Right ventricular dysfunction in left ventricular assist device candidates: is it time to change our prospective?

The use of left ventricular assist devices (LVAD) has significantly increased in the last years, trying to offer a therapeutic alternative to heart transplantation, in light also to the significant heart donor shortage compared to the growing advanced heart failure population. Despite technological improvements in the devices, LVAD-related mortality is still fairly high, with right heart failure being one of the predominant predictors. Therefore, many efforts have been made toward a thorough right ventricular (RV) evaluation prior to LVAD implant, considering clinical, laboratory, echocardiographic, and invasive hemodynamic parameters. However, there is high heterogeneity regarding both which predictor is the strongest as well as the relative cut-off values, and a consensus has not been reached yet, increasing the risk of facing patients in which the distinction between good or poor RV function cannot be surely reached. In parallel, due to technological development and availability of mechanical circulatory support of the RV, LVADs are being considered even in patients with suboptimal RV function. The aim of our review is to analyze the current evidence regarding the role of RV function prior to LVAD and its evaluation, pointing out the extreme variability in parameters that are currently assessed and future prospective regarding new diagnostic tools. Finally, we attempt to gather the available information on the therapeutic strategies to use in the peri-operative phase, in order to reduce the incidence of RV failure, especially in patients in which the preoperative evaluation highlighted some conflicting results with regard to ventricular function.

Detection of myocardial fibrosis by speckle-tracking echocardiography: from prediction to clinical applications.

Myocardial fibrosis (MF) represents the underlying pathologic condition of many cardiac disease, leading to cardiac dysfunction and heart failure (HF). Biopsy studies have shown the presence of MF in patients with decompensating HF despite apparently normal cardiac function. In fact, basic indices of left ventricular (LV) function, such as LV ejection fraction (EF), fail to recognize subtle LV dysfunction caused by MF. Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) is currently recognized as the gold standard imaging investigation for the detection of focal and diffuse cardiac chambers MF; however, its use is limited by its availability and the use of contrast agents, while echocardiography remains the first level cardiac imaging technique due to its low cost, portability and high accessibility. Advanced echocardiographic techniques, above all speckle-tracking echocardiography (STE), have demonstrated reliability for early detection of structural myocardial abnormalities and for the prediction of prognosis in acute and chronic HF. Myocardial strain of both ventricles and also left atrium has been shown to correlate with the degree of MF, providing useful prognostic information in several diseases, such as HF, cardiomyopathies and valvular heart disease. This paper aims to provide an overview of the pathophysiology of MF and the clinical application of STE for the prediction of left and right heart chambers MF in HF patients.

Left atrial myocardial intrinsic function remodeling response to repair of primary mitral regurgitation.

Severe mitral regurgitation (MR) is a common valve disease which is associated with high mortality, if only managed medically. MR produces chronic and progressive volume overload with left atrial (LA) and left ventricular (LV) dilatation and dysfunction, atrial fibrillation (AF) and eventually myocardial fibrosis, irrespective of ejection fraction (EF). Surgical correction (mitral valve repair) of MR removes the volume overload, hence unmasks pre-operative LV structure and function disturbances, including reduced EF and global longitudinal and circumferential strain, as well as LA volume and strain. This review aims at describing LA remodeling before and after surgical repair.

Early diagnosis, clinical management, and follow-up of cardiovascular events with ponatinib.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by neoplastic transformation of pluripotent cells due to a typical cytogenetic and molecular mutation known as Philadelphia (Ph) chromosome. In 2001, the introduction of the tyrosine kinasis inhibitor (TKI) imatinib as a therapeutic strategy for CML with PH chromosome mutation represented an important step towards treatment of these patients, and nowadays, this drug represents the gold therapeutic standard in this clinical setting. A second generation of TKIs (dasatinib, nilotinib, and bosutinib) showed an effective action in all patients with mutations resistant to imatinib. Ponatinib is a third-generation TKI and is the only inhibitor with activity against T3151 mutation. The impact of ponatinib on cardiovascular events was first evaluated in the PACE trial. We therefore report and discuss most relevant evidence currently available on cardiovascular events associated with the use of ponatinib. Though many exams can be used for diagnosis and follow-up of this kind of cardiotoxicity, echocardiography seems to have a pivotal role thanks to its feasibility, availability, and low cost.

