A MHz X-ray diffraction set-up for dynamic compression experiments in the diamond anvil cell.

An experimental platform for dynamic diamond anvil cell (dDAC) research has been developed at the High Energy Density (HED) Instrument at the European X-ray Free Electron Laser (European XFEL). Advantage was taken of the high repetition rate of the European XFEL (up to 4.5 MHz) to collect pulse-resolved MHz X-ray diffraction data from samples as they are dynamically compressed at intermediate strain rates (≤103 s-1), where up to 352 diffraction images can be collected from a single pulse train. The set-up employs piezo-driven dDACs capable of compressing samples in ≥340 µs, compatible with the maximum length of the pulse train (550 µs). Results from rapid compression experiments on a wide range of sample systems with different X-ray scattering powers are presented. A maximum compression rate of 87 TPa s-1 was observed during the fast compression of Au, while a strain rate of ∼1100 s-1 was achieved during the rapid compression of N2 at 23 TPa s-1.

Investigating Serious Adverse Drug Reactions in Patients Receiving Erythropoiesis-Stimulating Agents: A Root Cause Analysis Using the "ANTICIPATE" Framework.

BACKGROUND: Unexpected serious adverse drug reactions (sADRs) affecting patients with chronic kidney disease (CKD) who received erythropoiesis-stimulating agents were identified by study co-authors. These included pure red cell aplasia (PRCA) after administration of the Eprex formulation of epoetin or the epoetin biosimilar HX575 and fatal anaphylaxis associated with peginesatide, an erythropoietin receptor agonist. We developed and applied a structured framework to describe these sADRs, including root cause analyses and eradication efforts. METHODS: A 10-step framework termed "ANTICIPATE," focusing on signal identification, incidence, causality, and eradication guided our evaluations. RESULTS: Initial cases were identified by a hematologist (Eprex), clinical study monitors (HX575), and 4 nurses (peginesatide). The number of persons with individual ADRs was 13 PRCA cases for epoetin, 2 antibody-mediated PRCA cases for HX575, and 5 fatal anaphylaxis cases for peginesatide. Initial incidence estimates per 1000 treated persons were 0.27 for Eprex-associated PRCA, 11 for HX575-associated PRCA, and 0.38 for peginesatide fatalities. Likely causes were subcutaneous administration of epoetin formulated with polysorbate 80 (Eprex), tungsten leaching from pins included in product syringes (HX575), and inclusion of a phenol stabilizer (peginesatide). Eradication strategies included restricting Eprex administration to the intravenous route, excluding tungsten from HX575 syringes, and for peginesatide, proposed eradication was to return to single-dose vials without preservatives. CONCLUSION: Although the number of cases of each sADR was small, eradication was successful for 2 sADRs, and a proposed eradication was developed for a third sADR. The structured framework used to describe the above 3 sADRs in patients with CKD can also be used in other clinical settings.

Azithromycin and levofloxacin use and increased risk of cardiac arrhythmia and death.

PURPOSE: Azithromycin use has been associated with increased risk of death among patients at high baseline risk, but not for younger and middle-aged adults. The Food and Drug Administration issued a public warning on azithromycin, including a statement that the risks were similar for levofloxacin. We conducted a retrospective cohort study among US veterans to test the hypothesis that taking azithromycin or levofloxacin would increase the risk of cardiovascular death and cardiac arrhythmia compared with persons taking amoxicillin. METHODS: We studied a cohort of US veterans (mean age, 56.8 years) who received an exclusive outpatient dispensation of either amoxicillin (n = 979,380), azithromycin (n = 594,792), or levofloxacin (n = 201,798) at the Department of Veterans Affairs between September 1999 and April 2012. Azithromycin was dispensed mostly for 5 days, whereas amoxicillin and levofloxacin were dispensed mostly for at least 10 days. RESULTS: During treatment days 1 to 5, patients receiving azithromycin had significantly increased risk of death (hazard ratio [HR] = 1.48; 95% CI, 1.05-2.09) and serious arrhythmia (HR = 1.77; 95% CI, 1.20-2.62) compared with patients receiving amoxicillin. On treatment days 6 to 10, risks were not statistically different. Compared with patients receiving amoxicillin, patients receiving levofloxacin for days 1 to 5 had a greater risk of death (HR = 2.49, 95% CI, 1.7-3.64) and serious cardiac arrhythmia (HR = 2.43, 95% CI, 1.56-3.79); this risk remained significantly different for days 6 to 10 for both death (HR = 1.95, 95% CI, 1.32-2.88) and arrhythmia (HR = 1.75; 95% CI, 1.09-2.82). CONCLUSIONS: Compared with amoxicillin, azithromycin resulted in a statistically significant increase in mortality and arrhythmia risks on days 1 to 5, but not 6 to 10. Levofloxacin, which was predominantly dispensed for a minimum of 10 days, resulted in an increased risk throughout the 10-day period.

