Perioperative evaluation of the left ventricular systolic function is essential information to help diagnose and manage life-threatening perioperative emergencies. Although quantifying the left ventricular ejection fraction (LVEF) is recommended to determine the left ventricular function, it may not always be feasible in emergency perioperative settings. This study compared the visual estimation of LVEF  by noncardiac anesthesiologists with the quantitative LVEF measured using a modified Simpson’s biplane method.Transesophageal echocardiographic (TEE) studies of 35 patients were selected and 3 different echocardiographic views  were recovered from each study and displayed in random order. Two cardiac anesthesiologists certified in perioperative echocardiography independently measured LVEF using the modified Simpson method and categorized LVEF into five grades: hyperdynamic LVEF, normal, mildly reduced LVEF, moderately reduced LVEF and severely reduced LVEF. Seven noncardiac anesthesiologists with limited experience in echocardiography also reviewed the same TEE studies and estimated the LVEF and graded LV function. The precision of the LV function classification and the correlation between visual estimation of LVEF and quantitative LVEF were calculated. The agreement of measurements between the two methods was also assessed.p < 0.001). Of a total of 245 responses, 120 (49.0%) responses were correct grading of the LV function. Participants were able to classify the LV function more accurately in the LV function grades 1 and 5 (65.3%). The 95% level of agreement of the Bland-Altman method was − 11.3-24.5. -21.9-22.6, − 23.1-26.5, − 20.5-22.0 and − 26.6-11.1 for LV grade 1 to 5, respectively.Pearson’s correlation between the LVEF estimated by the participants and the quantitative LVEF using the modified Simpson method was 0.818 (Visual estimation of LVEF in perioperative TEE has acceptable accuracy in untrained echocardiographers and can be used for rescue TEE. • Estimation of LVEF by noncardiac anesthesiologists is essential to aid in diagnosing and managing life-threatening perioperative conditions.• Visual estimation of the LVEF is easy to perform with acceptable accuracy.• This method could be helpful as part of a rescue TEE protocol and in training programs for LVEF interpretation. Transesophageal echocardiography (TEE) is used for hemodynamic monitoring and to provide immediate assessment of cardiac function for anesthesiologists during cardiac surgery –3. IncreThe left ventricular ejection fraction (LVEF) is a widely used and accepted key parameter for assessing left ventricular (LV) function. Although calculating the two-dimensional (2D) LVEF using the modified Simpson method of discs is preferred –9, this Previous studies evaluating the precision of visual estimation of LVEF using transthoracic echocardiography (TTE) imaging views demonstrated 66–72% agreement between visual LVEF and quantitative methods among noncardiologists  with minimal training –15. We hTherefore, the study aimed to find the agreement on the LV function classification between the visual estimation of noncardiac anesthesiologists and the reference method of quantitative measurement using modified Simpson biplane discs.This study was approved by the Siriraj Institutional Review Board (Si 201/2020) and written informed consent was obtained from all participants.randomization.org).The TEE imaging studies were evaluated for image quality and 40 sets of intraoperative TEE studies were selected from the image management system database of the Department of Anesthesiology, Siriraj Hospital Faculty of Medicine, Bangkok  by two researchers (AN and KR). The TEE imaging studies were anonymously retrieved and three video clips were exported for each study set, including the mid-esophageal four chamber view, the mid-esophageal two chamber view, and the transgastric mid-papillary short axis view . Two carFor the purpose of the study, seven noncardiac anesthesiologists with limited experience in echocardiography (no previous training in perioperative TTE/ TEE) were recruited using purposeful sampling. All participants received a 10-minute reading on the concept of LVEF measurement, the orientation and planes of the images, the structures demonstrated in each view, and the LVEF classifications. The participants were then asked to review the same 35 sets of TEE imaging studies, estimate LVEF, and grade the LV function category without time limitation. All participants were blinded to the LVEF and the grade of the LV function measured by experts. Participants received immediate feedback on their responses compared to the quantitative LVEF and their grading after each set of clips once their responses were submitted. Age, sex, and experience in echocardiography of the participants were recorded. The participants were then asked to rate their confidence in the accuracy of their estimates after completion.The primary outcome of this study was the agreement of the LV function classification between the estimated LVEF of participants and the quantitative LVEF of trained experts. Acceptable agreement was determined when the participant and expert grades matched or were in adjacent categories (1 grading difference). The secondary outcome was the correlation between the LVEF estimated by the participants and the quantitative LVEF. The agreement between each LVEF estimated by the participants and the quantitative LVEF using the modified Simpson method was also evaluated.The sample size calculation was informed by a previous study that reported that emergency physicians and cardiologists agreed that the systolic function classification of LV was 0.9 . Based op-value < 0.05 was considered statistically significant.Statistical analyses were performed using SPSS 21 for Mac OS . Descriptive statistics are presented as number (percentage), mean (standard deviation), and median (interquartile range), where appropriate. Correlation was assessed using scatter plots and Pearson’s correlation coefficients. A Bland-Altman scheme was used to demonstrate agreement of LVEF between the estimates of the participants and quantitative LVEF. The bias and 95% limits of agreement (LOA) were calculated. A From the 35 TEE imaging studies, the mean LVEF measured using the modified Simpson method was 45.3% ± 19.8%, and the mean LVEF in each grade from 1 to 5 was 74.0% ± 0.8, 56.7% ± 1.9, 44.6% ± 0.6, 33.2% ± 0.5, and 17.8% ± 2.1%, respectively. The interrater reliability of the quantitative LVEF between the two authors was 0.97.Seven noncardiac anesthesiologists with a mean age of 38.1 ± 8.2 years and a median experience (IQR) of seven  years were recruited. A total of 245 responses from seven participants were collected and 120 (49%) of the visual estimation of LV function gradings were correct. For the LV function classifications, 32 (65.3%) of the answers in both extreme gradings (Grade 1: hyperdynamics and grade 5: severely reduced LVEF) were the same as those classified by the modified Simpson method. Meanwhile, only 29 (59.2%), 13 (26.5%) and 14 (28.6%) responses were correct in Grade 2 , Grade 3 (mildly reduced LVEF), and Grade 4 (moderately reduced LVEF), respectively. For estimates that did not match the LV function categories in the quantitative LVEF, 108 (44.1%) were in adjacent categories (1 grading difference), 15 (6.1%) answers were unmatched by two grading categories, and only two answers (0.8%) were unmatched by more than two gradings (Table p < 0.001), the Bland-Altman plot method revealed no systematic errors, and the plot for each LV function classification was in the same distribution pattern. The 95% LOA of the Bland-Altman method ranged from − 11.3 to 24.5, -21.9 to 22.6, − 23.1 to 26.5, − 20.5 to 22.0 and − 26.6 to 11.1 for LV grade 1 to 5, respectively  of 0.961 . The ICC was 0.754 (95% CI 0.366–0.949), 0.811 (95% CI 0.508–0.961), 0.769 (95% CI 0.417–0.952), 0.876 (95% CI 0.669–0.975), and 0.881 (95% CI 0.681–0.976) for the grade 1 to 5 respectively. The scatter plot shows a moderate, positive, linear association between the estimated LVEF by the participants and the quantified LVEF using the modified Simpson method .Visual estimation of LVEF is accurate and reliable in trained and experienced echocardiographers , 12. OurBoth the 2D and 3D volumetric methods accurately quantify LVEF better than the linear dimension method –9. The mFurthermore, based on our clinical experience, the difference in a single grade may not impact perioperative hemodynamic management. When combining the correct classification and ± 1 quality different from the correct classification, we found that untrained echocardiographers classified LV function within clinically acceptable ranges in 93.1% of cases. When applying this to rescue echocardiography, only the extreme gradation of hyperdynamic and severely reduced LV was an important cause of unstable patients in the perioperative period , 20. TheThe visual method of estimating LVEF has been closely correlated with other methods of assessing LVEF –13, 21. One of the most important parameters needed to manage hemodynamic problems is the systolic function of the LV . EchocarThis study has limitations. The nonexperimental nature of the study could not control many factors, such as the time the participants used for the study and their familiarity with the ultrasound images of the participants. Further studies with a more rigorous design would be valuable. In addition, this study focused only on the visual estimation of the LVEF. It did not include other skills and measurements to help diagnose during rescue TEE, such as probe placement, knobology, and image profiles to help diagnose specific conditions such as cardiac tamponade and embolic phenomena.Visual estimation of LVEF is easy to perform with acceptable accuracy in untrained echocardiographers with minimal training. This method could be helpful as part of a rescue TEE protocol and in training programs for LVEF interpretation.


