Native T1 values < 1073 ms were identified as independent predictor of postoperative reduction of LVEDV  and LVESV . Diffuse myocardial fibrosis assessed by myocardial native T1 correlates with LV reverse remodeling at six months after valvular surgery. T1 mapping may be a valuable tool to predict LV reverse remodeling in valvular heart disease.Myocardial native T1 is a known cardiovascular magnetic resonance (CMR) imaging biomarker to quantify diffuse myocardial fibrosis in valvular cardiomyopathy. We hypothesized that diffuse myocardial fibrosis assessed by preoperative T1 mapping might correlate with LV reverse remodeling after valvular surgery. A prospective monocentric cohort study was conducted including 79 consecutive patients with valvular cardiomyopathy referred for surgical treatment of severe aortic or severe functional mitral regurgitation. Native T1 values were assessed by CMR before surgery. LV geometry parameters  were obtained by 2D transthoracic echocardiography before and six months after surgery. Postoperative change of LV geometry parameters was calculated as delta (∆) variable . Mean native T1 was 1047 ± 39 ms, mean ∆LVEDV was −33 ± 42 mL, and mean ∆LVESV was −15 ± 27 mL. Native T1 values correlated with ∆LVEDV (Pearson r = 0.29;  Heart valve regurgitation is a common disease in the Western world and its prevalence increases with an advancing age . Even seCurrently, the extent to which LV function and dimensions recover after successful valve repair is unknown. In theory, the myocardial damage should recede following correction of heart valve regurgitation. Practically, not all patients achieve postoperative LV reverse remodeling, depending on the degree of myocardial fibrosis ,4. In adThe question of major clinical relevance is whether a more expeditious valvular surgery in case of severe asymptomatic aortic or mitral valve regurgitation may prevent the progression of LV remodeling at an early stage. Therefore, more sensitive biomarkers would be required to better and earlier quantify the ongoing myocardial damage that may precede a significant LV enlargement.Current cardiac magnetic resonance (CMR) quantitative mapping techniques show a strong correlation between native T1 and histologic collagen volume fraction, which determines the degree of myocardial fibrosis . A previWe hypothesized that diffuse myocardial fibrosis defined by T1 mapping in the preoperative CMR may correlate with LV reverse remodeling defined by a reduction of LVEDV and LVESV at six months after valvular surgery.The institutional ethics committee approved this prospective study, and all subjects gave written informed consent .Consecutive patients with severe AR or severe FMR referred to our institution for elective valvular surgery between July 2017 and August 2019 were prospectively enrolled in this study. Study exclusion criteria were as follows: predominant aortic or mitral valve stenosis, valvular redo procedures, common contraindications for MRI such as severe obesity (250 kg CMR table weight limit), and presence of a metallic foreign bodies.The severity of valve regurgitation was defined by established diagnostic criteria, including transthoracic echocardiography and clinical aspects .Study protocol imaging consisted of preoperative CMR with myocardial native T1 mapping and transthoracic 2D-echocardiography with measurement of LV size parameters: LV end-diastolic diameter (LVEDD), LV end-systolic diameter (LVESD), LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF). Follow-up echocardiographic re-evaluation was performed at 6-months after surgery.In addition, laboratory values of serum N-terminal prohormone of brain natriuretic peptide  and serum creatinine (mg/dL) were preoperatively assessed.Preoperative CMR was routinely performed within one week prior to surgery. All cardiac examinations were conducted by a 1.5-T MR scanner . CMR was performed using a standardized protocol including an electrocardiogram-gated, standard steady-state, free-precession cine MR sequence, acquired during breath holds in standard long-axis views  and short-axis slices covering the entire left ventricle . Native Native T1 measurements showed good inter-observer reliability .Baseline and follow-up 2D transthoracic echocardiography images were routinely recorded and analyzed in our echocardiographic core laboratory by two independent investigators. Baseline echocardiographic examination was conducted within one week prior to surgery. Follow-up echocardiographic examination was conducted six months after surgery.Using a standardized protocol, LV geometry parameters, including LVEF, LVEDD, LVESD, LVEDV, and LVESV, were measured in the 4- and 2-chamber view during end-systole or end-diastole according to the Recommendations for Cardiac Chamber Quantification by Echocardiography in Adults from the American Society of Echocardiography and the European Association of Cardiovascular Imaging . The metTo generate high accuracy and reproducibility of biplane two-dimensional echocardiographic measurements, the same investigators followed the same patients at baseline and follow-up as recommended by Otterstad et al.  Our studDepending on the underlying disease  surgical strategies differed. Surgical approach for AR cases were partial sternotomy or median sternotomy depending on the need of concomitant cardiac procedures and patients’ comorbidities. Treatment strategies for AR patients ranged from aortic valve repair to biological or mechanical aortic valve replacement.Surgical approach to FMR was either median sternotomy or right antero-lateral mini-thoracotomy. FMR was treated using a standard rigid complete annuloplasty ring, which was downsized by one size, according to the length of the anterior mitral leaflet. In case of severe leaflet tenting, subannular repair with repositioning of both papillary muscles was performed . There wt-test. Non-normally distributed, unpaired data was compared using the Mann–Whitney-U test. Fisher’s exact test was used for univariable comparisons of categorical variables. A Pearson correlation coefficient was used for correlation analyses.Normally distributed continuous variables are presented as mean ± standard deviation and categorical variables are expressed as percentages throughout the manuscript. Comparison of normally distributed continuous variables was performed by unpaired The difference of LVEF, LVEDD, LVESD, LVEDV, and LVESV at six months’ follow-up and at baseline were calculated as delta (∆) variable . In line with this, negative ∆ values of LVEDD, LVESD, LVEDV, and LVESV indicated postoperative reduction of LV geometry parameters and presence of LV reverse remodeling. While positive ∆ values of LVEDD, LVESD, LVEDV, and LVESV indicated increase of postoperative LV geometry parameters and absence of LV reverse remodeling. For ∆LVEF applied the opposite, negative ∆LVEF values indicated postoperative decrease of LVEF and absence of LV reverse remodeling, while positive ∆LVEF indicated presence of LV reverse remodeling.p-values < 0.05 were considered statistically significant. All statistical analyses were performed using the SPSS version 26.0 statistical package .We calculated receiver operating characteristic (ROC) curves to determine optimal cut-off points of myocardial native T1 values to predict postoperative reduction in LV geometry parameters. The optimal cut-off value was defined by Youden index. Predictors of reduction in LV geometry parameters were subsequently assessed by multivariable Cox regression analysis. All Primary study endpoint was the correlation between baseline T1 values and LV reverse remodeling defined by reduction of LVEDV and LVESV at six months postoperatively after valvular surgery.n = 46) or severe FMR (n = 33) were included in our study  with severe AR . Concomitant root enlargement was found in 11 cases (24%).Overall, there were 58/79 male (73%) and 36/79 female (27%) participants. The original aortic valve pathology included unicuspid aortic valve disease in five cases (11%) and bicuspid aortic valve disease in 16 cases (35%). All other AR patients presented with tricuspid aortic valves (n = 27), or aortic valve replacement (n = 19), or mitral valve repair using ring annuloplasty combined with subannular repair (n = 20) or isolated ring annuloplasty (n = 13). In the FMR cohort, concomitant surgeries included coronary artery bypass surgery (n = 13) and tricuspid valve repair (n = 5). None of the thirteen patients who underwent simultaneously CABG showed a regional myocardial fibrosis corresponding to the diseased coronary artery territory in CMR.Depending on the underlying disease, operative procedures consisted of aortic valve repair (n = 1), recurrence of AR after aortic valve repair due to suture dehiscence at eight months follow-up (n = 1), and recurrent severe FMR following isolated ring annuloplasty at one week follow-up and one month follow-up (n = 2). Echocardiographic grading of recurrent valve regurgitation at six months follow-up are depicted in During the follow-up period, four re-operations were required, including endocarditis following aortic valve replacement at six months follow-up  and in 56 patients (71%), respectively.The myocardial native T1 values of the study cohort were normally distributed with a mean baseline native T1 of 1047 ± 39 ms see .p = 0.03) and LVESV   0.64, 95%-CI: 0.51–0.78) and LVESV . Calculated in a Cox regression model using covariables age, gender, and level of creatinine, native T1 < 1073 ms was identified as an independent predictor for reduction of LVEDV  .n = 46) vs. FMR patients (n = 33) revealed significantly younger age , lower values of preoperative NT-proBNP , and serum creatinine  in the AR subgroup (p < 0.001). Similar, preoperative CMR revealed significantly lower native T1 values in AR vs. FMR patients .Comparison of the baseline characteristics between AR patients (subgroup . In linep < 0.001) and LVESV  were significant lower in AR patients vs. FMR patients at baseline. After six months, reduction of LVEDV and LVESV was found in 37 (80%) and 35 (75%) AR patients vs. 21 (64%) and 21 (64%) FMR patients, respectively. Therefore, contribution of the primary study endpoint was comparable between both study cohorts . Although, the mean ∆LVEDV improved more extensively in AR vs. FMR patients . Of note, there were no statistically significant difference between AR and FMR patients regarding the postoperative reduction of LVESV .Systolic echocardiographic LV geometry indexes including LVESD  were associated with an increased prevalence of LV reverse remodeling following valvular surgery. Based on