Virtual Hemodynamic Assessment of Coronary Lesions: The Advent of Functional Angiography and Coronary Imaging.

The fractional flow reserve (FFR) is well recognized as a gold standard measure for the estimation of functional coronary stenosis. Technological progressions in image processing have empowered the reconstruction of three-dimensional models of the coronary arteries via both non-invasive and invasive imaging modalities. The application of computational fluid dynamics (CFD) techniques to coronary 3D anatomical models allows the virtual evaluation of the hemodynamic significance of a coronary lesion with high diagnostic accuracy. METHODS: Search of the bibliographic database for articles published from 2011 to 2023 using the following search terms: invasive FFR and non-invasive FFR. Pooled analysis of the sensitivity and specificity, with the corresponding confidence intervals from 32% to 94%. In addition, the summary processing times were determined. RESULTS: In total, 24 studies published between 2011 and 2023 were included, with a total of 13,591 patients and 3345 vessels. The diagnostic accuracy of the invasive and non-invasive techniques at the per-patient level was 89% (95% CI, 85-92%) and 76% (95% CI, 61-80%), respectively, while on the per-vessel basis, it was 92% (95% CI, 82-88%) and 81% (95% CI, 75-87%), respectively. CONCLUSION: These opportunities providing hemodynamic information based on anatomy have given rise to a new era of functional angiography and coronary imaging. However, further validations are needed to overcome several scientific and computational challenges before these methods are applied in everyday clinical practice.

In-Hospital versus Out-of-Hospital Pulmonary Embolism: Clinical Characteristics, Biochemical Markers and Echocardiographic Indices.

BACKGROUND: A significant proportion of pulmonary embolisms (PEs) occurs in patients during hospitalisation for another reason. However, limited data regarding differences between out-of-hospital PE (OHPE) and in-hospital PE (IHPE) is available. We aimed to compare these groups regarding their clinical characteristics, biochemical markers, and echocardiographic indices. METHODS: This was a prospective, single-arm, single-centre study. Adult consecutive patients with non-COVID-related PE from September 2019 to March 2022 were included and followed up for 12 months. RESULTS: The study included 180 (84 women) patients, with 89 (49.4%) suffering from IHPE. IHPE patients were older, they more often had cancer, were diagnosed earlier after the onset of symptoms, they had less frequent pain and higher values of high sensitivity troponin I and brain natriuretic peptide levels compared to OHPE patients. Echocardiographic right ventricular (RV) dysfunction was detected in similar proportions in the 2 groups. IHPE had increased in-hospital mortality (14.6% vs. 3.3%, p = 0.008) and similar post-discharge to 12-month mortality with OHPE patients. CONCLUSIONS: In this prospective cohort study, IHPE differed from OHPE patients regarding age, comorbidities, symptoms, and levels of biomarkers associated with RV dysfunction. IHPE patients had higher in-hospital mortality compared to OHPE patients and a similar risk of death after discharge.

Is it time for a retinoic acid-eluting stent or retinoic acid-coated balloon? Insights from experimental studies of systemic and local delivery of retinoids.

Although the incidence of restenosis and stent thrombosis has substantially declined during the last decades, they still constitute the two major causes of stent failure. These complications are partially attributed to the currently used cytostatic drugs, which can cause local inflammation, delay or prevent re-endothelialization and essentially cause arterial cell toxicity. Retinoic acid (RA), a vitamin A (retinol) derivative, is a naturally occurring substance used for the treatment of cell proliferation disorders. The agent has pleiotropic effects on vascular smooth muscle cells and macrophages: it influences the proliferation, migration, and transition of smooth muscle cells to other cell types and modulates macrophage activation. These observations are supported by accumulated evidence from in vitro and in vivo experiments. In addition, systemic and topical administration of RA can decrease the development of atherosclerotic plaques and reduce or inhibit restenosis after vascular injury (caused by embolectomy, balloon catheters, or ligation of arteries) in various experimental models. Recently, an RA-drug eluting stent (DES) has been tested in an animal model. In this review, we explore the effects of RA in atherosclerosis and the potential of the local delivery of RA through an RA-DES or RA-coated balloon for targeted therapeutic percutaneous vascular interventions. Despite promising published results, further experimental study is warranted to examine the safety and efficacy of RA-eluting devices in vascular artery disease.

