Biomechanical factors and atherosclerosis localization: insights and clinical applications.

Although the entire vascular bed is constantly exposed to the same risk factors, atherosclerosis manifests a distinct intra-individual pattern in localization and progression within the arterial vascular bed. Despite shared risk factors, the development of atherosclerotic plaques is influenced by physical principles, anatomic variations, metabolic functions, and genetic pathways. Biomechanical factors, particularly wall shear stress (WSS), play a crucial role in atherosclerosis and both low and high WSS are associated with plaque progression and heightened vulnerability. Low and oscillatory WSS contribute to plaque growth and arterial remodeling, while high WSS promotes vulnerable changes in obstructive coronary plaques. Axial plaque stress and plaque structural stress are proposed as biomechanical indicators of plaque vulnerability, representing hemodynamic stress on stenotic lesions and localized stress within growing plaques, respectively. Advancements in imaging and computational fluid dynamics techniques enable a comprehensive analysis of morphological and hemodynamic properties of atherosclerotic lesions and their role in plaque localization, evolution, and vulnerability. Understanding the impact of mechanical forces on blood vessels holds the potential for developing shear-regulated drugs, improving diagnostics, and informing clinical decision-making in coronary atherosclerosis management. Additionally, Computation Fluid Dynamic (CFD) finds clinical applications in comprehending stent-vessel dynamics, complexities of coronary bifurcations, and guiding assessments of coronary lesion severity. This review underscores the clinical significance of an integrated approach, concentrating on systemic, hemodynamic, and biomechanical factors in atherosclerosis and plaque vulnerability among patients with coronary artery disease.

Introducing a Novel Innovative Technique for the Recording and Interpretation of Dynamic Coronary Angiography.

In the study of coronary artery disease (CAD), the mechanism of plaque formation and development is still an important subject for investigation. A limitation of current coronary angiography (CAG) is that it can only show static images of the narrowing of arterial channels without identifying the mechanism of the disease or predicting its progression or regression. To address this limitation, the CAG technique has been modified. The new approach emphasizes identifying and analyzing blood flow patterns, employing methodologies akin to those used by hydraulic engineers for fluid or gas movement through domestic or industrial pipes and pumps. With the new technique, various flow patterns and arterial phenomena-such as laminar, turbulent, antegrade, retrograde, and recirculating flow and potentially water hammer shock and vortex formation-are identified, recorded, and classified. These phenomena are then correlated with the presence of lesions at different locations within the coronary vasculature. The formation and growth of these lesions are explained from the perspective of fluid mechanics. As the pathophysiology of CAD and other cardiovascular conditions becomes clearer, new medical, surgical, and interventional treatments could be developed to reverse abnormal coronary flow dynamics and restore laminar flow, leading to improved clinical outcomes.

Long-term impact of transcatheter closure interatrial shunts on disabling migraine.

BACKGROUNDS: Effectiveness of patent foramen ovale (PFO) closure on relief of migraine, is still unclear. We sought to analyse the long-term (>10 years) effects of interatrial septal shunt repair on disabling migraine performing a retrospective non-randomised study. METHODS: Clinical records of patients with disabling, medication-refractory migraine and PFO or significant ASD referred to our centre for closure from 2006 to 2018, were analysed. RESULTS: Forty -six patients (38 female, mean age 40.0 ± 3.7 years) with PFO and 32 patients with significant ASD (28 female, mean age 38.0 ± 4.1 years) submitted to transcatheter closure had a pre-existing disabling migraine with mean Migraine Disability Assessment Score (MIDAS) of 35.8 ± 4.7. After a mean follow-up of 118.2 ± 19.1 months (range 96 to 144), 72 out of 78 patients were still followed-up: in all subjects, aura was abolished, and migraine improved also in patients without aura. The mean MIDAS significantly decreased from baseline value (p < 0.01). Complete migraine resolution was associated in PFO patients with a shorter history of migraine, a more severe thrombophilic profile, a more severe Right-to-Left Shunt (RLS) and larger left atrial diameter and volume, and in ASD patients with bidirectional shunt. CONCLUSIONS: Device-based repair of PFO/ASD in patients with migraine was associated with abolition of aura and symptoms reduction in the long-term period.

Risk of early clinical deterioration and 30-day mortality in pulmonary embolism intermediate-high-risk patients with patent foramen ovale.

