AIMS: Fragmented QRS complex with visible notching on standard 12-lead electrocardiogram (ECG) is understood to represent depolarization abnormalities and to signify risk of cardiac events. Depolarization abnormalities with similar prognostic implications likely exist beyond visual recognition but no technology is presently suitable for quantification of such invisible ECG abnormalities. We present such a technology. METHODS AND RESULTS: A signal processing method projects all ECG leads of the QRS complex into optimized three perpendicular dimensions, reconstructs the ECG back from this three-dimensional projection, and quantifies the difference (QRS 'micro'-fragmentation, QRS-μf) between the original and reconstructed signals. QRS 'micro'-fragmentation was assessed in three different populations: cardiac patients with automatic implantable cardioverter-defibrillators, cardiac patients with severe abnormalities, and general public. The predictive value of QRS-μf for mortality was investigated both univariably and in multivariable comparisons with other risk factors including visible QRS 'macro'-fragmentation, QRS-Mf. The analysis was made in a total of 7779 subjects of whom 504 have not survived the first 5 years of follow-up. In all three populations, QRS-μf was strongly predictive of survival (P < 0.001 univariably, and P < 0.001 to P = 0.024 in multivariable regression analyses). A similar strong association with outcome was found when dichotomizing QRS-μf prospectively at 3.5%. When QRS-μf was used in multivariable analyses, QRS-Mf and QRS duration lost their predictive value. CONCLUSION: In three populations with different clinical characteristics, QRS-μf was a powerful mortality risk factor independent of several previously established risk indices. Electrophysiologic abnormalities that contribute to increased QRS-μf values are likely responsible for the predictive power of visible QRS-Mf.

• Keywords
• Electrocardiogram, Fragmentation, Mortality prediction, QRS complex,
• MeSH
• Electrocardiography * methods   MeSH
• Humans MeSH
• Predictive Value of Tests MeSH
• Prognosis MeSH
• Risk Factors MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Three-dimensional angle between the QRS complex and T wave vectors is a known powerful cardiovascular risk predictor. Nevertheless, several physiological properties of the angle are unknown or poorly understood. These include, among others, intra-subject profiles and stability of the angle relationship to heart rate, characteristics of angle/heart-rate hysteresis, and the changes of these characteristics with different modes of QRS-T angle calculation. These characteristics were investigated in long-term 12-lead Holter recordings of 523 healthy volunteers (259 females). Three different algorithmic methods for the angle computation were based on maximal vector magnitude of QRS and T wave loops, areas under the QRS complex and T wave curvatures in orthogonal leads, and weighted integration of all QRS and T wave vectors moving around the respective 3-dimensional loops. These methods were applied to orthogonal leads derived either by a uniform conversion matrix or by singular value decomposition (SVD) of the original 12-lead ECG, giving 6 possible ways of expressing the angle. Heart rate hysteresis was assessed using the exponential decay models. All these methods were used to measure the angle in 659,313 representative waveforms of individual 10-s ECG samples and in 7,350,733 individual beats contained in the same 10-s samples. With all measurement methods, the measured angles fitted second-degree polynomial regressions to the underlying heart rate. Independent of the measurement method, the angles were found significantly narrower in females (p < 0.00001) with the differences to males between 10o and 20o, suggesting that in future risk-assessment studies, different angle dichotomies are needed for both sexes. The integrative method combined with SVD leads showed the highest intra-subject reproducibility (p < 0.00001). No reproducible delay between heart rate changes and QRS-T angle changes was found. This was interpreted as a suggestion that the measurement of QRS-T angle might offer direct assessment of cardiac autonomic responsiveness at the ventricular level.

