Prior Carpal Tunnel Syndrome and Early Concomitant Echocardiographic Findings Among Patients With Cardiac Amyloidosis.

BACKGROUND: We aimed to characterize patients with systemic amyloidosis stratified by a prior diagnosis of carpal tunnel syndrome (CTS) and to describe early echocardiographic parameters concomitant with CTS. METHODS AND RESULTS: Patients with suspected amyloidosis during CTS diagnosis were excluded. Our cohort included 108 patients with systemic amyloidosis of which 36% had a prior CTS at a median of 4 years (interquartile range [IQR] 2.8-6.7 years) before disease diagnosis. Patients with prior CTS were more likely to present subsequently with cardiac amyloidosis (78% vs 53%, P = .013), yet overall survival was comparable between groups (53% vs 61%, P = .825). Prior CTS was more commonly diagnosed in subsequent patients with transthyretin (62%) than in patients with immunoglobulin light chain (24%, P < .001). Furthermore, in a subanalysis of patients subsequently diagnosed with cardiac amyloidosis, findings at CTS diagnosis (n = 17) demonstrated a mild increase in septal thickness 1.3 cm (IQR 1.2-1.5 cm), increased relative wall thickness 0.46 cm (IQR 0.45-0.58 cm), and increased left ventricular mass index 155 g/m2(IQR 92-177 g/m2) compared with age-adjusted normal range echocardiographic values. Doppler mitral flow data was supportive of left ventricular diastolic dysfunction. CONCLUSIONS: Early echocardiographic findings at CTS diagnosis, preceding the diagnosis of cardiac amyloidosis by several years, are suggestive of increased wall thickness and diastolic dysfunction.

Standards on Digital Echocardiography: An Israel Heart Society Position Paper Presented by the Israel Working Group on Echocardiography.

BACKGROUND: The output settings of echocardiographic systems should be set to the full (original) frame rate and lossless compression (e.g., run-length encoding) in order to transmit echocardiographic videos so that they retain their original quality. In addition, monitors and display cards of echocardiography systems and workstations should be able to support an adaptive refresh rate for displaying video at an arbitrary frame rate, including a high frame rate (90+ fps) without dropping frames and preserving the original frame duration. Currently, the only available option for echocardiography monitors is 144-165 Hz (or higher) based on adaptive frame rate G-Sync or FreeSync technology monitors. These monitors should be accompanied by compatible display cards. Echocardiography systems and workstation video playback software should support G-Sync or FreeSync adaptive frame rate technology to display echocardiography videos at their original frame rates without the effects of jitter and frame drops. Echocardiography systems should support an online display of the videos on the workstations during acquisition with the original quality. The requirements for web-based workstations are the same as for desktops workstations. Hospital digital networks should provide transmission and long-term archiving of the echocardiographic videos in their original acquisition quality.

Preliminary experience using the transcatheter mitral valve leaflet repair procedure.

BACKGROUND: Mitral regurgitation (MR) causes increased morbidity and mortality in heart failure patients and is often associated with augmented surgical risk. OBJECTIVES: To assess the preliminary results oftranscatheter mitral valve leaflet repair (TMLR) in a single academic center. METHODS: Data were collected prospectively in the cardiology department of Rabin Medical Center in 2012. Ten consecutive patients (age 69.3 +/- 15.9 years, ejection fraction 36.5 +/- 9.4) who were poor surgical candidates with severe functional MR underwent general anesthesia, followed by trans-septal puncture and a TMLR procedure using the MitraClip device. RESULTS: All 10 patients were considered to have severe functional MR prior to TMLR treatment and were all symptomatic; the mean New York Heart Association (NYHA) class was 3.4 +/- 0.5. The MR severity was 4 +/- 0. There were no immediate complications or failures of the procedure. One patient died on day 5 due to massive gastrointestinal bleeding. Immediately following TMLR all 10 patients showed a profound MR reduction to a mean severity grade of 1.6 +/- 0.6. At one month after the procedure, NYHA had decreased to an average of 1.7 +/- 1.0 and was at least grade 2 in all but one patient. After 6 months the MR remained < or = 2 in six of eight patients, with a NYHA average of 1.4 +/- 0.5. CONCLUSIONS: The MitraClip procedure was shown to be relatively safe, providing significant clinical benefit to a relatively sick population with severe MR. It is therefore an important alternative to surgery in these high risk patients.

