Aigul Baltabaeva

Toward understanding response to cardiac resynchronization therapy: left ventricular dyssynchrony is only one of multiple mechanisms

AIM To date, most published echocardiographic methods have assessed left ventricular (LV) dyssynchrony (DYS) alone as a predictor for response to cardiac resynchronization therapy (CRT). We hypothesized that the response is instead dictated by multiple correctable factors. METHODS AND RESULTS A total of 161 patients (66 +/- 10 years, EF 24 +/- 6%, QRS > 120 ms) were investigated pre- and post-CRT (median of 6 months). Reduction in NYHA Class >/=1 or LV reverse remodelling (end-systolic volume reduction >/= 10%) defined response. Four different pathological mechanisms were identified. Group1: LVDYS characterized by a pre-ejection septal flash (SF) (87 patients, 54%). Elimination of SF (77 of 87 patients) resulted in reverse remodelling in 100%. Group 2: short-AV delay (21 patients, 13%) resolution (19 of 21 patients) resulted in reverse remodelling in 16 of 19. Group 3: long-AV delay (16 patients, 10%) resolution (14 of 16 patients) resulted in NYHA Class reduction >/=1 in 11 with reverse remodelling in five patients. Group 4: exaggerated LV-RV interaction (15 patients, 9%) reduced post-CRT. All responded clinically with fall in pulmonary artery pressure (P = 0.003) but did not volume respond. Group 5: patients with none of the above correctable mechanisms (22 patients, 14%). None responded to CRT. CONCLUSION CRT response is dictated by correction of multiple independent mechanisms of which LVDYS is only one. Long-axis DYS measurements alone failed to detect 40% of responders.

Maternal Cardiac Dysfunction and Remodeling in Women With Preeclampsia at Term

Preeclampsia is a disease associated with significant cardiovascular morbidity during pregnancy and in later life. This study was designed to evaluate cardiac function and remodeling in preeclampsia occurring at term. This was a prospective case–control study of 50 term preeclampsia and 50 normal pregnancies assessed by echocardiography and tissue Doppler analysis. Global diastolic dysfunction was observed more frequently in preeclampsia versus control pregnancies (40% versus 14%, P=0.007). Increased cardiac work and left ventricular mass indices suggest that left ventricular remodeling was an adaptive response to maintain myocardial contractility with preeclampsia at term. Approximately 20% of patients with preeclampsia at term have more evident myocardial damage. Diastolic dysfunction usually precedes systolic dysfunction in the evolution of ischemic or hypertensive cardiac diseases and is of prognostic value in the prediction of long-term cardiovascular morbidity. The study findings also have significant implications for the acute medical management of preeclampsia.

Low-dose dobutamine stress echo to quantify the degree of remodelling after cardiac resynchronization therapy

AIMS Presence of contractile reserve during low-dose dobutamine stress echo (DSE) appears predictive of cardiac resynchronization therapy (CRT) outcome. We hypothesize that changes in left bundle branch block (LBBB)-induced dyssynchronous motion during low-dose DSE could be related to the extent of reverse remodelling. METHODS AND RESULTS Fifty-two patients (69 +/- 2 years, EF: 24 +/- 7%, QRS > 120 ms) were studied pre- and post-CRT (7 +/- 1 months). Reduction in left ventricular end-systolic volume (LVESV) >/=10% defined response. A clinical improvement was sought additionally prior to implant and after CRT (NYHA class reduction >1), increase in 6 min walk test (>10%), and fall in BNP (>/=30%). To identify the presence of septal scar and its impact on our assessment during low-dose DSE, a cardiac magnetic resonance was performed pre-CRT. Presence of an abnormal short-lived septal motion occurring during the isovolumic contraction time [septal flash (SF)] identified LBBB-induced dyssynchrony. Septal flash extent was quantified from M-mode and radial velocity traces. At baseline, 31/52 patients had an SF. In all patients, DSE increased SF. Twenty-nine out of thirty-one patients responded with reverse remodelling post-CRT. The degree of peak low-dose stress SF correlated with the extent of reverse remodelling (R = 0.6, P < 0.0001). Additionally, SF increase correlated with greater fall in BNP post-CRT (R = 0.4, P = 0.01). Among patients with no SF at rest (21/52 patients), low-dose DSE induced an SF and a fall in stroke volume (SV) in five patients who all showed reverse remodelling after CRT. With low-dose DSE, the remaining 16 patients all failed to demonstrate a SF, and all but one patient with additional atrioventricular dyssynchrony were non-responders. CONCLUSION Low-dose DSE increases and unmasks LBBB-induced dyssynchronous motion, easing its detection. The degree of clinical and echocardiographic response correlated with the extent of peak SF seen during low-dose DSE.

