Concepts of Cardiac Dyssynchrony and Dynamic Approach.

Cardiac conduction involves electrical activity from one myocyte to another, creating coordinated contractions in each. Disruptions in the conducting system, such as left bundle branch block (LBBB), can result in premature activation of specific regions of the heart, leading to heart failure and increased morbidity and mortality. Structural alterations in T-tubules and the sarcoplasmic reticulum can lead to dyssynchrony, a condition that can be treated by cardiac resynchronization therapy (CRT), which stands as a cornerstone in this pathology. The heterogeneity in patient responses underscored the necessity of improving the diagnostic approach. Vectocardiography, ultra-high-frequency ECG, 3D echocardiography, and electrocardiographic imaging seem to offer advanced precision in identifying optimal candidates for CRT in addition to the classic diagnostic methods. The advent of His bundle pacing and left bundle branch pacing further refined the approach in the treatment of dyssynchrony, offering more physiological pacing modalities that promise enhanced outcomes by maintaining or restoring the natural sequence of ventricular activation. HOT-CRT emerges as a pivotal innovation combining the benefits of CRT with the precision of His bundle or left bundle branch area pacing to optimize cardiac function in a subset of patients where traditional CRT might fall short.

AV-optimized conduction system pacing for treatment of AV dromotropathy: A randomized, cross-over study.

BACKGROUND: Severe first-degree atrioventricular (AV) block may produce symptoms similar to heart failure due to AV dyssynchrony, a syndrome termed AV dromotropathy. According to guidelines, it should be considered for permanent pacemaker implantation, yet evidence supporting this treatment is scarce. OBJECTIVES: This study aimed to determine the impact of AV-optimized conduction system pacing (CSP) in patients with symptomatic severe first-degree AV block and echocardiographic signs of AV dyssynchrony. METHODS: Patients with symptomatic first-degree AV block (PR > 250 ms), preserved left ventricular ejection fraction, narrow QRS, and AV dyssynchrony were included in the study. In a single-blind cross-over design, patients were randomized to AV sequential CSP or backup VVI pacing with a base rate of 40 bpm. We compared exercise capacity, echocardiographic parameters, and symptom occurrence at the end of 3 months of each period. RESULTS: Fourteen patients completed the study. During the AV-optimized CSP compared to the backup pacing period, patients achieved a higher workload on exercise test (147.2 ± 50.9 vs. 140.7 ± 55.8 W; p = .032), with a trend towards higher peak VO2 (23.3 ± 7.1 vs. 22.8 ± 7.1 mL/min/kg; p = .224), and higher left ventricular stroke volume (LVSV 74.5 ± 13.8 vs. 66.4 ± 12.5 mL; p < .001). Symptomatic improvement was recorded, with fewer patients reporting general tiredness and 71% of patients preferring the AV-optimized CSP (p = .008). CONCLUSIONS: AV-optimized CSP could improve symptoms, exercise capacity and LVSV in patients with severe first-degree AV block.

Potential Underestimation of Left Ventricular Mechanical Dyssynchrony in Dyssynchrony and Outcomes Assessment.

Objective: Left ventricular (LV) mechanical dyssynchrony (LVMD) is fundamental to the progression of heart failure and ventricular remodeling. The status of LVMD in different patterns of bundle branch blocks (BBB) is unclear. In this study, we analyzed the relationship between LVMD and left ventricular systolic dysfunction using real-time three-dimensional echocardiography (RT-3DE). Methods: RT-3DE and conventional two-dimensional echocardiography were performed on 68 patients with left bundle branch block (LBBB group), 106 patients with right bundle branch block (RBBB group), and 103 patients without BBB (Normal group). The RT-3DE data sets provided time-volume analysis for global and segmental LV volumes. The LV systolic dyssynchrony index (LVSDI) was calculated using the standard deviation (SD) and maximal difference (Dif) of time to minimum segmental volume (tmsv) for LV segments adjusted by the R-R interval. LVMD was considered if the LVSDI (Tmsv-16-SD) was greater than or equal to 5%. Results: LVSDI is negatively and significantly correlated with left ventricular ejection fraction (LVEF), but not with BBB or QRS duration. The proportion of LVMD in the LBBB, RBBB, and Normal group was 30.88%, 28.30%, and 25.24%, respectively, and there was no significant difference. Conclusion: In dilated cardiomyopathy, LVMD is more closely related to LVEF reduction than QRS morphology and duration.

Multidisciplinary approach to long-standing left bundle branch block with dyssynchrony and aortic stenosis: case report.