• Keywords
• ECG measurements, healthy volunteers, heart rate, heart rate hysteresis, long-term ECG, polynomial regression, sex differences, spatial QRS-T angle,
• Publication type
• Journal Article MeSH

To facilitate the precision of clinical electrocardiographic studies of J-to-Tpeak (JTp) and Tpeak-to-Tend (Tpe) intervals, the study investigated their differences between healthy females and males, and between subjects of African and Caucasian origin. In 523 healthy subjects (254 females; 236 subjects of African origin), repeated Holter recordings were used to measure QT, JT, JTp, and Tpe intervals preceded by both stable and variable heart rates. Subject-specific curvilinear regression models were used to obtain individual QTc, JTc, JTpc and Tpec intervals. Rate hysteresis, i.e., the speed with which the intervals adapted after heart rate changes, was also investigated. In all sex-race groups, Tpe intervals were not systematically heart rate dependent. Similar to QTc intervals, women had JTc, and JTpc intervals longer than males (difference 20-30 ms, p < 0.001). However, women had Tpec intervals (and rate uncorrected Tpe intervals) shorter by approximately 10 ms compared to males (p < 0.001). Subjects of African origin had significantly shorter QTc intervals than Caucasians (p < 0.001). Gradually diminishing race-difference was found for JTc, JTpc and Tpec intervals. JTc and JTpc were moderately increasing with age but Tpe/Tpec were not. Rate hysteresis of JTp was approximately 10% longer compared to that of JT (p < 0.001). In future clinical studies, Tpe interval should not be systematically corrected for heart rate and similar to the QT interval, the differences in JT, JTp and Tpe intervals should be corrected for sex. The differences in QT and JT, and JTp intervals should also be corrected for race.

• MeSH
• Adult MeSH
• Electrocardiography * MeSH
• Humans MeSH
• Sex Characteristics * MeSH
• Heart Conduction System physiology   MeSH
• Racial Groups * MeSH
• Heart Rate physiology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH

AIMS: The clinical effectiveness of primary prevention implantable cardioverter defibrillator (ICD) therapy is under debate. The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators (EU-CERT-ICD) aims to assess its current clinical value. METHODS AND RESULTS: The EU-CERT-ICD is a prospective investigator-initiated non-randomized, controlled, multicentre observational cohort study performed in 44 centres across 15 European Union countries. We will recruit 2250 patients with ischaemic or dilated cardiomyopathy and a guideline indication for primary prophylactic ICD implantation. This sample will include 1500 patients at their first ICD implantation and 750 patients who did not receive a primary prevention ICD despite having an indication for it (non-randomized control group). The primary endpoint is all-cause mortality; the co-primary endpoint in ICD patients is time to first appropriate shock. Secondary endpoints include sudden cardiac death, first inappropriate shock, any ICD shock, arrhythmogenic syncope, revision procedures, quality of life, and cost-effectiveness. At baseline (and prior to ICD implantation if applicable), all patients undergo 12-lead electrocardiogram (ECG) and Holter ECG analysis using multiple advanced methods for risk stratification as well as detailed documentation of clinical characteristics and laboratory values. Genetic biobanking is also organized. As of August 2018, baseline data of 2265 patients are complete. All subjects will be followed for up to 4.5 years. CONCLUSIONS: The EU-CERT-ICD study will provide a necessary update about clinical effectiveness of primary prophylactic ICD implantation. This study also aims for improved risk stratification and patient selection using clinical and ECG risk markers.

• Keywords
• Implantable cardioverter defibrillator, Mortality, Risk factors, Sudden cardiac death,
• MeSH
• Defibrillators, Implantable * MeSH
• Cardiomyopathy, Dilated complications   mortality   therapy   MeSH
• Electrocardiography MeSH
• Risk Assessment * MeSH
• Quality of Life MeSH
• Humans MeSH
• Survival Rate trends   MeSH
• Death, Sudden, Cardiac epidemiology   etiology   prevention & control   MeSH
• Follow-Up Studies MeSH
• Primary Prevention methods   MeSH
• Prospective Studies MeSH
• Patient Selection MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Observational Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH
• Geographicals
• Europe epidemiology   MeSH