these findings, we conclude that preoperative native T1 values might be a valuable tool to predict reverse LV remodeling after surgery for aortic or mitral regurgitation. Furthermore, shorter native T1 times may indicate a reversible myocardial dysfunction, which improves after valve surgery, while higher T1 values could imply a rather fixed defect.Post-hoc subgroup analysis revealed significantly longer T1 times in FMR patients indicating a more severe LV disease in FMR patients in comparison to AR patients. Accordingly, FMR patients showed lower degree of postoperative LV reverse remodeling. These findings confirm our clinical observation, that FMR patients present mostly with a more advanced LV disease as compared to AR patients.Native T1 mapping has previously been proposed to be a valuable diagnostic marker for several cardiac pathologies ,16,17,18Currently, there is a lack of robust evidence from adequately powered clinical trials on the role of fibrosis variables in informing clinical decisions for surgical or catheter-based interventions. If confirmed by future studies, our findings may have important clinical implications. By means of native T1 mapping, risk stratification and treatment selection in patients with valvular cardiomyopathy may be further improved. Especially, timing of surgical intervention may be optimized before severe myocardial damage occurs. In line with this, patients with valvular heart and an irreversible myocardial defect may benefit from less invasive treatment strategies .2) as a trigger for valvular intervention [Unfortunately, the current treatment recommendations for AR or FMR of the ESC/EACTS guidelines of management valvular heart disease do only refer to LVEF < 50% and LVESD > 50 mm LVESDi > 25 mm/m5 mm/m2 aOur study possesses all the limitations of a single-center experience with a relatively low-numbered study cohort.(1)Our study cohort consisted of patients with different valve pathologies including tricuspid (TAV) and bicuspid (BAV) aortic valve disease and functional mitral valve disease. This could be a confounder to our analysis. However, the development of diffuse myocardial fibrosis and valvular cardiomyopathy has the same pathophysiological background in both TAV and BAV patients. Chronic volume overload results in eccentric LV hypertrophy and LV remodeling, which is independent of valve morphology. Due to the common pathophysiological pathway in TAV and BAV, we analyzed both valve pathologies as a uniform entity, the AR subgroup. Furthermore, we aimed to demonstrate that the correlation between baseline T1 and LV reverse remodeling after valvular surgery is independent of the type of valvular disease . To evaluate this assumption, we included valve type  into our Cox regression model. Cox regression model confirmed the correlation between native dichotomized T1 and LV reverse remodeling to be independent of the type of valvular disease . In other words, the correlation between native T1 mapping and post-surgical LV reverse remodeling was comparable between AR and FMR patients.(2)Our study cohort included thirteen study patients, who underwent simultaneous CABG surgery. Even though the presence of CAD was the main pathophysiological mechanism leading to cardiomyopathy, none of them had a regional myocardial fibrosis corresponding to the diseased coronary artery territory. Therefore, this patient cohort with CAD represents a very selective patient subgroup with predominantly diffuse myocardial fibrosis.(3)Four patients underwent redo surgery during the study period, which might have influenced the LV reverse remodeling course as defined by reduction of LVEDV and LVESV. However, the redo surgeries were performed at the first month or after the 6 months follow-up echocardiographic examination. Therefore, in all four cases, there was presumably enough time for the LV to remodel.(4)The ROC analyses of our study, which we performed to determine the cut-off point of the prediction variable native T1, revealed only acceptable AUC values for reduction of LVEDV and LVESV. In addition, the confidence intervals of AOCs showed a wide range of values due to the low number of study patients.(5)Analysis and interpretation of echocardiographic measurements of LV remodeling parameters relied on the test-retest variability published by Baron et al. .In summary, our current findings need to be confirmed by a consecutive prospective large multicenter study.Diffuse myocardial fibrosis assessed by myocardial native T1 correlates with LV reverse remodeling at six months after valvular surgery. T1 mapping may be a valuable tool to predict LV reverse remodeling in valvular heart disease; however, this should be validated in a larger prospective multicenter study.


Journal of Clinical Medicine.Cardiovascular diseases (CVD), including coronary heart disease (CHD), heart attacks, stroke, heart failure (HF), and peripheral artery disease, still represent the leading cause of death globally, taking an estimated 17.9 million lives each year. However, mortality from CVD has significantly decreased in recent decades, particularly thanks to advances in cardiovascular basic and translational research and clinical progress; this has led to the development of drugs targeting selective pathways and other effective cardioprotective strategies, resulting in improved clinical outcomes . Interesting evidence has indicated a significant relationship between specific endogenous factors and AMI. In particular, in a prospective cohort study of STEMI patients who underwent coronary artery angiography, the authors suggested that higher levels of the B cell activating factor (BAFF), a member of the tumor necrosis factor (TNF) superfamily with a significant role in MI/R and atherosclerosis lesions and progression, could represent, in the acute phase, an independent predictor of the incidence of major adverse cardiovascular events in the post-MI period . On the On the other hand, recent mechanistic studies have significantly contributed to enhancing the knowledge surrounding pathophysiological determinants of specific heart diseases. This is the case of dilated cardiomyopathy (DCM), a complex myocardial disorder representing a major cause of HF and death, where genetic components play an important role in its pathogenesis, accounting for at least one-third of cases of “idiopathic” DCM. A study recruiting 62 patients presenting with idiopathic DCM elucidated a complex series of events, linking alterations of proteostasis with inflammation, where numerous molecular actors, including miR-22, the phosphatase PP2Cm, branched-chain amino acids, mTOR, and an autophagy lysosomal pathway, could participate in DCM pathogenesis and may serve as therapeutic targets for myocardial disease .Clinical and experimental evidence indicates that excessive aldosterone signaling could negatively affect cardiovascular function; indeed, inhibiting aldosterone receptors has been shown to mitigate LV hypertrophy and decrease cardiovascular-related mortality. A recent study indicated, in human failing hearts independent of etiology, a strict relationship between the high myocardial expression of aldosterone receptor and aquaporin-1 and intracellular water overloading and cardiomyocyte swelling, which can culminate in cardiac dysfunction, providing a key cellular and morpho-molecular basis underlying aldosterone-dependent human HF progression .Extensive evidence has shown that another important health problem refers to cardiotoxicity arising from cancer treatments. Pre-clinical and clinical data demonstrated that chemotherapy, radiotherapy, and cancer itself could induce functional or structural heart damage, affecting life expectancy amongst cancer survivors, thus representing a relevant issue in clinical practice. Accordingly, experimental and clinical cardio-oncology has emerged as a key area aimed at studying, identifying, and treating cardiovascular complications following cancer therapy . Cardiotoxicity can manifest as an early or late event after therapy and may vary from subclinical myocardial dysfunctions to irreversible HF. Numerous pharmacological cardioprotective interventions, including angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, and beta-blockers, could be combined with cancer regimens in clinics. However, at the moment, these drugs may not be used for all patients since additional population evidence is required to determine their efficacy and optimal dosage. Therefore, the early identification of cancer therapy-related cardiovascular toxicity remains a critical issue in adequately managing CVD caused directly or indirectly by cancer. Echocardiography, in combination with relative changes in the global longitudinal strain (GLS) and levels of serum cardiac biomarkers , is recommended in the cardio-oncology guidelines to monitor cardiac functions and detect early changes in the LV function during anticancer therapy, as well as the entire management of cardiotoxicity. In this context, recently, a single-center observational study proposed serial myocardial work measurements through a non-invasive LV pressure-strain loop for patient risk stratification and the early detection of cardiotoxicity following chemotherapy (anthracycline therapy w/wo trastuzumab) in 50 breast cancer patients that were monitored before and 3, 6, and 12 months after the initiation of chemotherapy. The authors investigated temporal changes and longitudinal trajectories in myocardial work indices during cancer treatment, providing evidence of the clinical effectiveness of serial myocardial work analysis as an additional confirmatory marker. Interestingly, non-invasive myocardial work indices derived from LV pressure–strain loops could overcome the load-dependent limitations of GLS, which was affected by blood pressure changes. Therefore, this study further contributed to validating this method in cancer patients exposed to chemotherapeutics, for which the available evidence is still limited .Together with additional approaches for the early detection of cardiotoxicity, strong evidence derived from current guidelines indicates how additional cardiac-specific biomarkers and more efficient cardioprotective strategies are crucial for the early detection and treatment of CVD in cancer patients, respectively. In particular, Mauro and collaborators (2023)  recentlyLooking ahead, there is a need to adhere to the conventional guidelines for managing CVD while implementing basic, translational, and clinical cardiovascular research as a fundamental step for identifying the specific causes of CVD and the set-up of precision therapies.


