Efficacy of a web-based healthcare innovation to advance the quality of life and care of patients with an implantable cardioverter defibrillator (ACQUIRE-ICD): a randomized controlled trial.

AIMS: Modern clinical management of patients with an implantable cardioverter defibrillator (ICD) largely consists of remote device monitoring, although a subset is at risk of mental health issues post-implantation. We compared a 12-month web-based intervention consisting of goal setting, monitoring of patients' mental health-with a psychological intervention if needed-psychoeducational support from a nurse, and an online patient forum, with usual care on participants' device acceptance 12 months after implantation. METHODS AND RESULTS: This national, multi-site, two-arm, non-blinded, randomized, controlled, superiority trial enrolled 478 first-time ICD recipients from all 6 implantation centres in Denmark. The primary endpoint was patient device acceptance measured by the Florida Patient Acceptance Survey (FPAS; general score range = 0-100, with higher scores indicating higher device acceptance) 12 months after implantation. Secondary endpoints included symptoms of depression and anxiety. The primary endpoint of device acceptance was not different between groups at 12 months [B = -2.67, 95% confidence interval (CI) (-5.62, 0.29), P = 0.08]. Furthermore, the secondary endpoint analyses showed no significant treatment effect on either depressive [B = -0.49, 95% CI (-1.19; 0.21), P = 0.17] or anxiety symptoms [B = -0.39, 95% CI (-0.96; 0.18), P = 0.18]. CONCLUSION: The web-based intervention as supplement to usual care did not improve patient device acceptance nor symptoms of anxiety and depression compared with usual care. This specific web-based intervention thus cannot be recommended as a standardized intervention in ICD patients.

Workforce affiliation in primary and secondary prevention Implantable Cardioverter Defibrillator patients - a nationwide Danish study.

BACKGROUND AND AIM: There are a paucity of studies investigating workforce affiliation in connection with first-time ICD-implantation. This study explored workforce affiliation and risk markers associated with not returning to work in patients with ICDs. METHODS: Using the nationwide Danish registers, patients with a first-time ICD-implantation between 2007-2017 and of working age (30-65 years) were identified. Descriptive statistic and logistic regression models were used to describe workforce affiliation and to estimate risk markers associated with not returning to work, respectively. All analyses were stratified by indication for implantation (primary and secondary prevention). RESULTS: Of the 4,659 ICD-patients of working age, 3,300 patients (71%) were members of the workforce (employed, on sick leave or unemployed) (primary: 1428 (43%); secondary:1872 (57%)). At baseline, 842 primary and 1477 secondary prevention ICD-patients were employed. Of those employed at baseline, 81% primary and 75% secondary prevention ICD-patients returned to work within one-year, whereof more than 80% remained employed the following year. Among patients receiving sick leave benefits at baseline, 25% were employed after one-year. Risk markers of not returning to work were 'younger age' in primary prevention ICD-patients, while 'female sex', 'LVEF ≤40', 'lower income' and '≥3 comorbidities' were risk markers in secondary prevention ICD-patients. Lower educational level was a risk marker in both patient groups. CONCLUSIONS: High return-to-work proportions following ICD-implantation, with a subsequent high level of employment maintenance were found. Several significant risk markers of not returning to work were identified including 'lower educational level', that posed a risk in both patient groups.Trial registration number: Capital Region of Denmark, P-2019-051.

Atrial pacing minimization in sinus node dysfunction and risk of incident atrial fibrillation: a randomized trial.

BACKGROUND AND AIMS: High percentages of atrial pacing have been associated with an increased risk of atrial fibrillation. This study is aimed at evaluating whether atrial pacing minimization in patients with sinus node dysfunction reduces the incidence of atrial fibrillation. METHODS: In a nationwide, randomized controlled trial, 540 patients with sinus node dysfunction and an indication for first pacemaker implantation were assigned to pacing programmed to a base rate of 60 bpm and rate-adaptive pacing (DDDR-60) or pacing programmed to a base rate of 40 bpm without rate-adaptive pacing (DDD-40). Patients were followed on remote monitoring for 2 years. The primary endpoint was time to first episode of atrial fibrillation longer than 6 min. Secondary endpoints included longer episodes of atrial fibrillation, and the safety endpoint comprised a composite of syncope or presyncope. RESULTS: The median percentage of atrial pacing was 1% in patients assigned to DDD-40 and 49% in patients assigned to DDDR-60. The primary endpoint occurred in 124 patients (46%) in each treatment group (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.76-1.25, P = .83). There were no between-group differences in atrial fibrillation exceeding 6 or 24 h, persistent atrial fibrillation, or cardioversions for atrial fibrillation. The incidence of syncope or presyncope was higher in patients assigned to DDD-40 (HR 1.71, 95% CI 1.13-2.59, P = .01). CONCLUSIONS: Atrial pacing minimization in patients with sinus node dysfunction does not reduce the incidence of atrial fibrillation. Programming a base rate of 40 bpm without rate-adaptive pacing is associated with an increased risk of syncope or presyncope.