Right ventricular function after cardiac surgery: the diagnostic and prognostic role of echocardiography.

Cardiac surgical techniques and circulatory supports have strongly evolved in the last years. Right ventricular (RV) function during the post-operatory period is still subject of study, although its relevant prognostic impact has been variably described in different papers. RV post-surgical dysfunction's underlying mechanisms are still not clear and include a different hypothesis. Echocardiography, with both first and second level parameters, offers the possibility to accurately analyze the right ventricle and optimize these patients' management. This paper describes the pathophysiology of the right ventricle, the most used echo indexes of RV function, whether they alter after surgery, the different supposed mechanisms of RV dysfunction and its role in the prognosis of patients undergoing cardiac surgery.

Effects of levosimendan in heart failure: The role of echocardiography.

Heart failure (HF) represents a deadly epidemic that nowadays affects more than 2% of the general population, representing a major public health concern that implies a high economic burden for the health system. Levosimendan in HF patients is usually used for its inotropic and vasodilator effects that act without myocardial oxygen consumption, differently from other inotropic drugs. The symptoms and hemodynamic profile improve together with the myocardial function, and this can be demonstrated by an echocardiographic examination. Currently, the available data about the effects of levosimendan assessed by echocardiography are still lacking. This review discusses the role of echocardiography in the evaluation of therapeutic effects of levosimendan in HF.

Speckle tracking analysis in intensive care unit: A toy or a tool?

The use of conventional echocardiography in the intensive care unit (ICU) is today established to assess left and right ventricular systolic function, for preload determination and procedural guidance. Next step in ICU echocardiography could be the use of novel ultrasound techniques such as strain echocardiography to assist in the management of patients with acute coronary syndrome, heart failure, or pulmonary embolism. This review has gathered the available evidence supporting the incremental value of strain in the diagnostic workup of cardiac diseases treated in ICU.

Left Ventricular Deformation and Myocardial Fibrosis in Patients With Advanced Heart Failure Requiring Transplantation.

PURPOSE: To evaluate potential relationships between different components of left ventricular (LV) function and histopathological evidence for myocardial fibrosis in patients undergoing heart transplantation. METHODS: The study population included patients with advanced heart failure, referred for an echocardiographic examination before heart transplantation. Traditional LV function measurements and global longitudinal strain (GLS) by speckle tracking echocardiography, averaging all LV segments in 4-, 2-, and 3-chamber views were obtained in all subjects. LV tissue samples were obtained from all patients who underwent heart transplantation. Myocardial fibrosis was assessed using Masson's staining. RESULTS: Of 106 patients referred for cardiac transplantation, 47 underwent cardiac transplantation and were enrolled in the study. LV myocardial fibrosis and its grade strongly correlated with GLS (r = 0.75, P = .0001), modestly with global circumferential strain and LV torsion (r = 0.61, P = .001 and r = 0.52, P = .01, respectively) and weakly with mitral S' wave (r = -0.41; P = .01) and mitral annular plane systolic excursion (r = -0.35; P = .05) but did not correlate with LV ejection fraction (r = -0.12; P = NS). GLS had the strongest accuracy for detecting LV fibrosis (area under the curve, 0.92). None of the echo parameters correlated with patient's exercise capacity. CONCLUSION: Global longitudinal strain is the most accurate LV global function measure that correlates with the extent of myocardial fibrosis in patients with advanced systolic HF requiring heart transplantation.

Echocardiographic assessment of left ventricular systolic function: from ejection fraction to torsion.

Assessment of left ventricular (LV) systolic function is the cornerstone of the echocardiographic examination. There are many echocardiographic parameters that can be used for clinical and research purposes, each one with its pros and cons. The LV ejection fraction is the most used one due to its feasibility and predictability, but it also has many limits, related to both the imaging technique used for calculation and to the definition itself. LV longitudinal function is expression of subendocardial fibers contraction. Because the subendocardium is often involved early in many pathological processes, its analysis has been a fertile field for the development of sensitive parameters. Longitudinal function can be evaluated in many ways, such as M-mode echocardiography, tissue Doppler imaging, and speckle tracking echocardiography. This latter is a relatively new tool to assess LV function through measurement of myocardial strain, with a high temporal and spatial resolution and a better inter- and intra-observer reproducibility compared to Doppler strain. It is angle independent, not affected by translation cardiac movements, and can assess simultaneously the entire myocardium along all the three-dimensional geometrical (longitudinal, circumferential, and radial) axes. Speckle tracking echocardiography also allows the analysis of LV torsion. The aim of this paper was to review the main echocardiographic parameters of LV systolic function and to describe its pros and cons.

