Brady-arrhythmias requiring permanent pacemaker implantation during and after staged Fontan palliation.

BACKGROUND: Brady-arrhythmia requiring pacemaker implantation remains one of the Fontan-specific complications before and after total cavopulmonary connection. METHODS: A retrospective analysis of 620 patients who underwent total cavopulmonary connection between 1994 and 2021 was performed to evaluate the incidence of brady-arrhythmia and the outcomes after pacemaker implantation. Factors associated with the onset of brady-arrhythmia were identified. RESULTS: A total of 52 patients presented with brady-arrhythmia and required pacemaker implantation. Diagnosis included 16 sinus node dysfunctions, 29 atrioventricular blocks, and 7 junctional escape rhythms. Pacemaker implantation was performed before total cavopulmonary connection (n = 16), concomitant with total cavopulmonary connection (n = 8), or after total cavopulmonary connection (n = 28, median 1.8 years post-operatively). Freedom from pacemaker implantation following total cavopulmonary connection at 10 years was 92%. Twelve patients needed revision of electrodes due to lead dysfunction (n = 9), infections (n = 2), or dislocation (n = 1). Lead energy thresholds were stable, and freedom from pacemaker lead revision at 10 years after total cavopulmonary connection was 78%. Congenitally corrected transposition of the great arteries (odds ratio: 6.6, confidence interval: 2.0-21.5, p = 0.002) was identified as a factor associated with pacemaker implantation before total cavopulmonary connection. Pacemaker rhythms for Fontan circulation were not a risk factor for survival (p = 0.226), protein-losing enteropathy/plastic bronchitis (p = 0.973), or thromboembolic complications (p = 0.424). CONCLUSIONS: In our cohort of patients following total cavopulmonary connection, freedom from pacemaker implantation at 10 years was 92% and stable atrial and ventricular lead energy thresholds were observed. Congenitally corrected transposition of the great arteries was at increased risk for pacemaker implantation before total cavopulmonary connection. Having a pacemaker in the Fontan circulation had no adverse effect on survival, protein-losing enteropathy/plastic bronchitis, or thromboembolic complications.

Tachyarrhythmia after the total cavopulmonary connection: incidence, prognosis, and risk factors.

OBJECTIVE: The purpose of this study is to evaluate the incidence and outcomes regarding tachyarrhythmia in patients after total cavopulmonary connection. METHODS: A retrospective analysis of 620 patients who underwent total cavopulmonary connection between 1994 and 2021 at our institution was performed. Incidence of tachyarrhythmia was depicted, and results after onset of tachyarrhythmia were evaluated. Factors associated with the onset of tachyarrhythmia were identified. RESULTS: A total of 52 (8%) patients presented with tachyarrhythmia that required medical therapy. Onset during hospital stay was observed in 27 patients, and onset after hospital discharge was observed in 32 patients. Freedom from late tachyarrhythmia following total cavopulmonary connection at 5, 10, and 15 years was 97, 95, and 91%, respectively. The most prevalent late tachyarrhythmia was atrial flutter (50%), followed by supraventricular tachycardia (25%) and ventricular tachycardia (25%). Direct current cardioversion was required in 12 patients, and 7 patients underwent electrophysiological study. Freedom from Fontan circulatory failure after onset of tachyarrhythmia at 10 and 15 years was 78% and 49%, respectively. Freedom from occurrence of decreased ventricular systolic function after the onset of tachyarrhythmia at 5 years was 85%. Independent factors associated with late tachyarrhythmia were dominant right ventricle (hazard ratio, 2.52, p = 0.02) and weight at total cavopulmonary connection (hazard ratio, 1.03 per kilogram; p = 0.04). Type of total cavopulmonary connection at total cavopulmonary connection was not identified as risk. CONCLUSIONS: In our large cohort of 620 patients following total cavopulmonary connection, the incidence of late tachyarrhythmia was low. Patients with dominant right ventricle and late total cavopulmonary connection were at increased risk for late tachyarrhythmia following total cavopulmonary connection.

Mid-Term Electrical Remodeling after Percutaneous Atrial Septal Defect Closure with GCO Device in a Pediatric Population.