Isolated left ventricular noncompaction cardiomyopathy (LVNC), also known as spongy myocardium, is an extremely rare congenital disorder belonging to unclassified cardiomyopathies by the World Health Organization and classified as a genetic cardiomyopathy by the American Heart Association. Adult prevalence is 0.017-0.26% in observational echocardiographic studies. The disease occurs due to the intrauterine arrest of normal myocardial compaction, leading to left ventricular dysfunction. Reported mortality is high, ranging from 35 to 47% over a 42- to 72-month follow-up period. Knowledge regarding proper diagnosis, morbidity, and prognosis is limited; thus, this disease is subdiagnosed. Our aim is to highlight a diagnostic approach to LVNC in an elderly patient and to stress specific diagnostic signs that make the disease more recognizable. We are reporting a case of noncompaction cardiomyopathy in a 62-year-old male without any significant past medical history who was referred to our clinic for arrhythmia evaluation. The patient had several brief episodes of palpitations over the past two months. On physical examination, he presented a blowing systolic murmur at the apex and an irregularly irregular rhythm. The 12-lead electrocardiogram (ECG) demonstrated atrial fibrillation and ST-T segment depression in the V4-V6 leads. A transthoracic echocardiogram (TTE) showed signs of dilated cardiomyopathy, severe eccentric left ventricular hypertrophy, decreased contractility with an ejection fraction (EF) <30%, moderate mitral and tricuspid regurgitations, and moderate pulmonary hypertension. Multiple prominent trabeculations were noticed in the middle and apical segments of the left ventricle. The noncompacted to compacted myocardium ratio was >2.5:1. Cardiac catheterization excluded ischemic heart disease. Cardiac magnetic resonance (CMR) imaging confirmed the diagnosis of LVNC. The patient started treatment with carvedilol, ramipril, verospiron, torasemide, and rivaroxaban. An implantable cardioverter-defibrillator (ICD) was recommended. In conclusion, the diagnosis of LVNC in the adult population is often delayed because of similarities with more frequently diagnosed diseases. TTE is the initial diagnostic test of choice. Additional imaging modalities  can help confirm the diagnosis. Early diagnosis is crucial because of the high incidence of life-threatening complications related to heart failure, thromboembolic events, and ventricular arrhythmias. Additional prospective studies are needed to improve the management and outcomes of this rare cardiomyopathy. Isolated left ventricular noncompaction cardiomyopathy (LVNC), also known as spongy myocardium, is an extremely rare congenital disorder belonging to unclassified cardiomyopathies by the World Health Organization  and clasAmong the different gene mutations, sarcomere gene mutations are the most common (82%): 71% of MYH7, MYBPC3, and TTN mutations; 11% of ACTC1, ACTN2, MYL2, TNNC1, TNNT2, and TPM1 mutations . Non-sarThe atypical structure of the myocardium leads to left ventricular dysfunction and dilation, followed by heart failure (HF) symptoms. LVNC causes life-threatening complications related to HF, thromboembolic events, and ventricular arrhythmias. Reported mortality from case series is high, ranging from 35 to 47% over a 42- to 72-month follow-up period from diagnosis ; thus, eA 62-year-old white male, without any significant past medical history, no risk factors, and a noncontributory family history, was referred to our clinic for arrhythmia evaluation. The patient had several brief episodes of palpitations and shortness of breath on moderate physical exertion for the past two months. The patient's vital signs were blood pressure (BP)-120/85 mmHg and heart rate (HR)-78 bpm. On physical examination, the apical impulse was displaced to the left, a blowing systolic murmur at the apex with radiation to the left axilla was revealed, and an irregularly irregular rhythm was noticed. The 12-lead ECG demonstrated atrial fibrillation and ST-T segment depression in the V5-V6 leads  <30%). Multiple prominent trabeculations were noticed in the middle and apical segments of the lateral and posterior walls of the left ventricle. The noncompacted to compacted myocardium ratio (NC/C) in the midventricular segments was >2.5:1 in both parasternal short axis and apical four-chamber views  demonstrated signs of dilated cardiomyopathy with enlarged left cardiac chambers: left ventricle (LV), 73 mm; left atrium (LA), 55 mm; severely abnormal LA volume index, 82 mL/mTaking into consideration the patient’s complaints and his age, ischemic heart disease was included in the differential diagnosis. Troponin I levels were negative. Cardiac catheterization was performed, and ischemic heart disease was excluded. A 24-hour Holter monitor showed couplets of premature ventricular contractions, one triplet with a wide QRS complex Figure .Cardiac magnetic resonance (CMR) imaging revealed characteristics suggestive of noncompaction cardiomyopathy (bilayered myocardium with a NC/C >2.3:1), confirming the diagnosis Figures , 5.The patient was prescribed heart failure therapy, including beta-blocker carvedilol, angiotensin-converting enzyme inhibitor (ACEi) ramipril, diuretics verospiron and torasemide, as well as anticoagulant rivaroxaban. In several months, ACEi was switched to sacubitril/valsartan, which was gradually adjusted to the maximum tolerated dosage. The patient had improved clinically, and left ventricular ejection fraction (LVEF) increased to 35%. The patient's two sons underwent cardiological family screening with electrocardiography and echocardiography, which did not reveal any pathology. The patient was followed up every six months for five years with periodic worsening of heart failure, which was corrected with pharmacological adjustments.The diagnosis of LVNC in an adult population is often delayed or missed because of similarities with more frequently diagnosed diseases, such as ischemic and nonischemic dilated cardiomyopathy, hypertensive heart disease, myocarditis, apical thrombi, and apical hypertrophic and restrictive cardiomyopathy. Physiological trabeculations, false tendons, and aberrant chords may also imitate LVNC. Other diseases mimicking LVNC must be considered as a differential diagnosis, including eosinophilic heart disease, endomyocardial fibroelastosis, cardiac fibroma, cardiac metastases, and intramyocardial abscesses .Clinical presentation of the disease is highly variable. There are nine clinical types of LVNC, including (1) the isolated or benign form with normal systolic function, (2) the arrhythmogenic form, 3) the dilated form, (4) the hypertrophic form, (5) the mixed form, (6) the restrictive form, (7) the biventricular form, 8) the right ventricular hypertrabeculation with normal left ventricle form, and (9) the congenital heart disease form of LVNC [ the righ the dilaTwo-dimensional echocardiography is the standard diagnostic test of choice. It can detect a two-layer myocardium in the mid-ventricular and apical levels with a thin compacted layer and a thick noncompacted layer, which consists of trabeculations with deep intertrabecular recesses . There aAlternatively, some clinicians use the Chin or Stöllberger criteria, which have also been validated. The Chin, or California, criterion defines LVNC as the ratio X-to-Y less than or equal to 0.5, where X is the distance from the epicardium to the trough of a trabeculation and Y is the distance from the epicardium to the peak of a trabeculation . This crCMR imaging helps identify LVNC more precisely. CMR criteria by Peterson with sensitivity of 86% and specificity of 99% include assessment of the noncompacted to compacted ratio, which has to be more than 2.3 during the diastole in any long-axis LV image to make a diagnosis of LVNC . JacquieCardiac catheterization is needed to rule out coronary artery disease in an adult population. Cardiological family screening with electrocardiography and echocardiography is important to identify LVNC in family members. Genetic testing may provide unique information to research the genetic heterogeneity of the disease and the genotype‐phenotype correlation.The incidence of life-threatening complications is high. They are related to HF, ventricular arrhythmias, and thromboembolic events. According to the German LV noncompaction (LVNC) registry, 61% of the patients experience HF symptoms at the time of initial diagnosis . The sev2/m2) are associated with cardiovascular death [Decreased LV contractility <50%, in particular in patients with midbasal extent of noncompaction, is a statistically significant predictor of overall mortality . HF, graar death . It is car death .Twenty-three previously published cases of noncompaction cardiomyopathy reported for the past 10 years (2012-2022) in the patient population aged 60 years and older are presented in Table The diagnosis of LVNC in the adult population is often delayed because of similarities with more frequently diagnosed diseases, such as ischemic and nonischemic dilated cardiomyopathy, apical hypertrophic cardiomyopathy, and hypertensive heart disease. Two-dimensional echocardiography is the standard diagnostic test of choice. Using strict Jenni, Chin, and Stöllberger echocardiographic criteria, we can increase recognition of this disease. Additional imaging modalities  can help confirm the diagnosis. Early detection and treatment of the disease are crucial to prevent life-threatening complications. Life expectancy can be extended through early treatment of heart failure, use of oral anticoagulants, and automatic ICD implantation. Heart transplantation is the last resort treatment for such patients. Definitive screening for family members should be established. Additional prospective studies are needed to improve the management and outcomes of this rare cardiomyopathy.