Altered calsequestrin glycan processing is common to diverse models of canine heart failure.

Calsequestrin-2 (CSQ2) is a resident glycoprotein of junctional sarcoplasmic reticulum that functions in the regulation of SR Ca(2+) release. CSQ2 is biosynthesized in rough ER around cardiomyocyte nuclei and then traffics transversely across SR subcompartments. During biosynthesis, CSQ2 undergoes N-linked glycosylation and phosphorylation by protein kinase CK2. In mammalian heart, CSQ2 molecules subsequently undergo extensive mannose trimming by ER mannosidase(s), a posttranslational process that often regulates protein breakdown. We analyzed the intact purified CSQ2 from mongrel canine heart tissue by electrospray mass spectrometry. The average molecular mass of CSQ2 in normal mongrel dogs was 46,306 ± 41 Da, corresponding to glycan trimming of 3-5 mannoses, depending upon the phosphate content. We tested whether CSQ2 glycan structures would be altered in heart tissue from mongrel dogs induced into heart failure (HF) by two very different experimental treatments, rapid ventricular pacing or repeated coronary microembolizations. Similarly dramatic changes in mannose trimming were found in both types of induced HF, despite the different cardiomyopathies producing the failure. Unique to all samples analyzed from HF dog hearts, 20-40 % of all CSQ2 contained glycans that had minimal mannose trimming (Man9,8). Analyses of tissue samples showed decreases in CSQ2 protein levels per unit levels of mRNA for tachypaced heart tissue, also indicative of altered turnover. Quantitative immunofluorescence microscopy of frozen tissue sections suggested that no changes in CSQ2 levels occurred across the width of the cell. We conclude that altered processing of CSQ2 may be an adaptive response to the myocardium under stresses that are capable of inducing heart failure.

Ticlopidine-, clopidogrel-, and prasugrel-associated thrombotic thrombocytopenic purpura: a 20-year review from the Southern Network on Adverse Reactions (SONAR).

Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrel-associated TTP (p < 0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ.

Statin therapy significantly reduces risk of ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator.

A few observational studies have shown the protective effect of statins on preventing ventricular tachycardia/ventricular fibrillation (VT/VF). However, the disparate study results prompt further exploration of this concept. We performed a meta-analysis to assess whether statin therapy is associated with a decrease in the incidence or recurrence of VT/VF in patients with an implantable cardioverter-defibrillator (ICD).The MEDLINE(®) and Cochrane databases were searched from 1980 to July 2009 for studies examining the effect of statins on VT/VF in recipients of ICDs. We retrieved all prospective cohort studies that examined this association. The endpoint was defined as appropriate ICD therapy for VT/VF. The quality of individual studies was assessed using the Newcastle Ottawa Scale.Seven prospective cohort studies met our inclusion criteria with a total of 2278 patients with a mean follow-up of 19.7 months. Pooled analysis of the eligible studies revealed that statin therapy was associated with a 45% reduction in the risk of developing VT/VF in recepients of ICDs [pooled odds ratio (pOR): 0.55; 95% confidence interval: 0.34-0.90; heterogeneity I(2) = 81%, P = 0.02]. In a subgroup analysis, the magnitude of the risk reduction in patients with ischemic cardiomyopathy was 54% (pOR: 0.46, P = 0.05). Sensitivity analysis including studies with higher methodological qualities alone showed a significant protective effect (pOR: 0.48, P = 0.01). There was no evidence of publication bias in the analysis.Our meta-analysis suggests an association between the use of statin and a reduction in the VT/VF occurrence in recipients of ICDs, mainly in patients with ischemic cardiomyopathy.

Clinical applications of magnets on cardiac rhythm management devices.

