Impact of renal denervation on patients with coronary microvascular dysfunction: study rationale and design.

AIMS: Long-standing hypertension may cause an impairment in microvascular coronary circulation, which is involved in many different cardiac conditions. Renal sympathetic denervation (RDN) has been successfully proven as a valuable therapeutic choice for patients with resistant hypertension; moreover, the procedure looks promising in other settings, such as heart failure and atrial fibrillation, given its ability to downregulate the sympathetic nervous system, which is a recognized driver in these conditions as well as in microvascular dysfunction progression. The aim of this study is to explore the effect of RDN on coronary physiology in patients with ascertained coronary microvascular dysfunction and resistant hypertension. METHODS: This is a multicenter, prospective, nonrandomized, open-label, interventional study. Consecutive patients with resistant hypertension, nonobstructive coronary artery disease (NOCAD) and documented microvascular dysfunction will be enrolled. Patients will undergo RDN by Spyral Symplicity 3 (Medtronic Inc, Minneapolis, Minnesota, USA) and reassessment of coronary microvascular function 6 months after the procedure. Primary endpoint will be the difference in the index of microcirculatory resistance. CONCLUSION: The IMPRESSION study seeks to evaluate if there is any pleiotropic effect of the RDN procedure that results in modulation of microvascular function; if observed, this would be the first evidence showing RDN as a valuable therapy to revert hypertension-related microvascular dysfunction.

Safety and efficacy of everolimus-eluting bioresorbable vascular scaffold for cardiac allograft vasculopathy (CART).

BACKGROUND: Cardiac allograft vasculopathy (CAV) is still the main drawback of heart transplantation (HTx) and percutaneous coronary intervention (PCI) is a palliative measure because of the high incidence of failure. OBJECTIVE: This study aimed to investigate the safety and efficacy of bioresorbable scaffolds (BRSs) as potential novel therapeutic tool for the treatment of coronary stenoses in CAV. METHODS: This is a multicenter, single-arm, prospective, open-label study (CART, NCT02377648), that included patients affected by advanced CAV treated with PCI and second-generation ABSORB BRS (Abbott Vascular). The primary endpoint was the incidence of 12-month angiographic in-segment scaffold restenosis (ISSR). Secondary endpoints were the incidence of major adverse cardiac events (MACEs) at 12- and 36-month follow-up and the incidence of ISSR at 36 months. A paired intracoronary imaging analysis at baseline and follow-up was also performed. RESULTS: Between 2015 and 2017 35 HTx patients were enrolled and treated for 44 coronary lesions with 51 BRSs. The primary endpoint occurred in 13.5% of the lesions (5/37), with a cumulative ISSR rate up to 3 years of 16.2% (6/37). Angiographic lumen loss was 0.40 ± 0.62 mm at 12 months and 0.53 ± 0.57 mm at 36 months. Overall survival rate was 91.4% and 74.3%, and MACEs incidence 14.2% and 31.4% at 12 and 36 months, respectively. At the paired intracoronary imaging analysis, a significant increase of the vessel external elastic membrane area in the treated segment and some progression of CAV proximally to the BRS were detected. CONCLUSIONS: BRS-based PCI for the treatment of CAV is feasible and safe, with an ISSR incidence similar to what reported in retrospective studies with drug-eluting stents.

A Five-Year Follow-up of Left Main Coronary Artery Stenting 8 Years After Arterial Switch Operation.

The fate of coronary artery stenting in children several years after implantation is unknown. We previously reported the case of an 8-year-old child undergoing stent implantation for a total left main coronary artery occlusion after arterial switch operation. Six months later, she needed another stent implantation for in-stent restenosis. Here we report the angiographic, intravascular ultrasound and optical coherence tomography findings at 5-year follow-up. Despite nongrowth of the left main coronary artery inherent to the stents, luminal patency, adequate struts apposition, and the absence of in situ complications were confirmed.

On ne sait rien de ce qu'il advient des endoprothèses coronariennes plusieurs années après l'implantation chez les enfants. Nous avons déjà présenté le cas d'une fillette de huit ans chez qui une endoprothèse a été implantée pour corriger une occlusion totale de l'artère coronaire principale gauche après une intervention de détransposition artérielle. Six mois plus tard, la patiente avait besoin d'une autre endoprothèse en raison d'une resténose de l'endoprothèse. Nous rapportons ici les observations effectuées à l'angiographie, à l'échographie intravasculaire et à la tomographie par cohérence optique à l'évaluation de suivi à cinq ans. Malgré l'absence de croissance de l'artère coronaire principale gauche en raison de la présence des endoprothèses, la perméabilité luminale, l'apposition adéquate des entretoises et l'absence de complications in situ ont été confirmées.

