One-year results from the Assessing MICRO-vascular resistances via IMR to predict outcome in ST-elevation myocardial infarction patients with multivessel disease undergoing primary PCI (AMICRO) trial.

Background: In ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary angioplasty (PPCI) the index of microcirculatory resistance (IMR) correlates to the extent of myocardial damage and left ventricular (LV) function recovery. Data on the IMR time-course and impact on clinical outcome in STEMI patients with multi-vessel disease (MVD) are scarce. Aims: We designed a prospective, multicenter clinical trial to assess the infarct-related artery (IRA)-IMR in STEMI patients with MVD undergoing PPCI and to explore its potential in relationship with outcome and LV remodeling. Methods: The study enrolled 242 STEMI patients with MVD. Both fractional flow reserve (FFR) and IMR of the IRA were assessed after successful PPCI. Then, FFR/IMR measurements were repeated in the IRA at a staged angiography, and FFR-guided angioplasty was performed in non-IRA lesions. The primary endpoint was the composite of cardiovascular death, re-infarction, re-hospitalization for heart failure, resuscitation or appropriate ICD shock at 1-year follow-up. Results: A significant improvement of IRA-IMR values (from 47.9 to 34.2, p < 0.0001) was observed early after PPCI. Staged FFR-guided angioplasty was performed in 102 non-IRA lesions. We failed to find a correlation between IRA-IMR, clinical events and LV remodeling. Notwithstanding, in patients with anterior STEMI an inverse correlation between initial IMR values and LV function at follow-up was observed. Conclusion: After successful PPCI, a significant proportion of patients with STEMI and MVD had coronary microvascular dysfunction as assessed by IMR that recovered early after reperfusion. Higher IMR values predicted lack of improvement of LV function only in anterior STEMI. Clinical trial registration: https://clinicaltrials.gov/, identifier [NCT02325973].

Epicardial and microvascular coronary vasomotor dysfunction and its relation to myocardial ischemic burden in patients with non-obstructive coronary artery disease.

AIM: To assess the relative contribution of epicardial endothelium-dependent (EDD) and microvascular endothelium-independent (EIMVD) coronary vasomotor dysfunction to the extent of myocardial ischemia in patients with normal angiograms or non-obstructive coronary artery disease (NOCAD). METHODS: Coronary vasomotion was evaluated by quantitative angiography and blood flow (CBF) measurements during intracoronary acetylcholine, nitroglycerine, and adenosine in 101 patients. Myocardial SPECT ischemic burden was evaluated by semi-quantitative scoring of summed stress (SSS) and summed ischemic (SDS) perfusion defect size. RESULTS: Coronary vasomotor dysfunction was found in most patients (83; 77%) with a divergent behavior of EDD and EIMVD in one half of them (52.4%). There was no significant difference in SDS between patients with and without EIMVD, whereas SDS was significantly greater in subjects with EDD as compared to patients with normal response to acetylcholine (4.31 ± 2.44 vs 1.35 ± 1.45; P < .0001). Patients with EDD, either alone or in combination with EIMVD, had significantly higher SSS as compared to patients with lone EIMVD or normal vasomotor function (8.50 ± 5.32; 5.55 ± 3.21; 2.60 ± 2.14; and 1.74 ± 1.66, respectively; P < .0001). Acetylcholine CBF correlated inversely with both SDS (r = -0.545; P < .001) and SSS (r = 0.538; P < .001). CONCLUSIONS: In NOCAD patients with symptoms and signs of myocardial ischemia, vasomotor dysfunction is common. EDD is associated with greater extent of ischemia as compared to isolated EIMVD. Thus, assessment of both EIMVD and EDD is needed to recognize mechanisms of ischemia and identify patients with greater ischemic burden.

Abnormal coronary vasoreactivity in transient left ventricular apical ballooning (tako-tsubo) syndrome.

