Clinical effectiveness of primary prevention implantable cardioverter-defibrillators: results of the EU-CERT-ICD controlled multicentre cohort study.

AIMS: The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter-Defibrillators (EU-CERT-ICD), a prospective investigator-initiated, controlled cohort study, was conducted in 44 centres and 15 European countries. It aimed to assess current clinical effectiveness of primary prevention ICD therapy. METHODS AND RESULTS: We recruited 2327 patients with ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and guideline indications for prophylactic ICD implantation. Primary endpoint was all-cause mortality. Clinical characteristics, medications, resting, and 12-lead Holter electrocardiograms (ECGs) were documented at enrolment baseline. Baseline and follow-up (FU) data from 2247 patients were analysable, 1516 patients before first ICD implantation (ICD group) and 731 patients without ICD serving as controls. Multivariable models and propensity scoring for adjustment were used to compare the two groups for mortality. During mean FU of 2.4 ± 1.1 years, 342 deaths occurred (6.3%/years annualized mortality, 5.6%/years in the ICD group vs. 9.2%/years in controls), favouring ICD treatment [unadjusted hazard ratio (HR) 0.682, 95% confidence interval (CI) 0.537-0.865, P = 0.0016]. Multivariable mortality predictors included age, left ventricular ejection fraction (LVEF), New York Heart Association class

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.

Echocardiographic assessment of revascularization completeness impact on diastolic dysfunction in ischemic heart disease.

Diastolic dysfunction indicates a functional abnormality of diastolic relaxation, filling, or distensibility of the left ventricle (LV), regardless of whether the LVEF is normal or abnormal. Diastolic dysfunction is practically always progressive and connected with higher morbidity and mortality rates, and, if not treated may lead to a diastolic heart failure. The golden standard for evaluation of diastolic function is echocardiography. One of the most important causes of diastolic dysfunction is ischemic heart disease. The revascularization of chronic myocardial ischemia can be partial (incomplete) or complete. Previous data have shown that the completeness of revascularization could have influence on clinical outcomes. The aim of this study was to asses, by means of echocardiography, the impact of completeness of revascularization on diastolic dysfunction in ischemic heart disease. This study included 65 consecutive patients with previously recognized diastolic dysfunction that met criteria for PCI revascularization. Two groups of patients were identified; one with complete revascularization achieved and another one with incomplete one. There were no statistical differences between two groups considering gender age, arterial hypertension, hyperlipoproteinaemia, previous CABG and left ventricle systolic function. In the incomplete revascularization group, the proportion of patients that had diabetes mellitus, previous myocardial infarction and previous PCI procedure were statistically higher (p < 0.05). The diastolic function recovery was statistically significant in both groups (p < 0.001), and there was no statistically significant difference in recovery between the two groups. Lack of recovery was registered in 18.2% patients with incomplete revascularization achieved, and 15.6% in the complete group, which was not significant, but shows a trend. The causes of somewhat worse recovery in the incomplete revascularization group could be attributed to the higher proportion of diabetics, to the somewhat older population and ultimately to the incomplete revascularization. The E/A ratio on diastolic transmitral flow as well as the E/E lat ratio on tissue doppler were found as the best echocardiographic parameters in diastolic function evaluation. In follow up recovery after complete or incomplete revascularization the tissue doppler (E/E lat) was recognized as the best parameter. In conclusion, we found that echocardiographic assessment of diastolic function recovery was a safe method, and our results showed that even in incomplete revascularization group of patients the recovery of diastolic function could be as good as in the complete one, if the indication for revascularization was correct.

The N-Glycosylation of Total Plasma Proteins and IgG in Atrial Fibrillation.

Atrial fibrillation is a disease with a complex pathophysiology, whose occurrence and persistence are caused not only by aberrant electrical signaling in the heart, but by the development of a susceptible heart substrate. These changes, such as the accumulation of adipose tissue and interstitial fibrosis, are characterized by the presence of inflammation. N-glycans have shown great promise as biomarkers in different diseases, specifically those involving inflammatory changes. To assess the changes in the N-glycosylation of the plasma proteins and IgG in atrial fibrillation, we analyzed the N-glycosylation of 172 patients with atrial fibrillation, before and six months after a pulmonary vein isolation procedure, with 54 cardiovascularly healthy controls. An analysis was performed using ultra-high-performance liquid chromatography. We found one oligomannose N-glycan structure from the plasma N-glycome and six IgG N-glycans, mainly revolving around the presence of bisecting N-acetylglucosamine, that were significantly different between the case and control groups. In addition, four plasma N-glycans, mostly oligomannose structures and a derived trait that was related to them, were found to be different in the patients who experienced an atrial fibrillation recurrence during the six-month follow-up. IgG N-glycosylation was extensively associated with the CHA2DS2-VASc score, confirming its previously reported associations with the conditions that make up the score. This is the first study looking at the N-glycosylation patterns in atrial fibrillation and warrants further investigation into the prospect of glycans as biomarkers for atrial fibrillation.