The incidence of MACCE was lower in the CCR compared to PCR at both hospital discharge  and at follow-up . Patients receiving CABG or CABG with PCI in PCR had higher mortality risks after MV surgery than CCR patients . Whereas in the PCR group, MV repair and MV replacement achieved similar survival probability , MV repair in the CCR group led to improved survival compared to MV replacement . In MV replacement, LAD-CABG improved survival compared to LAD-PCI , and a substantial impact of arterial IMA-LAD grafting was revealed in the Cox-regression analysis  as opposed to venous-LAD grafting . Conclusion: Early treatment of IMR concomitant to coronary revascularization enhances long-term survival compared to delayed MV surgery after PCR. MV repair is not superior to MV replacement when performed late after coronary revascularization; however, MV repair leads to better survival than MV replacement when performed concomitantly with CABG with arterial LAD revascularization.Objective: Long-term outcomes of mitral valve (MV) repair versus MV replacement for ischemic mitral regurgitation (IMR) in patients undergoing either prior (PCR) or concomitant coronary revascularization (CCR) by surgery (CABG) or intervention (PCI) are uncertain. Methods and Results: Of 446 patients receiving MV surgery for IMR between July 2006 and December 2010, 125 patients—87 CCR (69.1%) and 38 PCR (30.9%)—were eligible for inclusion in the study. Survival was higher in CCR versus PCR at long-term follow-up (78.83% vs. 57.9%,  Ischemic mitral valve regurgitation (IMR) caused by coronary artery disease is found in approximately 3% of all patients undergoing coronary angiography , and theDue to its inhomogeneous pathophysiology, IMR appears with all types of valve regurgitation as described in the Carpentier classification ,4. ThereGiven the prevalence of IMR and the negative sequelae associated with chronic regurgitation ,7,8, manWhereas MV repair demonstrably provides better preservation of LV function  than MV Moreover, recent studies ,11,16 reThe aim of this study is to explore how the timing and the type of coronary revascularization influence the outcome after MV surgery for IMR, thus potentially aiding in surgical decision-making.More precisely, the goal of this study was to determine whether survival was better after MV surgery with concomitant coronary revascularization (CCR) or when performed at a secondary point in time after previous coronary revascularization (PCR) in order to discover whether the type of MV surgery has an impact on survival as well as how the characteristics of coronary revascularization influence outcome after MV repair and replacement.This study was approved by the institutional review Board at the Philipps University of Marburg, including a waiver of informed consent (ek_mr_110221_Wensauer-1).n = 467).All patients who underwent mitral valve surgery from January 2010 to December 2017 were evaluated for inclusion (n = 97), patients receiving concomitant tricuspid valve and/or aortic valve surgery (n = 189) and patients without coronary artery disease (n = 58) were excluded , whereas 38 patients received coronary revascularization at an earlier point in time (PCR). Mitral regurgitation was judged to be ischemic in origin when the valve leaflets and chordae were normal, and the regurgitation was caused by the consequences of myocardial infarction ,18. All Relevant history, preoperative, and postoperative study variables were obtained from clinical records. The extent of coronary disease was obtained from coronary angiograms. The type and timing of coronary revascularization were obtained from the interventional and surgical records. Echocardiography was performed in all patients to assess left ventricular function and quantify the degree of MV regurgitation according to the recommendations of the ESC Guidelines . The opePrimary stratification was based on the timing of the coronary revascularization: prior coronary revascularization (PCR) versus concomitant coronary revascularization (CCR). Secondary stratification was based on the type of MV surgery: repair versus replacement. The third stratification was based on the type of coronary revascularization: CABG versus PCI.The primary outcome measure was operative mortality and late mortality after MV surgery for IMR. Operative mortality was defined as 30-day or in-hospital death.Survival of the IMR patients with PCR and CCR stratified by type of MV surgery (repair versus replacement) was evaluated as a secondary outcome measure.The impact of the type of coronary revascularization on mortality after MV surgery was evaluated as a tertiary outcome measure.t-tests or Mann–Whitney U tests.Categorical variables are presented as numbers with percentages and compared using Fisher’s exact test. Continuous variables are expressed as means with standard deviation and compared using two-sided Kaplan–Meier analysis was conducted to determine the probability of survival. Differences in survival rates between the PCR and CCR groups were examined by Mantel–Cox log-rank test. Similar analyses were conducted for patients undergoing MV repair and MV replacement.The impact of the type of coronary revascularization on survival after MV repair and MV replacement was evaluated by logistic regression analysis and the Mann–Whitney U test.The study population consisted of 123 patients who met the inclusion criteria and underwent MV surgery for IMR, of whom 38 (30.9%) received PCR, and 85 (69.1%) received CCR.Baseline demographic and clinical characteristics are listed in p = 0.428). Coronary angiography showed similar distribution and incidence of coronary pathology in the PCR and CCR groups with predominant triple-vessel disease , respectively.Preoperative cardiac echography revealed a similar Carpentier classification of mitral pathology with predominant regurgitation Grade III-IV  underwent elective surgery, with Redo-Sternotomy more often performed in PCR than in CCR .Characteristics of the surgical treatment and postoperative outcome are presented in p = 0.334) and 34.21% and 31.76% receiving MV replacement with a biological prosthesis, respectively (p = 0.836).The type of MV surgery did not differ between the groups, with 39.47% of PCR patients and 49.41% of CCR patients receiving MV repair (p = 0.00003), with the LAD treated more often in the CCR than in the PCR .Surgical coronary revascularization was more often performed in the CCR than in the PCR group  and length of hospital stay .Postoperative outcome was similar in PCR and CRR patients in terms of reoperation rates , whereas the early mortality was similar between the two groups (p = 0.399).The rate of MACCE at hospital discharge was significantly higher in the PCR group compared to CCR (p = 0.016), mortality at follow-up was significantly lower in the CCR than in the PCR group . This difference seems to be the consequence of the more frequent non-cardiac causes of death encountered in PCR patients (Although the average follow-up occurred significantly later in the CCR compared to the PCR group (patients .p = 0.016).Survival at five years after MV surgery A was sigp = 0.013 and p = 0.148, respectively), whereas PCR by CABG and PCR by combined PCI + CABG were associated with significantly lower survival than CCR (p = 0.005).Stratification by type of coronary revascularization B revealep = 0.213) in the PCR patients (p = 0.048).Survival looking at any cardiac cause was similar between MR repair and MR replacement , whereas no significant impact could be found in the MV repair subgroup (p = 0.916). This finding was confirmed by Mann–Whitney-U test and Wilcoxon-w test, revealing that surgical revascularization of the LAD is superior to PCI of the LAD when concomitant MV replacement is performed  MV surgery for IMR performed at the time as CABG (CCR) leads to a long-term survival benefit when compared to MV surgery performed late after coronary revascularization (PCR), especially when the prior revascularization involved surgical treatment; no. (2) MV repair shows no significant advantage over MV replacement when performed late after prior revascularization but is shown to improve long-term survival when performed concomitantly to CABG; and no. (3) grafting of the LAD with the internal mammary artery enhanced survival after MV replacement for IMR, without significant effect when performed concomitantly with MV repair.According to many early publications on IMR ,20,21, tTrichon et al.  found a The findings of our present study revealed that patients receiving MV surgery at a delayed stage after coronary revascularization (PCR group) had comparable survival to the CCR when early revascularization was performed by PCI, whereas patients who received CABG or CABG plus PCI had lower survival after MV surgery B. This dHowever, Miller  recognizAlthough MV repair demonstrably provides better preservation of LV function  than MV Moreover, the amount of relative benefit of MV repair versus replacement in terms of survival was nearly erased in the PCR group, which is consistent with prior works describing that similar conclusions of MV surgical procedures were drawn whenever chronic LV wall motion abnormality was present .Similarly, the CTSN severe IMR randomized controlled trial demonstrated that MV replacement for severe IMR resulted in a lower rate of recurrence of moderate or severe mitral regurgitation compared with MV repair along with lessened signs of heart failure and fewer cardiovascular readmissions; however, there was no difference in the number of adverse events or survival at two years post-treatment . Mid-terAccordingly, our findings reveal that MV repair was not superior to replacement in the PCR group, probably because an improvement of LV contractility was not achievable late after ischemia and after delayed isolated MV surgery. Thus, our results confirm that chronic IMR is more of a LV disease than a valve disease.Nonetheless, the efficacy of adding MV repair at the time of CABG is well demonstrated by Fattouch K et al.  and ChenAlthough current guidelines favor chordal-sparing mitral valve replacement over downsized annuloplasty repair for severe IMR , the proportion of patients undergoing MV repair vs. MV replacement did not change over time in our patient cohort (PCR vs. CCR). This might have been the consequence of a row of publications similar to that of Cohn et al.  reportinIn our study, MV repair was demonstrated to yield superior results to MV replacement in CCR patients where surgical coronary revascularization seems to be capable of saving the viability of a significant amount of myocardium B. This fThe negative effect of MV replacement on ventricular geometry and LV function can be reduced by preserving parts of the subvalvular apparatus of the MV ,37.Vassileva et al.  demonstrIn agreement with these previous findings ,39, our Gillinov et al.  revealedFinally, our data emphasize that detecting and quantifying IMR is essential for risk stratification before MV surgery.This study was limited by its observational nature. Given the retrospective nature, there is a selection bias due to a lack of explanation of why surgeons performed MV repair or MV replacement in some patients but not in others.The small patient number in the PCR group did not permit further stratification of MV repair and replacement based on the type of coronary revascularization .IMR addressed at the time of coronary revascularization improves long-term outcomes when compared to MV surgery performed at a later point in time after coronary revascularization. Although PCI tends to lead to a better outcome than CABG in PCR patients, CABG, or the addition of CABG to PCI before MV surgery, significantly worsens the outcome.Although MV repair is not superior to MV replacement when performed late after coronary revascularization, MV repair leads to better survival than MV replacement when performed concomitantly with CABG.Surgical arterial revascularization of the LAD plays a significant role in improving long-term outcomes after MV replacement; however, it is not superior to PCI when associated with MV repair.Having the prerequisite of MV repair concomitant with CABG, our results might suggest that hybrid interventional therapy of IMR by PCI and Mitral-Clip implantation might be at least as good as full surgical treatment.Such an alternative approach could be considered for IMR patients whenever PCI would be capable of recruiting and maintaining substantial myocardial viability of the left ventricle; however, additional research is required to prove this hypothesis.


