Left Atrium: A New Prognostic Marker and Therapeutic Target in Secondary Mitral Regurgitation?

Mitral regurgitation (MR) is one of the most common valvular abnormalities worldwide and can be subdivided into primary and secondary causes. Atrial MR consists of a novel type of secondary MR (SMR), most often observed in patients with AF and heart failure with preserved ejection fraction. The main pathophysiological mechanism of atrial MR is mitral valve annular dilatation. Recently published studies have highlighted the clinical significance of left atrium (LA) evaluation in the early diagnosis and prognosis of patients with primary MR. However, there are little data regarding the role of the LA in SMR. The present literature review aims to elucidate the use of the echocardiographic parameters regarding LA evaluation in the prognosis prediction and therapeutic strategy of patients with SMR.

Multimodality Imaging in a Patient With Double Aortic Arch Undergoing Transcatheter Aortic Valve Implantation: J Am Coll Cardiol Case Rep 2024;29:102224.

[This retracts the article DOI: 10.1016/j.jaccas.2024.102224.].

Atrial Fibrillation After Patent Foramen Ovale Closure: Incidence, Pathophysiology, and Management.

This comprehensive review explores the incidence, pathophysiology, and management of atrial fibrillation (AF) following percutaneous closure of patent foramen ovale (PFO). Although AF is considered a common adverse event post PFO closure, its incidence, estimated at <5%, varies based on monitoring methods. The review delves into the challenging task of precisely estimating AF incidence, given subclinical AF and diverse diagnostic approaches. Notably, a temporal pattern emerges, with peak incidence around the 14th day after closure and a subsequent decline after the 45th day, mimicking general population AF trends. The pathophysiological mechanisms behind post PFO closure AF remain elusive, with proposed factors including local irritation, device-related interference, tissue stretch, and nickel hypersensitivity. Management considerations encompass rhythm control, with flecainide showing promise, and anticoagulation tailored to individual risk profiles. The authors advocate for a personalized approach, weighing factors like age, comorbidities, and device characteristics. Notably, postclosure AF is generally considered benign, often resolving spontaneously within 45 days, minimizing thromboembolic risks. Further studies are required to refine understanding and provide evidence-based guidelines.

Mortality Rates in Patients Undergoing Urgent Versus Elective Transcatheter Aortic Valve Replacement: A Meta-analysis.

Patients with severe aortic stenosis (AoS) often present with acute heart failure and compensation, frequently leading to cardiogenic shock. Transcatheter Aortic Valve Replacement (TAVR) has been recently performed as a bailout treatment in such patients. The aim of our meta-analysis is to compare urgent TAVR with elective procedures. We systematically screened three databases searching for studies comparing urgent vs elective TAVR. Primary endpoint is the 30-days mortality. Secondary endpoints included in-hospital mortality, device success, periprocedural vascular complications, 30-days stroke, 30-days acute kidney injury (AKI), permanent pacemaker implantation (PPM), moderate or severe paravalvular leakage, and 30-days bleeding. Seventeen studies were included, with a total of 84,495 patients. Urgent TAVR was associated with an increased risk for 30-days mortality [Risk Ratio (RR): 2.53, 95% Confidence Intervals (CI): 1.81-3.54)], in-hospital mortality (RR: 2.67, 95% CI: 1.94-3.68), periprocedural vascular complications (RR: 1.91, 95% CI: 1.28-2.85) and AKI (RR: 2.83, 95% CI: 1.93-4.14), compared with elective procedure. No differences were observed in the other secondary endpoints. Urgent TAVR was associated with higher in-hospital and 30-days mortality, possibly driven by the increased incidence of AKI and vascular complications in urgent TAVR. The results highlight the importance of early TAVR in stable AoS patients.

Multimodality Imaging in a Patient With Double Aortic Arch Undergoing Transcatheter Aortic Valve Implantation.

Double aortic arch is a rare congenital malformation often identified as an incidental finding during routine imaging. In our case, we describe aortic hemodynamics of double aortic arch in a patient with severe aortic stenosis and the procedural process of transcatheter aortic valve implantation.

The Contemporary Role of Speckle Tracking Echocardiography in Cirrhotic Cardiomyopathy.