BACKGROUND: The exact etiology and pathophysiologic mechanisms of tako-tsubo syndrome (TTS) remain controversial. OBJECTIVE: To further evaluate the abnormal coronary vasoreactivity and its possible anatomical substrate in TTS. METHODS: We studied 47 patients (46 women; age 67±12years) who underwent diagnostic cardiac catheterization and evaluation of coronary vasoreactivity by sequential acetylcholine (Ach), nitroglycerine and adenosine testing with angiographic and intracoronary pressure-Doppler flow monitoring. Coronary artery wall morphology was also evaluated by intravascular ultrasound (IVUS) imaging in 45 vessels of 43 patients. RESULTS: Abnormal coronary vasoconstriction to Ach stimulation was elicited in 40 patients (85%) involving the LAD artery and its branches in 39 (83%). Abnormal microvascular function was seen in 39 (83%) patients. Overall, hyperemic microvascular resistance index (HMR) was higher and Doppler coronary flow velocity reserve (CFVR) was lower in the LAD artery territory as compared to the reference territories (2.64±1.23 vs 2.05±0.56; p=0.008 and 1.95±0.7 vs 2.3±0.6; p=0.018, respectively). IVUS revealed no plaque rupture, dissection or thrombosis but occult plaque formation and myocardial bridging were found as a possible anatomical substrate of endothelial dysfunction in 67% and 48.8% patients respectively. CONCLUSIONS: A global failure of coronary vasomotor function was demonstrated in most TTS patients. These findings implicate abnormal vasoconstrictive response to the activation of the sympathetic system as a potential mechanism involved in the pathogenesis of myocardial stunning in TTS. PERSPECTIVES: Competency in medical knowledge: Abnormal coronary vasoconstriction secondary to endothelial dysfunction may actively contribute to the clinical manifestation of acute coronary syndromes in patients with non-obstructive coronary disease. Translational outlook 1: TTS patients reveal a global failure of vasomotor function with both vasoconstrictive response to acetylcholine and increased hyperemic microvascular resistances in the territory of myocardial stunning. They may also show occult coronary atherosclerosis and myocardial bridging as the anatomic substrates of endothelial dysfunction. Translational outlook 2: The cardiac phenotype of TTS includes a high prevalence of coronary vasomotor disturbances. These findings implicate abnormal vasoconstrictive response to the activation of the sympathetic system as a potential mechanism involved in the pathogenesis of TTS in post-menopausal women. Thus, a systematic evaluation of coronary vasoreactivity could better characterize the syndrome.

Assessing MICRO-vascular resistances via IMR to predict outcome in STEMI patients with multivessel disease undergoing primary PCI (AMICRO): Rationale and design of a prospective multicenter clinical trial.

BACKGROUND: In STEMI patients treated with primary percutaneous coronary angioplasty (PPCI) the evaluation of coronary microcirculatory resistance index (IMR) predict the extent of microvascular damage and left ventricular (LV) remodeling. However, the impact of IMR on the clinical outcome after PPCI in patients with multivessel disease (MVD) remains unsettled. AIM: We designed a prospective multicenter controlled clinical trial to evaluate the prognostic value of IMR in terms of clinical outcome and left ventricular remodeling in STEMI patients with MVD undergoing PPCI. METHODS AND DESIGN: The study will involve 242 patients with MVD defines as the presence of at least a non-culprit lesion of >50% stenosis at index coronary angiography. Both fractional flow reserve (FFR) and IMR will be measured in the infarct-related artery (IRA) after successful PPCI. Measurements of FFR and IMR will be repeated in the IRA and performed in the non-culprit vessels at staged angiography. The non-culprit vessel lesions will be treated only in the presence of a FFR<0.75. A 2D echocardiographic evaluation of the left ventricular (LV) volumes and ejection fraction will be performed before hospital discharge and at 1-year follow-up. The primary end-point of the study will be the composite of cardiovascular death, re-hospitalization for heart failure and resuscitation or appropriate ICD shock during 1-year of follow-up. Secondary end-points will be the impact of IMR in predicting LV remodeling during follow-up and correlations between IMR and ST-segment resolution. Other secondary endpoints will be need for new revascularization, stent thrombosis and re-infarction of the non-culprit vessels territory. IMPLICATIONS: If IMR significantly correlates with differences in outcome and LV remodeling, it will emerge as a potential prognostic index after PPCI in patients with MVD.

Clinical role of post-angioplasty hyperemic microvascular resistances in chronic ischemic left ventricular dysfunction.