Right ventricular (RV) function is currently being evaluated solely according to the properties of RV myocardium. We have tested a concept that in patients with heart failure with reduced ejection fraction (HFrEF), RV assessment should integrate the information about both RV function as well as size.A total of 836 stable patients with HFrEF  underwent echocardiographic evaluation and were prospectively followed for a median of 3.07  years for the occurrence of death, urgent heart transplantation or implantation of mechanical circulatory support.1) was significantly associated with an adverse outcome independent of RV dysfunction grade (p = 0.0002). The prognostic power of RVD1 was further improved by indexing to body surface area . A novel parameter named RV global dysfunction score (RVGDs) was calculated as a product of RVD1i and the degree of RV dysfunction . RVGDs showed a superior prognostic role compared to RV dysfunction grade alone . In every subgroup of RVGDs , patients with milder degree of RV dysfunction but more dilated RV had similar outcome as those with more severe degree of RV dysfunction but smaller RV size , independent of tricuspid regurgitation severity and degree of pulmonary hypertension.RV size (measured as RV-basal diameter, RVDRV dilatation is a manifestation of RV dysfunction. The evaluation of RV performance should integrate the information about both RV size and function. Echocardiographic evaluation of right ventricular (RV) function is complicated due to its complex geometry. Nevertheless, a correct RV function assessment is crucial as RV dysfunction is associated with an adverse outcome in multiple pathologic conditions including pulmonary artery hypertension and heart failure –4. RV fuTraditional parameters for RV function assessment  are currently being replaced by more sophisticated measures (RV strain) , 7. HoweThe goal of the study was to test a novel concept that the information about RV size and function should be integrated into one parameter that would offer more accurate information about RV disease.This is a retrospective analysis of prospectively enrolled patients; subjects with stable HFrEF (LVEF <40%) of at least 6 months duration  were enrolled in the study between 2008 and 2016 and prospectively followed. In all subjects, LVEF was assessed by echocardiography. Patients had to be on stable medical therapy for at least three months. Those with potentially reversible LV dysfunction  were excluded. Patients were followed until July 2019.Echocardiography and blood sample testing were performed upon enrollment. The protocol was approved by the Institutional Ethics Committee, and all subjects signed an informed consent. Patients were prospectively followed and the adverse outcome was defined as the combined endpoint of death, urgent heart transplantation, or ventricular assist device implantation. Due to the fact that time to non-urgent transplantation reflects donor availability rather than recipient's condition, patients who received a non-urgent heart transplant were censored as having no outcome event at the day of transplantation, as previously reported .1)  as end-diastolic diameter, LV ejection fraction was assessed by the Simpson method . Right v1) . All son1) . RV dila1 was performed using body surface area (BSA) that was calculated as BSA = 0.007184. weight (kg)^(0.425). height(m)^(0.725).Right ventricular dysfunction was quantified semiquantitatively . The assessment of RV function was performed in an apical 4-chamber view by using tricuspid annular systolic excursion (M-mode TAPSE)  and tissin vivo labeled by intravenous injection of 740 MBq 99 mTc isotope. The heart chambers were imaged using a D-SPECT camera  equipped with collimated, pixilated cadmium zinc telluride crystals detectors allowing rapid (7 min) data acquisition with superior spatial resolution. RV end-systolic and end-diastolic volumes were measured from three-dimensional reconstructed chambers using semiautomatic plug-in software  by a single experienced physician.RV end-systolic and end-diastolic volumes (and subsequently RV ejection fraction) was assessed using electrocardiogram-gated three-dimensional equilibrium Tc-labeled blood pool single photon emission computed tomography (SPECT). Patients received an injection of stannous pyrophosphate  and 30 min later erythrocytes were t-test or Mann–Whitney test were used to compare continuous variables between groups as appropriate. Cox univariate and multivariable models were used to test the effect of analyzed variables on prognosis. Event-free survival of patients was analyzed by Kaplan–Meier analysis with log-rank test comparison between groups. Calculations were performed using JMP 11  and R . Regression package for R (version 2020.12.08) was used to compare the area under the curve (AUC) of the Cox Proportional Hazard Regression models at four different time points.Data are presented as mean ± standard deviation, median with interquartile ranges (IQRs), or frequency (percent). Unpaired A group of 836 patients with HFrEF were enrolled in the study. Over the follow up of 3.07  years 508 patients (60.8%) experienced an adverse outcome . Furthermore, 35 patients (4.2%) underwent HTx as non-urgent recipients. Patients achieved a high degree of guideline-directed pharmacotherapy and device therapy—78.5% had ACEi/ARB, 87.4% beta-blockers, 76.7% mineralocorticoid receptor antagonist, 57.0% ICD, A total of 271 patients (32.4%) had preserved RV function, 190, 280 and 95 patients  had mild, moderate and severe RV dysfunction, respectively.p < 0.001, p < 0.0001). Similarly to RV dysfunction, RV size was also found to be significantly associated with adverse outcome . We have further analyzed whether an indexation of RV size brings any improvement in outcome prediction; absolute RV size was compared with RV size indexed to body surface area (RVD1i) that showed significantly higher area under the curve (AUC), RV dysfunction grade was associated with progressively deteriorating outcome (1 was found to be independently associated with prognosis after the adjustment for TAPSE/PASP ratio (surrogate of RV-PA coupling), HR 1.02, 95% CI , p = 0.009. RVD1 showed a loose but significant correlation with TAPSE/PASP ratio ; this correlation was tighter  in patients without the history of pericardial opening (n = 632) and looser  in patients with the history of pericardial opening (n = 202).Moreover, RVD1 was high  underwent RV size and function assessment by nuclear imaging. In all cases, echocardiography and scintigraphy was performed within 48 h during stable clinical conditions (stable p.o. medication). The scintigraphic examination was a part of a broader research project performer in our hospital, we have strived to have balanced number of patients in all subgroups of RV function. Patients with preserved RV function had a RV-ejection fraction (RVEF) of 53.64% (±3.93%), patients with mild, moderate and severe RV dysfunction had a RVEF of 46.10% (±3.63%), 34.93% (±4.01%), and 27.57% (±2.96%), respectively , As RV size contributes to an adverse outcome independently of RV dysfunction, we suggest it should be considered as a manifestation of RV dysfunction. We have developed a parameter called “RV global dysfunction score” (RVGDs) that integrates the information about both RV size and the degree of dysfunction. It was calculated as a product of RVDThis closely reflects a progressive increase in hazard ratio with RV function worsening . We have further compared the prognostic power of RVGDs with RV dysfunction grade only using AUC and found out that RVGDs was significantly superior .The contribution of RV dilatation and RV dysfunction grade on outcome was analyzed more in detail. We have compared patients with better RV function but more dilated RV with those with worse RV function but smaller RV size. Patients were divided into four groups according to RVGDs ; these intuitive cut-off values tightly reflect the distribution of RVGDs . A total of 204, 172, 183 and 277 patients were involved in the respective subgroups .p < 0.0001, 1i below median (≤18.9 mm/m2 for this subgroup) and mild RV dysfunction had the same outcome as those with RVD1i > 18.9 mm/m2, but preserved RV function (1i below median (≤19.8 mm/m2 for this subgroup) and moderate RV dysfunction had similar outcome as those with RVD1i > 19.8 mm/m2 but mild RV dysfunction (1i below median (23.6 mm/m2 for this subgroup) and severe RV dysfunction had similar outcome as those with RVD1i > 23.6 mm/m2 but moderate RV dysfunction  and enlarged LV cavity, more severe mitral and tricuspid regurgitation, lower plasma sodium and higher BNP level, worse renal function and were more often diabetic. Nevertheless, RV global dysfunction score was associated with an adverse outcome even after the adjustment for all these variables .This study shows that RV dilatation in HFrEF patients independently adds to an adverse outcome and should be considered as a marker of impaired RV function per se. Integrating the information about RV size and degree of dysfunction into one score parameter reflects more accurately the degree of RV disease.The assessment of RV function in HFrEF patients is extremely important as RV dysfunction was repeatedly shown to be independently associated with impaired survival , 3. Currper se is a specific manifestation of RV dysfunction; patients with lower degree of RV dysfunction but larger RV size had similar outcome as those with worse RV dysfunction but smaller RV size. Importantly, this phenomenon is independent of tricuspid regurgitation severity (volume overload) and degree of pulmonary hypertension (pressure overload). The negative prognostic impact of larger RV size is thus attributable neither to more severe tricuspid regurgitation nor pulmonary hypertension. Currently, the estimates of RV systolic function are being replaced by surrogates reflection RV-PA coupling that can be noninvasively estimated as the TAPSE/PASP ratio. Increased RV size leads to increased wall stress that is an important determinant of oxygen consumption  RV initially responds with homeometric remodeling characterized with preserved volume, concentric hypertrophy and normal or only slowly declining RV function. When this adaptive remodeling is exhausted, progressive RV dilatation occurs (heterometric remodeling) . In HFrEsumption . Increassumption , which w1, RV dysfunction grade assessed semi-quantitatively). Parameters assessing longitudinal RV function  are known to be reduced after cardiac surgery involving pericardial opening (1 and RV dysfunction grade (assessed semi-quantitatively) are parameters that can be established with a reasonable degree of precision even in patients with very poor acoustic windows. Importantly, the coefficients used for the construction of RVGDs very closely reflect the increasing risk of an adverse outcome. RV function can be associated with renal dysfunction through increased central venous pressure and decreased renal perfusion. Although we have observed a loose association between eGFR and RV function , RV function and eGFR were independently associated with impaired outcome. Therefore, RV function seems to be associated with prognosis regardless of renal function.In our study we have demonstrated that the combined parameter integrating the information about both RV size and the degree of dysfunction provides improved information about the prognosis compared with the degree of RV dysfunction alone. To the best of our knowledge, it is the first study testing this concept. Our data suggest that rather than focusing on RV dysfunction grade only, “RV disease” is more complex and RV size needs to be taken into account as well. As it is a retrospective echocardiographic analysis , we used parameters available in all patients  and size (RV end-diastolic or end-systolic volumes measured by 3D-echocardiography) might be superior to parameters chosen in the current study. Nevertheless, this is a proof-of-concept study showing that an integration of RV size and degree of dysfunction more accurately reflects the degree of RV disease. This new concept of RV evaluation should be further validated in other cohorts and it needs to be further investigated whether it is a general concept valid for other conditions associated with RV dysfunction .1 measurement, RV global dysfunction score may lack generalizability if RVD1 was assessed using RV-dedicated 4-chamber projection.Apical 4-chamber view was used for RVDOnly a part of echocardiograms were stored electronically and thus available for off-line analysis. Fractional area change (FAC) was not routinely measured in all patients, so the RV global dysfunction score based on quantitative parameters could have not been obtained. Similarly, LV/RV strain parameters were measured only in a minority of patients. Patients were treated not only conservatively , but some of them underwent heart transplantation or implantation of mechanical circulatory support, which may bias outcome analysis. As the patients were enrolled between 2009 and 2016, none were treated with sacubitril-valsartan or SGLT2 inhibitors at the time of enrollment. Sacubitril-valsartan was first reimbursed for HFrEF patients in 2018 and SGLT2i in 2021 and virtually no patients with HFrEF were treated with these agents before the reimbursement. Although patients were prospectively enrolled, not all of them were followed in our hospital, so the information about changes in pharmacotherapy throughout the follow-up period is not available from all the patients. Similarly, data about cardiac decompensation were not available from all the patients, so it was not possible to analyze this endpoint. Our study cohort included rather young patients with more advanced HF; consequently, the results might not be fully applicable to patients with milder HF or to older patients.RV dilatation should be considered to be a manifestation of RV dysfunction in HFrEF patients. A parameter integrating the information about both RV size and the degree of dysfunction provides superior prognostic assessment than the degree of RV dysfunction only.


