Integration and evaluation of a gradient-based needle navigation system for percutaneous MR-guided interventions.

The purpose of the present study was to integrate an interactive gradient-based needle navigation system and to evaluate the feasibility and accuracy of the system for real-time MR guided needle puncture in a multi-ring phantom and in vivo in a porcine model. The gradient-based navigation system was implemented in a 1.5T MRI. An interactive multi-slice real-time sequence was modified to provide the excitation gradients used by two sets of three orthogonal pick-up coils integrated into a needle holder. Position and orientation of the needle holder were determined and the trajectory was superimposed on pre-acquired MR images. A gel phantom with embedded ring targets was used to evaluate accuracy using 3D distance from needle tip to target. Six punctures were performed in animals to evaluate feasibility, time, overall error (target to needle tip) and system error (needle tip to the guidance needle trajectory) in vivo. In the phantom experiments, the overall error was 6.2±2.9 mm (mean±SD) and 4.4±1.3 mm, respectively. In the porcine model, the setup time ranged from 176 to 204 seconds, the average needle insertion time was 96.3±40.5 seconds (min: 42 seconds; max: 154 seconds). The overall error and the system error was 8.8±7.8 mm (min: 0.8 mm; max: 20.0 mm) and 3.3±1.4 mm (min: 1.8 mm; max: 5.2 mm), respectively.

Kalman filter-based EM-optical sensor fusion for needle deflection estimation.

PURPOSE: In many clinical procedures such as cryoablation that involves needle insertion, accurate placement of the needle's tip at the desired target is the major issue for optimizing the treatment and minimizing damage to the neighboring anatomy. However, due to the interaction force between the needle and tissue, considerable error in intraoperative tracking of the needle tip can be observed as needle deflects. METHODS: In this paper, measurements data from an optical sensor at the needle base and a magnetic resonance (MR) gradient field-driven electromagnetic (EM) sensor placed 10 cm from the needle tip are used within a model-integrated Kalman filter-based sensor fusion scheme. Bending model-based estimations and EM-based direct estimation are used as the measurement vectors in the Kalman filter, thus establishing an online estimation approach. RESULTS: Static tip bending experiments show that the fusion method can reduce the mean error of the tip position estimation from 29.23 mm of the optical sensor-based approach to 3.15 mm of the fusion-based approach and from 39.96 to 6.90 mm, at the MRI isocenter and the MRI entrance, respectively. CONCLUSION: This work established a novel sensor fusion scheme that incorporates model information, which enables real-time tracking of needle deflection with MRI compatibility, in a free-hand operating setup.

Real-time probe tracking using EM-optical sensor for MRI-guided cryoablation.

BACKGROUND: A method of real-time, accurate probe tracking at the entrance of the MRI bore is developed, which, fused with pre-procedural MR images, will enable clinicians to perform cryoablation efficiently in a large workspace with image guidance. METHODS: Electromagnetic (EM) tracking coupled with optical tracking is used to track the probe. EM tracking is achieved with an MRI-safe EM sensor working under the scanner's magnetic field to compensate the line-of-sight issue of optical tracking. Unscented Kalman filter-based probe tracking is developed to smooth the EM sensor measurements when occlusion occurs and to improve the tracking accuracy by fusing the measurements of two sensors. RESULTS: Experiments with a spine phantom show that the mean targeting errors using the EM sensor alone and using the proposed method are 2.21 mm and 1.80 mm, respectively. CONCLUSION: The proposed method achieves more accurate probe tracking than using an EM sensor alone at the MRI scanner entrance.

A Simple Adaptive Transfer Function for Deriving the Central Blood Pressure Waveform from a Radial Blood Pressure Waveform.