One-year clinical results of the Italian diffuse/multivessel disease ABSORB prospective registry (IT-DISAPPEARS).

AIMS: The present multicentre prospective study, IT-DISAPPEARS, was designed with the aim of evaluating early and long-term clinical outcomes of the Absorb BVS in patients with long coronary lesions and/or multivessel coronary artery disease. The aim of this article is to present the one-year clinical results of this study. METHODS AND RESULTS: Between November 2014 and January 2016, we enrolled 1,002 patients undergoing BVS implantation (long lesion [≥ 24 mm] of a single vessel in 80.4%, at least two BVS in two or three coronary vessels in 8.6% and both criteria in 11%). Clinical presentation was an acute coronary syndrome in 59.8% of patients, including ST-elevation myocardial infarction in 21.8%. The primary endpoint was the device-oriented composite endpoint (DOCE) of cardiac death, target vessel MI, and ischaemia-driven TLR at one year. We implanted 2,040 BVS according to a pre-specified technique. One-year follow-up was available in 956 patients (95.4%). The rate of DOCE was 9.9% (95 patients). Cardiac death occurred in five patients (0.5%), while target vessel MI and TLR each occurred in 45 (4.7%) patients. The one-year rates of all-cause death, non-fatal MI, and any revascularisation were 1.2%, 5.4%, and 10.9%, respectively. The rate of definite/probable scaffold thrombosis was 0.9%. CONCLUSIONS: This is the first study specifically investigating the Absorb technology in patients with a high atherosclerotic burden and multivessel disease. The mandatory adherence to a pre-specified implantation technique led to minimising the risk of device failure reported by other studies, in particular with respect to the rate of DOCE and scaffold thrombosis.

Optical coherence tomography for characterization of cardiac allograft vasculopathy in late survivors of pediatric heart transplantation.

BACKGROUND: Optical coherence tomography (OCT) has been shown to reliably detect cardiac allograft vasculopathy (CAV). In recent studies performed in adult heart transplant (HTx) recipients, OCT revealed the presence of vulnerable plaques and complicated coronary artery lesions, thus challenging the current concept that CAV disease is a diffuse concentric and fibrosing vasculopathy. The aim of our study was to characterize CAV by OCT in a young population of HTx recipients. METHODS: We prospectively enrolled 21 young HTx recipients (mean age 27 years, range 22 to 38 years) to undergo OCT of the left anterior descending coronary artery (LAD) in addition to annual CAV screening by coronary angiography and virtual histology intravascular ultrasound (VH-IVUS). Quantitative OCT analysis was performed at the site of maximal intimal thickness (MIT) for each LAD segment. RESULTS: Patients were 27 years old with a mean time from cardiac transplantation of 14.7 ± 6.8 years. All patients exhibited intimal hyperplasia with an abnormal (>1) intima-to-media ratio. The median (interquartile range) MIT values by OCT were 0.37 (0.22 to 0.54) mm, 0.46 (0.29 to 0.54) mm and 0.34 (0.25 to 0.49) mm in the distal, middle and proximal LAD segments, respectively. Qualitative OCT analysis rarely showed features of vulnerable plaque or complicated lesions. Consistently, at VH-IVUS, the prevalent component at the site of MIT per vessel assessed by OCT was fibrous tissue. CONCLUSIONS: Unlike recent evidence in adult HTx recipients, OCT findings of vulnerable plaque and complicated coronary lesions were found to be rare among late survivors of pediatric HTx.

Everolimus-Eluting Bioresorbable Vascular Scaffold System in the Treatment of Cardiac Allograft Vasculopathy: the CART (Cardiac Allograft Reparative Therapy) Prospective Multicenter Pilot Study.

Cardiac allograft vasculopathy (CAV) is a form of accelerated atherosclerosis, which represents the leading cause of late morbidity and mortality after heart transplantation. The recent bioresorbable vascular scaffold (BVS) technology represents a potential novel therapeutic tool, in the context of CAV, by allowing transient scaffolding and concomitant vessel healing. Eligible subjects will be treated by using the Absorb Everolimus-Eluting BVS (Abbott Vascular, Santa Clara, CA, USA), and evaluated at pre-determined time points, up to 3 years since the index procedure. Both clinical and imaging data will be collected in dedicated case report forms (CRF). All imaging data will be analyzed in an independent core laboratory. The primary aim of the study is to evaluate the angiographic performance at 1 year of second-generation Absorb BVS, in heart transplant recipients affected by CAV.

