Diastolic Interval Research Articles

Stochastic pacing reveals the propensity to cardiac action potential alternans and uncovers its underlying dynamics.

Beat-to-beat alternation (alternans) of the cardiac action potential duration is known to precipitate life-threatening arrhythmias and can be driven by the kinetics of voltage-gated membrane currents or by instabilities in intracellular calcium fluxes. To prevent alternans and associated arrhythmias, suitable markers must be developed to quantify the susceptibility to alternans; previous theoretical studies showed that the eigenvalue of the alternating eigenmode represents an ideal marker of alternans. Using rabbit ventricular myocytes, we show that this eigenvalue can be estimated in practice by pacing these cells at intervals varying stochastically. We also show that stochastic pacing permits the estimation of further markers distinguishing between voltage-driven and calcium-driven alternans. Our study opens the perspective to use stochastic pacing during clinical investigations and in patients with implanted pacing devices to determine the susceptibility to, and the type of alternans, which are both important to guide preventive or therapeutic measures. Alternans of the cardiac action potential (AP) duration (APD) is a well-known arrhythmogenic mechanism. APD depends on several preceding diastolic intervals (DIs) and APDs, which complicates the prediction of alternans. Previous theoretical studies pinpointed a marker called λalt that directly quantifies how an alternating perturbation persists over successive APs. When the propensity to alternans increases, λalt decreases from 0 to -1. Our aim was to quantify λalt experimentally using stochastic pacing and to examine whether stochastic pacing allows discriminating between voltage-driven and Ca(2+) -driven alternans. APs were recorded in rabbit ventricular myocytes paced at cycle lengths (CLs) decreasing progressively and incorporating stochastic variations. Fitting APD with a function of two previous APDs and CLs permitted us to estimate λalt along with additional markers characterizing whether the dependence of APD on previous DIs or CLs is strong (typical for voltage-driven alternans) or weak (Ca(2+) -driven alternans). During the recordings, λalt gradually decreased from around 0 towards -1. Intermittent alternans appeared when λalt reached -0.8 and was followed by sustained alternans. The additional markers detected that alternans was Ca(2+) driven in control experiments and voltage driven in the presence of ryanodine. This distinction could be made even before alternans was manifest (specificity/sensitivity >80% for -0.4>λalt >-0.5). These observations were confirmed in a mathematical model of a rabbit ventricular myocyte. In conclusion, stochastic pacing allows the practical estimation of λalt to reveal the onset of alternans and distinguishes between voltage-driven and Ca(2+) -driven mechanisms, which is important since these two mechanisms may precipitate arrhythmias in different manners.

Myocardial Performance Index (Tei Index): A simple tool to identify cardiac dysfunction in patients with diabetes mellitus

BackgroundCardiac dysfunction is the major cause of morbidity and mortality in diabetes. Myocardial Performance Index (MPI/Tei Index) includes both systolic and diastolic time intervals to assess the global cardiac dysfunction. Our aim was to assess the MPI in patients with type 2 diabetes. Material and methodsThis hospital-based analytic observational study was performed in the tertiary care center. The conventional Doppler parameters, tissue Doppler-derived E/E′ and MPI, were measured in all patients. Results100 patients with type 2 diabetes were included in the study. 65 patients showed diastolic dysfunction, 33 with Grade I diastolic dysfunction, 23 with Grade II diastolic dysfunction, and 14 patients with Grade III diastolic dysfunction. The conventional Doppler showed abnormality in 44% of patients (33 patients with Grade I and 14 patient with Grade III). 23 patients were in Grade II diastolic dysfunction (12 patients showed reversal E/A on valsalva maneuver and 11 patients showed abnormality in tissue Doppler-derived E/E′, E/E′>15). MPI with cut-off 0.36 was found to have 94% sensitivity, 100 specificity, and 94% PPV for the detection of cardiac dysfunction. MPI negatively correlated with systolic dysfunction (rho=0.455, p<0.001) and positively correlated with grade of diastolic dysfunction (rho=0.832, p<0.001) and NYHA grading of dyspnea (rho=0.872, p<0.001) ConclusionsMPI as a single parameter can be used for assessment in diabetic cardiac dysfunction.

