Wojciech Wanha

Effects of Trans-Endocardial Delivery of Bone Marrow-Derived CD133+ Cells on Left Ventricle Perfusion and Function in Patients With Refractory Angina: Final Results of Randomized, Double-Blinded, Placebo-Controlled REGENT-VSEL Trial.

Rationale: New therapies for refractory angina are needed. Objective: Assessment of transendocardial delivery of bone marrow CD133+ cells in patients with refractory angina. Methods and Results: Randomized, double-blinded, placebo-controlled trial enrolled 31 patients with recurrent Canadian Cardiovascular Society II–IV angina, despite optimal medical therapy, ≥1 myocardial segment with inducible ischemia in Tc-99m SPECT who underwent bone marrow biopsy and were allocated to cells (n=16) or placebo (n=15). Primary end point was absolute change in myocardial ischemia by SPECT. Secondary end points were left ventricular function and volumes by magnetic resonance imaging and angina severity. After 4 months, there were no significant differences in extent of inducible ischemia between groups (summed difference score mean [±SD]: 2.60 [2.6] versus 3.63 [3.6], P=0.52; total perfusion deficit: 3.60 [3.6] versus 5.01 [4.3], P=0.32; absolute changes of summed difference score: −1.38 [5.2] versus −0.73 [1.9], P=0.65; and total perfusion deficit: −1.33 [3.3] versus −2.19 [6.6], P=0.65). There was a significant reduction of left ventricular volumes (end-systolic volume: −4.3 [11.3] versus 7.4 [11.8], P=0.02; end-diastolic volume: −9.1 [14.9] versus 7.4 [15.8], P=0.02) and no significant change of left ventricular ejection fraction in the cell group. There was no difference in number of patients showing improvement of ≥1 Canadian Cardiovascular Society class after 1 (41.7% versus 58.3%; P=0.68), 4 (50% versus 33.3%; P=0.63), 6 (70% versus 50.0%; P=0.42), and 12 months (55.6% versus 81.8%; P=0.33) and use of nitrates after 12 months. Conclusion: Transendocardial CD133+ cell therapy was safe. Study was underpowered to conclusively validate the efficacy, but it did not show a significant reduction of myocardial ischemia and angina versus placebo. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01660581.

Bioresorbable vascular scaffolds in saphenous vein grafts (data from OCTOPUS registry)

Percutaneous coronary intervention (PCI) of saphenous vein grafts (SVG) with metallic stents is associated with a high rate of restenosis (19–21%) and target vessel failure in the long-term follow-up [1]. Potentially, implantation of a bioresorbable vascular scaffold (BVS) (ABSORB, Abbott Laboratories) into the stenotic SVG may be an alternative to metallic stents [2]. Although the effectiveness of BVS in treatment of de novo coronary lesions in native vessels is well documented [3], none of the previous studies evaluated the results of BVS implantation into SVG. Recently, we reported an imaging follow-up of a case of successful BVS implantation to treat a de novo stenotic SVG lesion [4–6]. Therefore, in this report we present pilot results from the OCTOPUS registry of a subgroup of patients with significant de novo SVG stenosis treated with BVS implantation.

Treatment of left main coronary artery stenosis with the STENTYS self-expandable drug-eluting stent - a pilot registry

Percutaneous coronary intervention (PCI) of the left main coronary artery (LMCA) for revascularization after stenosis is still considered controversial therapy. Previous studies were performed with balloon-expandable drug-eluting stents (DES). Balloon-expandable stents presented a challenge because they were not able to adapt effectively to variation in the vessel lumen. There are limited data on LMCA therapy with self-expandable DES for treatment of medial and distal lesions. The advantages of a self-apposing stent are adaptation to vessel size, vessel tapering, stent sizing, and good apposition. This was a pilot study to determine safety and device success rate in patients with middle and distal LMCA stenosis treated with the STENTYS self-expanding coronary DES stent. The primary endpoints were device success, acute procedural success and in-hospital and 30-day MACE. Twenty-four patients were included. Median logistic EuroSCORE was 1.6% (1.1–2.6%). Median Syntax score was 20.0 (20.0–27.2) points. Significant stenosis according to the anatomical region was in the middle of the LMCA in 5 cases (21%) and the distal part in 19 (79%). Stent sizes used were: 3.0 × 3.5 mm in 9 (37.5%); 3.5 × 4.0 mm in 3 (12.5%); 3.5 × 4.5 mm in 12 (50%). Device success and acute procedural success were achieved in 23 patients (95.8%), with no edge dissection in any patient. In 1 patient the proximal end of the stent protruded into the aorta. In all patients during their hospitalization and 30-day follow-up there were no adverse events. The data compiled from this small, single-center pilot study suggest that the STENTYS self-expanding coronary stent may be a reasonable approach to treat lesions within the LMCA. These results warrant a larger future clinical trial.

