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Background: Recurrent pericarditis (RP) is a complex condition associated with significant morbidity. Prior studies have evaluated which variables are associated with clinical remission. However, there is currently no established risk-stratification model for predicting outcomes in these patients., Objectives: We developed a risk stratification model that can predict long-term outcomes in patients with RP and enable identification of patients with characteristics that portend poor outcomes., Methods: We retrospectively studied a total of 365 consecutive patients with RP from 2012 to 2019. The primary outcome was clinical remission (CR), defined as cessation of all anti-inflammatory therapy with complete resolution of symptoms. Five machine learning survival models were used to calculate the likelihood of CR within 5 years and stratify patients into high-risk, intermediate-risk, and low-risk groups., Results: Among the cohort, the mean age was 46 ± 15 years, and 205 (56%) were women. CR was achieved in 118 (32%) patients. The final model included steroid dependency, total number of recurrences, pericardial late gadolinium enhancement, age, etiology, sex, ejection fraction, and heart rate as the most important parameters. The model predicted the outcome with a C-index of 0.800 on the test set and exhibited a significant ability in stratification of patients into low-risk, intermediate-risk, and high-risk groups (log-rank test; P < 0.0001)., Conclusions: We developed a novel risk-stratification model for predicting CR in RP. Our model can also aid in stratifying patients, with high discriminative ability. The use of an explainable machine learning model can aid physicians in making individualized treatment decision in RP patients., Competing Interests: Funding Support and Author Disclosures Dr Cremer has served on the scientific advisory board of Kiniksa Pharmaceuticals and Cardiol Therapeutics. Dr Klein has received a research grant from Kiniksa Pharmaceuticals, Ltd, and Cardiol Therapeutics; and has served on the scientific advisory board of Kiniksa Pharmaceuticals, Ltd, Pfizer, Inc, and Cardiol Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Remarkable advances have occurred in the understanding of the pathophysiology of pericardial diseases and the role of multimodality imaging in this field. Medical therapy and surgical options for pericardial diseases have also evolved substantially. Pericardiectomy is indicated for chronic or irreversible constrictive pericarditis, refractory recurrent pericarditis despite optimal medical therapy, or partial agenesis of the pericardium with a complication (eg, herniation). A multidisciplinary evaluation before pericardiectomy is essential for optimal patient outcomes. Overall, given the good outcomes reported, radical pericardiectomy on cardiopulmonary bypass, if feasible, is the preferred approach. Due to patient complexity, as well as the technical aspects of the surgery, pericardiectomy should be performed at high-volume centers that have the required expertise. The current review highlights the essential features of this multidisciplinary approach from diagnosis to recovery in patients undergoing pericardiectomy., Competing Interests: Funding Support and Author Disclosures Dr Al-Kazaz has received research grant and speaking honoraria from Kiniksa pharmaceuticals. Dr Klein has received research grant and scientific advisory board honoraria from Kiniksa pharmaceuticals and Cardiol Therapeutics. Dr Cremer has served on scientific advisory boards for Kiniksa pharmaceuticals and Cardiol Therapeutics. Dr Tong has received consulting and speaking honoraria from Abbott and Abiomed. Dr Johnston has received consulting honoraria from Edwards Lifesciences, Medtronic, Terumo Aortic, and Artivion. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Derangements in the innate and adaptive immune responses observed in systemic inflammatory syndromes contributes to unique elevated atherosclerotic risk and incident cardiovascular disease. Novel multimodality imaging techniques may improve diagnostic precision for the screening and monitoring of disease activity. The integrated application of these technologies lead to earlier diagnosis and noninvasive monitoring of cardiac involvement in systemic inflammatory diseases that will aid in preclinical studies, enhance patient selection, and provide surrogate endpoints in clinical trials, thereby improving clinical outcomes. We review the common cardiovascular manifestations of immune-mediated systemic inflammatory diseases and address the clinical and investigational role of