This pilot study aimed to develop a new, reliable, and easy-to-use method for the evaluation of diastolic function through the M-mode measurement of mitral valve (MV) movement in the parasternal long axis (PSLA), similar to E-point septal separation (EPSS) used for systolic function estimation. Thirty healthy volunteers from a tertiary emergency department (ED) underwent M-mode measurements of the MV anterior leaflet in the PSLA view. EPSS, A-point septal separation (APSS), A-point opening length (APOL), and E-point opening length (EPOL) were measured in the PSLA view, along with the E and A velocities and e’ velocity in the apical four-chamber view. Correlation analyses were performed to assess the relationship between M-mode and Doppler measurements, and the measurement time was evaluated. No significant correlations were found between M-mode and Doppler measurements in the study. However, M-mode measurements exhibited high reproducibility and faster acquisition, and the EPOL value consistently exceeded the APOL value, resembling the E and A pattern. These findings suggest that visually assessing the M-mode pattern on the MV anterior leaflet in the PSLA view may be a practical approach to estimating diastolic function in the ED. Further investigations with a larger and more diverse patient population are needed to validate these findings. Point-of-care ultrasound (POCUS) is a vital tool in the emergency department (ED) for the evaluation of heart function in time-sensitive situations, particularly in patients presenting with dyspnea, chest pain, shock, or cardiac arrest ,2,3. EchSpectral Doppler echocardiography can generally be used to assess diastolic function by measuring various parameters, such as the E/A ratio , the deceleration time, and the E/e’ ratio  in the apical four-chamber (A4C) view ,14. AlthThe investigators observed, in some cases, that the pattern of mitral inflow velocity assessed by pulsed-wave (PW) Doppler in the A4C view, specifically the E/A pattern, was similar to the movement pattern of the MV anterior leaflet observed while measuring the EPSS with the M-mode in the PSLA view. When the E/A ratio was reversed, the M-mode movements of the MV anterior leaflet in the PSLA view were also reversed. Patients with normal diastolic function exhibited M-mode movements of the MV anterior leaflet that resembled the normal E/A pattern. The MV is located between the left atrium (LA) and left ventricle (LV). During the relaxation period, the MV opens and blood flow in the LA moves to the LV. Therefore, the amount of blood flow entering the ventricle changes according to the diastolic function of the LV, and MV movement is affected accordingly. Some studies have evaluated diastolic function by observing the movement of the MV using the M-mode in the PSLA view ,22,23,24Therefore, analyzing the correlation between these measurements could provide a new diastolic measurement method that simply evaluates the septal separation of the MV anterior leaflet using M-mode in the PSLA view, instead of relying on spectral Doppler evaluation, which requires accurate Doppler angle matching in the A4C view. This study aimed to develop a new, reliable, and easy-to-use method for the evaluation of diastolic function that can be implemented in ED clinical practice, similar to the EPSS used for systolic function estimation.This was a prospective observational pilot study to develop a novel diastolic function evaluation method using M-mode measurements of the distances between the anterior leaflet of the MV and the septum in the PSLA view. This study was conducted at an urban tertiary academic ED in Seoul, Republic of Korea, with more than 70,000 annual ED visits. The study was performed in accordance with the Declaration of Helsinki and approved by the Samsung Medical Center Institutional Review Board (IRB file number 2022-11-033). All participants provided written informed consent prior to inclusion in the study.Between December 2022 and February 2023, we recruited 30 healthy volunteers for bedside echocardiography who met the following inclusion criteria: age of at least 18 years, no history of cardiovascular disease, and no structural or valvular heart abnormalities. Exclusion criteria consisted of specific findings on the myocardium, pericardium, or valve on echocardiography; failure to measure all indices required for the study of echocardiography; or refusal of consent.All the participants were asked to complete a simple demographic survey. Before performing the evaluation required for the study, an investigator performed a screening test using a simple scan to determine whether there were any functional or structural abnormalities in the heart . The participants were positioned in the supine or left lateral supine position unless they experienced discomfort. Electrocardiogram (ECG) leads were then attached to their chests. The study protocol involved taking M-mode measurements of the MV anterior leaflet through a PSLA view scan, followed by PW Doppler and tissue Doppler measurements on an A4C view for diastolic function evaluation. The time required for each measurement was recorded. An EM resident and faculty member with experience in performing more than 200 echocardiography assessments conducted the study. One investigator measured the research image, while the other performed pre-screening. The investigators used pre-designated cardiac presets of Venue Go with a 1–3 MHz phased array transducer .This study used the M-mode technique to obtain mitral valve separation measurements in the PSLA view. Specifically, EPSS refers to the separation distance between the anterior leaflet and the septum during early diastole. Additionally, the distance between the anterior leaflet of the MV and the interventricular septum during late diastole is defined as the A-point septal separation (APSS). Furthermore, the investigators measured the vertical distance between the imaginary line where the MV is closed at systole and the tip of the anterior leaflet of the mitral valve during early diastole, which is defined as the E-point opening length (EPOL). Similarly, the distance to late diastole is defined as the A-point opening length (APOL). Using the M-mode technique, the time between the peak early diastolic point and nadir (EPSS deceleration time) was obtained A. To ensMV, mitral valve; PSLA, parasternal long axis; PW, pulsed-wave; A4C, apical 4-chamber; EPSS and APSS, E-point and A-point septal separation; EPOL and APOL, E-point and A-point opening length; RV, right ventricle; IVS, interventricular septum; LVPW, left ventricular posterior wall; E and A, early and late diastole velocity of the mitral inflow; E dec time, E deceleration time.PW Doppler was used to obtain mitral inflow measurements, which included the peak trans-mitral inflow velocities during early diastole (E) and late diastole (A), the E/A ratio, and the deceleration time of early diastolic flow (E deceleration time) B. TissueDemographic data, including vital signs, sex, and age, were collected at the time of examination. The following M-mode measurements were obtained from the PSLA view: EPSS, APSS, APOL, EPOL, and EPSS deceleration time. The following Doppler measurements were obtained in the A4C view: E velocity, A velocity, E deceleration time, e’ velocity, and EF. The time required for each measurement was recorded.p-values were adjusted using Bonferroni’s method. The reproducibility of the primary and secondary MV measurement values was evaluated using a Bland–Altman plot and the intra-class correlation coefficient (ICC). Sample size calculation was not performed as this was a pilot study, and the relationship between M-mode measurements of the MV anterior leaflet in the PSLA view and Doppler measurements of the MV inflow velocity in the A4C view has not yet been established. Statistical significance was set at p < 0.05 for all analyses. SAS version 9.4  and R version 4.1.0  were used for all statistical analyses.Continuous variables are reported as the mean  or median , and categorical variables as a number and percentage. The mean values of the first and second M-mode measurements were used for analysis. Non-normally distributed variables were log-transformed prior to the analysis. Spearman’s and Pearson’s correlation analyses were used to evaluate the correlation between the MV measurements in the PSLA view and spectral Doppler measurements in the A4C view. Wilcoxon’s signed-rank test was used to assess the time differences between measurement methods, and The primary outcomes of this study were the correlation between the E, A, and E/A ratio measured by PW Doppler in the A4C view and the EPSS, APSS, APSS/EPSS ratio, EPOL, APOL, and