Diabetes mellitus (DM) is associated with increased risk of cardiovascular disease. Detection of early cardiac changes before manifest disease develops is important. We investigated early alterations in cardiac structure and function associated with DM using cardiovascular magnetic resonance imaging.Participants from the UK Biobank Cardiovascular Magnetic Resonance Substudy, a community cohort study, without known cardiovascular disease and left ventricular ejection fraction ≥50% were included. Multivariable linear regression models were performed. The investigators were blinded to DM status.P=0.065), LV mass , or right ventricular ejection fraction . However, both LV and right ventricular volumes were significantly smaller in DM, , LV mass/volume: 0.026 (0.01 to 0.04) g/mL, P=0.006. Both left atrial and right atrial emptying fraction were lower in DM . LV global circumferential strain was impaired in DM .A total of 3984 individuals, 45% men, (mean [SD]) age 61.3 (7.5) years, hereof 143 individuals (3.6%) with DM. There was no difference in left ventricular (LV) ejection fraction (DM versus no DM; coefficient [95% CI]: −0.86% [−1.8 to 0.5]; In a low-risk general population without known cardiovascular disease and with preserved LV ejection fraction, DM is associated with early changes in all 4 cardiac chambers. These findings suggest that diabetic cardiomyopathy is not a regional condition of the LV but affects the heart globally. Diabetic cardiomyopathy has typically been described as a condition related to changes in the left ventricle (LV). In the present study, participants from the UK Biobank without known cardiovascular disease and with preserved LV ejection fraction (EF) were examined with cardiac magnetic resonance imaging to study early changes in cardiac morphology and function associated with diabetes mellitus. We find that diabetes mellitus is associated with discrete but significant cardiac remodeling affecting all 4 cardiac chambers. LV volumes were smaller and mass-to-volume ratios were larger in diabetes mellitus despite no differences in LVEF or LV mass. Furthermore, subtle changes in cardiac LV deformation could be detected using cardiac magnetic resonance imaging-tagging even in the presence of preserved EF. Changes in the right ventricle (RV) related to diabetes mellitus has so far remained largely unexplored. In parallel with our findings in the LV, diabetes mellitus was also associated with smaller RV volumes without changes in RVEF. A consistent pattern also emerged for both atria, demonstrating smaller left atrial volumes, smaller right atrial volumes, and lower atrial emptying fractions, which occurred despite no changes in LVEF or RVEF. Thus, our findings suggest that diabetic cardiomyopathy is not a regional condition of the LV but affects the heart globally. These changes can be observed despite no impairment in LVEF or RVEF and before manifest heart disease develops. The present findings therefore significantly add to our current understanding of diabetic cardiac complications and open a new direction for early detection and research into diabetic cardiomyopathy.Lima and XieSee Editorial by 1 Cardiovascular disease (CVD) is the leading cause of death in DM, and the risk of mortality is doubled compared to individuals without DM.3 Accelerated heart failure is a common manifestation of CVD in patients with DM and can be unrelated to macrovascular ischemic heart disease.5 A special subset of heart disease in DM has been proposed, diabetic cardiomyopathy, which can lead to diastolic and systolic heart failure.7Globally, >500 million people currently have diabetes mellitus (DM) and this prevalence is expected to increase in the coming decades.9 and, in the later stages, affected systolic function. Diabetic cardiomyopathy has been described in 3 stages: the early stage with normal left ventricular (LV) size, mass, and wall thickness, and only discrete changes in diastolic function; the second stage, characterized by abnormal diastolic function and no or only discrete changes in systolic function; and the late stage of diabetic cardiomyopathy where both systolic and diastolic function are affected.12The hemodynamic and biomechanical evidence of early changes related to DM stems from echocardiography, suggesting premature diastolic dysfunction,13 Discrete changes in LV systolic function have been detected using sensitive methods, such as speckle-tracking echocardiography and cardiovascular magnetic resonance imaging (CMR) tagging.17 Small studies suggest that DM could also potentially affect right ventricular (RV) function. Changes in RV morphology and function related to DM, however, are not well described.20Typical early morphological findings relating to DM, as currently understood, are LV hypertrophy and decreased LV chamber size, often with preserved LV ejection fraction (LVEF).21 Improved image quality is particularly relevant in patients with DM, where echocardiography can often be difficult to perform because of concomitant obesity. Measurement of strain using CMR-tagging, which at present is the CMR-modality of choice for measuring deformation, can provide insights into discrete myocardial dysfunction.22CMR is, at present, considered the method of choice for measuring cardiac morphology and function. Compared to echocardiography, CMR demonstrates superior reproducibility, better interobserver and intraobserver variability, better imaging quality, and use of fewer geometric assumptions.In the present study within the UK Biobank cohort, we investigated how the presence of DM is associated with cardiac morphology and function in a subsample of participants who has undergone CMR. We hypothesized that CMR would detect early cardiac changes related to DM in a low-risk general population without known CVD and with preserved ejection fraction.23 The UK Biobank encourages and provides as wide access as possible to its data and samples for health-related research in the public interest by all bona fide researchers from the academic, charity, public, and commercial sectors, both in the UK and internationally, without preferential or exclusive access for any user. Data can be sought directly from UK Biobank via online application at http://www.ukbiobank.ac.uk/register-apply/.The UK Biobank is a large prospective cohort study of ≈500 000 unselected community volunteers aged 40 to 69 at the time of enrollment, living in the United Kingdom. The design and conduct of the study have both been described in detail previously.The present study population consisted of the 5065 individuals who underwent CMR examination as part of the pilot phase (April 2014–August 2015) of the UK Biobank imaging enhancement.In the present study, 172 participants were excluded due to poor cine image quality, 467 were excluded due to poor quality/not analyzable tagging imaging quality, 190 participants were excluded due to known CVD, and 252 participants were excluded due to a LVEF below 50%  was used in all participants. LV and RV long-axis cines and a short-axis stack of balanced steady-state free precession cines were acquired using following typical parameters: Repetition Time/Echo Time=2.6/1.1 ms, flip angle 80°, Grappa factor 2, voxel size 1.8 mm×1.8 mm×8 mm (6 mm for long axis).The UK Biobank CMR protocol has been described in detail elsewhere.25 Investigators were blinded to DM status.Manual analyses were performed of the LV, RV, left atrium (LA), and right atrium (RA) by observers across 2 core laboratories. Analysis software was cvi42 . LV papillary muscles were included in blood pool volumes and thus excluded from LV mass. Detailed methodology and intraobserver and interobserver variability has been described elsewhere.26 Atrial emptying fraction was calculated as . Atrial and ventricular measures were assessed in absolute measures and also indexed to body surface area using Du Bois formula.27The LV mass/volume ratio was determined by dividing the LV mass by the LV end-diastolic volume. Mass/volume ratio indexes wall thickness to cavity size and is conceptually equivalent to the echocardiogram-derived relative wall thickness .28 A grid was aligned automatically to the myocardial tagging planes at end diastole. End systole was determined visually, and tags were manually adjusted at key phases during the cardiac cycle including the end systolic and last frame. Circumferential myocardial strain was calculated by the software from the motion of the intersected tag lines at basal, mid, and apical levels. As previously described, global circumferential strain (GCS) at the mid-level has been shown to have the greatest degree of reproducibility.29 Torsion, the wringing motion induced by contracting myofibers in the LV wall during systole, was calculated from the basal and apical strain measures.30 For those cases where a basal or apical slice was missing or not analyzable, torsion was calculated between mid-ventricular and the other available slice. Torsion has been shown to be a sensitive marker of myocardial dysfunction.32Semiautomated analysis of tagged cine images was performed using CIM software , which has been validated previously in phantoms and patients.33 Gestational DM alone was determined as no DM. Ethnicity was categorized as white versus nonwhite. Systolic and diastolic blood pressures were defined as the mean of two measurements . Duration of DM was estimated from self-reported age at DM and age at imaging. HbA1c (glycated hemoglobin) was measured twice in the UK Biobank, first instance was during the initial visit in 2006 to 2010 , second instance was during first repeat visit in 2012 to 2013 ; both values are provided in Table 34 The present study population was categorized into tertiles of metabolic equivalent minutes/d and a high physical activity level was determined as the participants in the highest tertile. Use of cholesterol medication, blood pressure medication, and DM medication were determined by self-report. Alcohol consumption was categorized into daily alcohol consumption versus less than daily alcohol consumption by self-report.Comorbidities were determined during the imaging visit by self-reported through an electronic questionnaire and by an interview with a healthcare professional. In cases where data from the imaging visit were unavailable information from the enrollment visit were used except for height, weight, blood pressure, heart rate, and smoking status, which were captured exclusively at the time of imaging. DM status was determined by participants’ response to the binary questionnaire item DM diagnosed by a doctor or self-reported use of DM medication.2 test and continuous variables with Student t test.All analyses were performed with STATA 15.1 . For demographics, categorical variables were analyzed with the χ18 This, however, was not found in the present study (P for interaction >0.9). Other relevant interactions were tested, and none were found to be significant. In a sensitivity analysis, propensity score matching was performed using the covariables from the multivariable model on representative outcomes. A P<0.05 was considered statistically significant.The association between DM and cardiac measures was analyzed in 3 different linear regression models: a crude model; a model including age and sex; and a multivariable model including age, sex, body mass index, systolic blood pressure, diastolic blood pressure, physical activity (highest tertile versus lowest 2 tertiles), current smoking (yes versus no), daily alcohol consumption (yes versus no), use of blood pressure medication (yes versus no), use of cholesterol medication (yes versus no), and ethnicity (white versus nonwhite). An interaction between DM, RV volumes, and sex has previously