Generalized transfer functions (GTFs) are available to compute the more relevant central blood pressure (BP) waveform from a more easily measured radial BP waveform. However, GTFs are population averages and therefore may not adapt to variations in pulse pressure (PP) amplification (ratio of radial to central PP). A simple adaptive transfer function (ATF) was developed. First, the transfer function is defined in terms of the wave travel time and reflection coefficient parameters of an arterial model. Then, the parameters are estimated from the radial BP waveform by exploiting the observation that central BP waveforms exhibit exponential diastolic decays. The ATF was assessed using the original data that helped popularize the GTF. These data included radial BP waveforms and invasive reference central BP waveforms from cardiac catheterization patients. The data were divided into low, middle, and high PP amplification groups. The ATF estimated central BP with greater accuracy than GTFs in the low PP amplification group (e.g., central systolic BP and PP root-mean-square-errors of 3.3 and 4.2 mm Hg versus 6.2 and 7.1 mm Hg; p ≤ 0.05) while showing similar accuracy in the higher PP amplification groups. The ATF may permit more accurate, non-invasive central BP monitoring in elderly and hypertensive patients.

Phosphoproteomic profiling of tumor tissues identifies HSP27 Ser82 phosphorylation as a robust marker of early ischemia.

Delays between tissue collection and tissue fixation result in ischemia and ischemia-associated changes in protein phosphorylation levels, which can misguide the examination of signaling pathway status. To identify a biomarker that serves as a reliable indicator of ischemic changes that tumor tissues undergo, we subjected harvested xenograft tumors to room temperature for 0, 2, 10 and 30 minutes before freezing in liquid nitrogen. Multiplex TMT-labeling was conducted to achieve precise quantitation, followed by TiO2 phosphopeptide enrichment and high resolution mass spectrometry profiling. LC-MS/MS analyses revealed phosphorylation level changes of a number of phosphosites in the ischemic samples. The phosphorylation of one of these sites, S82 of the heat shock protein 27 kDa (HSP27), was especially abundant and consistently upregulated in tissues with delays in freezing as short as 2 minutes. In order to eliminate effects of ischemia, we employed a novel cryogenic biopsy device which begins freezing tissues in situ before they are excised. Using this device, we showed that the upregulation of phosphorylation of S82 on HSP27 was abrogated. We thus demonstrate that our cryogenic biopsy device can eliminate ischemia-induced phosphoproteome alterations, and measurements of S82 on HSP27 can be used as a robust marker of ischemia in tissues.

Unstable QT interval dynamics precedes ventricular tachycardia onset in patients with acute myocardial infarction: a novel approach to detect instability in QT interval dynamics from clinical ECG.

BACKGROUND: Instability in ventricular repolarization in the presence of premature activations (PA) plays an important role in arrhythmogenesis. However, such instability cannot be detected clinically. This study developed a methodology for detecting QT interval (QTI) dynamics instability from the ECG and explored the contribution of PA and QTI instability to ventricular tachycardia (VT) onset. METHODS AND RESULTS: To examine the contribution of PAs and QTI instability to VT onset, ECGs of 24 patients with acute myocardial infarction, 12 of whom had sustained VT (VT) and 12 nonsustained VT (NSVT), were used. From each patient ECG, 2 10-minute-long ECG recordings were extracted, 1 right before VT onset (onset epoch) and 1 at least 1 hour before it (control epoch). To ascertain how PA affects QTI dynamics stability, pseudo-ECGs were calculated from an MRI-based human ventricular model. Clinical and pseudo-ECGs were subdivided into 1-minute recordings (minECGs). QTI dynamics stability of each minECG was assessed with a novel approach. Frequency of PAs (f(PA)) and the number of minECGs with unstable QTI dynamics (N(us)) were determined for each patient. In the VT group, f(PA) and N(us) of the onset epoch were larger than in control. Positive regression relationships between f(PA) and N(us) were identified in both groups. The simulations showed that both f(PA) and the PA degree of prematurity contribute to QTI dynamics instability. CONCLUSIONS: Increased PA frequency and QTI dynamics instability precede VT onset in patients with acute myocardial infarction, as determined by novel methodology for detecting instability in QTI dynamics from clinical ECGs.

