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Cardiac resynchronization therapy (CRT) greatly reduces morbidity and mortality in patients with dyssynchronous heart failure. However, despite tremendous efforts, response has been variable and can be further improved. Although optimizing left ventricular lead placement (LVLP) is arguably the cornerstone of CRT, the procedure of LVLP using the transvenous approach has remained largely unchanged for more than 2 decades. Improvements have been developed using scar location and electrical and/or mechanical mapping, and interest in conduction system pacing as an alternative to biventricular pacing has emerged recently. Conduction system pacing is promising but may not be suitable for all patients with dyssynchronous heart failure. This review underscores the importance of a patient-tailored approach and discusses the potential applications of both conduction system pacing and targeted biventricular CRT. [ABSTRACT FROM AUTHOR]

Background: Segment length in cine (SLICE) strain analysis on standard cardiovascular magnetic resonance (CMR) cine images was recently validated against gold standard myocardial tagging. The present study aims to explore predictive value of SLICE for cardiac resynchronization therapy (CRT) response. Methods and results: Fifty-seven patients with heart failure and left bundle branch block (LBBB) were prospectively enrolled in this multi-center study and underwent CMR examination before CRT implantation. Circumferential strains of the septal and lateral wall were measured by SLICE on short-axis cine images. In addition, timing and strain pattern parameters were assessed. After twelve months, CRT response was quantified by the echocardiographic change in left ventricular (LV) end-systolic volume (LVESV). In contrast to timing parameters, strain pattern parameters being systolic rebound stretch of the septum (SRSsep), systolic stretch index (SSIsep-lat), and internal stretch factor (ISFsep-lat) all correlated significantly with LVESV change (R − 0.56; R − 0.53; and R − 0.58, respectively). Of all strain parameters, end-systolic septal strain (ESSsep) showed strongest correlation with LVESV change (R − 0.63). Multivariable analysis showed ESSsep to be independently related to LVESV change together with age and QRSAREA. Conclusion: The practicable SLICE strain technique may help the clinician to estimate potential benefit from CRT by analyzing standard CMR cine images without the need for commercial software. Of all strain parameters, end-systolic septal strain (ESSsep) demonstrates the strongest correlation with reverse remodeling after CRT. This parameter may be of special interest in patients with non-strict LBBB morphology for whom CRT benefit is doubted. [ABSTRACT FROM AUTHOR]

Background: The anesthetized, complete chronic atrioventricular block (CAVB) dog model allows reproducible inducibility of torsades de pointes (TdP) arrhythmias due to ventricular remodeling and after a challenge with an IKr blocker. High-rate pacing (HRP) prevents ventricular arrhythmias but has long-term detrimental effects on cardiac function when applied continuously. Temporal dispersion of repolarization, quantified as short-term variability (STV), increases before ventricular arrhythmias and has been proposed as a marker to guide HRP.Objective: The purpose of this proof-of-principle study was to show that automatically determined STV can guide HRP to prevent imminent ventricular arrhythmias.Methods: Eight CAVB dogs were implanted with an implantable cardioverter-defibrillator (ICD) with software to automatically determine STV (STVICD) in real time. During HRP, STV was measured offline from right ventricular (RV) electrograms (EGMs) and left ventricular (LV) monophasic action potential durations (MAPDs) (STVRV,EGM/LV,MAPD). The CAVB dogs were challenged twice with dofetilide (0.025 mg/kg intravenously over 5 minutes or until the first TdP). In experiment 1, the individual STVICD threshold before the first arrhythmic event was determined and programmed into the ICD. In experiment 2, HRP with 100 bpm was initiated automatically once the STVICD threshold was reached.Results: In experiment 1, 8 of 8 dogs had repetitive TdP, and STVICD increased from 0.96 ± 0.42 ms to 2.10 ± 1.26 ms (P <.05). In experiment 2, all dogs reached the STV threshold. HRP decreased STVRV,EGM/LV,MAPD from 2.02 ± 1.12 ms to 0.78 ± 0.28 ms, which was accompanied by prevention of TdP in 7 of 8 dogs.Conclusion: STV can guide HRP automatically by an ICD to prevent ventricular arrhythmias. [ABSTRACT FROM AUTHOR]

