Real-world validation of smartphone-based photoplethysmography for rate and rhythm monitoring in atrial fibrillation.

AIMS: Photoplethysmography- (PPG) based smartphone applications facilitate heart rate and rhythm monitoring in patients with paroxysmal and persistent atrial fibrillation (AF). Despite an endorsement from the European Heart Rhythm Association, validation studies in this setting are lacking. Therefore, we evaluated the accuracy of PPG-derived heart rate and rhythm classification in subjects with an established diagnosis of AF in unsupervised real-world conditions. METHODS AND RESULTS: Fifty consecutive patients were enrolled, 4 weeks before undergoing AF ablation. Patients used a handheld single-lead electrocardiography (ECG) device and a fingertip PPG smartphone application to record 3907 heart rhythm measurements twice daily during 8 weeks. The ECG was performed immediately before and after each PPG recording and was given a diagnosis by the majority of three blinded cardiologists. A consistent ECG diagnosis was exhibited along with PPG data of sufficient quality in 3407 measurements. A single measurement exhibited good quality more often with ECG (93.2%) compared to PPG (89.5%; P < 0.001). However, PPG signal quality improved to 96.6% with repeated measurements. Photoplethysmography-based detection of AF demonstrated excellent sensitivity [98.3%; confidence interval (CI): 96.7-99.9%], specificity (99.9%; CI: 99.8-100.0%), positive predictive value (99.6%; CI: 99.1-100.0%), and negative predictive value (99.6%; CI: 99.0-100.0%). Photoplethysmography underestimated the heart rate in AF with 6.6 b.p.m. (95% CI: 5.8 b.p.m. to 7.4 b.p.m.). Bland-Altman analysis revealed increased underestimation in high heart rates. The root mean square error was 11.8 b.p.m. CONCLUSION: Smartphone applications using PPG can be used to monitor patients with AF in unsupervised real-world conditions. The accuracy of AF detection algorithms in this setting is excellent, but PPG-derived heart rate may tend to underestimate higher heart rates.

Orally Inhaled Flecainide for Conversion of Atrial Fibrillation to Sinus Rhythm: INSTANT Phase 2 Trial.

BACKGROUND: INSTANT (INhalation of flecainide to convert recent-onset SympTomatic Atrial fibrillatioN to sinus rhyThm) was a multicenter, open-label, single-arm study of flecainide acetate oral inhalation solution (FlecIH) for acute conversion of recent-onset (≤48 hours) symptomatic atrial fibrillation (AF) to sinus rhythm. OBJECTIVES: This study investigated the efficacy and safety in 98 patients receiving a single dose of FlecIH delivered via oral inhalation. METHODS: Patients self-administered FlecIH over 8 minutes in a supervised medical setting using a breath-actuated nebulizer and were continuously monitored for 90 minutes using a 12-lead Holter. RESULTS: Mean age was 60.5 years, mean body mass index was 27.0 kg/m2, and 34.7% of the patients were women. All patients had ≥1 AF-related symptoms at baseline, and 87.8% had AF symptoms for ≤24 hours. The conversion rate was 42.6% (95% CI: 33.0%-52.6%) with a median time to conversion of 14.6 minutes. The conversion rate was 46.9% (95% CI: 36.4%-57.7%) in a subpopulation that excluded predose flecainide exposure for the current AF episode. Median time to discharge among patients who converted was 2.5 hours, and only 2 patients had experienced AF recurrence by day 5. In the conversion-no group, 44 (81.5%) patients underwent electrical cardioversion by day 5. The most common adverse events were related to oral inhalation of flecainide (eg, cough, oropharyngeal irritation/pain), which were mostly of mild intensity and limited duration. CONCLUSIONS: The risk-benefit of orally inhaled FlecIH for acute cardioversion of recent-onset AF appears favorable. FlecIH could provide a safe, effective, and convenient first-line therapeutic option. (INhalation of Flecainide to Convert Recent Onset SympTomatic Atrial Fibrillation to siNus rhyThm [INSTANT]; NCT03539302).

Smartphone-based atrial fibrillation screening in the general population: feasibility and impact on medical treatment.