advanced multimodality cardiac imaging., Competing Interests: Funding Support and Author Disclosures Dr Weber has received funding support from the National Institutes of Health National Heart, Lung, and Blood Institute K23HL159276-02 and American Heart Association 21CDA851511; and has served on the Scientific Advisory Board of Novo Nordisk, Horizon Therapeutics, and Kiniksa. Dr Paik has received funding support from the National Institutes of Health NIAMS K23AR073927-03. Dr Klein has received research grants from and served on the scientific advisory board of Kiniksa and Cardiology Therapeutics. Dr Yu has received funding support from the National Institutes of Health National Heart, Lung, and Blood Institute R01HL159443-02 and National Institutes of Health NIAMS R01AR057374-09. Dr Mukherjee has received funding support from the National Institutes of Health National Heart, Lung, and Blood Institute R01HL162851 and National Scleroderma Foundation; and has served on the Data Safety Monitoring Board of Advarra, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: There is a lack of knowledge in the current medical literature about native aortic valve thrombosis., Objectives: The aim of this systematic review was to summarize the characteristics, presentations, underlying etiologies, and outcomes of native aortic valve thrombosis and to present a meta-analysis of the best available data., Methods: The authors performed a literature search, identified published cases of patients with native aortic valve thrombosis, and pooled the data in this meta-analysis. The statistical analysis included calculations of the prevalence of the various presentations, underlying etiologies, aortic cusp involvement, as well as choices of diagnostic testing. They calculated the sensitivities of the various diagnostic testing as well as in-hospital mortality event rates and the univariate ORs of the risk factors for poor outcomes., Results: The search strategy and screening process yielded 74 cases of native aortic valve thrombosis, which are included in this meta-analysis. The data revealed that the most common presentation was myocardial infarction in 36%, and the most common underlying etiology was hypercoagulable state in 30%. In-hospital clinical deterioration after presentation including recurrent embolism occurred in ∼38%, and in-hospital mortality rate was ∼20%., Conclusions: Native aortic valve thrombosis is clinically relevant, especially in patients presenting with embolic events. Awareness about native aortic valve or root thrombosis as well as its underlying etiologies, diagnostic work-up, and management is essential, because this condition can be associated with poor outcomes., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The diagnosis of heart failure may be challenging because symptoms are rather nonspecific. Elevated left ventricular (LV) filling pressure may be used to confirm the diagnosis, but cardiac catheterization is often not practical. Echocardiographic indexes are therefore used as markers of filling pressure., Objectives: This study investigated the feasibility and accuracy of comprehensive echocardiography in identifying patients with elevated LV filling pressure., Methods: We conducted a multicenter study of 450 patients with a wide spectrum of cardiac diseases referred for cardiac catheterization. Left atrial volume index, in combination with flow velocities and tissue Doppler velocities, was used to estimate LV filling pressure. Invasively measured pressure was used as the gold standard., Results: Mean left ventricular ejection fraction (LVEF) was 47%, with 209 patients having an LVEF <50%. Invasive measurements showed elevated LV filling pressure in 58% of patients. Clinical assessment had an accuracy of 72% in identifying patients with elevated filling pressure, whereas echocardiography had an accuracy of 87% (p < 0.001 vs. clinical assessment). The combination of clinical and echocardiographic assessment was incremental, with a net reclassification improvement of 1.5 versus clinical assessment (p < 0.001)., Conclusions: Echocardiographic assessment of LV filling pressure is feasible and accurate. When combined with clinical data, it leads to a more accurate diagnosis, regardless of LVEF., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Most patients with acute pericarditis have a benign course and a good prognosis. However, a minority of patients develop complicated pericarditis, and the care of these patients is the focus of this review. Specifically, we address risk factors, multimodality imaging, pathophysiology, and novel treatments. The authors conclude that: 1) early high-dose