Calcified coronary lesions.

The treatment of calcific coronary lesions is still a major interventional issue in haemodynamics laboratories. The prevalence of the disease is even increasing, considering the general ageing of the population undergoing coronarography, as well as the often associated comorbidities. In recent years, new devices have been developed that allow both better identification and also better treatment of these lesions. The aim of this review is to summarize both imaging modalities and dedicated techniques and materials, thus providing a kind of compendium for the treatment approach.

Acute coronary syndromes and multivessel coronary artery disease.

Patients with acute coronary syndromes (ACS) and multivessel coronary artery disease are frequently encountered during clinical practice and those patients are at higher risk of subsequent acute cardiovascular events. In patients presenting with both ST-segment elevation myocardial infarction and non-ST-segment elevation acute coronary syndromes, complete revascularization is associated with decreased risk of major adverse cardiovascular events. Nevertheless, the optimal timing of the intervention and treatment modality are still in discussions. Furthermore, non-culprit lesions assessment based on stenosis severity, either on visual or on functional evaluation, may not provide information about vulnerable plaques prone to thrombosis. Therefore, insights from intracoronary imaging could further identify high-risk plaque and patients at higher risk of future adverse events. This article aims to provide an overview of current guideline recommendations, envisioning future perspectives for the treatment of patients with ACS and multivessel disease.

Endothelial progenitor cells in morbid obesity.

BACKGROUND: The aim of this study was to assess the relationship among anthropometric indexes of adiposity (body mass index [BMI], waist circumference [WC]), endothelial progenitor cells (EPC) and carotid intima-media thickness (IMT) in patients with morbid obesity, and the effect of diabetes and weight loss. METHODS AND RESULTS: BMI, WC, IMT and circulating EPC (defined as CD34+/KDR+/CD45- cells) were assessed in 100 patients (37 with diabetes). Fifty patients underwent bariatric surgery, and in 48 of them a complete re-assessment after an average follow-up of 252±108 days was carried out. In 29 of them subcutaneous and visceral adipose tissue samples were obtained at the time of intervention and analyzed for the presence and number of EPC. EPC were directly correlated with weight, BMI, WC and insulin level, and inversely with mean IMT. All correlations were confined to non-diabetic patients. EPC were found in both subcutaneous and visceral adipose tissue specimens. Circulating EPC significantly decreased after weight loss (P=0.002). CONCLUSIONS: EPC are positively related to markers of adiposity in severe obesity, when not complicated by diabetes. Weight loss is associated with decrease in EPC level. EPC are inversely correlated with IMT, confirming their protective role also in severe obesity. Diabetes has a negative modulating action.

Prognostic value of combined fractional flow reserve and pressure-bounded coronary flow reserve: outcomes in FFR and Pb-CFR assessment.

BACKGROUND: Coronary flow reserve (CFR) has an emerging role to predict outcome in patients with and without flow-limiting stenoses. However, the role of its surrogate pressure bounded-CFR (Pb-CFR) is controversial. We investigated the usefulness of combined use of fractional flow reserve (FFR) and Pb-CFR to predict outcomes. METHODS: This is a sub-study of the PROPHET-FFR Trial, including patients with chronic coronary syndrome and functionally tested coronary lesions. Patients were divided into four groups based on positive or negative FFR (cut-off 0.80) and preserved (lower boundary ≥2) or reduced (upper boundary <2) Pb-CFR: Group1 FFR≤0.80/ Pb-CFR <2; Group 2 FFR≤0.80/Pb-CFR≥2; Group 3 FFR >0.80/Pb-CFR<2; Group 4 FFR>0.80/Pb-CFR≥2. Lesions with positive FFR were treated with PCI. Primary endpoint was the rate of major adverse cardiac events (MACEs), defined as a composite of death from any cause, myocardial infarction, target vessel revascularization, unplanned cardiac hospitalization at 36-months. RESULTS: A total of 609 patients and 816 lesions were available for the analysis. At Kaplan-Meier analysis MACEs rate was significantly different between groups (36.7% Group 1, 27.4% Group 2, 19.2% Group 3, 22.6% Group 4, P=0.019) and more prevalent in groups with FFR≤0.80 irrespective of Pb-CFR. In case of discrepancy, no difference in MACEs were observed between groups stratified by Pb-CFR. FFR≤0.80 was associated with an increased MACEs rate (30.2% vs. 21.5%, P<0.01) while Pb-CFR<2 was not (24.5% vs. 24.2% Pb-CFR≥2 P=0.67). CONCLUSIONS: FFR confirms its ability to predict outcomes in patients with intermediate coronary stenoses. Pb-CFR does not add any relevant prognostic information.

