Clonal hematopoiesis is associated with cardiovascular events in patients with stable coronary artery disease.

Clonal hematopoiesis (CH) is a risk factor for atherosclerotic cardiovascular disease, but the impact of smaller clones and the effect on inflammatory parameters is largely unknown. Using ultrasensitive single-molecule molecular inversion probe sequencing, we evaluated the association between CH and a first major adverse cardiovascular event (MACE) in patients with angiographically documented stable coronary artery disease (CAD) and no history of acute ischemic events. CH was associated with an increased rate of MACE at four years follow-up. The size of the clone predicted MACE at an optimal cut-off value of 1.07% variant allele frequency (VAF). Mutation carriers had no change in monocytes subsets or cytokine production capacity but had higher levels of circulating tissue factor, matrilysin, and proteinase-activated receptor-1. Our study identified CH driver mutations with a VAF as small as 1.07% as a residual cardiovascular risk factor and identified potential biomarkers and therapeutic targets for patients with stable CAD.

Intermediate monocytes are associated with the first major adverse cardiovascular event in patients with stable coronary artery disease.

BACKGROUND: Traditional risk stratification modestly predicts adverse cardiovascular events in patients with coronary artery disease (CAD). Our aim was to investigate the association between monocyte subsets numbers and function, and the first major adverse cardiovascular event (MACE) in patients with symptomatic stable CAD and angiographically documented coronary atherosclerosis. METHODS: Patients with stable CAD were screened for inclusion. Using flow cytometry, we identified classical, intermediate, and non-classical monocyte subsets and we assessed cytokine production capacity after ex-vivo stimulation of peripheral blood mononuclear cells. Clinical follow-up was performed after four years. The endpoint was the composite of cardiovascular death, acute myocardial infarction, and ischemic stroke. RESULTS: A cohort of 229 patients was recruited. The percentage of intermediate monocytes was positively associated with adverse cardiovascular events at follow-up (HR 1.09; 95%CI 1.02-1.16; p = 0.006), while the percentage of classical monocytes was identified as a protective factor for adverse outcomes (HR 0.96; 95%CI 0.94-0.99; p = 0.02). The percentage of intermediate monocytes remained independently associated with outcomes after adjusting for age, systolic blood pressure, and left ventricular ejection fraction (HR 1.07; 95% CI 1.01-1.14; p = 0.04). Several correlations were identified between monocyte subsets and stimulated cytokine production, but cytokine production capacity was not associated with adverse outcomes. CONCLUSIONS: In patients with stable CAD, intermediate monocytes were associated with MACE at follow-up. The association was not due to an increased cytokine production capacity. Novel biomarkers could improve risk stratification in patients with stable CAD and could represent new pharmacological targets against atherosclerosis progression.

The Influence of the Learning Curve on Clinical Outcomes in Balloon-Expandable versus Self-Expandable Transfemoral Transcatheter Aortic Valve Implantation.

INTRODUCTION: Balloon-expandable (BE) and self-expandable (SE) prostheses are the main types of devices currently used in transcatheter aortic valve implantation (TAVI). Despite the different designs, clinical practice guidelines do not make any specific recommendation on the selection of one device over the other. Most operators are trained in using both BE and SE prostheses, but operator experience with each of the two designs might influence patient outcomes. The aim of this study was to compare the immediate and mid-term clinical outcomes during the learning curve in BE versus SE TAVI. METHODS: The transfemoral TAVI procedures performed in a single center between July 2017 and March 2021 were grouped according to the type of implanted prosthesis. The procedures in each group were ordered according to the case sequence number. For each patient, a minimum follow-up time of 12 months was required for inclusion in the analysis. The outcomes of the BE TAVI procedures were compared with the outcomes of the SE TAVI procedures. Clinical endpoints were defined according to the Valve Academic Research Consortium 3 (VARC-3). RESULTS: The median follow-up time was 28 months. Each device group included 128 patients. In the BE group, case sequence number predicted mid-term all-cause mortality at an optimal cutoff value ≤58 procedures (AUC 0.730; 95% CI: 0.644-0.805; p < 0.001), while in the SE group, the cutoff value was ≤85 procedures (AUC 0.625; 95% CI: 0.535-0.710; p = 0.04). A direct comparison of the AUC showed that case sequence number was equally adequate in predicting mid-term mortality, irrespective of prosthesis type (p = 0.11). A low case sequence number was associated with an increased rate of VARC-3 major cardiac and vascular complications (OR 0.98 95% CI: 0.96-0.99; p = 0.03) in the BE device group, and with an increased rate of post-TAVI aortic regurgitation ≥ grade II (OR 0.98; 95% CI: 0.97-0.99; p = 0.03) in the SE device group. CONCLUSIONS: In transfemoral TAVI, case sequence number influenced mid-term mortality irrespective of prosthesis type, but the learning curve was longer in the case of SE devices.