AIMS: To investigate the impact of hyperemic microvascular resistances (HMRs) on myocardial perfusion and contractility after percutaneous coronary intervention (PCI) in chronic ischemic left ventricular dysfunction (CILVD). METHODS: The current retrospective study included 48 patients with CILVD of the left anterior descending territory undergoing HMRs assessment before and after PCI with a dual-sensor intracoronary pressure-flow wire. The severity of resting myocardial underperfusion and contractile dysfunction of the left anterior descending territory was scored as summed rest score (SRS-T) by single photon emission tomography, wall motion score index (WMSI-T) and left ventricular ejection fraction (LVEF) by transthoracic echocardiography before PCI and after 3 months. Patients were divided into two groups according to the mean post-PCI HMRs. RESULTS: Mean post-PCI HMRs were 2.05 ±â€Š0.43 mmHg/cm/s; increased HMRs (i.e. >2 mmHg/cm/s) were found in 17 patients (35.4%, group B) (3.29 ±â€Š0.77 mmHg/cm/s), whereas 31 patients (64.6%, group A) showed lower values (1.35 ±â€Š0.34 mmHg/cm/s; P < 0.001). Pre-PCI HMRs, WMSI-T and SRS-T were similar among groups.After PCI, a significant improvement of LVEF, WMSI-T and SRS-T was observed only in group A (6.6 ±â€Š7.4%, 0.44 ±â€Š0.42 and 3.9 ±â€Š2.9, respectively) compared with group B (1.3 ±â€Š1.9%, 0.02 ±â€Š0.07 and 1.1 ±â€Š1.9; P = 0.011, P < 0.001 and P = 0.028, respectively).Post-PCI HMRs predicted the absence of improvement of LVEF and WMSI-T at a cutoff value of 1.95 mmHg/cm/s (area under the curve 0.69 and 0.73; P = 0.038 and 0.017, respectively), with a positive predictive value of 96 and 100%, respectively. CONCLUSION: Increased post-PCI HMRs may predict the lack of functional improvement of the revascularized myocardium in CILVD.

A mathematical model for the vessel recruitment in coronary microcirculation in the absence of active autoregulation.

This paper proposes a mathematical model for vessel recruitment in the microvascular coronary network. The model is based on microvascular network units (MVNUs), where we define a MVNU as a portion of the microvascular network comprising seven generations of identical, parallel-arranged vessels (upstream arteries, large and small arterioles, capillaries, small and large venules, and downstream veins). The model implements a new mechanism to describe the variation in the number of MVNU in response to sudden variations of the local input pressure. In particular, it describes a recruitment mechanism dependent on distal pressure which operates in the coronary microcirculatory network even in maximally dilated conditions. We apply the model to interpret data from 29 patients who underwent revascularization by percutaneous coronary intervention (PCI). Treated vessels were the left anterior descending coronary artery, the left circumflex and the right coronary artery in 26, 2 and 1 patients, respectively. Following intracoronary adenosine administration, distal coronary pressure and blood flow were 48 ± 18 mmHg and 45 ± 30 ml/min before PCI, respectively, and significantly increased afterwards to 80 ± 17 mmHg and 68 ± 32 ml/min (p<0.001). The model predicts an increase in MVNU number in patients with preserved wall motion in the myocardial region which underwent PCI. On the contrary, a decrease in MVNU number is predicted by the model in patients with regional dysfunction and implies a relatively lower response of maximal flow to revascularization.

[Position paper on the theoretical basis, practical application and health economic evaluation of the functional assessment of coronary lesions endorsed by the Italian Society of Invasive Cardiology (SICI-GISE)]. / Documento di posizione della Società Italiana di Cardiologia Invasiva-Gruppo Italiano Studi Emodinamici (SICI-GISE) sulle basi teoriche, applicazioni pratiche e valutazione economico-sanitaria dell'utilizzo della guida di pressione intracoronarica.

Functional assessment of coronary lesions has become an integral part of routine practice in most cath labs. Such evaluation is performed using a pressure wire that allows measurement of fractional flow reserve (FFR). The latter has received a class I indication with level of evidence A according to the most recent European guidelines on myocardial revascularization for the assessment of angiographically moderate coronary lesions. The present document has the following objectives: 1) to summarize the theoretical basis of FFR; 2) to provide a guideline for vasodilator therapy; 3) to summarize scientific evidence supporting FFR; 4) to provide a model of health economy evaluation focusing on resource sparing associated with the use of FFR.

Prognostic value of fractional flow reserve: linking physiologic severity to clinical outcomes.

