Immunomodulation Therapies for Atherosclerosis: The Past, the Present, and the Future.

Atherosclerotic cardiovascular disease is the most common cause of morbidity and death worldwide. Recent studies have demonstrated that this chronic inflammatory disease of the arterial wall can be controlled through the modulation of immune system activity. Many patients with cardiovascular disease remain at elevated risk of recurrent events despite receiving current, state-of-the-art preventive medical treatment. Much of this residual risk is attributed to inflammation. Therefore, finding new treatment strategies for this category of patients became of common interest. This review will discuss the experimental and clinical data supporting the possibility of developing immune-based therapies for lowering cardiovascular risk, explicitly focusing on vaccination strategies.

Pacemaker dependency and conduction system recovery following transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI)-related conduction system disorders are dynamic and may resolve over time. The purpose of this study was to investigate predictive factors of PM dependency among patients receiving permanent PM implantation after TAVI. METHODS: We included 37 consecutive patients who underwent PPM implantation within six days after TAVI and who completed a 12-month follow-up. Patients were divided into two groups according to PPM dependency at follow-up: PPM-dependent group and non-PPM-dependent group. Device follow-ups were performed at one, six and 12 months. RESULTS: There were no significant differences in either baseline clinical characteristics or procedural data and results. Analysis of baseline ECGs showed a statistical difference in PR interval (200.1±17.2 ms in the PPM-dependent group vs. 175±23.3 ms in the non PPM-dependent group [P=0,003]) and in the presence of RBBB (four patients in the PPM-dependent group vs. no patients in the non PPM-dependent group [P=0.02]) as well as QRS duration (117.3±27.4 ms in the PPM-dependent group and 99±18.3 msec in the non PPM-dependent group [P=0.04]). CONCLUSIONS: The rate of PPM dependency was significantly reduced at 12-month follow-up: from 62,2% at the time of implantation to 35,1%. PR interval and RBBB were the most important predictive factors for PPM dependency. Persistent AVB and alternating BBB were prevalent in the PPM-dependent group. In the absence of persistent AVB or alternating BBB, we suggest that patients without long PR interval and RBBB at baseline ECG be carefully evaluated before permanent PM implantation, as conduction system recovery is possible.

Holographic mixed reality for planning transcatheter aortic valve replacement.

BACKGROUND: Using three-dimensional (3D) modalities for optimal pre-procedure planning in transcatheter aortic valve replacement (TAVR) is critical for procedural success. However, current methods rely on visualizing images on a two-dimensional screen, using shading and colors to create the illusion of 3D, potentially impeding the accurate comprehension of the actual anatomy structures. In contrast, a new Mixed Reality (MxR) based software enables accurate 3D visualization, imaging manipulation, and quantification of measurements. AIMS: The study aims to evaluate the feasibility, reproducibility, and accuracy of dimensions of the aortic valve complex as measured with a new holographic MxR software (ARTICOR®, Artiness srl, Milano, Italy) compared to a widely used software for pre-operative sizing and planning (3mensio Medical Imaging BV, Bilthoven, The Netherlands). METHODS: This retrospective, observational, double-center study enrolled 100 patients with severe aortic stenosis who underwent cardiac computed tomography (CCT) before TAVR. The CCT datasets of volumetric aortic valve images were analyzed using 3Mensio and newly introduced MxR-based software. RESULTS: Ninety-eight percent of the CCT datasets were successfully converted into holographic models. A higher level of agreement between the two software systems was observed for linear metrics (short, long, and average diameter). In comparison, agreement was lower for area, perimeter, and annulus-to-coronary ostia distance measurements. Notably, the annulus area, annular perimeter, left ventricular outflow tract (LVOT) area, and LVOT perimeter were significantly and consistently smaller with the MxR-based software compared to the 3Mensio. Excellent interobserver reliability was demonstrated for most measurements, especially for direct linear measurements. CONCLUSIONS: Linear measurements of the aortic valve complex using MxR-based software are reproducible compared to the standard CCT dataset analyzed with 3Mensio. MxR-based software could represent an accurate tool for the pre-procedural planning of TAVR.

Effect of acute CORticosteroids on conduction defects after Transcatheter Aortic Valve Implantation: the CORTAVI study.

