Prevalence and prognostic significance of malnutrition in patients with secondary mitral regurgitation undergoing transcatheter edge-to-edge repair.

BACKGROUND: Malnutrition is associated with poor prognosis in several cardiovascular diseases; however, its role in patients with secondary mitral regurgitation (SMR) is poorly known. AIMS: To evaluate the impact of nutritional status, assessed using different scores, on clinical outcomes in patients with SMR undergoing transcatheter edge-to-edge repair (TEER) in a real-world setting. METHODS: A total of 658 patients with SMR and complete nutritional data were identified from the MIVNUT registry. Nutritional status has been assessed using controlling nutritional status index (CONUT), prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI) scores. Outcomes of interest were all-cause mortality and all-cause mortality or heart failure (HF) hospitalization. RESULTS: Any malnutrition grade was observed in 79.4%, 16.7%, and 47.9% of patients by using CONUT, PNI, and GNRI, respectively, while moderate to severe malnutrition was noted in 24.7%, 16.7%, and 25.6% of patients, respectively. At a median follow-up of 2.2 years, 212 patients (32.2%) died. Moderate-severe malnutrition was associated with a higher rate of all-cause mortality (HR: 2.46 [95% CI: 1.69-3.58], HR: 2.18 [95% CI: 1.46-3.26], HR: 1.97 [95% CI: 1.41-2.74] for CONUT, PNI, and GNRI scores, respectively). The combined secondary endpoint of all-cause mortality and HF rehospitalization occurred in 306 patients (46.5%). Patients with moderate-severe malnutrition had a higher risk of the composite endpoint (HR: 1.56 [95% CI: 1.20-2.28], HR: 1.55 [95% CI: 1.01-2.19], HR: 1.36 [95% CI: 1.02-1.80] for CONUT, PNI, and GNRI scores, respectively). After adjustment for multiple confounders, moderate-severe malnutrition remained independently associated with clinical outcomes. CONCLUSIONS: Moderate-severe malnutrition was common in patients with SMR undergoing TEER. It was independently associated with poor prognosis regardless of the different scores used.

STAR procedure becomes SAFER: First-in-man case series of a new antegrade dissection re-entry technique.

INTRODUCTION: Antegrade dissection and re-entry (ADR) is an integral part of the hybrid algorithm, which has allowed for improved outcomes in chronic total occlusion (CTO) coronary intervention (PCI). METHODS: A new ADR method, Subintimal Antegrade FEnestration and Re-entry (SAFER), is described. The results of a first-in-man series are presented. RESULTS: SAFER was performed on seven consecutive patients with angiographic and clinical success in all patients. CONCLUSIONS: This first-in-man study has shown that the SAFER technique is feasible and effective with the possibility of improving the antegrade PCI CTO success rate.

Transcatheter therapies for secondary mitral regurgitation in advanced heart failure: what are we aiming for?

A severe secondary mitral regurgitation (SMR) can be found in a significant portion of patients affected by advanced heart failure (AHF). Conventional therapies (optimal medical therapy, devices, surgery) present restricted clinical efficacy in this stage of the left ventricle disease which is burdened by high mortality and morbidity rates. Although the treatment of choice is represented by heart transplantation (HTx), there is an unmet need related to the limited supply of donor hearts (as opposed to the growing prevalence of AHF) and the low eligibility of highly symptomatic patients. In case of concomitant severe SMR, transcatheter mitral valve therapies (repair and replacement) may play a crucial role in this setting. While a direct prognostic improvement after correction of SMR has yet to be proved, AHF patients can benefit from the following: hemodynamic stabilization, symptomatic relief, normalization of pulmonary arterial pressures, and reduction in hospitalizations for acute heart failure. Obtaining these results may lead to the clinical consequences of reaching the HTx in good enough clinical status (bridge to heart transplantation), becoming eligible for the HTx (bridge to HTx candidacy), and being delisted for clinical improvement (bridge to recovery). Therefore, achieving traditional secondary endpoints in patients with AHF and SMR can translate into significant clinical implications.

Direct oral anticoagulants in patients with nonvalvular atrial fibrillation and extreme body weight.