Quantification of Regional Left and Right Ventricular Deformation Indices in Healthy Neonates by Using Strain Rate and Strain Imaging

BACKGROUND Color Doppler myocardial imaging (CDMI) allows the calculation of local longitudinal or radial strain rate (SR) and strain (epsilon). The aims of this study were to determine the feasibility and reproducibility of longitudinal and radial SR and epsilon in neonates during the first hours of life and to establish reference values. METHODS Data were obtained from 55 healthy neonates (29 male; mean age, 20 +/- 14 hours; mean birth weight, 3,174 +/- 374 g). Apical and parasternal views quantified regional longitudinal and radial SR and epsilon in differing ventricular wall segments. Values at peak systole, early diastole, and late diastole were calculated from the extracted curves. CDMI data acquired at 300 +/- 50 frames/s were analyzed offline. Three consecutive cardiac cycles were measured during normal respiration. The timing of specific systolic or diastolic regional events was determined. Multiple comparisons between walls and segments were made. RESULTS Left ventricular (LV) longitudinal deformation showed basal differences compared with apical segments within one specific wall. Right ventricular (RV) longitudinal deformation was not homogeneous, with significant differences between basal and apical segments. Longitudinal epsilon values were higher in the RV free basal and middle wall segments compared with the left ventricle. In the RV free wall apical segment, longitudinal SR and epsilon were maximal. LV systolic SR and epsilon values were higher radially compared with longitudinally (radial peak systolic SR midportion, 2.9 +/- 0.6 s(-1); radial peak systolic epsilon, 53.8 +/- 19%; longitudinal peak systolic SR midportion, -1.8 +/- 0.5 s(-1); longitudinal peak systolic epsilon, -24.8 +/- 3%; P < .01). Longitudinal systolic epsilon and SR interobserver variability values were 1.2% and 0.7%, respectively. CONCLUSION Ultrasound-based SR and epsilon imaging is a practical and reproducible clinical technique in neonates, allowing the calculation of regional longitudinal and radial deformation in RV and LV segments. These regional SR and epsilon indices represent new, noninvasive parameters that can quantify normal neonate regional cardiac function. Independent from visual interpretation, they can be used as reference values for diagnosis in ill neonates.

The Heart in Friedreich Ataxia Definition of Cardiomyopathy, Disease Severity, and Correlation With Neurological Symptoms