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.

Relationship of genetic markers for atherosclerosis and long-term outcome after percutaneous coronary intervention with stenting.

The aim of the study was to describe the relationship of clinical outcome after percutaneous coronary intervention (PCI) with stenting and genetic polymorphisms (GP) which are known to relate to the incidence of in-stent restenosis and late thrombotic complications. The study included 190 patients with standardized clinical follow-up over 5 years, which were initially treated with PCI. We investigated clinical data, angiographic characteristics, 10 polymorphisms involved in neointimal hyperplasia and late thrombosis at 6 different levels and their relationship with the major adverse cardiac events (MACE). The long-term clinical outcome was defined by MACE: death, target vessel revascularization (PCI or coronary bypass grafting, CABG) and myocardial infarction. Angiotensin receptor type I (AGTR A1166C) and angiotensinogen (AGT MET235THR) GPs correlated with repeat revascularization and total MACE. Carriers of G allele for NOS3 A922G GP were shown to have a significantly lower repeat revascularization rate in comparison with the AA genotype, as did the T allele carriers in the NOS3 C690T GP analysis when compared to the CC genotype. The Asp genome carriers with the NOS3 GLU298ASP GP were also shown to have significantly less re-PCI in contrast to the Glu/Glu genotype. The study could document the protective influence of the 4G/5G GP for plasminogen inhibitor activator-1, which carried the lowest rate of re-PCI and total MACE during the follow-up. GPs for beta-1 G-protein subunit GNB3 C825T, fibrinogen FGB G455A and E-selectins Ser128Arg and Leu554Phe did not show statistical correlation with the clinical outcome. The results illustrate the potential use of genetic markers in defining patients with possibly worse clinical outcome after PCI, who may profit from more aggressive prevention of restenosis and late thrombotic complications.

Angiographic control and percutaneous treatment of myocardial ischemia immediately after CABG.

Perioperative myocardial ischemia is rare but serious complication of CABG. Graft dysfunction, coronary artery thrombosis and incomplete revascularization are main causes. Pharmacological treatment, intra aortic counter pulsation and immediate additional grafting have limited results. Treatment strategy based on coronary angiography findings could lessen the burden of high mortality rate in these patients. The purpose of this study was to analyze the causes of perioperative ischemia and angiography based treatment strategy including percutaneous intervention. We enrolled all 55 consecutive patients that went early coronary angiography for perioperative myocardial ischemia in a prospective longitudinal study. Incorrect graft anastomosis, graft spasm, displacement and dissection were found in 49%, 7%, 5% and 4% of patients, respectively. Acute coronary artery thrombotic occlusion was found in 5% of patients and ischemia due to incomplete revascularization in 6% of patients. In 22% of patients no cause of myocardial ischemia could be detected. There were no complications of coronary angiography. Based on coronary angiography findings percutaneous intervention was performed in 30 patients, additional grafting in 8 patients and no action was taken in 17 patients. Percutaneous intervention with stenting was performed on coronary arteries (78%) and graft anastomosis (22%) with primary success 97%. One anastomosis rupture with treatable tamponade and one lethal stent thrombosis were complications of percutaneous treatment. Overall in hospital mortality was 30%. We concluded that graft dysfunction is usual cause of myocardial ischemia due to incorrect anastomosis and that percutaneous intervention on bypass graft or coronary artery can lessen high mortality rate in these patients.

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 perioperative myocardial ischaemia after isolated coronary artery bypass graft surgery.

Objectives: Updated knowledge about perioperative myocardial ischaemia (MI) after coronary artery bypass grafting (CABG) and treatment of acute graft failure is needed. We analysed main factors associated with perioperative MI and effects of immediate coronary angiography-based treatment strategy on patient outcome. Methods: Among 1119 consecutive patients with coronary artery disease who underwent isolated CABG between January 2011 and December 2015, 43 (3.8%) patients underwent urgent coronary angiography due to suspected perioperative MI. All the data were prospectively collected and retrospectively analysed. The primary endpoint was 30-day mortality; postoperative left ventricular ejection fraction) and major adverse cardiac events were secondary endpoints.ResultsOverall, 30-day mortality in patients with CABG was 1.4% while in patients who developed perioperative MI was 9% (4 patients). Angiographic findings included incorrect graft anastomosis, graft spasm, dissection, acute coronary artery thrombotic occlusion and ischaemia due to incomplete revascularisation. Emergency reoperation (Redo) was performed in 14 (32%), acute percutaneous coronary intervention (PCI) in 15 (36%) and conservative treatment (Non-op) in 14 patients. Demographic and preoperative clinical characteristics between the groups were comparable. Postoperative LVEF was significantly reduced in the Redo group (45% post-op vs 53% pre-op) and did not change in groups PCI (56% post-op vs 57% pre-op) and Non-op (58% post-op vs 57% pre-op). Conclusions: Urgent angiography allows identification of the various underlying causes of perioperative MI and urgent treatment when this is needed. Urgent PCI may be associated with improved clinical outcome in patients with early graft failure.

