Sirolimus-Eluting Balloon for the Treatment of Coronary Lesions in Complex ACS Patients: The SELFIE Registry.

BACKGROUND: Sirolimus-coated balloons (SCBs) represent a novel therapeutic option for both in-stent restenosis (ISR) and de novo coronary lesions treatment, especially in small vessels. Our registry sought to evaluate the procedural and clinical outcomes of such devices in a complex acute coronary syndrome (ACS) clinical setting. METHODS AND RESULTS: We treated 74 consecutive patients with percutaneous coronary intervention (PCI) with at least 1 SCB used for ISR and/or de novo coronary lesion in small vessels at our institution. Sixty-two patients presented with ACS, and their data were included in our analysis. The mean age was 67 ± 10 years, and patients presenting with ST-elevated myocardial infarction (STEMI) were 14 (23%). De novo lesions were 52%, whereas ISR was 48%. Procedural success occurred in 100% of the cases. At the 11 ± 7 months follow-up, major adverse cardiovascular events (MACEs) were 3 (4.8%). Cardiovascular death (CD) occurred in 1 (1.6%) patient and myocardial infarction (MI) in 2 patients (3.2%) as well as ischemia-driven target lesion revascularization (TLR). One probable subacute thrombosis occurred (1.6%) with no major bleedings. In a subgroup analysis, the incidence of MACE did not show significant differences between patients treated for de novo lesions and ISR (HR: 0.239; CI 95%: 0.003-16.761, p=0.509). CONCLUSIONS: In the SELFIE prospective registry, SCB showed a good safety and efficacy profile for the treatment of coronary lesions, both ISR and/or de novo in small vessels, in a complex ACS population of patients at the 11 ± 7 months follow-up.

Closed versus open cell stent for high-risk percutaneous coronary interventions in ST-elevation acute myocardial infarction: the Closed versus Open Cells stent for High risk percutaneous coronary Interventions in ST-Elevation acute myocardial infarction (COCHISE) pilot study.

BACKGROUND: Stent deployment may be associated with distal embolization and slow flow in coronary thrombotic lesions. There are no data on the risk of distal thrombus embolization according to the stent design. The aim was to evaluate coronary flow after percutaneous coronary interventions (PCI) in acute myocardial infarction according to the employed stent (closed versus open cell design). METHODS: From March 2010 to December 2011, 223 consecutive patients with acute ST-elevation myocardial infarction were randomized to primary PCI either with an open cell (112 patients, 88 men) or with a closed cell stent design (111 patients, 92 men). The primary endpoint was the corrected TIMI frame count (cTFC) after the procedure. RESULTS: There were no significant differences in procedural success nor in-stent deployment in the 2 groups. At baseline, there were no significant differences in cTFC between the 2 groups (70 ± 37 and 67 ± 39, P = .65, respectively). After the procedure, the open cell group showed significantly higher cTFC compared to the closed cell group (18 ± 11 and 15 ± 5, P = .003 respectively). This difference was associated with a significant lower rate of TIMI 3 flow (87% and 95%, P = .037) and myocardial blush grade 3 (65% and 87%, P = .001) in the open compared to the closed cell group. There were 2 cases of death in the open cell and 1 case in the closed cell group. CONCLUSIONS: The use of a closed cell stent design rather than an open cell during PCI for acute ST-elevation myocardial infarction is associated with better coronary angiographic flow after PCI.

REabsorbable vs. DUrable Polymer Drug-Eluting Stents in All-Comer PatiEnts: the REDUCE registry.

BACKGROUND: While the superiority of reabsorbable-polymer drug-eluting stents (RP-DES) over bare-metal stents and first-generation durable-polymer (DP)-DES has been largely established, their advantage compared with new-generation DP-DES is still controversial. This study aimed was to compare clinical outcomes of all-comer patients undergoing percutaneous coronary intervention (PCI) with new generation DP-DES or RP-DES implantation. METHODS: We prospectively enrolled 679 consecutive patients treated with PCI with RP-DES or DP-DES. The primary endpoint was the 1-year incidence of major adverse clinical events (MACE), a composite of death, myocardial infarction (MI), and target vessel revascularization (TVR). Target lesion revascularization (TLR) and definite stent thrombosis were also recorded. RESULTS: A total of 439 (64.6%) received RP-DES and 240 (36.4%) received DP-DES. No significant difference in the incidence of MACE (5.9 vs. 4.9%; hazard ratio, 1.23; 95% confidence interval (CI), 0.61-2.49; P = 0.569), death (1.8 vs. 1.7%; hazard ratio, 1.09; 95% CI, 0.33-3.64; P = 0.882), MI (2.3 vs. 2.1%; hazard ratio, 1.05; 95% CI, 0.36-3.08; P = 0.927), TVR (2.3 vs. 1.3%; hazard ratio, 1.70; 95% CI, 0.47-6.20; P = 0.418), TLR (1.4 vs. 0.4%; hazard ratio, 3.06; 95% CI, 0.37-25.40; P = 0.301), and definite stent thrombosis (0.5 vs. 0.4%; hazard ratio, 1.09; 95% CI, 0.10-12.10; P = 0.942) was observed between RP-DES and DP-DES patients at 1-year follow-up. These results were confirmed in a propensity score-matched cohort (n = 134 per group). CONCLUSION: In our registry including a real-world population of all-comer patients undergoing PCI, RP-DES, or durable polymer-DES showed similar efficacy and safety at a 1-year follow-up.