Fractional Flow Reserve-Guided Coronary Revascularization: Evidence from Randomized and Non-Randomized Studies.

Simple visual estimation of coronary angiography is limited by several factors that can hinder the proper classification of coronary lesions. Fractional flow reserve (FFR) is the most widely used tool to perform a physiological evaluation of coronary stenoses. Compared to isolated angiography, FFR has been demonstrated to be more effective in selecting those lesions associated with myocardial ischemia and, accordingly, impaired outcomes. At the same time, deferring coronary intervention in those lesions that do not show ischemic FFR values has proven safe and not associated with adverse events. Despite a major randomized clinical trial (RCT) and several non-randomized studies showing that FFR-guided revascularization could be superior to isolated angiography in improving clinical outcomes, subsequent RCTs have reported conflicting results. In this review, we summarize the principles behind FFR and the data currently available in the literature, highlighting the main differences between randomized and non-randomized studies that investigated this topic.

Acute haemodynamic impact of transcatheter aortic valve implantation in patients with severe aortic stenosis.

AIMS: There are limited data about the intraprocedural haemodynamic study performed immediately before and after transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis (AS). We aimed to evaluate the acute haemodynamic impact of TAVI in patients with severe AS and to investigate invasive and non-invasive parameters predicting all-cause mortality. METHODS AND RESULTS: A total of 245 consecutive AS patients (43% male, mean age 80.3 ± 7.3 years) undergoing TAVI were enrolled. Intraprocedural left heart catheterization (LHC) and echocardiogram before and after TAVI were performed. The clinical endpoint was the death for any cause. LHC after TAVI revealed significant changes in aortic and left ventricular (LV) pressures, including indexes of intrinsic myocardial contractility and diastolic function such as positive dP/dT (1128.9 ± 398.7 vs. 806.3 ± 247.2 mmHg/s, P Ë‚ 0.001) and negative dP/dT (1310.7 ± 431.1 vs. 1075.1 ± 440.8 mmHg/s, P Ë‚ 0.001). Post-TAVI echo showed a significant reduction in LV end-diastolic (P = 0.036) and end-systolic (P Ë‚ 0.001) diameters, improvement in LV ejection fraction (from 55 ± 12% to 57.2 ± 10.5%, P Ë‚ 0.001), and pulmonary artery systolic pressure (42.1 ± 14.2 vs. 33.1 ± 10.7 mmHg, P < 0.001). After a mean follow-up time interval of 24 months, 47 patients died. Post-TAVI significant aortic regurgitation at echocardiography was the only independent predictor of mortality (hazard ratio 5.592, confidence interval 1.932-16.184, P = 0.002). CONCLUSIONS: Left heart catheterization performed immediately before and after prosthesis release offers a unique insight in the assessment of LV adaptation to severe AS and the impact of TAVI on LV, catching changes in indexes of intrinsic contractility and myocardial relaxation. Aortic regurgitation assessed by echocardiography was the only independent predictor of mortality in patients undergoing TAVI.

Safety and effectiveness of post percutaneous coronary intervention physiological assessment: Retrospective data from the post-revascularization optimization and physiological evaluation of intermediate lesions using fractional flow reserve registry.