AIMS: Conduction abnormalities, requiring a permanent pacemaker (PPM), are the most common electrical complications after transcatheter aortic valve implantation (TAVI). The exact mechanism for conduction system defects is not yet clear. The local inflammatory process and edema are thought to play a role in the development of electrical disorders. Corticosteroids are effective anti-inflammatory and antiedematous agents. We aim to investigate the potential protective effect of corticosteroids on conduction defects after TAVI. METHODS: This is a retrospective study of a single center. We analyzed 96 patients treated with TAVI. Thirty-two patients received oral prednisone 50 mg for 5 days after the procedure. This population was compared with the control group. All patients were followed up after 2 years. RESULTS: Of the 96 patients included, 32 (34%) were exposed to glucocorticoids after TAVI. No differences in age, preexisting right bundle branch block or left bundle branch block, or valve type were seen among patients exposed to glucocorticoids versus those who were unexposed. We observed no significant differences between the two groups in the overall frequency of new PPM implantations during hospitalization (12% vs. 17%, P  = 0.76). The incidence of atrioventricular block (AVB) (STx 9% vs. non-STx 9%, P  = 0.89), right bundle branch block (STx 6% vs. non-STx 11%, P  = 0.71), and left bundle branch block (STx 34% vs. non-STx 31%, P  = 0.9) was not significantly different between the STx and non-STx groups. At 2 years after TAVI, none of the patients had implanted PPM or had severe arrhythmias documented by 24-h Holter ECG or cardiac examination. CONCLUSION: Oral prednisone treatment does not appear to significantly reduce the incidence of AVB requiring acute PPM implantation after TAVI.

Advances in Imaging for Tricuspid Transcatheter Edge-to-Edge Repair: Lessons Learned and Future Perspectives.

Severe tricuspid valve (TV) regurgitation (TR) has been associated with adverse long-term outcomes in several natural history studies, but isolated TV surgery presents high mortality and morbidity rates. Transcatheter tricuspid valve interventions (TTVI) therefore represent a promising field and may currently be considered in patients with severe secondary TR that have a prohibitive surgical risk. Tricuspid transcatheter edge-to-edge repair (T-TEER) represents one of the most frequently used TTVI options. Accurate imaging of the tricuspid valve (TV) apparatus is crucial for T-TEER preprocedural planning, in order to select the right candidates, and is also fundamental for intraprocedural guidance and post-procedural follow-up. Although transesophageal echocardiography represents the main imaging modality, we describe the utility and additional value of other imaging modalities such as cardiac CT and MRI, intracardiac echocardiography, fluoroscopy, and fusion imaging to assist T-TEER. Developments in the field of 3D printing, computational models, and artificial intelligence hold great promise in improving the assessment and management of patients with valvular heart disease.

Transcatheter aortic valve implantation results are not superimposable to surgery in patients with aortic stenosis at low surgical risk.

BACKGROUND: The aim of this meta-analysis was to compare the impact of transcatheter aortic valve implantation (TAVI) vs. surgical aortic valve replacement (SAVR) in patients with severe aortic valve stenosis (AS) at low surgical risk. METHODS: All randomized controlled trials (RCTs) and observational studies (Obs) published from January 2014 until March 31st, 2020 were retrieved through the PubMed computerized database and at the site https://www. CLINICALTRIALS: com. The relative risk (RR) with the 95% confidence interval (CI) was used to evaluate the effect of the intervention under comparison. The primary endpoints were all-cause 30-day mortality and 1-year mortality. The 30-day safety endpoints were: stroke, acute kidney injury stage 2 or 3, major bleeding, moderate/severe paravalvular leak, need for new permanent pacemaker (PM) implantation. RESULTS: After detailed review 9 studies, related to 4 RCTs and 5 Obs, were selected. The overall analysis of RCTs plus Obs showed a significantly lower 30-day mortality for TAVI (RR = 0.55; 95% CI 0.45-0.68, p < 0.00001; I2 = 0%). However, an increased risk of new PM implantation (RR = 2.87; 95% CI 2.01-3.67, p < 0.00001, I2 = 0%) and of paravalvular leak (RR = 7.28; 95% CI 3.83-13.81, p < 0.00001, I2 = 0%) was observed in TAVI compared to SAVR. On the contrary, a lower incidence of major bleeding (RR = 0.38; 95% CI 0.27-0.54, p < 0.00001, I2 = 0%) and of acute kidney injury was observed (RR = 0.33; 95% CI 0.19-0.56, p < 0.0001, I2 = 0%) in TAVI. CONCLUSIONS: TAVI and SVAR in the treatment of AS in the patients at low surgical risk are not superimposable. In particular, if 30-day and 1-year mortality, major bleeding and acute kidney injury were significantly lower for TAVI, the need of new PM implantation and paravalvular leak were significantly lower in SAVR. Consequently, we suggest the need of more trials to evaluate the effectiveness of TAVI as routine therapeutic procedure in the treatment of patients with low surgical risk AS.