Impact of Short-Acting Disopyramide on Left Ventricular Mechanics Evaluated by Strain Analysis in Patients with Hypertrophic Obstructive Cardiomyopathy.

Background: Disopyramide is a class Ia antiarrhythmic drug that has been used for the second-line treatment of symptomatic hypertrophic obstructive cardiomyopathy (HOCM). The aim of the study was to assess the impact of short-acting disopyramide in patients with hypertrophic obstructive cardiomyopathy (HOCM) using two-dimensional speckle-tracking echocardiography. Methods: This prospective study included patients with HOCM on chronic treatment with short-acting disopyramide. Two sequential comprehensive echocardiographic examinations were performed: after temporary disopyramide suspension and 2.5 h after disopyramide intake. Results: 19 patients were included in the study. The effect of disopyramide on the left ventricle was not uniform. After the intake of disopyramide, the mean global strain peak was −17 ± 2% before disopyramide intake and −14 ± 2% after (p < 0.0001). There was a significant reduction in strain in the basal septal (p = 0.015), basal inferior (p = 0.019), basal posterior (p = 0.05), apical anterior (p = 0.0001), and apical lateral segments (p = 0.021). In all other segments, there was no significant change. Disopyramide also caused a significant accentuation of the base-apex strain gradients (p = 0.036). No change was noted in circumferential and left atrial strain. While the left ventricular ejection fraction and outflow gradients did not change, the significant reduction in global and segmental longitudinal strain demonstrated the acute negative inotropic effect of disopyramide on the myocardium in patients with HOCM. Conclusion: A strain analysis may be a useful tool to assess the negative inotropic effect of cardiovascular medication on the left ventricle in patients with HOCM.

The value of intraoperative transesophageal echocardiography in patients undergoing aortic valve replacement.

BACKGROUND AND AIM OF THE STUDY: While the role of intraoperative transesophageal echocardiography (IOTEE) in valve repair surgery is well documented, its value in patients undergoing valve replacement is debatable. The study aim was to assess the impact of IOTEE on the management of a large cohort of patients referred for aortic valve replacement (AVR). METHODS: The departmental echocardiography database for patients undergoing AVR with IOTEE between April 1999 and September 2006 at the authors' institution was reviewed. Patients with a diagnosis of infective endocarditis, aortic dissection, or those in whom a composite graft was implanted, were excluded from the study. RESULTS: The study group included 604 patients (319 males, 285 females; mean age 70 +/- 11 years) who underwent AVR for either predominant aortic stenosis (n = 520; 86.1%) or aortic regurgitation (n = 84; 13.9%). Pre-pump IOTEE was performed in 440 patients (72.8%), and post-pump IOTEE in 586 (97.0%). Overall major preoperative findings influencing the operative plan were found in 106 of the 440 patients (24.1%); decisions regarding the mitral valve were the most frequent. The post-pump study revealed unexpected findings requiring a second pump run in 20 patients (3.4%), of whom nine cases (1.5%) applied to the replaced aortic prostheses (paravalvular leak in five patients, coronary obstruction by an aortic bioprosthesis in two, and detection and closure of a pseudoaneurysm in the mitral-aortic fibrosa and incompetent bioprosthesis in one patient each). Eleven patients (1.8%) required a second pump run because of failed mitral/tricuspid repair or hemodynamic compromise. CONCLUSION: The main use of a routine application of IOTEE among patients undergoing AVR was to detect additional lesions preoperatively, and technical failures postoperatively.

Long Term Outcomes of Patients Treated With Transcatheter Aortic Valve Implantation.

