MV) disease. Although mitral valve repair (MV‐repair) is the “gold standard” treatment for MV disease, in elderly patients, there is controversy about whether MV‐repair is superior to mitral valve replacement. We reviewed results after MV surgery in elderly patients treated over the past 20 years.Because of demographic changes, a growing number of elderly patients present with mitral valve  and tricuspid valve surgery in 50 patients (14.7%). Thirty‐day mortality was 5.4% (MV‐repair) versus 9.2% . Overall 1‐ and 5‐year survival was 90.7%, 74.2% versus 81.3%, 61.0% (P<0.01). Median survival after MV‐repair was 7.8 years, close to 8.5 years (95% CI: 8.2–9.4) in the age‐matched UK population (ratio 0.9). Rate of re‐operation for MV‐dysfunction was 2.3% versus 2.5% . After propensity matching, patients after MV‐repair still had improved survival at 1, 2, and 5 years .Our in‐hospital database was explored for patients who underwent MV surgery in elderly patients. Long‐term survival is superior after MV‐repair and the re‐operation rate is low. MV‐repair should be the preferred surgical approach in elderly patients.Excellent outcomes can be achieved after  In patients with degenerative mitral valve (MV) disease, MV repair (MV‐repair) is the generally accepted “gold standard” treatment, as it has demonstrated superiority over MV replacement (MVR) in various clinical settings.Data obtained from administrative American databases revealed a low rate of MV‐repair in elderly patients of <50% and identified higher age as an independent predictor of MVR.Therefore, although outcomes after MV surgery in elderly patients have improved markedly during recent years,P=0.10). This yielded 126 patients after MV‐repair (n=63) and MVR (n=63). Both cohorts, unmatched and matched, were included in this study for further analyses  and MVR (n=120) and were compared regarding all documented baseline variables. Variables with significant difference between the groups were included for propensity matching  was present when asymmetrical left ventricular dilatation led to ring dilatation and displacement of the papillary muscle due to cardiomyopathy. Rheumatic valve pathology was defined as reduced leaflet motion in systole and diastole associated with leaflet thickening and commissural fusion. The decision in favor of or against MV‐repair was at the discretion of the operating surgeon, but generally MV‐repair has been the preferred treatment at our institution. MV‐repair was always associated with annuloplasty, while various repair techniques for the valve itself were used. In case of MVR, the subvalvular apparatus was preserved as per surgeon's preference; however, at least the posterior leaflet was preserved if anatomically possible and tissue valves were implanted in all cases.Data collection of baseline and perioperative data was prospective, as part of our dedicated in‐hospital database and completeness of data set was secured by a data manager throughout the observational period. Data collection and audit was approved by the institutional R&D committee and every patient consented to data collection prior to operation. Survival data were obtained via the National Health Service central register and were complete for all patients. Data from outpatient visits and re‐admissions to our institution were retrospectively obtained by exploration of the electronic patient records.www.ons.gov.uk, http://ec.europa.eu/eurostat/web/population-demography-migration-projections/deaths-life-expectancy-data/database) and compared to our study cohort. In addition, a time‐related, combined end point was created, defined as time to one of the following events: death, re‐operation for MV dysfunction or any observation of moderate or severe MR on echocardiography. In this context, the word “re‐operation” refers to any kind of re‐intervention on the MV, including transcatheter valve‐in‐valve implantation. The secondary end points were acute perioperative complications, New York Heart Association Class (NYHA) at 6 weeks, re‐admission for Heart Failure (HF), LV‐function during follow‐up, and grade of MR at 1 year. Re‐admission for HF was counted if there was a re‐admission in the time period between the initial discharge and the first outpatient visit, which is routinely performed at 6 weeks postsurgery at our institution. To strengthen analysis of follow‐up data, data available for left ventricular (LV) function at 3 and 12 months were compared to the baseline data only from those individuals for whom follow‐up was available.The primary end point was long‐term survival. Deaths were considered to be cardiovascular in the presence of a proximate cardiac cause, any extracardiac vascular cause, procedure‐related death , sudden death, or death of unknown cause. Median survival of the age‐ and sex‐matched general UK population was obtained from the office for national statistics and the Eurostat data from the European Commission  was performed to calculate the probability of allocation to either MV‐repair or MVR. This was used as a propensity score to create homogeneous study groups. For matching algorithm, nearest‐neighbor method with an accepted maximum difference of 10% between matched individuals was applied. Analysis of baseline variables was then repeated to check for balance.All data obtained were retrospectively analyzed. Data are presented as absolute numbers and percentages for categorical variables and as mean values and standard deviation for continuous variables unless stated otherwise. Dichotomous variables were compared by Fisher's exact test and χNo methods were used to account for any possible correlation that may arise between the 2 groups. For survival analyses, Kaplan–Meier calculations were performed and groups were compared on behalf of the Gehan–Breslow–Wilcoxon method to account for early deaths due to the naturally limited life expectancy among this age group and the length of the observational period. Median follow‐up was calculated with the Shemper and Smith method. All statistical analyses were performed by M.S. and reviewed independently by S.C. All computation was carried out using the statistical softwares GraphPad Prism 5.0  and SPSS 19.0 .P=0.03), were more frequently in NYHA class I/II (P=0.01), and were more likely to have pulmonary disease and coronary artery disease . Left ventricular end‐diastolic diameter was significantly higher in MV‐repair . Patients undergoing MV‐repair more often also had a history of prior myocardial infarction (P<0.01) and differed significantly with regard to the underlying valve pathology. They mainly presented with pure MV regurgitation  and the majority had degenerative MV disease  , patients undergoing MV‐repair were significantly younger  and in both cohorts, 96.8% of patients had pure MV regurgitation (P=1.0). Left ventricular end‐diastolic diameter was not significantly different, being 53.7±7.1 mm in MV‐repair and 51.7±6.4 mm in MVR (P=0.21). Moreover, most patients had degenerative MV disease , although other pathologies were still present after matching.After propensity matching n=126), baseline characteristics between the cohorts were balanced, as there were no significant differences measured  and aortic cross‐clamp times (ACC)  were not significantly different between the 2 groups and in the propensity‐matched cohorts with cardiopulmonary bypass times of 97.2±31.2 minutes (MV‐repair) and 115.9±83.2 minutes  and aortic cross‐clamp times of 71.4±24.0 minutes (MV‐repair) and 75.0±22.8 minutes .Cardiopulmonary bypass times ; however, there was no significant difference regarding additional procedures after propensity matching (Table Patients undergoing MV‐repair were more likely to receive concomitant coronary artery bypass graft (CABG) . One of the patients with conversion after attempted repair died on day 2 due to a LV rupture with subsequent pericardial tamponade. Postoperative length of stay was shorter after MV‐repair in the unmatched cohort  but although still shorter, not significantly different after propensity matching . Acute in‐hospital complications were not significantly different, as shown in Table P=0.26), but was significantly lower after MV‐repair in the matched cohorts . In the propensity‐matched cohort, deaths after MV‐repair were due to severe sepsis in 1 patient and hypoxic brain injury after cardiac arrest in a second patient. After MVR, 4 patients died of perioperative congestive heart failure with low cardiac output. One additional patient had a postoperative myocardial infarction with subsequent heart failure. From the remaining 2, 1 patient had multiorgan failure after a pericardial tamponade and another had multiorgan failure after LV rupture with extensive surgical repair. In 1 patient after MVR, cause of death at 30 days was unknown.Conversion of planned MV‐repair to MVR after invasive inspection of the MV occurred in 18.3% of MVR (n=22). MV‐repair was attempted but converted to MVR during 1 cardiopulmonary bypass in 2.5% (n=3), and conversion during a second cardiopulmonary bypass graft but within the index procedure in 0.8% (n=1). Comparison of 30‐day mortality after “unplanned MVR” versus “planned MVR” yielded no significant difference  and did not change after the cohorts were propensity matched .Between discharge from the index procedure to the first outpatient visit at 6 weeks, re‐admission for HF occurred in 7.7% (n=17) after MV‐repair versus 5.0% (n=6) after MVR, which was not significantly different . In the MV‐repair cohort, 80.2% were in NYHA class I/II at 6 weeks, compared to 80.0% in the MVR cohort (P=1.0).Of all survivors, 75.7% (n=237) attended the surgical outpatient clinic 6 weeks after surgery and were questioned with regard to exertional dyspnea. Patients of both cohorts had improved significantly in NYHA class compared to the same individuals at baseline (P<0.01). In patients with degenerative MV pathology, survival at 1 and 5 years was 95.0% and 81.8% (MV‐repair) versus 81.8% and 64.9% . This survival benefit was still seen after propensity matching with 1‐, 2‐, and 5‐year survival of 93.4%, 91.6%, and 76.9% versus 77.2%, 75.2%, and 58.7% (P=0.03). Cause of death was identified in 95.6% of deaths at 30 days (22/23) and 73.8% of deaths at 12 months (31/42). At 12 months, deaths were noncardiovascular in 5.0% in MV‐repair (1/20) and 9.1% in MVR . Comparison to the age‐ and sex‐matched population showed that patients who survived the first year after MV‐repair had similar life expectancy as the general UK population  in the overall cohort, being 5.1 years in MV‐repair (1849 days) and 6.7 years in MVR (2443 days). Long‐term survival of the total cohort was superior after MV‐repair with Kaplan–Meier survival at 1, 2, and 5 years of 90.7%, 89.0%, and 74.2% versus 81.3%, 77.1%, and 61.0% (0 days inP=1.0). However, time to re‐operation was significantly shorter after MV‐repair with 181.8±122.7 and 2544±1445 days, respectively (P<0.01). All patients who had a re‐operation survived the procedures and at least the first 2 years afterwards .During follow‐up, re‐operations for MV dysfunction were performed in 5 cases of the MV‐repair cohort (2.3%) after a mean time of 181.8±122.7 days. In 4 of these patients, the indication was a failure of the repaired MV (1.8%) with recurrent MR: 1 patient presented with MV stenosis attributable to calcific degeneration of the repaired valve. This patient underwent