Outcomes of Patients with Normal LDL-Cholesterol at Admission for Acute Coronary Syndromes: Lower Is Not Always Better.

BACKGROUND AND AIM: There are few prospective data on the prognostic value of normal admission low-density lipoprotein cholesterol (LDL-C) in statin-naïve patients with acute coronary syndromes (ACS) who are treated with a preemptive invasive strategy. We aimed to analyze the proportion of patients with normal LDL-C at admission for ACS in our practice, and their characteristics and clinical outcomes in comparison to patients with high admission LDL-C. PATIENTS AND METHODS: Two institutions' prospective registries of patients with confirmed ACS from Jan 2017 to Jan 2023 were used to identify 1579 statin-naïve patients with no history of prior coronary artery disease (CAD), and with available LDL-C admission results, relevant clinical and procedural data, and short- and long-term follow-up data. Normal LDL-C at admission was defined as lower than 2.6 mmol/L. All demographic, clinical, procedural, and follow-up data were compared between patients with normal LDL-C and patients with a high LDL-C level (≥2.6 mmol/L) at admission. RESULTS: There were 242 (15%) patients with normal LDL-C at admission. In comparison to patients with high LDL-cholesterol at admission, they were significantly older (median 67 vs. 62 years) with worse renal function, had significantly more cases of diabetes mellitus (DM) (26% vs. 17%), peripheral artery disease (PAD) (14% vs. 9%), chronic obstructive pulmonary disease (COPD) (8% vs. 2%), and psychological disorders requiring medical attention (19% vs. 10%). There were no significant differences in clinical type of ACS. Complexity of CAD estimated by coronary angiography was similar between the two groups (median Syntax score 12 for both groups). There were no significant differences in rates of complete revascularization (67% vs. 72%). Patients with normal LDL-C had significantly lower left ventricular ejection fraction (LVEF) at discharge (median LVEF 52% vs. 55%). Patients with normal LDL-C at admission had both significantly higher in-hospital mortality (5% vs. 2%, RR 2.07, 95% CI 1.08-3.96) and overall mortality during a median follow-up of 43 months (27% vs. 14%, RR 1.86, 95% CI 1.45-2.37). After adjusting for age, renal function, presence of diabetes mellitus, PAD, COPD, psychological disorders, BMI, and LVEF at discharge in a multivariate Cox regression analysis, normal LDL-C at admission remained significantly and independently associated with higher long-term mortality during follow-up (RR 1.48, 95% CI 1.05-2.09). CONCLUSIONS: A spontaneously normal LDL-C level at admission for ACS in statin-naïve patients was not rare and it was an independent risk factor for both substantially higher in-hospital mortality and mortality during long-term follow-up. Patients with normal LDL-C and otherwise high total cardiovascular risk scores should be detected early and treated with optimal medical therapy. However, additional research is needed to reveal all the missing pieces in their survival puzzle after ACS-beyond coronary anatomy, PCI optimization, numerical LDL-C levels, and statin therapy.

From statistical inference to machine learning: A paradigm shift in contemporary cardiovascular pharmacotherapy.

AIMS: Heart failure with reduced ejection fraction (HFrEF) poses significant challenges for clinicians and researchers, owing to its multifaceted aetiology and complex treatment regimens. In light of this, artificial intelligence methods offer an innovative approach to identifying relationships within complex clinical datasets. Our study aims to explore the potential for machine learning algorithms to provide deeper insights into datasets of HFrEF patients. METHODS: To this end, we analysed a cohort of 386 HFrEF patients who had been initiated on sodium-glucose co-transporter-2 inhibitor treatment and had completed a minimum of a 6-month follow-up. RESULTS: In traditional frequentist statistical analyses, patients receiving the highest doses of beta-blockers (BBs) (chi-square test, P = .036) and those newly initiated on sacubitril-valsartan (chi-square test, P = .023) showed better outcomes. However, none of these pharmacological features stood out as independent predictors of improved outcomes in the Cox proportional hazards model. In contrast, when employing eXtreme Gradient Boosting (XGBoost) algorithms in conjunction with the data using Shapley additive explanations (SHAP), we identified several models with significant predictive power. The XGBoost algorithm inherently accommodates non-linear distribution, multicollinearity and confounding. Within this framework, pharmacological categories like 'newly initiated treatment with sacubitril/valsartan' and 'BB dose escalation' emerged as strong predictors of long-term outcomes. CONCLUSIONS: In this manuscript, we not only emphasize the strengths of this machine learning approach but also discuss its potential limitations and the risk of identifying statistically significant yet clinically irrelevant predictors.

Case report: State-of-the-art risk-modifying treatment of sudden cardiac death in an asymptomatic patient with a mutation in the SCN5A gene and a review of the literature.

