Enrico Fabris

Bioabsorbable vascular scaffold overexpansion: insights from in vitro post-expansion experiments

AIMS While bioresorbable vascular scaffolds (BVS) are increasingly used in clinical practice, their behaviour when post-dilated beyond their recommended maximum overexpansion diameter remains sparsely documented. We aimed to test the overexpansion of the BVS scaffold in vitro and evaluate the impact of excessive scaffold oversizing on focal point support. METHODS AND RESULTS We examined the post-expansion behaviour of the bioresorbable vascular scaffold (3.0 mm and 3.5 mm Absorb BVS; Abbott Vascular, Santa Clara, CA, USA) after overexpansion with non-compliant (NC) balloons of increasing diameters. After each oversizing step, the scaffolds were measured and inspected for strut disruption using microscope and optical coherence tomography imaging. Point force mechanical measurements on single scaffold struts were also performed to evaluate the impact of excessive scaffold overstretching on focal mechanical support. 3.0 mm and 3.5 mm scaffold sizes could be post-expanded up to 1 mm above their nominal diameters without any strut fracture when deployed without an external constraining model. Importantly, when overexpansion of both scaffold sizes was repeated using a constraining silicone lesion model, only post-expansion with an NC balloon size 0.5 mm larger than the scaffold nominal sizes could be performed without strut fractures. Point force compression analysis on single struts shows that overstretched struts with fractures provided lower focal strength compared to overexpanded ring segments without fractures and normal segments expanded at nominal pressure. CONCLUSIONS In our experiments, only overexpansion with an NC balloon 0.5 mm larger than the BVS size was feasible for BVS deployed inside an arterial lesion model. Overexpansion of the BVS scaffold beyond recommended post-dilation limits can lead to strut disconnections and focal loss of mechanical support.

Is high pressure postdilation safe in bioresorbable vascular scaffolds? Optical coherence tomography observations after noncompliant balloons inflated at more than 24 atmospheres.

Optical coherence tomography (OCT) was used to investigate integrity and expansion of bioresorbable drug‐eluting scaffolds (BVS) after high‐pressure postdilation (HPPD).

Early Improvement of Functional Mitral Regurgitation in Patients With Idiopathic Dilated Cardiomyopathy

The aim of the study was to assess the clinical and prognostic impact of early functional mitral regurgitation (FMR) improvement on the outcome of patients with idiopathic dilated cardiomyopathy (IDC). The prevalence and prognostic role of FMR improvement, particularly at early follow-up, in patients with IDC are still unclear. From 1988 to 2009, we enrolled 470 patients with IDC with available FMR data at baseline and after 6 ± 2 months. According to the evolution of FMR, patients were classified into 3 groups: stable absent-mild FMR, early FMR improvement (downgrading from moderate-severe to absent-mild), and persistence/early development of moderate-severe FMR. At baseline, 177 of 470 patients (38%) had moderate-severe FMR. Patients with early FMR improvement had significantly better survival rate-free from heart transplant with respect to those with persistence/early development of moderate-severe FMR (93%, 81%, and 66% vs 91%, 64%, and 52% at 1, 6, and 12 years, respectively; p = 0.044). At 6-month follow-up multivariate analysis, FMR improvement was associated with better prognosis (hazard ratio 0.78, 95% confidence interval [CI] 0.64 to 0.96, p = 0.02); the other independent predictors were male gender, heart failure duration, and early re-evaluation of the New York Heart Association class and left ventricle systolic function. This model provided more accurate risk stratification compared with the baseline model (Net Reclassification Index 80% at 12 months and 41% at 72 months). In conclusion, in a large cohort of patients with IDC receiving optimal medical treatment, early improvement of FMR was frequent (53%) and emerged as a favorable independent prognostic factor with an incremental short- and long-term power compared with the baseline evaluation.

Near-infrared spectroscopy-intravascular ultrasound: scientific basis and clinical applications

Coronary angiography underestimates the magnitude of the atherosclerotic burden and cannot detect the presence of disease in the early phases. Recognition of these inherent limitations of angiography has been an impetus for the development of other coronary imaging techniques. The novel near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) catheters can detect and quantify the presence of lipid core in the atherosclerotic plaque and associate it with other features such as lumen size and plaque architecture. Lipid-rich plaques are known to pose a higher risk of distal embolization during interventions and plaque disruption. The aim of this manuscript is the review of the potential clinical and research applications of this technology as highlighted by recent studies.