Short-term variability of repolarization predicts ventricular tachycardia and sudden cardiac death in patients with structural heart disease: a comparison with QT variability index.

BACKGROUND: Monitoring arrhythmic risk may improve management of patients with implantable cardioverter-defibrillators (ICD) and prevent ICD shocks. Changes in repolarization duration between subsequent beats quantified as short-term variability (STV) is associated with ventricular arrhythmias in several animal models. OBJECTIVE: We evaluated STV of QT from right ventricular intracardiac ICD electrograms in patients with structural heart disease and compared its predictive value with the QT variability index (QTVI). METHODS: In 233 patients, STV over 60 beats for QT and RR intervals and their ratio was calculated (STV(QT), STV(RR), STV(Ratio), respectively). QTVI was derived from mean and SD of QT and heart rate. Follow-up duration was 26 ± 15 months. Predictive value was determined for sudden arrhythmic death (SAD) defined as sudden cardiac death or fast ventricular tachycardia/fibrillation [CL < 240 ms]. RESULTS: In univariate analysis, STV(Ratio), but not STV(QT) or STV(RR), was predictive of SAD. Hazard ratios for highest quartile STV(Ratio) and QTVI were comparable (STV(Ratio): 1.9, 95% confidence interval [CI] 1.1 to 3.3, P = .038, QTVI: 2.2, 95% CI 1.2 to 3.8, P = .010). In a multivariate model, highest quartile STV(Ratio) was predictive of SAD after adjustment for New York Heart Association class, history of ischemia, ICD indication, and use of class I antiarrhythmics (hazard ratio 1.8, 95% CI 1.0 to 3.4, P < .050). A combined criterion of highest quartile for both STV(Ratio) and QTVI identified patients at highest risk (hazard ratio 2.4, 95% CI 1.3 to 4.3, P = .005, positive predictive value 38%, negative predictive value 82%). CONCLUSION: STV(Ratio) from ICD electrograms is predictive of SAD. Predictive value is similar for order-based STV(Ratio) and distribution-based QTVI, but the combination of both parameters can further improve results.

A new electrocardiogram marker to identify patients at low risk for ventricular tachyarrhythmias: sum magnitude of the absolute QRST integral.

OBJECTIVE: We proposed and tested a novel electrocardiogram marker of risk of ventricular arrhythmias (VAs). METHODS: Digital orthogonal electrocardiograms were recorded at rest before implantable cardioverter-defibrillator (ICD) implantation in 508 participants of a primary prevention ICDs prospective cohort study (mean ± SD age, 60 ± 12 years; 377 male [74%]). The sum magnitude of the absolute QRST integral in 3 orthogonal leads (SAI QRST) was calculated. A derivation cohort of 128 patients was used to define a cutoff; a validation cohort (n = 380) was used to test a predictive value. RESULTS: During a mean follow-up of 18 months, 58 patients received appropriate ICD therapies. The SAI QRST was lower in patients with VA (105.2 ± 60.1 vs 138.4 ± 85.7 mV ms, P = .002). In the Cox proportional hazards analysis, patients with SAI QRST not exceeding 145 mV ms had about 4-fold higher risk of VA (hazard ratio, 3.6; 95% confidence interval, 1.96-6.71; P < .0001) and a 6-fold higher risk of monomorphic ventricular tachycardia (hazard ratio, 6.58; 95% confidence interval, 1.46-29.69; P = .014), whereas prediction of polymorphic ventricular tachycardia or ventricular fibrillation did not reach statistical significance. CONCLUSION: High SAI QRST is associated with low risk of sustained VA in patients with structural heart disease.

Ventricular arrhythmia is predicted by sum absolute QRST integralbut not by QRS width.