Background: While the importance of invasive physiological assessment (IPA) to choose coronary lesions to be treated is ascertained, its role after PCI is less established. We evaluated feasibility and efficacy of Physiology-guided PCI in the everyday practice in a retrospective registry performed in a single high-volume and "physiology-believer" center. Materials and methods: The PROPHET-FFR study (NCT05056662) patients undergoing an IPA in 2015-2020 were retrospectively enrolled in three groups: Control group comprising patients for whom PCI was deferred based on a IPA; Angiography-Guided PCI group comprising patients undergoing PCI based on an IPA but without a post-PCI IPA; Physiology-guided PCI group comprising patients undergoing PCI based on an IPA and an IPA after PCI, followed by a physiology-guided optimization, if indicated. Optimal result was defined by an FFR value ≥ 0.90. Results: A total of 1,322 patients with 1,591 lesions were available for the analysis. 893 patients (67.5%) in Control Group, 249 patients (18.8%) in Angiography-guided PCI Group and 180 patients (13.6%) in Physiology-guided PCI group. In 89 patients a suboptimal functional result was achieved that was optimized in 22 cases leading to a "Final FFR" value of 0.90 ± 0.04 in Angiography-Guided PCI group. Procedural time, costs, and rate of complications were similar. At follow up the rate of MACEs for the Physiology-guided PCI group was similar to the Control Group (7.2% vs. 8.2%, p = 0.765) and significantly lower than the Angiography-guided PCI Group (14.9%, p < 0.001), mainly driven by a reduction in TVRs. Conclusion: "Physiology-guided PCI" is a feasible strategy with a favorable impact on mid-term prognosis. Prospective studies using a standardized IPA are warrant to confirm these data.

Physiological assessment after percutaneous coronary intervention: the hard truth.

Physiologically guided revascularization, using fractional flow reserve (FFR) or instantaneous wave free ratio (iFR) has been demonstrated to be associated with better long-term outcomes compared to an angiographically-guided strategy, mainly avoiding inappropriate coronary stenting and its associated adverse events. On the contrary, the role of invasive physiological assessment after percutaneous coronary intervention (PCI) is much less well established. However, a large body of evidence suggests that a relevant proportion of patients undergoing PCI with a satisfying angiographic result show instead a suboptimal functional product with a potentially negative prognostic impact. For this reason, many efforts have been focused to identify interventional strategies to physiologically optimize PCI. Measuring the functional result after as PCI, especially when performed after a physiological assessment, implies that the operator is ready to accept the hard truth of an unsatisfactory physiological result despite angiographically optimal and, consequently, to optimize the product with some additional effort. The aim of this review was to bridge this gap in knowledge by better defining the paradigm shift of invasive physiological assessment, from a simple tool for deciding whether an epicardial stenosis must be treated, to a thoroughly physiological approach to PCI with the suggestion of a practical flow chart.

Prognostic impact of FFR/contrast FFR discordance.

BACKGROUND: Contrast fractional flow reserve (cFFR) is a relatively new tool for the assessment of intermediate coronary artery stenosis and represents a reliable surrogate of FFR with the advantage of potentially simplifying functional evaluation. We aimed to compare the incidence of major adverse cardiac events (MACE) in patients undergoing functional evaluation with both FFR and cFFR based on the results of the two indexes. METHOD AND RESULT: We retrospectively analyzed outcomes in 488 patients who underwent functional evaluation with FFR and cFFR. Patients were divided into four groups using the cutoff values of 0.80 for FFR and 0.85 for cFFR: -/- (n = 298), +/+ (n = 134), -/+(n = 31) and +/- (n = 25). All patients were treated according to FFR value. MACE rate was assessed in each group, including death, myocardial infarction and urgent target vessel revascularization (TVR). Mean follow-up time was 22 ± 15 months. Incidence of MACE at follow-up was 8.3% in FFR-/cFFR-, 14.0% in FFR+/cFFR+, 16.0% in FFR-/cFFR+ and 8.0% in FFR+/cFFR- without a significant difference amongst the 4 groups (p = 0.2). Nevertheless, a significant difference in the rate of TVR comparing FFR-/cFFR- (n = 17) and FFR-/cFFR+ (n = 5) was found at 24 months (5.7% vs 16.0%; p = 0.027). CONCLUSION: cFFR is accurate in predicting FFR and consequently reliable in guiding coronary revascularization. In the rare case of discordance, while FFR+/cFFR- patients show a prognosis similar to FFR-/cFFR- patients, FFR-/cFFR+ patients show a prognosis similar to FFR+/cFFR+ patients.

Invasive versus medically managed acute coronary syndromes with prior bypass (CABG-ACS): insights into the registry versus randomised trial populations.

