Artur Filipecki

The implications of genetic mutations in the sodium channel gene (SCN5A)

Mutations in sodium channel alpha-subunit gene (SCN5A) result in multiple arrhythmic syndromes, including long QT3 (LQT3), Brugada syndrome (BS), an inherited cardiac conduction defect, sudden unexpected nocturnal death syndrome (SUNDS) and sudden infant death syndrome (SIDS), constituting a spectrum of disease entities termed Na+ channelopathies. These diseases are allelic disorders, if not the same disease with variable penetrance and variable modifiers worldwide. Interestingly, death occurs during sleep in all of these disorders, suggesting a common mechanism. To date, mutational analyses have revealed about 103 distinct mutations in SCN5A, of which at least more than 30 mutations are associated with LQT3, whereas the rest of the mutations are affiliated with the remaining sodium channel disorders. The majority of these mutations are missense. However, other types such as deletions, insertions, frameshifts, nonsense and splice-donor errors have also been reported.

Value of Heart Rate Variability Parameters for Prediction of Serious Arrhythmic Events in Patients with Malignant Ventricular Arrhythmias

Heart rate variability (HRV) assesses the electrical stability of the heart and can identify patients at risk of sudden cardiac death (SCD). The value of 10 HRV parameters from 24 hour ECG (in both time and frequency domain) to predict serious arrhythmic events (SAE) in a group of 56 patients with ventricular tachycardia and/or ventricular fibrillation of different etiologies not due to acute myocardial infarction was explored. Eighteen patients had low left ventricular ejection fractions (LVEF). During follow‐up (6–46 months, mean = 24) 8 SCD and 12 recurrences of malignant ventricular arrhythmias or ICD discharges were recorded. Proportional hazard analysis (Cox model) for SAE revealed that the mean of all 5 minute standard deviation of RR intervals (SD) and the amplitude of low frequency spectrum (L) were independent risk factors of SAE (P < 0.05). The best models were: SD+EF and L+EF where predictive values were high (sensitivity approximately 60%, specificity over 95%, positive predictive value over 90% and negative predictive value approximately 80%). Event‐free survival curves revealed a significantly shorter survival in patients with EF < 40%: 47% vs. 92%, SD < 43 ms; 56% vs. 92% and L < 16 ms; 56% vs. 89% (all P < 0.001) after 2 years. The subgroup with low EF and SD < 43 ms revealed a significantly shortened survival (27% vs 83% at 2 years, P < 0.01). Some HRV parameters, SD from the time and L from the frequency domain, were predictive of a fatal outcome in VT/VF patients. Combined SD +EF and L +EF values are powerful predictors of serious arrhythmic events.

QT/RR relationship in patients after remote anterior myocardial infarction with left ventricular dysfunction and different types of ventricular arrhythmias.

Background: QT/RR relationship was found to be both rate‐dependent and rate‐independent, what suggests the influence of autonomic drive and other not‐autonomic related factors on it. The steeper QT/RR slope in patients after acute myocardial infarction (MI) was described, but the relationship to ventricular arrhythmias is unknown. The purpose of this study was to calculate differences in QT/RR relationship in patients after remote anterior MI with left ventricular dysfunction and different types of ventricular arrhythmias.

Predictive value of ischemic mitral regurgitation during the acute phase of ST elevation myocardial infarction treated with primary coronary intervention for left ventricular remodeling in long-term follow-up.

Reperfusion therapy, mainly primary percutaneous coronary intervention (PCI), has improved survival and lowered complication rate in patients with ST elevation myocardial infarction (STEMI). Nevertheless, some patients develop left ventricular remodeling (LVR) during long-term follow-up. AimsTo assess the incidence of ischemic mitral regurgitation (MR) in the acute phase of STEMI treated with primary PCI. To assess prognostic value of MR during acute STEMI for prediction of LVR during long-term follow-up. MethodsThis is a prospective, single-center study in 83 patients with the first STEMI. Inclusion criteria were as follows: time from symptom onset to PCI less than 12 h and successful restoration of blood flow (thrombolysis in myocardial infarction 3) in the infarct-related coronary artery. Transthoracic echocardiography was performed at discharge and 6 months after the MI. ResultsAt hospital discharge, ischemic MR was found in 35 (42%) patients. At 6 months follow-up, LVR was present in 21 (25%) patients. Univariate analysis revealed that remodeling could be predicted by age, weight, treatment with abciximab, left ventricular ejection fraction (LVEF), leaflets coaptation, coaptation height, tenting area, presence of MR, degree of MR. The best multivariate logistic regression model for remodeling prediction at 6 months was combination of ischemic MR degree (odds ratio (OR)=14.5; 95% confidence interval (CI): 3.89–54.0, P<0.00005), abciximab therapy (OR=0.09; 95% CI: 0.01–0.84, P<0.03) and LVEF (OR=0.89; 95% CI: 0.81–0.99, P<0.03). ConclusionIschemic MR in STEMI is frequent, even despite effective primary PCI. The regurgitation grade and lower LVEF assessed at hospital discharge and lack of abciximab administration could predict development of LVR at 6 months.