Background— This cross-sectional study provides a practical approach for the clinical assessment of Friedreich ataxia (FA) cardiomyopathy (FA-CM). Methods and Results— A comprehensive cardiac assessment, including standard echocardiography, color Doppler myocardial imaging, cardiac magnetic resonance imaging, ECG, and exercise stress testing, was performed in 205 FA patients. To assess myocardial hypertrophy in FA-CM, the end-diastolic interventricular septal wall thickness (IVSTd) was found to be the best echocardiographic parameter compared with cardiac magnetic resonance imaging–determined left ventricular mass. With the use of this parameter, 4 groups of patients with FA-CM could be defined. Patients with normal values for IVSTd (31.7%) were classified as having no FA-CM. Patients with an IVSTd exceeding the predicted normal IVSTd were classified as having mild FA-CM (40%) if IVSTd exceeded the normal value by <18% or as having intermediate FA-CM (16.1%) if IVSTd exceeded the normal value by ≥18%. Patients with ejection fraction <50% were classified as having severe FA-CM (12.2%). In addition to increased myocardial mass, severe FA-CM was further characterized by dilatation of the left ventricle, reduced systolic strain rate of the posterior wall, and ECG abnormalities. Regional myocardial function correlated negatively with FA-CM groups. Younger patients had a tendency for more advanced FA-CM. Importantly, no clear correlation was found between FA-CM groups and neurological function. Conclusions— We provide and describe a readily applicable clinical grouping of the cardiomyopathy associated with FA based on echocardiographic IVSTd and ejection fraction data. Because no distinct interrelations between FA-CM and neurological status could be determined, regular follow-up of potential cardiac involvement in FA patients is essential in clinical practice. Clinical Trial Registration— https://www.clinicaltrials.gov. Unique identifier: NCT00905268.Background— This cross-sectional study provides a practical approach for the clinical assessment of Friedreich ataxia (FA) cardiomyopathy (FA-CM). Methods and Results— A comprehensive cardiac assessment, including standard echocardiography, color Doppler myocardial imaging, cardiac magnetic resonance imaging, ECG, and exercise stress testing, was performed in 205 FA patients. To assess myocardial hypertrophy in FA-CM, the end-diastolic interventricular septal wall thickness (IVSTd) was found to be the best echocardiographic parameter compared with cardiac magnetic resonance imaging–determined left ventricular mass. With the use of this parameter, 4 groups of patients with FA-CM could be defined. Patients with normal values for IVSTd (31.7%) were classified as having no FA-CM. Patients with an IVSTd exceeding the predicted normal IVSTd were classified as having mild FA-CM (40%) if IVSTd exceeded the normal value by <18% or as having intermediate FA-CM (16.1%) if IVSTd exceeded the normal value by ≥18%. Patients with ejection fraction <50% were classified as having severe FA-CM (12.2%). In addition to increased myocardial mass, severe FA-CM was further characterized by dilatation of the left ventricle, reduced systolic strain rate of the posterior wall, and ECG abnormalities. Regional myocardial function correlated negatively with FA-CM groups. Younger patients had a tendency for more advanced FA-CM. Importantly, no clear correlation was found between FA-CM groups and neurological function. Conclusions— We provide and describe a readily applicable clinical grouping of the cardiomyopathy associated with FA based on echocardiographic IVSTd and ejection fraction data. Because no distinct interrelations between FA-CM and neurological status could be determined, regular follow-up of potential cardiac involvement in FA patients is essential in clinical practice. Clinical Trial Registration— [https://www.clinicaltrials.gov][1]. Unique identifier: [NCT00905268][2]. # Clinical Perspective {#article-title-30} [1]: https:www.clinicaltrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00905268&atom=%2Fcirculationaha%2F125%2F13%2F1626.atom

Sequential Changes of Longitudinal and Radial Myocardial Deformation Indices in the Healthy Neonate Heart

BACKGROUND Significant hemodynamic changes, including preload and afterload modifications, occur during the transition from the fetal to the neonatal environment. The ductus arteriosus closes, pulmonary vascular resistance decreases, and pulmonary blood flow increases. Strain rate (SR) and strain (epsilon) have been proposed as ultrasound indices for quantifying regional wall deformation. This study was designed to determine if these indices can detect variations in regional deformation between early and late neonatal periods. METHODS Data were obtained from 30 healthy neonates (15 male). The initial study was performed at a mean age of 20.1+/-14 hours (exam 1) and the second at 31.9+/-2.9 days (exam 2). Apical and parasternal views were used to quantify regional left ventricular (LV) and right ventricular (RV) longitudinal and radial SR and epsilon, and systolic, early, and late diastolic values were calculated from these curves. A paired-samples t test was performed comparing the two groups. RESULTS Compared with exam 1, LV radial deformation showed significant reductions in peak systolic epsilon in the basal and mid segments (51+/-15% vs 46+/-9%, P<.01). LV longitudinal deformation behaved similarly, showing significant peak systolic epsilon reductions in all measured segments. Systolic SR showed reductions only in the basal and apical segments of the lateral wall and in the mid portion of the inferior wall (-1.9+/-0.5 vs -1.7+/-0.3 s(-1) and -1.9+/-0.4 vs -1.7+/-0.2 s(-1), respectively, P=.03). RV longitudinal free and inferior wall systolic SR and epsilon values were significantly higher in exam 2. CONCLUSIONS LV peak systolic epsilon decreases in exam 2 were possibly due to afterload increase and preload decrease. The lower RV initial deformation indices could be attributed to increased afterload caused by physiologic pulmonary hypertension or immature RV contractile properties. SR seemed to be a more robust index than epsilon and less influenced by preload and afterload hemodynamic alteration.