One-year outcome from an all-comers population of patients with ST-segment elevation myocardial infarction treated with biolimus-eluting stent with biodegradable polymer.

OBJECTIVES: To evaluate the performance of biolimus-eluting stent (BES) in patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) in a real world clinical scenario. BACKGROUND: Randomized studies suggest that the BES with biodegradable polymer is more effective and safe than early generation coronary stents in patients with STEMI. METHODS: We included all consecutive STEMI patients undergoing PCI in this prospective, multicenter registry. The primary endpoint of the study was the rate of major adverse cardiac events (MACE), a composite of cardiac death, recurrent myocardial infarction and ischemia-driven target vessel revascularization at 1-year follow-up. RESULTS: Between June and December 2012 we enrolled 311 STEMI patients. The primary endpoint occurred in 3.2% (95% confidence interval: 1.6-5.8) of patients: cardiac death, re-infarction, and ischemia-driven TVR occurred in 2.3%, 1.3%, and 0.6% of patients, respectively. One-year MACE-free survival was 96.8% ± 1.0%. CONCLUSIONS: In a real-world cohort of STEMI patients undergoing PCI, the use of BES is associated with good 1-year clinical outcome. These results confirm and expand previous findings showing the efficacy and safety of BES in the setting of randomized trials.

Randomized Comparison of Xience V and Multi-Link Vision Coronary Stents in the Same Multivessel Patient With Chronic Kidney Disease (RENAL-DES) Study.

BACKGROUND: Percutaneous coronary interventions in patients with chronic kidney disease have shown suboptimal results. Drug-eluting stents (DES) might reduce the rate of target vessel revascularization in comparison with bare-metal stents (BMS) in patients with chronic kidney disease. However, given the multiple concomitant individual variables present in such patients, the comparison of neointimal growth after percutaneous coronary intervention is complex and difficult to assess. METHODS AND RESULTS: Randomized Comparison of Xience V and Multi-Link Vision Coronary Stents in the Same Multivessel Patient with Chronic Kidney Disease (RENAL-DES) was a prospective, randomized, multicenter study to directly compare the efficacy in the prevention of clinical restenosis of everolimus-eluting stent (Xience V) and BMS with an identical design (Multi-Link Vision), both implanted in the same patient with multivessel coronary artery disease and chronic kidney disease (estimated glomerular filtration rate <60 mL/min). The primary end point of the study was the ischemia-driven target vessel revascularization as detected with myocardial scintigraphy at 12 months. In 215 patients, 512 coronary vessels were successfully treated with the randomly assigned DES (n=257) or BMS (n=255). At 1 year, the rate of ischemia-driven target vessel revascularization for DES and BMS groups was 2.7% (95% confidence interval, 1.1%-5.6%) and 11.4% (95% confidence interval, 7.8% to 16%), respectively, P<0.001. For the multivariate analysis, independent predictors of the ischemia-driven target vessel revascularization were BMS implantation (odds ratio, 4.95; 95% confidence interval, 2.1-11.6; P<0.001) and vessel size (odds ratio, 0.32; 95% confidence interval, 0.1-0.7; P=0.006). CONCLUSIONS: This is the first randomized trial showing a reduction of clinical restenosis with a new-generation DES in comparison with a BMS of equal design, in patients who have chronic kidney disease with multivessel coronary artery disease. CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov. Unique identifier: NCT00818792.

Coronary plaque composition assessed by intravascular ultrasound virtual histology: association with long-term clinical outcomes after heart transplantation in young adult recipients.