The growing indications for permanent pacemaker and implantable cardioverter defibrillator (ICD) implantation have increased the number of patients with these cardiac rhythm management devices (CRMDs). Cardiac rhythm management devices occasionally perform inappropriately in response to electromagnetic interference (e.g. surgical electrocautery) or lead noise over-sensing (e.g. lead fracture). Temporary reprogramming of the CRMDs using device programmers can prevent these untoward device responses. However, these programmers are device manufacturer specific and require technically qualified personnel to operate. This could cause delayed patient care and increased use of resources in certain clinical situations. Alternatively, clinical magnets, when appropriately positioned over the device site, can change the pacing to an asynchronous mode in pacemakers and suspend tachycardia therapies in ICDs. Although readily available, clinical magnets have not been widely used for this purpose, perhaps due to the unfamiliarity with the variable responses of CRMDs to magnet application. This article provides a comprehensive overview of the current literature on the mechanism of action and the specific responses of various CRMDs to clinical magnets.

Pharmacotherapy of atrial fibrillation: a pathophysiological perspective and review.

Atrial fibrillation (AF) is one of the most common arrhythmia encountered in clinical practice. Although AF is due to the structural and electrophysiological alterations in the atria, its sustainability is multifactorial, and the actual mechanisms are still not clear. Despite the recent advances in catheter ablation technology and techniques, pharmacotherapy still remains the first-line therapy for the management of AF. Current pharmacotherapy targets ion channel alterations that in fact represent only one aspect of the management of this complex arrhythmia. Successful pharmacological treatment of AF and restoration of sinus rhythm is limited and is in part due to its potential deleterious side effects. Newer agents having diverse mechanisms acting on the recently uncovered pathophysiological processes are on the horizon. These include atrial repolarization delaying agents, newer class III agents, Na(+)-Ca(2+) channel blockers, stretch receptor blockers, I(KACH) blockers, gap junction modifiers, upstream therapies, and agents targeting ischemia-induced AF. Gene- and cell-specific therapies including 'tailored nanopharmacy,' newer rate control medications with minimal side effects and the emergence of novel drugs targeting multiple areas of AF arrhythmogenesis in tandem with electrical therapy may be the future direction in the management of AF.

Low referral pattern for implantable defibrillator therapy in a tertiary hospital: referral physician survey and Monte Carlo simulation.

Although implantable cardioverter defibrillator (ICD) therapy is the standard of care for prevention of sudden cardiac death (SCD), its underutilization is a clinical concern. We performed a retrospective study on patients who underwent cardiac catheterization at a tertiary medical center to identify those who were eligible for ICD therapy as per the guidelines and those who actually received it as a part of treatment. Surprisingly, only 4.4% of eligible patients received ICD for SCD prevention. Assuming that the major cause of this underutilization of ICD therapy was low referral, we performed a structured survey among the referring physicians to assess specialists' availability, primary care physicians' role in ICD referral, patient management concerns, familiarity with ICD guidelines, and economics of ICD implantation. Physician response rate of the survey was 51% (35/68). Survey results showed that the common reasons for underreferral included nonavailability of electrophysiologists (34%), poor quality of life of patients (25.7%), patients not being on optimal therapy (25.7%), and low awareness (22.85%). Subsequently, a Monte Carlo simulation was used to assess a hypothetical survival of the study cohort, which showed that in an "ideal scenario" of ICD implantation, the mortality in the study cohort was decreased by 6.9% and 12.3% at 2- and 5-year follow-up, respectively. This study highlights the underutilization of ICDs and the referring physicians' approach to this therapy.

Effect of substance abuse on defibrillation threshold in patients with implantable cardioverter-defibrillator.

BACKGROUND: The use of recreational drugs has been observed to have deleterious effects on the heart. The aim of our study was to evaluate the effect of substance abuse on the defibrillation threshold (DFT) in patients with implantable cardioverter-defibrillators (ICDs). METHODS: A retrospective analysis was conducted on patients who had undergone ICD placement at a tertiary university medical center in Detroit, Michigan. Subjects were identified based on self-reported drug use and placed into one of the three groups: controls, cocaine, and other illicit drugs. Due to a disparity in race among groups, the main analysis on DFT value was conducted on African-American patients only. Furthermore, exploratory analyses were conducted to investigate the effects of marijuana use and race on DFT values. RESULTS: A history of cocaine use (n = 17) significantly increases DFT among African Americans (17.3 ± 8 Joule [J] vs 12.5 ± 5 J in cases vs controls, P < 0.05), while previous use of marijuana does not significantly influence DFT. African-American patients with a history of illicit drug use had indications for ICD implantation at an earlier age and that within the control (nondrug using) group; African Americans (n = 73) had higher DFT compared to Caucasians (n = 32), (14.5 ± 0.5 J vs 9.7 ± 0.6 J, P < 0.05). CONCLUSIONS: A history of cocaine use in African Americans with ICD is a risk factor for high DFT and race itself (being African American) may be a risk for high DFT. Use of high-energy ICDs and other DFT lowering techniques may be considered for patients who have used or continue to use cocaine or in whom DFT testing cannot be performed at the time of implantation.