been reported.This study was covered by the general ethical approval for UK Biobank studies from the National Health Service National Research Ethics Service on 17 June 2011 (Ref 11/NW/0382). All participants gave written informed consent.A total of 3984 participants were included, hereof 1792 men (45%), mean age 61.3 years. In the present population, 3.6% of the participants had DM. Participants with DM were more likely to be older, be men, have higher body mass index, higher systolic blood pressure, and be less physically active  was lower in DM compared to participants with no DM.In the age- and sex-adjusted models, there were no significant differences in LA measures. Following full multivariable adjustments, DM was associated with smaller LAmaxIndexed and RVSVIndexed were smaller in the DM population.Similar to LV measures, RVEF did not differ between participants with and without DM. However, as with LV dimensions, RVEDVIndexed and RAminIndexed were smaller in participants with DM. In addition, right atrial emptying fraction was significantly lower in participants with DM.In both age- and sex-adjusted models, and following multivariable adjustments, RA measures were all significantly different in DM versus no DM. Thus, both RAmaxP=0.14, n=3654; and for LAEF, the effect size was estimated to −7.85 (−12.9 to −2.8), P=0.002, n=3680.In a sensitivity analysis, we performed propensity score matching using covariates from the multivariable model to match participants without DM to participants with DM. The treatment effects from the propensity score matching were essentially similar to the linear regression coefficients. Thus, for the LVEDVI the effect size was estimated to (average treatment effect on the treated [95% CI]) −2.61 (−6.1 to 0.8), 35 our findings suggest that diabetic cardiomyopathy is not a regional condition of the LV but affects the heart globally. These changes can be observed before impairment in LVEF or RVEF occurs and before manifest heart disease develops. The present findings, therefore, significantly add to our current understanding of early cardiac alterations related to DM and open a new direction for early detection and research into diabetic cardiac complications.In the present study, individuals without known CVD and with preserved LVEF from the UK Biobank, a low-risk general population study, were examined to study early changes in cardiac morphology and function associated with DM. The findings of this comprehensive study suggest that DM is associated with discrete but significant cardiac remodeling affecting all 4 cardiac chambers. Thus, in contrast to the current paradigm,35CVD is the most common complication in DM, which is the reason why both American and European DM and cardiology associations have developed common recommendations for detecting, preventing, and treating CVD in DM. Present guidelines, and the majority of research, have so far described diabetic cardiomyopathy as a disease typically related to the LV.6 presented evidence of a special myocardial involvement in DM from autopsies of 4 patients with heart failure, DM, and kidney disease without major disease of the coronary arteries. Research in the last decades have demonstrated that early changes can be detected in the diabetic LV using conventional echocardiography, tissue Doppler imaging, and deformation imaging.11In 1972, Rubler et al36 Furthermore, using CMR-tagging, which is considered the gold standard for CMR deformation imaging,37 we find global strain to be impaired even in the presence of normal LVEF. Thus, these findings correspond to studies of type 2 DM,16 heart failure with preserved ejection fraction patients,38 and findings from type 1 DM without known heart disease11 studied with speckle-tracking echocardiography, and other similar research.In the present study of changes in LV morphology and function, findings from previous decades of research are confirmed in that we find subtle changes in LV volumes and in the relationship between LV mass-to-volume. These findings are important as they demonstrate that subtle changes are present even before LV mass increases and before impairment in LVEF, and these changes are associated with adverse events.18 found smaller RV volumes using CMR but only in men and not in women, and Widya et al39 found similar findings but only studied men. In contrast, we find RV morphology to be altered similarly in both men and women with DM.Changes in the RV associated with DM remain largely unexplored; the present study, therefore, provides a novel direction for future research. Parallel to our findings in the LV, we find that, while RVEF was unaffected, there were significant changes in RV volumes, which were smaller in individuals with DM. Recent reports in smaller populations have suggested changes in RV related to DM: Patscheider et al41 With the current understanding of diabetic cardiomyopathy, the finding of smaller LA volumes seems counterintuitive in that larger atrial volumes would be expected in relation to possibly increased LV filling pressures. It is important, however, to remember that the present findings represent very early cardiac changes associated with DM. In The Thousand & 1 Study, a population of 1100 type 1 DM patients without known heart disease with a mean DM duration of 25 years, LA volume indexed for body surface area was not different when compared to 200 healthy controls.11 LA enlargement, therefore, probably represents a later finding in the pathogenesis of diabetic cardiomyopathy. Significantly, the present finding of lower LAEF indicates that reduction in LA function develops before impairment in LV function. In addition, RA morphology and function were examined in the present study. Here, RA volumes were found to be smaller in DM, and right atrial emptying fraction was found to be lower. To the best of our knowledge, this study is the first to systematically report alterations in RA morphology and function in relation to DM.In the present study, we find smaller LA volumes and lower LAEF associated with DM. Low LAEF has previously been shown to be a strong predictor of atrial fibrillation, which is common in patients with DM.In summary, CVD is the most important complication in DM and early detection of cardiac involvement is of pivotal importance. In the present study of 3984 participants without known heart disease and with preserved LVEF from the UK Biobank Cardiac Magnetic Resonance Substudy, early alterations in cardiac morphology and function were observed. Specifically, DM was associated with alterations in all 4 cardiac chambers. LV volumes were smaller and mass-to-volume ratios were larger in DM before differences in LVEF or LV mass could be detected. Furthermore, subtle changes in cardiac LV deformation could be detected using CMR-tagging even in the presence of preserved ejection fraction. DM was also associated with smaller right ventricular volumes without changes in right ventricular ejection fraction. A consistent pattern also emerged for both atria, demonstrating smaller LA volumes, smaller RA volumes, and poorer function with lower emptying fractions. The present findings, therefore, corroborate previous findings of changes in the LV and extend current knowledge of diabetic alterations to include changes in the RV, LA, and RA.42 Also, DM is associated with cardiac autonomic neuropathy, increased blood pressure, and metabolic disturbances, leading to increased resting heart rate,43 as seen in the present study. It is possible that increases in resting heart rate contribute to an initial remodeling and thereby smaller chamber sizes to match cardiac output with circulatory requirements. A similar mechanism could be at play in pulmonary disease where smaller chamber sizes45 are matched by increases in resting heart rate.46 It is, however, also possible that smaller chamber sizes contribute to higher resting heart rates as causality cannot be determined from the present study. Furthermore, there may be a mechanical explanation in which chambers sizes are decreased to maintain ejection/emptying fraction.47 Other unexplored mechanisms may also be at play and should be studied in future research.Pathophysiological considerations should briefly be considered. A possible contributing mechanism for the smaller chamber sizes could be increased fibrosis and ventricular hypertrophy, and thereby relative enlargement in wall thickness.48 The findings, therefore, possibly represent changes earlier in the natural history of diabetic cardiomyopathy compared to other populations. Second, the population consisted mainly of ethnically white (96%). Although interaction analyses did not reveal a difference in the relationship between cardiac changes, DM, and ethnicity, findings may be different in other populations. Third, there could have been a misclassification of participants with unknown or unreported DM as not having DM. This, however, would draw the findings toward to null-hypothesis and can, therefore, not explain our findings. Last, there may be subclinical ischemic heart disease, which we cannot account for.Possible limitations should be considered. First, the UK Biobank population represents a low-risk cohort and have been shown to be healthier than the background population, as demonstrated by the low prevalence of DM compared with data from the Health Survey for England.In conclusion, diabetic cardiomyopathy is a global condition affecting all 4 chambers of the heart. In the early phase, DM is associated with smaller cardiac chambers as well as discrete or subclinical impairments in chamber functions. These findings represent a shift in the understanding of diabetic cardiomyopathy, and, if confirmed in other studies, are a significant step forward in identifying early myocardial changes related to DM.


The magnetic resonance (MR) has taken nowadays a crucial role in the evaluation of ischemic heart disease, which is regarded as the technique of reference for the assessment of myocardial viability. Delay enhanced cardiovascular magnetic resonance (DE-CMR) is a specific marker of myocardial necrosis, using this technique can determine the presence of infarct localization, size and transmurality, parameters of great importance for determining treatment and prognosis.To determine if infarct size measured by DE-CMR is a prognostic factor for mortality in patients with ischemic heart disease.Sixty eight patients were referred to cardiovascular magnetic resonance because of suspicion or knowledge of ischemic heart disease between September 2004 and September 2008. CMR imaging was performed using GE 1.5 T system. Steady state free precession (SSFP) cine MR images were acquired in long and short axis orientation. Evaluation of functional parameters including end diastolic volume (EDV), end systolic volume (ESV), left ventricle ejection fraction (LVEF) and systolic volume (SV) indexed a body surface area (BSA).The average age of the study population was 65.6 +/- 10.7 SD) years, 12% patients were in functional class III-IV NYHA, the mortality rate was 16.1%. We evaluate 1156 segments and the 39.7% of this presented delay enhancement. The myocardial infarction size was significantly higher in patients who died (21.6% vs. 14.4% p = 0.01). The relationship between infarct size, end-sistolic volume index, end-diastolic volume index, ejection fraction of left ventricle and systolic volume index, were statically significative (p < 0.001). The mayor adverse cardiac events (MACE) were presented in 90% of the group of death patients (p = 0.001). Figure 0.7 SD yeInfarct size measured by delay enhanced cardiovascular magnetic resonance (DE-CMR) is a prognostic factor for mortality in patients with ischemic heart disease.