Exercise promotes angiogenesis and improves beta-adrenergic receptor signalling in the post-ischaemic failing rat heart.

AIMS: We investigated whether exercise training could promote angiogenesis and improve blood perfusion and left ventricular (LV) remodelling of the post-myocardial infarction (MI) failing heart. We also explored the contribution of ameliorated beta-adrenergic receptor signalling and function on the overall improvement of cardiac contractility reserve induced by exercise. METHODS AND RESULTS: Adult Wistar male rats were randomly assigned to one of four experimental groups. Sham-operated and post-MI heart failure (HF) rats were housed under sedentary conditions or assigned to 10-weeks of a treadmill exercise protocol. At 4 weeks after MI, sedentary HF rats showed LV eccentric hypertrophy, marked increase of LV diameters associated with severely impaired fractional shortening (14 +/- 5%), increased LV end diastolic pressure (20.9 +/- 2.6 mmHg), and pulmonary congestion. In addition, cardiac contractile responses to adrenergic stimulation were significantly blunted. In trained HF rats, exercise was able to (i) reactivate the cardiac vascular endothelial growth factor pathway with a concurrent enhancement of myocardial angiogenesis, (ii) significantly increase myocardial perfusion and coronary reserve, (iii) reduce cardiac diameters, and (iv) improve LV contractility in response to adrenergic stimulation. This latter finding was also associated with a significant improvement of cardiac beta-adrenergic receptor downregulation and desensitization. CONCLUSIONS: Our data indicate that exercise favourably affects angiogenesis and improves LV remodelling and contractility reserve in a rat model of severe chronic HF.

An active lifestyle improves outcome of primary angioplasty in elderly patients with acute myocardial infarction.

BACKGROUND: Regular physical activity has been shown to improve outcome of acute myocardial infarction (AMI) in the elderly population. The aim of this study was to evaluate whether the positive role of an active lifestyle on cardiac prognosis extends to elderly patients with AMI who undergo primary percutaneous transluminal coronary angioplasty (PTCA). METHODS: We prospectively studied 180 patients with AMI aged > or = 70 years and treated with primary PTCA. In all patients, physical activity levels before AMI were quantified by a score derived from the Physical Activity Scale for the Elderly (PASE). Cardiac deaths and nonfatal cardiac events were evaluated within 30 days and 1-year from primary PTCA. RESULTS: A high PASE score was significantly associated with a strong reduction of 30-day cardiac deaths (from 23.1% to 4%; P for trend = .021) and overall nonfatal events (from 21.1% to 10%; P for trend = .01). Accordingly, at 1 year of follow-up, the incidence of cardiac mortality and nonfatal events significantly decreased with increasing PASE score (from 28.8% to 8% and from 55.7% to 14.5%, respectively). Logistic regression analysis indicated that physical activity before AMI was an independent predictor of increased survival in those patients that showed the highest PASE scores. In addition, at 6 months of follow-up, although low ejection fraction and recurrent angina strongly predicted 1-year mortality, high PASE scores still predicted a better outcome. CONCLUSIONS: Our data indicate that an active lifestyle may favorably affect early and late outcomes of primary PTCA in the elderly population.

Prior exercise improves age-dependent vascular endothelial growth factor downregulation and angiogenesis responses to hind-limb ischemia in old rats.

Downregulation of hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF) are shown to be involved in age-dependent impairment of angiogenesis. In this study, we explore whether prior exercise is able to affect these molecular patterns favorably and to enhance neoangiogenesis in old Wistar rats with hind-limb ischemia. At day 7 after surgery, HIF-1alpha and VEGF expression increased in the ischemic muscle of trained animals. Exercise increased capillary density and limb perfusion as revealed by histologic, angiographic, and dyed bead techniques. Furthermore, exercise capacity and limb trophism have significantly improved in trained aged rats. In these animals, the reduction of VEGF serum levels has reflected the comprehensive improvement in local ischemia evoked by exercise. In conclusion, prior exercise represents a valid tool to counteract age-related molecular alterations resulting in impaired angiogenesis in response to ischemia.