Relationship between red cell distribution width and microalbuminuria: a population-based study of multiethnic representative US adults.

INTRODUCTION: Microalbuminuria (MA), a renal marker of vascular injury, is an independent predictor of cardiovascular (CV) events. Red cell distribution width (RDW), an emerging CV risk predictor, has not been evaluated for its association with MA. METHODS: We evaluated 8,499 participants of the National Health and Nutrition Examination Survey (NHANES) 1999-2006, where RDW was evaluated as a continuous variable and in quartiles (Q(1) ≤ 12.1, Q(2) 12.2-12.5, Q(3) 12.6-13 and Q(4) >13). Multivariate adjusted logistic regression analysis was performed to estimate the odds of having MA (n = 1,736; adjusted for traditional CV risk factors, race, BMI, estimated glomerular filtration rate, hemoglobin, mean corpuscular volume, high-sensitivity C-reactive protein and nutritional factors deficiencies of iron, folate and vitamin B(12)). RESULTS: The prevalence of MA increased with increasing RDW (13.52% in Q(1) vs. 30.02% in Q(4), p < 0.001). The odds of having MA for those in Q(4) was 2.49 (95% CI: 1.95-3.18, p < 0.001) compared to those in Q(1) after the adjustments. No effect modification was observed by covariates on the association between RDW and MA. CONCLUSION: Elevated RDW is independently associated with a higher risk of MA. An interaction between chronic inflammation, oxidative stress, neurohumoral overactivity and endothelial dysfunction may explain this association and the attendant elevated CV/renal risk.

Preserved or slightly depressed ejection fraction and outcomes after myocardial infarction.

BACKGROUND Left ventricular ejection fraction (EF) in post-myocardial infarction (MI) patients is a strong predictor of adverse cardiovascular events. Although resting EF as measured by transthoracic echocardiography (TTE), contrast ventriculography (CNV), and radionuclide angiography (RNA) exhibit high correlation, there is only modest agreement between these modalities. This study sought to explore whether modality of EF assessment influences prognostication of post-MI patients with normal or slightly reduced EF. METHODS AND RESULTS The National Heart, Lung, and Blood Institute (NHLBI) limited access dataset of the Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) Trial (1996-2003, n=8290) comparing trandolapril versus placebo was used. The cohort was partitioned into TTE (n=2582), RNA (n=816), and CNV (n=1155) groups based on modality of EF assessment. EF was a significant predictor of cardiovascular mortality (HR 0.97, 95% CI 0.95 to 0.98; p<0.005) and all cause mortality (HR 0.98, 95% CI 0.97 to 0.99; p=0.0002) on multivariate analysis in this population with preserved or mildly depressed EF. Although CNV, TTE, and RNA groups differed significantly in terms of baseline variables, no appreciable differences were noted between RNA (HR 1.13, 95% CI 0.85 to 1.50; ns) and CNV (HR 1.13, 95% CI 0.99 to 1.27; ns) groups, compared with TTE for all cause mortality. Similarly, no significant differences were observed for cardiovascular mortality between RNA (HR 1.23, 95% CI 0.82 to 1.84; p=0.31) and CNV (HR 1.14, 95% CI 0.78 to 1.67, p=0.49) versus TTE. CONCLUSION EF is a significant predictor of all-cause mortality and cardiovascular mortality in patients with preserved or mildly depressed EF. Modalities of EF measurement are interchangeable and do not play a significant role in prognostication in a post-MI population.

Sensing performance of a new wireless implantable loop recorder: a 12-month follow up study.