corticosteroids, a lack of colchicine, and an elevated high-sensitivity C-reactive protein are associated with the development of complicated pericarditis; 2) in select cases, cardiovascular magnetic resonance imaging may aid in the assessment of pericardial inflammation and constriction; 3) given phenotypic similarities between recurrent idiopathic pericarditis and periodic fever syndromes, disorders of the inflammasome may contribute to relapsing attacks; and 4) therapies that target the inflammasome may lead to more durable remission and resolution. Finally, regarding future investigations, the authors discuss the potential of cardiovascular magnetic resonance to inform treatment duration and the need to compare steroid-sparing treatments to pericardiectomy., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to examine the ability of left ventricular (LV) global longitudinal strain (GLS) to assess disease severity in patients with chronic systolic heart failure (HF)., Background: Left ventricular GLS is a sensitive measure of LV mechanics. Its relationship with standard clinical markers and long-term adverse events in chronic systolic HF is not well established., Methods: In 194 chronic systolic HF patients, we performed comprehensive echocardiography with assessment of GLS by velocity vector imaging averaged from apical 4-chamber and 2-chamber views. Death, cardiac transplantation, and HF hospitalization were tracked for 5 years., Results: In our study cohort (age 57 ± 14 years, left ventricular ejection fraction [LVEF] 26 ± 6%, median N-terminal pro-B-type natriuretic peptide [NT-proBNP] 1,158 pg/ml), the mean GLS was -7.1 ± 3.3%. The GLS worsened with increasing New York Heart Association functional class (rank-sum p < 0.0001) and higher NT-proBNP (r = 0.42, p < 0.0001). The GLS correlated with LV cardiac structure (LV mass index: r = 0.35, p < 0.0001; LV end-diastolic volume index: r = 0.43, p < 0.0001) and LVEF (r = -0.66, p < 0.0001). A lower magnitude of GLS was associated with worsening LV diastolic function (E/e' septal: r = 0.33, p < 0.0001), right ventricular (RV) systolic function (RV s': r = -0.30, p < 0.0001), and RV diastolic function (RV e'/a': r = 0.16, p = 0.033). GLS predicted long-term adverse events (hazard ratio: 1.55, 95% confidence interval: 1.21 to 2.00; p < 0.001). Worsening strain (GLS ≥-6.95%) predicted adverse events after adjustment for age, sex, ischemic etiology, E/e' septal, and NT-proBNP (hazard ratio: 2.04, 95% confidence interval: 1.09 to 3.94; p = 0.025) and age, sex, ischemic etiology, and LVEF (hazard ratio: 2.15, 95% confidence interval: 1.19 to 4.02; p = 0.011)., Conclusions: In chronic systolic HF, worsening LV GLS is associated with more severe LV diastolic dysfunction and RV systolic and diastolic dysfunction, and provides incremental prognostic value to LVEF., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The goals of this study were to determine: 1) if low-risk patients assessed by a CHADS(2) score, a clinical scoring system quantifying a risk of stroke in patients with atrial fibrillation (AF), require a routine screening transesophageal echocardiogram (TEE) before pulmonary vein isolation (PVI); and 2) the relationship of a CHADS(2) score with left atrial (LA)/left atrial appendage (LAA) spontaneous echo contrast, sludge, and thrombus., Background: There is no clear consensus of whether a screening TEE before catheter ablation of AF should be performed in every patient., Methods: Initial TEEs for pre-PVI of 1,058 AF patients (age 57 +/- 11 years, 80% men) were reviewed and compared with a CHADS(2) score., Results: CHADS(2) scores of 0, 1, 2, 3, 4, 5, and 6 were present in 47%, 33%, 14%, 5%, 1%, 0.3%, and 0% of patients, respectively. The prevalence of LA/LAA thrombus, sludge, and spontaneous echo contrast were present in 0.6%, 1.5%, and 35%. The prevalence of LA/LAA thrombus/sludge increased with ascending CHADS(2) score (scores 0 [0%], 1 [2%], 2 [5%], 3 [9%], and 4 to 6 [11%], p < 0.01). No patient with a CHADS(2) score of 0 had LA/LAA sludge/thrombus. In a multivariate model, history of congestive heart failure and left ventricular ejection fraction <35% were significantly associated with sludge/thrombus., Conclusions: The prevalence of LA/LAA sludge/thrombus in patients with AF undergoing a pre-PVI screening TEE is very low (<2%) and increases significantly with higher CHADS(2) scores. This suggests that a screening TEE before PVI should be performed in patients with a CHADS(2) score of >or=1, and in patients with a CHADS(2) score of 0 when the AF is persistent and therapeutic anticoagulation has not been maintained for 4 weeks before the procedure.

