COVID-19 pandemic: Impact on the cardiac implantable electronic devices' implantation rates in Croatia.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) pandemic has influenced health-care organization worldwide, including management of non-communicable diseases. The aim of this study was to determine the impact of COVID-19 pandemic on cardiac implantable electronic devices' (CIEDs) implantation rates in Croatia. METHODS: A retrospective, observational, national study was conducted. The data on CIEDs' implantation rates from 20 Croatian implantation centres, between January 2018 and June 2021, were extracted from the national Health Insurance Fund registry. Implantation rates before and after COVID-19 pandemic started, were compared. RESULTS: The overall numbers of CIED implantations in Croatia during COVID-19 pandemic were not different in comparison to 2 years pre-COVID-19 time (2618 vs. 2807, p = .081). The pacemaker implantation rates decreased significantly (by 45%) during April (122 vs. 223, p < .001) and May 2020 (135 vs. 244, p = .001), as well as during November 2020 (177 vs. 264, p = .003), but significantly increased during summer months 2020 comparing to 2018 and 2019 (737 vs. 497, p<0.001). The ICD implantation rates decreased significantly by 59% in April 2020 (26 vs. 64, p = .048). CONCLUSION: To the authors best knowledge this is a first study including complete national data on CIED implantation rates and COVID-19 pandemic impact. A significant reduction in number of both pacemaker and ICD implants during specific months of the COVID-19 pandemic was determined. However, afterwards compensation in implants resulted in similar total number when the complete year was evaluated.

Ablation of residual potentials along the circumferential line reduces acute pulmonary vein reconnection.

INTRODUCTION: Acute pulmonary vein (PV) reconnection is frequently encountered in patients undergoing PV isolation (PVI) procedure for the treatment of atrial fibrillation. In this study, we investigated whether the identification and ablation of residual potentials (RPs), after the initial achievement of PVI, reduces acute PV reconnection rate. METHODS: Following PVI in 160 patients, mapping along the ablation line was performed to identify RPs, defined as bipolar amplitude ≥0.2 mV or 0.1-0.19 mV combined with a negative component of the unipolar electrogram. Ipsilateral PV sets with RPs were randomized to either no further ablation (Group B) or to additional ablation of the identified RPs (Group C). The primary study endpoint was spontaneous or adenosine-mediated acute PV reconnection after a 30-min waiting period and was also evaluated in ipsilateral PV sets without RPs (Group A). RESULTS: After isolation of 287 PV pairs, 135 had no RPs (Group A), whereas the remaining PV pairs were randomized to either Group B (n = 75) or Group C (n = 77). Ablation of RPs resulted in a reduction of spontaneous or adenosine-mediated PV reconnection rate (16.9% in Group C vs 48.0% in Group B; p < 0.001). Group A was associated with a significantly lower percentage of acute PV reconnection as compared to Group B (5.9% vs 48.0%; p < 0.001) and Group C (5.9% vs 16.9%; p = 0.016). CONCLUSION: After PVI achievement, the absence of RPs along the circumferential line is associated with a low likelihood of acute PV reconnection rate. Ablation of RPs significantly reduces spontaneous or adenosine-mediated acute PV reconnection rate.

Differences in activated clotting time and total unfractionated heparin dose during pulmonary vein isolation in patients on different anticoagulation therapy.

BACKGROUND: Periprocedural pulmonary vein isolation (PVI) anticoagulation requires balancing between bleeding and thromboembolic risk. Intraprocedural anticoagulation is monitored by activated clotting time (ACT) with target value >300 s, and there are no guidelines specifying an initial unfractionated heparin (UFH) dose. METHODS: We aimed to assess differences in ACT values and UFH dosage during PVI in patients on different oral anticoagulants. We conducted an international, multi-center, registry-based study. Consecutive patients with atrial fibrillation (AF) undergoing PVI, on uninterrupted anticoagulation therapy, were analyzed. Before transseptal puncture, UFH bolus of 100 IU/kg was administered regardless of the anticoagulation drug. RESULTS: Total of 873 patients were included (median age 61 years, IQR 53-66; female 30%). There were 248, 248, 189, 188 patients on warfarin, dabigatran, rivaroxaban, and apixaban, respectively. Mean initial ACT was 257 ± 50 s, mean overall ACT 295 ± 45 s and total UFH dose 158 ± 60 IU/kg. Patients who were receiving warfarin and dabigatran compared to patients receiving rivaroxaban and apixaban had: (i) significantly higher initial ACT values (262 ± 57 and 270 ± 48 vs. 248 ± 42 and 241 ± 44 s, p < .001), (ii) significantly higher ACT throughout PVI (309 ± 46 and 306 ± 44 vs. 282 ± 37 and 272 ± 42 s, p < .001), and (iii) needed lower UFH dose during PVI (140 ± 39 and 157 ± 71 vs. 171 ± 52 and 172 ± 70 IU/kg). CONCLUSION: There are significant differences in ACT values and UFH dose during PVI in patients receiving different anticoagulants. Patients on warfarin and dabigatran had higher initial and overall ACT values and needed lower UFH dose to achieve adequate anticoagulation during PVI than patients on rivaroxaban and apixaban.