transcatheter valve‐in‐ring implantation and made an uneventful recovery. In the MVR cohort, re‐operation for MV‐dysfunction occurred in 3 cases (2.5%), due to structural deterioration of the implanted tissue valves. Re‐operation rates were not significantly different between the cohorts before and after matching (P=0.13) and matched cohorts (P=0.11). There was 1 patient with suspicious MV endocarditis observed in the MVR cohort (0.8%) after 92 days; this patient was treated successfully with antibiotic medication.Significant MR (moderate/severe) was observed in 15 cases after MV‐repair (6.8%) after a mean time period of 838.1±1063 days; in 4 of these cases, re‐operation was performed as mentioned above. After MVR, significant MR was observed in 3 cases (2.5%) after a mean period of 2087±1964 days. All of these were due to structural valve degeneration and were re‐operated. Rate of significant MR during the observational period was not significantly different in the unmatched (P=0.05) but not significantly different between the propensity‐matched cohorts , with 6.5% of patients (6/92) demonstrating moderate or severe MR. In addition, “mild to moderate” MR was observed in 7.6% of patients (7/92) and “mild” MR in 39.1% (36/92). In contrast, MVR patients presented with moderate or severe MR in 2.9% (1/35), “mild to moderate” in 2.9% (1/35), and “mild” in 17.1% (6/35).Data on severity of MR at 1 year postsurgery were available in 127 cases (47.7% of survivors) and are visualized in Figure S1. Grade of MR at 1 year was significantly different after MV‐repair (Ptrend=1.00 and 0.63), but showed significant improvement in LV function after MV‐repair at 12‐month follow‐up, as the proportion of patients with a normal LV ejection fraction of >50% increased from 50.0% to 76.0% (Ptrend=0.04). After MVR, individuals presented with the same LV function at 12 months compared to baseline (Ptrend=0.78). Left ventricular end‐diastolic diameter at 3 months showed improvement from 56.6±6.5 to 50.4±7.0 mm in MV‐repair (P<0.01) and from 51.0±0.7 to 48.2±8.2 mm in MVR (P=0.03). In patients with 12‐month follow‐up, LV end‐systolic volume index improved from 34.2±14.1 to 29.2±12.7 mL/m2 after MV‐repair  and remained stable after MVR, being 30.2±14.4 mL/m2 at baseline and 27.3±15.2 mL/m2 at 12 months .Data on LV function were available in 148 cases either at 3 or 12 months postsurgery (55.6% of survivors) and are summarized in Figure S2. Direct individual correlation, which included only data of the same individuals at baseline and follow‐up, showed no significant change at 3 months after MV‐repair and MVR, respectively  was not possible, due to missing variables required for assessment, comparisons to published cohorts are made on the basis of single variables. Compared to the cohort of a randomized trial comparing percutaneous MV‐repair with surgery, patients of our cohort less often had concomitant coronary artery disease but were more than 10 years older.P<0.01). Correspondingly, MV‐repair was performed in 87.9% (116/132) in ischemic MV disease compared to 100% (64/64) in the most experienced surgeon (P<0.01). This also emphasizes that patients in whom MV‐repair is seen to be complex should be managed by experienced and specialized surgeons to increase the likelihood of a successful MV‐repair with minimal operative trauma.Age has previously been identified as an independent predictor of MVR..Symptom relief at 6 weeks of follow‐up was equally achieved in both our cohorts as reflected by NYHA class. The rate of re‐admission for heart failure during this period was equally low. We conclude that both procedures are clinically effective in the short term. Unfortunately, long‐term data on valve‐related symptoms were not available for our cohort as patients were not followed up systematically. Nevertheless, a rate of >90% long‐term efficiency of MV‐repair in degenerative disease has been widely reported.In our experience, short‐ and long‐term survival was superior after MV‐repair. The higher 30‐day mortality of MVR patients, also confirmed in the propensity‐matched cohort, is a strong argument to repair the MV even in elderly patients. This is even more impressive as significantly more patients with MV‐repair underwent concomitant coronary artery bypass graft in the unmatched cohort. A higher short‐term mortality after MVR as compared to MV‐repair has been described widely for patients of all age groups,Nevertheless, the burden of MV surgery is better reflected by 6‐month mortality as most deaths occur during the first 6 months.Survival at 5 years in a large retrospective analysis of outcomes after MV surgery was 57%, compared to 74% after MV‐repair in our cohort.In contrast to the belief that the rate of recurrent MR is high in elderly patients with calcified and frail tissue, the rate of significant MR in our cohort was low after MV‐repair at 1‐year follow‐up, but may be underestimated due to incomplete echo data. Although the rate of recurrent MR was higher after MV‐repair, it also did not translate into a higher rate of re‐operation or mortality, as the rate of re‐operation for valve dysfunction during the observational period was identical between the cohorts. The improved survival may be triggered by the significantly improved LV ejection fraction and LV end‐systolic volume index after MV‐repair at 1‐year follow‐up. Furthermore, life with a valve prosthesis may be an additional risk factor for adverse survival in MVR patients. However, the majority of patients in our analysis had degenerative mitral valve pathology. Fundamentally, the etiology of MV disease dictates repair feasibility and success. In a recently published, randomized controlled trial comparing MVR and MV‐repair for ischemic MV disease, there was no difference in the mortality rate between these procedures, but there was a higher incidence of recurrent MR after MV‐repair.™ therapy , which imitates the surgical technique of the Alfieri stitch by building a bridge between the anterior and posterior mitral leaflet. However, recent reports of MitraClip™ therapy observed a rate of recurrent severe MR of around 55% at 12 months,™ therapy, underwent MV surgery later on. In patients who undergo surgical “Alfieri procedures,” the combination of valvuloplasty and annuloplasty is believed to create a durable and successful MV‐repair. The missing component of annuloplasty in MitraClip™ procedures may therefore be one cause of recurrent MR. Moreover, MitraClip™ therapy can complicate future MV‐repair, as valves after failed MitraClip™ procedures are often not repairable, especially if more than one clip has been placed.These findings must be considered when assessing outcomes of interventional treatment options. While transcatheter mitral valve‐in‐valve implantation for failed prostheses or rings in mitral position in high‐risk patients is a promising concept, interventional treatment of the native MV, especially in patients with degenerative MV disease, proves to be more challenging. The most established interventional treatment for native MR is the MitraClipThe MV plays a fundamental role in the structural and functional integrity of the LV. The anterior MV leaflet is believed to act like a rudder during systole, supporting blood flow through the LV outflow tract. The chordae tendineae prevent ventricular dilatation, and discontinuation of this geometry results in progressive LV stress.In an elderly, propensity‐matched patient cohort, survival after MV‐repair is superior to MVR. Moreover, MV‐repair is associated with a low re‐operation rate and recurrent severe MR. This survival benefit may be due to the improvement in LV function seen after MV‐repair over a period of 12 months, while LV function was unchanged after MVR. We therefore conclude that in elderly patients, the same guidelines for choosing operative strategies for treating MV disease should be applied based on the underlying pathology, irrespective of a patients' age. In degenerative MV disease, MV‐repair should be the preferred surgical treatment given the increasing use of interventional techniques to treat mitral regurgitation in this elderly group of patients. The data of this investigation and others should be used as a benchmark for future outcomes of these new techniques.Although propensity matching was performed to account for differences between the study cohorts, a retrospective analysis of results may still be biased, as propensity scores only balance measurable confounders; unmeasured confounders still occur and may bias treatment analyses. Due to the limited number of patients available, patients with different MV pathologies were included for analyses, which may weaken the conclusions made from its results. While 100% completeness of survival data is a strength of our analysis, patients were not followed up systematically and clinical data were available only for a part of the study population as specified in the respective sections of this article. In addition, observation of a patient population over a period of more than 20 years may be biased by improvements in surgical techniques over time, change in population characteristics, and different skills of surgeons. Although we have accounted for time of surgery in a logistic regression analysis, the effect of such a long observational period on outcomes cannot be eliminated completely. Symptoms of patients in the long term could not be assessed.Dr Silaschi's research post is funded through the King's College Hospital Charity.None.Figure S1. Grade of MR 1 year after MV‐repair and MVR (P<0.01). Data were available for 127 patients (47.4% of survivors). MV indicates mitral valve; MVR, mitral valve replacement.Figure S2. Direct correlation of LV function in individuals with available follow‐up. LV indicates left ventricular.Click here for additional data file.


To investigate the MR characteristics of hypertrophic cardiomyopathy (HCM) with restrictive phenotype.19 patients of HCM with obviously restrictive characteristics and 19 typical patients with non obstructive HCM, matched with age and gender, were retrospectively collected. The clinical features, MR morphological characteristics, and the function parameters of the two groups were compared. The paired sample test and Fisher's exact probability method were used for statistical analysis.Patients of HCM with restrictive phenotype have more severe clinical symptoms including sustained artrial fibrillation, pericardial effusion, and worse heart function classifications compared with controls; The left and right atrium diameter were 55.79 ± 5.34 mm and 61.33 ± 11.05 mm on MR, which were significantly greater than the controls (p < 0.001); The segments with late gadolinium enhancement were 7.68 ± 2.98 in patients with restrictive phenotype, which were significantly greater than controls . The left ventricular end-diastolic volume index, the cardiac index, and the left heart ejection fraction of patients with restrictive phenotype were all significantly less than those of the controls.Restrictive phenotype is a special manifestation of HCM. The MR features include mild-to-moderate left ventricular hypertrophy, huge atriums, normal or small ventriculars, pericardial effusion and a wide range of late gadalinum enhancement(LGE). These patients often have severe clinical symptoms and poor prognosis. MRI has important application value in the diagnosis of the disease.