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.

[The impact of heparin bolus from dysfunctional lumen of dual lumen central venous catheter on activated partial thromboplastin time during hemodialysis: is additional heparinization necessary?]. / Utjecaj bolusa heparina iz nefunkcionalnog lumena dvoluminalnog centralnog venskog katetera na vrijednosti aktiviranog parcijalnog tromboplastinskog vremena tijekom hemodijalize: da li je potrebna dodatna heparinizacija tijekom hemodijalize?

AIM: The aim of the study was to determine the influence of the heparin bolus, which was administered to a patient due to incapability to aspire heparin from the dysfunctional lumen of dual lumen central venous catheter (CVK), on activated partial thromboplastin time (APTT) values during hemodialysis (HD), as well as to determine the need of additional administration of heparin during HD. PATIENTS AND METHODS: The first group of examinees consisted of 19 patients with chronic renal failure (CRF) on whom the dual lumen CVK was applied as temporary vascular access, whereby the aspiration of heparin from one of its lumens was impossible. Prior to HD, a coagulogram was determined for all the patients. The testing of this group was carried out in accordance with two different protocols: protocol A and protocol B. Under protocol A, 7,500 IU of unfractioned heparin was injected into the patients' circulation from the dysfunctional lumen of CVK. During the four-hour HD process, APTT were determined after ten minutes, after hours 1, 2 and 3, and at the end of HD. During HD, no heparin was administered and every hour during HD there was visual evidence of blood clots in portions of the extracorporeal circuit system. Under protocol B, the APTT values were determined in the same group of patients according to the previous protocol, with the exception of 750 IU of heparin per hour being administered by continuous infusion to the patients during hours 3 and 4. The second group of examinees consisted of patients with CRF who have undergone dialysis via an arteriovenous fistula, while the testing was carried out under protocol C. The examinees in this group received a bolus of 2,500 IU of heparin at the beginning of HD, followed by a continuous administration of 750 IU of heparin per hour during the first three hours of HD (a total of 4,750 IU during the entire HD). During hour 4, HD was carried out without the administration of heparin. The protocol of determining APTT was identical to that carried out on the previous group of patients. RESULTS: APTT values prior to HD: A=34.5 +/- 4.27 sec., B=32.38 +/- 4.16 sec. (p=0.457), C=33.66 +/- 3.63 sec. (p=0.245 in relation to protocol A and p=0.281 in relation to protocol B). APTT values ten minutes after the administration of the heparin bolus: A=210 +/- 21.42 sec., B=204.83 +/- 20.82 sec. (p=0.453), C=47.88 +/- 4.26 sec. (p=0.000 in relation to protocols A and B). APTT values after one hour: A=156 +/- 32.76 sec., B=159.66 +/- 30.39 sec. (p=0.377), C=43.88 +/- 4.5 sec. (p=0.000 in relation to protocols A and B). APTT values after two hours: A=81.54 +/- 0.41 sec., B=74.61 +/- 36.39 sec. (p=0.331), C=40.55 +/- 5.29 sec. (p=0.000 in relation to protocols A and B). APTT values after three hours: A=49.6 +/- 8.38 sec., B=59 +/- 8.93 sec. (p=0.395), C=37.88 +/- 2.58 sec. (p=0.000 in relation to protocols A and B). APTT values at the end of HD: A=40.5 +/- 3.97 sec., B=51.44 +/- 5.07 sec. (p=0.154), C=36.66 +/- 4.22 sec. (p=0.399 in relation to protocol A and p=0.222 in relation to protocol B). Clotting was noticed during the third hour of HD in 11 (57.89%) patients under protocol A, in two (10.5%) patients under protocol B and in three (15.78%) patients under protocol C. After comparing proportions for protocols A and C p=0.02, for protocols B and C p=0.998 and for protocols A and B p=0.006 CONCLUSION: Patients who received the heparin bolus from the dysfunctional lumen of dual lumen CVK needed an additional administration of heparin during hours 3 and 4 of HD in order to reduce the frequency of clotting in the extracorporeal circuit system. The frequency of clotting during HD in this study was not dependent on the total dosage of administered heparin, but rather on the means of its administration.