Treatment-induced increase in total body potassium in patients at high risk of ventricular arrhythmias; a randomized POTCAST substudy.

OBJECTIVE: Hypokalemia is associated with increased risk of arrhythmias and it is recommended to monitor plasma potassium (p-K) regularly in at-risk patients with cardiovascular diseases. It is poorly understood if administration of potassium supplements and mineralocorticoid receptor antagonists (MRA) aimed at increasing p-K also increases intracellular potassium. METHODS: Adults aged≥18 years with an implantable cardioverter defibrillator (ICD) were randomized (1:1) to a control group or to an intervention that included guidance on potassium rich diets, potassium supplements, and MRA to increase p-K to target levels of 4.5-5.0 mmol/l for six months. Total-body-potassium (TBK) was measured by a Whole-Body-Counter along with p-K at baseline, after six weeks, and after six months. RESULTS: Fourteen patients (mean age: 59 years (standard deviation 14), 79% men) were included. Mean p-K was 3.8 mmol/l (0.2), and mean TBK was 1.50 g/kg (0.20) at baseline. After six-weeks, p-K had increased by 0.47 mmol/l (95%CI:0.14;0.81), p = 0.008 in the intervention group compared to controls, whereas no significant difference was found in TBK (44 mg/kg (-20;108), p = 0.17). After six-months, no significant difference was found in p-K as compared to baseline (0.16 mmol/l (-0.18;0.51), p = 0.36), but a significant increase in TBK of 82 mg/kg (16;148), p = 0.017 was found in the intervention group compared to controls. CONCLUSIONS: Increased potassium intake and MRAs increased TBK gradually and a significant increase was seen after six months. The differentially regulated p-K and TBK challenges current knowledge on potassium homeostasis and the time required before the full potential of p-K increasing treatment can be anticipated. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT03833089).

A web-based intervention for patients with an implantable cardioverter defibrillator - A qualitative study of nurses' experiences (Data from the ACQUIRE-ICD study).

Objective: The aim of this study was to explore cardiac nurses' experiences with a comprehensive web-based intervention for patients with an implantable cardioverter defibrillator. Methods: We conducted an explorative qualitative study based on individual semi-structured interviews with 9 cardiac nurses from 5 Danish university hospitals. Results: We found one overall theme: "Between traditional nursing and modern eHealth". This theme was derived from the following six categories: (1) comprehensive content in the intervention, (2) patient-related differences in engagement, (3) following the protocol is a balancing act, (4) online communication challenges patient contact, (5) professional collaboration varies, and (6) an intervention with potential. Cardiac nurses were positive towards the web-based intervention and believe it holds a large potential. However, they felt challenged by not having in-person and face-to-face contact with patients, which they found valuable for assessing patients' wellbeing and psychological distress. Conclusion: Specific training in eHealth communication seems necessary as web-based care entails a shift in the nursing role and requires a different way of communication.InnovationFocusing on the user experience in web-based care from the perspective of cardiac nurses is innovative, and by applying implementation science this leads to new knowledge to consider when developing and implementing web-based care.

Patients with an implantable cardioverter defibrillator at risk of poorer psychological health during 24 months of follow-up (results from the Danish national DEFIB-WOMEN study).

