Measuring intracardiac kinetic energy using four-dimensionl flow cardiac magnetic resonance provides important information on the decline in the early diastolic kinetic energy of blood with aging. The decline is comparable with that seen in those with heart failure and may be a marker of cardiac function. P = 0.182) and ejection fraction (P = 0.921) were preserved through all age groups. Older adults showed a lower early peak diastolic KE compared with children (P < 0.0001) and young adults (P = 0.025). Subjects with LV dysfunction had reduced ejection fraction (P < 0.001) and compared with older healthy adults exhibited a similar early peak diastolic KE (P = 0.142) but with the addition of an elevated KE in diastasis (P = 0.029). In healthy individuals, peak diastolic KE progressively decreases with age, whereas systolic peaks remain constant. Peak diastolic KE in the oldest subjects is comparable to those with LV dysfunction. Unique age-related changes in ventricular diastolic energetics might be physiological or herald subclinical pathology.Aging has important deleterious effects on the cardiovascular system. We sought to compare intraventricular kinetic energy (KE) in healthy subjects of varying ages with subjects with ventricular dysfunction to understand if changes in energetic momentum may predispose individuals to heart failure. Four-dimensional flow MRI was acquired in 35 healthy subjects (age: 1–67 yr) and 10 patients with left ventricular (LV) dysfunction (age: 28–79 yr). Healthy subjects were divided into age quartiles . KE was measured in the LV throughout the cardiac cycle and indexed to ventricular volume. In healthy subjects, two large peaks corresponding to systole and early diastole occurred during the cardiac cycle. A third smaller peak was seen during late diastole in eight adults. Systolic KE ( Measuring intracardiac kinetic energy using four-dimensionl flow cardiac magnetic resonance provides important information on the decline in the early diastolic kinetic energy of blood with aging. The decline is comparable with that seen in those with heart failure and may be a marker of cardiac function.during healthy aging, the left ventricle (LV) and cardiovascular system are known to undergo adverse changes including increased stiffness of blood vessels, ventricular remodeling, and decreased ventricular compliance  phase-contrast (PC) flow MRI to noninvasively measure intracardiac kinetic energy (KE) 5–11). 4-D flow MRI provides a detailed overview of the velocity of blood in three directions, helping to capture the intricacies of blood flow within the heart. This detail is not adequately captured by two-dimensional (2-D) Doppler echocardiography or 2-D PC flow MRI, which are limited to a single imaging plane and measure velocities in only one direction. Early work qualifying ventricular blood flow characteristics in a small group of healthy subjects of different ages has shown that the number of blood vortexes decreases with age . This af–11. 4-D Data were collected prospectively on 35 adults and children (27 adults and 8 children) and 10 patients with LV dysfunction. Patients with LV dysfunction were defined by the signs and symptoms of heart failure with additional echocardiographic evidence of ventricular dilatation and systolic dysfunction as measured by depressed ejection fraction (EF). Patients with LV dysfunction were age and sex matched to a subsection of the healthy volunteer group.All healthy subjects were without cardiovascular disease, in sinus rhythm, with normal ECG and normal blood pressure. As per institutional preference, subjects under the age of 10 yr were scanned under general anesthesia using low-dose inhaled sevofluorane with remifentanyl while maintaining normocarbia. Subjects with LV dysfunction were clinically New York Heart Association class I or II. All subjects underwent cardiac MRI on a 1.5-T scanner . The local research ethics committee approved the study design, and all adult participants gave written consent (10/H0802/65). The local research and ethics committee approved that children undergoing a clinically indicated MRI scan (anesthetized or unanesthetized) could undergo an additional 15 min of scanning for research purposes (09/HO802/78). The attending medical professional identified children with structurally and functionally normal hearts who were felt suitable for inclusion into the study. The family was provided with verbal and written information about the study and was allowed to consider whether they wished to participate and to seek further information if necessary. A signed consent form was completed for all experimetns. Assent was taken from younger children where they wished and was sought in all children who were deemed competent.Retrospectively ECG-gated balanced steady-state free precession cine four-chamber views and short-axis stacks were performed with the short axis planned parallel to the mitral valve plane. Images were acquired during end-expiratory breath holds covering the apex to base. Typical imaging parameters were as follows: repetition time (TR), 3.0–3.6 ms; echo time (TE), 1.5–1.8 ms; parallel imaging factor (using SENSE), 2; flip angle, 60°; field of view, 200–400 mm; slice thickness, 6–10 mm depending on patient size; in-plane resolution, 1.3–2.0 mm; acquired temporal resolution, 30–40 phases, and breath-hold duration, 5–7 s/slice with 10–14 slices to cover the whole heart including the proximal aorta. A 15-mm respiratory gating window was used to ensure that breath holds were consistent between slices to reduce spatial misalignment. Analysis of volumetric data was performed using a Viewforum workstation . Segmentation of the ventricular cavity involved manual tracing of the endocardial contour for each slice at end systole and end diastole . TrabecuA free-breathing retrospectively ECG triggered 2-D PC scan orthogonal to the ascending aorta at the level of the right pulmonary artery was acquired with three signal averages, a spatial resolution of 1.5 × 1.5 × 6 mm, and an acquired temporal resolution of 30 phases. The peak velocity of flow in the aorta was used to target the velocity encoding range of the 4-D flow PC scan.A free-breathing prospectively ECG triggered 4-D flow whole heart MRI sequence was acquired using a targeted velocity encoding based on 2-D PC aortic peak velocity. The mean field of view was 300 × 70 × 150 mm, with the following spatial resolution specific to the size of the patient: small children (<20 kg), 2.0-mm isotropic voxels; large children and adults (20–90 kg), 2.5-mm isotropic voxels; and large adults (>90 kg), 3-mm isotropic voxels. The number of phases was adjusted to between 24 and 32 phases to acquire a temporal resolution of <35 ms. Other imaging parameters included the following: TR, 3.8 ms; TE, 2.4 ms; flip angle, 5; acceleration kt+, 8; and bandwidth, 500 Hz. Respiratory gating for motion correction was applied giving a nominal scan time of 5–7 min , 15. DatInitially, the endocardial border of the LV was manually segmented in the first timeframe from the short-axis cine stack balanced steady-state free precession images using CardioViz3D software . This alParticles from the 4-D flow sequence were seeded within the mask at a density equivalent to the voxel size of the 4-D flow images for each timeframe and the 4-D PC data used to measure the velocity.2. The mass of blood was derived from multiplying the mean density of blood  by the voxel volume represented by each particle.KE was calculated by taking the instantaneous velocity magnitude of a particle and applying the following formula: KE = ½ mass × velocityTo allow comparison between hearts of different sizes, KE values were expressed as KE density based on the instantaneous volume blood present in the ventricle at that phase of the cardiac cycle. The resultant parameter was expressed in the form of energy per milliliter of blood (in mJ/ml). KE values were expressed as a fraction of the R-R interval. KE was measured throughout the cardiac cycle. KE in different parts of the cardiac cycle is shown in t-tests were used for intergroup comparisons in cohorts containing only two subgroups . Paired t-tests were used for comparison of KE in the age- and sex-matched subjects. For cohorts with four subgroups , one-way ANOVA with Bonferroni-adjusted, post hoc t-tests were used for the majority of variables, provided the assumptions for ANOVA were met . P values of <0.05 were considered significant. Allometric cardiac growth occurs with age, so linear indexing to body surface area is permissible only between fully grown adults of different sizes . Healthy subjects were divided into age quartiles . Unpaired n = 3), assessment for tortuosity of the head and neck vessels (n = 2), assessment for arrhythmogenic RV cardiomyopathy (n = 2), and exclusion of partial anomalous venous drainage (n = 1). All children included in the study were confirmed to have structurally and functionally normal hearts by a cardiologist experienced in reporting cardiac magnetic resonance (CMR). Ten patients with compensated LV dysfunction were used as positive controls (age: 28–79 yr).Thirty-five individuals ranging in age from 1 to 67 yr were recruited and divided into four age quartiles: 8 children (<16 yr), 11 young adults (17–32 yr), 11 middle-aged adults (33–48 yr), and 5 older adults (49–64 yr). The reasons for the MRI referrals in children were as follows: exclusion of vascular ring (P = 0.007). The LV dysfunction group had reduced EF (P < 0.001) and dilated hearts (P < 0.034) compared with the healthy older adult group.R2 = 0.206, P = 0.007). However, there were no significant differences between LV outflow tract velocities or ventricular volumes at which peak systolic KE occurred to explain this . In healthy subjects, there were no differences in mean systolic KE peaks at any age. There were distinct differences in mean early LV diastolic peaks with age (P = 0.0001). A progressive fall in mean early diastolic KE peaks occurred between the 1st and 2nd age quartiles (P = 0.007) and a second further fall between the 2nd and 4th age quartiles (P = 0.025). This is most clearly seen in the box and whisker plots shown in Changes in intracardiac KE during the cardiac cycle are shown in ain this . Peak eaR2 = 0.273, P < 0.002). There was a negative correlation with age .Comparison was made between mitral inflow velocities segmented from the 4-D flow and peak early diastolic KE . Peak miP = 0.024). Importantly, there were no differences detected among fully grown adults represented by the 2nd, 3rd, and 4th mass quartiles. Peak diastolic KE did not vary significantly between HR quartiles (P = 0.051).There is a potential confounding effect of LV mass and HR on KE. Quartiles were additionally analyzed for indexed LV mass and HR. Using mass indexed to body surface area, a significant decrease in early peak KE between the 1st and 4th index LV mass quartiles was seen , giving an overall broad flattening to the KE profile and an increased KE during diastasis (P = 0.029) compared with the older adult group. Age and sex matching of those with LV dysfunction to healthy LV subjects showed that 9 of 10 patients had reduced systolic and diastolic KE values compared with their counterparts. LV dysfunction subjects displayed a lower mean peak systolic KE  and mean peak diastolic KE  acquisition. Grothues et al.  showed CThe 4-D flow MRI sequences used prospective ECG triggering, which acquired 90% of the cardiac cycle, missing some of late diastole. This meant that atrial peaks were not evident in all subjects. However, given that the majority of changes seemed to occur in systole and early diastole, we were still able to draw interesting conclusions from the data.The present study examined age-related changes in comparably large age ranges. More volunteers and further subgroups of age extending toward the older population would allow quantification of when age-related changes tend to manifest themselves. Although the children included in this study were free of cardiovascular disease, it should be noted that they were undergoing a MRI scan for other medically indicated reasons.This study used CMR data. Therefore, although the results are in keeping with other studies measuring KE in the heart, they were not validated against invasive data.In summary, we found that a decline in diastolic KE is apparent with age, whereas systolic KE is preserved. These changes may represent a spectrum of physiological deterioration that predisposes toward pathological outcomes. The motion of blood through the heart is highly sensitive to changes in myocardial properties. Flow-derived KE might therefore allow earlier insights into physiological and pathological changes than currently possible.Wellcome Trust and Engineering and Physical Sciences Research Council, Grant WT 088641/Z/09/Z) as well as the British Heart Foundation (BHF) Centre of Excellence (BHF Award RE/08/03) and BHF New Horizons program (Grant NH/11/5/29058).The Division of Imaging Sciences receives support as the Centre of Excellence in Medical Engineering  Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust.No conflicts of interest, financial or otherwise, are declared by the author(s).Author contributions: J.W., R.C., A.d.V., N.D., E.S., T.S., and R.R. conception and design of research; J.W., R.C., and E.S. performed experiments; J.W., R.C., and A.d.V. analyzed data; J.W., R.C., A.d.V., N.D., E.S., T.S., and R.R. interpreted results of experiments; J.W. prepared figures; J.W. and R.R. drafted manuscript; J.W., R.C., A.d.V., N.D., E.S., T.S., and R.R. edited and revised manuscript; J.W., R.C., A.d.V., N.D., E.S., T.S., and R.R. approved final version of manuscript.