Background: Cardiac resynchronization therapy (CRT) is recommended for patients with symptomatic heart failure in sinus rhythm with left ventricular ejection fraction (LVEF) ≤ 35%, QRS duration ≥ 150 ms, and left bundle branch block (LBBB) morphology. However, when severe left ventricular dysfunction and cardiogenic shock are present, treatment paradigms are often limited to palliative medical therapy or advanced therapies with durable left ventricular assist device or heart transplant as the functional and survival benefit of CRT in these patients remains uncertain. Case summary: A 77-year-old white man with long-standing LBBB with dyssynchrony, severely reduced LVEF of 4%, and severe bicuspid aortic stenosis (AS) presented with worsening heart failure symptoms. After multidisciplinary heart team evaluation and pre-operative optimization, the patient underwent a surgical aortic valve replacement with simultaneous intraoperative initiation of CRT with pacemaker (CRT-P) and temporary mechanical circulatory support. Echocardiography at 44 days and 201 days post-discharge showed an LVEF of 29% and 40%, respectively. Discussion: This case demonstrates that reverse remodelling and native heart recovery were successfully achieved in a patient with advanced structural heart disease, presenting with cardiogenic shock, through an early and aggressive approach involving multidisciplinary heart team evaluation, treatment of severe AS with surgical aortic valve replacement, prophylactic intraoperative initiation of temporary mechanical circulatory support, and early initiation of CRT-P.

Prevalence and progression of LV dysfunction and dyssynchrony in patients with new-onset LBBB post TAVR.

BACKGROUND: The impact of new-onset left bundle branch block (N-LBBB) developing after Transcatheter Aortic Valve Replacement (TAVR) on cardiac function and mechanical dyssynchrony is not well defined. METHODS: We retrospectively screened all patients who underwent TAVR in our centre between Oct 2018 and Sept 2021 (n = 409). We identified 38 patients with N-LBBB post-operatively (of which 28 were persistent and 10 were transient), and 17 patients with chronic pre-existent LBBB (C-LBBB). We excluded patients requiring pacing post TAVR. For all groups, we retrospectively analysed stored echocardiograms at 3 time points: before TAVR (T0), early after TAVR (T1, 1.2 ± 1.1 days), and late follow-up (T2, 1.5 ± 0.8 years), comparing LV mass and volumes, indices of LV function (LV ejection fraction, LVEF; global longitudinal strain, GLS), and mechanical dyssynchrony indices (systolic stretch index, severity of septal flash). RESULTS: At baseline (T0), C-LBBB had worse cardiac function, and larger LV volumes and LV mass, compared with patients with N-LBBB. At T1, N-LBBB resulted in mild dyssynchrony and decreased LVEF and GLS. Dyssynchrony progressed at T2 in persistent N-LBBB but not C-LBBB. In both groups however, LVEF remained stable at T2, although individual response was variable. Patients with better LVEF at baseline demonstrated a higher proportion of developing LBBB-induced LV dysfunction at T2. Lack of improvement of LVEF immediately after TAVR predicted deteriorating LVEF at T2. In transient LBBB, cardiac function and most dyssynchrony indices returned to baseline. CONCLUSIONS: N-LBBB after TAVR results in an immediate reduction of cardiac function, in spite of only mild dyssynchrony. When LBBB persists, patients with better cardiac function before TAVR are more likely to have LBBB-induced LV dysfunction after TAVR.

Ultra-High-Frequency ECG in Cardiac Pacing and Cardiac Resynchronization Therapy: From Technical Concept to Clinical Application.

Identifying electrical dyssynchrony is crucial for cardiac pacing and cardiac resynchronization therapy (CRT). The ultra-high-frequency electrocardiography (UHF-ECG) technique allows instantaneous dyssynchrony analyses with real-time visualization. This review explores the physiological background of higher frequencies in ventricular conduction and the translational evolution of UHF-ECG in cardiac pacing and CRT. Although high-frequency components were studied half a century ago, their exploration in the dyssynchrony context is rare. UHF-ECG records ECG signals from eight precordial leads over multiple beats in time. After initial conceptual studies, the implementation of an instant visualization of ventricular activation led to clinical implementation with minimal patient burden. UHF-ECG aids patient selection in biventricular CRT and evaluates ventricular activation during various forms of conduction system pacing (CSP). UHF-ECG ventricular electrical dyssynchrony has been associated with clinical outcomes in a large retrospective CRT cohort and has been used to study the electrophysiological differences between CSP methods, including His bundle pacing, left bundle branch (area) pacing, left ventricular septal pacing and conventional biventricular pacing. UHF-ECG can potentially be used to determine a tailored resynchronization approach (CRT through biventricular pacing or CSP) based on the electrical substrate (true LBBB vs. non-specified intraventricular conduction delay with more distal left ventricular conduction disease), for the optimization of CRT and holds promise beyond CRT for the risk stratification of ventricular arrhythmias.

