Sudden cardiac death after myocardial infarction: individual participant data from pooled cohorts.

BACKGROUND AND AIMS: Risk stratification of sudden cardiac death after myocardial infarction and prevention by defibrillator rely on left ventricular ejection fraction (LVEF). Improved risk stratification across the whole LVEF range is required for decision-making on defibrillator implantation. METHODS: The analysis pooled 20 data sets with 140 204 post-myocardial infarction patients containing information on demographics, medical history, clinical characteristics, biomarkers, electrocardiography, echocardiography, and cardiac magnetic resonance imaging. Separate analyses were performed in patients (i) carrying a primary prevention cardioverter-defibrillator with LVEF ≤ 35% [implantable cardioverter-defibrillator (ICD) patients], (ii) without cardioverter-defibrillator with LVEF ≤ 35% (non-ICD patients ≤ 35%), and (iii) without cardioverter-defibrillator with LVEF > 35% (non-ICD patients >35%). Primary outcome was sudden cardiac death or, in defibrillator carriers, appropriate defibrillator therapy. Using a competing risk framework and systematic internal-external cross-validation, a model using LVEF only, a multivariable flexible parametric survival model, and a multivariable random forest survival model were developed and externally validated. Predictive performance was assessed by random effect meta-analysis. RESULTS: There were 1326 primary outcomes in 7543 ICD patients, 1193 in 25 058 non-ICD patients ≤35%, and 1567 in 107 603 non-ICD patients >35% during mean follow-up of 30.0, 46.5, and 57.6 months, respectively. In these three subgroups, LVEF poorly predicted sudden cardiac death (c-statistics between 0.50 and 0.56). Considering additional parameters did not improve calibration and discrimination, and model generalizability was poor. CONCLUSIONS: More accurate risk stratification for sudden cardiac death and identification of low-risk individuals with severely reduced LVEF or of high-risk individuals with preserved LVEF was not feasible, neither using LVEF nor using other predictors.

Changes of Right Ventricular Function After Transcatheter Aortic Valve Replacement and Association With Outcomes.

BACKGROUND: Baseline right ventricular (RV) dysfunction represents a predictor for poor outcome in patients undergoing transcatheter aortic valve replacement (TAVR). However, RV function may improve after TAVR, which could have important implications on outcomes. The aim of the present study was to assess changes in RV function after TAVR and its prognostic value regarding clinical outcome. METHODS AND RESULTS: Patients undergoing TAVR at our institution were consecutively enrolled and categorized into 4 groups according to changes in RV function during echocardiographic follow-up at 6 months. A total of 188 patients were included. Of those showing normal function at baseline, 87% (130/149) had preserved RV function at follow-up (group 1), whereas 13% (19/149) developed new RV dysfunction (group 2). Of those with RV dysfunction at baseline (39 patients), RV function normalized in 46% (18/39) (group 3) and remained impaired in 54% (21/39) (group 4). The Kaplan-Meier estimated survival at 3 years was highest in patients in group 1 (83%), intermediate in group 2 (65%) and 3 (69%), whereas group 4 had the worst survival (37%; P < .001). Furthermore, new or persistent RV dysfunction was identified to be independently associated with mortality during follow-up (hazard ratio 2.55; interquartile range 1.03-6.47, P = .004). CONCLUSIONS: Patients with preserved RV function have a high 3-year survival. Normalization of RV function showed improved survival compared with patients with persistent RV dysfunction, who had a dismal prognosis despite TAVR.

Polyscore of autonomic parameters for risk stratification of the elderly general population: the Polyscore study.

