Giorgio Bassanelli

Predictors of cardiac death in patients with coronary chronic total occlusion not revascularized by PCI

BACKGROUND Limited data are available on clinical outcome of patients with previously failed or not attempted chronic total occlusion (CTO) recanalization by percutaneous coronary intervention (PCI). The aim of the study is to determine prevalence and predictors of cardiac death in patients with CTO not revascularized by PCI. METHODS Double-center study analyzing data of 1.345 consecutive patients with at least one CTO between 1998 and 2008. Of these, 847 patients were successfully revascularized (Revascularized group) and 498 patients were not revascularized (Not revascularized group) either due to failure of CTO-PCI (n=337) or because no attempt was made (n=161). RESULTS At 4-year clinical follow-up, Not revascularized patients had a significantly higher rate of cardiac mortality (8.5% vs. 2.5%, p<0.0001) and sudden cardiac death (2.7% vs. 0.5%, p=0.001) compared to those Revascularized. The separate adjusted Cox-model analysis made for Not revascularized patients showed the most significant independent predictors of cardiac death were: chronic renal failure [HR (CI), 6.0 (2.66-13.80)], low-LVEF [5.7 (2.84-11.58)], insulin-dependent diabetes mellitus (IDDM) 4.6 [(1.96-10.97)]. In the Revascularized group, the presence of 3-vessel disease was the only significant independent predictor of cardiac death [4.4 (1.40-13.70)]. CONCLUSIONS CTO patients Not revascularized had a significant higher rate of cardiac mortality and sudden cardiac death compared to those Revascularized. Within Not revascularized patients, the presence of low-LVEF, or CRF or IDDM was associated with an incidence of cardiac death at least 4 times higher than those without the same risk factors.

Coronary chronic total occlusions: mid-term comparison of clinical outcome following the use of the guided-STAR technique and conventional anterograde approaches.

Aim: There are limited data on the mid‐term safety following the use of the guided‐subintimal tracking and re‐entry (guided‐STAR) technique for the treatment of chronic total occlusions (CTO) and concerns have arisen about a potential increased risk of stent thrombosis (ST). Objectives: The aim of this study was to evaluate the mid‐term safety in terms of cardiac death and ST after recanalization using the contrast guided‐STAR technique when compared to conventional anterograde CTO recanalization (CA‐CTO). Methods and Results: This retrospective study analyzed 355 consecutive patients with successful angiographic recanalization (residual stenosis <20% and TIMI flow grade ≥2) of CTO lesion. Seventy‐four (20.8%) underwent guided‐STAR and 281 (79.2%) had CA‐CTO. Survival rates were estimated using the Kaplan‐Meier method. Compared to CA‐CTO patients, the rate of the following clinical, angiographic, and procedural characteristics were significantly higher in guided‐STAR patients: hypercholesterolemia (84 vs. 67%, P = 0.004), previous CABG (41.3 vs. 15.7%, P < 0.0001), three‐vessel disease, (62.7 vs. 47%, P = 0.019), right coronary artery CTO (62.7 vs. 41.6%, P = 0.002), stent length (68.15 vs. 54.05 mm, P < 0.0001). A drug‐eluting stent was implanted in the majority of cases (89.2% guided‐STAR vs. 93.5% CA‐CTO). At a median follow‐up of 779 days (IQR 495–1035), there were no significant differences in cardiac survival (97.2 vs. 97.5%, Log‐rank P = 0.912) and cumulative ARC ST rates (2.8 vs. 1.8%, Log‐rank P = 0.610) for guided‐STAR and CA‐CTO patients, respectively. The rate of restenosis was significantly higher in the guided‐STAR group compared to the CA‐CTO group (54 vs. 30%, Log‐rank P < 0.0001). The adjusted Cox proportional‐hazard analysis for procedural technique showed that the only significant independent predictor of restenosis was the stent length (HR, 1.017; 95% CI, 1.008–1.027; P < 0.0001). Conclusion: At mid‐term follow‐up, the guided‐STAR was not inferior to CA‐CTO in terms of safety. The only significant independent predictor of restenosis was the stent length.