EPOL/APOL ratio measured by M-mode in the PSLA view. Secondary outcomes were the comparison of the measurement times for both methods and the ICC of the primary and secondary measurement values for the MV measurements.Thirty healthy participants were recruited between December 2022 and February 2023. Of these patients, 20 (67%) were male, with a mean age of 29 years . In the The dots represent the individual values for each participant, the orange line represents the mean value, and the interrupted lines indicate the standard deviation. E and A, early and late diastole velocity of the mitral inflow; A4C, apical 4-chamber; EPOL and APOL, E-point and A-point opening length; PSLA, parasternal long axis.p = 0.045). However, this correlation was not statistically significant when reanalyzed using a rank-based method  because of the skewed APSS/EPSS ratio data. Correlation analysis revealed only one significant correlation between M-mode measurements in the PSLA view and Doppler measurements in the A4C view: a moderate positive correlation between the APSS/EPSS ratio and the E value . No other significant correlations were observed    s and 81 (32.5) s, respectively, with M-mode measurement taking significantly less time (< 0.001) . The ICC< 0.001) .PSLA, parasternal long axis; EPSS and APSS, E-point and A-point septal separation; EPOL and APOL, E-point and A-point opening lengths.This pilot study explored a new method for the evaluation of LV diastolic function using M-mode measurements of MV motion in the PSLA view. The study found that although there was no statistically significant correlation between the EPOL/APOL and E/A ratios, both values showed a notable trend in participants with normal diastolic function. The EPOL value was consistently higher than the APOL value and the E value was higher than the A value in all patients. In addition, the EPOL/APOL ratio had a more limited distribution range, from 1 to 2. The M-mode measurements were also quick and highly reproducible compared with the Doppler measurements. These findings suggest that visually assessing the M-mode pattern on the MV anterior leaflet in the PSLA view may be a practical approach to estimating diastolic function in the ED, similar to the EPSS method used for systolic function estimation.The accurate evaluation and diagnosis of diastolic function are crucial in the ED because of its association with a wide range of heart diseases and clinical symptoms. Diastolic dysfunction can be observed in conditions such as hypertension, coronary artery disease, and diabetes and can also serve as a predictor of mortality and morbidity ,26. ImpoThe assessment of diastolic function commonly employs PW Doppler to evaluate mitral inflow velocities. The E and A velocities represent early and late diastolic filling and are influenced by factors such as preload, LV relaxation and compliance, and LA contractile function ,14,27. Ip-value < 0.001), and the time required for M-mode measurements was significantly less (p < 0.001). Therefore, in a time-sensitive ED setting where patient cooperation may be limited, the convenience of M-mode measurements in the PSLA view makes it a valuable method for the evaluation of diastolic function.Compared with the apical view, the PSLA view offers several advantages. It provides superior visualization of the LV, mitral and aortic valves, and LA, resulting in higher-resolution images owing to the perpendicular imaging plane. In contrast, the oblique angle required in the apical view makes it more challenging to obtain clear images and precise measurements; thus, emergency physicians prefer the PSLA view to other views when performing echocardiography . EPSS meIn this study, no significant correlations were found between most M-mode and Doppler measurements, including the EPOL/APOL and E/A ratios, making it challenging to establish a clear index linking M-mode measurements to E/A values. However, a significant correlation was observed between the APSS/EPSS ratio and E value (Spearman’s correlation coefficient = 0.4). The study included 30 healthy participants with normal cardiac function, a small median EPSS value of 2.7 mm, a median APSS/EPSS ratio of 4.3, and a mean E-value of 0.8 m/s. These findings suggest that in individuals with normal diastolic function, the LV inflow velocity (E) increases during early diastole through active volume suction from the LA, resulting in a decrease in EPSS and an increase in EPOL. Consequently, LV filling during late diastole (A) may be reduced, leading to a decrease in A and an increase in APSS, ultimately increasing the APSS/EPSS ratio. Therefore, this new diastolic function measurement method using the M-mode in the PSLA view provides a better understanding of relaxation function in individuals with normal diastolic function. However, the clinical application of this correlation to quantitatively assess diastolic dysfunction may have limitations.The evaluation of diastolic function using the MV anterior leaflet has inherent limitations, offering only a partial assessment and disregarding factors such as MV stenosis or regurgitation. It may not be applicable to patients with abnormal LV systolic function or significant mitral valve pathology, necessitating a comprehensive evaluation with multiple parameters. The objective of this pilot study was to develop a reliable and user-friendly method that does not require spectral Doppler. While the M-mode approach may not be directly incorporated into routine cardiac POCUS protocols, it shows potential as an auxiliary tool to estimate diastolic function in the ED, where challenges with image quality and complex calculations exist.Our study had several limitations. First, this was a pilot study conducted in a small number of healthy volunteers with normal cardiac function. We did not perform sample size calculation because the relationship between M-mode measurements of the MV anterior leaflet in the PSLA view and Doppler measurements of the MV inflow velocity in the A4C view has not yet been established. Therefore, generalizing these findings to a wider range of cardiac functions and the general population is challenging. To overcome this limitation, a follow-up study involving a larger and more diverse population is necessary to determine whether similar EPOL and APOL patterns can be applied to patients with reduced systolic and diastolic function due to underlying cardiopulmonary diseases, for the evaluation of diastolic function.Second, the evaluation of diastolic function through echocardiography typically includes additional measurements, such as pulmonary vein flow Doppler, the LA volume index, and systolic pulmonary arterial pressure using the maximal tricuspid regurgitation velocity. These comprehensive evaluations help to determine the stage of diastolic dysfunction and the presence of increased LV filling pressure. However, in our study, we focused only on the mitral inflow velocity and M-mode measurements from the PSLA perspective, which provided a simplified assessment. While this approach has its advantages, it should be noted that it does not encompass the entire spectrum of diastolic function evaluation.Lastly, in our study, echocardiography was performed by two emergency physicians, and we did not assess the image quality or interrater reliability. Furthermore, the median EPSS value was very small, 2.7 mm, raising the possibility of measurement error. These factors could have influenced the accuracy and consistency of the results. Further studies should include assessments of image quality and interrater reliability to enhance the reliability and reproducibility of the diastolic function evaluation method. Although our study provides valuable insights into the evaluation of diastolic function using the MV anterior leaflet in the PSLA view, it is important to acknowledge these limitations. Future studies should address these limitations to validate and refine the proposed method.Although the study aimed to establish correlations between M-mode and spectral Doppler measurements for LV diastolic function assessment, no statistically significant correlations were observed. However, M-mode measurements were quick and reproducible. Additionally, the EPOL value consistently exceeded the APOL value in all patients with normal diastolic function, similar to the E/A pattern. This pilot study suggests that visually assessing the pattern by utilizing M-mode on the MV anterior leaflet in the PSLA view may be a practical approach to estimating overall diastolic function in the ED. Further studies with larger sample sizes are necessary to validate these findings, particularly in patients with diastolic dysfunction.