Background and Objectives: Cardiac resynchronization therapy (CRT) is a successful treatment option for appropriately selected patients. However, one–third of recipients do not experience any positive outcome or their condition even declines. We aimed to assess preimplantation factors associated with worse survival after the CRT. Materials and Methods: This was a retrospective unicenter trial. The study cohort included 183 consecutive CRT-treated patients. Baseline demographic, clinical, electrocardiographic, and echocardiographic characteristics were analyzed. Results: After the median follow-up of 15.6 months (9.3–26.3), 20 patients had died (11%). In multivariate Cox regression analysis, ischemic origin of heart failure (HF) was a significant predictor of poor survival (adjusted hazard ratio (aHR) 15.235, 95% confidence interval (CI) (1.999–116.1), p = 0.009). In univariate Cox regression, tricuspid annular plane systolic excursion (TAPSE) <15.5 mm , p = 0.012), post-implantation prescribed antiplatelet agents , p = 0.037), statins , p = 0.025), and nitrates , p = 0.011) appeared to be related with adverse outcome. Conclusions: ischemic etiology of HF is a significant factor associated with worse survival after the CRT. Decreased TAPSE is also related to poor survival. Heart failure (HF) is a major public health problem associated with significant hospital admission and mortality rates, as well as costly health care expenditures . It is eCardiac resynchronization therapy (CRT) is an established treatment for symptomatic New York Heart Association (NYHA) class III–IV patients resistant to treatment with optimal medical therapy, who have left bundle branch block (LBBB), QRS >130 ms, and left ventricular (LV) ejection fraction <35% . CRT impDespite the recent progress, 30%–40% of patients do not respond favorably to CRT, or their condition even declines ,12. Due Ischemic cardiomyopathy is another issue. The Predictors of Response to CRT (PROSPECT) trial concluded that the nonischemic etiology was associated with more significant improvement in clinical state and LV reverse remodeling . AccordiEchocardiographic parameters to predict CRT response have also been widely investigated. Although studies have proposed some single prognostic factors or their combinations, in prospective multicenter double-blinded trials, neither was eligible to guide for CRT patient selection ,25.Our study aimed to assess the baseline prognostic factors related to worse survival after CRT.This was a retrospective study to review the patients who underwent implantation of a cardiac resynchronization device at the Hospital of Lithuanian University of Health Sciences between January 2014 and May 2019. Data were manually collected between 10 March and 15 May 2019, in the “Hospital Information System”. Participants were included according to The Australian Refined Diagnosis Related Groups (AR-DRGs) classification codes Z95 and I50. We included both patients who had novel device implantation and those who upgraded from previous right ventricular pacing. Missing echocardiographic measurements were calculated using EchoPac  software. Patients who lacked the below mentioned clinical data in their records or whose echocardiographic images were not available to assess were excluded. Equally, we omitted three patients who died during the first three months of the follow-up and those who later experienced cardiac resynchronization device removal without replacement. Finally, 183 cases proceeded to further analysis. We divided the total cohort into two sub-groups according to survival status, which was evaluated on 13 May 2019.The study protocol was approved by Kaunas Regional Biomedical Research Ethics Committee at the Lithuanian University of Health Sciences (No. BE-2-86) and all subjects provided written informed consent.(a)Gender, age;(b)Type of the implanted device (CRT-D or CRT-P);(c)Echocardiographic characteristics: LV end-diastolic diameter and index , LV systolic and diastolic volumes and indices , LVEDV, LVEDV(i)), LV ejection fraction (LVEF) and diastolic function, left atrium diameter (LA) and volume (LAV), right atrium (RA) and right ventricular (RV) diameters, tricuspid annular plane systolic excursion (TAPSE), pulmonary artery systolic pressure (PASP), and grade of mitral regurgitation. All measurements were performed following guidelines of the American Society of Echocardiography and the European Association of Cardiovascular Imaging ,27,28. A(d)Functional status: 6 min walking test (6MWT), NYHA functional class;(e)Comorbidities: diabetes, chronic obstructive pulmonary disease, chronic kidney disease, malignancies, permanent AF, hypertensive heart disease, and ischemic cardiomyopathy. Ischemic etiology was considered when a patient had one or more of the followings: myocardial infarction, coronary artery bypass surgery, percutaneous transluminal coronary angioplasty, at least one coronary narrowing more than 75%, or left main artery stenosis more than 50%;(f)Medications: beta-adrenoceptor blockers (BB), angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), mineralocorticoid antagonists, loop diuretics, antiplatelets, anticoagulants, glycosides, antiarrhythmics, statins, and nitrates.The following demographic, clinical, electrocardiographic, and echocardiographic characteristics were analyzed:p value of 0.05 was considered statistically significant. Statistical analysis was performed with IBM SPSS 22.0 software. Categorical variables were presented as a percentage and were analyzed with chi-square statistics. The Shapiro–Wilk test was used to assess the normality of continuous data. Non-Gaussian distributed variables were described as median with 25–75th percentiles and analyzed with Mann–Whitney U test, normally distributed variables were expressed as mean ± standard deviation (SD) and compared using Student’s t test. To find out the significance of parameters in predicting the CRT outcome, receiver operating characteristic (ROC) curves were used. The optimal cut-off points were selected based on the maximal Youden index (sensitivity + specificity − 1). Cox regression survival analysis was applied to evaluate the predictive value of multiple factors on mortality. Variables that were significant in univariate analysis were adjusted for the multivariate analysis. To compare the risks of observed mortality, Cox proportional hazard models were used. Kaplan–Meier curves and the log-rank test were used to assess observed cumulative survival. A two-sided Over a study period of 63.6 months, a total of 183 patients were included. Most of the patients were senior men with the mean age of 66.4 ± 11.4 years. There were 155 (84.7%) novel implantations. Complete left bundle branch block was observed in 76.6% patients and wide QRS duration (>130 ms) in 84.8% of patients, while average QRS duration was 165.3 ± 31.8 ms. Two-thirds of the group had CRT-P and NYHA functional class III. Hypertensive heart disease occurred in 82.2%, atrial fibrillation 30.7%, and diabetes in 22.2% of the cases. Ischemic etiology of HF was more common than non-ischemic. Pathogenetic heart failure medical treatment was prescribed as follows: Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) were received by 69.7%, beta-adrenoceptor blockers by 81.9%, and mineralocorticoid antagonists by 66.7% of patients. Loop diuretics were taken by 68.4%, amiodarone by 20.3%, and oral anticoagulants by 52.0% of the patients .During a median follow-up of 15.6 months (9.3–26.4), 20 (11%) patients died. The median follow-up duration of survivors was 39.3 months (23.7–57.1), of the dead, 15.2 months (7.4–26.7).There were relatively more males in the fatal outcome group. The predominant cause of HF in this group was ischemic cardiomyopathy. Moreover, chronic kidney disease was more prevalent in the fatal outcome group. Indeed, patients of the survivors’ group demonstrated significantly better right ventricular function, as indicated by superior TAPSE and lower pulmonary hypertension. Patients of the fatal outcome group were more often prescribed with statins, antiplatelets, and nitrates .p = 0.054). There were no differences between the groups in other analyzed parameters during the follow-up.During the follow-up, a more considerable relative increase (Δ) in LVEF in the survivors was noted compared with that of the fatal outcome group  vs. 0 , According to the ROC analysis, baseline TAPSE values lower than 15.5 mm and PASP values higher than 39.5 mmHg were associated with an increased risk of death . In the Kaplan–Meier survival analysis, male gender, ischemic origin and TAPSE <15.5 mm were related to decreased survival. PASP values less than 39.5 mmHg were also linked to a better prognosis (log-rank = 0.107). The survival curves according to these predictors are shown in Gender; ischemic origin; TAPSE; PASP; and treatment with antiplatelets, statins, and nitrates were included in the univariate Cox regression analysis. Ischemic etiology and treatment with statins, nitrates, antiplatelets, and TAPSE were significantly associated with the decreased survival after the CRT. Multivariate Cox regression analysis was performed to acknowledge the independent effect of these predictors. Ischemic cardiomyopathy was established as a significant independent risk factor associated with worse survival after the CRT .This was a retrospective single-center trial comprised of all patients who underwent cardiac resynchronization device implantation in our hospital from January 2014 to May 2019. In contrast to other trials, we included all patients independently of their heart rhythm status (sinus rhythm or AF), cause of the conduction disorder, origin of the HF, NYHA class, and their comorbidities. We included both novel implantations and upgrades from a permanent pacemaker or implantable cardioverter-defibrillator. Moreover, we could precisely evaluated patients’ survival as we had access to the national database.The main limitation of this study is a retrospective single-center design with relatively small sample size. Therefore, we could not take into account all the risk factors, clinical situations, psychoemotional factors, and each of the newest concepts. The latest studies in this field also report significant findings about the importance of patients’ nutritional status and body mass index before the CRT and their impact on treatment outcomes . MoreoveComparing the baseline of our study participants’ characteristics with patients enrolled in the CRT Survey II, we found that the median age of our population was below the median of the European survey (67 years (60–75) vs. 70 years (62–76). In both studies there was a similar rate of males (78% vs. 76), patients with LBBB (77% vs. 73%), atrial fibrillation (30.7% vs. 26.0%), QRS duration >130 ms (84% vs. 87%), and CRD-P implantations (69% vs. 70%) involved. Our study included more patients with NYHA class III–IV (76.1% vs. 60%) and novel device implantation (85% vs. 72%). On the other hand, our participants had more advanced systolic heart failure (LVEF 23% (18–30%) vs. 29% (23–34%)) and ischemic etiology was more often an underlying cause of heart failure (56.1% vs. 45%). There were slight differences in adherence to pathogenetic HF medications at discharge: Beta-blockers were prescribed for 81.9% of our patients and 89% of the CRT Survey II participants, ACE inhibitor or ARB blockers for 69.7% vs. 89%, and mineralocorticoid antagonist for 66.7% vs. 63%, respectively [As we have seen, not all participants of our study totally matched conventional CRT indications . The underlying reason is that patients do not have equally pronounced CRT indications, for example, there can be relatively asymptomatic (NYHA class <III) patients with prolonged QRS duration who require defibrillator implantation for the prevention of sudden cardiac death or, contrarily, patients with moderately reduced left ventricular ejection fraction with high NYHA class and QRS >130 ms. Until 2016, guidelines recommended CRT for patients with QRS 120–150 ms [After a univariate adjustment, male gender; application of statins, nitrates, and antiplatelet agents; the ischemic origin of heart failure; TAPSE <15.5 mm; and PASP ≥39.5 mmHg appeared to be indicators of adverse long term survival. A univariate association between these medications and the unfortunate outcome could be explained because they are used for the pathogenetic treatment of ischemic cardiomyopathy and its complications. As we have seen after a multivariate adjustment, the ischemic origin of heart failure remained the only significant prognostic marker associated with worse survival after the CRT. Statins, nitrates, nor antiplatelets negatively impacted on CRT outcome.Researchers have not yet concluded whether the ischemic origin of heart failure is associated with worse survival after the CRT ,13. PatiThe most recent clinical trials led by Francisco  and JianReduced RV function has been associated with adverse prognosis in HF patients, but there is less data available about whether preimplantation RV function is associated with CRT outcome. Our study showed that decreased baseline RV function expressed by TAPSE is related to poor survival after the CRT. Values of TAPSE represent RV function and are also negatively affected by pulmonary hypertension, which in our study also appeared to be related to the adverse CRT outcome. Usually, TAPSE evaluation is part of a routine echocardiographic examination, so if TAPSE could lead to reliable CRT outcome predictions, it would be simple to use in clinical practice. However, the role of this and other RV function parameters in CRT patient selection is still under dispute. Trials demonstrate different TAPSE cut-off values associated with CRT outcome  but thePulmonary hypertension is another factor correlating with poor prognosis in patients with HF. However, there is a lack of data about whether it also affects the outcome of the CRT. In retrospective studies by Wang  and SterIn the context of larger clinical trials, our research has an additive prognostic value in CRT patient selection. Due to our study design, any strict practical recommendations can be admitted. However, these findings can act as a stimulating factor to further larger-scale prospective studies to ensure the real scientific impact of heart failure etiology and right ventricular function on CRT outcome.This study has revealed that ischemic origin of heart failure is a significant predictor related to worse survival after CRT. Decreased right ventricular function is also a negative prognostic factor associated with inferior long term outcome. Patients require further clinical evaluation and reconsideration of CRT indications in case of ischemic cardiomyopathy, severe RV dysfunction, or pulmonary hypertension.


