Lights and shadows on left atrial appendage occlusion: mind the gap in knowledge and think twice on long-term outcomes.

Ischemic stroke prevention represents a crucial concern in health systems, being associated with high morbidity and mortality. Atrial fibrillation is associated with 15-20% of ischemic strokes, in the presence of thrombus in the left atrial appendage in 90% of patients with nonvalvular atrial fibrillation. Oral anticoagulation represents the standard of care. However, left atrial appendage occlusions have been developed for selected patients with nonvalvular atrial fibrillation. With regard to the latter, particularly, some important concerns have been raised on the selection of patients potentially amenable to the procedure, seemingly emphasizing a gap in knowledge, real-life clinical practice, and current management guidelines. In light of the recent evidence regarding the current indications for management of left atrial appendage in presence of nonvalvular atrial fibrillation, the purpose of this critical review is to highlight the blind spots of left atrial appendage occlusion indications, taking into account the evidence-based mid- to long-term outcomes. Apparently, many unsolved concerns and problems are still present, mainly including mid- and long-term device-related potential complications, the possibility of concurrent sources of embolization, ethical and economic issues. Furthermore, larger, well designed, long-term, multicentric, and more inclusive studies, as well as shared/integrated registries are needed, aiming at comparing direct oral anticoagulation with left atrial appendage occlusion in the long run.

The relationship between mitral valve prolapse and thoracic skeletal abnormalities in clinical practice: a systematic review.

BACKGROUND: Literature data suggest high inter-study variability in mitral valve prolapse (MVP) prevalence among individuals with thoracic skeletal abnormalities (TSA). This systematic review aimed at estimating the overall prevalence of MVP in individuals with the most common TSA, including not only the oldest studies (before the year 2000) but also the most recent ones (after the year 2000). METHODS: PubMed and EMBASE databases were systematically reviewed in November 2023. Studies assessing the relationship between MVP and TSA and estimating the MVP prevalence in pectus excavatum (PE), pectus carinatum (PC), scoliosis, straight back syndrome (SBS) and Marfan syndrome (MS) were included. There was no limitation on time periods. RESULTS: Twenty-five studies with a total of 2800 patients (27.9 ±â€Š13.9 years, 48.2% females) were analyzed. The highest prevalence of MVP was observed among MS patients (47.3%), while the lowest was detected in PC individuals (23%). Prevalence of MVP was similar among PE (30.8%), scoliosis (26.3%) and SBS (25.5%) patients. When dividing the studies on the basis of temporal period, the average MVP prevalence was approximately two-fold higher in all studies conducted before the year 2000 in comparison with the most recent ones, regardless of TSA type. This discrepancy might be primarily ascribed to relevant differences in the echocardiographic criteria employed for MVP diagnosis before (less specific) and after (more specific) the year 2000, respectively. CONCLUSIONS: The estimated MVP prevalence in TSA individuals is significantly higher than that observed in the general population. Individuals with TSA should be screened for MVP presence on transthoracic echocardiography.

Is It Possible to Predict False-Positive Exercise Stress Echocardiography Results by Measuring the Left Atrial Antero-Posterior Diameter?

BACKGROUND: Left atrial (LA) size is a well-known prognostic determinant in the setting of coronary artery disease (CAD). No previous study has evaluated LA antero-posterior (A-P) diameter as a potential screening method for identifying individuals with a low probability of CAD. We aimed to assess the influence of LA A-P diameter adjusted for chest wall conformation (A-P thoracic diameter) on the occurrence of false-positive (FP) results on exercise stress echocardiography (ESE) in patients with suspected CAD. METHODS: All consecutive patients who had undergone coronary angiography at MultiMedica IRCCS (via San vittore 12, 20123, Milan, Italy) within two months from a positive ESE over a seven-year period were retrospectively analyzed. All patients underwent LA A-P diameter/A-P thoracic diameter ratio assessment, resting transthoracic echocardiography, and subsequent ESE. The primary endpoint was FP-ESE, defined as a positive ESE with no evidence of obstructive CAD (≥70% stenosis in any epicardial coronary artery) on subsequent coronary angiography. RESULTS: A total of 160 patients (64.4±13.0 years, 56.9% females) with a positive ESE were retrospectively analyzed. In light of coronary angiography results, 129 patients (80.6%) had an obstructive CAD, while 31 (19.4%) did not (FP). On the multivariate logistic regression analysis, the LA A-P diameter/A-P thoracic diameter ratio (odds ratio (OR) 0.42, 95% confidence interval (CI) 0.31-0.57) showed a strong inverse correlation with the primary endpoint. An LA A-P diameter/A-P thoracic diameter ratio ≤0.25 had 100% sensitivity and 85% specificity for predicting FP-ESE results (area under the curve (AUC) = 0.94). A strong linear correlation was demonstrated between the LA A-P diameter and A-P thoracic diameter (r = 0.85), whereas the correlation between the LA volume index and A-P thoracic diameter was moderate (r = 0.47). CONCLUSIONS: Echocardiographic assessment of the LA A-P diameter adjusted for the A-P thoracic diameter may allow clinicians to identify, among individuals with suspected CAD, those at lower risk of obstructive CAD.