OBJECTIVES: To assess coronary plaque composition by virtual histology intravascular ultrasound (VH-IVUS) analysis in young adult recipients and to correlate these findings with time from heart transplant (HTx) and long-term outcomes. BACKGROUND: Rapid progression of coronary allograft vasculopathy after heart transplantation is a powerful predictor of mortality and clinical events at long-term. METHODS: Forty consecutive young adult recipients transplanted during childhood undergoing VH-IVUS during coronary surveillance have been prospectively included in this study. According to the time interval from HTx to VH-IVUS assessment, our cohort was divided into two groups (group A: ≤5 years, n = 13; group B: >5 years, n = 27). RESULTS: Group B showed an higher percentage of necrotic core and dense calcium (12 ± 2 vs. 5 ± 1%, P = 0.04; 8.2 vs. 2.1%, P = 0.03; respectively). An "inflammatory plaque" (necrotic core and dense calcium ≥30%) was detected in 34.8% of patients in group B and in none among group A patients (P = 0.03). Patients in group B had a number of adverse clinical events significantly higher than group A patients (53.8 vs. 14.3%; HR 4.45; 95% CI 1.62-12.16; P = 0.029) at long-term follow-up (4.2 years). The multivariate regression analysis showed that age (HR 1.5; 95% CI 1.1-2.0; P = 0.007), time from HTx (HR 1.8; 95% CI 1.6-4.8; P = 0.02), and inflammatory plaque (HR 2.4; 95% CI 1.1-5.3; P = 0.03) were independent predictors of adverse clinical events. CONCLUSIONS: This study supports the hypothesis that time-dependent differences in plaque composition, as assessed by VH-IVUS, occur after HTx in young adult recipients, probably determining an increased risk of long-term clinical events.

Long-term outcome of provisional side-branch T-stenting for the treatment of unprotected distal left main coronary artery disease.

Percutaneous coronary intervention (PCI) on distal left main (LM) remains an independent predictor of poor outcome. The strategy of implanting one stent on the main branch (MB), with provisional stenting on the side-branch (SB) only when required (provisional T-stenting), has become the default approach to most bifurcation lesions. This prospective registry sought to investigate the long-term safety and efficacy of provisional SB T-stenting for the treatment of unprotected distal LM disease in patients undergoing PCI. From January 2006 to May 2009, 107 consecutive patients affected by unprotected distal LM disease underwent PCI at our center with the intent to use a provisional SB-stenting technique. We evaluated the rate of major adverse cardiac events (MACE) at long-term follow-up (up to 12-41 months). Procedural success was obtained in 98% of patients. A final kissing balloon inflation was performed in 95% and intravascular ultrasound in 83% of patients. Additional stenting on the SB after provisional stenting on MB was required in 29% of lesions. Long-term follow-up (3.5 years; 25-75th percentile and 1.1-4.5 years) was completed in 97% of patients. The cumulative incidence of MACE was 32.7%: all-cause death was 15.8%, nonfatal myocardial infarction 8.4%, and target vessel revascularization 21.5%. At multivariable analysis, age (hazard ratio, 2.08; 95% confidence interval: 2.01-3.32, P = 0.03), European System for Cardiac Operative Risk Evaluation (HR 1.20, 95% CI: 1.04-1.33, P = 0.02), and diabetes mellitus (HR 3.48, 95% CI: 1.12-6.87, P = 0.01) were identified as independent predictors of MACE. In patients with unprotected distal LM disease undergoing PCI, a provisional strategy of stenting the MB only is associated with good long-term clinical outcomes.

Rationale and design of the Randomized comparison of XiEnce V and Multilink VisioN coronary stents in the sAme muLtivessel patient with chronic kiDnEy disease (RENAL-DES) study.

BACKGROUND: Percutaneous coronary intervention with bare metal stents (BMS) in patients with chronic kidney disease (CKD) has shown suboptimal results. Drug-eluting stents (DESs) might reduce the incidence of restenosis and therefore of target lesion revascularization in these patients. Of note, in patients with CKD, multiple concomitant individual variables may be responsible for neointimal hyperplasia after coronary stenting, thus making the comparison of BMS and DES in different patient groups difficult. STUDY DESIGN: The RENAL-DES is a prospective, randomized, multicenter, not-sponsored study to directly compare the efficacy in the prevention of clinical restenosis, of everolimus-eluting stent (Xience V) and BMS with identical design (Multilink Vision), both implanted in the same patient with multivessel coronary artery disease and CKD in order to obviate the multiple and unpredictable baseline differences. The primary endpoint of the study is 9-month ischemia-driven target vessel revascularization. SAMPLE SIZE: The expected primary endpoint rates are 20% for BMS and 10% for DES. According to these estimates, with a significant level of 0.05, a sample size of 194 patients provides an 80% statistical power. Assuming a 10% dropout rate, the goal is to enroll 213 patients (426 treated vessels) from five Italian centers. As 20% of the patients will likely require stent implantation in three vessels, approximately 500 treated vessels will be analyzed. CONCLUSION: This intraindividual, randomized study will provide, for the first time, data on the efficacy, in the prevention of clinical restenosis, of DES compared to BMS in patients with multivessel coronary artery disease and CKD (ClinicalTrials.gov Identifier: NCT 00818792).

