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.

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%).

Stroke prevention in elderly patients with non-valvular atrial fibrillation in the BALKAN-AF survey.

BACKGROUND: Atrial fibrillation (AF) is common amongst the elderly, but this group tends to be suboptimally treated. Limited data are available on the stroke prevention strategies in the elderly, especially in the Balkan region. AIM: We investigated the use of oral anticoagulant therapy (OAC) amongst elderly AF patients in clinical practice in the Balkan region. METHOD: A 12-week prospective snapshot survey (2014-2015) of consecutive non-valvular AF patients was conducted in Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Montenegro, Romania and Serbia. Data were collected via an electronic case report form. RESULTS: Of 2671 patients, 418 (15.6%) were ≥80 years old. Overall, OAC was used in 1965 patients (73.6%). Compared with younger patients, the elderly (age ≥ 80) had a higher mean CHA2 DS2 -VASc score (3.22 ± 1.71 vs 4.89 ± 1.35, P < .001) and more often a HAS-BLED score of ≥3 (n = 198 [47.0%] vs n = 625 [27.3%], P < .001), but were less likely to receive OAC (n = 269 [64.4%] vs n = 1696 [75.3%], odds ratio [OR] 0.91; 95%CI 0.86-0.97, P = .003). There was no significant association between OAC use and mean CHA2 DS2 -VASc (OR 0.86; 95%CI 0.75-1.00, P = .053) or HAS-BLED score (OR 1.21; 95%CI 0.81-1.81, P = .349) in the elderly. CONCLUSION: In the BALKAN-AF Survey, elderly AF patients were less likely to receive the guideline-adherent treatment despite their less favourable risk profile. Since OAC nonuse among the elderly was not associated with increased HAS-BLED score, factors other than patients' risk profile could influence the implementation of guideline-adherent treatment for thromboprophylaxis in the elderly AF patients.

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.

LEFT VENTRICULAR LEAD PLACEMENT FOR PACING AND SENSING IN A PATIENT WITH ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY UNDERGOING ICD IMPLANTATION.

We present a case of a 64-year-old female patient scheduled for implantable cardioverter defibrillator (ICD) implantation due to arrhythmogenic right ventricular cardiomyopathy (ARVC). Dual coil, active fixation ICD lead was introduced through the axillary vein. More than 20 positions were changed in the right ventricle (RV) (outflow tract, high, mid and apical septum, infero-basal, apical and lateral wall). Maximum R wave amplitude was 2 mV with pacing threshold of 0.5 V. Since the sensing was inappropriate, we decided to place the pace/sense lead of the ICD in the coronary sinus. The lead was placed in the basal part of the lateral vein. The pacing threshold was 1.0 V/0.40 ms and R wave was 9 mV. The lead was connected to the ICD sense-pace port and high voltage coils were connected in the usual way. The RV sense-pace lead was capped off. The device sensed an R wave of 7.0 mV 48 hours later. The purpose of this report is to show a possible solution of sensing problems during an ICD implantation in a patient with ARVC.

ROUTINELY AVAILABLE BIOMARKERS AS LONG-TERM PREDICTORS OF DEVELOPING SYSTOLIC DYSFUNCTION IN COMPLETELY REVASCULARIZED PATIENTS WITH ACUTE ST ELEVATION MYOCARDIAL INFARCTION.

The aim of this study was to assess the efficacy of high-sensitivity C-reactive protein (hsCRP), cardiac troponin T (cTnT) and creatine kinase (CK) as long-term predictors of reduced systolic function in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) with complete revascularization. This prospective study evaluated consecutive patients with acute STEMI who had normal left ventricular ejection fraction (LVEF ≥50%) at admission with single-vessel disease and underwent complete revascularization. Blood samples were collected from admission to day 7. The primary endpoint was reduction of LVEF <50% after 12 months. The study included 47 patients, median age 59±10 years, 74.5% of them men. Patients who developed systolic dysfunction (LVEF <50%) had significantly higher mean values of cTnT after 24 hours (5.11 vs. 2.82 µg/L, p=0.010) and peak values of CK (3375.5 vs. 1865 U/L, p=0.008). There was no significant relation between hsCRP and development of reduced LVEF (p=0.541). In conclusion, cTnT and CK could serve as long-term predictors of reduced left ventricular systolic function (<50%) in acute STEMI patients with normal systolic function at admission, single-vessel coronary disease and complete revascularization during primary PCI.

Failure of Intracardiac Pacing After Fatal Propafenone Overdose: A Case Report.

