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The normal physiologic range of QRS complex duration spans between 80 and 125 ms with known differences between females and males which cannot be explained by the anatomical variations of heart sizes. To investigate the reasons for the sex differences as well as for the wide range of normal values, a technology is proposed based on the singular value decomposition and on the separation of different orthogonal components of the QRS complex. This allows classification of the proportions of different components representing the 3-dimensional representation of the electrocardiographic signal as well as classification of components that go beyond the 3-dimensional representation and that correspond to the degree of intricate convolutions of the depolarisation sequence. The technology was applied to 382,019 individual 10-s ECG samples recorded in 639 healthy subjects (311 females and 328 males) aged 33.8 ± 9.4 years. The analyses showed that QRS duration was mainly influenced by the proportions of the first two orthogonal components of the QRS complex. The first component demonstrated statistically significantly larger proportion of the total QRS power (expressed by the absolute area of the complex in all independent ECG leads) in females than in males (64.2 ± 11.6% vs 59.7 ± 11.9%, p

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. 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. 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. 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. Angiodysplasien (AD) sind häufig Ursache von gastrointestinalen Blutungen. Wir wissen wenig über Risikofaktoren, die Blutungen aus diesen Gefäßmissbildungen begünstigen können. Die gegenwärtige Studie hatte zum Ziel, Faktoren zu bestimmen, die nur bei Patienten mit symptomatischen, nicht aber bei Patienten mit asymptomatischen AD eine Rolle spielen. Fallkontrollstudie mit AD-Patienten entweder mit oder ohne Nachweis einer gastrointestinalen Blutung. Die beiden Gruppen wurden hinsichtlich klinischer, laborchemischer und endoskopischer Parameter verglichen. 80 Patienten mit blutenden (58, f 31, mitt. Alter 72) oder nicht blutenden AD (22, f 12, mitt. Alter 61) aus vier Krankenhäusern in München wurden eingeschlossen. Eine Blutung aus AD war signifikant mit der absoluten Zahl der AD (OR 1,4 (95 %-KI 1,1–1,7) P = 0,01) und der Verschlusszeit im PFA/Adrenalin-Test (OR 6,6 (95 %-KI 1,8–23,4) P = 0,004) assoziiert. Die absolute Zahl von AD korrelierte signifikant mit dem Alter (r = 0,369, P = 0,001). Die Mehrzahl der AD wurde im oberen Dünndarm ( 30 %) diagnostiziert. Obwohl Patienten mit Aortenstenose nicht signifikant häufiger aus AD bluteten, wiesen sie einen Verlust der hochmolekularen Multimere des Von-Willebrand-Faktors auf. Die Zahl der AD korreliert signifikant mit dem Alter der Patienten. Eine höhere Zahl von AD und eine Hemmung der primären Hämostase sind Hauptrisikofaktoren für eine mit AD assoziierte Blutung.

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.

Long-term health consequences in survivors of severe COVID-19 remain unclear. Eighteen COVID-19 patients admitted to the intensive care unit at the University Hospital Rechts der Isar, Munich, Germany, between 14 March and 23 June 2020, were prospectively followed-up at a median of 36, 75.5, 122 and 222 days after discharge. The health-related quality of life (HrQoL) (36-item Short Form Health Survey and St. George’s Respiratory Questionnaire, SGRQ), cardiopulmonary function, laboratory parameters and chest imaging were assessed longitudinally. The HrQoL assessment revealed a reduced physical functioning, as well as increased SGRQ impact and symptoms scores that all improved over time but remained markedly impaired compared to the reference groups. The median radiological severity scores significantly declined; persistent abnormalities were found in 33.3% of the patients on follow-up. A reduced diffusion capacity was the most common abnormal pulmonary function parameter. The length of hospitalization correlated with role limitations due to physical problems, the SGRQ symptom and the impact score. In conclusion, in survivors of severe COVID-19, the pulmonary function and symptoms improve over time, but impairments in their physical function and diffusion capacity can persist over months. Longer follow-up studies with larger cohorts will be necessary to comprehensively characterize long-term sequelae upon severe COVID-19 and to identify patients at risk.