AIMS: Present society is constantly ageing and elderly frequently suffer from conditions that are difficult and/or costly to treat if detected late. Effective screening of the elderly is therefore needed so that those requiring detailed clinical work-up are identified early. We present a prospective validation of a screening strategy based on a Polyscore of seven predominantly autonomic, non-invasive risk markers. METHODS AND RESULTS: Within a population-based survey in Germany (INVADE study), participants aged ≥60 years were enrolled between August 2013 and February 2015. Seven prospectively defined Polyscore components were obtained during 30-min continuous recordings of electrocardiogram, blood pressure, and respiration. Out of 1956 subjects, 168 were excluded due to atrial fibrillation, implanted pacemaker, or unsuitable recordings. All-cause mortality over a median 4-year follow-up was prospectively defined as the primary endpoint. The Polyscore divided the investigated population (n = 1788, median age: 72 years, females: 58%) into three predefined groups with low (n = 1405, 78.6%), intermediate (n = 326, 18.2%), and high risk (n = 57, 3.2%). During the follow-up, 82 (4.6%) participants died. Mortality in the Polyscore-defined risk groups was 3.4%, 7.4%, and 17.5%, respectively (P < 0.0001). The Polyscore-based mortality prediction was independent of Framingham score, diabetes, chronic kidney disease, and major stroke and/or myocardial infarction history. It was particularly effective in those aged <75 years (n = 1145). CONCLUSION: The Polyscore-based mortality risk assessment from short-term non-invasive recordings is effective in the elderly general population, especially those aged 60-74 years. Implementation of a comprehensive Polyscore screening of this age group is proposed to advance preventive medical care.

Risk factors for bleeding from gastrointestinal angiodysplasia: a case-control study in patients with bleeding and non-bleeding angiodysplasia.

OBJECTIVES: Angiodysplasia (AD) is a common source of gastrointestinal bleeding. Yet, little is known about factors forwarding bleeding in these vascular malformations. The presented study aims to determine risk factors for bleeding that occurs only in patients with symptomatic, but not with asymptomatic, AD. METHODS: Case-control study in patients with AD and either a positive or a negative history of gastrointestinal bleeding in Munich, Germany. Groups were compared by clinical, laboratory, and endoscopic features. RESULTS: 80 patients with (58, f 31, med. age 72) or without bleeding AD (22, f 12, med. age 61) were included. Bleeding from AD was significantly associated with the total number of AD (OR 1.4 (95 % CI 1.1-1.7) p = 0.01) and closure time in PFA/collagen-epinephrine test (OR 1.0 (95 % CI 1.0-1.0) p < 0.01). The total number of AD correlated significantly with age (r = 0.36; p = 0.01). AD were mainly detected in the upper small intestine (> 30 %). Although patients with aortic stenosis suffered not significantly more frequently from bleeding from AD, they demonstrated a loss of high molecular multimers of VWF. CONCLUSIONS: The amount of AD is clearly correlated to the age of the patient. A higher number of ADs and inhibition of primary hemostasis increase the risk of bleeding.

Clinical value of different QRS-T angle expressions.

Aims: Increased spatial angle between QRS complex and T wave loop orientations has repeatedly been shown to predict cardiac risk. However, there is no consensus on the methods for the calculation of the angle. This study compared the reproducibility and predictive power of three most common ways of QRS-T angle assessment. Methods and results: Electrocardiograms of 352 healthy subjects, 941 survivors of acute myocardial infarction (MI), and 605 patients recorded prior to the implantation of automatic defibrillator [implantable cardioverter defibrillator (ICD)] were used to obtain QRS-T angle measurements by the maximum R to T (MRT), area R to T (ART), and total cosine R to T (TCRT) methods. The results were compared in terms of physiologic reproducibility and power to predict mortality in the cardiac patients during 5-year follow-up. Maximum R to T results were significantly less reproducible compared to the other two methods. Among both survivors of acute MI and ICD recipients, TCRT method was statistically significantly more powerful in predicting mortality during follow-up. Among the acute MI survivors, increased spatial QRS-T angle (TCRT assessment) was particularly powerful in predicting sudden cardiac death with the area under the receiver operator characteristic of 78% (90% confidence interval 63-90%). Among the ICD recipients, TCRT also predicted mortality significantly among patients with prolonged QRS complex duration when the spatial orientation of the QRS complex is poorly defined. Conclusion: The TCRT method for the assessment of spatial QRS-T angle appears to offer important advantages in comparison to other methods of measurement. This approach should be included in future clinical studies of the QRS-T angle. The TCRT method might also be a reasonable candidate for the standardization of the QRS-T angle assessment.