BackgroundDespite automated defibrillation and compression-first resuscitation, out-of-hospital cardiac arrest (OHCA) survival remains low. Resuscitation guidelines recommend that chest compressions should be done over the lower half of the sternum, but evidence indicates that this is often associated with outflow obstruction. Emerging studies suggest that compression directly over the left ventricle (LV) may improve survival and outcomes, but rapid and reliable localization of the LV is a major obstacle for those first responding to OHCA. This study aimed to determine if a simplified, easy-to-use ultrasound device (bladder scanner) can reliably locate the heart when applied over the intercostal spaces of the anterior thorax in supine patients. Furthermore, we sought to describe the association between largest scan volumes and underlying cardiac anatomy with particular attention to the long axis of the LV.MethodologyWe recruited healthy male and female volunteers over 40 years of age. Using a bladder scanner to evaluate the left sternal border and mid-clavicular lines, we determined the maximal scan volumes at 10 intercostal spaces for each participant. Cardiac ultrasound was then used to evaluate the corresponding underlying cardiac anatomy and determine the area overlying the long-axis view of the LV. Descriptive statistics  were used to quantify demographic information, typical scan volumes across the chest, the frequencies of the best long-axis LV view location. This was then repeated for left sternal border assessments only. Kappa was determined when evaluating agreement between the largest left sternal border scan volume and the best long-axis LV view location.ResultsThe long-axis LV was the predominant structure underlying the largest scan volume in 39/51 (76.5%) patients. When limited to left sternal border volumes only, the long axis of the LV was underlying the maximum volume intercostal space in 46/51 . The largest left sternal border scan volumes were located over the best long-axis LV view in 39/51  of the study participants with a Kappa statistic of 0.68 . ConclusionsIn this cross-sectional study of healthy volunteers, an easy-to-use ultrasound device (bladder scanner) was able to reliably localize the heart. Largest scan volumes over the left sternal border showed substantial agreement with the intercostal space overlying the long axis of the LV. Further investigations are warranted to determine if such localization is reliable in cardiac arrest patients. Despite automated defibrillation and compression-first resuscitation, out-of-hospital cardiac arrest (OHCA) survival remains low at approximately 10% . Chest cA recent porcine study  reportedBladder scanners are ultrasound devices used to identify bladder location and volume . InformaThe primary objective of this study was to determine if an easy-to-use ultrasound device (bladder scanner) could reliably locate the heart when applied to the chest of healthy adult volunteers. We also explored the association between the largest scan volumes and underlying cardiac anatomy with particular attention to the LV.2 and classified as normal (<25), overweight (25-29.9), or obese (≥30). We pretested our scanning protocol  on a sample of 15 patients [After obtaining approval from the Research Ethics Board of University of Saskatchewan Bio #461), we recruited male and female volunteers over 40 years of age through the Clinical Learning and Resource Center’s Standardized Patient Program at the University of Saskatchewan. We collected biometric data including weight, height, and chest circumference at the nipple line. Body mass index (BMI) was calculated as weight (kg)/height (m)patients . We then, we recrExperimental localization of the heart was performed using a Verathon BladderScan Prime Plus bladder scanner . After training during our pretest of 15 patients, each member of our inter-professional study team performed scans on several patients following a standardized approach and assessing each space on the grid. The transducer was placed perpendicular to the chest and volumes were recorded. This was followed by cardiac ultrasonography with GE Venue 40 machines . Cardiac ultrasonography was done by PO and RW to determine whether the bladder scanner had correctly identified the heart, as well as to describe the underlying cardiac anatomy associated with the largest scan volumes Figure . The ultDescriptive statistics  were used to quantify demographic information, typical bladder scan volumes across the chest, and the frequencies of the best long-axis LV view location. This assessment also evaluated the proportion of scanner-determined intercostal spaces that were located over a significant portion of the long axis of the LV. Recognizing that assessment of 10 points during a resuscitation would be impractical, a repeat analysis was performed utilizing the largest scanner volumes only among the five left sternal border locations, again assessing the proportion of participants who would presumably receive LV compression if the maximal volume location was targeted. A second, more conservative evaluation was also undertaken to assess how frequently the predicted location by scanner volumes at the left sternal border overlay not just a substantial portion of the long axis of the LV but the best view of the LV. Both of these assessments limited to the left sternal border were further explored for differences by sex and BMI. To further quantify agreement between the ICS of the best LV view and the largest left sternal border volume, the associated Cohen’s Kappa statistic was calculated with its 95% confidence interval (CI). Proportions were compared between subgroups using Fisher’s exact test, given cells frequently had expected values less than five.Interim analysis was planned at 50 patients . Based on the analysis  and limitations of the current cohort (beating versus arrested hearts), the study team decided to conclude this study at 51 patients.2. One participant had asthma and one participant had chronic obstructive pulmonary disease; no pleural or pericardial effusions were seen on imaging. The long-axis view of the LV was most commonly identified along intercostal spaces five to seven along the left sternal border .Demographic and anatomical details of participants are outlined in Table The largest scan volume reliably localized the heart in all participants (51/51); median scanner volumes determined at each of the 10 assessment points on the chest wall are presented in Table When considering the largest volumes over the left sternal border exclusively, the long axis of the LV was the underlying cardiac structure in 46/51 . Of the remaining five participants, the aortic root was the predominant underlying structure in three participants, and the cardiac apex and the right ventricle in the other two. In this revised approach, the seven individuals who previously had their largest scanner volume detected in the mid-clavicular zone, all of their largest left sternal border volumes were associated with views of the LV in its long axis Table . The larOur findings suggest that the heart can be reliably localized using a simple, easy-to-use ultrasound device (bladder scanner). Our cardiac ultrasound findings reveal that the LV lies directly under the left sternal border across three intercostal spaces in the majority of our participants. Furthermore, the location of the largest scan volume along the left sternal border appears to correlate highly with the area overlying the long axis of the LV. As suggested by a previous porcine study , this reRadiological studies evaluating the location of critical cardiac structures have shown that midline compressions over the lower half of the sternum would compress the ascending aorta or the top of the left atrium 74% of the time -11. ThisWe propose that compressions over the long axis of the LV, and specifically over the best long-axis view, may prove superior to compressions performed entirely away from the LV, which previous and emerging literature ,9-11 sugGiven the strong association between EMS-initiated or bystander CPR and increased survival, it is crucial to avoid delays in initiating chest compressions . Much liOur study has several limitations. When the bladder scanner system is actuated, it analyzes the two-dimensional echoes from several sonographic planes and renders a three-dimensional reconstruction from which a volume is determined. Alnaif and Drutz  reportedIn this cross-sectional study, a simple ultrasound device (bladder scanner) was used to reliably localize the heart. In the healthy volunteers, the intercostal space of the largest scan volume was most often associated with the area overlying the long-axis view of the LV. This location, as identified through the scanner, represents a theoretically optimal area of compression. Further investigation into rapid sonographic localization of the heart to guide the area of compression for OHCA is warranted.


