Drug Coated Balloon in the Treatment of De Novo Coronary Artery Disease: A Narrative Review.

Drug coated balloons (DCBs) are currently indicated in guidelines as a first choice option in the management of instant restenosis, whereas their use in de novo lesions is still debated. The concerns raised after the contrasting results of the initial trials with DCBs in de novo lesions have been more recently overcome by a larger amount of data confirming their safety and effectiveness as compared to drug-eluting stents (DES), with potentially greater benefits being achieved, especially in particular anatomical settings, as in very small or large vessels and bifurcations, but also in selected subsets of higher-risk patients, where a 'leave nothing behind' strategy could offer a reduction of the inflammatory stimulus and thrombotic risk. The present review aims at providing an overview of current available DCB devices and their indications of use based on the results of data achieved so far.

A more-Comers populAtion trEated with an ultrathin struts polimer-free Sirolimus stent: an Italian post-maRketing study (the CAESAR registry).

Introduction: The use of contemporary drug-eluting stents (DES) has significantly improved outcomes of patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). However, concerns exist regarding the long-term proinflammatory effects of durable polymer coatings used in most DES, potentially leading to long-term adverse events. First-generation polymer-free stent technologies, such as sirolimus- and probucol-eluting stents (PF-SES), have shown an excellent safety and efficacy profile. The aim of this study was to evaluate the safety and efficacy of the new ultrathin Coroflex ISAR NEO PF-SES, in a more-comers PCI population. Methods: The CAESAR (a more-Comers populAtion trEated with an ultrathin struts polimer-free Sirolimus stent: An Italian post-maRketing study) registry is a multicenter, prospective study conducted in Italy, enrolling more-comers CAD patients undergoing PCI with the Coroflex ISAR NEO stent. Patients with left main (LM) disease, cardiogenic shock (CS), or severely reduced left-ventricular ejection fraction (LVEF) were excluded. The primary endpoint was target-lesion revascularization (TLR) at 1 year. Results: A total of 425 patients were enrolled at 13 centers (mean age 66.9 ± 11.6 years, Diabetes mellitus 29%, acute coronary syndrome 67%, chronic total occlusion 9%). Of these, 40.9% had multivessel disease (MVD) and in 3.3% cases, the target lesion was in-stent restenosis (ISR). Clinical device success was reached in 422 (99.6%) cases. At 1 year, only two (0.5%) subjects presented ischemia-driven TLR. The 1-year rates of target vessel revascularization and MACE were 0.5% and 5.1%, respectively. Major bleeding was observed in four (1.0%) patients. Conclusion: In this multicenter, prospective registry, the use of a new ultrathin Coroflex ISAR NEO PF-SES in a more-comers PCI population showed good safety and efficacy at 1 year.

[ANMCO Position paper: Cardiovascular disease in women - prevention, diagnosis, treatment and organization of care]. / Position paper ANMCO: Malattie cardiovascolari nella donna ­ prevenzione, diagnosi, terapia e organizzazione delle cure.

Cardiovascular diseases are still the main cause of death among women despite the improvements in treatment and prognosis achieved in the last 30 years of research. The determinant factors and causes have not been completely identified but the role of "gender" is now recognized. It is well known that women tend to develop cardiovascular disease at an older age than men, and have a high probability of manifesting atypical symptoms not often recognized. Other factors may also co-exist in women, which may favor the onset of specific cardiac diseases such as those with a sex-specific etiology (differential effects of estrogens, pregnancy pathologies, etc.) and those with a different gender expression of specific and prevalent risk factors, inflammatory and autoimmune diseases and cancer. Whether the gender differences observed in cardiovascular outcomes are influenced by real biological differences remains a matter of debate.This ANMCO position paper aims at providing the state of the research on this topic, with particular attention to the diagnostic aspects and to care organization.

ImpaCt of an Optimal Implantation Strategy on Absorb Long-Term Outcomes: The CIAO Registry.