Right ventricular dyssynchrony for the prediction of prognosis in patients with systemic lupus erythematosus-aaociated pulmonary arterial hypertension: a study with two-dimensional speckle tracking.

Pulmonary arterial hypertension (PAH) is a common complication of systemic lupus erythematosus (SLE), and PAH can cause right ventricle (RV) remodel and dyssynchrony. The aim of this study was to explore the value of RV dyssynchrony in predicting adverse clinical events in patients with systemic lupus erythematosus-aaociated pulmonary arterial hypertension (SLE-PAH) using two-dimensional speckle tracking echocardiography (2D-STE). A total of 53 patients with SLE-PAH were enrolled in this study. The dyssynchrony of the RV (RV-SD6) was evaluated by 2D-STE. The clinical data of all participants were collected, and routine cardiac function parameters were measured by two-dimensional echocardiography, and analyzed for their correlation with RV-SD6. The predictive value of RV-SD6 in clinical adverse event was evaluated. RV-SD6 was negatively correlated with RV-FLS, RV-FAC, and TAPSE (r = - 0.788, r = - 0.363 and r = - 0.325, respectively, all P < 0.01), while the correlation with RV-FLS was the strongest. linear regression analysis showed that RV-FLS was an independent risk factor for RV-SD6 (ß = - 1.40, 95% CI - 1.65 ~ - 1.14, P < 0.001). Cox regression analysis showed that RV-SD6 was a predictor with clinical adverse events (HR = 1.03, 95% CI 1 ~ 1.06, P < 0.05). RV-SD6 was highly discriminative in predicting clinical adverse events (AUC = 0.764), at a cutoff of 51.10 ms with a sensitivity of 83.3% and specificity of 68.3%. RV-FLS was negatively correlated with RV-SD6 and was an independent risk factor for it. RV-SD6 can serve as an indicator for predicting the occurrence of adverse clinical events in SLE-PAH patients, with high sensitivity and specificity.

Case Report: Ventricular preexcitation-induced dilated cardiomyopathy improved by the pharmacologic suppression of ventricular preexcitation in three infants, and literature review.

The therapy of ventricular preexcitation-induced dilated cardiomyopathy in very small infants or infants with a high risk of ablation is tough and related articles are rare. Effective pharmacotherapy to suppress ventricular preexcitation is valuable. Aims: To evaluate the effectiveness and safety of pharmacotherapy for cardiac resynchronization in infants with ventricular preexcitation-induced dilated cardiomyopathy. Methods and results: Three infants with ventricular preexcitation-induced dilated cardiomyopathy, due to the disappearance of ventricular preexcitation during the placement of catheter, intermittent WPW pattern, and right mid septal accessory pathway respectively, had received pharmacotherapy for cardiac resynchronization. The initial dosage of oral amiodarone was 5 mg/kg.d and it was followed by the maintenance dosage of 2-2.5 mg/kg.d 4 weeks later. Propafenone (15 mg/kg.d) served as a supplement since amiodarone was not adequate in case 3. The three infants achieved successful pharmacologic suppression of ventricular preexcitation 10, 6.5, and 4.5 weeks after the initiation of amiodarone respectively. They all got normalized contraction of interventricular septum and LVEF as well as reduced LVEDD gradually after the disappearance of ventricular preexcitation. No side effects associated with pharmacotherapy happened during the follow-up. Amiodarone had been withdrawn for 2 years and 5 months in Cases 1 and 2. They both remained free from ventricular preexcitation and retained normal LVEF and LVEDD. Conclusions: Pharmacotherapy for cardiac resynchronization with oral amiodarone or in combination with propafenone for infants with ventricular preexcitation-induced dilated cardiomyopathy is effective and safe. Pharmacotherapy for cardiac resynchronization served as another therapeutic choice besides ablation.

Quantifiable identification of flow-limited ventilator dyssynchrony with the deformed lung ventilator model.