Right ventricular strain as a novel approach to analyze right ventricular performance in patients with heart failure.

Speckle tracking echocardiography (STE) has recently applied as imaging technique to accurately evaluate right ventricular (RV) function. STE provides a non-Doppler, angle-independent and objective quantification of RV myocardial deformation. Data regarding feasibility, accuracy and clinical applications of RV strain are rapidly gathering, especially in the setting of heart failure patients. This review describes the fundamental concepts of RV-STE and discusses its emerging clinical applications, focusing on the useful of this technique in the clinical management of patients with advanced heart failure.

The Role of Speckle Tracking Echocardiography in the Evaluation of Advanced-Heart-Failure Patients.

Health care is currently showing a fall in heart failure (HF) incidence and prevalence, particularly in developed countries, but with only a subset receiving appropriate therapy to protect the heart against maladaptive processes such as fibrosis and hypertrophy. Appropriate markers of advanced HF remain unidentified, which would help in choosing the most suitable therapy and avoid major compliance problems. Speckle tracking echocardiography (STE) is a good choice, being a non-invasive imaging technique which is able to assess cardiac deformation in a variety of conditions. Several multicenter studies and meta-analyses have demonstrated the clinical application and accuracy of STE in early and late stages of HF, as well as its association with both left ventricular (LV) filling pressures and myocardial oxygen consumption. Furthermore, STE assists in assessing right ventricular free-wall longitudinal strain (RVFWLS), which is a solid predictor of right ventricle failure (RVF) following LV assist device (LVAD) implantation. However, STE is known for its limitations; despite these, it has been shown to explain symptoms and signs and also to be an accurate prognosticator. The aim of this review is to examine the advantages of STE in the early evaluation of myocardial dysfunction and its correlation with right heart catheterization (RHC) parameters, which should have significant clinical relevance in the management of HF patients.

Left ventricular fibrosis as a main determinant of filling pressures and left atrial function in advanced heart failure.

AIMS: Advanced heart failure (AdHF) is characterized by variable degrees of left ventricular (LV) dysfunction, myocardial fibrosis, and raised filling pressures which lead to left atrial (LA) dilatation and cavity dysfunction. This study investigated the relationship between LA peak atrial longitudinal strain (PALS), assessed by speckle-tracking echocardiography (STE), and invasive measures of LV filling pressures and fibrosis in a group of AdHF patients undergoing heart transplantation (HTX). METHODS AND RESULTS: We consecutively enrolled patients with AdHF who underwent HTX at our Department. Demographic and basic echocardiographic data were registered, then invasive intracardiac pressures were obtained from right heart catheterization, and STE was also performed. After HTX, biopsy specimens from explanted hearts were collected to quantify the degree of LV myocardial fibrosis. Sixty-four patients were included in the study (mean age 62.5 ± 11 years, 42% female). The mean LV ejection fraction (LVEF) was 26.7 ± 6.1%, global PALS was 9.65 ± 4.5%, and mean pulmonary capillary wedge pressure (PCWP) was 18.8 ± 4.8 mmHg. Seventy-three % of patients proved to have severe LV fibrosis. Global PALS was inversely correlated with PCWP (R = -0.83; P < 0.0001) and with LV fibrosis severity (R = -0.78; P < 0.0001) but did not correlate with LVEF (R = 0.15; P = 0.2). Among echocardiographic indices of LV filling pressures, global PALS proved the strongest [area under the curve 0.955 (95% confidence interval 0.87-0.99)] predictor of raised (>18 mmHg) PCWP. CONCLUSION: In patients with AdHF, reduced global PALS strongly correlated with the invasively assessed LV filling pressure and degree of LV fibrosis. Such relationship could be used as non-invasive indicator for optimum patient stratification for therapeutic strategies.