BACKGROUND AND AIM: The GORE® CARDIOFORM (GCO) septal occluder is an atrial septal defect/patent foramen ovale closure device with theoretical advantages over other commercialized devices thanks to its softness and anatomical compliance. Our aim was to evaluate the short- and medium-term electrocardiographic changes after percutaneous ASD closure with GCO in a pediatric population. METHODS: We enrolled 39 patients with isolated ASD submitted to trans-catheter closure from January 2020 to June 2021. ECG was performed before, at 24 h and 6 months after the procedure. P wave dispersion, QTc and QTc dispersion were calculated. ECG Holter was recorded at 6 months after implantation. RESULTS: Patients' age and body surface area (BSA) were 8.2 ± 4.2 years and 1.0 ± 0.3 m2 respectively. At the baseline, mean P wave dispersion was 40 ± 15 msec and decreased at 24 h (p < 0.002), without any further change at 6 months. At 24 h, PR conduction and QTc dispersion significantly improved (p = 0.018 and p < 0.02 respectively), while the absolute QTc value considerably improved after 6 months. During mid-term follow-up, QTc dispersion remained stable without a significant change in PR conduction. The baseline cardiac frequency was 88.6 ± 12.6 bpm, followed by a slight reduction at 24 h, with a further amelioration at 6 months after the procedure (87.3 ± 14.2, p = 0.9 and 81.0 ± 12.7, p = 0.009, respectively). After device deployment, two patients developed transient, self-limited junctional rhythm. One of them needed a short course of Flecainide for atrial ectopic tachycardia. No tachy/brady-arrhythmias were recorded at the 6-month follow-up. ASD closure resulted in a marked decrease in right heart volumes and diameters at 6 months after percutaneous closure. CONCLUSIONS: Percutaneous ASD closure with the GCO device results in significant, sudden improvement of intra-atrial, atrio-ventricular and intraventricular electrical homogeneity. This benefit persists unaltered over a medium-term follow-up. These electrical changes are associated with a documented positive right heart volumetric remodeling at mid-term follow-up.

Development of Weight and Height Age z-Score after Total Cavopulmonary Connection.

OBJECTIVE: We aimed to analyze somatic growth of patients after total cavopulmonary connection (TCPC) as well as to identify factors influencing postoperative catch-up growth. METHODS: A total of 309 patients undergoing TCPC at 4 years old or less between 1994 and 2021 were included. Weight for age z-score (WAZ) and height for age-z-score (HAZ) at TCPC and at postoperative time between 1 and 3 years were calculated. Factors influencing somatic growth were analyzed. RESULTS: Most frequent diagnosis and initial palliation were hypoplastic left heart syndrome (HLHS) (34%) and the Norwood procedure (51%), respectively. Median age and weight at TCPC were 2.0 (IQR: 1.7-2.5) years and 11.3 (10.5-12.7) kg, respectively. Median 519 days after TCPC, a significant increase in WAZ (-0.4 to -0.2, p < 0.001) was observed, but not in HAZ (-0.6 to -0.6, p = 0.38). Older age at TCPC (p < 0.001, odds ratio [OR]: 2.6) and HLHS (p = 0.007, OR: 2.2) were risks for low WAZ after TCPC. Older age at TCPC (p = 0.009, OR: 1.9) and previous Norwood procedure (p = 0.021, OR: 2.0) were risks for low HAZ after TCPC. Previous bidirectional cavopulmonary shunt (BCPS) was a protective factor for both WAZ (p = 0.012, OR: 0.06) and HAZ (p = 0.028, OR: 0.30) at TCPC. CONCLUSION: In patients undergoing TCPC at the age of 4 years or less, a significant catch-up growth was observed in WAZ after TCPC, but not in HAZ. Previous BCPS resulted to be a protective factor for a better somatic development at TCPC. HLHSs undergoing Norwood were considered as risks for somatic development after TCPC.

Rescue atrial septal defect closure with the new GORE® cardioform atrial septal defect occluder.

Atrioventricular block (AVB) is an infrequent but life-threatening complication of transcatheter closure of atrial septal defect (ASD), accounting for 0.1%-6.2% of cases in large series. It has been related to unfavorable defect anatomy as well as size and intrinsic stiffness of the occluding device. In this setting, the new GORE® cardioform ASD occluder (GCA) device could be an appealing technical advance in ASD treatment. We report a case of complete AVB after ASD closure with an Amplatzer septal occluding (Abbott, Plymouth MN, USA) device successfully treated by its percutaneous retrieval and "rescue" deployment of GCA device few months later.