Background: Acute effects of positive airway pressure (PAP)  on functional mitral regurgitation (fMR) in patients with heart failure (HF) with left ventricular (LV) systolic dysfunction remain unclear. Thus, whether PAP therapy reduces fMR in such patients with HF was investigated.Methods and Results: Twenty patients with HF and LV systolic dysfunction defined as LV ejection fraction (LVEF) <50%  with fMR underwent echocardiography during 10-min CPAP (4 and 8 cm H2O) and adaptive servo-ventilation. For fMR assessment, MR jet area fraction, defined as the ratio of MR jet on color Doppler to the left atrial area, was measured. The forward stroke volume (SV) index (fSVI) was calculated from the time-velocity integral, cross-sectional area of the aortic annulus, and body surface area. fMR significantly reduced on CPAP at 8 cm H2O (0.30 ± 0.12) and adaptive servo-ventilation (0.29 ± 0.12), compared with the baseline phase (0.37 ± 0.12) and CPAP at 4 cm H2O (0.34 ± 0.12) (P < 0.001). The fSVI did not change in any of the PAP sessions (P = 0.888). However, significant differences in fSVI responses to PAP were found between sexes , with a significant reduction in fSVI in women (P = 0.041) and between patients with baseline fSVI ≥ and < the median value , with a significant fSVI reduction in patients with high baseline fSVI (P = 0.028). In addition, significant differences were found in fSVI responses to PAP between patients with LV end-systolic volume (LVESV) index ≥ and < the median value , with a significant fSVI increase in patients with a high LVESV index (P = 0.023).Conclusion: In patients with HF, LV systolic dysfunction, and fMR, PAP can alleviate fMR without any overall changes in forward SV. However, MR alleviation due to PAP might be associated with a decrease in forward SV in women with high baseline SV, whereas MR alleviation due to PAP might be accompanied by increased forward SV in patients with a dilated LV. Positive airway pressure (PAP) delivered by face masks has been used in the wide spectrum of heart failure (HF) care , which is a frequent complication known to be associated with worse clinical outcomes  if they met following criteria: (1) men and women aged ≥20 years, (2) HF due to ischemic or non-ischemic cardiomyopathy, (3) LVEF <50% on echocardiography, (4) mild to severe fMR, (5) stable clinical status evidenced by the absence of acute exacerbations of dyspnea, and (6) underwent overnight polysomnography to assess for SDB. The exclusion criteria were (1) patients with shock, (2) those requiring catecholamine and/or inotrope infusion, (3) those requiring mechanical ventilation or supplemental oxygen, (4) those with organic MR, (5) those with moderate to severe aortic regurgitation and/or stenosis, (6) those with a history of chronic lung disease, and (7) those with dialysis.The subjects' characteristics and medications at the time of this study were recorded. The estimated glomerular filtration rate . Left ventricular end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), stroke volume (SV), and LVEF were calculated using Simpson's biplane method. LVEDV, LVESV, and SV were divided by the body surface area and expressed as the LVEDV, LVESV, and SV indexes. The degree of MR was assessed from 0 (none) to 4 (severe) and was based on the MR jet area fraction, which was defined as the ratio of MR jet area to the left atrial (LA) area. Because SV determined using Simpson's method may consist of both forward and MR flows , with the patients awake. After BP and HR were stabilized, the baseline step was started without PAP for 10 min, during which baseline echocardiography was performed. BP and HR were measured twice on the right upper arm in each step, using an automated vital signs monitoring device . Subsequently, CPAP at 4 cm He Figure  were app2), presence or absence of AF, type of predominant SDB, BNP level , right ventricular systolic pressure (RVSP) by echocardiography , baseline LVEDV index , baseline LVESV index , baseline fSVI , and baseline MR degree. The first-order interactions in two-way repeated measures ANOVA models for fMR, forward SV and SVR were examined by entering interaction terms between PAP steps  and the above-mentioned subgroup . If significant step-by-subgroup interactions were found, one-way repeated-measures ANOVA was performed within each subgroup. A P < 0.05 indicated statistical significance. Analyses were performed using SPSS ver. 23.0 .In this study, values are expressed as mean ± standard deviation or median (interquartile range) for continuous variables and numbers (%) for nominal variables. Variations in echocardiography parameters across each step were assessed with one way repeated-measures analysis of variance (ANOVA) and the Tukey test for multiple comparisons. To assess the potential heterogeneity of the effect of PAP on fMR, forward SV index (fSVI), and SVR index, we performed subgroup analyses as exploratory analyses. The subgroups included sex, age , body mass index  and 4–8 cm H2O, although no difference was observed in the reduction of MR jet area fraction between CPAP at 8 cm H2O and ASV. Representative color Doppler images for fMR are shown in Figure 2O. HR significantly decreased in CPAP at 4 cm H2O compared to baseline. However, no significant variations were found in the other parameters, although they tended to increase the diameter of the IVC.As shown in Figure P = 0.454), whereas in women, the fSVI decreased (P = 0.041) as the applied PAP levels increased. In addition, in patients with a low LVESV index, the fSVI tended to decrease (P = 0.071), whereas in those with a high LVESV index, fSVI significantly increased (P = 0.023). In patients with a low fSVI at baseline, fSVI remained stable (P = 0.438), whereas in those with a high fSVI at baseline, fSVI significantly decreased (P = 0.028). In terms of SVR index, although no step-by-subgroup interactions were found between variations of the SVR index and the subgroups of BMI, AF, central-dominant, BNP, baseline RVSP, baseline LVEDV index, baseline LVESV index, and baseline MR degree, a significant difference was found in the variations of the SVR index based on the baseline fSVI (P for interaction = 0.003), and sex and age subgroups tended to have different variations of the SVR index , whereas those with a high fSVI at baseline showed no change in the SVR index (P = 0.204).No interactions were found between each subgroup and variation of MR jet area fraction. On the contrary, although no step-by-subgroup interactions were found between the variation of the fSVI and the subgroups of age, BMI, AF, type of predominant SDB, BNP, baseline RVSP, baseline LVEDV index, and baseline MR degree, significant differences were found in the variations of fSVI based on sex, baseline LVESV index, and baseline fSVI  can result in a significant alleviation of fMR, although no changes were found in the overall fSVI. Despite being results from exploratory analyses, sex, degree of LV dilatation, and degree of baseline forward SV may play some roles in hemodynamic changes that are accompanied by alleviation of fMR in response to PAP therapy.This study has several important findings that provide insight into the alleviation of fMR due to PAP in patients with HF and LV systolic dysfunction. First, the degree of fMR in patients with HF and LV systolic dysfunction was rapidly alleviated by PAP therapy. In addition, fMR revealed a stepwise reduction as the CPAP level increased, but no difference was found between CPAP at 8 cm H2O or bi-level PAP with an EPAP of 5 cm H2O and PS at 10 cm H2O for 30 min each significantly reduced the area of MR, accompanied by an increase in LVEF and a reduction in LVEDV.Two studies have shown the acute effects of PAP on fMR in patients with systolic HF. In one study, Bellone et al.  found th2O, PS of 3–10 cm H2O, and the automated backup mode did not affect the severity of MR despite significant increases in LVEF and SV and significant reductions in LVESV and SVR  by PAP through an increase in intrathoracic pressure leads to decongestion and reductions in LV volume and filling pressure, enhancing LVEF, and SV will occur in patients with highly dilated LV based on the Frank-Starling principle. In most previous studies on the effects of the acute application of PAP on SV, patients with high LV filling pressure and/or enlarged LV had increased SV by application of PAP . However, it is of great interest that ASV with an even lower net applied PAP  showed similar fMR alleviation and fSVI changes to CPAP at 8 cm H2O  in the present study. This may be associated with the stabilization of respiration by ASV, which has sympathoinhibitory effects (Ushijima et al., 2O. Further studies assessing the effects of ASV on fMR and fSVI in consideration of the presence or absence of periodic breathing while being awake are needed to clarify this.A recent study suggested that adding PS favorably affects SV compared with isolated CPAP, possibly through lung inflation and reflex inhibition of sympathetic nerve activity (Yoshida et al., The present study has several limitations. First, the number of enrolled subjects was small. However, the patients' hemodynamic responses to PAP therapy in the present study are basically compatible with the results of previous studies, which indicated that PAP therapy resulted in favorable hemodynamic responses in patients who are thought to have high filling pressure (Bradley et al., 2O and ASV, can alleviate fMR without any overall changes in fSVI in patients with HF, LV systolic dysfunction, and fMR. However, significant differences might be found in the responses of fSVI between sexes, patients with and without dilated LV, and those with and without low baseline SV despite no such differences in the alleviation of MR. These suggest that alleviation of MR due to PAP is not always a good sign and should be interpreted with caution, particularly in patients with HF and a less dilated LV. Although the effectiveness of the long-term application of PAP for the alleviation of fMR and improvement of LV function in these patients remains unclear, patients with dilated LV who have fMR may benefit from CPAP at 8 cm H2O or ASV.In conclusion, PAP therapy, including CPAP at 8 cm HTakaoK: Experimental design, data acquisition, and analysis, drafting of the manuscript, and final approval of the manuscript submitted. TakatoshiK and SY: Experimental design, execution, data acquisition, and analysis, drafting of the manuscript, and final approval of the manuscript submitted. AM, MH, and SM: Experimental design and analysis, drafting of the manuscript, and final approval of the manuscript submitted. HM and NS: Data analysis and drafting of the manuscript, and final approval of the manuscript submitted. MK, FK, and SS: Data analysis, revision of the manuscript, and final approval of the manuscript submitted. HD: Research financing, experimental design, data analysis, revision and final approval of the manuscript submitted.TakatoshiK, SS, HM, NS, MK, and FK are affiliated with a department endowed by Philips Respironics, ResMed, Teijin Home Healthcare, and Fukuda Denshi. HD received manuscript fees, research funds, and scholarship funds from Kirin Co., Ltd., Kaken Pharmaceutical Co., Ltd., Abbott Japan Co., Ltd., Astellas Pharma Inc., Astrazeneca K.K., Bayer Yakuhin, Ltd., Boston Scientific Japan K.K., Bristol-Myers Squibb, Daiichi Sankyo Company, MSD K.K., Pfizer Inc., Philips Respironics, Sanofi K.K., and Takeda Pharmaceutical Co. Ltd. The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


