Background: We aimed to review the indications and outcomes of adults undergoing combined heart-liver transplantation (CHLT) in the US using national registry data.Methods: Adult (≥18 years) CHLT recipients in the United Network for Organ Sharing database were included . Survival analysis was conducted by means of Kaplan-Meier method, log-rank test, and Cox regression.Results: We identified 369 adults receiving CHLT between 12/1989–08/2020. The number of adult CHLT recipients  and centers performing CHLT  have increased over the study period. The most common cardiac diagnosis in the first two eras was restrictive/infiltrative cardiomyopathy, while the most common in era 3 was congenital heart disease (p = 0.03). The 1-, 3-, and 5-years patient survival was 86.8, 80.1, and 77.9%, respectively. In multivariable analysis, recipient diabetes , CHLT between 1989-2000 compared with 2011–2020 , and sequential-liver first CHLT compared with sequential-heart first CHLT  were associated with increased risk of mortality. Higher left ventricular ejection fraction was associated with decreased risk of mortality .Conclusion: CHLT is being increasingly performed with evolving indications. Excellent outcomes can be achieved with multidisciplinary patient and donor selection and surgical planning.  Since the first combined heart-liver transplant (CHLT) in 1984, its indications, patient demographics, and outcomes have evolved significantly . Once a The growing practice of CHLT is partially credited to the poor outcomes associated with isolated heart transplantation in the context of concurrent end-stage liver disease. Mortality has been reported to be as high as 50% for patients with known cirrhosis undergoing isolated heart transplantation . In suchIn the contemporary era, increasing heterogeneity of indications for CHLT as well as variability in listing practices, patient selection, and perioperative management exist. Recipients’ complex pathologies vary broadly—from congenital, ischemic, or infiltrative heart diseases with associated congestive hepatopathy, to liver-based metabolic disorders with systemic complications, to cirrhotic cardiomyopathy , 9. As CThe United Network for Organ Sharing (UNOS) database administers the Organ Procurement and Transplantation Network under contract with the US Department of Health and Human Services. This database contains data on all transplant candidates listed for solid organ transplantation in the US since October 1987. All data are de-identified, and thus no Institutional Review Board approval was required.We included all adult (≥18 years) patients undergoing CHLT between September 30th, 1987, and September 4th, 2020, in the US. Patient pre-transplant, transplant, and follow-up data were obtained from the UNOS Standard Transplant Analysis and Research data file .1.154 × (age in years)−0.203 × 1.212 (if black) × 0.742 ]  . Model fp-values were based on two-sided statistical tests, and significance was set at <0.05.Categorical variables are described as frequencies and percentages and compared with the chi-square or Fisher’s exact test, while continuous variables are presented as medians [interquartile ranges (IQR)] and compared with the Kruskal-Wallis test. Univariable linear regression was used to assess the number of patients receiving and the number of centers performing CHLT over the study period. Patient survival was the main outcome of interest and was determined as the duration from the date of CHLT until the date of last patient contact or death. Survival analysis was performed using the Kaplan-Meier method, and between-group comparisons were performed with the log-rank test. Cox proportional hazards regression models were fitted to estimate the hazard ratio (HR) and 95% confidence interval (CI). The variables incorporated in the multivariable model were pre-specified to avoid the inferential limitations around selecting covariates for multivariable analysis based on stepwise procedures or univariable comparisons . The mul2 = 0.75, p < 0.001; 2 = 0.80, p < 0.001) increased significantly over the study period. The number of centers performing CHLT was 10 between 1989 and 2000, 20 between 2001 and 2010, and 46 between 2011 and 2020.A total of 369 adult patients who received CHLT between December 1989 and August 2020 were identified. No CHLT recipients were identified between October 1987 and December 1989. The median follow-up time was 49.2 months (95% CI: 42.7–60.9) for the whole cohort. Both the number of adult patients receiving CHLT (Rp = 0.007). On the other hand, median MELD-XI was lower in patients transplanted in more recent eras . Among the three eras, median waitlist time was significantly shorter in the most recent era . Cardiac diagnosis was also significantly different among the three eras (p = 0.03); the most common cardiac diagnosis in the first two eras was restrictive/infiltrative cardiomyopathy, while the most common cardiac diagnosis in the most recent era was congenital heart disease (CHD). During the first two eras, nearly all CHLTs were sequential-heart first , while in the most recent era 79.9% were sequential-heart first, 13.8% sequential-liver first, and 6.3% simultaneous (p = 0.001). Two donor livers in era 3 underwent machine perfusion. A detailed comparison of patient characteristics among the three transplant eras is depicted in Several differences in patient characteristics were identified among the three transplant eras. The median MELD score at transplant was higher in patients transplanted between 2011 and 2020 compared with those transplanted between 2001 and 2010 . The CHD group had lower median age (p < 0.001) and MELD-XI at transplant (p = 0.01) compared with the other diagnosis groups, and together with the restrictive/infiltrative cardiomyopathy group had longer median waitlist times compared with the other three diagnosis groups (p < 0.001). Additionally, as compared with other cardiac diagnosis groups, a higher proportion of the CHD group had undergone prior cardiac surgery at transplant (p < 0.001) and had received sequential-liver first and simultaneous CHLT (p < 0.001). A detailed comparison of patient characteristics among the five cardiac diagnosis groups is depicted in Several differences in patient characteristics were identified among the cardiac diagnosis groups. The majority of patients in the restrictive/infiltrative cardiomyopathy, ischemic heart disease, and dilated non-ischemic cardiomyopathy groups were male, while the sex proportions were more equally distributed in the CHD and other groups (n = 286), the 3- and 5-years cumulative patient survival point estimates were 92.6 and 90.3%, respectively. Six patients required liver retransplant over a median post-CHLT period of 19 days (IQR: 13.0–441.0) with indications being hepatic artery thrombosis (n = 2), acute rejection (n = 1), primary graft failure (n = 1), severe preservation injury (n = 1), and unknown (n = 1). One patient required heart retransplant 12 days post-CHLT due to primary nonfunction. In the total cohort, statistically significant differences in unadjusted patient survival were observed between the three transplant eras  compared with those undergoing CHLT between 2011 and 2020, while no statistically significant differences in survival were observed between those undergoing CHLT between 2001 and 2010 and between 2011 and 2020   and higher donor left ventricular ejection fraction with a decreased risk of patient mortality . Nevertheless, no statistically significant difference between the groups was determined, when classifying each center performing CHLT as low, medium, or high volume based on either their annual isolated heart transplant (p = 0.18) volume or their annual isolated liver transplant volume (p = 0.87).The 1-, 3-, and 5-years cumulative patient survival point estimates after CHLT for the total cohort were 86.8, 80.1, and 77.9%, respectively . For tho = 0.19) . No statp = 0.009), receiving CHLT between 1989 and 2000 compared with 2011–2020 , and receiving sequential-liver first CHLT compared with sequential-heart first CHLT  were associated with an increased risk of patient mortality after CHLT. Higher donor left ventricular ejection fraction was associated with a decreased risk of patient mortality after CHLT .In multivariable Cox regression analysis , recipieThe annual number of adult CHLT in the US has risen sharply, with more CHLT performed during the past 2 years than during either of the previous 2 decades, and a more than four-fold increase over time in the number of centers offering this therapy. While our data demonstrate progressive, era-related improvements in outcomes after CHLT, an appreciation for evolving patient characteristics and indications for CHLT, as well as best practices in surgical techniques, will be critical to ensure appropriate patient selection and favorable outcomes going forward.Among the most significant changes in CHLT in recent decades has been an evolution in the indications for this procedure. Although restrictive/infiltrative cardiomyopathies secondary to diseases such as amyloidosis and hemochromatosis were the most common indication for CHLT in the early era, CHD is now the most common indication, accounting for nearly one third of CHLT. This trend corresponds to the rising prevalence of liver disease among children with single-ventricle physiology palliated with Fontan. Current life-expectancy post-Fontan exceeds 25 years, by which point many patients develop advanced heart failure and Fontan-associated liver disease manifesting with peri-central and peri-sinusoidal hepatic fibrosis which may progresses to cirrhosis, with increased risk of hepatocellular carcinoma , 16. EveAs would be expected, we identified significant differences in the characteristics of patients undergoing CHLT, based on cardiac diagnosis. Interestingly, however, cardiac diagnosis in and of itself was not associated with differences in post-transplant survival, nor was recipient age, prior tobacco use or MELD-XI score at transplant. Conversely, recipient diabetes, liver-first surgical sequence, and lower donor left ventricular ejection fraction were each independently associated with worse post-CHLT outcomes. These findings underscore the importance of appropriate patient and donor selection for CHLT based on individual patient and donor characteristics, as well as the need for thoughtful pre-operative planning among surgeons from both heart and liver disciplines , 17–20. The issue of identification of specific donor factors impacting outcomes persists and may be confounded by changes in donor selection criteria over the years to identify excellent donors, but also a change towards more lenient selection criteria as experience grows. This is supported by the higher donor age, liver and heart CIT, proportion of diabetic donors, as well as by the more optimal donor-recipient height matching and the lower left ventricular ejection fraction in the most recent era. At our center, candidates for CHLT are evaluated jointly by our heart and liver transplant teams and discussed in a multidisciplinary forum that includes transplant cardiologists and hepatologists, adult (and sometimes pediatric) surgeons and, when appropriate, members of the adult CHD team. Upon listing of patients and prior to transplant, surgeons agree on a peri-operative strategy. Team members of both organ programs take part in donor selection. Future research on the optimization of donor selection would enable improved donor-recipient matching. Additionally, the advent and increasing utilization of donor liver machine perfusion may be particularly useful in CHLT as it can mitigate the effects of increased liver graft preservation time while allowing the heart transplant to occur without time pressure constraints .Although the present analysis represents the largest, most comprehensive review of US patients undergoing CHLT during recent decades, certain limitations should be considered when interpreting the results of our study. Due to its retrospective nature, the present study imparts a degree of selection bias regarding patient selection and management. Additionally, there is inconsistency or lack of reporting of parameters that may influence patient survival . Lastly, the statistically insignificant results in certain variables may be attributed to lack of power to detect the presence of a potential association.In conclusion, as more CHD patients survive to adulthood and the prevalence of ischemic and other heart diseases complicated by cirrhosis increases, CHLT will be increasingly necessary to help extend lives. Our data suggest that in the contemporary era, appropriate patient selection for CHLT combined with thoughtful surgical planning and donor selection allow for excellent patient outcomes.