Heart Rate Variability: Its Association with Hemodynamic Function of the Left Ventricle in Patients with Coronary Heart Disease

Patients with heart failure secondary to coronary heart disease (CHD) are characterized by an imbalance of the autonomic nervous system, which can be assessed by analysis of the heart rate variability (HRV). However it is still unclear whether all patients with CHD reveal suppression of HRV and if it is related to hemodynamic function and contractile disturbances of the left ventricle. To answer these questions data from 105 consecutive patients were analyzed and compared with 17 healthy subjects. All study participants underwent 24‐hour ambulatory ECG recordings with calculation of HRV parameters and angiographic examination after collection of clinical data and other noninvasive evaluations. Time‐ (SDRR, SDANN, SD, pNN50) and frequency‐ (LF, HF) domain parameters of HRV were assessed. All ventriculographic and hemodynamic measurements were used in the analysis. Highly significant correlations were found between all HRV parameters, and left ventricular ejection fraction (LVEF) and left ventricular end‐diastolic pressure (P < 0.001). Patients with LVEF < 40% were characterized by significantly lower values of HRV and impairment or lack (LVEF < 20%) of diurnal variation of frequency‐domain measurements of HRV. Patients with segmental akinesis or dyskinesis also had lower values of HRV. The group with dyskinesis was characterized by significantly lower diurnal rhythms of LF and HF, independent of LVEF.

Microvascular damage prevention with thrombaspiration during primary percutaneous intervention in acute myocardial infarction.

BackgroundDespite rapid and complete recanalization of infarct-related artery with percutaneous coronary intervention, microvascular integrity is not often preserved. Several mechanical devices have been proposed to prevent distal embolization, but the impact of these devices on myocardial perfusion remains controversial. AimThe aim of our study was to assess microvascular damage reduction with quantitative myocardial contrast perfusion echocardiography among patients with the first anterior acute myocardial infarction treated with thromboaspiration during percutaneous coronary intervention. MethodsForty-two patients (57.4±10 years, 74% males) with first anterior acute myocardial infarction were randomized 1 : 1 to intracoronary thromboaspiration followed by stenting, or to a conventional strategy of stenting alone. Echocardiogram and quantitative myocardial contrast echocardiography were performed 7 days and 1 month later, respectively. Parameter A (reflecting myocardial blood volume), &bgr; (reflecting velocity, myocardial blood flow), and product of A and &bgr; as indicator of myocardial blood flow were analyzed. For each patient mean value of A, &bgr;, and A×&bgr; from all dysfunctional segments was calculated. ResultsThe study population was divided into two groups: thromboaspiration (group I, 19 patients) and stenting alone (group II, 23 patients). No difference was observed between the both groups in demographic, clinical, echocardiographic, and angiographic data. Parameter A and A×&bgr; were significantly higher in group I than in group II: 8.58±2.54 versus 5.29±3.18 dB (P<0.001) and 5.29±3.73 versus 2.78±3.03 dB/s (P<0.001). Multivariate step-down regression analysis revealed that only thromboaspiration before stenting and lower maximum troponin I have been associated with viability preservation in infarcted region. ConclusionThromboaspiration before stenting in patients with the first anterior myocardial infarction improves myocardial perfusion at the tissue level assessed by quantitative myocardial contrast echocardiography.

Impact of left ventricular remodeling on ventricular repolarization and heart rate variability in patients after myocardial infarction treated with primary PCI: prospective 6 months follow-up.

Background: The relation between postinfarction left ventricle remodeling (LVR), autonomic nervous system and repolarization process is unclear. Purpose of the study was to assess the influence of LVR on the early (QTpeak) and late (TpeakTend) repolarization periods in patients after myocardial infarction (MI) treated with primary PCI. The day‐to‐night differences of repolarization parameters and the relation between QT and heart rate variability (HRV) indices, as well left ventricle function were also assessed.