Aims: The aim of this study is to determine the feasibility, detection rate, and therapeutic implications of large-scale smartphone-based screening for atrial fibrillation (AF). Methods and results: Subjects from the general population in Belgium were recruited through a media campaign to perform AF screening during 8 consecutive days with a smartphone application. The application analyses photoplethysmography traces with artificial intelligence and offline validation of suspected signals to detect AF. The impact of AF screening on medical therapy was measured through questionnaires. Atrial fibrillation was detected in the screened population (n = 60.629) in 791 subjects (1.3%). From this group, 55% responded to the questionnaire. Clinical AF [AF confirmed on a surface electrocardiogram (ECG)] was newly diagnosed in 60 individuals and triggered the initiation of anti-thrombotic therapy in 45%, adjustment of rate or rhythm controlling strategies in 62%, and risk factor management in 17%. In subjects diagnosed with known AF before screening, a positive screening result led to these therapy adjustments in 9%, 39%, and 11%, respectively. In all subjects with clinical AF and an indication for oral anti-coagulation (OAC), OAC uptake increased from 56% to 74% with AF screening. Subjects with clinical AF were older with more co-morbidities compared with subclinical AF (no surface ECG confirmation of AF) (P < 0.001). In subjects with subclinical AF (n = 202), therapy adjustments were performed in only 7%. Conclusion: Smartphone-based AF screening is feasible at large scale. Screening increased OAC uptake and impacted therapy of both new and previously diagnosed clinical AF but failed to impact risk factor management in subjects with subclinical AF.

Detecting Paroxysmal Atrial Fibrillation From an Electrocardiogram in Sinus Rhythm: External Validation of the AI Approach.

BACKGROUND: Atrial fibrillation (AF) may occur asymptomatically and can be diagnosed only with electrocardiography (ECG) while the arrhythmia is present. OBJECTIVES: The aim of this study was to independently validate the approach of using artificial intelligence (AI) to identify underlying paroxysmal AF from a 12-lead ECG in sinus rhythm (SR). METHODS: An AI algorithm was trained to identify patients with underlying paroxysmal AF, using electrocardiographic data from all in- and outpatients from a single center with at least 1 ECG in SR. For patients without AF, all ECGs in SR were included. For patients with AF, all ECGs in SR starting 31 days before the first AF event were included. The patients were randomly allocated to training, internal validation, and testing datasets in a 7:1:2 ratio. In a secondary analysis, the AF prevalence of the testing group was modified. Additionally, the performance of the algorithm was validated at an external hospital. RESULTS: The dataset consisted of 494,042 ECGs in SR from 142,310 patients. Testing the model on the first ECG of each patient (AF prevalence 9.0%) resulted in accuracy of 78.1% (95% CI: 77.6%-78.5%), area under the receiver-operating characteristic curve of 0.87 (95% CI: 0.86-0.87), and area under the precision recall curve (AUPRC) of 0.48 (95% CI: 0.46-0.50). In a low-risk group (AF prevalence 3%), the AUPRC decreased to 0.21 (95% CI: 0.18-0.24). In a high-risk group (AF prevalence 30%), the AUPRC increased to 0.76 (95% CI: 0.75-0.78). This performance was robust when validated in an external hospital. CONCLUSIONS: The approach of using an AI-enabled electrocardiographic algorithm for the identification of patients with underlying paroxysmal AF from ECGs in SR was independently validated.

Reduced Left Atrial Appendage Flow Is Associated With Future Atrial Fibrillation After Cryptogenic Stroke.

BACKGROUND: Hemostasis within the left atrial appendage (LAA) is a common cause of stroke, especially in patients with atrial fibrillation (AF). Although LAA flow provides insights into LAA function, its potential for predicting AF has yet to be established. The aim of this study was to explore whether LAA peak flow velocities early after cryptogenic stroke are associated with future AF on prolonged rhythm monitoring. METHODS: A total of 110 patients with cryptogenic stroke were consecutively enrolled and underwent LAA pulsed-wave Doppler flow assessment using transesophageal echocardiography within the early poststroke period. Velocity measurements were analyzed offline by an investigator blinded to the results. Prolonged rhythm monitoring was conducted on all participants via 7-day Holter and implantable cardiac monitoring devices, with follow-up conducted over a period of 1.5 years to determine the incidence of AF. The end point of AF was defined as irregular supraventricular rhythm with variable RR interval and no detectable P waves lasting ≥30 sec during rhythm monitoring. RESULTS: During a median follow-up period of 539 days (interquartile range, 169-857 days), 42 patients (38%) developed AF, with a median time to AF diagnosis of 94 days (interquartile range, 51-487 days). Both LAA filling velocity and LAA emptying velocity (LAAev) were lower in patients with AF (44.3 ± 14.2 and 50.7 ± 13.3 cm/s, respectively) compared with patients without AF (59.8 ± 14.0 and 76.8 ± 17.3 cm/sec, respectively; P < .001 for both). LAAev was most strongly associated with future AF, with an area under the receiver operating characteristic curve of 0.88 and an optimal cutoff value of 55 cm/sec. Age and mitral regurgitation were independent determinants of reduced LAAev. CONCLUSIONS: Impaired LAA peak flow velocities (LAAev < 55 cm/sec) in patients with cryptogenic stroke are associated with future AF. This may facilitate the selection of appropriate candidates for prolonged rhythm monitoring to improve its diagnostic accuracy and implementation.