Absolute zero-contrast percutaneous coronary interventions: An intravascular ultrasound-guided case series and literature review.

PURPOSE: Contrast media (CM)-associated adverse effects including mainly acute kidney injury and hypersensitivity reactions still remain a significant treatment burden to vulnerable patients requiring percutaneous coronary intervention (PCI). The complete omission of CM administration accompanied by intravascular ultrasound (IVUS) guidance may offer an appropriate revascularization treatment. METHODS: We hereby present a case series of four patients with challenging coronary lesions and relative/absolute contraindications to CM use [(hypersensitivity reaction owning to CM, history of contrast-induced acute kidney injury, solitary kidney, or advanced chronic kidney disease (CKD)] who underwent absolute zero-contrast IVUS-guided PCI following a predetermined protocol. RESULTS: The initial diagnostic angiography was reviewed for landmark identification, and multiple guidewires created a metallic road map providing additional landmarks and protected side branches. IVUS imaging was performed to determine lesion length, reference segments and landing zones, assess stent expansion/apposition and identify major complications. All procedures were successfully completed without any CM administration, renal function deterioration, pericardial effusion, or stent edge dissection. CONCLUSIONS: We demonstrated the feasibility of absolute zero-contrast IVUS-guided PCI in patients with complex coronary lesions susceptible to CM-associated adverse effects. Since the safety of this strategy is well-documented in patients with CKD and challenging lesions morphology even in acute settings, evidence-based validation of this approach is capable of changing the otherwise conservative treatment of vulnerable patients where even minimum doses of CM may have detrimental effects. SUMMARY FOR THE ANNOTATED TABLE OF CONTENTS: Patients with vulnerable renal function as well as former hypersensitivity reaction to contrast media encounter a significant treatment burden regarding coronary artery disease. Zero-contrast IVUS-guided strategy based on a predetermined protocol provides a feasible alternative approach in patients susceptible to contrast media-associated adverse effects even in the presence of complex coronary lesions.

Role of FGF21 and Leptin for the Diagnosis of Metabolic Health in Children with and without Obesity.

Obesity and unfavorable metabolic profiles increase the risk for cardiovascular complications in adults. Although it is important to distinguish different metabolic health states at an early stage, there are limited data on the related value of biomarkers in childhood. We aimed to identify biomarkers for the detection of different metabolic health states in children with and without obesity. The serum levels of metabolic regulators (fibroblast growth factor 21 [FGF21], leptin, adiponectin and insulin-like growth factor binding protein 1) and vascular indices (flow-mediated dilation [FMD] and carotid intima-media thickness) were assessed in 78 children. Differences between the metabolically healthy and unhealthy state within children with normal weight (MHN vs. MUN), and within children with overweight/obesity (MHO vs. MUO) were investigated; the discriminatory power of the biomarkers was studied. Both MUN and MUO groups expressed altered lipid and glucose homeostasis compared to their healthy counterparts. The metabolic unhealthy state in children with normal weight was linked to higher FGF21 levels which had good discriminatory ability (area under the curve [AUC]: 0.71, 95% CI: 0.54-0.88; p = 0.044). In overweight/obese children, leptin was increased in the metabolically unhealthy subgroup (AUC: 0.81, 95% CI: 0.68-0.95; p = 0.01). There was a decrease in FMD indicating worse endothelial function in overweight/obese children versus those with normal weight. Distinct states of metabolic health exist in both children with normal weight and overweight/obese children. FGF21 and leptin may help to identify the metabolic unhealthy state in children with normal weight and in overweight/obese children, respectively, early in life.

Safety and Efficacy of an Innovative Everolimus-Coated Balloon in a Swine Coronary Artery Model.

