Peak Apical Recoil Rate is a Simplified Index of Left Ventricular Untwist: Validation and Application for Assessment of Diastolic Function in Children

AimsTo simplify measurement of untwist by measuring the recoil rate of LV apex only, to validate and apply peak apical recoil rate (PARR) as an index of diastolic dysfunction (DD) in pediatric subjects during increased and decreased lusitropic states. Methods and ResultsWe recruited 153 healthy subjects (mean age 13.8+2.9 years), of whom 48 performed straight leg raising exercise and an additional 46 patients (mean 8.4+5.6 years) with documented pulmonary capillary wedge pressures (PCWP) (validation cohort). In addition, we studied 16 dilated cardiomyopathy patients (mean age 9.5+6.3years) (application cohort). PARR and isovolumic relaxation time (IVRT) were compared to PCWP. Both PARR and PARR normalized by heart rate (nPARR) were excellent in detecting patient with PCWP >12 mmHg and greatly superior to IVRT in this respect (AUC: 0.98, 95% CI [0.96, 1.0] vs. AUC: 0.7 95%CI [0.54,0.86]). In DCM patients, PARR and nPARR were greatly decreased compared to controls (-38.58+18.59º/s vs -63.07+16.35º /s, p< 0.001) and (-0.43+0.20 º/ s/min vs -0.83+0.28º/s/min, p<0.0001) but increased with straight leg raising exercise (-59.4+19.4º/s vs -97.82+39.0 º/s, p<0.01) and -0.85+0.36 vs -1.4+0.62 º/s/min (p< 0.0001). The intra-observer and inter-observer intraclass correlation (ICC) coefficients were 0.95 and 0.88, respectively.ConclusionPARR successfully detected increased and decreased lusitropic states and was not affected by age when normalized with heart rate. Both PARR and nPARR are superior to IVRT in their correlation with PCWP and offer incremental value over traditional indices of DD. This highly reproducible parameter may potentially serve as a useful index of elevated PCWP in children.

Global constructive myocardial work predicts left ventricular disfunction onset beyond longitudinal strain in patients with significant primary mitral regurgitation

Accurate surgical timing for significant primary mitral regurgitation (PMR) still remains an issue despite of several ways of left ventricular (LV) hidden disfunction detection, including LV global longitudinal strain (GLS). Since novel modalities such as myocardial work (MW) or area strain (AS) are currently available we assumed that they might predict surgical timing beyond known parameters. Methods 58 patients (31 female) 63±8 years, asymptomatic and with pulmonary systolic pressure (PSP) ≤45 mmHg on exercise echo test (ET), with PMR, in sinus rhythm, with ejection fraction (EF) ≥65% and GLS &lt;−19.5% were enrolled into the study along with 23 healthy subjects matched by age and sex and followed up for 1 year. Comprehensive echocardiography (EchoCG) was performed with offline analysis including MW and AS by one experienced specialist. GW index (GWI) was obtained from pressure-strain loops derived from speckle tracking analysis multiplied by brachial systolic blood pressure.Global constructive work (GCW) as the sum of positive work due to myocardial shortening during systole and negative work due to lengthening during isovolumic relaxation, global wasted work (GWW) aa energy loss by myocardial lengthening in systole and shortening in isovolumic relaxation, and GW efficiency (GWE) as the percentage ratio of constructive work to the sum of constructive work and wasted work were obtained by the dedicated software. Results 13 (22%) patients with PMR became symptomatic or increase PSP &gt;50 mmHg on ET in 1 year follow up. EF, GLS, AS and GWI did not differ between symptomatic patients and those who remained asymptomatic during follow up, however these patients had significantly lower values of GCW, and higher values of GWW (EF 68.3±6.1% vs 69.2±6.5%, p=NS; GLS –22.4±2.3% vs 23.1±3.2%, p=NS, GWI 2452±161 mmHg% vs 2479±147 mmHg%, p=NS; GCW 1875±119 mmHg% vs 2321±124 mmHg%, p&lt;0.01; GWW 118±9 mmHg% vs 88±7 mmHg%, p&lt;0.03; GWE 93±8% vs 96±9%, p=NS; AS −32.5±5.4% vs −34.3±6.1%, p=NS;). Patients with subsequent symptoms development had significantly lower values of GCW and higher values of GWW. Among all parameters GCW was the predictor of MR clinical course worsening (AUC 0.769). Conclusion MR GCW is able to predict clinical course of patients with PMR beyond known conventional parameters. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): City Hall resources