From ejection fraction, to myocardial strain, and myocardial work in echocardiography: Clinical impact and controversies.

Enhancing an echocardiographic tool, aimed to detect even subtle left ventricular (LV) systolic function abnormalities, capable of obtaining both early diagnosis and risk prediction of heart disease, represents an ambitious, attractive, and arduous purpose in the modern era of cardiovascular imaging. Ideally, that tool should be simple, reliable, and reproducible, in order to be concretely applied in routine clinical practice. Importantly, that technique should be physiologically plausible and useful both at the population-level, as well as in the individual subject. For a long time, LV ejection fraction (EF) has been considered the first-line parameter for assessing LV global systolic function, strictly related to the prognosis, at least in some settings. However, LV EF limitations are well-known, even though frequently overemphasized, including its load-dependency. Therefore, myocardial strain techniques have been proposed, deemed able to disclose even subtle early LV function anomalies. Nevertheless, many disadvantages of myocardial strain have been reported as well. More recently, myocardial work (MW) analysis has been introduced as a new echocardiographic tool for the evaluation of LV global systolic function, attempting to overcome EF and strain disadvantages. However, MW has shown many limits as well. Notwithstanding, LV EF still remains a landmark functional classification marker for heart failure and cardiac oncology, allowing reliable fast reassessment of LV function changes during patient management, in order to guide treatment in individual cases as well. Notably, global longitudinal strain and MW parameters seem to show better meaningful results at the population-level, but controversial clinical impact, major limitations, wide cut-offs spread and overlap, when the single value needs to be applied to the single case. Taking into account the recent literature-based evidence, the scope of the present narrative critical review is trying to delineate the different types of information given by the described LV global systolic function parameters, both at the population-level and in the individual case, in order to trace a comparative analysis of advantages and limitations in clinical practice.

The Influence of Anthropometrics on Cardiac Mechanics in Healthy Women With Opposite Obesity Phenotypes (Android vs Gynoid).

BACKGROUND: The possible influence exerted by mechanical factors and/or compressive phenomena on myocardial strain parameters in healthy individuals with opposite obesity phenotypes (android vs gynoid) has never been previously investigated. Accordingly, we aimed at evaluating the relationship between anthropometrics, such as the waist-to-hip ratio (WHR), modified Haller index (MHI, the ratio of chest transverse diameter over the distance between sternum and spine), and epicardial adipose tissue (EAT), and left ventricular (LV)-global longitudinal strain (GLS), in healthy women with opposite obesity phenotypes (android vs gynoid). METHODS: Forty healthy women with obesity (body mass index (BMI) ≥30 Kg/m2) and WHR ≥0.85 ("android group") (52.5±13.2 yrs), 40 age- and BMI-matched healthy women with obesityand WHR <0.78 ("gynoid group") (49.8±13.4 yrs) and 40 age-matched healthy women without obesity (BMI <30 Kg/m2) (controls) (50.3±12.5 yrs) were retrospectively analyzed. All women underwent transthoracic echocardiography implemented with echocardiographic strain analysis of all cardiac chambers. Correlation between LV-GLS and anthropometrics (WHR, MHI, and EAT) was assessed in both groups of obese women. Age, WHR, homeostasis model assessment for insulin resistance (HOMA-IR), and left ventricular mass index (LVMi) were included in the logistic regression analysis performed for evaluating the independent predictors of reduced LV-GLS magnitude (less negative than -20%) in women with android obesity. RESULTS: Compared to the other groups of women, those with android obesity were found with significantly greater LVMi, higher LV filling pressures, and lower biventricular and biatrial deformation indices. A strong inverse correlation between LV-GLS and all anthropometrics (WHR, MHI, and EAT) was demonstrated in both groups of women with obesity. Univariate logistic regression analysis revealed that WHR (OR 1.58, 95%CI 1.22-2.03, p<0.001) and LVMi (OR 1.09, 95%CI 1.02-1.16, p=0.006) were independently correlated with LV-GLS impairment in women with android obesity. On multivariate logistic regression analysis, the WHR maintained a statistically significant association with the above-mentioned outcome (OR 1.68, 95%CI 1.14-2.48, p=0.009). Receiver operating characteristic (ROC) curve analysis showed that a WHR value ≥1.01 had 93% sensitivity and 100% specificity for detecting LV-GLS impairment in women with android obesity (AUC=0.98; 95%CI 0.96-1.00). CONCLUSIONS: Anthropometrics may strongly influence cardiac mechanics in healthy women with obesity. The WHR is associated with reduced LV-GLS magnitude in healthy women with android obesity, independent of age, glycometabolic status, and LV size.