To characterize the temporal alterations in native T1 and extracellular volume (ECV) of remote myocardium after acute myocardial infarction (AMI), and to explore their relation to left ventricular (LV) remodeling.Forty-two patients with AMI successfully treated with primary PCI underwent cardiovascular magnetic resonance after 4–6 days and 3 months. Cine imaging, late gadolinium enhancement, and T1-mapping (MOLLI) was performed at 1.5T. T1 values were measured in the myocardial tissue opposite of the infarct area. Myocardial ECV was calculated from native- and post-contrast T1 values in 35 patients, using a correction for synthetic hematocrit.Native T1 of remote myocardium significantly decreased between baseline and follow-up . High remote native T1 at baseline was independently associated with a high C-reactive protein level  and the presence of microvascular injury . ECV of remote myocardium significantly decreased over time in patients with no LV dilatation . In patients with LV dilatation, remote ECV remained similar over time, and was significantly higher at follow-up compared to patients without LV dilatation .In reperfused first-time AMI patients, native T1 of remote myocardium decreased from baseline to follow-up. ECV of remote myocardium decreased over time in patients with no LV dilatation, but remained elevated at follow-up in those who developed LV dilatation. Findings from this study may add to an increased understanding of the pathophysiological mechanisms of cardiac remodeling after AMI. Following acute myocardial infarction (AMI), the infarcted myocardium undergoes a sequence of pathophysiological changes including myocardial necrosis, myocardial edema, microvascular injury, and subsequent healing with scar tissue formation . There iIn vivo, pathological changes in myocardial tissue composition can be evaluated using cardiovascular magnetic resonance (CMR) imaging. In the past few years, several technological advances have occurred that improved the capability of CMR to characterize the myocardium. Native (i.e. pre-contrast) T1 mapping now permits direct quantification of the absolute T1 relaxation times, and can therefore be used to detect and quantify myocardial edema, without the need for a reference region –6. FurthFindings from recent studies using T1 mapping suggest that tissue changes may also occur in remote myocardium after AMI, and that these changes are associated with adverse cardiac remodeling –12. HoweThe study was conducted in accordance with the Declaration of Helsinki and, approved by the local Medical Ethics Review Committee , and all patients gave written informed consent . PatientA 12-lead ECG was acquired before reperfusion and 1 hour afterwards. Absence of ST-segment resolution (STR) was defined as <30% resolution of ST-segment elevation from before to after reperfusion. Venous blood samples were collected 4 days following hospitalization. For each sample, high sensitive C-reactive protein (CRP) concentration was measured on a Cobas 6000 analyzer (Roche Diagnostics) according to the manufacturer’s instructions, and fibrinogen antigen was measured by enzyme-linked immunosorbent assay (ELISA) using antibodies from Kordia B.V. .CMR was performed on a 1.5T clinical MR system . All patients underwent CMR imaging 4–6 days and 3 months after AMI. Considering that the greatest changes in LV volume, mass and function are observed during the first few months after AMI , and theAll CMR images were analyzed offline using dedicated software . Cine images were manually traced for the measurement of LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV mass, and to calculate LV ejection fraction (LVEF) . MyocardSignificant LV dilatation was defined as an increase in LV end-diastolic volume of ≥15% 3 months after AMI .Analysis of the T1 maps were preceded by examining the eleven raw T1-weighted SSFP images for the presence of off-resonance artifacts, diaphragmatic movement and variation in cardiac phase. Myocardial slices or areas with artifacts were excluded for T1 measures. For T1 measurements, infarct zone was defined as myocardial tissue with hyperenhancement on the LGE images. Remote zone was defined as myocardial tissue opposite of this infarct zone, with no visual evidence of hyper-enhancement. Continuous variables are presented as mean with standard deviation (±) for normally distributed variables, median and interquartile range (IQR) for non-normally distributed variables, and as frequencies and percentages for categorical data. Histograms were used to determine if continuous variables were normally distributed. CRP was log transformed to obtain a normal distribution. Mean values were compared between subgroups of patients using an independent-samples t-test with Welch’s correction when appropriate. Means of baseline and follow-up measurements were compared using a paired t-test. Univariate and multivariate linear regression analyses were used to identify the baseline variables that were associated with dependent variables including remote native T1, and the change in LVESV and LVEDV between baseline and follow-up at 3 months. Variables that were statistically significant in univariate analyses (p<0.05) were subsequently included in a multivariate regression using forward selection. The strict criterion for inclusion in multivariate analysis, being p < 0.05, was chosen in order to adhere to the rule of thumb of at least 10 observations per variable included in the model. All statistical analyses were performed using SPSS statistics . A p value of < 0.05 was considered statistically significant.Forty-two of the 60 AMI patients underwent a complete CMR exam 4–6 days and 3 months after primary PCI. Baseline CMR scanning was not performed in 8 patients due to technical problems (n = 1), claustrophobia (n = 4), obesity (n = 2), and PCI procedure complicated by proximal dissection (n = 1). Additionally, 6 patients refused repeat MRI and another 4 patients had an incomplete CMR exam without T1 mapping. Post-contrast T1 maps were available for 35 subjects. From the 504 T1 maps, 443 (88%) were eligible for analysis. Clinical demographics and procedural characteristics of the 42 AMI patients with complete paired cine, LGE and native T1 mapping images are shown in CMR exams were performed at a mean of 4 ± 1 days and 96 ± 11 days after AMI. In the total cohort of 42 patients, median LGE infarct size at baseline was 16% (IQR: 8–26%), and LGE defined MVI was present in 55% of the patients. The 35 patients with both native- and post-contrast T1 mapping performed and the 8 patients with only native T1 mapping performed had comparable infarct sizes  and similar rates of MVI .At baseline, average native T1 of remote myocardium was 1002 ± 39ms. Three months after the MI, native T1 values of remote myocardium showed a minor but significant decrease to 985 ± 30ms, p<0.01 , suggestNative T1 values of remote myocardium were significantly higher in patients with MVI  and in patients with a large MI size at baseline . Remote Median plasma level of CRP measured 4 days after AMI was 9.7mg/L (5.0–19.1mg/L). CRP levels were significantly correlated with both remote native T1  and remote ECV . These associations remained significant after correcting for the presence of MVI and infarct size . Mean plasma level of fibrinogen measured 4 days after AMI was 4.1±0.9 g/L. Plasma fibrinogen was significantly associated with remote ECV , and showed a trend towards a significant correlation with remote native T1 .Significant LV dilatation occurred in 8 patients (19%). Remote native T1 values, both at baseline and at follow-up, did not significantly differ between patients with and without significant LV dilatation . Further(a) native T1 values of remote myocardium decreased from baseline to 3 months follow-up, most likely reflecting resolution of inflammatory edema, (b) remote native T1 values at baseline were associated with the severity of myocardial damage after AMI and CRP concentration, (c) ECV of remote myocardium did not show a significant change over time in the total group, but values significantly decreased in patients without LV dilatation, and (d) remote ECV values were significantly higher at follow-up in patients who developed LV dilatation.This study aimed to characterize the temporal alterations in native T1 and ECV of remote myocardium after AMI, and to explore their relation to LV remodeling. The main findings of the present study were as follows: In the present study, T1 mapping of remote myocardium was performed 4–6 days and 3 months after AMI. During this period, a slight but significant decrease in remote native T1 was observed. Our findings are consistent with a recent study by Bulluck et al. who have described a reduction in native T1 values of remote myocardium 5 months after STEMI . As natiHowever, data on native T1 and T2 of remote myocardium in patients with AMI have been conflicting. In a study by Carberry et al. , remote In addition to native T1 mapping, we also performed post-contrast T1 mapping to assess for changes in ECV of remote myocardium after AMI. ECV is a measure of the extracellular space of the myocardium and is considered a surrogate marker of fibrosis . BesidesIn agreement with a previous study , remote In the present study, remote native T1 was not significantly associated with changes of LV volumes at 3 months. Our results differ from the study of Carrick et al. , who fouT1 mapping and ECV calculation provide important non-invasive insight into the pathophysiological mechanisms of cardiac remodeling after AM. However, considering the small effect sizes, the conflicting results between studies, and the unresolved technical issues in general, further studies are warranted to determine the clinical relevance of remote T1 and ECV mapping in long-term follow-up.There are some limitations in this study. First, this study is limited by its relatively small sample size, and as a consequence, a lack of significance does not necessarily exclude the existence of an association. We found a statistically significant decrease in remote native T1 over time, and also higher remote ECV at follow-up in patients who developed LV dilation. Second, synthetic ECV, in which the hematocrit is not known but rather calculated from measured native T1 of blood, was used in the present study. As a result, there might be some measurement error of ECV. Nevertheless, Treibel et al. demonstrated that synthetic ECV is highly correlated to conventional ECV, with a similar relationship to histological collagen volume fraction . MoreoveNative T1 of remote myocardium decreased from baseline to 3 months in patients with reperfused first-time AMI, suggesting the resolution of remote edema. ECV of remote myocardium decreased over time in patients with no LV dilatation, but remained elevated at follow-up in those who developed LV dilatation. Findings from this study may add to an increased understanding of the pathophysiological mechanisms of adverse remodeling after AMI, which could help to define therapeutic targets for future studies to prevent adverse remodeling post-AMI.