The history of cardiac pacing dates back to the 1930s with externalized pacing and has evolved to incorporate transvenous, multi-lead, or even leadless devices. Annual implantation rates of cardiac implantable electronic devices have increased since the introduction of the implantable system, likely related to expanding indications, and increasing global life expectancy and aging demographics. Here, we summarize the relevant literature on cardiac pacing to demonstrate the enormous impact it has had within the field of cardiology. Further, we look forward to the future of cardiac pacing, including conduction system pacing and leadless pacing strategies. The history of cardiac implantable electronic devices (CIED) has been one of continued technological development and refinement to serve ever evolving clinical applications. After the initial description of syncope associated with a slowed pulse rate by Adams and Stokes, interest in device therapies for bradycardia began to flourish. The first pacing systems were developed in the 1930s and were externalized and operated by a hand crank to supply energy via a direct current generator. A needle was introduced directly into the right atrium after a transthoracic puncture was performed . EventuaA major leap forward in the history of cardiac pacing came with the introduction of transvenous pacing leads that could be implanted and fixed to endocardium. This allowed for more effective and reliable pacing and sensing compared to epicardial pacing. In most cases, endocardial transvenous leads connect to a pulse generator that is implanted into a surgical pocket created in the pectoral region. Various modes of venous access are available. Original cardiac pacing devices utilized epicardial pacing techniques where an extravascular lead was implanted on the epicardium and connected to a pulse generator, originally implanted in the abdomen. Current epicardial pacing systems are used in patients with congenital heart disease, lack of venous access, history of recurrent device infections, or subjects who require CRT in whom a coronary sinus (CS) lead is not feasible. Current epicardial leads are implanted through various minimally invasive surgical techniques.Technological innovations have led to the miniaturization of CIEDs and made leadless pacing possible. These percutaneous devices do not require surgical pocket formation or endovascular leads. Completely intracardiac systems can be deployed to the right ventricle for endocardial pacing using catheter-based implantation techniques. This technology is being rapidly adopted and holds significant promise for the future of cardiac pacing.The indications for cardiac pacing have expanded significantly since the initial reports describing pacing as a viable treatment option for the management of symptomatic bradycardia. Pivotal randomized controlled trials (RCT) of cardiac pacing for bradycardia are summarized in A major leap forward in our understanding of cardiac pacing came in the 1980s with the conceptualization of “physiological pacing” techniques to maintain AV synchrony and restore chronotropic competence with rate-responsive pacing technologies. A meta-analysis by Healey et al. revealed that atrial-based pacing is associated with 20% lower risk of incident atrial fibrillation (AF) and 19% lower risk of stroke compared to ventricular-based pacing . No mortp = 0.002) and higher health care expenditures  [Annual CIED implantation numbers have generally increased since the introduction of the implantable system, likely related to expanding indications, and increasing global life expectancy and aging demographics ,15,16. C< 0.001) . These uIt is important to understand the complications associated with CIED implantation so that patients are well informed, but also to weigh the risks compared to the benefits of various CIED implantation strategies and select the best approach to individualize patient care and minimize the risks of harm. CRT implantation is associated with higher peri-procedural risks compared to PPM or ICD implant. A systematic review and meta-analysis of 8 RCTs, including 5674 patients, revealed implantation success rates ranging from 88.3% to 98.4%, with an overall pooled success rate of 95.3% . Peri-imp = 0.04). Envelope use has been shown to be cost effective when implant is guided by a CIED infection risk score [Importantly, CIED systems are associated with a risk of infection ranging from 0.6–3.4% . Patientsk score .Permanent transvenous leads pose a non-trivial lifelong risk of infective endocarditis (IE). A Danish nationwide registry analysis that included more than 40,000 patients who had undergone transvenous CIED system implants, with a total follow-up time of 168,343 person-years, found that the incidence of IE per 1000 patient-years ranged from 2.1 (95% CI 1.7–2.6) to 6.3 (95% CI 4.4–9.0) . The lowp = 0.0001) [There is significant heterogeneity in implantation techniques involving the venous access site and the mode of guiding vascular access. Each method has unique advantages and disadvantages that modify the risks of CIED implantation. The most common approaches to venous access are the subclavian vein puncture under fluoroscopic guidance and the cephalic vein cutdown. A review of almost 140,000 PPM implants from 2010 to 2014 revealed that the cephalic approach resulted in significantly fewer complications compared to the subclavian technique  . Althoug 0.0001) . More re 0.0001) . A prosp 0.0001) .We have come a long way since the advent of cardiac pacing and the introduction of transvenous systems. Thanks to new implantation techniques and technological developments, we are now observing several paradigms shifts in the established principles of cardiac pacing. A significant paradigm shift occurred with the adoption of pacing strategies in the form of CRT for patients with left ventricular (LV) dysfunction and symptomatic HF. Early data revealed that patients with systolic dysfunction who have electrical dyssynchrony (QRS duration ≥120 ms) have a 15% higher rate of mortality compared to those patients without dyssynchrony . These fp = 0.004) [A separate indication for CRT is the pace/ablate strategy, which describes implantation of a CIED for bradytherapy followed by total AV node ablation, in patients who have had difficulty with AF rate control . The APA= 0.004) . The benMultiple studies have revealed that acute narrowing of QRS duration after CRT is associated with improved clinical outcomes, such as lower risk of all-cause mortality, urgent heart transplantation, and heart failure hospitalization ,52. AddiProcedural failures related to LV lead placement during CRT implantation have been decreasing, yet finding an anatomically appropriate location for CS lead placement that is stable and affords adequate resynchronization remains challenging. In fact, this now accounts for over two-thirds of all procedural failures . CS leadp < 0.0001) and all-cause mortality  at 12 months post-implant [The Achilles Heel of CRT remains the high rate of non-responders, which is variably defined as failure to achieve HF symptom relief, improvements in LVEF, or LV dimensions. Rates of CRT non-response range from 30% to 50% of implants . Through-implant . While t-implant . However-implant ,65,66,67Multisite pacing (MSP) was proposed as a solution to CRT non-response. In experimental studies, MSP led to significant hemodynamic and electrophysiologic improvements . MSP wasp = 0.031). Further, the targeted group had higher clinical response  and lower rates of the combined endpoint of mortality and HF hospitalization (p = 0.031). A longer-term follow-up study (median 39 months) revealed that targeted LV lead placement resulted in lower all-cause mortality  [p = 0.006) [Another emerging technique to improve CRT response rates involves targeted delivery of the LV lead. Taking into account that patients who have LV leads implanted in areas of scar have poor response to CRT , and tha= 0.024) . The STA= 0.024) . Targete= 0.006) . More re= 0.006) . Pre-proFor almost 60 years, pacing from the RV apex has been the standard approach for long-term management of bradycardia given the demonstrated safety and efficacy of the procedure. However, RV apical pacing causes pre-excitation of the interventricular septum, and delayed activation of the lateral LV wall that results in electrical and mechanical dyssynchrony . This trInitial attempts at implantation of pacing leads within the HB were conducted using standard leads with reshaped stylets, and mapping for the largest His deflection while recording intracardiac electrical signals. Although this resulted in capture of the His, initial studies revealed elevated pacing thresholds, acutely high rates of lead dislodgements, and procedural success rate under 70%, mostly related to failure to localize the His bundle . Over tip = 0.04). However, the need for lead revision (6.7% vs. 3%) and generator change (9% vs. 1%) were both higher in the HBP group. Pacing thresholds increased over time in both groups at 5 years compared to implant, but thresholds were significantly higher in the HBP group .Initially, small observational studies demonstrated the low complication rates and