A Novel Approach to Cardiac Magnetic Resonance Scar Characterization in Patients Affected by Cardiac Amyloidosis: A Pilot Study.

Background and Objectives: Cardiac magnetic resonance (CMR) imaging has become an essential instrument in the study of cardiomyopathies; it has recently been integrated into the diagnostic workflow for cardiac amyloidosis (CA) with remarkable results. An additional emerging role is the stratification of the arrhythmogenic risk by scar analysis and the possibility of merging these data with electro-anatomical maps. This is made possible by using a software (ADAS 3D, Galgo Medical, Barcelona, Spain) able to provide 3D heart models by detecting fibrosis along the whole thickness of the myocardial walls. Little is known regarding the applications of this software in the wide spectrum of cardiomyopathies and the potential benefits have yet to be discovered. In this study, we tried to apply the ADAS 3D in the context of CA. Materials and Methods: This study was a retrospectively analysis of consecutive CMR imaging of patients affected by CA that were treated in our center (Marche University Hospital). Wherever possible, the data were processed with the ADAS 3D software and analyzed for a correlation between the morphometric parameters and follow-up events. The outcome was a composite of all-cause mortality, unplanned cardiovascular hospitalizations, sustained ventricular arrhythmias (VAs), permanent reduction in left ventricular ejection fraction, and pacemaker implantation. The secondary outcomes were the need for a pacemaker implantation and sustained VAs. Results: A total of 14 patients were deemed eligible for the software analysis: 8 patients with wild type transthyretin CA, 5 with light chain CA, and 1 with transthyretin hereditary CA. The vast majority of imaging features was not related to the composite outcome, but atrial wall thickening displayed a significant association with both the primary (p = 0.003) and the secondary outcome of pacemaker implantation (p = 0.003). The software was able to differentiate between core zones and border zones of scars, with the latter being the most extensively represented in all patients. Interestingly, in a huge percentage of CMR images, the software identified the highest degree of core zone fibrosis among the epicardial layers and, in those patients, we found a higher incidence of the primary outcome, without reaching statistical significance (p = 0.18). Channels were found in the scar zones in a substantial percentage of patients without a clear correlation with follow-up events. Conclusions: CMR imaging plays a pivotal role in cardiovascular diagnostics. Our analysis shows the feasibility and applicability of such instrument for all types of CA. We could not only differentiate between different layers of scars, but we were also able to identify the presence of fibrosis channels among the different scar zones. None of the data derived from the ADAS 3D software seemed to be related to cardiac events in the follow-up, but this might be imputable to the restricted number of patients enrolled in the study.

Effect on Clinical Restenosis of an Ultra-Thin-Strut Bare Metal Cobalt-Chromium Stent Versus a Thin-Strut Stainless Steel Stent.

OBJECTIVES: To prospectively compare the impact of ultrathin-strut cobalt-chromium (Cro-Co) bare metal stent (BMS) versus thin-strut stainless steel (SS) BMS on clinically driven target lesion revascularization (TLR). BACKGROUND: Stent characteristics are an important determinant of restenosis. Thinner strut Cro-Co BMS is associated with a reduction of neointimal formation compared to SS BMS. The advantages of Cro-Co BMS in a real-world population is not clear. METHODS: Patients undergoing percutaneous coronary intervention (PCI) with BMS for any reason were enrolled. Patient with multi-vessel PCI, multi-lesions PCI, PCI of unprotected left main and coronary grafts were not excluded. They were divided in two groups according to stent type: Cro-Co or SS group. The primary endpoint was clinically driven TLR at follow-up. RESULTS: A total of 383 patients were enrolled: 222 in SS and 161 in Cro-Co group. During the follow-up, Cro-Co patients had a significantly lower occurrence of TLR compared to SS patients (1.9% vs 8.6%, P = 0.006). There were no significant differences for the composite endpoint of death, myocardial infarct, and stroke (4.9% in Cro-Co group vs 9.5% in SS group, P = 0.119). At multivariate analysis, the variables that were predictors of TLR were: use of SS stent (OR 4.43, P = 0.019) and diabetes (OR 2.84, P = 0.025). CONCLUSIONS: Ultra-thin strut Cro-Co BMS is associated with a significant reduction of clinically driven TLR in all comers population with any type of coronary disease complexity. (J Interven Cardiol 2016;29:300-310).