Prognostic value of strain rate during isovolumic relaxation in a general population

Background Left ventricular (LV) strain rate (SR) during isovolumic relaxation (SRIVR) has been shown to correlate with invasive measurements of diastolic function, namely the time constant of LV relaxation (τ), and has thus been proven useful in the assessment of diastolic function. Tissue Doppler imaging (TDI) has an adequate frame rate to resolve the SR during a short-lived mechanical event such as IVR. Purpose The purpose of this study was to assess the additive prognostic value of SRIVR on top of conventional cardiovascular risk factors in a general population. Methods We included 670 subjects (age: 51.2±14.2, 48.8% males) that were already recruited in the Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO), from May 2005 to February 2009. Subjects were followed up on average 5 years after their recruitment, either by a follow-up visit or by telephone. Exclusion criteria at baseline were atrial fibrillation, presence of an artificial pacemaker, more than mild valvular disease and segmental wall motion abnormalities. All patients underwent echocardiographic examination with a state of the art ultrasound machine. Using an in-house developed software package (SPEQLE), we extracted the velocity, strain and SR curves from the color TDI images (FR &gt;180Hz) and imposed timing information on the IVR based on valve opening/closing as determined from PW Doppler data. The sample volume was positioned at the mid portion of the inferolateral wall, in an apical 3 chamber view, manually tracked over the cardiac cycle and all curves were averaged over 3 subsequent cardiac cycles. Then, SRIVR was estimated as the peak SR value during IVR (Fig. 1). Outcome data consisted of major adverse cardiac events (MACE) during the follow-up period. The hazard ratio (HR) associated with SRIVR values was estimated using Cox regression analysis; we included age, sex, body mass index, systolic blood pressure, smoking and serum cholesterol as co-variables in the model. Results An accurate assessment of the SRIVR in the inferolateral wall was not possible in 34 participants, so further analysis was confined to 636 subjects. In total, 65 adverse cardiac events were recorded over the period of 8.7 years of follow-up. Figure 2 demonstrates the cumulative incidence estimates (1-Kaplan-Meier survival estimates) of composite cardiac events in quartiles of SRIVR measured in the inferolateral wall (log-rank test p=0.005). Overall, after adjustment for the important cardiovascular risk factors, SRIVR of the inferolateral wall analyzed as a continuous variable was a significant predictor of fatal and nonfatal cardiac events (HR 1.94 (95% CI 1.09–3.47); p=0.025). Conclusion SRIVR measured in the inferolateral wall is an important biomarker not only in assessing diastolic function but also as a significant predictor of future adverse outcomes. FUNDunding Acknowledgement Type of funding sources: None.

Fetal Hemodynamic Responses to Arterial Occlusion of Acardiac Twins

The objective of this study was to comprehensively assess fetal hemodynamic adaptions to occlusive procedures. Twin pregnancies complicated with acardiac twin and hydrops fetalis of the pump twin were recruited. The occlusive procedures — either alcoholization, radiofrequency ablation, coil embolization or occlusive glue — were performed under ultrasound guidance. Various hemodynamic parameters were assessed before, shortly after, then every 6 h for 48 h and 2−4 weeks after the procedures. Seven pregnancies were recruited. The median (range) gestational age of intervention was 21 (17−26) weeks of gestation. Before the procedures, all cases showed normal cardiac function. Just after the procedures, all cases showed an increase in Tei index and isovolumic relaxation time but returned to preocclusion levels within 6−48 h, except for two cases that were persistently high. Increased preload and poor shortening fraction were observed in two cases, leading to heart failure, with one recovery and one death in utero. Five out of the seven cases got through the critical period with a gradual return to normal hemodynamics, ending with the disappearance of hydrops and successful outcomes. It was concluded that the occlusive procedure could aggravate the overworked heart, leading to heart failure. Preocclusion preload index and Tei index may predict risk of heart failure due to the occlusion. This small series strongly suggests that the occlusion should be performed before the deterioration of cardiac function.