IntroductionSudden cardiac death (SCD) is the leading cause of death in patients with myocardial infarction (MI) and can be prevented by the implantable cardioverter defibrillator (ICD). Currently, risk stratification for SCD and decision on ICD implantation are based solely on impaired left ventricular ejection fraction (LVEF). However, this strategy leads to over- and under-treatment of patients because LVEF alone is insufficient for accurate assessment of prognosis. Thus, there is a need for better risk stratification. This is the study protocol for developing and validating a prediction model for risk of SCD in patients with prior MI.Methods and AnalysisThe EU funded PROFID project will analyse 23 datasets from Europe, Israel and the US (∼225,000 observations). The datasets include patients with prior MI or ischemic cardiomyopathy with reduced LVEFEthics and disseminationLocal ethical approval was obtained. The final model will be disseminated through scientific publications and a web-calculator. Statistical code will be published through open-source repositories.

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 p-value between 0.033 and

QT interval variability, mostly expressed by QT variability index (QTVi), has repeatedly been used in risk diagnostics. Physiologic correlates of QT variability expressions have been little researched especially when measured in short 10-second electrocardiograms (ECGs). This study investigated different QT variability indices, including QTVi and the standard deviation of QT interval durations (SDQT) in 657,287 10-second ECGs recorded in 523 healthy subjects (259 females). The indices were related to the underlying heart rate and to the 10-second standard deviation of RR intervals (SDRR). The analyses showed that both QTVi and SDQT (as well as other QT variability indices) were highly statistically significantly (p &lt, 0.00001) influenced by heart rate and that QTVi showed poor intra-subject reproducibility (coefficient of variance approaching 200%). Furthermore, sequential analysis of regression variance showed that SDQT was more strongly related to the underlying heart rate than to SDRR, and that QTVi was influenced by the underlying heart rate and SDRR more strongly than by SDQT (p &lt, 0.00001 for these comparisons of regression dependency). The study concludes that instead of QTVi, simpler expressions of QT interval variability, such as SDQT, appear preferable for future applications especially if multivariable combination with the underlying heart rate is used.

The electrocardiographic (ECG) assessment of the T peak–T end (Tpe) intervals has been used in many clinical studies, but several related physiological aspects have not been reported. Specifically, the sources of the Tpe differences between different ECG leads have not been systematically researched, the relationship of Tpe duration to underlying heart rate has not been firmly established, and little is known about the mutual correspondence of Tpe intervals measured in different ECG leads. This study evaluated 796,620 10-s 12-lead ECGs obtained from long-term Holters recorded in 639 healthy subjects (311 female) aged 33.8 ± 9.4 years. For each ECG, transformation to orthogonal XYZ lead was used to measure Tpe in the orthogonal vector magnitude (used as a reference for lead-to-lead comparisons) and to construct a three-dimensional T wave loop. The loop roundness was expressed by a ratio between its circumference and length. These ratios were significantly related to the standard deviation of Tpe durations in different ECG leads. At the underlying heart rate of 60 beats per minute, Tpe intervals were shorter in female than in male individuals (82.5 ± 5.6 vs 90.0 ± 6.5 ms, p < 0.0001). When studying linear slopes between Tpe intervals measured in different leads and the underlying heart rate, we found only minimal heart rate dependency, which was not systematic across the ECG leads and/or across the population. For any ECG lead, positive Tpe/RR slope was found in some subjects (e.g., 79 and 25% of subjects for V2 and V4 measurements, respectively) and a negative Tpe/RR slope in other subjects (e.g., 40 and 65% for V6 and V5, respectively). The steepest positive and negative Tpe/RR slopes were found for measurements in lead V2 and V4, respectively. In all leads, the Tpe/RR slope values were close to zero, indicating, on average, Tpe changes well below 2 ms for RR interval changes of 100 ms. On average, longest Tpe intervals were measured in lead V2, the shortest in lead III. The study concludes that the Tpe intervals measured in different leads cannot be combined. Irrespective of the measured ECG lead, the Tpe interval is not systematically heart rate dependent, and no heart rate correction should be used in clinical Tpe investigations.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) prevent sudden cardiac death. ICD implantation decisions are currently based on reduced left ventricular ejection fraction (LVEF≤35%). However, in some patients, the non-arrhythmic death risk predominates thus diminishing ICD-therapy benefits. Based on previous observations, we tested the hypothesis that compared to the others, patients with nocturnal respiratory rate (NRR) ≥18 breaths per minute (brpm) benefit less from prophylactic ICD implantations. METHODS: This prospective cohort study was a pre-defined sub-study of EU-CERT-ICD trial conducted at 44 centers in 15 EU countries between May 12, 2014, and September 6, 2018. Patients with ischaemic or non-ischaemic cardiomyopathy were included if meeting primary prophylactic ICD implantation criteria. The primary endpoint was all-cause mortality. NRR was assessed blindly from pre-implantation 24-hour Holters. Multivariable models and propensity stratification evaluated the interaction between NRR and the ICD mortality effect. This study is registered with ClinicalTrials.gov (NCT0206419). FINDINGS: Of the 2,247 EU-CERT-ICD patients, this sub-study included 1,971 with complete records. In 1,363 patients (61.7 (12) years; 244 women) an ICD was implanted; 608 patients (63.2 (12) years; 108 women) were treated conservatively. During a median 2.5-year follow-up, 202 (14.8%) and 95 (15.6%) patients died in the ICD and control groups, respectively. NRR statistically significantly interacted with the ICD mortality effect (p = 0.0070). While the 1,316 patients with NRR