Right ventricle (RV) dysfunction is a key outcome determinant and a leading cause of death for patients with chronic thromboembolic pulmonary hypertension (CTEPH). In this report, we followed the 5-year clinical journey of a patient with CTEPH. The tricuspid pressure gradient was significantly increased in the early phase of CTEPH and “normalized” at the late phase of this patient’s clinical journey, but this “normalized” gradient is not a positive treatment response but rather an ominous sign of advancing right heart failure owing to an exhaustion of RV contractile function. Thus, appropriate interpretation of the tricuspid pressure gradient change is of importance for assessing RV dysfunction and treatment outcome during follow-up in patients with CTEPH. Besides systolic pulmonary artery pressure (SPAP), other RV functional parameters such as tricuspid annular plane systolic excursion, RV fractional area change, and RV longitudinal strain, together with clinical markers, may provide additional guidance regarding functional improvement or progression in patients with CTEPH. Pulmonary thromboembolism serves as a common cause of pulmonary hypertension (PH), termed chronic thromboembolic pulmonary hypertension  ,2. Fibro2 30 mmHg; PO2 64 mmHg; O2 saturation 94%). Initial transthoracic echocardiography  and sinus tachycardia (heart rate = 120 beats/min). Blood tests evidenced elevated serum D-dimer . Computed tomography (CT) revealed extensive bilateral thrombi in proximal and peripheral pulmonary arteries plus RV dilation and hypertrophy , and invasive hemodynamic monitoring suggested that severe PH existed during the whole disease journey. Extremely enlarged RV and RA, dilated main PA diameter, and decreased cardiac output, as well as increased pulmonary vascular resistance also provided circumstantial evidence on progressive worsening in both RV volume and pressure overload in this patient. However, significantly elevated tricuspid pressure gradient in the early phase of CTEPH normalized at the late phase of this patient’s clinical journey. The potential reasons for pseudo-normalization of SPAP during development in this patient remain an issue of speculation. This decline of the pressure gradient is not due to improvement of tricuspid regurgitation but rather a feature of progressive right ventricular dysfunction, as indicated by a sustained reduction in TAPSE, RV FAC, and correspondingly reduced RV longitudinal strain in STI Figure . PreviouAdditionally, we observed the discrepancy between echocardiographic-derived SPAP (reduced) and right heart catheterization measured pulmonary artery systolic pressure (increased) during the late course of PH in this patient. The underlying reason might be that echocardiographic-derived SPAP reflects the pressure gradient between RV and RA, which is low due to increased RA pressure in this patient at late disease phase. While invasive right heart catheterization-measured SPAP presents the real increased pressure situation at pulmonary artery.In comparison with tricuspid pressure gradient, some clinical indices and other echocardiographic parameters might be additionally useful for predicting the outcome in this case. When retrospectively reviewing the full journey of this patient, sustained elevated NT-proBNP levels and a significantly low 6MWD were observed. Previous studies showed that BNP and NT-proBNP correlated well with RV function and prognosis in several forms of pulmonary hypertension -9. The 6In conclusion, “normalized” echocardiography-derived SPAP with the progression of the disease is a feature of progressive right heart dysfunction in patients with CTEPH. Besides SPAP, other RV functional parameters such as TAPSE, RV FAC, and RV longitudinal strain, together with clinical markers, may provide additionally useful guidance regarding functional improvement or progression in patients with CTEPH.The study was approved by Local Ethics Committee at the University of Würzburg and conducted in accordance to the Declaration of Helsinki.Written informed consent was obtained from the patient’s guardian for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.


We aimed to define the prognostic value of the heart rate range during a 24 h period in patients with chronic heart failure (CHF).Prospective observational cohort study of 791 patients with CHF associated with left ventricular systolic dysfunction. Mode-specific mortality and hospitalisation were linked with ambulatory heart rate range  in univariate and multivariate analyses. Findings were then corroborated in a validation cohort of 408 patients with CHF with preserved or reduced left ventricular ejection fraction.2=0.2; p<0.001) and with peak exercise-test heart rate . Analysis of the validation cohort revealed AHRR to be associated with all-cause and mode-specific death as described in the derivation cohort.After a mean 4.1 years of follow-up, increasing AHRR was associated with reduced risk of all-cause, sudden, non-cardiovascular and progressive heart failure death in univariate analyses. After accounting for characteristics that differed between groups above and below median AHRR using multivariate analysis, AHRR remained strongly associated with all-cause mortality (HR 0.991/bpm increase in AHRR (95% CI 0.999 to 0.982); p=0.046). AHRR was not associated with the risk of any non-elective hospitalisation, but was associated with heart-failure-related hospitalisation. AHRR was modestly associated with the SD of normal-to-normal beats (RAHRR is a novel and readily available prognosticator in patients with CHF, which may reflect autonomic tone and exercise capacity. Resting heart rate offers important prognostic information in patients with chronic heart failure (CHF), and its reduction is an important target during the titration of mortality-reducing pharmacotherapy.Declaration of Helsinki. All 791 patients with available ambulatory ECG data were included in this analysis. Inclusion in the study required the presence of stable signs and symptoms of heart failure for at least 3 months, and left ventricular ejection fraction ≤45% on transthoracic echocardiography; recruiting clinics reviewed adult patients only (age ≥18 years).We conducted a prospective cohort study aiming to define prognostic markers in patients with CHF, associated with left ventricular systolic dysfunction (LVSD), receiving contemporary evidence-based therapies. Between June 2006 and December 2011, all patients attending specialist cardiology clinics in four UK hospitals were approached to participate.As described previously,Twenty-four hour ambulatory three-lead ECGs  were obtained during normal, unrestricted, out-of-hospital activity.All patients were registered with the UK Office of Population Censuses and Surveys, which provided details of death. Classification criteria for the mode of death were defined before the study commenced, based upon previous publications.In order to assess the validity of our observations, analyses were repeated in a second cohort of patients from the previously published UK-HEART study.2 tests. Cox proportional hazards regression analysis was used in univariate and multivariate mortality analyses . Continuous data are displayed as mean (SE of mean), and categorical data are displayed as percentage (number); normality of distribution was confirmed on skewness testing. Continuous data are compared with unpaired Student's t tests, or analysis of variance (ANOVA) as appropriate, and categorical data with χDescriptive data for the 791 patients with available ambulatory ECG data, divided into quartiles of AHRR , are provided in After a mean follow-up period of 4.1 years (SE 0.07 years), a total of 268 deaths occurred . As illustrated in During the first year of follow-up, 180 patients underwent an unplanned hospitalisation, with 46 attributable to heart failure. AHRR was not associated with the risk of any non-elective hospitalisation , but was associated with the risk of heart-failure-related hospitalisation .AHRR declined by 7.6% (49.8 (0.1) vs 46 (0.9) bpm; p<0.001) between recruitment and follow-up (after 354 (7) days) in the subset of 328 patients with repeat ambulatory ECG data. Notably, β-blocker titration in this period was not associated with either changes in AHRR or absolute AHRR at follow-up . Follow-2max (R2=0.06 (95% CI 0.001 to 0.20); p=0.015). However, differences in peak heart rate during cardiopulmonary exercise testing accounted for one-third of variation in AHRR (2=0.33 (95% CI 0.1 to 0.55); p<0.001).To explore what AHRR might tell us about patients with