Transcatheter closure of "Surgical" ostium secundum atrial septal defects with GORE® Cardioform ASD Occluder.

OBJECTIVE: To evaluate the GORE® Cardioform ASD Occluder (GCA)(WL Gore & Associates) device for closure of ostium secundum atrial septal defects (ASDs) with predicted indication for surgical correction. BACKGROUND: Closure of large ASD in small children by transcatheter approach is still challenging. This study evaluated the results of GCA in this subset of patients in a tertiary referral center. METHODS: Between January 2020 and March 2022, 97 children underwent transcatheter ASD closure at our Institution. Of them, 38 had a large defect (diameter/weight > 1.2 or diameter/body surface area > 20 mm/m2 ), predicted suitable for surgery and underwent closure with GCA. Procedure results and midterm outcome are reported. RESULTS: Patients' age and weight were 5.5 ± 1.5 years and 19.7 ± 4.7 kg, respectively. Absolute and relative ASD size was 21.5 ± 3.6 mm, 1.1 ± 0.2 mm/kg, and 27.7 ± 4.6 mm/m2 , respectively, resulting in QP/QS of 2.0 ± 0.8. Three patients were sent to surgery after balloon sizing. Four of the remaining 35 patients who underwent device deployment, needed rescue or elective surgery due to device embolization (n = 1), device instability (n = 2) or new-onset tricuspid valve regurgitation (n = 1). Procedure feasibility was 88.6%. Major complications were recorded in two patients (5.7%). Minor complications were recorded in five patients (14.3%). Complete closure at discharge was 90.3% (28/31 pts) rising to 100% at the last follow-up evaluation. Wireframe fracture rate at the 6 months examination was 52%, without clinical and instrumental consequences. CONCLUSIONS: Percutaneous treatment with GCA device is effective and safe in a high percentage of ASD children with predicted indications for surgical correction.

Transcatheter Treatment of Ascending Aorta Pseudoaneurysm Guided by 3D-Model Technology.

Ascending aorta pseudoaneurysm is a rare but potentially life-threatening complication of atherosclerosis, infections, chest trauma, transcatheter or surgical interventions. Due to high surgical risk, percutaneous closure is considered a valuable cost-effective therapeutic alternative. In this setting, 3D printing technology is emerging as a powerful tool to plan transcatheter repair. (Level of Difficulty: Advanced.).

Role of cardiac MRI in the prediction of pre-Fontan end-diastolic ventricular pressure.

BACKGROUND: Growing evidence has emphasised the importance of ventricular performance in functionally single-ventricle patients, particularly concerning diastolic function. Cardiac MRI has been proposed as non-invasive alternative to pre-Fontan cardiac catheterisation in selected patients. AIM OF THE STUDY: To identify clinical and cardiac magnetic resonance predictors of high pre-Fontan end-diastolic ventricular pressure. METHOD: In a retrospective single-centre study, 38 patients with functionally univentricular heart candidate for Fontan intervention, who underwent pre-Fontan cardiac catheterisation, beside a comprehensive cardiac MRI, echocardiographic, and clinical assessment were included. Medical and surgical history, cardiac magnetic resonance, cardiac catheterisation, echocardiographic, and clinical data were recorded. We investigated the association between non-invasive parameters and cardiac catheterisation pre-Fontan risk factors, in particular with end-diastolic ventricular pressure. Moreover, the impact of conventional invasive pre-Fontan risk factor on post-operative outcome as also assessed. RESULTS: Post-operative complications were associated with higher end-diastolic ventricular pressure and Mayo Clinic indexes (p < 0.01 and p = 0.05, respectively). At receiver operating characteristic curve analysis end-diastolic ventricular pressure ≥ 10.5 mmHg predicted post-operative complications with a sensitivity of 75% and specificity of 88% (AUC: 0.795, 95% CI 0.576;1.000, p < 0.05). At multivariate analysis, both systemic right ventricle (OR: 23.312, 95% CI: 2.704-200.979, p < 0.01) and superior caval vein indexed flow (OR: 0.996, 95% CI: 0.993-0.999, p < 0.05) influenced end-diastolic ventricular pressure ≥ 10.5 mmHg. CONCLUSIONS: A reduced superior caval vein flow, evaluated at cardiac magnetic resonance, is associated with higher end-diastolic ventricular pressure a predictor of early adverse outcome in post-Fontan patients.

