Early change in invasive measures of microvascular function can predict myocardial recovery following PCI for ST-elevation myocardial infarction.

AIMS: Predicting the likely success of primary PCI to salvage potential infarcted myocardium is desirable. We compared early invasive parameters of coronary microcirculation function with the levels of circulating endothelin (ET-1) and 6-month ejection fraction after STEMI. METHODS AND RESULTS: Forty-four STEMI patients underwent assessment of coronary flow reserve (CFR) and index of myocardial resistance (IMR) on completion of PPCI and one day later. Cardiac magnetic resonance (CMR) at 24 h and 6 months assessed ejection fraction, oedema, late gadolinium enhancement, and salvage. In patients with depressed EF, there was no difference in IMR or CFR measured immediately after PPCI compared with those with preserved EF. However, by Day 1, CFR was significantly lower in those with depressed EF [2.0(1.5-2.3) vs. 2.6(2.1-3.3), P = 0.008]. In multivariable models, higher CFR post-PPCI [EST: +8.9 (SE 3.7) per 1 CFR unit, P = 0.03] and greater increase in CFR between post-PPCI and Day 1 [EST: +8.5 (SE 3.4) per 1 CFR unit, P = 0.01] were associated with higher salvage index. Circulating endothelin levels were significantly elevated in the low EF group at both 6 and 24 h, and 24 h levels correlated with CFR. CONCLUSION: Changes of the coronary microcirculation in the first day after PPCI are associated with 6-month ejection fraction and myocardial salvage. Depressed CFR at 24 h is associated with CMR imaging indices of MVO and haemorrhage and elevated endothelin levels.

Custom-made endograft with left subclavian artery branch in a patient with Takayasu aortitis complicated by type-B dissection and inflammatory involvement of the epiaortic vessels.

Type-B aortic dissection in a patient affected by Takayasu disease is a rarely described condition and its management can be challenging. A 47-year-old woman with Takayasu aortitis and previous aortic valve and ascending aorta replacement was admitted to hospital for type-B aortic dissection. The recent instabilization of aortic disease, the persistence of episodes of transient chest pain and the largest size of the aneurismatic tract of thoracic descending aorta rendered an invasive approach mandatory. Since the patient presented a complete bilateral occlusion of the subclavian artery just after the origin of the vertebral artery and a subcritical, smooth, bilateral stenosis of the common carotid artery, a custom-made endograft with left subclavian artery branch was successfully positioned, thus allowing the preservation of antegrade left vertebral circulation. This is the first case reporting an entirely endovascular exclusion of type-B dissection in a patient affected by Takayasu aortitis using a custom-made endograft with a subclavian branch allowing the preservation of the antegrade flow to left vertebral artery.

Influence of left ventricular hypertrophy on microvascular dysfunction and left ventricular remodelling after acute myocardial infarction.

AIMS: To ascertain whether the presence of left ventricular (LV) hypertrophy in patients with ST-segment elevation myocardial infarction (STEMI) influences microvascular dysfunction and LV remodelling at 6 months of follow-up. METHODS AND RESULTS: Fifty-six consecutive STEMI patients successfully treated with primary or rescue percutaneous coronary intervention underwent conventional two-dimensional and myocardial contrast echocardiography within 24 h and at 6 months. Left ventricular mass, end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction, and wall motion score index (WMSI) were measured. Left ventricular hypertrophy was defined as LV mass index >116 g/m(2) in men and >104 g/m(2) in women. In order to evaluate the potential influence of microvascular dysfunction on LV remodelling, myocardial perfusion was semiquantitatively scored by contrast score index (CSI). Patients with LV hypertrophy had higher EDV and ESV both at 24 h and at 6 months, compared with patients without LV hypertrophy (P < 0.05). No significant changes over time were observed in both groups. Both WMSI and CSI were similar between groups at 24 h and at follow-up, but improved in both groups over time (P < 0.05). CONCLUSION: Left ventricular hypertrophy does not appear to influence the development of post-acute myocardial infarction LV remodelling. Hypertrophic and non-hypertrophic left ventricles showed the same extent and temporal improvement in regional contractile function and microvascular perfusion.

Choice of access site and type of anticoagulant in acute coronary syndromes with advanced Killip class or out-of-hospital cardiac arrest.