Lymphocyte G-protein-coupled receptor kinase-2 is upregulated in patients with Alzheimer's disease.

Alterations in signal transduction pathway of G-protein-coupled receptors (GPCRs) have been found in the cerebrocortex and in the peripheral cultured tissues of patients with Alzheimer's disease (AD). The G-protein-coupled receptor kinase-2 (GRK2) plays an important role in regulating the GPCRs signaling: its increased expression is associated with receptor desensitization. The aim of this study was to explore GRK2 levels in peripheral lymphocytes of AD patients and to establish a correlation between lymphocyte protein concentrations and the degree of cognitive impairment. GRK2 mRNA and protein expression were evaluated in the lymphocytes of AD patients with mild or moderate/severe cognitive impairment and in age-matched healthy subjects. Both GRK2 mRNA and protein expression were higher in AD patients lymphocytes compared to controls. Furthermore, lymphocyte GRK2 levels were significantly correlated to the degree of cognitive decline. Our preliminary data suggest that GRK2 is involved in GPCRs coupling dysfunction observed in AD patients. Further studies are needed in order to verify whether the lymphocyte GRK2 might be utilized as a novel biomarker in AD diagnosis and clinical monitoring.

[Fractional flow reserve: a practical guide for interventional cardiologists and the cardiologist's point of view]. / Riserva frazionale di flusso: una breve guida pratica all'utilizzo per l'interventista e il punto di vista del cardiologo clinico.

Fractional flow reserve (FFR) is considered the gold standard for functional assessment of coronary stenosis in stable coronary artery disease. The use of FFR enables an ischemia-guided revascularization with improvement of clinical outcomes in a cost-effective fashion. Both clinical and interventional cardiologists should be aware of the advantages and potential pitfalls of this technique. We focus on FFR with the aim to provide the clinical cardiologist with information on indications and technical aspects to confirm a correct execution of FFR in different coronary anatomical settings.

The combined use of Drug-eluting balloon and Excimer laser for coronary artery Restenosis In-Stent Treatment: The DERIST study.

AIM: Stents reduce angiographic restenosis in comparison with balloon angioplasty. The rate of in-stent restenosis (ISR), although less frequent than post-angioplasty restenosis, is becoming increasingly prevalent due to the recent exponential increase in the use of intracoronary stents. The aim of this study is to evaluate angiographic and clinical outcomes of PTCA in combination with the use of excimer laser coronary angioplasty (ELCA) and drug-eluting balloon (DEB) in treatment of in-stent restenosis (ISR). METHODS AND RESULTS: This multi-centric case-control study evaluated angiographic and clinical outcomes of PTCA with excimer laser coronary angioplasty (ELCA) and drug-eluting balloon (DEB) in 80 patients with in-stent restenosis (ISR). All patients underwent nine months of clinical and a coronary angiography follow-up. This study showed clinical and angiographic long-term success in the 91% of the patients. The incidence of myocardial infarctions and deaths was lower than the rate after plain balloon angioplasty within the stent. CONCLUSIONS: This study showed that excimer laser coronary angioplasty (ELCA) and drug-eluting balloon (DEB) may be an alternative treatment for in-stent restenosis (ISR).

Early outcome of high energy Laser (Excimer) facilitated coronary angioplasty ON hARD and complex calcified and balloOn-resistant coronary lesions: LEONARDO Study.

AIM: An innovative xenon-chlorine (excimer) pulsed laser catheter (ELCA X80) has been recently used for the treatment of complex coronary lesions, as calcified stenosis, chronic total occlusions and non-compliant plaques. Such complex lesions are difficult to adequately treat with balloon angioplasty and/or intracoronary stenting. The aim of this study was to examine the acute outcome of this approach on a cohort of patients with coronary lesions. METHODS AND RESULTS: Eighty patients with 100 lesions were enrolled through four centers, and excimer laser coronary angioplasty was performed on 96 lesions (96%). Safety and effectiveness data were compared between patients treated with standard laser therapy and those treated with increased laser therapy. Laser success was obtained in 90 lesions (93.7%), procedural success was reached in 88 lesions (91.7%), and clinical success in was obtained in 87 lesions (90.6%). There was no perforation, major side branch occlusion, spasm, no-reflow phenomenon, dissection nor acute vessel closure. Increased laser parameters were used successfully for 49 resistant lesions without complications. CONCLUSIONS: This study suggests that laser-facilitated coronary angioplasty is a simple, safe and effective device for the management of complex coronary lesions. Furthermore, higher laser energy levels delivered by this catheter improved the device performance without increasing complications.