GORE® Cardioform ASD Occluder experience in transcatheter closure of "complex" atrial septal defects.

OBJECTIVE: To evaluate the GORE® Cardioform ASD Occluder (GCO) (WL Gore & Associates, Flagstaff, AZ) device for "complex" atrial septal defects (ASD) closure. BACKGROUND: Transcatheter ASD closure is still challenging in "complex" clinical/anatomic settings. This study evaluated the results of GCO in closure of "complex" ASD in a tertiary referral center. METHODS: Between January 2020 and March 2021, 72 patients with significant ASD were submitted to transcatheter closure with GCO at our Institution. Based on clinical/anatomic characteristics, they were classified as "complex" (n = 36, Group I) or "simple" (n = 36, Group II). We considered as "complex", defects with rim deficiency (< 5 mm) other than antero-superior, relatively large (diameter/patient weight > 1.2 or diameter/patient BSA > 20 mm/m2 ) or within a multifenestrated septum. Procedure results and early outcome were compared between the groups. RESULTS: Absolute and relative ASD size (20 ± 4 vs. 15 ± 3 mm, p < 0.0001; 0.9 ± 0.3 vs. 0.4 ± 0.2 mm/kg, p < 0.0001; 23 ± 7 vs. 12 ± 5 mm/m2 , p < 0.0001), QP/QS (2.0 ± 0.8 vs. 1.4 ± 0.3, p < 0.001), procedure and fluoroscopy times (73 ± 36 vs. 43 ± 21 min, p < 0.0001; 16 ± 9 vs. 9 ± 4 min, p < 0.0001, procedure feasibility (94.4 vs. 100%, p < 0.0001) and overall complication rate (13.9 vs. 0%, p < 0.0001) were significantly different between the groups. Successful closure of "surgical" ASDs was achieved in 92% of cases. Complete closure at last follow-up evaluation did not significantly differ between the groups (97.1 vs. 100%, p = NS), as was wireframe fractures rate (49.1% in the overall population), without clinical, EKG and echocardiographic consequences. CONCLUSIONS: Percutaneous treatment with GCO device is effective and safe in high percentage of "complex" ASDs.

3D model-guided transcatheter closure of ascending aorta pseudoaneurysm with the novel Amplatzer Trevisio intravascular delivery system.

Ascending aorta pseudoaneurysm (AAP) is a rare but life-threatening complication of atherosclerosis, endocarditis, chest trauma, transcatheter or cardio-thoracic procedures. Since surgical repair is burdened by high morbidity and mortality, percutaneous closure is nowadays considered a valuable cost-effective therapeutic alternative. Due to unpredictability and complexity of local anatomy, no standardized technique and device are advised. In this setting, 3D printing technology could significantly help in planning trans-catheter approach. This article reports on a 3D printed model-guided percutaneous closure of a huge AAP using an Amplatzer Septal Occluder (Abbott, Plymouth MN) implanted by the recently commercialized Amplatzer Trevisio Intravascular Delivery System.

Transcatheter Treatment of "Complex" Aortic Coarctation Guided by Printed 3D Model.

The transcatheter approach is nowadays considered a cost-effective alternative to surgery in adults with "complex" aortic coarctation. The printed 3D model was crucial in planning transcatheter treatment of a complex case of postsurgical aortic re-coarctation, due to coexistence of transverse aortic arch stenosis and pseudoaneurysm as well as aneurysm of the descending aorta. (Level of Difficulty: Advanced.).

The different surgical impact of the superior cavoatrial incision in children and adults.