Individualized QT interval (QTi) is a powerful diagnostic tool in long QT syndrome: results from a large validation study.

Aims: Diagnosis of Long QT syndrome (LQTS) is based on prolongation of the QT interval corrected for heart rate (QTc) on surface ECG and genotyping. However, up to 25% of genotype positive patients have a normal QTc interval. We recently showed that individualized QT interval (QTi) derived from 24 h holter data and defined as the QT value at the intersection of an RR interval of 1,000 ms with the linear regression line fitted through QT-RR data points of each individual patient was superior over QTc to predict mutation status in LQTS families. This study aimed to confirm the diagnostic value of QTi, fine-tune its cut-off value and evaluate intra-individual variability in patients with LQTS. Methods: From the Telemetric and Holter ECG Warehouse, 201 recordings from control individuals and 393 recordings from 254 LQTS patients were analysed. Cut-off values were obtained from ROC curves and validated against an in house LQTS and control cohort. Results: ROC curves indicated very good discrimination between controls and LQTS patients with QTi, both in females (AUC 0.96) and males (AUC 0.97). Using a gender dependent cut-off of 445 ms in females and 430 ms in males, a sensitivity of 88% and specificity of 96% were achieved, which was confirmed in the validation cohort. No significant intra-individual variability in QTi was observed in 76 LQTS patients for whom at least two holter recordings were available (483 ± 36 ms vs. 489 ± 42 ms, p = 0.11). Conclusions: This study confirms our initial findings and supports the use of QTi in the evaluation of LQTS families. Using the novel gender dependent cut-off values, a high diagnostic accuracy was achieved.

The MADIT-ICD benefit score helps to select implantable cardioverter-defibrillator candidates in cardiac resynchronization therapy.

AIMS: The aim of this study is to evaluate whether the MADIT-ICD benefit score can predict who benefits most from the addition of implantable cardioverter-defibrillator (ICD) to cardiac resynchronization therapy (CRT) in real-world patients with heart failure with reduced ejection fraction (HFrEF) and to compare this with selection according to a multidisciplinary expert centre approach. METHODS AND RESULTS: Consecutive HFrEF patients who received a CRT for a guideline indication at a tertiary care hospital (Ziekenhuis Oost-Limburg, Genk, Belgium) between October 2008 and September 2016, were retrospectively evaluated. The MADIT-ICD benefit groups (low, intermediate, and high) were compared with the current multidisciplinary expert centre approach. Endpoints were (i) sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) and (ii) non-arrhythmic mortality. Of the 475 included patients, 165 (34.7%) were in the lowest, 220 (46.3%) in the intermediate, and 90 (19.0%) in the highest benefit group. After a median follow-up of 34 months, VT/VF occurred in 3 (1.8%) patients in the lowest, 9 (4.1%) in the intermediate, and 13 (14.4%) in the highest benefit group (P < 0.001). Vice versa, non-arrhythmic death occurred in 32 (19.4%) in the lowest, 32 (14.6%) in the intermediate, and 3 (3.3%) in the highest benefit group (P = 0.002). The predictive power for ICD benefit was comparable between expert multidisciplinary judgement and the MADIT-ICD benefit score: Uno's C-statistic 0.69 vs. 0.69 (P = 0.936) for VT/VF and 0.62 vs. 0.60 (P = 0.790) for non-arrhythmic mortality. CONCLUSION: The MADIT-ICD benefit score can identify who benefits most from CRT-D and is comparable with multidisciplinary judgement in a CRT expert centre.

Improving long QT syndrome diagnosis by a polynomial-based T-wave morphology characterization.