BACKGROUND: Propafenone is a sodium-channel blocker, class IC antiarrhythmic drug, frequently used to manage supraventricular dysrhythmias, especially atrial fibrillation. We report a self mono-intoxication with propafenone. CASE REPORT: A 68-year-old woman presented with a decreased level of consciousness, hypotension, and electrocardiogram showing QRS widening with atrial asystole and extreme bradycardia < 20 beats/min. After initial stabilization with transcutaneous pacing, laboratory findings detected normal electrolyte ranges and metabolic acidosis, and her medical history revealed availability of propafenone due to paroxysmal atrial fibrillation and depressive syndrome, which led to the suspicion of intoxication. Despite intravenous sodium bicarbonate, calcium, norepinephrine, and aggressive fluid replacement (10% glucose with insulin), hemodynamic stability was not achieved. Temporary intracardiac pacing was implanted. However, even with multiple electrode positions, effective capture could not be achieved. At that time, transcutaneous pacing was also ineffective. Consequently, the patient died in refractory asystole due to complete myocardial nonexcitability. The concentration of 5270 ng/mL of propafenone was found in the blood at autopsy, using gas spectrometry-mass chromatography. It is the third highest reported propafenone lethal concentration and the first case in which the myocardial nonexcitability refractory to intracardiac pacing was seen despite normal electrode position in the right ventricle, with failure to achieve the patient's hemodynamic stability. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should be aware of possible propafenone ingestion causing toxicity, which is probably more frequent than previously described, especially because propafenone is widely available due to its use in managing atrial fibrillation, the most common arrhythmia nowadays.

Auxiliary diagnostic potential of ventricle geometry and late gadolinium enhancement in left ventricular non-compaction; non-randomized case control study.

BACKGROUND: There are still ambiguities existing in regard to left ventricular non-compaction (LVNC) diagnostic imaging. The aim of our study was to analyze diagnostic potential of late gadolinium enhancement (LGE) and ventricle geometry in patients with LVNC and controls. METHODS: Data on cardiac magnetic resonance imaging (CMR) studies for LVNC were reassessed from the hospital's database (3.75 years; n=1975 exams). Matching sample of controls included cases with no structural heart disease, hypertrophic or dilative cardiomyopathy, arrhythmogenic right ventricular dysplasia or subacute myocarditis. Eccentricity of the left ventricle was measured at end diastole in the region with pronounced NC and maximal to minimal ratio (MaxMinEDDR) was calculated. RESULTS: Study included 255 patients referred for CMR, 100 (39.2%) with LVNC (prevalence in the studied period 5.01%) and 155 (60.8%) controls. Existing LGE had sensitivity of 52.5% (95%-CI:42.3-62.5), specificity of 80.4% (95%-CI:73.2-86.5) for LVNC, area under curve (AUC) 0.664 (95%-CI:0.603-0.722);p<0.001. MaxMinEDDR>1.10 had sensitivity of 95.0% (95%-CI:88.7-98.4), specificity of 82.6% (95%-CI: 75.7-88.2) for LVNC, AUC 0.917 (95%-CI:0.876-0.948); p<0.001. LGE correlated with Max-Min-EDD-R (Rho=0.130; p=0.038) and there was significant difference in ROC analysis ΔAUC0.244 (95%-CI:0.175-0.314); p<0.001. LGE also correlated negatively with stroke volume and systolic function (both p<0.05, respectively). CONCLUSIONS: LGE was found to be frequently expressed in patients with LVNC, but without sufficient power to be used as a discriminative diagnostic parameter. Both LGE and eccentricity of the left ventricle were found to be relatively solid diagnostic landmarks of complex infrastructural and functional changes within the failing heart.

Impact of cardiovascular treatments and systolic dysfunction on nutritional risk in patients with ischemic and valvular heart disease.

OBJECTIVE: There is a limited knowledge about connections existing between impaired systolic function and nutritional risk. The aim of our study was to evaluate nutritional risk in patients recently treated for valvular or ischemic heart disease, depending on the impairment of left ventricle systolic function and chronic cardiovascular therapy. METHODS: Nutritional risk screening was applied using a nutritional risk screening (NRS)-2002 [ 1 ] tool in cross-sectional study settings on patients scheduled for cardiovascular rehabilitation. There were 105 patients with impairment of left ventricle systolic function (LVEF ≤ 40) vs 145 consecutive matching peers with preserved LVEF. Percentage weight loss history (WLH) from preceding cardiovascular treatments was available for more than 85% of studied patients. RESULTS: Mean WLH was 7.7 ± 4.6%, and NRS-2002 was 3.6 ± 1.5. Significant differences in percentage WLH and NRS-2002 were found for age groups (p < 0.001, p < 0.001, respectively), cardiovascular treatments (p < 0.001, p < 0.001, respectively), and grades of renal function (p < 0.001, p < 0.001, respectively), whereas there was no difference on the basis of systolic function preservation (both p > 0.05, respectively). Utilization of proton pump inhibitors, loop diuretics, and calcium channel antagonists increased the odds for pronounced nutritional risk, 2.60 (95% confidence interval [CI], 1.23-5.47), p = 0.012, vs 2.15 (95% CI, 1.00-4.62), p = 0.049, vs 2.18 (95% CI, 1.01-4.68), p = 0.046, respectively. Conversely, angiotensin-converting enzyme (ACE) inhibitors exhibited protective effects to the nutritional risk, 0.20 (95% CI, 0.05-0.89), p = 0.035. CONCLUSION: Clinically, most evocative connections of nutritional risk screening and unintentional weight loss were found in relation to invasiveness of preceding cardiovascular treatments, rather than preservation of systolic function. Protective effects on nutritional risk were found for ACE inhibitors, whereas loop diuretics and proton pump inhibitors increased the nutritional risk and unintentional loss of weight.