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 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.

Zusammenfassung Hintergrund Seit Ende März wurde deutschlandweit das Gesundheitswesen auf einen Notbetrieb umgestellt, um Ressourcen für die sich ausbreitende Coronavirus-disease-2019-Pandemie (COVID-19-Pandemie) zu schaffen. Ziel der Arbeit ist es, das Aufkommen von Notfallpatienten zur Zeit der Pandemie zu untersuchen, um Rückschlüsse auf den Einfluss der COVID-19-Pandemie auf das Patientenaufkommen in einer Notaufnahme ziehen zu können. Material und Methoden Im Rahmen einer deskriptiven epidemiologischen Studie wurden in dem Zeitraum vom 01.02. bis zum 30.04.2019 sowie vom 01.02. bis zum 30.04.2020 patientenbezogene Daten von insgesamt 19.357 Fällen in der zentralen Notaufnahme des Klinikums rechts der Isar erhoben und anonymisiert ausgewertet. Ergebnisse Trotz steigender Patientenzahlen von 2019 auf 2020 kam es von Februar auf März 2020 zu einem deutlichen Abfall der Notfälle bis auf ein Niveau unter das von 2019, der im April weiter anhielt. Dies betraf insbesondere den Fachbereich Unfallchirurgie mit einem Rückgang des mittleren Patientenaufkommens um etwa 40 %. Im Hinblick auf die Beschwerdebilder im März 2020 zeigte sich, dass ein vermehrtes Aufkommen von Unwohlsein (+47 %) und Atemproblemen (+36 %) zu verzeichnen war, wohingegen Rückenschmerzen (−41 %), Wunden (−29 %), thorakale (−24 %) sowie abdominelle Schmerzen (−23 %) deutlich seltener vertreten waren als im Vorjahr. Bezogen auf den Schweregrad der Beschwerden wirkte sich der Rückgang vor allem auf Beschwerdebilder mit niedriger Dringlichkeitsstufe aus. Schlussfolgerung Im Rahmen der COVID-19-Pandemie kam es zu einem deutlichen Rückgang des Patientenaufkommens in einer der größten Notaufnahmen in München. Dies sollte bei bestehenden Krankenhauskapazitäten vermieden werden, um potenziell gesundheitlichen Schäden durch eine aufgeschobene oder ausbleibende notfallmäßige Vorstellung vorzubeugen.

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.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).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.