Inferior Q waves in apparently healthy subjects: Should we take a deep breath? An electrocardiographic, echocardiographic and cardiac magnetic resonance study.

AIM: To evaluate the diagnostic accuracy of electrocardiographic inferior Q waves persistence during inspiration and echocardiographic segmental wall motion abnormalities for the detection of previously unsuspected silent myocardial infarction, by using cardiac magnetic resonance as the gold standard. METHODS: We prospectively enrolled 50 apparently healthy subjects with inferior Q waves on routine electrocardiogram and high atherosclerotic risk profile. Patients underwent electrocardiogram during deep inspiration, standard transthoracic echocardiography, and cardiac magnetic resonance. RESULTS: Inferior Q waves during deep inspiration persisted in 10 subjects (20%) and cardiac magnetic resonance was positive in 10 (20%). Between the 10 positive cardiac magnetic resonance subjects 8 showed persistence of inferior Q waves, giving a sensitivity of 80% (95%;CI 44.4-97.5%) and a specificity of 95% (95%;CI 83.1-99.4%). Segmental wall motion abnormalities were present overall in 10 subjects (20%), but only in 5 of the 10 positive cardiac magnetic resonance subjects, giving a sensitivity of 87.5% (95% CI 73.2-95.8) and specificity of 50% (95% CI 18.7-81.3). CONCLUSIONS: Electrocardiographic inferior Q waves persistence during deep inspiration is a simple test with a high accuracy for diagnosis of silent myocardial infarction. Standard echocardiography resulted less accurate.

Characteristics and Clinical Value of Electroanatomic Voltage Mapping in Cardiac Amyloidosis.

BACKGROUND: Cardiac amyloidoses (CAs) are an increasingly recognised group of infiltrative cardiomyopathies associated with high risk of adverse cardiac events. We sought to characterise the characteristics and clinical value of right ventricular (RV) electroanatomic voltage mapping (EVM) in CA. METHODS: Fifteen consecutive patients undergoing endomyocardial biopsy (EMB) for suspected CA (median age 75 years, 1st-3rd quartiles 64-78 years], 67% male) were enrolled in an observational prospective study. Each patient underwent RV high-density EVM using a multipolar catheter and EMB. The primary outcome was death or heart failure hospitalisation at 1-year follow-up. We recorded electrographic features at EMB sampling sites and electroanatomic data in the overall RV, and explored their correlations with histopathologic findings and primary outcomes events. RESULTS: A final EMB-proven diagnosis of immunoglobulin light chain or transthyretin CA was formulated in 6 and 9 patients, respectively. Electrogram amplitudes in the bipolar and unipolar configurations averaged 1.55 ± 0.44 mV and 5.14 ± 1.50 mV, respectively, in the overall RV, with lower values in AL CA patients. We found a significant inverse correlation between both bipolar and unipolar electrogram amplitude and amyloid burden according to EMB (P = 0.001 and P = 0.025, respectively). At 1-year follow-up, 7 patients (47%) experienced a primary outcome event; the extent of bipolar dense scar area at RV EVM was an independent predictor of primary outcome events at multivariable analysis (odds ratio 2.40; P = 0.037). CONCLUSIONS: In CA, electrogram amplitudes are around the lower limit of normal yet disproportionately low compared with the increased wall thickness. Out data suggest that RV electrogram amplitude may be a quantitative marker of amyloid burden, and that RV EVM may have prognostic value.

Real-world candidacy to mavacamten in a contemporary hypertrophic obstructive cardiomyopathy population.