BACKGROUND: There is a controversy regarding the association between QRS width and ventricular arrhythmias (VAs). We hypothesized that predictive value of the QRS width could be improved if QRS width were considered in the context of the sum magnitude of the absolute QRST integral in 3 orthogonal leads sum absolute QRST integral (SAI QRST). We explored correlations between QRS width, SAI QRST, and VA in primary prevention implantable cardioverter-defibrillator (ICD) patients with structural heart disease. METHODS: Baseline orthogonal electrocardiograms were recorded at rest in 355 patients with implanted primary prevention ICDs (mean age, 59.5 ± 12.4 years; 279 male [79%]). Patients were observed prospectively at least 6 months; appropriate ICD therapies because of sustained VA served as end points. The sum magnitude of the absolute QRST integral in 3 orthogonal leads (SAI QRST) was calculated. RESULTS: During a mean follow-up of 18 months, 48 patients had sustained VA and received appropriate ICD therapies. There was no difference in baseline QRS width between patients with and those without arrhythmia (114.9 ± 32.8 vs 108.9 ± 24.7 milliseconds; P = .230). SAI QRST was significantly lower in patients with VA at follow-up than in patients without VA (102.6 ± 27.6 vs 112.0 ± 31.9 mV·ms; P = 0.034). Patients with SAI QRST (≤145 mV·ms) had a 3-fold higher risk of ventricular tachycardia (VT)/ventricular fibrillation (VF) (hazard ratio [HR], 3.25; 95% confidence interval [CI], 1.59-6.75; P = .001). In the univariate analysis, QRS width did not predict VT/VF. In the bivariate Cox regression model, every 1 millisecond of incremental QRS widening with a simultaneous 1 mV·ms SAI QRST decrease raised the risk of VT/VF by 2% (HR, 1.02; 95% CI, 1.01-1.03; P = .005). CONCLUSION: QRS widening is associated with ventricular tachyarrhythmia only if accompanied by low SAI QRST.

Optimal left ventricular endocardial pacing sites for cardiac resynchronization therapy in patients with ischemic cardiomyopathy.

OBJECTIVES: We sought to investigate the impact of left ventricular (LV) pacing site on mechanical response to cardiac resynchronization therapy (CRT) in patients with ischemic cardiomyopathy (ICM). BACKGROUND: CRT reduces morbidity and mortality in patients with dyssynchronous LV failure; however, variability in response, particularly in ICM patients, poses ongoing challenges. Endocardial biventricular (BiV) stimulation may provide more flexibility in LV site selection and yield more natural transmural activation patterns. Whether this applies to ICM and whether optimal LV endocardial pacing locations vary among ICM patients remain unknown. METHODS: Peak rate of LV pressure increase (dP/dt(max)) was measured at baseline, during VDD pacing at the right ventricular apex, and during BiV pacing from the right ventricular apex and 51 +/- 14 different LV endocardial sites in patients with ICM (n = 11). Seven patients already had an epicardial LV lead (CRT) in place, allowing comparison of epicardial BiV stimulation with that using an endocardial site directly transmural to the CRT-coronary sinus lead tip. Electroanatomic 3-dimensional maps with color-coded dP/dt(max) response defined optimal pacing regions delivering >or=85% of maximal increase in dP/dt(max). RESULTS: Endocardial BiV pacing improved dP/dt(max) over right ventricular apex pacing in all patients (mean increase 241 +/- 38 mm Hg/s; p < 0.0001). In patients with pre-existing CRT leads, LV endocardial versus epicardial pacing at transmural sites yielded equivalent dP/dt(max) values. However, dP/dt(max) at the best endocardial site exceeded that achieved with the pre-implanted CRT device (mean increase 111 +/- 25 mm Hg/s; p = 0.004). An average of approximately 2 optimal endocardial sites were identified for each patient, located at the extreme basal lateral wall (8 of 11 patients) and other regions (9 of 11). Standard mid-LV free wall pacing yielded suboptimal LV function in 73% of patients. Optimal pacing sites were typically located in LV territories remote (9.3 +/- 3.6 cm) from the infarct zone. CONCLUSIONS: CRT delivered at best LV endocardial sites is more effective than via pre-implanted coronary sinus lead pacing. The location of optimal LV endocardial pacing varies among patients with ICM, and individual tailoring may improve CRT efficacy in such patients.