AIM: To compare the long-term outcomes of patients implanted with Absorb bioresorbable scaffold (BRS) with optimal versus suboptimal technique. METHODS AND RESULTS: All patients who received an Absorb between March 2012 and January 2016 were selected from 19 Italian centers databases to assess the impact of an optimal implantation technique (CIAO criteria) on long-term device-oriented composite end-point (DOCE) - including cardiac death (CD), target-vessel myocardial infarction (TV-MI) and ischemia-driven target lesion revascularization (ID-TLR) - on its single components and on scaffold thrombosis (ScT). CIAO criteria consist of predilation (balloon/vessel ratio 1:1), correct sizing (BRS/proximal reference vessel diameter -RVD- ratio 0.8-1.2) and high-pressure postdilation with non-compliant (NC) balloon (≥20 atm for balloon/BRS ratio 1:1 or ≥16 atm for a 0.25-0.5 mm oversized balloon). Among the 1.434 patients analyzed, 464 (32.4%) fulfilled all CIAO criteria for every BRS implanted (CIAO 3 group), while 970 (67.6%) did not in at least one of the received BRS (CIAO 0-1-2 group). At 31.0 (interquartile range -IQR- 24.8-38.5) months follow-up, CIAO criteria did not impact on DOCE (8.2% vs. 8.0%, p = 0.92), ID-TLR (6.9% vs. 7.1%, p = 0.72) or ScT (1.9% vs. 1.8%, p = 0.80) in the overall population. At multivariate analysis overall BRS length (p = 0.001), severely calcified lesions (p = 0.03) and absence of CIAO criteria (CIAO 0, p = 0.005) were independent predictors of DOCE in long-term follow-up. CONCLUSION: Our data suggest that strict application of an optimal Absorb implantation technique doesn't improve long-term DOCE or ScT but may mitigate the worse outcome of patients with calcific lesions.

Meta-Analysis Comparing Outcomes After Everolimus-Eluting Bioresorbable Vascular Scaffolds Versus Everolimus-Eluting Metallic Stents in Patients with Acute Coronary Syndromes.

Acute coronary syndromes (ACS) may represent an intriguing clinical scenario for implantation of bioresorbable vascular scaffold (BRS). Nevertheless, the knowledge about the performance of these devices in patients with ACS is limited. Therefore, we performed a meta-analysis of clinical studies aiming to assess the safety and efficacy of everolimus-eluting-BRS versus everolimus-eluting-metallic stents (EES) in ACS patients undergoing percutaneous coronary intervention. Six studies enrolling 2,318 patients were included and analyzed for the risk of primary safety outcome (stent or scaffold thrombosis [ST/ScT]), primary efficacy outcome (target lesion revascularisation [TLR]), and secondary outcomes (myocardial infarction, cardiac death, all-cause death). Median follow-up was 9.5 (6 to 19.5) months. Patients treated with BRS had a significantly higher risk of definite ST/ScT compared with those receiving EES (2.3% vs 1.08%, odds ratio [OR] 2.22, 95% confidence interval [CI] 1.10 to 4.45, p = 0.03, I2 = 0%). Similarly, the risk of TLR was significantly higher in the BRS compared with EES group (3.5% vs 2.5%, OR 1.79, 95% CI 1.02 to 3.16, p = 0.04, I2 = 0%). When TLRs due to thrombosis were excluded, the difference in risk estimates between the 2 groups was no longer significant (OR 1.19, 95% CI 0.48 to 2.98, p = 0.71, I2 = 25%). Risk for secondary endpoints did not differ between the 2 groups. Results were confirmed when clinical and procedural variables were tested as potential effect modifiers in the meta-regression analysis for both primary endpoints. In conclusion, compared with those receiving EES, patients with ACS treated with BRS had increased risk of definite device thrombosis and TLR at mid-term follow-up.

Clinical findings after bioresorbable vascular scaffold implantation in an unrestricted cohort of patients with ST-segment elevation myocardial infarction (from the RAI registry).

BACKGROUND: The bioresorbable vascular scaffold (BVS) technology may be an appealing option in ST-segment elevation myocardial infarction (STEMI) patients. However, the available evidence on its use in this challenging subset is limited. METHODS: Registro Absorb Italiano (RAI) is a multicenter, prospective registry that aims to assess BVS performance through a 5-year follow-up of all consecutive patients who undergone at least 1 successful BVS implantation. As a part of it, a subgroup analysis in STEMI patients was performed and the outcomes of this cohort compared to the remaining population (defined as "non-STEMI") are reported here. RESULTS: Among the 1505 patients enrolled, 317 (21.1%) had STEMI on admission. Among those, 232 (73.2%) underwent primary percutaneous coronary intervention (PCI) within 12 h from symptom onset; 64 (20.2%) were late-comers (>12 h); 16 (5%) underwent PCI after successful thrombolysis while 5 (1.6%) underwent rescue-PCI. At a median follow-up time of 12 months (IQR 6-20 months) no differences were noticed between STEMI and "non-STEMI" groups in terms of device-oriented composite endpoint (4.1% vs. 5.6%; p = 0.3) and its singular components: ischemia-driven target lesion revascularization (3.2% vs. 3.6%; p = 0.7), target-vessel myocardial infarction (3.2% vs. 2.8%; p = 0.7) and cardiac death (0.6% vs. 0.6%; p = 0.9). The rate of definite/probable scaffold thrombosis (ScT) was numerically higher but not significant in the STEMI group (2.5% vs. 1.3%; p = 0.1). CONCLUSIONS: BVS implantation in an unrestricted cohort of STEMI patients is associated with a numerically higher rate of ScT compared to the non-STEMI group. Further studies exploring the potential clinical impact of a pre-specified BVS implantation strategy in this high-risk clinical setting are needed.