BACKGROUND: The implantable loop recorder (ILR) is a cost-effective tool with a high diagnostic yield in the evaluation of unexplained recurrent syncope. The Sleuth ILR (Transoma Medical, St. Paul MN, USA) is a new-generation ILR with wireless transmission capability approved by the Food and Drug Administration. We report the feasibility of achieving appropriate sensing over 1-year follow-up at the traditional midclavicular and alternative inframammary implantation sites without preimplant electrocardiogram (ECG) mapping. METHODS AND RESULTS: We studied 32 patients with unexplained syncope, aged 58.4+/-18.44 years, with an ILR implanted at the left midclavicular location (n = 17) or the left inframammary site (n = 15) over 1-year post implant. No preimplant electrocardiogram (ECG) mapping was performed. The highest R-wave amplitudes were observed at the inframammary site, but over the entire follow-up period, amplitudes were not significantly different from those at the midclavicular site. At both sites, R-wave amplitudes at the 6-month follow-up were significantly higher than those measured at 1 week. P-waves were visible in 80-90% of the patients. There was no discernible difference in P-waves (amplitude) relative to implant location. Body mass index, left ventricular ejection fraction, and age did not significantly influence the R-wave amplitude or the ability to discern P-waves. CONCLUSION: Our findings show that the Sleuth ILR implanted at both the midclavicular and inframammary locations without preimplant ECG mapping achieves acceptable "R" waves. This may simplify implantation procedures and improve patient satisfaction.

Acute myocarditis: can novel echocardiographic techniques assist with diagnosis?

Two-dimensional echocardiography has historically played a limited role in the diagnosis of acute myocarditis because of a lack of specific diagnostic features. The emergence of novel echocardiographic modalities such as strain and myocardial perfusion imaging have greatly augmented the scope of echocardiography, permitting the assessment of myocardial contractility, blood flow, and microvascular integrity. However, the application of these cutting-edge techniques in the diagnosis of acute myocarditis is still at a nascent stage. We present a case of acute myocarditis where echo-based strain imaging/mapping and real-time myocardial contrast echocardiography enabled the detection of regional contractile and perfusion abnormalities, not otherwise apparent with conventional echocardiography. These findings and the final diagnosis were later confirmed by cardiac magnetic resonance imaging. This case highlights the potential utility of novel echocardiographic techniques in the diagnostic workup of acute myocarditis and underscores the need for prospective studies to assess the sensitivity and specificity of these newer technologies. To our knowledge, this is the first report of a multimodality echocardiographic approach towards the diagnosis of myocarditis.

Renal disease and cardiac mortality in survivors of sudden cardiac death.

OBJECTIVE: Renal disease is associated with increased all-cause mortality and cardiovascular mortality. However, the role of ICD implantation on cardiac mortality in patients with renal disease has not been well studied. Implantable cardioverter-defibrillator (ICD) implantation is protective against cardiac death in a secondary prevention population with renal disease. METHODS: The Antiarrhythmics Versus Implantable Cardioverter Defibrillators (AVID) Trial (n = 1016) was a multicentre trial comparing ICD (n = 507) and anti-arrhythmic drugs (AAD) (n = 509) for secondary prevention of life-threatening ventricular tachyarrhythmias. We performed a post-hoc analysis of the AVID trial using the National Heart, Lung, and Blood Institute limited access dataset. Individuals in the original AVID study with history of renal disease (n = 82) were included in this analysis. Outcomes of our analysis were cardiac death and all-cause mortality. RESULTS: 41 patients had renal disease in both the ICD and AAD arms. A total of 116 patients died in the ICD arm, while 162 died in the AAD arm. Renal disease was an independent predictor (HR, 95% CI) of cardiac death (1.967, 1.09-3.57, P = 0.02) and all-cause mortality (2.04, 1.23-3.39, P = 0.01) in the AAD arm. Renal disease was also a predictor of all-cause mortality in the ICD arm (1.75, 1.01-3.01, P = 0.04). However, renal disease did not influence cardiac death in the ICD arm. CONCLUSIONS: Our study investigates the effect of ICD implantation in an entirely secondary prevention population with renal disease. ICD implantation appears to be equally protective against cardiac death in renal disease when compared to AAD.

A novel approach to ICD lead revision in a patient with extensive vascular thrombosis.

