Ondrej Toman

Sex and race differences in QRS duration

AIMS The study investigated healthy subjects to study sex and race differences in QRS durations and the dependency of QRS durations on heart rates and other physiologic correlates. METHODS AND RESULTS QRS duration and its heart rate dependency were evaluated in 420 615 electrocardiograms obtained in 523 healthy subjects including 111 females of African origin, 130 Caucasian females, 125 males of African origin, and 129 Caucasian males. The distributions of QRS/RR slopes and QRS durations at RR intervals of 1 and 0.5 s were compared between sex- and race-defined subgroups. At high heart rates, QRS duration was increased in ∼35% of all subjects, while in the others, QRS was shortened (no differences between the subgroups). At RR interval of 1 s, the QRS duration was 97.4 ± 4.6, 99.8 ± 6.0, 101.6 ± 5.3, and 104.8 ± 6.3 ms in African females, Caucasian females, African males, and Caucasian males, respectively (all differences P < 0.001). Similar statistical differences were found at an RR of 0.5 s. When accounting for the differences in lean body mass, the difference between African and Caucasian subjects was as large as the difference between females and males. Within each subgroup, the normal QRS durations differed by 15-20 and 18-25 ms at RR intervals of 1 and 0.5 s, respectively. CONCLUSION The QRS widths are heart rate dependent and different not only between women and men but also between African and Caucasian individuals. Difference in cardiac resynchronization therapy efficacy might be expected between patients of African and Caucasian origin stratified by QRS duration.

GRACE Score among Six Risk Scoring Systems (CADILLAC, PAMI, TIMI, Dynamic TIMI, Zwolle) Demonstrated the Best Predictive Value for Prediction of Long-Term Mortality in Patients with ST-Elevation Myocardial Infarction.

Aim To compare the prognostic accuracy of six scoring models for up to three-year mortality and rates of hospitalisation due to acute decompensated heart failure (ADHF) in STEMI patients. Methods and Results A total of 593 patients treated with primary PCI were evaluated. Prospective follow-up of patients was ≥3 years. Thirty-day, one-year, two-year, and three-year mortality rates were 4.0%, 7.3%, 8.9%, and 10.6%, respectively. Six risk scores—the TIMI score and derived dynamic TIMI, CADILLAC, PAMI, Zwolle, and GRACE—showed a high predictive accuracy for six- and 12-month mortality with area under the receiver operating characteristic curve (AUC) values of 0.73–0.85. The best predictive values for long-term mortality were obtained by GRACE. The next best-performing scores were CADILLAC, Zwolle, and Dynamic TIMI. All risk scores had a lower prediction accuracy for repeat hospitalisation due to ADHF, except Zwolle with the discriminatory capacity for hospitalisation up to two years (AUC, 0.80–0.83). Conclusions All tested models showed a high predictive value for the estimation of one-year mortality, but GRACE appears to be the most suitable for the prediction for a longer follow-up period. The tested models exhibited an ability to predict the risk of ADHF, especially the Zwolle model.

The homozygous KCNQ1 gene mutation associated with recessive Romano-Ward syndrome.

In a 7‐year‐old boy with normal hearing suffering from repeated syncope an extremely prolonged QTc interval (up to 700 ms) was found. The mother was completely asymptomatic and the father had an intermittently borderline QTc interval (maximum 470 ms) but no symptoms. In the proband a mutation analysis of KCNQ1 gene revealed a homozygous 1893insC mutation. The parents were heterozygous for this mutation. There was no consanguineous marriage in the family. The clinical relevance of these findings is that apparently normal individuals may have a latent reduction of repolarizing currents, a “reduced repolarization reserve,” because they are carriers of latent ion channel genes mutations.

Prognostic impact of neutrophil gelatinase-associated lipocalin and B-type natriuretic in patients with ST-elevation myocardial infarction treated by primary PCI: a prospective observational cohort study

Objectives Neutrophil gelatinase-associated lipocalin (NGAL) from a pathophysiological perspective connects various pathways that affect the prognosis after myocardial infarction. The objective was to evaluate the benefits of measuring NGAL for prognostic stratification in addition to the Thrombolysis in Myocardial Infarction (TIMI) score, and to compare it with the prognostic value of B-type natriuretic peptide (BNP). Design Prospective observational cohort study. Setting One university/tertiary centre. Participants A total of 673 patients with ST segment elevation myocardial infarction were treated by primary percutaneous coronary intervention. NGAL and BNP were assessed on hospital admission. Outcomes Primary outcome: 1-year mortality. Secondary outcomes: 1-year hospitalisation due to acute heart failure, unplanned revascularisation, reinfarction, stroke and combined end point of 1-year mortality and hospitalisation due to heart failure. Statistical methods Using the c-statistic, the ability of NGAL, BNP and TIMI score to predict 1-year mortality alone and in combination with readmission for heart failure was evaluated. The addition of the predictive value of biomarkers to the score was assessed by category free net reclassification improvement (cfNRI) and the integrated discrimination index (IDI). Results The NGAL level was significantly higher in non-survivors (67 vs 115 pg/mL; p<0.001). The area under the curve (AUC) values for mortality prediction for NGAL, BNP and TIMI score were 75.5, 78.7 and 74.4, respectively (all p<0.001) with optimal cut-off values of 84 pg/mL for NGAL and 150 pg/mL for BNP. The addition of NGAL and BNP to the TIMI score significantly improved risk stratification according to cfNRI and IDI. A BNP and the combination of the TIMI score with NGAL predicted the occurrence of the combined end point with an AUC of 80.6 or 82.2, respectively. NGAL alone is a simple tool to identify very high-risk patients. NGAL >110 pg/mL was associated with a 1-year mortality of 20%. Conclusions The measurement of NGAL together with the TIMI score results in a strong prognostic model for the 1-year mortality rate in patients with STEMI.