Effects of Single and Multiple Energy Shots on Blood Pressure and Electrocardiographic Parameters

We assessed the effects of single and multiple caffeinated energy shots on hemodynamic and electrocardiographic (ECG) parameters. This was a randomized, double-blinded, placebo-controlled, crossover study in otherwise healthy volunteers (n = 26) where a caffeinated energy shot or matching placebo was ingested. The study drink was consumed twice daily for 7 days during each phase, with a 7-day washout period in between. The primary end points of interest were systolic and diastolic blood pressure (BP), heart rate, PR interval, QRS duration, and QT and QTc intervals. All parameters were evaluated at baseline, 1, 3, and 5 hours on the first and seventh day of each phase. Systolic BP after a single energy shot consumption was significantly higher than placebo at 3 and 5 hours (p = 0.050 and p = 0.038, respectively). Similarly, diastolic BP after a single energy shot consumption was significantly higher at 1 and 5 hours (p = 0.019 and p = 0.043, respectively). The systolic and diastolic BP elevations were not significant after consistent consumption (all p values ≥ 0.079). None of the ECG parameters were significantly affected (all p values ≥ 0.108) compared with placebo. In conclusion, a single shot of a caffeinated energy drink significantly raised systolic and diastolic BPs. However, these elevations were not sustained with chronic consumption. ECG parameters were not altered.

The RyR2-P2328S mutation downregulates Nav1.5 producing arrhythmic substrate in murine ventricles

Catecholaminergic polymorphic ventricular tachycardia (CPVT) predisposes to ventricular arrhythmia due to altered Ca2+ homeostasis and can arise from ryanodine receptor (RyR2) mutations including RyR2-P2328S. Previous reports established that homozygotic murine RyR2-P2328S (RyR2S/S) hearts show an atrial arrhythmic phenotype associated with reduced action potential (AP) conduction velocity and sodium channel (Nav1.5) expression. We now relate ventricular arrhythmogenicity and slowed AP conduction in RyR2S/S hearts to connexin-43 (Cx43) and Nav1.5 expression and Na+ current (INa). Stimulation protocols applying extrasystolic S2 stimulation following 8 Hz S1 pacing at progressively decremented S1S2 intervals confirmed an arrhythmic tendency despite unchanged ventricular effective refractory periods (VERPs) in Langendorff-perfused RyR2S/S hearts. Dynamic pacing imposing S1 stimuli then demonstrated that progressive reductions of basic cycle lengths (BCLs) produced greater reductions in conduction velocity at equivalent BCLs and diastolic intervals in RyR2S/S than WT, but comparable changes in AP durations (APD90) and their alternans. Western blot analyses demonstrated that Cx43 protein expression in whole ventricles was similar, but Nav1.5 expression in both whole tissue and membrane fractions were significantly reduced in RyR2S/S compared to wild-type (WT). Loose patch-clamp studies similarly demonstrated reduced INa in RyR2S/S ventricles. We thus attribute arrhythmogenesis in RyR2S/S ventricles resulting from arrhythmic substrate produced by reduced conduction velocity to downregulated Nav1.5 reducing INa, despite normal determinants of repolarization and passive conduction. The measured changes were quantitatively compatible with earlier predictions of linear relationships between conduction velocity and the peak INa of the AP but nonlinear relationships between peak INa and maximum Na+ permeability.

Effects of an Isolated Complete Right Bundle Branch Block on Mechanical Ventricular Function.

The purpose of this study was to investigate the effects of an isolated complete right bundle branch block on mechanical ventricular function. Two groups of participants were enrolled in this study: a block group, consisting of 98 patients with isolated complete right bundle branch blocks without structural heart disease, and a control group, consisting of 92 healthy adults. The diameter, end-diastolic area, end-systolic area, and right ventricular (RV) fractional area change were obtained to evaluate morphologic and systolic function by 2-dimensional sonographic technology. Systolic and diastolic velocities and time interval parameters were measured to assess mechanical ventricular performance using pulsed wave tissue Doppler imaging. Although there was no significant difference in the RV fractional area change between the patients with blocks and controls, the diameter, end-diastolic area, and end-systolic area of the RV were significantly larger in the patients with blocks (P < .05). In the patients with blocks, the peak velocities during systole and early diastole and the ratio of the peak velocities during early and late diastole decreased. The block group had a prolonged pre-ejection period, electromechanical delay time, and isovolumic relaxation time, a decreased ejection time, and an increased pre-ejection period/ejection time ratio, and the myocardial performance index (Tei index) at the basal RV lateral wall was significantly increased. There were no significant differences in any echocardiographic parameters at different sites of the left ventricle. In patients with isolated complete right bundle branch blocks, systolic and diastolic functions are impaired in the RV, and follow-up is needed.