Transcatheter aortic-valve implantation (TAVI) is an established treatment option in patients with severe symptomatic aortic stenosis. Intermediate and long-term follow up data of these patients is limited. Data was taken from a large all-comer single center prospective registry (2008 to 2019). The primary end point was all-cause mortality. The secondary endpoints were long-term valve hemodynamic performance; paravalvular leak (PVL) at 5-year follow-up. We also report on temporal trends in this cohort. Our cohort included 998 patients with a mean age of 82.3 ± 7.2 years and 52.2% females. TAVI was performed via the transfemoral, trans-apical, subclavian and other access routes in 93.9%, 3.6%, 2.5%, and 0.6% of patients, respectively. A self-expandable device was used in 69.4% of cases, balloon expandable device in 28.1% and in 2.5% other devices. The cumulative risk for all-cause mortality at 5 years was 43.4% (95% CI 39.1 to 47.7). The immediate and long-term valve gradients were low and maintained. On durability analysis at 5 years, severe structural valve deterioration was present in 1.6% of cases. At 5-year follow-up, PVL was moderate in 3.3% and no patients has severe PVL. On temporal trends analysis, we found that the procedural aspects of TAVI improved over time with lower rates of significant PVL and significantly lower procedural mortality. In conclusion, TAVI patients have a favorable long-term outcome, with excellent valve hemodynamic parameters and good clinical outcomes. Over time and with increasing experience, procedural and patient outcomes have improved.

Natural History and Disease Progression of Early Cardiac Amyloidosis Evaluated by Echocardiography.

Since the diagnosis of cardiac amyloidosis (CA) is often delayed, echocardiographic findings are frequently indicative of advanced cardiomyopathy. We aimed to describe early echocardiographic features in patients subsequently diagnosed with CA. Preamyloid diagnosis echocardiographic studies were screened for structural and functional parameters and stratified according to the pathogenetic subtype (immunoglobulin light-chain [AL] or amyloid transthyretin [ATTR]). Abnormalities were defined based on published guidelines. Our cohort included 75 CA patients of whom 42 (56%) were diagnosed with AL and 33 (44%) with ATTR. Forty-two patients had an earlier echocardiography exam available for review. Patients presented with increased wall thickness (1.3 [interquartile range {IQR} 1.0, 1.5] cm) ≥3 years before the diagnosis of CA and relative wall thickness was increased (0.47 [IQR 0.41, 0.50]) ≥7 years prediagnosis. One to 3 years before CA diagnosis restrictive left ventricular (LV) filling pattern was present in 19% of patients and LV ejection fraction ≤50% was present in 21% of patients. Right ventricular dysfunction was detected concomitantly with disease diagnosis. The echocardiographic phenotype of ATTR versus AL-CA showed increased relative wall thickness (0.74 [IQR 0.62, 0.92] versus 0.62 [IQR 0.54, 0.76], p = 0.004) and LV mass index (144 [IQR 129, 191] versus 115 [IQR 105, 146] g/m2, p = 0.020) and reduced LV ejection fraction (50 [IQR 44, 58] versus (60 [IQR 53, 60]%, p = 0.009) throughout the time course of CA progression, albeit survival time was similar. In conclusion, increased wall thickness and diastolic dysfunction in CA develop over a time course of several years and can be diagnosed in their earlier stages by standard echocardiography.

Percutaneous aortic valve implantation: early clinical experience and future perspectives.

The incidence of aortic valve stenosis is growing rapidly in the elderly. Nonetheless, many symptomatic patients are not referred for surgery usually because of high surgical risk. Unfortunately, percutaneous balloon valvuloplasty is unsatisfactory due to high recurrence rates. In 2002, Cribier and colleagues were the first to describe percutaneous aortic valve implantation in a patient, opening a new era of aortic stenosis management. In the present review we report a patient treated by this novel method, discuss and assess how it is implanated, report the findings of studies conducted to date, and suggest future directions for percutaneous treatment of aortic valve disease.

Long-Term Outcomes After Mitral Valve Replacement and Tricuspid Annuloplasty in Rheumatic Patients.

BACKGROUND: Late tricuspid regurgitation is a common finding in patients with rheumatic valvular disease after mitral valve replacement surgery. However, the long-term benefit of concomitant tricuspid valve annuloplasty has not been established in this population. METHODS: This was a single-center retrospective study in a tertiary hospital. The final cohort included 285 rheumatic patients who underwent either isolated mitral valve replacement (147 patients) or mitral valve replacement with concomitant tricuspid valve annuloplasty (138 patients). Tricuspid regurgitation severity grade was assessed according to current echocardiography guidelines and graded using a 0 to 3 scale (none or trivial, mild, moderate, severe). RESULTS: Patients were followed for a total median duration of 10.8 (interquartile range, 6.8 to 14.5) years. The majority of patients undergoing mitral valve replacement were women, with a median age at operation of 59 (interquartile range, 48 to 68) years. Patients undergoing concomitant tricuspid valve annuloplasty had a 3.4-fold odds of improving their tricuspid regurgitation grade at long-term follow-up by multivariate logistic regression. Furthermore, concomitant tricuspid valve annuloplasty was independently associated with a long-term survival benefit in patients with preoperative moderate or severe tricuspid regurgitation (hazard ratio, 0.44; 95% confidence interval, 0.23 to 0.87; p = 0.018). CONCLUSIONS: This study demonstrates good long-term results in patients with rheumatic heart disease undergoing mitral valve replacement with concomitant tricuspid valve annuloplasty.