Transcatheter aortic valve implantation in a patient with interventricular membranous septal aneurysm resulted in cardiac tamponade of unclear etiology.

An 86-year-old lady with severe aortic stenosis and interventricular membranous septal aneurysm underwent transfemoral transcatheter aortic valve implantation (TAVI). A balloon-expandable valve was deployed after a difficult native valve crossing. Transesophageal echocardiography showed a rapidly accumulating pericardial effusion, with pericardial thrombus and subsequent cardiac tamponade. The angiographic views raised suspicion of aortic root perforation. Median sternotomy was performed because of sudden hemodynamic collapse.The report presents the uncommon association between severe aortic stenosis and interventricular membranous septal aneurysm in an octogenarian and discusses its impact on the development of a post-TAVI major complication.

Development of a Novel Approach for Detection of Equine Lameness Based on Inertial Sensors: A Preliminary Study.

Both as an aid for less experienced clinicians and to enhance objectivity and sharp clinical skills in professionals, quantitative technologies currently bring the equine lameness diagnostic closer to evidence-based veterinary medicine. The present paper describes an original, inertial sensor-based wireless device system, the Lameness Detector 0.1, used in ten horses with different lameness degrees in one fore- or hind-leg. By recording the impulses on three axes of the incorporated accelerometer in each leg of the assessed horse, and then processing the data using custom-designed software, the device proved its usefulness in lameness identification and severity scoring. Mean impulse values on the horizontal axis calculated for five consecutive steps above 85, regardless of the leg, indicated the slightest subjectively recognizable lameness, increasing to 130 in severe gait impairment. The range recorded on the same axis (between 61.2 and 67.4) in the sound legs allowed a safe cut-off value of 80 impulses for diagnosing a painful limb. The significance of various comparisons and several correlations highlighted the potential of this simple, affordable, and easy-to-use lameness detector device for further standardization as an aid for veterinarians in diagnosing lameness in horses.

Relation Between Plasma Proteomics Analysis and Major Adverse Cardiovascular Events in Patients With Stable Coronary Artery Disease.

OBJECTIVE: Despite the advances in the control of traditional risk factors, coronary artery disease (CAD) remains the greatest cause of morbidity and mortality. Our aim was to establish the relation between plasma proteomics analysis and the risk of cardiovascular events in patients with stable CAD. MATERIALS AND METHODS: Patients with stable CAD and documented coronary atherosclerosis were screened for inclusion. Using proximity extension assays, 177 plasma proteins were simultaneously measured. The endpoint consisted of the first major adverse cardiovascular event (MACE) and was the composite of cardiovascular death, acute coronary syndrome, stroke, transient ischemic attack, or acute limb ischemia at 18 months follow-up. Cox proportional-hazards regression with adjustment for multiple comparisons was used to identify biomarkers for the outcomes of interest. RESULTS: The cohort consisted of 229 patients. Six mediators were associated with MACE (p < 0.001). For these markers, the risk of MACE was calculated: tumor necrosis factor receptor superfamily member 13B (HR = 1.65; 95% CI: 1.30-2.10), C-C motif chemokine-3 (HR = 1.57; 95% CI: 1.23-1.98), decorin (HR = 1.65; 95% CI: 1.26-2.16), fibroblast growth factor-23 (HR = 1.56; 95% CI: 1.23-1.99), tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) (HR = 1.61; 95% CI: 1.23-2.11), and tumor necrosis factor receptor superfamily member 10A (HR = 1.69; 95% CI: 1.25-2.29). Except for TRAIL-R2, the other proteins were associated with MACE independent of age, sex, diabetes mellitus, or estimated glomerular filtration rate. CONCLUSIONS: In patients with stable CAD, five novel biomarkers were identified as independent risk factors for adverse outcomes. Novel biomarkers could represent pharmacological targets for the prevention of adverse cardiovascular events.