Bedside autonomic risk stratification after myocardial infarction by means of short-term deceleration capacity of heart rate.

Aims: Twenty-four-hour deceleration capacity (DC24h) of heart rate is a strong predictor of mortality after myocardial infarction (MI). Assessment of DC from short-term recordings (DCst) would be of practical use in everyday clinical practice but its predictive value is unknown. Here, we test the usefulness of DCst for autonomic bedside risk stratification after MI. Methods and results: We included 908 patients after acute MI enrolled in Munich and 478 patients with acute (n = 232) and chronic MI (n = 246) enrolled in Tuebingen, both in Germany. We assessed DCst from high-resolution resting electrocardiogram (ECG) recordings (<30 min) performed under standardized conditions in supine position. In the Munich cohort, we also assessed DC24h from 24-h Holter recordings. Deceleration capacity was dichotomized at the established cut-off value of ≤ 2.5 ms. Primary endpoint was 3-year mortality. Secondary endpoint was 3-year cardiovascular mortality. In addition to DC, multivariable analyses included the Global Registry of Acute Coronary Events score >140 and left ventricular ejection fraction ≤ 35%. During follow-up, 48 (5.3%) and 48 (10.0%) patients died in the Munich and Tuebingen cohorts, respectively. On multivariable analyses, DCst ≤ 2.5 ms was the strongest predictor of mortality, yielding hazard ratios of 5.04 (2.68-9.49; P < 0.001) and 3.19 (1.70-6.02; P < 0.001) in the Munich and Tuebingen cohorts, respectively. Deceleration capacity assessed from short-term recordings ≤ 2.5 ms was also an independent predictor of cardiovascular mortality in both cohorts. Implementation of DCst ≤ 2.5 ms into the multivariable models led to a significant increase of C-statistics and integrated discrimination improvement score. Conclusion: Deceleration capacity assessed from short-term recordings is a strong and independent predictor of mortality and cardiovascular mortality after MI, which is complementary to existing risk stratification strategies.

Cryoballoon vs. radiofrequency ablation for paroxysmal atrial fibrillation: an updated meta-analysis of randomized and observational studies.

AIMS: Radiofrequency (RF) ablation represents a standard of care for pulmonary vein isolation in patients with drug-refractory paroxysmal atrial fibrillation (AF). In this setting, cryoballoon (CB) ablation has emerged as alternative therapy. However, the efficacy and safety of CB vs. RF ablation in patients with paroxysmal AF remain a matter of debate. METHODS AND RESULTS: We searched electronic scientific databases for studies of CB vs. RF ablation in patients with paroxysmal AF. Aggregate data were pooled to perform a meta-analysis. The primary efficacy and safety outcomes were the recurrence of any atrial arrhythmia and procedure-related complications, respectively. A total of 6473 participants from 10 studies (CB, n = 2232 vs. RF, n = 4241) were studied. After a median follow-up of 16 months, the risk of any atrial arrhythmia recurrence (risk ratio, RR 95% confidence interval [95% CI] = 1.01 [0.90-1.14], P = 0.83) and procedure-related complications (RR [95% CI] = 0.92 [0.66-1.28], P = 0.61) were comparable between CB vs. RF ablation. Cryoballoon ablation led to a higher risk of persistent phrenic nerve palsy (RR [95% CI] = 13.60 [3.87-47.81], P < 0.01) and a lower risk of cardiac tamponade (RR [95% CI] = 0.48 [0.25-0.89], P = 0.02) compared with RF ablation. There was a trend of statistically significant interaction between the type of CB and the duration of ablation (P for interaction = 0.09). CONCLUSION: In patients with paroxysmal AF, ablation therapy with CB is associated with efficacy and safety comparable to that of RF. Second-generation CB catheters seem to reduce procedure duration. Further studies are warranted to disclose the impact of second-generation CB catheters compared with RF for ablation of paroxysmal AF.