Background: Coronary autoregulation is a feedback system, which maintains near-constant myocardial blood flow over a range of mean arterial pressure (MAP). Yet in emergency or peri-operative situations, hypotensive or hypertensive episodes may quickly arise. It is not yet established how rapid blood pressure changes outside of the autoregulation zone (ARZ) impact left (LV) and right ventricular (RV) function. Using cardiovascular magnetic resonance (CMR) imaging, measurements of myocardial tissue oxygenation and ventricular systolic and diastolic function can comprehensively assess the heart throughout a range of changing blood pressures.Design and methods: In 10 anesthetized swine, MAP was varied in steps of 10–15 mmHg from 29 to 196 mmHg using phenylephrine and urapidil inside a 3-Tesla MRI scanner. At each MAP level, oxygenation-sensitive (OS) cine images along with arterial and coronary sinus blood gas samples were obtained and blood flow was measured from a surgically implanted flow probe on the left anterior descending coronary artery. Using CMR feature tracking-software, LV and RV circumferential systolic and diastolic strain parameters were measured from the myocardial oxygenation cines.Results: LV and RV peak strain are compromised both below the lower limit  and above the upper limit  of the ARZ in comparison to a baseline of 70 mmHg. LV strain demonstrates a non-linear relationship with invasive and non-invasive measures of oxygenation. Specifically for the LV at hypotensive levels below the ARZ, systolic dysfunction is related to myocardial deoxygenation  in OS-CMR and both systolic and diastolic dysfunction are linked to reduced coronary blood flow . These relationships were not observed at hypertensive levels.Conclusion: In an animal model, biventricular function is compromised outside the coronary autoregulatory zone. Dysfunction at pressures below the lower limit is likely caused by insufficient blood flow and tissue deoxygenation. Conversely, hypertension-induced systolic and diastolic dysfunction points to high afterload as a cause. These findings from an experimental model are translatable to the clinical peri-operative environment in which myocardial deformation may have the potential to guide blood pressure management, in particular at varying individual autoregulation thresholds. Coronary autoregulation ensures near constant coronary blood flow (CBF) over a wide range of blood pressure, known as the autoregulatory zone (ARZ). The general relationship of mean arterial pressure (MAP) to CBF has been well-established . In healMyocardial strain analysis allows for a more detailed quantitative analysis of myocardial deformation and performance on a global and segmental level. Diagnostically, deficiencies in resting CMR-FT of both the left and right ventricle has been shown to be linked to outcome in multiple ischemic and non-ischemic cohorts –10. In tThe objective of this analysis was to implement advanced assessments of myocardial deformation by CMR-FT to investigate the impact of systemic mean arterial blood pressure changes on left and right ventricular strain in an anesthetized swine model. Additionally, we aimed to establish the relationship of biventricular strain with changes in myocardial oxygenation, invasive measures of blood oxygen and coronary blood flow within and beyond the boundaries of the coronary autoregulation zone.This study was approved by the Veterinary Services at the Department of Agriculture and Nature of the Canton Bern, Switzerland [#BE 103/14] . The stu2-partial pressures of 35–40 mmHg were targeted. A venous line was placed in the femoral vein and anesthesia was maintained with continuous intra-venous fentanyl (5–30 μg/kg/h) as well as propofol (4–8 mg/kg/h) as required. 5'000 IU of heparin for prophylaxis of thrombosis as well as 75 mg of amiodarone for antiarrhythmic prophylaxis was administered. The femoral artery was cannulated for continuous invasive blood pressure measurements as well as intermittent blood gas analysis. Via access through the right internal jugular vein, an indwelling catheter was placed in the coronary sinus under surgical control. This was used to take blood gas measurements for determining myocardial oxygen extraction and derived invasive oxygenation measures. Afterwards a left-sided thoracotomy was performed and a perivascular flow probe  was surgically attached to the proximal left anterior descending (LAD) coronary artery  were pre-medicated with 20 mg/kg ketamine and 2 mg/kg intra-muscular xylazine. The animals were induced with 10 mg of midazolam and 1 mg atropine and intubated. The animals were ventilated with a tidal volume of 6–8 ml/kg with a positive end-expiratory pressure of 5 mbar. Normocapnic end-tidal COy artery .Inside of a clinical 3T magnetic resonance imaging scanner , MAP was adjusted in steps of 10–15 mmHg from a baseline level of 70 mmHg using urapidil and phenylephrine , as publ42 .Oxygenation-sensitive (OS) cines were acquired in two short axis planes at base and mid-ventricle using a triggered balanced steady-state free precession sequence as reported before . Images For every subject the FT data were compared to the individual baseline-values 70 mmHg). The autoregulation zone (ARZ) was determined from the coronary blood flow data, from which a non-linear regression curve accounting for repeated measurements per subject was generated from 55'368 data points. The limits of the autoregulation zone were calculated from the first and second derivative of the flow curve, defined previously by Guensch et al. (0 mmHg. Tlmer function in R (lme4 package) accounting for multiple measurements per animal by including subject identification as a random intercept. To assess the categorical differences in CMR-FT and invasive measures inside and outside of the ARZ, data at each level was categorized into three groups, levels below the ARZ (<52 mmHg), levels within the ARZ (52–127 mmHg), and a third group of levels above the ARZ (>127 mmHg). These groups were compared with a mixed effects model and the emmeans package , R software  were used for analysis.Initially, the linear relationship between continuous CMR-FT variables to different parameters of flow and oxygenation was assessed using R Studio  with mixed linear models fitted with the  package  accountiMean arterial blood (MAP) pressure in anesthetized swine was manipulated through a range of 29–196 mmHg from a baseline blood pressure of 70 mmHg. In total, 105 levels were targeted from 10 different subjects, at which CMR imaging, and invasive measures of CBF and blood oxygenation were acquired. Five of the fifteen animals were excluded prior to analysis: two suffered ventricular fibrillation during surgery; one had underlying peri-myocarditis that was discovered during surgery; there were experimental hardware problems with the remaining two. FT could be performed on 99 of the levels (94%), with 6 levels excluded due to gating issues.p < 0.05) where a more positive value represented poorer strain, which was confirmed with categorical assessments (p = 0.041 vs. ARZ), and also attenuated by 2.1 ± 0.4% when MAP was higher than 127 mmHg (p < 0.001 vs. ARZ). This was even more pronounced in the RV, with an attenuation in GCS of 4.4 ± 1.2% below the ARZ (p = 0.004 vs. ARZ), and an attenuation of 5.4 ± 1.4% above the ARZ (p < 0.001). On the other hand, time to peak strain (TTP) increased only above the upper limit with a prolongation of 52 ± 21 ms for the LV (p = 0.008 vs. ARZ) and 67 ± 30 ms for the RV. This trend was matched by a reduction in systolic strain rate above the upper ARZ limit, whereas diastolic strain rate was not associated to mean arterial blood pressure. When assessing the end-diastolic area of the mid-ventricle, a larger ventricular lumen area was observed for both the LV and the RV above the ARZ in comparison to area at levels within the ARZ, while hypotension below the ARZ only resulted in a small but significant decrease in RV area in the short axis images with no impact on the LV.As can be seen in essments . In compp = 0.036, As observed in p = 0.047, sSR: β = −0.004, p = 0.017) and diastolic measures , but no association was observed between strain and CBF at high MAP.Similar relationships were observed for CBF, where only below the autoregulation zone did a decrease in CBF relate to attenuated FT systolic  and oxygen extraction ratio (O2er) were linearly correlated to GCS across the entire MAP range  and diastolic parameters . In line with the LV, RV-GCS and sSR improved with a greater coronary sinus saturation and reduced oxygen extraction ratio (O2er). These systolic strain measures also improved with enhanced CBF, while none of the invasive measures were correlated with RV diastolic strain rate. In contrast to conditions in the LV, these associations between FT and CBF and oxygen measures were not observed when investigating only MAP levels below the ARZ.RV strain measurements showed multiple associations with CBF of the LAD and oxygen measures when assessing the entire MAP range . In partWe demonstrate in an anesthetized swine model that biventricular systolic function was compromised at blood pressures outside the coronary autoregulation zone. Left ventricular circumferential peak strain (GCS) was attenuated in a non-linear relationship with decreasing myocardial oxygenation in OS-CMR cine images. Specifically, below the autoregulation zone (ARZ), LV-GCS compromise was associated in linear fashion with myocardial deoxygenation, invasive measures of blood deoxygenation and reduced CBF in the LAD.Many of the reported markers for investigating adverse effects of blood pressure depressions and elevations do not convey their immediate risk to the patient, nor suggest corrective measures. These include blood biomarkers such as the troponins, which take a few hours to rise, markers of other organ injury, or post-surgical morbidity and mortality. By the time such abnormalities develop, it is usually too late for causative treatment. Functional imaging is advantageous in this regard as it can usually be non-invasively acquired within a short time period in a point-of-care setting. In this study we utilized CMR cine images, as information on myocardial oxygenation and function can be simultaneously investigated and linked. OS-CMR sequences use the blood oxygen level-dependent (BOLD) effect to delineate changes in the myocardial oxygen supply and demand balance, avoiding the requirement of contrast agents.Multiple studies investigating myocardial oxygenation responses in healthy animal models as well as in various disease models , 17–21 hA mildly lowered blood pressure can be beneficial as it is easier for the ventricle to unload when there is less systemic resistance. However, afterload reduction, as during anesthesia, is only beneficial to a point where diastolic myocardial or other organ perfusion pressures become critically low. Peri-operative hypotension is a common occurrence, and is associated with a greater risk of peri-operative myocardial infarction . EspeciaWe, as well as others, observed that lower autoregulatory limits differ on an individual level as well. Consequently, intraoperative measures of strain, through using intraoperative echocardiography, may guide anesthesiologists along individualized blood pressure management corridors. Beyond cardiac protection, other organs will benefit from adequate perfusion pressure management, too. For instance, ischemic