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.

Transcatheter closure of atrial septal defect using intracardiac echocardiography: a two-center, retrospective study.

AIMS: We present the experience and long-term results of intracardiac echocardiography (ICE)-guided closure of ostium secundum atrial septal defects (ASDs) in two Italian centers and investigate its systematic applicability as the gold standard in routine clinical practice. METHODS: We retrospectively evaluated all consecutive patients who underwent an ASD percutaneous closure procedure from March 2008 to February 2020. All patients underwent a preprocedural transesophageal echocardiography (TEE) evaluation. The closures were carried out under fluoroscopic and ICE guidance. A follow-up visit was performed at 1, 3 and 12 months, followed by telephone evaluations approximately every 2 years. RESULTS: Sixty-six patients (29% male individuals), mean age 43 ±â€Š16 years, were treated. In 15 cases, the TEE defect diameter was less than 10 mm, and in 8 of these patients, the ICE intraprocedural sizing increased the maximum diameter by more than 5 mm. Sizing balloon of the defect was performed in 51 cases; 2 patients received an ASD 38 mm device. Eight patients had multiple defects; in three of these, it was necessary to apply two devices. Four patients showed nonsignificant residual shunt; no complications related to the use of ICE were observed. One patient presented the migration of the ASD device into the abdominal aorta, percutaneously retrieved with a snare. No major complications were recorded during the entire follow-up period. CONCLUSION: This study confirms that ICE monitoring during ASD percutaneous closure is well tolerated and effective; it might be achievable as a routine gold standard by operators willing to use ICE systematically in all transcatheter closure interventions of interatrial communications.

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.

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.

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.

Adenosine-Free Indexes vs. Fractional Flow Reserve for Functional Assessment of Coronary Stenoses: Systematic Review and Meta-Analysis.

BACKGROUND: Adenosine-free indexes (AFIs), including resting Pd/Pa, instantaneous wave-free ratio (iFR) and contrast-FFR (cFFR), have been proposed to circumvent the use of vasodilators, in order to simplify the functional evaluation of coronary stenoses. Aims of this study were to analyze the correlation between AFIs and Fractional Flow Reserve (FFR) and to compare their diagnostic accuracy when FFR is used as reference. METHODS: We conducted a systematic review and meta-analysis of observational studies in which AFIs were compared to FFR. We produced paired forest plots to show the variation of the sensitivity and specificity estimates. We used a hierarchical summary ROC model (HSROC) to summarize the sensitivity and specificity of AFIs in detecting the concordance with FFR assessment. RESULTS: Eighteen studies were included in this meta-analysis. Overall, 4424, 4822 and 2021 coronary lesions in 4410, 4472 and 1898 patients, respectively, were evaluated by Pd/Pa, iFR and cFFR, respectively. The overall Pearson's correlations were 0.81 (95%CI 0.78-0.83), 0.80 (95%CI 0.78-0.81) and 0.92 (95%CI 0.90-0.94) for Pd/Pa, iFR and cFFR, respectively. cFFR showed a significantly higher correlation with FFR compared to Pd/Pa and iFR (p < 0.0001). The area under the HSROC estimating the discriminating accuracy of cFFR was 0.95 (95%CI 0.94-0.96) and it was significantly higher compared to Pd/Pa (0.86, 95%CI 0.80-0.93) and iFR (0.89, 95%CI 0.84-0.94) (p < 0.0001). CONCLUSIONS: AFIs show a good correlation with the gold standard FFR. Among AFIs, cFFR shows the highest correlation with FFR and the best diagnostic accuracy.

The Effects of Granulocyte Colony-Stimulating Factor in Patients with a Large Anterior Wall Acute Myocardial Infarction to Prevent Left Ventricular Remodeling: A 10-Year Follow-Up of the RIGENERA Study.