The effect of the learning curve on paravalvular aortic regurgitation and mid-term mortality in transfemoral transcatheter aortic valve implantation.

OBJECTIVE: Paravalvular aortic regurgitation is an important independent mortality predictor in transcatheter aortic valve implantation (TAVI). Our study evaluated the association between paravalvular aortic regurgitation and mid-term mortality in relation with the learning curve, in patients with severe aortic stenosis who underwent transfemoral TAVI in the first 3 years since the establishment of the program. METHODS: Patients with severe aortic stenosis who underwent transfemoral TAVI between 2017 and 2020 were included in the analysis. Paravalvular aortic regurgitation was assessed by transthoracic echocardiography at 48 hours after the procedure. All-cause mortality was evaluated after 30 days and at mid-term follow-up. RESULTS: Paravalvular aortic regurgitation ≥grade II was associated with mid-term all-cause mortality (OR 4.4; 95%CI 1.82-11.55; p < 0.001), their prevalence declining after the first 60 cases. Baseline characteristics did not significantly differ in the first 60 patients from the rest of the cohort. Male sex (p = 0.006), advanced age (p = 0.04), coronary artery disease (p = 0.003), or elevated STS Score (p = 0.02) influenced mid-term survival. When adjusting for the presence of these factors, only age (OR 1.1; 95%CI 1.0-1.2), paravalvular aortic regurgitation ≥grade II (OR 3.9; 95%CI 1.3-12.9), and the number of days spent in the intensive care unit (OR 1.4; 95%CI 1.1-1.8) were independent predictors of mid-term all-cause mortality. CONCLUSIONS: In a group of patients with severe aortic stenosis who underwent transfemoral TAVI in the first 3 years since the establishment of the program, paravalvular aortic regurgitation ≥grade II was associated with mid-term mortality, both declining after the first 60 cases.

The invasive intracoronary imaging assessment of left main coronary artery disease.

Left main coronary artery disease is associated with an unfavorable prognosis. Evidence-based decision making regarding the optimal revascularization strategy in patients with left main disease has become a challenge, in view of the recently published data. An improvement in outcomes following left main percutaneous interventions could be achieved by reducing the rate of repeat target lesion revascularization through stent optimization techniques. In the setting of left main disease, procedural guidance by intravascular ultrasound or optical coherence tomography is essential for good long-term results, in such a way that intravascular imaging has gained more of a therapeutic connotation. Besides stent optimization, intracoronary imaging quantifies lesion severity, guides lesion preparation through morphological data, facilitates stent selection through accurate vessel sizing, identifies the landing zones, diagnoses acute vessel wall complications such as stent-related edge dissection or intramural hematoma, and defines procedural success.This review focuses on the two main intracoronary imaging techniques used for diagnostic evaluation and procedural guidance in left main coronary artery disease: intravascular ultrasound and optical coherence tomography. Based on the most recently published data, the review discusses each technique's advantages and pitfalls, and summarizes their indications.

Long-Term Mortality After Renal Artery Stenting in Patients With Severe Atherosclerotic Renal Artery Stenosis and High-Risk Clinical Manifestations.