symptoms of the central nervous system can arise at lower MAP limits of 45–55 mmHg in supine subjects . ImportaOur animal data indicate that hypertension did not limit myocardial perfusion and oxygenation. Nevertheless, biventricular function was compromised and there was end-diastolic dilation of both ventricles. Not only is systolic function limited, but systolic contraction also becomes prolonged as seen by time to peak strain, although there is no change in heart rate . One reaThe RV must match the output of the LV. Peri-operative RV dysfunction not only leads to LV underfilling but can also cause upstream problems like venous organ congestion , 32. In Particularly with functional imaging modalities, the RV appears less well-researched than the LV. FT of the RV free wall offers functional monitoring. It signifies already deterioration before RVEF declines and is therefore of prognostic values .2 and O2er, also reflect global myocardial oxygenation and are not specific to the RV, since the coronary sinus drains venous blood from both ventricles. RV venous drainage both into the coronary sinus and directly into the right atrial and RV cavum precludes any accurate measure of total RV oxygen consumption.While the OS cine modality is suitable for assessing the LV, the myocardial oxygenation response of the RV is not as reliably described with the sequence used. This is due to limitations of spatial resolution defined by the thin RV wall. An advantage of FT and functional analysis is therefore that the RV can be studied even when the target myocardium is thin. Although phenylephrine is reported to increase pulmonary arterial pressure , we cannAlthough changes in RV systolic and diastolic parameters appeared to correlate linearly with many of LV-biased physiological measures it is also known that both RV perfusion and oxygen extraction have key characteristics that differ from the LV . The RV Our study shows that repetitive assessments of myocardial strain within a single subject across a range of MAP at both hypotension and hypertension demonstrate that alteration of blood pressure is an independent variable driving oxygenation and functional changes. We used an animal model since such a protocol could not be conducted in humans. The advantage of the repetitive measures in an animal model, is that the setting can be highly controlled, however in a clinical setting the changes in myocardial strain are likely a multifactorial process that can also be impacted additional variables such as preload, intracellular calcium dynamics and other factors. This is supported by some of the lower-dependency statistical relationships between strain and invasive measures, indicating further variables may play a role as well. Another advantage of the animal model is that multiple invasive measurements can be obtained to investigate both the impact of blood and oxygen supply represented by CBF vs. and variables depicting the oxygen-supply demand balance. Although there is a physiological link between the two components, a dissociation between perfusion and oxygenation measurements can occur based on the tissue oxygen requirements  and consAlthough strain values appear consistent with those in human studies , furtherBiventricular function interrogated by cardiovascular magnetic resonance feature-tracking (CMR-FT) is compromised at blood pressures outside of both the upper and lower limit of the coronary autoregulation zone. Ventricular dysfunction at very low blood pressure was shown to be associated both with coronary sinus oximetry data and non-invasive assessment of myocardial tissue oxygenation measured by OS-CMR. During induced hypertension beyond the upper autoregulatory limit, myocardial deformation appears primarily related to the increase in afterload. Further studies are required to understand the effects of acute blood pressure swings on simultaneous myocardial function assessments. Since there are still no consistent definitions of intraoperative hypotension and hypertension , myocardThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The animal study was reviewed and approved by the Veterinary Services at the Department of Agriculture and Nature of the Canton Bern, Switzerland (#BE 103/14). The study was carried out in accordance with national and local animal care regulations and adheres to the ARRIVE guidelines.This study was conceptualized by DG, KF, AV, and BE. Data was acquired and analyzed by KF, MN, CJ, SH, BW, SPH, BJ, and KF, MN, and DG wrote the first draft. All authors critically reviewed and approved the final manuscript.This work was funded by institutional funds of the Department of Anaesthesiology and Pain Medicine at the Bern University Hospital, Inselspital, University of Bern and the Foundation for Research in Anaesthesiology and Intensive Care Medicine in Bern Switzerland.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Modern imaging techniques, such as TTE with cardiac strain, are contributing to the evaluation of patients with HFrEF, increasing the chances of CRT success, and allowing physicians to anticipate and plan for case management.Cardiac resynchronization therapy (CRT) represents an increasingly recommended solution to alleviate symptomatology and improve the quality of life in individuals with dilated cardiomyopathy (DCM) and heart failure (HF) with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal medical therapy (OMT). However, this therapy does have the desired results all cases, in that sometimes low sensing and high voltage stimulation are needed to obtain some degree of resynchronization, even in the case of perfectly placed cardiac pacing leads. Our study aims to identify whether there is a relationship between several transthoracic echocardiographic (TTE) parameters characterizing left ventricular (LV) performance, especially strain results, and sensing and pacing parameters. Between 2020–2021, CRT was performed to treat persistent symptoms in 48 patients with a mean age of 64 (53.25–70) years, who were diagnosed with DCM and HFrEF, and who were still symptomatic despite OMT. We documented statistically significant correlations between global longitudinal strain, posterolateral strain, and ejection fraction and LV sensing (r = 0.65, 0.469, and 0.534, respectively,  Dilated cardiomyopathy (DCM) carries a significant burden for the patients and for the health care system and physicians as well. As the disease progresses, treatment options involving medication become limited as heart failure (HF) continues to worsen, severely limiting the patient’s ability to perform even the smallest of daily tasks . FortunaThis study aims to investigate whether several TTE parameters characterizing cardiac performance, and especially the strain imaging techniques such as LV global longitudinal strain (LV-GLS) and LV postero-lateral strain (LV-PLS) could be considered as predictors for suboptimal CRT functional parameters, namely low sensing, and high pacing, in patients with DCM and HFrEF.A single cohort of 48 patients suffering from DCM and HFrEF, who were implanted during January 2020 and June 2021 with three-lead pacemaker CRT (CRT-P) and three-lead intracardiac defibrillator (CRT-D) devices at the Institute of Cardiovascular Diseases from Timisoara, Romania, represent our study population. All patients were symptomatic despite optimal medical therapy (OMT), all had LBBB and were implanted with these devices according to current European Society of Cardiology (ESC) guidelines . PatientAll patients signed the standardized informed consent form required by the Health Authority of Romania at hospital admission, and their data were anonymized before data collection. The Ethics Committee of the Institute of Cardiovascular Diseases, Timisoara approved this study, Nr. 4052/19.06.2020.A complete bidimensional TTE evaluation was performed by a single blinded cardiologist, with advanced training in echocardiography, in all patients approximately 1 day before CRT intervention, using the General Electric VIVID E95 ultrasound system . Several parameters reflecting LV  and right ventricular  morphological and functional status, as well as atrial morphological status , were selected to be analyzed for this study.The left atrial volume (LAV) was measured by planimetry in a biplane manner, in 4 chambers and 2 chambers views, respectively, according to the European Association of Cardiovascular Imaging (EACVI) recommendations .The LV volumes (end-diastolic volume—EDV and end-systolic volume—ESV) were measured by planimetry (tracing the interface between the myocardium and the cavity), also in a biplane manner, in 4 chambers and 2 chambers views, respectively. The LV ejection fraction (LVEF) was measured by using the biplane modified Simpson’s method ,19.The longitudinal strain was evaluated by using the speckle tracking technique, in 4, 2, and 3 chamber views. The region of interest (ROI) was automatically rendered, with subsequent manual adjustments to obtain the best delineation of the myocardium to be analyzed. Care was taken not to include the pericardium in the ROI, and thus obtain falsely decreased absolute strain values. The LV was divided into 6 segments to be analyzed-basal, mid-ventricular, and apical, in each view. Three cardiac cycles were recorded for offline analysis in each view, at a frame rate between 40 and 90 frames/s, depending on the heart rate (higher frame rate for higher heart rates). The global longitudinal strain was calculated on the resultant bull’s eye model ,20,21.The longitudinal contraction of the RV was evaluated by measuring the tricuspid annular plane systolic excursion (TAPSE). This parameter was measured according to the EACVI chamber quantification recommendations, by M-mode, between end-diastole and peak-systole ,19.The systolic pulmonary artery pressure (sPAP) was evaluated by measuring the tricuspid regurgitation flow maximal pressure. The estimated right atrial pressure (RAP) was added to this value (5 mmHg if the diameter of the inferior vena cava (IVC) was <2.1 cm with >50% inspiratory collapse, 10 mmHg if the diameter of the IVC was >2.1 cm with >50% inspiratory collapse or the diameter of the IVC was <2.1 cm with <50% inspiratory collapse and 15 mmHg if the diameter of the IVC was >2.1 cm with <50% inspiratory collapse).In most patients, the implantation technique consisted of inserting a defibrillator/RV pacing lead into the RV cavity via the cephalic vein which was isolated in the deltopectoral groove. If the vein permitted, the atrial lead was inserted using the same route, if not, the atrial lead was inserted via the subclavian vein after positioning the coronary-sinus (CS) lead. Using the cephalic vein for the insertion of the RV lead allowed us to avoid difficulties in positioning because of lead interactions via the route of the subclavian vein, thus facilitating our control in cannulating the CS and maneuvering the CS lead into the optimal position. Arguably the most difficult step of the procedure is positioning the LV lead. This is mainly due to two anatomical variabilities (1) CS ostium and (2) cardiac veins themselves. Once the CS has been cannulated using the purpose built catheters, contrast is injected to visualize the particular anatomy of the cardiac veins, which presents significant interindividual variety . A guideWe consider ideal functioning parameters for pacing around 1 ± 0.5 V for the RV and right atrium leads and around 2 ± 