BACKGROUND: the RIGENERA trial assessed the efficacy of granulocyte-colony stimulating factor (G-CSF) in the improvement of clinical outcomes in patients with severe acute myocardial infarction. However, there is no evidence available regarding the long-term safety and efficacy of this treatment. METHODS: in order to evaluate the long-term effects on the incidence of major adverse events, on the symptom burden, on the quality of life and the mean life expectancy and on the left ventricular (LV) function, we performed a clinical and echocardiographic evaluation together with an assessment using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the Seattle Heart Failure Model (SHFM) at 10-years follow-up, in the patients cohorts enrolled in the RIGENERA trial. RESULTS: thirty-two patients were eligible for the prospective clinical and echocardiography analyses. A significant reduction in adverse LV remodeling was observed in G-CSF group compared to controls, 9% vs. 48% (p = 0.030). The New York Heart Association (NYHA) functional class was lower in G-CSF group vs. controls (p = 0.040), with lower burden of symptoms and higher quality of life (p = 0.049). The mean life expectancy was significantly higher in G-CSF group compared to controls (15 ± 4 years vs. 12 ± 4 years, p = 0.046. No difference was found in the incidence of major adverse events. CONCLUSIONS: this longest available follow-up on G-CSF treatment in patients with severe acute myocardial infarction (AMI) showed that this treatment was safe and associated with a reduction of adverse LV remodeling and higher quality of life, in comparison with standard-of-care treatment.

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.

Principles of hemodynamics for mechanical circulatory support: patho-physiological key aspects of assisted PCI.

It is essential to understand the pathophysiology of cardiogenic shock and the possible deterioration of contractile function during high-risk PCI in order to select those patients who could benefit from mechanical support thus choosing the most suitable device in every situation. Percutaneous ventricular assist devices (pVAD) provide hemodynamic support by improving cardiac output and mean arterial pressure, but their specific features result in different hemodynamic effects and degrees of myocardial ischemic protection and left ventricle unloading. These features, together with ease of use, specific contraindications and individual risk of complications, must be taken into account in the evaluation and selection of the device. The aim of this review is to illustrate the principles of left ventricular mechanic, including the pressure-volume loop analysis, in order to better understand and to quantify the different hemodynamic effects of pVAD supports and to explain the pathophysiological key aspects of assisted PCI.

[How to choose between intra-aortic balloon pump, Impella and extracorporeal membrane oxygenation]. / Come orientarsi tra contropulsatore, Impella e ossigenazione a membrana extracorporea.

The use of percutaneous mechanical circulatory support systems in the setting of both high-risk percutaneous coronary intervention (PCI) and cardiogenic shock is an emerging, controversial issue in contemporary clinical cardiology. The most common devices are the intra-aortic balloon pump (IABP), the Impella and the extracorporeal membrane oxygenator (ECMO). Technical progress, equipment improvement and growing cath-lab team expertise are allowing to offer critical patients different levels of assistance according to the selected device. Indeed, they are extremely different and the selection of the proper device for each clinical scenario might be tricky. In high-risk PCI, mechanical hemodynamic support serves the purpose of preventing hemodynamic collapse during the procedure. According to baseline risk stratification, IABP or Impella are usually considered whereas ECMO is seldom considered as a third option for highly selected patients.Cardiogenic shock and cardiac arrest are still associated with high mortality rates. In these conditions mechanical support may be promising. The lack of benefit observed with the systematic use of the IABP (combined with the increased mortality associated with higher number of inotropic drugs) is actually prompting to increasingly consider Impella and ECMO use in critically ill patients. The development of multidisciplinary local protocols is considered pivotal to improve management and outcome of those patients requiring percutaneous circulatory support devices.

The combined effect of subcutaneous granulocyte- colony stimulating factor and myocardial contrast echocardiography with intravenous infusion of sulfur hexafluoride on post-infarction left ventricular function, the RIGENERA 2.0 trial: study protocol for a randomized controlled trial.