Percutaneous edge-to-edge repair of the mitral valve in patients with degenerative versus functional mitral regurgitation.

OBJECTIVES: To prospectively assess the outcome of percutaneous edge-to-edge repair in patients with degenerative versus functional mitral regurgitation (MR). BACKGROUND: The optimal patient population eligible for percutaneous edge-to-edge repair has yet to be defined. METHODS: We analyzed 119 patients treated by percutaneous edge-to-edge repair for symptomatic MR, 72 patients with degenerative and 47 patients with functional MR. The primary endpoints were defined as procedural success (MR grade reduction ≥1 grade) as well as a composite endpoint defined as freedom from MR 3+ or 4+, mitral valve reintervention and death 12 months after clip implantation. In patients with successful clip placement we further analyzed MR grade, New York Heart Association (NYHA) functional class, distance in the 6 min walking test and left ventricular volumes 12 months after clip implantation. RESULTS: The primary success rate of all intended clipping procedures was 83.3% for degenerative and 89.4% for functional MR (P = 0.42). Regarding the composite endpoint we observed an event free survival of 59.7% in patients treated for degenerative MR and 63.8% in patients treated for functional MR (P = 0.73). We observed a highly significant reduction in MR grade as well as improvement in NYHA functional status in both groups 12 months after clip implantation. However, there was a more pronounced MR grade reduction in patients treated for degenerative MR compared with patients treated for functional MR. CONCLUSIONS: Percutaneous edge-to-edge repair of the mitral valve is feasible and comparably effective in patients with degenerative and functional MR.

In-silico assessment of the dynamic effects of amiodarone and dronedarone on human atrial patho-electrophysiology.

AIMS: The clinical efficacy in preventing the recurrence of atrial fibrillation (AF) is higher for amiodarone than for dronedarone. Moreover, pharmacotherapy with these drugs is less successful in patients with remodelled substrate induced by chronic AF (cAF) and patients suffering from familial AF. To date, the reasons for these phenomena are only incompletely understood. We analyse the effects of the drugs in a computational model of atrial electrophysiology. METHODS AND RESULTS: The Courtemanche-Ramirez-Nattel model was adapted to represent cAF remodelled tissue and hERG mutations N588K and L532P. The pharmacodynamics of amiodarone and dronedarone were investigated with respect to their dose and heart rate dependence by evaluating 10 descriptors of action potential morphology and conduction properties. An arrhythmia score was computed based on a subset of these biomarkers and analysed regarding circadian variation of drug concentration and heart rate. Action potential alternans at high frequencies was observed over the whole dronedarone concentration range at high frequencies, while amiodarone caused alternans only in a narrow range. The total score of dronedarone reached critical values in most of the investigated dynamic scenarios, while amiodarone caused only minor score oscillations. Compared with the other substrates, cAF showed significantly different characteristics resulting in a lower amiodarone but higher dronedarone concentration yielding the lowest score. CONCLUSION: Significant differences exist in the frequency and concentration-dependent effects between amiodarone and dronedarone and between different atrial substrates. Our results provide possible explanations for the superior efficacy of amiodarone and may aid in the design of substrate-specific pharmacotherapy for AF.

Sex differences in the non-invasive risk stratification and prognosis after myocardial infarction.