BACKGROUND: Coronary artery bypass graft (CABG) patients are under-represented in acute coronary syndrome (ACS) trials. We compared characteristics and outcomes for patients who did and did not participate in a randomised trial of invasive versus non-invasive management (CABG-ACS). METHODS: ACS patients with prior CABG in four hospitals were randomised to invasive or non-invasive management. Non-randomised patients entered a registry. Primary efficacy (composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction (MI), heart failure) and safety outcomes (composite of bleeding, stroke, procedure-related MI, worsening renal function) were independently adjudicated. RESULTS: Of 217 patients screened, 84 (39%) screenfailed, of whom 24 (29%) did not consent and 60 (71%) were ineligible. Of 133 (61%) eligible, 60 (mean±SD age, 71±9 years, 72% male) entered the trial and 73 (age, 72±10 years, 73% male) entered a registry (preferences: physician (79%), patient (38%), both (21%)).Compared with trial participants, registry patients had more valve disease, lower haemoglobin, worse New York Heart Association class and higher frailty.At baseline, invasive management was performed in 52% and 49% trial and registry patients, respectively, of whom 32% and 36% had percutaneous coronary intervention at baseline, respectively (p=0.800). After 2 years follow-up (694 (median, IQR 558-841) days), primary efficacy (43% trial vs 49% registry (HR 1.14, 95% CI 0.69 to 1.89)) and safety outcomes (28% trial vs 22% registry (HR 0.74, 95% CI 0.37 to 1.46)) were similar. EuroQol was lower in registry patients at 1 year. CONCLUSIONS: Compared with trial participants, registry participants had excess morbidity, but longer-term outcomes were similar. TRIAL REGISTRATION NUMBER: NCT01895751.

Hard Events AfteR Orsiro Sirolimus-Eluting Stent (HEROES) in STEMI: A Multicenter Registry.

OBJECTIVES: To evaluate the safety and efficacy of the Orsiro sirolimus-eluting stent (Biotronik) in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (pPCI). Specific drug-eluting stent (DES) platforms might influence pPCI success rate in the mid-to-long term. Orsiro, a hybrid sirolimus DES with thin struts and a biodegradable polymer, may potentially cause less stent malapposition, stent-induced inflammation, and mechanical damage, improving clinical outcomes. METHODS: We retrospectively enrolled all patients who received 1 or more Orsiro DES in the target vessel of pPCI at 9 Italian centers from January 2012 to March 2016. The primary endpoint was a device-oriented composite endpoint (DOCE) of cardiac death, any myocardial infarction clearly attributable to the intervention culprit vessel (TVMI), and ischemic-driven target-lesion revascularization (ID-TLR) at 1-year follow-up. Secondary endpoints were: (1) DOCE at 6-month and 3-year follow-up; (2) any definite/probable stent thrombosis; and (3) any major bleeding. RESULTS: The study cohort comprised 353 patients. At 1-year follow-up, we observed a 3.7% cumulative incidence of DOCE, consisting of 11 cardiac deaths (3.1%), 2 TVMIs (0.6%), and 2 ID-TLRs (0.6%). There was only 1 definite stent thrombosis (0.3%) and 8 bleedings (2.4%). Kaplan-Meier analysis showed DOCE-free survival rates of 96.6% at 6 months, 96.3% at 1 year, and 93.8% at 3 years. CONCLUSIONS: Our findings support the real-world safety and efficacy of the Orsiro stent for pPCI.

Fractional flow reserve in acute coronary syndromes and in stable ischemic heart disease: clinical implications.

BACKGROUND: Fractional Flow Reserve (FFR) in Stable Ischemic Heart Disease (SIHD) is universally accepted, while in Acute Coronary Syndromes (ACS) is less established. Aims of this retrospective study were: to compare in patients undergoing FFR assessment the prognostic impact of ACS vs SIHD, to evaluate the clinical relevance of the modality of utilization and timing of FFR assessment and to assess the different outcomes associated with an FFR> or ≤0.80. METHODS: Major cardiac adverse events were assessed at a follow up of 16.4 ±â€¯10.5 months in 543 patients with SIHD and 231 with ACS needing functional evaluation. FFR was used for lesions of ambiguous significance in the absence of a clear culprit vessel (first intention, FI) and for incidental lesions in the presence of a clear culprit vessel (second intention, SI). The decision to perform FFR and the identification of the stenosis needing functional assessment were left to the operator's discretion. Revascularization was performed when FFR was ≤0.80. RESULTS: SIHD and ACS patients were not significantly different for principal clinical characteristics. ACS patients had significantly more events than SIHD, due to an excess of death and myocardial infarction. This was confirmed when FFR was used as FI, in particular if FFR was >0.80. On the contrary, when FFR was used as SI, event rates were similar between ACS and SIHD patients, regardless of FFR value. CONCLUSIONS: Our study shows that using FFR the risk of recurrent events in ACS is significantly higher than in SIHD. This different outcome is confined to those patients in whom FFR is utilized for lesions of ambiguous significance in the absence of a clear culprit vessel.