Predicting if a fetus with borderline left heart structures and coarctation of the aorta (CoA) will require single ventricle palliation (SVP) is challenging, partly due to the limitations of fetal echocardiography in defining valvar abnormalities. Fetal echocardiographic findings predictive of SVP, particularly in relation to the mitral valve (MV), are not well defined.We performed a retrospective review of fetuses with postnatally confirmed CoA from 2010 to 2020. Fetuses with complex congenital heart disease or unequivocal hypoplastic left heart syndrome were excluded. Data were compared between those who underwent biventricular repair (BVR) vs. SVP cardiac death or orthotopic heart transplant (OHT) to determine differences in fetal echocardiograms.Of 67 fetuses with 131 total echocardiograms, 62 (93%) underwent BVR and 5 (7%) experienced SVP, cardiac death or OHT. Fetuses with confirmed CoA who experienced SVP cardiac death, or OHT, had fetal MV z-scores that were 2.06 lower, on average, than those who underwent BVR . The incidences of MV anomalies and left to right flow across the foramen ovale were higher in the SVP cardiac death and OHT group.SVP, cardiac death or OHT in fetuses with confirmed CoA were associated with fetal MV hypoplasia, MV anomalies and left to right flow across the foramen ovale. These findings may help guide prenatal counseling about the likelihood of SVP, cardiac death or OHT in fetuses with CoA and borderline left heart structures. Coarctation of the aorta (CoA) is one of the more common forms of congenital heart disease, accounting for about 8% of cardiac defects . Aortic Prenatal counseling for fetuses with a suspected CoA and borderline LV is challenging. The false positive detection of fetal anomalies is not benign and has been shown to negatively affect the developing maternal-infant bond . In the The objective of this study was to determine if prenatally identified MV abnormalities could predict postnatal surgical outcomes (isolated CoA repair versus SVP) in fetuses with postnatally confirmed CoA. We hypothesized that fetuses with CoA who underwent SVP postnatally had smaller and more abnormal mitral valves compared to those who underwent biventricular repair (BVR).This retrospective, single-center, cohort study was approved by the Vanderbilt Institutional Review Board prior to initiation. Vanderbilt Pediatric Heart Institute’s fetal quality assurance database, established in 2010, was queried for all fetal studies between 2010 and 2020 with aortic arch hypoplasia, CoA, or right greater than left ventricular size discrepancy. The transthoracic echocardiographic database was queried simultaneously for infants less than 60 days of age with diagnosis of CoA and compared to the fetal database for consideration . Exclusionary criteria included heterotaxy syndrome, hypoplastic left heart syndrome or severe LV hypoplasia, atrioventricular septal defects, conotruncal anomalies, anomalous pulmonary venous return, and moderate or larger ventricular septal defects. Patients were also excluded for normal or absent postnatal echocardiograms. Patients with genetic and extracardiac anomalies were included in the study.parameterz.com) . BVR was recommended in 62 patients (93%). There were six deaths (9%) in the BVR group prior to surgery that were attributed to non-cardiac causes including congenital diaphragmatic hernia (4), trisomy 13 (1), and holoprosencephaly (1). The remaining 56 patients underwent neonatal BVR with repair of CoA; 33 (53%) underwent aortic arch augmentation via midline sternotomy, and 23 (37%) underwent coarctectomy with end-to-end anastomosis via lateral thoracotomy. There were five patients (7%) in the SVP cardiac death or OHT including two patients who underwent SVP , two who underwent balloon aortic valvuloplasty for critical aortic stenosis (one of whom passed on ECMO following the procedure and the other who subsequently underwent OHT for poor cardiac output), and one who underwent a BVR and died at one year of age following MV revision for residual stenosis. There were no surgical conversions between single and biventricular physiologies. There were three postoperative and two late BVR deaths attributed to non-cardiac causes. The three postoperative deaths were attributed to respiratory failure in the setting of pulmonary vein stenosis, pulmonary hypertension and trisomy 21 (1), complications from tracheoesophageal fistula and a neural tube defect (1), and renal failure due to renal dysplasia (1). The two late deaths were due to multiple anomalies in the setting of Trisomy 19/Monosomy 18 (1) and presumed septic shock remote from repair . Pathologic genetic conditions were identified in 13 patients (only in the BVR group) including Turner syndrome (6), trisomy 21 (3), trisomy 13 (1), or other (3), and were associated with one preoperative (trisomy 13) and three postoperative mortalities.Echocardiographic parameters for each outcome group are outlined in Prenatally there were 43 patients (69%) in the BVR group with abnormal mitral valves, including 41 with hypoplastic annulus measurements (z-score less than −2.0). Abnormal mitral morphology was noted in four fetuses including three with suspected parachute valves and two with dysplastic or restricted leaflets. Isolated MV dysfunction was identified in three patients, including two with insufficiency and one with restricted leaflets. All five fetuses in the SVP cardiac death or OHT group had hypoplastic mitral valves prenatally, including four with morphologic or functional differences .Postnatally there were 31 patients (50%) in the BVR group with abnormal mitral valves, including 17 (27%) with a hypoplastic annulus on initial echocardiogram (z-score less than −2.0). Abnormal mitral morphology was noted in 11 patients (18%), including four with short/thickened chordae, three with parachute valves, two with asymmetric papillary muscles, one with a supramitral ring, and one with a double-orifice MV. Isolated MV dysfunction was identified in 13 patients, including five with insufficiency, four with stenosis, and four with both stenosis and insufficiency. Four of the five patients (80%) in the SVP, cardiac death or OHT group had significant structural or functional MV abnormalities including a supramitral ring, parachute valve, arcade, and abnormal chordae and papillary muscles . The senPrenatal counseling was fully concordant with postnatal outcomes in 45 patients (67%). In the BVR group, 18 (29%) patients were counseled about the possibility of SVP. All patients in the SVP group were counseled about the possibility of SVP. Prenatal counseling about postnatal ventricular outcomes changed course in 11 patients  based on subsequent fetal echocardiograms with either increasing (6) or decreasing (5) confidence with respect to postnatal BVR.Prenatal diagnosis of CoA remains challenging, with several studies focusing on improvements in detection  – 15. WhSome studies seeking to identify fetal echocardiographic features predictive of postnatal surgical outcomes have included a heterogeneous group of congenital heart lesions including unbalanced atrioventricular septal defects, conotruncal defects, aortic stenosis and hypoplastic left heart syndrome , 6. OtheFetal MV z-scores associated with SVP in other studies have ranged from less than a low normal of −1.9 to more significantly hypoplastic scores of less than − 3.6 or −4.5 . Some ofIn this study, those in the SVP, cardiac death or OHT outcome group had a significantly different predicted MV z-score that was 2.06 lower, on average, than the BVR group . Morphologic and functional differences of the MV were also more common in those who experienced SVP, cardiac death or OHT (80% vs. 11 %), as well as being generally prevalent across the entire cohort (16%). Fetal echocardiography was relatively sensitive in detecting anomalies of the MV, but with a high false-positive rate. There was also less MV hypoplasia noted postnatally, likely due to differences between fetal and postnatal physiology .Left to right or bidirectional flow across the foramen ovale was more prevalent in the SVP, cardiac death or OHT group (100% vs. 27%). There were no fetuses with consistent right to left flow across the foramen ovale that experienced SVP, cardiac death or OHT, similar to previous studies reflecting the low likelihood of these patients to experience SVP , 7. AlthOur cohort was restricted to fetuses who required postnatal cardiac surgery and was not designed to discriminate parameters for those who did not require intervention . There was a limited number of SVP, cardiac death and OHT outcomes which precluded traditional univariate and multivariate analyses. MV measurements were specifically evaluated using linear regression given the primary aims of this study, but this technique was not broadly applied to other measurements due to statistical limitations. Further studies with larger sample sizes are indicated to evaluate other echocardiographic parameters.The usual limitations of a retrospective, single center study apply. Fetal measurements were obtained over the course of a decade, concurrent with advancements in ultrasound technology and changes in fetal imaging protocols. Echocardiographic measurements were used as reported in the original studies with interobserver variability in MV measurements as reported for the initial studies only. Observations in the echocardiogram studies were subject to the interpretation of the original observers, including the degree of left ventricular hypoplasia. While z-scores allow for the normalization of measurements to GA, their use has known limitations , 23, 24.SVP, cardiac death or OHT in fetuses with confirmed CoA was associated with fetal MV hypoplasia, MV anomalies and left to right flow across the foramen ovale. Prenatal MV z-scores for fetuses in this group were, on average, 2.06 lower than for fetuses who underwent postnatal BVR. Z-scores for fetuses undergoing BVR were as low as −4.15. These findings may help guide prenatal counseling about the likelihood of SVP, cardiac death or OHT in fetuses with CoA and borderline left heart structures.