OBJECTIVE: Identify implantable cardioverter defibrillator (ICD) patients at risk of distress (i.e., depression, anxiety, and ICD concerns) and associated risk factors. METHOD: First-time ICD patients (n = 1503) from the Danish national DEFIB-WOMEN study completed questionnaires at baseline, 3, 6, 12 and 24 months. RESULTS: Of patients with low scores on distress, only 4%-7.2% experienced an increase in distress during 24 months of follow-up (FU), while 30.5%-52.5% with increased levels were likely to maintain increased levels at FU. Higher education, higher age, female sex, and good physical functioning at baseline were associated with less depression, anxiety and ICD concerns at FU. Previous psychological problems, smoking, Type D personality, NYHA class III-IV - all assessed at baseline - and shocks during FU were associated with depression, anxiety and ICD concerns. CONCLUSIONS: Generally, patients' psychological health improved, but patients with increased baseline scores were more likely to have increased scores at FU. We need to be vigilant if patients report elevated distress, particularly if they have depression at baseline, as depression seems more persistent. Given the impact of depression on health-related quality of life and prognosis, they should be screened and monitored closely.

Impact of Nationwide COVID-19 Lockdowns on the Implantation Rate of Cardiac Implantable Electronic Devices.

AIM: The COVID-19 pandemic resulted in a significant decrease in the number of hospital admissions for severe emergent cardiovascular diseases during lockdowns worldwide. This study aimed to determine the impact of both the first and the second Danish nationwide lockdown on the implantation rate of cardiac implantable electronic devices (CIEDs). METHODS: We retrospectively analysed the number of CIED implantations performed in Denmark and stratified them into 3-week intervals. RESULTS: The total number of de novo CIED implantations decreased during the first lockdown by 15.5% and during the second by 5.1%. Comparing each 3-week interval using rate ratios, a significant decrease in the daily rates of the total number of de novo and replacement CIEDs (0.82, 95% CI [0.70, 0.96]), de novo CIEDs only (0.82, 95% CI [0.69, 0.98]), and non-acute pacemaker implantations (0.80, 95% CI [0.63, 0.99]) was observed during the first interval of the first lockdown. During the second lockdown (third interval), a significant decrease was seen in the daily rates of de novo CIEDs (0.73, 95% CI [0.55, 0.97]), and of pacemakers in total during both the second (0.78, 95% CI [0.62, 0.97]) and the third (0.60, 95% CI [0.42, 0.85]) intervals. Additionally, the daily rates of acute pacemaker implantation decreased during the second interval (0.47, 95% CI [0.27, 0.79]) and of non-acute implantation during the third interval (0.57, 95% CI [0.38, 0.84]). A significant increase was observed in the number of replacement procedures during the first interval of the second lockdown (1.70, 95% CI [1.04, 2.85]). CONCLUSIONS: Our study found only modest changes in CIED implantations in Denmark during two national lockdowns.

Targeted potassium levels to decrease arrhythmia burden in high risk patients with cardiovascular diseases (POTCAST): Study protocol for a randomized controlled trial.

BACKGROUND: Low plasma potassium (p-K) is associated with increased risk of malignant arrhythmia and observational studies indicate protective effects of p-K in the upper reference level. However, randomized clinical studies are needed to document whether actively increasing p-K to high-normal levels is possible and safe and improves cardiovascular outcomes. OBJECTIVE: To investigate if increased p-K reduces the risk of malignant arrhythmia and all-cause death in high-risk patients with a cardiovascular disease treated with an implantable cardioverter defibrillator (ICD) for primary or secondary preventive causes. Secondly, to investigate whether high-normal p-K levels can be safely reached and maintained using already available medications and potassium-rich dietary guidance. METHODS: This is a prospective, randomized, and open-labelled study enrolling patient at high-risk of malignant arrhythmias. According to sample size calculations, 1,000 patients will be randomized 1:1 to either an investigational regiment that aims to increase and maintain p-K at high-normal levels (4.5-5.0 mmol/L) or to usual standard of care and followed for an expected four years. The trial will run until a total of 291 events have occurred providing an α = 0.05 and 1-ß = 0.80. The composite primary endpoint includes ventricular tachycardia >125 bpm lasting >30 seconds, any appropriate ICD-therapy, and all-cause mortality. At present, 739 patients have been randomized. CONCLUSIONS: We present the rationale for the design of the POTCAST trial. The inclusion was initiated 2019 and is expected to be finished 2022. The study will show if easily available treatments to increase p-K may be a new treatment modality to protect against malignant arrythmias.