Current Options and Future Perspectives in the Treatment of Dyslipidemia.

Low-density lipoprotein cholesterol (LDL-C) plays a crucial role in the development of atherosclerosis. Statin therapy is the standard treatment for lowering LDL-C in primary and secondary prevention. However, some patients do not reach optimal LDL-C target levels or do not tolerate statins, especially when taking high doses long-term. Combining statins with different therapeutic approaches and testing other new drugs is the future key to reducing the burden of cardiovascular disease (CVD). Recently, several new cholesterol-lowering drugs have been developed and approved; others are promising results, enriching the pharmacological armamentarium beyond statins. Triglycerides also play an important role in the development of CVD; new therapeutic approaches are also very promising for their treatment. Familial hypercholesterolemia (FH) can lead to CVD early in life. These patients respond poorly to conventional therapies. Recently, however, new and promising pharmacological strategies have become available. This narrative review provides an overview of the new drugs for the treatment of dyslipidemia, their current status, ongoing clinical or preclinical trials, and their prospects. We also discuss the new alternative therapies for the treatment of dyslipidemia and their relevance to practice.

Combined MitraClip and Left Atrial Appendage Occlusion: Is It Still a Utopia?

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting 32 million individuals worldwide, particularly the elderly. It is the main cause of ischemic strokes. Oral anticoagulation (OAC) is the gold standard strategy for stroke prevention. Still, there is a not negligible share of patients who have contraindications to this therapy, more frequently due to an increased risk of bleeding. AF is often associated with moderate-severe mitral regurgitation (MR), the second most frequent valvular disease in elderly patients. Data from the literature reported that more than half of patients with severe mitral regurgitation are not suitable candidates for cardiac surgery. Given the progressive aging of the population and the simultaneous increase in the number of patients with comorbidities, the advent of new therapeutic strategies, such as the combined approach of Left Atrial Appendage Occlusion (LAAO) and MitraClip procedure, is acquiring great interest. At present, the category of patients who may benefit from combined percutaneous therapies and the long-term risks and benefits might not have been identified. Despite the efforts of researchers, the correct selection of patients is a very important clinical need that has not yet been met to avoid committing human and financial resources to interventions that may be unnecessary. It is conceivable that the most modern and recent innovations in cardiovascular imaging, particularly three-dimensional echocardiography and new methods of volume imaging, could improve our ability to select patients appropriately. Since data in the literature are scarce, future studies will be needed to evaluate the efficacy and safety of combined MitraClip and LAA occlusion.

The Transaxillary Route as a Second Access Option in TAVI Procedures: Experience of a Single Centre.

Background: The aim of our study was to determine the feasibility and efficacy of transaxillary (TAX) TAVI in patients not eligible for the transfemoral route. Methods: This is a retrospective study of a single center. We analysed 262 patients treated with TAVI. In 17 patients (6.5%), the procedure was performed with the TAX approach. Procedural and hospital data, 30-day safety, and clinical efficacy were assessed and compared between the transfemoral and TAX groups. Results: In the TAX groups, we found a higher prevalence of men (p = 0.001), smokers (p = 0.033), and previous strokes (p = 0.02). The EUROSCORE II was higher in the TAX group (p = 0.014). The success rate of the device was 100%. TAX was associated with a longer procedure time (p = 0.001) and shorter median device time (p = 0.034) in minutes. Patients treated with TAX had a longer hospital stay (p = 0.005) and higher overall bleeding rate (p = 0.001). Peripheral neurological complications were more frequent with TAX (p = 0.001), which almost completely resolved by 30 days. Conclusions: TAX TAVI is safe and effective and should be considered as a second choice when transfemoral TAVI is not feasible due to severe comorbidities.

Lambl's excrescence in transcatheter aortic valve implantation: prevalence and risk of embolic events.