Brugada syndrome is a rare hereditary disorder characterized by distinct ECG findings, complex genetics, and a high risk of sudden cardiac death. Recognition of the syndrome is crucial as it represents a paradigm of sudden death tragedy in individuals at the peak of their lives. Notably, Brugada syndrome accounts for more than 20% of sudden cardiac deaths in individuals with structurally normal hearts. Although this syndrome follows an autosomal dominant inheritance pattern, it is more prevalent and severe in males. Diagnosis is primarily based on the characteristic ECG pattern observed in the right precordial leads. Mutations in the SCN5A gene, resulting in loss of function, are the most common genetic cause. We presented a 36-year-old proband with a family history of sudden cardiac death. Although the patient was asymptomatic for Brugada syndrome, his father had experienced sudden death at the age of 36. The proband was admitted to St. Catherine's Specialty Hospital where blood was taken and subjected to next-generation sequencing (NGS) using a "Sudden cardiac death" panel. The analysis identified a pathogenic variant in the SCN5A gene [c.4222G > A(p.Gly1408Arg)], which is associated with autosomal dominant Brugada syndrome. Based on the positive genetic test result, the patient was referred for further examination. ECG with modified precordial lead positioning confirmed the presence of the Brugada phenotype, displaying the type-2 and type-1 ECG patterns. Therefore, we made the diagnosis and decided to implant an implantable cardioverter-defibrillator (ICD) based on the results of broad genetic NGS testing, diagnostic criteria (ECG), and considering the high burden of sudden cardiac death in the patient's family, as well as his concerns that limited his everyday activities. This case shows that genetics and personalized medicine hold immense potential in the primary prevention, diagnosis, and treatment of Brugada syndrome and sudden cardiac death.

Novel protocol for optimal utilization of HPSD approach for pulmonary vein isolation.

Background: The efficiency of pulmonary vein isolation (PVI) depends on the durability of RF lesions. Recent studies documented sustained continuity of ablation lines, improvements in durability, and expected clinical outcomes through altered settings in duration and power. However, the ablation strategy has not been adapted to this new approach and different biophysics of lesion formation. Purpose: The aim of this study was to demonstrate that by adjusting the ablation approach to the broader geometry of lesions by increasing the minimal spacing between adjacent RF, a further significant reduction of procedural time while maintaining sufficient long-term outcomes is achievable. Methods: The presented study was a prospective, observational multi-center trial. The periprocedural data were compared with data from a consecutively collected historical cohort. Results: In total, 196 patients were included (mean age 62 ± 11 years, male 64.3%). Procedural duration, RF time, and LA dwelling time were significantly shorter in the HPSD group compared with the standard group (73 ± 26 min vs. 98 ± 36 min, p < .001; 14 ± 7 min vs. 33 ± 12 min, p < .001; and 59 ± 21 min vs. 77 ± 32 min, p < .001, respectively). Mean AF-free survival in the first year of follow-up was 304 ± 14 days in the HPSD group versus 340 ± 10 days in the standard group (log-rank p = .403). There were no statistically significant differences in the complication rates between the groups. Conclusion: Increasing the minimal distance between individual application points simplifies AF ablation and further reduces procedure time without negative effects on efficacy and safety. Larger studies are needed to optimally utilize this approach.

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.

Risks associated with prior oral anticoagulation use in hospitalized COVID-19 patients - A retrospective cohort study on 5392 patients from a tertiary centre.

INTRODUCTION: There are conflicting data on prior oral-anticoagulant (OAC) use and outcomes of hospitalized COVID-19 patients. Due to uncertainties regarding associated risks with the prior OAC use, we have investigated this issue in a large cohort of hospitalized COVID-19 patients from our institution. METHODS: We have retrospectively evaluated a total of 5392 consecutive COVID-19 patients hospitalized in our tertiary center institution in period 3/2020 to 6/2021. Majority of patients received low-molecular-weight-heparin thromboprophylaxis and corticosteroids during hospitalization. Patients' characteristics and clinical outcomes were documented as a part of a hospital registry project and were evaluated according to the prior non-OAC, warfarin and direct oral anticoagulants (DOAC) use. RESULTS: Median age was 72 years, median Charlson comorbidity index (CCI) was 4 points. There were 56.2% male patients. Majority of patients had severe (70.5%) or critical (15.8%) COVID-19 on admission. A total of 84.8% patients did not receive prior OAC, 9% were previously anticoagulated with warfarin and 6.2% were previously anticoagulated with DOACs. In the multivariate regression analyses, prior warfarin use was associated increased in-hospital mortality (OR 1.24, P = 0.048) independently of older age (OR 2.12, P < 0.001), male sex (OR 1.27, P < 0.001), higher CCI (OR 1.26, P < 0.001) and severe or critical COVID-19 on admission (OR 22.66, P < 0.001). Prior DOAC use was associated with higher occurrence of major bleeding (OR 1.72, P = 0.045) independently of higher CCI (OR 1.08, P = 0.017). CONCLUSION: Prior OAC use could be associated with worse clinical outcomes during COVID-19 hospitalization. These phenomena might be OAC type specific and persist after multivariate adjustments.