BACKGROUND: Drug-coated balloons have been used as a non-stenting treatment in coronary and peripheral artery disease. Until recently, only sirolimus- and paclitaxel-coated balloons have been investigated in clinical trials. We evaluated the safety and efficacy of an innovative everolimus-coated balloon (ECB) in a swine coronary artery model. METHODS: thirty-two swine coronary arteries were prepared through dilatation with a non-coated angioplasty balloon in a closed-chest model. During a period of 90 days, the following four groups (four animals per group, two coronary arteries per animal) were compared for safety and efficacy: A, Rontis ECB with 2.5 µg/mm2 of drug per balloon surface; B, Rontis ECB with 7.5 µg/mm2; C, Rontis Europa Ultra bare balloon; and D, Magic Touch, Concept Medical, sirolimus-coated balloon with a drug load of 1.3 µg/mm2. RESULTS: Differences in local biological effects (arterial reaction scores) and surface of intimal area (mm2) were not statistically significant between the treatment groups. Numerically, group A showed the lowest intimal area and intimal mean thickness, while group B showed the lowest stenosis among all groups. CONCLUSIONS: ECB was safe and effective in a porcine coronary artery model. The dose of everolimus may play a role in the biocompatibility of the balloon.

The Potential Role of Salivary NT-proBNP in Heart Failure.

BACKGROUND: Serum natriuretic peptides (NPs) have an established role in heart failure (HF) diagnosis. Saliva NT-proBNP that may be easily acquired has been studied little. METHODS: Ninety-nine subjects were enrolled; thirty-six obese or hypertensive with dyspnoea but no echocardiographic HF findings or raised NPs served as controls, thirteen chronic HF (CHF) patients and fifty patients with acute decompensated HF (ADHF) requiring hospital admission. Electrocardiogram, echocardiogram, 6 min walking distance (6MWD), blood and saliva samples, were acquired in all participants. RESULTS: Serum NT-proBNP ranged from 60-9000 pg/mL and saliva NT-proBNP from 0.64-93.32 pg/mL. Serum NT-proBNP was significantly higher in ADHF compared to CHF (p = 0.007) and in CHF compared to controls (p < 0.05). There was no significant difference in saliva values between ADHF and CHF, or between CHF and controls. Saliva and serum levels were positively associated only in ADHF patients (R = 0.352, p = 0.012). Serum NT-proBNP was positively associated with NYHA class (R = 0.506, p < 0.001) and inversely with 6MWD (R = -0.401, p = 0.004) in ADHF. Saliva NT-proBNP only correlated with age in ADHF patients. CONCLUSIONS: In the current study, saliva NT-proBNP correlated with serum values in ADHF patients, but could not discriminate between HF and other causes of dyspnoea. Further research is needed to explore the value of saliva NT-proBNP.

What is the real incidence of right ventricular affection in patients with acute pulmonary embolism?

BACKGROUND: Echocardiographic markers of right ventricular dysfunction or pressure overload (RVd/PO) have been used in risk assessment of patients with acute pulmonary embolism (APE). Nevertheless, the role of echocardiography in these patients is incompletely determined. We evaluated the right ventricular function using 'non-conventional' markers of RVd/PO in patients with APE. METHODS: This was a prospective, single-arm, single-centre study. Consecutive adult patients hospitalised for APE were included. The RV free wall longitudinal strain (RV-FWLS), the fractional area change (FAC), the ratio tricuspid annular plane systolic excursion (TAPSE)/pulmonary arterial systolic pressure (PASP), and the pulmonary vascular resistance (PVR) were evaluated. RESULTS: One hundred patients (mean age 70.0 ± 13.9 years, female 48%) were screened and 73 had adequate RV-FWLS images. The most common abnormal echocardiographic marker was RV-FWLS (44/73; p < 0.001, for all other echocardiographic indices). Thirty-one patients had either PASP ≥ 36 mmHg or PVR > 2 WU (49.2% of the patients with both indices available). There were significant correlations between RV-FWLS, TAPSE/PASP and PVR with both D-Dimers and B-type natriuretic peptide (BNP), and between FAC and BNP. RF-FWLS differed significantly between patients with a simplified pulmonary embolism severity index (sPESI) score 0 and those with a score ≥1 (p < 0.001). CONCLUSIONS: RVd/PO coexists with APE in a large proportion of patients. RV-FWLS is the most abnormal echocardiographic sign and is related to clinical and biochemical prognostic indices.

Transcatheter Aortic Valve Implantation with the Portico Valve: 2-Year Outcomes of a Multicenter, Real-World Registry.

