Both native T1 and T2 reduced significantly following HD . These changes presumably reflect acute reduction in myocardial water content rather than regression of LV hypertrophy. CMR with multiparametric mapping is a promising tool to assess the cardiac changes associated with HD.In patients with chronic kidney disease (CKD), reverse left ventricular (LV) remodelling, including reduction in LV mass, can be observed following long-term haemodialysis (HD) and has been attributed to regression of LV hypertrophy. However, LV mass can vary in response to changes in myocyte volume, edema, or fibrosis. The aims of this study were to investigate the acute changes in structural  and tissue characterization parameters (native T1 and T2) following HD using cardiovascular magnetic resonance (CMR). Twenty-five stable HD patients underwent non-contrast CMR including volumetric assessment and native T1 and T2 mapping immediately pre- and post-HD. The mean time between the first and second scan was 9.1 ± 1.1 hours and mean time from completion of dialysis to the second scan was 3.5 ± 1.3 hours. Post-HD, there was reduction in LV mass (pre-dialysis 98.9 ± 36.9 g/m Left ventricular hypertrophy (LVH) and left ventricular cavity dilatation are common findings in patients with ESRF and are associated with increased mortality and cardiac arrhythmias4. It has been demonstrated that daily HD when compared to traditional thrice weekly dialysis results in significant reduction in LV mass6. However, interventions to reduce left ventricular (LV) mass do not appear to translate to a reduction in mortality7.Patients with end-stage renal failure (ESRF) have increased risk of cardiovascular morbidity and mortality, and around 50% of all deaths in patients on haemodialysis (HD) are due to cardiovascular disease8. Post-mortem and endomyocardial biopsy studies have both demonstrated the presence of myocardial fibrosis in patients on HD10. Greater myocardial extracellular water content may also cause increase in LV mass but the contribution and effects of this in patients with CKD have not previously been investigated.It has been suggested that increased afterload and preload in patients with chronic kidney disease (CKD) results in myocardial fibrosis and myocyte cell hypertrophy, and that regression in LVH following chronic HD is due to reduction in both fibrosis and myocyte cell volume11 but it can also provide unique information on tissue composition. CMR with late gadolinium enhancement is uniquely informative for the detection and quantification of myocardial fibrosis in a variety of conditions but the use of gadolinium contrast in patients with ESRF is constrained by concerns about the risk of nephrogenic systemic fibrosis12. However, contemporary T1 and T2 mapping methods can surmount some of the shortcomings of non-contrast CMR. Native T1, measured in milliseconds (ms), is increased when the interstitial space is expanded, for example by fibrosis or amyloid deposition, or edema17. T2 measurements provide an estimate of free tissue water content. For example, T2 is elevated during acute myocarditis and following acute myocardial infarction, and it is proposed that T2 is elevated in the presence of myocardial edema irrespective of myocardial fibrosis17.Cardiovascular magnetic resonance (CMR) is now established as the gold standard for quantification of ventricular volumes, mass and functionThe aims of this study were (1) To assess the changes in myocardial volumes and mass pre- and post-HD and (2) To assess the changes in native T1 and myocardial T2 pre- and post-HD.Twenty-five patients established on thrice weekly HD were recruited at the Royal Free Hospital, London, United Kingdom between October 2017 and June 2018. All participants provided written informed consent. Ethical approval was obtained from the Joint University College London/University College London Hospitals Research Ethics Committee (REC reference: 07/H0715/101). All research-related procedures were performed in accordance with local guidelines and regulations.Patients with standard contraindications to non-contrast CMR  were excluded.st inversion, 3 sec recovery, and images acquired for 3 sec following a 2nd inversion18. Typical protocol parameters for T1 mapping were: matrix 256 × 144, field-of-view 360 × 270 mm2, spatial resolution 1.4 × 1.9 mm2, slice thickness 8 mm, flip angle 35 degrees, bandwidth 1085 Hz/pixel, echo spacing 2.7 ms. T2 mapping used the Siemens MyoMap sequence which acquired 3 T2 weighted measurements and performed an exponential fit for each pixel after respiratory motion correction. The imaging used a T2-prepared single shot b-SSFP readout with T2 preparation times (TE) = 0, 25, and 55 ms with a recovery period of 3 heartbeats between measurements. Typical protocol parameters for T2 mapping were: matrix 192 × 108, field-of-view 360 × 270 mm2, spatial resolution 1.9 × 2.5 mm2, slice thickness 8 mm, flip angle 70 degrees, bandwidth 1184 Hz/pixel, echo spacing 2.6 ms. To assess intra-scan reproducibility, all native T1 and T2 maps were repeated after at least a 5-minute interval in 7 patient scans.All CMR scans were performed at 1.5 T . Patients underwent non-contrast CMR before and then again immediately after a haemodialysis session. Patients were weighed immediately before each CMR scan. A standard protocol was used that included localizers, cine imaging, native T1 mapping and T2 mapping. Cine imaging (long-axis and short axis stack covering the entire ventricles) was performed using electrocardiographic (ECG)-gated breath-hold steady state free precession (SSFP) or Realtime where the patient was unable to breath-hold or in the presence of arrhythmia. For native T1 and T2 mapping, basal, mid and apical short axis, and a 4-chamber long-axis were acquired after regional shimming. T1 mapping used a Siemens research works-in-progress sequence (WIP1041B) that acquired images using a modified look-locker inversion recovery (MOLLI) protocol using a 5 s (3 s) 3 s sampling scheme: 2 inversions, with images acquired each heartbeat for 5 sec following the 1All images were analysed offline using Osirix MD 9.0 . The endo- and epicardial borders were manually delineated for each basal-, mid-ventricular and apical short axis map. Obvious image artefacts and coronary arteries were excluded from the regions of interest. Native T1 and T2 were averaged over all three short-axis slices to calculate global averages. Initial analysis of the maps was performed by TK. All mapping images were then independently reanalysed by AMN who was blinded to the initial analysis to assess inter-observer variability. Ventricular cavity volumes and mass were calculated by tracing epicardial and endocardial borders on each end-diastolic short axis cine and endocardial borders on each end-systolic cine. Papillary muscles and trabeculations were included as part of the ventricular mass.Normally distributed metrics are summarized as mean ± standard deviation and non-normally distributed data are expressed as median . The paired Student’s T-test was used when comparing parameters between pre- and post-dialysis scans. Correlations between continuous variables were evaluated using the Pearson’s correlation co-efficient. Inter-observer and intra-study reproducibility were assessed using intraclass correlation co-efficient (ICC) with 95% confidence intervals (CI), coefficient of variance (CoV) and Bland-Altman analysis (expressed as bias ± 2 SD for limits of agreement). Reproducibility analysis was performed using MedCalc 13.2.1.0 . All other statistical analysis was performed using IBM SPSS statistics version 24 .2 .Twenty-five HD patients  male) underwent pre- and post-dialysis scans. Baseline characteristics are summarised in Table 2 vs post-dialysis 93.3 ± 35.8 g/m2, p = 0.003, Fig. Following HD, there was significant reduction in indexed LV mass . However, in patients with impaired pre-HD LV function  there was significant improvement in systolic function post-HD   , CoV 0.55% 0.44–0.66%), bias 2.4 ms) and T2 mapping (ICC 0.982 (0.968–0.990), CoV 1.32% (1.05–1.59%), bias 0.75 ms) was excellent  maps of precision27. The mean SD for the native T1 protocol is approximately 30 ms (per pixel). The product T2 mapping sequence did not provide a SD estimate or goodness of fit, however estimates of the SD for the T2 mapping protocols used in this study are 2–3 ms (per pixel). The precision of the region of interest measurements is improved several-fold over the pixel wise SD depending on the number of pixels averaged. The inter-observer and intra-study repeatability of both T1 and T2 were excellent and comparable to previously published data30.The T2 mapping sequence used in this study was the single shot based SSFP method which is part of the SIEMENS MyoMap product, and the T1 mapping sequence was a works-in-progress MOLLI sequence (WIP 1041B) that allowed for a more flexible sampling strategy with acquisition and recovery periods defined in seconds to further reduce heart rate variability. The technical characteristics of these sequences and comparisons to other methods and protocols have been described previouslyThis was a small single centre study but is the first to use CMR to assess cardiac changes acutely following dialysis. Dialysis patients included had different aetiologies for their renal failure. Due to the sample size, the effects of this and other potential confounders such as age, gender, hypertension and diabetes were not investigated.In summary, our findings provide useful information about the acute effects of HD on cardiac function and tissue changes. It is the first to study patients using CMR pre- and post-dialysis sessions demonstrating reduction in LV mass following HD which we attribute to reduction in myocardial edema. Our data suggest that T1 and T2 both fall acutely following a dialysis session and this has implications when dialysis patients undergo repeated follow up scans. When tracking longer term changes (for example over months or years) we would suggest that scans be performed at the same timepoint in their weekly dialysis schedule  and both T1 and T2 should be measured, together with standard structural parameters, to better assess changes in myocardial tissue composition. Furthermore, the acute changes in T1, T2 and LV mass could potentially be used to tailor the HD session to the individual patient, but this would require further large-scale studies.Dataset