Utility of ductus venosus blood flow in the study of cardiac function in fetuses with intracardiac echogenic focus.

The purpose of this study was to investigate fetal ductus venosus (DV) wave velocities, DV velocity ratios, and DV diastolic time intervals to derive additional information on fetal cardiac function in the presence of an intracardiac echogenic focus (IEF). Seventy fetuses at 19-28 weeks of gestation with an IEF and 63 control fetuses were screened using two-dimensional and power Doppler echocardiography. DV wave velocities, DV velocity ratios, and diastolic time intervals were measured. The aortic peak velocity, pulmonary artery peak velocity, left ventricular shortening fraction, and right ventricular shortening fraction, atrioventricular early-diastolic filling velocity (E), atrial contraction velocity (A), and E/A ratio were also measured. The study and control groups were similar in terms of maternal age, body mass index, and gestational age in weeks at the time of examination (p > 0.05). Significant between-group differences were found in DV v-descent (p = 0.03) and a-wave velocities (p = 0.04). Although the presence of an IEF in the fetal heart does not influence conventional measurements (DV velocity ratios and DV diastolic time intervals), it is associated with changes in DV v-descent and a-wave velocities. These changes may be indirectly related to reduced end-systolic relaxation and augmented atrial contraction in the fetal heart. We therefore suggest examination of DV flow velocities in fetuses with IEF.

Association between Hypertension and the Prevalence of Low Back Pain and Osteoarthritis in Koreans: A Cross-Sectional Study.

BackgroundHypertension and musculoskeletal disorders are highly prevalent in adult populations. The objective of this study was to investigate the association between hypertension and prevalence of low back pain (LBP) and osteoarthritis in Koreans.MethodsA total 17,128 participants (age ≥20 years) who answered low back pain and osteoarthritis items in the 4th Korean National Health and Nutrition Examination Survey (2007–2009) were analyzed. Odds ratios were calculated using logistic regression and were adjusted for age, sex, income level, education, occupation, BMI, smoking status, alcohol consumption, and physical activity.ResultsLifetime prevalence of LBP in hypertensive subjects was 34.4%, and that of osteoarthritis 26.2%. LBP prevalence was significantly lower in hypertensives (fully adjusted OR 0.79; 95% CI 0.70–0.90), and both LBP and osteoarthritis prevalence was significantly lower in participants with systolic blood pressure ≥140mmHg than those with <120mmHg (fully adjusted OR 0.81; 95% CI 0.70–0.94, and 0.81; 95% CI 0.68–0.96, respectively). Prevalence of LBP in subjects with diastolic blood pressure ≥90mmHg was also significantly lower than those with <80mmHg (fully adjusted OR 0.73; 95% CI 0.63–0.85). LBP and osteoarthritis prevalence did not differ by systolic or diastolic blood pressure interval in respondents taking antihypertensive medication. LBP and osteoarthritis prevalence increased with longer hypertension duration (fully adjusted p for trend 0.028, and 0.0008, respectively).ConclusionsHypertension showed an inverse relationship with LBP and osteoarthritis prevalence, which may be ascribed to hypertension-associated hypalgesia, and antihypertensive medication intake and longer hypertension duration attenuated this association.

Real-time feedback based control of cardiac restitution using optical mapping.

Cardiac restitution is the shortening of the action potential duration with an increase in the heart rate. A shorter action potential duration enables a longer diastolic interval which ensures that the heart gets adequate time to refill with blood. At higher rates however, restitution becomes steep and thus, can lead to unstable electrical activity (alternans) in the heart, leading to fatal cardiac rhythms. It has been proposed that maintaining a shallow slope of cardiac restitution could have potentially anti-arrhythmic effects. Previous studies involved the control of action potential duration (APD) or diastolic interval (DI) in isolated tissue samples based on the feedback from single microelectrode recordings. This limited the spatial resolution of the feedback system. Here, we aimed to develop a real time feedback control system that enabled the detection of APDs from various single pixels based on optical mapping recordings. Stimuli were applied after a predefined fixed DI after detection of an APD. We validated our algorithm using optical mapping movies from an ex-vivo rabbit heart. Thus, we provide an optical mapping based approach for the control of cardiac restitution and a potential means to validate its anti-arrhythmic effects.