CHF, exploratory association analyses were performed. AHRR falls progressively as NYHA functional impairment classification rises (p=0.001 by ANOVA). Within the 98 patients in our AHRR cohort referred for cardiopulmonary exercise testing, there was very weak correlation between AHRR and VO2=0.2 (0.08 to 0.34); p<0.001). Interestingly, when both AHRR and SDNN were included in a multivariate analysis using these 199 highly selected patients, only SDNN was associated with risk of all-cause mortality (HRs (95% CI) SDNN 0.99 (0.981 to 0.998); AHRR 0.994 (0.976 to 1.012)).Given the influence of the autonomic nervous system upon heart rate variation, we next explored the correlation between AHRR and SDNN. Data available for a subgroup of 199 patients collected as part of a separate substudy were included in this analysis; by definition, these patients were selected by virtue of being in sinus rhythm for sustained periods of monitoring. AHRR modestly correlated with SDNN ; p<0.001).After a mean 3 years’ follow-up, 144 patients had died . In univariate analyses, AHRR remained associated with the risk of all-cause death (HR 0.973 (95% CI 0.962 to 0.984); p<0.001), progressive heart failure death (0.956 (0.939–0.974); p<0.001) and sudden death (0.981 (0.963 to 0.999); p=0.037). AHRR was associated with all-cause mortality in subgroups with reduced (n=261) or preserved (n=126) LV ejection fraction . In a muIn this manuscript, we provide the first ever assessment of the prognostic value of the daily heart rate range in patients with CHF. To summarise, AHRR is associated with all-cause and mode-specific death, along with heart-failure-related hospitalisation; even after accounting for potentially confounding prognostic factors, AHRR remains associated with all-cause mortality. Notably, the relationship between AHRR and mortality persisted when assessed in an independently recruited cohort with CHF, within subgroups with either reduced or preserved left ventricular ejection fraction. The factors underpinning the association between AHRR and CHF outcome remain unclear, although our exploratory analyses indicate associations between AHRR and both functional capacity and autonomic dysfunction.It is well established that elevated resting heart rate represents an important adverse prognostic factor, and also a therapeutic target, in patients with CHF associated with LVSD.4SDNN, a marker of beat-to-beat variation in cycle length, is perhaps the best established measure of HRV in clinical research, and is recognised as a powerful prognosticator. However, it is also limited by the requirement of prolonged high-quality ECGs during uninterrupted sinus rhythm, essentially excluding more than half of a typical CHF population.While the data we present clearly suggest AHRR can assist in the prediction of mode-specific mortality and hospitalisation, we cannot offer an assessment of whether it acts as a marker or a mediator of adverse prognosis. However, our exploratory analyses suggest that AHRR is associated with important biological phenomena, which may themselves influence CHF outcome. First, we have demonstrated that as functional capacity and peak exercise heart rate decline, so too does AHRR. However, only a relatively small proportion of the variation in AHRR could be explained by peak exercise heart rate. Moreover, it remains unclear whether the link between AHRR and NYHA class is simply a reflection of physical inactivity, or whether this tells us something more about the disease process per se. A second biological link was between AHRR and autonomic tone, as assessed using SDNN—lower SDNN (an adverse prognostic feature) was noted as AHRR decreased. While it is interesting that a multivariate analysis including SDNN and AHRR suggested that only SDNN was associated with the risk of all-cause mortality, this analysis is limited by selection bias entailed in acquiring SDNN data. However, these analyses do add further support to the suggestion that autonomic tone is associated with AHRR, and notably diabetes is substantially more common in people with low AHRR. Interestingly, recently published data suggest that regular physical activity is also associated with increased HRV in older adults without CHF, potentially linking the phenomena we noted to be associated with AHRR.17While our observations are novel and have the potential to be readily adopted in routine clinical practice, they also have limitations. Our study population is relatively small, although it is important to note that this allowed us to phenotype our patients in more detail than is generally possible in large clinical trials . It will therefore be important to further validate our findings in larger and more diverse CHF populations, although the recapitulation of our observations in a second CHF cohort adds significant strength to our findings. The observational nature of the study also prevents us from drawing any firm conclusions regarding the biological phenomena controlling AHRR, which is important in understanding its link to outcomes. Moreover, we are likely not to have accounted for all confounding factors in our multivariate analyses, but hope that these at least demonstrate that AHRR adds value to other readily available clinical data. In particular, we are unable to comment on NT-proBNP in our population or the value of AHRR as part of an established prognostic model. Finally, it will also be important to understand whether properties of the daily heart rate profile beyond its range offer further value.As discussed earlier in this section, our data raise many other questions regarding the value of measuring AHRR during the assessment and management of patients with CHF. First, it will be important to assess the incremental value of AHRR beyond established prognostic scores (eg, the Seattle Heart Failure ModelAHRR is a simple to derive index of HRV during a 24 h period, which is associated with both indices of exercise physiology and autonomic function, and offers important prognostic information, independent of other established prognostic factors.Resting heart rate and indices of heart rate variability are powerful predictors of adverse outcome in patients with chronic heart failure. However, most indices of heart rate variability are complex to derive and exclude patients without sustained periods of sinus rhythm.The heart rate range during 24 h of ambulatory electrocardiography is associated with mode-specific mortality and hospitalisation in patients with heart failure, irrespective of left ventricular function or cardiac rhythm. After accounting for potential confounding factors, each one beat increase in heart rate range is associated with a 0.9% relative reduction in all-cause mortality.While traditional heart rate variability indices offer valuable prognostic data, they are rarely applied in clinical practice due to complex analytical techniques and exclusion of patients with atrial arrhythmias and paced rhythms. Ambulatory heart rate range may circumvent these issues and offer other novel opportunities in the monitoring of patients with implantable cardiac devices.


As a consequence of limited donor availability, there has been a growing interest for alternative strategies, such as left ventricular assist devices (LVAD) as either a bridge to transplantation (BTT) or as destination therapy (DT) for the treatment of the advanced heart failure. The heart transplant program in Kazakhstan is in a nascent stage and therefore patients that are determined to be BTT are expected to have an extended duration of LVAD support.The objective of this study was to determine outcomes of patients with left ventricular assist devices in country with restricted transplantation.We analyzed outcomes for 135 patients between November 2011 and November 2014 , HeartWare=40 ). The median duration of support is 474 ± 329,4 days.In 75 patients  the LVAD is used as a BTT and in 60  as a DT, but only 3 of 135 LVAD patients were transplanted. Before 30 days after implantation of LVAD right ventricular failure , renal failure  and bleeding  were the most common adverse events. After 30 days driveline infections  and strokes  were the most common complications. Cumulative survival rates at 1, 6 months, 1, 2 and 3 years after LVAD implantation is 93%, 86%, 77%, 62% and 51% accordingly. Older age and more acute INTERMACS profiles were related to reduced survival.The Center's experience shows that LVADs can be implanted as an alternative to heart transplantation with the outcomes that are comparable to those in existing world centers of excellence.