Heart-sparing techniques are time and resource intensive, although not all patients require the use of these strategies. This study evaluates the performance of different distance metrics in predicting the need for breath-hold radiotherapy in left-sided breast cancer patients receiving adjuvant radiotherapy.Fifty left-sided breast cancer patients treated with breast conserving surgery and adjuvant radiotherapy to the breast from a single institution were retrospectively studied. The left breast and organs at risk were contoured in accordance to guidelines and a plan with tangents was obtained using the free-breathing CT in supine position. Heart (mean heart dose (MHD), heart V25 Gy) and left anterior descending artery dosimetry were computed and compared against distance metrics under investigation . Recursive partitioning analysis (RPA) was used to determine optimal cut-points for distance metrics for dosimetric end points. Receiver operating characteristic curves and Pearson correlation coefficients were used to evaluate the association between distance metrics and dosimetric endpoints. Univariable and multivariable logistic regression analysis was performed to identify significant predictors of dosimetric end points.3, respectively. With tangents, constraints for MHD (< 1.7 Gy and V25 Gy < 10 cm3) were unattainable in 80% and 46% of patients, respectively. Optimal RPA thresholds included: Contact Heart (73 mm), 4th Arch (7 mm) and 5th Arch (41 mm). Of these, the 4th Arch had the highest overall accuracy, sensitivity, concordance index and correlation coefficient. All metrics were statistically significant predictors for MHD ≥ 1.7 Gy based on univariable logistic regression. Fifth Arch did not reach significance for heart V25 Gy ≥ 10 cm3. Fourth Arch was the only predictor to remain statistically significant after multivariable analysis.The mean MHD and heart V25 Gy were 2.3 Gy and 10.4 cmWe propose a novel “4th Arch” metric as an accurate and practical tool to determine the need for breath-hold radiotherapy for left-sided breast cancer patients undergoing adjuvant radiotherapy with standard tangents. Further validation in an external cohort is necessary. Adjuvant breast irradiation after breast-conserving surgery leads to similar oncological outcomes as mastectomy in patients with early breast cancer , 2 and iA landmark population-based study determined that adjuvant breast radiation was associated with a 1.7 fold increased risk of cardiac death when compared to patients treated with surgery alone . This riDifferent techniques have been proposed to mitigate radiation-induced heart damage. Breath-hold (BH) radiotherapy represents one option that holds promise as it can be employed in the context of a standard supine position and tangential delivery technique. In doing so, a dosimetric advantage can commonly be achieved with a deep inspiration BH due to the simultaneous effect of lung inflation and heart displacement out of the radiation field . HoweverA study by Lee et al  evaluateWe propose two novel and practical predictors based on anatomic landmarks that could be helpful in predicting the need for BH-radiotherapy. In this study, these metrics will be evaluated along with the metric previously suggested by Lee et al  in patieFifty consecutive left-breast cancer patients treated with BH-radiotherapy between 2014 and 2015 were selected and evaluated in this planning study. All patients had histological proof of breast malignancy in core-biopsy. Nodal staging work-up was initially performed with clinical examination ± axilla ultrasound followed by sentinel nodal mapping during surgery.The BH-radiotherapy institutional protocol was as follows: free-breathing and BH image sets were acquired by using Lightspeed computed tomography (CT) scan . CT images were acquired with patients in supine position on a 10 degrees breast board and with both arms elevated and abducted over 90 degrees. Slices of 3.5 mm thickness were obtained as per institutional protocol and a Real-time Position Management (RPM) device was used to obtain the breathing trace during simulation and treatment delivery.For the purpose of this study only free-breathing images were used to predict the need of BH technique by analyzing possible predictors. Breast, lungs and heart were contoured according to the RTOG guidelines  and leftA set of anatomically-based distance metrics were obtained from each patient including the previously proposed “Contact Heart” metric  depicted3 of the heart receives 25 Gy or more. As there is no definitive dosimetric parameter for LAD dose, we hypothesized that maximum LAD dose correlated with MHD and Heart V25Gy and the already known cut-points for these parameters.All plans were reviewed in quality assurance rounds after being approved by a radiation oncologist. Retrospectively, the primary end points of MHD, heart V25 Gy and maximum LAD point dose were collected and compared against the distance metrics previously described. MHD reflects the average dose received by the entire heart. This metric was previously correlated with cardiac events by Darby et al. . Heart Vn = 50). Univariable recursive partitioning analysis (RPA) was performed based on MHD and heart V25 Gy BH end points to determine optimal cut-points separately for Contact Heart, 4th Arch and 5th Arch distance metrics and maximum LAD dose followed by rounding of cut-points to represent more clinically meaningful values. The association between distance metrics  and BH end points  were evaluated using accuracy, sensitivity and specificity (for binary distance metrics) and concordance index and Pearson correlation coefficients (for continuous distance metrics). Pearson correlation coefficients were calculated using continuous BH endpoints. Receiver operating characteristic (ROC) curves were generated for MHD ≥ 1.7 Gy and heart V25 Gy ≥ 10 cm3 to further evaluate the association with Contact Heart, 4th and 5th Arch distance metrics. Univariable and multivariable logistic regression analysis were performed to identify significant predictors of BH end points. All statistical analysis was performed using SAS version 9.4 software  and the R language environment for statistical computing version 3.3.3 , using two-sided statistical testing at the 0.05 significance level.Descriptive statistics were generated for patient and treatment baseline characteristics for all patients , 4th Arch (p <  0.001) and 5th Arch (p = 0.001) were each statistically significant predictors for MHD ≥ 1.7 Gy. Fifth Arch did not reach significance for Heart V25 Gy ≥ 10 cm3 (p = 0.131). Following multivariable logistic regression analysis, only 4th Arch remained statistically significant for both MHD (p <  0.001) and Heart V25 Gy (p <  0.001).Univariable logistic regression analysis is shown in Table Breath-hold radiotherapy has been shown to significantly reduce cardiac dose , which mPreviously, Lee et al. investigated predictors of heart dose and observed that the para-sagittal heart surface contact distance with the anterior chest wall (“Contact Heart”) demonstrated good accuracy . DespiteIn this study, we proposed two alternative predictors and would contend that they are more practical than previously proposed metrics. Both involve a simple linear measurement from the left edge of the sternum to the anterior portion of the left lung either to the 4th (“4th Arch”) or 5th (“5th Arch”) costal arch level, respectively Fig. . These mA useful predictor should be simple yet also accurate. This study compared and evaluated 3 distance metrics using a variety of accuracy and prediction based techniques. Fifty patients with left-side breast cancer treated with adjuvant radiotherapy after breast-sparing surgery were randomly selected for inclusion in the study. Heart dosimetric parameters were used to quantify the need for the BH-technique. After comprehensive analysis, the 4th Arch metric was found to have the highest overall predictive accuracy and sensitivity for MHD and Heart V25 Gy as well as maximum LAD dose. This metric was also associated with the largest concordance index and correlation coefficient when compared to the 5th Arch and Contact Heart metrics for all BH end points. Moreover, the 4th Arch metric was observed to be the strongest predictor of each BH end point from univariable logistic regression and remained the only statistically significant predictor following multivariable analysis.3 were considered in this study as hard-constraints, as these dosimetric values were correlated with cardiovascular toxicity in previous publications [MHD ≥ 1.7 Gy and Heart V25 ≥ 10 cmications , 12. TheRecent publication by Rahimy et al. underscores the continuous value of breast tangents in the modern era . In thisThis planning study needs to be considered in the context of its limitations. First, although patients were randomly sampled from an institutional database, the generalizability of the diagnostic performance of our proposed metric needs to be validated with an independent dataset. Second, the imaging protocol, in particular the slice thickness, was different from the protocol reported by Lee et al. . It is pIn conclusion, we propose that the 4th Arch metric is a simple and practical method that has demonstrated a strong correlation with heart and LAD dosimetry in left sided-breast cancer patients treated with standard tangential radiation therapy. Prospective and independent validation of this metric should be considered in the future for quantification of the need for heart sparing using BH or other techniques before its routine employment.


The traditional approach for adult congenital heart disease combined with valvular disease is surgical treatment under cardiopulmonary bypass (CPB). This approach has a high incidence of postoperative complications, especially in patients with pulmonary hypertension and old age. We present two patients in whom the hybrid procedure was used to treat congenital malformations, followed by valve formation and replacement surgery.A 63-year-old man had a muscular ventricular septal defect complicated by mitral regurgitation and a 57-year-old man had patent ductus arteriosus complicated by aortic stenosis. In both of the patients, the congenital malformation was successfully treated by the hybrid procedure, followed by valve repair or replacement. Both patients had no complications. A post-procedure echocardiogram showed no residual shunt across the duct.Our findings suggest that the hybrid procedure is a useful alternative for treating adult congenital heart disease with valvular heart disease. This procedure reduces the surgical incision and difficulty of surgery, shortens the CPB time, avoids residual leakage after surgery, and reduces recovery and hospitalization times. With advancement of medical technology, the incidence of congenital heart disease in adults has increased yearly, with more than 1.4 million adults with congenital heart disease in the USA alone  or are cA 63-year-old man presented with dyspnea during exercise for longer than 1 month. A physical examination showed a systolic murmur of grade 3/6 at the left third to fifth intercostal spaces. Echocardiography showed an increase in the left ventricle, muscular VSD, and moderate mitral regurgitation. We decided to perform mitral valve repair after closure of the muscular VSD under direct vision with CPB. After median sternotomy was performed, we established CPB. After the heart stopped, the right atrium and the interatrial septum were cut. The left ventricular surface was examined to view the ventricular septal defect near the apex, and the diameter was approximately 6 mm. The P1214 PDA occluder  was selected and the end was pre-stitched with 3–0 prolene suture. The occluder was placed into the left ventricle through the right ventricular surface, and the occluder was released. The pre-stitched 3–0 prolene suture was reinforced and stitched to the right ventricular surface , and moderate aortic regurgitation. We decided to first perform occlusion of the PDA by transesophageal echocardiography (TEE) under direct vision and then perform aortic valve replacement under CPB. After median sternotomy, we sutured a purse-string in the pulmonary artery. TEE of the PDA showed a diameter of approximately 6 mm and it was the tubular type. The P1214 PDA occluder was selected and the PDA was occluded through the pre-made purse-string of the pulmonary artery  The surgical incision is reduced, the operation is simpler, and the difficulty of surgery is greatly reduced. (2) The CPB time and aortic cross clamp time are shortened, and the myocardial protection effect is good. (3) Tissue damage is minimal to avoid residual leakage after surgery. (4) There is a fast recovery and shorter hospital stay. However, relatively high treatment costs may hinder implementation of this method.