BACKGROUND: Atherosclerotic renal artery stenosis is a risk factor for cardiovascular death. Observational studies support the benefit of renal revascularization on outcomes in patients with high-risk clinical manifestations. In this context, we evaluated the factors associated with long-term mortality after renal artery stenting in patients with severe renal artery stenosis, impaired kidney function, and/or uncontrolled hypertension. METHODS: The medical records of patients undergoing renal artery stenting between 2004 and 2014 were extracted. Blood pressure and creatinine were recorded at baseline, 24 hours poststenting and in the 1-month to 1-year interval that followed revascularization. Long-term follow-up was performed in March 2020. RESULTS: The cohort consisted of 65 patients. Median follow-up was 120 months. In the first year after stenting, less patients had chronic kidney disease (CKD) class 3b-5 as compared with baseline (35.3% vs. 56.9%, P = 0.01). The number of patients with controlled blood pressure after revascularization increased with 69.2% (P < 0.001). Long-term all-cause mortality reached 44.6%. Age (odds ratio (OR) 1.1; 95% confidence interval (CI) 1.0-1.2; P = 0.01), male gender (OR 7.9; 95% CI 1.9-43.5; P = 0.008), poststenting CKD class 3b-5 (OR 5.8; 95% CI 1.5-27.9; P = 0.01), and postrevascularization uncontrolled hypertension (OR 8.9; 95% CI 1.7-63.5; P = 0.01) were associated with long-term mortality independent of diabetes mellitus and coronary artery disease. CONCLUSIONS: Improved CKD class and blood pressure were recorded in the first year after renal artery stenting in patients with severe renal artery stenosis and high-risk clinical manifestations. The lack of improvement in kidney function and blood pressure was independently associated with long-term mortality.

An integrative model of cardiometabolic traits identifies two types of metabolic syndrome.

Human diseases arise in a complex ecosystem composed of disease mechanisms and the whole-body state. However, the precise nature of the whole-body state and its relations with disease remain obscure. Here we map similarities among clinical parameters in normal physiological settings, including a large collection of metabolic, hemodynamic, and immune parameters, and then use the mapping to dissect phenotypic states. We find that the whole-body state is faithfully represented by a quantitative two-dimensional model. One component of the whole-body state represents 'metabolic syndrome' (MetS) - a conventional way to determine the cardiometabolic state. The second component is decoupled from the classical MetS, suggesting a novel 'non-classical MetS' that is characterized by dozens of parameters, including dysregulated lipoprotein parameters (e.g. low free cholesterol in small high-density lipoproteins) and attenuated cytokine responses of immune cells to ex vivo stimulations. Both components are associated with disease, but differ in their particular associations, thus opening new avenues for improved personalized diagnosis and treatment. These results provide a practical paradigm to describe whole-body states and to dissect complex disease within the ecosystem of the human body.

The Best Approach for Patients with Stable Coronary Disease: The Importance of a Multidisciplinary Heart Team.

Background: A multidisciplinary Heart Team (HT) is nowadays considered to be of great importance for a complete and accurate assessment of patients with stable coronary disease (CAD). This study evaluates the role of the HT approach in the selection of best therapeutic strategies for patients with stable CAD. Methods: The study included 200 patients with stable coronary artery disease. The weekly HT meetings consisted of open discussion taking into consideration the latest recommended therapies. HT outcome options included medical therapy (MT), percutaneous coronary intervention (PCI), or surgical intervention (CABG). Following HT implementation, the 1-, 3-, and 6-month outcomes in addition to the distribution of baseline characteristics were assessed. Results: The following HT strategies were implemented: PCI - 46%, CABG - 10% and MT - 44% of patients. Patients selected for surgical treatment were more likely to have multi-vessel coronary disease (p=0.011). The survival rates at 6 months according to HT strategy were 96.8% for PCI, 95% for CABG, and 94.2% for MT. Conclusions: The HT multidisciplinary decision is mandatory for optimal patient care and can prevent specialty biases. Tertiary care institutions should develop and implement interdisciplinary protocols for common CAD cases.