ZusammenfassungDer Baroreflex ist ein Mechanismus zur Aufrechterhaltung der kardiovaskulären Homöostase. Ein Anstieg des Blutdruckes führt, vermittelt durch das vegetative Nervensystem, gegenregulatorisch zu einem Abfall der Herzfrequenz und zu einer Dilatation der Widerstandsgefäße und umgekehrt. Dadurch werden überschießende Blutdruckschwankungen verhindert. Das Ausmaß der Baroreflexantwort ist ein starker und unabhängiger Prädiktor für Überleben und kardiale Ereignisse. Bei Erkrankungen des Herzkreislaufsystems liegt häufig ein pathologisch abgeschwächter Baroreflex vor. Adäquates Therapieansprechen dieser Patienten kann neben einer verbesserten Prognose mit einer Normalisierung der Baroreflexantwort einhergehen. Eine quantitative Beschreibung der Baroreflexantwort auf Blutdruckschwankungen ist die Baroreflexsensitivität (BRS). Es existieren verschiedene Methoden zur Bestimmung der Baroreflexsensitivität. Um die flächendeckende Implementierung dieser Verfahren in der klinischen Routine voranzutreiben, werden in Zukunft eine Optimierung in Bezug auf Messbarkeit und Reliabilität, die Etablierung von Referenzwerten sowie große prospektive Validierungsstudien vonnöten sein.

Objective Phase synchronization between two weakly coupled oscillators occurs in many natural systems. Since it is difficult to unambiguously detect such synchronization in experimental data, several methods have been proposed for this purpose. Five popular approaches are systematically optimized and compared here. Approach We study and apply the automated synchrogram method, the reduced synchrogram method, two variants of a gradient method, and the Fourier mode method, analyzing 24h data records from 1455 post-infarction patients, the same data with artificial inaccuracies, and corresponding surrogate data generated by Fourier phase randomization. Main results We find that the automated synchrogram method is the most robust of all studied approaches when applied to records with missing data or artifacts, whereas the gradient methods should be preferred for noisy data and low-accuracy R-peak positions. We also show that a strong circadian rhythm occurs with much more frequent phase synchronization episodes observed during night time than during day time by all five methods. Significance In specific applications, the identified characteristic differences as well as strengths and weaknesses of each method in detecting episodes of cardio-respiratory phase synchronization will be useful for selecting an appropriate method with respect to the type of systematic and dynamical noise in the data.

Improvement in interventional and medical treatment of myocardial infarction has significantly reduced mortality and morbidity after myocardial infarction in recent decades. However, coronary heart disease remains the most common cause of death in both men and women. There are differences between men and women suffering from an acute myocardial infarction. Women are older, have more comorbidities and their mortality rate is significantly higher than that of men, but this cannot be explained solely by their age and comorbidities. In contrast to excess mortality, women have a lower incidence of malignant ventricular arrhythmias and sudden cardiac death. The cause of death in women after myocardial infarction appears to be more often heart failure. Early recognition and treatment must be improved.

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

The clinical outcome of patients with severe primary and secondary mitral regurgitation (MR) and heart failure or significantly reduced left ventricular ejection fraction (LVEF) who underwent percutaneous mitral valve repair (pMVR) is yet not well known. This study compares midterm outcome of patients with severe left ventricular dysfunction (EF ≤30%) versus patients with slightly or moderately reduced or normal LVEF (EF30%) after pMVR. One hundred thirty-six consecutive patients were enrolled: 42 patients displayed severe left ventricular dysfunction, group 1 (logistic EuroSCORE I 27.7 ± 21.8%; secondary MR in 37 patients), and 94 patients displayed slightly or moderately reduced or normal LVEF, group 2 (logistic EuroSCORE I 17 ± 18.2%; secondary MR in 21 patients). The primary efficacy endpoint was death of any cause, repeat mitral valve intervention, and/or New York Heart Association class ≥III, which was reached in 31% of patients in group 1 versus 40% in group 2 (p = 0.719) at a median follow-up of 371 days. MR, graded by transthoracic echocardiography, was reduced in both groups (p0.001) and New York Heart Association class improved in each group (p0.001), with no differences between groups (p0.05). In conclusion, at midterm follow-up, the pMVR provided significant clinical benefits with comparable results achieved both in patients with significantly reduced and in patients with moderately reduced to normal LVEF. Thus, pMVR represents a feasible and effective treatment in high-risk patients who otherwise have limited therapeutic options and no safe option to reduce MR.