0.5 V for the CS lead with ideal sensing parameters exceeding 10 mV in the case of the CS and RV lead and over 3 mV for the right atrium lead.p < 0.05, exclusion criteria p > 0.10) so as to obtain the most appropriate theoretical model that fit the collected data. The quality of the model was described using the accuracy of prediction and R squared. Data analysis was performed using the Statistical Package for the Social Sciences v.26 . A p-value < 0.05 was considered statistically significant.We employed the Shapiro–Wilk test to evaluate the distribution of numeric variables. Numeric variables were presented as the median and interquartile range (IQR), and categorical variables were presented as frequency and percentages. We employed Wilcoxon test to compare the QRS duration before and after CRT implantation. To evaluate the association between LV sensing/pacing and different echocardiographic parameters we used the Spearman correlation test. To assess the independent factors that influenced the LV sensing/pacing we built several multivariate linear regression models. In the final regression equations, the predictors were accepted according to a repeated backward-stepwise algorithm  years. Thirty-seven of them were men (77%) and 11 women (23%). Referring to the etiology, 37 had idiopathic DCM (64.6%) and 17 ischemic forms (35.4%). According to their symptomatology, most patients were in class NYHA III (47.9%), followed by class II (41.6%) and class IV (10.4%). The characteristics of the study population, as well as their therapy, are presented in All patients were treated according to the ESC guidelines  with OMTp < 0.001, Wilcoxon test). The median values of sensing and pacing parameters of CRT’ devices are presented in We observed a statistically significant shorter QRS duration after the CRT implantation (p = 0.049).By analyzing the existence of statistically significant correlations between several echocardiographic results and LV sensing and pacing, we identified that the most significant ones were evidenced between the strain parameters, followed by the LVEF and LAV both for LV sensing, but especially for LV pacing, To determine which independent factors, namely the LV sensing and LV pacing thresholds, could be predicted in our study group we employed a multivariate linear regression model. We used the forward stepwise method, and the best models were selected based on Akaike information criteria (AIC). We included in our models parameters such as age, sex, echocardiographic parameters, and patients’ comorbidities.2 = 0.721), the details being presented in The regression equation for the LV sensing proved to be adequate for the model, explaining 72.1% of the LV sensing variance (R2 = 0.446). Lower values of LV-GLS, RV-GLS, and TAPSE increase the LV pacing threshold, as well as the presence of diabetes mellitus.Referring to the LV pacing, the model presented in According to the newest ESC guidelines, CRT represents a Class I, Level A recommendation for the treatment of HFrEF, with LVEF under 35%, regardless of the NYHA class, in patients who are still symptomatic, despite OMT, to reduce morbidity and mortality, and especially, to alleviate their complaints and to improve their quality of life ,10,23. TAs they were evaluated before the procedure, a comprehensive TTE exam, followed by strain imaging was performed to characterize LV performance, to observe the severity of kinesis abnormalities, and the existence of mechanical asynchronism ,26. The As debated in the medical literature ,24,29,31Our results are explained by the fact that GLS  reflects the fibrosis burden in the myocardium. It is demonstrated that scar tissue does not have any electrical activity therefore no pacing and/or sensing is possible ,33. It iIn the same manner, even if there is no consistent scar on the LV lead targeted wall, a high amount of diffuse/interstitial or replacement fibrosis explain the altered of the pacing and sensing thresholds. The low response to CRT in these patients is induced, as demonstrated previously by several authors ,33,34,35It is true that longitudinal strain evaluates the longitudinal fibers contraction, fibers that are best represented (but not exclusively) in the subendocardial layer , and theThe main limitation of our study is represented by the small number of patients treated with CRT. The low case numbers were due to the COVID-19 pandemic with admission of non-COVID patients and reduced access to the interventional laboratory. As a consequence of the small patient population, we could not further analyze the impact of other factors, especially of associated diseases, on our results.Modern imagistic techniques, such as cardiac strain, are contributing to the evaluation of patients with heart failure with HFrEF who are referred for CRT implantation, also suggesting a course of treatment. Cardiac strain imaging results might be able to predict the chances of CRT being successful or not, allowing the interventional cardiologist to anticipate and plan for improved patient outcomes.


Functional tricuspid regurgitation (FTR) is a strong and independent predictor of patient morbidity and mortality if left untreated. The development of transcatheter procedures to either repair or replace the tricuspid valve (TV) has fueled the interest in the pathophysiology, severity assessment, and clinical consequences of FTR. FTR has been considered to be secondary to tricuspid annulus (TA) dilation and leaflet tethering, associated to right ventricular (RV) dilation and/or dysfunction  for a long time. Atrial FTR (A-FTR) has recently emerged as a distinct pathophysiological entity. A-FTR typically occurs in patients with persistent/permanent atrial fibrillation, in whom an imbalance between the TA and leaflet areas results in leaflets malcoaptation, associated with the dilation and loss of the sphincter-like function of the TA, due to right atrium enlargement and dysfunction. According to its distinct pathophysiology, A-FTR poses different needs of clinical management, and the various interventional treatment options will likely have different outcomes than in V-FTR patients. This review aims to provide an insight into the anatomy of the TV, and the distinct pathophysiology of A-FTR, which are key concepts to understanding the objectives of therapy, the choice of transcatheter TV interventions, and to properly use pre-, intra-, and post-procedural imaging. Functional tricuspid regurgitation (FTR), secondary to tricuspid annulus (TA) dilation, tricuspid valve (TV) leaflet tethering, or a combination of both, resulting in leaflet malcoaptation , accountFTR has been traditionally considered secondary to the dilation and/or dysfunction of the right ventricle (RV), mainly associated to pulmonary hypertension. Only recently, atrial FTR (A-FTR) has been recognized as a distinct pathophysiological entity, and its peculiar mechanisms have begun to being elucidated ,21,22,23Accordingly, the aim of this review is to provide an insight into the anatomy of the TV, and the pathophysiology of A-FTR, which are key concepts to understanding the objectives of therapy, the choice of TTVI, and to properly use pre-, intra-, and post-procedural imaging .The TV is a complex structure that includes the TA, the TV leaflets, and a sub-valvular apparatus (chordae and papillary muscles). Both the anatomic integrity of the TV apparatus and the normal shape and function of the right heart chambers are needed for the correct functioning of the valve ,34,35.The healthy TA has a dynamic, three-dimensional (3D) saddle-shaped elliptical geometry  34,35,3,37, charThe size of the TA is larger during diastole and smaller during systole. In pathological conditions of TA dilation, it tends to become more planar and circular . The antHowever, the prevalence of significant FTR is extremely variable with the same degree of RA and TA dilation, and TA dilation secondary to RA remodeling in patients with persistent/permanent AF is not always associated with the development of significant FTR . The imbAlthough several studies have elegantly described the pathophysiological mechanisms of A-FTR (previously-referred to as “idiopathic” or “isolated” TR), it represents nevertheless an overlooked consequence of persistent/permanent AF. A-FTR is characterized by TA remodeling associated with RA enlargement, and normal/mildly abnormal RV size and function, especially in the initial stages of the disease . YamasakAlthough still under development and underused in clinical practice, TV interventions should be considered in patients with severe symptomatic FTR, in the absence of severe left ventricular or RV dysfunction, or severe pulmonary hypertension (class IIa) ,29, and 2) and torrential TR (VC width ≥ 7 mm and EROA ≥ 80 mm2) has been useful in predicting patient outcomes in significant FTR .,72.70,72Additionally, 3DE can easily visualize the structures surrounding the TV, which may serve as landmarks for TV interventions or may have implications for TR, such as the inferior and superior vena cava, the CS inflow, the RV outflow tract, the ascending aorta ,70.Due to the complex, 3D configuration and variable spatial orientation of the TA, and since both the 2DE view and the timing of the measurement during the cardiac cycle significantly influence TA size ,78, 3DE A semi-automated 3DE dedicated software for the quantification of TV size and morphology has recently been developed  36]. Th. Th36]. While 2DE may also significantly underestimate right heart chambers’ sizes due to foreshortening or geometrical assumptions, 3DE-derived methods allow a more precise and reliable measure of both the RV and the RA ,83,84.Lastly, several echocardiographic features have been correlated with procedural failure, suboptimal results, or worse outcomes after transcatheter edge-to-edge TV repair, and they should be assessed when considering patient eligibility. These factors are the presence of more severe leaflets tethering, higher tenting volume, greater coaptation depth (>1 cm), large TR coaptation gap size (>7.2 mm), and non-central/non-anteroseptal TR jet ,61,85,86The reference imaging technique for evaluating RV size and systolic function, which are important elements in distinguishing between A-FTR and V-FTR, is CMR. Moreover, CMR can provide accurate TR severity grading based on the measurement of the RegVol and the regurgitant fraction, indirectly calculated by subtracting the pulmonic forward volume from the RV stroke volume , or direCMR and CCT acquisitions and postprocessing can be hampered by motion artifacts in AF patients. However, the use of new pulse sequences and imaging reconstruction algorithms allow real-time free-breathing cine sequences with good spatial and temporal resolution, and can provide precise results in the CMR evaluation of the right heart chambers ,96,97. SFinally, although CCT is the method of choice for assessing TA dimensions ,37,101, A-FTR is a distinct pathophysiological and clinical entity, with different needs of clinical management as well as choice of TV intervention, and most likely with different outcomes than V-FTR. Defining the etiology of FTR, and distinguishing between A-FTR and V-FTR plays a crucial role in the management and selection of the patients for TTVIs. Multimodality imaging is key for confirming the indication for the interventions, the guiding and monitoring of TTVIs, and in the assessment and follow-up of the results of the procedure.