BACKGROUND: Women have unfavorable prognosis after myocardial infarction (MI). This text describes sex differences in mortality and in the power of risk predictors in contemporarily-treated MI patients. METHODS: A population of 4141 MI patients (26.5% females) was followed up for 5years. Effects of sex and age on total mortality were investigated by multivariable Cox analysis. Mortality predictors were investigated by receiver-operator characteristics analysis. Stepwise multivariable Cox regression was used to create sex-specific predictive models. RESULTS: Thirty-day mortality was 1.5-fold higher in women. However, sex was not a significant mortality predictor in a model adjusted for age. Predictors for 5-year mortality performed differently in male and female patients. In women, a sex-specific model provided better risk stratification than a sex-neutral model. CONCLUSION: The unfavorable prognosis of female MI patients can be explained by advanced age. Sex-specific predictive models might improve risk stratification in female survivors of acute MI.

Assessment of mean respiratory rate from ECG recordings for risk stratification after myocardial infarction.

BACKGROUND: We recently reported that nocturnal respiratory rate (NRR) predicts non-sudden cardiac death in survivors of myocardial infarction (MI). Here, we present the details of the technique deriving NRR from ECG recordings. METHODS: Continuous ECG and respiratory chest excursions were simultaneously recorded in 941 MI survivors who were followed-up for 5-years. Mean respiratory rate was derived from the ECG based on RR intervals, QRS amplitudes, and QRS vectors and compared to chest belt measurements. NRR was calculated from Holter-ECGs accordingly using the same ECG processing. RESULTS: Directly-measured and ECG-derived respiratory rates were in good agreement. Areas under the ROC curve for 10-min-ECG- and Holter-derived respiratory rate were well in the confidence intervals of that of the chest belt measurement. The optimum dichotomy of NRR for the prediction of mortality was ≥18.6 breaths per minute. CONCLUSIONS: The mean respiratory rate can be precisely derived from continuous ECGs.

Respiratory rate predicts outcome after acute myocardial infarction: a prospective cohort study.

AIMS: Risk stratification after acute myocardial infarction (MI) remains imperfect and new indices are sought that might improve the post-MI risk assessment. In a contemporarily-treated cohort of acute MI patients, we tested whether the respiratory rate provides prognostic information and how this information compares to that of established risk assessment. METHODS AND RESULTS: A total of 941 consecutive patients (mean age 61 years, 19% female) presenting with acute MI were enrolled between May 2000 and March 2005. The last follow-up was performed May 2010. Main outcome measure was total mortality during a follow-up period of 5 years. Patients underwent 10-min resting recordings of the respiratory rate within 2 weeks after MI in addition to the measurement of the left ventricular ejection fraction (LVEF) and standard clinical assessment including the GRACE score. During the follow-up, 72 patients died. The respiratory rate was a significant predictor of death in univariable analysis (hazard ratio 1.19 per 1/min, 95% confidence interval: 1.12-1.27) as was the GRACE score [1.04 (1.03-1.05) per point], LVEF [0.96 (0.94-0.97) per 1%], and the diagnosis of diabetes mellitus [2.78 (1.73-4.47)], all P < 0.0001. On multivariate analysis, the GRACE score (P < 0.0001), respiratory rate (P < 0.0001), LVEF (P = 0.013), and diabetes (P = 0.016) were independent prognostic markers. CONCLUSION: The respiratory rate provides powerful prognostic information which is independent and complementary to that of existing risk assessment. Simple and inexpensive assessment of the respiratory rate should be considered a complementary variable for the assessment of risk after acute MI.

QRS fragmentation does not predict mortality in survivors of acute myocardial infarction.