BACKGROUND: Ventilator dyssynchrony (VD) can worsen lung injury and is challenging to detect and quantify due to the complex variability in the dyssynchronous breaths. While machine learning (ML) approaches are useful for automating VD detection from the ventilator waveform data, scalable severity quantification and its association with pathogenesis and ventilator mechanics remain challenging. OBJECTIVE: We develop a systematic framework to quantify pathophysiological features observed in ventilator waveform signals such that they can be used to create feature-based severity stratification of VD breaths. METHODS: A mathematical model was developed to represent the pressure and volume waveforms of individual breaths in a feature-based parametric form. Model estimates of respiratory effort strength were used to assess the severity of flow-limited (FL)-VD breaths compared to normal breaths. A total of 93,007 breath waveforms from 13 patients were analyzed. RESULTS: A novel model-defined continuous severity marker was developed and used to estimate breath phenotypes of FL-VD breaths. The phenotypes had a predictive accuracy of over 97% with respect to the previously developed ML-VD identification algorithm. To understand the incidence of FL-VD breaths and their association with the patient state, these phenotypes were further successfully correlated with ventilator-measured parameters and electronic health records. CONCLUSION: This work provides a computational pipeline to identify and quantify the severity of FL-VD breaths and paves the way for a large-scale study of VD causes and effects. This approach has direct application to clinical practice and in meaningful knowledge extraction from the ventilator waveform data.

Association between an early revascularization strategy and major cardiac events based on left ventricular dyssynchrony in patients at intermediate risk of major cardiac events using the J-ACCESS risk model.

Objective This retrospective study aimed to investigate the association between therapeutic strategies and the development of major cardiac events (MCEs) in intermediate-risk patients by using the J-ACCESS risk model in combination with the stress phase bandwidth (SPBW), an index of left ventricular dyssynchrony. Methods Patients were followed-up for three years to confirm their prognosis. Based on the estimated propensity scores, the patients who underwent revascularization within the first 60 days after SPECT and those who did not were matched 1:1 (n = 367 per group). The composite endpoint was the occurrence of MCEs, consisting of cardiac death, non-fatal myocardial infarction, and severe heart failure. SPBW was calculated by a phase analysis using the Heart Risk View-F software program, and the MCE rate was compared between the two groups by applying the normal value of SPBW (38°). Patients The study included 2,053 patients with either known or suspected CAD who underwent electrocardiogram-gated single-photon emission computed tomography myocardial perfusion imaging and were at intermediate risk of MCE according to the J-ACCESS risk model. Results During follow-up, 54 of the 734 patients (7.4%) experienced MCEs. The overall incidence of MCE in intermediate-risk patients was not significantly different between the two groups. However, the incidence of MCE in patients with an abnormal SPBW was significantly lower in those who underwent early revascularization (4.8% vs. 11.9%, P = 0.0407). Conclusion The combination of the J-ACCESS risk model and the SPBW is thus considered to be an optimal treatment strategy for patients at intermediate risk of MCE, and early revascularization may lead to an improved prognosis in intermediate-risk patients with an abnormal SPBW.

Association of epicardial fat volume with subclinical myocardial damage in patients with type 2 diabetes mellitus.

Background: In type 2 diabetes mellitus (T2DM) patients, left ventricular systolic dyssynchrony (LVSD) with normal left ventricular ejection fraction (LVEF) and normal myocardial perfusion could referred to as subclinical myocardial damage, which is difficult to diagnose at an early stage. Epicardial adipose tissue, a distinctive heart-specific visceral fat, is closely related to various cardiovascular diseases. The objective of this study was to investigate the correlation between epicardial fat volume (EFV) and subclinical myocardial damage in T2DM patients. Methods: This retrospective cross-sectional study included 117 T2DM patients with normal myocardial perfusion by single photon emission computed tomography-computed tomography (SPECT-CT) and normal LVEF by echocardiography. The study was conducted from January 2018 to December 2022. Patient data were collected through electronic medical records including basic patient information, medical history, laboratory tests, and medication data. The EFV was quantified through a non-contrast CT scan. Quantitative indicators of LVSD including phase standard deviation (PSD) and phase histogram bandwidth (PBW) were obtained through phase analysis of the gated rest myocardial perfusion imaging (MPI). Additionally, 83 healthy individuals at the same time were selected to gain the reference threshold of LVSD indicators (13.1° for PSD and 37.6° for PBW). Univariate and multivariable logistic regression models were performed to analyze factors influencing LVSD. A generalized additive model (GAM) was applied to explore the relationship between EFV and LVSD. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of EFV for LVSD. Results: Among all patients, 32 (27.4%) patients had LVSD. Compared with the non-LVSD group, the body mass index (BMI) and EFV were higher in the LVSD group (25.83±2.66 vs. 23.94±3.13 kg/m2; 142.41±44.17 vs. 108.01±38.24 cm3, respectively, both P<0.05). Multivariate regression analysis revealed that EFV was independently associated with LVSD [odds ratio (OR) =1.19; 95% confidence interval (CI): 1.06-1.34; P=0.003]. Age, BMI, incidence of hypertension, and LVSD were increased with tertiles of EFV (all P<0.05). The GAM indicated a linear association between EFV and LVSD. The ROC curve analysis concluded that the area under the curve (AUC) of EFV for predicting subclinical myocardial damage in T2DM patients was 0.732 (95% CI: 0.633-0.831, P<0.001), with the optimal threshold of 122.26 cm3, sensitivity of 71.9%, and specificity of 69.4%. Conclusions: EFV is an independent risk factor for LVSD in T2DM patients with normal LVEF and normal MPI, which could potentially serve as a novel imaging marker and a potential therapeutic target for subclinical myocardial damage.