Soluble ST2 (sST2) has recently emerged as a promising biomarker in the field of acute cardiovascular diseases. Several clinical studies have demonstrated a significant link between sST2 values and patients’ outcome. Further, it has been found that higher levels of sST2 are associated with an increased risk of adverse left ventricular remodeling. Therefore, sST2 could represent a useful tool that could help the risk stratification and diagnostic and therapeutic work-up of patients admitted to an emergency department. With this review, based on recent literature, we have built sST2-assisted flowcharts applicable to three very common clinical scenarios of the emergency department: Acute heart failure, type 1, and type 2 acute myocardial infarction. In particular, we combined sST2 levels together with clinical and instrumental evaluation in order to offer a practical tool for emergency medicine physicians. Indeeese mice ,6. Furthese mice . Concernese mice . sST2, iThe soluble variant of ST2 results in being overexpressed in specific pathologic conditions of myocardial stress or injury and is associated with inflammation and immune response .Recent observations suggest an important prognostic value of sST2, either in chronic heart failure, where it predicts patients outcome beyond N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T , or in aThis review offers some possible therapeutic decision flowcharts for acute cardiovascular diseases, based on the evaluation of sST2 levels in the emergency department.Acute dyspnea is a common complaint in the Emergency Department (ED) that is complicated by its wide spectrum of possible differential diagnoses. Indeed, the emergency clinician frequently has to distinguish ADHF from the other causes of dyspnea.Heart failure (HF) is currently one of the main public health problems, affecting at least 26 million people worldwide . The conp < 0.001) [sST2, reflecting pathophysiological processes that link the inflammatory and neurohormonal systems, is a promising biomarker in the field of HF that could guide clinicians in the identification of patients at a high risk for ADHF necessitating hospitalization. Further, sST2 could be used as a guide for therapeutic strategies . In addi< 0.001) . Thereaf< 0.001) . They re< 0.001) ,26,27. T< 0.001) . Januzzi< 0.001) .In patients with dyspnea and elevated NPs, a sST2 flowchart  could bep = 0.0025), resulting in a more precise risk stratification [Myocardial infarction is a major cause of morbidity and mortality worldwide. Type 1 acute myocardial infarction (type 1 AMI) is related to a coronary plaque rupture, or dissection with intraluminal thrombosis and consequent perfusion imbalance between demand and supply. After an AMI, cardiomyocyte necrosis and myocardial fibrosis induce a geometrical and biomechanical modification of the cardiac structure, leading to the process of cardiac remodeling, which is coupled with functional impairment . The viafication . sST2 lefication . At 30 dfication .Therefore, even if sST2 does not add anything to the initial diagnosis of AMI, its prognostic role has become remarkable. Actually, early sST2 levels in AMI seem to reflect the extent of myocardial necrosis, given its negative correlation with LV ejection fraction at 1 day after AMI . FurtherThe research group of Jenkis et al. were able to divide a cohort of 1401 patients with incident MI into 3 cardiovascular risk classes on the basis of early sST2 values . ImportaAmong patients presenting to an ED with elevated cardiac troponin and symptoms indicative of acute coronary syndrome, the prevalence of type 2 myocardial infarction (type 2 AMI) has a wide variability, ranging from 1.6–71% . Type 2 In all type 2 AMI conditions, an accurate clinical examination, together with an echocardiographic evaluation, is, generally, a useful diagnostic strategy, crucial for therapeutic decision-making. However, a decisional flow chart for risk stratification and management of type 2 AMI patients in ED could take advantage of sST2 measurement. sST2 is involved in pathophysiology of cardiac fibrosis and inflammation and is a powerful predictor of adverse outcomes . This coWe propose a flow chart based on sST2 levels for the management of patients with type 2 AMI . It shouIn conclusion, sST2, represents, especially when combined with NPs, troponins, and clinical variables, a promising tool that could improve the risk stratification and diagnostic–therapeutic work-up of patients admitted to the ED. Therefore, in this review, we are suggesting a sST2-assisted patient stratification approach in three clinical scenarios , whose clinical usefulness should be validated in larger prospective clinical studies. However, we are confident in our conclusion that sST2 plasma levels above 70 ng/mL seem to be associated with a significant activation of both neurohormonal and fibrotic pathways and can help to identify those patients that are affected by ADHF, type 1, and type 2 AMI that are at increased risk of adverse LV remodeling. Serial assessment of sST2 should also be considered for a better management of patients and more appropriate therapeutic decisions, since clinical data suggest that the kinetics of sST2 plasma levels can discriminate patients with different outcomes.


Recordings of aortic root movement represent one of the first accomplishments of ultrasound in medicine and mark the beginning of functional cardiac imaging. However, the underlying mechanism is not completely understood. Since the aortic root is directly connected to the cardiac skeleton we hypothesize, that the amplitude of systolic aortic root motion (SARM) may be mainly caused by displacement of the cardiac base towards the apex and might therefore be used as measure of left ventricular longitudinal function (LV-LF). One hundred and eighty patients with dilated cardiomyopathy and 180 healthy controls were prospectively included into this study. SARM was lower in patients compared to controls  and lowest in patients with cardiovascular events . During a median follow-up time of 38 months, the combined end-point of cardiovascular death or hospitalization for heart failure was reached by 25 patients (13.9%). Reduced SARM had significant prognostic impact on outcome  and remained an independent predictor in the multivariate analysis. Compared to parameters with potential influence on its mechanism, SARM correlated best  with global longitudinal strain (GLS). SARM may therefore represent an alternative echocardiographic parameter for the assessment of LV-LF, particularly when GLS is not feasible or apical views are not available. Beyond that diagnostic significance, LV longitudinal function (LF) has additive prognostic value when EF is already reduced3. Therefore, techniques that enable assessment of LV-LF are highly relevant and should nowadays complement every cardiac imaging report5.Left ventricular (LV) contraction is determined by a complex arrangement of muscle fiber layers and comprises longitudinal shortening and axial twist. Impairment of the longitudinal component is often the first sign of LV dysfunction even when ejection fraction (EF) is still normal7 but they still face limitations especially when dealing with poor acoustic windows. In such cases M-mode echocardiography is a helpful alternative. Due to its high temporal resolution movement of echogenic structures can easily be visualized even when image quality is reduced8.Echocardiography is by far the most widely used imaging modality in cardiology. 2- and 3-dimensional systems have improved its diagnostic potential continuously9. By contrast enhanced echocardiography using saline injection in the supravalvular position Gramiak et al. confirmed that undulating parallel signals medial to the mitral valve actually arise distal from the aortic valve and thus represent a portion of the aorta. Furthermore, they could demonstrate, that the pattern of motion obtained from the aortic root equals that of earlier M-mode recordings from the mitral ring11. Aortic root motion has subsequently been investigated as a surrogate parameter of left ventricular systolic and diastolic function.The first description of moving ultrasound signals using M-mode echocardiography dates back to the early fifties when Edler assumed these patterns to originate from the anterior left atrial wallAs part of the cardiac skeleton the aortic annulus and the attached aortic root follow the valvular plane displacement during the heart cycle. Therefore, we hypothesize, that the amplitude of systolic aortic root motion (SARM) obtained by M-Mode echocardiography may be used as a measure of global LV-LF Figs  and 2.FiOne hundred and eighty patients with dilated cardiomyopathy were matched by age and gender with 180 healthy control subjects. Median follow-up time was 1,150 days (38 months), 4 patients were lost to follow-up. Clinical, laboratory, and echocardiographic parameters are summarized in Table A potential association between different hemodynamic as well as functional cardiac parameters and SARM was tested by linear regression analysis. Results of correlation between SARM and global longitudinal strain (GLS), EF, LV stroke volume (SV), left atrial volume change (LA-VC) and mean arterial pressure (MAP) are presented in Table Total excursion of SARM was lower in the patient cohort compared with healthy individuals  and was even stronger diminished in patients with compared to patients without an event . The ability of SARM to differentiate patients with DCM from healthy subjects was tested by Receiver operating characteristic (ROC) analysis and Youden’s index and yielded a cutoff value of 11 mm .The combined end point of cardiovascular death or hospitalization for heart failure was observed in 25 patients, including 22 patients with acute heart failure with need for hospital admission and 3 cases of cardiovascular death. An optimal cutoff value for SARM to discriminate patients at risk for a cardiac event was found to be <7 mm calculated by ROC analysis and Youden’s index . The frequency of cardiac events over time is displayed by Kaplan-Meier curves Fig. , which wReproducibility analysis revealed coefficients of variation of 5.8 for intra- and 7.6 for interobserver variability.In the present study we investigated basic properties, influencing factors as well as the diagnostic and prognostic value of systolic aortic root motion (SARM) assessed by M-mode echocardiography.SARM can be described in two different ways: on the one hand in relation to the cardinal axes and planes of the body and on the other hand in relation to the main axis of the heart within the thorax.21. This assumption is insufficient though and might be due to the fact that M-mode echocardiography is an unidimensional technique and therefore obtains signals only in one direction. However, the echo-probe is not only directed posteriorly but the imaging plane additionally has to be angulated medial and cephalic to display SARM10 which already indicates that a pure forward-backward motion may not completely be true. Two-dimensional B-Mode echocardiography can already display motion in 2 directions simultaneously but the restriction to specific cardiac ultrasound windows still hinders an exact alignment of SARM to the anatomic body planes. Using cardiac magnetic resonance (CMR) imaging, however, the direction of SARM was exemplary analyzed in one of the authors (MA) applying strictly orientated cine slices in the coronal and sagittal plane of the thorax. In the coronal plane the aortic root shows a downward and lateral-left displacement . Thus, they concluded that SARM is a response to the action of the whole LV12. Keltai et al. and Burggraf et al. confirmed some of the earlier observations, even though the correlation of SARM with LV stroke volume was weaker in their studies23  as it was in ours (r = 0.57). Slightly conflicting results were reported by Rosenblatt et al. who found only a poor correlation24 (r < 0.5). While an exercise induced rise in blood pressure (BP) did not affect SARM in the study by Pratt et al., pharmacological lowering of BP resulted in an increase in amplitude12. Furthermore, the onset of SARM coincides with the rise of blood pressure and flow velocity in the ascending aorta and thus reflects the hemodynamic changes caused by LV contraction15. Nevertheless, no conclusive connection between mean arterial pressure and the amplitude of SARM could be established in our study (r = 0.21).Different attempts have been made to identify potential influence factors on SARM. Pratt et al. and Biamino et al. offered an alternative explanation and hypothesized that posterior aortic wall motion is largely determined by left atrial (LA) volume change17. This idea has subsequently been further investigated in patients with valvular heart disease14. By calculating peak relative volume change between atrial diastole and systole our results reveal a moderate relationship with total excursion of the aortic root (r = 0.61). In our opinion this relationship seems logical because both, the aortic root and the LA, share a same anatomical wall. Nevertheless, this connectivity does not explain the simultaneous motion of the aorta’s root anterior wall whose motion parallels that of the posterior wall and has an even higher amplitude12. Except for active contraction in sinus rhythm, the atrial volume change occurs passively as a result of valvular plane displacement caused by ventricular contraction. Thus, we believe that SARM is related to but not exclusively caused by left atrial volume change and that SARM has to be attributed mainly to LV systolic function.At the same time Strunk This could be confirmed in our study by correlating SARM to LV ejection fraction, the parameter most frequently used to grade systolic performance (r = 0.74). A comparable result was found between SARM and LV longitudinal deformation determined by global longitudinal strain (r = 0.75). This association was even higher when SARM was normalized to body surface area (r = 0.78).et al. found a reduced SARM after myocardial infarction and significant differences according to Killip classification with highest amplitude for Killip class I and lowest for Killip class IV21. In a study investigating various cardiac disorders Hall et al. described significant elevated SARM in patients with severe mitral