Dilated cardiomyopathy (DCM) and chronic mitral valve disease (CMVD) in dogs are associated with heart chamber enlargement, also of the left atrium. DCM is often accompanied by rhythm disturbances . In CMVD, arrhythmias are observed less frequently. It is still unclear whether left atrial enlargement in these diseases results from volume overload or if it is also connected with other factors (e.g. rhythm disturbances).This study was conducted on the left atrial myocardial specimens from 31 dogs, including those from 16 dogs with clinically diagnosed DCM and 15 dogs with CMVD. After fixation and staining (using haematoxylin-eosin and Masson-Goldner trichrome stain), the specimens underwent evaluation. Parenchymal changes , degenerative changes  and the presence of inflammatory infiltrates were assessed.p < 0.05) and less perivascular fibrosis  was observed in the DCM group compared to the CMVD group. Moreover, less distinct vessel narrowing was observed in the DCM group than in the CMVD group . Dogs with DCM showed more strongly defined degenerative changes than the CMVD dogs .More interstitial fibrosis (median 4 vs. 2.5 grid fields; The obtained results indicate a different nature of changes occurring in the left atrial myocardium of dogs with DCM compared to dogs with mitral valve disease, including differences in vessel narrowing, cardiomyocyte degeneration and in the distribution of connective tissue. Dilated cardiomyopathy (DCM) is a polyetiological disease characterised by a dilation of heart chambers (mainly the left ventricle and left atrium) without other significant structural heart defects. In some cases, it is combined with myocardial failure , 2. It iThe histopathologic examination of the samples obtained from dogs with DCM demonstrates changes in the myocardial structure. There are two well-described forms of histopathologic lesions in the ventricular specimens of dogs with DCM: the attenuated wavy fibre type (AWF) and the fatty infiltration-degenerative (FID) type. Those lesions are mostly encountered in specimens from the left ventricle, but can also occur in the myocardium of the right ventricle and interventricular septum , 8, 10. The mechanism of changes occurring in the atrial myocardial structure in DCM is not well defined. It is suspected that the structural protein defects, impaired tissue oxygen supply and other factors may play a role in the development of the disease , 2. It iCanine chronic mitral valve disease (CMVD) is the most common cardiovascular disease in dogs and the most frequent cause of congestive heart failure in those animals. The disease predominantly occurs in small breed dogs  and progresses with age –14. The The purpose of the study was a histopathologic comparison of the left atrial wall specimens obtained from dogs with severe left atrial enlargement resulting from clinically diagnosed dilated cardiomyopathy (DCM) or chronic mitral valve disease (CMVD). To the authors’ knowledge, there are no detailed studies comparing histopathologic changes occurring in the atria in those diseases.Thirty-one dogs aged from 4 to 19 years  with either CMVD or DCM were included in the study. Dogs met the inclusion criteria if they had an enlarged left atrium according to an echocardiographic examination -to-aortic root (Ao) diameter ratio; LA/Ao >1.7 ), which All animals underwent a clinical examination, echocardiography and electrocardiography, and were treated and re-examined every 6 months, until they died or were euthanized due to heart failure refractory to treatment. Only the LA/Ao ratio from the last examination of each dog served as an inclusion criterion.The ECG was performed in right lateral recumbency using a 6-channel BTL SD08 device  with I, II, III, aVL, aVR, aVF, and precordial (V1-V6) lead recordings. The echocardiographic examination was performed in standard views using the Aloka SSD 4000 and Aloka Alpha7 machines and included the assessment of the LA/Ao ratio, end-systolic and end-diastolic left ventricular measurements, ejection fractions and FS, blood velocity through the aortic and pulmonic valve, and the function of the atrioventricular valves. The relative left atrial size was estimated based on the LA/Ao. This parameter was determined using standard images acquired from a right short-axis view at the base of the heart. Estimates of left ventricular systolic function were obtained from the index of circumferential myocardial contraction and FS using the formula: FS[%] = ([LVIDd – LVIDs]/LVIDd) ×100, where LVIDd and LVIDs are the internal left ventricular dimensions at end-diastole and end-systole, respectively. Left ventricular dilation was estimated based on the comparison of chamber measurements  to standard breed-specific or body-weight specific values . The funThe results of the echocardiographic examination  were confirmed during the post-mortem examination, where the type of mitral valve lesion was determined. Heart measurements were taken using a manual 150 mm Beerendonk caliper, measured to the nearest 1/20 mm. The measurements were taken in planes compatible with those used during the echocardiographic examination. Specimens from the left atrial wall were collected from each dog for further histopathologic analysis. They were fixed in 7 % buffered formalin, embedded in paraffin blocks, sectioned at 6 μm, stained using the standard haematoxylin-eosin (H&E) method and Masson-Goldner trichrome , and underwent a light microscopy evaluation. Photomicrographs of each studied specimen were subjected to computer-assisted image analysis, using a computer coupled to an optical Olympus BX53 microscope, equipped with a Color View IIIu digital Olympus camera . A morphometric analysis was performed using Cell^A software .To accurately describe the histopathological changes in the atria, specimens were evaluated for the presence and severity of fibrosis, fatty infiltration, inflammatory infiltration, intra-myocardial arterial narrowing and degenerative changes in cardiomyocytes. The latter was expressed as the presence of abnormal cell nuclei , loss of striation, and other features of degeneration .The presence and severity of interstitial fibrosis and fatty infiltration were evaluated after superimposing a 16-field grid over the digital image and counting the number of fields that showed the presence of fatty infiltration or fibrosis , as proposed by Lobo et al. .The severity of perivascular fibrosis was assessed using the following scoring system: 0, no fibrosis; 1, mild; 2, moderate; 3, severe fibrosis .Inflammatory infiltrates were evaluated according to the number of inflammatory cells in a field at a 400× magnification (H&E staining).Intra-myocardial arterial narrowing was assessed using the lumen area ratio , as proposed by Falk et al.   were assessed using the following scoring system: 0, none or involving <25 % of the myofibres; 1, involving 25–50 % of the myofibres; 2, involving 50–75 % of the myofibres; 3, involving >75 % of the myofibres .Each of the features was evaluated in 20 randomly chosen fields per slide  or in at least 10 vessels per slide (for perivascular fibrosis and LAR), and a mean score was subsequently calculated for the slide.According to the Polish law , standarU test  or Student’s t test  were used to compare groups. The level of statistical significance was set at P < 0.05.A statistical analysis was performed using StatisticaPL® software . The Shapiro-Wilk analysis was used to test the data normality. The Mann–Whitney The results are shown as range and median values.The DCM group consisted of 16 dogs . Seven specimens from the left ventricle presented with an AWF type of lesion, while nine specimens had features of a FID type of lesion. The CMVD group comprised 15 dogs  diagnosed with mitral valve disease combined with an enlarged left ventricle and left atrium  by performing an accurate ante-mortem and post-mortem examination.Dogs with dilated cardiomyopathy show a different distribution of connective tissue, have less severe intra-myocardial arterial narrowing, and have more severe degenerative changes in the cardiomyocytes of the left atrium compared to dogs with chronic mitral valve disease. The changes noted in the atrial tissue from dogs in both groups resemble lesions noted in the ventricular tissue of dogs with the same diseases. Those differences may indicate that the atrial enlargement noted in DCM and CMVD has a different, disease-specific underlying mechanism and does not result only from volume overload.


Transient left ventricular apical ballooning syndrome is characterized by transient akinesis of the left ventricular apex with basal wall hyperkinesis; this is also known as Takotsubo cardiomyopathy. There are three distinct contractile LV patterns described in the literature: apical, midventricular, and basal ballooning. The apical ballooning pattern is the most frequent pattern. We describe the case of a transient anterolateral left ventricular ballooning fulfilling the definition of Takotsubo cardiomyopathy except for the contractile LV pattern. The diagnosis was supported by cardiac magnetic resonance imaging and by the fact that the anterolateral ballooning resolved completely after 6 weeks. Transient left ventricular apical ballooning syndrome characterized by transient akinesis of the left ventricular apex with basal wall hyperkinesis was first described as Takotsubo-type cardiomyopathy in 1990 . The majWe report the case of a stress-induced left ventricular anterolateral ballooning in a 61-year-old female patient matching the diagnostic criteria of TTC but with a distinct pattern of ballooning/dyskinesia. The 61 year old female patient presented the day after new years eve with typical anginal chest pain at rest with radiation to the jaw. The ECG at presentation showed minimal ST-elevation (0.5 mm) in I and aVL and poor R wave progression V1–V4. Regarding cardiovascular risk factors the patient had mild hypertension and dyslipidemia (currently not treated). Troponin test was positive with normal values vor CK/CK-MB. An emergency coronary angiography was performed which revealed normal coronary arteries. The left ventricular angiogram showed anterolateral ballooning with globally preserved ejection fraction . 24 h laThe patient was diagnosed with an atypical form of takotsubo cardiomyopathy and discharged one day later with an ACE-inhibitor and a betablocker. 6 weeks later, the patient was seen as an outpatient. She was asymptomatic and LV function was completely normal on echo.Our case fulfills the current diagnostic criteria of stress-induced cardiomyopathy or takotsubo cardiomyopathy except for the contractile LV pattern . In formCardiovascular magnetic resonance (CMR) imaging is uniquely suited for the evaluation of patients with TTC. In addition to accurate visualization of regional wall motion abnormalities, it allows for precise quantification of right ventricular (RV) and LV function and the assessment of additional abnormalities . Importantly, CMR imaging also provides markers for reversible  and irreversible (necrosis/fibrosis) injury, which may be particularly important to verify TTC and exclude similar acute cardiac diseases such as myocardial infarction or myocarditis . In conclusion we suggest that TTC can present not only with the classical LV ballooning patterns  but also with segmental  ballooning, and CMR is a useful tool in the diagnosis of TTC.


