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.

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.

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.

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.

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.

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.

Symptomatic Total Aortic Occlusion.

BACKGROUND Aortic occlusion, whether acute or subacute, is a rare but very serious entity with disastrous consequences if not treated in a timely fashion. Rapid diagnosis is crucial in this setting. In surgically treated patients there is a high degree of mortality and morbidity; therefore, percutaneous revascularization, whenever possible and independent of the available techniques, is much more desirable. CASE REPORT A 62-year-old woman with a history of diabetes mellitus, dyslipidemia, hypertension, and peripheral vascular disease, with previous femoral-femoral bypass for right common iliac artery occlusion, and with recent conventional angiography showing near occlusion of the ostial left common iliac artery (the donor vessel for the previous bypass), was referred to our hospital for conventional angioplasty. We faced were surprised to find a total infrarenal aortic occlusion and decided to perform emergency and rescue recanalization. We successfully recanalized the aorta and left iliac artery by stent implantation and stabilized the patient, considering that surgical intervention has very high risk for morbidity and mortality in this particular setting. CONCLUSIONS Although revascularization is rarely performed in this life-threating condition, endovascular recanalization of a subacute aortic occlusion in a patient with femoral-femoral bypass is feasible and can be life-saving.

Benefits and Risks of Extended Duration Dual Antiplatelet Therapy After PCI in Patients With and Without Acute Myocardial Infarction.

BACKGROUND: The benefits and risks of prolonged dual antiplatelet therapy may be different for patients with acute myocardial infarction (MI) compared with more stable presentations. OBJECTIVES: This study sought to assess the benefits and risks of 30 versus 12 months of dual antiplatelet therapy among patients undergoing coronary stent implantation with and without MI. METHODS: The Dual Antiplatelet Therapy Study, a randomized double-blind, placebo-controlled trial, compared 30 versus 12 months of dual antiplatelet therapy after coronary stenting. The effect of continued thienopyridine on ischemic and bleeding events among patients initially presenting with versus without MI was assessed. The coprimary endpoints were definite or probable stent thrombosis and major adverse cardiovascular and cerebrovascular events (MACCE). The primary safety endpoint was GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries) moderate or severe bleeding. RESULTS: Of 11,648 randomized patients (9,961 treated with drug-eluting stents, 1,687 with bare-metal stents), 30.7% presented with MI. Between 12 and 30 months, continued thienopyridine reduced stent thrombosis compared with placebo in patients with and without MI at presentation (MI group, 0.5% vs. 1.9%, p < 0.001; no MI group, 0.4% vs. 1.1%, p < 0.001; interaction p = 0.69). The reduction in MACCE for continued thienopyridine was greater for patients with MI (3.9% vs. 6.8%; p < 0.001) compared with those with no MI (4.4% vs. 5.3%; p = 0.08; interaction p = 0.03). In both groups, continued thienopyridine reduced MI (2.2% vs. 5.2%, p < 0.001 for MI; 2.1% vs. 3.5%, p < 0.001 for no MI; interaction p = 0.15) but increased bleeding (1.9% vs. 0.8%, p = 0.005 for MI; 2.6% vs. 1.7%, p = 0.007 for no MI; interaction p = 0.21). CONCLUSIONS: Compared with 12 months of therapy, 30 months of dual antiplatelet therapy reduced the risk of stent thrombosis and MI in patients with and without MI, and increased bleeding. (The Dual Antiplatelet Therapy Study [The DAPT Study]; NCT00977938).

Successful management of the no-reflow syndome after venous graft stenting.

The no-reflow phenomenon is often found in venous grafts and every effort to prevent it is worthwhile. We performed an angioplasty on a venous graft in a patient with a NSTE acute coronary syndrome with previous inferior myocardial infarction (1996) and CABG (3 venous grafts ), respectively. The native coronary vessels had significant lesions: 70% left main stenosis, distal circumflex artery occlusion, LAD occlusion after the first diagonal branch and proximal occlusion of the RCA. All of the venous grafts,with the exception of the circumflex, were patent. The latter showed subocclusion and slow flow. This was the culprit lesion for the unstable syndrome. After stenting it, no residual stenosis appeared, but severe no-reflow ensued. The no-reflow phenomenon disappeared after intracoronary eptifibatide infusion and aspiration of the slugging contrast from the vein. Clinically, the patient had no chest pain and his ECG changes normalized.