Failure in short-term prediction of ventricular tachycardia and ventricular fibrillation from continuous electrocardiogram in intensive care unit patients.

BACKGROUND: Patients in the intensive care unit (ICU) setting are prone to malignant ventricular arrhythmias. We sought to test whether electrocardiographic (ECG) markers of autonomic tone, ventricular irritability, and repolarization lability could be used in short-term prediction of ventricular arrhythmias in this patient population. METHODS: We studied 38 patients with sustained (>30 seconds) monomorphic ventricular tachycardia, polymorphic ventricular tachycardia, or ventricular fibrillation while monitored in the ICU and 30 patients without arrhythmia in the ICU who served as controls. All patients had at least 12 hours of continuously recorded multilead ECG before arrhythmic event. Mean heart rate and measures of heart rate variability, QT variability, and ventricular ectopy were quantified in 1-hour epochs for the 12 hours before the arrhythmic event and in 5-minute epochs for the last hour preevent (and using a random termination time point in controls). RESULTS: A modest downward trend in QT variability and a rise in heart rate were observed hours before polymorphic ventricular tachycardia and ventricular fibrillation events, although no significant changes heralded monomorphic ventricular tachycardia and no changes in any parameter predicted imminent ventricular arrhythmia of any type. There were no significant differences in ECG parameters between arrhythmia patients and controls. CONCLUSIONS: In ICU patients, sustained ventricular arrhythmias are not preceded by change in ECG measures of autonomic tone, repolarization variability, and ventricular ectopy. Short-term arrhythmia prediction may be difficult or impossible in this patient population based on ECG measures alone.

Prediction of ventricular tachyarrhythmias by intracardiac repolarization variability analysis.

BACKGROUND: Arrhythmic sudden cardiac death (SCD) is generally mediated by ventricular fibrillation (VF) or fast ventricular tachycardia (FVT). We studied the predictive value of temporal QT variability detected from various sources of cardiac electric signal: surface ECG, far-field (FF), and near-field (NF) intracardiac electrograms (EGMs) in patients with implantable cardioverter-defibrillators (ICDs). METHODS AND RESULTS: Surface ECG and FF and NF intracardiac EGMs were simultaneously recorded at rest (mean heart rate, 74+/-15 bpm) for 4.5+/-1.3 minutes in 298 patients (mean age, 59+/-14; 216 male [73%]) with structural heart disease and an implanted Medtronic ICD for primary (231 patients, 78%) or secondary (67 patients, 22%) prevention of SCD. During mean follow-up of 16+/-8 months, 52 (13.1% per person-year of follow-up) patients sustained VT/VF and received appropriate ICD therapies, but only 19 (4.8% per person-year of follow-up) patients sustained FVT/VF with cycle length

Transient local injury current in right ventricular electrogram after implantable cardioverter-defibrillator shock predicts heart failure progression.