Impact of abciximab on coronary restenosis in diabetic patients undergoing elective paclitaxel-eluting stent implantation. A prospective, randomized, placebo-controlled study.

AIMS: Recent studies suggested that abciximab reduces the risk of restenosis in diabetic patients receiving coronary bare metal stent. We sought to evaluate whether abciximab may reduce in-segment late luminal loss (LLL), in patients with diabetes mellitus undergoing elective drug-eluting stents (PES) implantation. METHODS AND RESULTS: We conducted a prospective, randomized, double-blind study on diabetic patients after a paclitaxel-eluting stent (PES) implantation on de novo coronary artery lesions. 132 consecutive patients with diabetes (mean age 63.1+/-7.4 years, 82 males) were randomized to abciximab (n=66) or placebo (n=66). Among the 124 (93.9%) patients who underwent a 6-months angiographic follow-up, the mean difference in in-segment LLL between patients who received abciximab and placebo was 0.02 mm (P=0.8). In addition, the rates of angiographic in-segment restenosis were comparable between the two groups (14.3 versus 9.8%, P=0.5). Cumulative rates of clinical events did not differ (death: 1.5 versus 1.5, P=0.9 and MI: 1.5 versus 3%, P=0.8) between abciximab and placebo group, respectively. Similarly, the incidence of target lesion revascularization was 9.1% and 6.1% (P=0.7) at six months, in the two groups. CONCLUSIONS: Abciximab does not seem to have any impact on the extent of in-segment LLL in diabetic patients undergoing an elective PES implantation.

The effect of thrombectomy on myocardial blush in primary angioplasty: the Randomized Evaluation of Thrombus Aspiration by two thrombectomy devices in acute Myocardial Infarction (RETAMI) trial.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI), primary percutaneous coronary intervention (PCI) may cause thrombus dislodgment leading to microvascular function impairment, which is a negative independent predictor of myocardial function recovery. Compared with conventional stenting, pretreatment with aspiration thrombectomy during primary PCI significantly improves coronary epicardial flow and myocardial tissue perfusion parameters. We sought to evaluate the angiographic findings of two different manual aspiration thrombectomy devices (Diver-Invatec (DI) and Export-Medtronic (EM)) in STEMI patients undergoing primary angioplasty. METHODS: We randomized 103 STEMI patients referred to our hospital to undergo primary PCI (<12 hr from symptoms onset) to DI (n = 52) and EM (n = 51) devices. The primary angiographic composite end-points were the rates of post-thrombectomy thrombus score (TS) < or =2, TIMI flow grade > or =2, and post-stenting myocardial blush grade (MBG) > or =2 in the two groups. RESULTS: Baseline, clinical, and angiographic preprocedural findings did not differ between the two groups. After aspiration thrombectomy, a TS < or = 2 was more frequently present in EM group (92.3 vs. 69.3%, P = 0.0052). Also the rate of post-thrombectomy TIMI > or = 2 (69.3 vs. 92.2%, P = 0.0052) and post-stenting MBG > or =2 (88.2 vs. 69.3%, P = 0.029) were significantly higher in EM group. No significative differences were observed in terms of clinical events at 1 and 12 months. CONCLUSIONS: In this single-center, prospective, randomized study, a EM use before stenting in STEMI patients seems to remove more thrombotic burden compared with DI, providing a greater post-thrombectomy epicardial flow and a better post-stenting microvascular perfusion.

Benefits on coronary restenosis from elective paclitaxel-eluting stent implantation in patients aged 75 years and older.

OBJECTIVE: Elderly patients are increasingly referred for revascularisation yet have been underrepresented in some large clinical trials. Although the advent of drug-eluting stents has dramatically reduced clinical events related to restenosis, older age remains one of the most important correlates of adverse outcome, even after an elective percutaneous coronary intervention (PCI). We sought to evaluate the impact of paclitaxel-eluting stents on coronary restenosis in elderly patients undergoing elective PCI. METHODS: Patients undergoing successful elective PCI with stenting of de novo coronary artery lesions were identified and screened for participation in this study. All patients included in our analysis were divided into two cohort groups: patients aged <75 years (younger cohort) and patients aged >or=75 years (elderly cohort). We evaluated the six-month incidence of target lesion revascularisation (TLR) and major adverse cardiac events, which included TLR, death and myocardial infarction. RESULTS: A total of 171 (58 aged >or=75 years) consecutive patients were enrolled in the study. At six months, TLR rate was similar in both groups [1.77 vs. 1.72%, odds ratio (OR) 0.97, 95% confidence interval (CI) 0.08-10.9, P = 0.98, in the younger and elderly group, respectively]. Even the rate of major adverse cardiac events was comparable between the two groups (7.96 vs. 8.62%, OR 1.09, 95% CI 0.34-3.41, P = 0.88, in the younger and elderly group, respectively). Also the angiographic restenosis rates were comparable between patients <75 or >or=75 years (4.42 vs. 3.46%, P = 0.76). CONCLUSIONS: After elective paclitaxel-eluting stent implantation, there is no difference in coronary restenosis in younger and elderly patients, suggesting an age-independent efficacy.