Stent malapposition, strut coverage and atherothrombotic prolapse after percutaneous coronary interventions in ST-segment elevation myocardial infarction.

AIMS: Stent implantation in ST-segment elevation myocardial infarction (STEMI) patients can be challenging and sometimes associated with immediate and long-term suboptimal results. Stent malapposition and strut uncoverage, predictors of stent thrombosis, are frequently detected in STEMI patients at medium/long-term follow-up. Nevertheless, data at a short follow-up are missing. We aimed to assess the extent of stent malapposition and struts coverage in the subacute phase of STEMI after stent implantation in primary or rescue percutaneous coronary intervention (PCI). METHODS: STEMI patients undergone primary or rescue PCI and scheduled for a second coronary angiography after 2-7 days were enrolled. During the second procedure, frequency domain optical coherence tomography (FD-OCT) was performed to assess percentage of malapposed struts (MS%), percentage area of malapposition (MA%), percentage of uncovered struts (US%), percentage area of atherothrombotic prolapse (PA%) and optical coherence tomography thrombus score (OCT-TS). RESULTS: Twenty patients were included and 21 stents (19 865 struts) were evaluated. Strut uncoverage was relatively limited [US% = 11.1 (8.1-13.6) %]. Stent malapposition was observed frequently, even if at low degree [MS% = 6.4 (3.3-13.3) %, MA% = 1.80 (0.46-2.76) %] as well as atherothrombotic prolapse [PA% = 0.09 (0.00-1.06) %]. Both MA% and PA% were significantly related to residual OCT-TS (R = -0.52, P = 0.02 and R = 0.71, P < 0.001, respectively), use of thrombolysis (P = 0.001 and P = 0.004, respectively) and time elapsed from PCI to FD-OCT analysis (P = 0.001). CONCLUSION: In the subacute phase after stenting in STEMI patients, strut uncoverage is relatively limited, while stent malapposition and atherothrombotic prolapse are common albeit limited features. Residual thrombus burden influences the degree of both stent malapposition and atherothrombotic prolapse.

Invasive Versus Medical Management in Patients With Prior Coronary Artery Bypass Surgery With a Non-ST Segment Elevation Acute Coronary Syndrome.

BACKGROUND: The benefits of routine invasive management in patients with prior coronary artery bypass grafts presenting with non-ST elevation acute coronary syndromes are uncertain because these patients were excluded from pivotal trials. METHODS: In a multicenter trial, non-ST elevation acute coronary syndromes patients with prior coronary artery bypass graft were prospectively screened in 4 acute hospitals. Medically stabilized patients were randomized to invasive management (invasive group) or noninvasive management (medical group). The primary outcome was adherence with the randomized strategy by 30 days. A blinded, independent Clinical Event Committee adjudicated predefined composite outcomes for efficacy (all-cause mortality, rehospitalization for refractory ischemia/angina, myocardial infarction, hospitalization because of heart failure) and safety (major bleeding, stroke, procedure-related myocardial infarction, and worsening renal function). RESULTS: Two hundred seventeen patients were screened and 60 (mean±SD age, 71±9 years, 72% male) were randomized (invasive group, n=31; medical group, n=29). One-third (n=10) of the participants in the invasive group initially received percutaneous coronary intervention. In the medical group, 1 participant crossed over to invasive management on day 30 but percutaneous coronary intervention was not performed. During 2-years' follow-up (median [interquartile range], 744 [570-853] days), the composite outcome for efficacy occurred in 13 (42%) subjects in the invasive group and 13 (45%) subjects in the medical group. The composite safety outcome occurred in 8 (26%) subjects in the invasive group and 9 (31%) subjects in the medical group. An efficacy or safety outcome occurred in 17 (55%) subjects in the invasive group and 16 (55%) subjects in the medical group. Health status (EuroQol 5 Dimensions) and angina class in each group were similar at 12 months. CONCLUSIONS: More than half of the population experienced a serious adverse event. An initial noninvasive management strategy is feasible. A substantive health outcomes trial of invasive versus noninvasive management in non-ST elevation acute coronary syndromes patients with prior coronary artery bypass grafts appears warranted. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01895751.

