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.

Respirable quartz dust exposure and airway obstruction: a systematic review and meta-analysis.

Studies on exposure to respirable quartz dust at the workplace and the development of chronic obstructive pulmonary disease (COPD) were selected into a systematic review and meta-analysed to obtain an overall estimate of forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) reduction. PubMed and Embase were searched from 1970 to 2010. In total, 257 cross-sectional and longitudinal studies were identified that reported on inorganic dust exposure and had available lung function data. Of the 55 publications which met our inclusion criteria, 11 reported on associations with occupational exposure to respirable quartz dust. The combined average effect estimate of respirable quartz dust on spirometric parameters was obtained using a random effects model meta-analysis. Between-study heterogeneity was assessed via the I(2) statistic. Most studies found a significant negative association of FEV1 and FEV1/FVC related to increasing exposure to crystalline quartz at the workplace. One study found an effect only for smokers, and one did not observe such an effect at all. The meta-analysis of cross-sectional studies showed that the mean ratio FEV1 to FVC was reduced and FEV1 of workers exposed to respirable quartz dust was 4.6% less than predicted compared with workers with no/low exposure. Both results showed a statistically significant difference. Occupational exposure to respirable quartz dust was associated with a statistically significant decrease in FEV1 and FEV1/FVC, revealing airway obstruction consistent with COPD.

Medical risks in older pilots: a systematic review on incapacitation and age.

PURPOSE: Our ageing society faces an ageing work force. The target of this systematic review was to analyse whether pilots have a measurable age-dependent increased risk of incapacitation due to medical reasons. METHODS: Publications listed in PubMed, NCBI and EMBASE were identified using defined terms. Two independent raters analysed 2,342 retrieved publications by predefined criteria. Ten publications met the inclusion criteria. RESULTS: Four publications use a similar numerator (in-flight incapacitation) and identical denominator (flight hours) and show in-flight incapacitation of pilots happening 0.19-0.45 times/10(6) flight hours. Two of these studies did not analyse the possible correlation of incapacitation and age, and two did not use the denominator flight hours here. Age dependency of incapacitation is analysed in seven publications: Three analyse in-flight incapacitation and four analyse general incapacitation to fly. All but one--the only one including professional pilots older than 60 years--show an age-depending increase in incapacitation. The increase in in-flight incapacitation is far less than the increase in general flight incapacitation. CONCLUSIONS: Medical in-flight incapacitation is a very rare event. Whether the increase in in-flight incapacitation results in an increase in accidents or can be compensated for by error reduction through experience cannot be answered. A register of all pilots with a clear identification system to follow their career and health, their accidents and impairments, might help to reconsider the grounding of pilots over 60 and to define better criteria than mere age.

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.

Pilots' age and incidents in helicopter emergency medical services: a 5-year observational study.

BACKGROUND: Helicopter emergency medical services (HEMS) are considered to have a higher risk of incidents compared to other airborne operations. As HEMS poses high cognitive demands, age-related cognitive changes of helicopter pilots might become a safety risk. The aim of this study was to estimate the association between the age of pilots and incidents in HEMS. METHODS: We conducted a retrospective observational study of incidents during HEMS operations of one Austrian and two German air rescue organizations between 2007 and 2011. The sample included 257 regularly operating HEMS pilots. Age of the pilots varied between 44.52 yr (SD = 7.80) in 2007 and 46.57 yr (SD = 8.14) in 2011. Incidents were categorized as the number of HEMS operations with at least one liability damage (LD). Statistical analyses used multilevel growth curve modeling with generalized linear mixed models. RESULTS: 1770 LD were observed during 402.372 HEMS operations (approximately four LD per 1000 operations). From 2007 to 2011 the average number of LD per year varied between M = 0.95-1.77 for pilots < 35 yr to M = 0.25-1.53 for pilots > or = 60 yr. There was no statistically significant main effect of pilot's age on the number of LD. There was a trend of an interaction effect between age and time, which suggests that pilots with higher age tended to be involved in slightly fewer LD with time than younger pilots. DISCUSSION: In sum, findings provide no evidence that older pilots have a higher risk than younger pilots of being involved in an incident during HEMS operations.