Effect of partial inhibition of fatty acid oxidation by trimetazidine on whole body energy metabolism in patients with chronic heart failure

Objective Trimetazidine may have beneficial effects on left ventricular (LV) function in patients with systolic heart failure. The authors assessed whether long-term addition of trimetazidine to conventional treatment could improve, along with LV function, resting whole body energy metabolism in patients with chronic systolic heart failure. Design Single blind randomised study. Setting University Hospital. Patients 44 patients with systolic heart failure receiving full medical treatment. Interventions Indirect calorimetry and two-dimensional echocardiography at baseline and after 3 months. Main outcome measures Whole body resting energy expenditure (REE), percentage of predicted REE, LV ejection fraction (EF), NYHA class, quality of life. Results Trimetazidine increased EF compared with conventional therapy alone (from 35±8% to 42±11% vs from 35±7% to 36±6%; p=0.02, analysis of variance for repeated measures). NYHA class and quality of life also improved compared with conventional therapy (p<0.0001). REE (from 1677±264 to 1580±263 kcal/day) and percentage of predicted REE (based on the Harris–Benedict equation: from 114±10% to 108±9%) decreased in the trimetazidine group, but not in the control group (REE from 1679±304 to 1690±337 kcal/day and percentage of predicted REE from 113±12% to 115±14%). The variation was different between groups (p=0.03 and 0.023, respectively). Conclusions In patients with systolic heart failure, improvement in functional class and LV function induced by middle-term trimetazidine therapy is paralleled by a reduction in whole body REE. The beneficial cardiac effects of trimetazidine may be also mediated by a peripheral metabolic effect.

Clinical Outcomes After Unrestricted Implantation of Everolimus-Eluting Stents

OBJECTIVES The aim of this study was to evaluate the efficacy and safety of unrestricted everolimus-eluting stent (EES) implantation in a contemporary cohort of real-world patients. BACKGROUND The randomized SPIRIT (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions) trials have evaluated the performance of EES, resulting in their approval by the Food and Drug Administration, but data regarding unselected usage, including off-label indications are lacking. METHODS Consecutive patients treated with EES (either PROMUS, Boston Scientific Corp., Natick, Massachusetts, or XIENCE-V, Abbott Vascular Devices, Santa Clara, California) between October 2006 and February 2008 were analyzed. End points were cardiac death, myocardial infarction (MI), ischemic-driven target lesion revascularization (TLR), stent thrombosis (ST), and major adverse cardiac events (MACE) (a composite of cardiac death, MI, TLR) during follow-up. RESULTS We identified 345 patients (573 lesions) treated with EES. The majority of patients (71.9%) were treated for > or =1 off-label or untested indication. Clinical follow-up was completed in 99%. At a median follow-up of 378 days (interquartile range 334 to 473), MACE occurred in 36 (10.6%) patients, TLR in 27 (7.9%), MI in 7 (2.1%), and cardiac death in 7 (2.1%). Definite and probable ST was observed in 3 (0.9%) cases. Off-label EES implantation was not associated with a statistically significant increased risk of MACE (12.2% vs. 6.3%, p = 0.17), TLR (9.3% vs. 4.2%, p = 0.18), or ST (0.8% vs. 1.1%, p = 1.0). On multivariable analysis, previous bypass surgery (p = 0.002) and diabetes (p = 0.03) were associated with MACE. CONCLUSIONS In unrestricted daily practice, EES were implanted predominantly for off-label indications and associated with a relative low rate of MACE and TLR.

Nitric-oxide mediated effects of transdermal capsaicin patches on the ischemic threshold in patients with stable coronary disease.

Background Capsaicin has been shown to exert direct vasodilating effects through increased calcitonin gene-related peptide (CGRP) release. However, no data exist on its effect following systemic administration in humans. Methods Twelve male patients with stable coronary disease and a persistently positive exercise were selected for study. According to a double blind, placebo-controlled, cross-over study, patients were randomized to placebo or 3 g oleic capsaicin-containing patches, on 2 different days and with a 2-day interval between treatments. Patients performed treadmill exercise testing according to the Bruce protocol. Time to 1 mm ST segment depression and to peak exercise, maximal ST segment depression, and the number of ECG leads showing diagnostic changes were also measured. Blood samples for nitric oxide (NO) and CGRP were drawn at baseline, 2, 6, and 24 hours after exercise. Results On placebo, all patients had a positive ECG during exercise test. Only 1 patient experienced angina, on both treatments. With capsaicin, 1 patient had a negative exercise, while 8 patients significantly increased time to 1 mm ST depression from 328 ± 167 to 401 ± 174 seconds (P = 0.01). Of the remaining patients, 1 did not show any changes and 2 showed a worse ischemic threshold when on capsaicin. CGRP levels were not significantly different between placebo and capsaicin treatment. Conversely, when on capsaicin, NO significantly increased at 6 hours. Conclusions Transdermal capsaicin may improve ischemic threshold in patients with stable coronary disease, probably through arteriolar vasodilation. Increased capsaicin-induced NO availability could represent the principal mechanism of action.

Metabolic therapy of heart failure.