Bioresorbable vascular scaffold versus everolimus-eluting stents or drug eluting balloon for the treatment of coronary in-stent restenosis: 1-Year follow-up of a propensity score matching comparison (the BIORESOLVE-ISR Study).

OBJECTIVES: to compare the 1-year outcome between bioresorbable vascular scaffold (BVS), everolimus-eluting stent (EES), and drug-eluting balloon (DEB) for in-stent restenosis (ISR) treatment. BACKGROUND: BVS has been proposed as alternative for ISR treatment. To date a direct comparison between BVS and DES or DEB for ISR treatment is lacking. METHODS: We retrospectively analyzed all ISR lesions treated with BVS, DEB, and EES from January 2012 to December 2014. A total of 548 lesions (498 patients) were included. By applying two propensity-score matching, 93 lesions treated with BVS were compared with 93 lesions treated with DEB, and 100 lesions treated with BVS were compared to 100 lesions treated with EES. RESULTS: At 1-year follow-up the incidence of device-oriented cardiovascular events (DOCE) and its components did not significantly differ between BVS and DEB (DOCE: 10.9 vs. 11.8%, HR, 0.91; 95% CI, 0.33-2.52; P = 0.86; Cardiac death: 2.2 vs. 1.2%, HR, 1.74, 95% CI 0.16-18.80, P = 0.65; ID-TLR: 8.9 vs. 10.7%, HR, 0.81, 95% CI 0.27-2.48, P = 0.71; TV-MI: 3.3 vs. 1.2%, HR, 2.39, 95% CI 0.27-21.32, P = 0.43) and BVS vs. EES (DOCE: 10.1 vs. 5.2% HR, 1.81, 95% CI, 0.63-5.25; P = 0.27; Cardiac death: 3.0 vs. 1.1%; HR, 2.83, 95% CI 0.29-27.4, P = 0.37; ID-TLR: 7.2 vs. 4.2%, HR, 1.57, 95% CI 0.47-5.23, P = 0.46; TV-MI: 3.1 vs. 0%). CONCLUSION: At 1-year follow-up the use of BVS as ISR treatment is associated with a higher, even if not significant, DOCE rate compared with EES while a similar rate compared to DEB.

Are acute coronary syndromes an ideal scenario for bioresorbable vascular scaffold implantation?

Bioresorbable vascular scaffolds (BRS) represent the latest innovation in the field of interventional cardiology. BRS have recently been introduced in routine clinical practice and their use has progressively extended in everyday clinical practice. The BRS use appears theoretically attractive in patients presenting with acute coronary syndromes (ACS) as they are generally young with long life expectancy, thus possibly benefiting more of the so-called vascular reparative therapy. Furthermore, "culprit" lesions are usually softer and more easily expandable by current BRS compared to stable chronic lesions. However an increased risk of BRS thrombosis has been reported in clinical trials excluding ACS patients. Therefore, concerns have been raised on the safety of BRS implantation in the ACS setting in which the risk of thrombotic recurrences is definitely higher (compared to stable lesions) independently by the device implanted. Aim of this review is to provide an overview of the available data on the BRS performance in ACS patients.

ß1-adrenergic receptor and sphingosine-1-phosphate receptor 1 (S1PR1) reciprocal downregulation influences cardiac hypertrophic response and progression to heart failure: protective role of S1PR1 cardiac gene therapy.

BACKGROUND: The sphingosine-1-phosphate receptor 1 (S1PR1) and ß1-adrenergic receptor (ß1AR) are G-protein-coupled receptors expressed in the heart. These 2 receptors have opposing actions on adenylyl cyclase because of differential G-protein coupling. Importantly, both of these receptors can be regulated by the actions of G-protein-coupled receptor kinase-2, which triggers desensitization and downregulation processes. Although classic signaling paradigms suggest that simultaneous activation of ß1ARs and S1PR1s in a myocyte would simply result in opposing action on cAMP production, in this report we have uncovered a direct interaction between these 2 receptors, with regulatory involvement of G-protein-coupled receptor kinase-2. METHODS AND RESULTS: In HEK (human embryonic kidney) 293 cells overexpressing both ß1AR and S1PR1, we demonstrated that ß1AR downregulation can occur after stimulation with sphingosine-1-phosphate (an S1PR1 agonist), whereas S1PR1 downregulation can be triggered by isoproterenol (a ß-adrenergic receptor agonist) treatment. This cross talk between these 2 distinct G-protein-coupled receptors appears to have physiological significance, because they interact and show reciprocal regulation in mouse hearts undergoing chronic ß-adrenergic receptor stimulation and in a rat model of postischemic heart failure. CONCLUSIONS: We demonstrate that restoration of cardiac plasma membrane levels of S1PR1 produces beneficial effects that counterbalance the deleterious ß1AR overstimulation in heart failure.