BACKGROUND: The role of aortic valve Lambl's excrescence (LEs) in determining ischemic events has not been well clarified, but they can represent a potential embolic source during procedures with catheter/device manipulation through the aortic valve. Aim of our study was to assess the prevalence of LEs and the rate of embolism in patients with aortic valve stenosis scheduled for transcatheter aortic valve implantation (TAVI). METHODS: Our population was divided into two groups, named LEs and no-LEs. In each group, the rate of cerebral embolic events was assessed, as well as other TAVI-related complications. RESULTS: In our study population 28 patients (37%) had aortic strands and 48 (63%) did not have them. A cerebral protection device was used in four patients of LEs group (14% vs. 0, P=0.03). The mean procedural time was similar in the two groups: 50±19 and 55±26 minutes (P=0.38) in LEs and no-LEs groups, respectively. The device success was achieved in 96% of LEs and 88% of no-LEs patients (P=0.37). Two patients of no-LEs group died during the procedure. Major complications were observed in both groups without any significant differences. Only one case of stroke occurred in the population without LEs (0 LEs vs. 2% no-LEs, 0.78). No cases of peripheral embolism were observed. CONCLUSIONS: In our population the observation of LEs is not uncommon. Despite the presumed high risk of embolism, we have not observed an increase in the rate of cerebral ischemic events or other TAVI related complications in patients with LEs.

Transcatheter aortic valve implantation in patients with unruptured aortic root pseudoaneurysm: an observational study.

AIMS: Unruptured aortic root pseudoaneurysm (UARP) is a rare complication of aortic valve endocarditis. Infectious spread to the valvular annulus or myocardium can cause septic complications that manifest as wall thickening, and spontaneous abscess drainage leads to pseudoaneurysm formation. We report the first patient series in which transcatheter aortic valve implantation (TAVI) using a single valve-resolved aortic valvulopathy associated with UARP was performed. METHODS: At our center, from December 2017 to October 2019, 138 patients underwent TAVI for aortic valve stenosis and/or regurgitation, 20 of whom (12 female patients, 8 male patients) had associated incidental UARP and were considered as our study population. The average age of these patients was 76.9 ±â€Š5.2 years. All patients were assessed using preprocedural and postprocedural multimodality imaging, including transthoracic echocardiography, transesophageal echocardiography, and cardiac computed tomography angiography (CCTA). RESULTS: In all cases, the final angiographic examination showed correct valve positioning with complete coverage of the false aneurysm. Post-TAVI CCTA showed presence of total or subtotal UARP thrombosis. The mean follow-up period was 17.5 months (12-23 months). During follow-up, imaging showed normal prosthetic valve function, no significant leakage (trace or mild), and complete UARP exclusion in all patients, without any complications. CONCLUSION: In conclusion, percutaneous valve positioning can simultaneously solve pseudoaneurysm complications by excluding the sac and promoting thrombosis.

Clinical and angiographical features of first episode of acute coronary syndrome in patients with human immunodeficiency virus infection.

BACKGROUND: Patients affected by the human immunodeficiency virus (HIV) show an increased risk of myocardial infarction. Clinical and angiographic features of HIV positive (HIV+) patients presenting with the first episode of an acute coronary syndrome (ACS) are not well defined in previous studies. OBJECTIVE: To demonstrate that HIV + patients with acute coronary syndrome had different features than non-HIV patients. METHODS: We identified 48 HIV + patients without previous cardiovascular events admitted to our Emergency Department with ACS diagnosis between 2012 and 2020. Clinical and angiographic characteristics were compared with a control group of 48 non-HIV consecutive patients affected by ACS as first episode. RESULTS: HIV + patients were most frequently men (87.5% vs 62.5%, p = 0.009) and younger about a decade (mean age 53.8 ± 8.2 vs 63.7 ± 11.9 years old, p < 0.0001); statistically significant hypertriglyceridemia has been found in the HIV group (178,6 ± 59,8 mg/dl vs 142,7 ± 63,7 mg/dl, p = 0.005). HIV(+) patients had a higher rate of anterior ST-elevation myocardial infarction (STEMI) (65% vs 33%, p = 0.03) and significant lesions on left anterior descending (LAD) coronary artery (83% vs 58% p = 0.01). CONCLUSIONS: HIV + patients with the first episode of ACS are generally young men with higher triglycerides and most frequently presenting with anterior STEMI and LAD involvement. The strict control of risk factors and a program for the early identification of coronary artery disease are strongly recommended in this subset of patients.