Dapagliflozin Effects on Cardiac Deformation in Heart Failure and Secondary Clinical Outcome.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors were shown to reduce morbidity and mortality in patients with heart failure. OBJECTIVES: This study aims to assess potential effects of dapagliflozin in nondiabetic patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF) on cardiac function assessed by speckle tracking echocardiography (STE). METHODS: This randomized, prospective, single-center, open-label trial compared consecutive nondiabetic outpatients with HFrEF or HFmrEF receiving dapagliflozin with patients treated with optimal medical therapy (OMT) except sodium-glucose cotransporter type 2 inhibitors. Primary endpoint was the presence of a significant modification of left ventricular global longitudinal strain, diastolic function (as peak atrial longitudinal strain) and right ventricular function by STE from baseline to 6 months. Cardiovascular events and parameters of congestion were assessed as safety-exploratory endpoints. RESULTS: Overall, 88 patients (38% HFmrEF) were enrolled and randomized to start dapagliflozin on top of OMT (n = 44) or to continue with OMT (n = 44). All STE values improved in the dapagliflozin group after 6 months, whereas there was a nonsignificant improvement in OMT group. Moreover, when comparing the modification of STE parameters at follow-up in patients with HFrEF and HFmrEF, only the main treatment effect resulted statistically significant in both groups (P < 0.0001), indicating a significant difference between dapagliflozin and OMT. CONCLUSIONS: This study provided randomized data on the beneficial effect of dapagliflozin in nondiabetic patients with HFrEF and HFmrEF in terms of myocardial performance measured by the most sensitive echocardiographic technique, ie, STE. This suggests its usefulness for left ventricular reverse remodeling and better quality of life in patients with HFrEF and HFmrEF. (Effects of Dapagliflozin on cardiac deformation and clinical outcomes in heart failure with reduced and mildly reduced ejection fraction [DAPA ECHO trial]; EudraCT number: 2021-005394-66).

Heart transplantation and anti-HLA antibodY: myocardial dysfunction and prognosis - HeartLAy study.

AIMS: The presence of anti-human leucocyte antigen (HLA) antibodies has been implicated in a higher incidence of complications as well as mortality rate in heart transplantation. The aim of the study was to identify through non-invasive parameters early signs of myocardial dysfunction in the presence of anti-HLA antibodies but without evidence of antibody-mediated rejection (AMR) and its possible prognostic impact. METHODS AND RESULTS: A total of 113 heart-transplanted patients without acute cellular rejection (ACR) and AMR or cardiac allograft vasculopathy (CAV) were prospectively enrolled and divided into two groups ['HLA+' (50 patients) and 'HLA-' (63 patients)], based on the presence of anti-HLA antibodies. Each patient was followed for 2 years after the enrolment, recording episodes of AMR, ACR, CAV, and mortality. Clinical characteristics were similar between the two groups. Among laboratory data, N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin values were significantly higher in the presence of anti-HLA antibodies (P < 0.001 and P = 0.003, respectively). The echocardiographic parameters that showed a statistically significant difference between the two groups were deceleration time of E wave (DecT E, P < 0.001), left ventricular global longitudinal strain (P < 0.001), tricuspid annular plane systolic excursion (P = 0.011), tricuspid S' wave (P = 0.002), and free wall right ventricular longitudinal strain (fwRVLS, P = 0.027), whereas left atrial strain did not differ significantly (P = 0.408). Univariate analysis showed that anti-HLA antibodies were associated with the development of CAV at both 1 and 2 year follow-up [odds ratio (OR) 11.90, 95% confidence interval (CI) 1.43-90.79, P = 0.022 and OR 3.37, 95% CI 1.78-9.67, P = 0.024, respectively]. Bivariate analysis demonstrated that both fwRVLS and DecT E were predictors of CAV development independently from HLA status. CONCLUSIONS: The presence of circulating anti-HLA antibodies is correlated with a mild cardiac dysfunction, even in the absence of AMR, and CAV development. Interestingly, reduced values of DecT E and fwRVLS were predictors of future development of CAV, independently from anti-HLA antibody.

Right ventricular longitudinal strain correlates well with right ventricular stroke work index in patients with advanced heart failure referred for heart transplantation.