regurgitation and atrial septal defect16. Similar results for mitral regurgitation were reported by Akgün et al.14 while SARM was diminished in mitral stenosis. A flattened profil of SARM was also observed by Chandraratna et al.15 in patients with hypertrophic obstructive cardiomyopathy and by Ochs et al.25 in patients with cardiac involvement of light chain Amyloidosis.SARM can be altered by different pathologic conditions. Keltai 26 which could be confirmed by our present data. When adjusted for clinical parameters, diminished SARM is an independent predictor of cardiac death and hospitalization due to cardiac decompensation in DCM patients while a value below 7 mm was associated with worse outcome. Among multivariate models including only echocardiographic parameters, however, neither SARM nor any other measured value of longitudinal or systolic LV function could be detected as independently predictive. Although both EF and GLS are approved indicators of cardiac outcome in patients with heart failure, the contradicting information gained through the several multivariate models in our analyses might be caused by the low number of adverse events during follow-up. Furthermore, cases in which it is impossible to calculate EF and/or GLS are rare, especially in times of echocardiography contrast agents. This might limit the use of SARM as a general index of systolic LV function.The present study investigated SARM in a prospectively recruited cohort of DCM patients and an age and gender matched control group. Like in former studies, systolic heart failure lead to a significantly reduced amplitude of total aortic root excursion compared to healthy control subjects . Furthermore, our results indicate that SARM is primarily driven by LV systolic function, in particular by longitudinal deformation. It is well established, that an impaired LV longitudinal function is associated with a poor prognosis in cardiac diseaseFirst, this was a monocentric study conducted with a specific echocardiographic machine for image acquisition and its proprietary software package was used for analysis. Second, due to the divergent acoustic window, the displacement axis of SARM may not be completely concordant with the global longitudinal motion of the LV. Thus, compared to speckle tracking echocardiography SARM serves only as a surrogate parameter of global longitudinal LV deformation and is not suitable to determine regional abnormalities. Third, discrepancy in information obtained by multivariate models in our analyses might be caused by the low number of adverse events during follow-up.Due to its high echogenicy, SARM can easily be visualized by M-mode echocardiography. Contrary to many previous reports we demonstrated that SARM is not exclusively directed anterior but shows an additional downward and lateral-left displacement similar to the systolic movement of the cardiac base towards the apex.Abnormal SARM is a frequent finding in cardiac disease. Alterations are, however, not specific to a particular pathology but can generally be regarded as a prognostically unfavorable sign in patients with systolic heart failure.Our data suggest that SARM is closely related to global longitudinal strain and thus might represent an alternative measure of LV longitudinal function especially when strain assessment is not feasible or available.27.The present study is part of the project “New echocardiographic parameters for assessment of longitudinal left ventricular function” . A corresponding recruitment strategy, inclusion and exclusion criteria as well as the follow-up process have therefore already been described in detail previouslyInitial analysis for the current study is based on data derived from a recent trial and included the complete cohort of 202 patients with dilated cardiomyopathy who were recruited between January 2009 and December 2015 in our cardiology department and the same number of age and gender matched control subjects. Digitally stored echocardiographic examinations were screened for availability of SARM measurements and all suitable datasets have subsequently been re-matched for age and gender. The final study population consisted of 180 patients and 180 healthy controls.This study was carried out after approval by the ethics committee of the University of Heidelberg in concordance with the Declaration of Helsinki. Written informed consent was provided by all participants of this study.28 using commercially available software . Global longitudinal strain (GLS) was determined using the embedded Automated Function Imaging tool.Echocardiography was conducted with a commercially available ultrasound machine  using a 1.5- to 4.6-MHz phased-array probe (M5S-D). The sampling rate was adjusted to 55 to 60 frames/sec for B-mode, M-mode was recorded at 1.000 to 2.000 frames/sec. Images from 3 consecutive heart cycles were acquired and stored digitally in RAW-DICOM format for later offline analysis. Measurements were performed according to the recommendation of the American Society of Echocardiography and the European Association of Cardiovascular ImagingSARM was displayed starting from a left parasternal B-mode short axis view of the left ventricle with the echo probe directing posteriorly. The imaging plane was then tilted medial and angulated cephalic until the opening and closing of the aortic valve was visible. Finally, the M-mode beam was placed through the center of the aortic roots cross section Figs  and 2.Statistical data analysis was performed using SPSS version 24 . Continuous variables are presented as mean ± SD or as median with interquartile range as appropriate. Values were compared with Student’s t test for normally distributed data, otherwise the Wilcoxon signed rank test for paired observations (patients vs control subjects) or the Mann-Whitney-Wilcoxon test for unpaired observations (patients with or without events) was used. Categorical values are expressed as number (percentage) and were compared using χ2 or McNemar depending on data distribution. All analyses were of explorative nature. A p-value of < 0.05 was denoted statistically significant.Association between SARM and potential influence factors was explored by Pearson’s correlation and linear regression analysis. The ability of SARM to discriminate patients with DCM from healthy individuals as well as to discriminate patients with from those without a cardiac event was tested using receiver operating characteristic analyses. Cutoff values were calculated using Youden’s index.29 and hospitalization for heart failure was defined. The occurrence of events over time is displayed by Kaplan-Meier curves. Groups were compared using the Log-rank test. Univariate Cox regression was used to calculate hazard ratios of clinical and echocardiographic variables. Parameters with significant impact on patient outcome were put into different multivariate models to identify independently prognostic factors. Hazard ratios with 95% confidence intervals and p-values are provided. According to the number of events in this study and with the intention not to overfit the analysis, multivariate models were restricted to a maximum of 4 variables.To evaluate the prognostic value of SARM a combined end-point consisting of cardiovascular deathReproducibility of SARM measurements was tested by reanalyzing 20 randomly chosen patients and control subjects in a blinded fashion by the same and by a second experienced investigator. Intra- and interobserver variability results are expressed as coefficients of variation.The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.Supplementary figure S1Supplementary video 1Supplementary video 2Supplementary video 3


A 70-year-old male with a medical history significant for long-standing ischemic cardiomyopathy (ICM) and heart failure with reduced ejection fraction (HFrEF) was admitted to the hospital with shortness of breath (SOB) five days after an acute heart failure (HF) exacerbation. He had non-radiating chest pressure now at rest, but without evidence of an acute coronary syndrome (ACS). Diagnostic work-up on readmission included a transthoracic echocardiogram (TTE), which revealed worsening left ventricular (LV) systolic dysfunction with new wall motion abnormalities and an incidental echo density in the LV apex, suggestive of an LV thrombus. These findings were unseen on imaging 20 months prior. The patient was initiated on warfarin to be maintained for three months, and discharged in stable condition after optimization of his anginal symptoms. Cardiac catheterization was not attempted secondary to the patient’s chronic kidney disease (CKD). The incidental finding of an LV thrombus occurred despite compliance with guideline-directed medical therapy of HFrEF and ICM, including adjunctive use of clopidogrel. With the poor survival associated with thromboembolism, the prevention, risk stratification and appropriate therapeutic approach to LV thrombus are poorly delineated in patients with HFrEF in sinus rhythm. Currently, the screening guidelines for the identification of LV thrombus in patients with HFrEF are also unknown. Given mixed evidence regarding prophylactic anticoagulation, we present this case of an incidental LV thrombus found during an episode of acute decompensated HF in the setting of long-standing ICM to emphasize the need to suspect LV thrombus formation after such presentations with closer follow-up for prompt detection and timely treatment. A left ventricular (LV) thrombus is a complication of severe LV systolic dysfunction, most notably secondary to anterior myocardial infarction (MI), chronic heart failure (CHF) and dilated cardiomyopathy -2. The pA 70-year-old Caucasian male with a medical history significant for long-standing ICM with HFrEF (EF = 40% w/ grade I diastolic dysfunction), chronic kidney disease (CKD) stage III B, and hypertension presented to the emergency room (ER) with complaints of acute onset non-radiating exertional chest pressure, orthopnea, and shortness of breath (SOB). Eight months prior, the patient had presented with similar symptoms and was treated medically for an acute exacerbation of his HF (New York Heart Association Class III). Physical examination revealed 2+ bilateral pitting pedal edema and diffuse crackles on lung auscultation. Review of outpatient medications revealed optimized HFrEF guideline-directed medical therapy and the patient endorsed compliance. Initial workup was significant for notable elevations in N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP) (to >4000 pg/mL) and low suspicion of the acute coronary syndrome (ACS) from unchanged electrocardiogram (ECG) findings Figure  and stabHowever, the patient returned to the ER five days after initial discharge with complaints of SOB and similar non-radiating chest pressure now present at rest. He was admitted for observation given persistent chest pain in the setting of significant cardiac history. Diagnostic workup included ECG, which was significant for new T-wave changes in the inferior leads concerning for possible ischemia Figure  and tranThe presence of LV thrombus secondary to severe LV systolic dysfunction (<35%) has been reported at a rate of around 20%, with ICM alone found to be an independent predictor of thrombus formation and thromboembolism . Using tCurrently, the screening guidelines for identification of LV thrombus in patients with HFrEF are unknown. After AMI, it has been suggested that TTE should be performed in patients at high risk for apical LV thrombus (i.e. anterior MI or delayed reperfusion) within 24 hours of admission and consideration of follow up imaging within one to three months . Unlike In the case described, the patient had long-standing ICM of nearly 13 years with associated HFrEF that had been both optimized by revision of his three-vessel coronary artery bypass (CABG) five years prior and medical management. Additionally, the patient’s last TTE, 20 months prior to his presentation, failed to show significant changes in pump function and major wall motion abnormalities since his revision. It is likely that his HFrEF, perhaps in relation to worsening ICM, became refractory to optimized medical management, noted by his initial presentation of acute decompensated HF eight months prior to identifying his LV thrombus. Considering worsening ICM, the patient’s advanced CKD prohibited cardiac catheterization to characterize this further. In this case, repeated cardiac imaging would have provided temporal information regarding the thrombus formation in the last 20 months. Given that ICM is an independent risk factor for LV thrombus formation, in addition to severe LV systolic dysfunction alone with sinus rhythm, it may be that acute decompensated HF, particularly refractory HF requires closer follow-up that is guided temporally. After compensation of the patient’s exacerbation occurring eight months prior, cardiac imaging would not only have been helpful to identify an LV thrombus, it would have assessed worsening and permanent wall motion abnormalities  associated with increased risk for its formation. In the patient’s subsequent course described, these were found with the incidental identification of the LV thrombus. While the patient was scheduled for outpatient follow-up for echocardiography after the first admission detailed, the detection of his LV thrombus would remain incidental to the concern of worsening ventricular function. Additionally, only a 42% utilization rate was noted by Goyfman et al. with follow-up echocardiogram performed during an index admission for acute decompensated HF in the setting of medication noncompliance where such risk is higher . IrrespeWith the poor survival associated with thromboembolism, the prevention, risk stratification and appropriate therapeutic approach to LV thrombus are poorly delineated in patients with HFrEF in sinus rhythm. We present a case of an incidental LV thrombus found after acute decompensated HF in the setting of long-standing ICM and HFrEF to emphasize the need to consider LV thrombus formation in such patients with close follow-up. Likewise, without evidence for prophylactic anticoagulation, identifying patients at highest risk of LV thrombus formation will refine guidelines for cardiac imaging to increase the prompt detection and treatment of these patients to thereby prevent fatal thromboembolism.