effectiveness of HBP for resynchronization pacing in patients with HF ,93,94,95p = 0.0001), increase in LVEF , and improvement in NYHA functional class  compared to baseline.The efficacy of BiV-CRT is limited in patients with right bundle branch block (RBBB) and no pacing indication, and CSP has been proposed as an alternative CRT approach for this group of patients. In a prospective observational study, Sharma et al. report outcomes in patients with HF, LV dysfunction, and RBBB with QRS duration ≥120 ms who underwent HBP . During p < 0.001), NYHA functional class  compared to baseline. A systematic review and meta-analysis of early HBP literature for patients who underwent device upgrade from conventional RV pacing to HBP for documented pacing-induced cardiomyopathy has been published by Zheng et al. . This inp = 0.014) and lower LV end systolic diameters . In meta-analyses which compared HBP vs. BiV pacing for CRT, HBP resulted in significantly better QRS duration narrowing (mean difference range −23.17–43.50 ms), LV activation time (LVAT), and LV dyssynchrony index, when reported [Several RCTs have compared ventricular resynchronization using HBP with CRT . The Hisreported ,102. No p < 0.01). Additionally, NYHA class, cardiac biomarkers, and echocardiographic parameters had significantly improved compared to baseline. Other observational studies have corroborated these results, with high success rates of LBBP (85.0 to 97.8%) [p < 0.001), LVEF improvements  after mean follow-up 12 ± 10.1 months. Risk of death or HF hospitalization was lower in those patients who underwent LBBP for CS lead failure compared to CRT non-responders . Resynchronization therapy using a LBBP strategy has been reported in a cohort of elderly patients as well. In a prospective, observational study, Grieco et al. enrolled patients aged 75 years and older with indications for CRT who underwent LBBP for resynchronization [In 2017, the first case report demonstrating the clinical feasibility of LBBP was published by Huang et al. . Initialo 97.8%) ,106,107.o 97.8%) . This stnization . This cop = 0.039). Apart from LV end systolic volume and cardiac biomarker changes that favoured LBBP, there were no significant differences in other echocardiographic or clinical outcomes between groups. Similar findings were reported in the LEVEL-AT trial, a non-inferiority RCT including 70 patients with an indication for resynchronization therapy [p = 0.013). Wu et al. have reported the results of a non-randomized on-treatment comparison between LBBP versus HBP versus BiV-CRT (N = 137) [Chen et al. reported on a prospective, multicenter, non-randomized, observational trial comparing the efficacy of LBBP against BiV pacing CRT with an adaptive BiV algorithm in 100 consecutive patients with HF and LBBB . Success therapy . The fir therapy . A totalN = 137) . ClinicaIn a recent multicenter international collaboration, Jastrzebski et al. reported outcomes of LBBP in a registry-based observational study . This laIn both HBP and LBBP procedures, continuous intracardiac electrogram and 12-lead ECG recording should be utilized, ideally with an EP recording system. After venous access is obtained, a specialized sheath shaped to direct the lead to the HB or LBB area is advanced over a guidewire through the tricuspid valve, the RV, and to the RV outflow tract. Once the guidewire is removed, the sheath can be withdrawn to the approximate location of interest and a pacing lead is advanced through the sheath so just the helix is exposed. This allows for unipolar mapping of local intracardiac electrograms to more precisely find the appropriate location to begin lead fixation. Once this location is determined, an active fixation lead is deployed, and lead parameters are checked in both unipolar and bipolar modes .Selective response: capture of the HB alone, with ventricular capture exclusively through the conduction system;Non-selective response: activation of HB and local myocardium. Ventricular capture results from fusion of both wavefronts.In HBP, both atrial and ventricular components of the membranous septum can be interrogated for a His signal during unipolar sensing. Several permutations to the implantation technique have been described to guide localization to the area of the His. The use of contrast injection to visualize the tricuspid valve annulus has been shown to reduce fluoroscopy times . Fluoro-Although selective His capture is ideal, there have been studies demonstrating preservation of electromechanical synchrony with non-selective HB capture ,118.V1—QS complex with notch in the descending limb near the nadir (“W” complex);Tall R-waves in leads II, III ;Discordant QRS in leads aVR (negative) and aVL (positive).In selected cases, a pre-implantation echocardiogram may be helpful to assess the thickness of the interventricular septum for procedural planning. Similar to the HBP approach, unipolar sensing is utilized, and a specialized introducer sheath can help guide leads to the area of interest. The sheath is positioned distal to the location of the HB in the right anterior oblique view and faces 1 to 2 o’clock position. Fluoro-less approaches to LBBP have been described . Pace maGradual increase in R’ wave in V1 with progression of R wave to the terminal component of the QRS (Qr pattern or rSr’ pattern);Gradual increase in impedance before drop of 100–200 Ohms prior to LV subendocardium;Myocardium current of injury;Gradual deployment while monitoring the paced QRS morphology and impedance;PVC morphology changes from wide QRS to narrowed QRS with RBBB morphology (duration < 130 ms).Rapid deployment with monitoring of PVC morphology;Lead deployment can be performed, guided by two outcomes:RBBB pattern during pacing;Presence of LBB potential during pacing ;Short and constant LVAT high- (5 V) and low- (1 V) pacing outputs;Demonstration of selective and non-selective LBB pacing;Evidence for direct LBB capture.Through this process, a LBB potential may be visualized, which indicates an ideal spot. A drop in paced impedance of more than 200 Ohms, unipolar impedance of <400 Ohms, or poor R-wave sensing with diminished current of injury suggests perforation through to the LV endocardium. Programmed extra stimulus testing can be performed to differentiate LBB capture from septal myocardial capture based on differences in refractory periods. Jastrzebski et al. have described an approach that uses an 8-beat drive train at 600 ms with an extra stimulus with coupling interval at 450 ms . The extAs previously outlined, the complications related to CIED systems that utilize transvenous leads are not trivial. Leadless pacing was developed to eliminate both pocket- and lead-related device complications . A percup < 0.001); nevertheless, device optimization through serial clinic follow-ups was able to improve AV synchrony. An analysis of patients enrolled in the MARVEL 2 trial found that the strongest predictors of high AV synchrony  were an E/A ratio of <0.94 on echocardiogram, and low sinus rate variability at rest [Despite these very promising efficacy and outcomes studies, one significant limitation of LP was the lack of AV synchrony. The first LP trials strictly enrolled patients with an indication for single-chamber pacing. In fact, most trials had a very high representation of patients with AF-related bradycardia and pacing indications. The Micra AV LP takes advantage of a three-axis accelerometer that can sense atrial contractions and time a ventricular pacing event to maintain AV synchrony. A device algorithm has been developed that disregards motion related to AV valve and semilunar valve closures, ventricular diastole, and passive ventricular filling, but can sense mechanical events related to atrial contraction. This initiates a programmed AV delay, hence providing VDD pacing in essence. The initial feasibility study (MARVEL 1) of the AV algorithm was published in 2018 and demonstrated 87.0% (95% CI 81.8–90.9%) AV synchrony at rest . Examina at rest . CurrentAbsence of subcutaneous pocket;Substantially reduced device surface area;Minimal physical handling of device pre-implant;Extensive encapsulation of device after implant;Turbulent hemodynamic environment with high-velocity blood flow;Parylene-coated titanium material that may reduce bacterial adherence.Over time, LP have demonstrated significant safety advantages over transvenous systems. In a systematic review and meta-analysis that pooled the results of 36 observational trials, over 98% of patients had adequate pacing thresholds at 1 year . The poop < 0.01). A retrospective study comparing outcomes in patients with AF and HF, who underwent CSP (n = 37) versus BiV-CRT (n = 13) and subsequent AV node ablation, revealed that NYHA class improved in the CSP group irrespective of CSP approach , but not in the BiV group (p = 0.096) [p < 0.001; LBBP: p = 0.041), and not in the BiV group (p = 0.916). The CONDUCT-AF trial (NCT05467163) will be a multicenter RCT; it plans to enroll patients with AF and HF with narrow QRS durations who are appropriate for pace/ablate strategy, and aims to randomize to CRT with BiV pacing compared to CSP.The feasibility and efficacy of CSP for patients undergoing AVN ablation as a component of a pace/ablate strategy for AF management has been demonstrated in several small, observational studies ,140,141.