Der QRS-Komplex bildet die Erregungsausbreitung des ventrikularen Myokards elektrokardiographisch ab. Ist sie ungestort, findet sich ein unauffallig konfigurierter QRS-Komplex von normaler Dauer. Ist sie aufgrund pathologischer Veranderungen gestort, kommt es zu einer Verbreiterung des QRS-Komplexes. Bei Unterbrechung eines Tawara-Schenkels findet sich das Bild eines klassischen Schenkelblocks. Ist eine Zuordnung zu einem klassischen Schenkelblock aufgrund einer atypischen QRS-Konfiguration nicht moglich und finden sich Einkerbungen der R- oder der S-Zacken, spricht man von fragmentierten QRS-Komplexen. Das pathophysiologische Korrelat der fragmentierten QRS-Komplexe ist vielfaltig: Es kann sich um Myokardnarben im Rahmen einer koronaren Herzerkrankung, um fibrotische Myokardareale anderer Genese, um primare Herzerkrankungen oder systemische Erkrankungen mit kardialer Beteiligung handeln. Auch Funktionsstorungen auf zellularer Ebene, z. B. von Ionenkanalen, konnen mit fragmentierten QRS-Komplexen einhergehen. Neben der diagnostischen Bedeutung werden fragmentierte QRS-Komplexe zunehmend auch prognostische Eigenschaften zugesprochen, z. B. bei der Identifikation von Hochrisikopatienten bei koronarer Herzerkrankung, Kardiomyopathien, Brugada-Syndrom und Long-QT-Syndrom. Allerdings konnen fragmentierte QRS-Komplexe auch beim Gesunden beobachtet werden.

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.

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.

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.

How to select patients who will not benefit from ICD therapy by using heart rate and its variability? Jerzy Sacha ⁎, Szymon Barabach , Gabriela Statkiewicz-Barabach , Krzysztof Sacha , Alexander Muller , Jaroslaw Piskorski , Petra Barthel , Georg Schmidt d,1 a Department of Cardiology, Regional Medical Center, Opole, Poland b Institute of Physics, Wroclaw University of Technology, Wroclaw, Poland c Instytut Fizyki imienia Mariana Smoluchowskiego and Mark Kac Complex Systems Research Center, Uniwersytet Jagiellonski, ulica Reymonta 4, PL-30-059 Krakow, Poland d 1. Medizinische Klinik und Deutsches Herzzentrum Munchen der Technischen Universitat Munchen, Munich, Germany e Department of Cardiology-Intensive Therapy, University School of Medicine, Poznan, Poland f Institute of Physics, University of Zielona Gora, Zielona Gora, Poland

Single leaflet clip attachment (SLA) is a prevalent complication in percutaneous edge-to-edge repair of the mitral valve, leading to the recurrence of significant mitral regurgitation. The objective of this retrospective analysis was to evaluate a novel 3-D transoesophageal echocardiographic method for the assessment of clip attachment to the mitral leaflets.We analysed a total of 87 patients treated for symptomatic mitral regurgitation. In 47 patients, clip attachment to the leaflets was assessed by conventional 2-D transoesophageal echocardiography supported by biplane TEE images (biplane TEE group). In 40 patients, clip attachment to the leaflets was assessed by the intraprocedural 3-D volume method in addition to the conventional method (volumetric TEE group). The primary endpoint was defined as clip complications consisting of SLA and clip displacement at any time after clip implantation. Clip complications occurred in nine patients (19.1%) in the biplane TEE group and in two patients (5%) in the volumetric TEE group (p=0.06). Regarding the grade of mitral regurgitation, in the follow-up period we observed a more pronounced deterioration in the biplane TEE group than in the volumetric TEE group.These findings suggest that the additional use of 3-D volumetric transoesophageal echocardiography for the assessment of clip attachment to the mitral leaflets may contribute to a reduced rate of subsequent clip complications.