BACKGROUND: Limited clinical data exist describing the use of direct oral anticoagulants (DOACs) in patient with extreme body weight. Thus, the International Society of Thrombosis and Haemostasis (ISTH) recommends avoiding DOACs in patients with weight >120 Kg, and on the contrary, no restrictions exist for underweight patients. OBJECTIVE: To evaluate the effects of extreme body weight on DOAC activity and to compare the clinical outcomes of patients with an extreme body weight versus patients with a normal weight (61-119 Kg) treated with DOACs. METHODS: Single tertiary care Italian centre multidisciplinary registry including nonvalvular atrial fibrillation (NVAF) patients treated with DOACs. Based on weight, three subcohorts were defined: (i) underweight patients (≤60 Kg); (ii) patients with a normal weight (61-119 Kg, as control group); and (iii) overweight patients (≥120 Kg). Primary efficacy endpoint was 2-year rate of thromboembolic events. Primary safety endpoint was 2-year rate of major bleeding. Event-free survival curves among groups were compared using Cox-Mantel test. RESULTS: 812 NVAF patients were included, 108 patients weighed ≤60 Kg (13%, underweight), 688 weighed between 61 and 119 Kg (85%, normal weight), and 16 weighed ≥120 Kg (2%, overweight). In particular, among underweight patients, dabigatran was prescribed in 26% patients, apixaban in 27%, rivaroxaban in 28% and edoxaban in 22% ones. Instead, among overweight patients, 44% were treated with dabigatran, 25% with apixaban, 25% with rivaroxaban and 4% with edoxaban. Underweight patients were older, more frequently women, with lower creatinine clearance and a history of previous strokes, resulting in higher CHA2DS2-VASc score than in both remaining groups. Up to 2 years, no statistically significant difference was observed between the three groups of weight for thromboembolic events (P = .765) and for overall bleeding (P = .125), but a trend towards decreased overall bleeding rates was noticed as weight increased (24.1% vs 16.7% vs 12.5%, respectively). CONCLUSION: In this tertiary care centre registry, 15% of patients treated with DOACs presented an extreme weight. Compared to patients with a normal weight, no significant rates of thromboembolic events were observed for underweight or overweight patients. A trend towards decreased overall bleeding frequency as weight increased was highlighted up to 2 years. The present results should be considered as preliminary and hypothesis generating.

Predictors of optimal procedural result after transcatheter edge-to-edge mitral valve repair in secondary mitral regurgitation.

BACKGROUND: Procedural success after transcatheter edge-to-edge mitral valve repair (TEER) is defined as a reduction of mitral regurgitation (MR) degree to

Monotherapy with a P2Y12 inhibitor or aspirin for secondary prevention in patients with established atherosclerosis: a systematic review and meta-analysis.

BACKGROUND: Antiplatelet therapy is recommended among patients with established atherosclerosis. We compared monotherapy with a P2Y12 inhibitor versus aspirin for secondary prevention. METHODS: In this systematic review and meta-analysis, all randomised trials comparing P2Y12 inhibitor with aspirin monotherapy for secondary prevention in patients with cerebrovascular, coronary, or peripheral artery disease were evaluated for inclusion. On Dec 18, 2019, we searched PubMed, Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of Controlled Trials. Additionally, we reviewed references from identified articles and searched abstracts from 2017 to 2019 presented at relevant scientific meetings. Data about year of publication, inclusion and exclusion criteria, sample size, baseline patients' features including the baseline condition determining study inclusion (ie, cerebrovascular, coronary, or peripheral artery disease), P2Y12 inhibitor type and dosage, aspirin dosage, endpoint definitions, effect estimates, follow-up duration, and percentage of patients lost to follow-up were collected. Odds ratios (ORs) and 95% CIs were used as metric of choice for treatment effects with random-effects models. Co-primary endpoints were myocardial infarction and stroke. Key secondary endpoints were all-cause death and vascular death. Heterogeneity was assessed with the I2 index. This study is registered with PROSPERO (CRD42018115037). FINDINGS: A total of nine randomised trials were identified and included in this study, and 42 108 patients randomly allocated to a P2Y12 inhibitor (n=21 043) or aspirin (n=21 065) were included in our analyses. Patients who received a P2Y12 inhibitor had a borderline reduction for the risk of myocardial infarction compared with those who received aspirin (OR 0·81 [95% CI 0·66-0·99]; I2=10·9%). Risks of stroke (OR 0·93 [0·82-1·06]; I2=34·5%), all-cause death (OR 0·98 [0·89-1·08]; I2=0%), and vascular death (OR 0·97 [0·86-1·09]; I2=0%) did not differ between patients who received a P2Y12 inhibitor and those who received aspirin. Similarly, the risk of major bleeding (OR 0·90 [0·74-1·10]; I2=3·9%) did not differ between patients who received a P2Y12 inhibitor and those who received aspirin. The number needed to treat to prevent one myocardial infarction with P2Y12 inhibitor monotherapy was 244 patients. Findings were consistent regardless of the type of P2Y12 inhibitor used. INTERPRETATION: Compared with aspirin monotherapy, P2Y12 inhibitor monotherapy is associated with a risk reduction for myocardial infarction and a comparable risk of stroke in the setting of secondary prevention. The benefit of P2Y12 inhibitor monotherapy is of debatable clinical relevance, in view of the high number needed to treat to prevent a myocardial infarction and the absence of any effect on all-cause and vascular mortality. FUNDING: Italian Ministry of Education.