Objectives: We sought to determine which surgical technique of left atrial appendage (LAA) closure is most successful by assessing them with transesophageal echocardiography (TEE)., Background: Atrial fibrillation is a risk factor for stroke, with 90% of clots occurring in the LAA. Several surgical techniques of LAA closure are used to theoretically reduce the stroke risk, with varying success rates., Methods: A total of 137 of 2,546 patients who underwent surgical LAA closure from 1993 to 2004 had a TEE after surgery. Techniques consisted of either excision or exclusion by sutures or stapling. The TEE measurements included color Doppler flow in the LAA and interrogation for thrombus. Patent LAA, remnant LAA (residual stump >1 cm), or excluded LAA with persistent flow into the LAA were identified as unsuccessful closure., Results: Of the 137 patients, 52 (38%) underwent excision and 85 (62%) underwent exclusion (73 suture and 12 stapler). Only 55 of 137 (40%) of closures were successful. Successful LAA closure occurred more often with excision (73%) than suture exclusion (23%) and stapler exclusion (0%) (p < 0.001). We found LAA thrombus to be present in 28 of 68 patients (41%) with unsuccessful LAA exclusion versus none with excision. At time of TEE, 6 patients with successful LAA closure (11%) and 12 with unsuccessful closure (15%) had evidence of stroke/transient ischemic attack (p = 0.61)., Conclusions: There is a high occurrence of unsuccessful surgical LAA closure. Of the various techniques, excision appears to be the most successful.

Objectives: The purpose of this study was to explore the relationship between myeloperoxidase (MPO) and cardiac structure, performance, and prognosis., Background: Myeloperoxidase is an inflammatory marker that is elevated in patients with heart failure (HF) and cardiac dysfunction, with mechanistic links to plaque vulnerability and left ventricular (LV) remodeling., Methods: We evaluated plasma MPO levels (CardioMPO, PrognostiX, Inc., Cleveland, Ohio) in 140 patients with chronic systolic HF (LV ejection fraction <35%) and examined the plasma MPO levels' relationships with echocardiographic indexes of systolic and diastolic performance, as well as long-term clinical outcomes (death, cardiac transplantation, or HF hospitalization)., Results: Within the overall cohort, increasing plasma MPO levels were associated with increasing likelihood of more advanced HF (restrictive diastolic stage, right ventricular systolic dysfunction > or =3+, and tricuspid regurgitation area > or =1.8 cm2). Plasma MPO levels were predictive of long-term clinical outcomes (risk ratio [95% confidence interval] = 3.35 [1.52 to 8.86]), even after adjustment for age, LV ejection fraction, plasma B-type natriuretic peptide (BNP), creatinine clearance, or diastolic stage. In receiver-operator characteristic curve analyses, addition of MPO to BNP testing augmented the predictive accuracy of future adverse clinical events (area under the curve 0.66 for BNP only [chi-square test = 12.9, p = 0.0003], and 0.70 for BNP plus MPO [chi-square test = 15.87, p = 0.0004])., Conclusions: In chronic systolic HF, elevated plasma MPO levels are associated with an increased likelihood of more advanced HF. Moreover, elevated plasma MPO levels within a HF subject seem to be predictive of increased adverse clinical outcomes.

Atrial fibrillation (AF) is he most commonly encountered arrhythmia in clinical practice, with an overall prevalence of 0.4% in the general population. Recent advances in technology and in the understanding of the pathophysiology of AF have led to more definitive and potentially curative therapeutic approaches. Echocardiography has a well-established role in the assessment of cardiac structure and function and risk stratification, and has become an essential part of the guidelines for management of AF. The development of intracardiac echocardiography has led to real-time guidance of percutaneous interventions, including radiofrequency ablation and left atrial appendage closure procedures for patients with AF. Other imaging modalities, including computed tomography and magnetic resonance angiography, have allowed for more accurate measurement and better understanding of the cardiac anatomy. We review the impact of various imaging modalities in the evaluation and management of AF.