Left Bundle Branch Area Pacing Versus Conventional Pacing in Patients with Advanced Atrioventricular Conduction Abnormalities: a Prospective Cohort Study.

BACKGROUND: Left bundle branch area pacing (LBBAP) is an emerging pacing method, which may prevent the deleterious effects of right ventricular pacing. The aim of this study is to compare the effects of LBBAP with right ventricular septal pacing (RVSP) in patients with advanced atrioventricular conduction abnormalities and preserved left ventricular ejection fraction. METHODS: The effect of pacing was evaluated by echocardiographic indices of dyssynchrony, including global myocardial work efficiency (GWE) and peak systolic dispersion (PSD). The primary endpoint was GWE postprocedural, at 3, 6 and 12 months after the procedure. RESULTS: Twenty patients received LBBAP and 18 RVSP. Complete follow-up was accomplished in 37 patients (97.4%), due to the death of a patient (RVSP arm), from non-related cause. GWE was significantly increased in the group of LBBAP compared to RVSP at all timepoints (90.8% in LBBAP vs 85.8% in RVSP group at 12 months, p=0.01). PSD was numerically lower in the LBBAP arm at all timepoints, yet not statistically significant (56.4 msec in LBBP vs 65.1 msec in RVSP arm at 12 months, p=0.178). The implantation time was increased (median 93 min in LBBAP vs 45 min in RVSP group, p<0.01), along with fluoroscopy time and dose area product (DAP), in the arm of LBBAP. There were no severe perioperative acute complications in either group. CONCLUSIONS: LBBAP is an emerging and safe technique for patients with a pacing indication. Despite the longer procedural and fluoroscopy time, as well as higher DAP, LBBAP seems to offer better left ventricular synchrony compared to RVSP, according to GWE measurements.

Determination of sensed and paced atrial-ventricular delay in cardiac resynchronization therapy.

BACKGROUND: Optimization of atrial-ventricular delay (AVD) during atrial sensing (SAVD) and pacing (PAVD) provides the most effective cardiac resynchronization therapy (CRT). We demonstrate a novel electrocardiographic methodology for quantifying electrical synchrony and optimizing SAVD/PAVD. METHODS: We studied 40 CRT patients with LV activation delay. Atrial-sensed to RV-sensed (As-RVs) and atrial-paced to RV-sensed (Ap-RVs) intervals were measured from intracardiac electrograms (IEGM). LV-only pacing was performed over a range of SAVD/PAVD settings. Electrical dyssynchrony (cardiac resynchronization index; CRI) was measured at each setting using a multilead ECG system placed over the anterior and posterior torso. Biventricular pacing, which included multiple interventricular delays, was also conducted in a subset of 10 patients. RESULTS: When paced LV-only, peak CRI was similar (93 ± 5% vs. 92 ± 5%) during atrial sensing or pacing but optimal PAVD was 61 ± 31 ms greater than optimal SAVD. The difference between As-RVs and Ap-RVs intervals on IEGMs (62 ± 31 ms) was nearly identical. The slope of the correlation line (0.98) and the correlation coefficient r (0.99) comparing the 2 methods of assessing SAVD-PAVD offset were nearly 1 and the y-intercept (0.63 ms) was near 0. During simultaneous biventricular (BiV) pacing at short AVD, SAVD and PAVD programming did not affect CRI, but CRI was significantly (p < .05) lower during atrial sensing at long AVD. CONCLUSIONS: A novel methodology for measuring electrical dyssynchrony was used to determine electrically optimal SAVD/PAVD during LV-only pacing. When BiV pacing, shorter AVDs produce better electrical synchrony.