BACKGROUND: Diagnosing long QT syndrome (LQTS) remains challenging because of a considerable overlap in QT interval between patients with LQTS and healthy subjects. Characterizing T-wave morphology might improve LQTS diagnosis. OBJECTIVE: The purpose of this study was to improve LQTS diagnosis by combining new polynomial-based T-wave morphology parameters with the corrected QT interval (QTc), age, and sex in a model. METHODS: A retrospective cohort consisting of 333 patients with LQTS and 345 genotype-negative family members was used in this study. For each patient, a linear combination of the first 2 Hermite-Gauss (HG) polynomials was fitted to the STT segments of an average complex of all precordial leads and limb leads I and II. The weight coefficients as well as the error of the best fit were used to characterize T-wave morphology. Subjects were classified as patients with LQTS or controls by clinical QTc cutoffs and 3 support vector machine models fed with different features. An external cohort consisting of 72 patients and 45 controls was finally used to check the robustness of the models. RESULTS: Baseline QTc cutoffs were specific but had low sensitivity in diagnosing LQTS. The model with T-wave morphology features, QTc, age, and sex had the best overall accuracy (84%), followed by a model with QTc, age, and sex (79%). The model with T-wave morphology features especially performed better in LQTS type 3 patients (69%). CONCLUSION: T-wave morphologies can be characterized by fitting a linear combination of the first 2 Hermite-Gauss polynomials. Adding T-wave morphology characterization to age, sex, and QTc in a support vector machine model improves LQTS diagnosis.

Clinical and ECG variables to predict the outcome of genetic testing in hypertrophic cardiomyopathy.

Knowledge on the influence of specific genotypes on the phenotypic expression of hypertrophic cardiomyopathy (HCM) is emerging. The objective of this study was to evaluate the genotype-phenotype relation in HCM patients and to construct a score to predict the genetic yield based to improve counseling. Unrelated HCM patients who underwent genetic testing were included in the analysis. Multivariate logistic regression was performed to identify variables that predict a positive genetic test. A weighted score was constructed based on the odds ratios. In total, 378 HCM patients were included of whom 141 carried a mutation (global yield 37%), 181 were mutation negative and 56 only carried a variant of unknown significance. We identified age at diagnosis <45 years, familial HCM, familial sudden death, arrhythmic syncope, maximal wall thickness ≥20 mm, asymmetrical hypertrophy and the absence of negative T waves in the lateral ECG leads as significant predictors of a positive genetic test. When we included these values in a risk score we found very high correlation between the score and the observed genetic yield (Pearson r = 0.98). MYBPC3 mutation carriers more frequently suffered sudden cardiac death compared to troponin complex mutations carriers (p = 0.01) and a similar trend was observed compared to MYH7 mutation carriers (p = 0.08) and mutation negative patients (p = 0.11). To conclude, a simple score system based on clinical variables can predict the genetic yield in HCM index patients, aiding in counseling HCM patients. MYBPC3 mutation carriers had a worse outcome regarding sudden cardiac death.

Atrial fibrillation screening with photo-plethysmography through a smartphone camera.

AIMS: This cross-sectional study was set up to assess the feasibility of mass screening for atrial fibrillation (AF) with only the use of a smartphone. METHODS AND RESULTS: A local newspaper published an article, allowing to subscribe for a 7-day screening period to detect AF. Screening was performed through an application that uses photo-plethysmography (PPG) technology by exploiting a smartphone camera. Participants received instructions on how to perform correct measurements twice daily, with notifications pushed through the application's software. In case of heart rhythm irregularities, raw PPG signals underwent secondary offline analysis to confirm a final diagnosis. From 12 328 readers who voluntarily signed up for screening (49 ± 14 years; 58% men), 120 446 unique PPG traces were obtained. Photo-plethysmography signal quality was adequate for analysis in 92% of cases. Possible AF was detected in 136 individuals (1.1%). They were older (P < 0.001), more frequently men (P < 0.001), and had higher body mass index (P = 0.004). In addition, participants who strictly adhered to the recommended screening frequency (i.e. twice daily) were more often diagnosed with possible AF (1.9% vs. 1.0% in individuals who did not adhere; P = 0.008). Symptoms of palpitations, confusion, and shortness of breath were more frequent in case of AF (P < 0.001). The cumulative diagnostic yield for possible AF increased from 0.4% with a single heart rhythm assessment to 1.4% with screening during the entire 7-day screening period. CONCLUSION: Mass screening for AF using only a smartphone with dedicated application based on PPG technology is feasible and attractive because of its low cost and logistic requirements.