Ventricular premature contractions (VPCs) may trigger lethal ventriculararrhythmias in patients with structural heart disease. However, this role ofVPCs in healthy people remains controversial once that not enough clinicaltrials are available. Recently, some myocardial repolarization markers, suchas Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios, have been reported to beuseful for predicting lethal ventricular arrhythmias in various clinicaldisorders without structural heart disease.In this study, we aimed to investigate the relation between VPC frequent andmyocardial repolarization markers in individuals without structural heartdisease.This study included 100 patients who had complaints of dizziness andpalpitations. Twelve-lead electrocardiography and 24-hour ambulatory Holterrecordings were obtained from all patients. VPC burden was calculated as thetotal number of VPCs divided by the number of all QRS complexes in the totalrecording time. P-values < 0.05 were considered significant.Tp-e interval and Tp-e/QTc ratio were significantly higher in patients withhigher VPC burden than in patients with lower VPC burden, and a positivecorrelation was found between these markers and VPC burden. Tp-e  and Tp-e/QTc  in the leadV5 were identified as independent predictors of increased VPC burden.Tp-e interval and Tp-e/QTc ratio increased in patients with high VPC number.Our study showed that VPCs may have a negative effect on myocardialrepolarization. This interaction may lead to an increased risk of malignantarrhythmias. Inaddition to these symptoms, frequent VPCs may cause more serious disorders. Recentstudies on adults with frequent VPCs  have reported leftventricular dilation and/or dysfunction,4diastolic dysfunction,5 andmalignant ventricular arrhythmias in patients with structural heartdisease.6 However, whetherfrequent VPCs are associated with malignant arrhythmias in individuals withoutstructural heart disease remains uncertain.Ventricular premature contractions (VPCs) are commonly seen in theelectrocardiography (ECG) of patients with hypertension, obesity, and structuralheart disease. Some studies reported VPCs to occur in about 4% of the generalpopulation.8 In this study, we investigated the relation between VPC burdenand myocardial repolarization by using some ECG markers in individuals withoutstructural heart disease.T wave is commonly used in assessing myocardial repolarization. Increased transmuraldispersion of myocardial repolarization in a normal heart is associated with theirtendency toward cardiac arrhythmias. Recently, some myocardial repolarizationmarkers, such as QT interval (QT), corrected QT (QTc), QT dispersion (QTd), Tp-einterval (Tp-e), and Tp-e/QT ratio have been found to be useful in predictinglife-threatening cardiac arrhythmias in several clinical disorders withoutstructural heart disease. Some studies showed that increased Tp-e, Tp-e/QT, andTp-e/QTc were related to the elevated risk of occurrence of malignant ventriculararrhythmias.One hundred patients with at least 1 VPC in the 12-lead ECG with diagnosis ofdizziness, syncope, and palpitation without structural heart disease admitted tothe Cardiology Department of our university hospital, between July 2016 andMarch 2017, were enrolled for this cross-sectional study. Twenty-four-hourambulatory Holter recordings were obtained from all patients. VPC burden wascalculated as the total number of VPCs divided by the number of all QRScomplexes in the total recording time. A frequency of < 1% VPCs/24 h wasdenoted as "rare-group 1 (n = 32)", 1-5% VPCs/24 h was denoted as"occasional-group 2 (n = 36)", and > 5% VPCs/24 h was denoted as"frequent-group 3 (n = 32)". The exclusion criteria for all groups werenon-reliable T waves on the ECG, atrial fibrillation, bundle branch block,moderate or severe valvular heart diseases, thyroid disorders, cardiomyopathies,congenital heart diseases, malignancy, pulmonary hypertension, electrolytedisturbances, acute coronary syndromes, heart failure, history of myocardialinfarction, history of coronary artery bypass grafting, implanted permanentpacemaker, and LV segmental motion defect in the echocardiographic exam. Thelocal ethics committee approval and informed consent from all patients wereobtained.Twelve-lead ECGs were obtained at rest at 10 mm/mV amplitude and 25 mm/sec rate, with the patient in thesupine position. All ECGs were transferred to a computer through a scanner andthen used for × 300% magnification using the Paint software. Holterrecordings were performed by using Lifecard CF recorders (Del-Mar Reynolds).Patients were warned not to smoke and not to consume coffee and/or alcoholduring the Holter recording. Measurements were performed on the computer by twocardiologists who were blinded to the clinical data of each patient. Ventriculartachycardia (VT) was defined as the line-up of at least three or moreconsecutive VPCs. The ventricular couplet (Vc) was defined as a sequentialordering of two VPCs.9 QTc = QT/√R -R interval. QTd was defined as the difference between the longest and theshortest QT interval of the 12leads. Subjects with U waves in their ECGs wereexcluded from the study. In the measurement of Tp-e interval, the tail andtangent methods can be used, but the former is a better predictor of mortalitythan the latter.10 Thus, thetail method was used in this study. The tail method was defined as the intervalfrom the peak to the end of the T wave to the point where the wave reached theisoelectric line.9 Measurementof the Tp-e interval was obtained from leads V2 and V5, which were corrected forheart rate (cTp-e).11 TheTp-e/QT and Tp-e/QTc ratios were calculated from these measurements.RR interval, QRS duration, QT, and QTd were measured in all derivations. QT wasdefined as the time from the start of the QRS to the point at which the T wavereturns to the isoelectric line. The average value of at least two readings wascalculated for each lead. QTc was calculated by using Bazett'sformula:12 Leftventricular ejection fraction (LVEF) was assessed using Simpson's method.All echocardiography examinations were performed by an experienced cardiologist in all subjects using a 2.5-3.5MHz transducer in the left decubitus position. Two-dimensional and pulsedDoppler measurements were obtained using the criteria of the American Society ofEchocardiography and the European Association of CardiovascularImaging.2test for independence. Correlations between two variables were performed byPearson's correlation. Multiple linear regression analysis was used to evaluatethe association between an increased VPC burden and independent variables thatdiffered significantly in Pearson's correlation analyses (p < 0.1). Amultivariate logistic regression analysis was performed to demonstrate theeffect of presence of CAD on ECG parameters. P-values < 0.05 were consideredsignificant.All tests were performed by using PASW Statistics . Shapiro-Wilk test was used to test for normal distribution.Continuous variables were described as the mean (± standard deviation),and categorical variables were described as frequency (percentage). Allcontinuous parameters were compared among groups by using one-way ANOVA. Thepost hoc Tukey's test was used for significant intergroup differences.Categorical factors were compared among groups using the χThe baseline demographics and laboratory characteristics of the three groups aresummarized in According to the comparison of the ECG parameters among the three groups in lead V2,QT interval was significantly longer in groups 2 and 3 than in group 1. Tp-einterval in group 3 was significantly longer than those in groups 1 and 2. TheTp-e/QTc ratio significantly increased in groups 2 and 3 in comparison with group 1.When the groups were compared, no significant difference was found in QTc intervaland Tp-e/QT ratio .In the comparison of ECG parameters among the three groups in lead V5, QT intervalwas significantly longer in group 3 than in group 1. Tp-e interval was significantlylonger in group 3 than in groups 1 and 2. Tp-e/QTc ratio was significantly increasedin the group 3 when compared to the group1. When the groups were compared, nosignificant difference was found in QTc interval and Tp-e/QT ratio .A total of 28 patients had coronary artery disease (CAD) . Non-critical lesions that did not causesignificant narrowing were evident in the angiographic reports. The presence of CADwas greater in group 3 than in groups 1 and 2, but statistical significance was notobserved (p = 0.538). In the multivariate logistic regression analysis, CAD had noeffect on ECG parameters. Vc was observed in 51 patients  and VT in 26 patients . The QTd duration of group 3 was significantlylonger than those in groups 1 and 2 .According to Pearson's correlation test, positive correlations were observed betweenVPC burden and Tp-e (in leads V2 and V5) and Tp-e/QTc (in leads V2 and V5)  . Table3In this study, we demonstrated that Tp-e interval and Tp-e/QTc ratios weresignificantly higher in patients with higher VPC burden than in those with lesserVPC burden and that a positive correlation was observed between these markers andVPC frequency. However, we did not find a relationship between Tp-e/QT ratio and VPCburden. Tp-e interval and Tp-e/QTc ratio in lead V5 were identified as independentpredictors of increased VPC burden. The prolongation of the duration of myocardialrepolarization in patients with increased VPC burden is important because thiscondition may be related to the increased risk of life-threatening arrhythmia.According to our results, myocardial repolarization parameters deteriorated withincreasing VPC frequency. Therefore, we concluded that both VPC frequency and stageof myocardial repolarization were affected by similar causes.16 Although VPCs are known to bebenign in individuals with a structurally normal heart, they have been shown tocause malignant arrhythmias in some cases. However, the clinical significance of VPCfrequency in these individuals remains unclear once adequate human studies have notbeen performed.17 Tilz etal.18 found thatventricular fibrillation (VF) was triggered by VPCs after an implantablecardioverter-defibrillator was used on a 29-year-old patient, who was