How to detect early left atrial remodelling and dysfunction in mild-to-moderate hypertension.

Background and objectives Early changes in left atrial function in hypertension are difficult to assess quantitatively. Measuring atrial reversal flow into the pulmonary veins and regional left atrial deformation parameters assessed by Tissue Doppler-derived strain/rate (S/SR) imaging could provide quantitative assessment of left atrial deformation. We aimed to quantify changes in left atrial volume and deformation and pulmonary flow reversal (PVREVERS) in hypertension to detect subclinical left atrial dysfunction. Design, setting and patients In 74 hypertensive and 34 age-matched normotensive patients (mean age 49 ± 1.4 vs. 44.2 ± 2.1 years) echo studies were performed, including measurements of LAV during reservoir, conduit and pump phases and standard indices reflecting left ventricular filling. S/SR was measured in the lateral left atrial wall. Total deformation (STOTAL) and the contribution to early (SE-index) and late (SA-index) filling were calculated. Results Hypertensive patients had significantly impaired diastolic function and increased left atrial volume during all phases. Only LAVCONDUIT significantly correlated with both ventricular hypertrophy and parameters of diastolic function. Velocity time integral of PVREVERS correlated with blood pressure and LAVCONDUIT. In hypertensive patients STOTAL was significantly higher (54.9 ± 2.6 vs. 45.5 ± 2.7%, P < 0.03) and SE-index was lower (P < 0.0001). This was compensated for by an increased SA-index (P < 0.0001) and SR during atrial contraction (−4.9 ± 0.2 vs. −2.9 ± 0.3 1/s, P < 0.0001). SA-index correlated significantly with blood pressure (R = 0.4; P < 0.0001) and PVREVERS (R = 0.3; P < 0.001). Conclusion Changes in left atrial function due to hypertensive diastolic impairment are best reflected by LAVCONDUIT expansion. Hypertensive atrial dilatation is related to increase in PVREVERS. Left atrial S/SR offers a clinically valuable approach to detecting subclinical atrial dysfunction.

Persistent dysfunction of viable myocardium after revascularization in chronic ischaemic heart disease: implications for dobutamine stress echocardiography with longitudinal systolic strain and strain rate measurements

AIMS Studies of functional recovery after revascularization in chronic coronary artery disease are contradictory and mark a lack of knowledge of persistent dysfunction in the non-scarred myocardium. Based on tissue Doppler-derived regional longitudinal systolic strain and strain rate (SR), both at rest and during dobutamine stress (DS), we assessed to what extent ischaemia-related reduced myocardial function would recover after revascularization in hearts with predominantly viable myocardium. METHODS AND RESULTS Reference peak systolic strain and SR values were determined from tissue Doppler imaging in 15 healthy volunteers. Fifty-seven patients scheduled for coronary artery bypass grafting (CABG), with an average ejection fraction of 49%, underwent pre-operative magnetic resonance imaging (MRI) with late enhancement, resting echocardiography, and DS echocardiography (DSE), with assessment of systolic strain and SR and post-systolic strain (PSS). Eight to 10 months after CABG, myocardial function was reassessed. Forty per cent of all segments had reduced longitudinal systolic strain pre-operatively despite only 1.4% of segments with transmural infarctions on MRI. After revascularization, 38% of prior dysfunctional segments improved their resting strain, whereas 72% were improved by DS. Positive resting systolic strain indicated the absence of significant scar tissue. Resting systolic strain and DS strain responses were good prognosticators for functional improvement with areas under the receiver operating characteristic curve of 0.753 (0.646-0.860) and 0.790 (0.685-0.895), respectively. CONCLUSION Persistently reduced longitudinal function was observed in more than half of pre-operatively viable but dysfunctional segments after CABG. We propose that such a functional impairment marks a regional remodelling process not amendable to re-established blood flow.