Sacubitril/valsartan reduces ventricular arrhythmias in parallel with left ventricular reverse remodeling in heart failure with reduced ejection fraction.

BACKGROUND: Sacubitril/valsartan reduced the occurrence of sudden cardiac death in the PARADIGM-HF trial. However, limited information is available about the mechanism. METHODS: Heart failure (HF)-patients receiving sacubitril/valsartan for a class-I indication equipped with an implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) with remote tele-monitoring were retrospectively analyzed. Device-registered arrhythmic-events were determined [ventricular tachycardia/fibrillation (VT/VF), appropriate therapy, non-sustained VT (NsVT; > 4beats and < 30 s), hourly premature ventricular contraction (PVC)-burden], following sacubitril/valsartan initiation (incident-analysis) and over an equal time period before initiation (antecedent-analysis). Reverse remodeling to sacubitril/valsartan was defined as an improvement of left ventricular ejection fraction of ≥ 5% between baseline and follow-up. RESULTS: A-total of 151 HF-patients with reduced LVEF (29 ± 9%) were included. Patients were switched from ACE-I or ARB to equal doses of sacubitril/valsartan (expressed as %-target-dose; before = 58 ± 30% vs. after = 56 ± 27%). The mean follow-up of both the incident and antecedent analysis was 364 days. Following the initiation, VT/VF-burden dropped (individual patients with VT/VF pre_n = 19 vs. post_n = 10, total-episodes of VT/VF pre_n = 51 vs. post_n = 14, both p < 0.001), resulting in reduced occurrence of appropriate therapy (pre_n = 16 vs. post_n = 6; p < 0.001). NsVT-burden per patient also dropped (mean episodes pre_n = 7.7 ± 11.8 vs. post_n = 3.7 ± 5.4; p < 0.001). There was no impact on atrial-fibrillation burden. PVC-burden dropped significantly which was associated with an improvement in BiV-pacing in patients with < 90% BiV-pacing at baseline. A higher degree of reverse remodeling was associated with a lower burden of NsVT and PVCs (both p < 0.05). CONCLUSION: Initiation of sacubitril/valsartan is associated with a lower degree of VT/VF, resulting in less ICD-interventions. This beneficial effect on ventricular arrhythmias might be related to cardiac reverse remodeling.

Prognostic value of electrocardiographic time intervals and QT rate dependence in hypertrophic cardiomyopathy.

INTRODUCTION: Preventing sudden cardiac death (SCD) is one of the main goals in hypertrophic cardiomyopathy (HCM). Many variables have been proposed, however the European and American guidelines do not incorporate any ECG or Holter monitoring derived variables other than the presence of ventricular arrhythmia in their risk stratification models. In the present study we evaluated electrocardiographic parameters in risk stratification of HCM. METHODS AND RESULTS: Novel electrocardiographic parameters including the index of cardio-electrophysiological balance (iCEB), individualized QT correction (QTi) and QT rate dependence were evaluated along with established risk factors. A composite endpoint of SCD was defined as out of hospital cardiac arrest, appropriate ICD shock and sustained ventricular tachycardia. Cox regression analysis was used to evaluate predictors of SCD. Out of the 466 HCM patients, 31 reached the composite endpoint during a follow up of 75 ±â€¯86 months. In a multivariate model, nor iCEB, QTi or QT rate dependence were predictors of SCD. Only male gender (p < 0.01; OR 13.1; CI 1.74-98.83), negative T waves in the inferior leads (p = 0.04; OR 2.51; CI 1.03-6.13) and familial sudden death (p < 0.01; OR 3.03; CI 1.39-6.59) were significant predictors. On top of either the ESC risk score or the 3 traditional 'American risk factors', only male gender was a significant predictor of SCD. CONCLUSION: No ECG or Holter monitoring parameters added in risk stratification for SCD in HCM. However, male gender and negative T waves in the inferior leads are promising novel markers to evaluate in larger cohorts.

Genotype-phenotype relationship and risk stratification in loss-of-function SCN5A mutation carriers.