resuscitatedfollowing sudden cardiac death. All examinations, including echocardiography,angiography, ajmaline test, and myocardial biopsy, were normal. At the same time,some cases demonstrated that polymorphic VT and idiopathic VF were induced becausespecific VPCs with short coupling intervals could promote intracellular calciumoverload.20 In a study examining the records of 21 patients who experiencedcardiac arrest during ambulatory ECG recording, heart rate and VPC frequencyincreased before the onset of VF.21 Savelieva et al.22 found significant QT turbulence after VPC in individuals with astructurally healthy heart. Although these data provide information on the cause ofmalignant arrhythmias for VPC, they do not provide enough information about theimportance of VPC frequency.Idiopathic VPCs, generally regarded as a benign condition in healthy individualswithout structural heart disease, are formed by the spread of an early stimulusoriginating from an ectopic focus. VPCs may cause serious complications, such asangina, syncope, or heart failure, when the ectopic beat number increases.17 Increased sympathetic tonus due to anxiety or physiologicalstress may cause the release of catecholamines such as adrenaline. This conditioncauses the flow of calcium from an extracellular space into the myocyte cells byincreasing the production of cyclic AMP (cAMP). The contraction force of themyocytes increases, and the myocyte is depolarized rapidly. For this reason,myocytes become more sensitive than normal and may depolarize spontaneously withoutsino-atrial node depolarization. Therefore, VPC formation and frequency mayincrease.24 Armaganijan et al.25 reported the relationship of sympathetic activation withpatients with ventricular arrhythmias and suggested the effectiveness of renalsympathetic denervation by catheter to reduce arrhythmic burden.Several mechanisms have been proposed to explain the relationship between VPC andlife-threatening arrhythmias. VPC may play a key role in the initiation of malignantcardiac arrhythmias. Various factors such as increased sympathetic tonus, alteredhemodynamic status, or electrolyte imbalances , which all disrupt the stability of the myocardium, may cause atransition from VPC to malignant arrhythmia.27Another factor that increases the frequency of VPC is excessive caffeine consumption.Caffeine, a phosphodiesterase inhibitor, is also a central stimulant that canenhance sympathetic activity. It can increase intracellular calcium concentration byinhibiting the enzyme that catalyzes the breakdown of cAMP. Animal studies showedthat caffeine administration at high doses could induce and increase the frequencyof VPCs.29 Recently, some myocardial repolarization markers, such asTp-e interval, Tp-e/QT, and Tp-e/QTc ratios, have been reported to be useful inpredicting lethal ventricular arrhythmias in various clinical disorders withoutstructural heart disease.31Tp-e interval is considered a new marker of increased risk of SCD. Yamaguchi etal.32 showed that Tp-einterval is more significant than QTd or QTc in predicting Torsade de Pointes inpatients with acquired long QT syndrome. At the same time, an increase in Tp-einterval and Tp-e/QT ratios was shown to be associated with Brugadasyndrome.8 Tp-e/QT andTp-e/QTc ratios were found to be relatively more constant than other markers becausethey were not affected by changes in heart rate and body weight.9Prolongation in the dispersion of myocardial repolarization predisposes the malignantventricular arrhythmia and has prognostic importance in terms of sudden cardiacdeath (SCD). Prolongation of QT and QTd durations may be associated with polymorphicventricular tachycardia, Torsades de pointes, and SCD.33assessed the myocardial repolarization parameters before and after RFA in patientswith a VPC burden of more than 5% on a 24 h Holter recording. After the successfulprocedure, Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio significantly decreasedmore than before RFA . In accordance with this data, the higherdetection of Tp-e interval in patients with increased VPC frequency suggests thatthe risk of malignant arrhythmias might be higher in these patients. In our study,malignant arrhythmias, such as Vc and VT, were seen more in group 3 patients, thussupporting our predictions. This important link can be used to closely follow up onand manage their treatment of patients with increased VPC frequency.Although we found an increase in Tp-e interval and Tp-e/QTc ratios as VPC frequencyincreased, the slight increase observed in Tp-e/QT ratio was not statisticallysignificant. Yayla et al.Our study has several major limitations. First, our study was single centered andincluded a small number of patients. Therefore, statistical power was limited.The results should be verified in a larger prospective cohort study. Second,because we did not have other ambulatory Holter measures, such as heart ratevariability and heart rate turbulence, we could not exclude the effect of thesemeasurements on the VPC frequency. Third, we did not have data on cardiac eventrates for this study because we could not follow up on the patientsprospectively for future arrhythmic events. Fourth, we aimed to record arelatively young patient profile to exclude occult CAD in our study. However, weabandoned this goal because of the limited number of patients. Furthercomprehensive studies should be conducted with a larger number of patients and alonger follow-up time to increase the consistency of our results.In conclusion, Tp-e interval and Tp-e/QTc ratios increased in patients with high VPCnumber. Our study showed that VPCs could have a negative effect on myocardialrepolarization. This interaction could lead to an increased risk of malignantarrhythmias.


To investigate biatrial mechanics and their relation with left ventricular outflow tract (LVOT) obstruction (LVOTO), the degree of hypertrophy, indices of ventricular diastolic function and fibrosis in children with hypertrophic cardiomyopathy (HCM).Fifty-five consecutive, prospectively recruited children with HCM , 19 (34.5%) of whom had LVOTO, underwent cardiac magnetic resonance and echocardiography with quantification of phasic components of biatrial function, biventricular diastolic function and fibrosis. Twenty healthy, sex-matched subjects served as controls.p < 0.05) in children with HCM compared with controls. Nearly all of the LA dynamics markers attained a significant association with the LVOT gradient (p < 0.05), the RA volumes and contractile functions were affected by LV fibrosis and mass (p < 0.05), and the RA mechanical components were related to the degree of LVOTO (p < 0.05). The minority of biatrial dynamics markers were associated with indices of ventricular diastolic function.We found a significant increase of left atrial (LA) and right atrial (RA) volumes and reduction in the majority of indices of contractile function, strains and strain rates (The majority of biatrial volumetric and functional indices were severely compromised in children with HCM compared with controls. The degree of LVOTO appears to trigger LA volumetric and LA and RA mechanical malfunction. On the other hand, the deterioration of RA volumetric components was linked to LV fibrosis and mass.• Biatrial function was severely compromised in children with HCM.• Left atrial malfunction was associated with the degree of LVOTO.• Fibrosis and LV mass were related to RA volumetric and contractile dysfunction.• The degree of LVOTO was linked to right atrial mechanical abnormalities. Hypertrophic cardiomyopathy (HCM) is a primary, genetically triggered myocardial disease characterised by uncontrolled left ventricular (LV) muscle proliferation, diverse clinical presentation and significant outcomes , 2. Its Cardiovascular magnetic resonance (CMR), in both adults and children, has emerged as an adjunctive imaging modality that may, besides yielding volumetric analysis, provide deeper insights into the distribution and degree of cardiac hypertrophy and fibrosis –11. MoreThis study was approved by the institutional ethics committee and written informed consent to participate in the study was obtained from all of the subjects and their parents.The study cohort comprised 55 consecutive, prospectively recruited children with HCM, 19 of whom had LVOTO. Criteria for inclusion in the study included an age younger than 18 years at the time of diagnosis and echocardiographic evidence of LV hypertrophy defined as a diastolic septal thickness or LV diastolic wall thickness z-score greater than 2 [determined as more than two standard deviations from the mean value for the population corrected for body surface area (BSA)] in the absence of haemodynamic conditions that could account for the observed hypertrophy [Normal values of CMR volumetric and mechanical parameters were sourced from the scans of 20 healthy sex-matched, young adult volunteers with no significant medical history, normal physical examination and normal 12-lead ECG.A standard CMR study was performed using a 1.5-Tesla scanner . Late gadolinium enhancement (LGE) images in long-axis and short-axis imaging planes were obtained with a breath-hold, segmented inversion recovery sequence performed 10 min after contrast injection . The control subjects did not receive gadolinium contrast agent.Two-dimensional, conventional pulsed Doppler and M-mode echocardiography was performed at rest using standard methods . Conventional pulsed Doppler was used to record the mitral and tricuspid inflow patterns at the leaflet tips in the apical four-chamber view. Peak velocities of E and A waves (cm/s) and their ratio (E/A) were measured.To determine maximal degree of LVOTO, two-dimensional and Doppler echocardiography was performed during the Valsalva manoeuvre in the sitting position, and then during standing if no gradient was provoked. A maximum gradient greater than 30 mmHg was considered significant. Neither pharmacological stimuli nor exercise tests were used to determine maximal LVOT gradients. Furthermore, CMR cine images were visually assessed for the presence of LVOTO.Steady-state free precession images were used for calculating ventricular volumes and ejection fractions with the aid of