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.

The Acoustics of Instant Ear Tips and Their Implications for Hearing-Aid Fitting.

OBJECTIVES: Today, approximately 70 to 80% of hearing aid fittings are made with silicone instant ear tips rather than custom earmolds. Nevertheless, little is known about the impact of instant ear tips on the acoustic coupling between the hearing aid receiver and the individual ear canal, even though it can have a major impact on the overall sound of the hearing aids. This study aimed to investigate the acoustic properties of different instant ear tip types and their across-subject variability, the within-subject reliability of those properties, and the influence of the users' level of experience with ear-tip insertion on the acoustics. Furthermore, subjective ratings of occlusion produced by the ear tips were considered. DESIGN: Five types of instant ear tips (Open, Tulip, Round [2-vent], Round [1-vent], Double Domes) provided by the hearing aid manufacturer Widex were considered in this study. Probe-microphone measurements were performed at the eardrums of 30 participants (60 ears). In the first experiment, the real ear occluded insertion gain and the vent effect (VE) were measured, and the listeners rated the subjective occlusion experienced with each ear tip. In the second experiment, the same measurements were repeated six times per participant. The within-subject variability of the acoustic ear tip properties was investigated as well as the impact of the degree of users' experience with ear tip insertion on the resulting real ear measurements. RESULTS: All tested ear tips were, on average, acoustically transparent up to 1 kHz except Double Domes, which were only transparent up to 600 Hz. Distinct VE profiles were found for each ear tip type, but a large across-subject variability was observed for both real ear occluded insertion gain and VE. However, the within-subject reliability was high. The measured VE was highly correlated with the perceived occlusion. Finally, no significant effect of the level of experience in ear tip insertion on the acoustic properties of the ear tips was found, but the within-subject variability was larger in the less experienced group. CONCLUSIONS: These results suggest that the acoustic properties of instant ear tips and their coupling to the individual ear canal impact the resulting hearing aid fitting and should be considered by the hearing care professionals and reflected in the fitting software. The high within-subject reliability indicates that the ear tip acoustics remain stable for the individual in daily use. Finally, real ear measurements should be considered an essential part of the hearing aid fitting process in clinical practice to ensure an optimal fit for the individual hearing aid user.

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.

Patients with atrial fibrillation and mid-range ejection fraction differ in anticoagulation pattern, thrombotic and mortality risk independently of CHA2DS2-VASC score.

Atrial fibrillation (AF) patients with mid-range left ventricular ejection fraction (mrEF) of 40-49% have neither preserved (pEF > 50%) nor reduced (rEF < 40%) EF and are increasingly being recognized as a distinct group with specific clinical risks. We aimed to retrospectively investigate clinical characteristics and associated thrombotic, bleeding and mortality risks of mrEF in comparison to pEF and rEF in a cohort of 1000 non-valvular AF patients presenting in our institution during the period 2013-2018. Patients with mrEF presented with older age (P < 0.001) and a higher frequency of arterial hypertension (P = 0.001) in comparison to both pEF and rEF patients. In comparison to pEF, mrEF patients were more likely to have diabetes mellitus (P = 0.004), lower HDL-cholesterol (P < 0.001) and lower estimated glomerular filtration rate (P < 0.001), significantly higher CHA2DS2-VASC score (P < 0.001), significantly higher HAS-BLED score (P = 0.002) and had a higher likelihood of receiving anticoagulant therapy, mostly warfarin (P = 0.001). In addition, mrEF patients had a significantly higher risk of thrombotic events (HR = 2.22; P = 0.015), death (HR = 1.71; P = 0.005) and composite endpoint of thrombosis, bleeding or death (HR = 1.65; P = 0.003) in comparison to pEF patients, but did not significantly differ in comparison to rEF patients. There was no significant difference regarding major bleeding risk. Associations with clinical outcomes remained statistically significant in multivariate models independently of CHA2DS2-VASC. Our findings support defining AF patients with mrEF as a subgroup with distinct clinical characteristics and increased risk for thrombotic events and death, irrespective of predetermined CHA2DS2-VASC risk. These patients seem to require special clinical considerations and more intensive control of cardiovascular risk factors.

Pharmacogenomics at the center of precision medicine: challenges and perspective in an era of Big Data.