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.

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.

Cutting edge: memory CD8 T cell compartment grows in size with immunological experience but nevertheless can lose function.

The size of the adaptive immune system is considered to be kept constant by the attrition of pre-existing memory. However, recently it was shown that the CD8 memory compartment can grow in size and the number of pre-existing memory is largely preserved, predicting that pre-existing immunity should be maintained (Vezys et al.; Nature 457: 196-199). Experimental proof for this assumption is still lacking. We address this question in the Listeria monocytogenes (L.m.) infection model and confirm the growth of size of the memory compartment by subsequent vaccination with modified vaccinia virus Ankara. We also find only modest attrition of pre-existing L.m.-specific memory CD8 T cells. However, pre-existing protective immunity toward L.m. is not preserved. Pre-existing L.m.-specific effector-memory cells, in contrast to central memory cells, become altered, and this results in a significant loss of pre-existing protective immunity. Our findings are clinically relevant for vaccines introducing new CD8 memory cells in high numbers, as this might influence pre-existing immunity.

Specific CD8 T cells in IgE-mediated allergy correlate with allergen dose and allergic phenotype.

RATIONALE: Studies in humans and rodents have indicated a causative role for CD8(+) T cells in IgE-mediated allergic inflammation, but their function is still controversial. OBJECTIVES: To analyze the role of allergen-specific CD8(+) T cells during the development of allergic airway inflammation in two parallel but diverging outcome models. METHODS: We used H2-Kb SIINFEKL (OVA(257-264)) multimers to analyze induction, natural distribution, and phenotype of allergen-specific CD8(+) T cells in a murine C57BL/6 model of ovalbumin (OVA)-induced allergic airway inflammation using low-dose or high-dose OVA sensitization. MEASUREMENTS AND MAIN RESULTS: The low-dose protocol was characterized by a significant induction of total and OVA-specific IgE, eosinophilic airway inflammation, IL-4 levels in bronchoalveolar lavage fluid. And significant alterations in lung function. The high dose protocol was characterized by a significant reduction of the allergic phenotype. Using OVA(257-264) H2-Kb multimers, we observed lung and airway infiltrating OVA-specific CD8(+) T cells showing an effector/effector-memory phenotype. The high-dose protocol caused significantly higher infiltration of allergen-specific CD8(+) cells to the airways and enhanced their cytotoxicity. Adoptive transfer with CD8(+) T cells from transgenic OT-I mice to TAP1(-/-) or wild-type mice showed their migration to the lungs and TAP1-dependent proliferation after OVA-aerosol exposure. TAP1(-/-) mice defective in CD8(+) T cells showed exacerbated symptoms in the low-dose sensitization model. CONCLUSIONS: Allergen-specific CD8(+) T cells seem to protect from allergic inflammation in the lungs. Their number, which is dependent on the sensitization dose, appears to be a critical predictor for the severity of the allergic phenotype.

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.

Spatial distribution of physiologic 12-lead QRS complex.

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 < 0.00001-measured at resting heart rate of 60 beats per minute) while the second component demonstrated larger proportion of the QRS power in males compared to females (33.1 ± 11.9% vs 29.6 ± 11.4%, p < 0.001). The analysis also showed that the components attributable to localised depolarisation sequence abnormalities were significantly larger in males compared to females (2.85 ± 1.08% vs 2.42 ± 0.87%, p < 0.00001). In addition to the demonstration of the technology, the study concludes that the detailed convolution of the depolarisation waveform is individual, and that smoother and less intricate depolarisation propagation is the mechanism likely responsible for shorter QRS duration in females.

Nocturnal respiratory rate predicts ICD benefit: A prospective, controlled, multicentre cohort study.