Fatiguing exercise initiated later in life reduces incidence of fibrillation and improves sleep quality in Drosophila.

As the human body ages, the risk of heart disease and stroke greatly increases. While there is evidence that lifelong exercise is beneficial to the heart's health, the effects of beginning exercise later in life remain unclear. This study aimed to investigate whether exercise training started later in life is beneficial to cardiac aging in Drosophila. We examined 4-week-old wild-type virgin female flies that were exposed to exercise periods of either 1.5, 2.0, or 2.5 h per day, 5 days a week for 2 weeks. Using M-mode traces to analyze cardiac function by looking at parameters including heart rate, rhythmicity, systolic and diastolic diameter, and interval and fractional shortening, we found that cardiac function declined with age, shown by an increase in the number of fibrillation events and a decrease in fractional shortening. About 2.0 and 2.5 h of exercise per day displayed a reduced incidence of fibrillation events, and only physical exercise lasting 2.5-h period increased fractional shortening and total sleep time in Drosophila. These data suggested that training exercise needs to be performed for longer duration to exert physiological benefits for the aging heart. Additionally, climbing ability to assess the exercise-induced muscle fatigue was also measured. We found that 2.0 and 2.5 h of exercise caused exercise-induced fatigue, and fatiguing exercise is beneficial for cardiac and healthy aging overall. This study provides a basis for further study in humans on the impact of beginning an exercise regimen later in life on cardiac health.

DFOXO overexpression ameliorates age‐related degeneration of heart performance in Drosophila

Despite increased life expectancy, a decrease in healthy heart function with age persists. Age-related heart degeneration can manifest itself as decreased heart rate and fractional shortening and increased arrhythmias and diastolic intervals. Such changes are conserved from humans to flies and are possibly related to a decreased ability of protein quality control systems to maintain normal protein homeostasis over time through autophagy and/or the ubiquitin-proteosome system. Elevated expression of muscle-specific FOXO transcription factors has been previously shown to positively affect autophagy in Drosophila and ameliorate the accumulation of ubiquitinated proteins systemically with age. We hypothesize that mild overexpression of heart-specific dFOXO will have a cardioprotective effect in aging Drosophila. By aging FOXO and control flies to seven weeks, we compared indices of cardiac function at various time points using video microscopy and semi-automated optical heart analysis (SOHA). Our data suggest that overall, age-dependent changes in heart function in old FOXO flies were significantly ameliorated relative to controls. Ubiquitin levels were measured by quantitative western blot analysis. Geriatric control flies displayed higher ubiquitin levels relative to FOXO, suggesting enhanced proteostasis contributes to improved heart function. Additionally, FOXO-specific RNAi lines were used to further evaluate the effects of FOXO on cardiac function. These preliminary data indicate that knocking down FOXO expression with small interfering RNA can have detrimental effects on heart performance. Grant Funding Source: APS, NSF IOS-1238831

Right ventriculo-arterial coupling in repaired Fallot patients with pulmonary valve regurgitation before and after pulmonary valve implantation: a CMR study

Background Right ventricular-pulmonary arterial coupling plays an important role in the occurrence of right ventricular failure. Ventricular-arterial coupling is defined as Ea/ Emax. Ea is the effective arterial elastance and an index of the post-load, and includes vascular resistances, vessel compliance, vascular impedance, systolic and diastolic time intervals. Ea = (arterial end-systolic pressure/stroke volume), where arterial end-systolic pressure = (mean pulmonary arterial pressure wedge capillary pressure). The role of wedge capillary pressure can be considered negligible in subjects with normal pulmonary artery pressure and normal left ventricular (LV) function. Therefore, the formula can be simplified to Ea = (mean pulmonary arterial pressure/stroke volume). Emax is the maximal systolic ventricular elastance. This is a loadindependent index. It occurs at the end of the systole and is given by the formula Emax = [end-systolic pressure/(end-systolic volume volume (theorical) at zero load)]. Volume at zero load can be considered negligible, and end-systolic pressure can be approximated by mean pulmonary arterial pressure. Therefore Emax = (mean pulmonary artery pressure/end-systolic volume). Consequently, Ea/Emax = [(mean pulmonary artery pressure/ stroke volume)/(end-systolic volume/mean pulmonary artery pressure)] and results in Ea/Emax = (end-systolic volume/stroke volume). Optimal ventricular-arterial coupling is when Ea/Emax=1. Objective of this study is to evaluate by CMR the right ventricular-arterial coupling before and after surgical or transcatheter pulmonary valve implantation (PVI) in subjects who underwent surgery for tetralogy of Fallot (ToF) and have pulmonary valve (PV) regurgitation and/ or stenosis.

