If we had catheters, those stents would be sufficient only for patients with STEMI. To round up this situation regarding cost savings, the Department for acute heart diseases and interventional cardiology has been abolished, and now it is annexed to the Internal Medicine Department. Given the new circumstance we shall see what the results in 2014 will be like not only in healthcare, but also in tourism, because tourists’ and tour operators’ comments may appear on the websites about medical insecurity in our medical facilities on the coast.