BACKGROUND: Fractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear. OBJECTIVES: The study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization. METHODS: Meta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold. RESULTS: A total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief. CONCLUSIONS: FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy.

Safety and efficacy of first-generation and second-generation drug-eluting stents in the setting of acute coronary syndromes.

Drug-eluting stents (DESs) are known to reduce in-stent restenosis rate, compared with bare metal stents (BMSs). Stent thrombosis, one of the most dangerous complications of DES, has emerged as a major concern. This issue has limited the use of DES in unstable coronary artery disease till recent years. In fact, acute coronary syndrome (ACS) and the subsequent activation of the hemocoagulative pathway could represent a prothrombotic environment, thus limiting the use of DES in this situation. Nowadays, there is increasing evidence in literature of similar stent thrombosis rates both for BMS and DES in ACS, and most interventional cardiologists are confident with the use of DES in ACS. The aim of this article is to review the current literature on this topic in order to compare first-generation and second-generation DES vs. BMS as concerns safety and efficacy.

Evaluation of baseline contractile reserve vs dyssynchrony as a predictor of functional improvement and long term outcome after resynchronization pacing therapy: a radionuclide stress study.

AIM: To assess the predictive value of baseline ventricular dyssynchrony and myocardial contractile reserve (mCR) in identifying responders to cardiac resynchronization therapy (CRT). METHODS: We prospectively studied 57 patients selected for CRT according to current recommendations. Regional dyssynchrony was evaluated by parametric phase imaging of ecg-gated equilibrium radionuclide angiography (ERNA). The mean inter-ventricular phase delay and the standard deviation to mean left ventricular (LV) phase angle were used as a measure of inter- and intra-ventricular dyssynchrony, respectively. Change in LV ejection fraction (LVEF) during low-dose dobutamine (LDD) was measured to assess mCR. ERNA was repeated at 6 months to evaluate changes in LVEF after CRT. Combined end-points of re-hospitalization for heart failure, heart transplantation, and cardiac death were assessed over a period of 76 months (mean 43 ± 31). RESULTS: Baseline dyssynchrony was present in most patients (85%). After CRT only one half of patients showed a reduction in intra-ventricular dyssynchrony and 33% an increase in LVEF by >5%. Improvement of LVEF was not predicted by baseline LVEF, clinical presentation, dyssynchrony parameters or QRS duration. There was a significant relationship between changes in LVEF during LDD testing and after CRT (r = 0.65; P < .0001). Logistic regression analysis identified mCR as independent predictor of improvement in LVEF (P = .039; OR = 3.84; CI 95% = 1.06-13.9), resynchronization (P = .046; OR = 4.20; CI 95% = 1.03-17.2), and event-free survival (P = .002; OR = 0.10; CI 95% = 0.02-0.43). CONCLUSIONS: In patients with left ventricular dysfunction and baseline dyssynchrony as assessed by ERNA, evaluation of mCR during LDD may help predicting functional improvement and selecting potential responders to CRT.

Variant angina associated with coronary artery endothelial dysfunction and myocardial bridge: a case report and review of the literature.

The association of variant angina (VA) and myocardial bridges is a rare finding. We describe a case of VA with recurrent coronary spasm triggered by different stimuli at the site of a myocardial bridge. The interplay of endothelial dysfunction, coronary vasoconstriction and myocardial bridging was detected by intracoronary acetylcholine test and IVUS. We speculate that mechanical stimulation at the bridge site caused endothelial dysfunction and enhanced local susceptibility to vasoconstrictor stimuli. Variant angina should always be suspected in cases of ST-elevation acute coronary syndrome without any significant angiographic coronary stenosis.

Larger perfusion defects with exercise compared with dipyridamole SPECT (exercise-dipyridamole mismatch) may reflect differences in epicardial and microvascular coronary dysfunction: when the stressor matters.