MANAGEMENT OF PATIENTS WITH CARDIAC IMPLANTABLE ELECTRONIC DEVICES UNDERGOING MAGNETIC RESONANCE IMAGING - PROPOSAL FOR UNIFIED HOSPITAL PROTOCOL: CROATIAN WORKING GROUP ON ARRHYTHMIAS AND CARDIAC PACING.

For many years, magnetic resonance imaging (MRI) was contraindicated in patients with cardiac implantable electronic devices (CIED). Today, there is a growing amount of evidence that MRI can be performed safely in the majority of patients with CIEDs. Firstly, there are devices considered MRI conditional by manufacturers that are available on the market and secondly, there is clear evidence that even patients with MRI non-conditional devices can also undergo MRI safely. Protocols have been developed and recommendations from different cardiac and radiologic societies have been published in recent years. However, the majority of physicians are still reluctant to refer these patients to MRI. Therefore, this document is published as a joint statement of the Croatian Working Group on Arrhythmias and Cardiac Pacing and Department of Radiology, Sestre milosrdnice University Hospital Centre to guide and ease the management of patients with CIED undergoing MRI. Also, we propose a unified protocol and checklist that could be used in Croatian hospitals.

Present criteria for prophylactic ICD implantation: Insights from the EU-CERT-ICD (Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators in EUrope) project.

BACKGROUND: The clinical effectiveness of primary prevention implantable cardioverter defibrillator (ICD) therapy is under debate. It is urgently needed to better identify patients who benefit from prophylactic ICD therapy. The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators (EU-CERT-ICD) completed in 2019 will assess this issue. SUMMARY: The EU-CERT-ICD is a prospective investigator-initiated non-randomized, controlled, multicenter observational cohort study done in 44 centers across 15 European countries. A total of 2327 patients with heart failure due to ischemic heart disease or dilated cardiomyopathy indicated for primary prophylactic ICD implantation were recruited between 2014 and 2018 (>1500 patients at first ICD implantation, >750 patients non-randomized non-ICD control group). The primary endpoint was all-cause mortality, and first appropriate shock was co-primary endpoint. At baseline, all patients underwent 12­lead ECG and Holter-ECG analysis using multiple advanced methods for risk stratification as well as documentation of clinical characteristics and laboratory values. The EU-CERT-ICD data will provide much needed information on the survival benefit of preventive ICD therapy and expand on previous prospective risk stratification studies which showed very good applicability of clinical parameters and advanced risk stratifiers in order to define patient subgroups with above or below average ICD benefit. CONCLUSION: The EU-CERT-ICD study will provide new and current data about effectiveness of primary prophylactic ICD implantation. The study also aims for improved risk stratification and patient selection using clinical risk markers in general, and advanced ECG risk markers in particular.

Rationale and design of the EU-CERT-ICD prospective study: comparative effectiveness of prophylactic ICD implantation.

AIMS: The clinical effectiveness of primary prevention implantable cardioverter defibrillator (ICD) therapy is under debate. The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators (EU-CERT-ICD) aims to assess its current clinical value. METHODS AND RESULTS: The EU-CERT-ICD is a prospective investigator-initiated non-randomized, controlled, multicentre observational cohort study performed in 44 centres across 15 European Union countries. We will recruit 2250 patients with ischaemic or dilated cardiomyopathy and a guideline indication for primary prophylactic ICD implantation. This sample will include 1500 patients at their first ICD implantation and 750 patients who did not receive a primary prevention ICD despite having an indication for it (non-randomized control group). The primary endpoint is all-cause mortality; the co-primary endpoint in ICD patients is time to first appropriate shock. Secondary endpoints include sudden cardiac death, first inappropriate shock, any ICD shock, arrhythmogenic syncope, revision procedures, quality of life, and cost-effectiveness. At baseline (and prior to ICD implantation if applicable), all patients undergo 12-lead electrocardiogram (ECG) and Holter ECG analysis using multiple advanced methods for risk stratification as well as detailed documentation of clinical characteristics and laboratory values. Genetic biobanking is also organized. As of August 2018, baseline data of 2265 patients are complete. All subjects will be followed for up to 4.5 years. CONCLUSIONS: The EU-CERT-ICD study will provide a necessary update about clinical effectiveness of primary prophylactic ICD implantation. This study also aims for improved risk stratification and patient selection using clinical and ECG risk markers.