Understanding the Application of Mechanical Dyssynchrony in Patients with Heart Failure Considered for CRT.

Over the past two decades of CRT use, the failure rate has remained around 30-35%, despite several updates in the guidelines based on the understanding from multiple trials. This review article summarizes the role of mechanical dyssynchrony in the selection of heart failure patients for cardiac resynchronization therapy. Understanding the application of mechanical dyssynchrony has also evolved during these past two decades. There is no role of lone mechanical dyssynchrony in the patient selection for CRT. However, mechanical dyssynchrony can complement the electrocardiogram and clinical criteria and improve patient selection by reducing the failure rate. An oversimplified approach to mechanical dyssynchrony assessment, such as just estimating time-to-peak delays between segments, should not be used. Instead, methods that can identify the underlying pathophysiology of HF and are representative of a substrate to CRT should be applied.

Dyssynchronous heart failure models in canines: New insights into electrocardiographic, echocardiographic and histological features.

BACKGROUND: We investigated the similarities and differences between two experimental approaches using tachy-pacing technology to induce desynchronized heart failure in canines. METHODS: A total of eight dogs were included in the experiment, four were tachy-paced in right ventricle apex (RVAP) and 4 were paced in right atrium after the ablation of left bundle branch to achieve left bundle branch block (RAP+LBBB). Three weeks of follow-up were conducted to observe the changes in cardiac function and myocardial staining was performed at the end of the experiment. RESULTS: Both experimental approaches successfully established heart failure with reduced ejection fraction models, with similar trends in declining cardiac function. The RAP+LBBB group exhibited a prolonged overall ventricular activation time, delayed left ventricular activation, and lesser impact on the right ventricle. The RVAP approach led to a reduction in overall right ventricular compliance and right ventricular enlargement. The RAP+LBBB group exhibited significant reductions in left heart compliance (LVGLS, %: RAP+LBBB -12.60 ± 0.12 to -5.93 ± 1.25; RVAP -13.28 ± 0.62 to -8.05 ± 0.63, p = 0.023; LASct, %: RAP+LBBB -15.75 ± 6.85 to -1.50 ± 1.00; RVAP -15.75 ± 2.87 to -10.05 ± 6.16, p = 0.035). Histological examination revealed more pronounced fibrosis in the left ventricular wall and left atrium in the RAP+LBBB group while the RVAP group showed more prominent fibrosis in the right ventricular myocardium. CONCLUSION: Both approaches establish HFrEF models with comparable trends. The RVAP group shows impaired right ventricular function, while the RAP+LBBB group exhibits more severe decreased compliance and fibrosis in left ventricle.

Pressure overload is associated with right ventricular dyssynchrony in heart failure with reduced ejection fraction.

AIMS: The determinants and relevance of right ventricular (RV) mechanical dyssynchrony in heart failure with reduced ejection fraction (HFrEF) are poorly understood. We hypothesized that increased afterload may adversely affect the synchrony of RV contraction. METHODS AND RESULTS: A total of 148 patients with HFrEF and 36 controls underwent echocardiography, right heart catheterization, and gated single-photon emission computed tomography to measure RV chamber volumes and mechanical dyssynchrony (phase standard deviation of systolic displacement timing). Exams were repeated after preload (N = 135) and afterload (N = 15) modulation. Patients with HFrEF showed higher RV dyssynchrony compared with controls (40.6 ± 17.5° vs. 27.8 ± 9.1°, P < 0.001). The magnitude of RV dyssynchrony in HFrEF correlated with larger RV and left ventricular (LV) volumes, lower RV ejection fraction (RVEF) and LV ejection fraction, reduced intrinsic contractility, increased heart rate, higher pulmonary artery (PA) load, and impaired RV-PA coupling (all P ≤ 0.01). Low RVEF was the strongest predictor of RV dyssynchrony. Left bundle branch block (BBB) was associated with greater RV dyssynchrony than right BBB, regardless of QRS duration. RV afterload reduction by sildenafil improved RV dyssynchrony (P = 0.004), whereas preload change with passive leg raise had modest effect. Patients in the highest tertiles of RV dyssynchrony had an increased risk of adverse clinical events compared with those in the lower tertile [T2/T3 vs. T1: hazard ratio 1.98 (95% confidence interval 1.20-3.24), P = 0.007]. CONCLUSIONS: RV dyssynchrony is associated with RV remodelling, dysfunction, adverse haemodynamics, and greater risk for adverse clinical events. RV dyssynchrony is mitigated by acute RV afterload reduction and could be a potential therapeutic target to improve RV performance in HFrEF.