There were no significant differences between the groups, with the exception of arterial hypertension, which was more common in the chemotherapy group . In resting echocardiography, only LV posterior wall LS differed significantly and was impaired in patients treated with chemotherapy . DSE, performed in 21 patients after a median of 166 months from the end of cancer treatment, detected new contractility disorders in 1 patient (4.8%) and decreased LVCR in the majority of patients when determined using changes in LVEF or LV GLS, and in all patients when assessed with changes in Force. Conclusions: Most asymptomatic mediastinal lymphoma survivors showed preserved ventricular function on resting echocardiography. However, all of them showed impaired LV contractile reserve on DSE, as assessed with a simple parameter—Force. This may indicate subtle LV dysfunction and confirms the need for long-term monitoring of patients with potentially cardiotoxic cancer treatment.Patients treated due to mediastinal lymphomas are at risk of cardiovascular complications, as they receive chemotherapy, usually containing anthracyclines, often combined with thoracic radiotherapy. The aim of this prospective study was to assess early asymptomatic cardiac dysfunction using resting and dobutamine stress echocardiography (DSE) at least 3 years after the end of mediastinal lymphoma treatment. Two groups of patients were compared: those treated with chemoradiotherapy and those exclusively treated with chemotherapy. Left ventricular contractile reserve (LVCR) during DSE was assessed using changes in LV ejection fraction (LVEF), LV global longitudinal strain (LV GLS), and a novel parameter—Force, which is the ratio of the systolic blood pressure to the LV end-systolic volume. The study included 60 patients examined at a median of 89 months after the end of treatment. Resting echocardiography showed normal LVEF of 58.9 ± 9.6%, borderline LV GLS of −17.7 ± 3%, decreased mean stroke volume (SV) of 51.4 ± 17 mL, and indexed SV of 27.3 ± 8 mL/m Progress in anticancer therapies in recent decades has significantly improved disease prognosis ,2. HowevThe present study aimed to evaluate cardiac function by means of echocardiography in asymptomatic patients who underwent chemoradiotherapy or chemotherapy alone for mediastinal lymphoma. Apart from standard visual assessment of global and regional systolic ventricular function, a speckle-tracking echocardiography (STE) was used to examine LV and right ventricular (RV) systolic function at rest and during dobutamine stress echocardiography (DSE). We also wanted to assess the usefulness of the new parameter, which is Force, in detecting subclinical LV dysfunction depending on the applied oncological treatment. Force is calculated as the ratio of systolic blood pressure to LV end-systolic volume. This novel variable is easy to obtain and does not increase the imaging time. Force reflects a decrease in the pressure-volume loop slope, a decrease in systolic blood pressure, and transient ischemic LV dilatation during DSE. All these results are associated with a poor prognosis and allow the sensitivity of DSE to be extended to LV dysfunction ,5,6. We The study was prospective and included patients treated with chemoradiotherapy or chemotherapy alone for mediastinal lymphoma at least 3 years prior to enrollment. Data on their treatment were obtained from local oncology centers: the Department of Haematology and Transplantology, and the Department of Pediatrics, Hematology and Oncology of the Medical University of Gdansk and the Provincial Cancer Center in Gdansk, Poland. The exclusion criteria were heart disease diagnosed prior to study enrollment, current anti-cancer treatment, and lack of the patient’s consent to participate in the study. All patients were under the care of the Cardio-Oncology Outpatient Clinic, where great attention was paid to proper control of CVRF.2.The study protocol included a medical history, physical examination, CVRF and comorbidities assessment, transthoracic echocardiography (TTE), DSE, and Charlson comorbidity index. Fasting blood samples were collected to determine blood counts and concentration of brain natriuretic peptide (BNP), creatinine, glucose, and parameters of the lipid profile . Dyslipidemia was defined as a low-density lipoprotein level (LDL cholesterol) > 130 mg/dL or statin use. Chronic kidney disease was recognized when the estimated glomerular filtration rate was <60 mL/min/1.73 mData on the treatment of lymphoma were analyzed, which included the chemotherapy regimen and the radiation technique, a total and fractional dose of radiation therapy, and the time since completion of anti-cancer therapy. The control group consisted of 11 healthy individuals, matched for age and sex, who were referred for a DSE examination for the diagnosis of coronary artery disease (CAD). The study was approved by the local Institutional Ethics Committee (NKBBN/419/2017) and written informed consent was obtained from all patients.i indicated SV depending on the patient’s body surface area, and values < 35 mL/m2 were considered abnormal [TTE was performed using a Vivid S6 or Vivid E95 cardiovascular ultrasound system , and images were analyzed offline using a GE EchoPAC PC work station . All measurements were made using two-dimensional (2D) imaging and speckle-tracking echocardiography, and were performed according to the recommendations of the American Society of Echocardiography (ASE) [abnormal ,8,9.Right ventricular systolic function was determined by assessing the RV fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), RV peak systolic velocity (RV s’) obtained from pulsed-wave tissue Doppler imaging, and RV free wall LS. The LS cut-off values were adapted from the ASE guidelines: LV LS below −16%  was considered abnormal, LS between −18% and −16% borderline, and RV free wall LS below −20%  abnormal ,6,7,8,9.DSE was performed in addition to routine echocardiography, according to a standard protocol with a graded dobutamine infusion starting from a dose of 5 µg/kg per minute. It was increased every 3 min to a dose of 10, 20 (low dose), 30, and finally 40 µg/kg per minute (peak dose). The goal of dobutamine infusion was to achieve 85% of the maximal predicted heart rate for the patient’s age. In patients without a planned increase in heart rate, atropine 0.5 mg to 1 mg was administered.During DSE, images were obtained in standard views: in the parasternal long axis; parasternal short axis ; apical 4-, 2-, 3-chamber views; and the RV-focused view. All measurements were performed at rest, at low and peak doses of dobutamine, and in the recovery with a frame rate of at least 50 per second. The test was terminated at the targeted heart rate, infusion protocol completion, in cases of systolic blood pressure (BP) increase over 220 mmHg or diastolic BP rise to over 120 mmHg, when symptomatic hypotension or a drop in systolic BP of more than 40 mmHg occurred, or in cases of symptomatic ischemia or serious arrhythmia.To evaluate changes in LV contractility during DSE, LV contractile reserve (LVCR) was determined. Preserved LVCR was defined as an increase in LVEF or LV GLS of at least 20% when compared with baseline values ,11. The In order to reduce measurement errors of echocardiographic parameters, patients with poor acoustic windows were excluded from analysis.t-test and Pearson’s correlation. When analyzing variables without normal distribution, the Mann–Whitney U test, and ANOVA, a Spearman’s rank correlation coefficient were used.All data are presented as mean ± standard deviation or number and percentage. A normal distribution was confirmed via Shapiro–Wilk test and further analyses were made using Student’s p value < 0.05 was considered significant.The patients were divided into two groups according to the applied lymphoma treatment: chemoradiotherapy or exclusively chemotherapy. The results obtained in both groups in echocardiography at rest and during DSE were compared. The DSE results were compared between the study patients and the control group. All calculations were performed using Statistica software, version 13, Dell Inc. 2016, Tulsa, OK, USA. The The study group consisted of 60 patients, 36 (60%) women and 24 (40%) men with a mean age of 49 ± 15 years (range 18–79), who underwent treatment between 1976 and 2018. Demographic and clinical data of the study group are presented in 2 (250–399 mg/m2). There were no significant differences in chemotherapy regimens between the groups. Additionally, in 28 (46.7%) patients, irradiation of mediastinal lymph nodes was performed with a mean dose of 34.3 ± 8.8 Gy and in a mean of 18.7 ± 6 fractions.The majority of patients were treated for Hodgkin lymphoma (60%) or diffuse large B-cell lymphoma (32%), while 8% were treated for other types of non-Hodgkin lymphoma. All patients received systemic chemotherapy, most commonly according to the R-CHOP  or ABVD regimen . The mean total doxorubicin dose in the study group was 292 ± 87 mg/mWith regard to radiation therapy, in eight patients who were treated in the years 1976–2008, data on the technique of irradiation were missing. Among the remaining 20 patients, for 12 patients a new radiotherapy technique, intensity-modulated radiation therapy (IMRT), was used, and shielding was used with 3 patients.When assessing CVRF, arterial hypertension and dyslipidemia were most commonly recognized and arterial hypertension was more common in patients treated exclusively with chemotherapy. Additionally, the Charlson comorbidity index was greater in these patients.i were decreased, but did not differ between groups. RV systolic function reflected by TAPSE, RV FAC, RV s’ was not impaired. RV free wall LS was abnormal in 25 patients, which resulted in a decreased mean value in all patients (−19.9 ± 6.3%), although without significant differences between the groups.Echocardiography was performed at a median of 89 (38–508) months after completion of anticancer treatment, and results are presented in Twenty-four patients were initially disqualified from DSE due to a poor acoustic window on echocardiography and seven patients did not attend DSE. In eight patients, DSE was terminated prematurely because of the occurrence of serious abnormalities, and they were excluded from further analysis. One patient had a premature termination of DSE due to frequent premature ventricular beats, three patients reported chest pain, three had a symptomatic BP drop, and one patient developed transient second degree atrioventricular block (type one). Thus, DSE results were analyzed in 21 (35%) patients with a mean age of 51 ± 13 years, after a median of 166 months from the completion of anticancer therapy. Demographics of these patients and results of DSE are presented in p = 0.049). LVCR obtained from Force was lower in cancer survivors compared with controls (p = 0.01). There were no significant differences in other echocardiographic parameters.All subjects in the control group had a negative DSE result for the diagnosis of CAD. 2. He reported no symptoms, cardiovascular risk factors, or comorbidities. Baseline BP was 134/83 mmHg, and heart rate was 62 bpm. Resting echocardiography showed LVEF 56%, LV GLS −18.5%, and no contractility disorders. DSE was performed with the peak dobutamine dose of 50 mcg/kg/min and the addition of 1 mg atropine.Results of the DSE performed in one of the patients treated with chemotherapy are shown in Using modern echocardiography techniques at rest in asymptomatic mediastinal lymphoma