Interventricular interaction as a possible mechanism for the presence of a biphasic systolic velocity profile in normal left ventricular free walls

Background: In normal subjects, systolic longitudinal regional velocity profiles (SVP) (measured both based on pulsed or tissue Doppler) have a non-uniform pattern. SVP from the right ventricle (RV), the septal (Sep) and the inferior wall are similar in shape and tend to be monophasic. Their shape differs markedly from the lateral wall (LW), the posterior wall and the anterior wall, which are biphasic. We studied the hypothesis that the double-peaked SVP in the left ventricular free walls are caused by interventricular interaction. This might have additional implication in understanding the measurements of the timing of SVP maxima in pathology as, for example, used to determine intraventricular dyssynchrony in heart failure. Methods: 38 healthy individuals underwent a standard echo examination and a tissue Doppler study. SVP from the RV, Sep and LW basal segments were acquired in an apical four-chamber view. The amplitude and timing of the peak velocities were measured. If a double peak was present, the amplitude and timing of the dip was calculated. Results: RV and Sep had a single systolic velocity peak, while the LW had two peaks with a clear dip between both peaks. The first peak in the LW was the earliest event in the cycle (119 (19) ms) followed by the peak Sep (123 (20) ms; p = 0.34). Peak RV velocity occurred at the same time as the dip in the LW (200 (30) vs 203 (30) ms, respectively; p = 0.53). Conclusion: Our study suggests that the biphasic SVP in the free walls is probably caused by interventricular interaction. Therefore the timing of maxima on SVP should be used with great caution when looking for intraventricular dyssynchrony as the peaks are influenced by RV function.

Rate-adaptive AV delay and exercise performance following cardiac resynchronization therapy

BACKGROUND Physiological shortening of the atrioventricular (AV) interval with increasing heart rate is well documented in normal human beings and is an established component of dual-chamber pacing for bradycardia. OBJECTIVES To assess the effect of exercise on optimal AV delay and the impact of a patient-specific rate-adaptive AV delay (RAAVD) on exercise capacity in patients with heart failure following cardiac resynchronization therapy. METHODS Phase 1: We performed iterative AV optimization at rest and exercise in 52 cardiac resynchronization therapy patients in atrial-sensed mode (mean age 71.6 ± 9.2 years, 25% females). Phase 2: Subsequently, 20 consecutive volunteers from this group (mean age 69.2 ± 9.6 years, 15% females) underwent cardiopulmonary exercise testing with RAAVD individually programmed ON (RAAVD-ON) or OFF (RAAVD-OFF). RESULTS Phase 1: In 94% of the patients, there was a marked reduction (mean 50%) in optimal AV delay with exercise. The optimal resting vs exercise AV delay was 114.2 ± 29 ms at a heart rate of 64.4 ± 7.1 beats/min vs 57 ± 31 ms at a heart rate of 103 ± 13 beats/min (P < .001). No patients required an increase in AV delay with exercise, and 3 (6%) showed no change. Phase 2: With RAAVD-ON, significantly better exercise times were achieved (8.7 ± 3.2 minutes) compared with RAAVD-OFF (7.9 ± 3.2 minutes; P = .003), and there was a significant improvement in Vo(2)max (RAAVD-ON 16.1 ± 4.0 vs RAAVD-OFF 14.9 ± 3.7 mL/(kg · min); P = .024). CONCLUSIONS There was a dramatic reduction in optimal AV delay with physiological exercise in the majority of this heart failure cardiac resynchronization therapy cohort. Replicating this physiological response with a programmable RAAVD translated into a 10% improvement in exercise capacity.