BACKGROUND: Several clinical trials and recent meta-analyses have demonstrated that administration of recombinant human granulocyte-colony stimulating factor (G-CSF) is safe and, only in patients with large acute myocardial infarction (AMI), is associated with an improvement in left ventricular ejection fraction. Moreover, the mobilization and engraftment of the bone marrow-derived cells may differ significantly among patients, interfering with the restoration of left ventricular function after treatment. Therefore, the clinical potential application of the G-CSF has not yet been fully elucidated. METHODS/DESIGN: The RIGENERA 2.0 trial is a multicenter, phase II, placebo-controlled, randomized, open-label, with blinded evaluation of endpoints (PROBE) trial in which 120 patients with an acute ST-elevation myocardial infarction (STEMI) undergoing successful revascularization but with residual myocardial dysfunction will be enrolled. In cases where there is a left ventricular ejection fraction (LVEF) ≤ 45% the patient will be electronically randomized (1:1 ratio) to receive either subcutaneous recombinant human G-CSF (group 1) or placebo (group 2) both added on top of optimal standard of care. Both groups will undergo myocardial contrast echocardiography with intravenous infusion of sulfur hexafluoride (MCE) whilst undergoing the echocardiogram. The primary efficacy endpoint is the evaluation of the LVEF at 6 months after AMI assessed by cardiac magnetic resonance. Secondary efficacy endpoints are the evaluation of LVEF at 6 months after AMI assessed by echocardiography, left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) assessed by cardiac magnetic resonance and echocardiography at 6 months, together with the incidence of major adverse clinical events (MACE) defined as death, myocardial infarction, sustained cardiac arrhythmias, cardiogenic shock, stroke and re-hospitalization due to heart failure at 1 year. DISCUSSION: The RIGENERA 2.0 trial will test whether G-CSF administration and MCE, through the enhancement of the bone marrow-derived cells homing in the myocardium, determines an improvement in regional and global contractile function, myocardial perfusion and infarct extension in patients with large AMI. The results of the present study are expected to envision routine clinical use of this safe, affordable and reproducible approach in patients with successful revascularization after AMI. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02502747 (29 June 2015); EudraCT: 2015-002189-21 (10 July 2015).

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.

Increased risk of myocardial infarction with dabigatran: fact or fiction?

Dabigatran is a direct, competitive inhibitor of thrombin recently approved for the prophylaxis of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. In some of the clinical trials evaluating the efficacy and safety of dabigatran in different clinical settings [i.e., prevention of venous thromboembolism (VTE) after orthopedic surgery, secondary prevention of VTE, and acute coronary syndromes (ACS)], a trend toward an increase in acute coronary events among patients receiving dabigatran has been reported, thus raising concerns of a possible relationship between dabigatran and myocardial infarction, especially in high-risk patients. However, as shown in our article, current evidence is inconclusive on this topic; more data are needed to detail this hypothetical association, and other considerations, such as the well-known protective effect of warfarin against ACS, should be taken into account as a possible explanation.

Outcomes in Women Undergoing Electrophysiological Procedures.

The number of invasive electrophysiological procedures is steadily increasing in Western countries, as the age of the population increases and technologies advance. In recent years, gender-related differences in cardiac rhythm disorders have been increasingly appreciated, which can potentially have a great impact on the outcomes of invasive electrophysiological procedures. Among supraventricular arrhythmias, women have a higher incidence of atrioventricular nodal re-entrant tachycardia and a significantly lower incidence of atrioventricular re-entrant tachycardia compared with males, and present to ablation procedures later and after having failed more antiarrhythmic drugs. The results of catheter ablation of atrial fibrillation in women have been reported worse than in men. This finding is possibly due to a later referral of females to ablation procedures, who present older and with a higher incidence of long-standing persistent atrial fibrillation. With regard to cardiac device implantation procedures, a smaller survival benefit from prophylactic implantable cardioverter defibrillator (ICD) implantation has been shown in women, essentially due to gender-specific differences in the clinical course of patients with severe left ventricular dysfunction, with women dying predominantly from non-arrhythmic causes. On the other side, the clinical outcome of cardiac resynchronisation therapy seems to be more favourable in women, who experience a greater degree of reverse left ventricular remodelling and a striking decrease of heart failure events or mortality after biventricular pacing. This review will summarise the available evidence on gender-related differences in outcomes of invasive electrophysiological procedures.