[Update in aortic valve diseases].

Aortic valve disease is currently the commonest valve disease. The prevalence of aortic stenosis reaches 2% to 5% of very elderly patients. It is the second commonest indication for cardiac surgery, and the commonest indication for valve surgery today. In the European survey, aortic valve disease constituted 60% of all valve diseases. There are two important reasons for this finding; 1) 1-2% of the population is born with bicuspid aortic valve; 2) the ageing population is growing to the stage where significant degenerative aortic valve disease is developing. Although the disease is associated with substantial clinical consequences, there is currently no effective therapy for the disease other than surgical aortic valve replacement. This review focuses on innovations in the pathophysiology, diagnosis and treatment of aortic valve diseases (stenosis and regurgitation) with special emphasis on the new ACC/AHA 2006 guidelines for the management of patients with valvular heart disease. A comparison with the older ACC/AHA guidelines and the European guidelines is also presented.

Pregnancy outcome in patients with pulmonary arterial hypertension receiving prostacyclin therapy.

BACKGROUND: Pregnancy is contraindicated in cases of pulmonary hypertension, a highly morbid disease affecting young women of childbearing age. CASES: We describe the pregnancies of 3 patients with pulmonary arterial hypertension (idiopathic, Eisenmenger syndrome, and related to systemic lupus erythematosus). They received epoprostenol and low-molecular-weight heparin throughout pregnancy. The patient with Eisenmenger syndrome started epoprostenol in gestational week 16. Cesarean delivery under general anesthesia was performed at 28-33 weeks of gestation; early delivery was necessary in the patient with Eisenmenger syndrome because of fetal growth restriction. All deliveries were uneventful, and birth weights were 1,700, 1,500, and 795 g. There were no postpartum complications. CONCLUSION: Pregnancy in women with pulmonary hypertension should still be considered high risk for both mother and child, but stable patients on epoprostenol may successfully complete pregnancy.

Association Between Mitral Annular Calcium and Flail Mitral Leaflet in Degenerative Mitral Valve Disease.

The aim of this study was to assess the association between mitral annular calcium (MAC) and flail mitral leaflets in a cohort of patients with degenerative mitral valve disease. A retrospective study was conducted of consecutive patients with degenerative mitral valve disease who underwent echocardiography at Rabin Medical Center from 2003 to 2012. Special focus was attended to the presence and grade of MAC and characterization of valve pathology (myxomatous vs nonmyxomatous, prolapse vs flail). Patients were excluded if they had undergone previous mitral valve surgery and/or had infective endocarditis. Multivariate logistic regressions were used to control for confounders. The study included 1,912 patients (60.8% men, mean age 63.8 ± 17.4 years) divided into 3 groups: 1,627 (86%) without MAC, 183 (10%) with either mild or moderate MAC, and 94 (5%) with severe MAC. The presence of flail leaflet was 27%, 30%, and 46% in these groups, respectively (p <0.001). After adjustment for age, gender, and co-morbidities, the odd ratio for flail mitral leaflet with severe MAC versus no MAC was 1.76 (95% confidence interval 1.10 to 2.83, p = 0.019). In conclusion, this study demonstrates that degenerative mitral valve disease with severe MAC is significantly associated with flail mitral leaflet.

Clinical and Echocardiographic Features of Mitral Annular Calcium in Patients Aged ≤50 Years.