This study investigated if earlier planar images (1 hour p.i.) are beneficial and if SPECT/CT acquisition should be preferred in H-mode (180° detector angle) or L-mode (90°).In [In SPECT/CT phantom measurements , peak contrast recovery (CRpeak) was derived from sphere inserts or myocardial insert . In 25 positive and 38 negative patients , Perugini scores and heart-to-contralateral (H/CL) count ratios were derived from planar images 1 hour and 3 hour p.i.In phantom measurements, accuracy of myocardial CRpeak at SBR 10:1  and reproducibility at 5:1  was comparable for H-mode and L-mode. However, L-mode showed higher variability of background counts and sphere CRpeak throughout the field of view than H-mode. In patients, sensitivity/specificity were ≥ 95% for H/CL ratios at both time points and visual scoring 3 hour. At 1 hour, visual scores showed specificity of 89% and reduced reader’s confidence.Early DPD images provided no additional value for visual scoring or H/CL ratios. In SPECT/CT, H-mode is preferred over L-mode, especially if quantification is applied apart from the myocardium.The online version contains supplementary material available at 10.1007/s12350-021-02715-6. Scintigraphy with bisphosphonates, such as [99mTc]Tc-DPD at (2-)3 hour p.i. In contrast, an earlier time point at 1 hour p.i. is recommended if [99mTc]Tc-pyrophosphate (PYP) is used, while additional imaging at 3 hour p.i. would be recommended if cardiac uptake is superimposed by high blood pool activity at 1 hour p.i.6 Furthermore, SPECT/CT in a dedicated cardiac acquisition protocol using L-mode (90°) detector configuration is recommended, while H-mode acquisition  would only be optional.A recent multi-institutional consensus report defined a standardized method of imaging.99mTc]Tc-PYP in patients examined at 1 hour p.i. compared to patients examined at 3 hour p.i. .99mTc]Tc-DPD.Castano et al. reported higher diagnostic accuracy for cardiac involvement using 9mTcTc-PY99mTc]Tc-PYP—early planar images (1 hour p.i.) provide additional diagnostic value using [99mTc]Tc-DPD. Furthermore, extensive comparative phantom measurements were performed to assess if H- or L-mode acquisition provides superior accuracy and reproducibility of myocardial DPD quantification. Three different dual-head general-purpose SPECT/CT cameras were compared, equipped with either sodium iodide (NaI) or cadmium zinc telluride (CZT) detectors.The current investigation aimed at determining if—in line with [Methods regarding the phantom measurements are described in Online Resource 1. Imaging was performed with three general-purpose SPECT/CT cameras. The NaI cameras were equipped with a low-energy high-resolution (LEHR) collimator . The CZT camera (GE Discovery 670 CZT) used a wide-energy high-resolution (WEHR45) collimator.99mTc]Tc-DPD scintigraphy for suspicion of cardiac ATTR amyloidosis. Suspicion was either based on (a) biopsy-proven ATTR amyloidosis in other organs, (b) typical findings of cardiac amyloidosis in echocardiography  or magnetic resonance imaging (increased extracellular volume > 0.4 and positive late gadolinium enhancement) or (c) heart failure with preserved left ventricular ejection fraction of unclear etiology. In 63 of these 69 patients (45 men), a standard of reference (SOR) was available, and these patients were included into this retrospective analysis. Positive SOR (25 of 63 patients) required histological diagnosis of cardiac ATTR amyloidosis by endomyocardial biopsy (N = 21) or by extracardiac biopsy combined with typical findings in echocardiography or cardiac MRI (N = 4) according to consensus recommendations.Between 05/2019 and 08/2020, 69 patients were referred consecutively for [99mTc]Tc-DPD (IQR 13.1 to 14 mCi [483 to 518 MBq]) corresponding to 0.18 mCi·kg  was injected intravenously. Using one of the three dual-head cameras that were used for the phantom measurements, a static planar image (anterior and posterior view) of the thorax was obtained after a median of 64 minutes (IQR 58 to 73 minutes) p.i. and at 207 minutes p.i. (IQR 197 to 225 minutes). Images were acquired for 5 min each .A median of 13.5 mCi (500 MBq) Tc-DPD scintigraphy in patients with suspicion for cardiac ATTR amyloidosis.This study examined a comprehensive imaging protocol for Tc-DPD scintigraphy are available. However, the current results partly differ from Castano et al. who used [99mTc]Tc-PYP in 171 patients with suspicion for cardiac ATTR amyloidosis. Similar to the current analysis, visual assessment in 126 patients examined at 1 hour p.i. showed specificity of 79%, which was lower than 100% in 45 different patients scanned at 3 hour p.i. However, in contrast to the current results, sensitivity in patients examined at 3 hour p.i. was substantially lower than in patients with early imaging (58% vs 95%). Notably, intra-individual comparison was not provided, and comparability of sensitivity and specificity between both groups could be limited. The discrepant sensitivity at 3 hour p.i. between both studies may not be explained by the different tracer used, because similar blood pool clearance has been reported for [99mTc]Tc-DPD and [99mTc]Tc-PYP in a rat model.To the best of our knowledge, no other reports on early vs late planar images for 9mTcTc-DP99mTc]Tc-DPD (H/CL ratios) or even inferior accuracy and reader confidence . Therefore, in contrast to [99mTc]Tc-PYP imaging, the standard time point for planar images with [99mTc]Tc-DPD should remain at 3 hour p.i., which also allows for a concise imaging protocol . Notably, quantification of [99mTc]Tc-DPD in reference organs outside the left anterior hemithorax  was recently proposed by Scully et al. in patients with suspicion for cardiac ATTR amyloidosis. The authors used H-mode with automated body contouring.Another source of controversy relates to the optimal SPECT/CT acquisition protocol for quantification of myocardial uptake. The current consensus of several international societies of cardiology or nuclear medicineConsequently, H-mode with body contouring should be preferred over L-mode for quantitative purposes. In additional serial measurements using H-mode (Online Resource 2), myocardial CRpeak varied—on average—between 0.95 and 0.99 at SBR 10:1 using the three cameras. Such inter-camera variability of approximately ± 5% and variability between scans (1-2 hour difference) of ± 10% would be acceptable for inter- or intraindividual comparison in clinical application. Variability at SBR of 7:1 remained similar (average CRpeak between 1.0 and 1.04). This implies that in patients with less intense uptake or if uptake varies considerably between two examinations over time . Scully et al. demonstrated almost perfect differentiation of DPD positive and negative cases based on the cardiac peak standardized uptake value (SUVpeak) in 100 patients (AUC 0.999).18CRpeak was decisive of diagnostic accuracy and reconstruction protocol optimization. CRmax may be more common, but usually overestimate sphere activity concentrations and only served for comparison.99mTc]Tc-DPD blood pool activity concentration that can be expected in patient examinationsTo ensure representativeness for clinical conditions, filling of the cardiac phantom was based on the [99mTc]Tc-DPD for a convenient diagnostic workflow.To ensure accurate and reproducible quantification of cardiac SPECT/CT in patients with ATTR amyloidosis, the proposed workflow of optimized image acquisition (H-mode) and image reconstruction  can be employed. This facilitates comparable quantitative accuracy for myocardial uptake between different general-purpose SPECT/CT cameras (NaI and CZT detectors). Early planar images may be safely omitted with [99mTc]Tc-DPD as they provided no additional value for Perugini scoring or H/CL ratios compared to the reference at 3 hour p.i. In SPECT/CT phantom measurements, both H-mode and L-mode acquisition accurately quantified myocardial [99mTc]Tc-DPD uptake using the CRpeak. However, L-mode would impair quantitative accuracy in localizations other than the heart. These results suggest that H-mode acquisition with automated body contouring is preferable and imply that the current consensus recommendations may require reevaluation.Early planar images (1 hour p.i.) can be omitted for [Supplementary file1 (M4A 9267 kb)Supplementary file2 (PPTX 629 kb)Below is the link to the electronic supplementary material.


The quality of life in the realm, emotional realm, and other realms has been significantly improved. For elderly patients with chronic heart failure, reasonable exercise rehabilitation training can provide them with effective preventive measures and protective measures, improve the patients' heart function and quality of life, and play an important and key role.With the acceleration of the aging process, there are more and more elderly patients with chronic heart failure. Chronic heart failure has severely affected the heart function and quality of life of the elderly. This article aims to study the further improvement of the heart function and the quality of life of elderly patients with chronic heart failure through exercise rehabilitation. In this paper, experimental analysis and comparative analysis are adopted, the experimental group and the control group are designed, the adaptive heart rate and breathing rate algorithm is adopted, the heart failure symptom assessment scale and the quality of life assessment tool are selected, and the two groups of different rehabilitation forms are compared. Data collection, sorting, and analysis of the patient's conditions are utilized. Through the use of exercise rehabilitation, the heart failure process will be slower and the recovery of heart strength will be faster than the control group. Before the experiment, the probability of shortness of breath in the two groups of patients with chronic heart failure symptoms was as high as 84.08%, and the symptom clusters were more serious; after the experiment, the SV and EF values after exercise rehabilitation were higher than those of the control group ( Chronic heart failure (CHF) is the initial myocardial infarction caused by some myocardial damage and other reasons, which leads to complex clinical symptoms. Myocardial infarction, myocardial disease, and overload of blood circulation mechanics  can cause changes in myocardial structure and function and ultimately lead to a decrease in ventricular pump or filling function. Chronic heart failure is a disease with high morbidity and mortality. It is also the advanced stage of various cardiovascular diseases, which greatly reduces the quality of life and well-being of patients. The mortality of chronic heart failure is positively correlated with the age of the patients. In our country, as the aging of the population accelerates the process, the prevention and treatment of heart failure is an important public health issue.Exercise rehabilitation is an effective secondary prevention measure for CHF patients. In 2013, according to the guidelines of the American College of Cardiology Foundation, rehabilitation training was recorded as an important recommendation for HR patients. Many foreign studies have shown that while reducing treatment costs, restarting exercise can effectively reduce the prevalence and mortality of heart failure, thereby improving the exercise resistance and quality of life of HR patients. In recent years, HR sports rehabilitation has developed in our country, but many medical staff still lack understanding of it. HR patients and their families cannot effectively use sports training for self-management and support. This article will observe the sports rehabilitation of HR patients, provide a basis for the sports rehabilitation of HR patients, and promote the development of cardiac rehabilitation training in China.p < 0.05). The use of ACEI and beta blockers from moderate to severely reduced groups is very small. Diuretics and spironolactone were used (p < 0.05). Compared with the normal renal function group, the use rate of ACEIs is low, and the use rate of diuretics is low. However, their experimental method has limitations and there are many restrictive factors  of the heartbeat signal and breathing signal through three estimators , and calculate the most likely Yj.In this algorithm, we will evaluate each possible interval length of each analysis window (1) Three Estimators