dedicated software . Manual delineation of endocardial and epicardial contours was performed in end-diastolic and end-systolic phases. Left ventricular end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV mass (LVM) and LV ejection fraction (LVEF) were calculated. LVEDV, LVESV and LVM were indexed to BSA . Also, on the basis of two- and four-chamber views, maximal LV wall thickness was measured. Images were visually assessed for the presence of LGE areas for each LV myocardial segment using the 17-segment cardiac model. In addition, the quantitative extent of LV LGE was determined using dedicated software . Regions of elevated signal intensity had to be confirmed in two spatial orientations. A region of interest (ROI) was selected in effectively nulled myocardium. The mean signal intensity and SD of the ROI were measured. The LV myocardium was delineated by endocardial and epicardial contours, which were traced manually. Enhanced myocardium was defined as myocardium with a signal intensity exceeding 6 SDs above the mean of the ROI. The extent of LGE was expressed as a percentage of the LV mass (LGE%LV).Left atrial and RA volumes were quantified using dedicated software . The LA volumes were calculated according to the biplane area–length method . Manual Atrial strains and strain rates were analysed using dedicated software . Left atrial endocardial borders were tracked in two- and four-chamber views. Right atrial borders were tracked in four-chamber view Fig. . The atrt test or the Wilcoxon–Mann–Whitney U test for continuous variables and the chi-square or Fisher’s exact test for categorical variables, as appropriate.All of the continuous variables were expressed as mean ± SD or as median and interquartile range and were tested for normal distribution using the Kolmogorov–Smirnov test. Comparisons between groups were performed using the Student’s –Altman test. The reproducibility analysis was performed by two experienced operators . Duplicability analysis was assessed using intraclass correlation coefficients (ICCs) and coefficients of variation (CoVs).Intraobserver and interobserver variability of the indices of atrial performance and quantitative analysis of LV fibrosis were evaluated using the Blandr > 0.50 were not included in the same multivariable model.Linear, multivariable regression analysis was conducted separately in three models, each for LA and RA, to determine the association between each index of atrial performance and the LVOT gradient , indices of atrial performance vs LGE%LV  and indices of atrial performance vs LVMI . Correlations between continuous variables were tested using Spearman correlation coefficients. The variables with p value less than 0.05 was considered to indicate statistical significance. The statistical analyses were performed using MedCalc 12.1.4.0 software .A two-sided p = 0.01) and greater maximal LV wall thickness (p < 0.01) compared with controls. By qualitative evaluation, fibrosis was detected in 27 patients (41.1%). Of those 12 children (21.8%) had LGE in RV insertion points, while in 15 subjects (27.1%) diffuse fibrosis was observed. The diffuse collagen deposits were mainly localised in hypertrophied parts of myocardium. Visually, there was no scarring within the RV myocardium. The fibrosis extent was 1.76 ± 3.2% of the LV mass. Table p < 0.01), larger LA size (p < 0.01) and more fibrosis (p = 0.02) than individuals without LVOTO. The baseline demographic and CMR data for subjects with and without LVOTO are presented in Table As expected, children with HCM had higher myocardial mass indexed to BSA p = 0.0 and greap = 0.01–0.02). Furthermore, children with HCM had conduit (p = 0.04) and booster (p = 0.03) fractional volume changes significantly lower than those of the controls. There were no differences in strain or strain rate booster functions between HCM juveniles and controls ; all other LA mechanics indices were significantly compromised in the study group compared with the controls (p = 0.01–0.04).The comparisons of volumetric and mechanical components of biatrial function between children with HCM and healthy controls are presented in Table p < 0.01) and volume just before contraction (p = 0.01) were higher in HCM subjects than in the controls. All emptying fractions were decreased in patients with HCM compared with the controls (p < 0.01–0.04). Moreover, the majority of markers of atrial deformation (p < 0.01–0.03), with the exception of the strain rate reservoir component (p = NS), were reduced in children with HCM compared with the control subjects.Right atrial minimal volume (p < 0.01–0.03). Furthermore, the reservoir (p = 0.02) and conduit (p < 0.01) emptying fraction were decreased in children with LVOTO. It is noteworthy that the active booster contractile function (p = 0.02) as well as the reservoir (p < 0.01) and booster (p = 0.01) strain mechanical components were higher in children with vs without LVOTO. All other emptying fractions and strain rates (p < 0.01–0.04) were significantly reduced in children with LVOTO . Moreover, there were no differences in booster pump or total RA contractile functions between subjects with and without LVOTO (p = NS). On the other hand, all deformation indices of RA were significantly lower in patients with LVOTO than in subjects without LVOTO (p < 0.01–0.02)  Fig. .Fig. 3Cop < 0.01–0.04). On the other hand, the LA volume prior to atrial contraction (p = 0.04), total volume (p = 0.04) and booster (p = 0.03) fractional volume change were related to LV mass. Lastly, only the LA conduit emptying fraction (p = 0.03) could be linked to the amount of LV fibrosis.The associations of indices of LA and RA dynamics with the amount of fibrosis, the extent of hypertrophy and the degree of LVOTO are summarised in Tables p < 0.01) fractional function exhibited an association with the degree of LVOTO (p = NS). However, all of the markers of RA deformation, with the exception of the strain booster component (p = NS), exhibited an association with LVOT gradient (p < 0.01–0.04). The maximum RA volume (p = 0.03) and volume before atrial contraction (p = 0.03) were associated with the extent of LV fibrosis. Finally, the minimum RA volume (p = 0.01) and the total (p = 0.01) and booster (p = 0.01) pump functions with strain rate booster component (p = 0.04) were linked to the LV mass.None of the RA volumes and only the RA conduit (p = NS). Only maximal RA volume was linked to transtricuspid A wave velocity . On the other hand, transmitral A wave velocity was associated with maximal LA volume  and E wave velocity with LA volume just before contraction .None of the indices of RV diastolic function had detectable association with LA dynamics and vice versa—none of transmitral velocities was connected with RA dynamics  and interobserver ICCs ranged 0.78 to 0.94 (CoV = 0.21–1.62). The ICCs and CoVs for the intraobserver and interobserver reproducibility regarding the quantification of LV fibrosis were 0.98 (CoV = 5.42) and 0.99 (CoV = 6.02), respectively.The majority of biatrial dynamics were severely compromised in children with HCM compared with healthy controls.The degree of LVOTO was predominantly associated with the volumetric and functional indices of LA performance.The RA volumes and contractile functions were affected by LV fibrosis and mass, and the RA mechanical components were related to the degree of LVOTO.The primary findings of our work are:In this study we compared atrial performance indices in HCM children versus controls. The control group was not age matched. This was mainly due to ethical concerns, which limited the recruitment of healthy children for CMR examination. For this reason, a limited number of studies recruited entirely healthy juvenile cohorts who underwent CMR , 19; butIn the human heart, it appears that LV systolic function largely influences LA reservoir function while LV relaxation and compliance are key modulators of atrial conduit and contractile functions , 24, 25.Previous studies have identified diastolic dysfunction as a prominent factor of LA remodelling and dysfunction in adult populations –31. In oOur contemporary understanding of atrial physiology and function stems predominantly from studies of the left adult heart. It appears that RA size and performance are likely to be subject to similar regulations as its left-sided counterpart. Even so, existing reports exploring human right atrium mechanics are very sparse. To date, there have been no CMR-derived studies focused on RA dynamics in an HCM juvenile population. Willens and colleagues, in an echocardiographic study of patients with pulmonary hypertension, demonstrated a decreased RA passive function associated with increased contribution of active atrial contraction to RV filling . SimilarReports analysing diastolic function in HCM children are limited to LV only. Abnormal LV and RV relaxation, based on echocardiographic transatrioventricular valve velocities and tissue Doppler measurements, was found in the majority of adult HCM patients , 35. HowThe limitations of our study are mostly inherent to its design. This study recruited a relatively small sample size with no genetic testing. No myocardial T1 mapping was available during data acquisition; thus, fibrosis was quantified using classical LGE technique and was limited to LV myocardium only. Also, data on diastolic function of healthy subjects was not available; hence, the comparison of ventricular relaxation indices between HCM children and controls was not possible.The majority of biatrial volumetric and functional indices were severely compromised in children with HCM. Unlike in adults, the magnitude of LA volumetric and mechanical malfunction in children appears to be related to the degree of LVOTO rather than to the substrates of diastolic dysfunction. On the other hand, RA volumes and contractile function were impacted by the amount of LV fibrosis and mass, while the RA mechanical components were linked to the degree of LVOTO. The indices of atrial performance may provide additional data that may serve for determining the stage of the disease. However, its clinical and prognostic usefulness in paediatric populations with HCM has yet to be determined.