Giant ascending aortic aneurysm after aortic valve replacement.

Giant ascending aortic aneurysms are rare clinical entities and are accompanied by a high annual risk of rupture. We present the imaging, intraoperative, and pathology findings of such a case.

New Predictors of Early and Late Outcomes after Primary Percutaneous Coronary Intervention in Patients with ST-Segment Elevation Myocardial Infarction and Unprotected Left Main Coronary Artery Culprit Lesion.

OBJECTIVES: The study evaluated the correlation between baseline SYNTAX Score, Residual SYNTAX Score, and SYNTAX Revascularization Index and long-term outcomes in ST-elevation myocardial infarction (STEMI) patients with primary percutaneous coronary intervention (PCI) on an unprotected left main coronary artery lesion (UPLMCA). BACKGROUND: Previous studies on primary PCI in UPLMCA have identified cardiogenic shock, TIMI 0/1 flow, and cardiac arrest, as prognostic factors of an unfavourable outcome, but the complexity of coronary artery disease and the extent of revascularization have not been thoroughly investigated in these high-risk patients. METHODS: 30-day, 1-year, and long-term outcomes were analyzed in a cohort of retrospectively selected, 81 consecutive patients with STEMI, and primary PCI on UPLMCA. RESULTS: Cardiogenic shock (p=0.001), age (p=0.008), baseline SYNTAX Score II (p=0.006), and SYNTAX Revascularization Index (p=0.046) were independent mortality predictors at one-year follow-up. Besides cardiogenic shock (HR 3.28, p<0.001), TIMI 0/1 flow (HR 2.17, p=0.021) and age (HR 1.03, p=0.006), baseline SYNTAX Score II (HR 1.06, p=0.006), residual SYNTAX Score (HR 1.03, p=0.041), and SYNTAX Revascularization Index (HR 0.9, p=0.011) were independent predictors of mortality at three years of follow-up. In patients with TIMI 0/1 flow, the presence of Rentrop collaterals was an independent predictor for long-term survival (HR 0.24; p=0.049). CONCLUSIONS: In this study, the complexity of coronary artery disease and the extent of revascularization represent independent mortality predictors at long-term follow-up.

Percutaneous valve-in-valve procedure and simultaneous paravalvular leak closure.

Concern for early degeneration limits the use of bioprosthetic heart valves. A 77-year-old man who underwent surgical aortic valve replacement at age 70 for severe aortic stenosis (AoS) presented with premature bioprosthesis degeneration and AoS recurrence. Transthoracic echocardiography demonstrated severe AoS and aortic regurgitation, a 30% ejection fraction, and pulmonary hypertension. Transesophageal echocardiography revealed that the aortic regurgitation was due to a 5-mm paravalvular leak (PVL). A high EuroScoreII excluded surgical treatment. Simultaneous transcatheter aortic valve replacement and PVL closure with an Occlutech PLD Square 5 Twist PVL closure device were performed with good results and improved clinical status.

Microvascular obstruction in acute myocardial infarction: an old and unsolved mystery.

In the setting of acute myocardial infarction, flow restoration in the culprit epicardial coronary artery is not synonymous with efficient reperfusion. Microvascular obstruction occurs in 50% of cases and represents a predictor of a long-term unfavorable outcome. Its prevalence has remained constant in recent years despite various treatment attempts. However, the success of targeted therapies could be mainly a problem of timing. Recent data bring evidence with regard to the role of pre-procedural distal embolization and highlight the relation between distal embolism, microvascular obstruction and intramyocardial inflammation. As a result, early detection of microvascular injury represents the first step in the development of targeted, individualized therapeutic approaches. In this context, the identification of new invasive surrogate parameters for the timely assessment and quantification of microvascular obstruction in the catheterization laboratory has become an important subject of current research. Among these, coronary wedge pressure is the most practical and revealing in the setting of primary percutaneous coronary intervention. It may offer comprehensive details on the mechanisms of microvascular injury and may therefore offer guidance for appropriate treatment selection.