BACKGROUND: Despite advances in coronary revascularization and in heart failure management, myocardial infarction survivors remain at substantially increased mortality risk. Precise risk assessment and risk-adapted follow-up care are crucial to improve their outcomes. Recently, the fragmented QRS complex, i.e. the presence of additional spikes within the QRS complexes on a 12-lead electrocardiogram, has been discussed as a potential non-invasive risk predictor in cardiac patients. HYPOTHESIS: The aim of this study was to evaluate the prognostic meaning of the fragmented QRS complex in myocardial infarction survivors. METHODS: 609 patients with narrow QRS complexes <120 ms were included in a prospective cohort study while hospitalized for myocardial infarction and followed for 5 years. RESULTS: The prevalence of the fragmented QRS complex in these patients amounted to 46.8% (285 patients). These patients had no increased hazard of all-cause death (HR 0.84, 95%-CI 0.45-1.57, p = 0.582) with a mortality rate of 6.0% compared to 7.1% in patients without QRS fragmentations. Furthermore, the risks of cardiac death (HR 1.28, 95%-CI 0.49-3.31, p = 0.613) and of non-cardiac death (HR 0.6, 95%-CI 0.26-1.43, p = 0.25) were not significantly different in patients with QRS fragmentations. However, patients with QRS fragmentations had increased serum creatine kinase concentrations (1438U/l vs. 1160U/l, p = 0.039) and reduced left ventricular ejection fractions (52% vs. 54%, p = 0.011). CONCLUSIONS: The hypothesis that QRS fragmentation might be a prognostic parameter in survivors of myocardial infarction was not confirmed. But those with QRS fragmentation had larger myocardial infarctions, as measured by creatine kinase and left ventricular ejection fraction.

Bivariate phase-rectified signal averaging for assessment of spontaneous baroreflex sensitivity: normalization of the results.

BACKGROUND: Previously proposed technique for assessment of spontaneous baroreflex sensitivity (BRS) based on bivariate phase-rectified signal averaging measures averaged R-R interval (RRI) changes triggered by beat-to-beat increases in systolic blood pressure (SBP). In this study, we investigate a normalized version of the method that relates the averaged RRI changes to the triggering blood pressure changes, thus providing the results in measurement units comparable with existing literature. METHODS: Data of previously reported prospective observational study were used. In each of 146 heart failure patients presenting with sinus rhythm, 10-minute recordings of electrocardiogram and arterial and blood pressures were obtained in the supine resting position. The averaged RRI increases initiated by beat-to-beat SBP increases were measured (original BRS result in milliseconds) and normalized for the averaged beat-to-beat SBP increases (normalized BRS result in milliseconds per millimeters of mercury). Both results were compared in terms of predicting all-cause mortality during a mean follow-up of 2.7 ± 1.1 years when 42 patients (28.8%) died. RESULTS: Both types of results were highly correlated (r = 0.938, P < .001) and led to similarly strong separation of high- and low-risk groups. The receiver operator characteristics of both indices were well within the 95% confidence intervals of each other, and the areas under the characteristics were practically identical: 71.1% (95% confidence interval, 60.7%-80.9%) for original BRS and 69.7% (58.9%-79.2%) for normalized BRS. CONCLUSION: The results might question the concept of a linear relationship between the SBP changes and RRI changes. The phase-rectified signal averaging-based assessment of BRS may be used with equal legitimacy in the nonnormalized and normalized forms; the normalized form provides results in conventional measurement units.

Heart rate deceleration runs for postinfarction risk prediction.

UNLABELLED: A method for counting episodes of uninterrupted beat-to-beat heart rate decelerations was developed. METHODS: The method was set up and evaluated using 24-hour electrocardiogram Holter recordings of 1455 (training sample) and 946 (validation sample) postinfarction patients. During a median follow-up of 24 months, 70, 46, and 19 patients of the training sample suffered from total, cardiac, and sudden cardiac mortality, respectively. In the validation sample, these numbers were 39, 25, and 15. Episodes of consecutive beat-to-beat heart rate decelerations (deceleration runs [DRs]) were characterized by their length. RESULTS: Deceleration runs of 2 to 10 cycles were significantly less frequent in nonsurvivors. Multivariate model of DRs of 2, 4, and 8 cycles identified low-, intermediate-, and high-risk groups. In these groups of the training sample, the total mortalities were 1.8%, 6.1%, and 24%, respectively. In the validation sample, these numbers were 1.8%, 4.1%, and 21.9%. CONCLUSION: Infrequent DRs during 24-hour Holter indicate high risk of postinfarction mortality.