Infarct-related artery occlusion, tissue markers of ischaemia, and increased apoptosis in the peri-infarct viable myocardium.

AIMS: Unfavourable cardiac remodelling often complicates acute myocardial infarction (AMI) as a result of increased cardiomyocyte apoptosis. It is currently unclear whether ongoing or recurrent ischaemia is an independent determinant for increased apoptosis in peri-infarct viable myocardium. METHODS AND RESULTS: In order to assess the link between infarct-related artery (IRA) occlusion, ischaemia, and apoptosis, 30 subjects dying 7-120 days after AMI (16 with IRA occlusion and 14 with patent IRA) and five control subjects were selected at autopsy. Cardiomyocytes were defined as apoptotic if co-expressing TUNEL and activated caspase-3. Expression of both hypoxia-inducible factor-1 and cyclo-oxygenase-2 was assessed in the peri-infarct myocardium and considered as tissue markers of ischaemia. Evidence of ischaemia was significantly more frequent in cases with IRA occlusion (53%) than in cases with patent IRA (15%) or control hearts (0%, P=0.026). The finding of IRA occlusion and markers of ischaemia identified cases with higher apoptotic rates (ARs) in the peri-infarct viable myocardium [12.2% (8.2-14.0), P<0.001 vs. others], whereas IRA occlusion without ischaemia was associated with lower AR, not significantly different from patent IRA [3.0% (1.0-7.9) vs. 2.2% (1.0-5.8), respectively, P=0.42] CONCLUSION: Ischaemia in the peri-infarct viable myocardium is present in over 50% of subjects dying late after AMI with IRA occlusion, and it is associated with increased apoptosis. Relief of ischaemia after AMI may prove of benefit in preventing apoptosis and its consequences.

Hypoxia inducible factor-1 expression mediates myocardial response to ischemia late after acute myocardial infarction.

We report hypoxia-inducible factor-1 (HIF-1) expression in myocardium of patients with recent acute myocardial infarction (AMI), supporting the hypothesis of HIF-1 as a possible mediator of response to ischemia. A potential diagnostic role of determining tissue expression of HIF-1 as a marker of ischemia, and potential therapeutic implications by trying to modulate HIF-1 activity in order to promote beneficial effects of HIF-1 related genes (e.g. expression of vascular endothelial growth factor (VEGF)) may derive.

Clinical relevance of apoptosis in early and late post-infarction left ventricular remodeling.

Apoptosis may represent an important pathophysiological mechanism causing progressive myocardiocyte loss and left ventricular dilation, even late after acute myocardial infarction (AMI). This review discusses the role of myocardial apoptosis on the basis of findings from experimental studies in animals and from observational studies in humans with the purpose of assessing the clinical relevance, determinants and mechanisms of myocardial apoptosis and the potential therapeutic implications. A more profound understanding of the impact of myocardiocyte loss on prognosis and of the mechanisms involved may lead to an improved understanding of cardiac remodeling and possibly to an improved patient care. In fact, among the potential modulators of myocardial apoptosis, angiotensin-converting enzyme inhibitors and beta-adrenergic receptor blockers have already been shown to improve the prognosis and symptoms in patients with post-infarction heart failure, and a reduction in myocardial apoptosis could partly contribute to such a beneficial effect. Several other putative factors could also modulate myocardial apoptosis after AMI, and many are currently under intense investigation. In particular, the infarct-related artery patency late after AMI may be a major clinical determinant of myocardial apoptosis and clinical benefits deriving from an open artery (the "open-artery hypothesis"), such as a slowing down of the remodeling process and a reduced arrhythmic risk, could be due, at least in part, to a reduced apoptotic myocardiocyte loss.