AIMS: In the EXPLORER-HCM trial, mavacamten reduced left ventricular outflow tract obstruction (LVOTO) and improved functional capacity of symptomatic hypertrophic obstructive cardiomyopathy (HOCM) patients. We sought to define the potential use of mavacamten by comparing real-world HOCM patients with those enrolled in EXPLORER-HCM and assessing their eligibility to treatment. METHODS AND RESULTS: We collected information on HOCM patients followed up at 25 Italian HCM outpatient clinics and with significant LVOTO (i.e. gradient ≥30 mmHg at rest or ≥50 mmHg after Valsalva manoeuvre or exercise) despite pharmacological or non-pharmacological therapy. Pharmacological or non-pharmacological therapy resolved LVOTO in 1044 (61.2%) of the 1706 HOCM patients under active follow-up, whereas 662 patients (38.8%) had persistent LVOTO. Compared to the EXPLORER-HCM trial population, these real-world HOCM patients were older (62.1 ± 14.3 vs. 58.5 ± 12.2 years, p = 0.02), had a lower body mass index (26.8 ± 5.3 vs. 29.7 ± 4.9 kg/m2 , p < 0.0001) and a more frequent history of atrial fibrillation (21.5% vs. 9.8%, p = 0.027). At echocardiography, they had lower left ventricular ejection fraction (LVEF, 66 ± 7% vs. 74 ± 6%, p < 0.0001), higher left ventricular outflow tract gradients at rest (60 ± 27 vs. 52 ± 29 mmHg, p = 0.003), and larger left atrial volume index (49 ± 16 vs. 40 ± 12 ml/m2 , p < 0.0001). Overall, 324 (48.9%) would have been eligible for enrolment in the EXPLORER-HCM trial and 339 (51.2%) for treatment with mavacamten according to European guidelines. CONCLUSIONS: Real-world HOCM patients differ from the EXPLORER-HCM population for their older age, lower LVEF and larger atrial volume, potentially reflecting a more advanced stage of the disease. About half of real-world HOCM patients were found eligible to mavacamten.

Baseline white blood cell count is an independent predictor of long-term cardiovascular mortality in patients with non-ST-segment elevation acute coronary syndrome, but it does not improve the risk classification of the GRACE score.

OBJECTIVES: To investigate the prognostic significance of baseline white blood cell count (WBCc) in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and its additive predictive value beyond the Global Registry of Acute Coronary Events (GRACE) score. METHODS: We included 1,315 consecutive NSTE-ACS patients. Patients were divided in quartiles according to the WBCc (cells per 1 mm(3)) i.e. Q1 <6,850, Q2 = 6,850-8,539, Q3 = 8,540-10,857 and Q4 ≥10,858. The study end point was 3-year cardiovascular death (CVD). RESULTS: The median age of the study population was 76 years. Overall, 335 patients (25.5%) died with 211 of these (16%) suffering from CVD. Patients in Q4 showed a higher cumulative probability of CVD compared to patients in Q1-Q3. On multivariable analysis, patients in Q4 were at higher risk of CVD [hazard ratio (HR) = 1.47, 95% confidence interval (CI) 1.09-1.98, p = 0.011]. WBCc as a continuous variable was also independently associated with the study end point (HR = 1.043; 95% CI 1.02-1.07; p = 0.001). However, the incorporation of WBCc into the GRACE score did not improve either prediction of risk (C-index = 0.796 for GRACE score with or without WBCc) or classification of risk [relative integrated discrimination improvement = 0.0154, 95% CI) -0.029 to 0.0618; continuous net reclassification improvement = -0.0676, 95% CI -0.2149-0.0738). CONCLUSIONS: WBCc was an independent predictor of 3-year CVD in patients with NSTE-ACS. However, it did not add prognostic information beyond the GRACE score.

Conduction disorders after aortic valve replacement: what is the real impact of sutureless and rapid deployment valves?

BACKGROUND: Although sutureless and rapid deployment aortic valve replacement (SURD-AVR) has been associated with an increased rate of permanent pacemaker (PPM) implantation compared to conventional AVR (c-AVR), the predictors of new conduction abnormalities remain to be clarified. This study aimed to identify risk factors for conduction disorders in patients undergoing AVR surgery. METHODS: Data from 243 patients receiving minimally invasive AVR were prospectively collected. SURD-AVR was performed in 103 (42.4%) patients and c-AVR in 140 (57.6%). The primary endpoint was the occurrence of new-onset conduction disorders, defined as first degree atrioventricular (AV) block, advanced AV block requiring PPM implantation, left anterior fascicular block (LAFB), left bundle branch block (LBBB) and right bundle branch block (RBBB). RESULTS: The unadjusted comparison revealed that SURD-AVR was associated with a higher rate of advanced AV block requiring PPM when compared with c-AVR (10.5% vs. 2.1%, P=0.01). After adjusting for other measured covariates (OR: 1.6, P=0.58) and for the estimated propensity of SURD-AVR (OR: 5.1, P=0.1), no significant relationship between type of AVR and PPM implantation emerged. On multivariable analysis, preoperative first-degree AV block (OR: 6.9, P=0.04) and RBBB (OR: 6.9, P=0.03) were independent risk factors for PPM. Subgroup analysis of patients with normal preoperative conduction revealed similar incidence of PPM between SURD-AVR and c-AVR (1.3% vs. 1.9%, P=0.6). When compared with c-AVR, SURD-AVR was associated with a greater incidence of postoperative new onset LBBB (18.1% vs. 3.2%, P<0.001). This finding was confirmed after adjusting for the estimated propensity of SURD-AVR (OR: 6.3, P=0.009). CONCLUSIONS: Our study revealed that the risk of PPM implantation in patients receiving surgical AVR is heavily influenced by the presence of pre-existing conduction disturbances rather than the type of valve prosthesis. Conversely, SURD-AVR emerged as an independent predictor for LBBB and was associated with an increased risk of PPM in patients presenting with RBBB.