= 0.096) . AdditioCSP holds significant promise, but large comparator studies are required to confirm the safety and efficacy that has been suggested by smaller exploratory studies. Two future trials will evaluate the application of CSP for patients at risk of pacing-induced cardiomyopathy or with HF, both comparing CSP strategies to established therapies in larger RCT formats. In the LEFT-HF trial (NCT05015660), investigators plan to recruit at least 100 patients with normal to mild LV dysfunction and high grade AVB, and randomize to LBBP versus RV apical pacing. Primary outcome measures will include LV dimensions on echocardiography and implant success. In the “Left Versus Left” trial (NCT05650658), investigators aim to recruit more than 2000 patients with HF and either a wide QRS or an anticipated pacing burden of greater than 40%. Patients will be randomized by receiving CSP (HPB or LBBP) versus BiV pacing for resynchronization. The primary outcome will be a combination of all-cause mortality and hospitalization for HF.The first reported case of lead extraction of a LBBP system was published by Vijayaraman et al. in 2020 . They deSubcutaneous implantable cardioverter defibrillators (S-ICD) have been developed to avoid the complications associated with transvenous lead implantation, while maintaining the ability to treat life-threatening ventricular tachyarrhythmias ,152. WhiIn addition to resynchronization through QRS narrowing by HBP, the utility of this mode of pacing has been investigated as an adjunction to traditional CRT with left ventricular endocardial pacing with a CS lead. This so-called “His-Optimized CRT” (HOT-CRT) has been studied for a subset of patients who had CRT indications and had failed to completely correct HP conduction abnormalities with HBP alone, or who were clinical or echocardiographic non-responders to HB pacing. The feasibility study by Vijayaraman et al. enrolled 27 patients to HOT-CRT pacing . In 93% Similar to HOT-CRT, achieving resynchronization through pacing the LBB has led to investigation into the feasibility of “Left Bundle Branch-Optimized Cardiac Resynchronization Therapy” (LOT-CRT). Initial feasibility data were published by Dr. Vijayaraman in 2021 . The larThe WiSE-CRT  system is a promising application of leadless pacing that attempts to deliver endocardial LV pacing via a very small (9.1 × 2.6 × 3.6 mm) anchoring electrode implanted onto the LV endocardium to achieve CRT. In addition to the LV electrode, the system requires a small transmitter implanted at a pre-determined intercostal space, and a generator implanted at the left mid-axillary line . The orip < 0.001) decrease in the supply costs of ICD implantation over this period. However, there was no significant decrease in the overall costs associated with these encounters, meaning that other costs were rising to offset improving supply costs [It will be important to bear in mind the economic challenges that accompany ongoing technological developments in the field of CIED implantation. In general, as technologies mature, there is a steady decrease in the price of the associated goods . This trly costs . Technolly costs ,163. As Cardiac pacing has a long and storied past with several revolutions and paradigm shifts. The introduction of new technologies, procedural techniques, and increasing demand for new clinical applications for pacing therapy has pushed the field of cardiac pacing forward. From this vantage point, the future looks bright.


Additionally, ROC analysis revealed higher AUC for TRV/TAPSE than for TAPSE and TRV alone. Conclusions: TRV/TAPSE is a promising practicable echocardiographic parameter reflecting RVPAC. Moreover, TRV/TAPSE could be viable risk stratification parameter and could have prognostic value in patients with PH.Background: Tricuspid annular plane systolic excursion (TAPSE) and tricuspid regurgitation velocity (TRV) are two echocardiographic parameters with prognostic value in patients with pulmonary hypertension (PH). When analyzed concurrently as the TRV/TAPSE ratio, they allow the ventricular–pulmonary artery coupling (RVPAC) to be assessed. This could better predict disease severity in patients with PH. Objective: Our study aimed to evaluate the prognostic value of the TRV/TAPSE ratio echocardiographic parameter in adults with precapillary PH. Methods: This study included 39 patients  with precapillary PH  The mean follow-up period was 16.6 ± 13.3 months. Twelve patients (31%) died during the observation time. We measured TAPSE as a surrogate of RV contractility and TRV reflecting RV afterload, while ventricular–arterial coupling was evaluated by the ratio between these two parameters (TRV/TAPSE). To assess disease progression and the patient’s functional capacity, the World Health Organization functional class (WHO FC) was determined. Patient physical capacity was also evaluated using the 6 min walk test (6MWT). The analysis included values of N-terminal prohormone brain natriuretic peptide (NT-proBNP), which were taken routinely during the follow-up visit. Results: The mean calculated TRV/TAPSE ratio was 0.26 ± 0.08 m/s/mm. Upon comparison of the TRV/TAPSE ratio to the disease prognostic indicators, we observed a statistically significant correlation between TRV/TAPSE and the results of the WHO FC, 6MWT, and NT-proBNP. The TRV/TAPSE ratio is thus a good predictor of mortality in PH patients . Patients with a TRV/TAPSE ratio > 0.30 m/s/mm had a shorter survival time, with log-rank test  Pulmonary hypertension (PH) is a disease characterized by elevated blood pressure in the pulmonary arteries. PH is not a homogeneous clinical or pathological entity. It most often occurs in the course of diseases of the left heart and lungs. Currently, there are five subtypes of PH, including pulmonary arterial hypertension (PAH), PH associated with left heart disease, PH associated with lung disease, chronic thromboembolic PH (CTEPH), and PH with unclear and/or multifactorial mechanisms . PAH is CTEPH, like PAH, is classified as precapillary PH. It develops as a result of the obliteration of the lumen of the pulmonary vessels caused by emboli and/or thrombosis in situ. In the chronic form, thromboembolic masses undergo secondary fibrosis, which leads to reduced lumen and increased resistance in the pulmonary circulation . CTEPH iDue to the crippling nature of the disease and the high mortality rate, it is important to make a timely diagnosis, implement effective treatment, and constantly monitor the patient’s condition. According to the latest guidelines, in order to monitor the clinical condition of the patient, a four-stage risk stratification scale was proposed. It is based on the World Health Organization functional class (WHO-FC), the 6 min walk test (6MWT), and B-type natriuretic peptide (BNP) or N-terminal (NT)-proBNP, and it categorizes patients as low, medium-low, medium-high, or high risk [Echocardiography is one of the most frequently performed imaging modalities used to assess the structure and function of the heart. It is an extremely useful test to assess the probability of PH. It provides information about the possible etiology of PH and its severity and prognosis, allowing for the planning of observation and treatment. From a pathophysiological point of view, in patients with PH, the structure and systolic and diastolic functions of the right ventricle (RV), with a measurement of tricuspid regurgitation, the size of the right atrium and inferior vena cava, and the pulmonary artery pressure, should be assessed . New echIn recent studies, longitudinal systolic RV function indicators, such as TAPSE, and RV pressure afterload indicators, such as TRV, have been analyzed in combination. Also, a novel parameter, the TRV/TAPSE ratio, demonstrated a strong correlation with the New York Heart Association (NYHA) performance class in pediatric patients with PH .This study aimed to assess the prognostic value of the TRV/TAPSE ratio echocardiographic parameter in adults with PH.The study group included 39 adult patients  with PAH or CTEPH treated at a single referral center. The inclusion criteria included a diagnosis of PAH or CTEPH after right heart catheterization based on the current guidelines of the European Society of Cardiology ,13 and aTo assess disease progression, the patient’s functional capacity was ascertained according to the World Health Organization WHO classification. Assessment of the amount of exertion that caused clinical symptoms  determined the functional capacity class. The WHO functional class (WHO FC) was decided by two independent physicians on the day of the echocardiographic examination.Patient physical capacity was evaluated using the 6 min walk test (6MWT), which measured the distance the patient could cover in 6 min of steady walking, with simultaneous measurement of oxygen saturation and blood pressure. The 6MWT was performed after each echocardiographic examination on the same day.Most measurements of N-terminal prohormone brain natriuretic peptide (NT-proBNP) were taken routinely during the follow-up visit on the day of the echocardiographic