Intra-subject stability of different expressions of spatial QRS-T angle and their relationship to heart rate.

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.

Short-Term Beat-to-Beat QT Variability Appears Influenced More Strongly by Recording Quality Than by Beat-to-Beat RR Variability.

Increases in beat-to-beat variability of electrocardiographic QT interval duration have repeatedly been associated with increased risk of cardiovascular events and complications. The measurements of QT variability are frequently normalized for the underlying RR interval variability. Such normalization supports the concept of the so-called immediate RR effect which relates each QT interval to the preceding RR interval. The validity of this concept was investigated in the present study together with the analysis of the influence of electrocardiographic morphological stability on QT variability measurements. The analyses involved QT and RR measurements in 6,114,562 individual beats of 642,708 separate 10-s ECG samples recorded in 523 healthy volunteers (259 females). Only beats with high morphology correlation (r > 0.99) with representative waveforms of the 10-s ECG samples were analyzed, assuring that only good quality recordings were included. In addition to these high correlations, SDs of the ECG signal difference between representative waveforms and individual beats expressed morphological instability and ECG noise. In the intra-subject analyses of both individual beats and of 10-s averages, QT interval variability was substantially more strongly related to the ECG noise than to the underlying RR variability. In approximately one-third of the analyzed ECG beats, the prolongation or shortening of the preceding RR interval was followed by the opposite change of the QT interval. In linear regression analyses, underlying RR variability within each 10-s ECG sample explained only 5.7 and 11.1% of QT interval variability in females and males, respectively. On the contrary, the underlying ECG noise contents of the 10-s samples explained 56.5 and 60.1% of the QT interval variability in females and males, respectively. The study concludes that the concept of stable and uniform immediate RR interval effect on the duration of subsequent QT interval duration is highly questionable. Even if only stable beat-to-beat measurements of QT interval are used, the QT interval variability is still substantially influenced by morphological variability and noise pollution of the source ECG recordings. Even when good quality recordings are used, noise contents of the electrocardiograms should be objectively examined in future studies of QT interval variability.

The Polyscore of autonomic parameters predicts mortality and identifies low-risk individuals among diabetic survivors of acute myocardial infarction.

Survivors of an acute myocardial infarction with diabetes mellitus retain an increased mortality risk. Reliable assessment of individual risk is required for effective and cost-efficient medical care in these patients. The Polyscore is a previously established risk predictor consisting of seven autonomic tests derived from electrocardiogram, blood pressure, and respiration. The Polyscore allows classification of survivors of myocardial infarction in groups at low, intermediate and high mortality risk. The aim of this study was to investigate the prognostic value of the Polyscore in diabetic survivors of acute myocardial infarction, which may be impaired by the presence of diabetic autonomic neuropathy. Survivors of an acute myocardial infarction were included in a prospective cohort study during hospitalisation due to the index event at two university hospitals in Munich, Germany. The Polyscore was determined from simultaneous non-invasive 30-min recordings of electrocardiogram, continuous arterial blood pressure, and respiration which were performed in all participants. Patients were followed for 5 years. The primary and secondary outcomes were all-cause mortality and cardiac mortality. 184 of 941 enrolled patients (19.6%) suffered from diabetes mellitus. 5-year-mortality was higher in diabetic patients (15.2%) compared to non-diabetic patients (5.8%). A multivariable Cox regression model confirmed the Polyscore as a strong predictor of mortality in diabetic post-MI patients (intermediate risk: HR 6.56, 95% CI 1.61-26.78, p = 0.004, mortality 22.8%; high risk: HR 18.76, 95% CI 4.35-80.98, p < 0.001, mortality 68.8%). There was no interaction between diabetes mellitus and the Polyscore regarding mortality prediction (p = 0.775). Interestingly, in contrast to the groups at intermediate and high risk (73 patients, 39.7%), the Polyscore identified a majority of diabetic patients (111, 60.3%) with a low mortality risk, comparable to that of low-risk non-diabetic patients (3.6% and 2.1%, respectively, p = 0.339). Consistent results were observed for cardiac mortality. This analysis shows that the Polyscore predicts all-cause and cardiac mortality in diabetic survivors of acute myocardial infarction. Within these patients it identifies a large population not affected by the excess mortality associated with diabetes in this setting. Thus, the Polyscore may facilitate risk-adapted follow-up strategies in diabetic survivors of myocardial infarction.