Role of empirical isolation of the superior vena cava in patients with recurrence of atrial fibrillation after pulmonary vein isolation-a multi-center analysis.

BACKGROUND: Non-pulmonary vein (PV) triggers play a role in the initiation of atrial fibrillation (AF), with the superior vena cava (SVC) being a common location. The aim of the current study was to investigate a strategy of empirical SVC isolation (SVCI) in addition to re-isolation of PV in patients with recurrence of AF after index PV isolation (PVI). METHODS: We retrospectively analyzed consecutive patients from two centers with recurrence of AF after index PVI, undergoing a repeat ablation. Whereas only a re-isolation of the PV was intended in patients with reconnections of equal or more than two PV (PVI group), an additional SVCI was aimed for in patients with < 2 isolated PV in addition to the re-isolation of the PV (PVI + group). Analysis was performed as-treated and per-protocol. RESULTS: Of the 344 patients included in the study (age 60 ± 10 years, 73% male, 66% paroxysmal AF), PVI only was performed in 269 patients (77%) and PVI plus SVCI (PVI +) in 75 patients (23%). Overall, freedom from AF/AT after repeat PVI was 80% (196 patients) in the PVI group and 73% in the PVI + group (p = 0.151). In multivariable Cox regression analysis, presence of persistent AF (HR 2.067 (95% CI 1.389-3.078), p < 0.001) and hypertension (HR 1.905 (95% CI 1.218-2.980), p = 0.005) were identified as only significant predictors of AF/AT recurrence. The per-protocol results did not differ from this observation. CONCLUSIONS: A strategy of an empirical additional SVCI at repeat PVI ablation for recurrence of AF/AT does not improve outcome compared to a PVI only approach.

Red Cell Distribution Width in Acute Pulmonary Embolism Patients Improves 30-Day Mortality Risk Stratification Based on the Pulmonary Embolism Severity Index.

PURPOSE: To validate red cell distribution width (RDW) as an improvement in 30-day mortality risk stratification based on the Pulmonary Embolism Severity Index (PESI) in acute pulmonary embolism (PE). PATIENTS AND METHODS: Prospective observational analysis of consecutive adult acute PE patients. RESULTS: Among 731 patients, 30-day mortality was 11.9%. With adjustment for the PESI score and number of covariates, higher RDW was associated with higher mortality (RDW continuous: OR 1.21, 95% CI 1.06-1.38; Bayesian OR 1.22, 1.07-1.40; RDW 'high' [>14.5% in men >16.1% in women] vs normal: OR 3.83, 1.98-7.46; Bayesian OR 3.98, 2.04-7.68]. Crude mortality was 3.6% if PESI 86-105 (intermediate risk), but 1.2% if RDW normal and 7.1% if RDW high; 11.8% if PESI 106-125 (high risk), but 3.6% if RDW normal and 18.8% if RDW high. Adjusted probabilities showed higher mortality (ORs between 3.5-5.8) if RDW was high in any PESI risk subgroup. Crude mortality rates in two random-split subsets (n=365 and n=366) again showed the same patterns. CONCLUSIONS: On-admission RDW above the normal range improves 30-day mortality risk stratification based on PESI score in acute PE. Particularly, it corrects PESI-based intermediate-risk or high-risk allocation by reclassification into very low-risk (<3.5%) or very high-risk (>11.0%).

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.

Sudden Cardiac Death-A New Insight Into Potentially Fatal Genetic Markers.

Sudden cardiac death (SCD) is an unexpected and dramatic event. It draws special attention especially in young, seemingly healthy athletes. Our scientific paper is based on the death of a young, 23-year-old professional footballer, who died on the football field after a two-year history of cardiac symptoms. In this study we analyzed clinical, ECG and laboratory data, as well as results of genetic testing analysis in family members. To elucidate potential genetic etiology of SCD in this family, our analysis included 294 genes related to various cardiac conditions.

Delayed radiofrequency ablation efficacy in slow pathway ablation: a case report.

BACKGROUND: The delayed effect of radiofrequency (RF) ablation was described in cases of accessory pathway and premature ventricular contraction ablation, as well as delayed atrioventricular (AV) block after slow pathway ablation. CASE SUMMARY: We report a case of a female patient with AV nodal re-entry tachycardia (AVNRT), in whom the first electrophysiology study ended with acute failure of slow pathway ablation, despite using long steerable sheath, both right and left-sided ablation with >15 min of RF energy application and repeatedly achieving junctional rhythm. Six weeks afterwards, during scheduled three-dimensional electroanatomical mapping procedure, there was no proof of dual AV nodal conduction nor could the tachycardia be induced. Also, the patient did not have palpitations between the two procedures nor during the 12-month follow-up period. DISCUSSION: This case illustrates that watchful waiting for delayed RF ablation efficacy in some cases of AVNRT ablation could be reasonable, in order to reduce the risk of complications associated with slow pathway ablation.