We assess the prognostic role of patent foramen ovale (PFO) for the estimation of 30-day mortality and risk of 48-h clinical deterioration since admission, in intermediate-high-risk pulmonary embolism (PE) patients. A post-hoc analysis of intermediate-high-risk PE patients enrolled in the Italian Pulmonary Embolism Registry (IPER) (Trial registry: ClinicalTrials.gov; No.: NCT01604538) was performed. The entire cohort was divided according to the presence or absence of PFO after transthoracic echocardiography (TTE) evaluation. Among 450 intermediate-high-risk PE patients (mean age 71.4 ± 13.8 years, 298 males), PFO was diagnosed in 68 (15.1%) cases. A higher mortality rate (29.4% vs. 3.1%, p < 0.001) as well as occurrence of clinical deterioration within 48 h from admission (38.2% vs. 3.6%, p < 0.001) were observed in intermediate-high-risk PE patients with PFO compared to those without multivariate Cox regression analysis showed that the presence of a PFO predicts 30-day mortality (HR: 3.21, 95% CI 3.16-3.27, p < 0.001) and was also associated with a significantly higher risk of 48-h clinical deterioration [HR: 2.24 (95% CI 2.20-2.29), p < 0.0001] in intermediate-high-risk PE patients. The presence of a PFO in intermediate-high-risk PE patients is associated with a higher risk of clinical deterioration within 48 h from admission and 30-day mortality.

Side branch predilatation during percutaneous coronary bifurcation intervention: Long-term mortality analysis.

BACKGROUND: Side branch predilatation (SBPD) during coronary bifurcation interventions is a technique that is not recommended by the latest guidelines. However, the data about the clinical outcomes after SBPD are surprisingly few. AIMS: The current study aimed to explore the association between SBPD and mortality in long-term follow-up. METHODS: All patients with coronary bifurcation stenoses revascularized with percutaneous coronary intervention were included in a prospective registry. Patients with stable angina and a bifurcation lesion with ≥50% diameter stenosis were included in the current analysis. Patients were assigned to two groups - those with SBPD(+) and those without SBPD(-). Propensity score matching was performed to equalize the risk factors and severity of coronary artery disease between the groups. A Kaplan-Meier analysis with a log-rank test for between-group differences was also performed. RESULTS: From January 2013 to June 2021, 813 patients were included in the final study population. The mean age was 67 (10) years. After propensity score matching, 648 patients remained for analysis - 324 in each group. At a median follow-up of 57 months patients in the SBPD(+) group had a higher all-cause mortality (n = 107 (33%) vs. n = 98 [30.2%]; P = 0.045) and cardiovascular mortality (n = 82 [25.3%] vs. n = 70 [21.6%]; P = 0.03) when compared with SBPD(-) patients. SBPD was independently associated with all-cause and cardiovascular mortality. CONCLUSION: SBPD treatment of coronary bifurcation stenoses is associated with worse patient survival in the follow-up of up to 8 years. SBPD treatment gives better angiographic results, but this did not translate into better clinical outcomes.

Trends in mortality related to venous thromboembolism in the European Union, 2012-2020.

We sought to assess the sex- and age-specific trends in venous thromboembolism (VTE) mortality in the 27 European Union Member States (EU-27) between years 2012 and 2020. Data on cause-specific deaths and population numbers by sex for each country of the EU-27 were retrieved through the publicly available European Statistical Office (EUROSTAT) dataset for the years 2012-2020. VTE-related deaths were ascertained when ICD-10 codes I26, I80, and I82.9 were listed as the primary cause of death in the medical death certificate. To calculate annual trends, we assessed the average annual percent change (AAPC) with relative 95% confidence intervals (CIs) using Joinpoint regression. During the study period, 96,037 (55,278 males and 40,759 females) died for VTE. The age-adjusted mortality rate (AAMR) linearly declined from 2.86 (95% CI 2.84-2.90) deaths per 100,000 individuals in 2012 to 2.53 (95% CI 2.50-2.56) deaths per 100,000 population in 2020 [AAPC: - 2.1% (95% CI - 3.6 to - 0.6), p = 0.001] without differences between sexes (p = 0.60). The higher AAMR was observed in some eastern European countries such as Bulgaria, Czech Republic, and Lithuania. On the contrary, the lower AAMR was mainly clustered in the Mediterranean area (Italy, Spain, and Cyprus). Over the last decade, the age-adjusted VTE-related mortality has been continuously declining in most of the in EU-27 Member States. However, some disparities still exist between western and eastern European countries.