Background: Cardiac resynchronization therapy (CRT) is an established treatment in patients with heart failure and conduction abnormalities. However, a significant number of patients do not respond to CRT. Currently employed criteria for selection of patients for this therapy (QRS duration and morphology) have several shortcomings. QRS area was recently shown to provide superior association with CRT response. However, its assessment was not fully automated and required the presence of an expert.Objective: Our objective was to develop a fully automated method for the assessment of vector-cardiographic (VCG) QRS area from electrocardiographic (ECG) signals.Methods: Pre-implantation ECG recordings (N = 864, 695 left-bundle-branch block, 589 men) in PDF files were converted to allow signal processing. QRS complexes were found and clustered into morphological groups. Signals were converted from 12‑lead ECG to 3‑lead VCG and an average QRS complex was built. QRS area was computed from individual areas in the X, Y and Z leads. Practical usability was evaluated using Kaplan-Meier plots and 5-year follow-up data.Results: The automatically calculated QRS area values were 123 ± 48 μV.s (mean values and SD), while the manually determined QRS area values were 116 ± 51 ms; the correlation coefficient between the two was r = 0.97. The automated and manual methods showed the same ability to stratify the population (hazard ratios 2.09 vs 2.03, respectively).Conclusion: The presented approach allows the fully automatic and objective assessment of QRS area values.Significance: Until this study, assessing QRS area values required an expert, which means both additional costs and a risk of subjectivity. The presented approach eliminates these disadvantages and is publicly available as part of free signal-processing software. [ABSTRACT FROM AUTHOR]

Background: In the chronic atrioventricular block (CAVB) dog model, beat-to-beat variation of repolarization in the left ventricle (LV) quantified as short-term variability of the left monophasic action potential duration (STVLVMAPD) increases abruptly upon challenge with a proarrhythmic drug. This increase occurs before the first ectopic beat (EB), specifically in subjects who demonstrate subsequent repetitive torsades de pointes arrhythmias (TdP).Objective: The purpose of this study was to demonstrate that STV is feasible to monitor arrhythmic risk through use of the intracardiac electrogram (EGM) derived from the right ventricular (RV) lead from pacemakers or implantable cardioverter-defibrillators.Methods: In 30 anaesthetized, inducible (≥3 TdP) CAVB dogs, STV between LV and RV monophasic action potential duration (STVLVMAPD and STVRVMAPD) was compared. In prospectively enrolled CAVB dogs, STV of the activation-recovery interval (ARI) derived from the RV EGM (STVRVARI) was measured before and after a challenge with dofetilide under anesthesia (2a; n = 10) and cisapride under awake conditions (2b; n = 8).Results: Both STVLVMAPD and STVRVMAPD increased before the first EB (1.29 ± 0.58 ms to 3.05 ± 1.70 ms and 1.11 ± 0.53 ms to 2.18 ± 1.43 ms, respectively; P = 0.001). STVRVARI increased from 2.82 ± 0.33 ms to 3.77 ± 0.69 ms (P = .001). Inducible subjects (4/8) showed an increase in STVRVARI from 2.65 ± 0.55 ms to 3.45 ± 0.33 ms (in the first hour; P = .02) and 4.20 ± 1.33 ms (before the first EB; P = .04).Conclusion: Behavior of STV from the RV and LV is comparable. STVRVARI increases significantly before the occurrence of an arrhythmia in awake and anaesthetized conditions. This finding can be integrated into devices to monitor arrhythmic risk. [ABSTRACT FROM AUTHOR]