Clinical Spectrum of PRKAG2 Syndrome

PRKAG2 syndrome (PS) is a rare, early-onset autosomal dominant inherited disease, characterized by ventricular pre-excitation, supraventricular arrhythmias, and cardiac hypertrophy. It is frequently accompanied by chronotropic incompetence and advanced heart blocks, leading to premature pacemaker implantation. The association of these clinical features had previously been recognized by several studies since the second half of the 20th century.1–3 In 1991, PRKAG2 syndrome was mapped to the locus 7q 36,4 and in 2001, Gollob et al5 identified the responsible gene. The syndrome is caused by mutations in the gene encoding for the 5′ AMP-activated protein kinase (AMPK), specifically for its γ2 regulatory subunit (PRKAG2). AMPK is an enzyme deeply involved in cellular ATP metabolic regulation.6 PRKAG2 genetic mutations are rare and have been recognized mainly in the context of patients with nonsarcomeric familial hypertrophic cardiomyopathy associated with Wolff–Parkinson–White syndrome.7 PS can show different expressivity both of ventricular hypertrophy and arrhythmic features, ranging from an asymptomatic condition to sudden cardiac death (SCD). PS can occasionally lead to heart failure (HF) or demonstrate systemic involvement.7–9 This review aims to describe the various features and clinical implications of PS, providing clinicians and researchers with a summary of the published literature to improve the diagnosis and to better manage the clinical course of the disease. A search of the English literature was performed using PubMed up to September 2014 on the clinical features, genetics, and pathophysiology of PS syndrome. The term PRKAG2 combined with either cardiomyopathy, Wolff–Parkinson–White syndrome, atrial fibrillation, familial, left ventricular hypertrophy, atrioventricular (AV) block, pacemaker, SCD, HF, clinical characteristics, genotype, phenotype, or mutations was used. Observational studies, case reports, and reviews were included in our search. References were carefully evaluated for …

Cardiac hypertrophy, accessory pathway, and conduction system disease in an adolescent: the PRKAG2 cardiac syndrome.

![Figure][1] [![Graphic][3] ][3][![Graphic][4] ][4] A 17-year-old asymptomatic boy was referred to our hospital for family screening because of his fathers unexplained left ventricular hypertrophy (LVH). The father received a pacemaker at 35 years of age for sick sinus syndrome

Optical coherence tomography guidance for percutaneous coronary intervention with bioresorbable scaffolds.

BACKGROUND The effect of optical coherence tomography (OCT) guidance on the implantation strategy during all phases of percutaneous coronary intervention (PCI) with bioresorbable vascular scaffolds (BVSs) in a real-world scenario has been poorly investigated. METHODS Consecutive patients undergoing BVS implantation at our institution were included in this registry. Frequency-domain OCT pullbacks were performed at the operators discretion during all phases of BVS implantation procedures to optimize preparation of lesions, confirm BVS size, and optimize expansion and apposition of scaffolds. RESULTS Between September 2012 and July 2015, 203 BVSs were implanted in 101 consecutive patients at our institution (2.01 BVSs/patient). In 66 patients, the procedure was performed under OCT guidance. In the OCT subgroup, 66 (77.6%) of the 85 treated lesions were complex (B2/C AHA/ACC type). Overall, 147 OCT pullbacks were performed and 72/147 (49.0%) pullbacks indicated the need for changing strategy. After angiography-only-guided optimisation of BVS in 27 (31.8%) lesions, an OCT examination prompted performance of a second post-expansion. This resulted in an increase in the minimal scaffold area (5.5 to 6.3mm(2), p=0.004) and a decrease in the incomplete scaffold apposition area (1.1 to 0.6mm(2), p=0.082), with no new stent fractures. When the population was divided according to the time of BVS implantation, an initial learning adaptation became evident, with the number of OCT-guided changes in strategy significantly decreasing between the initial and final time periods (p=0.017). CONCLUSIONS OCT guidance for BVS implantation significantly affects the procedural strategy, with favourable effects on acute results and the learning curve.

Prognostic significance of atrial fibrillation and severity of symptoms of heart failure in patients with low gradient aortic stenosis and preserved left ventricular ejection fraction.

The aims of this study were to investigate the clinical outcomes of patients with low-gradient aortic stenosis despite preserved left ventricular ejection fraction and to assess reliable prognostic clinical-instrumental features in patients experiencing or not experiencing aortic valve replacement (AVR). Clinical-laboratory and echocardiographic data from 167 patients (median age 78 years, interquartile range 69 to 83) with aortic valve areas <1.0 cm(2), mean gradients ≤30 mm Hg, and preserved left ventricular ejection fraction (≥55%), enrolled from 2005 to 2010, were analyzed. During a mean follow-up period of 44 ± 23 months, 33% of patients died. On multivariate analysis, independent predictors of death were baseline New York Heart Association functional class III or IV (hazard ratio 2.16, p = 0.038) and atrial fibrillation (hazard ratio 2.00, p = 0.025). Conversely, AVR was protective (hazard ratio 0.25, p = 0.01). The magnitude of the protective effect of AVR seemed to be relatively more important in patients with atrial fibrillation than in those in sinus rhythm, independently of the severity of symptoms. Age >70 years showed a trend toward being a prognostic predictor (p = 0.082). In conclusion, in patients with low-gradient aortic stenosis despite a preserved left ventricular ejection fraction, AVR was strongly correlated with a better prognosis. Patients with atrial fibrillation associated with advanced New York Heart Association class had the worst prognosis if treated medically but at the same time a relative better benefit from surgical intervention.