BACKGROUND: Previous studies have reported larger myocardial perfusion defects with exercise as compared with dipyridamole. The aim of this study was to assess the hypothesis that this mismatch may reflect differences in epicardial and microvascular coronary vasomotor function. METHODS AND RESULTS: The response to intracoronary acetylcholine, nitroglycerin, and adenosine was studied in 36 patients with suspected angina and normal or near-normal coronary angiography findings who underwent both exercise and dipyridamole perfusion imaging. Of the patients, 27 (75%) had reversible defects with exercise (group I) and 9 had normal scans or nonreversible defects (group II). Repeated imaging with dipyridamole showed significant improvement or disappearance of perfusion defects in group I patients. The mean summed difference score (SDS) decreased from 5.52 +/- 3.19 with exercise to 1.11 +/- 1.60 with dipyridamole (P = .0001) in group I and did not change in group II. An abnormal epicardial response to acetylcholine, reflecting endothelial dysfunction, occurred in 93% of group I patients compared with only 33% of group II patients (chi(2) = 9.46, P = .002) and was significantly related to exercise SDS (r = 0.49, P = .002) but not to dipyridamole SDS. By contrast, most patients showed normal epicardial and microvascular responses to the mainly non-endothelium-dependent vasodilators nitroglycerin and adenosine with no differences in coronary flow reserve between groups (2.91 +/- 0.72 vs 2.98 +/- 0.52, P = .79). CONCLUSIONS: Exercise-dipyridamole perfusion mismatch may reflect differences in epicardial endothelial and microvascular dysfunction.

Assessment of cardiac asynchrony by radionuclide phase analysis: correlation with ventricular function in patients with narrow or prolonged QRS interval.

BACKGROUND: Conflicting data exist on the relation between the synchronism of cardiac contraction and ventricular function. AIM AND METHODS: A resting radionuclide ventriculography (RNV) was performed in 380 consecutive patients to evaluate the relationship between the synchronism of cardiac contraction and ventricular function. RESULTS: A significant, non-linear, relation was found between LVEF and intra-ventricular asynchrony or QRS, but not between inter-ventricular asynchrony and LVEF. A linear correlation was observed between QRS and intra-ventricular or inter-ventricular asynchrony. Intra-ventricular asynchrony was identified as the major, independent, determinant of LV function. With the increase in QRS duration, a decrease in LVEF (p<0.001), and a worsening of either intra-ventricular (p<0.001) or inter-ventricular synchronism (p<0.05), was documented. However, 48% of patients with QRS 120-150 ms had abnormal inter-ventricular and 42% abnormal intra-ventricular synchronism, while 27% of patients with QRS>150 ms had normal inter-ventricular and 25% normal intra-ventricular synchronism. CONCLUSIONS: Intra-ventricular asynchrony was identified as the major determinant of ventricular dysfunction. A consistent proportion of patients had asynchrony despite preserved QRS duration or normal synchronism with a QRS>150 ms. Fourier phase analysis of RNV may detect asynchrony better than QRS. The role of RNV for detection of individual patients who may most benefit from resynchronization therapy requires additional investigations.

Steroid-eluting stents in patients with acute coronary syndrome: the dexamethasone eluting stent Italian registry.

OBJECTIVE: To assess immediate and mid-term clinical and angiographic outcomes of the dexamethasone drug-eluting stent (D-DES) in patients with acute coronary syndrome (ACS). PATIENTS AND METHODS: A prospective, nationwide, controlled, registry. Inflammation plays a key role in ACS, and the anti-inflammatory effects of local elution of dexamethasone in unstable plaques may represent a valid therapeutic approach. All patients had ACS on admission (n = 332). 81.5% of the patients had unstable angina and 18.5% had non-ST elevation myocardial infarction (MI). 47% had ST-T segment changes, 59% had troponin elevation, 77% had elevated C-reactive protein levels and 48% had intermediate-high Thrombolysis in Myocardial Infarction risk score. Patients were treated according to an early invasive approach with 420 D-DES in 387 coronary lesions. Primary end point was the cumulative incidence of death, MI and ischaemia-driven target vessel revascularisation (TVR) at 6 months. RESULTS: At 30 days, 2 (0.6%) patients died, and sub-acute stent thrombosis occurred in 2 patients. At 6 months, 328 (98.8%) patients were controlled, 3 (0.9%) patients had died, 7 (2.1%) had MI and 28 (8.5%) underwent ischaemia-driven TVR. Therefore, the primary end point occurred in 11.5% of patients. At multivariate analysis, multi-vessel coronary artery disease (odds ratio (OR) = 2.16, 95% CI = 1.47 to 3.17, p = 0.0001) and vessel diameter < or =2.75 mm (OR = 1.64, 95% CI = 1.08 to 2.49, p = 0.02) were independent predictors of 6-month clinical events. Global angiographic restenosis rate was 33.3%. CONCLUSION: This is the first large, multicentre analysis of the clinical and angiographic outcomes obtained with D-DES implanted in ACS. D-DES offers a low rate of clinical events at 6 months, but has no anti-restenosis effect.