In ST-segment elevation myocardial infarction, the echocardiographic parameters of microvascular obstruction are not associated with left ventricular remodeling at five years of follow-up.

OBJECTIVE: The correlation between the echocardiographic Doppler flow parameters of microvascular obstruction (MVO) and coronary wedge pressure (CWP) measured as a marker of severe compressive microvascular dysfunction and a predictor of adverse left ventricular remodeling was evaluated in a group of high-risk acute anterior myocardial infarction survivors. METHODS: Twenty-four patients with mechanically reperfused anterior STEMI were divided into two groups based on the 38 mm Hg CWP cutoff for adverse left ventricular remodeling. Diastolic deceleration time (DDT), coronary flow reserve (CFR), systolic retrograde flow, peak systolic and peak diastolic velocities in the infarct-related artery were determined 3-5 days after revascularization. An echocardiographic 20% increase in left ventricular volumes defined adverse remodeling. RESULTS: No significant differences were recorded between groups with regard to the echocardiographic parameters of MVO. No significant correlation was identified between CWP on one side and DDT (P = 0.30) and CFR (P = 0.39) on the other, irrespective of total ischemic time and extracted thrombus length. No difference in 5 years of follow-up left ventricular remodeling was detected in patients with DDT<900 msec as compared to those with DDT≥900 msec. The medium increase in left ventricular end-systolic volume in patients with low CWP was 24.78%, while it reached 127.27% (P = 0.03) in patients with CWP>38 mm Hg. CONCLUSIONS: Coronary wedge pressure did not correlate with the surrogate parameters for MVO, but it was a predictor of left ventricular remodeling. None of the echocardiographic MVO parameters was associated with adverse remodeling at 5 years of follow-up.

Renal Failure Impact on the Outcomes of ST-Segment Elevation Myocardial Infarction Patients Due to a Left Main Coronary Culprit Lesion Treated Using a Primary Percutaneous Coronary Intervention.

BACKGROUND: Patients with ST-segment elevation myocardial infarction (STEMI) and primary percutaneous coronary intervention (PPCI) on a left main culprit lesion have very high mortality rates. The interaction of chronic kidney disease (CKD) with such a catastrophic acute event on the background of their highly complex atherosclerotic lesions is not well established. Therefore, we sought to evaluate in these patients the influence of the estimated glomerular filtration rate (eGFR) on short- and long-term mortality. METHODS: We retrospectively analyzed renal function in 81 patients with STEMI and PPCI on a left main culprit lesion from two tertiary centers. RESULTS: Patients were divided in two groups according to an eGFR cut-off of 60 mL/min/1.73 m2: 40 patients with CKD and 41 without CKD. Patients with renal failure were older, had more diabetes, and had experienced more frequent myocardial infarction MIs. CKD patients had a higher baseline-SYNTAX score (p = 0.015), higher residual-SYNTAX score (p < 0.001), and lower SYNTAX revascularization index-SRI (p = 0.003). Mortality at 30-day, 1-year, and 3-year follow-ups were not significantly different between the two groups. However, when analyzed as a continuous variable, eGFR emerged as a predictor of 1-year mortality, both in univariate analysis (OR = 0.97, 95% CI: 0.95-0.99, p = 0.005) and in multivariate analysis, after adjusting for cardiogenic shock and Thrombolysis in Myocardial Infarction TIMI 0/1 flow (OR = 0.975, 95% CI: 0.95-0.99, p = 0.021). CONCLUSIONS: In STEMI with PPCI on a left main culprit lesion, renal failure was associated with more complex coronary lesions and less complete revascularization, and turned out to be an independent predictor of mortality at 1-year follow-up.