OBJECTIVES: This study aimed to identify an early marker of functional impairment after an implantable cardioverter-defibrillator (ICD) shock as a predictor of heart failure progression. BACKGROUND: The ICD population has substantial risk of death due to progressive pump failure. METHODS: Near-field (NF) bipolar right ventricular (RV) electrograms (EGMs) during induced ventricular fibrillation (VF) and 10 s after rescue ICD shock were analyzed in 310 patients (mean age 59 +/- 14.5 years, 219 men [71%]) with structural heart disease, New York Heart Association functional class I to III, and implanted with a single- or dual-chamber Medtronic (Minneapolis, Minnesota) ICD for primary (245 patients, 79%) or secondary prevention of sudden cardiac arrest. A local injury current (LIC) on NF RV EGM was defined as a deviation of EGM potential > or =1 mV or > or =15% of the preceding R-wave peak-to-peak amplitude. RESULTS: During mean follow-up of 29.3 +/- 15.0 months, the combined end point of death or hospitalization due to congestive heart failure (CHF) exacerbation was documented in 40 patients (12.9%, or 5.3% per person-year of follow-up). LIC was observed in 106 patients. In multivariate risk analysis, after adjustment for baseline prognostic factors (ejection fraction, history of atrial fibrillation, diabetes mellitus) and appropriate ICD shocks during follow-up, patients with observed LIC after induced VF rescue ICD shock at ICD implantation were more likely to die or to be hospitalized (hazard ratio: 2.69; 95% confidence interval: 1.41 to 5.14; p = 0.003). CONCLUSIONS: Transient LIC on bipolar NF RV EGM after induced VF rescue ICD shock is associated with increased risk of CHF progression, future hospitalizations due to CHF exacerbation, and subsequent heart failure death.

Intracardiac QT variability in patients with structural heart disease on class III antiarrhythmic drugs.

We previously showed that increased intracardiac repolarization lability predicts life-threatening ventricular arrhythmias in patients with structural heart disease. Patients with structural heart disease frequently take antiarrhythmic drugs (AADs), which directly affect repolarization. The effect of AADs on the predictive value of repolarization lability is unknown. We hypothesized that increased intracardiac beat-to-beat QT variability predicts sustained ventricular tachyarrhythmias in structural heart disease patients on class III AADs. Intracardiac electrograms and surface electrocardiogram were simultaneously recorded at rest for 5 minutes in 500 patients (mean +/- SD age, 61 +/- 14 years; 368 male [74%]) with implanted implantable cardioverter-defibrillator for primary (295 patients, or 79%) or secondary prevention of sudden cardiac death. Mean (SD) follow-up currently reached 24.8 (11.7) months. Intracardiac QT variability index was an independent predictor of ventricular tachycardia/ventricular fibrillation events and fast ventricular arrhythmias with cycle length of 240 ms or less in the multivariate Cox model. Intracardiac QT variability was higher in patients on class III AADs than in those not taking these drugs. Increased intracardiac QT variability after adjustment for class III AADs use carried independent risk of life-threatening ventricular tachyarrhythmias.

Ibutilide-induced changes in the temporal lability of ventricular repolarization in patients with and without structural heart disease.

INTRODUCTION: Ibutilide has been shown to prolong repolarization times and increase the risk of ventricular tachyarrhythmias particularly in patients with structural heart disease. The mechanisms underlying its proarrhythmic effects remain incompletely understood. We sought to define the effects of ibutilide on the temporal lability of ventricular repolarization in patients with and without structural heart disease. METHODS: Twenty-four patients referred for electrophysiology study underwent monophasic action potential (MAP) recordings in the right ventricle during sinus rhythm and random interval right atrial pacing (RIAP). Ibutilide was subsequently administered and the recordings repeated both in sinus rhythm and with RIAP. Digitized recordings were analyzed offline for calculation of the QT variability index (QTVI) based on surface ECG, and the MAP duration variability index (MAPDVI) based on the intracardiac MAP signal. RESULTS: Of 24 patients enrolled, analyses were performed in 21 patients (mean age 59 +/- 15 years, 38% women). In three patients, the data were not analyzed due to frequent premature ventricular complexes. Ibutilide resulted in significant changes in heart rate (mean difference: -7.4 +/- 0.91 bpm, P < 0.0001) and the surface QT interval (mean difference: 59.6 +/- 12.2 ms, P = 0.0001) during sinus rhythm. After ibutilide, QTVI remained unchanged from baseline during sinus rhythm but was significantly different in the setting of RIAP (mean difference: 0.345 +/- 0.098, P = 0.0022). With subgroup analyses, these differences remained significant regardless of the presence or absence of heart disease. CONCLUSION: Ibutilide results in overall prolongation of ventricular repolarization and reductions in baseline sinus rates. Ibutilide increases temporal lability of repolarization only with enriched fluctuations in heart rate.