Response to cardiac resynchronization therapy (CRT) varies significantly among patients. This study aimed to identify baseline characteristics that could predict super-response to CRT and to evaluate the long-term prognosis in super-responders. We retrospectively reviewed the data of 73 consecutive patients who received CRT. Patients were considered as super-responders after 6-month follow-up when NYHA class reduction to I or II combined with left ventricular ejection fraction (LVEF) ≥ 50% was observed. Patients were divided into super-responders group and non-super-responders group. All-cause mortality or hospitalization for heart failure (HF) was referred to the combined end point. 17 (23.3%) patients were super-responders. HF duration, left atrial dimension (LAD), and left bundle branch block (LBBB) were independent predictors of super-response to CRT. The combination of HF duration and LAD could provide more robust prediction of super-response than standalone HF duration  or standalone LAD . super-responders had excellent LV reverse remodeling. The cumulative incidences of combined end point were significantly lower in the super-responders group, LAD ≤ 42mm group, and combination of HF duration ≤ 48 months and LAD ≤ 42mm group. LBBB remained associated with a lowered risk of the combined end point , whereas LAD was associated with a raised risk of the combined end point . HF duration, LAD, and LBBB independently predicted super-response. The combination of HF duration and LAD makes more robust prediction of CRT super-response. Super-responders had excellent LV reverse remodeling and decreased the incidences of the combined end point. LBBB and LAD were independently associated with the combined end point. Cardiac resynchronization therapy (CRT) has become standard therapy for heart failure (HF) patients with left bundle branch block (LBBB) and prolonged QRS duration except optimum medical therapy . It not Hence, it is of clinical importance to identify baseline characteristics which are predictive of super-response. It has been reported that shorter duration of HF symptoms, smaller LV, smaller left atrial dimension (LAD), LBBB, wider QRS, and nonischemic cardiomyopathy (NICM) are associated with super-response , 7, 8. HThe aim of the present retrospective study is (1) to identify baseline characteristics that could predict super-response to CRT, (2) to evaluate the value of independent predictors in predicting super-response, and (3) to analyze the long-term prognosis in super-responders.β-blockers, and aldosterone antagonists] ≥ 3 months, (2) left ventricular ejection fraction (LVEF) ≤ 35%, and (3) QRS duration ≥ 130 ms. Patients with narrow QRS, myocardial infarction ≤ 3 months previously, or optimal medical therapy ≤ 3 months were excluded from this study. The study was approved by the Clinical Research Ethics Board at the Third Military Medical University. All participants volunteered to participate in the study and signed informed consent.This single center, retrospective study enrolled 73 consecutive patients who received CRT with or without an implantable defibrillator (CRT-P/D) from June 2014 to December 2017. The inclusion criteria were as follows: (1) New York Heart Association (NYHA) classes II to IV despite optimal medical therapy [angiotensin-converting-enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB), Echocardiography was performed at baseline and after 6-month follow-up using the commercially available system . Images were obtained using a 3.5 MHz transducer at an appropriate depth. The LVEF was calculated using the biplane Simpson's method from conventional apical four-chamber images. LV end-diastolic diameter (LVEDD) and left atrial diameter (LAD) were measured from M-mode. The area of mitral regurgitation (MR) was assessed semiquantitatively.CRT was performed with standard techniques via the left subclavian vein. It was a routine procedure to insert the transvenous LV pacing lead into a branch of the coronary sinus. The LV lead was preferentially placed into the lateral or posterolateral vein or an alternative vein if the lateral or posterolateral vein could not be accessed. In summary, the position of the LV lead was determined by the coronary sinus angiographic data. Wherever the LV lead was placed, it was ensured that there were satisfactory pacing parameters without phrenic nerve stimulation. The right atrial lead was placed in the right atrial appendage and the right ventricular lead was placed in the right ventricular apex conventionally.First follow-up visit was scheduled 1 month after CRT implantation and every 6 months thereafter. Echocardiography and HF symptoms were assessed at 6-month follow-up. Patients were considered as super-responders after 6-month follow-up when NYHA class reduction to I or II combined with near normalization of LVEF (defined as LVEF ≥ 50%) was observed. All-cause mortality or hospitalization for heart failure was referred to combined end point. U test for nonparametric variables, and chi-square test for categorical variables. Intergroup comparisons were performed with paired t-test. Only variables with P < 0.1 in the univariate logistic regression were entered into multivariate logistic regression analysis to identify independent predictors of super-response using backward stepwise procedure. Receiver operator characteristic (ROC) curve was used for evaluation of continuous variables to predict super-response, and the Youden index was used to determine the optimal cut-off value. Kaplan-Meier curves, with Log Rank P test, compared all-cause death or HF hospitalization. Multivariate Cox proportional hazards models were constructed to identify independent predictors of combined end point, using the variables with P < 0.1 in the univariate Cox proportional hazards models. A two-sided P value < 0.05 was considered statistically significant. SPSS 19.0  and MedCalc 18.6.0  were used to perform the statistical analysis.Continuous variables were expressed as mean ± standard deviation or medians (25th–75th percentile) according to their normality following Kolmogorov–Smirnov test. Categorical variables were presented as count and percentage. Differences between groups were analyzed using Student's t-test for parametric variable, Mann-WhitneyIn the present study, a total of 73 patients  who fulfilled the inclusion criteria were enrolled. 46 patients had LBBB, 2 patients had right bundle branch block (RBBB), and 16 patients had intraventricular conduction delay (IVCD). Moreover, 1 patient upgraded from dual-chamber pacemaker (DDD) and 2 patients replaced CRT. Of all patients, 17 patients (23.3%) were considered as super-responders ; others were therefore regarded as non-super-responders. There were no significant differences with regard to age, gender, NYHA class, hypertension, diabetes, atrial fibrillation, ischemic etiology, LVEF, LVEDD, MR, QRS duration, ACE-I/ARB, and beta-blockers as well as spironolactone between the two groups. However, the super-responders group had shorter HF duration (P < 0.001) and smaller LAD (P = 0.001) and contained more frequent LBBB (P = 0.020) compared with the non-super-responders group .As shown in Receiver operating characteristic (ROC) curve analysis was performed to evaluate the value of HF duration, LAD and LBBB in predicting super-response to CRT. The area under the curve (AUC) for baseline HF duration was 0.789 , with HF duration ≤ 36 months having 88% sensitivity and 70% specificity. Baseline LAD ≤ 42 mm was 82% sensitive and 71% specific for predicting super-response to CRT . For combination of HF duration and LAD, the AUC was 0.899 , with HF duration ≤ 48 months together with LAD ≤ 42 mm having 88% sensitivity and 79% specificity. There was no significant difference between the AUC of HF duration and LAD . Combination of HF duration and LAD significantly increased the AUC compared with standalone HF duration  or standalone LAD  , Table 3Three patients died within 6 months after CRT in the non-super-responders group. Therefore, a total of 70 patients completed the echocardiographic, clinic visit, or telephone surveys at 6-month follow-up. Patients' characteristics including cardiac function and echocardiographic data at baseline and follow-up in two groups are summarized in During a mean follow-up of 22.56 ± 10.38 months, the combined end point of hospitalization for HF or all-cause death occurred in 17 patients. In the super-responders group, 1 (5.9%) hospitalization for HF and 0 (0%) deaths were reported, compared with 10 (17.9%) hospitalizations for HF and 6 (10.7%) deaths in the non-super-responders group. As shown in the Kaplan-Meier curves , the cumA multivariate Cox regression model was carried out adjusting for LAD, LVEDD, and LBBB . LBBB remained associated with a lowered risk of the combined end point , whereas LAD was associated with a raised risk of the combined end point  .The main findings of our study were as follows: (1) HF duration, LAD, and LBBB were independent predictors of super-response to CRT; (2) the combination of HF duration and LAD could provide better prediction of CRT super-response; (3) super-responders had excellent LV reverse remodeling and clinical prognosis during follow-up; (4) the cumulative incidences of combined end point were significantly lower in the super-responders group, LAD ≤ 42mm group, and combination of HF duration ≤ 48 months and LAD ≤ 42mm group compared with the non-super-responders group, LAD > 42mm group, and others, respectively; (5) LBBB showed a decreased risk for combined end point, whereas LAD was associated with an increased risk of combined end point.LVEF was used to diagnose HF and evaluate the prognosis of HF treatments. Reduced LVEF was associated with poor survival . MoreoveIn the MADIT-CRT study by Hsu et al. of 752 CRT recipients, smaller LA volume was independently associated with super-response to CRT therapy , 13. In In the present study, HF duration was an independent predictor of super-response to CRT, with HF duration ≤ 36 months having 88% sensitivity and 70% specificity , in line with a previous study which showed that HF duration ≤ 12 months remained significantly associated with super-response in multivariate analysis . HoweverAbnormal left ventricular activation sequence in LBBB might lead to electrical and mechanical dyssynchrony . Thus, CSeveral other variables, including female sex, smaller LV, NICM, BMI, and wider QRS duration, were reported to be associated with super-response to CRT. Unfortunately, those variables could not predict super-response in our study, which could be due to differences with the super-response definition adopted and patients enrolled.In the study, super-responders had greater reductions in LVEDD (P < 0.001) and MR (P < 0.001) than non-super-responders. In other words, super-responders had excellent LV reverse remodeling, which was associated with favourable clinical outcome, in line with a previous study. The incThis study has a few limitations. First, the retrospective nature of this study probably resulted in unidentified confounders. Second, patients in our study came from a single center and the sample size was relatively small; therefore, it may not be sufficiently representative. Third, the duration of follow-up in our study was relatively short and therefore predictors of delayed improvement of LVEF could not be evaluated. Last, patients who were lost to follow-up were not included in our study, so there may be patient selection bias. However, those aspects were inherent limitations of the “real world” studies, despite our best efforts to avoid these limitations. Therefore, further large multiple-center prospective trials were needed to confirm our results in the future.HF duration, LAD, and LBBB were independent predictors of super-response to CRT. The combination of HF duration and LAD strongly predicted CRT super-response. Super-responders had excellent LV reverse remodeling and clinical prognosis during follow-up. LAD ≤ 42mm and the combination of HF duration ≤ 48 months and LAD ≤ 42mm decreased the incidences of combined end point. LBBB and LAD were independently associated with all-cause death and HF hospitalization.


Acute decompensated heart failure (ADHF) is a difficult clinical problem with poor outcomes. High in-hospital mortality and readmissions remain a concern despite advancement of treatment options for heart failure , 2. The The previously dreaded ventricular arrhythmias in chronic heart failure have been managed much more effectively since the introduction of the implantable cardioverter–defibrillators (ICDs) . HoweverRenal dysfunction in a heart failure patient is common and cardiorenal syndrome is now an established term. ADHF often brings with it worsening renal function and acute kidney injury that can raise concerns about the use of the much needed intravenous diuretic therapy as well as demand adjustment in ACE inhibitors, angiotensin receptor antagonists, or sacubutril valsartan . ProgresAlthough research involving hibernating myocardium is almost exclusively confined to the stable chronic heart failure population, the heart failure clinician frequently encounters it in ischaemic acute heart failures with a troponin rise. Ryan and Perera highlight the importance of considering coronary angiography if appropriate and where possible in ADHF for better management planning. We are also informed of the important REVIVED-BCIS2 trial, a UK multicentre study that randomises ischaemic heart failure into revascularisation by percutaneous intervention or optimal medical treatment and incorporates hibernating myocardium.The reviews in this series on complicated acute heart failure syndromes bring up exciting future directions in managing these difficult subsets which often overlap. Tackling these subsets effectively is likely to go a long way in reducing mortality and hospitalisation rates.