Performing versus deferring coronary angioplasty based on functional evaluation of vessel stenosis by pressure measurements: a clinical outcome study.

AIM: The present study aimed to prospectively evaluate whether application of the concept of fractional flow reserve (FFR) guides the immediate decision to perform or to defer coronary angioplasty in unselected consecutive patients with one or more angiographically intermediate (50-70%) stenoses and non-conclusive or lacking non-invasive testing. METHODS: We studied 112 patients (81 males and 31 females, aged 31-81 years) including 71 multivessel disease patients (63%) and 30 patients (27%) with unstable symptoms. FFR was measured with the use of a pressure-wire after adenosine-induced hyperaemia and compared with quantitative coronary angiography in 171 stenoses. Coronary angioplasty was performed in the presence of an FFR < 0.75 and deferred if FFR was > or = 0.75. Cardiac events including death, myocardial infarction, recurrent angina or symptoms requiring repeated hospitalization and target vessel revascularization (TVR) were recorded during a median period of 34 months (interquartile range 9-54 months). RESULTS: Coronary angioplasty was deferred based on FFR results in 54 patients (group I). In the remaining 58 patients, angioplasty was performed in one or more stenoses that were significant by FFR and deferred in non-significant stenoses (group II). Overall, coronary angioplasty was performed in 71 vessels (41%) and deferred in 100 (59%). Cumulative cardiac events occurred in 12.9% of group I patients and in 24.1% of group II patients (chi-squared = 1.57, P = 0.20). TVR was required in 5% of the stenoses untreated based on FFR result in both groups and in 12.6% of stenoses that underwent coronary angioplasty (chi-squared = 3.25, P = 0.07; relative risk = 2.5, 95% confidence interval = 0.88-8.61). CONCLUSIONS: In patients with angiographically intermediate stenoses, functional evaluation by FFR to select lesions that do not need to be treated invasively is safe. Unnecessary angioplasty and stenting may be saved in more than one half of individual coronary stenoses. The risk of major cardiac events and TVR of functionally non-significant stenoses is lower than the risk associated with coronary angioplasty. Our observations further support the use of pressure wire for physiological assessment of coronary artery stenosis in the catheterization room.

Coronary stent implantation is superior to balloon angioplasty for chronic coronary occlusions: six-year clinical follow-up of the GISSOC trial.

OBJECTIVES: We investigated whether the benefits of stent implantation over balloon percutaneous transluminal coronary angioplasty (PTCA) for treatment of chronic total coronary occlusions (CTO) are maintained in the long term. BACKGROUND: Several randomized trials have shown that in CTO, stent implantation confers clinical and angiographic mid-term outcomes superior to those observed after PTCA. However, limited information on the long-term results of either technique is available. METHODS: Six-year clinical follow-up of patients enrolled in the Gruppo Italiano di Studio sullo Stent nelle Occlusioni Coronariche (GISSOC) trial was performed by direct visit or telephone interview. Major adverse cardiac events (MACE), defined as cardiac death, myocardial infarction, target lesion revascularization (TLR), and anginal status, were recorded. RESULTS: Freedom from MACE at six years was 76.1% in the stent group, compared with 60.4% in the PTCA group (p = 0.0555). This difference was due mainly to TLR-free survival rates (85.1% vs. 65.5% for the stent and PTCA groups, respectively; p = 0.0165). Eleven patients underwent TLR after the nine-month follow-up visit (stent group: n = 5; PTCA group: n = 6); however, in most cases, restenosis of the study occlusion was evident at nine-month angiography. CONCLUSIONS: This study represents the longest reported clinical follow-up of patients after percutaneous recanalization of CTO and demonstrates that the superiority of stent implantation over balloon PTCA is maintained in the long term. Stent and PTCA results appear to remain stable after nine-month angiographic follow-up. Stent implantation in CTO that can be recanalized percutaneously is therefore a valuable long-term therapeutic option.