Omecamtiv mecarbil evokes diastolic dysfunction and leads to periodic electromechanical alternans

Omecamtiv mecarbil (OM) is a promising novel drug for improving cardiac contractility. We tested the therapeutic range of OM and identified previously unrecognized side effects. The Ca2+ sensitivity of isometric force production (pCa50) and force at low Ca2+ levels increased with OM concentration in human permeabilized cardiomyocytes. OM (1 µM) slowed the kinetics of contractions and relaxations and evoked an oscillation between normal and reduced intracellular Ca2+ transients, action potential lengths and contractions in isolated canine cardiomyocytes. Echocardiographic studies and left ventricular pressure–volume analyses demonstrated concentration-dependent improvements in cardiac systolic function at OM concentrations of 600–1200 µg/kg in rats. Administration of OM at a concentration of 1200 µg/kg was associated with hypotension, while doses of 600–1200 µg/kg were associated with the following aspects of diastolic dysfunction: decreases in E/A ratio and the maximal rate of diastolic pressure decrement (dP/dtmin) and increases in isovolumic relaxation time, left atrial diameter, the isovolumic relaxation constant Tau, left ventricular end-diastolic pressure and the slope of the end-diastolic pressure–volume relationship. Moreover, OM 1200 µg/kg frequently evoked transient electromechanical alternans in the rat in vivo in which normal systoles were followed by smaller contractions (and T-wave amplitudes) without major differences on the QRS complexes. Besides improving systolic function, OM evoked diastolic dysfunction and pulsus alternans. The narrow therapeutic window for OM may necessitate the monitoring of additional clinical safety parameters in clinical application.

IMPROVEMENT OF THE PREOPERATIVE ECHOCARDIOGRAPHIC SCREENING METHODS IN DWARF BREEDS DOGS

The article presents the results of assessing the informativeness of the improved technique of preoperative echocardiographic screening study in dwarf dog breeds. Evaluation of the ratio of the sizes of the left atrium to the root of the aorta, the pulmonary vein to the right branch of the pulmo-nary artery, normalized to the body weight of the end-systolic and end-diastolic dimensions, the fraction of the shortening of the left ventricle, the velocity of the peak E of the transmitral blood flow and the time of isovolumic relaxation makes it possible to carry out an effective preoperative assessment functional state of the cardiovascular system in dwarf dogs. These indicators do not de-pend on the body weight of dogs and characterize the state of remodeling, systolic and diastolic functions of the left chambers of the heart. Determination of the complex of these echocardiograph-ic parameters within 8-11 minutes makes it possible to assess the pumping function of the heart, to predict and reduce the risk of developing cardiogenic pulmonary edema.

Studies on Pulsed-wave Doppler Echocardiographic Parameters of Blood Flow through Mitral, Tricuspid and Aortic Valves in Healthy Indian Spitz Dogs

Background: Pulsed-wave Doppler measures blood flow at specific point and provides information on velocity, direction and uniformity of blood flow throughout cardiac cycle. Till date, there is no published data on study of cardiac parameters using pulsed-wave Doppler echocardiography in Indian Spitz dogs.Methods: Twenty-four clinically normal Indian Spitz dogs were subjected to pulsed-wave Doppler echocardiography to determine the reference intervals for Doppler parameters of blood flow through mitral, tricuspid and aortic valves. Mitral peak E and A-wave velocities, E/A ratio, deceleration time, isovolumic relaxation time, E and A-wave velocity time integral, E duration and A duration were 0.69±0.09 m/s, 0.43±0.12 m/s, 1.69±0.45, 111.25±35.94 ms, 48.50±24.77 ms, 0.07±0.01 m and 0.04±0.02 m, 196.88±44.38 ms and 181.25±64.89 ms, respectively. Tricuspid peak E and A-wave velocities, E/A ratio and E and A-wave velocity time integral were 0.57±0.11 m/s, 0.38±0.08 m/s, 1.56±0.32 and 0.07±0.02 m and 0.05±0.01 m, respectively. Aortic peak velocity, velocity time integral and ejection time were 0.87±0.07 m/s, 0.11±0.02 m and 0.25±0.04 s, respectively. Conclusion: The reference values of flow parameters across mitral, tricuspid and aortic valves using pulsed-wave Doppler echocardiography were determined. Mitral, tricuspid and aortic valve flow variables were unaffected by gender whereas isovolumic relaxation correlated positively with body weight.