INTRODUCTION: Loss-of-function (LoF) mutations in the SCN5A gene cause multiple phenotypes including Brugada Syndrome (BrS) and a diffuse cardiac conduction defect. Markers of increased risk for sudden cardiac death (SCD) in LoF SCN5A mutation carriers are ill defined. We hypothesized that late potentials and fragmented QRS would be more prevalent in SCN5A mutation carriers compared to SCN5A-negative BrS patients and evaluated risk markers for SCD in SCN5A mutation carriers. METHODS: We included all SCN5A loss-of-function mutation carriers and SCN5A-negative BrS patients from our center. A combined arrhythmic endpoint was defined as appropriate ICD shock or SCD. RESULTS: Late potentials were more prevalent in 79 SCN5A mutation carriers compared to 39 SCN5A-negative BrS patients (66% versus 44%, p = .021), while there was no difference in the prevalence of fragmented QRS. PR interval prolongation was the only parameter that predicted the presence of a SCN5A mutation in BrS (OR 1.08; p < .001). Four SCN5A mutation carriers, of whom three did not have a diagnostic type 1 ECG either spontaneously or after provocation with a sodium channel blocker, reached the combined arrhythmic endpoint during a follow-up of 44 ± 52 months resulting in an annual incidence rate of 1.37%. CONCLUSION: LP were more frequently observed in SCN5A mutation carriers, while fQRS was not. In SCN5A mutation carriers, the annual incidence rate of SCD was non-negligible, even in the absence of a spontaneous or induced type 1 ECG. Therefore, proper follow-up of SCN5A mutation carriers without Brugada syndrome phenotype is warranted.

Repeat genetic testing with targeted capture sequencing in primary arrhythmia syndrome and cardiomyopathy.

In inherited primary arrhythmia syndromes (PAS) and cardiomyopathies (CMP), the yield of genetic testing varies between 20 and 75% in different diseases according to studies performed in the pre next-generation sequencing (NGS) era. It is unknown whether retesting historical negative samples with NGS techniques is worthwhile. Therefore, we assessed the value of NGS-based panel testing in previously genotype negative-phenotype positive probands. We selected 107 patients (47 PAS and 60 CMP) with a clear phenotype who remained genotype negative after genetic analysis of the main genes implicated in their specific phenotype. Targeted sequencing of the coding regions of 71 PAS- and CMP-related genes was performed. Variant interpretation and classification was done according to a cardiology-specific scoring algorithm ('Amsterdam criteria') and the ACMG-AMP criteria. Co-segregation analysis was performed when DNA and clinical data of family members were available. Finally, a genetic diagnosis could be established in 21 patients (20%), 5 PAS (11%) and 16 CMP (27%) patients, respectively. The increased detection rate was due to sequencing of novel genes in 52% of the cases and due to technical failures with the historical analysis in 48%. A total of 118 individuals were informed about their carrier state and either reassured or scheduled for proper follow-up. To conclude, genetic retesting in clinically overt PAS and CMP cases, who were genotype negative with older techniques, resulted in an additional genetic diagnosis in up to 20% of the cases. This clearly supports a policy for genetic retesting with NGS-based panels.

Incremental benefit of cardiac resynchronisation therapy with versus without a defibrillator.

OBJECTIVE: To determine the incremental value of implantable cardioverter defibrillators (ICD) in contemporary optimally treated patients with heart failure (HF) undergoing cardiac resynchronisation therapy (CRT). METHODS: Consecutive patients with HF undergoing CRT-pacemaker (CRT-P) or CRT-defibrillator (CRT-D) implantation in a single tertiary care centre between October 2008 and August 2015 were retrospectively evaluated. For patients with a primary prevention indication of the CRT-D, no benefit of the ICD was defined as absence of appropriate therapy (device analysis) or lethal ventricular tachyarrhythmias (mode of death analysis) during follow-up. RESULTS: 687 patients (CRT-P/CRT-D; n=361/326) were followed for 38±22 months. CRT-P recipients were older (75.7±9.1 vs 71.8±9.3 years; p<0.001) and had a higher comorbidity burden. Five patients with CRT-P (1%) experienced episodes of sustained ventricular-tachycardia vs 64 (20%) patients with CRT-D (p<0.001). Remote tele-monitoring detected the episodes of sustained ventricular tachycardia in four patients with CRT-P, allowing for elective upgrade to CRT-D. All-cause mortality was higher in patients with CRT-P versus CRT-D (21% vs 12%, p=0.003), even after adjusting for baseline characteristics (HR 2.5; 95% CI 1.36 to 4.60; p=0.003). However, mode of death analysis revealed a predominant non-cardiac mode of death in CRT-P recipients (n=47 (71%) vs n=13 (38%) in CRT-D, p=0.002). Multivariate analysis revealed that age >80 years, New York Heart Association class IV, intolerance to beta-blockers and underlying non-ischaemic cardiomyopathy were independently associated with little incremental value of a primary prevention ICD on top of CRT. CONCLUSIONS: The majority of patients with contemporary HF as currently selected for CRT-P exhibit mainly non-cardiac-driven mortality. Weighing risk of ventricular-tachyarrhythmic death versus risk of all-cause mortality helps to address the incremental value of an ICD to CRT-P.