Estimation of central pressure augmentation using automated radial artery tonometry.

BACKGROUND: Peripheral wave reflection augments central blood pressure and contributes to cardiac load. This pressure augmentation is not quantifiable from brachial cuff pressure but can be determined from carotid pulsations using the augmentation index (AI). However, carotid tonometry is technically challenging and difficult to standardize in practice. We tested whether automated radial pressure analysis provides a viable alternative. METHODS AND RESULTS: Carotid and radial AI (cAI, rAI) were measured in 46 volunteers with a broad range of arterial properties. Data were assessed at rest, during a cold-pressor test, and following 0.4 mg of sublingual nitroglycerin. cAI correlated with rAI independent of age, mean blood pressure (BP), gender or body mass (cAI = 0.79 x rAI - 0.467, r = 0.81, P < 0.00001), with zero mean bias. There was individual variability in the prediction (difference of -4 +/- 23%), though 65% of the estimates fell within 15% of each other. Change in rAI and cAI with provocative maneuvers also correlated (r = 0.77, P < 0.001). Both cAI and rAI were nonlinearly related to late-systolic pressure-time integral (PTI), an index of cardiac load. At cAI < 0.1 or rAI < 0.69, PTI was unaltered, while greater values correlated with increased PTI. rAI accurately predicted this cut-off in 88% of cases, with a 5.5% false negative rate. CONCLUSIONS: Automated rAI analysis is an easily applied method to assess basal and dynamic central pressure augmentation. While individual predictive accuracy of cAI was variable, overall population results were consistent, supporting use of rAI in clinical trials. Its prediction of when AI is associated with greater LV loading (i.e. cardiac risk) is good and may help stratify individual risk along with brachial cuff pressure.

Functional impact of rate irregularity in patients with heart failure and atrial fibrillation receiving cardiac resynchronization therapy.

AIMS: Atrial fibrillation (AFib) with a rapid ventricular response may adversely impact cardiac performance, especially in patients with heart failure. However, it remains uncertain whether rhythm irregularity per se has unfavourable effects apart from tachycardia, and whether rate regularization alone can improve heart function. METHODS AND RESULTS: Nine subjects with chronic AFib, atrioventricular nodal block, and symptomatic heart failure (ejection fraction 14-30%) were studied using a pressure-volume catheter. Ventricles were biventricularly paced (RV-apex, LV-lateral wall) at 80 or 120 min(-1) mean rate, using regular or irregular, Poisson-distributed stimulation. At 80 min(-1), ventricular function was similar between the two pacing modes. However, at 120 min(-1), irregular pacing impaired systolic (dP/dt(max): -8.2%, P<0.001) and diastolic function (dP/dt(min): +21%, P<0.001, LV end-diastolic pressure: +26%, P=0.007) compared with regular rate pacing. Contractile function during irregular pacing varied with the ratio of preceding/pre-preceding intercycle (RR) interval (dP/dt(max): 80 b.p.m.: r=0.69; 120 b.p.m.: r=0.74), whereas pre-load had little effect on instantaneous contractility. CONCLUSION: In heart failure subjects with AFib, RR-interval irregularity worsens cardiac function at elevated but not at normal range heart rate. Overall rate control is most important in these patients while rate regularization of rapid AFib may impart additional benefits.

Short-term effects of right-left heart sequential cardiac resynchronization in patients with heart failure, chronic atrial fibrillation, and atrioventricular nodal block.