Croatian National Data and Comparison with European Practice: Data from the Cardiac Resynchronization Therapy Survey II Multicenter Registry.

AIMS: The Cardiac Resynchronization Therapy (CRT) Survey II was conducted between October 2015 and December 2016 and included data from 11088 CRT implantations from 42 countries. The survey's aim was to report on current European CRT practice. The aim of this study was to compare the Croatian national CRT practice with the European data. METHODS: Five centres from Croatia recruited consecutive patients, in a 15-month period, who underwent CRT implantation, primary or an upgrade. Data were collected prospectively by using online database. RESULTS: A total of 115 patients were included in Croatia, which is 33.2% of all CRT implants in Croatia during the study period (total n=346). Median age of the study population was 67 (61-73) years, and 21.2% were women. Primary heart failure (HF) aetiology was nonischemic in 61.1% of patients, and HF with wide QRS was the most common indication for the implantation (73.5%). 80% of patients had complete left bundle branch block, and over two-third had QRS ≥150 ms. Device-related adverse events were recorded in 4.3% of patients. When compared with European countries, Croatian patients were significantly younger (67 vs. 70 years, p=0.012), had similar rate of comorbidities with the exception of higher prevalence of hypertension. Croatian patients significantly more often received CRT-pacemaker when compared with European population (58.3 vs. 29.9%, OR 3.27, 95%CI 2.25-4.74, p < 0.001). CONCLUSION: Our data indicate strict selection of patients among HF population and adherence to guidelines with exception of higher proportion of CRT-pacemaker implantation. This is likely to be influenced by healthcare organization and reimbursement issues in Croatia.

Recommendations for Perioperative Management of Patients with Cardiac Implantable Electronic Devices.

Four thousand cardiac implantable electronic devices (CIED) are implanted yearly in Croatia with constant increase. General anesthesia and surgery carry some specific risk for the patients with implanted CIEDs. Since most of the surgical procedures are performed in institutions without reprogramming devices available, or in the periods when they are unavailable, these guidelines aim to standardize the protocol for perioperative management of these patients. With this protocol, most of the procedures can be performed easily and, more importantly, safely in the majority of surgical patients.

Ventricular diastolic dimension over maximal myocardial thickness is robust landmark of systolic impairment in patients with hypertrophic cardiomyopathy.

BACKGROUND The effects of focal hypertrophy on geometry of the left ventricle and systolic function have not been studied in patients with hypertrophic cardiomyopathy (HCM), despite the fact that the former is the most prominent disease characteristic. The aim of our study was to analyze systolic function over ventricle geometry, generating a functional index made from left ventricle end diastolic dimension (LVEDD) divided by end diastolic thickness of the region with maximal extent of hypertrophy and interventricular septum. MATERIAL AND METHODS Our hospital database of cardiac magnetic resonance was screened for HCM. Geometric functional index (GFI) was calculated for LVEDD over maximal end diastolic thickness (MaxEDT) giving GFI-M, while LVEDD over interventricular septum was expressed as GFI-I. There were 55 consecutive patients with HCM. RESULTS There were 43 males (78.2%) and 12 females (21.8%). The mean age was 52.3±16.7 years (range: 15.5-76.4 years). A significant difference of GFI was found for preserved versus impaired systolic function of the left ventricle (preserved systolic function); GFI-M 2.28±0.60 versus 3.66±0.50 (p<0.001), and GFI-I 2.75±0.88 versus 3.81±0.87 (p<0.001), respectively. Diagnostic value was tested using receiver operating curve (ROC) analyzes, with GFI-M area under curve (AUC)=0.959 (95% CI: 0.868-0.994); (p<0.001) and GFI-I-AUC=0.847 (0.724-0.930); (p<0.001). GFI-M was superior to GFI-I for appraisal of left ventricle systolic dysfunction in HCM; ΔAUC=0.112 (0.018-0.207); (p=0.020). CONCLUSIONS GFI is a simple tool, with high sensitivity and specificity for detecting impairment of systolic function in patients with HCM. Further studies would be necessary to investigate its clinical and prognostic impacts, as well as reproducibility with prospective validation.