Driving following defibrillator implantation: a nationwide register-linked survey study.

AIMS: Patients are restricted from driving following implantable cardioverter defibrillator (ICD) implantation or shock. We sought to investigate how many patients are aware of, and adhere to, the driving restrictions, and what proportion experience an ICD shock or other cardiac symptoms while driving. METHODS AND RESULTS: We performed a nationwide survey of all living Danish residents 18 years or older who received a first-time ICD between 2013 and 2016 (n = 3913) and linked their responses with nationwide registers. Of 2741 respondents (47% primary prevention, 83% male, median age 67 years), 2513 (92%) held a valid driver's license at ICD implantation, 175 (7%) of whom had a license for professional driving. Many drivers were unaware of driving restrictions: primary prevention 58%; secondary prevention 36%; post-appropriate shock 28%; professional drivers 55%. Almost all (94%) resumed non-professional driving after ICD implantation, more than one-third during the restricted period; 35% resumed professional driving. During a median follow-up of 2.3 years, 5 (0.2%) reported receiving an ICD shock while driving, one of which resulted in a traffic accident. The estimated risk of harm was 0.0002% per person-year. CONCLUSION: In this nationwide study, many ICD patients were unaware of driving restrictions, and more than one third resumed driving during a driving restriction period. However, the rate of reported ICD shocks while driving was very low.

Sex differences in echocardiographic predictors of bradycardia detected by implantable loop recorder in patients with syncope and palpitations.

OBJECTIVE: Our aim was to investigate whether echocardiography may aid in identifying patients, specifically men, at risk of bradycardia as detected by implantable loop recorders (ILR) in patients evaluated for syncope and palpitations. METHODS: We included ambulatory patients undergoing ILR implantation for syncope (84%), presyncope (9%), and palpitations (8%). Echocardiographic examination was performed prior to implantation (2.9 months [IQR 1.0-6.0 months]). Echocardiograms were analyzed for conventional and speckle tracking parameters. We examined time to first event of bradycardia, defined as (a) heart rate <30 beats/min and (b) ≥4 beats, including sinus arrest, asystole, sinoatrial block, and second- and third-degree atrioventricular nodal block. We applied Cox proportional hazards models. RESULTS: A total of 285 patients we enrolled, and during a median time of 2.7 years [IQR 1.0, 3.3 years] of continuous heart rhythm monitoring, 84 (29%) had bradycardia detected by ILR. Patients with bradycardia were older (61 ± 19 years vs 55 ± 18 years, P = .01) and more frequently men (62% vs 44%, P = .01). Sex modified the association between echocardiographic parameters and bradycardia (P interaction <0.05 for all), such that left ventricular LV mass index (HR: 1.02 per 1g/m2 increase [1.01-1.04], P < .001), LV ejection fraction (HR: 1.04 per 1% decrease [1.01-1.08], P = .02), and global longitudinal strain (HR: 1.09 per 1% decrease [1.01-1.19], P = .03) were associated with bradycardia in men but not women (P > .05 for all in female). After adjusting for baseline clinical characteristics, medical therapy, and loop indication, the abovementioned parameters remained significantly associated with incident bradycardia in men. CONCLUSION: Echocardiographic parameters of LV structure and function may potentially be more useful for predicting bradycardia in men than women, among patients undergoing ILR implantation for syncope, presyncope, and palpations.

Usefulness of echocardiography for predicting ventricular tachycardia detected by implantable loop recorder in syncope patients.

Ventricular tachycardia (VT) may lead to syncope and sudden cardiac death. Implantable loop recorders (ILR) are recommended in the clinical work-up of patients with unexplained syncope. Our aim was to evaluate if echocardiographic parameters assessed prior to ILR implantation in patients with unexplained syncope may aid in identifying individuals with an increased risk of VT. The present study included 288 ambulatory patients (mean age 58 ± 19 years, 51% women) with syncope (90%) and presyncope (10%) who had an ILR implanted in the diagnostic workup. All patients underwent an echocardiographic examination prior to device implantation (median 3 months [IQR 1 to 6 months]). We examined incident VT, defined as a first-time episode of VT (> 30 s) or non-sustained VT (< 30 s) detected by the ILR. During median follow-up of 2.9 years [IQR 1.3 to 3.5 years] of continuous rhythm monitoring, 36 patients (13%) were diagnosed with incident VT (n = 25 non-sustained VT, n = 11 sustained VT). In unadjusted Cox proportional hazards models, left ventricular (LV) mass index (HR: 1.04 per 1 g/m2 increase [1.00 to 1.08], P = 0.047), mean LV wall thickness (HR: 1.36 per 1 mm increase [1.08 to 1.71], P = 0.009), and global longitudinal strain (HR: 1.15 per 1% decrease [1.05 to 1.25], P = 0.002) were significantly associated with VT. After adjusting for age, sex, implantable loop recorder indication and known heart failure, the above-mentioned parameters remained significantly associated with incident VT. LV mass index, LV wall thickness, and GLS may aid in identifying patients with increased risk of incident VT among patients with syncope. Echocardiography may potentially help select patients who can benefit from ILR.