Chronic extensive thrombosis of the venous system is a commonly encountered problem in end stage renal disease (ESRD) patients undergoing transvenous device implantation, lead extraction or lead revision. We describe a case of an ESRD patient with an implantable cardioverter defibrillator (ICD) that failed to deliver therapy due to lead fracture. Patient needed revision of the ICD lead system, but had extensive axillary-subclavian-superior vena cava occlusion. Patient refused a thoracotomy approach as well as lead extraction as he had a complicated course of lead extraction in the past. We successfully improvised a novel technique to revise the ICD system.

High defibrillation threshold: the science, signs and solutions.

Defibrillation threshold (DFT) testing has traditionally been an integral part of implantable cardioverter defibrillator (ICD) implantation. With the increasing number of patients receiving ICDs, physicians are encountering high DFT more often than before. Tackling the problem of high DFT, warrants an in-depth understanding of the science of defibrillation including the key electrophysiological concepts and the underlying molecular mechanisms. Numerous factors have been implicated in the causation of high DFT. Due consideration to the past medical history, pharmacotherapy, laboratory data and cardiac imaging, help in assessing the pre-procedural risk for occurrence of high DFT. Drugs, procedural changes, type and location of ICD lead system are some of the key players in predicting DFT during implantation. In the event of encountering an unacceptably high DFT, we recommend to follow a step-wise algorithm. Ruling out procedural complications like pneumothorax and tamponade is imperative before embarking on a search for potentially reversible clinical or metabolic derangements. Finally, if these attempts fail, the electrophysiologist must choose from a wide range of options for device adjustment and system modification. Although this review article is meant to be a treatise on the science, signs and solutions for high DFT, it is bound by limitations of space and scope of the article.

Pericardial effusion impending tamponade: a look beyond Beck's triad.

Clinical diagnosis of chronic or slowly progressing pericardial effusion with impending tamponade remains a challenge, particularly when classical physical signs are subtle or absent. A high index of suspicion should be entertained in such cases in the appropriate setting even when the clinical signs and symptoms are missing. We present two cases where the pericardial effusion was missed in the emergency department due to subtle clinical features or mistaken for a more familiar "look-a-like" presentation. A review of the literature and an analysis of various clinical parameters of published cases were performed. It is pivotal that physicians should not only be aware of the limitations of the traditional clinical signs, but also be familiar with the use of other subtle findings and the importance of other modalities that may potentially enhance the sensitivity in diagnosing chronic pericardial effusion impending tamponade.

Global and regional left ventricular contractile impairment in patients with wolff-Parkinson-white syndrome.

BACKGROUND: To assess regional systolic function and global contractile function in patients with WPW Syndrome. METHOD: Eleven cases with manifest Wolff-Parkinson-White (WPW) syndrome in sinus rhythm were compared to 11 age matched controls. 2D strain analysis was performed and peak segmental radial strain (pRS) values obtained from basal ventricular parasternal short-axis images (70 +/- 5 frames/sec) using a dedicated software package. Heterogeneity of radial strain pattern in six circumferential basal left ventricular segments was measured in terms of standard deviations of peak RS (SD(pRS)) or range (difference between maximum and minimum peak RS i.e. Range(pRS)). Spectral Doppler (continuous wave) measurements were acquired through the left ventricular outflow tract to determine Pre Ejection Period (PEP), Left Ventricular Ejection Time (LVET) and measures of left ventricular systolic performance. RESULTS: LV segmental radial strain was profoundly heterogeneous in WPW cases in contrast to fairly homogenous strain pattern in normal subjects. Wide SD(pRS) values 17.5 +/- 8.9 vs 3.3 +/- 1.4, p<0.001 and Range(pRS) 42.7 +/- 20.8 vs.8.5 +/- 3.6 , p<0.001 were observed among WPW and healthy subjects respectively. PEP (132.4 +/- 14.7 vs 4.7 +/- 0.5ms, p<0.001) and corrected PEP (76.1 +/- 8.0 vs 2.7 +/- 0.4ms, p<0.001) were significantly longer in WPW patients compared to controls. The PEP/LVET ratio was also significantly greater in WPW cohort (0.49 +/- 0.04 vs. 0.28 +/- 0.05, p <0.001) suggesting global systolic dysfunction. CONCLUSIONS: Patients with manifest preexcitation (predominantly those with right-sided pathways) have regional and global contractile dysfunction resulting from aberrant impulse propagation inherent to the preexcited state.