Objectives: We sought to determine the association of etiology of constrictive pericarditis (CP), pericardial calcification (CA), and other clinical variables with long-term survival after pericardiectomy., Background: Constrictive pericarditis is the result of a spectrum of primary cardiac and noncardiac conditions. Few data exist on the cause-specific survival after pericardiectomy. The impact of CA on survival is unclear., Methods: A total of 163 patients who underwent pericardiectomy for CP over a 24-year period at a single surgical center were studied. Constrictive pericarditis was confirmed by the surgical report. Vital status was obtained from the Social Security Death Index., Results: Etiology of CP was idiopathic in 75 patients (46%), prior cardiac surgery in 60 patients (37%), radiation treatment in 15 patients (9%), and miscellaneous in 13 patients (8%). Median follow-up among survivors was 6.9 years (range 0.8 to 24.5 years), during which time there were 61 deaths. Perioperative mortality was 6%. Idiopathic CP had the best prognosis (7-year Kaplan-Meier survival: 88%, 95% confidence interval [CI] 76% to 94%) followed by postsurgical (66%, 95% CI 52% to 78%) and postradiation CP (27%, 95% CI 9% to 58%). In bootstrap-validated proportional hazards analyses, predictors of poor overall survival were prior radiation, worse renal function, higher pulmonary artery systolic pressure (PAP), abnormal left ventricular (LV) systolic function, lower serum sodium level, and older age. Pericardial calcification had no impact on survival., Conclusions: Long-term survival after pericardiectomy for CP is related to underlying etiology, LV systolic function, renal function, serum sodium, and PAP. The relatively good survival with idiopathic CP emphasizes the safety of pericardiectomy in this subgroup.

Objectives: The aim of this study was to compare the relative cost of a transesophageal echocardiography (TEE)-guided strategy versus conventional strategy for patients with atrial fibrillation (AF) >2 days duration undergoing electrical cardioversion over an eight-week period., Background: The Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) trial found no difference in embolic rates between the two approaches. However, the TEE-guided strategy had a shorter time to cardioversion and a lower rate of composite bleeding. While similar clinical efficacy was concluded, the relative cost of these two strategies has not been explored., Methods: Two economic approaches were employed in the ACUTE trial. The first approach was based on hospital charge data from complete hospital Universal Billing Code of 1992 forms, a detailed hospital charge questionnaire, or imputation. Regression analysis was used to investigate the added cost of adverse events. The second economic approach involved the development of an independent analytic model simulating treatment and actual ACUTE outcome costs as a validation of clinically derived data. Sensitivity analysis was performed on the analytic model to investigate the potential range in cost differences between the strategies., Results: A total of 833 of the 1,222 patients were enrolled from 53 U.S. sites; TEE-guided (n = 420) and conventional (n = 413). At eight-week follow-up, total mean costs did not significantly differ between the two groups, respectively (6,508 dollars vs. 6,239 dollars; difference of 269 dollars; p = 0.50). Cumulative costs were 24% higher in the conventional group, primarily due to increased incidence of bleeding and hospital costs associated with bleeding. A separate analytic model showed that treatment costs were higher for the TEE-guided strategy, but outcome costs were higher for the conventional strategy. Sensitivity analysis of the analytic model illustrated that varying the incidence and cost of major bleeding and the cost of TEE had the greatest impact on cost differences between the two groups., Conclusions: In patients with AF >2 days duration undergoing electrical cardioversion, the TEE-guided group showed little difference in patient costs compared with the conventional group. The TEE strategy had higher initial treatment costs but lower outcome-associated costs. Cumulative costs were 24% higher in the conventional group, primarily due to bleeding. The TEE-guided strategy is an economically feasible approach compared with the conventional strategy.