Atrial electromechanical delay (EMD) is used to predict atrial fibrillation,measured by echocardiography.The aim of this study was to assess atrial EMD and mechanical function afteranthracycline-containing chemotherapy.2of Adriamycin, 2400 mg/m2 ofcyclophosphamide, and 960 mg/m2 of paclitaxel were included inthis retrospective study, as were 42 healthy subjects (47 ± 9 yearsold). Echocardiographic measurements were performed 11 ± 7 months(median 9 months) after treatment with anthracyclines.Fifty-three patients with breast cancer (48 ± 8 years old) whoreceived 240 mg/mLeft intra-atrial EMD  andinter-atrial EMD  wereprolonged; LA passive emptying volume and fraction were decreased (p=0.0001and p=0.0001); LA active emptying volume and fraction were increased(p=0.0001 and p=0.0001); Mitral A velocity  and mitral E-wave deceleration time  were increased; Mitral E/A ratio and mitral Em  were decreased; Mitral Am and mitral E/Em ratio were increased in thepatients.In patients with breast cancer after anthracycline therapy: Leftintra-atrial, inter-atrial electromechanical intervals were prolonged.Diastolic function was impaired. Impaired left ventricular relaxation andleft atrial electrical conduction could be contributing to the developmentof atrial arrhythmias. Left atrial (LA) volume and mechanical function haverecently been identified as a potential indicator of cardiac dysfunction andarrhythmias.3 Intra- and inter-atrialelectromechanical delays are well-known electrophysiological features of the atriumprone to fibrillation.4Echocardiography is a sensitive and reproducible technique for the assessment ofatrial mechanical and electromechanical features.6 Atrialelectromechanical delay had been shown to be prolonged in patients with nonrheumaticparoxysmal atrial fibrillation, obesity, hyperthyroidism, and celiacdisease.10 The pathophysiology and predictors of arrhythmiasafter treatment with AC are poorly defined. The hypothesis of the present study wasthat atrial mechanical and electromechanical features might be affected in patientstreated with AC. Therefore, we aimed to assess atrial mechanical andelectromechanical features in patients after the administration of anthracyclinechemotherapy and to compare them with healthy controls and then to evaluate theirrelationship with parameters of left ventricular function on echocardiography.The anthracyclines (AC), which are a key component of many chemotherapy regimens, areclearly the most cardiotoxic chemotherapeutic agents producing left ventriculardysfunction and arrhythmias.2 ofAdriamycin, 2400 mg/m2 of cyclophosphamide, and 960 mg/m2of paclitaxel at our institution between January 1, 2013 and December 31, 2013.A power analysis was performed before the study. Accordingly, when a referencestudy was considered, 28 subjects (14 in each group) would have resulted in 95%confidence and 90% power. We included 95 subjects (53 patients and 42 controls)in the present study. The power analysis showed that our results, when examinedfor inter-atrial EMD values, reached 95% confidence and 94% power. These womenhad a comprehensive echocardiographic examination before the treatment, whichshowed truly normal LV systolic and diastolic function. The control group wascomprised by 42 age-and sex-matched healthy female office staff. Exclusioncriteria were ischemic heart disease, moderate-to-severe valvular heart disease,heart failure, hypertension, diabetes mellitus, obesity, systolic and/ordiastolic dysfunction, atrial fibrillation, bundle branch block,atrioventricular conduction abnormalities on electrocardiogram, acute or chronicrenal failure, collagen tissue disease, thyroid dysfunction, electrolyteimbalance, pulmonary disease, anemia, chronic liver disease, prior history ofradiation therapy, life expectancy< 1 year, and insufficientechocardiographic imaging. None of the participants were taking anyantiarrhythmics, tricyclic antidepressants, antihistaminics,angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, andantipsychotics. Heart rate, blood pressure, and routine biochemistry weremeasured in all participants. Exercise tolerance test to exclude ischemic heartdisease was performed in all subjects. A total of 750 women with breast cancerwere examined as to their eligibility for our study.The study design was retrospective. Fifty-three women with breast cancer wereselected from consecutive patients who received 240 mg/mThe institution's Medical Ethics Review Committee approved the study protocol. Informedconsent was obtained from all participants. The study protocol conforms to theethical guidelines of the 1975 Declaration of Helsinki.10 All volumes were indexed to BSA and expressed inml/m2. Atrial electromechanical coupling (PA) was defined as thetime interval from the onset of the P wave on surface electrocardiogram to thebeginning of the late diastolic wave (Am wave). PA was obtained from the lateralmitral annulus , septal mitral annulus (PA septum), and rightventricular tricuspid annulus (PA tricuspid) . Allparticipants were examined in the left lateral decubitus position by 2-D,M-mode, pulsed and color flow Doppler, and tissue Doppler echocardiography.Continuous 1-lead ECG recording was performed during the examination. LVejection fraction was obtained from two- or apical four-chamber views throughthe modified Simpson method. To obtain maximum filling velocities, thepulsed-Doppler sampling volume was placed between the tips of the mitral valveleaflets in the apical four-chamberview. Myocardial velocity profiles of thelateral and septal mitral annuli were obtained. Tissue Doppler measurements wereobtained by placing the sample volume at the junction of the mitral annulus andthe septum, and lateral wall. All measurements were recorded as an average of 3cardiac cycles. Left atrial volumes (LA V) were obtained from apicalfour-chamber view through the discs method and indexed for body surface area(BSA). LA V measurements were performed at the mitral valve opening , the onset of atrial systole , and themitral valve closure  -C. The ficuspid) -C. ValueOne experienced operator blinded to clinical and laboratory characteristics ofthe participants analyzed all echocardiographic data. Intraobserver variabilitywas assessed in 30 selected subjects randomly from the both groups by repeatingthe measurements. Measurements were repeated 1 week apart. Only one readerconducted this analysis. The reader was allowed to select the best measurementeach time and was blinded to previous measurements. Intraobserver variabilitywas calculated as the difference between two measurements of the same patient bya single cardiologist divided by the mean value.Categorical variables are expressed as percentages and continuous variables asmean ± standard deviation and median with minimum-maximum values.Continuous variables were compared between groups using independent t tests  or a Mann-Whitney U test . Categorical data were compared with the chi-square test.A multiple linear regression analysis was used to identify independentpredictors of LA mechanical function impairment and electromechanical delays. Pvalues < 0.05 were considered to indicate statistical significance. Allanalyses were performed using SPSS version 15.0 .Clinical and echocardiographic findings of the patients  and controls  are listed in LA volume measurements of the study subjects are presented in The atrial electromechanical coupling intervals measured from different sites areshown in Among patients, the body mass index, diastolic blood pressure, mitral Edeceleration time were independent predictors for LAPEF. The systolic bloodpressure, diastolic blood pressure, mitral E deceleration time were independentpredictors for LAAEV. Among controls, age, mitral E/A ratio were independentpredictors for LAAEF .Table 4Multiple linear regression analysis of subject characteristicsinfluencing LA mechanical function impairmentIntra-observer variability was less than 5% for all echocardiographicmeasurements.The present study showed that left intra-atrial and inter-atrial EM intervals wereprolonged; LV diastolic function was impaired in patients with breast cancer treatedwith AC, despite preservation of LA mechanical functions.11 There are alimited number of studies investigating diastolic function in patients treated withAC. There is no consensus regarding whether diastolic function is impaired in thosepatients.This study suggests that proarrhythmogenic mechanisms could be the result of changesin cardiac function, including LV diastolic dysfunction and delayed electricalconduction, which create an arrhythmogenic substrate. This arrhythmogenic substrateleads to a decrease in intracardiac conduction and to a heterogeneous dispersion ofrepolarization, two effects that facilitate the genesis of cardiac arrhythmias inthose patients. This study also showed that diastolic function parameters weresignificantly impaired in the patients. We were not able to demonstrate systolicdysfunction in our patients because we could not perform global strain evaluation.The most common cardiotoxicity of AC is left ventricular systolic dysfunction withpossible arrhythmias. Studies examining the occurrence of arrhythmia in patientstreated with AC are scarce. Atrial fibrillation appears to be a rather commoncomplication of AC and in one study, it was described in 2-10% of thepatients.12 LA mechanical functionis an