Mild hypothermia induces incomplete left ventricular relaxation despite spontaneous bradycardia in pigs.

Mild hypothermia (MH) decreases left ventricular (LV) end-diastolic capacitance. We sought to clarify whether this results from incomplete relaxation. Ten anaesthetized pigs were cooled from normothermia (NT, 38 °C) to MH (33 °C). LV end-diastolic pressure (LVPed), volume (LVVed) and pressure-volume relationships (EDPVRs) were determined during stepwise right atrial pacing. LV capacitance (i.e. LVVed at LVPed of 10 mmHg, LV VPed10) was derived from the EDPVR. Pacing-induced changes of diastolic indices (LVPed, LVVed and LV VPed10) were analysed as a function of (i) heart rate and (ii) the ratio between diastolic time interval (t-dia) and LV isovolumic relaxation constant τ, which was calculated using a logistic fit (τL ) and monoexponential fit with zero asymptote (τZ ) and nonzero asymptote (τNZ ). Mild hypothermia decreased heart rate (85 ± 4 to 68 ± 3 bpm), increased τL (22 ± 1 to 57 ± 4 ms), τZ (26 ± 2 to 56 ± 5 ms) and τNZ (41 ± 1 to 96 ± 5 ms), decreased t-dia/τ ratios, and shifted the EDPVR leftwards compared to NT (all P < 0.05). During NT, pacing at ≥140 bpm shifted the EDPVR progressively leftwards. During MH, relationships between diastolic indices and heart rate were shifted towards lower heart rates compared to NT. However, relationships between diastolic indices and t-dia/τ during NT and MH were superimposable. We conclude that the loss of LV end-diastolic capacitance during MH can be explained at least in part by slowed LV relaxation. MH thereby is an example of incomplete LV relaxation at a spontaneous low heart rate. Caution may be advised, when heart rate is increased in patients treated with MH.

Analyzing Systolic-Diastolic Interval Interaction Characteristics in Diabetic Cardiac Autonomic Neuropathy Progression.

Cardiac autonomic neuropathy (CAN), one of the major complications in diabetes, if detected at the subclinical stage allows for effective treatment and avoiding further complication including cardiovascular pathology. Surface ECG (Electrocardiogram)-based diagnosis of CAN is useful to overcome the limitation of existing cardiovascular autonomic reflex tests traditionally used for CAN identification in clinical settings. The aim of this paper is to analyze the changes in the mechanical function of the ventricles in terms of systolic-diastolic interval interaction (SDI) from a surface ECG to assess the severity of CAN progression [no CAN, early CAN (ECAN) or subclinical CAN, and definite CAN (DCAN) or clinical CAN]. ECG signals recorded in supine resting condition from 72 diabetic subjects without CAN (CAN-) and 70 diabetic subjects with CAN were analyzed in this paper. The severity of CAN was determined by Ewing’s Cardiovascular autonomic reflex tests. Fifty-five subjects of the CAN group had ECAN and 15 subjects had DCAN. In this paper, we propose an improved version of the SDI parameter (i.e., TQ/RR interval ratio) measured from the electrical diastolic interval (i.e., TQ interval) and the heart rate interval (i.e., RR interval). The performance of the proposed SDI measure was compared with the performance of the existing SDI measure (i.e., QT/TQ interval ratio). The proposed SDI parameter showed significant differences among three groups (no CAN, ECAN, and DCAN). In addition, the proposed SDI parameter was found to be more sensitive in detecting CAN progression than other ECG interval-based features traditionally used for CAN diagnosis. The modified SDI parameter might be used as an alternative measure for the Ewing autonomic reflex tests to identify CAN progression for those subjects who are unable to perform the traditional tests. These findings could also complement the echocardiographic findings of the left ventricular diastolic dysfunction by providing additional information about alteration in systolic and diastolic intervals in heart failure.