INTRODUCTION: The self-expanding, resheathable, repositionable transcatheter aortic heart valve Portico is being used successfully for transcatheter aortic valve implantation procedures (TAVI) in patients with severe aortic stenosis. The aim of this study was to evaluate outcomes at 2 years after TAVI with the Portico valve. METHODS: Multicenter registry of clinical, echocardiographic and survival data from consecutive patients treated with the Portico TAVI system (Abbott, Chicago, IL, USA) in three cath labs in Northern Greece and Epirus during 2017-2020. The primary end point was all-cause mortality at 24 months. Secondary end points included procedural outcomes (efficacy and safety) and echocardiographic measurements. RESULTS: A total of 90 patients (81 ± 6 years, 50% females, mean age 81 ± 6 years) were included in the registry. The indication for implantation was severe, symptomatic aortic stenosis (NYHA III, IV) in eighty-two (91.1%) and degeneration of a prosthetic aortic valve in eight (8.9%) patients. All patients were categorized as high surgical risk (mean Logistic Euroscore 25.9 ± 10, Euroscore II 7.7 ± 4.4 and STS score 10.8 ± 8.9). The procedure was performed transfemorally in all patients, under general anesthesia in 95.6%, under TOE guidance in 21.1%, with native valve predilatation in 46.7%, and the "resheath" option was used in 31.1% of the cases. The implantation was successful in 97.8% and there was a need for a second valve in 2.2% of the cases. Complications included permanent pacemaker implantation (16.7%), access cite complications (15.6%), arrythmias (23.3%), paravalvular leak (moderate 7.8%, severe 1.1%), acute kidney injury (7.8%), no strokes and one death during the procedure. Aortic valve peak velocity, peak and mean pressure gradients, were significantly reduced after the procedure. All-cause mortality at 1, 12 and 24 months was 4.4%, 6.7% and 7.8%, respectively. CONCLUSIONS: TAVI with the Portico system comprises an effective and safe solution for the management of severe, symptomatic aortic stenosis in high-risk surgical patients.

The role of endothelial shear stress, shear stress gradient, and plaque topography in plaque erosion.

BACKGROUND AND AIMS: Plaque erosion is a common underlying cause of acute coronary syndromes. The role of endothelial shear stress (ESS) and endothelial shear stress gradient (ESSG) in plaque erosion remains unknown. We aimed to determine the role of ESS metrics and maximum plaque slope steepness in plaques with erosion versus stable plaques. METHODS: This analysis included 46 patients/plaques from TOTAL and COMPLETE trials and Brigham and Women's Hospital's database who underwent angiography and OCT. Plaques were divided into those with erosion (n = 24) and matched stable coronary plaques (n = 22). Angiographic views were used to generate a 3-D arterial reconstruction, with centerlines merged from angiography and OCT pullback. Local ESS metrics were assessed by computational fluid dynamics. Among plaque erosions, the up- and down-slope (Δ lumen area/frame) was calculated for each culprit plaque. RESULTS: Compared with stable plaque controls, plaques with an erosion were associated with higher max ESS (8.3 ± 4.8 vs. 5.0 ± 1.9 Pa, p = 0.02) and max ESSG any direction (9.2 ± 7.5 vs. 4.3 ± 3.11 Pa/mm, p = 0.005). Proximal erosion was associated with a steeper plaque upslope while distal erosion with a steeper plaque downslope. Max ESS and Max ESSG any direction were independent factors in the development of plaque erosion (OR 1.32, 95%CI 1.06-1.65, p = 0.014; OR 1.22, 95% CI 1.03-1.45, p = 0.009, respectively). CONCLUSIONS: In plaques with similar luminal stenosis, plaque erosion was strongly associated with higher ESS, ESS gradients, and plaque slope as compared with stable plaques. These data support that ESS and slope metrics play a key role in the development of plaque erosion and may help prognosticate individual plaques at risk for future erosion.

The burden of atrial fibrillation and heart failure in hospitalized patients: A real-world survey in a nationwide snapshot.