Individualized corrected QT interval is superior to QT interval corrected using the Bazett formula in predicting mutation carriage in families with long QT syndrome.

BACKGROUND: Long QT syndrome (LQTS) is characterized by reduced penetrance and variable QT prolongation over time, resulting in an estimate of 25% carriers of a pathogenic mutation with a normal corrected QT (QTc) interval on the resting electrocardiogram (ECG). OBJECTIVE: The purpose of this study was to test the hypothesis that an individualized corrected QT interval derived from 24-hour Holter data more accurately predicts carriage of a pathogenic LQTS mutation than did QT derived from a standard 12-lead ECG and corrected using the Bazett formula (QTc interval). METHODS: Carriers of a pathogenic LQTS mutation and their genotype-negative family members who had both resting ECG and Holter recordings available were included. Automated and manual measurements of QTc were performed. QTi was derived from 24-hour Holter recordings and defined as the QT value at the intersection of an RR interval of 1000 ms, with the linear regression line fitted through QT-RR data points of each individual patient. RESULTS: In total, 69 patients with LQTS (23 long QT type 1, 39 long QT type 2, and 7 long QT type 3) and 55 controls were selected. Demographic characteristics were comparable. A comparison of the receiver operating characteristic curves indicates that the test added diagnostic value compared to manual measurement (P = .02) or automated measurement (P = .005). The diagnostic accuracy of manually measured QTc using conventional cutoff criteria was 72%, while it was 92% using a sex-independent QTi cutoff of 445 ms. This was caused by a 39% increase in sensitivity without compromising the specificity. CONCLUSION: QTi derived from Holter recordings is superior to conventional QTc measured from a standard 12-lead ECG in predicting the mutation carrier state in families with LQTS.

Evaluation of Index of Cardio-Electrophysiological Balance (iCEB) as a New Biomarker for the Identification of Patients at Increased Arrhythmic Risk.

BACKGROUND: Recently a new risk marker for drug-induced arrhythmias called index of cardio-electrophysiological balance (iCEB), measured as QT interval divided by QRS duration, was evaluated in an animal model. It was hypothesized that iCEB is equivalent to the cardiac wavelength λ (λ = effective refractory period (ERP) x conduction velocity) and that an increased or decreased value of iCEB would potentially predict an increased susceptibility to TdP or non-TdP mediated VT/VF, respectively. METHODS: First, the correlation between QT interval and ERP was evaluated by invasively measuring ERP during a ventricular stimulation protocol in humans (N = 40). Then the effect of administration of sotalol and flecainide on iCEB was measured in 40 patients with supraventricular tachycardias. Finally iCEB was assessed in carriers of a long QT syndrome (LQTS, N = 70) or Brugada syndrome (BrS, N = 57) mutation and compared them with genotype negative family members (N = 65). RESULTS: The correlation between QT interval and ERP was established (Pearson R(2) = 0.25) which suggests that iCEB≈ERPxCV≈QT/QRS. Sotalol administration increased iCEB (+ 0.23; P = 0.01), while it decreased with the administration of flecainide (-0.21, P = 0.03). In the LQTS group iCEB was increased (5.22 ± 0.93, P < 0.0001) compared to genotype negative family members (4.24 ± 0.5), while it was decreased in the BrS group (3.52 ± 0.43, P < 0.0001). CONCLUSIONS: Our data suggest that iCEB (QT/QRS) is a simple but effective ECG surrogate of cardiac wavelength. iCEB is increased in situations that predispose to TdP and is decreased in situations that predispose to non-TdP mediated VT/VF. Therefore, iCEB might serve as a noninvasive and readily measurable marker to detect increased arrhythmic risk.