Abstract 17253: The Late Sodium Current Contributes to Electromechanical Defects Occurring With Aging

To establish the contribution of the late sodium current (I NaL ) on cardiovascular defects occurring with aging, mice with phosphomimetic mutation of Na + channel Nav1.5 at Ser571 (S571E), which causes I NaL enhancement in cardiomyocytes (I NaL gain-of-function), and mice with ablation of the Nav1.5 Ser571 (S571A), preventing CaMKII-mediated I NaL increase under stress condition (I NaL loss-of-function) were studied together with C57Bl/6 mice (wild-type, WT). Male mice at 2-6 (~4 m), 10-16 (~12 m), 17-20 (~18 m), and 20-27 (~24 m) months of age underwent electrocardiographic and echocardiographic evaluation. In WT mice, the QT interval duration of the ECG in the anesthetized state was similar at ~4 and ~12 months (56±5 ms and 58±5 ms, respectively) and was prolonged at ~18 and ~24 months (66±4 ms and 67±3 ms, respectively). In S571E mice, QT interval at ~4 months was prolonged with respect to WT animals (67±4 ms) and remained protracted at ~12, ~18, and ~24 months (65±3 ms, 68±6 ms, and 69±5 ms). S571A animals at ~4 months presented intermediate QT interval duration with respect to the other two strains (61±3 ms), and remained unchanged at ~12, ~18, and ~24 months (63±4 ms, 62±4 ms, and 64±4 ms). Ejection fraction was not altered with age and was comparable for the three mouse groups. In contrast, by transmitral flow Doppler echocardiography diastolic function, quantified here by the isovolumic relaxation time, was normal in WT mice at ~4 (17.4±1.6 ms) and ~12 months (16.8±1.6 ms) and became depressed at ~18 (21.5±2.5 ms) and ~24 months (21.4±1.7 ms). Defective diastolic function was apparent in S571E mice at ~4 months (19.7±2.9 ms) and persisted at ~12, ~18, and ~24 months (19.1±1.7 ms, 21.0±1.9 ms, and 22.1±2.2 ms, respectively). Interestingly, S571A mice at ~4 months had normal diastolic function (16.2±2.2 ms) and minor alterations were observed at ~12, ~18, and ~24 months (17.1±1.5 ms, 18.4±1.6 ms, and 19.3±3.3 ms, respectively). Overall, collected results suggest that I NaL enhancement in S571E mice is associated with premature appearance of prolonged electrical recovery and defective diastolic function, with respect to aging WT animals. In contrast, S571A mice, with inability to increase I NaL , are protected from electromechanical defects occurring with aging.

Exercise induced reduction in myocardial work predicts significant coronary artery disease in patients with false negative stress echocardiography