One-Year Mortality for Bivalirudin vs Heparins Plus Optional Glycoprotein IIb/IIIa Inhibitor Treatment Started in the Ambulance for ST-Segment Elevation Myocardial Infarction: A Secondary Analysis of the EUROMAX Randomized Clinical Trial

Importance Uncertainty exists regarding potential survival benefits of bivalirudin compared with heparin with routine or optional use of glycoprotein IIb/IIIa inhibitors (GPIs) in patients with ST-segment elevation myocardial infarction (STEMI). Few data are available regarding long-term mortality in the context of contemporary practice with frequent use of radial access and novel platelet adenosine diphosphate P2Y12 receptor inhibitors. Objective To assess the effect of bivalirudin monotherapy compared with unfractionated or low-molecular-weight heparin plus optional GPIs on 1-year mortality. Design, Setting, and Participants This international, randomized, open-label clinical trial (EUROMAX [European Ambulance Acute Coronary Syndrome Angiography]) included 2198 patients with STEMI undergoing transport for primary percutaneous coronary intervention from March 10, 2010, through June 20, 2013, and followed up for 1 year. Patients were randomized (1:1) in ambulance to bivalirudin monotherapy vs unfractionated or low-molecular-weight heparin plus optional GPIs (control group). Analysis was based on intention to treat. Main Outcomes and Measures The primary outcome of this prespecified analysis was 1-year mortality. All deaths were adjudicated as cardiac or noncardiac by an independent, blinded clinical events committee. One-year mortality was assessed and examined across multiple prespecified subgroups. Results Of the 2198 patients enrolled (1675 men [76.2%] and 523 women [23.8%]; median [interquartile range] age, 62 [52-72] years), complete 1-year follow-up data were available for 2164 (98.5%). All-cause 1-year mortality occurred in 118 patients (5.4%). The number of all-cause deaths was the same for both treatment groups (59 deaths; relative risk [RR], 1.02; 95% CI, 0.72-1.45; P = .92). No differences were noted in the rates of 1-year cardiac death (44 [4.0%] for the bivalirudin group vs 48 [4.3%] for the control group; RR, 0.93; 95% CI, 0.63-1.39; P = .74) or noncardiac death (15 [1.4%] for the bivalirudin group vs 11 [1.0%] for the control group; RR, 1.39; 95% CI, 0.64-3.01; P = .40). Results were consistent across the prespecified patient subgroups. The rate of deaths occurring from 30 days to 1 year was also similar (27 [2.5%] in the bivalirudin group vs 25 [2.3%] in the control group; RR, 1.10; 95% CI, 0.64-1.88; P = .73). Conclusions and Relevance In patients with STEMI who were being transported for primary percutaneous coronary intervention, treatment with bivalirudin or with heparin with optional use of GPI resulted in similar 1-year mortality. The reduced composite end point of death and/or major bleeding at 30 days in the bivalirudin arm of the EUROMAX trial did not translate into reduced cardiovascular or all-cause death at 1 year. Trial Registration clinicaltrials.gov Identifier: NCT01087723

A prospective, randomized, open-label trial of 6-month versus 12-month dual antiplatelet therapy after drug-eluting stent implantation in ST-elevation myocardial infarction: Rationale and design of the “DAPT-STEMI trial”

BACKGROUND The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with second-generation drug eluting stents (DESs) is unclear. Because prolonged DAPT is associated with higher bleeding risk and health care costs, establishing optimal DAPT duration is of paramount importance. No other randomized controlled trials have evaluated the safety of shorter DAPT duration in ST-elevation myocardial infarction (STEMI) patients treated with second-generation DESs and latest P2Y12 platelet receptor inhibitors. HYPOTHESIS Six months of DAPT after Resolute Integrity stent implantation in STEMI patients is not inferior to 12 months of DAPT in clinical outcomes. STUDY DESIGN The Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation In ST-elevation Myocardial Infarction (DAPT-STEMI) trial is a randomized, multicenter, international, open-label trial designed to examine the safety (noninferiority) of 6-month DAPT after Resolute Integrity stent implantation in STEMI patients compared with 12-month DAPT. Event-free patients on DAPT at 6month will be randomized (1:1 fashion) between single (aspirin only) versus DAPT for an additional 6 months and followed until 2 years after primary percutaneous coronary intervention. The primary end point is a patient-oriented composite endpoint of all-cause mortality, any myocardial infarction, any revascularization, stroke, and major bleeding (net adverse clinical events [NACE]) at 18 months after randomization. To achieve a power of 85% for a noninferiority limit of 1.66, a total of 1100 enrolled patients are required. SUMMARY The DAPT-STEMI trial aims to assess in STEMI patients treated with second-generation DESs whether discontinuation of DAPT after 6 months of event-free survival is noninferior to routine 12-month DAPT.