A 70-year-old man with an abdominal aortic aneurysm presented with a 2-day dysarthria and gait disorder. Cranial magnetic resonance imaging identified subacute ischaemic lesions within both hemispheres suggestive for embolic origin. Transoesophageal echocardiogram performed to exclude a cardiac source of embolism did not give insight in the left atrial appendix but instead showed a large circular mass …

Numerous patients are treated with the MitraClip, although they do not fulfill the stringent inclusion criteria of the Endovascular Valve Edge-to-Edge Repair Study (EVEREST) trials. The outcome of those patients is not well known. Therefore, we compared the long-term outcome after MitraClip treatment between patients who matched (group 1) and did not match (group 2) the EVEREST criteria. One hundred thirty-four consecutive patients were treated from September 2009 to July 2012: 59 patients (44%) in group 1 versus 75 patients (56%) in group 2. Investigated end points were acute procedural success (for group 1 vs 2: 97% vs 95%; p = 0.694), all-cause mortality (28% vs 27%; p = 0.656), reintervention (RI) rate (11% vs 37%; p = 0.010), and improvement in mitral regurgitation (MR) (−1.3 ± 1 vs −1.5 ± 1, p = 0.221) and in New York Heart Association functional class (−0.7 ± 1 vs −0.9 ± 0.8, p = 0.253) during the follow-up of 33 months (27.9 to 38.3). The morphologic extent of a flail leaflet was an independent predictor for RI. In conclusion, although the overall outcome was comparable between both groups, recurrent symptomatic MR with need for RI was higher in group 2, mainly because of complex valve pathologies: especially flail width >15 mm and gap ≥10 mm. Improvements in the interventional strategy are warranted for reducing the need for RI in patients with primary MR.

Background: The debate on whether sex-specific predictive models improve risk stratification after myocardial infarction is ongoing. Methods: This review summarises the current clinical knowledge on sex-specific differences in post-infarction risk stratification parameters. Particular focus is given to electrocardiographic risk factors and indices of cardiac autonomic status. Results: Differences in the underlying pathophysiology between men and women are known. However, clinical findings often lead to uncertain conclusions for a number of risk predictors including, among others, resting heart rate, heart rate variability, heart rate turbulence, QT interval duration, and QRS-T angle. The review links recent findings in prognostic parameters with successful approaches in sex-specific non-invasive risk stratification. Conclusion: Disparities are described in the current clinical opinions on the relevance of investigated parameters in women and possible directions for further research in the field are given.

Respiratory sinus arrhythmia (RSA), a measure of cardiac vagal modulation, provides cardiac risk stratification information. RSA can be quantified from Holter recordings as the high-frequency component of heart rate variability or as the variability of RR intervals in individual respiratory cycles. However, as a risk predictor, RSA is neither exceptionally sensitive nor specific.This study aimed to improve RSA determination by quantifying the amount of sinus arrhythmia related to expiration (expiration-triggered sinus arrhythmia [ETA]) from short-term recordings of electrocardiogram and respiratory chest excursions, and investigated the predictive power of ETA in survivors of acute myocardial infarction.Survivors of acute myocardial infarction (N = 941) underwent 30-min recordings of electrocardiogram and respiratory chest excursions. ETA was quantified as the RR interval change associated with expiration by phase-rectified signal averaging. Primary outcome was 5-year all-cause mortality. Univariable and multivariable Cox regression was used to investigate the association of ETA with mortality.ETA was a strong predictor of mortality, both in univariable and multivariable analysis. In a multivariable model including respiratory rate, left ventricular ejection fraction, diabetes mellitus, and GRACE score, ETA ≤0.19 ms was associated with a hazard ratio of 3.41 (95% confidence interval: 1.10 to 5.89, p 0.0001). In patient subgroups defined by abnormal left ventricular ejection fraction, increased respiratory rate, high GRACE score, or presence of diabetes mellitus, patients were classified as high or low risk on the basis of ETA.Expiration-triggered sinus arrhythmia (ETA) is a potent and independent post-infarction risk marker.