Recent efforts to increase CRT response by multiSPOT pacing (MSP) from multiple bipols on the same left ventricular lead are still inconclusive.The Left Ventricular (LV) MultiSPOTpacing for CRT (iSPOT) study compared the acute hemodynamic response of MSP pacing by using 3 electrodes on a quadripolar lead compared with conventional biventricular pacing (BiV).Patients with left bundle branch block (LBBB) underwent an acute hemodynamic study to determine the %change in LV+dP/dtmax from baseline atrial pacing compared to the following configurations: BiV pacing with the LV lead in a one of lateral veins, while pacing from the distal, mid, or proximal electrode and all 3 electrodes together (i.e. MSP). All measurements were repeated 4 times at 5 different atrioventricular delays. We also measured QRS-width and individual Q-LV durations.Protocol was completed in 24 patients, all with LBBB (QRS width 171±20 ms) and 58% ischemic aetiology. The percentage change in LV+dP/dtmax for MSP pacing was 31.0±3.3% (Mean±SE), which was not significantly superior to any BiV pacing configuration: 28.9±3.2% , 28.3±2.7% (LV-mid), and 29.5±3.0% (LV-prox), respectively. Correlation between LV+dP/dtmax and either QRS-width or Q-LV ratio was poor.In patients with LBBB MultiSPOT LV pacing demonstrated comparable improvement in contractility to best conventional BiV pacing. Optimization of atrioventricular delay is important for the best performance for both BiV and MultiSPOT pacing configurations.NTC01883141ClinicalTrials.gov  Cardiac Resynchronization Therapy (CRT) is an effective treatment for patients with systolic heart failure and a wide QRS, however approximately 30% of patients fail to respond. Several The iSPOT study intended to assess the positive LV +dP/dt max achieved by multiple (3) LV pacing SPOTs, i.e. MultiSPOT configuration in comparison to the response achieved by the current standard BiV pacing configuration. The protocol included a rigorous methodology to decrease measurement variability and to be patient-tailored  in order to provide a justified conclusion to the acute hemodynamic benefit of MSP . In addiThe study was an international, prospective, interventional, non-randomized research study conducted at 7 high-volume sites. Inclusion and exclusion criteria are listed in PerformaTM, Medtronic plc, Minneapolis, MN or QuartetTM, St Jude Medical, Sylmar, CA) or a decapolar catheter  was advanced to the target vein by subclavian approach: the LV electrode positions were determined using a qualitative approach; using the MRI images to determine the length of the LV axis (AV-plane of the coronary sinus vein (designated base of the heart), to the apex) and the fluoroscopy images to qualitatively determine the distance of the electrodes from the base. CRT contractility was measured using LV+dP/dt via a Micro-Cath™catheter Millar,Texas, USA placed in the left ventricle via the femoral artery.Following a coronary venogram to identify the target vessels for LV stimulation a quadripolar lead  synchronized by a Model 2090 programmer were used for simultaneous, independent, multi-site pacing of the left ventricle. To facilitate connections and improve safety during the EP procedure, a custom-made connection box was used for simultaneous stimulation at various sites.Four individual cardiac stimulators  and recorded using customized software. All configurations and experimental settings were annotated digitally on the same system. Signals were visualized on the laptop computer throughout the study to assess signal quality and to confirm adequate therapy delivery. No data analysis was performed at this stage.Throughout the procedure all physiological signals  were acquired real time with a 32 channel physiological recording system Biventricular pacing with pacing RV and LV on the mid electrode (LV-mid)Biventricular pacing with pacing RV and LV on the proximal electrode (LV-prox)RV and simultaneous LV pacing on all three electrodes (MSP)CardioSyncTM algorithm, the optimal AV delay +/-20 and +/-40 ms [To avoid the effects exerted on LV performance by different heart rates, pacemakers were programmed to pace in DDD mode at a lower rate of 100 bpm to ensure atrial and ventricular capture. It was decided to have one fixed heart rate for all patients and 100 bpm was well tolerated. In addition, the higher heart rate was found to be more sensitive to changes in contractility when using the different CRT configurations. For all configurations the VV delay was set at 0 ms. For each configuration, measurements were performed at 5 different AV delays: the patient specific optimal AV delay determined by using the +/-40 ms . All meaMatlab™.Data analysis was reviewed off-line and where needed the correct start and end of the AAI and DDD pacing sequences were manually corrected. Premature complexes, and beats with loss of capture were manually annotated. Thereafter, final analysis was done on annotated data files using a validated custom-made program written in The paced QRS duration was measured from the beginning of the ventricular pacing spike to the end of the QRS complex in surface ECG. The Q-LV interval was defined as the interval from the onset of the intrinsic QRS on the surface ECG to the first large positive or negative peak of the LV electrogram. Q-LV-timing data are expressed as Q-LV-ratio which is the ratio of the Q-LV-time and QRS-width.Statistical analysis was performed using SAS 9.4  and R (versions up to 3.2.0). The primary objective was to compare the acute hemodynamic response of a MultiSPOT LV pacing configuration to a BiV configuration using %-change LV+dP/dtmax from baseline (AAI pacing). In the first step, the maximal average—change LV+dP/dtmax response was calculated for each subject and each configuration by a regression analysis constructing a quadratic curve through all AV-delays. From this step, a %-change of LV+dP/dtmax value for each patient within each configuration was obtained. In the second step, paired t-tests were performed to compare the configurations to each other. A subgroup analysis was performed comparing MultiSPOT and BiV configurations within ischemic and non-ischemic patients. Superiority testing at a 0.05 significance level was performed after significance of non-inferiority at a 0.025 level and 4% non-inferiority margin. Since non-inferiority testing was significant in most comparisons, only p-values for superiority are presented (unless indicated otherwise). The hypotheses are explained below:multispot indicates the percentage change LV dP/dt max for the multispot pacing configuration and ΔBiV indicates the percentage change for a given BiV pacing configuration.The null hypothesis for non-inferiority was as follows:This null hypothesis was tested against the alternative hypothesis:A p-value smaller than 0.025 was considered significant, and consequently the null hypothesis was rejected. Testing at 0.025 level means that p-values smaller than 0.025 are considered significant. The non-inferiority margin of 4% was chosen based on literature research. The non-inferiority margin is here 4% and represents the acceptable difference between multispot and BiV pacing above which we would declare multispot to be non-inferior.After rejection of non-inferiority of multispot to BiV pacing, superiority of multispot pacing to BiV pacing was tested. The following null hypothesis was considered:This analysis was pre-specified in the statistical analysis plan of the iSPOT study, and is in line with standard statistical analysis for non-inferiority trials.No correction for multiple testing was performed. To determine the correlations between absolute LV+dP/dtmax value and Q-LV or QRS duration as well as the correlations between % change LV+dP/dtmax value and Q-LV ratio or QRS ratio, linear multiple regression analysis was used. Data are expressed as mean±SD (unless indicated otherwise).Full protocol was obtained in 24 subjects (77%) from the 31 patients enrolled in the iSPOT study. One subject was excluded from the cohort for not fulfilling all the inclusion criteria. CardioSyncTM Algorithm  but MultiSPOT was not significantly different to BiV distal pacing in non-ischemic patients . No significant differences in LV+dP/dt were noted when comparing MSP versus BiV mid or MSP versus BIV prox in both ischemic and non-ischemic patients (p > 0.083).Patients were categorized according to their max response in LV +dP/dtmax . It was Conventional BiV pacing decreased the QRS-width from 167±19ms to 149±19ms, 145±19ms, 147±19ms during LV-distal, LV-mid and LV-prox pacing, respectively. There was a small additional decrease in QRS width during MSP pacing to 143±17ms, which was significant in comparison to BiV-dist (p = 0.004) but to none of the other configurations . No strong correlations between absolute LV+dP/dtmax and QRS-width (R = -0.310) or % change LV+dP/dtmax and QRS-width ratio (i.e. QRS-pacing setting/QRS-baseline) were noted (R = -0.136). Figs limitations). The study also included less invasive measurements  which are linked to the acute possible beneficial effect of multipoint pacing. The study demonstrated that after AV delay optimization MSP had no additional acute improvement in systolic LV pump function compared to conventional biventricular pacing in LBBB patients with heart failure. In this patient cohort the optimal hemodynamic response could be achieved by tailored AV-delay optimization using the CardioSyncTM algorithm.The present study was designed to investigate the feasibility of increased efficacy of multipoint pacing in CRT-eligible patients, using invasive measurements only in experienced hospitals to execute safely this type of research (see: section The differences in hemodynamic benefit of BiV pacing compared to AAI) using the different electrodes on the multipolar lead were small  but the absolute value relatively high when compared to other studies. The high acute response to CRT in the current study is likely explained by the optimal positioning of the LV lead in the lateral vein , 18, 19 The findings of the current study do not support the hypothesis that simultaneous pacing using all three electrodes  increased the acute hemodynamic CRT response through activation of a greater amount of LV tissue in patients with LBBB beyond conventional CRT. For comparison of our results to published data, we can classify prior studies of multisite pacing into those using simultaneous stimulation with a VV-delay of 0 ms (simultaneous MSP) and those using varying delays between the LV electrodes . In the simultaneous MSP studies, the acute hemodynamic benefit of MSP was either small and non-significant, 20 or sIn our study it was noted that MSP performed better (defined as an increase in LV+dP/dt max of more than 10% over best BiV) in 2 patients. Previous studies have indicated that MSP could be more beneficial in ischemic patients, 26 and Intuitively a more simultaneous activation of the LV with MSP would be expected to enhance resynchronization and thereby result in hemodynamic benefit. Data on QRS-narrowing as an indicator for CRT-response are controversial., 28, 29 The present study used the change in invasively measured left ventricular +dP/dtmax as parameter to define acute CRT response, while other hemodynamic parameters can be used such as stroke work using pressure-volume loops or blood pressure for acute CRT-feedback . An acutIn this heart failure population with wide left bundle branch block and indication for cardiac resynchronization therapy, tested in a noise-minimizing high-replicate protocol with optimized atrio-ventricular delay, MultiSPOT left ventricular pacing demonstrated no significant acute improvement in contractility over the one best biventricular pacing site. Future studies to assess the long term effect and possible multisite pacing benefits in patients with ischemic aetiology and other forms of intraventricular conduction disorders are warranted. Optimization of atrioventricular delay affected the best performance of all pacing configurations.S1 Protocol(PDF)Click here for additional data file.S1 TREND Checklist(PDF)Click here for additional data file.