Every minute counts: in-hospital changes of left ventricular regional and global function in patients with ST-segment elevation myocardial infarction.

AIMS: The aim of our study was to assess the effects of an early percutaneous coronary intervention on changes of in-hospital left ventricular ejection fraction (LVEF) and wall motion score index (WMSI) in patients with ST-segment elevation myocardial infarction. METHODS: The study population consisted of 324 consecutive patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention, divided into two groups, according to the first medical contact (FMC)-to-reperfusion time, respectively, 90 min or less (n = 173) and more than 90 min (n = 151). Moreover, we performed a sub-analysis in the group of patients who showed at discharge an improvement in the LVEF of at least 10%. RESULTS: In both groups at baseline, patients suffered from a moderately reduced LVEF (40.88 ±â€Š8.38% in ≤90 min group vs. 40.70 ±â€Š8.98% in >90 min group; P = 0.858). A WMSI of more than 1 was recorded uniformly: 1.71 ±â€Š0.37 in patients with FMC-to-reperfusion 90 min or less and 1.72 ±â€Š0.38 in patients more than 90 min (P = 0.810). At the time of discharge, a significant improvement in LVEF (43.82 ±â€Š8.38%, P = 0.001) and WMSI (1.60 ±â€Š0.41, P = 0.009) exclusively emerged in the 90 min or less group. Furthermore, we identified 105 patients who experienced an improvement in the LVEF of at least 10% compared with baseline values. In these patients FMC-to-reperfusion and total ischemic time resulted as significantly shorter, when compared with patients with LVEF improvement of less than 10%. CONCLUSION: Our study confirms and reinforces the concept that reducing the duration of the time between FMC and reperfusion, as well as the total ischemic time influences a positive recovery of left ventricular global and regional function during in-hospital stay.

A rare case of a giant circumflex coronary artery aneurysm 10 years after bentall surgery.

In this paper, we describe a rare case of coronary artery aneurysms occasionally found on a pre interventional Coronary Computed Tomography Angiography performed on a 67-year-old man with a history of aneurysm of the ascending aorta previously treated with Bentall surgery, who arrived at our hospital to have a percutaneous valve-in-valve implantation procedure. Even though the patient was considered not eligible for the procedure, due to his many comorbidities, and conservatively managed, at 1-year followup his angiographic condition remained stable.

Who Has Seen Patients With ST-Segment-Elevation Myocardial Infarction? First Results From Italian Real-World Coronavirus Disease 2019.

Background After the coronavirus disease 2019 outbreak, social isolation measures were introduced to contain infection. Although there is currently a slowing down of the infection, a reduction of hospitalizations, especially for myocardial infarction, was observed. The aim of our study is to evaluate the impact of the infectious disease on ST-segment-elevation myocardial infarction (STEMI) care during the coronavirus disease 2019 pandemic, through the analysis of recent cases of patients who underwent percutaneous coronary intervention. Methods and Results Consecutive patients affected by STEMI from March 1 to 31, 2020, during social restrictions of Italian government, were collected and compared with patients with STEMI treated during March 2019. During March 2020, we observed a 63% reduction of patients with STEMI who were admitted to our catheterization laboratory, when compared with the same period of 2019 (13 versus 35 patients). Changes in all time components of STEMI care were notably observed, particularly for longer median time in symptom-to-first medical contact, spoke-to-hub, and the cumulative symptom-to-wire delay. Procedural data and in-hospital outcomes were similar between the 2 groups, whereas the length of hospitalization was longer in patients of 2020. In this group, we also observed higher levels of cardiac biomarkers and a worse left ventricular ejection fraction at baseline and discharge. Conclusions The coronavirus disease 2019 outbreak induced a reduction of hospital access for STEMI with an increase in treatment delay, longer hospitalization, higher levels of cardiac biomarkers, and worse left ventricular function.

Cardiac magnetic resonance detection of left ventricular thrombus in acute myocardial infarction.