Low baroreflex sensitivity (BRS) indicates poor prognosis after acute myocardial infarction. Noninvasive BRS assessment is complicated by nonstationarities and noise in electrocardiogram and pressure signals. Phase-rectified signal averaging is a novel signal processing technology overcoming these problems.To prospectively validate a BRS measure (baroreflex sensitivity assessed by means of phase-rectified signal averaging [BRS(PRSA)]) based on this technology.Nine hundred forty-one consecutive acute myocardial infarction survivors aged 80 years or younger in sinus rhythm were prospectively enrolled at 2 German university hospitals. All patients underwent 30-minute recordings of electrocardiogram and arterial blood pressures (Portapres; TNO-TPD Biomedical Instrumentation, Amsterdam, Netherlands) within the first 2 weeks after myocardial infarction. BRS(PRSA) was prospectively dichotomized at 1.58 ms/mm Hg. Primary end point was all-cause mortality at 5 years. Multivariable analyses included Global Registry of Acute Coronary Events score (dichotomized at ≥120), sex, BRS(PRSA), left ventricular ejection fraction (dichotomized at ≤35%), and diabetes mellitus. BRS(PRSA) was compared with 3 standard noninvasive BRS measures, that is, the sequence method, the transfer function method, and the correlation method.During follow-up, 72 patients (7.7%) died. BRS(PRSA) stratified the study population into a high-risk group of 405 patients (≤1.58 ms/mm Hg) with an estimated 5-year mortality of 14.2% and a low-risk group of 536 patients (1.58 ms/mm Hg) with a 5-year mortality of 2.8% (P.0001). On multivariable analysis, BRS(PRSA) ≤ 1.58 ms/mm Hg was associated with a hazard ratio of 3.1 (confidence interval 1.7-5.6; P = .001). Predictive power of BRS(PRSA) ≤ 1.58 ms/mm Hg was particularly strong in patients with a Global Registry of Acute Coronary Events score of ≥120 or with a left ventricular ejection fraction of ≤35%.BRS(PRSA) is a powerful and independent predictor of mortality in postinfarction patients especially when assessed in patients with a Global Registry of Acute Coronary Events score of ≥120 or a left ventricular ejection fraction of ≤35%.

Background Assessment of spontaneous baroreflex sensitivity (BRS), an index of autonomic function, poses practical challenges. In this pilot study, we propose a novel technique for assessment of spontaneous BRS based on bivariate phase-rectified signal averaging (PRSA). This is an extension of the monovariate PRSA technology used for calculation of deceleration capacity. Methods A prospective, observational study was conducted in a training cohort of 146 patients with heart failure (New York Heart Association class 2.7 ± 0.8, left ventricular ejection fraction 23.6% ± 9.0%) presenting with sinus rhythm. In all patients, 10-minute recordings of ECG and arterial and blood pressure were obtained in the supine resting position. The algorithm for BRS assessment based on bivariate PRSA (BRS PRSA ) included (1) identification of heartbeat intervals occurring at the time of systolic pressure increases, (2) selection of heartbeat adjacent interval sections, (3) alignment and (4) averaging of these segments, and (5) quantification of the average heart beat interval change by Haar wavelet analysis. Primary end point was death of any cause. During mean follow-up of 2.7 ± 1.1 years, 42 patients (28.8%) died. Results BRS PRSA was significantly associated with the primary end point (3.7 ± 5.3 ms vs −0.33 ± 6.6 ms in survivors and nonsurvivors, respectively). BRS PRSA yielded an area under the receiver operating characteristics curve of 69.8% (95% confidence interval, 59.9-79.7), which was comparable to the area under the curve of left ventricular ejection fraction (70.4%; 95% confidence interval, 61.3-79.5). Using the optimum dichotomy for BRS PRSA of 1.14 milliseconds, 52 (36%) patients had an abnormal BRS PRSA . The 3-year mortality risk of these patients was 45.3% compared to 19.0% in patients with normal BRS PRSA . On multivariate analysis, abnormal BRS PRSA was an independent risk factor from left ventricular ejection fraction ≤ 30% and New York Heart Association class > II. Conclusion BRS PRSA is an independent and strong predictor of mortality in patients with heart failure. Prospective validation and comparisons with standard measures of BRS are needed.