Atrial fibrillation (AF) may cause systolic abnormality via inadequate diastolic filling and tachycardia-induced cardiomyopathy. Global longitudinal strain (GLS) is a very sensitive method for detecting subtle left ventricular systolic dysfunction. Hence, this study aimed to evaluate whether AF patients had a more impaired GLS, AF was a major determinant of GLS, and determine the major correlates of GLS in AF patients.The study included 137 patients with persistent AF and left ventricular ejection fraction (LVEF) above 50% and 137 non-AF patients matched according to age, gender, and LVEF. Comprehensive echocardiography with GLS assessment was performed for all cases.P < 0.001) but comparable E/Ea. After adjustment for baseline and echocardiographic characteristics, the presence of AF remained significantly associated with impaired GLS . In addition, multivariate analysis of AF patients indicated that faster heart rates and decreased E, Ea, and LVEF were associated with more impaired GLS.Compared with non-AF patients, AF patients had a more impaired GLS, a larger left atrial volume index, higher transmitral E wave velocity (E), and early diastolic mitral velocity (Ea) (all This study demonstrated that AF patients had a more impaired GLS than non-AF patients, although LVEF was comparable between the 2 groups. AF was a major determinant of GLS even after adjustment for relevant clinical and echocardiographic parameters. When AF evolves, the ventricular filling may be impaired due to loss of active atrial contraction and shortening of the diastolic time, resulting in a 15% to 20% reduction of cardiac output. In addition, paroxysmal tachycardia is frequent in AF patients and may lead to systolic impairment through a mechanism characterized by tachycardia-induced cardiomyopathy, resulting in a further decrease in cardiac output.–4 Therefore, AF per se may cause impairment of left ventricular (LV) systolic function.Atrial fibrillation (AF) is the most commonly sustained arrhythmias in chronic heart failure.,6 LV ejection fraction (LVEF) remains the simplest and the most commonly used parameter for assessing LV systolic function. However, there are several technical limitations. Particularly, the quantitative measurements of LVEF require accurate tracing of the endocardial border and the use of formulae that make assumptions about the geometry of LV. Thus, because LVEF denotes global LV function and does not take into account any regional differences, global LV longitudinal systolic strain (GLS) derived from 2-dimensional (2D) speckle-tracking echocardiography has recently emerged as a more sensitive measure of LV systolic function and is used to detect early systolic abnormalities when LVEF is still normal.,8–10 This imaging method can discriminate between active and passive myocardial motion and quantify myocardial deformations in 2 dimensions.Evaluation of LV systolic function is a fundamental function and an important indication for echocardiographic examination.,12 have found that, using the index beat to measure LV longitudinal systolic strain in AF patients is as accurate as averaging multiple cardiac cycles. Consequently, although GLS measured from index beat should be a good systolic parameter in AF patients, no study till date evaluating the influence of AF on GLS has been published. Hence, this study aimed to compare GLS between patients with and without AF in a normal LVEF stage, verify whether AF patients have a more impaired GLS, determine whether AF per se is a major determinant of GLS, and evaluate the major determinants of GLS in AF patients.Because of beat-to-beat variation, it has always been difficult to estimate LV systolic function in AF. However, our research group and Kusunose et al22.1Patients with persistent AF referred for echocardiography between April 1, 2010, and June 30, 2012, at Kaohsiung Municipal Hsiao-Kang Hospital were prospectively and consecutively included in this study. We defined persistent AF as AF that lasted longer than 7 days, which was confirmed by 12-lead electrocardiography (ECG), a 24-hour Holter monitor, or an ECG recording during echocardiographic examination. Patients with moderate and severe mitral stenosis, severe mitral regurgitation, moderate and severe aortic stenosis or regurgitation, LVEF <50%, and inadequate echocardiographic visualization were excluded from the analysis (n = 11). Finally, 137 patients with persistent AF were included in this study. In addition, 137 patients with sinus rhythm who were matched by age, gender, and LVEF and who were referred for echocardiographic examination during the same period were selected as the non-AF patient group. The study protocol was approved by the Institutional Review Board of Kaohsiung Municipal Hsiao-Kang Hospital and written informed consent was obtained from all patients.2.2,14 The raw ultrasonic data were stored for offline analysis using commercially available software . The cardiologist was blinded to the medical history of all participants, including diabetes mellitus, hypertension, and coronary artery disease. We recorded 2D and M-mode images from standard views, and using the apical 4-chamber view, we obtained LV inflow waveforms and lateral mitral annular tissue Doppler by placing the sample volume at the mitral leaflet tips and lateral annulus, respectively. We measured LVEF using the modified Simpson method, LV mass using the Devereux-modified method, and left atrial volume using the biplane area-length method. LV mass index (LVMI) was calculated by dividing the LV mass by the body surface area. Left atrial volume index (LAVI) was calculated by dividing the left atrial volume by the body surface area.Echocardiographic examination was performed using VIVID 7  by an experienced cardiologist using a standard protocol, as described in our previous studies.LV apical 4-chamber, 2-chamber, and long-axis views were acquired using the frame rate between 50 and 90 frames/s. After manually tracing the endocardial border using a point-and-click technique, the system then automatically delineated the epicardial border, thus generating a region of interest cover the entire myocardial wall. A time-strain plot was then automatically produced by the software, and GLS was assessed from the 18 LV segments. Average values were obtained for further analysis, with the minimum acceptable number of LV segments required to perform GLS measurements set to 15.,12,17 Because of their simple and fast measurements, the transmitral E-wave velocity (E), E-wave deceleration time (EDT), and early diastolic mitral annulus velocity (Ea) were obtained from 5 beats, and average values were calculated for further analysis. Heart rate was determined using 5 consecutive cardiac cycles. In non-AF patients, echocardiographic data were obtained from 3 consecutive beats to get average values for further analysis.In AF patients, we measured echocardiographic data using the index beat method.2.3We obtained demographic and medical data, including age, gender, diabetes mellitus, hypertension, heart failure, cerebrovascular accident, blood pressures, total cholesterol, and triglyceride. Body mass index was calculated as weight in kilograms divided by the square of height in meters. In addition, information regarding each patient's use of medications during the study period was obtained, including angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), β blockers, calcium channel blockers, diuretics, and metformin.2.4t tests and Chi-square tests, respectively. The relationship between continuous variables was assessed using a bivariate correlation method (Pearson correlation); if the covariates were significant in the univariate analysis, they were selected for multivariate analysis. A stepwise multiple linear regression analysis was employed to identify the determinants of GLS. All tests were 2-sided, and a P value of <0.05 was considered statistically significant.SPSS 18.0 software  was used for all statistical analyses. The data are expressed as mean ± standard deviation or percentage. Dummy coding (one and zero) was used when analyzing categorical variables. Continuous and categorical variables were compared between groups using independent sample 3Comparisons of clinical and echocardiographic characteristics between patients with and without AF are summarized in Table Determinants of GLS for all patients are summarized in Table P ≥ 0.392) between AF patients with and without antihypertensive medications .Determinants of GLS in AF patients are summarized in Table 4In this study, clinical and echocardiographic parameters were compared between patients with and without AF, alongside determinants of GLS in all patients and in AF patients. Compared with age, gender, and LVEF-matched non-AF patients, AF patients demonstrated significantly impaired GLS. Thus, AF per se was a major determinant of GLS, even after adjustment for baseline and echocardiographic characteristics. Furthermore, heart rate, LVEF, E, and Ea were important determinants of GLS in the AF patients. In addition, paroxysmal tachycardia, frequently noted in AF patients, may lead to cardiomyopathy and consequently cause systolic dysfunction. Although insufficient ventricular filling in AF patients can be greatly improved by good rate control, the lack of atrial booster pump function may still impair LV systolic function. Therefore, AF should be an important determinant of LV systolic function. In the present study, even after adjustment for systolic and diastolic blood pressures, heart rate, diabetes, cerebrovascular accident, chronic heart failure, LAVI, LVMI, LVEF, and LV diastolic parameters, AF per se was still a major determinant of GLS.AF is characterized by a loss of atrial mechanical contraction, which leads to an inability to enhance LV filling that may compromise hemodynamic performance and cause LV systolic dysfunction. investigated whether GLS could present an alternative method to measure LVEF in 62 patients with previous infarctions. These authors found that GLS was an efficient method for quantifying global LV function and had a strong correlation with LVEF. In this study, we also found a strong correlation between GLS and LVEF. Similarly, Ea was reported to be a useful parameter for assessing LV diastolic function.,21 Galderisi et al reported that GLS was significantly correlated with LV diastolic function. This study has demonstrated that lower Ea was significantly associated with more impaired GLS in all patients, including those with AF.Using magnetic resonance imaging as the reference standard, Brown et al Heart rate is frequently increased in patients with chronic heart failure and is positively correlated with mortality.,25 Heart rate may impact cardiac function; however, compared with a higher heart rate, a lower heart rate may be more beneficial to patients with systolic heart failure. In addition, a clearly inverse relationship exists between heart rate and LV systolic function. In this study, we have consistently revealed herein that faster heart rate was associated with a more impaired GLS.There is a growing interest in the influence of heart rate on several cardiovascular diseases, such as atherosclerosis, hypertension, myocardial infarction, and heart failure.,29 However, till date, there has been no work evaluating the influence of AF on GLS, which has recently emerged as a more sensitive measure of early systolic abnormality and a superior predictor of cardiovascular outcome.,31 This study found that AF might impair GLS even when LVEF was normal.It is known that AF may impair LV diastolic function through the lack of active atrial contraction.4.1 The longitudinal strain is thus considered to be the most sensitive and reproducible method among various strain measurements.,33 Final, because the sample size was small and only patients with persistent AF were included, the findings might be less generalized. In addition, although the retrospective nature of our case–control study was susceptible to the effects of selection bias, we minimized this by using strict selection criteria, consecutively including only those patients with persistent AF. In addition, control patients were selected among those referred for echocardiography during the same period, and all echocardiographic examinations were performed by an experienced cardiologist using the same machine .There were several limitations of this study. First, in AF patients, many echocardiographic parameters in AF patients were not obtained by averaging multiple cardiac cycles, but were measured using the index beat. Nevertheless, previous studies on AF patients have shown that using the index beat method to measure echocardiographic parameters, including left atrial and LV systolic parameters, was as accurate as the time-consuming method of averaging several cardiac cycles. Second, a majority of the patients in this study were treated chronically with antihypertensive medications, including β blockers in 43% of AF patients and 38% of non-AF patients. For ethical reasons, we did not withdraw these drugs. Therefore, although the effect of antihypertensive drugs on the present findings cannot be excluded, we adjusted the use of drugs in the multivariate analysis. Third, although 2D speckle-tracking echocardiography can generate longitudinal, radial, and circumferential strain measurements and LV twist, only the longitudinal strain was measured and analyzed herein. However, because the subendocardial longitudinal fibers are most vulnerable to several diseases, the longitudinal strain deteriorates earlier than radial and circumferential strains.5This study demonstrated that AF patients had a more impaired GLS than non-AF patients. AF was significantly associated with GLS even after adjustment for relevant clinical and echocardiographic parameters.