Andersen-Tawil syndrome: Clinical presentation and predictors of symptomatic arrhythmias – Possible role of polymorphisms K897T in KCNH2 and H558R in SCN5A gene

BACKGROUND Andersen-Tawil syndrome (ATS) is rare channelopathy caused by KCNJ2 mutation and probably KCNJ5. It is characterized by arrhythmias, neurological symptoms, and dysmorphic features. The present study retrospectively examined the characteristics of 11 unrelated families with ATS. METHODS This study consisted of 11 probands positive for KCNJ2 variants and 33 family members (mean age 30.0±17.3 years, female n=31). Additional genetic screening of 3 LQTS genes (KCNQ1, KCNH2, SCN5A) was performed in 9 families. Predictors of arrhythmias [premature ventricular beats>2000/24h, biventricular and polymorphic ventricular tachycardia (VT)], syncope, and/or cardiac arrest (CA) were evaluated. RESULTS In KCNJ2 mutation carriers vs non-carriers (n=25 vs n=19) significant differences were observed in U-wave manifestations in V2-V4, Tpeak-Tend duration, QTUc duration (p<0.0001), dysmorphic features, and neurological symptoms. Compared to asymptomatic carriers (n=9), in those with arrhythmias and/or syncope and/or CA (n=16) micrognathia (p=0.004), periodic paralysis (p=0.019), palpitation (p=0.005), U-wave n V2-V4 (p=0.049) were more frequent; QTU (p=0.045) and Tpeak-Tend (p=0.014) were also longer (n=9). In the subgroup of carriers with syncope and/or cardiac arrest (n=10, 90% women), K897T-KCNH2 polymorphism (p=0.02), periodic paralysis (p=0.004), muscle weakness (p=0.04), palpitations (p=0.04), arrhythmias (biventricular VT, p=0.003; polymorphic VT, p=0.009) were observed more frequently. Tpeak-Tend duration was longer (p=0.007) and the percentage of patients with premature ventricular contraction >2000/24h was higher (p=0.005). CONCLUSION A higher risk of arrhythmia, syncope, and/or CA is associated with the presence of micrognathia, periodic paralysis, and prolonged Tpeak-Tend time. Our findings suggest that K897T may contribute to the occurrence of syncope.

Postextrasystolic repolarization abnormalities in ST-U segment in patients with ventricular arrhythmias.

Background: Changes in U‐wave amplitude after premature ventricular contractions (PVC) are known as prognostic markers in the long QT syndrome dependent on bradycardia. The purpose of the study was to find correlation between postextrasystolic ST‐U segment changes and a history of sustained ventricular tachycardia or ventricular fibrillation (VT/VF).

Role of left atrial speckle tracking echocardiography in predicting persistent atrial fibrillation electrical cardioversion success and sinus rhythm maintenance at 6 months.

PURPOSE We assessed the value of left atrium speckle tracking imaging (STI) indices, and clinical and other echocardiographic parameters in persistent atrial fibrillation (AF) patients to predict the efficacy of electrical cardioversion (EC) and sinus rhythm (SR) maintenance at 6 months. MATERIAL/METHODS Eighty persistent AF patients planned to receive EC, underwent echocardiography including STI. After 24h, patients with successful EC were examined to predict SR maintenance. After 6 months patients with no AF recurrence in electrocardiogram (ECG) underwent 7-day ECG to exclude silent AF. Every AF>1 min was a recurrence. RESULTS SR restored in 61 patients, 19 unsuccessful. Prior use of statins (68.8% vs. 42.1%, p=0.03) was the only factor, determined later by univariate analysis to be a significant EC success predictor (OR=1.09, CL ± 95% 1.001-1.019, p<0.03). Both groups received similar antiarrhythmics and had similar echocardiographic parameters. After 6 months, SR was maintained in 19 patients (31.1%, Group I); AF recurrences were registered in 42 patients (68.8%, Group II). In Group I, only the mitral valve deceleration time (MVDT) 224.18 ± 88.13 vs. 181.6 ± 60.6 in Group II, p=0.04) and the dispersion of time to peak longitudinal strain (dTPLS) (86.0 ± 68.3 vs. 151.8 ± 89.6, p=0.03) differed significantly. The univariate analysis revealed dTPLS as a significant predictor of SR maintenance. CONCLUSION High EC efficacy and frequent AF recurrences were observed. The dispersion of time to the maximal longitudinal strain (LS) of left atrial segments facilitated prediction of SR maintenance. The value of 7-day ECG monitoring for detection of arrhythmia after 6 months was limited.