Objectives: This study was designed to characterize the importance of echocardiographic indexes, including newer indexes of diastolic function, as determinants of plasma B-type natriuretic peptide (BNP) levels in patients with systolic heart failure (SHF)., Background: Plasma BNP levels have utility for diagnosing and managing heart failure. However, there is significant heterogeneity in BNP levels that is not explained by left ventricular size and function alone., Methods: In 106 patients with symptomatic SHF (left ventricular ejection fraction [LVEF] <0.35), we measured plasma BNP levels and performed comprehensive echocardiography with assessment of left ventricular diastolic function, including color M-mode (CMM) and tissue Doppler imaging (TDI), and of right ventricular (RV) function., Results: Median plasma BNP levels were elevated and increased with greater severity of diastolic dysfunction. We found significant correlations (p < 0.001 for all) between BNP and indexes of myocardial relaxation (early diastolic velocity: r = -0.26), compliance (deceleration time: r = -0.55), and filling pressure (early transmitral to early annular diastolic velocity ratio: r = 0.51; early transmitral flow to the velocity of early left ventricular flow propagation ratio: r = 0.41). In multivariate analysis, overall diastolic stage, LVEF, RV systolic dysfunction, mitral regurgitation (MR) severity, age and creatinine clearance were independent predictors of BNP levels (model fit r = 0.8, p < 0.001)., Conclusions: Plasma BNP levels are significantly related to newer diastolic indexes measured from TDI and CMM in SHF. Heterogeneity of BNP levels in patients with SHF reflects the severity of diastolic abnormality, RV dysfunction, and MR in addition to LVEF, age, and renal function. These findings may explain the powerful relationship of BNP to symptoms and prognosis in SHF.

Objectives: This study was designed to determine the characteristics and outcomes of spontaneous conversion (SC) to sinus rhythm (SR) in patients with atrial fibrillation (AF) of more than two days., Background: The Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) multicenter study was a prospective trial in which transesophageal echocardiography (TEE)-guided treatment was compared with conventional anticoagulation treatment for the management of patients with AF >2 days undergoing direct current cardioversion (DCC). In an ancillary analysis, we evaluated the baseline and outcome data in patients who underwent SC to SR before scheduled DCC., Methods: We identified 1,041 patients for this analysis after excluding patients on pre-existing antiarrhythmic agents. Patients with SC in the TEE-guided and conventional groups were first compared then pooled and compared with non-spontaneous conversion (No-SC) patients., Results: Overall, 167 of 1,041 (16%) patients underwent SC, with twice as many in the conventional compared with the TEE-guided group (110/523 [21%] vs. 57/518 [11%]; p < 0.001). When compared with No-SC patients, a higher proportion of SC patients maintained SR at eight weeks (87.2% vs. 48.9%, p < 0.001), without statistically significant differences in bleeding, thromboembolism or mortality. Multivariate predictors of SC were shorter duration of AF, New York Heart Association (NYHA) functional class 1 or 2, smaller left atrial size, and absence of left atrial spontaneous echo contrast., Conclusions: Spontaneous conversion was associated with shorter duration of AF, lower NYHA class, smaller left atrial size, and absence of left atrial spontaneous echo contrast. There was a better SR outcome in the SR group, but no differences in the other clinical end points. The conventional treatment strategy allowed greater opportunity for SC. In the absence of favorable predictors of SC, the TEE-guided approach should be considered.

In 2003, pulmonary venous flow (PVF) evaluation by Doppler echocardiography is being used daily in clinical practice. Twelve years ago, we reviewed the potential uses of PVF in various conditions. Some of its important uses in cardiology have materialized, while others have not and have been supplanted by newer approaches. Current applications of measuring PVF have included: differentiating constrictive pericarditis from restriction, estimation of left ventricular (LV) filling pressures, evaluation of LV diastolic dysfunction and left atrial (LA) function, and grading the severity of mitral regurgitation (MR). However, there have been a number of controversies raised in the use of PVF profiles. Using transthoracic echocardiography, there may be technical issues in measuring the atrial reversal flow velocity. The use of PVF in the evaluation of the severity of MR is not always specific and can be affected by atrial fibrillation (AF) and elevated mean LA pressure. Mitral valvuloplasty and radiofrequency ablation for AF, which are the newer applications of PVF in monitoring invasive procedures, are mentioned. This article reviews the important clinical role of Doppler evaluation of PVF, discusses its limitations and pitfalls, and highlights its newer applications.