[Epidemiology and risk factors for heart failure in the elderly]. / Epidemiologia clinica e fattori di rischio per scompenso cardiaco nell'anziano.

Heart failure achieves particular relevance and different characteristics in the elderly population, especially for the clinical complexity related to the presence of comorbidity and chronicity, which are common conditions in these patients. Despite recent advances in clinical approach, diagnosis and therapeutic management of heart failure, the incidence and prevalence of this syndrome are still increasing, owing to the better control of the disease, and, largely, to the aging of the population. Epidemiologic data indicate that heart failure represents a crucial problem in the elderly population in terms of social, economic, and health burden. Despite their importance in the worsening of heart failure and prevention of the progression of this syndrome, the risks of hospital readmission and the causes of exacerbation have not been systematically evaluated in controlled trials. This explains why the precipitating factors of heart failure remain unknown in more than 40% of cases. For these reasons, prospective studies are needed in order to assess and clearly define the risk of hospital readmission and the causes related to heart failure exacerbation in the elderly population.

An active lifestyle prior to coronary surgery is associated with improved survival in elderly patients.

BACKGROUND: An active lifestyle is associated with a reduced cardiovascular risk in middle-aged as well as in elderly patients. In the present study, we investigated the association between physical activity habits of elderly participants prior to coronary artery bypass grafting (CABG) and survival free from both all-cause and cardiac death. METHODS AND RESULTS: Study population consisted of 587 elderly patients (>or=70 years) CABG patients stratified, according to the Physical Activity Scale for the Elderly (PASE), into less active (low PASE) and exercised (high PASE) groups. At follow-up (mean: 44.3 +/- 21.0 months), 33 (37.1%) of 89 total deaths occurred for cardiac causes. Sixty-month survival rate was 65% and 96% for low-PASE and high-PASE groups, respectively (log rank = 49.460, p < .0001). Cox survival analysis indicated a significant (p < .0001) nonlinear association between PASE score increments and improved survival with the most evident differences in the lowest score categories. A robust association was also found between low PASE score and increased cardiac-related mortality (p < .0001). CONCLUSIONS: Our data indicate that a more active lifestyle is significantly associated with improved survival in elderly CABG patients. The nonlinearity of the relation suggests that more sedentary patients could have the most benefit on survival by increasing their exercise lifestyle habits. The improved outcome is explained by both cardiac and overall mortality reduction.

Exercise training and beta-blocker treatment ameliorate age-dependent impairment of beta-adrenergic receptor signaling and enhance cardiac responsiveness to adrenergic stimulation.

Cardiac beta-adrenergic receptor (beta-AR) signaling and left ventricular (LV) responses to beta-AR stimulation are impaired with aging. It is shown that exercise and beta-AR blockade have a favorable effect on cardiac and vascular beta-AR signaling in several cardiovascular diseases. In the present study, we examined the effects of these two different strategies on beta-AR dysregulation and LV inotropic reserve in the aging heart. Forty male Wistar-Kyoto aged rats were randomized to sedentary, exercise (12 wk treadmill training), metoprolol (250 mg.kg(-1).day(-1) for 4 wk), and exercise plus metoprolol treatment protocols. Ten male Wistar-Kyoto sedentary young rats were also used as a control group. Old trained, old metoprolol-treated, and old trained plus metoprolol-treated rats showed significantly improved LV maximal and minimal first derivative of the pressure rise responses to beta-AR stimulation (isoproterenol) compared with old untrained animals. We found a significant reduction in cardiac sarcolemmal membrane beta-AR density and adenylyl cyclase activity in old untrained animals compared with young controls. Exercise training and metoprolol, alone or combined, restored cardiac beta-AR density and G-protein-dependent adenylyl cyclase activation in old rats. Although cardiac membrane G-protein-receptor kinase 2 levels were not upregulated in untrained old compared with young control rats, both exercise and metoprolol treatment resulted in a dramatic reduction of G-protein-receptor kinase 2 protein levels, which is a further indication of beta-AR signaling amelioration in the aged heart induced by these treatment modalities. In conclusion, we demonstrate for the first time that exercise and beta-AR blockade can similarly ameliorate beta-AR signaling in the aged heart, leading to improved beta-AR responsiveness and corresponding LV inotropic reserve.