Cardiac and sudden death after chronic total occlusion percutaneous coronary intervention: Prognostic role of the target vessel.

BACKGROUND: The role of the target vessel in percutaneous revascularization of chronic total occlusion (CTO) is unclear. OBJECTIVE: We sought to assess the long-term results of percutaneous coronary intervention (PCI) for CTO lesions in each coronary artery and to investigate the impact of successful revascularization and previous myocardial infarction (MI) in the territory of the target vessel. METHODS AND RESULTS: Cohort observational study on 1,124 patients who have undergone CTO PCI attempt: 371 on left anterior descending artery (LAD), 485 right coronary artery, and 268 left circumflex. Patients were further stratified by successfully revascularized and not-revascularized CTO (CTO-NR). Vessels affected by a previous MI were defined as infarct-related artery (IRA). The primary endpoint was cardiac death; the secondary endpoint was the combined rate of sudden cardiac-death and sustained ventricular-arrhythmias (SCD/SVAs). Propensity score-matching was performed to evaluate LAD versus NON-LAD CTO. Up to 12-year follow-up, the clinical benefit associated with successful PCI was consistent across the three groups. CTO-NR had the greatest association with cardiac death and SCD/SVAs in each coronary artery and in IRA-CTO patients. CONCLUSIONS: Unsuccessful percutaneous CTO revascularization was associated with lower cardiac survival and freedom from SCD/SVAs, irrespective of the vessel treated. This result was mainly driven by patients with an IRA CTO.

Use of edge-to-edge percutaneous mitral valve repair for severe mitral regurgitation in cardiogenic shock: A multicenter observational experience (MITRA-SHOCK study).

OBJECTIVES: The aim of this study was to evaluate the impact of edge-to-edge PMVR on short and mid-term clinical outcomes in patients with CS and severe MR. BACKGROUND: Severe mitral regurgitation (MR) in the setting of cardiogenic shock (CS) is associated with three times higher risk of 1-year mortality. In refractory CS, edge-to-edge percutaneous mitral valve repair (PMVR) can be a potential therapeutic option. METHODS: We retrospectively included consecutive patients with refractory CS and concomitant severe MR treated with MitraClip® system. CS was defined according to the criteria used in the SHOCK trial and procedural success according to Mitral Valve Academic Research Consortium (MVARC) criteria. The 30-day and 6-month mortality were the primary and secondary endpoints respectively. RESULTS: Thirty-one patients (median age 73 years [interquartile range, IQR 66-78], 25.8% female), STS mortality score 37.9 [IQR 30.4-42.4]), with CS and concomitant severe MR treated with edge-to-edge PMVR were retrospectively enrolled. Procedural success was 87.1%. Thirty-day and 6-month survival rates were 78.4 and 45.2% respectively. Univariate Cox Regression Model analysis showed that procedural success was a predictor of both 30-day (HR = 0.12, 95% CI 0.03-0.55, p < .01) and 6-month survival (HR = 0.22, 95% CI 0.06-0.84, p = .027). CONCLUSIONS: Edge-to-edge PMVR in patients with CS and concomitant severe MR was associated with good procedural safety and success with acceptable short and mid-term survival rates. It could be considered a bailout option in this setting of patients.

One-year clinical outcome of biodegradable polymer sirolimus-eluting stent in diabetic patients: Insight from the ULISSE registry (ULtimaster Italian multicenter all comerS Stent rEgistry).