Dynamic properties of selected repolarization descriptors.

A number of morphological indices have been proposed to characterize electrocardiographic patterns of ventricular repolarization mostly studying spatial and temporal patterns of T waves. Comparisons between different clinical populations exist but data on the suitability of the T-wave descriptors to characterize and quantify physiologic regulations of ventricular repolarization are lacking. To initiate such investigations, a study was conducted comparing the influence of provoked heart rate changes on the duration of QT interval, the roundness of T wave loop expressed by the relative T wave area, and on the 3-dimensional QRS-T angle. A population of 40 healthy subjects (18 women, mean age 30.4 ± 8.1 years) was studied. In each subject, provocative tests involving changes from strict supine to unsupported sitting and to unsupported standing positions were repeated twice during each of 3 separate monitoring days. Continuous 12-lead electrocardiograms were obtained during the provocative tests. The speed of the adaptation of the repolarization descriptors to heart rate changes was characterized by λ parameters of previously published exponential decay model of R-R interval related hysteresis. The comparisons showed that the adaptation of QT interval to heart rate changes was much slower than that of the investigated T-wave morphological descriptors: the mean (SD) values of λ parameters were 5.01 ± 1.13, 12.72 ± 8.66, and 12.90 ± 11.37 for QT interval, QRS-T angle, and relative T-wave area, respectively (P < .001 for the difference between QT interval and both morphological descriptors). The study suggests that the different numerical quantifiers of vertricular repolarization that may be derived from standard electrocardiographic tracings likely represent separate and distinct physiologic entities.

The Association Between Levels of Tissue Inhibitor of Metalloproteinase-1 with Acute Heart Failure and Left Ventricular Dysfunction in Patients with ST Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention

AIMS Tissue inhibitors of metalloproteinase (TIMPs) bind to active matrix metalloproteinase (MMPs), and thereby inhibit their proteolytic activity. We investigated the role of polymorphisms in the gene for TIMP-1 and serum levels of TIMP-1 in association with postmyocardial infarction (MI), left ventricular (LV) dysfunction, and symptoms of acute heart failure (AHF) in patients treated with primary percutaneous coronary intervention. METHODS In total, 556 patients with STEMI were evaluated. Levels of TIMP-1 were measured at admission and 24 h after MI onset. The TIMP-1 exon 5 SNP rs4898 (F124F with T>C) located at X chromosome was assayed. RESULTS TIMP-1 levels were higher for men with AHF as well as for men with LV dysfunction (ejection fraction [EF]<40%). According to multivariate analysis, the TIMP-1 level was a factor with an independent negative relationship to EF and AHF in men. An independent relationship between exon 5 TIMP-1 gene polymorphism and EF, AHF or TIMP-1 level was not documented. CONCLUSION These results provide evidence that a higher level of circulating TIMP-1 is independently associated with worse EF and AHF.

ACE gene insertion/deletion polymorphism has a mild influence on the acute development of left ventricular dysfunction in patients with ST elevation myocardial infarction treated with primary PCI.

BackgroundWe evaluated the associations among angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism, ACE activity and post-myocardial infarction (MI) left ventricular dysfunction and acute heart failure (AHF) early after presentation with MI with ST-segment elevation (STEMI).MethodsA total of 556 patients with STEMI treated by primary PCI (421 patients without AHF and 135 patients with AHF) were the study population. The activity of BNP, NT-ProBNP and ACE were measured at hospital admission and 24 h after MI onset. Left ventricular angiography was done before PCI; echocardiography was undertaken between the third and fifth day after MI.ResultsIn comparison with the II genotypes group, the DD/ID group had a higher level of ACE activity upon hospital admission (p < 0.001). We found a significantly higher level of ACE activity in patients with moderate LV dysfunction (EF 40-54%) in comparison both with patients with preserved LV function (EF ≥55%) and with patients with severe LV dysfunction (p = 0.028). A non-significant trend towards a higher incidence of mild AHF (22.1% vs. 16.02%, p = 0,093), a significantly higher value of end-systolic volume (ESV/BSA) (30.0 ± 12.3 vs. 28.5 ± 13.0; p < 0.05) and lower EF (50.2 ± 11.1 vs. 52.7 ± 11.7; p < 0.05) in the DD/ID genotypes group was noted. Even after multiple adjustments according to multivariate models, the EF for the DD/ID group remained significantly lower (p = 0,033). The DD/ID genotypes were associated with a significantly higher risk of EF <45% (OR 2.04 [95% CI 1.28; 3.25]).ConclusionsThese results suggest that the I/D polymorphism of ACE is associated with the development of LV dysfunction in the acute phase after STEMI. We demonstrated for the first time an association of the low ACE activity with the severe LV dysfunction, although patients with moderate LV dysfunction had higher level ACE activity than patients with preserved LV function.