Stress echocardiography (SE) is a reliable technique for the diagnosis of coronary artery disease (CAD) with high sensitivity and specificity. However in patients with small left ventricular (LV) cavity caused by marked concentric hypertrophy the sensitivity of SE is low. We assumed that in patients with false negative SE evaluation of global myocardial work (GW) might detect significant CAD. Methods 238 patents with chest pain (98 female, mean age 61±5 years) without history of CAD were referred to SE for CAD confirmation. 94 (39.5%) patients had negative SE and were enrolled in our study for re-examination. Age and gender matched 50 healthy subjects served as controls. GW index (GWI) was obtained from pressure-strain loops composed from speckle tracking analysis indexed to brachial systolic blood pressure. Global constructive work (GCW) as the sum of positive work due to myocardial shortening during systole and negative work due to lengthening during isovolumic relaxation, global wasted work (GWW) as energy loss by myocardial lengthening in systole and shortening in isovolumic relaxation, and GW efficiency (GWE) as the percentage ratio of constructive work to the sum of constructive work and wasted work were measured after submaximal treadmill SE at the heart rate of 100–110 beats per minute (109±11 s after SE) using EchoPac software by blinded experienced echocardiographer. All patients were referred to coronary angiography after re-examination. Results 42 (44.7%) patients had lower GWI values than the lowest limit of GWI value in controls. These patients had significant reduction in GWI, compared with remaining 52 patients in whom GWI did not differ from those of controls (GWI 1897±112 mmHg% vs 2518±243 mmHg%, p&lt;0.01). GCW, GWE and GWW were comparable between patients with or without reduced GWI (GCW 2283±107mmHg% vs 2321±110 mmHg%, p=NS; GWE 96.9±1.1% vs 97.4±1.2%, p=NS; GWW 57±3 mmHg% vs 53±4 mmHg%, p=NS). 28 (66.7%) of 42 patients with GWI reduction and 8 (15.0%) of 52 patients without GWI reduction had at least one vessel significant CAD. GWI had sensitivity, specificity, and accuracy in detection of CAD 78%, 76%, 77% respectively with 67% positive predictive value, and 85% negative predictive value. 29 (80.5%) patients out of 36 with significant CAD had concentric increase in LVMi compared with true negative SE patients (83±6 g/m2 vs 71±4 g/m2, p&lt;0.01). GWI was the predictor of significant CAD (area under the curve 0.793). Conclusion GWI extends diagnostic power of conventional SE in detection of CAD, especially in patients with smaller LV cavity due to concentric hypertrophy when sensitivity of conventional SE is low. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Committee of Sience at Ministry of Education of Republic of Armenia

Global constructive work and left atrial reservoir function is reduced in patients with heart failure with preserved ejection fraction compared with patients with preclinical diastolic dysfunction

Heart failure with preserved ejection fraction (HFpEF) remains an unresolved issue with morbidity and mortality comparable with that of reduced EF HF. Diastolic dysfunction (DD) is the hallmark of HFpEF but it is unclear why some patients do not develop symptoms and remain in preclinical DD (PDD) stage with the same degree of DD as patients with HFpEF. We assumed that patients with HFpEF might have more deteriorated global myocardial work (GW) and left atrial reservoir longitudinal strain (LALS) parameters compared with PDD patients. Methods 210 patients (150 female, mean age 71±5 years) of which 118 with PDD and 92 with HFpEF were enrolled in this study. PDD was diagnosed if patients had normal NT-proBNP values, and at least 3 of the following echocardiographic criteria at rest or after diastolic stress echocardiography: end-systolic left atrial volume index (LAVi) &gt;34 ml/m2, LV E/e' &gt;13, average LV e' &gt;8.5, and systolic pulmonary artery pressure &gt;30 mmHg. GW index (GWI) was obtained from pressure-strain loops composed from speckle tracking analysis indexed to brachial systolic blood pressure, global constructive work (GCW) was measured as the sum of positive work due to myocardial shortening during systole and negative work due to lengthening during isovolumic relaxation, global wasted work (GWW) was calculated as energy loss by myocardial lengthening in systole and shortening in isovolumic relaxation, and GW efficiency (GWE) as the percentage ratio of constructive work to the sum of constructive work and wasted work. LALS was measured by speckle tracking echocardiography as average value of two basal segments in apical 4 chamber view along LAVi and 4D LV mass index (LVMi) offline by experienced echocardiographer who was unaware of the study aims. Results Patients with PDD and HFpEF have comparable values of LAVi, LVMi, GWI, GWW, and GWE (LAVi 38.4±3.9 ml/m2 vs 39.1±4.1 ml/m2, p=NS; LVMi 82.8±11.4 g/m2 vs 83.5±10.2 g/m2, p=NS; PDD GWI 2389±154 mmHg% vs 2368±139 mmHg%, p=NS; GWW 62±5 mmHg% vs 65±4 mmHg%, p=NS; GWE PDD 89±9% vs 87±11%, p=NS). LALS and GCW were significantly reduced in patients with HFpEF compared with PDD patients (LALS 21.3±7% vs 29±5%, p&lt;0.01; GCW 1964±112 mmHg% vs 2259±164 mmHg%, p&lt;0.01). Conclusion Patients with HFpEF have reduced LALS and GCW compared with PDD patients. Both parameters are indicative for LA and LV myocardial fibrotic burden respectively which might be one of the probable explanations of PDD transition to HFpEF. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Committee of Science at Ministry of Education of Republic of Armenia