Background: Pacing at higher rates is known to suppress torsade de pointes (TdP) arrhythmias. Nevertheless, exact application and mechanism need further clarification. In the anesthetized canine chronic atrioventricular block model, ventricular remodeling is responsible for a high and reproducible incidence of TdP upon a challenge with dofetilide.Objective: We used this model to investigate by what mechanism accelerated pacing averts TdP and what repolarization parameter could be used to guide temporary accelerated pacing (TAP).Methods: Ten dogs with repetitive TdP after administration of dofetilide when paced at 60 beats/min were selected. In a serial experiment, TAP was initiated at 100 beats/min after the first ectopic beat. Electrocardiogram and right and left ventricular (LV) monophasic action potential durations (MAPDs) were recorded. In a subset, vertical dispersion was determined with a duodecapolar catheter. Temporal dispersion was quantified as short-term variability (STV). Arrhythmias were quantified with the arrhythmia score.Results: The increase in repolarization parameters observed after administration of dofetilide was counteracted by TAP (eg, LV MAPD from 381 ± 94 ms back to 310 ± 17 ms; P < .05). Temporal dispersion (STVLVMAPD) increased from 0.69 ± 0.37 to 2.59 ± 0.96 ms (P < .05) after administration of dofetilide and back to 1.15 ± 0.54 ms (P < .05) with TAP. This was accompanied by suppression of recurrent TdP in 7 of 10 dogs (P < .05) and a trend toward reduction in vertical (spatial) dispersion from 56 ± 25 to 31 ± 4 ms (P = .06). In those dogs, seconds after capture of TAP, almost all ectopy disappeared, causing a decrease in arrhythmia score from 21 ± 12 to 4 ± 3 (P < .05).Conclusion: TAP is effective in averting TdP by decreasing spatial and temporal measures of repolarization. Increase in temporal dispersion (STV) can guide TAP. [ABSTRACT FROM AUTHOR]

Background: Prolonged ventricular fibrillation (VF) detection has been shown to reduce implantable cardioverter-defibrillator (ICD) therapies and improve prognosis in primary prevention ICD patients. Data in secondary prevention patients are limited.Objective: The PainFree SST secondary prevention study is the largest trial of secondary prevention patients randomized between standard and prolonged detection to assess the safety of this strategy in these patients.Methods: A total of 705 secondary prevention patients implanted with an ICD in the PainFree SST trial were enrolled in this substudy; 353 patients were randomized to VF detection of 18/24 intervals and 352 patients to 30/40. All other VF parameters were standardized by protocol.Results: The 1-year arrhythmic syncope-free rates in the standard and prolonged groups were 97.7% vs 96.9%, respectively, (P = .0034 for noninferiority). Freedom from all-cause syncope was 96% in both arms (P = .0013 for noninferiority). There was no difference in the time to first appropriate or inappropriate VF therapy. However, the rates of treated VF episodes were lower in the prolonged arm (1.48 per patient per year vs 0.44 per patient per year, P = .0001). A trend toward lower mortality in the prolonged group was not statistically different (5.6% 1 year, 12% 2 years vs 3.8% 1 year, 7.7% 2 years, adjusted hazard ratio = 0.60, P = .061).Conclusion: This large prospective randomized study shows that prolonged detection can safely be programmed in secondary prevention ICD patients with new or existing devices. This programming strategy decreases the rate of treated events and is not associated with an increased risk of syncope or mortality. [ABSTRACT FROM AUTHOR]

Background: Studies on the relationship between left ventricular reverse remodeling and cardiopulmonary exercise capacity in heart failure patients undergoing cardiac resynchronization therapy (CRT) are scarce and inconclusive.Methods and Results: Eighty-four patients with a 1st-time CRT-defibrillator (mean age 65 ± 11; 73% male) underwent echocardiography and cardiopulmonary exercise testing (CPX) before implantation (baseline) and 6 months after implantation. At baseline, patients also completed a set of questionnaires measuring mental and physical health. The association between echocardiographic response (left ventricular end-systolic volume decrease ≥15%) and a comprehensive set of CPX results was examined. Echocardiographic responders (54%) demonstrated higher peak oxygen consumption and better exercise performance than nonresponders at baseline and at 6-month follow-up. Furthermore, only echocardiographic responders showed improvements in ventilatory efficiency during follow-up. Multivariable repeated measures analyses revealed that, besides reverse remodeling, New York Heart Association functional class II and good patient-reported health status before implantation were the most important correlates of higher average oxygen consumption during exercise, and that nonischemic etiology and smaller pre-implantation QRS width were associated with better ventilatory efficiency over time.Conclusions: During the first 6 months of CRT there was a significant positive association between reverse remodeling and cardiopulmonary exercise capacity. [ABSTRACT FROM AUTHOR]