PURPOSE: Atrial fibrillation (AF) and heart failure (HF) are common and commonly coexisting cardiovascular diseases in hospitalized patients. We report the absolute number and interrelation between AF and HF, assess the daily burden of both diseases on the healthcare system, and describe the medical treatment in a real-world, nationwide conducted snapshot survey. METHODS: A questionnaire was equally distributed to various healthcare institutions. Data on the baseline characteristics, prior hospitalizations, and medical treatments of all hospitalized patients with AF and HF at a predefined date were collected and analyzed. RESULTS: Seventy-five cardiological departments participated in this multicenter Greek nationwide study. A total of 603 patients (mean age, 74.5 ± 11.4 years) with AF, HF, or the combination of both were nationwide admitted. AF, HF, and the combination of both were registered in 122 (20.2%), 196 (32.5%), and 285 (47.3%) patients, respectively. First-time hospital admission was recorded in 273 (45.7%) of 597 patients, whereas 324 (54.3%) of 597 patients had readmissions in the past 12 months. Of the entire population, 453 (75.1%) were on beta-blockers (BBs), and 430 (71.3%) were on loop diuretics. Furthermore, 315 patients with AF (77.4%) were on oral anticoagulation, of whom 191 (46.9%) were on a direct oral anticoagulant and 124 (30.5%) were on a vitamin K antagonist. CONCLUSION: Hospitalized patients with AF and/or HF have more than one admission within a year. Coexistence of AF and HF is more common. BBs and loop diuretics are the most commonly used drugs. More than three-quarters of the patients with AF were on oral anticoagulation.

Coronary microcirculation and left ventricular diastolic function but not myocardial deformation indices are impaired early in patients with chronic kidney disease.

AIM: To investigate abnormalities in myocardial strain and classic echocardiographic indices and coronary flow reserve (CFR), in younger versus older CKD patients. METHODS: Sixty consecutive CKD patients (<60 years old n = 30, ≥60 years old n = 30) and 30 healthy controls (age- and gender-matched with younger CKD patients) were recruited. An echocardiographic assessment including myocardial strain indices (i.e. global longitudinal strain -GLS -, TWIST, UNTWIST rate) was performed at baseline and following dipyridamole administration in all participants. RESULTS: Younger CKD patients had higher E/e', left ventricular mass index and relative wall thickness and lower E' (p < .005 for all) compared to healthy controls. Older CKD patients had lower E/A and E' (p < .05 for both) compared to younger CKD patients; these differences did not remain significant after adjustment for age. CFR was higher in healthy controls compared to younger and older CKD patients (p < .05 for both) without a significant difference between CKD groups. There were no significant differences in GLS, TWIST or UNTWIST values among the three groups of patients. Dipyridamole-induced changes did not differ significantly among the three groups. CONCLUSIONS: Compared to healthy controls, impaired coronary microcirculation and left ventricular diastolic function, but not myocardial strain abnormalities, are found in young CKD patients and deteriorate with aging.

The Role of Myocardial Perfusion Imaging in the Prediction of Major Adverse Cardiovascular Events at 1 Year Follow-Up: A Single Center's Experience.

BACKGROUND: Myocardial perfusion imaging via single-photon emission computed tomography (SPECT MPI) is a well-established method of diagnosing coronary artery disease (CAD). The purpose of this study was to assess the role of SPECT MPI in predicting major cardiovascular events. METHODS: The study population was composed of 614 consecutive patients (mean age: 67 years, 55% male) referred for SPECT MPI due to symptoms of stable CAD. The SPECT MPI was performed using a single-day protocol. We conducted a follow-up on all patients at 12 months via a telephone interview. RESULTS: The majority of our patients (78%) presented findings suggestive of reversible ischemia, fixed defects or both. Extensive perfusion defects were found in 18% of the population, while LV dilation was found in 7%. During the 12-month follow-up, 16 deaths, 8 non-fatal MIs and 20 non-fatal strokes were recorded. There was no significant association of SPECT findings with the combined endpoint of all-cause death, non-fatal MI and non-fatal stroke. The presence of extensive perfusion defects was an independent predictor of mortality at 12 months (HR: 2.90, 95% CI: 1.05, 8.06, p = 0.041). CONCLUSIONS: In a high-risk patient population with suspected stable CAD, only large reversible perfusion defects in SPECT MPI were independently associated with mortality at 1 year. Further trials are needed to validate our findings and refine the role of SPECT MPI findings in the diagnosis and prognosis of cardiovascular patients.