INTRODUCTION: The single- and double-patch repairs are undoubtedly the most commonly used techniques for the surgical management of partial anomalous pulmonary venous connection associated with sinus venosus atrial septal defect. The aim of this study was to retrospectively compare early and long-term surgical outcomes in paediatric and adult patients, focusing in particular on the occurrence of ectopic atrial rhythm. MATERIAL AND METHODS: Seventy patients (male: 38, 54.2%) underwent surgical repair for partial anomalous pulmonary venous connection with sinus venosus atrial septal defect. Forty-nine patients (70%) underwent surgical repair in paediatric age (<16 years old), while 21 of (30%) patients were operated in adulthood. Thirty patients (42.8%) underwent single-patch repair and 39 patients (55.7%) underwent double-patch repair. In only one patient, the Warden procedure was performed (1.4%). Median follow-up time was 52 months (IQ 15.1-113). RESULTS: The type of surgical technique didn't affect the incidence of ectopic atrial rhythm (26.6% in single-patch group and 25.6% in double-patch groups, p = 0.9). At long-term follow-up, ectopic atrial rhythm, as an expression of sinoatrial node disturbance, was however significantly more frequent in the paediatric population (28.8% paediatric group and 4.7% adult group, p = 0.02). CONCLUSIONS: The higher incidence of ectopic atrial rhythm in children is probably related to the closer position of the sinus node to the superior cavoatrial incision, which makes irreversible iatrogenic traumatism more likely to occur. Surgical techniques that avoid any manipulation on the superior cavoatrial junction should, therefore, be preferred for children undergoing partial anomalous pulmonary venous connection repair.

Trans-catheter atrial septal defect closure with the new GORE® Cardioform ASD occluder: First European experience.

BACKGROUND: This perspective, observational study evaluated safety and efficacy of the GORE® Cardioform ASD Occluder (WL Gore & Associates, Flagstaff, AZ), compliant and potentially innovative prosthesis recently approved for closure of ostium secundum atrial septal defects (ASD). METHODS: Between January and June 2020, 43 unselected patients with -significant ASD were submitted to trans-catheter closure with GORE® Cardioform ASD Occluder at two high-volume Italian Pediatric Cardiology centers. Primary endpoints were procedural success and safety. Secondary endpoints were closure rate and clinical safety at 1-month follow-up. RESULTS: Patients' age and weight were 8.2 ± 3.9 years (range 3-21, median 9.9) and 29.6 ± 15.3 kg (range 16-57, median 33.3), respectively. ASD diameter was 16.6 ± 4.5 mm (median 10), resulting in QP/QS of 1.7 ± 0.7 (median 1.6). Seventeen pts. (39.5%) were considered "surgical" candidates due to challenging septum morphology, ASD rim deficiency or ASD diameter/patient weight ratio ≥ 1.2. Device placement was successfully achieved in all but one patient (97.7%), in whom it embolized early after deployment, resulting in rescue surgical repair. No cross-over with different devices was recorded. Median procedure and fluoroscopy times were 40 and 6.8 min, respectively. Major adverse events were recorded in 7.0% (3 pts). Complete closure rate was 78.5% at discharge, rising to 92.9% (39/42 pts) at 1 month evaluation, without cardiac or extra-cardiac adverse events. "Challenging" procedures were more time-consuming but as effective and safe as the "simple" ones. CONCLUSIONS: The GORE® Cardioform ASD Occluder device was highly effective and versatile in closure of ASDs with different anatomy and size, even in challenging settings.

3D model-guided transcatheter closure of left ventricular pseudoaneurysm: a case series.

Left ventricular pseudoaneurysm (LVPsA) is a rare complication of myocardial infarction, cardiac surgery, chest trauma, infection or transcatheter interventions. It may cause arrhythmias, mass effect, thromboembolism and life-threatening rupture. The transcatheter approach is nowadays considered a cost-effective alternative to surgery. In this setting, 3D printing could be an emerging, powerful tool to plan transcatheter closure and choose the best occluding device. This study reports on three cases of complex LVPsA successfully treated by transcatheter device implantation guided by printed 3D heart models.

Cardiac CT angiography: normal and pathological anatomical features-a narrative review.

The normal and pathological anatomy of the heart and coronary arteries are nowadays widely developed topics and constitute a fundamental part of the cultural background of the radiologist. The introduction of cardiac ECG-gated synchronized CT scanners with an ever-increasing number of detectors and with increasingly high structural characteristics (increase in temporal resolution, increase in contrast resolution with dual-source, dual energy scanners) allows the virtual measurement of anatomical in vivo structures complying with heart rate with submillimetric precision permitting to clearly depict the normal anatomy and follow the pathologic temporal evolution. Accordingly to these considerations, cardiac computed tomography angiography (CCTA) asserts itself as a gold standard method for the anatomical evaluation of the heart and permits to evaluate, verify, measure and characterize structural pathological alterations of both congenital and acquired degenerative diseases. Accordingly, CCTA is increasingly used as a prognostic model capable of modifying the outcome of diseased patients in planning interventions and in the post-surgical/interventional follow-up. The profound knowledge of cardiac anatomy and function through highly detailed CCTA analysis is required to perform an efficient and optimal use in real-world clinical practice.