Pharmacological safety evaluation of (pro) drugs includes cardiac safety assessment of proarrhythmic liability in healthy tissue with emphasis on the rapid component of the delayed rectifier (IKr). The lack of (1) an arrhythmic end point, (2) tests in remodeled, predisposed tissue, and (3) testing chronic drug influence on channel trafficking impairs on the drawn conclusions of these assays regarding drug safety. Moreover, the currently used human ether-à-go-go-related gene assays, action potential duration, prolongation in multicellular preparations, or the QT interval have significant shortcomings in their prediction of an increased risk for drug-induced torsades de pointes arrhythmia. In this review, it will be proposed that beat-to-beat variability of repolarization quantified as short-term variability can (1) discriminate between safe and unsafe drugs even under predisposed and highly arrhythmogenic conditions despite accompanying QT prolongation and (2) identify the individual at risk for subsequent arrhythmic events. [Copyright &y& Elsevier]

Abstract: Background: Septal rebound stretch (SRSsept) is a distinctive characteristic of discoordination-related mechanical inefficiency. We assessed how intermediate- and long-term outcome after cardiac resynchronization therapy (CRT) relate to baseline SRSsept. Methods and Results: A total of 101 patients (age 65 ± 11 years, 69 men, 18 New York Heart Association (NYHA) class IV, QRS 173 ± 23 ms) scheduled for CRT underwent clinical assessment, echocardiography, and brain-type natriuretic peptide (BNP) measurements before and 6.4 ± 2.3 months after CRT. Baseline SRSsept (all systolic stretch after initial shortening in the septum) was quantified by speckle tracking echocardiography. Primary composite end point was death, urgent cardiac transplantation, or left ventricular assist device implantation at the end of the study. Secondary end points were intermediate-term (6 months) response, quantified as decreases in left ventricular end-systolic volume (ΔLVESV) and BNP (ΔBNP). After a mean clinical follow-up of 15.6 ± 9.0 months; 23 patients had reached the primary end point. Baseline SRSsept (hazard ratio [HR] 0.742; 95% confidence intervals [CI] 0.601–0.916, P < .01]) was independently associated with a better outcome and NYHA class (HR 5.786: 95% CI 2.341–14.299, P < .001) with a worse outcome. Contrary to baseline NYHA class, baseline SRSsept was an independent predictor of both ΔLVESV (beta 0.53; P < .001) and ΔBNP (beta 0.29; P < .01). Intermediate-term ΔLVESV and ΔBNP were associated with a favorable long-term outcome. Conclusions: SRSsept at baseline is a strong, independent predictor of long-term prognosis after CRT and of improvements in left ventricular remodeling and neurohormonal activation at intermediate term. [Copyright &y& Elsevier]

Background: Implantable cardioverter-defibrillators (ICDs) are widely used to prevent fatal outcomes associated with life-threatening arrhythmic episodes in a variety of cardiac diseases. These ICDs rely on transvenous leads for cardiac sensing and defibrillation. A new entirely subcutaneous ICD overcomes problems associated with transvenous leads. However, the role of the subcutaneous ICD as an adjunctive or primary therapy in patients at risk for sudden cardiac death is unclear. Study Design: The PRAETORIAN trial is an investigator-initiated, randomized, controlled, multicenter, prospective 2-arm trial that outlines the advantages and disadvantages of the subcutaneous ICD. Patients with a class I or IIa indication for ICD therapy without an indication for bradypacing or tachypacing are included. A total of 700 patients are randomized to either the subcutaneous or transvenous ICD (1:1). The study is powered to claim noninferiority of the subcutaneous ICD with respect to the composite primary endpoint of inappropriate shocks and ICD-related complications. After noninferiority is established, statistical analysis is done for potential superiority. Secondary endpoint comparisons of shock efficacy and patient mortality are also made. Conclusion: The PRAETORIAN trial is a randomized trial that aims to gain scientific evidence for the use of the subcutaneous ICD compared with the transvenous ICD in a population of patients with conventional ICD with respect to major ICD-related adverse events. This trial is registered at ClinicalTrials.gov with trial ID NCT01296022. [ABSTRACT FROM AUTHOR]