An uncommon case of spontaneous conversion from AV re-entry tachycardia to AV nodal re-entry tachycardia in a patient with dual tachycardia.

We report the case of a 46-year old patient in whom an electrophysiology study (EP) was performed due to paroxysmal supraventricular tachycardia documented in 12-lead ECG. During the EP study, supraventricular tachycardia was induced easily and it corresponded to orthodromic AV reentry tachycardia (AVRT) using a concealed left free wall accessory pathway. However, during the study AVRT spontaneously and repeatedly converted to the typical slow-fast AV node reentry tachycardia (AVNRT). Both accessory and AV nodal slow pathways were ablated, due to the finding that both AVRT and AVNRT were independently inducible during the EP study.

Heart Failure with Mid-Range or Mildly Reduced Ejection Fraction in the Era of Sodium-Glucose Co-Transporter 2 Inhibitors: Do We Now Provide Better Care for the "Middle Child of HF"? Real-World Experience from a Single Clinical Centre.

Heart failure (HF) with mid-range or mildly reduced ejection fraction (HFmrEF) is a separate clinical entity in the HF spectrum, with a left ventricular ejection fraction ranging from 40 to 49%. While sodium glucose co-transporter 2 inhibitors have become the cornerstone therapy for the entire HF spectrum, there are a few clinical trials of HFmrEF. This prospective observational study was conducted at Dubrava University Hospital, Zagreb, Croatia, from May 2021 to October 2023. We recruited 137 participants diagnosed with HFmrEF at admission. The majority were male, with a median age of 72 and overweight. A total of 110 participants were followed for 6 months and LVEF remained the same in the majority of patients (n = 62, 56.4%), improved in 32 patients (29.1%), and decreased in 3 patients (2.73%). A total of 64 participants were followed for 12 months: 39 remained the same (60.94%) and 25 improved. There were 13 deaths in (9.5%). While the empagliflozin group had a lower BMI at 6-month- and lower HbA1c at 12-month follow-up, there were no differences in death, HF hospitalizations, ER visits, or urinary tract infections in between groups. Despite recent and daily advances in the treatment of all HF phenotypes, HFmrEF still represents a challenge in everyday clinical practice.

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.

The association of ventricular tachycardia and endothelial dysfunction in the setting of acute myocardial infarction with ST elevation.

BACKGROUND: Ventricular tachycardia (VT) is frequently seen in ischemic settings like acute myocardial infarction with ST segment elevation (STEMI). Endothelial dysfunction (ED) represents inflammation and the loss of all protective features of the endothelium. We aimed to examine the association between VT and ED in patients with STEMI. MATERIAL/METHODS: The study included 90 subjects (30 with VT and acute STEMI, 30 with STEMI without VT, and 30 controls). Sera of all subjects were tested on ED markers by enzyme immunoassay: sICAM-1 (intracellular adhesive molecule-1), sVCAM-1 (vascular adhesive molecule-1), P- and E-selectins, and VEGF (vascular endothelial growth factor). In addition, CRP (C-reactive protein) was detected. RESULTS: Significantly increased values of low-density lipoprotein, triglycerides, leukocytes, creatinine, and the number of cigarettes smoked were observed among patients with VT+STEMI in comparison to controls. The levels of E-selectin were significantly lower in the VT+STEMI group than in the other groups, while the levels of VCAM-1 were significantly higher in the groups with STEMI and VT+STEMI compared to the controls. Lower levels of VEGF were recorded in STEMI and VT+STEMI groups compared to the control group. A significant correlation between CRP and VCAM-1 in patients with VT +STEMI was demonstrated. CONCLUSIONS: We showed that ED may have a role in the immunopathogenesis of VT in patients with STEMI. The role of sE- selectin and correlation of sVCAM-1 with CRP as possible ED predictive markers in patients with VT+STEMI should be further investigated in a large cohort of patients.

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.

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.