Normal left ventricular torsion mechanics in healthy children: age related changes of torsion parameters are closely related to changes in heart rate.

Background and ObjectivesThis study was aimed at assessing left ventricular torsion (LVtor) mechanics using speckle tracking echocardiography (STE), establishing normal reference values of principal LVtor parameters, and analyzing the age-related changes in normal children.Subjects and MethodsEighty children (aged 3 months to 15 years) with normal cardiac function and rhythm were recruited. LVtor parameters including rotations, twist and untwist, torsion, and their rate indices were measured using STE. Age and heart rate related changes of the parameters were analyzed.ResultsSpeckle tracking echocardiography analyses for LVtor parameters had excellent reliability in 64 of 80 subjects (80%) (intraclass correlation coefficients; 0.93-0.97). Early systolic twist (EST) motions (-8.4--0.1°) were observed in all subjects during an early 20±7% of systolic time intervals. The peak systolic twist and torsion were 17.0±6.5° and 2.9±1.3°/cm, respectively. The peak twist velocity was recorded at 51±13% of systolic time and the peak untwist velocity at 13.8±11.5% of diastolic time intervals. Multivariate analysis showed that heart rate change was an independent predictor of changes in torsion parameters; significantly decreasing LV length-normalized apical and basal rotation, torsion, and twist and untwist rate with increasing age. Isovolumetric recoil rate was independent of change in age and heart rate.ConclusionLeft ventricle showed unique torsion mechanics in children with EST, torsion, and untwists. Heart rate was an independent predictor of the change in torsion parameters with aging.

High Order Statistics and Time-Frequency Domain to Classify Heart Sounds for Subjects under Cardiac Stress Test.

This paper considers the problem of classification of the first and the second heart sounds (S1 and S2) under cardiac stress test. The main objective is to classify these sounds without electrocardiogram (ECG) reference and without taking into consideration the systolic and the diastolic time intervals criterion which can become problematic and useless in several real life settings as severe tachycardia and tachyarrhythmia or in the case of subjects being under cardiac stress activity. First, the heart sounds are segmented by using a modified time-frequency based envelope. Then, to distinguish between the first and the second heart sounds, new features, named α opt, β, and γ, based on high order statistics and energy concentration measures of the Stockwell transform (S-transform) are proposed in this study. A study of the variation of the high frequency content of S1 and S2 over the HR (heart rate) is also discussed. The proposed features are validated on a database that contains 2636 S1 and S2 sounds corresponding to 62 heart signals and 8 subjects under cardiac stress test collected from healthy subjects. Results and comparisons with existing methods in the literature show a large superiority for our proposed features.

An innovative intelligent system based on automatic diagnostic feature extraction for diagnosing heart diseases

An innovative intelligent diagnostic system is proposed in this study, which is primarily reflected in first heart sound (S1) and second heart sound (S2) automatic extraction, frequency feature matrix (FFM) automatic extraction, diagnostic feature y1 and y2 generation based on principal components analysis (PCA) and diagnostic method definition based on the classification boundary curves. Four stages corresponding to the diagnostic system implementation are summarized as follows. Stage 1 describes an envelope ET extraction from heart sound signals. In stage 2, heart sound segmentation points and peaks are first automatically located based on a novel method STMHT, and then S1 and S2 are automatically extracted according to the relationship between the systolic time interval and the diastolic time interval. In stage 3, in the frequency domain, a novel method is first proposed to generate the secondary envelopes SES1 and SES2 for S1 and S2, respectively, and then an STMHT-based FFM is automatically extracted from SES1 and SES2. Finally, the PCA-based diagnostic features y1 and y2 are generated from the FFM. In stage 4, support vector machine (SVM)-based classification curves for the dataset consisting of y1 and y2 are first generated, and then, based on the classification curves, the scatter diagram diagnostic result (SDDR) and numerical diagnostic result (NDR) are defined for diagnosis of heart diseases. The proposed intelligent diagnosis system is validated by sounds from online heart sound databases and by sounds from clinical heart diseases. As a result, the classification accuracies (CA) achieved are 91.7%, 98.8%, 98.4%, 99.8%, 98.7%, 97.8%, 98.1% and 96.5% for the detection of atrial fibrillation (AF), aortic regurgitation(AR), mitral regurgitation (MR), normal sound (NM), pulmonary stenosis (PS), small ventricular septal defect (SVSD), medium ventricular septal defect (MVSD) and large ventricular septal defect (LVSD), respectively.