Trends of hypertrophic cardiomyopathy-related mortality in United States young adults: a nationwide 20-year analysis.

AIMS: Data regarding hypertrophic cardiomyopathy (HCM)-related mortality in United States young adults, defined as those aged between 25 and 44 years, are lacking. We sought to assess the trends in HCM-related mortality among US young adults between 1999 and 2019 and determine differences by sex, race, ethnicity, urbanization and census region. METHODS: Mortality data were retrieved by the Centers for Disease Control and Prevention (CDC) Wide-Ranging Online Data for Epidemiologic Research (WONDER) dataset from January 1999 to December 2019. Age-adjusted mortality rates (AAMRs) were assessed using the Joinpoint regression modeling and expressed as estimated average annual percentage change (AAPC) with relative 95% confidence intervals (95% CIs). RESULTS: Over 20-year period, the AAMR from HCM in US young adults linearly decreased, with no differences between sexes [AAPC: -5.3% (95% CI -6.1 to -4.6), P  < 0.001]. The AAMR decrease was more pronounced in Black patients [AAPC: -6.4% (95% CI -7.6 to -5.1), P  < 0.001], Latinx/Hispanic patients [AAPC: -4.8% (95% CI -7.2 to -2.36), P  < 0.001] and residents of urban areas [AAPC: -5.4% (95% CI -6.2 to -4.6), P  < 0.001]. The higher percentages of HCM-related deaths occurred in the South of the country and at the patient's home. CONCLUSION: HCM-related mortality in US young adults has decreased over the last two decades in the United States. Subgroup analyses by race, ethnicity, urbanization and census region showed ethnoracial and regional disparities that will require further investigation.

Prognostic Role of Tricuspid Annular Plane Systolic Excursion to Systolic Pulmonary Artery Pressure Ratio for the Identification of Early Clinical Deterioration in Intermediate-High-Risk Pulmonary Embolism Patients.

The ratio of tricuspid annular plane systolic excursion (TAPSE) to echocardiographically measured systolic pulmonary artery pressure (PASP) has been proposed as a surrogate of RV-arterial coupling. In this analysis, we assess the prognostic role of TAPSE/PASP for early clinical deterioration and short-term mortality in an often clinically challenging population of intermediate-high-risk patients with pulmonary embolism (PE). A post hoc analysis of intermediate-high-risk patients with PE enrolled in the Italian Pulmonary Embolism Registry (ClinicalTrials.gov: NCT01604538) was performed. All patients underwent transthoracic echocardiography at admission. The primary and secondary outcomes were clinical deterioration within 48 hours from admission and 30-day all-cause mortality, respectively. In 422 intermediate-high-risk patients with PE (mean age 71.2 ± 5.3 years, 238 men), 37 (8.7%) experienced clinical deterioration within 48 hours of admission. The 30-day mortality rate was 6.6% (n = 28). The receiver operating characteristic analysis established 0.33 as the optimal cut-off value for the TAPSE/PASP in predicting 48-hour clinical deterioration (area under the curve 0.79 ± 0.1). The sensitivity, specificity, positive predictive value, and negative predictive value were 81%, 88.5%, 40.5%, and 97.9%, respectively. The multivariate Cox regression analysis showed that a TAPSE/PASP ≤0.33 was an independent predictor of 48-hour clinical deterioration (hazard ratio 2.06, 95% confidence interval 1.98 to 2.11, p <0.0001) and 30-day mortality (hazard ratio 2.28, 95% confidence interval 2.25 to 2.33, p <0.001). TAPSE/PASP shows promise as a noninvasive prognostic predictor to identify intermediate-high-risk patients with PE at a higher risk of early clinical deterioration and short-term mortality.

Residence time in complex left main bifurcation disease after stenting.