Left ventricle, LV wringing wall motion relies on physiological muscle fiber orientation, fibrotic status, and electromechanics (EM). The loss of proper EM activation can lead to rigid-body-type (RBT) LV rotation, which is associated with advanced heart failure (HF) and challenges in resynchronization. To describe the EM coupling and scar tissue burden with respect to rotational patterns observed on the LV in patients with ischemic heart failure with reduced ejection fraction (HFrEF) left bundle branch block (LBBB). Thirty patients with HFrEF/LBBB underwent EM analysis of the left ventricle using an invasive electro-mechanical catheter mapping system . The following parameters were evaluated: rotation angle; rotation velocity; unipolar/bipolar voltage; local activation time, LAT; local electro-mechanical delay, LEMD; total electro-mechanical delay, TEMD. Patients underwent late-gadolinium enhancement cMRI when possible. The different LV rotation pattern served as sole parameter for patients’ grouping into two categories: wringing rotation  and RBT rotation . All parameters were aggregated into a nine segment, three sector and whole LV models, and compared at multiple scales. Segmental statistical analysis in Group B revealed significant inhomogeneities, across the LV, regarding voltage level, scar burdening, and LEMD changes: correlation analysis showed correspondently a loss of synchronization between electrical (LAT) and mechanical activation (TEMD). On contrary, Group A (relatively low number of patients) did not present significant differences in LEMD across LV segments, therefore electrical (LAT) and mechanical (TEMD) activation were well synchronized. Fibrosis burden was in general associated with areas of low voltage. The rotational behavior of LV in HF/LBBB patients is determined by the local alteration of EM coupling. These findings serve as a strong basic groundwork for a hypothesis that EM analysis may predict CRT response.Clinical trial registration: SUM No. KNW/0022/KB1/17/15. Furthermore, muscle fibers are organized in a three-dimensional (3D) counter-directional orientation across the myocardium (right-handed in the subendocardium and left-handed in subepicardium). These factors cause a endocardial-epicardial activation, followed by an endocardial isovolumetric shortening and subsequent epicardial shortening/twisting. Consequently, during systole, LV base and apex rotate in opposite directions—clockwise and counterclockwise, respectively. The synchrony between electrical and mechanical activation patterns is influenced by the presence of fibrosis and the tissue EM coupling.The electromechanical (EM) activation pattern is not transmurally homogenous because of the subendocardial location of the His-Purkinje system and the anisotropic conduction along muscle fibers4. This can manifest in reduction of LV ejection fraction (LVEF), as well as changes in LV rotational pattern5. Rigid body-type (RBT) rotation—with basal and apical segments rotating in the same direction—was described by Setser et al. in patients with end-stage HF6. These findings were previously reported with the support of cardiac magnetic resonance tagging and speckle tracking echocardiography11. High RBT prevalence (up to 76%) was observed among the HF population with ischemic and non-ischemic etiology6.In patients with heart failure (HF) and co-existing left bundle branch block (LBBB), the abnormal electrical activation, combined with post-ischemic EM coupling remodeling and geometrical alterations, may lead to dyssynchronous mechanical activation12, which can be optimized based on the LV patient-specific dynamics. The analysis of the LV electromechanical activation and torsion is increasingly gaining interest over the last years as a potential new diagnostic parameter of cardiac dysfunction and CRT optimization in HF patients13. Nevertheless, it is not clear to what extent the fibrotic burden or EM coupling alterations contribute to the LV rotation drastic alterations, which, in case of RBT rotation, could provide challenging to restore via CRT.Patients with ventricular dyssynchrony are eligible for the implantation of resynchronization devices that provide cardiac resynchronization therapy (CRT). CRT can restore LVEF, LV activation and pre-remodeling status, but 35–40% of patients do not respond to the therapy. Non-response to CRT is multifactorial, primarily depending on the site of pacingIn the presented study, we describe the EM coupling and scar tissue burden with respect to rotational patterns observed on the LV in patients with ischemic heart failure with reduced ejection fraction (HFrEF) and LBBB, referred to CRT. We elucidate from the multiscale and multimodal comparative analysis which parameters and their interplay are significantly altered in presence of different LV rotation kinetics.Patient baseline characteristics is presented in Table Based on quantitative (clockwise [< − 3°]/counterclockwise [> 3°]) and qualitative (apex-base relative rotation) analysis of LV rotation at each endocardial mapping point, patients were classified as: wringing rotation , while 80% in Group B (n = 24). Group B showed predominantly clockwise rigid body-type rotation in 73% of patients (n = 22), and predominantly counterclockwise rigid body-type rotation in 7% of individuals (n = 2). Importantly, there were no statistically significant differences between groups in NYHA functional class . Mean LVEF was 26 ± 5%, mean LVEDV and LVESV were 240.5 ± 52.4 ml and 178.4 ± 41.2 ml, respectively. LV sphericity index (long-to-short LV axis ratio) was 1.65 ± 0.13 vs. 1.59 ± 0.16 for Group A and Group B, respectively, p = 0.42.Global rotational and EM parameters values and group comparisons are detailed in Table Across the LV, patients’ groups showed significant differences in LV peak and mean torsion . No significant difference was found regarding the rotation rate .No difference was observed between groups in terms of interventricular delay, LV electrical activation time , electro-mechanical delay , electrical/mechanical cycle length, and fibrosis burden . LGE signal was higher at the apico-septal region, with varying involvement of the anterior or posterior wall. A significant difference was observed for unipolar  and bipolar voltage .This evidence suggests that, at the global level, the groups present similar electrical activation times, EM coupling, contraction dynamics, and fibrosis burden, albeit with increased voltage amplitudes for Group B.Sectorial rotational and EM parameters values and group comparisons are detailed in Supplementary Tables Intergroup comparisons between the two groups showed significant difference between all the sectors  and the medial/basal sectors.The findings at the sectorial level are presented in the Box 1.Box 1: Summary of findings at the sectorial levelGroup B shows basal and medial higher voltage.The electrical activation pattern quantified by LAT is physiological for both groups.In Group B the apex presents a faster EM coupling in the medial and basal sectors.Mechanical activation is similar in and between both groups.Scar burden was preferentially apical in both groups, with no differences between.Segmental rotational and EM parameters values and group comparisons are detailed in Supplementary Tables Intergroup comparisons showed significant difference between the apex and midlateral segment  of 12 ± 19 ms and 10 ± 11 ms, respectively (p > 1.000); basolateral segments were activated late at LAT 67 ± 23 ms and 60 ± 17 ms, respectively (p = 0.986). Electrical activation front in both groups travels from the midseptal region to the basolateral one Fig. a, yet inGroup A did not present significant differences in LEMD across its segments. In contrast, Group B showed statistically significant differences in LEMD between the apical vs. posterobasal ones. No difference was found when comparing segments of Group A vs. Group B. Nevertheless, we observed that in Group A the postero-lateral side is the one that presents the longer LEMD; in Group B the longest LEMD is found in the medial anteroseptal segments and in the apex.TEMD segmental analysis between groups showed lower posterobasal TEMD in Group B , and no difference in the intragroup segmental analysis. In Group A, TEMD propagation shows that contraction originates from the mid-anterior segment, which travels to the apex and then spreads in a single front—counterdirectional from the LAT pattern—from the septal-anterior segments to the latero-posterior ones ; this correlation is lost in Group B probably due to the voltage increase in the midposterior segment Fig.  top. TheBox 3: Summary of LV segments parameter correlationScar location is associated with low voltage areas unless electrical changes are underway.In Group B, with pathological RBT rotation, electrical propagation and EM coupling are uncorrelated.In Group A, electrical propagation and mechanical activation are highly overlapping, whereas in Group B there is evidence of electromechanical dissociation.1.In healthy individuals, electrical signals propagate through the conduction system at a high velocity allowing synchronized yet anisotropic depolarization of left and right ventricle. Furthermore, mechanical function of LV is correlated with several factors: Homogeneous EM coupling; activation of transmural counter-directionally oriented myocardial fibers; epicardially-dominating torque. These factors guarantee a LV wringing motion, which results in clockwise rotation of the base and counterclockwise rotation of the apex14. However, in patients with LBBB, mechanical function of LV is often disturbed, with a heterogeneous conduction pattern presentation, which depends on anatomical location of the block and co-existence of other heart diseases 17. Interestingly, the global prevalence of isolated LBBB is approximately 1.5%18. This form of conduction delay was reported to affect global longitudinal strain in asymptomatic hypertensive patients19, and decrease apical rotation thus, consequently, reduce LV twist21. This was suggested to serve as a biophysical marker of subtle LV dysfunction21. LBBB is reported to affect 20–30% of all patients with HF22 and recent studies support incorporation of rotational parameters to evaluate LV function in this population24. We have observed in our study that similar manifestation of LBBB can present remarkably different patterns of LV rotation.In a normal adult heart this wringing mechanism plays a pivotal role to achieve LVEF of up to 60% with only 15% myocardial fiber shortening27. Remarkably, these changes can affect myocardium proximal to the ischemic region, as well as the remote one28. Similarly to our findings, Paoletti Perini et al.4 demonstrated, that, in patient with HF and co-existing LBBB, reduction of LV apex–basal rotation and global twist was associated with segmental rotational dyssynchrony. Moreover, authors reported the strongest impairment at the apical level confirming previous published outcomes30.Importantly, ischemic HFrEF with concomitant LBBB may result in remodeling of ventricular EM coupling and geometry, disrupting LV mechanical activity and rotation patternIn our study, aside from the different rotation pattern which served as sole parameter for grouping, the most striking differences between the two patients’ groups were: A stronger electromechanical correlation in Group A, lost in Group B upon inhomogeneous LEMD and negative correlation with electrical activation; inhomogeneous and higher voltage levels in Group B, which can represent a marker of electrical remodeling; locally higher scar burden in Group B.31. In that sense, Group B presented the most sever changes in this property. The reason for a different local electro-mechanical delay can be multivariate: β-adrenergic stimulation is drastically deranged during HF, but intriguingly a role of β3 receptors has been shown to compensate β1 de-sensitization, providing sustained inotropic effect (with improvement of EM coupling) and paracrine modulation with benefits in patients with LVEF < 40%. An overregulated adrenergic stimulation could explain also the increased unipolar and bipolar voltage levels observed in RBT rotation group. On the other hand, progressing HF is characterized by cardiomyocyte hypertrophy32, which affects calcium signaling33 and might explain the regional differences found in RBT group34. Together with these biomolecular remodeling, coupling and contraction alterations can derive also at the tissue-level from scar tissue presence, myofibers geometry rearrangement, and right ventricle mechanics under influence of interventricular delays.LEMD is reported to have a regional gradient from apex to base, as tested in porcine heartsRegarding the effect of scar tissue, we did not observe significant differences between the two groups, rather the LGE intensity was similar between the two groups. LGE intensity was correlated with low voltage area when electrical changes are not undergoing . This does not exclude that a non-detected portion of diffuse fibrosis might have determined the LEMD changes.28. This is accordance with our findings, although we could not distinguish between significant and non-significant scar burden, due to small sample size.As of many comparisons in this study, we found an internal heavier burden in the midseptal region of Group B, which is also the region in which the mechanical activation front splits in two, lingering before activating the neighboring apical and anterolateral regions. Maffesanti et al. showed, with a similar setup to the one presented here, how a significant scar burden can significantly alter electromechanical synchronization and activation centroidsWe concluded that electromechanical coupling changes are paramount to determine the LV kinetics, whether these electromechanical changes derive from a substantial scar burden or other underlying remodeling  phenomena. A working model of our fions is shown in Fig. 35, feature tracking MRI36, tissue Doppler37, and speckle tracking echocardiography1). Important methodological advantages of the NOGA XP system include: (1) direct and simultaneous measurement of electrical and mechanical activation at segmental level, (2) utilization of the earliest electrical activation of LV instead of (a) surface ECG or (b) normalized percentage of systolic and diastolic duration based on aortic valve closure, which gives more precise time reference point in case of NOGA XP system. The data presented here serve therefore as a strong basic groundwork: if the working hypothesis is proven