Comparison of First- and Second-Generation Drug-Eluting Stents in an All-Comer Population of Patients with Diabetes Mellitus (from Katowice-Zabrze Registry)

Background This study compared safety and efficacy of first- and second-generation DES in an unrestricted, real-life population of diabetic patients undergoing PCI. Material/Methods The study was a subanalysis of diabetic patients from the all-comer Katowice-Zabrze Registry of patients undergoing PCI with the implantation of either first- (Paclitaxel-, Sirolimus-eluting stents) or second-generation DES (Zotarolimus-, Everolimus-, Biolimus-eluting stents). Efficacy defined as major adverse cardiac and cerebrovascular events (MACCE: death, myocardial infarction, target vessel revascularization, stroke) and safety defined as stent thrombosis (ST) were evaluated at 1 year. Results From the total of 1916 patients, 717 were diabetics. Among them, 257 (36%) were treated with first-generation DES (230 [89%] Paclitaxel-eluting stents, 27 [11%] Sirolimus-eluting stents), 460 with second-generation DES (171 [37%] Zotarolimus-eluting stents, 243 [53%] Everolimus-eluting stents, 46 [10%] Biolimus-eluting stents). Rate of MACCE was equal in both groups (p=0.54). Second-generation DES had a better safety profile than first-generation DES (log-rank for cumulative ST at 1 year p<0.001). First-generation DES was a risk factor for ST (HR 5.75 [1.16–28.47], p=0.03) but not for MACCE (HR 0.89 [0.6–1.32], p=0.57). Conclusions In a real-life setting of diabetic patients undergoing PCI, second-generation DES had lower risk of ST and similar MACCE rate compared to first-generation DES.

Long-Term Percutaneous Coronary Intervention Outcomes of Patients with Chronic Kidney Disease in the Era of Second-Generation Drug-Eluting Stents

Background: The following registry (Katowice-Zabrze retrospective registry) aimed to assess the influence of a chronic kidney disease (CKD) on long-term clinical outcomes in patients undergoing percutaneous coronary intervention (PCI) using either first-generation (DES-I) or second-generation (DES-II) drug-eluting stents. Methods: The study group consisted of 1,908 consecutive patients, of whom 331 (17.3%) had CKD. CKD was defined as an estimated glomerular filtration rate of <60 mL/min/m2. We evaluated the major adverse cardiac and cerebral events (MACCE), i.e., the composite of death, myocardial infarction (MI), stroke, and target vessel revascularization at the 12-month follow-up. Results: CKD patients had a lower left ventricular ejection fraction and more often a history of MI and PCI. Coronary angiography revealed that multivessel coronary artery disease, intracoronary thrombus, and extensive calcifications were more frequent in patients with CKD. However, the SYNTAX score did not vary between patients with or without CKD. There was a higher rate of in-hospital bleedings requiring blood transfusion in patients with CKD. At the 1-year follow-up, MACCE (17.8 vs. 12.6%, HR = 1.46 [95% CI 1.05-2.03], p = 0.009) and death (8.4 vs. 2.3%, HR = 3.9 [95% CI 2.0-7.5], p < 0.001) were more often observed in CKD patients. Multivariable Cox analysis revealed that CKD was an independent risk predictor of death after PCI at the 1-year follow-up (HR = 2.1 [95% CI 1.2-3.6], p = 0.004). In comparison to DES-I, the use of DES-II did not decrease the adverse effect of CKD on MACCE. Conclusion: CKD patients had an increased risk of in-hospital bleeding requiring blood transfusion and a higher risk of MACCE and death at the 12-month follow-up. The use of second-generation DES did not improve clinical outcomes in patients with CKD at the 12-month follow-up.