The Multi-center Evaluation of the Accuracy of the Contrast MEdium INduced Pd/Pa RaTiO in Predicting FFR (MEMENTO-FFR) Study.

AIMS: Adenosine administration is needed for the achievement of maximal hyperaemia fractional flow reserve (FFR) assessment. The objective was to test the accuracy of Pd/Pa ratio registered during submaximal hyperaemia induced by non-ionic contrast medium (contrast FFR [cFFR]) in predicting FFR and comparing it to the performance of resting Pd/Pa in a collaborative registry of 926 patients enrolled in 10 hospitals from four European countries (Italy, Spain, France and Portugal). METHODS AND RESULTS: Resting Pd/Pa, cFFR and FFR were measured in 1,026 coronary stenoses functionally evaluated using commercially available pressure wires. cFFR was obtained after intracoronary injection of contrast medium, while FFR was measured after administration of adenosine. Resting Pd/Pa and cFFR were significantly higher than FFR (0.93±0.05 vs. 0.87±0.08 vs. 0.84±0.08, p<0.001). A strong correlation and a close agreement at Bland-Altman analysis between cFFR and FFR were observed (r=0.90, p<0.001 and 95% CI of disagreement: from -0.042 to 0.11). ROC curve analysis showed an excellent accuracy (89%) of the cFFR cut-off of ≤0.85 in predicting an FFR value ≤0.80 (AUC 0.95 [95% CI: 0.94-0.96]), significantly better than that observed using resting Pd/Pa (AUC: 0.90, 95% CI: 0.88-0.91; p<0.001). A cFFR/FFR hybrid approach showed a significantly lower number of lesions requiring adenosine than a resting Pd/Pa/FFR hybrid approach (22% vs. 44%, p<0.0001). CONCLUSIONS: cFFR is accurate in predicting the functional significance of coronary stenosis. This could allow limiting the use of adenosine to obtain FFR to a minority of stenoses with considerable savings of time and costs.

Three-dimensional quantitative coronary angiography and quantification of jeopardised myocardium to predict functional significance of intermediate coronary artery stenosis.

AIMS: Despite the fact that fractional flow reserve (FFR) is better than angiography in guiding PCI, in the real world the choice to perform PCI is generally based on angiography. Three-dimensional quantitative coronary angiography (3D-QCA) may increase the accuracy of angiography, especially in intermediate coronary artery stenosis (ICAS). The aim of the study was to assess the best cut-off values of area stenosis % (AS%) and the extent of jeopardised myocardium for predicting FFR and for excluding the need to perform FFR. METHODS AND RESULTS: FFR, AS% and Myocardial Jeopardy Index (MJI) were assessed in 211 ICAS. MJI (=-0.36; p=0.001), AS% (=-0.35; p=0.001) and presence of a chronic total occlusion (CTO) (=-0.15; p=0.01) were independent predictors of FFR. In patients without CTO (174 lesions), the best cut-offs for the detection of FFR ≤0.80 for AS% and MJI were 61% (AUC=0.76; p<0.001) and 30% (AUC=0.71; p<0.001), respectively. More importantly, the cut-offs of AS% safely to exclude (100% sensitivity) an FFR ≤0.80 were 40% (AUC=0.85, p<0.001) for an MJI ≥30% and 50% (AUC=0.70, p<0.04) for an MJI <30%, respectively. CONCLUSIONS: AS%, MJI and the presence of a CTO predicted FFR values. 3D-QCA in addition to MJI allows the safe exclusion of FFR ≤0.80, limiting FFR assessment to doubtful cases with considerable reduction of costs.

Efficacy of contrast medium induced Pd/Pa ratio in predicting functional significance of intermediate coronary artery stenosis assessed by fractional flow reserve: insights from the RINASCI study.