Improve Autocorrelation. Autocorrelation is widely used in signal processing, and the similarity of signals can be detected through autocorrelation. In this algorithm, we use a mature and improved autocorrelation function to estimate the length of each possible interval of each analysis window Qj[b] of the heartbeat signal and breathing signal. The autocorrelation function formula is shown in (2) Improve the Average Amplitude Difference. The traditional average amplitude difference takes the minimum value of Q[b] − Q[b − M] when the signals are similar. This parameter can be used to infer the similarity of the signal. In this algorithm, we unify the value of the estimator and obtain the maximum value when the signal has high similarity, so the traditional average amplitude difference is reversed, so that it is unified with the values of other estimators and is convenient for analysis. The specific improved average amplitude difference formula is shown in (3) Maximum Amplitude Pair. The maximum amplitude pair is the best representation of the amplitude information of the signal. In the successive periods before and after the signal, the amplitude sum of N corresponding to the peak of the signal and the peak is the largest, which is beneficial to the direct detection of the signal peak. Because this estimator relies on the peak amplitude information of the signal, it is susceptible to the influence of signal quality, but it can greatly improve the accuracy of signal estimation while combining the first two estimates. The calculation formula of the specific maximum amplitude pair is shown in the following formula:b ∈ {−Ymax · gs, ⋯, Ymax · gs} in different interval threshold ranges M ∈ {Mmin, ⋯, Mmax} for each sliding window Qj[b]. Calculate the most likely local signal interval length by combining the values of three different estimators at different points.In this algorithm, we will calculate three estimator values M is correct. In this algorithm, we look at the output of the above three estimators  separately. It is formed into three Bayesian posterior probability density functions. These three probability density functions describe the probability of each estimator so that its output N is the true signal interval length. The N with the highest probability is the most common interval length:The estimator through the above calculation method provides a possible value of the interval at which each According to the Bayesian principle, the probability density function can be described asAssuming that the similarity between estimators is only related to the true interval length of the signal and not related to the output of other estimators, formula  can be sUsing Bayesian principle again, we can getM and use Bayesian formula to getIgnore the fixed factors that have nothing to do with P (M) as a prior probability with uniform distribution; then, formula Y=MgThis article conducted a research experiment to improve the heart function and quality of life in elderly patients with chronic heart failure. The experimental group and the control group were selected for comparative experiments. The experimental group adopted exercise rehabilitation and the control group adopted traditional rehabilitation methods to compare the performance between the two groups. Changes in heart function and improvement in quality of life were noticed. This article selects heart failure symptom assessment scale and quality of life assessment tools to investigate from physical, emotional, and other fields. The experimental results show that exercise rehabilitation is beneficial to the recovery of heart function in elderly patients with chronic heart failure, and it can also improve the quality of life of patients and life happiness.In this experiment, a total of 163 patients who were diagnosed and hospitalized in the Department of Cardiology, Geriatrics, and Cardiology Rehabilitation Department of Y Hospital from March (2019) to July (2019) were selected. It is divided into experimental group and control group. The experimental group takes the form of exercise rehabilitation, and the control group takes traditional rehabilitation. Through comparative experiments, the cardiac function and quality of life of the two groups of patients are studied. The included experimental subjects of heart failure patients must be unconscious and have basic communication skills. In addition, their participation in this trial has been approved by their family members. Those with liver and kidney failure, advanced malignant tumors, and other serious diseases should be excluded. It is mainly aimed at the physiological and psychological states of these patients under different intervention periods.Patient general information questionnaire: This questionnaire is designed by the author to understand basic information such as age, course of disease, prevalence, gender, education level, and other basic information of patients. Among them, the symptoms of elderly patients were collected specifically during the data collection process.Heart failure symptom assessment scale: This scale selects MSAS-HF, which includes the patient's physical, psychological, and heart failure symptoms, and has more than 30 subitems for testing to understand whether the patient has heart failure, degree of heart failure, frequency of occurrence, distress, etc.Quality of life evaluation tools: The quality of life evaluation tools for patients with chronic heart failure are divided into nonspecific quality of life evaluation tools and specific quality of life evaluation tools.  Experimental group: According to the different degrees of heart failure of patients, exercise training with different intensities is designed. The training mainly includes aerobic exercise; muscle strength training; flexibility training, including walking, jogging, Tai Chi, aerobic gymnastics; and reasonable control of exercise duration; all exercises are carried out under no physical load, and exercise frequency is average exercise every other day making appropriate adjustments based on your physical condition.  Control group: Traditional rehabilitation training adopts conservative treatment methods. Exercise is not suitable, and it is best to maintain a happy mood.Both groups of patients received physical rehabilitation training on the basis of conventional drug treatment. The experimental group received sports rehabilitation, and the control group took traditional rehabilitation methods. The specific process is as follows:The whole process of exercise is monitored by adaptive heart rate and breathing rate algorithm, and the stroke volume (SV) and left ventricular ejection fraction (EF) of all patients before and after exercise are measured. And the patient wear a monitoring bracelet to keep abreast of their cardiac function status and record the mood status, changes in the situation, appetite, and other related indicators every day.This experiment explained the situation of all patients, signed an informed consent form, and completed the questionnaire independently. Researchers completed and sorted out the questionnaire on the spot to ensure the validity and completeness of the questionnaire.x ± s, and some are expressed in medians. All data are valid; this article also uses multifactor analysis to analyze the impact on the quality of life of patients and heart function research.The experimental data in this article are all used SPSS17.0 for data sorting and analysis. The measurement data are expressed in General data and clinical data surveys were conducted on the 163 study subjects that were finally included. The results of the survey are shown in It can be seen from It can be seen from p < 0.05). The difference in the original data between the two groups was not large. After the intervention of the test group, the maximum value of SV increased from 39.3 to 45.41; the maximum value of EF increased from 44.26 to 51.01. Regardless of SV or EF, the data of the control group and the experimental group have increased to a certain extent before the intervention, but it is obvious that the data presented by the test group have greater fluctuations, indicating that the left ventricular systolic function is more. With coordination, the patient's heart rate tends to move more toward the normal range, indicating that the intervention has a significant therapeutic effect on heart rate failure.We measured the ventricular systolic function of patients, and the test results are shown in The results of disease characteristics classification variables are shown in r = −0.494/−0.385, p < 0.01); NT-proBNP is significantly positively correlated with quality of life .Factors affecting their quality of life mainly include changes in their physiological functions, decreased exercise endurance (due to insufficient cardiac output and insufficient oxygen), high psychological stress , cognitive impairment, individual psychological characteristics , and lack of social support (burden and pressure on family members). According to the Pearson correlation analysis between the heart function indexes  of patients with chronic heart failure and the Minnesota heart failure quality of life scores, the results in In order to verify the influence of other factors on the survey results, this paper assigns a single factor and introduces a multifactor logistic regression model for analysis. The assignment results are shown in The step-by-step method is adopted, with 0.05 as the significance level of the introduced variable and 0.10 as the significance level of the excluded variable. This is based on the algorithm of the expected range of heartbeat and respiration. In the previous article, the multifactor analysis method was used to estimate and predict the amplitude of this fluctuation. Pearson correlation analysis can provide sufficient basis for it. The results in F = 11.48, p=0.001); there were differences in the total quality of life scores between different time points  and rehabilitation There is an interaction between method and time .Two-factor (group factor and time factor) repeated measures analysis of variance was used to compare the differences in the total quality of life scores between the two groups of patients. The experimental results are shown in It can be seen from p < 0.05). The results show that different per capita income, heart failure at first diagnosis, and the number of combined diseases enter the regression equation, which can explain 14.8% of the variation in quality of life.It can be seen from In order to further reveal the relationship between symptom burden, self-efficacy, social support, and quality of life, the quality of life is used as a dependent variable, with different per capita income, heart failure at first diagnosis, number of combined diseases and symptom burden, self-efficacy, and social support. Carry out regression analysis for the independent variables and incorporate all the independent variables into the regression equation. The results are shown in This article mainly focuses on the research of exercise rehabilitation to improve the heart function and quality of life of elderly patients with chronic heart failure. Through literature data method, experimental analysis method, and comparative analysis method, it shows that exercise rehabilitation can effectively improve the elderly patients with chronic heart failure. Cardiac function, self-efficacy, social support, and other aspects have been very effective, which can effectively improve the quality of life of patients. The innovation of this paper is to use adaptive heart rate and respiration rate algorithm to detect the heart function of the patient. While protecting the health of the patient, observe the changes of the patient's heart rate and other indicators to keep abreast of the patient's heart function. And this article has strong pertinence in topic selection and design, and it is original and innovative. The limitation of this article is that the sampling range is narrow, the representativeness of the sample is not strong, and the exercise risk is not accurately grasped, which limits the experimental process of the research object. Future research can expand the scope and age of research, increase the sample base, and make reasonable arrangements from a more professional sports rehabilitation perspective to ensure and improve the health of patients.