Left ventricular mechanical dyssynchrony after chemotherapy in breast cancer patients with normal rest gated SPECT-MPI.

OBJECTIVES: Early diagnosis of chemotherapy-induced cardiotoxicity plays an important role in preventing heart failure. The main aim of our study was to assess left ventricular (LV) dyssynchrony measured by phase analysis of gated single-photon emission computed tomography (SPECT) as an early sign of cardiotoxicity after breast cancer chemotherapy. METHODS: This cross-sectional study was conducted on patients with stage ≤ 3 breast cancer and no history of cardiovascular disease or diabetes. After mastectomy, the patients underwent rest gated SPECT myocardial perfusion imaging (MPI). Sixty patients with normal gated SPECT-MPI were selected and the imaging was performed after chemotherapy with doxorubicin, cyclophosphamide and paclitaxel. LV function and contractility parameters were extracted by QGS software and the results were compared with the t test method. The abnormality of at least one of the three phase analysis indices was considered as left ventricular dyssynchrony (LVD). RESULTS: The average LV end-systolic volume and ejection fraction (LVEF) before and after chemotherapy were (16.2 ± 8.0 ml and 21.6 ± 11.6 ml) and (73.4 ± 7.9% and 67.5 ± 9.2%) respectively, which showed a significant decrease (P < 0.05). In 2 patients (3.3%), the LVEF decreased to less than 50% after chemotherapy. The average parameters of left ventricular contractility before and after chemotherapy were, respectively, as follows: PHB (24.1 ± 7.5 and 33.8 ± 16.4), PSD (9.4 ± 6.1 and 5.7 ± 1.9) and entropy (28.9 ± 7.1 and 35.6 ± 9.7), which showed a significant increase (P < 0.05). LVD was observed in 14 patients (23.4%) after chemotherapy and prevalence of LVD was significantly higher in patients who had received a cumulative dose of doxorubicin of more than 400 mg/m2 (P = 0.005). There was no relationship between age and body mass index with the incidence of LVD after chemotherapy (P > 0.05). CONCLUSION: Using phase analysis of gated SPECT-MPI, chemotherapy-induced LVD was seen in a significant number of patients with breast cancer, especially with a high cumulative dose of doxorubicin. LVD might indicate chemotherapy-induced cardiotoxicity before LVEF becomes abnormal.

Biventricular intraventricular mechanical and electrical dyssynchrony in pulmonary arterial hypertension.

Background: Pulmonary arterial hypertension (PAH) leads to myocardial remodeling, manifesting as mechanical dyssynchrony (M-dys) and electrical dyssynchrony (E-dys), in both right (RV) and left ventricles (LV). However, the impacts of layer-specific intraventricular M-dys on biventricular functions and its association with E-dys in PAH remain unclear. Methods: Seventy-nine newly diagnosed patients with PAH undergoing cardiac magnetic resonance scanning were consecutively recruited between January 2011 and December 2017. The biventricular volumetric and layer-specific intraventricular M-dys were analyzed. The QRS duration z-scores were calculated after adjusting for age and sex. Results: 77.22 % of patients were female (mean age 30.30 ± 9.79 years; median follow-up 5.53 years). Further, 29 (36.71 %) patients succumbed to all-cause mortality by the end of the study. At the baseline, LV layer-specific intraventricular M-dys had apparent transmural gradients compared with RV in the radial and circumferential directions. However, deceased patients lost the transmural gradients. The LV longitudinal strain rate time to late diastolic peak in the myocardial region (LVmyoLSRTTLDPintra) predicted long-term survival. The Kaplan-Meier curve revealed that patients with PAH with LVmyoLSRTTLDPintra <20.01 milliseconds had a worse prognosis. Larger right ventricle (RV) intraventricular M-dys resulted in worse RV ejection fraction. However, larger LV intraventricular M-dys in the late diastolic phase indicated remarkable exercise capacity and higher LV stroke volume index. E-dys and intraventricular M-dys had no direct correlations. Conclusions: The layer-specific intraventricular M-dys had varying impacts on biventricular functions in PAH. PAH patients with LVmyoLSRTTLDPintra <20.01 milliseconds had a worse prognosis. LV intraventricular M-dys in the late diastolic phase needs more attention to precisely evaluate LV function.

Fourier Phase Analysis of Dynamic Antral Contraction Scintigraphy: New Software, Reference Values, and Comparisons to Conventional Gastric Emptying.