The effect of gestational diabetes mellitus on carotid artery intima-media thickness in and after pregnancy: a systematic review and meta-analysis.

AIMS: The association between gestational diabetes mellitus (GDM) and common carotid artery (CCA) intima-media thickness (IMT) is still controversial. This systematic review and meta-analysis was performed to assess the correlation between GDM and CCA-IMT in and after pregnancy. METHODS: PubMed and EMBASE databases were systematically reviewed on April 2023. Studies measuring CCA-IMT in both pregnant women with GDM and women with previous history of GDM (pGDM) vs. healthy controls were included. The subtotal and overall standardized mean differences (SMDs) of CCA-IMT were calculated using the random-effect model. RESULTS: Nineteen studies with a total of 302 GDM and 861 pGDM women were analyzed. The average value of CCA-IMT measured in GDM/pGDM (0.59 ± 0.12 mm) was slightly increased in comparison to the accepted reference limits of IMT according to age classes. Substantial heterogeneity was detected for the studies involving both GDM and pGDM women, with an overall statistic I2 of 86.0% (p < 0.001). Large SMDs were obtained for the studies conducted on both GDM and pGDM women, with an overall SMD of 0.89 (95%CI 0.63-1.15, p < 0.001). Egger's test for a regression intercept gave a p-value of 0.37, indicating no publication bias. On meta-regression analysis, all potential confounders (number of patients, age at pregnancy, body mass index, measuring time, follow-up duration and GDM criteria) were not significantly associated with effect modification. CONCLUSIONS: GDM in and after pregnancy is independently associated with subclinical atherosclerosis. The association between GDM and carotid remodeling is potentially mediated by the longstanding underlying risk.

Influence of gestational diabetes mellitus on subclinical myocardial dysfunction during pregnancy: A systematic review and meta-analysis.

OBJECTIVE: The correlation between gestational diabetes mellitus (GDM) and subclinical myocardial dysfunction has been poorly investigated. Accordingly, we performed a meta-analysis to examine the influence of GDM on left ventricular (LV) global longitudinal strain (GLS), assessed by speckle tracking echocardiography (STE), during pregnancy. STUDY DESIGN: All echocardiographic studies assessing conventional echoDoppler parameters and LV-GLS in GDM women vs. healthy controls, selected from PubMed and EMBASE databases, were included. The risk of bias was assessed by using the National Institutes of Health (NIH) Quality Assessment of Case-Control Studies. The subtotal and overall standardized mean differences (SMDs) of LV-GLS were calculated using the random-effect model. RESULTS: The full-texts of 10 studies with 1147 women with GDM and 7706 pregnant women without diabetes were analyzed. GDM women enrolled in the included studies were diagnosed with a small reduction in LV-GLS in comparison to controls (average value -19.4 ± 2.5 vs -21.8 ± 2.5 %, P < 0.001) and to the accepted reference values (more negative than -20 %). Substantial heterogeneity was detected for the included studies, with an overall statistic value I2 of 94.4 % (P < 0.001). Large SMDs were obtained for the included studies, with an overall SMD of -0.97 (95 %CI -1.32, -0.63, P < 0.001). Egger's test for a regression intercept gave a P-value of 0.99, indicating no publication bias. On meta-regression analysis, all moderators and/or potential confounders (age at pregnancy, BMI, systolic blood pressure and ethnicity) were not significantly associated with effect modification (all P < 0.05). CONCLUSIONS: GDM is independently associated with subclinical myocardial dysfunction in pregnancy. STE analysis allows to identify, among GDM women, those who might benefit of targeted non-pharmacological and/or pharmacological interventions, aimed at reducing the risk of developing type 2 diabetes and cardiovascular complications later in life.