The long-term post-LVEF reached a plateau of approximately 60% when the pre-LVEF was ≥50%, but it seemed to show a downward trend after reaching a peak at approximately 3–4 years after MVr when the pre-LVEF was ≥70%. The patterns of short- and long-term changes in post-LVEF differed according to pre-LVEF and pre-LVESD values in patients with chronic primary mitral regurgitation after MVr.This study sought to identify the short- and long-term changes in left ventricular ejection fraction (LVEF) after mitral valve repair (MVr) in patients with chronic primary mitral regurgitation according to preoperative LVEF (pre-LVEF) and preoperative left ventricular end-systolic diameter (pre-LVESD). This study evaluated 461 patients. Restricted cubic spline regression models were constructed to demonstrate the long-term changes in postoperative LVEF (post-LVEF). The patients were divided into four groups according to pre-LVEF . The higher the pre-LVEF was, the greater was the decrease in LVEF immediately after MVr. In the same pre-LVEF range, immediate post-LVEF was lower in patients with pre-LVESD ≥ 40 mm than in those with pre-LVESD < 40 mm. The patterns of long-term changes in post-LVEF differed according to pre-LVEF ( Mitral valve surgery is recommended for chronic primary mitral regurgitation (MR) depending on the patient’s symptoms and left ventricular (LV) systolic function according to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines [Some studies have investigated the changes in LVEF after mitral valve surgery in patients with chronic severe MR ,4,5,6,7.No study to date has examined the serial long-term changes in LVEF after MVr in patients with chronic primary MR with a wide range of pre-LVEF values. Identifying such changes may be helpful in predicting long-term outcomes after MVr in these patients based on pre-LVEF values. In addition, the extent of the decrease in LVEF immediately after MVr has not been extensively evaluated in patients with chronic MR, although a decrease in LVEF has been known to occur immediately after MVr in patients with chronic MR ,7. In thThis retrospective observational study included patients who underwent MVr for chronic MR with grade ≥ moderate caused by excessive motion of mitral valve leaflets, at Asan Medical Center  from January 2005 to July 2015. Patients were excluded if remnant MR with grade ≥ moderate  was detected at the immediate postoperative echocardiography; if they had coronary artery disease, concomitant aortic valve disease of grade ≥ mild, infective endocarditis, rheumatic MR, and acute MR; if they underwent redo surgery, concomitant coronary artery bypass graft surgery, or repeated mitral valve surgery after the index hospitalization; and if they did not have at least one postoperative echocardiographic examination. The research protocol was approved by our Institutional Review Board (AMC IRB 2017-0052), which waived the requirement for written informed consent. Data were acquired from a retrospective review of electronic medical records.All patients underwent transthoracic echocardiographic examination before and during the follow-up after MVr. The details of the echocardiographic examination, including the assessment of MR severity, are described in the Preoperative echocardiographic data obtained closest to the day of surgery were used in the analysis. At our institution, all patients undergo routine echocardiographic evaluation before discharge. The details of the analyzed immediate postoperative echocardiographic data are described in the TR) were collected.The measurements for LVEF, LV end-systolic and LV end-diastolic volume index , left atrial (LA) diameter, ratio of peak early diastolic velocity of mitral inflow to mitral annulus early diastolic velocity (E/e’), and the pressure gradient calculated from peak tricuspid regurgitation  to assess LV contractility. The details of the calculation of actual and predicted mFS, circumferential end-systolic wall stress (cESS), and stress corrected mFS (sc-mFS) are described in the During the follow-up, re-developed MR was defined as the recurrence of MR with grade ≥ moderate, regardless of the measurement time point. All-cause mortality was obtained during the follow-up.<50 = pre-LVEF < 50%, Gr50–60 = 50% ≤ pre-LVEF < 60%, Gr60–70 = 60% ≤ pre-LVEF < 70%, and Gr≥70 = pre-LVEF ≥ 70%. We adopted a cut-off of 40 mm for preoperative LVESD (pre-LVESD) to indicate LV dysfunction, as suggested in the ACC/AHA guidelines for patients with chronic primary MR [Continuous data are presented as mean ± standard deviation or median (interquartile range), and categorical data are presented as frequencies (percentages). The patients were classified into four groups according to pre-LVEF: Grimary MR .p < 0.05 was considered statistically significant. The other details are described in the The P for trend test using linear regression analysis or Spearman’s correlation analysis was performed to investigate whether the immediate postoperative echocardiographic parameters had a linear trend across the four groups. To evaluate the effect of time on post-LVEF, linear mixed models were constructed, with group, time, and the interaction between group and time as fixed effects, and patient effect as random effects. Kaplan-Meier analysis was performed to compare long-term mortality using log-rank sum test, and Bonferroni correction was used as the post hoc test (adjusted α = 0.05/6 = 0.0083). Multivariable Cox proportional hazards regression analysis was performed to evaluate the impact of pre-LVEF groups on long-term mortality. During the study period, 1030 patients underwent mitral valve surgery for MR. Among them, 569 did not satisfy the inclusion criteria ; thus, tA total of 2654 echocardiographic examinations were performed during 3.6 (1.8–7.1) years of follow-up. The immediate postoperative echocardiography, performed at 4.0 (3.0–5.0) days after the surgery, was analyzed in 455 patients .<50, Gr50–60, Gr60–70, and Gr≥70 comprised 15, 76, 284, and 86 patients, respectively. The proximal isovelocity surface area radius was 13.2 ± 4.0, 13.9 ± 4.0, 13.6 ± 3.2, and 14.3 ± 3.4 mm in Gr<50, Gr50–60, Gr60–70, and Gr≥70, respectively (p = 0.431). The comparisons of preoperative PGTR, E/e’, and LA across groups are described in the The patients’ demographic, clinical, and preoperative echocardiographic data are presented in P for trend < 0.001) (P for trend < 0.001) (The immediate postoperative LVEDVI (post-LVEDVI) decreased more in the order of ascending pre-LVEF groups (< 0.001) . The amo< 0.001) .<50, Gr50–60, Gr60–70, and Gr≥70, respectively (P for trend <0.001) (p < 0.001)  are described in the The immediate post-LVEF values were 39.0 ± 9.4%, 50.9 ± 9.9%, 53.8 ± 8.6%, and 56.5 ± 7.2% in Grectively A. The hi <0.001) B. When c< 0.001) . We coul<50  values were >100%, except in Gr<50 A. Convernd Gr≥70 B.<50, post-LVEF increased until about 1 year after MVr, and thereafter showed a plateau of approximately 50%. In Gr50–60 and Gr60–70, post-LVEF increased until about 3–4 years after MVr, and thereafter formed a plateau of approximately 60% in the long-term. Conversely, in Gr≥70, post-LVEF decreased and thereafter subsequently increased until approximately 3 years, after which it seemed to decrease to a lower level than that in Gr50–60 over time. After excluding patients with re-developed MR (n = 59), similar patterns were observed in the long-term changes in post-LVEF , with the lowest mortality rate in Gr60–70 , when Gr60–70 was considered as a reference group.A total of 33 patients died during the follow-up. Kaplan–Meier analysis showed a difference in mortality rate among the groups  the higher the pre-LVEF was, the greater was the decrease in LVEF immediately after MVr; (2) the long-term post-LVEF reached a plateau of approximately 60% when the pre-LVEF was ≥50%, but seemed to show a downward trend after reaching a peak at approximately 3–4 years after MVr when the pre-LVEF was ≥70%; (3) among patients with the same pre-LVEF, the post-LVEF was lower in those with pre-LVESD ≥ 40 mm than in those with pre-LVESD < 40 mm during both short- and long-term follow-ups; (4) the long-term mortality rate was lowest in patients with 60% ≤ pre-LVEF < 70%.60–70 and Gr≥70, or the patient groups with a LVEF considered normal for chronic primary MR according to the 2017 ACC/AHA guidelines [≥70 than in Gr60–70. This might have led to a greater decrease in post-LVEF in Gr≥70 than in Gr60–70. We found that immediate postoperative cESS decreased more in Gr≥70 than in Gr60–70 (≥70 than in Gr60–70, because LVESVI is mainly dependent on afterload. However, our results showed that immediate post-LVESVI did not change in Gr≥70 but that it decreased in Gr60–70. From these findings, we could not exclude the effect of intrinsic LV contractility, which could be revealed in the absence of volume overload, on the immediate post-LVEF.Theoretically, the decrease in LVEF immediately after MVr can be attributed to a decrease in preload, an increase in afterload, or a decrease in contractility of left ventricle. When exploring Gr Gr60–70 ; therefoIn this study, we assessed sc-mFS which provided an afterload-independent estimate of LV systolic function . Because≥70 was lower than that in Gr60–70, although there was no statistically significant difference. Furthermore, preoperative PGTR was higher in Gr≥70 than in Gr60–70, with similar E/e’ and LA diameter, showing that all values exceeded the normal ranges (≥70 than in Gr60–70, suggesting the potential for the development of reactive pulmonary hypertension in Gr≥70. We speculated that a preoperative supra-normal LVEF may reflect the condition in which the left ventricle maximally compensates for volume overload. Supra-normal LVEF may be a surrogate for a greater MR burden, rather than being the generally known concept of LVEF.Circumferential fiber contraction has been reported to aid in maintaining global ventricular systolic function in patients with severely impaired longitudinal fiber function, so that LVEF can be preserved ,14,15. Wl ranges . These f60–70 than in Gr50–60. The 2017 ACC/AHA guidelines offer LVEF 60% as a cut-off for LV dysfunction, and suggest that mitral valve surgery is reasonable before LVEF reaches 60% in asymptomatic patients with chronic primary MR, with a level of evidence of B or C-LD [With respect to long-term changes, post-LVEF reached a plateau of approximately 60% in patients with preoperative LVEF ≥ 50%. Notably, the mortality rate was lower in Gr or C-LD . Most pr or C-LD , or comp or C-LD ,5,7,19. ≥70, the long-term post-LVEF seemed to decrease after reaching a peak. A previous study reported that pre-LVEF > 60% did not guarantee LVEF recovery during 10 years of follow-up after MVr in patients with primary chronic MR, in that LVEF returned to the preoperative level only in two thirds of patients with postoperative LV dysfunction although all patients showed pre-LVEF > 60% [≥70 may be in line with this recent report, in that both studies suggest that supra-normal LVEF should not be considered the same as normal LVEF. Further studies are definitely needed to elucidate this issue. Various modalities for LV assessment, including cardiac magnetic resonance imaging to evaluate myocardial fibrosis [In GrEF > 60% . We thinfibrosis , B-type fibrosis , and venfibrosis , may imp<50, further studies including larger numbers of such patients are necessary to identify the long-term changes in post-LVEF, because there were only 15 patients in this group.In GrLVESD is known to be indicative of reduced LV systolic function in patients with chronic MR ,25,26. AThe present study had some limitations. First, this was a retrospective observational study. The measurement time points for follow-up echocardiography were determined at the physician’s discretion. Therefore, the intervals between the measurement time points differed according to individual patients and were variable even in the same patient. Some patients underwent echocardiographic examination less frequently over time after surgery, and the interpretation of these estimates of long-term results may be limited. This should be considered when interpreting the results. In addition, systolic blood pressure measurement was available in a few patients; therefore, the same was true for sc-mFS. Second, since the present study had a small number of deaths, the number of covariates included in the multivariable model was limited to avoid a potential problem of overfitting. Further studies including a large number of patients are needed to confirm independent association between pre-LVEF and long-term mortality. In addition, our result of multivariable analysis showed a wide range of 95% confidence interval that may be attributed to a small number of deaths, which should be taken into account when interpreting the result. Third, we did not have information about MR-related symptoms, symptom duration, or the time interval between the onset of symptoms and MVr, which may be related to the extent of LV remodeling. Therefore, these factors may be indicative of the LV function even in the same LVEF range. Further studies are needed to elucidate these issues.In terms of short-term change, the higher the pre-LVEF was, the greater was the decrease in the immediate post-LVEF, and the immediate post-LVEF decreased more with larger pre-LVESD in the same pre-LVEF range. In terms of long-term changes, post-LVEF showed a plateau in patients with pre-LVEF > 50%, and lowest mortality was observed in patients with 60% ≤ pre-LVEF < 70%. In addition, there may also be a possibility that post-LVEF showed a decreasing trend in the long-term in patient with pre-LVEF ≥ 70%. Further studies are needed to confirm our findings.