Clinical characteristics, management and outcomes of patients with acute coronary syndrome and atrial fibrillation: real-world data from two nationwide registries in Italy.

BACKGROUND: Atrial fibrillation is common in the setting of acute coronary syndromes (ACS) although its impact on ACS remains controversial. AIM: To describe in-hospital management of patients with atrial fibrillation and ACS evaluating the impact of atrial fibrillation on in-hospital and mid-term outcome. METHODS: We analysed the data of two prospective multicentre nationwide registries (IN-ACS Outcome and MANTRA) to assess clinical characteristics, management, and outcomes of patients with ACS and atrial fibrillation. Study outcomes included death from any cause and a composite end-point of death/re-infarction/stroke/major bleeding within index admission and 6 months' follow-up. RESULTS: Out of 12 288 ACS patients, 1236 (10.1%) had atrial fibrillation at admission or developed it during hospitalization. Atrial fibrillation patients were older, more often female, and had higher burden of comorbidities. In-hospital mortality was higher among atrial fibrillation patients (8.7 vs. 2.4%, P < 0.001). Patients with atrial fibrillation had a higher incidence of re-infarction (3.5 vs. 1.7%, P < 0.0001) and ischemic stroke (1.7 vs. 0.4%, P < 0.001) compared with those in sinus rhythm. Major bleedings were also more frequent among atrial fibrillation patients (1.9 vs. 0.9%, P < 0.001). In-hospital and at 6 months' follow-up death from any cause occurred more often in atrial fibrillation patients than in those without atrial fibrillation (9.4 vs. 3.5%, P < 0.0001). At multivariable analysis, atrial fibrillation was an independent predictor of the in-hospital composite end-point (OR 1.67, 95% CI 1.35-2.06, P < 0.0001) but not at 6 months' follow-up. The independent role of atrial fibrillation on the in-hospital composite end-point was also confirmed by propensity score analyses. CONCLUSION: Atrial fibrillation was an independent predictor for adverse in-hospital outcome in ACS. This effect disappeared at mid-term follow-up, whereas noncardiac comorbidities emerged as prognostic factors of adverse outcomes.

[ANMCO Position paper: New perspectives on the role of n-3 polyunsaturated fatty acids in cardiovascular prevention]. / Position paper ANMCO: Nuove prospettive sul ruolo degli acidi grassi polinsaturi n-3 nella prevenzione cardiovascolare.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the most important long-chain polyunsaturated fatty acids of the n-3 series (n-3 PUFA). Recent studies have clarified that EPA and DHA have different tissue distribution and influence target organs in a distinct way. In addition to the main effect of reducing triglycerides (TG), they exert antithrombotic, antiarrhythmic, anti-inflammatory, anti-atherogenic, and hemodynamic effects. The different action of PUFA n-3 depends on the dosage and duration of treatment: the effect on TG requires high doses and a few weeks/months of treatment.Several epidemiological studies have shown a relationship between hypertriglyceridemia and cardiovascular risk, confirmed by post-hoc analysis of statin trials and by recent genetic linkage studies. Moreover in secondary prevention, the evidence of a significant "residual risk", even in the presence of an adequate control of LDL-cholesterol, has led the scientific community to consider further intervention objectives in the context of the individual lipid profile, the most promising of which is certainly hypertriglyceridemia.The recent landmark REDUCE-IT study is the first major lipid intervention study to demonstrate a benefit deriving from an approach not based on the LDL target, focusing on a determinant factor of residual risk such as hypertriglyceridemia and treating it with high doses of n-3 PUFA (4 g/day).Overall, the "lipid residual risk" approach involves two integrated actions: (i) the achievement of the LDL-cholesterol target (<70 mg/dl) by using statins, ezetimibe, PCSK9 inhibitors; (ii) checking TG levels in order to start n-3 PUFA in case of TG values >150 mg/dl, at an initial dosage of 2-3 g/day (up to 4 g/day after 10-12 weeks).