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<18 brpm showed a marked ICD benefit on mortality (adjusted HR 0.529 (95% CI 0.376-0.746); p = 0.0003), no treatment effect was demonstrated in 655 patients with NRR≥18 brpm (adjusted HR 0.981 (95% CI 0.669-1.438); p = 0.9202). INTERPRETATION: In the EU-CERT-ICD trial, patients with NRR≥18 brpm showed limited benefit from primary prophylactic ICD implantation. Those with NRR<18 brpm benefitted substantially. FUNDING: European Community's 7th Framework Programme FP7/2007-2013 (602299).

Remote monitoring of COVID-19 positive high-risk patients in domestic isolation: A feasibility study.

BACKGROUND: If a COVID-19 patient develops a so-called severe course, he or she must be taken to hospital as soon as possible. This proves difficult in domestic isolation, as patients are not continuously monitored. The aim of our study was to establish a telemonitoring system in this setting. METHODS: Oxygen saturation, respiratory rate, heart rate and temperature were measured every 15 minutes using an in-ear device. The data was transmitted to the Telecovid Centre via mobile network or internet and monitored 24/7 by a trained team. The data were supplemented by daily telephone calls. The patients´ individual risk was assessed using a modified National Early Warning Score. In case of a deterioration, a physician initiated the appropriate measures. Covid-19 Patients were included if they were older than 60 years or fulfilled at least one of the following conditions: pre-existing disease (cardiovascular, pulmonary, immunologic), obesity (BMI >35), diabetes mellitus, hypertension, active malignancy, or pregnancy. FINDINGS: 153 patients (median age 59 years, 77 female) were included. Patients were monitored for 9 days (median, IQR 6-13 days) with a daily monitoring time of 13.3 hours (median, IQR 9.4-17.0 hours). 20 patients were referred to the clinic by the Telecovid team. 3 of these required intensive care without invasive ventilation, 4 with invasive ventilation, 1 of the latter died. All patients agreed that the device was easy to use. About 90% of hospitalised patients indicated that they would have delayed hospitalisation further if they had not been part of the study. INTERPRETATION: Our study demonstrates the successful implementation of a remote monitoring system in a pandemic situation. All clinically necessary information was obtained and adequate measures were derived from it without delay.

Heart Rate Influence on the QT Variability Risk Factors.

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 < 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 < 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.

Heart Rate Dependency and Inter-Lead Variability of the T Peak - T End Intervals.

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.

Physiologic heart rate dependency of the PQ interval and its sex differences.

On standard electrocardiogram (ECG) PQ interval is known to be moderately heart rate dependent, but no physiologic details of this dependency have been established. At the same time, PQ dynamics is a clear candidate for non-invasive assessment of atrial abnormalities including the risk of atrial fibrillation. We studied PQ heart rate dependency in 599 healthy subjects (aged 33.5 ± 9.3 years, 288 females) in whom drug-free day-time 12-lead ECG Holters were available. Of these, 752,517 ECG samples were selected (1256 ± 244 per subject) to measure PQ and QT intervals and P wave durations. For each measured ECG sample, 5-minute history of preceding cardiac cycles was also obtained. Although less rate dependent than the QT intervals (36 ± 19% of linear slopes), PQ intervals were found to be dependent on underlying cycle length in a highly curvilinear fashion with the dependency significantly more curved in females compared to males. The PQ interval also responded to the heart rate changes with a delay which was highly sex dependent (95% adaptation in females and males after 114.9 ± 81.1 vs 65.4 ± 64.3 seconds, respectively, p < 0.00001). P wave duration was even less rate dependent than the PQ interval (9 ± 10% of linear QT/RR slopes). Rate corrected P wave duration was marginally but significantly shorter in females than in males (106.8 ± 8.4 vs 110.2 ± 7.9 ms, p < 0.00001). In addition to establishing physiologic standards, the study suggests that the curvatures and adaptation delay of the PQ/cycle-length dependency should be included in future non-invasive studies of atrial depolarizations.