Drug-Coated Balloon Versus Drug-Eluting Stent in Primary Percutaneous Coronary Intervention: A Feasibility Study.

BACKGROUND: Drug-eluting stents (DES) represent a significant evolution in the treatment of patients with acute myocardial infarction with ST elevation. However, stent-related adverse events have led to an introduction of drug-coated balloons (DCB) applied particularly to bifurcation lesions, in-stent restenosis and small vessel disease. The aim of this study was to determine whether a DCB-only strategy has a similar safety profile and equal angiographic and clinical outcomes to DES implantation in primary percutaneous coronary intervention (pPCI). MATERIALS AND METHODS: Seventy-five patients with acute myocardial infarction with ST elevation were randomized into DES and DCB groups of 37 and 38 patients, respectively. The study end-points were major adverse cardiac events and late lumen loss during the 6 months following the pPCI. RESULTS: Reinfarction occurred in 5.4% of patients in the DES and 5.3% of patients in the DCB group after 1 month (risk ratio = 1.03, 95% CI [0.15-6.91], P = 0.98). After 6 months, major adverse cardiac events were reported in 5.4% of patients in the DES group and none in the DCB group (risk ratio = 5.13, 95% CI [0.25-103.42], P = 0.29). Late lumen loss in the DES group was 0.10 ± 0.19mm and -0.09 ± 0.09mm in the DCB group (P < 0.05). CONCLUSIONS: A DCB-only strategy is safe and feasible in the pPCI setting and showed good clinical and angiographic outcomes in a 6-month follow-up period.

The Patterns of Non-vitamin K Antagonist Oral Anticoagulants (NOACs) Use in Patients with Atrial Fibrillation in Seven Balkan Countries: a Report from the BALKAN-AF Survey.

INTRODUCTION: Data on management of atrial fibrillation (AF) in the Balkan Region are scarce. To capture the patterns in AF management in contemporary clinical practice in the Balkan countries a prospective survey was conducted between December 2014 and February 2015, and we report results pertinent to the use of non-vitamin K antagonist oral anticoagulants (NOACs). METHODS: A 14-week prospective, multicenter survey of consecutive AF patients seen by cardiologists or internal medicine specialists was conducted in Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Montenegro, Romania, and Serbia (a total of about 50 million inhabitants). RESULTS: Of 2712 enrolled patients, 2663 (98.2%) had complete data relevant to oral anticoagulant (OAC) use (mean age 69.1 ± 10.9 years, female 44.6%). Overall, OAC was used in 1960 patients (73.6%) of whom 338 (17.2%) received NOACs. Malignancy [odds ratio (OR), 95% confidence interval (CI) 2.06, 1.20-3.56], rhythm control (OR 1.64, 1.25-2.16), and treatment by cardiologists were independent predictors of NOAC use (OR 2.32, 1.51-3.54) [all p < 0.01)], whilst heart failure and valvular disease were negatively associated with NOAC use (both p < 0.01). Individual stroke and bleeding risk were not significantly associated with NOAC use on multivariate analysis. CONCLUSIONS: NOACs are increasingly used in AF patients in the Balkan Region, but NOAC use is predominantly guided by factors other than evidence-based decision-making (e.g., drug availability on the market or reimbursement policy). Efforts are needed to establish an evidence-based approach to OAC selection and to facilitate the optimal use of OAC, thus improving the outcomes in AF patients in this large region.

Stroke prevention in atrial fibrillation and 'real world' adherence to guidelines in the Balkan Region: The BALKAN-AF Survey.

Data on the management of atrial fibrillation (AF) in the Balkan Region are limited. The Serbian AF Association (SAFA) prospectively investigated contemporary 'real-world' AF management in clinical practice in Albania, Bosnia&Herzegovina, Bulgaria, Croatia, Montenegro, Romania and Serbia through a 14-week (December 2014-February 2015) prospective, multicentre survey of consecutive AF patients. We report the results pertinent to stroke prevention strategies. Of 2712 enrolled patients, 2663 (98.2%) with complete data were included in this analysis (mean age 69.1 ± 10.9 years, female 44.6%). Overall, 1960 patients (73.6%) received oral anticoagulants (OAC) and 762 (28.6%) received antiplatelet drugs. Of patients given OAC, 17.2% received non-vitamin K antagonist oral anticoagulants (NOACs). CHA2DS2-VASc score was not significantly associated with OAC use. Of the 'truly low-risk' patients (CHA2DS2-VASc = 0 [males], or 1 [females]) 56.5% received OAC. Time in Therapeutic Range (TTR) was available in only 18.7% of patients (mean TTR: 49.5% ± 22.3%). Age ≥ 80 years, prior myocardial infarction and paroxysmal AF were independent predictors of OAC non-use. Our survey shows a relatively high overall use of OAC in AF patients, but with low quality of vitamin K antagonist therapy and insufficient adherence to AF guidelines. Additional efforts are needed to improve AF-related thromboprophylaxis in clinical practice in the Balkan Region.