INTRODUCTION: Left ventricular thrombosis (LVT) is a possible complication of acute myocardial infarction. Aim of our study was to evaluate incidence and clinical characteristics of patients with LVT after ST elevation myocardial infarction (STEMI) using contrast- enhanced magnetic resonance (CMR). METHODS AND RESULTS: In a prospective cohort of 36 consecutive patients with STEMI acutely reperfused with primary percutaneous coronary intervention, CMR was performed within one week. LVT was found in 7 patients (19%), and was located in left ventricle apex or adherent to antero-septum. Compared to the rest of population patients with LVT have lower ejection fraction (38 ± 7% versus 51 ± 6%, P = 0.009), larger left ventricle end systolic volume (95.8 ± 19 ml versus 68.9 ± 19 ml, P = 0.02), higher time to reperfusion (9.3 ± 7.2 versus 5 ± 3.6, P = 0.03) and left anterior descending artery was constantly involved (100% versus 41 %, P = 0.06). In 5 cases the LVT was also detected by echocardiography, however, in 2 cases it was missed. CONCLUSIONS: The incidence of LVT after STEMI is not negligible and was accurately detected by CMR. Localization of myocardial infarction, time to reperfusion, ejection fraction and left ventricle end systolic volume are the most important predictors of left ventricle thrombus formation.

Evaluation of coronary in-stent restenosis by 64-slice computed tomography in patients with optimal heart rate control by systematic administration of beta-blocker drugs.

BACKGROUND: Imaging artifacts due to metallic stent struts can reduce the diagnostic accuracy of multislice computed tomography (MSCT) in the evaluation of in-stent restenosis (ISR). Our aim was to determine the accuracy of binary ISR exclusion using a 64-slice MSCT scanner and a systematic administration of beta-blockers having an aggressive heart rate (HR) control. METHODS: We performed 64-slice MSCT in 218 consecutive patients revascularized by stenting. All patients were treated with oral/intravenous beta-blocker drugs in order to obtain a HR less than 65 beats/min in the prescan phase. Coronary stents were evaluated by two experienced observers in order to rule out the presence of significant (>50%) ISR. Quantitative conventional coronary angiography (CCA) served as a standard for reference. RESULTS: Five patients (2.3%) were excluded from the analysis; mean HR was 59 +/- 3 beats/min in the prescan phase and 62 +/- 5 beats/min during acquisition. In the 321 stented coronary segments, CCA found 27 significant ISRs. MSCT correctly diagnosed 26 significant ISRs, with two false-positive and one false-negative case. In a per-segment analysis, the sensitivity was 96%, specificity 99%, positive predictive value (PPV) 92.8%, and negative predictive value (NPV) 99%. In a per-patient analysis, the sensitivity was 100%, specificity 98.9%, PPV 92.8%, and NPV 100%. CONCLUSION: In our study, the evaluation of significant ISR by MSCT showed an excellent diagnostic accuracy with a PPV of 92.8% and a NPV of 99%. Selection criteria and radiation exposure can be considered a limitation of the method.

Regression and shift in composition of coronary atherosclerotic plaques by pioglitazone: insight from an intravascular ultrasound analysis.

BACKGROUND: Plaque reduction with the use of pioglitazone and statin combination therapy has been observed in carotid plaque. We sought to investigate the effect of combination therapy with statins and pioglitazone on coronary plaque regression and composition with the use of intravascular ultrasound (IVUS) and intravascular ultrasound-virtual histology (IVUS-VH). METHODS: We analysed 29 plaques in 25 diabetic patients with angiographic evidence of nonsignificant coronary lesions with IVUS-VH. Patients were treated with 80 mg of atorvastatin and 30 mg of pioglitazone daily for 6 months. After 6 months of therapy, IVUS-VH of each lesion was reacquired. RESULTS: Mean elastic external membrane volume was significantly reduced between baseline and follow-up (343.9 vs. 320.5 mm; P < 0.05) as was mean total atheroma volume (179.3 vs. 166.6 mm; P < 0.05). Change in total atheroma volume showed a 6.3% mean reduction. Areas of fibrous tissue, fibrolipidic tissue and calcium decreased over the 6 months of follow-up, although not significantly. On the other hand, the necrotic core increased from 9 to 14% (P < 0.05). CONCLUSION: Our data demonstrated that atorvastatin/pioglitazone association is able to induce significant regression of coronary atherosclerosis, acting on plaque composition. Our findings are preliminary results and will be confirmed in an ongoing randomized placebo-controlled multicenter trial (PIPER; Pioglitazone for Prevention of Restenosis in Diabetics with Complex Lesion; trial registration: clinical trials.gov. Identifier: NCT 00376870).