Cirrhotic cardiomyopathy (CCM) is characterized by elevated cardiac output at rest, an inability to further increase contractility under stress, and diastolic dysfunction. The diagnosis of CCM is crucial as it can lead to complications during liver transplantation. However, its recognition poses challenges with conventional echocardiography techniques. Speckle tracking echocardiography (STE), particularly global longitudinal strain (GLS), is a novel index that enhances the diagnostic efficacy of echocardiography for both ischemic and non-ischemic cardiomyopathies. GLS proves more sensitive in identifying early systolic dysfunction and is also influenced by advanced diastolic dysfunction. Consequently, there is an expanding scope for GLS utilization in cirrhotic cases, with newly updated diagnostic criteria for CCM incorporating GLS. Specifically, systolic dysfunction is now defined as either a left ventricular ejection fraction below 50% or an absolute GLS below 18%. However, conflicting data on GLS alterations in liver cirrhosis patients persist, as many individuals with advanced disease and a poor prognosis exhibit a hyperdynamic state with preserved or increased GLS. Consequently, the presence of CCM, according to the updated criteria, does not exhibit a significant association-in the majority of studies-with the severity of liver disease and prognosis. Furthermore, information on other indices measured with STE, such as left atrial and right ventricular strain, is promising but currently limited. This review aims to offer a critical assessment of the existing evidence concerning the application of STE in patients with liver cirrhosis.

Multimodality imaging for the global evaluation of aortic stenosis: The valve, the ventricle, the afterload.

Aortic stenosis (AS) is the most common valvular heart disease growing in parallel to the increment of life expectancy. Besides the valve, the degenerative process affects the aorta, impairing its elastic properties and leading to increased systemic resistance. The composite of valvular and systemic afterload mediates ventricular damage. The first step of a thorough evaluation of AS should include a detailed assessment of valvular anatomy and hemodynamics. Subsequently, the ventricle, and the global afterload should be assessed to define disease stage and prognosis. Multimodality imaging is of paramount importance for the comprehensive evaluation of these three elements. Echocardiography is the cornerstone modality whereas Multi-Detector Computed Tomography and Cardiac Magnetic Resonance provide useful complementary information. This review comprehensively examines the merits of these imaging modalities in AS for the evaluation of the valve, the ventricle, and the afterload and ultimately endeavors to integrate them in a holistic assessment of AS.

A "Snake-Like" Vessel in the Thorax.

We report a congenital extracardiac arteriovenous fistula revealed incidentally in a patient undergoing computed tomographic coronary angiography for angina. This clinical vignette panel describes the origin and the trajectory of this rare vascular lesion.

Resting strain analysis to identify myocardial ischemia in patients with advanced chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is associated with higher incidence of cardiovascular death. Screening for coronary artery disease in asymptomatic or mildly symptomatic patients is challenging. OBJECTIVE: The aim of this study was to investigate the incremental value of resting deformation analysis in predicting positive results for myocardial ischemia during stress transthoracic echocardiography in patients with end-stage CKD. METHODS: Sixty-one patients (mean age: 62.3 ± 11.8, 65.7% men) with end-stage CKD were included in the study. Patients underwent a resting transthoracic echocardiogram and a dobutamine stress contrast echo (DSE) protocol. Positive results of DSE were defined as stress-induced left ventricular (LV) wall motion abnormalities. RESULTS: The study cohort had normal or mildly impaired systolic function: mean LV ejection fraction (EF) was 49.2% (±10.4) and mean LV global longitudinal strain (GLS) was 14.4% (±4.5). Half of our population had impaired left atrial (LA) strain: mean LA reservoir, conduit, and contractile reserve were 24.1% (±12.6), 10.6% (±5.9), and 13.6% (±9.2), respectively. DSE was positive for ischemia in 55.7%. A significant negative association with DSE results was found for LV EF, LV GLS and the conduit phase of LA strain. Both LV and LA dimensions showed positive correlation with presence of ischemia in DSE. Multivariate logistic regression analysis showed that LV GLS was independently associated with DSE (p = 0.007), after controlling for covariates, with high diagnostic accuracy. CONCLUSION: Resting LV deformation could predict positive results during DSE, thus may be useful to better identify renal patients who might benefit from coronary artery screening.

Management of patent foramen ovale; findings from a nationwide survey.

OBJECTIVES: Several clinical trials have provided evidence supporting the transcatheter closure of patent foramen ovale (PFO) in selected patients following a cryptogenic stroke. However, it remains unknown to what extent these guidelines have been implemented in everyday clinical practice and the familiarity of physicians from different specialties with PFO closure. The aim of our nationwide survey is to explore the implementation of transcatheter PFO occlusion in Greek clinical practice. MATERIALS AND METHODS: Attending level cardiologists, internal medicine physicians and neurologists involved in the management of PFO-related strokes working in Greece were invited to complete an online questionnaire. The questionnaire consisted of 19 questions and was designed to obtain comprehensive data on provider demographics, PFO characteristics, and specific clinical scenarios. RESULTS: A total of 51 physicians (56.9 % cardiologists, 25.5 % neurologists and 17.6 % internal medicine physicians) completed the survey, resulting in a response rate of 53 %. Cardiologists, internal medicine physicians and neurologists agree on several issues regarding PFO closure, such as PFO closure as first line treatment, management of patients with DVT or prior decompression sickness, and post-closure antithrombotic treatment, but different approaches were reported regarding closure in patients with thrombophilia treated with oral anticoagulation (p=0.012) and implantable loop recorder placement for atrial fibrillation exclusion (p=0.029 and p=0.020). CONCLUSIONS: Our findings show that cardiologists, internal medicine physicians and neurologists agree in numerous issues, but share different views in the management of patients with thrombophilia and rhythm monitoring duration. These results highlight the significance of collaboration among physicians from different medical specialties for achieving optimal results.