BACKGROUND: The ULISSE registry evaluated the real-world performance of the Ultimaster® biodegradable polymer sirolimus-eluting stent (BP-SES) in a multicenter-independent cohort of patients undergoing percutaneous coronary intervention, including a large proportion of diabetes mellitus (DM) patients. METHODS: In this subgroup analysis, 1,660 consecutive patients, 2,422 lesions, treated with BP-SES enrolled in the ULISSE registry were divided in two groups: DM (485 patients, 728 lesions) and non-DM (1,175 patients, 1,694 lesions). Primary endpoint was target lesion failure (TLF), a composite endpoint of cardiac-death, target-vessel myocardial infarction (TV-MI), and clinically driven target lesion revascularization (TLR) at 1-year. Secondary endpoint was TLR at 1-year. RESULTS: At 1-year follow-up TLF occurred in 5% overall patients and was significantly higher in DM patients (8 vs. 3.7%; p = .001), due to more cardiac deaths (3.4 vs. 1.1%; p = .002). TLR occurred in 3.2% overall patients, and it was not significantly higher in DM compared to non-DM patients (4.4 vs. 2.8%; p = .114). The incidence of stent thrombosis was low and similar between groups (0.4 vs. 0.9%; p = .526). Insulin-treated DM (ITDM) patients showed higher rate of TLF as compared to non-ITDM patients (13 vs. 6.5%; p = .041), but similar rate of TLR (6 vs. 4%; p = .405). After adjustment for relevant comorbidities, DM was not significantly associated with TLF or cardiac death in patients undergoing BP-SES implantation. CONCLUSIONS: This study is the first all-comers evaluation of BP-SES in DM patients. Our findings show that DM patients, mostly those with ITDM, still represent a vulnerable population and experience significantly higher rate of TLF. Overall BP-SES efficacy is considerable, although not statistically significant higher rate of TLR is still present in DM compared to non-DM patients.

Association of different oral anticoagulants use with renal function worsening in patients with atrial fibrillation: A multicentre cohort study.

AIMS: To investigate the decline of estimated glomerular filtration rate (eGFR) in patients with atrial fibrillation (AF) treated with vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs). METHODS: Multicentre prospective cohort study including 1667 patients with nonvalvular AF. The eGFR was assessed by the CKD-EPI formula at baseline and during follow-up. The primary endpoint of the study was the median annual decline of eGFR according to VKA (n = 743) or NOAC (n = 924) use. As secondary endpoints, we analysed the transition to eGFR <50 mL/min/1.73 m2 and the eGFR class worsening. RESULTS: Median age was 73.7 ± 9.1 years and 43.3% were women. VKA-treated patients showed an eGFR decline of -2.11 (interquartile range [IQR] -5.68/-0.62), which was -0.27 (IQR -9.00/4.54, P < 0.001 vs VKAs), -1.21 (IQR -9.98/4.02, P = 0.004 vs VKAs) and -1.32 (IQR -8.70/3.99, P = 0.003 vs VKAs) in patients on dabigatran, rivaroxaban and apixaban, respectively. Transition to eGFR <50 mL/min/1.73 m2 was lower in dabigatran- and apixaban-treated patients: odds ratio (OR) 0.492, 95% confidence interval (CI) 0.298-0.813, P = 0.006 and OR 0.449, 95% CI 0.276-0.728, P = 0.001, respectively. A lower rate of eGFR class worsening was found in all groups of NOACs compared to VKAs. No difference between full and reduced dose of NOAC was found. Subgroup analysis showed that the association between NOAC and eGFR changes was markedly reduced in diabetic patients. CONCLUSION: Patients prescribed NOACs showed a lower decline of renal function compared to those prescribed VKAs. This effect was partially lost in patients with diabetes.

One-year clinical outcome of biodegradable polymer sirolimus-eluting stent in patients presenting with acute myocardial infarction: Insight from the ULISSE registry.

BACKGROUND: The ULISSE registry has demonstrated the real-world performance of the Ultimaster biodegradable polymer sirolimus-eluting stent (BP-SES) in a large cohort of patients undergoing percutaneous coronary intervention, including a large proportion of patients presenting with acute myocardial infarction (AMI). METHODS: We performed a subgroup analysis of the ULISSE registry in AMI patients and compared the outcomes of this vulnerable cohort with that of patients presenting without AMI (non-AMI). The primary end point was the incidence of 1-year target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (TV-MI), and clinically indicated target lesion revascularization (TLR). RESULTS: Of 1,660 patients included in the ULISSE registry, 381(23%) presented with AMI, 207(54.3%) non-ST elevation myocardial infarction, and 174(45.7%) ST-elevation myocardial infarction. Compared with non-AMI patients, those with AMI were more frequently female and smokers, with lower left ventricular ejection fraction (LVEF) and chronic kidney disease requiring dialysis. At 1 year, TLF rate was significantly higher in AMI than non-AMI patients (7.9 vs. 4.1%; HR 1.98, CI 95% 1.22-3.23; p = .005) driven by higher rate of cardiac death (4.0 vs. 1.1%; HR 3.59, CI 95% 1.64-7.88; p = .01) and TV-MI (2.8 vs 0.9%; HR 2.99,CI 95% 1.22-7.37; p = .01), without differences in TLR rate (4.3 vs. 2.9%,HR 0.66, CI95% 0.35-1.25; p = .2). At multivariate Cox regression analysis, eGFR <40 mL/min (HR: 2.868) and LVEF <40% (HR: 2.394) were the only independent predictors of TLF. CONCLUSIONS: In AMI patients, Ultimaster BP-SES implantation was associated with higher rate of TLF and definite stent thrombosis compared with non-AMI patients. The high incidence of adverse events was mainly driven by the unfavorable baseline risk profile.