BACKGROUND: Right ventricular (RV) systolic function has a critical role in determining the clinical outcome and success of using left ventricular assist devices (LVADs) in patients with refractory heart failure. Tissue Doppler and M-mode measurements of tricuspid systolic motion (tricuspid S' and tricuspid annular plane systolic excursion [TAPSE]) are the most currently used methods for the quantification of RV longitudinal function; RV deformation analysis by speckle-tracking echocardiography (STE) has recently allowed the analysis of global RV longitudinal function. Using cardiac catheterization as the reference standard, this study aimed at exploring the correlation between RV longitudinal function by STE and RV stroke work index (RVSWI) in patients referred for cardiac transplantation. METHODS AND RESULTS: Right-side heart catheterization and transthoracic echo Doppler were simultaneously performed in 41 patients referred for cardiac transplantation evaluation for advanced systolic heart failure. Thermodilution RV stroke volume and invasive pulmonary pressures were used to obtain RVSWI. RV longitudinal strain (RVLS) by STE was assessed averaging all segments in apical 4-chamber view (global RVLS) and by averaging RV free-wall segments (free-wall RVLS). Tricuspid S' and TAPSE were also calculated. No significant correlations were found for TAPSE or tricuspid S' with RVSWI (r = 0.14; r = 0.06; respectively). Close negative correlations between global RVLS and free-wall RVLS with the RVSWI were found (r = -0.75; r = -0.82; respectively; both P < .0001). Furthermore, free-wall RVLS demonstrated the highest diagnostic accuracy (area under the receiver operating characteristic (ROC) curve 0.90) and good sensitivity and specificity of 92% and 86%, respectively, to predict depressed RVSWI using a cutoff value of less than -11.8%. CONCLUSIONS: In a group of patients referred for heart transplantation, TAPSE and tricuspid S' did not correlate with invasively obtained RVSWI. RV longitudinal deformation analysis by STE correlated well with RVSWI, providing a better estimation of RV systolic performance.

Novel echocardiographic techniques to assess left atrial size, anatomy and function.

Three-dimensional echocardiography (3DE) and speckle tracking echocardiography (STE) have recently applied as imaging techniques to accurately evaluate left atrial (LA) size, anatomy and function. 3DE and off-line quantification softwares, have allowed, in comparison to magnetic resonance imaging, the most time-efficient and accurate method of LA volume quantification. STE provides a non-Doppler, angle-independent and objective quantification of LA myocardial deformation. Data regarding feasibility, accuracy and clinical applications of LA analysis by 3DE and STE are rapidly gathering. This review describes the fundamental concepts of LA 3DE and STE, illustrates how to obtain respective measurements and discuss their recognized and emerging clinical applications.

Left Atrial Remodeling in Response to Aortic Valve Replacement: Pathophysiology and Myocardial Strain Analysis.

Severe aortic stenosis (AS) is the most common valve disease in the elderly and is associated with poor prognosis if treated only medically. AS causes chronic pressure overload, concentric left ventricular (LV) hypertrophy, myocardial stiffness, and diastolic dysfunction. This adverse remodeling also affects the left atrium (LA), which dilates and develops myocardial fibrosis, with a reduction in intrinsic function and a consequent high risk of the development of atrial fibrillation. Speckle-tracking echocardiography is able to detect myocardial dysfunction before other conventional parameters, such as LV ejection fraction, and also predict clinical outcomes. This review aims at describing LV and LA remodeling in AS and before and after aortic valve replacement and the usefulness of myocardial strain analysis in this clinical setting.

Left atrial strain by speckle tracking predicts atrial fibrosis in patients undergoing heart transplantation.