Effectiveness of a comprehensive interactive eHealth intervention on patient-reported and clinical outcomes in patients with an implantable cardioverter defibrillator [ACQUIRE-ICD trial]: study protocol of a national Danish randomised controlled trial.

BACKGROUND: In Denmark and other countries, there has been a shift in the management of patients with an implantable cardioverter defibrillator (ICD) with remote device monitoring largely replacing in-hospital visits. Less patient-nurse and patient-physician interaction may lead to gaps in patients' quality of care and impede patients' adaptation to living successfully with the ICD. A comprehensive eHealth intervention that include goal-setting, monitoring of symptoms of depression, anxiety, and quality of life, psychological treatment, information provision, supportive tools, online dialogues with nursing staff and access to an online community network, may help fill these gaps and be particularly beneficial to patients who suffer from anxiety and depression. This study will evaluate the effectiveness of the ACQUIRE-ICD care innovation, a comprehensive and interactive eHealth intervention, on patient-reported and clinical outcomes. METHODS: The ACQUIRE-ICD study is a multicenter, prospective, two-arm, unblinded randomised controlled superiority trial that will enroll 478 patients implanted with a first-time ICD or ICD with cardiac synchronisation therapy (CRT-D) from the six implanting centers in Denmark. The trial will evaluate the clinical effectiveness and cost-effectiveness of the ACQUIRE-ICD care innovation, as add-on to usual care compared with usual care alone. The primary endpoint, device acceptance, assessed with the Florida Patient Acceptance Survey, is evaluated at 12 months' post implant. Secondary endpoints, evaluated at 12 and 24 months' post implant, include patient-reported outcomes, return to work, time to first ICD therapy and first hospitalisation, mortality and cost-effectiveness. DISCUSSION: The effectiveness of a comprehensive and interactive eHealth intervention that relies on patient-centred and personalised tools offered via a web-based platform targeted to patients with an ICD has not been assessed so far. The ACQUIRE-ICD care innovation promotes and facilitates that patients become active participants in the management of their disease, and as such addresses the need for a more patient-centered disease-management approach. If the care innovation proves to be beneficial to patients, it may not only increase patient empowerment and quality of life but also free up time for clinicians to care for more patients. TRIAL REGISTRATION: The trial has been registered on https://clinicaltrials.gov/ct2/show/NCT02976961 on November 30, 2016 with registration number [ NCT02976961 ].

Effects of angiotensin II receptor blockade on cerebral, cardiovascular, counter-regulatory, and symptomatic responses during hypoglycaemia in patients with type 1 diabetes.

INTRODUCTION: High spontaneous activity of the renin-angiotensin system (RAS) results in more pronounced cognitive impairment and more prolonged QTc interval during hypoglycaemia in type 1 diabetes. We tested whether angiotensin II receptor blockade improves cerebral and cardiovascular function during hypoglycaemia. METHODS: Nine patients with type 1 diabetes and high spontaneous RAS activity were included in a double-blind, randomised, cross-over study on the effect of angiotensin II receptor antagonist (candesartan 32 mg) or placebo for one week on cognitive function, cardiovascular parameters, hormonal counter-regulatory response, substrate mobilisation, and symptoms during hypoglycaemia induced by two hyperinsulinaemic, hypoglycaemic clamps. RESULTS: Compared to placebo, candesartan did neither change performance of the cognitive tests nor the EEG at a plasma glucose concentration of 2.6±0.2 mmol/l. During candesartan treatment, the QT interval in the ECG was not affected. No effect of candesartan was observed in the hormonal counter-regulatory responses, in substrate concentrations, or in symptom scores. A 36% reduced glucose infusion rate during hypoglycaemia with candesartan was observed. CONCLUSION: In conclusion candesartan has no effect on cerebral function during mild experimental hypoglycaemia in subjects with type 1 diabetes and high RAS activity. Candesartan may reduce glucose utilisation or increase endogenous glucose production during hypoglycaemia.