Pharmacogenomics (PGx) is one of the core elements of personalized medicine. PGx information reduces the likelihood of adverse drug reactions and optimizes therapeutic efficacy. St Catherine Specialty Hospital in Zagreb/Zabok, Croatia has implemented a personalized patient approach using the RightMed® Comprehensive PGx panel of 25 pharmacogenes plus Facor V Leiden, Factor II and MTHFR genes, which is interpreted by a special counseling team to offer the best quality of care. With the advent of significant technological advances comes another challenge: how can we harness the data to inform clinically actionable measures and how can we use it to develop better predictive risk models? We propose to apply the principles artificial intelligence to develop a medication optimization platform to prevent, manage and treat different diseases.

Patients with higher body mass index treated with direct / novel oral anticoagulants (DOAC / NOAC) for atrial fibrillation experience worse clinical outcomes.

INTRODUCTION: Due to fixed dosing of direct oral anticoagulants (DOACs), uncertainty exists about their efficacy in a population of obese/overweight patients. PATIENTS AND METHODS: We retrospectively investigated a real-life cohort of 325 DOAC anticoagulated patients with atrial fibrillation [179 receiving dabigatran (55%), 74 apixaban (23%) and 72 rivaroxaban (22%)]. Patients were stratified according to the body mass index (BMI) into non-obese (233 with BMI <30 kg/m2), class I obesity (71 with BMI 30-34.9 kg/m2) and class II + obesity (21 with BMI ≥35 kg/m2). RESULTS: Patients with higher BMI receiving DOACs were more likely to experience stroke/systemic embolism sooner (P = 0.043), experience major bleeding sooner (P < 0.001) and have shorter time to composite event consisting of thrombosis, bleeding or death (P < 0.001) whereas there was no significant association with overall survival (P = 0.470). BMI was significantly associated with thrombosis but not bleeding among dabigatran treated patients, and significantly associated with bleeding but not thrombosis among patients treated with factor Xa inhibitors. Associations of higher thrombotic, bleeding and composite endpoint risks with higher BMI remained statistically significant in multivariate Cox regression models adjusted for age, gender, eGFR, CHA2DS2VASC and HAS-BLED. CONCLUSION: Our findings indicate that obese patients receiving DOACs, especially ones with class II + obesity, might be under higher risks of stroke/bleeding depending on DOAC subtype. Loss of efficacy might be associated with dabigatran, whereas higher risk of major bleeding might be associated with factor Xa inhibitors.

Immunoglobulin G4 Inflammatory Aortic Aneurysm Mimicking Acute Aortic Syndrome.

Immunoglobulin-G4-related disease (IgG4RD) is a novel clinical entity characterized by lymphoplasmacytic infiltrates presenting as an excessive fibrosis such as retroperitoneal inflammatory pseudotumor but rarely affecting the heart or the aorta. We describe a case of IgG4RD with multifocal aortic involvement presenting as an acute aortic syndrome.

High red cell distribution width at the time of ST segment elevation myocardial infarction is better at predicting diastolic than systolic left ventricular dysfunction: A single-center prospective cohort study.

Multiple studies have demonstrated the association of red cell distribution width (RDW) with the ultrasound parameters of both systolic and diastolic heart dysfunction. We aimed to further investigate the clinical associations of RDW in the setting of ST-elevation myocardial infarction (STEMI) and to comparatively evaluate its predictive properties regarding systolic and diastolic dysfunction.A total of 89 patients with STEMI were prospectively analyzed. RDW was obtained at the time of STEMI and compared to the parameters of systolic and diastolic dysfunction obtained by transthoracic heart ultrasound on the 5th through 7th day post-STEMI.The median RDW was 13.9%, and among other factors, RDW was significantly associated with older age (P < .001), arterial hypertension (P = .017), hyperlipoproteinemia 2, nonsmoking (P = .027), increased thrombolysis in myocardial infarction score (P = .004), and multivessel disease (P = .007). A higher RDW was observed in patients with parameters that indicated systolic and diastolic dysfunction (ejection fraction of the left ventricle < 50% [P = .009], early/late diastolic filling wave ratio [E/A] < 1 [P = .001], ratio of peak early transmitral velocity and early diastolic annular velocity [E/E'] >10 [P < .001], and combined E/A < 1 and E/E' > 10 [P < .001]). The best discriminatory properties were observed for combined E/A < 1 and E/E' > 10. RDW remained significantly associated with the aforementioned parameters in a series of multivariate regression models.Elevated RDW is significantly associated with the parameters of systolic and diastolic dysfunction even after adjusting for several confounding factors in the setting of STEMI and subsequent percutaneous coronary intervention. RDW seems to be better at discriminating patients with diastolic rather than systolic dysfunction.

Dilemma in clinical diagnosis of right ventricular masses.