AIMS: The need of adenosine administration for the achievement of maximal hyperaemia limits the widespread application of fractional flow reserve (FFR) in the real world. We hypothesised that Pd/Pa ratio registered during submaximal reactive hyperaemia induced by conventional non-ionic radiographic contrast medium (contrast medium induced Pd/Pa ratio: CMR) can be sufficient for the assessment of physiological severity of stenosis in the vast majority of cases. The aim of the present study was to test the accuracy of CMR in comparison to FFR. METHODS AND RESULTS: Eighty patients with 104 intermediate coronary stenoses were prospectively and consecutively enrolled. CMR was obtained after intracoronary injection of 6 ml of radiographic contrast medium, while FFR was measured after administration of adenosine. Despite the fact that CMR values were significantly higher than FFR values (0.88 [IR 0.80-0.92] vs. 0.87 [IR 0.83-0.94], p<0.001), a strong correlation between CMR and FFR values was observed (r=0.94, p<0.001) with a close agreement at Bland-Altman analysis (95% CI of disagreement: -0.029 to 0.072). ROC curve analysis showed an excellent accuracy of CMR cut-off of ≤0.83 in predicting FFR value ≤0.80 (AUC 0.97 [95% CI: 0.91-0.99, specificity 96.1, sensitivity 85.7]). Moreover, no FFR value ≤0.80 corresponded to a CMR ≥0.88. CONCLUSIONS: CMR is accurate in predicting the functional significance of coronary stenosis. This could allow limiting the use of adenosine to obtain FFR to doubtful cases. In particular, we suggest considering a CMR value ≤0.83 to be significant, a CMR value ≥0.88 as not significant, and inducing maximal hyperaemia using adenosine for FFR assessment when CMR is between 0.84 and 0.87.

Microparticles and microRNAs: new players in the complex field of coagulation.

Atherosclerosis is a complex process that begins with endothelial dysfunction, and continues with several inflammatory processes leading, eventually, to plaque rupture and formation of arterial thrombus. Increased platelet reactivity and classical coagulation pathways are not the only players of the whole thrombotic process: microparticles (MPs), irregularly shaped small vesicles released from the plasma membrane after cell activation, apoptosis, or exposure to shear stress have been demonstrated to be involved in such a process. MicroRNAs (MiRs), small-non-coding single-strand RNAs acting as post-transcriptional modulator of target gene expression are expressed in the large majority of eukaryotes. MiRs are implicated in several phenomena: control of metabolism, control of cell-differentiation, control of cell-proliferation and control of cell-apoptosis, therefore contributing to physiologic and pathogenic processes in hematologic, genetic, infective and cardiac diseases. Microparticles operate as a delivery system of MiRs, playing an active and important role in processes such as coagulation and thrombosis. These novel findings also suggest MPs and, in particular MIRs, as possible and promising therapeutic targets.

Infections, immunity and atherosclerosis: pathogenic mechanisms and unsolved questions.

The role of inflammation and immunity in the pathogenesis and clinical manifestations of atherosclerotic disease has been widely studied. Common infectious diseases can be associated with a chronic inflammatory state which is the hallmark of atherosclerosis, thus suggesting a possible link between the two pathological conditions. Therefore, a great number of studies have tested the "infection hypothesis", but their results are conflicting. Nevertheless, several molecular and biological mechanisms possibly involved in the complex relationship between infections, immune response, vascular wall damage and atherosclerosis onset and progression have been described. The purpose of this article is to offer an overview of the principal mechanisms and molecular pathways that probably constitute the most relevant biological substrate on which the infection hypothesis is founded; some of these mechanisms are not fully understood yet. Nevertheless, their comprehension could be essential for the development of new preventive and therapeutic strategies.

Inflammatory markers in heart failure: hype or hope?

Heart failure is a growing global epidemic that involves in its pathophysiology a proinflammatory state. Since the first description of elevated cytokine levels in this setting, there has been increasing interest in understanding the role of these molecules in left-ventricular remodeling and function. Over the years, intense research on the 'cytokine theory' of heart failure has allowed evaluation of the role of inflammatory biomarkers not only as pathogenetic mediators, but also as potential tools in the diagnosis and risk stratification of heart failure patients. Whereas current evidence does not support the use of inflammatory biomarkers for the diagnosis of heart failure, the assessment of their levels and the connection between their changes and changes in clinical status and prognosis has been well validated. At present, the utility of anti-inflammatory therapies in heart failure is still debated, since trials of anti-inflammatory agents in this setting have pointed out controversial results. On the contrary, established treatments of heart failure, including ß-blockers, renin-angiotensin system antagonists, and aldosterone-receptor blockers seem able to act by modulating cytokine expression, suggesting a new role for these molecules in guiding heart failure therapy. Therefore, the binomial topic of heart failure and inflammation still has a number of fields not completely explored: our aim is to update current knowledge and future perspectives.