First- Versus Second-Generation Drug-Eluting Stents in Acute Coronary Syndromes (Katowice-Zabrze Registry)

Background There are sparse data on the performance of different types of drug-eluting stents (DES) in acute and real-life setting. Objective The aim of the study was to compare the safety and efficacy of first- versus second-generation DES in patients with acute coronary syndromes (ACS). Methods This all-comer registry enrolled consecutive patients diagnosed with ACS and treated with percutaneous coronary intervention with the implantation of first- or second-generation DES in one-year follow-up. The primary efficacy endpoint was defined as major adverse cardiac and cerebrovascular event (MACCE), a composite of all-cause death, nonfatal myocardial infarction, target-vessel revascularization and stroke. The primary safety outcome was definite stent thrombosis (ST) at one year. Results From the total of 1916 patients enrolled into the registry, 1328 patients were diagnosed with ACS. Of them, 426 were treated with first- and 902 with second-generation DES. There was no significant difference in the incidence of MACCE between two types of DES at one year. The rate of acute and subacute ST was higher in first- vs. second-generation DES (1.6% vs. 0.1%, p < 0.001, and 1.2% vs. 0.2%, p = 0.025, respectively), but there was no difference regarding late ST (0.7% vs. 0.2%, respectively, p = 0.18) and gastrointestinal bleeding (2.1% vs. 1.1%, p = 0.21). In Cox regression, first-generation DES was an independent predictor for cumulative ST (HR 3.29 [1.30-8.31], p = 0.01). Conclusions In an all-comer registry of ACS, the one-year rate of MACCE was comparable in groups treated with first- and second-generation DES. The use of first-generation DES was associated with higher rates of acute and subacute ST and was an independent predictor of cumulative ST.

Renal Artery Stenting Associated With Improvement in Renal Function and Blood Pressure Control in Long-Term Follow-Up.

Background/Aims: Clinical benefits of percutaneous treatment of renal artery stenosis (RAS) remain controversial. The aim of this study was to evaluate the effects of renal artery stenting on kidney function and blood pressure (BP) control in the log-term follow-up. Additionally angiographic follow up was performed in selected subgroup of patients. Methods: The study was designed as international registry of 265 consecutive patients with RAS treated with renal artery stenting. The primary end-point of the study was the change in renal function and blood pressure at long-term follow-up as compared with baseline values. Evaluation of the renal function was based on estimated glomerular filtration rate (eGFR) with the use of the modification of diet in renal disease (MDRD) formula. Results: All patients had clinical follow-up at the median time of 23.8 (interquartile range: 3-90) months during ambulatory visits. At follow-up eGFR improved in 53,9% of patients. These patients had lower pre-procedural systolic BP, more severe lesion type at baseline and lower diameter stenosis in control angiography. At follow up visits, SBP improvement was observed in 77,4% of patients. The average number of anti-hypertensive medications before the procedure and at follow up did not change significantly (2,70±1,0 vs 2,49±0,9, p=0,1). Restenosis rate based on control angiography performed at median time of 15 months was 12%. Conclusion: The results of the study suggest that interventional treatment of RAS may preserve renal function and improve blood pressure control at long-term follow-up.

Impact of anaemia on long-term outcomes in patients treated with first- and second-generation drug-eluting stents; Katowice-Zabrze Registry

BACKGROUND Coexisting anaemia is associated with an increased risk of major adverse cardiac and cerebrovascular events (MACCE) and bleeding complications after percutaneous coronary intervention (PCI), especially in patients with acute coronary syndrome. AIM To assess the impact of anaemia in patients with coronary artery disease (CAD) treated with first- and second-generation drug-eluting stents (DES) on one-year MACCE. METHODS AND RESULTS The registry included 1916 consecutive patients (UA: n = 1502, 78.3%; NSTEMI: n = 283, 14.7%; STEMI/LBBB: n = 131, 6.8%) treated either with first- (34%) or second-generation (66%) DES. The study population was divided into two groups: patients presenting with anaemia 217 (11%) and without anaemia 1699 (89%) prior to PCI. Anaemia was defined according to World Heart Organisation (haemoglobin [Hb] level < 13 g/dL for men and < 12 g/dL for women). Patients with anaemia were older (69, IQR: 61-75 vs. 62, IQR: 56-70, p < 0.001), had higher prevalence of co-morbidities: diabetes (44.7% vs. 36.4%, p = 0.020), chronic kidney disease (31.3% vs. 19.4%; p < 0.001), peripheral artery disease (10.1% vs. 5.4%, p = 0.005), and lower left ventricular ejection fraction values (50, IQR: 40-57% vs. 55, IQR: 45-60%; p < 0.001). No difference between gender in frequency of anaemia was found. Patients with anaemia more often had prior myocardial infarction (MI) (57.6% vs. 46.4%; p = 0.002) and coronary artery bypass grafting (31.3% vs. 19.4%; p < 0.001) in comparison to patients without anaemia. They also more often had multivessel disease in angiography (36.4% vs. 26.1%; p = 0.001) and more complexity CAD as measured by SYNTAX score (21, IQR: 12-27 points vs. 14, IQR: 8-22 points; p = 0.001). In-hospital risk of acute heart failure (2.7% vs. 0.7%; p = 0.006) and bleeding requiring transfusion (3.2% vs. 0.5%; p < 0.001) was significantly higher in patients with anaemia. One-year follow-up showed that there was higher rate of death in patients with anaemia. However, there were no differences in MI, stroke, target vessel revascularisation (TVR) and MACCE in comparison to patients with normal Hb. There were no differences according to type of DES (first vs. second generation) in the population of patients with anaemia. CONCLUSIONS In patients with anaemia there is a significantly higher risk of death in 12-month follow-up, but anaemia has no impact on the incidence of MI, repeat revascularisation, stroke and MACCE. There is no advantage of II-DES over I-DES generation in terms of MACCE and TVR in patients with anaemia.