An Unusual Case of Ascending Aorta Dissection 4 Years after Perceval Sutureless Bioprosthesis Implantation: Easier Access to Diagnosis through the Right Parasternal Longitudinal Echocardiographic Window.

Sutureless bioprostheses are more frequently used for the surgical treatment of elderly patients with high burden of comorbidity, who are candidates to aortic valve replacement (AVR). Among the sutureless bioprostheses, the Perceval valve has shown a good midterm durability, with very few reports of valve deterioration and low risk of complications. Herein, we present an unusual case of ascending aorta dissection which occurred 4 years after AVR with a Perceval sutureless pericardial bioprosthesis, likely related to the peculiar prosthetic design. A high right parasternal longitudinal view of the aorta in the right lateral decubitus allowed to suspect the acute aortic syndrome, thus accelerating the subsequent diagnostic and therapeutic iter.

Presumed Takotsubo syndrome is associated with high in-hospital mortality in very elderly frail females: a case series.

Given the aging of general population, very elderly females with Takotsubo syndrome (TTS) are not rarely encountered in clinical practice. Although coronary angiography with left ventriculography is the gold standard diagnostic tool to exclude or confirm TTS, currently, this invasive procedure is less frequently performed in older patients with several comorbidities, such as renal failure, anemia, infections, neurological disorders, malignancy, and severe frailty. In these patients, a "presumed" TTS is diagnosed on the basis of clinical presentation, electrocardiogram, cardiac biomarkers, and echocardiographic findings without coronary angiography. While, in younger patients, TTS is generally a benign condition, in very elderly females, it is associated with higher in-hospital mortality and poor prognosis. Herein, we present four cases of ultra-octogenarian females diagnosed with "presumed TTS", who did not undergo coronary angiography due to severe frailty and multiple comorbidities and who exhibited poor outcome. This could arise the question if an early more aggressive approach could have changed final results. Probably, the solution could only be a personalized decision deriving from a profound and detailed discussion of each case through a multidisciplinary team approach.

Ejection fraction at hospital admission stratifies mortality risk in HFmrEF patients aged ≥ 70 years: a retrospective analysis from a tertiary university institution.

BACKGROUND: During the last few years, increasing focus has been placed on heart failure with mildly reduced ejection fraction (HFmrEF), an intermediate phenotype from preserved to reduced ejection fraction (EF). However, clinical features and outcome of HFmrEF in elderly patients aged ≥ 70 yrs have been poorly investigated. METHODS: The present study retrospectively included all consecutive patients aged ≥ 70 yrs discharged from our Institution with a first diagnosis of HFmrEF, between January 2020 and November 2020. All patients underwent transthoracic echocardiography. The primary outcome was all-cause mortality, while the secondary one was the composite of all-cause mortality + rehospitalization for all causes over a mid-term follow-up. RESULTS: The study included 107 HFmrEF patients (84.3 ± 7.4 yrs, 61.7% females). Patients were classified as "old" (70-84 yrs, n = 55) and "oldest-old" (≥ 85 yrs, n = 52) and separately analyzed. As compared to the "oldest-old" patients, the "old" ones were more commonly males (58.2% vs 17.3%, p < 0.001), with history of coronary artery disease (CAD) (54.5% vs 15.4%, p < 0.001) and significantly lower EF (43.5 ± 2.7% vs 47.3 ± 3.6%, p < 0.001) at hospital admission. Mean follow-up was 1.8 ± 1.1 yrs. During follow-up, 29 patients died and 45 were re-hospitalized. Male sex (HR 6.71, 95% CI 1.59-28.4), history of CAD (HR 5.37, 95% CI 2.04-14.1) and EF (HR 0.48, 95% CI 0.34-0.68) were independently associated with all-cause mortality in the whole study population. EF also predicted the composite of all-cause mortality + rehospitalization for all causes. EF < 45% was the best cut-off value to predict both outcomes. CONCLUSIONS: EF at hospital admission is independently associated with all-cause mortality and rehospitalization for all causes in elderly HFmrEF patients over a mid-term follow-up.