Young Patient with Advanced Heart Failure No Longer a Candidate for Heart Transplantation after MitraClip® Procedure.

In Europe, mitral regurgitation (MR) is the second most common form of valvular heart disease requiring surgical treatment. The case is presented of a 36-year-old woman with end-stage heart failure secondary to chemotherapy-induced cardiotoxicity, complicated by severe MR. She was listed for heart transplantation and underwent percutaneous MitraClip® implantation in order to preclude further clinical deterioration while awaiting a suitable donor. The one-year follow-up showed a strong improvement of symptoms and mostly reverse left ventricular remodelling, with consequent removal from the heart transplantation list. Video 1: Four-chamber view at baseline. Video 2: Four-chamber view at one-year follow up. Video 3: Tricuspid regurgitation and right ventricle at baseline. Video 4: Tricuspid regurgitation and right ventricle at one-year follow up.

Predictors of restenosis following contemporary subintimal tracking and reentry technique: The importance of final TIMI flow grade.

OBJECTIVES: To identify predictors of restenosis after recanalization of chronic total occlusions (CTOs) with the Subintimal Tracking And Reentry (STAR) technique. BACKGROUND: STAR is associated with high rates of restenosis but the associated factors are not clear. Understanding the underlying mechanisms may be important to improve STAR outcomes and possibly other contemporary CTO recanalization techniques utilizing extensive subintimal dissection and stenting. METHODS: We retrospectively analyzed 211 lesions that underwent a STAR procedure (between 2002 and 2013) with a final Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 or 3. One-hundred and nineteen lesions that received drug eluting stents (DES) and underwent follow-up angiography were included in the final analysis. RESULTS: Of the 119 lesions treated with DES following STAR, 75 restenoses were observed (63.0%). Utilizing multivariate analysis, TIMI flow grade in the recanalized artery following stent implantation at the end of the index procedure was the only independent predictor of restenosis. CONCLUSIONS: Following recanalization of a CTO with STAR, final TIMI flow predicted future restenosis or reocclusion. As a bailout technique, STAR resulted in a high acute success rate with good safety and acceptable long-term results. When poor flow is observed following recanalization, and prior to stent implantation, a two-step strategy whereby a second procedure is performed at an interval to maximize coronary flow at the end of the procedure may be considered with the goal to reduce the risk of future restenosis or total vessel occlusion following STAR.

Clinical outcomes of real-world patients treated with an amphilimus polymer-free stent versus new generation everolimus-eluting stents.

OBJECTIVES/BACKGROUND: To compare the 1-year clinical outcomes after implantation of the amphilimus, polymer-free stent (Cre8) versus new generation everolimus-eluting stents (EESs) in a real-world patient registry. METHODS: A total of 187 consecutive patients treated with Cre8 between January 2011 and August 2013 in four Italian centers were included. These were propensity matched with 150 patients treated with new generation EES during the same period. Primary outcome was 1-year major adverse cardiovascular events (MACE), defined as all-cause death, myocardial infarction, and target vessel revascularization. RESULTS: Both groups had similar baseline characteristics, including diabetes (28% Cre8 vs. 27.3% EES, P = 0.972) and previous percutaneous coronary intervention (56% Cre8 vs. 58% EES, P = 0.726). There was a higher prevalence of B2/C lesions in the EES group (70.1% vs. 83.8%, P < 0.001). Total stent length per patient was similar. There were no significant differences in 1-year estimated MACE (7.4% Cre8 vs. 10.2% EES, P = 0.261), all-cause mortality (1.3% Cre8 vs. 1.4% EES, P = 0.823), target vessel revascularization (5.2% Cre8 vs. 8.8% EES, P = 0.169), and target lesion revascularization (3% Cre8 vs. 7.4% EES, P = 0.108) between the two groups. When adjusting for differences in baseline lesion characteristics, hazard ratio(Cre8/EES) for MACE was not significantly different between the two groups (0.75, 95% confidence interval 0.37-1.53, P(noninferiority) = 0.001, P(superiority) = 0.432). In patients with diabetes (Cre8, n = 42; EEE, n = 41), 1-year target lesion revascularization was 2.5% in the Cre8 group versus 14.6% in the EES group (P = 0.056). CONCLUSIONS: In a "real-world" patient registry, the Cre8 stent is associated with noninferior 1-year MACE rates compared with that of new generation EES. Trends of superior efficacy in patients with diabetes treated with Cre8 require further investigation.