A handbook for the clinical cardiologist about CRT/ICD. A practical guide about how to survive during an on call shift.

Cardiac resynchronization therapies (CRTs) have been demonstrated to improve the clinical management and prognosis of selected patients with heart failure. CRT devices include both CRT pacemakers (CRT-P) and CRT defibrillators (CRT-D), with the latter being used to treat life-threatening ventricular arrhythmias. A significant advantage of CRTs is the ability to monitor several vital parameters which, thanks to advanced technology, may be remotely assessed. Personalized programming options allow patients to receive the maximum benefit from these treatments. In this review we report the main diagnostic and therapeutic algorithms used in clinical practice.

[Cardiogenic shock: from early diagnosis to multiparameter monitoring]. / Shock cardiogeno: dalla diagnosi precoce al monitoraggio multiparametrico.

Cardiogenic shock (CS) is a life-threatening condition that occurs in response to reduced cardiac output, in the presence of adequate intravascular volume, and results in tissue hypoxia. CS can occur as a result of several etiologies but the most common is acute myocardial infarction. Despite the introduction of emergency revascularization for CS complicating acute myocardial infarction, mortality still remains exceptionally high, particularly in patients with refractory CS. The diagnosis of CS is sometimes challenging and it is based on clinical, hemodynamic, and biochemical signs. A multidisciplinary technical platform as well as specialized and experienced medical teams are crucial to treat this group of patients.We briefly summarize the main aspects of diagnosis, etiology and pathophysiology with a particular focus on macro- and microhemodynamic parameters that are essential for the diagnosis and treatment of this patient population.

[Cardiogenic shock: from pharmacological treatment to mechanical circulatory support]. / Shock cardiogeno: dal trattamento farmacologico all'assistenza meccanica al circolo.

Cardiogenic shock (CS) is a state of critical end-organ hypoperfusion due to reduced cardiac output, despite adequate filling status. The development of multiorgan dysfunction is believed to be the major contributor to the high early mortality. Little evidence exists as to which vasopressor or inotrope should best be used for early treatment; however, customized pharmacological therapy, tailored on hemodynamic monitoring, is essential to achieve normal peripheral perfusion. Moreover, an increasing number of mechanical circulatory support devices are available for hemodynamic support in patients with CS but, at present, data derived from randomized clinical trials on the effectiveness, safety, differential indications for mechanical support devices, and optimal implant timing are limited.The aim of this review is to offer an overview of the pharmacological and device options, providing a practical approach to the treatment of patients with CS.

Utility of stress perfusion-cardiac magnetic resonance in follow-up of patients undergoing percutaneous coronary interventions of the left main coronary artery.

To assess the accuracy of cardiac magnetic resonance (CMR) for the diagnosis of angiographic stenosis after percutaneous coronary intervention (PCI) of left main coronary artery (LMCA). Patients undergone in the last year PCI of unprotected LMCA and scheduled for conventional X-ray coronary angiography (CXA) were evaluated with stress perfusion CMR within 2 weeks before CXA. Main contraindications to CMR were exclusion criteria. Stress perfusion CMR was performed to follow a bolus of contrast Gadobutrol after 3 min of adenosine infusion. Between the 50 patients enrolled, only 1 did not finish the CMR protocol and 49 patients with median age 71 (65-75) years (38 male, 11 female) were analyzed. Between 784 coronary angiographic segments evaluated we found 75 stenosis or occlusions (prevalence 9.5%), but only 13 stenosis or occlusions in proximal segments (prevalence 6.6%). Patients with coronary stenosis (n = 12, 24%) showed a significantly (p = 0.002) higher prevalence of diabetes (7 of 12, 58%). At CMR examination, late gadolinium enhancement was present in 25 (51%), reversible perfusion defects in 12 (24%), and fixed perfusion defects in 6 subjects (12%). The only patient with LMCA restenosis resulted positive at perfusion CMR. The accuracy of stress perfusion CMR in diagnosis of coronary stenosis was higher when the analysis was performed only in proximal coronary arteries (95%, CI 86-99) compared to overall vessels (84%, CI 70-92). Stress perfusion CMR could strongly reduce the need for elective CXA in follow up of LMCA PCI and should be validated in further multicenter prospective studies.