Patent foramen ovale closure after cryptogenic stroke: sometimes uncertain benefit maybe, or even potential harm in the long run?

The main published studies on patent foramen ovale (PFO) closure after cryptogenic stroke tend to consider it positively, in light of the reported both procedural risk profile and outcomes. On the other hand, many blind spots and controversial issues of the topic are still present, mainly including both early procedural complications, and mid- and long-term associated comorbidities as well. Oftentimes, several biases appear to be present, with the evident risk of modifying indications for both intervention, and decision-making process. Biases should be considered and discussed during the diagnostic approach as well, including the supposed evidence of correlation, or cause-effect relationship, between the clinical event and patent foramen ovale. Furthermore, such studies have mostly shown results based on short-term follow-up and very low event rates. Conversely, those patients will keep the device lifelong, generally with long life expectancy, and the increased possibility of recurrent stroke from any other cause over time, along with many potential device-related comorbidities (e.g. atrial fibrillation, nearby anatomical structures impairment, and thrombosis). Consequently, it is hard to demonstrate the mid-term and long-term device-related advantages, due to the possible higher incidence of stroke associated with iatrogenic or concurrent factors. Thus, larger, well designed, long-term, multicentric, and more inclusive studies are needed, aimed to demonstrate a net clinical benefit, ideally including a number-needed-to-treat calculation at short-term, mid-term, and long-term, as well as taking into account and comparing the long-term complications, related outcomes, and recurrent events in patients with and without devices.

Artificial Intelligence in Cardiology: Why So Many Great Promises and Expectations, but Still a Limited Clinical Impact?

Looking at the extremely large amount of literature, as summarized in two recent reviews on applications of Artificial Intelligence in Cardiology, both in the adult and pediatric age groups, published in the Journal of Clinical Medicine [...].

The influence of pectus excavatum on cardiac kinetics and function in otherwise healthy individuals: A systematic review.

BACKGROUND: A number of anterior chest wall deformities, most notably pectus excavatum (PE), may have a detrimental effect on cardiac motion and function. Interpretation of transthoracic echocardiography (TTE) and speckle-tracking echocardiography (STE) results may be hampered by the possible influence of PE on cardiac kinetics. METHODS: A comprehensive search of all articles assessing cardiac function in PE individuals was carried out. Inclusion criteria were: 1) individuals aged >10 years; 2) studies providing objective assessment of chest deformity (Haller index). Studies that measured myocardial strain parameters in PE patients were also included. RESULTS: The search (EMBASE and Medline) yielded a total of 392 studies, 36 (9.2%) of which removed as duplicates; a further 339 did not meet inclusion criteria. The full-texts of 17 studies were then analyzed. All studies concordantly reported impaired right ventricular volumes and function. With respect to left ventricle (LV), TTE studies uniformly demonstrated a significant impairment in conventional echoDoppler indices in PE individuals, whereas STE studies provided conflicting results. Importantly, LV functional alterations promptly reverted upon surgical correction of chest defect. In subjects with PE of mild-to-moderate severity, we observed that degree of anterior chest wall deformity, as noninvasively assessed by modified Haller index (MHI), was strongly associated with myocardial strain magnitude, in heterogenous cohorts of otherwise healthy PE individuals. CONCLUSIONS: Clinicians should be aware that in PE individuals, TTE and STE results may not always be indicative of intrinsic myocardial dysfunction, but may be, at least in part, influenced by artifactual and/or external chest shape determinants.

[Why artificial intelligence applied to the electrocardiogram is not yet clinical routine?] / Perché l'intelligenza artificiale applicata all'elettrocardiogramma non è ancora routine clinica?