clinically predictive of CRT responsiveness, this study could serve as reference for the collection of electromechanical biomarkers—nominally scar tissue burden, electrical activation pattern, mechanical activation and electromechanical coupling—with available combined non-invasive imaging, such as electro-cardiographic imaging and cMR.Noteworthy, to provide reliable and high-resolution segmental information about EM properties, we used NOGA XP catheter-based technology for a direct analysis of rotational behavior. In our opinion this methodological approach provides an unique analytical value in comparison to previously applied techniques , (4) no healthy control group due to invasiveness of NOGA XP mapping procedure.The presented results are hypothesis generating and should be considered with a caution due to relatively small number of study participants and other study limitations: (1) NOG-based EM characteristics of LV is dependent on the completeness of the endocardial cavity mapping , (2) endocardial contact mapping does not provide any information about epicardial mechanical function, (3) LEMD parameter was defined as a time interval between the local electrical activation of the segment and its peak of systolic rotation, not the onset of mechanical activation  Age 18–75 years, (2) Ischemic cardiomyopathy, (3) LVEF < 35%, (4) Functional class NYHA II/III or ambulatory IV, despite at least 30 days of optimal medical treatment, (5) Sinus rhythm, (6) Left Bundle Branch Block (LBBB), (7) QRS duration > 150 ms, (8) Signed written informed consent.Exclusion criteria (1) Coronary artery disease requiring revascularization, (2) Acute coronary syndrome < 3 months prior to study enrolment, (3) Implantation of pacemaker (4) Presence of implantable cardioverter-defibrillator, (5) Left ventricle thrombus or aneurysm, (6) Severe aortic stenosis, (7) Renal failure (GFR < 30 mL/min/1.73 m2), (8) History of neoplasm, (9) Bleeding diathesis, (10) HIV, HBV, HCV infection, (11) Pregnancy, (12) Contrast allergy.The study conforms to the Declaration of Helsinki. It was approved by the Ethics Committee of the Medical University of Silesia in Katowice. All patients have signed the informed consent form.38. Sector width and gain settings were adjusted for grayscale 2D imaging with second harmonic mode activated. From the complete echocardiographic report, the following parameters were evaluated: left ventricle end-diastolic volume (LVEDV) and left ventricle end-systolic volume (LVESV) and LVEF based on the Simpson method.Transthoracic echocardiography was performed using cardiac ultrasound machine  equipped with S5-1 probe (2.5–3.5 MHz) by expert cardiologist according to the American Society of Echocardiography recommendations28 Briefly, patients (5 for Group A and 20 for Group B) were scanned using a 1.5 T scanner  equipped with standard torso coil. Short-axis late gadolinium enhancement (LGE) images were obtained 7–12 min after the intravenous bolus injection of gadolinium (0.2 mmol/kg body weight). Scans were subsequently analyzed via CVI42 v.5.11.2. Each short-axis slice was subdivided into the 16 angular sectors, according to the AHA standard and the local scar burden was expressed as the percent of grey area per subregion. The resulting colormaps were converted into nine segments values by weighted mean based on segment area. The nine segment colormaps were post-processed as described below.Cardiovascular magnetic resonance imaging was performed as described by Maffesanti et al.39. Internal standardized NOGA-algorithms identified and eliminated points with unstable wall contact and inappropriate rhythm or wall movement.The 3D electro-mechanical mapping system NOGA XP  allows simultaneous measurement of local electrical activity and mechanical motion of myocardial tissue. The data are generated by electro-magnetic tracking of a miniaturized sensor located at the tip of the mapping catheter , as described in detail previouslyAfter filtering of the mapping points and assessment of an adequate catheter-endocardium contact, data were exported for analysis of rotation angles using external software algorithms. Rotational parameters were calculated by recording angular displacement of the individual mapping points around the heart axis, defined by the geocenter of all mapping points and the apex of the heart. The position of each mapping point was recorded in three dimensions at 10 ms intervals over a period of three heart cycles. Rotational values were calculated between LV end-diastolic to end-systolic phase. Similarly, local activation time (LAT), local rotational electro-mechanical delay (LEMD) and total rotational electro-mechanical delay (TEMD) were computed as shown in Fig. After processing, rotation data were also transferred into a NOGA 3D viewer and visualized as color-coded maps , as shown in Fig. A complete description of the computed and analyzed parameters is provided in Supplementary Table Values are presented as the mean ± standard deviation (SD) or median , according to data distribution. Normality was verified by Shapiro–Wilk test. Qualitative data are expressed as crude values and/or percentages. Difference between global parameters were analyzed by non-paired t-test  for normally distributed data or Mann–Whitney’s test for nonnormally distributed data. Differences between sectorial and segmental groups were analyzed using 2-way analysis of variance (ANOVA). Multiple comparisons within each group were corrected via Holm-Sidak’s method. To reduce the number of comparisons among segments in the intragroup analysis, we first computed all the possible pairs and chose as control the most repeated segment with lowest p-values. Statistical analysis and graphs were performed using MedCalc version 19.0.7  and Prism 8  and the significance level was p ≤ 0.05).No animal studies were carried out by the authors for this article.Supplementary Information 1.Supplementary Video S1.Supplementary Video S2.Supplementary Video S3.


Hypoplastic left heart syndrome (HLHS) is a spectrum of left heart underdevelopment leaving the left side unable to support the systemic circulation. If active management is pursued, then the condition is managed with staged palliation to the Fontan circulation, leaving a systemic right ventricle. Through all surgical stages, and even after completion of Fontan, there are multiple areas that may require intervention, most frequently the branch pulmonary arteries which are essential to a successful Fontan circulation. Echocardiography is the mainstay of assessment, but there is an increasing use of magnetic resonance imaging (MRI) and computed tomography (CT) particularly in relation to extracardiac structures which can be more challenging with echocardiography. Both MRI and CT require set-up, experience and training, and usually sedation or anesthetic in smaller children, but can provide excellent imaging to guide interventions. Cardiac MRI is also able to quantify right ventricular (RV) function which can be challenging on echocardiography. This article describes the modalities available and their use in assessing patients with HLHS prior to catheter interventions. Occurring in around 1–2% of patients with congenital heart disease , the lefThe first operative procedure is performed in the first few days of life – the choice of initial palliation is based on institutional preference as well as risk factors such as prematurity and birth weight. The Norwood procedure  consistsAs caval flow increases and pulmonary vascular resistance decreases, by around 3–6 months of age infants are able to undergo a superior cavopulmonary connection , leadingNoninvasive imaging modalities include echocardiography , cardiac computed tomography (CT) and magnetic resonance imaging (MRI). in utero leading to lymphangiectasia (The majority of infants with HLHS >70%) are correctly antenatally diagnosed , and pos0% are coiectasia . This maParticular attention is paid to the competence of the tricuspid valve (TV) and RV function, as significant tricuspid regurgitation (TR) or RV dysfunction are risk factors for mortality –12. The After NP, as well as ongoing assessment of the RV and valvar function, the operated areas must be interrogated for signs of function. Many patients may have epicardial  or transPrior to further surgical palliation, assessment is required to ensure adequate pulmonary artery size for SCPC. This article does not cover this area as this is pre-surgical assessment, but the assessment may take the form of cardiac CT, MRI or catheterization, with comparable outcomes with all modalities , 20.The BTTS and RV to PA conduit can both be seen on echocardiography , but theThe coronary artery flow in HLHS patients is reliant on the DKS – blood leaves the heart through the neo-aortic valve into the aorta, with some then flowing retrogradely into the native aorta to the coronaries. Depending on the size of the native aorta, this connection can be a similar size to a coronary, effectively behaving like a single coronary origin. A patient who develops ischemic ECG changes, RV dysfunction or TR without arch obstruction needs to be considered as having obstruction to the DKS until it can be proven otherwise. Echocardiography can illustrate flow into the DKS , and anyThe reconstructed aortic arch can be a source of obstruction, either with inadequate resection of ductal tissue leading to re-coarctation, or from torsion or twisting. This may be seen on echocardiography  as turbuIn HLHS there is obstructed egress from the left atrium due to mitral stenosis or atresia. The atrial communication therefore needs to be widely patent unless deliberately left restrictive to try and “grow” the left heart. Hypoplastic left heart complex (HLHC) where there is potential for use of the left heart is a very different condition and requires extensive discussions separately and so is not discussed in this paper. At NP, there is usually an atrial septectomy, but the anatomy, particularly in those with a very small left atrium (LA) can be challenging and some atrial tissue or ridge may remain.Echocardiography will demonstrate on 2D the atrial communication, and on color the flow should be low velocity and unrestricted . Transatin situ). Fenstermaker et al. describe the main areas of focus after HP which are also outlined below , it should remain widely patent with no significant constriction seen on 2D, color or Doppler. For patients with aortic atresia, coronary blood flow is also duct dependent.In patients with a ductal stent any narrowing should be noted on 2D and color . DopplerThe isthmal area and retrograde flow into the aortic arch are often challenging to see on echocardiography, but any increase in velocity into this area, particularly in patients with aortic atresia is likely to be significant and warrant further imaging or catheter intervention.Along with ongoing assessment of the RV and valvar function as well as the atrial communication, DKS and arch, the main foci of assessment after SCPC are the branch pulmonary arteries and caval anastomosis. With increasing age (and decreasing compliance) echocardiographic views become more challenging and cross-sectional imaging with cardiac CT or MRI may be useful to define the pulmonary arterial anatomy further. Assessment prior to TCPC is not described in detail here but can be performed using cardiac catheterization or MRI with measurement of jugular vein pressure as surrogate of pulmonary pressures with equivalent outcomes . If therAfter TCPC there should be continued review of the operated areas and RV and atrioventricular valvar function. The branch pulmonary arteries remain an area of concern and can continue to be assessed as above, usually more with CT/MRI as the acoustic windows worsen with age even if compliance increases. The inferior caval connection and tunnel now also need to be assessed, with phasic flow expected. If there is reduced distensibility of the IVC with dilatation and spontaneous contrast, suspicions should be raised of increased pressures. These pressures could be related to elevated pulmonary vascular resistance or high left atrial pressure, but they could also point to a narrowing in the TCPC circuit or thrombus .Creation of a fenestration in the TCPC varies by institution but is particularly necessary when there are concerns over the transpulmonary gradient or branch pulmonary artery narrowing. The communication between the Fontan circuit and atrial mass acts as a “blow off” valve if the Fontan pressures are increased, at the expense of saturations. Patency of the fenestration can be seen as flow on echocardiography, and Doppler interrogation will estimate the transpulmonary gradient and can be useful to monitor patients.For some patients who have satisfactory hemodynamics, the fenestration may be a source of unneeded desaturation or thrombus and interventional closure of the fenestration with a device may be indicated. Proportion of fenestration flow can be calculated on MRI, and this can be used in association with invasive pressure measurements to decide whether closure is appropriate. There will often be test occlusion in the catheter laboratory prior to complete occlusion with re-assessment of the pressures. Transesophageal echocardiography can aid the interventional team with crossing the fenestration and guiding device closure .Although for most patients with HLHS the left pulmonary veins drain normally to the left atrium, abnormalities of pulmonary venous drainage can be seen, and over time unfortunately pulmonary vein stenosis and sclerosis can be seen. This can be assessed with echocardiography on 2D, color and Doppler . AlthougPlastic bronchitis and protein losing enteropathy are life-threatening complications that can occur during single ventricle palliation. The role of the lymphatics in these conditions is currently under intense review. Cardiac MRI provides a noninvasive modality that can delineate the lymphatic drainage and potential foci for intervention  23–25).–25.23–25A further peril of the single ventricle pathway is thrombus . As the Multimodality imaging is essential prior to and throughout staged palliation for HLHS. The different modalities each carry their own advantages and disadvantages and complement each other well. Not only can imaging be used to assess before and after procedures, but also to help guide interventions in this very complex group of patients.The author confirms being the sole contributor of this work and has approved it for publication.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.