Data regarding characteristics of young patients with mitral annular calcification (MAC) and its associations with other cardiovascular risk factors are scarce. Hence, we sought to characterize patients aged <50 years with MAC and to examine whether in these patients, MAC is also associated with cardiovascular risk factors. Consecutive patients who underwent an echocardiographic study were prospectively entered into a database. The database included clinical, laboratory, and echocardiographic parameters. The present study included 56 patients aged <50 years with a diagnosis of MAC. The mean age was 44.2 ± 6.9 years with a male-to-female ratio of 2.5:1. The prevalence of cardiovascular risk factors (30 patients [53%] hypertension, 17 patients [30%] diabetes mellitus, 24 patients [43%] dyslipidemia, 22 patients [39%] smoking) and established cardiovascular disease (22 patients [39%] coronary artery disease, 11 patients [19%] previous stroke) was substantially higher than expected for this age group. Twenty-nine patients (52%) had chronic kidney disease. Of these, 18 patients (62%) had end-stage kidney disease and 7 patients (24%) underwent renal transplantation. Fourteen patients (25%) and 3 patients (5%) had moderate or severe mitral regurgitation and mitral stenosis, respectively. Aortic valve disease was present in 37 patients (66%). Moderate or severe left ventricular dysfunction and left ventricular hypertrophy were identified in 9 patients (16%) and 31 patients (56%), respectively. In conclusion, the detection of MAC in a young patient should be regarded as a marker of atherosclerotic disease, chronic kidney disease, and aortic valve disease.

Prognostic value of global myocardial performance indices in acute myocardial infarction: comparison to measures of systolic and diastolic left ventricular function.

STUDY OBJECTIVES: Assessment of global myocardial performance by a single index (ie, the myocardial performance index [MPI]) has been suggested as an appealing alternative to the individual assessment of systolic and diastolic left ventricular (LV) function We sought to test the prognostic value of MPI in comparison to clinical characteristics and echocardiographic parameters of LV filling and ejection in acute myocardial infarction (AMI). PATIENTS: Four hundred seventeen consecutive patients with AMI were examined within 24 h of hospital admission. INTERVENTIONS: Doppler echocardiographic measures of systolic, diastolic, and global myocardial performance were assessed within 24 h of hospital admission. In addition to MPI (ie, the sum of the isovolumic time intervals divided by ejection time), we determined the isovolumic/heterovolumic time ratio, which expresses the time "wasted" by the myocardium to generate and decrease LV pressure without moving blood. RESULTS: The end points of the study at 30 days were death (4.7%), congestive heart failure (23%), and recurrent infarction (4.8%), and occurred in 109 patients, who were compared as group B to 314 patients without an event (group A). Multivariate analysis identified only age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.07), LV ejection fraction (LVEF) < or = 40% (OR, 3.82; 95% CI, 2.15 to 6.87), and E-wave deceleration time (EDT) of < or = 130 ms (OR, 2.29; 95% CI, 1.0 to 5.21) as independent predictors of adverse events. CONCLUSION: LVEF and EDT are powerful and independent echocardiographic predictors of poor outcome following AMI, and are superior to indexes of global LV performance. Both parameters should be taken into consideration when deciding about the management of these patients.

Percutaneous coronary intervention of the left main artery before MitraClip implantation.

Functional mitral regurgitation (MR) is common in patients with ischemic cardiomyopathy. We present a case of an 83-year-old patient with ischemic heart disease and ischemic cardiomyopathy, who was repeatedly admitted for pulmonary edema and underwent a percutaneous trans-septal MitraClip procedure. During coronary angiography, a severe left main stenosis was demonstrated. Treatment included both percutaneous coronary intervention and the implantation of two MitraClip devices, with very good results. We believe that this case illustrates the need for comprehensive assessment of ischemia in patients with functional MR.

Use of an automatic application for wall motion classification based on longitudinal strain: is it affected by operator expertise in echocardiography? A multicentre study by the Israeli Echocardiography Research Group.

AIMS: Assessing the quality of wall motion (WM) on echocardiograms remains a challenge. Previously, we validated an automated application used by experienced echocardiographers for WM classification based on longitudinal two-dimensional (2D) strain. The aim of this study was to show that the use of this automatic application was independent of the user's experience. METHODS AND RESULTS: We compared the WM classifications obtained by the application when used by 12 highly experienced readers (Exp-R) vs. 11 inexperienced readers (InExp-R). Both classifications were compared with expert consensus classifications using the standard visual method. Digitized clips of cardiac cycles from three apical views in 105 patients were used for these analyses. Reproducibility of both groups was high (overall intra-class correlation coefficient: InExp-R = 0.89, Exp-R = 0.83); the lowest was noted for hypokinetic segments (InExp-R = 0.79, Exp-R = 0.72). InExp-R scores were concordant with Exp-R mode scores in 88.8% of segments; they were overestimated in 5.8% and underestimated in 3.2%. The sensitivity, specificity, and accuracy of InExp-R vs. Exp-R for classifying segments as normal/abnormal were identical (87, 85, and 86%, respectively). CONCLUSION: Classification of WM from apical views with an automatic application based on longitudinal 2D strain by InExp-R vs. Exp-R was similar to visual classification by Exp-R. This application may be useful for inexperienced echocardiographers/technicians and may serve as an automated 'second opinion' for experienced echocardiographers.