Unstable angina pectoris prior to ST elevation myocardial infarction in patients treated with primary percutaneous coronary intervention has no influence on prognosis.

BACKGROUND Pre-infarction unstable angina pectoris (UAP) can be considered ischemic preconditioning. The aim of this study was to compare short and long term outcomes in patients with or without pre-infarction UAP and ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). METHODS 593 patients with STEMI (388 without and 205 with UAP) were evaluated. Levels of biomarkers (troponin I, BNP, NT-ProBNP, neopterin, endoglin and pentraxin-3) at hospital admission and 24 h after STEMI onset were assessed. Echocardiography was undertaken on the fourth day after MI and after 12 months. The median follow-up was 37 months. RESULTS We found no significant differences in sex, age or risk factors for atherosclerosis between the UAP and non-UAP group. As the median time from the onset of chest pain to admission was significantly longer in the UAP group (228 min vs 258 min; P=0.009), we used a propensity score to obtain comparable matched groups for use in further analyses. The levels of NT-proBNP were significantly higher on admission and after 24 hours in the UAP group. Left ventricular functions according to invasive and echocardiographic parameters were entirely comparable at hospitalization and after 12 months. No differences were found in severity index of acute heart failure during hospitalization. The incidence of major acute coronary events during follow-up was comparable for the groups. CONCLUSIONS In patients with STEMI treated with primary PCI, pre-infarction UAP has no beneficial clinical effect during hospitalization or during long-term follow-up.

Effect of atorvastatin on dynamic parameters of myocardial repolarization in healthy subjects

BACKGROUND Antiarrhythmic properties of statins were suggested as a part of their pleiotropic effects. The aim of the present study was to evaluate the effects of atorvastatin on myocardial repolarization as manifested on surface electrocardiograms (ECGs) in healthy subjects. METHODS AND RESULTS Forty young healthy volunteers (20 men, 20 women) underwent a single-dose double-blind 3-way crossover study of 20 and 80 mg of atorvastatin and placebo. Long-term 13-hour 12-lead ECGs were obtained in each subject and each study period starting 15 minutes before drug administration. Each study period contained 18 time-points of 5-minute durations when the subjects were in resting supine positions. Digital ECG recordings were analyzed automatically, and the results were completed blindly before statistical analyses. Dynamic parameters of myocardial repolarization and T-wave morphology descriptors were evaluated. Although some trends were observed, no significant drug-related changes in any of investigated ECG repolarization descriptors were found. CONCLUSION In comparison with placebo, single doses of atorvastatin had no effect on repolarization heterogeneity in healthy subjects. The observation confirms safe profile of the drug with limited proarrhythmic potential.

Comparison of two modes of long-term ECG monitoring to assess the efficacy of catheter ablation for paroxysmal atrial fibrillation

AIMS Optimal ECG monitoring in detecting recurrences of atrial fibrillation (AF) or atrial tachycardia (AT) after catheter ablation has not been well established. The purpose of this prospective study was to compare the utility of daily ECG monitoring with episodic card recorder (ECR) vs. periodic monitoring with episodic loop recorder (ELR) for the detection of post-blanking AF/AT recurrences during early (Months 4-6) and late (Months 7-12) periods after catheter ablation for paroxysmal AF. METHODS The study included 105 consecutive patients, who received ECR for 12 months and were instructed to send at least 2 random ECG recordings daily with extra-recordings during symptoms. The patients were simultaneously monitored for one week with ELR at the end of each period (Months 6 and 12). RESULTS Thirty-one and 12 patients with AF/AT recurrence were identified by means of ECR and ELR, respectively. In patients with complete and valid data, ELR technology was inferior to ECR by detecting AF/AT in 5 (31%) of 16 and 5 (26%) of 19 patients with arrhythmia identified by ECR in the early and late period, respectively. Overall, ELR had a sensitivity of 8/23 (35%) for detecting AF/AT recurrence. There was no single patient with AF/AT recurrence on ELR that would not be known from ECR monitoring. Only 2 patients with arrhythmia recurrence were completely asymptomatic throughout the study period. CONCLUSION Daily ECG monitoring with ECR was better than periodic monitoring with ELR in detecting AF/AT recurrences during the follow-up periods. Entirely asymptomatic patients with AF/AT recurrences were rare.