Speckle tracking echocardiography and ß-thalassemia major. A systematic review.

Heart disease is among the primary causes of morbidity and mortality in ß-thalassemia major (ß-TM). Conventional echocardiography has failed to identify myocardial dysfunction at an early stage among these patients, thus speckle tracking echocardiography (STE) has been lately used. The objectives of this review were to 1) identify all published studies having evaluated myocardial strain among ß-TM patients, 2) gather their results, 3) compare their findings and 4) propose recommendations based on these data. Literature search was conducted in PubMed, SCOPUS and Cohrane Library. Data regarding left ventricular global longitudinal (LV-GLS), circumferential (LV-GCS) and radial strain (LV-GRS), right ventricular longitudinal strain (RV-GLS), left and right atrial strain were extracted. Thirty-five studies (34 original articles and 1 meta-analysis) have met the inclusion criteria. LV-GLS has been reported being worse in patients compared to controls in 13 of 21 studies, LV-GCS in 7 of 11 studies, LV-GRS in 6 of 7 studies, RV-GLS in 2 of 3 studies and left atrial strain in all case-control studies. Myocardial iron overload (MIO) patient subgroups had worse LV-GLS in 6 of 15 studies, LV-GCS in 2 of 7 studies and LV-GRS in none of 7 studies. A small number of studies suggest left atrial strain correlation with electrical atrial ectopy and atrial fibrillation. It is suggested that STE should be applied supplementary to conventional echocardiography for early identification of myocardial dysfunction among ß-TM patients. Potential myocardial strain utilities could be screening for myocardial iron overload, left ventricular diastolic dysfunction and atrial fibrillation.

Left atrial strain and ventricular global longitudinal strain in cirrhotic patients using the new criteria of Cirrhotic Cardiomyopathy Consortium.

BACKGROUND: The new criteria of Cirrhotic Cardiomyopathy Consortium (CCC) propose the use of left ventricular global longitudinal strain (LV-GLS) for evaluation of systolic function in patients with cirrhosis. The aim of this study was to evaluate LV-GLS and left atrial (LA) strain in association with the severity of liver disease and to assess the characteristics of cirrhotic cardiomyopathy (CCM). METHODS: One hundred and thirty-five cirrhotic patients were included. Standard echocardiography and speckle tracking echocardiography (2D-STE) were performed, and dual X-ray absorptiometry was used to quantify the total and regional fat mass. CCM was defined, based on the criteria of CCC, as having advanced diastolic dysfunction, left ventricular ejection fraction ≤50% and/or a GLS <18%. RESULTS: LV-GLS lower or higher than the absolute mean value (22.7%) was not associated with mortality (logrank, p = 0.96). LV-GLS was higher in patients with Model for end stage liver disease (MELD) score ≥15 compared to MELD score <15 (p = 0.004). MELD score was the only factor independently associated with systolic function (LV-GLS <22.7% vs. ≥22.7%) (Odds Ratio:1.141, p = 0.032). Patients with CCM (n = 11) had higher values of estimated volume of visceral adipose tissue compared with patients without CCM (median: 735 vs. 641 cm3 , p = 0.039). On multivariable Cox regression analysis, MELD score [Hazard Ratio (HR):1.26, p < 0.001] and LA reservoir strain (HR:0.96, p = 0.017) were the only factors independently associated with the outcome. CONCLUSION: In our study, absolute LV-GLS was higher in more severe liver disease, and LA reservoir strain was significantly associated with the outcome in patients with end-stage liver disease.

Novel Anti-Inflammatory Therapies in Coronary Artery Disease and Acute Coronary Syndromes.