Procedural sedation and analgesia for patients with adult congenital heart disease (ACHD) and highly elevated subpulmonic ventricular pressure require proper anesthesia care to prevent a pulmonary hypertensive crisis. We describe the monitored anesthesia care (MAC) of two patients with ACHD  and highly elevated subpulmonic ventricular pressure. In both patients, preprocedural transthoracic echocardiography was useful for detecting severely elevated subpulmonic ventricular pressure. The MAC involved the infusion of propofol, dexmedetomidine, and fentanyl. Norepinephrine was continuously administered from the preanesthetic period. No hemodynamic instability or respiratory depression was observed during the MAC. Continuous administration of norepinephrine from the preinduction period was helpful for preventing hypotension. We added dexmedetomidine to our MAC regimen of propofol and fentanyl because it exerts both sedative and analgesic effects. Dexmedetomidine does not cause respiratory depression; thus, our MAC regimen is believed to be theoretically safe for patients with ACHD and elevated subpulmonic ventricular pressure. Our findings suggest that safe MAC for patients with ACHD and highly elevated subpulmonic ventricular pressure may require careful consideration of the anesthetic regimen and close observation by adequately trained personnel, which is best provided at regional ACHD centers. The population of patients with adult congenital heart disease (ACHD) has been increasing in recent years –3. ThereE/A 0.94; E/e′ 4.9. Left ventricular function was also preserved with a fraction area change (FAC) of 56% and E/A 0.97; E/e′  20; E/e′  11. Since central venous catheter placement is an invasive procedure, MAC or general anesthesia with tracheal intubation (GETA) was required in this patient to avoid sudden increases in PVR because of noncooperation, crying, screaming, or struggling. Since MAC is less invasive than GETA, we scheduled the patient for CVC placement under MAC.A 22-year-old woman with Down syndrome and Eisenmenger syndrome due to a complete atrioventricular septal defect (cAVSD) that was diagnosed at birth was scheduled for central venous catheter (CVC) placement for acute myelocytic leukemia management. The patient was prescribed tadalafil and furosemide, and her condition was classified as New York Heart Association (NYHA) class II. The preprocedural brain natriuretic peptide (BNP) level was 22.6 pg/mL. Her electrocardiogram (ECG) showed sinus rhythm, northwest axis, incomplete right bundle branch block pattern, and biphasic QRS complexes in V2-5 and deep S waves in V5-6 . Transth2)—80% in room air. During MAC, 5 L/min of 100% oxygen was administered via face mask. End-tidal carbon dioxide (EtCO2) was monitored with capnography. Before the induction of anesthesia, a continuous peripheral venous infusion of norepinephrine was initiated at 0.1 μg/kg/min and maintained at 0.02–0.1 μg/kg/min to maintain the systolic systemic arterial blood pressure (sSABP) above 100 mmHg (her resting sSABP). MAC was provided with a continuous infusion of propofol (2 mg/kg/h), dexmedetomidine (a loading dose of 1 μg/kg over 10 minutes followed by a 0.5 μg/kg/h infusion), and fentanyl  to achieve optimal sedation and analgesia. Local anesthesia was obtained by a superficial injection of 1% lidocaine. During MAC, glossoptosis occurred temporarily and was easily rectified by a jaw lift. The CVC was placed successfully without hemodynamic instability, respiratory depression, or oxygen desaturation. The infusion of norepinephrine was tapered according to sSABP and discontinued after 30 minutes of the procedure. The level of consciousness was arousable on calling, and no airway obstruction was observed at the end of the MAC. The postprocedural course was uneventful. Chemotherapy was started on postprocedural day 4.The anesthesia record is shown in P wave, and Qr pattern in V1  of 20.9 mm, and E/A 1.91; E/e′  11; E/e′  10. Although TTE could not detect the Rastelli conduit, progression of conduit stenosis was suspected from her clinical course and other echocardiography data. She was scheduled for TEE under MAC for a detailed observation of the thrombus.A 39-year-old woman presented for transesophageal echocardiography (TEE) to rule out intracardiac thrombus. She had chronic cough and progressive dyspnea, and a history of a ventricular septal defect (VSD), pulmonary artery (PA) stenosis, and congenitally corrected transposition of the great arteries (ccTGA). At 8 years of age, she underwent the Rastelli procedure only, which connected the morphologic left ventricle (LV) to the PA via a conduit graft for PA stenosis. She did not undergo anatomic repair of the corrected transposition, in which an atrial inversion procedure (Senning or Mustard) is combined with either an arterial  or ventricular (Rastelli procedure) level repair. The patient was not prescribed any medications and was NYHA class II. The preprocedural BNP level was 50.1 pg/mL. The ECG showed sinus rhythm, northwest axis, notched rn in V1 . TTE sho2—82% in room air. During MAC, 3 L/min of 100% oxygen was administered via a nasal cannula. Her EtCO2 was monitored with capnography. Before the induction of anesthesia, a continuous peripheral venous infusion of norepinephrine was initiated at 0.05 μg/kg/min and maintained at 0.05–0.3 μg/kg/min to maintain the sSABP above 110 mmHg (her resting sSABP). MAC was provided with a continuous infusion of propofol (2–2.3 mg/kg/h) and dexmedetomidine (a loading dose of 1 μg/kg over 10 minutes followed by a 0.5 μg/kg/h infusion) to achieve optimal sedation and analgesia. For local anesthesia, 2% viscous lidocaine was used on the pharynx and larynx. No hemodynamic instability, respiratory depression, or oxygen desaturation was observed during MAC. The infusion of norepinephrine was tapered according to sSABP and discontinued after 20 minutes of the procedure. The level of consciousness was arousable on calling, and no airway obstruction was observed at the end of the MAC. The postprocedural course was uneventful. The patient was discharged on postprocedural day 1.The anesthesia record is shown in We successfully provided MAC to two patients with ACHD and elevated subpulmonic ventricular pressure with an intracardiac shunt. The clinical courses of these two patients suggest several important points for anesthesia providers.β1 effect of the former, which increases ventricular contractility and helps counteract the increase in PVR. Dopamine titration is more complicated than that of norepinephrine because of the dose-dependent shift in the predominant effects of dopamine. Vasopressin is a nonsympathomimetic vasopressor, which has the possibility of decreasing PVR without decreasing SVR [First, we found that a continuous infusion of norepinephrine from the preinduction period was helpful in maintaining hemodynamic stability in these patients. Many agents commonly used for sedation and anesthesia, such as propofol, decrease the systemic vascular resistance (SVR), which may increase the right-to-left shunt flow and cause oxygen desaturation , 7. Moresing SVR , 10. Howα2 adrenergic agonist with sedative, analgesic, and anxiolytic properties but does not promote respiratory depression [2 compared with baseline levels.Second, an increase in PVR also should be prevented. Any catecholamine surge caused by pain, agitation, or anxiety will abruptly increase PVR, so judicious doses of sedatives and analgesics should be provided to prevent it. Propofol is an intravenous sedative drug that provides effective sedation and rapid recovery from anesthesia. Owing to its extensive usage in anesthesia patients, we chose propofol as the first-choice sedative. Fentanyl is a commonly used analgesic for MAC, but may cause dose-dependent hypercarbia, which may increase PVR. To avoid this problem, we used local anesthetics and also added dexmedetomidine to our anesthetic regimen. Dexmedetomidine is a selective pression . Dexmedepression , 13. A ppression . We did 2 and other clinical signs of adequate airway patency who could intervene if airway obstruction occurred.Third, continuous and careful observation of airway patency is of paramount importance during MAC. We chose MAC with spontaneous breathing over general anesthesia with endotracheal intubation and positive pressure ventilation because we believe that the former might be more advantageous in lowering PVR compared with the latter. However, once the airway is compromised, hypoxia may ensue and increase PVR. Therefore, in both cases, we always had at least one designated anesthesiologist at the bedside who continuously monitored the EtCOProcedural sedation and analgesia without careful consideration of the anesthetic regimen can be harmful to patients with ACHD and highly elevated subpulmonic ventricular pressure. In fact, we suppose that these patients have periprocedural risks similar to those observed in patients with severe pulmonary arterial hypertension . There aIn the anesthetic management of patients with ACHD and highly elevated subpulmonic ventricular pressure, it is most important to prevent a pulmonary hypertensive crisis. Most anesthetic agents have a hypotensive effect, which causes poor coronary perfusion, right-to-left shunting, and subpulmonic ventricle dilation/failure. Continuous administration of adequate norepinephrine from during the preanesthetic period is crucial for the prevention of sudden systemic hypotension. Although MAC with a combination of propofol, dexmedetomidine, and fentanyl provides safe and effective sedation and analgesia, it may be better performed by a trained anesthesiologist. Patients with ACHD and highly elevated subpulmonic ventricular pressure may be treated at a regional ACHD center.