PFO closure with only fluoroscopic guidance: 7 years real-world single centre experience.

AIMS: To evaluate the safety and the efficacy of fluoroscopy-guided only (Fluo-G) and of echocardiography-guided (Echo-G; trans-esophageal echocardiography-TEE-or intracardiac echocardiography-ICE) percutaneous closure of patent foramen ovale (PFO). METHODS AND RESULTS: Single center retrospective registry enrolling 368 consecutive patients (mean age 50.5 years) who underwent PFO closure between June 2004 and December 2011. Most patients had prior cryptogenic stroke (n = 126; 34.2%), TIA (n = 218; 51.1%); some of these had recurrent neurological events [multiple strokes n = 28 (7.8%); multiple TIAs n = 72 (18.6%)]. All the patients underwent a preprocedure TEE. PFO closure was performed with Echo-G in 187 patients (50.8%) (TEE n = 69, 36.8% and ICE n = 124, 66.3%). In Fluo-G cases, PFO with atrial septal aneurysm (ASA) was significantly less present (P < 0.005) and smaller devices (<25 mm) were implanted more frequently (P < 0.001). Both fluoroscopy and total procedural time were lower in the Fluo-G group (P < 0.0001). No differences were found in terms of successful device deployment (98.3% Fluo-G vs. 98.3% Echo-G) and RtL-shunt at follow-up (11.7% Fluo-G vs. 7.6% Echo-G). The rate of conversion from Fluoro-G to Echo-G procedure was 4.4% (n = 8). At a median follow-up of 4 years, freedom from recurrent embolic events rate was similar between the two groups (Echo-G 94.5 vs. Fluo-G 95.7%). CONCLUSIONS: In our experience Fluoro-G PFO closure was performed mainly in cases of simple anatomy, with similar results in terms of safety and efficacy compared to Echo-G cases. Both fluoroscopy and total procedural times were lower in the Fluo-G cases.

The impact of main branch restenosis on long term mortality following drug-eluting stent implantation in patients with de novo unprotected distal left main bifurcation coronary lesions: the Milan and New-Tokyo (MITO) Registry.

BACKGROUND: In-stent restenosis (ISR) remains one of the main limitations for percutaneous coronary intervention of unprotected distal left main (UDLM). This study aims to demonstrate the impact of main-branch ISR (MB-ISR) on mortality and to clarify the optimal strategy. METHODS: Between 2002 and 2008, 482 consecutive UDLM patients treated with drug eluting stent (sirolimus and paclitaxel) were evaluated. RESULTS: During follow-up period (median 52.6 months), MB-ISR occurred in 29, SB-ISR in 65, and MB/SB-ISR in 24. Multivariable analysis demonstrated that the independent predictors of MB-ISR were calcification (HR 2.284, p = 0.016), true-bifurcation (HR 2.331, p = 0.024), insulin-dependent diabetes mellitus (insulin-DM) (HR 2.259, p = 0.048). Furthermore, final proximal postdilatation (FPPD) (HR 0.548, p = 0.077), full LM cover approach (FCA) (HR 0.605, p = 0.093) and greater MLD (HR 0.611, p = 0.062) had a tendency to reduce MB-ISR. Furthermore, the occurrence of MB-ISR within 1-year was associated with cardiac-death (HR 2.734, p = 0.017). CONCLUSIONS: The patients with MB-ISR had more comorbidities and complex lesions, resulting in higher risk of cardiac mortality as compared to the patients without MB-ISR. Presence of calcification, true-bifurcation and insulin-DM were associated with MB-ISR following UDLM intervention, while FCA, FPPD, and greater MLD seemed to be associated with the low occurrence of MB-ISR.