BACKGROUND: Single-site ventricular pacing in patients with heart failure, atrial fibrillation, and severe atrioventricular (AV) nodal block risks the generation of discoordinate contraction. Whether altering the site of stimulation can offset this detrimental effect and what role sequential right ventricular-left ventricular (RV-LV) stimulation might play in such patients remain unknown. METHODS AND RESULTS: Nine subjects with heart failure (ejection fraction, 14% to 30%), atrial fibrillation, and AV block were studied by pressure-volume analysis. Ventricular stimulation was applied to the RV (apex and outflow tract), LV free wall, and biventricular (BiV) at 80 and 120 bpm. BiV improved systolic function more than either site alone (dP/dt(max), 810+/-83, 924+/-98, 983+/-102 mm Hg/s for RV, LV, BiV, respectively; P<0.05), although LV pacing was significantly better than RV pacing. However, only BiV improved diastolic function (isovolumic relaxation) over RV or LV alone. Similar results were obtained for both heart rates. RV pacing site did not alter the BiV effect, and concomitant stimulation of both RV sites did not improve function over each alone. Finally, varying RV-LV delay revealed optimal responses with simultaneous pacing. CONCLUSIONS: Simultaneous BiV pacing acutely enhances both systolic and diastolic function over single-site RV or LV pacing in congestive heart failure patients with atrial fibrillation and advanced AV block. Sequential RV-LV stimulation offers minimal benefit on average and should perhaps be considered only in targeted subsets such as nonresponding patients.

Temporal repolarization lability differences among genotyped patients with the long QT syndrome.

The investigators sought to test whether certain long QT syndrome (LQTS) mutations are associated with increased repolarization lability and whether repolarization lability (quantified by the QT variability index [QTVI]) is increased in patients with LQTS compared with controls. In 32 genotyped patients with LQTS type 1 (LQT1), 32 genotyped patients with LQTS type 2 (LQT2), and 32 controls, the QTVI was increased in patients with LQT2 (-0.973 +/- 0.394, p = 0.01 vs controls) and in patients with LQT1 with mutations other than KCNQ1-FIN (-0.942 +/- 0.264, p = 0.04 vs controls) but was similar between the KCNQ1-FIN group and controls.

Combined ventricular systolic and arterial stiffening in patients with heart failure and preserved ejection fraction: implications for systolic and diastolic reserve limitations.

BACKGROUND: Heart failure with preserved ejection fraction (HF-nlEF) is common in aged individuals with systolic hypertension and is frequently ascribed to diastolic dysfunction. We hypothesized that such patients also display combined ventricular-systolic and arterial stiffening that can exacerbate blood pressure lability and diastolic dysfunction under stress. METHODS AND RESULTS: Left ventricular pressure-volume relations were measured in patients with HF-nlEF (n=10) and contrasted with asymptomatic age-matched (n=9) and young (n=14) normotensives and age- and blood pressure-matched controls (n=25). End-systolic elastance (stiffness) was higher in patients with HF-nlEF (4.7+/-1.5 mm Hg/mL) than in controls (2.1+/-0.9 mm Hg/mL for normotensives and 3.3+/-1.0 mm Hg/mL for hypertensives; P<0.001). Effective arterial elastance was also higher (2.6+/-0.5 versus 1.9+/-0.5 mm Hg/mL) due to reduced total arterial compliance; the latter inversely correlated with end-systolic elastance (P=0.0001). Body size and stroke volumes were similar and could not explain differences in ventricular-arterial stiffening. HF-nlEF patients also displayed diastolic abnormalities, including higher left ventricular end-diastolic pressures (24.3+/-4.6 versus 12.9+/-5.5 mm Hg), caused by an upward-shifted diastolic pressure-volume curve. However, isovolumic relaxation and the early-to-late filling ratio were similar in age- and blood pressure-matched controls. Ventricular-arterial stiffening amplified stress-induced hypertension, which worsened diastolic function, and predicted higher cardiac energy costs to provide reserve output. CONCLUSION: Patients with HF-lnEF have systolic-ventricular and arterial stiffening beyond that associated with aging and/or hypertension. This may play an important pathophysiological role by exacerbating systemic load interaction with diastolic function, augmenting blood pressure lability, and elevating cardiac metabolic demand under stress.