survivors years after the completion of cancer therapy, we found well-preserved LV and RV systolic function, with no differences between patients treated with chemoradiotherapy containing doxorubicin and chemotherapy alone. However, DSE revealed impaired LV contractile reserve in both groups. Our study is the first to use a new parameter—Force in cardio-oncology to assess LVCR. LVCR obtained from Force was impaired in all cancer survivors, with no differences between groups, indicating patients with early LV dysfunction. Force allowed early detection of subtle LV injury, while LVCR assessed using standard parameters, LVEF and LV GLS, was insufficient. According to Wierzbowska-Drabik et al., Force calculated at peak DSE stage was correlated with the extent of the coronary artery disease (CAD) assessed using SYNTAX and Gensini scores, while LVEF and LV GLS values showed a poor relationship. The authors explained this by hypercontraction of non-ischemic LV segments, masking regional impairment of contractility and improving LVEF and LV GLS values . In addi2. In addition, 28 patients, i.e., almost half of the study group, were treated with mediastinal irradiation, which increases the risk of cardiac damage [It has been shown that mediastinal lymphoma survivors have a four–six times higher cardiovascular risk compared with the general population , and LV c damage .2 of doxorubicin (250–399 mg/m2). In patients who underwent chemoradiotherapy, the risk was even very high, as the prescribed irradiation dose was 34.3 ± 8.8 Gy and the cumulative doxorubicin dose was ≥100 mg/m2.According to the newest ESC guidelines , patientThe results obtained in this study were not in line with our expectations. Despite the high CV toxicity risk, all patients were asymptomatic, echocardiography at rest was normal, and DSE revealed CAD in only one patient. Additionally, the DSE results did not differ between the groups. However, the risk of radiation-induced cardiotoxicity is time-dependent: the greater the longer the time elapsed since this treatment. In our group, it was (median) 127 months, and perhaps it was still too short to cause LV systolic dysfunction in resting echocardiography. Heidenreich et al. diagnosed CAD via stress test in 14% of patients after a median of 15 years from mediastinal irradiation with a dose of at least 35 Gy . In our It is known that restrictive control and management of CVRF significantly reduces the risk of cardiac dysfunction occurrence ,23,24. AWhen assessing the location of longitudinal deformation disorders at rest, we found only a significantly lower posterior wall LS in patients treated with chemotherapy. This is in contrast to the literature data, as it is the RV, interventricular septum, and LV anterior wall that are more at risk of injury because this region receives the highest doses of irradiation during mediastinal radiotherapy. What is more, similar localization of myocardial injury detected by LV LS was described by some authors in patients treated with anthracycline chemotherapy alone ,28,29,30In our study, we assessed LVCR during DSE using three methods: calculating the LVEF and LV GLS increase and Force. Force is the proportion of systolic blood pressure to LV end-systolic volume. It mirrors LV elastance and correlates the changes of the afterload to the preload . The ForPatients were treated with radiotherapy over many years and, thus, using different radiotherapy techniques, which could have influenced the results we obtained. In patients treated outside the Medical University of Gdansk, we did not obtain data on radiotherapy treatment, which did not allow us to establish the relationship between irradiation parameters and echocardiographic results. The size of the groups of patients in whom the DSE study was performed was small; therefore, we look critically at the obtained results and we realize that it still needs to be confirmed in larger groups of patients. Three-dimensional echocardiography, which would allow for a more accurate assessment of ventricular systolic function, including right ventricular ejection fraction (RVEF), was not performed. A comparison of Force with other methods of LV global systolic function assessment, such as dP/Dt, myocardial work, or post-systolic stress, is lacking.Most asymptomatic mediastinal lymphoma survivors years after treatment with chemoradiotherapy or chemotherapy showed normal ventricular function on resting echocardiography. However, all of them had impaired LV contractile reserve on DSE, as assessed with a novel parameter—Force. The usefulness of Force assessment in cardio-oncology is promising and may indicate patients at risk of future LV dysfunction in whom conventional screening at rest does not yet reveal LV impairment. Therefore, long-term monitoring of patients after potentially cardiotoxic oncological treatment is necessary, as well as close control of cardiovascular risk factors in this group of patients.


Severe leptospirosis is defined by multiple organ failure. Cardiac involvement is an uncommon complication in patients with leptospirosis, and the pathophysiology of it is not well understood. Diffuse myocardial calcifications connected with sepsis are infrequent, and their effect on heart function is hard to predict. They can lead to conduction disorders and arrhythmias, thereby causing sudden death. Myocardial calcifications are usually revealed incidentally by radiological investigations such as computed tomography (CT) scan in patients with or after sepsis and are commonly unidentified in practice because most cases progress gradually. This case report involves a 51-year-old male who presented to the emergency department with sepsis. The patient was diagnosed with leptospirosis, causing septic cardiomyopathy and diffuse calcifications of the myocardium of the left ventricle. This case highlights the importance of multimodality imaging and a multidisciplinary approach to diagnoses since early recognition and treatment are essential. Follow-up of such patients is necessary to monitor the systolic function of the left ventricle and cardiac arrhythmia. Leptospirosis is a well-known zoonosis with significant morbidity and mortality. Cardiac involvement is a rare complication, although dysfunction of the heart is a common complication of severe sepsis and shock . Myocard2. Laboratory results showed an elevated white blood cell count (21.5×109/L), as well as highly elevated C-reactive protein (474 mg/L) and troponins (high sensitivity troponin I (hsTNI) 9860 ng/L). He had elevated lactate levels (11.9 mmol/L), hemoglobin level was normal. At this time, a preliminary diagnosis of severe sepsis with septic cardiomyopathy was established. After ICU admission, a polymerase chain reaction (PCR) was positive for leptospirosis in serum and urine.A 51-year-old previously healthy male was presented to the emergency department with complaints of fever, headache, myalgia, diarrhea, and shortness of breath that had persisted for three days. The patient denied recent travel, sick contacts, or participation in adventure sports. Upon admission, the patient was hypotensive (blood pressure 88/65 mmHg), tachycardic (heart rate 124 beats/min), and subfebrile (temperature 37.5°C); he was in a state of shock. The electrocardiogram showed sinus tachycardia without ST-T abnormalities. He had acute renal failure with elevated serum creatinine (505 µmol/L) and a glomerular filtration rate of 11 mL/min/1.73 mInitial transthoracic echocardiography (TTE) on admission to the ICU showed left ventricular ejection fraction (LVEF) of 25% and no pericardial effusion. A computed tomography (CT) scan performed 20 days after hospital admission revealed an increased density in the myocardium of the left ventricle with myocardial calcifications in the apex, septum, anterolateral and inferior wall, and anterior papillary muscle Figure , as wellA final diagnosis of septic cardiomyopathy caused by leptospirosis was made on the basis of a combination of clinical, laboratory, and imaging findings. This was further affirmed by the rapid appearance of myocardial calcifications and the presence of normal serum calcium levels in the course of hospital admission.He was discharged after two months with heart failure medications, including beta-blockers and angiotensin-converting enzyme inhibitors, to manage his reduced cardiac function. The patient’s symptoms gradually improved; on follow-up 12 months after discharge, he reported a reduction in fatigue, improved exercise tolerance, and underwent an ultrasound (TTE), which showed normal LV size, restored systolic function of LV, and no pericardial effusion. The right ventricular function was normal. Leptospira. It is a rare infection, although the most widespread zoonosis, and is reappearing around the globe [Leptospirosis is a zoonotic disease caused by pathogenic spirochetes of the genus he globe . It is ahe globe ,3. The phe globe . Studieshe globe . Autopsyhe globe . The prehe globe .Leptospirosis can lead to various, usually transient, ECG abnormalities, such as atrial fibrillation, bundle branch conduction blocks, and non-specific ventricular repolarization disturbances. Abnormal serum electrolyte levels  are likely to contribute to ECG changes . HistopaOur patient developed extensive myocardial calcifications, which were caused by severe leptospirosis. Myocardial calcification can appear for a lot of reasons. Two basic forms are recognized: metastatic and dystrophic. Metastatic calcification occurs as a consequence of systemic process, i.e., hypercalcemia or abnormalities of calcium homeostasis, and can appear in normal or unhealthy tissue. Metastatic calcifications are usually found in patients on hemodialysis (with chronic kidney failure), but they have also appeared in patients with oxaluria, primary, secondary, or tertiary hyperparathyroidism, and a nutritional deficit of calcium and vitamin D ,9. DiffeSepsis-related myocardial injury is a very complex process ,11. In sCT scan is the gold standard for the noninvasive detection of calcifications, and the diagnosis of myocardial calcification is usually unexpected, achieved accidentally by thorax CT . In our The definition of sepsis-induced cardiomyopathy (SIC) has been summed up as a global and reversible heart dysfunction -17. A reThis case emphasizes the importance of using advanced imaging techniques like multi-parametric MRI to aid in diagnosis. Collaboration between infectious disease specialists, cardiologists, and radiologists is vital for comprehensive patient care and appropriate management.Myocardial inflammation and involvement in leptospirosis can go unacknowledged due to non-specific clinical findings and co-concomitant multi-organ dysfunction. Sepsis itself causes cardiomyopathy, characterized by ventricular dilatation and a decrease in EF. Diffuse myocardial calcifications related to sepsis caused by leptospirosis are an extremely uncommon phenomenon but can lead to greater morbidity and mortality. These calcifications are usually abundant and involve the LV wall or, less frequently, the right ventricular wall or papillary muscles. Myocardial calcification is usually an incidental finding on a CT in patients with, or after, sepsis and is unrecognized and underdiagnosed in everyday practice since most cases progress quietly; therefore, it is important to use advanced imaging techniques like multi-parametric MRI to aid in diagnosis. Regular follow-up is mandatory for surveillance of the systolic function of the left ventricle and arrhythmia.