important determinant of LV filling, especially in patients with end-stagesystolic or diastolic ventricular dysfunction.12 It consists of reservoir, conduit, and booster pumpfunctions. In previous studies, it was demonstrated that LA mechanical functionswere impaired in patients with hypertension, chronic obstructive lung disease, andtype 1 diabetes mellitus.14 In addition, LA volume has been shown to be a powerfulprognostic variable in a variety of cardiac disease states. Compared with APdiameter, LA volume has a stronger association with outcomes in cardiacpatients.15 Left atrialtotal emptying fraction was reported to be an independent and strong predictor forthe development of AF.10In this study, patients with breast cancer after AC did not display any significantchange in total LA emptying, despite the fact that we showed that LA active emptyingvolume and LA active emptying fraction were increased in those patients. This maysuggest preservation of atrial mechanical function early in the course of breastcancer survivors treated with AC. Yet it is possible to consider that the decreasein LA passive emptying volume is related to elevated end-diastolic LV pressure atleast due to LV diastolic dysfunction. The shift in early and late diastolicventricular filling might have occurred secondary to impaired relaxation. LAmechanical function plays a significant role to maintain cardiac output in patientswith DD.18 Therefore, the impaired conduction observed in the presentstudy could be associated with an increased risk of AF.The present study revealed that left intra- and interatrial EMD were significantlyprolonged in the patients. Only mitral E/A ratio was weakly associated with LA EMD.Increased EM delay was found to assist in the identification of subjects atincreased risk of AF. Atrial conduction time reflects both electrical and structuralatrial remodeling. Atrial EMD has been reported to be associated with low-gradeinflammation, insulin resistance, LA enlargement, early LV diastolic dysfunction,and oxidative stress.19 Prolonged EM intervals may alsoindicate atrial remodeling during arrythmogenic process and may be a predictor ofAF.20 Autonomic nervous system may play a role in thedevelopment of atrial fibrillation by its effects on atrial conduction time(heterogeneity).22 Studies looking at atrial functionin patients treated with cardiotoxic chemotherapy are limited. Our results areconsistent with a previous study by Ceyhan et al., which reported that intra- andinter-atrial conductions were delayed in patients treated with5-florouracil.23The prolonged EM intervals observed in this study could be explained byanthracycline-induced oxidative stress, which has been associated with autonomicdysfunction.The results of our multiple linear regression analysis are inconclusive due to low R²values. They may suggest that risk factors for diastolic dysfunction such as bloodpressure, BMI, age, and diastolic dysfunction itself may play role in LA mechanicalfunction impairment.These alterations may be an early form of subclinical cardiac involvement inbreast cancer survivors treated with AC and with no cardiovascular risk factors.We can speculate that these patients may be at a higher risk to develop new orrecurrent atrial arrhythmias particularly atrial fibrillation. Monitoring couldbe prudent in those patients to guide additional interventions such asanti-arrhythmic and/or anti-coagulant therapy. This could lead to a betterclinical management and improved patient outcome.2 smaller than apical two-chamber volumes.15 However, we used the sametechnique for both patients and controls. We excluded patients withcardiovascular risk factors that can create an arrhythmogenic substrate. Wecannot rule out systolic dysfunction, as we could not study global strain.Further research is needed to define a true incidence and clinical relevance ofatrial arrhythmias in those patients and to determine the role of Holtermonitoring for the early diagnosis, intervention and surveillance of thosepatients more susceptible to develop arrhythmia.In this study, patients also received cyclophosphamide and paclitaxelsimultaneously, which makes it difficult to decide which one caused theseadverse effects. Pretreatment evaluation with comprehensive echocardiographyincluding assessment of atrial mechanical and electromechanical features had notbeen done. However, the patients were selected among the ones who had trulynormal LV systolic and diastolic function on the baseline studies. Thesealterations might have been attributed incorrectly to the adverse effects ofchemotherapeutic agents. LA volume should be measured using the disk summationalgorithm in both the apical four- and two- chamber views. We had measured themfrom a single-plane apical four-chamber approach, which is typically 1 to 2mL/mOur study revealed that left intra- and inter-atrial EM were prolonged and that LVdiastolic function was impaired in breast cancer survivors treated with AC. Impairedelectrical conduction in those patients may be associated with the development ofarrhythmias.


Peak systolic myocardial stress was proposed as a stimulus for both adaptive and maladaptive left ventricular (LV) hypertrophy in hypertrophic cardiomyopathy (HCM). We aimed to map segmental myocardial stress and hypertrophy patterns in HCM and correlate them with indices of segmental contractile function.es/ASed), wherein ASed and ASes are end-diastolic and -systolic surface areas, respectively; and (6) stress-corrected AS (Sc-AS), expressed as ratio of AS and AS_predicted, the latter based on a regression equation derived from the normal subjects (AS_predicted = 0.445+3.329/WS). All segments in HCM patients were stratified into two groups: Group 1 with lower-than-normal myocardial stress  and excess hypertrophy ; Group 2 comprising all other segments. All segments from healthy subjects were considered normal reference.Cine cardiac magnetic resonance (CMR)  were performed in 19 HCM and 9 normal healthy subjects, from which 3D LV geometric models  were reconstructed. For each segment, the following were determined: (1) wall thickness (h); (2) curvature radius (r), automatically using in-house customized computer algorithm; (3) regional ejection fraction (EF); (4) end-systolic myocardial stress (WS), 0.9 × SBP × r/[2 h × (1+h/2r)], wherein SBP is systolic blood pressure; (5) area strain (AS) , ln(ASTable Lower-than-normal myocardial stress and excess hypertrophy is associated with worse segmental ventricular contractile performance.


We sought to determine if there were T1 abnormalities in remote regions (no LGE positive areas) in patients with prior myocardial infarction.Global left ventricular (LV) remodeling after myocardial infarction frequently occurs. Late Gadolinium Enhancement (LGE) CMR allows imaging of focal myocardial scar with areas remote from scar having no hyperenhancement. Myocardial T1 mapping using the slice interleaved T1 sequence in 5 short axis-slices . The sequence was acquired in a free-breathing ECG-triggered slice-selective bSSFP. T1 mapping of each scan was estimated by voxel-wise curve fitting using a 2-paramter fit model. All images were corrected for in-plane motion between different T1 weighted scans. Native myocardial T1 in healthy subjects were measured over the three mid-ventricular slices by manually drawing epicardial and endocardial contours. The native T1 times of the remote myocardium of the CAD patients were measured by manually drawing a region of interest (ROI) on the three mid-ventricular slices and excluding the infarct area. An unpaired-samples T-test analysis was used to test for statistically significant differences between the two groups.In a prospective IRB-approved study, 12 patients with a history of coronary artery disease (CAD) and chronic myocardial infarction  and 10 healthy subjects  were recruited to undergo CMR scans. All subjects were in sinus rhythm during CMR study. We assessed native T1 time in the remote area myocardium of the CAD patients was significantly higher than the native T1 value of the myocardium in the healthy group  (Figure Patient characteristics are summarized in Table 1 times in CAD patients with prior myocardial infarction. Further studies are needed to assess the prognostic value of an abnormal native T1 in the remote region among CAD patients.Our data suggest there are diffuse changes in remote/normal myocardium resulting in abnormal/higher native T


T1 quantification enables measurements of myocardial extracellular volume . The purThe T1 & T2 mapping modules were implemented in Segment  and suppThe proposed modules generated relaxation time maps from two free-breathing, single-shot bSSFP sequences. Saturation-Recovery (SR) and T2-preparation prepulses were used to create T1 & T2 weighting. Apart from T2-prepared images, a saturation prepared image was used in the T2 estimates, as previously proposed . In addiT1 and T2 reference values ranged from 214-1690 ms and 46-190 ms, respectively. Figure A T1 & T2 mapping software was developed and evaluated. Low bias and variability was found for the T1-SR sequence. The increased variability of MOLLI compared to the SR sequence may be explained by the reduced number of sampling points used in MOLLI and an increasing T1 error for low T2 values. The increased variability of the T2-prepared sequence may be explained by limited SNR.