BACKGROUND: Data regarding the mean resident time (RT) after left main (LM) bifurcation stenting are scant. In the present study we performed a patient-specific computational fluid dynamic (CFD) analysis to investigate the different post-stenting mean RT values in LM patients treated with single-or double stenting techniques. METHODS: Patients were identified after reviewing the local Optical Coherence Tomography (OCT) scans database. Overall, 27 patients (mean age 65.5 ± 12.4, 21 males) [10 patients treated with provisional cross-over stenting, 7 with the double kissing crush (DK crush) and 10 with the nano-inverted T (NIT) technique, respectively] with isolated and significant LM bifurcation disease were analyzed. RESULTS: After LM bifurcation stenting, the NIT showed a higher averages WSS values at all bifurcation sites compared to DK crush and provisional cross-over stenting. Moreover, the mean RT resulted lower after NIT compared to provisional or DK crush. During the diastolic phase, the average RT of the entire LM bifurcation was 0.46 s, 0.38 s and 0.33 s after using the provisional stenting, DK crush and NIT, respectively. Moreover, the average RT in the LM bifurcation decreased by 17.1 % using the DK crush and by 28.2 % using the NIT compared to the Provisional. CONCLUSION: The present OCT-derived CFD analysis revealed that, in patients with complex bifurcation LM disease, the provisional approach resulted in lower WSS values, while double stenting techniques, especially the NIT technique, resulted in a marked reduction of average RT compared to the provisional approach. CONDENSED ABSTRACT: In the present study we performed a patient-specific Optical coherence tomography (OCT)-based computational fluid dynamic (CFD) analysis to investigate the different post-stenting mean RT values in 27 patients treated with provisional cross-over stenting, DK crush and Nano-inverted-T (NIT) stenting. The NIT showed a higher averages WSS values at all bifurcation sites compared to DK crush and Provisional. The mean RT resulted lower in NIT compared to Provisional or DK crush. During the entire diastolic phase, the average RT of the entire LM bifurcation was 0.46 s, 0.38 s and 0.33 s after using the provisional stenting, DK crush and NIT, respectively. Moreover, the average RT in the entire LM bifurcation decreased by 17.1 % using the DK crush and by 28.2 % using the NIT compared to the Provisional.

Differences and similarities in interatrial shunts management.

Atrial septal defects (ASD) and Patent foramen ovale (PFO) represent the most common congenital heart diseases (CHD) adulthood. These two clinical entities, having different embryological origin, as well as clinical manifestations, clinical course and treatment must be carefully distinguished. Right heart failure and pulmonary hypertension are considered the major determinants of morbidity and mortality in ASD. Conversely, new pathophysiology concepts have been raised in the management of PFO as left atrium cardiopathy. New diagnostic tools, including cardiac magnetic resonance and intracardiac echocardiography have joint transthoracic and transesophageal echocardiography in the diagnostic definition of both ASD and PFO as well as in guiding their percutaneous closure. Moreover, several innovations have been developed in the field of percutaneous ASD and PFO closure devices including new evidence supporting the safety and efficacy of device-based closure. Aim of the present review is to present review we provided and update overview on ASD and PFO, focusing on the novel concepts regarding their pathophysiological and therapeutic aspects.

Trends in sudden cardiac death mortality in Italy, 2013-2019.

We sought to analyse the incidence of sudden cardiac deaths (SCDs) amongst subjects aged less than 39 years in Italy and its time trend between 2013 and 2019. Data regarding cause-specific mortality and population size by sex in 5-year age groups were extracted from the World Health Organization (WHO) mortality database. Decedents reporting the codes I46.1, I45.6, I47.2, I41.9, R09.2 and R96.0 of the International Classification of Disease-10 (ICD-10) coding system, were extracted. The age-adjusted mortality rates (AAMRs), with relative 95% confidence intervals (CIs) stratified by sex, were determined using the direct method. Joinpoint regression analyses were used to identify periods with statistically distinct log linear trends in SCD-related death rates. To calculate nationwide annual trends in SCD-related mortality, we assessed the annual and average annual per cent change (AAPC) and relative 95% CIs. Over the study period, 314 deaths [220 males (70.0%) and 94 females] were due to SCD corresponding to a 0.06 per 100,000 per year (0.10 per 100,000 in males and 0.04 per 100,000 in females, respectively). Proportional mortality slightly increased, without reaching the statistical significance (p = 0.82) from 3.06 to 3.56 per 100 deaths, with a similar trend in both sexes. Joinpoint regression analysis revealed a plateau in age-standardised SCD-related mortality over the period [AAPC: -4.2 (95% CI: -24.0 to 20.8, p = 0.71], which was consistent between males and females. In Italy, SCD remains a public health issue of concern in the last decade after adjusting for age.