Abstract 15985: Liver Transplantation Does Not Reverse Cirrhotic Cardiomyopathy

Background: Cirrhotic cardiomyopathy (CCM), a frequent finding in patients with end stage liver disease (ESLD), presents with diastolic dysfunction (DD), hyperdynamic state, and prolonged corrected QT interval (QTc). Liver transplantation (LT) is thought to be the only treatment for CCM. The aim of our study is to assess the reversibility of CCM after LT. Methods: We retrospectively assessed the data of 82 patients collected from the Cleveland Clinic LT database between the years 2007 to 2008 that had an echocardiogram (TTE) and an EKG pre and post-LT. The clinical characteristics were obtained from the electronic record and all EKG and TTE were analyzed by 2 independent observers in the standard manner. The frequency of CCM criteria in ESLD patients was compared with 74 matched controls with no history of liver disease. Results: The median age of patients was 57 years (IQR 19 to 72), 72% were males and 85% were Caucasian. The median time between LT and post-LT testing was 4 years (IQR 0.1 to 6). Compared to controls, patients with ESLD had a longer QTc (449 ±25 vs. 430 ±23 msec; p&lt;0.001) and higher cardiac output (CO) (5.9 ±1.8 vs. 4.8 ±1.1 L/min; p=0.001), left atrial (LA) volume index (33 ±10 vs. 25 ±7 ml/m 2 ; p&lt;0.001), left ventricular (LV) end diastolic volume index (60±14 vs. 49±12 ml/m 2 ; p=0.001 and mitral valve inflow velocity (E) (85 ±23 vs. 75 ±20 cm/sec; p=0.003). Post-LT, there was significant increase in LV mass index (LVMI) (107±38 vs 91±24 gm/ m 2 ; p=0.002) and prevalence of DD (75% vs. 47%; p&lt;0.001) but no difference in CO, LA and LV volumes. In contrast, there was a significant reduction of QTc (449 ±25 to 440 ±28 msec; p=0.04). Conclusions: In our study, patients with ESLD had a higher QTc and CO than matched controls. Post-LT, only QTc showed a significant improvement.

Echocardiographic evaluation of right ventricular function in congenital heart disease.

This review aims to provide an overview of conventional and novel indices used in clinical and research arenas for evaluation of right ventricular (RV) function in congenital heart diseases with a dual-chambered circulation. Articles cited in this review were selected using PubMed search of publications in English with no date limits. The search terms included "echocardiography", "right ventricle", "RV function", "cardiac function", and "congenital heart disease". Key references were also searched for additional publications. Articles related to description of echocardiographic techniques in the evaluation of subpulmonary or systemic RV function and their applications in congenital cardiac malformations were retrieved and reviewed. Three approaches have been used to evaluate subpulmonary and systemic RV function: (1) assessment of changes in RV size in the cardiac cycle, (2) determination of Doppler-derived velocities and systolic and diastolic time intervals, and (3) quantification of myocardial velocities and deformation. Conventional and novel echocardiographic techniques enable the evaluation of subpulmonary and systemic RV function. Novel echocardiographic techniques have further allowed quantification of RV volumes and direct interrogation of myocardial deformation. These new techniques show promise in a more comprehensive evaluation beyond "eye-balling" of RV function in the growing population of adolescent and adult congenital heart patients.

5Improving sudden cardiac death risk stratification in patients with ischaemic cardiomyopathy: a combined electrocardiogram and plasma biomarker approach