Cardiac MRI (CMRI) is reported to be accurate and reproducible in the assessment of left ventricular function. This, however, is generally by experienced observers using automated or semi-automated software. Many departments still rely on manual contour tracing with trainees increasingly performing analysis but is reproducibility still good? This study assess the impact of the observer experience on LV function assessment and the role of consensus guidelines in raising standards among trainees.20 LV data sets of varying volumes and ejection fractions (EF) were anonymized. Each data set comprised 2 and 4 chamber long axis cine SSFPs and contiguous short axis cine SSFPs from base to apex. LV volumes , end diastolic muscle mass (EDMM), and EF were manually evaluated using Argus software  by all those regularly analyzing data in our department (7 experienced operators (> 2 years CMR experience) and 4 inexperienced operators (< 1 year CMR experience)). Inter-observer variability for all parameters was assessed, using the mean of all expert observers as the reference. Analysis of saved contours for all observers showed a small number of common causes of variability. Based on these, consensus guidelines were agreed and instituted. 4 of the experienced and all the inexperienced observers repeated the analysis of the 10 most problematic data sets after 3 months. Inter-operator variances for analyses before and after introduction of guidelines were compared.The department as a whole showed wide inter-observer variation for all parameters . As expected, there was greater variation between inexperienced observers than experienced observers . Following introduction of consensus guidelines, mean SD for EF fell to 2.7%, LVEDV to 7.2 mls, LVESV to 6.7 mls. There was little change in mean SD for EDMM (18.8 gms). The use of guidelines eliminated differences between experienced and inexperienced observers for all parameters.Reported reproducibility of LV function measurements by CMRI is high for experienced observers but this may not be true in large departments or when observers are inexperienced. Internal audit should be routine for validating practice and consensus guidelines can help in raising standards to meet published values.None.


Noncompaction cardiomyopathy (NCC) is a rare genetic cardiomyopathy characterized by a thin, compacted epicardial layer and an extensive noncompacted endocardial layer. The clinical manifestations of this disease include ventricular arrhythmia, heart failure, and systemic thromboembolism.A 43-year-old male was anticoagulated by pulmonary thromboembolism for 1 year when he developed progressive dyspnea. Cardiovascular magnetic resonance imaging showed severe biventricular trabeculation with an ejection fraction of 15%, ratio of maximum noncompacted/compacted diastolic myocardial thickness of 3.2 and the presence of exuberant biventricular apical thrombus.Still under discussion is the issue of which patients and when they should be anticoagulated. It is generally recommended to those presenting ventricular systolic dysfunction, antecedent of systemic embolism, presence of cardiac thrombus and atrial fibrillation. In clinical practice the patients with NCC and ventricular dysfunction have been given oral anticoagulation, although there are no clinical trials showing the real safety and benefit of this treatment.The online version of this article (doi:10.1186/1471-2261-15-7) contains supplementary material, which is available to authorized users. The maiA 43-year-old male, obese, former-smoker patient was suffering from gout and had been anticoagulated by pulmonary thromboembolism for 1 year when he developed progressive dyspnea without anginal complaints. He was directed to a tertiary hospital for investigation of heart failure. Through echocardiographic evaluation, severe biventricular diffuse systolic dysfunction with suspicion of noncompacted cardiomyopathy was identified, even though such a hypothesis could not be confirmed [Figure et al., NCC does not present thromboembolic risk and there is no indication for anticoagulation [et al. recommended anticoagulation only in cases of left ventricular dilation and dysfunction or with previous embolic events [In 2008, according to Fazio gulation . On the c events . Recentlc events . It is gc events . CMRI plThis case report presents a patient with severe biventricular dysfunction in sinus rhythm, with previous pulmonary thromboembolism and biventricular thrombi. He presents a formal indication for anticoagulation. On the other hand, more studies are necessary to clarify this approach for patients presenting NCC with ventricular dysfunction in sinus rhythm.Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.Four-chamber view cine steady state free precession cardiac MRI. The left ventricle has increased diastolic volume and severe ventricular dysfunction. (ZIP 4 MB)Additional file 1:


MR tissue phase mapping (TPM) enables assessment of regional myocardial velocities. The purpose of this study was to compare regional myocardial velocities obtained by both TPM and speckle tracking echocardiography (STE) to assess agreement and potential systematic differences between modalities.N=19 patients with congenital heart abnormalities and biventricular physiology who had undergone cardiac MRI including TPM and transthoracic echocardiography within 6 months of MRI were identified (mean age=14 (7-20) years). Average time between MR and echo studies was 2.3±1.4 months. MRI was performed on a 1.5T MR-system . TPM were acquired data in short axis orientation using a black-blood prepared cine phase-contrast sequence with tri-directional phase encoding . Analysis included manual segmentation of the left ventricular contours and transformation of the acquired tri-directional velocities into radial, circumferential, and long-axis velocities.Echocardiograms were reviewed retrospectively. Mid-chamber short axis images with adequate endocardial visualization were selected. 2-dimensional STE assessment was performed offline using TomTec Image Arena (version 4.3) with determination of peak radial velocities and time-to-peak (TTP) analysis for both systole and diastole. Assessments were performed during a single cardiac cycle with imaging frame rate of 30 frames per second.To directly compare regional velocities, data from both modalities were mapped onto the mid-ventricular section of the AHA 16-segment model and systolic and diastolic radial peak velocities as well as TTP were calculated for each segment. Inter-modality differences for peak velocities and TTP were assessed using paired t-tests; p<0.05 was considered significant.2=0.82)   Figure . Compari) Figure . Mean ra) Figure .Regional myocardial velocities in pediatric patients can be measured by TPM and results correlate well with STE. Comparisons of regional velocities are similar, but systematically underestimated by STE. Diastolic TTP showed no significant difference. Further studies are needed to identify factors that may contribute to these differences.None.


To analyze the success rates and prognosis of heart valvuloplasty and valve replacement for elderly patients, and to provide clinical evidence.A total of 1240 patients who received heart valve surgeries in our hospital from June 2004 to October 2014 were selected and retrospectively analyzed. They were divided into two groups based on age (60), and those older than 60 (Group B) suffered from rheumatic valvular heart disease and nonrheumatic valvular heart disease including degenerative valve disease. Mitral valve replacement (MVR), tricuspid valve replacement (TVR), aortic valve replacement (AVR), double valve replacement (DVR), mitral valvuloplasty (MVP) and tricuspid valvuloplasty (TVP) were performed by using bioprosthetic and mechanical valves. Before surgery, coronary angiography, coronary artery bypass grafting (CABG), left atrial thrombectomy, left atrial wall folding and radiofrequency ablation were conducted. For the patients younger than 60 (Group A) who had congenital heart disease, rheumatic valvular heart disease and valvular heart disease, MVR, AVR, DVR, MVP, TVP and closed cuspid commissurotomy were performed with bioprosthetic and mechanical valves. The two groups were then monitored.The mortality rates of Group A and Group B were 2.7% (16 cases) and 3.1% (20 cases) respectively. They died mainly of malignant ventricular arrhythmias, multiple organ failure, left ventricular rupture, low cardiac output syndrome, acute renal failure, respiratory failure, upper gastrointestinal bleeding, mechanical valve failure and cerebrovascular accident. The two groups had significantly different application rates of bioprosthetic valve, times of auxiliary ventilation and hospitalization stay lengths (P<0.05), but left ventricular ejection fractions, left ventricular end-diastolic diameters (LVEDDs), mortality rates as well as times of aortic cross-clamping and cardiopulmonary bypass were similar (P>0.05). LVEDD, complicated coronary artery disease, CABG and grade of the New York Heart Association Functional Classification were independent risk factors for postoperative death.When heart valvuloplasty and valve replacement were performed for elderly patients, the success rate and prognosis could only be improved by optimizing preoperative preparation, shortening the times of cardiopulmonary bypass and aortic cross-clamping, and paying particular attention to myocardial protection and postoperative treatment. Recently, the elderly are more prone to hypertension, diabetes, obesity, renal failure and myocardial infarction due to lifestyle upgrade.This study was approved by the ethics committee of our hospital, and written consent has been obtained from all patients. A total of 1240 patients who received heart valve surgeries in our hospital from June 2004 to October 2014 were selected and retrospectively analyzed. There were 644 males and 596 females, aged 32-76 years old (average: 54.3±10.6). They were divided into two groups according to the age of 60, and those older than 60 (Group B) suffered from rheumatic valvular heart disease and nonrheumatic valvular heart disease including degenerative valve disease. The patients younger than 60 (Group A) had congenital heart disease, rheumatic valvular heart disease and valvular heart disease. The two groups had similar heart-related factors such as left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD), complications such as hypertension, diabetes and atrial fibrillation, and baseline clinical data such as gender (P>0.05).Before surgery, all patients received color Doppler ultrasonography to diagnose valvular heart disease, with clear indications for surgery.Coronary artery disease was diagnosed by coronary angiography or electrocardiogram together with symptoms, medical history and risk factors. Diabetes was defined as the intake of a diabetic diet or oral hypoglycemic agents or a FPG above 7 mM/L according to the new ADA criteria.10Under general anesthesia as well as medium, low-temperature cardiopulmonary bypass,All data were analyzed by SPSS 17.0. The categorical data were expressed as (x±s) and inter-group comparisons were performed with t test. The numerical data were subjected to Chi-square test. Independent risk factors were found by using the Logistic regression method. P<0.05 was considered statistically significant.The two groups had significantly different application rates of bioprosthetic valve, times of auxiliary ventilation and hospitalization stay lengths (P<0.05), but their mortality rates as well as times of aortic cross-clamping and cardiopulmonary bypass were similar (P>0.05) .The mortality rates of Group A and Group B were 2.7% (16 cases) and 3.1% (20 cases) respectively. They died mainly of malignant ventricular arrhythmias, multiple organ failure, left ventricular rupture, low cardiac output syndrome, acute renal failure, respiratory failure, upper gastrointestinal bleeding, mechanical valve failure and cerebrovascular accident. The incidence of postoperative complications such as cerebrovascular accident, respiratory failure and malignant ventricular arrhythmias as well as reoperation were significantly different (P<0.05) .LVEDD, complicated coronary artery disease, CABG and grade of the New York Heart Association Functional Classification were independent risk factors for postoperative death, as suggested by multivariate regression analysis .Elderly patients are vulnerable to brain, lung, liver and renal dysfunctions owing to long disease course,16In this study, surgery was simplified and success rate was elevated by using general anesthesia and low-temperature cardiopulmonary bypass and by completely exposing the heart and blood vessels. Since elderly patients are most prone to left atrial thrombi,18For the sake of the elderly with valvular heart disease, the surgical method should be cautiously selected, the time of aortic cross-clamping should be minimized, the myocardium should be well protected, and particular attention should be paid to postoperative treatment.In such a study design, selection of the population may introduce important biases in the findings. Two-thirds of our patients had ischemic symptoms (whether chronic or unstable angina) requiring coronary evaluation and do not represent a standard diabetic population. Coronary angiography has its own limitations in the study of coronary atherosclerosis. It may underestimate the early development of atheroma since compensatory enlargement of the vessel wall may initially accommodate young atheromatous plaques with limited lumen deformation.In summary, heart valvuloplasty and valve replacement are safe and reliable for elderly patients with valvular heart disease, ensuring satisfactory prognosis.