examination. In the absence of the result from the day of the echocardiography, NT-proBNP determined at the subsequent follow-up visit/hospitalization was used for the analysis. All NT-proBNP values used were marked +/− 40 days from the date of the echocardiographic examination.The gold standard for assessing the hemodynamic parameters of the pulmonary circulation is to measure the pressure in the right heart and the pulmonary vessels in cardiac catheterization. Although this test can diagnose PH, it is invasive and expensive. Therefore, among patients with suspected PH, transthoracic echocardiography (TTE) is used as the first-choice test for the noninvasive evaluation of pulmonary vascular hemodynamics and the initial assessment of RV, RA, and PA pressures .2 +RAP [Right atrial pressure (RAP) is usually estimated from the dimension and collapse ratio of the inferior vena cava (IVC) in the subcostal view . Typical2 +RAP . Longitu2 +RAP . Because2 +RAP .Transthoracic echocardiography using a Philips EPIQ 7G (Epiq Elite Diagnostic Ultrasound System) with 2.5–3.5 MHz transducers was performed by one investigator (AW), following the European Association of Cardiovascular Imaging recommendations. Patients were examined in the left lateral position. TAPSE, measured as the difference between the displacement of the lateral tricuspid valve annulus from end-diastole to end-systole, was evaluated in the M-mode presentation and the standard apical 4-chamber view (4CV). TRV measurement used Continuous Wave Doppler focused on the regurgitation wave of the tricuspid valve in the 4CV view. The mean values of three cardiac cycles in sinus rhythm or five cycles in cases of atrial fibrillation were calculated. TRV/TAPSE ratio was calculated and expressed as m/s/mm units.p < 0.05.Statistical analysis was performed using GraphPad Prism 9 . Data expressed on a quantitative scale were presented as mean with SD. Data expressed on a qualitative scale were presented as the number and percentage of the sample. Depending on the result of the Shapiro–Wilk test , Pearson’s or Spearman correlation analysis was applied. Additionally, one-way ANOVA with Tukey’s post hoc test and the Kruskal–Wallis test with Dunn’s post hoc test were used. Furthermore, the receiver operating characteristic (ROC) curves were analyzed to obtain the cut-off values of tested variables that best distinguished patient survival, and the Kaplan–Meyer method was employed to plot survival curves. A log-rank test was also used to compare survival curves with the Cox proportional hazard test. Results were considered statistically significant when n = 12; connective tissue diseases PAH, n = 7; PAH associated with congenital defects, n = 13; portopulmonary hypertension, n = 1; chronic thromboembolic pulmonary hypertension, n = 6). Twelve patients (31%) died during the observation time, while the rest received PH-specific treatment during the study period. Eighteen patients were in the WHO functional class IV (46%), fifteen were in class III (38%), and six were in class II (15%).The study group consisted of thirty-nine patients  with precapillary pulmonary hypertension, with a mean age of 63.1 ± 15.9 years . There were no statistically significant differences between the other groups (the power of the test was 0.618)  and the mean TRV was 4.23 ± 0.72 m/s . The mean calculated TRV/TAPSE ratio was 0.26 ± 0.08 m/s/mm . Other echocardiographic parameters are presented in s 0.618) .r = −0.37; p = 0.0193), as shown in In this study, we observed a significant negative correlation between TRV/TAPSE and the results of the 6MWT test   .Our analysis indicated that there were no statistically significant differences in the TRV/TAPSE values between the groups of patients of different etiologies  (the power of the test was 0.618) .p = 0.0115). The optimal cut-off point for predicting mortality was set at 16.50 mm . The ROC curve for the TRV variable has an AUC of 0.6049 (p = 0.3009), and one cut-off point was set at 4.43 m/s . The ROC curve for the TRV/TAPSE variable has an AUC of 0.781 (p = 0.0056). Two cut-off points were set, the first at 0.247 m/s/mm  and the second at 0.300 m/s/mm . Survival analyses were performed by taking both proposed values as the dividing point . Additionally, the ROC analysis revealed higher AUC for TRV/TAPSE than for TAPSE and TRV alone. The ROC curve for the TAPSE variable has an AUC of 0.756 (ng point .p < 0.0001) (the power of the test was 0.997)  .The schematic representation of the result is presented in Pulmonary hypertension (PH) is a condition where there is an abnormal increase in pressure in the pulmonary bed due to pulmonary vascular disease, lung parenchyma, and cardiac disease. Pulmonary arterial hypertension (PAH) is diagnosed in patients who have pre-capillary pulmonary hypertension on hemodynamic examination, defined as mPAP ≥ 20 mmHg, pulmonary artery wedge pressure (PAWP) ≤ 15 mm Hg, and pulmonary vascular resistance (PVR) > 3 Wood units (WU) . PAH is In assessing PH severity, several clinical, hemodynamic and biochemical parameters require determination. Echocardiography plays a crucial role in PH diagnosis, as it accurately assesses the correlation between RV contractility and RV afterload and the right ventricular–pulmonary artery coupling (RVPAC), while it is readily available, non-invasive and of low-cost . It can 2 + right atrial pressure (RAP), using TRV as an indicator of pulmonary artery pressure is considered a prognostic factor of PH and plays a vital role in the current PH diagnostic algorithm [TAPSE is one of the most recognized parameters reflecting RV systolic function , and it lgorithm ,26.Studies have shown, however, that over-reliance on one parameter for assessing the course of PH is an insufficient strategy . TherefoThis study aimed to determine the prognostic value of a novel alternative RVPAC assessment parameter, the TRV/TAPSE ratio, in adult PH patients. As such, the correlations between the TRV/TAPSE ratio and indicators of disease progression, including the WHO FC class, the 6MWT, NT-proBNP levels, and survival, were evaluated.A version of the NYHA functional class modified for PH by the WHO monitors the main PH symptom—the deterioration of physical fitness. Studies have revealed that the WHO FC correlates with PH patient life expectancy. Herein, class I and II patients have a better prognosis, while classes III and IV are associated with a poorer prognosis . SavaresBiochemical indicators of RV overload include BNP concentration and NT-proBNP levels. Moreover, the risk of PAH patient death increases with increased NT-proBNP plasma concentration ,37. A stIn the current study, the risk of death increased for patients with a higher TRV/TAPSE ratio. The Kaplan–Maier probability of survival analysis demonstrated that patients with a TRV/TAPSE ratio > 0.300 m/s/mm had a shorter survival time. Furthermore, receiver operating characteristic (ROC) curve analysis showed that the TRV/TAPSE ratio is a better predictor of PH-related death than TAPSE or TRV alone. Indeed, the area under the curve (AUC) was significantly higher for the TRV/TAPSE ratio than that for both TAPSE and TRV individually. Therefore, TRV/TAPSE may be a prognostic indicator in the course of PH in adult patients. The novel TRV/TAPSE ratio parameter correlated with disease severity indicators  in adults with PAH or CTEPH. Based on these results, the TRV/TAPSE ratio is a viable risk stratification parameter that can identify patients with poor prognoses. The statistical analysis highlighted TRV/TAPSE as a non-invasive indicator of RVPAC. As such, the findings may have important clinical significance for risk stratification and prognosis of PH patients. The TRV/TAPSE ratio is readily available for clinical use as it is measurable using the standard M-mode and Doppler echocardiography. Unlike the strong prognostic predictor TAPSE/sPAP, the TRV/TAPSE ratio does not require RAP estimation. Therefore, it could be used alternatively to evaluate RVPAC in cases with difficulties visualizing the inferior vena cava, such as with obese patients .A limitation of this study is the heterogeneity of patients in the etiology of precapillary PH and the relatively small size of the population with PAH. The TRV/TAPSE ratio parameter should be tested on a more substantial group of patients to confirm its clinical utility. In addition, the value of the parameter and its association with a worse prognosis should be validated in multicenter studies on a larger group of patients. What is more, the study group did not include WHO class I patients. Therefore, the clinical utility of the parameter in patients with mild PH remains unexplored. Data from right heart catheterization were not included in this study, due to the considerable time between the last RHC and the inclusion of patients in this study.In conclusion, the TRV/TAPSE ratio is a promising practicable echocardiographic parameter reflecting RVPAC. It strongly correlates with prognostic markers of PH, such as WHO FC class, the 6MWT, NT-proBNP levels, and survival, in adults with PH. Therefore, the TRV/TAPSE ratio may be a viable risk stratification parameter, and it may have prognostic value in patients with PH.