Alterations of cardiac metabolism can be present in several cardiac syndromes. Heart failure may itself promote metabolic changes such as insulin resistance, in part through neurohumoral activation, and determining an increased utilization of non-carbohydrate substrates for energy production. In fact, fasting blood ketone bodies as well as fat oxidation have been shown to be increased in patients with heart failure. The result is depletion of myocardial ATP, phosphocreatine and creatine kinase with decreased efficiency of mechanical work. A direct approach to manipulate cardiac energy metabolism consists in modifying substrate utilization by the failing heart. To date, the most effective metabolic treatments include several pharmacological agents, such as trimetazidine and perhexiline, that directly inhibit fatty acid oxidation. These agents have been originally adopted to increase the ischemic threshold in patients with effort angina. However, the results of current research is supporting the concept that shifting the energy substrate preference away from fatty acid metabolism and toward glucose metabolism could be an effective adjunctive treatment in patients with heart failure, in terms of left ventricular function and glucose metabolism improvement. In fact, these agents have also been shown to improve overall glucose metabolism in diabetic patients with left ventricular dysfunction. In this paper, the recent literature on the beneficial therapeutic effects of modulation of cardiac metabolic substrates utilization in patients with heart failure is reviewed and discussed.

Differential Long-term Effects of Carvedilol on Proinflammatory and Antiinflammatory Cytokines, Asymmetric Dimethylarginine, and Left Ventricular Function in Patients With Heart Failure

Neuroendocrine/inflammatory and endothelial functions have been indicated as crucial for heart failure (HF) patients. We evaluated relation in HF patients among cytokines and asymmetric dimethylarginine (ADMA) and left ventricular ejection fraction (LVEF) at baseline and after long-term administration of carvedilol. Interleukin 10 (IL-10), interleukin 18 (IL-18), and ADMA were measured in 22 NYHA class II to IV HF patients at baseline and after 40 ± 14 months of carvedilol treatment. Patients were divided into 2 groups according to whether, after treatment with carvedilol, LVEF had increased at least 5% (responders) or less than 5% (non-responders). In responders (11 of 22 patients), LVEF increased from 38 ± 6% to 50 ± 7%, (P < 0.001); in non-responders, it decreased from 36 ± 9% to 31 ± 6%, (P = 0.02); NYHA class significantly decreased in both groups. IL-18 decreased in responders (from 586.4 ± 128 to 183.13 ± 64.4 pg/mL; P < 0.001) and in non-responders (from 529.3 ± 116.25 to 142.4 ± 58.9 pg/mL; P < 0.001). IL-10 increased in responders (from 0.49 ± 0.25 to 2.01 ± 1.01 pg/mL; P < 0.001) and in non-responders (from 0.64 ± 0.31 to 1.33 ± 0.59 pg/mL; P < 0.001). Conversely, ADMA levels decreased only in responders (from 0.67 ± 0.16 to 0.44 ± 0.15 μmol/L; P < 0.001), and an inverse correlation was observed between basal ADMA levels and changes in LVEF after treatment. In HF patients, carvedilol appears to reduce symptoms and the expression of inflammation, regardless of the LV functional response. In those patients showing improvement of LVEF, the reduction of inflammation is paralleled by a reduction of ADMA. We surmise that carvedilol could be effective at various independent levels as a result of possible pleiotropic effects of this agent.

Long-term follow-up of multivessel percutaneous coronary intervention with drug-eluting stents for de novo lesions with correlation to the SYNTAX score

BACKGROUND Stent thrombosis (ST) and restenosis are concerns after percutaneous coronary intervention (PCI). Limited information exists concerning clinical and angiographic outcomes following multiple stent insertion. We therefore present the long-term outcome from drug-eluting stent (DES) insertion and correlate this with the Syntax score. METHODS AND RESULTS Between April 2002 and 2006, all patients that underwent multilesion PCI (defined as ≥4 DES) were included for analysis, and follow-up commenced from the point where the fourth stent was inserted. Three hundred and seventy-four patients were identified, comprising 1972 lesions; 99% had clinical (30±16 months), and 72% had angiographic follow-up. The mean number of stents implanted was 5.7±1.9 and with length of 137±50 mm and Syntax Score of 24±8. The Syntax score (SS) did not predict major adverse cardiac events (MACE) at long-term follow-up, which occurred in 33% in the low SS (<22), 34% intermediate SS (22-32) and 40% in the high SS (>33); P=ns. However, the number of stents implanted correlated with events [MACE: 12% (4 DES), 35% (4-6 DES), 61% (>6 DES)]. There were 11 (2.9%) definite and probable ST: four acute and subacute, three late, and four very late. CONCLUSIONS This study demonstrates an acceptable occurrence of myocardial infarction, death, repeat revascularisation, and ST in patients with multivessel de novo lesions, which had better correlation with the number of DES inserted than the Syntax score.