A new tool for automatic assessment of segmental wall motion based on longitudinal 2D strain: a multicenter study by the Israeli Echocardiography Research Group.

BACKGROUND: Identification and quantification of segmental left ventricular wall motion abnormalities on echocardiograms is of paramount clinical importance but is still performed by a subjective visual method. We constructed an automatic tool for assessment of wall motion based on longitudinal strain. METHODS AND RESULTS: Echocardiograms of 105 patients (3 apical views) were blindly analyzed by 12 experienced readers. Visual segmental scores (VSS) and peak systolic longitudinal strain were assigned to each of 18 segments per patient. Ranges of peak systolic longitudinal strain that best fit VSS (by receiver operating characteristic analysis) were used to generate automatic segmental scores (ASS). Comparisons of ASS and VSS were performed on 1952 analyzable segments. There was agreement of wall motion scores between both methods in 89.6% of normal, 39.5% of hypokinetic, and 69.4% of akinetic segments. Correlation between methods was r=0.63 (P<0.0001). Interobserver and intraobserver reliability using interclass correlation for scoring segmental wall motion into 3 scores by ASS was 0.82 and 0.83 and by VSS 0.70 and 0.69, respectively. Compared with VSS (majority rule), ASS had a sensitivity, specificity, and accuracy of 87%, 85%, and 86%, respectively. ASS and VSS had similar success rates for correct identification of wall motion abnormalities in territories supplied by culprit arteries. VSS had greater specificity and positive predictive values, whereas ASS had higher sensitivity and negative predictive values for identifying the culprit artery. CONCLUSIONS: Automatic quantification of wall motion on echocardiograms by this tool performs as well as visual analysis by experienced echocardiographers, with a greater reliability and similar agreement to angiographic findings.

Reliability of visual assessment of global and segmental left ventricular function: a multicenter study by the Israeli Echocardiography Research Group.

BACKGROUND: The purpose of this multicenter study was to determine the reliability of visual assessments of segmental wall motion (WM) abnormalities and global left ventricular function among highly experienced echocardiographers using contemporary echocardiographic technology in patients with a variety of cardiac conditions. METHODS: The reliability of visual determinations of left ventricular WM and global function was calculated from assessments made by 12 experienced echocardiographers on 105 echocardiograms recorded using contemporary echocardiographic equipment. Ten studies were reread independently to determine intraobserver reliability. RESULTS: Interobserver reliability for visual differentiation between normal, hypokinetic, and akinetic segments had an intraclass correlation coefficient of 0.70. The intraclass correlation coefficient for dichotomizing segments into normal versus other abnormal was 0.63, for hypokinetic versus other scores was 0.26, and for akinetic versus other scores was 0.58. Similar results were found for intraobserver reliability. Interobserver reliability for WM score index was 0.84 and for left ventricular ejection fraction was 0.78. Similar values were obtained for the intraobserver reliability of WM score index and ejection fraction. Compared to angiographic data, the accuracy of segmental WM assessments was 85%, and correct determination of the culprit artery was achieved in 59% of patients with myocardial infarctions. CONCLUSION: Among experienced readers using contemporary echocardiographic equipment, interobserver and intraobserver reliability was reasonable for the visual quantification of normal and akinetic segments but poor for hypokinetic segments. Reliability was good for the visual assessment of global left ventricular function by WM score index and ejection fraction.

Recent advances in medical treatment and percutaneous, transapical and surgical interventions in aortic-valve stenosis.

This review focuses on recent advances in the treatment of aortic-valve stenosis with special emphasis on medical treatment for preventing disease progression, and on novel surgical and percutaneous approaches.