Detection of an intracardiac mass always represents a clinical challenge. We present a 61-year-old female patient with symptoms of New York Heart Association class III. Two-dimensional transthoracic echocardiography revealed a hypoechogenic mass in the cavity of the dilated right ventricle (RV). Cardiac MRI described a pathologic structure of the RV free wall with pedunculated tumor in its cavity. Three months later, on a repeated echocardiography, there were three individual masses. The patient underwent surgery and the pathohistologic report demonstrated thrombotic masses. During the postoperative period, after reviewing all medical records, the conclusion was arrhythmogenic RV cardiomyopathy. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:362-369, 2017.

Association of chronic kidney disease with periprocedural myocardial injury after elective stent implantation: A single center prospective cohort study.

Coronary artery disease (CAD) is the leading cause of mortality in patients with chronic kidney disease (CKD). Patients with CKD who undergo percutaneous coronary intervention (PCI) may have more ischemic events than patients without CKD. The aim of our study was to determine the incidence of periprocedural myocardial injury (PMI) after elective stent implantation in patients with CKD using the Third Joint ESC/ACCF/AHA/WHF PMI definition.In a single center prospective cohort study, we enrolled 344 consecutive patients who underwent elective PCI in a period of 39 months. Serum troponin I (cTnI) concentrations were measured at baseline and at 8 and 16 hours after PCI. Periprocedural increase of cTnI, according to the most recent PMI definition, was used to define both the presence and intensity of PMI. Patients were further stratified according to the estimated glomerular filtration rate (eGFR) using 4 variable Modification of Diet in Renal Disease (MDRD) equation: control group with eGFR >90 mL/min/1.73 m and the CKD group with eGFR < 90 mL/min/1.73 m, with further subdivision according to the CKD stage.We found no significant difference in the incidence as well as intensity of the PMI in the control (>90 mL/min/1.73 m) and the CKD group (<90 mL/min/1.73 m) both 8 and 16 hours after PCI. When the CKD patients were further subdivided according to their CKD stage, there was again no difference in the intensity or incidence of PMI compared to the control group. Further analyses of our data showed angina pectoris CCS IV, bare metal stent (BMS) implantation, and treatment with angiotensin-converting enzyme inhibitors (ACEI) as independent predictors of PMI. Furthermore, the presence of hypertension was inversely related to the occurrence of PMI.Applying the new guidelines for PMI and using the eGFR equation most suitable for our patients, we found no association between PMI and CKD. Further analyses showed other factors that could potentially influence the occurrence of PMI.

The role of reverberation-related binaural cues in the externalization of speech.

The perception of externalization of speech sounds was investigated with respect to the monaural and binaural cues available at the listeners' ears in a reverberant environment. Individualized binaural room impulse responses (BRIRs) were used to simulate externalized sound sources via headphones. The measured BRIRs were subsequently modified such that the proportion of the response containing binaural vs monaural information was varied. Normal-hearing listeners were presented with speech sounds convolved with such modified BRIRs. Monaural reverberation cues were found to be sufficient for the externalization of a lateral sound source. In contrast, for a frontal source, an increased amount of binaural cues from reflections was required in order to obtain well externalized sound images. It was demonstrated that the interaction between the interaural cues of the direct sound and the reverberation strongly affects the perception of externalization. An analysis of the short-term binaural cues showed that the amount of fluctuations of the binaural cues corresponded well to the externalization ratings obtained in the listening tests. The results further suggested that the precedence effect is involved in the auditory processing of the dynamic binaural cues that are utilized for externalization perception.

The effect of interaural-level-difference fluctuations on the externalization of sound.

Real-world sound sources are usually perceived as externalized and thus properly localized in both direction and distance. This is largely due to (1) the acoustic filtering by the head, torso, and pinna, resulting in modifications of the signal spectrum and thereby a frequency-dependent shaping of interaural cues and (2) interaural cues provided by the reverberation inside an enclosed space. This study first investigated the effect of room reverberation on the spectro-temporal behavior of interaural level differences (ILDs) by analyzing dummy-head recordings of speech played at different distances in a standard listening room. Next, the effect of ILD fluctuations on the degree of externalization was investigated in a psychoacoustic experiment performed in the same listening room. Individual binaural impulse responses were used to simulate a distant sound source delivered via headphones. The ILDs were altered using a gammatone filterbank for analysis and resynthesis, where the envelopes of the left and right-ear signals were modified such that the naturally occurring fluctuations of the ILDs were restricted. This manipulation reduced the perceived degree of externalization. This was consistent with the analysis of short-term ILDs at different distances showing that a decreased distance to the sound source also reduced the ILD fluctuations.