The MitraClip system is a device for percutaneous edge-to-edge reconstruction of the mitral valve in patients with severe mitral regurgitation who are deemed at high risk for surgery. Studies have underlined the therapeutic benefit of the MitraClip system for patients at extreme and high risk for mitral valve surgery, suffering from either degenerative or functional mitral regurgitation. The MitraClip procedure shows low peri-procedural complication rates, and a significant reduction in mitral regurgitation, as well as an improvement in functional capacity and most importantly quality of life. It hereby widens the spectrum of mitral valve repair for the Heart Team. The current review underscores the efficacy of the procedure and describes the technique to simplify the procedure. The MitraClip  is a catheter-based technology that is similar to the Alfieri technique in that it connects the middle scallops of the anterior and the posterior leaflet of a regurgitant mitral valve. The data of the EVEREST  trials , 2 and rA large prospective, nonrandomised European study, ACCESS-EU  found 81.8% survival at 1 year and 78.9% freedom from severe mitral regurgitation (MR) . Data frSeveral ongoing trials will help clarify the role of MitraClip therapy in the treatment of functional MR. The COAPT trial , a prospective, randomised, parallel controlled study, is currently enrolling patients with severe functional MR and heart failure (left ventricular ejection fraction 20–50%). A similar study, the RESHAPE-HF trial , is enrolling patients with severe functional MR and a left ventricular ejection fraction of 15–40%, deemed non-surgical candidates who will be randomised to MitraClip therapy versus medical management.In this review we describe the technical aspects of the MitraClip procedure.Planning for the clip procedure requires definition of the mitral valve morphology and the specific pathology causing regurgitation. The depth/distance to the coaptation point of valve leaflets is crucial to determine the appropriate clip-landing site, but valve pathophysiology dictates the ideal transseptal puncture point .To guarantee safe positioning of the clip, anatomical eligibility criteria are recommended. A coaptation length of >2 mm, a coaptation depth of <11 mm, and in the case of degenerative disease, a flail gap of <10 mm and a flail width of <15 mm are favourable . The MitThe mitral valve morphology and the cause of MR should be assessed in detail by transoesophageal echocardiography (TEE), as suitable mitral valve morphology is essential to a successful MitraClip procedure. Transthoracic echocardiography is used to assess MR severity, but TEE is also useful to confirm the initial TTE findings .Characterisation of valve pathology is important for pre-procedural planning. Degenerative valves causing significant MR often have substantial portions of the leaflet that are either flail or prolapsed. Patients with a flail or prolapse distance greater than 1 cm width along the line of coaptation or greater than 1 cm into the left atrium do not meet the criteria for clip procedure and are likely to have poor procedural success .Assessment of the subvalvular apparatus and chordae is also important since the extended arms of the clip are easily entangled within these structures. Short chordae or unusual angles of chordae usually portend trouble and warrant careful avoidance when possible , 11.Two- and three-dimensional (2D/3D) TEE is used for guidance during the MitraClip procedure. Three-dimensional TEE provides en face views of the mitral valve, thus facilitating the assessment of mitral valve morphology and pathology, which is important for patient selection. Delivery catheters, wires, devices, and target structures can be visualised in one single view and in relation to each other, thus optimising transseptal puncture, steering of the delivery catheter in a 3D space (left atrium) towards the mitral valve and good MitraClip positioning perpendicular to the line of coaptation in the middle segments of the mitral valve.Biner et al.  demonstrThe MitraClip procedure is divided into the following steps: 1) Transseptal puncture; 2) Advancement of the steerable guide catheter into the left atrium; 3) Advancement of the clip delivery system into the left atrium and positioning of the MitraClip below the mitral valve leaflets; and 4) Grasping of the leaflets, assessment of the result and clip release.Transseptal puncture represents one of the most important aspects of the MitraClip procedure. The optimal puncture site is located superiorly and posteriorly in the interatrial septum and three TEE planes are used to determine the correct site: a short-axis view at the base for anterior-posterior orientation, a bi-caval view for superior -caudal (inferior) orientation, and a four-chamber view to direct the height above the mitral valve. The position of the BRK transseptal needle  can be seen by a tent-like indentation of the interatrial septum (‘tenting’). Thereby, the tip of the ‘tent’ points towards the left atrium. With a satisfactory posterior and superior location, the height above the valve is assessed in a four-chamber view Fig. . The sitThe steerable guide catheter with the dilator is gently advanced into the left atrium over an Amplatz extra stiff wire (placed in the left upper pulmonary vein) under fluoroscopic and TEE guidance. The dilator can be easily identified by a cone-shaped tip and a typical echogenic appearance of ridges on the catheter system. A radiopaque echo bright double ring characterises the tip of the guide catheter. The advancement of the steerable guide catheter should be carefully visualised under continuous 2D/3D TEE, and fluoroscopic monitoring to avoid injuries of the free left atrial wall. Once the catheter is safely placed in the left atrium, the Amplatz extra stiff wire is retrieved first, followed by the dilator.The clip delivery system is advanced via the steerable guide catheter under fluoroscopic guidance directed toward the left upper pulmonary vein. TEE is additionally necessary to ensure that the tip of the steerable guide catheter remains across the interatrial septum and that the delivery system with the clip at the tip does not cause injury to the free left atrial wall.As the clip delivery system carefully exits the sheath it is required that the markers in the system straddle the sheath markers before the clip can be moved toward the mitral valve Fig. .Fig. 3StTo position the clip delivery system above the mitral valve, a posterior torque of the steerable guide catheter and simultaneous medial deflection of the clip delivery system accompanied by retraction of the whole system are required. These steps are done in our centre under complete fluoroscopic guidance. After bypassing the pulmonary ridge and the left atrial appendage, a gentle anterior rotation of the clip delivery system accompanied with a simple lateral rotation brings the clip above the mitral valve. The aim of this manoeuver is to direct the clip in a horizontal direction as seen in the postero-anterior view fluoroscopically.Medial-lateral clip adjustments are monitored in 3D en face view and anterior-posterior adjustments in an orthogonal mid-oesophageal long-axis (LVOT) view. To achieve good clip alignment, both arms of the opened clip can be visualised in full length in the long-axis view. The tip of the clip should be directed towards the largest proximal isovelocity surface area (PISA). A single 3D en face view allows to determine when the clip is adequately positioned above the middle segments of the mitral valve and whether orientation is perpendicular to the line of mitral valve coaptation Fig. .Fig. 43DIn the routine practice, it is recommended to pass the opened clip into the left ventricle . In our A correct orientation of the MitraClip, with perpendicular alignment to the line of coaptation, verifying that both mitral leaflets are freely moving above the clip arms, is crucial for a successful grasp of the mitral valve leaflets. To shorten the time of the procedure, we depend on the orientation of the clip above the mitral valve using 3D-TEE Fig.  comparinOnce the MitraClip is in a satisfactory position, grasping of the leaflets as they are captured in between the clip arms and the gripper is usually monitored using a 2D LVOT view. It is recommended to do this with the help of a short breath-hold, controlled by the accompanying anaesthetist. Multiple planes are useful for assessment of proper leaflet insertion into the MitraClip. The insertion of the posterior leaflet is commonly best seen in the LVOT view, and the insertion of the anterior leaflet in the four-chamber view. The intercommissural view can add information such as entrapped chordae tendinae.After grasping of the leaflets, leaflet capture is evaluated by lowering the gripper and partially closing the clip to secure leaflet insertion Fig. . FormatiBefore and after the implantation of each clip, it is necessary to evaluate the grade of regurgitation and stenosis of the mitral valve, and in addition, the morphological result after clip placement .Residual MR can easily be detected by colour Doppler. However, for quantification, it has to be taken into consideration that the area of colour jets is larger with multiple jets, which commonly occurs after a MitraClip is implanted (due to the addition of multiple jet areas), than if there is a single jet . This maOur group has already proven that an optimal correction of MR after MitraClip placement should be advocated to optimise the benefits of the procedure and minimise the risk of adverse outcomes. As residual MR after MitraClip is associated with higher mortality than that for patients without MR .The orientation of the second clip is mostly done fluoroscopically without the use of echocardiography and should be aligned as parallel as possible to the first clip.During advancement of the MitraClip from the left atrium into the left ventricle under breath-holding, the clip should be closed to avoid any interference or entanglement with the chordae tendineae then re-opened in the left ventricle. Folding of leaflet tissue between two MitraClips should be avoided as this may cause uncorrectable residual MR .The MitraClip procedure is rapidly evolving as an important option among the current therapies for MR. The safety profile of this device appears to be good and data from experienced centres have shown that reduction of the severity of MR is achievable in almost all patients with low in-hospital complications and significant clinical improvement. Our simplified step-by-step approach helps us a lot.Patients with moderate to severe or severe MR and suitable anatomical characteristics must be properly defined to ensure optimal clinical outcomes. In addition, TEE plays the major role in guidance of the procedure and in follow-up.New technologies that synchronise echocardiographic and fluoroscopic imaging could potentially simplify and optimise procedural guidance, improve the degree of MR reduction, and enhance safety as well as shorten the duration of both fluoroscopy and the procedure time.


We assessed the CT attenuation density of the pulmonary tissue adjacent to the heart in patients with acute non-ST segment elevation myocardial infarction   Specifications TableValue of the data•The data can be used to evaluate inter-observer variability of semi-automated assessment of lung water assessed on cardiac computed tomography data sets.•This data can be used to evaluate the relation between subjective assessment of ground-glass opacification and pulmonary attenuation density.•These data on high attenuation density volume in patients with myocardial infarction can be used in further studies to compare values with other cohorts.1The visual severity of three levels of ground-glass opacification (GGO) is related to pulmonary attenuation densities. Further the interobserver variability of these automated measurements are presented.1.1Automated segmentation of the lungs was performed by two independent observers in 53 patients; 27 with left ventricular ejection fraction ≥45% and 26 patients with left ventricular ejection fraction <45%. No significant difference between observers was found in the measurement of pulmonary attenuation density: mean difference 4 HU (95% CI of −31 to 39 HU). Also no significant difference was found between observers in the measurement of high density ratio (Mean difference of 0.5% with a 95% CI of −2 to 3). Bland–Altman plot of pulmonary attenuation densities and high attenuation volumes are given in 1.2CT data sets from 367 patients with acute non-ST segment elevation myocardial infarction were analysed. No GGO was present in 292 patients mild-moderate GGO was found in 65 patients, and severe GGO in 10 patients. This categorization correlated with increasing mean pulmonary attenuation density and mean high pulmonary density ratio A and B.2Coronary computed tomography angiography data sets were acquired before invasive treatment from 367 patients with acute non-ST-segment elevation myocardial infarction high pulmonary density volume and the high pulmonary density ratio was assessed as: high pulmonary density volume / total measured lung tissue volume, in %.The pulmonary attenuation density and the high pulmonary density ratio was obtained using pulmonary densitometry in the following way: Full view images in 3 mm slice thickness were loaded into the workstation  using the pulmonary density analysis tool, which automatically traced the part of the left and right lung within the scan field A. VoxelsComparison between groups of subjective levels of GGO was tested using one way ANOVA. Interobserver variability in the assessment of lung water was evaluated using the Bland–Altman method