[Noninvasive ventilation: general characteristics, indications, and review of the literature]. / Ventilazione non invasiva: caratteri generali, indicazioni e revisione della letteratura.

Noninvasive ventilation (NIV), including both continuous and bilevel positive airway pressure, plays a pivotal role in the treatment of acute respiratory failure secondary to acute heart failure. For an appropriate use of NIV, it is essential to consider the underlying pathophysiological principles, the differences between the different modes of ventilation, the main indications, contraindications and complications. The aim of this review is also to give practical guidance on how and when to start NIV at the bedside, how to monitor the response and how to choose the most appropriate interface. A review of the literature supports the use of NIV in terms of efficacy (reduction in intubation and mortality) and safety (in particular, the risk of myocardial infarction associated with its use, suggested by a previous study, has been definitely confuted). Nevertheless, NIV is still largely underused in contemporary clinical practice, as reported by data from real-world registries. This may be due to several factors, including lack of knowledge/confidence, reluctance of application in particular settings (acute coronary syndromes) and the risk of adverse effects (hypotension), which need to be reappraised.

[Noninvasive ventilation and sedation: evidence and practical tools for its utilization]. / Ventilazione non invasiva e sedazione: evidenze a supporto e consigli pratici.

Noninvasive ventilation (NIV) has gained increased acceptance inside the critical area, since it has been shown to be effective in reducing or avoiding the need for oro-tracheal intubation. NIV efficacy is dependent on the selection of the appropriate patients and on their compliance to therapy. Actually, full collaboration is not easily reached especially in agitated patients.Sedation during NIV is useful to reduce the rate of treatment failure, but robust data to guide the development of best practice are limited and sometimes local customs appear to exert a strong influence on patterns of care. Different sedative drugs are ready for use but none of currently available agents fulfill the criteria for the ideal drug. Knowledge of the pharmacological and hemodynamic characteristics of every single sedative agent is crucial to choose the right drug for every clinical scenario. Close monitoring is mandatory to avoid adverse effects. The aim of this article is to review the currently available literature, to recognize the contraindications for sedation use and to provide practical guidance.

[Hemodynamic effects of positive end-expiratory pressure]. / Gli effetti emodinamici della pressione positiva di fine espirazione.

The application of a positive end-expiratory pressure (PEEP), the cornerstone of noninvasive ventilation (NIV), causes hemodynamic changes in the cardiovascular system. To understand the benefits of NIV it is necessary to resume concepts of cardiovascular physiology and pathophysiology about cardiac function determinants, venous return, ventricular interdependence and heart-lung interaction, and to understand how PEEP interacts with them. The hemodynamic effects of PEEP are mediated by the increase in transpulmonary pressure, which results in increased pulmonary vascular resistance and in an attending small reduction of venous return in conditions of euvolemia, in a substantial reduction of left ventricular afterload and a potential positive effect on left ventricular stroke volume.The aim of this review is to describe how the application of PEEP does not necessarily induce detrimental hemodynamic effects, but may decrease oxygen consumption and improve cardiac performance. These effects can justify the use of NIV in hemodynamically unstable patients.

Heart rate modulation in stable coronary artery disease without clinical heart failure: What we have already learned from SIGNIFY?