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.

Influence of the amount of myocardium subtended by a stenosis on fractional flow reserve.

BACKGROUND: Fractional flow reserve (FFR) specifically relates to the severity of a stenosis to the mass of tissue to be perfused. Accordingly, the larger the territory to be perfused, the greater the flow and the pressure gradient induced by maximal hyperemia. Although this notion may be considered intuitive, its unequivocal demonstration is still lacking. The aim of our study was to evaluate the influence of the amount of myocardium subtended to an intermediate stenosis on FFR, especially in relation to quantitative coronary angiography. METHODS AND RESULTS: The severity of each lesion was assessed by FFR and 2-dimensional quantitative coronary angiography. The amount of jeopardized myocardium was evaluated using 3 validated scores specifically adapted to this aim: the Duke Jeopardy Score (DJS), the Myocardial Jeopardy Index (MJI), and the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) Lesion Score (ALS). The presence of a concomitant collateralized chronic total occlusion was also reported. A total of 213 intermediate coronary stenoses in 184 patients were enrolled. FFR values were correlated to minimal lumen diameter (r=0.34; P<0.0001) and diameter stenosis (r=-0.28; P<0.0001). FFR was inversely correlated with DJS, MJI, and ALS (r=-0.28, P<0.0001; r=-0.40, P<0.0001; and r=-0.34, P<0.0001). Lesions localized on proximal left anterior descending were related to significantly lower FFR values and to a higher rate of a positive FFR compared with those in distal left anterior descending, left circumflex, and right coronary arteries (0.80±0.09 versus 0.84±0.08 versus 0.88±0.09 versus 0.91±0.04; P<0.0001). The presence of a collateralized chronic total occlusion was associated with significantly lower FFR values (0.80±0.07 versus 0.85±0.09; P<0.005). At multivariate analysis MJI, minimal lumen diameter, and presence of a collateralized chronic total occlusion were confirmed as significant predictors of FFR. CONCLUSIONS: A larger amount of perfused myocardium subtended by a stenosis is associated with a higher probability that an angiographically intermediate coronary stenosis is functionally significant.

Angiographic assessment of myocardial perfusion in Tako-Tsubo syndrome.

OBJECTIVES: To angiographically assess myocardial perfusion in patients with Tako-Tsubo syndrome (TTS) in comparison with control individuals and patients with ST-elevation myocardial infarction (STEMI). BACKGROUND: Coronary microvascular dysfunction has been proposed as the pathophysiological mechanism underlying TTS. METHODS: We retrospectively selected consecutive TTS patients showing typical left ventricular (LV) apical dysfunction admitted to our Department in the period 2007-2011 (n=25). We also enrolled an age and gender-matched control group showing normal coronary arteries (CTR, n=25), patients with STEMI undergoing primary percutaneous intervention with myocardial reperfusion (SR, n=25) or microvascular obstruction (SMVO, n=25). TIMI flow, TIMI frame count (TFC) and both qualitative and quantitative myocardial blush grade in LV apex were assessed. Specifically, myocardial perfusion was quantitatively evaluated using 'Quantitative Blush Evaluator' (QuBE), an open source software previously validated in the setting of STEMI. RESULTS: In TTS, TIMI flow on the LAD was significantly lower and TFC significantly higher compared to CTR and SR (p=0.008 for both), while it did not significantly differ compared to SMVO (p=0.06). In TTS, MBG was significantly lower than that in CTR and SR (p=0.001 for both), while it was significantly higher than that in SMVO (p<0.001). In TTS, QuBE score was significantly lower than that in CTR and SR (p=0.001 for both) and higher than in SMVO (p=0.02). CONCLUSIONS: Our data indicate that myocardial perfusion assessed during angiography is more impaired in patients with TTS than in patients with STEMI exhibiting myocardial reperfusion, while it is less impaired than in patients with STEMI exhibiting MVO.