Dynamic antral contraction scintigraphy (DACS) has been used to evaluate for gastric dysmotility by measuring antral contraction frequency and ejection fraction (EF). Fourier phase image analysis has the potential to assess gastric antral contractions for dyssynchrony as has been used for analyzing nuclear cardiology ventriculography (multigated acquisition studies) for cardiac dyssynchrony. The aims of this study were to determine whether Fourier phase analysis helps to characterize antral motility physiology, whether Fourier phase analysis correlates with conventional gastric emptying scintigraphy (GES), and which DACS parameters may aid in diagnosing gastric dysmotility, particularly delayed gastric emptying (GE). Methods: DACS and GES of healthy volunteers (n = 22) were compared with patients (n = 99) with symptoms of gastroparesis. New DACS Fourier phase analysis software was developed. Results: GE was delayed (n = 53) or normal (n = 46) in patients. There was a linear correlation between the time for the stomach to empty 50% of the meal and the percentage total proximal and distal in-phase antral pixels at 30 min (r = 0.37, P = 0.0001) and 60 min (r = 0.26, P = 0.007). In healthy volunteers, the mean proximal-to-distal ratio of in-phase antral pixels increased from 1.67 (30 min) to 2.65 (120 min) (P = 0.035), and EF increased from 23% (30 min) to 32% (120 min) (P = 0.022). Multivariable regressions of percentage total proximal and distal in-phase antral pixels (30 min) and EF (60 min) were the best predictors of abnormal GE (adjusted odds ratio, 3.30 [95% CI, 1.21-9.00] and 2.97 [95% CI, 1.08-8.21], respectively). Conclusion: This study used Fourier phase analysis to analyze DACS in healthy volunteers and patients with symptoms of gastroparesis. In addition to establishing reference values, new physiologic information on antral motility was obtained. In healthy volunteers, there was an increasing proximal-to-distal ratio of in-phase antral pixels and antral EF over time after meal ingestion. The percentage total proximal and distal in-phase antral pixels at both 30 and 60 min correlated well with GE values for the time for the stomach to empty 50% of the meal. For symptomatic patients, the percentage total proximal and distal in-phase antral pixels at 30 min and the EF at 60 min after meal ingestion correlated with delayed GE on conventional GES. Thus, Fourier phase analysis of DACS appears to have potential to further aid in diagnosing gastric dysmotility in GES.

MR Uniformity Ratio Estimates to Evaluate Ventricular Mechanical Dyssynchrony and Prognosis After ST-Segment Elevation Myocardial Infarction.

BACKGROUND: The impact of left ventricular mechanical dyssynchrony (LVMD) on the long-term prognosis of ST-segment elevation myocardial infarction (STEMI) is unclear. HYPOTHESIS: MR uniformity ratio estimates (URE) can detect LVMD and assess STEMI prognosis. STUDY TYPE: Retrospective analysis of a prospective multicenter registry (EARLY-MYO trial, NCT03768453). POPULATION: Overall, 450 patients (50 females) with first-time STEMI were analyzed, as well as 40 participants without cardiovascular disease as controls. FIELD STRENGTH/SEQUENCE: 3.0-T, balanced steady-state free precession cine and late gadolinium enhancement imaging. ASSESSMENT: MRI data were acquired within 1 week of symptom onset. Major adverse cardiovascular events (MACEs), including cardiovascular death, nonfatal re-infarction, hospitalization for heart failure, and stroke, were the primary clinical outcomes. LVMD was represented by circumferential URE (CURE) and radial URE (RURE) calculated using strain measurements. The patients were grouped according to clinical outcomes or URE values. Patients' clinical characteristics and MR indicators were compared. STATISTICAL TESTS: The Student's t-test, Mann-Whitney U test, chi-square test, Fisher's exact test, receiver operating characteristic curve analysis with area under the curve, Kaplan-Meier analysis, Cox regression, logistic regression, intraclass correlation coefficient, c-index, and integrated discrimination improvement were used. P < 0.05 was considered statistically significant. RESULTS: CURE and RURE were significantly lower in patients with STEMI than in controls. The median follow-up was 60.5 months. Patients with both lower CURE and RURE values experienced a significantly higher incidence of MACEs by 3.525-fold. Both CURE and RURE were independent risk factors for MACEs. The addition of UREs improved diagnostic efficacy and risk stratification based on infarct size and left ventricular ejection fraction (LVEF). The indicators associated with LVMD included male sex, serum biomarkers (peak creatine phosphokinase and cardiac troponin I), infarct size, and LVEF. DATA CONCLUSION: CURE and RURE may be useful to evaluate long-term prognosis after STEMI. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.