AIMS: In patients with heart failure (HF), chronically raised left ventricular (LV) filling pressures lead to progressive left atrial (LA) dysfunction and fibrosis. We aimed to assess the correlation of LA reservoir strain (peak atrial longitudinal strain, PALS) by speckle tracking echocardiography (STE) and LA fibrosis assessed by myocardial biopsy in patients undergoing heart transplantation (HTx). METHODS AND RESULTS: Forty-eight patients with advanced HF [mean age 51.2 ± 8.1 years, 29% females; LV ejection fraction ≤25% and New York Heart Association (NYHA) class III-IV] referred for HTx were enrolled and underwent pre-operative echocardiographic evaluation, right heart catheterization, and cardiopulmonary exercise testing. Exclusion criteria were non-sinus rhythm, mechanical ventilation, severe mitral/tricuspid regurgitation, or other valvular disease and poor acoustic window. After HTx, LA bioptic samples were collected and analysed to determine the extent of myocardial fibrosis (%). LA fibrosis showed correlation with PALS (R = -0.88, P < 0.0001), VO2max (R = -0.68, P < 0.0001), NYHA class (R = 0.66, P < 0.0001), LA stiffness (R = 0.58, P = 0.0002), and E/e' (R = 0.44, P = 0.005), while poorly correlated with E/A ratio (R = 0.23, P = 0.21). PALS had a good correlation with NYHA class (R = -0.64, P < 0.0001), PAoP (R = -0.61, P = 0.03) and VO2max (R = 0.57, P = 0.0001). Multivariate regression analysis identified PALS (beta = -0.91, P < 0.001) and LA Volume (beta = -0.19, P = 0.03) as predictors of LA Fibrosis, while E/e' was not a significant predictor (beta = 0.15, P = 0.08). CONCLUSION: Emerging as a possible index of myocardial fibrosis in patients with advanced HF, PALS could help to optimize the management and the selection of those patients with irreversible LA structural damage for advanced therapeutic strategies.

Physiologic determinants of left ventricular systolic torsion assessed by speckle tracking echocardiography in healthy subjects.

BACKGROUND: The associations of left ventricular (LV) systolic torsion with clinical and echocardiographic variables in physiological conditions have not been fully investigated. We explored the independent determinants of LV systolic torsion in a population of normal subjects. METHODS: In 119 healthy subjects, peak twist angle (LVtw) and torsion (LVtor) during ejection, and the QRS-LVtw interval (time-to-peak LVtw) were measured by speckle tracking. LV twisting rate and rotational deformation delay were also determined. RESULTS: Stepwise multiple regression showed that LVtw was independently associated with indexed end-systolic volume (ß=-0.200, P < 0.0001), peak early diastolic mitral annulus velocity (ß=-0.186, P = 0.0001), heart rate (ß= 0.178, P = 0.0003), and male gender (ß=-0.174, P = 0.0004). Similar results were found for LVtor. Age was the only parameter, which has demonstrated an independent correlation with time-to-peak LVtw (ß= 0.329, P < 0.0001). Despite significance of these associations, the proportions of variability explained by regression models were relatively low (range 11-26%), and no accurate predictive models were identifiable for LV twisting rate and rotational deformation delay. CONCLUSION: In normal individuals, indexed end-systolic LV volume, LV relaxation, heart rate, gender, and age correlate independently with LV torsion mechanics. However, conventional echocardiographic and clinical variables are not able to predict LV torsion mechanics.

Prognostic value of left atrial strain in patients with moderate asymptomatic mitral regurgitation.

For patients with asymptomatic mitral regurgitation (MR), the criteria identifying the groups at higher-risk and their clinical outcome are still uncertain. Therefore, in these patients, optimal time of surgery remains controversial. The purpose of this study was to compare left atrial (LA) strain to other echocardiographic left ventricular (LV) and LA parameters for the prediction of cardiovascular outcomes in patients with moderate asymptomatic MR. We enrolled 395 patients with primary degenerative moderate asymptomatic MR. Exclusion criteria were: history of atrial fibrillation, myocardial infarction, heart failure, cardiac surgery or heart transplantation, severe MR, mitral valve surgery during follow-up. Patients were prospectively followed for 3.5 ± 1.6 years for the development of cardiovascular events i.e. atrial fibrillation, stroke/transient ischaemic attack, acute heart failure, cardiovascular death. Of 276 patients (mean age 66 ± 8 years) who met eligibility criteria, 108 patients had 141 new events. Patients who developed cardiovascular events presented reduced global peak atrial longitudinal strain (PALS), reduced LA emptying fraction, larger LA volume indexed and lower LV strain at baseline (p < 0.0001). With receiving operating characteristics (ROC) curve analysis, global PALS < 35% showed the greatest predictive performance (AUC global PALS: 0.87). Bland-Altman analysis demonstrated good intra- and interobserver agreement with small bias and Kaplan-Meier analysis showed a graded association between PALS and event-free-survival rates. Speckle tracking imaging could provide a useful index, global PALS, to estimate LA function in asymptomatic moderate MR in order to optimize timing of surgery before the development of irreversible myocardial dysfunction.