Novel implantable cardioverter defibrillator (ICD) discrimination algorithms and programming strategies have significantly reduced the incidence of inappropriate shocks, but there are still gains to be made with respect to reducing appropriate but unnecessary antitachycardia pacing (ATP) and shocks. We examined whether programming a number of intervals to detect (NID) of 60/80 for ventricular tachyarrhythmia (VT)/ventricular fibrillation (VF) detection was safe and the impact of this strategy on (1) adverse events related to ICD shocks and syncopal events; (2) ATPs/shocks; and (3) patient-reported outcomes. The "ENHANCED Implantable Cardioverter Defibrillator programming to reduce therapies and improve quality of life" study (ENHANCED-ICD study) was a prospective, safety-monitoring study enrolling 60 primary and secondary prevention patients at the University Medical Center Utrecht. Patients implanted with any type of ICD with SmartShock technology and aged 18 to 80 years were eligible to participate. In all patients, a prolonged NID 60/80 was programmed. The cycle length for VT/fast VT/VF was 360/330/240 ms, respectively. Programming a NID 60/80 proved safe for ICD patients. Because of the new programming strategy, unnecessary ICD therapy was prevented in 10% of ENHANCED-ICD patients during a median follow-up period of 1.3 years. With respect to patient-reported outcomes, levels of distress were highest and perceived health status lowest at the time of implantation, which both gradually improved during follow-up. In conclusion, the ENHANCED-ICD study demonstrates that programming a NID 60/80 for VT/VF detection is safe for ICD patients and does not negatively impact their quality of life. [ABSTRACT FROM AUTHOR]

To date, no study has assessed the course of patient-reported health status in patients with an implantable cardioverter defibrillator (ICD). Studying health status trajectories and their baseline determinants would permit the identification of patients at risk for poor health outcomes after ICD implantation. A combined cohort of 1,222 patients with an ICD (79% men; age = 61.4 [11.2] years) completed the 12-Item Short-Form Health Survey at baseline and 2 to 3 months and 12 to 14 months after implantation. Latent class analyses were used to identify trajectories and predictors of health status over time. Most health status trajectories showed a stable pattern after short-term follow-up, with differences between trajectories being mainly related to differences in absolute levels of health status. Seven trajectories were identified for physical health status. Being unemployed, symptomatic heart failure, ICD shock, psychotropic medication, negative affectivity, and type D personality were identified as independent determinants of poorer physical health status. For mental health status, 6 trajectories were identified. Younger age, low educational level, symptomatic heart failure, renal failure, no use of ACE inhibitors, psychotropic medication, negative affectivity, and type D personality were identified as independent determinants of poorer mental health status. In conclusion, the population with an ICD seems to be heterogeneous in terms of patient-reported physical and mental health status. Patients with an ICD who present with poor health status and a distressed personality profile should be timely identified and monitored as they may benefit from cardiac rehabilitation in combination with behavioral intervention. [ABSTRACT FROM AUTHOR]

Abstract: In this article an international group of CRT specialists presents a comprehensive classification system for present and future schemes for optimising CRT. This system is neutral to the measurement technology used, but focuses on little-discussed quantitative physiological requirements. We then present a rational roadmap for reliable cost-effective development and evaluation of schemes. A widely recommended approach for AV optimisation is to visually select the ideal pattern of transmitral Doppler flow. Alternatively, one could measure a variable (such as Doppler velocity time integral) and “pick the highest”. More complex would be to make measurements across a range of settings and “fit a curve”. In this report we provide clinicians with a critical approach to address any recommendations presented to them, as they may be many, indistinct and conflicting. We present a neutral scientific analysis of each scheme, and equip the reader with simple tools for critical evaluation. Optimisation protocols should deliver: (a) singularity, with only one region of optimality rather than several; (b) blinded test–retest reproducibility; (c) plausibility; (d) concordance between independent methods; and (e) transparency, with all steps open to scrutiny. This simple information is still not available for many optimisation schemes. Clinicians developing the habit of asking about each property in turn will find it easier to winnow down the broad range of protocols currently promoted. Expectation of a sophisticated enquiry from the clinical community will encourage optimisation protocol-designers to focus on testing early (and cheaply) the basic properties that are vital for any chance of long term efficacy. [Copyright &y& Elsevier]