Percutaneous treatment of a aorto-caval fistula in a old high risk patient.

BACKGROUND: To remark the feasibility of endovascular treatment of an aorto-caval fistula in a old high risk patient with "hostile" abdomen for previous surgeries. METHODS: In September 2009 a 81-years-old patient was admitted in emergency at our department because of abdominal pain and massive oedema of the lower extremities associated to dyspnoea (New York Heart Association (NYHA) functional class III). A CT scan showed an aorto-caval fistula involving the abdominal aorta below the renal arteries. This abnormal communication was likely due to the previous abdominal surgeries, was complicated by occlusion of the inferior vena cava at the diaphragm and was responsible for the massive oedema of the lower extremities. Because of unstable conditions and hostile abdomen the patient was considered unfit for conventional surgery and an endovascular approach was planned. After unsuccessful attempt by positioning of an Amplatzer vascular ring into the fistula, a Medtronic covered stent-grafts were implanted from the renal arteries to the both common iliac arteries. The patient had an impressive improvement characterized by a 18 Kg weight loss and a complete restoration of the functional capacity (from NYHA class III to NYHA class I) associated to a complete resolution of the lower extremities oedema as confirmed at the a month-CT-scan. CONCLUSION: Endovascular surgery of aorto-caval fistula represents a good option in alternative to conventional surgery mostly in old high risk patient.

Transcatheter closure of patent ductus arteriosus reverses left ventricular dysfunction in a septuagenarian.

A 70-year-old man was admitted because of a 6-month history of progressive dyspnoea on exertion. The medical history showed that he suffered from patent ductus arteriosus (PDA) that was closed at 35 years of age by surgical ligation. Subsequently, up to year 1992, no evidence of residual left-to-right shunt was found. When he first came to our attention, we performed an echocardiographic test evidencing left ventricular dilation and contractile dysfunction and a recurrence of PDA. To exclude other possible causes of congestive heart failure, we performed several tests, including a coronary angiogram that showed coronary atherosclerosis without significant lesions. The haemodynamic study confirmed that the PDA was associated with a mild pulmonary hypertension with a QP: QS of 2: 1. The patient did not report any cardiovascular risk factor. Therefore, we concluded that PDA was responsible for congestive heart failure in this patient. We performed percutaneous closure of PDA, which was able to reverse left ventricular dilation and dysfunction, improving the patient's symptoms, at 1 month as well as 4 months after the interventional procedure. Although this kind of device is frequently used in the paediatric population, adult patients may present different challenges in proper management, such as poor visualization, calcification and pulmonary hypertension. In the description of the case reported here, we show that a PDA can present as congestive heart failure in the elderly. Percutaneous closure can be very effective in ameliorating left ventricular performance as well as symptoms.

Increased myocardial contractility and enhanced exercise function in transgenic mice overexpressing either adenylyl cyclase 5 or 8.

OBJECTIVE: ss-adrenergic receptors (ssARs) are powerful regulators of cardiac function in vivo, activating heterotrimeric G proteins and the effector molecule adenylyl cyclase (AC). Interestingly, cardiac-specific overexpression of different AC isoforms leads to variable changes in cardiac function. Whether AC overexpression affects intrinsic cardiac contractility in an isoform-specific fashion determining a change in exercise capacity is currently unknown. METHODS: To address this issue, we performed load-independent measurements of cardiac systolic and diastolic function by pressure-volume (PV) loop analysis in intact wild-type mice (WT) and transgenic mice overexpressing the AC isoforms 5 or 8. RESULTS: Here we show that cardiac overexpression of either AC5 or AC8 transgenic mice determined an increase in intrinsic cardiac contractility. Interestingly, AC8 transgenic mice displayed a significantly greater increase in cardiac contractility and improved active phase of relaxation. Despite these differences detected by PV loop analysis, both AC5 and AC8 mice showed a marked increase in exercise capacity on treadmill testing. CONCLUSIONS: Our results demonstrate that load-independent measurements of cardiac function are needed to compare different groups of genetically-modified mouse models and to detect subtle AC isoform-specific changes in cardiac performance.