Cardiac repolarization during hypoglycaemia in type 1 diabetes: impact of basal renin-angiotensin system activity.

AIMS: Hypoglycaemia-induced cardiac arrhythmias may be involved in the pathogenesis of the 'dead-in-bed syndrome' in patients with type 1 diabetes. Evidence suggests that the renin-angiotensin system (RAS) influences the occurrence of arrhythmias. The aim of this study was to explore if basal RAS activity affects cardiac repolarization during hypoglycaemia, thereby potentially carrying prognostic information on risk of the 'dead-in-bed syndrome'. METHODS AND RESULTS: Nine subjects with high RAS activity and nine subjects with low RAS activity were subjected to single-blinded placebo-controlled hypoglycaemia (nadir plasma glucose 2.4 mmol/L). QTc/QTcF and QT dynamics were registered by Holter monitoring. QTc prolonged during [8 (+/-2.3) ms, P < 0.01] and after [11 (+/-3) ms, P < 0.001] hypoglycaemia. Dynamic QT parameters reacted ambiguously. Low RAS activity was associated with a slightly more pronounced QT prolongation [6 (+/-3) ms, P = 0.04]. Adrenaline tended to increase more in the low-RAS group (P = 0.08) and was correlated to QTc (r = 0.67, P < 0.01) and QTcF (r = 0.58, P < 0.05) during hypoglycaemia. CONCLUSION: Low basal RAS activity may be associated with a slightly more pronounced QT prolongation during hypoglycaemia, when compared with high RAS activity. The impact, however, is modest and the clinical consequence is unclear.

Cardiac repolarization during hypoglycaemia and hypoxaemia in healthy males: impact of renin-angiotensin system activity.

AIMS: Activity in the renin-angiotensin system (RAS) may influence the susceptibility to cardiac arrhythmia. To study the effect of basal RAS activity on cardiac repolarization during myocardial stress induced by hypoglycaemia or hypoxaemia in healthy humans. METHODS AND RESULTS: Ten subjects with high RAS activity and 10 subjects with low RAS activity were studied on three different occasions: (i) hypoglycaemia (nadir P-glucose 2.7 +/- 0.5 mmol/L), (ii) hypoxaemia (nadir pO(2) 5.8 +/- 0.5 kPa), and (iii) normoglycaemic normoxia (control day). QT parameters were registered by Holter monitoring. Hypoglycaemia and hypoxaemia induced QTc prolongation (P < 0.001, both stimuli). The QT/RR slope and the VR increased as a function of hypoglycaemia, but were unaffected by hypoxaemia. Low RAS activity was associated with a steeper QT/RR slope in the recovery phase after both stimuli: hypoglycaemia: P = 0.04; hypoxia: P = 0.03. RAS activity had no impact on QTc [P = 0.48 (hypoglycaemia) and P = 0.40 (hypoxaemia)] or any of the other outcome variables. CONCLUSION: Basal RAS activity has significant impact on QT dynamics, but not the corrected QT interval, during recovery from hypoglycaemia and hypoxaemia. The impact, however, is modest and more subtle than initially expected. The clinical relevance is unclear.

Beat-to-beat QT dynamics in paroxysmal atrial fibrillation.