An elevated heart rate is a marker of cardiovascular risk in patients with stable coronary artery disease. Ivabradine selectively inhibits the "f" current in the sinus node and reduces heart rate without any modifications of blood pressure, myocardial contractility and arteriolar resistance. However the addition of ivabradine to standard therapy to reduce heart rate did not improve outcomes in the recent SIGNIFY trial. Moreover, a significant interaction between the effect of ivabradine among subgroups with and without angina was detected, with a worse outcome in patients in CCS class >II at baseline. The explanation for this surprising finding despite a significant reduction in angina and myocardial revascularization procedures is uncertain. A J-curve for heart rate was not demonstrated. We speculate a significant interference on adverse events (mainly atrial fibrillation and consequently acute coronary syndromes) and on the outcome of unfavorable interactions between ivabradine and diltiazem, verapamil and strong inhibitors of CYP3A4 (4.6% of the total population). Indeed, when these patients are excluded from subgroup analysis, the harmful effect of Ivabradine among patients with severe angina disappears. In conclusion, heart rate is a marker of risk but is not a risk factor and/or a target of therapy in patients with stable coronary artery disease and preserved ventricular systolic function. Standard doses of ivabradine are indicated for treatment of angina as an alternative or in addition to beta-blockers, but should not be administered in association with CYP3A4 inhibitors or heart rate-lowering calcium-channel blockers.

Long-term prognostic role of cerebrovascular disease and peripheral arterial disease across the spectrum of acute coronary syndromes.

BACKGROUND: In acute coronary syndromes (ACS), the influence of cerebro-vascular disease (CVD) and/or peripheral artery disease (PAD) on short-midterm outcome has been well established. Data on long-term outcome however, are limited. Our study aimed to explore the effect of CVD and PAD on long-term outcome in a cohort of unselected ACS patients, including ST-elevation (STE-ACS) and non-ST-elevation (NSTE-ACS). METHODS AND RESULTS: The population consisted of 2046 consecutive patients with a confirmed final diagnosis of ACS; 896 (44%) had STE-ACS and 1150 (66%) NSTE-ACS. CVD alone was present in 98 patients (5%), 282 (14%) had PAD alone, and 30 (1.5%) had both. All cause mortality at 5 years was lowest in patients without CVD/PAD (33%), intermediate in patients with either CVD or PAD (62% and 63%, respectively) reaching 80% in those with both CVD and PAD. These findings were confirmed in the STE-ACS and NSTE-ACS subgroups. CVD and PAD remained independent predictors of mortality after multivariable analysis, the combined presence of both carrying the highest risk within each ACS type (HR 4.15, 95% CI 1.83-9.44 for STE-ACS; HR 2.14, 1.29-3.54 for NSTE-ACS). Patients with CVD and/or PAD were less likely to be treated invasively and received less evidence-based treatment at discharge. CONCLUSIONS: Across the spectrum of ACS, extracardiac vascular disease harbors a negative long-term prognosis that worsens progressively with the number of affected arterial beds.

Troponin T elevation in acute aortic syndromes: Frequency and impact on diagnostic delay and misdiagnosis.

AIMS: Despite troponin assay being a part of the diagnostic work up in many conditions with acute chest pain, little is known about its frequency and clinical implications in acute aortic syndromes (AASs). In our study we assessed frequency, impact on diagnostic delay, inappropriate treatments, and prognosis of troponin elevation in AAS. METHODS AND RESULTS: Data were collected from a prospective metropolitan AAS registry (398 patients diagnosed between 2000 and 2013). Cardiac troponin test, using either standard or high sensitivity assay, was performed according to standard protocol used in chest pain units. Troponin T values were available in 248 patients (60%) of the registry population; the overall frequency of troponin positivity was 28% (ranging from 16% to 54%, using standard or high sensitivity assay respectively, p = 0.001). Troponin positivity was frequently associated with acute coronary syndromes (ACS)-like electrocardiogram findings, and with a twofold increased risk of long in-hospital diagnostic time (odds ratio (OR) 1.92, 95% confidence interval (CI) 1.05-3.52, p = 0.03). The combination of positive troponin and ACS-like electrocardiogram abnormalities resulted in a significantly increased risk of in-hospital delay/coronary angiography/antithrombotic therapy due to a misdiagnosis of ACS (OR 2.48, 95% CI 1.12-5.54, p = 0.02). However, troponin positivity was not associated with in-hospital mortality (OR 1.63, 95% CI 0.86-3.10, p = 0.131). CONCLUSIONS: Troponin positivity was a frequent finding in AAS patients, particularly when a high sensitivity assay was employed. Abnormal troponin values were strongly associated with ACS-like electrocardiogram findings and with in-hospital diagnostic delay but apparently they did not influence in-hospital mortality.