Influence of heart rate correction formulas on QTc interval stability.

Monitoring of QTc interval is mandated in different clinical conditions. Nevertheless, intra-subject variability of QTc intervals reduces the clinical utility of QTc monitoring strategies. Since this variability is partly related to QT heart rate correction, 10 different heart rate corrections (Bazett, Fridericia, Dmitrienko, Framingham, Schlamowitz, Hodges, Ashman, Rautaharju, Sarma, and Rabkin) were applied to 452,440 ECG measurements made in 539 healthy volunteers (259 females, mean age 33.3 ± 8.4 years). For each correction formula, the short term (5-min time-points) and long-term (day-time hours) variability of rate corrected QT values (QTc) was investigated together with the comparisons of the QTc values with individually corrected QTcI values obtained by subject-specific modelling of the QT/RR relationship and hysteresis. The results showed that (a) both in terms of short-term and long-term QTc variability, Bazett correction led to QTc values that were more variable than the results of other corrections (p < 0.00001 for all), (b) the QTc variability by Fridericia and Framingham corrections were not systematically different from each other but were lower than the results of other corrections (p-value between 0.033 and < 0.00001), and (c) on average, Bazett QTc values departed from QTcI intervals more than the QTc values of other corrections. The study concludes that (a) previous suggestions that Bazett correction should no longer be used in clinical practice are fully justified, (b) replacing Bazett correction with Fridericia and/or Framingham corrections would improve clinical QTc monitoring, (c) heart rate stability is needed for valid QTc assessment, and (d) development of further QTc corrections for day-to-day use is not warranted.

Sex and Rate Change Differences in QT/RR Hysteresis in Healthy Subjects.

While it is now well-understood that the extent of QT interval changes due to underlying heart rate differences (i.e., the QT/RR adaptation) needs to be distinguished from the speed with which the QT interval reacts to heart rate changes (i.e., the so-called QT/RR hysteresis), gaps still exist in the physiologic understanding of QT/RR hysteresis processes. This study was designed to address the questions of whether the speed of QT adaptation to heart rate changes is driven by time or by number of cardiac cycles; whether QT interval adaptation speed is the same when heart rate accelerates and decelerates; and whether the characteristics of QT/RR hysteresis are related to age and sex. The study evaluated 897,570 measurements of QT intervals together with their 5-min histories of preceding RR intervals, all recorded in 751 healthy volunteers (336 females) aged 34.3 ± 9.5 years. Three different QT/RR adaptation models were combined with exponential decay models that distinguished time-based and interval-based QT/RR hysteresis. In each subject and for each modelling combination, a best-fit combination of modelling parameters was obtained by seeking minimal regression residuals. The results showed that the response of QT/RR hysteresis appears to be driven by absolute time rather than by the number of cardiac cycles. The speed of QT/RR hysteresis was found decreasing with increasing age whilst the duration of individually rate corrected QTc interval was found increasing with increasing age. Contrary to the longer QTc intervals, QT/RR hysteresis speed was faster in females. QT/RR hysteresis differences between heart rate acceleration and deceleration were not found to be physiologically systematic (i.e., they differed among different healthy subjects), but on average, QT/RR hysteresis speed was found slower after heart rate acceleration than after rate deceleration.