BACKGROUND: QT dynamics parameters are used only in sinus rhythm. However, because many patients with paroxysmal atrial fibrillation undergo antiarrhythmic treatment that changes QT, developing methods for measuring QT dynamics during atrial fibrillation is important. OBJECTIVES: The purpose of this study was to evaluate whether QT dynamics in atrial fibrillation can be measured more reliably if additional RR intervals are included in the QT calculation. METHODS: QT and RR intervals were measured in 15 patients with atrial fibrillation and sinus rhythm on the same 24-hour Holter recording. Full QT adaptation is not instantaneous but lags behind over several beats. To correct for this lag, we adapted a weighted average method using five successive RR intervals. Linear regression was performed on (QT, RR) and (QT, RR(modified)) pairs. Variability ratio (standard deviation of all QT intervals/standard deviation of all RR intervals) and modified variability ratio (standard deviation of all QT intervals/modified standard deviation of all RR intervals) were calculated. RESULTS: QT-RR slope was reduced in atrial fibrillation compared with sinus rhythm (0.076 +/- 0.009 vs 0.113 +/- 0.0013, P = .0005). When correcting for lag, using the QT-RR(modified) slope, the slope in atrial fibrillation became similar to the slope in sinus rhythm (0.126 +/- 0.013 vs 0.126 +/- 0.013, P = .9547). The variability ratio was reduced in atrial fibrillation compared with sinus rhythm (0.175 +/- 0.017 vs 0.240 +/- 0.031, P = .009), but when correcting for the lag, the modified variability ratio was similar in atrial fibrillation and sinus rhythm (0.262 +/- 0.029 vs 0.267 +/- 0.038, P = .80). CONCLUSION: The results of this study demonstrate that QT dynamics can be measured reliably in atrial fibrillation using 24-hour Holter recordings.

QT dynamics in risk stratification after myocardial infarction.

OBJECTIVES: The purpose of this study was to compare measures of repolarization dynamics (QT dynamics) with other Holter risk predictors, left ventricular systolic function, and demographic characteristics to establish whether QT dynamics add independent information on risk stratification after myocardial infarction (MI). A novel QT dynamics parameter, the QT/RR variability ratio (VR), was introduced in this study. BACKGROUND: Abnormal repolarization contributes to arrhythmogenesis, and quantification of QT dynamics may have prognostic value after MI. METHODS: A 24-hour Holter recording was performed in 481 consecutive MI patients. Recordings from 311 patients were included in the analysis. QT/RR slope and intercept, mean and standard deviation of all QT, QTc, and RR intervals, and VR (defined as the ratio between the standard deviation of all QT intervals and the standard deviation of all RR interval) were calculated. Ventricular premature beats and ventricular tachycardia were counted. RESULTS: During 3-year follow-up, 70 deaths from all causes occurred. All parameters except mean of all QT intervals and standard deviation of all QTc intervals univariately predicted all-cause mortality. In multivariate Cox analysis, only VR per 0.1 (hazard ratio [HR]: 1.9 [1.5-2.4]), left ventricular ejection fraction per 5% (HR: 1.2 [1.1-1.3]), ventricular premature beats per 10 beats/hour (HR: 1.03 [1.002-1.06]), and age per 10 years (HR: 1.6 [1.3-2.0]) independently predicted all-cause mortality. CONCLUSIONS: Measures of QT dynamics univariately predicted total mortality. VR, left ventricular ejection fraction, ventricular premature beats, and age made up the optimal Cox model for risk stratification after MI. VR seems to be a promising risk factor for identifying sudden arrhythmic death.

Beat-to-beat QT dynamics in healthy subjects.

BACKGROUND: Measures of QT dynamics express repolarization abnormalities that carry prognostic information, but the reproducibility of beat-to-beat QT dynamics has never been established. The QT interval is prolonged at night, but how the circadian rhythm and heart rate influence the dynamic QT measurements is still unsettled. The aims of the present study were: (1) to describe the reproducibility of beat-to-beat QT dynamics with respect to intrasubject, between-subject, and between-observer variability and (2) to describe the normal range, circadian variation, and heart rate dependence of QT dynamics. METHODS: Ambulatory Holter recordings were performed three times on 20 healthy volunteers and were analyzed by two experienced cardiologists. Slope and intercept of the QT/RR regression, the variability of QT and R-R intervals expressed as the standard deviation, and the relation between QT and RR variability expressed as a variability ratio were measured among other QT dynamics. RESULTS: The reproducibility of all QT dynamics was good. All QT dynamics showed circadian variation when calculated on an hourly basis. The day/night variation in slope could be explained by the differences in heart rate, whereas the day/night variation in intercept was heart rate independent. CONCLUSION: The present study shows that reliable automatic QT measurements could be performed, encouraging further evaluation of the clinical value of QT dynamics in risk stratification of cardiac patients.