Introduction: Left ventricular (LV) dilatation and LV hypertrophy are acknowledged precursors of myocardial dysfunction and ultimately of heart failure, but the implications of abnormal LV geometry on myocardial function are not well-understood. Non-invasive LV myocardial work (MyW) assessment based on echocardiography-derived pressure-strain loops offers the opportunity to study detailed myocardial function in larger cohorts. We aimed to assess the relationship of LV geometry with MyW indices in general population free from heart failure.Methods and Results: We report cross-sectional baseline data from the Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) cohort study investigating a representative sample of the general population of Würzburg, Germany, aged 30–79 years. MyW analysis was performed in 1,926 individuals who were in sinus rhythm and free from valvular disease . In multivariable regression, higher LV volume was associated with higher global wasted work (GWW)  and lower global work efficiency (GWE) , while higher LV mass was associated with higher GWW  and global constructive work (GCW)  and lower GWE . This was dominated by the blood pressure level and also observed in participants with normal LV geometry and concomitant hypertension.Conclusion: Abnormal LV geometric profiles were associated with a higher amount of wasted work, which translated into reduced work efficiency. The pattern of a disproportionate increase in GWW with higher LV mass might be an early sign of hypertensive heart disease. The constant exposure to cardiovascular risk factors and/or adverse hemodynamic conditions induces complex changes in left ventricular (LV) geometry, often starting as a physiological compensatory response , 2. Alten = 5,000, free of symptomatic heart failure. The study design and baseline characteristics have been published previously . This group had been included between December 12, 2013, and September 2, 2016, was pre-specified for a planned interim analysis (Within the Characteristics and Course of Heart Failure STAges A/B and Determinants of Progression (STAAB) prospective cohort study, we recruited and comprehensively phenotyped a representative sample of the population of Würzburg, Germany, aged 30–79 years, eviously , 16. Theanalysis , and theParticipants were evaluated at the Joint Survey Unit of the Comprehensive Heart Failure Center and the Institute for Clinical Epidemiology and Biometry, University of Würzburg. Routine laboratory measurements were performed at the central laboratory of the University Hospital Würzburg, including fasting lipid profile, estimated glomerular filtration rate (eGFR), glycosylated hemoglobin (HbA1c), and NT-proBNP levels. Blood pressure (in a sitting position after 5 min of rest), body height and weight, hypertension history, and current anti-hypertensive pharmacotherapy were assessed according to standard operating procedures . Accordi−1 and stored digitally. We derived end-diastolic interventricular septum thickness (IVSd), LV posterior wall thickness (LVPWd), and LV end-diastolic diameter (LVEDD) in the parasternal long-axis from an M-Mode recording, or—in case of suboptimal angulation—from a 2D measurement (3 - LVEDD3)]) + 0.6 as well. LV relative wall thickness (RWT) was calculated as: /LV end-diastolic diameter  concentric LV remodeling (CR), LVMi ≤95 g/m2 in women or ≤115 g/m2 in men and RWT >0.42; (c) concentric LV hypertrophy (CH), LVMi >95 g/m2 in women or >115 g/m2 in men and RWT >0.42; (d) eccentric LV hypertrophy (EH), LVMi >95 g/m2 in women or >115 g/m2 in men and RWT ≤0.42.Image acquisition was performed by trained and certified sonographers employing one echocardiography machine  with presets maintained according to a pre-specified protocol. The utility of performance measures of the echocardiography quality assurance program has been published previously . A minimsurement . We calcsurement : LV massdiameter . We furtdiameter . Early ddiameter . LV massdiameter , we clasdiameter : (a) norMyW analysis was performed off-line based on the stored echocardiography images and blood pressure measurements. Aortic and mitral valve closure and opening times were assessed by CW Doppler of the aortic valve and PW Doppler of the mitral valve. However, as potential changes in heart rate during the examination might affect the loop area, these time points were visually verified in the apical three-chamber view and manually adjusted where necessary. LV apical four-, two-, and three-chamber views were analyzed off-line using Automated Functional Imaging  to determine global longitudinal strain (GLS). Provision of peripheral blood pressure allowed the derivation of the MyW parameters as detailed by others , 10, 20.A) Global constructive work [GCW (mmHg%)], i.e., the sum of positive work performed during shortening in systole and adding negative work during lengthening in isovolumic relaxation;B) Global wasted work [GWW (mmHg%)], i.e., the sum of negative work performed during lengthening in systole plus work performed during shortening against a closed aortic valve in isovolumic relaxation;C) Global work index [GWI (mmHg%)], i.e., the total work performed from mitral valve closure to mitral valve opening.D) Global work efficiency [GWE (%)], i.e., GWE= GCW / (GCW + GWW).All indices were calculated as the mean of respective segmental values (18-segment model). We excluded subjects from further analysis in whom >1 LV segment was unsuitable for analysis due to poor tracking or suboptimal image quality. Determination of MyW, as well as quality assurance measures, have been published previously . Figure t-test, non-normal distributed variables using the Mann-Whitney U-test, and categorical variables using the chi-square test, respectively. Differences between groups were tested using the Kruskal-Wallis test, median test, and chi-square test. To test the relationship between LV geometry and MyW, we first ran a univariable linear regression analysis for each of MyW indices. Because we wanted to describe the relative contribution of systolic blood pressure, this variable was also tested, despite the fact that it is part of the derivation of myocardial work indices. In subsequent multivariable models, however, systolic blood pressure was omitted. Models were based on results of univariable regression and their physiological context. Thus, the multivariable model included age, sex, body mass index (BMI), LVEF, GLS, heart rate, low-density lipoprotein (LDL), glycosylated hemoglobin (HbA1c), hypertension, and measures of LV geometry such as LVMi and LVEDVi. The Jonckheere-Terpstra test was used for trend analysis. All tests were performed 2-sided. P-value < 0.05 were considered statistically significant. Statistical analysis was performed using SPSS .Continuous variables are described as mean (standard deviation) and categorical variables as frequency (percent). Normal distribution was checked using the Shapiro-Wilk test. Normal distributed variables were compared using the n = 547 participants were excluded from the current analysis for different reasons including technical issues regarding required views, poor tracking or suboptimal image quality, or missing blood pressure values . Ninety-three percent of those had normal LV geometry, and 5% exhibited CR, 2% had EH, and <1% had CH, respectively. For the pre-planned interim analysis of the STAAB cohort study, 2,473 individuals were considered. Of those, a total of Participants with normal LV geometry were younger and had lower BMI, SBP, NT-proBNP, LDL cholesterol, and HbA1c compared to abnormal geometric LV patterns . AccordiIn multivariable linear regression analysis including age, sex, BMI, heart rate, LVEF, LDL, HbA1c, hypertension, LVMi, and LVEDVi, we found that higher LV muscle mass was associated with a higher GCW, but also with higher GWW, thus resulting in reduced GWE. In contrast, higher LV volume was associated with higher GWW only, which also resulted in lower GWE . In a fuThe current study investigated the association of altered LV geometry with MyW indices in a large, population-based sample. Three major findings emerged. First, while the majority of individuals studied exhibited a normal LV geometry, a relevant proportion of participants revealed an abnormal LV geometry; these subjects were older and presented with a less favorable profile of cardiovascular risk factors. Second, both LV enlargement and LV hypertrophy were adversely associated with GWE, predominantly through increasing the amount of GWW. Third, when compared to participants without hypertension, individuals with normal LV geometry and concomitant hypertension exhibited larger LV mass and LA volume and less favorable measures of systolic and diastolic function. Their MyW pattern was characterized by higher GCW and GWW and thus lower GWE, comparable to the pattern found in LV hypertrophy.Altered LV geometry, including its components LV mass and LV volume, constitute pivotal information of the standard echocardiography report , as theyAn increased hemodynamic load, induced either by pressure, e.g., in hypertension, or by volume, e.g., in valvular disease, or by a combination of both stimuli, contributes to LV hypertrophy and/or dilation, resulting in different geometric adaptations , 2. ReceCR dominated in our study sample, followed by EH and CH. CR is considered a late-stage response of the LV to adverse hemodynamic circumstances and is predominantly caused by pressure overload as induced by increased afterload  due to aArterial hypertension is one of the most prevalent cardiovascular risk factors and a major contributor to long-term changes in LV geometry , 43, 44.This phenotype is characterized by increased LV size  in the presence of normal wall thickness. EH is typically found in states of chronic volume overload, such as significant mitral regurgitation (which was excluded from our study sample), but also as an early manifestation of a cardiomyopathic process , 36. FurCardiomyopathies are characterized by heterogeneous patterns of LV hypertrophy and progressive LV enlargement leading to myocardial dysfunction –49 and, In this large population-based sample, cardiovascular risk factors were comprehensively and carefully assessed according to standard operating procedures. In particular, echocardiography was performed by well-trained and internally certified and quality-controlled sonographers . HoweverMyW analysis is a non-invasive, echocardiography-based method facilitating new insights into the relationship of LV geometry and myocardial performance in this population-based cohort free from heart failure. Any deviation from a normal LV geometric profile was associated with an alteration of MyW. While LV dilation was associated with solely higher GWW, concentric remodeling and hypertrophy were associated with both higher GCW and GWW. A disproportionately higher GWW resulted in lower GWE. These altered MyW patterns were already present in hypertensive individuals with normal LV geometry and might thus serve as an early sign of incipient hypertensive heart disease. Longitudinal studies are needed to test this hypothesis and improve our understanding on the mechanisms of hypertensive heart disease and the time course of its evolvement.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee of the Faculty of Medicine, University of Würzburg (vote #98/13) and data protection officer of the University of Würzburg (#J-117.605-09/13). The patients/participants provided their written informed consent to participate in this study.FS, CM, GG, PH, and SS concepted and designed the study. FS, CM, VC, JA, FE, GG, PH, and SS analysis and interpretation of data. FS drafted the manuscript. CM, VC, JA, FE, GG, PH, and SS revised the manuscript critically for intellectual content. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.