The majority of excess mortality among people with schizophrenia seems to be caused by cardiovascular complications, and in particular, coronary heart disease. In addition, the prevalence of heart failure and arrhythmias is increased in this population. Reduced efferent vagal activity, which has been consistently described in these patients and their healthy first-degree relatives, might be one important mechanism contributing to their increased cardiac mortality. A decrease in heart rate variability and complexity was often shown in unmedicated patients when compared to healthy controls. In addition, faster breathing rates, accompanied by shallow breathing, seem to influence autonomic cardiac functioning in acute unmedicated patients substantially. Moreover, low-physical fitness is a further and independent cardiac risk factor present in this patient population. Interestingly, new studies describe chronotropic incompetence during physical exercise as an important additional risk factor in patients with schizophrenia. Some studies report a correlation of the autonomic imbalance with the degree of positive symptoms  and some with the duration of disease. The main body of psychiatric research is focused on mental aspects of the disease, thereby neglecting obvious physical health needs of these patients. Here, a joint effort is needed to design interventional strategies in everyday clinical settings to improve physical health and quality of life. A large body of evidence has documented shortened life expectancy in patients with schizophrenia –4. It haSudden cardiac death happens when a malignant arrhythmia is triggered by an acute cardiac event  on the basis of a diseased myocardium . In addition to coronary artery disease or diseases of the myocardium, cardiac electrophysiological abnormalities might predispose to the development of ventricular fibrillation. This is especially important after acute myocardial infarction (AMI). Physicians found that various indices of heart rate variability (HRV) are of predictive value for the outcome of patients after AMI. Subsequently, these measures were transferred to other patient populations. Abnormalities were found for patients suffering from depression, anxiety disorders, alcohol dependence, and, in particular, patients suffering from schizophrenia –16. The The term HRV refers to a number of measures of different types. In general, nearly all HRV measures reflect mainly vagal (parasympathetic) modulation at the level of the heart. HRV is the physiological phenomenon of variation in the time interval between heart beats and it is determined by measuring the variation in the beat-to-beat interval (BBI). Although HRV measures can be obtained quite easily nowadays, there are numerous pitfalls. Autonomic indices depend very much on circadian rhythms, the duration and measurement procedure, the environment, and the artifact management. Time domain and frequency domain measures are most often used. In general, if time domain measures  are extremely low, true autonomic dysfunction can be assumed. Frequency domain measures , which are very susceptible to artifacts, quantify the amount of variance in heart rate at different underlying frequencies. Again, extremely low values of HF are associated with a lack of autonomic vagal modulation of heart rate.Besides linear HRV parameters describing the variance of BBIs, non-linear complexity measures have been developed to describe the regularity of heart rate time series. The application of these novel analyses has led to a higher sensitivity for detecting autonomic dysfunction , 18 and “Taking the pulse” has always been the first point of contact between physicians and the patient. It has recently been suggested that the heart rate corresponds to the rate of energy needed by the body. A reduction in heart rate of 10 bpm a day saves 5 kg of adenosintriphosphate (ATP). Furthermore, an increase in heart rate of 5 bpm corresponds to a significant increase in the atherosclerosis progression. Animal and human studies show that life expectancy is closely related to the medium heart rate. Increased resting heart rate has been shown to be a risk factor for reduced life expectancy in both the general population , 22 and In 1899, Emil Kraepelin described extensive autonomic alterations in patients with schizophrenia, including increased heart rates, altered pupillary function, increased sweating and salivation, as well as temperature changes . Most ofInvestigations in healthy first-degree relatives of patients displayed similarly increased heart rates although less pronounced –39. CompAs described above, HRV is the beat-to-beat oscillation of RR intervals around its mean value. It is the result of complex regulatory mechanisms through which the autonomic nervous system influences heart rate and keeps cardiovascular parameters within physiological health ranges.Both time and frequency domain parameters of HRV show reduced efferent vagal activity in unmedicated patients , 41–44. A concept that is closely connected to that of variability is complexity. It is important to realize that complexity is different from variability and there is no simple definition for it. A time series might show high variability and very low complexity. “Simple” time series are readily understood, and can be described concisely as having low information content or low complexity. Conversely, complex series are not easy to understand completely, they are full of unforeseeable shifting and require lengthy descriptions, making their information content high. Complex signals produced by healthy organisms might have dynamic properties such as non-linearity  or non-stationarity . Thus, high complexity describes to a certain degree healthy physiological properties, while low complexity describes reduced influence of various regulatory circuits. Vice versa, the more irregular and complex heart rate series are the more adaptive and stable is the underlying system. Such complexity is only in part reflected in measures of classical moment statistics such as means and SEs, which mainly describe the fluctuation of a biosignal . Since n®. Its application in RR time series has been described by Baumert et al.  is described below: the entropy (complexity) of a given text is defined in terms of the smallest algorithm that is capable of generating the text. Although it is theoretically impossible to develop such an algorithm, data compressors represent a sufficient approximation. The LZ77 algorithm for loss-less data compression introduced by Ziv and Lempel  is widelt et al. . The ratSimilarly to variability parameters, various studies during the last years have described reduced complexity of heart rate dynamics in patients with schizophrenia , 49–52. The evaluation of baroreflex sensitivity (BRS) is an established tool for the assessment of autonomic control of the cardiovascular system. The baroreflex or baroreceptor reflex is one of the body’s homeostatic mechanisms to maintain blood pressure at nearly constant levels. The baroreflex provides a negative feedback loop in which an elevated blood pressure reflexively causes the heart rate to decrease. By contrast, diminished blood pressure reduces baroreflex activation and causes heart rate to increase. A reduction in baroreflex control of heart rate has been reported in hypertension, coronary artery disease, myocardial infarction, and heart failure . There aStudies in unmedicated patients with schizophrenia show significantly reduced tachycardic and bradycardic slopes , 55, 56.During acute episodes, a putative relation between breathing rates and symptom severity were described in patients with schizophrenia 80 years ago , 60–63. Cardiorespiratory fitness is a strong and independent mortality predictor for humans . TherefoAutonomic dysfunction is most likely the consequence of long-lasting stressful experiences associated with the psychotic state, in addition to a genetic underlying predisposition to autonomic dysfunction as observed in relatives of patients. Therefore, the notion of a relation between the severity of the disease assessed by the global assessment of functioning scale (GAF) and autonomic dysfunction is not surprising . HoweverThere are three important areas for future research in patients with schizophrenia. First of all, studies need to investigate the definite relation between the degree of autonomic dysfunction and the potential risk of cardiovascular events for these patients. At a minimum, schizophrenic patients at increased risk should be identified. Second, the brain activations underlying autonomic dysfunction need to be assessed to elucidate pathophysiological mechanisms. Third, psychiatric research is focused mainly on mental aspects of the disease, thereby neglecting obvious physical health needs of patients with schizophrenia. Here, a joint effort is needed to design interventional strategies in everyday clinical settings to improve physical health and quality of life of our patients.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.