New cardiomechanic pacing lead sensor based on high frequency parameters: experimental studies in sheep.

UNLABELLED: Pacing Lead as a High Frequency Cardiomechanic Sensor. INTRODUCTION: The purpose of this study was to investigate the possibility of detecting and quantifying ventricular contraction in sheep utilizing the cardiomechanic sensor based upon the high frequency (HF) parameters measurements on bipolar cardiac pacing leads. Measurement of the HF reflection coefficient yields the lead-bending signal (LBS) caused by myocardial contraction. The correlation between the lead-bending acceleration (LBA) expressed as the rate of rise of LBS and LV dP/dt should reveal that LBS may be utilized as a cardiomechanic sensor in implantable cardiac electrotherapy devices. METHODS AND RESULTS: We implanted 3 different pacing leads and tested the measurement system in 9 sheep (42 ± 6 kg) at baseline and during acute hemodynamic intervention with dobutamine infusion and tachycardia induced by VVI pacing at 200 bpm. A stable, consistent, and reproducible LBS was obtained in all sheep during the implantation procedure and 4 months after the implantation during different experimental conditions that included hemodynamic interventions. The dependence between LBAmax and LV dP/dtmax was found to be statistically significant and with high Pearson's correlation coefficient (r = 0.855, P <0.001). We could also observe the hemodynamic deterioration caused by fast ventricular pacing with the decrease of LV dp/dt and LBA compared with sinus rhythm. CONCLUSION: This study confirms the feasibility and efficacy of the hemodynamic sensor based upon HF lead parameters. Moreover, it was demonstrated that LBAmax is highly correlated to the ventricular contractility and, therefore, can be efficiently used as a hemodynamic and cardiomechanic sensor. (J Cardiovasc Electrophysiol, Vol. 24, pp. 338-346, March 2013).

Acute and chronic high-frequency properties of cardiac pacing and defibrillation leads.

The purpose of our study was to investigate variety of cardiac lead conductor designs as high-frequency (HF) transmission lines. Special attention was given on evaluation of chronic HF applications in cardiac electrotherapy. We measured the characteristic impedance and the attenuation coefficient of six pacing leads between 1 and 21 MHz. They were subsequently immersed into the saline solution simulating the body fluid and the measurements were repeated 10 years later. Identical measurements were performed on 15 new pacing and defibrillation leads. The results revealed that lead geometry is the main factor affecting the HF parameters. Attenuation coefficients of old and contemporary leads do not differ significantly. Penetration of saline within the leads during a decade did not influence much their HF characteristics. Thus, a chronic cardiac contraction sensor based on lead's HF impedance variation is feasible. The signal losses of ultrasonic transducers mounted on the lead might be stable for years at acceptable levels without significant variation. Due to mutually similar values of HF parameters in different leads, design of tensiometric or ultrasonic applications could be universal for majority of commercially available leads. Automatic system calibration could be developed for each and every lead after determination of its HF parameters.

Acute animal and human study of tensiometric pacing lead sensor based on triboelectricity.

Cardiac contractions bend the implanted cardiac lead body, extend and compress the lead conductors, their insulation and the inserted stylet. Magnitude of lead deflection depends on cardiac muscle contraction forces. The purpose of study was to measure the charge generated due to triboelectric effect between one of the lead conductors and the inserted stylet. The charge was measured by differential charge amplifier being connected to isolation amplifier and power supply. Sensor signal, ECG and intracardiac electrograms were acquired. Three models of custom designed leads were implanted in 8 sheep. Measurements were done in 18 patients undergoing pacemaker implantation and replacement procedures. Atrial and ventricular tensiometric signals were recorded in dual chamber and in single-lead VDD patients. Recordings in sinus rhythm at various AV intervals and in supraventricular tachycardia were done. In average, charge variation between 1 and 600 pC was measured. Tensiometric stylet could be feasible hemodynamic sensor for myocardial contraction detection. Its main advantage is that it is easily exchangeable and universal for all leads.