Artificial intelligence opens up multiple application scenarios to the electrocardiogram (Ai-Ecg) in various clinical settings, with potentially extremely interesting expected results. However, the introduction of prediction models of clinical diagnosis, of the results of different therapies and of the different clinical risks based on artificial intelligence requires that the limits of this approach be adequately considered, limits ranging from conflicts of interest to the transparency of procedures, from product certification to cyber security, to the need for coordination between the most diverse professional figures involved. In order for the Ai-Ecg to become a routine clinical resource, it is necessary to institutionally invest in projects that have as their objectives an ever greater and more extensive attention to its developments and its applications in vast and heterogeneous extended clinical contexts.

The influence of chest wall conformation on myocardial strain parameters in a cohort of mitral valve prolapse patients with and without mitral annular disjunction.

PURPOSE: To evaluate the possible influence of chest wall conformation on myocardial strain parameters in a cohort of mitral valve prolapse (MVP) patients with and without mitral annular disjunction (MAD). METHODS: All consecutive middle-aged patients with MVP referred to our Outpatient Cardiology Clinic for performing two-dimensional (2D) transthoracic echocardiography (TTE) as part of work up for primary cardiovascular prevention between March 2018 and May 2022, were included into the study. All patients underwent clinic visit, physical examination, modified Haller index (MHI) assessment (the ratio of chest transverse diameter over the distance between sternum and spine) and conventional 2D-TTE implemented with speckle tracking analysis of left ventricular (LV) global longitudinal strain (GLS) and global circumferential strain (GCS). Independent predictors of MAD presence on 2D-TTE were assessed. RESULTS: A total of 93 MVP patients (54.2 ± 16.4 yrs, 50.5% females) were prospectively analyzed. On 2D-TTE, 34.4% of MVP patients had MAD (7.3 ± 2.0 mm), whereas 65.6% did not. Compared to patients without MAD, those with MAD had: 1) significantly shorter antero-posterior (A-P) thoracic diameter (13.5 ± 1.2 vs 14.8 ± 1.3 cm, p < 0.001); 2) significantly smaller cardiac chambers dimensions; 3) significantly increased prevalence of classic MVP (84.3 vs 44.3%, p < 0.001); 4) significantly impaired LV-GLS (-17.2 ± 1.4 vs -19.4 ± 3.0%, p < 0.001) and LV-GCS (-16.3 ± 4.1 vs -20.4 ± 4.9, p < 0.001), despite similar LV ejection fraction (63.7 ± 4.2 vs 63.0 ± 3.9%, p = 0.42). A-P thoracic diameter (OR 0.25, 95%CI 0.10-0.82), classic MVP (OR 3.90, 95%CI 1.32-11.5) and mitral annular end-systolic A-P diameter (OR 2.76, 95%CI 1.54-4.92) were the main independent predictors of MAD. An A-P thoracic diameter ≤ 13.5 cm had 59% sensitivity and 84% specificity for predicting MAD presence (AUC = 0.81). In addition, MAD distance was strongly influenced by A-P thoracic diameter (r = - 0.96) and MHI (r = 0.87), but not by L-L thoracic diameter (r = 0.23). Finally, a strong inverse correlation between MHI and both LV-GLS and LV-GCS was demonstrated in MAD patients (r = - 0.94 and - 0.92, respectively), but not in those without (r = - 0.51 and - 0.50, respectively). CONCLUSIONS: A narrow A-P thoracic diameter is strongly associated with MAD presence and is a major determinant of the impairment in myocardial strain parameters in MAD patients, in both longitudinal and circumferential directions.

Incidental Finding of Lipomatous Hypertrophy of the Right Atrial Free Wall in an Elderly Female With Severe Pulmonary Hypertension: Early Detection by Multimodality Imaging.

Lipomatous atrial hypertrophy (LAH) is a benign cardiac lesion characterized by fat accumulation in the interatrial septum that spares the fossa ovalis. It is associated with obesity and is more frequently observed in elderly and female patients. It is most often detected as an incidental finding on transthoracic echocardiography (TTE). The deposition of adipose tissue may rarely involve both the interatrial septum and the right atrial (RA) free wall. Herein, we describe an extremely rare case of LAH limited to a portion of the RA free wall only, mimicking a myxoma or a thrombotic formation. A multi-instrumental evaluation comprehensive of TTE implemented with pulsed-wave tissue Doppler imaging (PW-TDI), transesophageal echocardiography (TEE), and computed tomography (CT) angiography, performed during the patient's stay in the emergency department, allowed to quickly diagnose the benign RA pseudomass.