Limited data on the prognostic value of periprocedural changes of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) after transcatheter aortic valve replacement (TAVR).Data of plasma NT-proBNP were retrospectively collected in 357 patients before TAVR procedure and at discharge from January 1, 2018 to December 31, 2021 in our single center. Patients were grouped as responders and non-responders according to the NT-proBNP ratio . Responders were defined as NT-proBNP ratio < 1 and non-responders were defined as NT-proBNP ratio ≥ 1. Outcomes were defined according to the Valve Academy Research Consortium (VARC)-3 criteria.A total of 234 patients (65.5%) and 123 patients (34.5%) were grouped as the responders and the non-responders, respectively. Responders and non-responders were significantly different in both median preprocedural  and postprocedural  NT-proBNP levels. Patients in the non-responder group were more inclined to have comorbidities of hypertension , hyperlipidaemia , peripheral vascular disease  and pure aortic insufficiency . In the contrast, patients in the responder group had higher prevalence of maximum transvalvular velocity , reduced left ventricular ejection fraction , heart failure , mitral regurgitation ≥ moderate , tricuspid regurgitation ≥ moderate , and pulmonary hypertension . Patients in the non-responder group were moderately longer than the responder group in total hospitalization length . The non-responder group were significantly associated with cumulative all-cause mortality (p = 0.009) and cardiac mortality (p < 0.001) during the follow-up period.Periprocedural changes of NT-proBNP is clinically useful for the risk stratification of survival in patients after TAVR.The online version contains supplementary material available at 10.1186/s13019-023-02391-2. Transcatheter aortic valve replacement (TAVR) has emerged as a safe and effective treatment for severe aortic stenosis . A growiThe N-terminal pro-brain natriuretic peptide (NT-proBNP) is an inactive derivative of cerebral natriuretic peptide (BNP) and has a half-life of 120 min , 4. NT-pWe therefore investigated the association between NT-proBNP ratio  and clinical outcomes in TAVR patients, as well as the precise cut points of NT-proBNP at discharge after TAVR in predicting the cumulative late all-cause mortality. These findings may raise concerns about optimizing the timing of TAVR or medical therapy after TAVR to mitigate the pathobiological changes caused by NT-proBNP, thereby improving clinical outcomes.A total of 358 Patients underwent TAVR from January 1, 2018 to December 31, 2021 at our institution and 357 patients were included in the present study (1 patient died the day after TAVR immediately for multiple organ failure). NT-proBNP levels were measured in all patients at baseline before TAVR and at discharge after TAVR. This study was approved by the Medical Ethics Review Committee of Fuwai Hospital and informed consent was waived for the nature of retrospective analysis.TAVR was performed in a hybrid operating room by the heart team, and patients were under general anesthesia or local anesthesia and monitored by anesthesiologists. All patients underwent TAVR after discussions with the multidisciplinary heart team, and the access site and the type of prosthesis were determined thereafter. Transfemoral access was preferred in all patients with criteria unless prosthesis size, calcification and atheroma of the aorto-iliofemoral artery were considered. All TAVR procedures were performed according to established standards via transfemoral, trans-carotid, trans-subclavian, and contemporary devices of SE-valves  –11 or baPlasma NT-proBNP have been routinely measured within 48 h before TAVR procedure and 4 to 8 days after TAVR at the date of hospital discharge. Blood samples were drawn from the antecubital or dorsal hand vein and collected in EDTA-containing tubes and immediately processed by the Institute of Clinical Chemistry at Fuwai hospital. NT-proBNP were analyzed from Roche Diagnostics by electro-chemiluminescence immunoassay. The effective measuring range of the assay was 5-35000 pg/ml . Patients were considered as non-responders if their NT-proBNP value at discharge post-TAVR was equal or greater compared with the baseline value. Baseline characteristics, procedural, and hospitalization data were retrospectively recorded manually from institutional electronic medical record system and entered into a dedicated database. All data were anonymized, systematically collected and assessed for quality.All endpoints in this study were defined in line with the Valve Academic Research Consortium (VARC)-3 criteria . The prihttp://www.r-project.org).All continuous variables were tested for normality using the Shapiro-Wilk test. Continuous variables were presented as mean ± standard deviation (SD) and compared using the Student’s t-test, or medians (25th -75th quartile) compared using Mann-Whitney U test. Categorical variables were presented as numbers and percentages and compared using the Chi-square test or Fisher’s exact test. Cumulative clinical outcomes were calculated using the Kaplan-Meier survival analysis, and the log-rank test was used for comparison between the groups. To identify independent predictors of late all-cause mortality, all variables with a p value < 0.05 on univariate analysis were included in a stepwise multivariable Cox regression model. The proportional hazard assumption was confirmed by examination of log  curves and by testing of partial (Schoenfeld) residuals, and no relevant violations were found. The estimated hazard ratio (HR) with 95% confidence interval (CI) was provided by the Cox regression analysis. To find the cut-off value of NT-proBNP at discharge (1350.5 pg/ml), receiver-operating characteristic (ROC) curve evaluation was performed to assess the area under the curve (AUC) at the 95% confidence interval (CI) in predicting cumulative all-cause mortality. And NT-proBNP ≥ 1350.5 pg/ml was included in the stepwise multivariable Cox regression model. The trend of cumulative all-cause mortality across quartiles of NT-proBNP levels at discharge was analyzed using the Cochrane-Armitage test. To identify the determinants of NT-proBNP non-responders, a multivariable logistic regression analysis was performed using the following covariates selected from factors that were significantly different between NT-proBNP responders and non-responders: hypertension, hyperlipidaemia, NT-proBNP ≥ 1429.60 at baseline (median of NT-proBNP at baseline), peripheral vascular disease, heart failure, pure aortic insufficiency, left ventricular ejection fraction, maximum velocity, mitral regurgitation ≥ moderate, tricuspid regurgitation ≥ moderate, pulmonary hypertension, total length of hospitalization. All tests were 2-sided, and p values < 0.05 were considered to be statistically significant. All statistical analyses were performed using SPSS software version 26.0  and R software version 4.1.0 (available at 2), New York Heart Association functional class III or IV (70.3%), diabetes mellitus (23.5%), chronic obstructive pulmonary disease (3.6%), chronic kidney disease (3.4%), and coronary artery disease (38.7%). Responders and non-responders were significantly different in both median preprocedural  and postprocedural  NT-proBNP levels. However, patients in the non-responder group were more inclined to have comorbidities of hypertension , hyperlipidaemia , peripheral vascular disease  and pure aortic insufficiency . In the contrast, patients in the responder group showed significantly higher prevalence of maximum velocity , reduced left ventricular ejection fraction , chronic heart failure , mitral regurgitation ≥ moderate , tricuspid regurgitation ≥ moderate , and pulmonary hypertension . Patients in the non-responder group were moderately longer than the responder group in total hospitalization length .A total of 357 patients were included for analysis. According to NT-proBNP ratio, 234 patients were divided into responder group for NT-proBNP ratio < 1 and 123 patients were divided into non-responder group for NT-proBNP ratio ≥ 1. The main baseline characteristics of the study population are summarized in Table Procedural data and results are summarized in Table VARC-3-related clinical outcomes are summarized in Table In ROC analysis, NT-proBNP ratio significantly predicted cumulative all-cause mortality  and cardiac mortality . NT-proBNP at discharge also significantly predicted all-cause mortality  and cardiac mortality . However, NT-proBNP at baseline did not reach statistical significance in predicting cumulative all-cause mortality  or cardiac mortality .Multivariable logistic regression analysis revealed that baseline NT-proBNP ≥ 1429.60 pg/ml , peripheral vascular disease , left ventricular ejection fraction , maximum velocity  were independent determinants of NT-proBNP non-responders . Patients were grouped as responders (NT-proBNP ratio < 1) and non-responders (NT-proBNP ratio ≥ 1). The major findings of the present study were as follows:Median NT-proBNP levels decreased from 1429.6 pg/ml at baseline to 852.0 pg/ml at discharge.34.5% of the study patients were non-responders.Baseline NT-proBNP ≥ 1429.60 pg/ml, peripheral vascular disease, left ventricular ejection fraction, maximum transvalvular velocity were independent determinants of NT-proBNP non-responders.NT-proBNP ratio and NT-proBNP at discharge significantly predicted cumulative all-cause and cardiac mortality after TAVR.NT-proBNP non-responders, NT-proBNP ≥ 1350.5 pg/ml at discharge, baseline mitral regurgitation ≥ moderate, coronary artery disease, and length of intensive care unit were independently associated with lower survival rates during follow-up time.As levels of NT-proBNP at discharge increased, all-cause mortality significantly increased after TAVR.NT-proBNP has been identified as a diagnostic and prognostic biomarker for a number of cardiovascular diseases . The utiOf note, the NT-proBNP responders had higher baseline NT-proBNP levels, lower left ventricular ejection fraction, higher maximum transvalvular velocity and more patients with chronic heart failure. This finding was consistent with previous observation that TAVR in this patient group produced immediate effects in left ventricular unloading and decrease of myocardial stretch, resulting in an acute decrease in circulating NT-proBNP levels after TVAR. An intuitive hypothesis can be made from our findings that patients whose elevated NT-proBNP levels are primarily driven by severe AS and heart failure would benefit most from TAVR.The association of periprocedural changes of NT-proBNP with survival after TAVR was investigated by Seoudy et al.  The studGiven the adverse correlation between the increase of NT-proBNP level after TAVR and the poor clinical outcomes, two questions are raised: How to alleviate the increase of NT-proBNP level after TAVR? Will the efforts aimed at pathobiology driving the increase of NT-proBNP after TAVR improve the clinical outcomes? It needs to be clear that the potential therapeutic targets are underlying pathobiology, such as maladaptive hypertrophy, abnormal left ventricular function, increased wall stress, and volume overload, which lead to NT-proBNP release . OptimalIt is worth using NT-proBNP for risk stratification of TAVR patients, identifying NT-proBNP non-responders earlier, and reducing postprocedural circulating NT-proBNP levels by more optimal timing of TAVR procedure and medical management, which are of great help in improving the prognosis of TAVR patients.The study is limited inherently by its retrospective single-center design. Data on medical management were not systematically collected in this study. Serial changes of NT-proBNP were not measured in all patients after hospital discharge. The external validation is needed as for the cut-off value of NT-proBNP at baseline or discharge. The present study showed that about 20% of patients experienced second valve implantation mainly due to device migration to left ventricle. This might be explained by the immaturity of early technology, the characteristics of prosthesis, and the cardiac anatomical characteristics of patients. However, our study cohort represents a typical, unselected, real-world TAVR population with a considerable sample size.Periprocedural changes of NT-proBNP is associated with cumulative all-cause and cardiac mortality after TAVR. NT-proBNP ratio and NT-proBNP at discharge should be carefully monitored to improve postprocedural risk stratification and guide optimal treatment strategy selection.Below is the link to the electronic supplementary material.Supplementary Material 1