XLIMus drug eluting stent: A randomIzed controlled Trial to assess endothelialization. The XLIMIT trial.

BACKGROUND: Thin strut 3rd generation drug eluting stents offer the potential advantage over the previous generation of better technical performance and reduced neointimal proliferation parameters, which are linked to mid and late term device failure. AIM: To evaluate the performance of the Xlimus sirolimus-eluting stent (SES) against the Synergy everolimus-eluting stent (EES) in terms of device reendothelialization in patients undergoing PCI for coronary artery disease (CAD). METHODS: XLIMIT is a multicenter randomized controlled trial targeting 180 patients requiring percutaneous coronary interventions (PCI). Patients will be treated with Xlimus SES or Synergy EES implantation and randomization will be performed in a 2:1 ratio. The primary endpoint will be the reendothelialization grade of the Xlimus stent in terms of strut coverage and neointimal hyperplasia volume as compared to Synergy. Secondary endpoints will be represented by clinical and procedural outcomes. The first patient was enrolled on February 2019. CONCLUSIONS: A clearer understanding of the endothelialization process of new generation DES could significantly impact the treatment with dual antiplatelet therapy in the future. Moreover, although not powered for clinical end-points, the XLIMIT trial will provide randomized data in a population with minimal exclusion criteria. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03745053. Registered on November 19, 2018.

[Epidemiology of stroke and cerebral protection in patients undergoing transcatheter aortic valve replacement]. / Epidemiologia e prevenzione dell'ictus in pazienti sottoposti ad impianto transcatetere di valvola aortica.

The introduction into clinical practice of transcatheter aortic valve implantation (TAVI) has led to a significant change in the therapeutic paradigm for patients with valvular aortic stenosis. However, in parallel with the benefits obtained in prognosis and quality of life, an inherent risk of major cerebral thromboembolic events has been observed. In different studies this risk has been estimated between 2% and 6%. In order to reduce the incidence of cerebrovascular accidents during TAVI, several brain protection systems have been developed but, to date, none has obtained sufficient clinical evidence to be implemented on a large scale, and they are therefore used only in selected cases. Furthermore, periprocedural drug therapy and follow-up are still the subject of extensive discussion in the scientific community. This paper reviews the topic of stroke prevention in patients undergoing TAVI for both the periprocedural and postprocedural aspects.

Drug-coated balloon: Long-term outcome from a real world three-center experience.

OBJECTIVES: In-stent restenosis (ISR) and diffuse small vessel disease still represent challenging subsets for percutaneous coronary interventions, also in the new-generation DES era. We aim at reporting on the long-term clinical outcome of drug-coated balloons (DCB) in all-comers population. METHODS: Consecutive patients treated with DCB between January 2011 and December 2014 were retrospectively studied in three centers of northern Italy. The measured end-points were cardiac death, myocardial infarction (MI), target lesion revascularization (TLR), and major adverse cardiac events (MACE) defined as combination of cardiac death, MI, and TLR. RESULTS: We included 143 patients. Of the 167 lesions treated, 41 (24.5%) were de novo lesions in small coronary vessels (<2.5 mm) and 126 (75.4%) were ISR. Among ISR lesions, 78.5% were DES-ISR, 32.5% were focal, 15.8% multifocal, 30.1% diffuse, 18.2% proliferative, and 3.1% were total occlusions. Procedural success was achieved in 94.6% of cases. Overall survival free from MACEs was 91.6% at 12 months, and 75.3% at 48 months, with a total of 3 cardiac deaths, 8 MI, and 27 TLR. No thrombotic event occurred in the treated segments. There were no differences in MACESs between the ISR and de novo lesions groups. At multivariate analysis, acute coronary syndromes, previous MI, previous surgical revascularization, peripheral arterial disease and diabetes were independent predictors of MACEs at long-term follow-up. CONCLUSIONS: DCB proved a valid revascularization strategy in an all-comers population of patients with ISR and de novo lesions in small vessels, with an acceptable rate of cardiac events up to 48 months follow-up.