Role of proprotein convertase subtilisin/kexin type 9 inhibitors in patients with coronary artery disease undergoing percutaneous coronary intervention

ABSTRACT Introduction: Although novel therapies have improved outcomes in PCI patients, a sizeable number of patients still remain at high cardiovascular risk for recurrent event. There is therefore an unmet need for novel therapies that can improve clinical outcomes, with an associated satisfactory safety profile. Proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme is a novel lipid-lowering target with a potential to impact high-cardiovascular risk populations including patients with coronary artery disease (CAD), undergoing the percutaneous coronary intervention (PCI). A number of canonical and non-canonical pathways of PCSK9 action, including inflammation and platelet activation, as well as their inhibition, are undergoing intense investigation. Areas covered: This review will discuss the currently available evidence on PCSK9 inhibitors, pathways of PCSK9 enzyme action and results or its inhibition, the potential role of PCSK9 inhibitors in specific populations undergoing PCI, and completed and ongoing studies in patients with CAD. Expert commentary: PCSK9 inhibitors clinical outcomes in high risk cardiovascular disease patients and have the potential to function as powerful adjunctive therapy in patients undergoing PCI by a twofold mechanism on both lipid lowering and platelet/inflammation pathways.

Effects of Transendocardial Delivery of Bone Marrow–Derived CD133 + Cells on Left Ventricle Perfusion and Function in Patients With Refractory Angina

Rationale: New therapies for refractory angina are needed. Objective: Assessment of transendocardial delivery of bone marrow CD133+ cells in patients with refractory angina. Methods and Results: Randomized, double-blinded, placebo-controlled trial enrolled 31 patients with recurrent Canadian Cardiovascular Society II–IV angina, despite optimal medical therapy, ≥1 myocardial segment with inducible ischemia in Tc-99m SPECT who underwent bone marrow biopsy and were allocated to cells (n=16) or placebo (n=15). Primary end point was absolute change in myocardial ischemia by SPECT. Secondary end points were left ventricular function and volumes by magnetic resonance imaging and angina severity. After 4 months, there were no significant differences in extent of inducible ischemia between groups (summed difference score mean [±SD]: 2.60 [2.6] versus 3.63 [3.6], P=0.52; total perfusion deficit: 3.60 [3.6] versus 5.01 [4.3], P=0.32; absolute changes of summed difference score: −1.38 [5.2] versus −0.73 [1.9], P=0.65; and total perfusion deficit: −1.33 [3.3] versus −2.19 [6.6], P=0.65). There was a significant reduction of left ventricular volumes (end-systolic volume: −4.3 [11.3] versus 7.4 [11.8], P=0.02; end-diastolic volume: −9.1 [14.9] versus 7.4 [15.8], P=0.02) and no significant change of left ventricular ejection fraction in the cell group. There was no difference in number of patients showing improvement of ≥1 Canadian Cardiovascular Society class after 1 (41.7% versus 58.3%; P=0.68), 4 (50% versus 33.3%; P=0.63), 6 (70% versus 50.0%; P=0.42), and 12 months (55.6% versus 81.8%; P=0.33) and use of nitrates after 12 months. Conclusion: Transendocardial CD133+ cell therapy was safe. Study was underpowered to conclusively validate the efficacy, but it did not show a significant reduction of myocardial ischemia and angina versus placebo. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01660581.