An All-in-One Tool for 2D Atherosclerotic Disease Assessment and 3D Coronary Artery Reconstruction.

Diagnosis of coronary artery disease is mainly based on invasive imaging modalities such as X-ray angiography, intravascular ultrasound (IVUS) and optical coherence tomography (OCT). Computed tomography coronary angiography (CTCA) is also used as a non-invasive imaging alternative. In this work, we present a novel and unique tool for 3D coronary artery reconstruction and plaque characterization using the abovementioned imaging modalities or their combination. In particular, image processing and deep learning algorithms were employed and validated for the lumen and adventitia borders and plaque characterization at the IVUS and OCT frames. Strut detection is also achieved from the OCT images. Quantitative analysis of the X-ray angiography enables the 3D reconstruction of the lumen geometry and arterial centerline extraction. The fusion of the generated centerline with the results of the OCT or IVUS analysis enables hybrid coronary artery 3D reconstruction, including the plaques and the stent geometry. CTCA image processing using a 3D level set approach allows the reconstruction of the coronary arterial tree, the calcified and non-calcified plaques as well as the detection of the stent location. The modules of the tool were evaluated for efficiency with over 90% agreement of the 3D models with the manual annotations, while a usability assessment using external evaluators demonstrated high usability resulting in a mean System Usability Scale (SUS) score equal to 0.89, classifying the tool as "excellent".

Cerebro-/Cardiovascular Collateral Damage During the COVID-19 Pandemic: Fact or Fiction?

Numerous observational studies have identified a decline in cerebro-/cardiovascular (CV) admissions during the initial phase of the COVID-19 pandemic. Recent studies and meta-analyses indicated that the overall decrease was smaller than that found in initial studies during the first months of 2020. Two years later we still do not have clear evidence about the potential causes and impacts of the reduction of CV hospitalizations during the COVID-19 pandemic. It has becoming increasingly evident that collateral damage (i.e., incidental damage to the public and patients) from the COVID-19 outbreak is the main underlying cause that at least somewhat reflects the effects of imposed measures such as social distancing and self-isolation. However, a smaller true decline in CV events in the community due to a lack of triggers associated with such acute syndromes cannot be excluded. There is currently indirect epidemiological evidence about the immediate impact that the collateral damage had on excess mortality, but possible late consequences including a rebound increase in CV events are yet to be observed. In the present narrative review, we present the reporting milestones in the literature of the rates of CV admissions and collateral damage during the last 2 years, and discuss all possible factors contributing to the decline in CV hospitalizations during the COVID-19 pandemic. Healthcare systems need to be prepared so that they can cope with the increased hospitalization rates for CV events in the near future.

Systemic Thrombolysis for Treatment of Acute Life-threatening Pulmonary Embolism During Cesarean Section Followed by Post-partum Rescue Hysterectomy: A Case Report and Review of the Literature.

BACKGROUND/AIM: Acute pulmonary embolism during cesarean section is extremely rare and only a limited number of cases have been reported in literature. The aim of this study was to report a case of acute high risk pulmonary embolism during elective cesarean section treated with systemic thrombolysis and discuss the multidisciplinary management in both early recognition and prompt treatment. CASE REPORT: A 39-year-old, G5P2, ASA II parturient presented for repeat cesarean section under general anesthesia. A sudden drop in end-tidal CO2 after placenta delivery combined with significant hemodynamic instability after an uneventful intraoperative course was strongly indicative of pulmonary embolism. Urgent transthoracic ultrasound revealed a sizable thrombus in the inferior vena cava and the right atrium. Thrombolysis was carried out intraoperatively using recombinant tissue plasminogen activator, which was administered under continuous US monitoring until thrombus resolution. This resulted in significant bleeding that was treated in a stepwise manner beginning with implementation of massive transfusion protocol, Bakri balloon placement, and rescue hysterectomy several hours after the event. Follow-up was uneventful and she was discharged on the 12th postoperative day. CONCLUSION: Though pregnancy is one of the major risk factors of the development of venous thromboembolism, acute intraoperative pulmonary embolism is extremely rare. Specific guidelines for the management of such cases are difficult to issue due to the paucity of relevant data. Thus, an individualized approach by a multidisciplinary team for diagnosis and intervention is mandated.