Prognosis of mild/moderate chronic systolic heart failure

⁎ Corresponding author. Tel.: +39 02 26437366; fax: +39 02 26437358. E-mail address: gabriele.fragasso@hsr.it (G. Fragasso). Despite many advances in diagnosis and therapy, heart failure (HF) is still apparently related to poor prognosis, with reported mortality rates at 5-year over 40% (9% per year) — a six-fold adverse rate compared with the general population [1–3]. To address this important public health issue, we sought to determine morbidity and mortality rates in our population of chronic HF out-patients, followed-up in the heart failure clinic of our Institution and compare them with rates reported in previous surveys. Of a total of 403 systolic heart failure patients attending our clinic from March 1992 to December 2005 and on optimal medical and device therapy, 372 (269 males, age at diagnosis 66±11 yrs) were considered eligible for study analysis. The remaining 31 patients could not be traced. Patients lost at followup were tested for baseline variables (age, gender, NYHA class, ejection fraction) and were not statistically different compared with the group with complete followup. Mean follow-up from first diagnosis was 67±44 months (median 58.50, Q1=40.75, Q3=80.25). The diagnosis of HF was ascertained according to European Society of Cardiology criteria: I) symptoms of heart failure and II) objective evidence (by echocardiography) of cardiac systolic dysfunction (at rest) and (in cases where the diagnosis was in doubt) III) response to treatment directed towards heart failure. Criteria I and II had to be fulfilled in all cases. Furthermore, we selected only patients with a baseline ejection fraction (EF)≤45% (Simpson biplane). Cardiovascular mortality was calculated as the number of events per 1000 person-year at risk. Mortality and morbidity were compared with the national population by using standardized mortality ratios, referring to national data classified by age and sex (data from the Italian Central Statistics Institute – ISTAT – We found that application twice of 4.3 MHz intracardiac ultrasound for 60 s at an intensity of 1.0 W/cm were suitable parameters for higher efficiency of transfection and low percentage of myocardial tissue impairment. Furthermore, the EGFP mRNA of EGFP+MB/US group was significantly higher than those of other groups, which confirmed that that the combination of intracardiac ultrasonic exposure and intramyocardial injection of microbubbles could enhance gene transfection. The main findings of this investigation were: 1) the intracardiac ultrasonic exposure technology and injection system provides an accurate and reliable means of delivering an injectate transendocardially into the LV, 2) this system allows for the injection of a naked DNA gene into designated myocardial sites and results in successful gene transfer and protein expression. This novel approach could also obviously reduce gene and microbubble dosage. In sum, intramyocardial injection microbubble combination of intracardiac ultrasonic exposure can enhance gene expression. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [5].

History of vasomotor symptoms, extent of coronary artery disease, and clinical outcomes after acute coronary syndrome in postmenopausal women

Objective: Vasomotor symptoms (VMS) during menopausal transition have been linked to a higher burden of cardiovascular risk factors, subclinical vascular disease, and subsequent vascular events. We aim to investigate the association of VMS with the extent of coronary disease and their prognostic role after an acute coronary syndrome. Methods: The Ladies Acute Coronary Syndrome study enrolled consecutive women with an acute coronary syndrome undergoing coronary angiography. A menopause questionnaire was administered during admission. Angiographic data underwent corelab analysis. Six out of 10 enrolling centers participated in 1-year follow-up. Outcome data included the composite endpoint of all-cause mortality, recurrent myocardial infarction, stroke, and rehospitalization for cardiovascular causes within 1 year. Results: Of the 415 women with available angiographic corelab analysis, 373 (90%) had complete 1-year follow-up. Among them, 202 women had had VMS during menopausal transition. These women had the same mean age at menopause as those without VMS (50 years in both groups), but were younger at presentation (median age 71 vs 76 years; P < 0.001), despite a more favorable cardiovascular risk profile (chronic kidney dysfunction 4.5% vs 15.9%; P = 0.001; prior cerebrovascular disease 4.5 vs 12.2%; P = 0.018). Extent of coronary disease at angiography was similar between groups (mean Gensini score 49 vs 51; P = 0.6; mean SYNTAX score 14 vs 16; P = 0.3). Overall cardiovascular events at 1 year did not differ between groups (19% vs 22%; P = 0.5). Conclusions: In postmenopausal women with an acute coronary syndrome, a history of VMS was associated with younger age at presentation, despite a lower vascular disease burden and similar angiographically defined coronary disease as compared with women without VMS. No difference could be found in terms of overall clinical outcomes. These results should be interpreted cautiously as all analyses were unadjusted and did not account for risk factor differences between women with and without a history of VMS.