Evidence suggests that inflammation plays an important role in atherosclerosis and the consequent clinical presentation, including stable coronary artery disease (CAD) and acute coronary syndromes (ACS). The most essential elements are cytokines, proteins with hormone-like properties that are produced by the immune cells, endothelial cells, platelets, fibroblasts, and some stromal cells. Interleukins (IL-1ß and IL-6), chemokines, interferon-γ (IFN-γ), and tumor necrosis factor-alpha (TNF-α) are the cytokines commonly associated with endothelial dysfunction, vascular inflammation, and atherosclerosis. These molecules can be targeted by commonly used therapeutic substances or selective molecules that exert targeted anti-inflammatory actions. The most significant anti-inflammatory therapies are aspirin, statins, colchicine, IL-1ß inhibitors, and IL-6 inhibitors, along with novel therapies such as TNF-α inhibitors and IL-1 receptor antagonists. Aspirin and statins are well-established therapies for atherosclerosis and CAD and their pleiotropic and anti-inflammatory actions contribute to their efficacy and favorable profile. Colchicine may also be considered in high-risk patients if recurrent ACS episodes occur when on optimal medical therapy according to the most recent guidelines. Recent randomized studies have also shown that therapies specifically targeting inflammatory interleukins and inflammation can reduce the risk for cardiovascular events, but these therapies are yet to be fully implemented in clinical practice. Preclinical research is also intense, targeting various inflammatory mediators that are believed to be implicated in CAD, namely repeated transfers of the soluble mutant of IFN-γ receptors, NLRP3 inflammasome inhibitors, IL-10 delivery by nanocarriers, chemokine modulatory treatments, and reacting oxygen species (ROS) targeting nanoparticles. Such approaches, although intriguing and promising, ought to be tested in clinical settings before safe conclusions can be drawn. Although the link between inflammation and atherosclerosis is significant, further studies are needed in order to elucidate this association and improve outcomes in patients with CAD.

Lipoprotein(a) as a Predictive Biomarker and Therapeutic Target for Acute Coronary Syndromes.

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in Western societies, despite the significant advances that have improved primary and secondary prevention. Hence, several novel biomarkers have been identified as potential diagnostic and therapeutic targets which could improve outcomes even when traditional risk factors are well-controlled. Lipoprotein (a) [Lp(a)] has pro-atherogenic, pro-thrombotic, and pro-inflammatory properties, and its levels are relatively constant and genetically predetermined. Several epidemiological studies have associated high Lp(a) with increased risk for acute coronary syndromes (ACS) even when other CAD risk factors are included in the multivariate analysis. However, until recently, specific therapeutic options targeting Lp(a) were not associated, and thus, Lp(a) is currently used as a risk and treatment modifying biomarker with guidelines suggesting the intensified treatment of low-density lipoprotein in intermediate- to-high-risk patients with increased Lp(a) levels. Lately, specific treatment options targeting Lp(a) have become available and include antisense oligonucleotides and small-interfering RNA, which induce a robust reduction of Lp(a). Results of ongoing phase-3 trials will answer whether Lp(a) will become a biomarker specifically treated to reduce the burden of cardiovascular mortality. The scope of this review article is to present the current evidence regarding the use of Lp(a) as a biomarker, predictive of increased CAD risk, and to discuss the future perspectives on pharmaceutical reduction of Lp(a) as a therapeutic target in high-risk patients.

HFA-PEFF score as an independent predictor of 2-year mortality in liver cirrhosis patients.

BACKGROUND AND AIMS: Cardiovascular complications of liver cirrhosis include high cardiac output heart failure with reduced afterload and diastolic dysfunction. Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide, Functional testing, Final etiology (HFA-PEFF) (values 0-6) is a diagnostic tool for heart failure. It is a cluster of echocardiographic and biochemical parameters. The purpose of this prospective study was to assess if HFA-PEFF score is associated with the severity of liver disease and to determine its prognostic significance in patients with cirrhosis. METHODS: Patients with cirrhosis without an acute event were enrolled. A comprehensive echocardiography study was conducted, brain natriuretic peptide and N-terminal-pro-B-type Natriuretic Peptide levels were measured and HFA-PEFF score was calculated. All patients were prospectively followed up after enrollment. The study end-point was defined as the composite of all-cause death. RESULTS: Seventy-two consecutive patients [median age 59 years (inter-quartile range: 52-65), 72.2% males, Model for End-stage Liver Disease (MELD) 12.9 (8.5-16.3)] were included. The 52.8% had a high HFA-PEFF score (5 or 6) and the 47.2% intermediate/low score (0-4). HFA-PEFF score was correlated with MELD score (rho = 0.566, P < 0.001), but not with age, SBP and heart rate. The median follow-up was 24.2 (9.5-38.8) months. The 1- and 2-year cumulative mortality was higher in patients with high HFA-PEFF compared to those with intermediate/low (log-rank P < 0.001 for both). The predicted 2-year probability of survival in high vs intermediate/low HFA-PEFF was found to be a prognostic factor of death even when adjusted for age, gender and MELD score [hazard ratio = 3.539 (1.134-11.046), P = 0.029]. CONCLUSION: HFA-PEFF score is high among patients with liver cirrhosis, especially those with advanced liver disease. HFA-PEFF score is associated with survival even when adjusting for cirrhosis severity.