Sleep disorder breathing is a highly prevalent public health problem and is common among patients with cardio and cerebrovascular diseases. Respiratory events are associated with numerous consequences, such as the hyperadrenergic state, known as a predictor of premature mortality in patients with heart failure. On the other hand, reduced stroke volume is associated with fluid retention in patients with heart failure, leading to changes in the upper airflow dynamics. Whether and how to treat sleep disorder breathing enables chronic cardiovascular consequences to be reversed is not fully established. Few cases are known where sleep disordered breathing diagnosis was made several years before heart transplantation. To better understand how does sleep apnea evolve and to ponder about what is the best treatment approach in this context, is the objective with this case presentation. Fluids are redistributed during sleep lying position, with a nocturnal fluid shift to the rostral sections of body. Peri-pharyngeal edema could happen, leading to changes of the upper airflow dynamics and favoring pharyngeal collapse3,Concerning SDB treatment options in HF patients, the absence of treatment might promote the progression of cardiac disease. Treatment with continuous positive airway pressure (CPAP) improved cardiac function in HF patients with central sleep apnea (CSA) by stabilizing ventilation. However, CPAP use could have been limited in some cases due to reduced efficacy and intolerance. For this reason, large trials used adaptative servo-ventilation (ASV) instead of CPAP, since this ventilatory mode effectively suppresses CSA and is well tolerated4Treatment options for SDB are evolving. In general, however, CSA is more difficult to treat than obstructive sleep apnea (OSA). Several positive airway pressure (PAP) devices, including CPAP, bilevel and ASV have been tested. ASV equipment has been shown to be useful, however, the SERVE-HF trial cast doubts on this notion after the 2015 SERVE-HF study,Early case reports suggest that normalization of heart function after transplantation leads to complete abolition of CSA or the development of OSA4The expectation is that restoring cardiac function with HT might change the clinical history of CSA-CSR. Few cases are known where SA diagnosis was made several years before HT. The objective with this case presentation is to better understand how SDB evolves and to ponder with the best treatment approach in this context.Male patient, currently 67 years old, non-smoker and with normal body mass index (BMI). Followed through cardiology consultation at another institution since 1994 due to congenital atrio-ventricular block and aortic disease. The patient has been submitted to definitive pacemaker (PM) (DDD) implantation in April 2002. At that time, had mild to moderate degree of aortic insufficiency with normal ventricular dimensions and preserved left ventricular (LV) systolic function (SF). A sleep polygraphy was performed in July 2007 for reported snoring, frequent dreams, waking up with dry mouth and respiratory pauses . The exam revealed an apnea/hypopnea index (AHI) of 28.1/h and central apnea index (CAI) of 8.3/h . Due to Between 2007 and 2008, the patient was always well adapted to ASV. In August 2008 there was a clear LV function deterioration due to the aortic disease progression; the echocardiogram presented severely dilated LV with severely depressed global SF (LV ejection fraction (LVEF) estimated at 25%) and moderate aortic insufficiency with eccentric jet directed at the anterior leaflet of the mitral valve.Since it was an end-stage of HF, the individual was observed at a thoracic surgery consultation in September 2009. Medical treatment was maintained because the patient was considered not to meet conditions for classic aortic valve replacement surgery.Re-evaluation in September 2010 considered the individual a candidate for HT if the functional class aggravates. A reassessment by polysomnography (PSG) was made in February 2011 showing a respiratory disturbance index (RDI) of 14.2/h.In April 2011 the cardiac catheterization revealed absence of coronary disease, but severe aortic insufficiency with severely depressed LVEF; pulmonary vascular resistance (PVR) of 5.67 U/Wood, with pulmonary arterial systolic pressure (PASP) of 70 mmHg and pulmonary capillary wedge pressure (PCWP) of 37 mmHg.2; holodiastolic reverse flow in the descending aorta and slightly dilated right ventricle (RV) with compromised systolic function.In July 2011, given that it was time to replace the PM generator, it was decided to perform the upgrade to cardiac resynchronization therapy (CRT), to attempt to compensate for the cardiac insufficiency. The procedure was unsuccessful after a small dissection of the coronary sinus when trying to position the left ventricular probe. At that time, the echocardiogram revealed more marked dilated cardiomyopathy (LVEF 23%); severe aortic insufficiency due to prolapse of the right coronary cusp, conditioning an eccentric jet directed to the anterior leaflet of the mitral valve. ERROR - 0.52 cmThe patient was electively hospitalized in September 2011 for attempted CRT implantation, which occurred without complications. Repeated evaluation of the pulmonary resistances showing a clear improvement in the parameters . Therefore, it was decided to initiate a pre-transplant cardiac study: performed abdominal ultrasound and renal-vesicle-prostatic ultrasonography demonstrating prostatic hypertrophy  and complex cyst in the right kidney (classified as a lesion Bosniak IIF). Lung function tests were normal; serology for infections and vaccination was done; got indication to complete dental treatment; was also evaluated for infectious diseases and psychiatry consultations and histocompatibility study was performed.3, LVtd 80 mm); severe aortic insufficiency due to prolapse of the right coronary cusp conditioning an eccentric jet directed to the anterior leaflet of the mitral valve; non-dilated inferior vena cava presenting variability of about 50%; LV global hypokinesia with severely compromised systolic venous function, EF of 18%; compromised SF of the RV; electrocatheters were in the right cavities.In November 2011, an echocardiogram revealed severe dilation of the left heart chambers .The patient underwent HT in September 2015 . After HT was evaluated in the sleep consultation in March 2016, the individual continued with ASV by stating not being able to sleep without it. Adherence of 97% and residual AHI of 0.6/h. Approximately one year later, the patient maintains excellent adherence to the treatment.2O; nasal mask).During 2017, a revaluation sleep study revealed an RDI of 16.9/h with CAI of 0/h . The ech2O. A change to CPAP mode was programmed (based on APAP P95).In April 2018, card reading showed AHI<5/h, 73% usage > 4h and P95% of 11.6 cmHThe last echocardiogram information, from July 2018, showed: good left LV global SF (estimated EF: 61%); abnormal movement of the interventricular septum; good RV SF and TDI S wave - 0.11 m/s. Since HT always has dysthymic dysfunction, the cardiologist was of the opinion that it should continue with CPAP because it does not have CA. The patient continued well adapted to CPAP, referring to having good sleep quality until March 2019.International guidelines recommend the diagnosis and treatment of SDB in HF patients due to their bidirectional relationship. After HT, treatment with ASV mode -although no formal indication exists- seems to have been an acceptable ventilatory mode since there was no impact on cardiac function, keeping respiratory events and symptomatology controlled. We insisted on switching to CPAP mode since it only had obstructive events. Therapeutic implications of treating SDB in HF patients and treating HF in patients with SDB, remains to be fully elucidated. SDB treatment with PAP in HF patients should be started cautiously checking for possible hemodynamic changes and involving a multidisciplinary team.


FBN1) that encodes the extracellular matrix protein fibrillin-1. Limited evidence is available that Marfan syndrome is associated with a primary cardiomyopathy. Cardiovascular Magnetic Resonance (CMR) plays an important role in the identification and evaluation of cardiovascular disease in this population, the major source of morbidity and mortality. CMR was used to assess the prevalence and predictors of primary cardiomyopathy, in a Marfan population without evidence of significant valvular regurgitation or aortic disease.Marfan syndrome is the commonest inherited disorder of connective tissue affecting multiple organ systems, caused by heterozygous mutations in the gene (120 Marfan patients were consecutively referred to our centre for cardiovascular assessment with CMR between January 2003 and June 2007 (diagnosis based on Ghent criteria). Our study population consisted of 66 of these patients who had no significant valvular regurgitation, and no previous aortic or cardiac disease warranting surgery. This included 38 males (57.8%) and 28 females (42.1%), with a mean age of 33,2 years. Thoracic aortic dimensions were evaluated. Left ventricular (LV) volumes, ejection fraction, and mass were evaluated using semi-automated analysis software . The volumes and mass were then indexed to the body surface area. Aortic (AV) and mitral valves (MV) anatomy and function were assessed, and thoracic musculoskeletal deformities identified. The final values were compared with previously published normal values with values being considered abnormal if they were outside the 95% confidence interval. We similarly compared our population to an age and sex matched cohort of normal individuals when assessing aortic dimensions.A significant proportion of this population demonstrated reductions in LV ejection fraction (27%). LV indexed volumes were also significantly different. Annular and aortic root dimensions were increased in the population with reduced LV ejection fraction when compared with population with normal ejection fraction . There was no significant difference in global aortopathy indices or incidence of musculoskeletal deformities between the two groups.We confirm that Marfan syndrome is associated with a primary cardiomyopathy in a population without significant valvular disease. Moreover, annular and root dimensions are increased in patients with LV dysfunction when compared with patients with preserved LV systolic function, suggesting that aortopathy and cardiomyopathy could be related in this multi-systemic disorder. Recent advances in the molecular pathogenesis of Marfan syndrome suggest that modulation of abnormal fibrillin-1-TGF beta signalling by angiotensin-II receptor blockade in Marfan patients may reverse aortopathy. It remains to be determined whether angiotensin-II receptor blockade may reverse aortopathy and associated cardiomyopathy.