Introduction: Sudden cardiac death (SCD) risk prediction has substantial limitations. The Regional Restitution Instability Index (R2I2) is a promising new ECG-based biomarker of SCD. R2I2 uses the surface 12-lead ECG to quantify regional heterogeneity of electrical restitution, a property of ventricular myocardium implicated in arrhythmogenesis. We investigated the potential of a combined R2I2 and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) SCD risk marker in an ischaemic cardiomyopathy cohort. Methods: Blinded, prospective, observational study of 55 ischaemic cardiomyopathy patients (age: 67±9years, ejection fraction: 31±10%) undergoing risk stratification for an implantable cardioverter defibrillator (ICD). R2I2 was calculated using a pre-defined technique: an electrophysiology study is performed and ECG surrogates for action potential duration (QRS-onset to T-peak) and diastolic interval (T-peak to QRS-onset) are used to measure heterogeneity of electrical restitution. Plasma samples obtained on the day of the ICD procedure were assayed for NT-proBNP. A pre-defined R2I2 cut-off (1.03) was combined with an optimal log NT-proBNP cut-off (2.65) to investigate the potential of a combined risk marker. Results: During median follow up of 22 months, 15 patients experienced ventricular arrhythmia (VA)/SCD. R2I2 was significantly higher in patients experiencing VA/SCD than those not (mean±SEM:1.12±0.05 vs 0.84±0.09, p=0.004). R2I2 was independent of age, gender, left ventricular ejection fraction, QRS duration and log NT-proBNP in prediction of endpoint (Cox model, p=0.002). Partitioning patients using a log NT-proBNP ≥ 2.65 gave a significantly higher rate of VA/SCD in those with high versus low log NT-proBNP (38% vs. 6%, p=0.01). Patients with R2I2 ≥ 1.03 and log NT-proBNP ≥ 2.65 had a hazard ratio for VA/SCD 17.2 times that of patients negative for both (Cox model, p=0.007). Kaplan Meier analysis (Figure 1) showed significant separation in rates of VA/SCD in patients stratified by R2I2 ≥ 1.03 and log NT-proBNP ≥ 2.65 (log-rank, p<0.0001). Conclusion: A combined R2I2 + NT-proBNP risk marker identifies patients at particularly high risk of ventricular arrhythmia/SCD. These patients might benefit from careful treatment optimisation. R2I2 + NT-proBNP might retain sufficient positive predictive value for application to lower risk cohorts. ![Graphic][1] Figure 1 Kaplan-Meier curves illustrating rates of VA/SCD in patients stratified using R212 and NT-proBNP [1]: /embed/inline-graphic-1.gif

22Combining a novel electrical restitution based biomarker with heart rate variability analysis improves prediction of sudden cardiac death risk

Introduction: Sudden cardiac death (SCD) remains a significant cause of mortality worldwide. Current SCD risk markers have substantial limitations. Peak Electrical Restitution Slope (PERS) is a promising new SCD risk marker. PERS uses the surface 12-lead ECG to measure peak restitution gradient, a property of myocardium known to play a role in ventricular arrhythmogenesis. By combining PERS with heart rate variability (HRV) analysis, we sought to improve SCD risk prediction in patients with ischaemic cardiomyopathy (ICM). Methods: Blinded, prospective, observational study of 44 ICM patients (>18 years of age) undergoing risk stratification for an implantable cardioverter defibrillator. Patients underwent programmed ventricular stimulation for determination of PERS. Surface ECG surrogates for action potential duration (QRS-onset to T-peak) and diastolic interval (T-peak to QRS-onset) were used to measure peak restitution gradient. Patients underwent 24-hour ambulatory ECG monitoring to determine time-domain HRV (standard deviation of normal to normal RR intervals [SDNN]). A pre-defined SDNN cut off (100ms) was combined with an optimal PERS cut-off (1.21) to determine if combining these risk markers could improve SCD risk stratification. Results: During median follow up of 22 months, 11 patients experienced ventricular arrhythmia (VA)/SCD. PERS was significantly higher in patients experiencing VA/SCD than those not (mean±SEM:1.73±0.27 vs 1.07±0.08, p=0.002). PERS was independent of age, gender, left ventricular ejection fraction, QRS duration and SDNN in prediction of endpoint (Cox model, p=0.002). Patients with low SDNN (<100ms) experienced a non-significantly higher rate of VA/SCD than those with high SDNN (33% vs 19%, p=0.24). Patients with PERS ≥ 1.21 and SDNN<100ms had a hazard ratio for VA/SCD 17.4 times that of patients negative for both (Cox model, p=0.01). Kaplan Meier analysis (Figure 1) showed significant separation in rates of VA/SCD in patients stratified by PERS and SDNN (log-rank, p=0.002). Conclusions: Combining PERS with SDNN identifies patients at particularly high risk of ventricular arrhythmia/SCD. A combined PERS + SDNN risk marker may improve SCD risk stratification in patients with ischaemic cardiomyopathy. ![Graphic][1] Figure 1 Kaplan-Meier curves illustrating rates of VA/SCD in patients stratified using PERS and SDNN. [1]: /embed/inline-graphic-1.gif