Understanding cardiac mechanics is important for developing cardiac therapies. Current modalities for assessing cardiac mechanics sample patient’s heart at specific heart rate, contractility, preload, and afterload. The objective of this study was to test the feasibility of a novel system composed of intra-cardiac leads equipped with an inertial module chip (3D accelerometers and 3D gyroscopes) in monitoring continuous heart motion.In this descriptive study, four healthy pigs were anesthetized and instrumented with motion-sensitive intra-cardiac leads; the temporal correlation between signals from motion sensors and tissue Doppler from the chest wall were studied; changes in real-time heart accelerations (ACC) and angular velocity (ANGV) were reported as percentages of change from baseline.p = 0.125 for all changes expressed in percent). Temporal correlation between the ANGV signal and tissue Doppler signal was detected throughout all interventions.Heart motion signals were sensed continuously from the right ventricular apex (RVa) and coronary sinus (CS). Volume expansion did not produce significant changes in the ACC and ANGV signals. Increasing heart rate increased the peak systolic ACC signal recorded from RVa and CS by 94 and 76%, respectively, and increased both peak systolic (61% RVa and 27% CS) and diastolic ANGV (200% CS vs. 31% RVa). Epinephrine administration increased peak systolic ACC signals at both sites . Peak systolic and diastolic ANGV increased in response to epinephrine  (A novel system for continuously monitoring heart motion signals from within the heart was presented. Heart motion signals in response to physiologic manipulations were characterized. Understanding cardiac mechanics is crucial for planning novel therapeutic devices. Unfolding the mechanics of the heart is an ongoing process, with new technologies providing important insights . PressurWe hypothesized that a novel system of leads that continuously monitors heart motion from inside the heart will provide valuable physiologic information that is unattainable with current methods. In this work, we describe the feasibility of our technology in measuring continuous heart motion signals in a healthy porcine model. The complex beat-to-beat real-time cardiac motion is described as viewed from the right ventricular apex (RVa) and coronary sinus (CS), and is correlated with standard tissue Doppler (tD) signals.The motion of cardiac walls was assessed by motion sensors , we established the experimental model and tested the sensing and recording systems. In four pigs, the full system was tested using the same protocol. We report the results for these four pigs.The study was approved by the Institutional Animal Research committee at the Technion and all experimental procedures were performed in accordance with the guidelines for the utilization and care of animals used in research. Domestic pigs weighing 56–62 kg were anesthetized with isoflurane (2%), intubated and mechanically ventilated using room air. We studied 11 pigs. In the first pigs . Standard limb ECG was recorded throughout the study. Urine output was monitored using a urinary catheter. Figure All echocardiographic examinations were performed using a Vivid i machine . A complete comprehensive transthoracic echocardiographic and Doppler screening examination was performed to verify normal structure and function of the heart. During the study, we recorded tD images simultaneous with heart motion and hemodynamic signals.Control of sensors, data acquisition, and real-time settings (related to the process of data acquisition) were obtained using a PC that controlled a DAQ board . Signals were stored and analysis was performed off-line. A mutual time-line was documented for all devices and signals.After the animals were prepared and instrumented, three interventions were performed to characterize motion signals of the heart. Baseline measurements were determined. Then, the effect of rapid volume loading was studied by administering 1 L of normal saline 0.9% through the left jugular introducer within 10 min. The second intervention investigated the effect of different heart rates using RA pacing at an initial rate of 10 bpm above the animals’ baseline intrinsic HR. Pulse width was 1–1.5 ms and peak amplitude 6–8 V. Pulse width and amplitude were set so as to securely induce pacing. The pacing rate was increased by 10 bpm every 2 min to a maximal HR of 130 bpm.Third, the effects of epinephrine on both contractility and heart rate were studied by intravenously administering boluses of 0.01, 0.015, and 0.02 mg of epinephrine. Second and third boluses of epinephrine were administered after HR resumed the pre-injection rate. Ten-minute intervention-free intervals separated consecutive interventions. Reference hemodynamic, echocardiographic and cardiac motion signals were simultaneously recorded during interventions.C denotes the magnitude of the composite signal of X, Y, and Z, which are the signals recorded in each of the axes, and i denotes the time index. Ci represents ACC or ANGV. Recording Ci was defined as a sufficient goal, providing the magnitude of rotation in each of the twist–untwist directions. Recording and considering each of the axes of the ACC and ANGV signals would lead to dependence on the exact location and positioning of the lead. A change in the latter may result in a change in the signal. But calculating the composite lead, Ci, overcomes this variability.All signals were stored in a format accessible by MATLAB . Analysis was performed using proprietary software. Heart motion signals (3 axes of ACC and 3 axes of ANGV from 2 sensors) were recorded separately. The composite signals presented throughout this work are p value <0.05 was considered statistically significant.This study was a proof of concept and a feasibility study. To present trends of interventions, we calculated the mean (±STD) of baseline and last measurements for all animals in each of the interventions. Differences between mean baseline values (before intervention) and mean final measurement values (end of intervention) are presented in absolute and percent values. To test for significance of differences, we applied the Wilcoxon sign rank test. For all analyses performed, a Standard hemodynamic and heart motion signals were recorded simultaneously and showed normal physiology for the four animals: after the QRS complex, LV pressure increased to the point where the aortic valve opened and LV and aortic pressures equilibrated Fig. , arrow. All four animals were administered normal saline as described in the “p = 0.125) . Increasing heart rate with pacing increased peak-to-peak STOS recorded from RVa and CS by 94 and 76%, respectively p = 0.25 . Importantly, the most prominent increases in peak-to-peak STOS recorded from RVa and CS were observed after the first dose of epinephrine (0.01 mg). Further increases in heart motion were relatively smaller. Peak-to-peak STOS recorded from CS leveled to a plateau at epinephrine boluses greater than 0.015 mg. Peak systolic ANGV recorded from RVa and CS increased in response to epinephrine administration . The effect of epinephrine administration on peak diastolic ANGV at CS was greater than that recorded from RVa .All heart motion signals increased in response to epinephrine administration Fig. . Peak-toVariability in the intensity of motion was observed between animals and between sites of measurement. When heart motion signals were highly intensified in response to epinephrine as recorded from RVa, the signals recorded from CS were of lower magnitude, and vice versa. Two animals Nos. 9, 11) exhibited a greater peak-to-peak STOS response to epinephrine as recorded from RVa , whereas the opposite response was discerned from the CS lead  and ANGV signals are novel and their full significance is yet to be investigated. However, during all studies in all animals, the temporal correlation between these motion signals and the standard tD signal recorded from the animal body surface was preserved. Specifically, ANGV signals during systole occurred at the same time as the s′ tD signal. During diastole, ANGV components occurred with e′, and a′ tD signal Fig. . Though The goal of this study was to test, on a healthy porcine model, the feasibility of a novel system for continuously measuring heart motion signals. The motion signals, ACC and ANGV, recorded from sensors, were reproducible throughout heart cycles and three physiologic manipulations. STOS reflects systolic wall tension build up in the cardiac muscle, whereas ANGV reflects systolic and diastolic velocities of twisting–untwisting motions, respectively. A signal similar to STOS, PEA, was presented by Sorin   and was ANGV signals are obtained from speckle tracking echocardiography and MRI –7. Howevvolume loading  did not produce STOS and ANGV signals that were different from baseline; therefore, conclusions may not be drawn. The volume overloading protocol that we used was insufficient to induce a significant STOS and ANGV response [p < 0.05) [Rapid response . Hyler e < 0.05) . Grymyr pacing, STOS and ANGV signals recorded from the RVa were on average greater than those recorded from the CS. This finding is hypothesized to be related to three observations: (1) the twisting trajectory taken by the RVa sensor (positioned on a lead near the cardiac apex) is larger than that by the CS sensor (positioned near the cardiac base). Previous studies showed that the rotation of the apex of the heart is greater than that of the cardiac base [During vations:  the twisDuring epinephrine administration both the RVa and CS sensors responded similarly. The initial epinephrine bolus of 0.01 mg produced a prominent effect on STOS and ANGV, and subsequent higher doses had smaller incremental effects. The boluses of epinephrine used in this study forced the cardiac apex (RVa) and base (CS) to reach their maximum ability to rotate. These observations demonstrate that our system has the potential of assessing the maximal effect of an intervention on heart motion. This effect can be detected from the “Starling-like” curves such as shown in Figs. This study also shows that systolic twisting and diastolic untwisting, as reflected by ANGV, may occur mainly by the apex or by the base. Our system is able to distinguish between a mainly apical or basal twist–untwist response to epinephrine.In this work, the temporal correlation between the ANGV signals and the standard tD echocardiography was demonstrated. This correlation is predicted as both modalities sense myocardial tissue motion.mechanical synchronization between LA and LV, a mechanical event (not an electric event), i.e. ANGV signal, is proposed to be more appropriate for this purpose. Presently, the event of optimal LA emptying as the ideal timing for LV stimulation is determined using two components: (a) P wave detection and (b) a preset fixed time interval from the P wave [The novel system presented describes systolic and diastolic heart motion signals which reflect mechanical events of the heart cycle. As one of the goals of cardiac resynchronization therapy (CRT) is to optimize the e P wave . Severale P wave . TherefoA significant limitation of this study was the small number of animals studied, restricting our conclusions to a level of trends. Nevertheless, we showed detectable physiological signals of mechanical movement of the heart that was reproducible and showed a tendency that reflects a novel and unique real-time record of heart movements. The ANGV and ACC signals studied were composite signals that characterize the amplitude and not the direction of motion. Signals occurred reproducibly relative to hemodynamic signals, ECG and tD, but they differed from animal to animal. For a given animal, signals remained the same throughout the study. In addition, the indices used to characterize STOS and ANGV signals, namely peak-to-peak STOS and peak ANGV, were insensitive to minor deflections of the signals. Rotation signals recorded with this experimental system should be validated using “gold standard” systems as speckle tracking echocardiography or MRI. Signals recorded from humans may differ, and must be characterized at baseline to enable assessment of the effects of physiology and pathology. Using our measuring strategy, signals were sufficiently reproducible and reliable for real-time analysis. Many issues associated with the technology remain to be studied such as calculating the exact direction of motion, differentiating cardiac motion from respiration and whole body motion, understanding regional motion abnormalities among others.The volume overloading protocol was too mild to exert a detectable effect on the cardiac muscle. On the other hand, the effect of epinephrine administration was possibly too intense, as differences between RVa and CS leads were attenuated even with the lower epinephrine concentration.In conclusion, the system presented provides novel real-time continuous physiologic information related to systolic and diastolic mechanical events. This information may be used to study and possibly improve the effectiveness of various therapies such as CRT; however, much research, development and validations are required.