INTRODUCTION AND OBJECTIVES: Patients who are vulnerable to hemodynamic or electrical disorders (VP) are often excluded from clinical trials and data on the optimal access-site or antithrombotic treatment are limited. We assessed outcomes of transradial vs transfemoral access and bivalirudin vs unfractionated heparin (UFH) in VP with acute coronary syndrome undergoing invasive management. METHODS: The MATRIX trial randomized 8404 patients to radial or femoral access and 7213 patients to bivalirudin or UFH. Among them, 934 (11.1%) were deemed VP due to advanced Killip class (n = 808), cardiac arrest (n = 168), or both (n = 42). The 30-day coprimary outcomes were major adverse cardiovascular and cerebrovascular events (MACE: death, myocardial infarction, or stroke) and net adverse clinical events (NACE: MACE or major bleeding). RESULTS: MACE and NACE were similarly reduced with radial vs femoral access in VP and non-VP. Transradial access was also associated with consistent relative benefits in all-cause and cardiovascular mortality or Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding with greater absolute benefits in VP. The effects of bivalirudin vs UFH on MACE and NACE were consistent in VP and non-VP. Bivalirudin was associated with lower all-cause and cardiovascular mortality in VP but not in non-VP, with borderline interaction testing. Bivalirudin reduced bleeding in both VP and non-VP with a larger absolute benefit in VP. CONCLUSIONS: In acute coronary syndrome patients undergoing invasive management, the effects of randomized treatments were consistent in VP and non-VP, but absolute risk reduction with radial access and bivalirudin were greater in VP, with a 5- to 10-fold lower number needed to treat for benefits. Trial registry number: NCT01433627.

Impact of microvascular obstruction on the assessment of coronary flow reserve, index of microcirculatory resistance, and fractional flow reserve after ST-segment elevation myocardial infarction.

BACKGROUND: Invasive assessment of coronary physiology (IACP) offers important prognostic insights in ST-segment elevation myocardial infarction (STEMI) but the dynamics of coronary recovery are poorly understood. OBJECTIVES: This study sought to examine the evolution of coronary flow reserve (CFR), index of microcirculatory resistance (IMR), ratio of distal coronary pressure (Pd) to mean aortic pressure (Pa), and fractional flow reserve (FFR) in patients undergoing primary percutaneous coronary intervention (PPCI). METHODS: 82 patients with STEMI underwent IACP at PPCI. Repeat IACP was performed in 61 patients (74%) at day 1 and in 46 patients (56%) at 6 months. Contrast-enhanced cardiac magnetic resonance imaging (CMR) was performed in 45 patients (55%) at day 1 and in 41 patients (50%) at 6 months. Changes in IACP were compared between patients with and without microvascular obstruction (MVO) on CMR. RESULTS: MVO was present in 21 of 45 patients (47%). Patients with MVO had lower CFR at PPCI and day 1 (p < 0.05) and a trend toward higher IMR values (p = 0.07). At 6 months, CFR and IMR were not significantly different between the groups. Baseline flow and Pd/Pa remained stable over time but FFR reduced significantly between PPCI and 6 months (p = 0.008); this reduction was mainly observed in patients with MVO (p = 0.006) but not in those without MVO (p = 0.21). CONCLUSIONS: In PPCI-treated patients with STEMI, coronary microcirculation begins to recover within 24 h and recovery progresses further by 6 months. FFR significantly reduces from baseline to 6 months. The presence of MVO indicates a highly dysfunctional microcirculation.

Incidence, predictors and management of left main coronary artery stent restenosis: a comprehensive review in the era of drug-eluting stents.

International guidelines recommend surgical revascularisation for unprotected left main (ULM) coronary artery disease. The introduction of drug-eluting stents (DES) as an emergency therapy has resulted in increasing numbers of patients having stents placed in ULM. As a consequence, important data on the safety and long-term outcome of PCI for ULM have progressively accumulated over recent years, derived mainly from registries rather than prospective randomised trials. These studies indicate that restenosis of the ULM still represents the main predictor of clinical events following stenting. However, the observed incidence is highly variable amongst the published studies and there is little data about the clinical management of restenosis of stents placed in the ULM. In the present paper we review the available literature regarding ULM restenosis, identify its predictors and suggest an algorithm for optimal management.

Protecting the heart: biological targets and clinical strategies.

The pathophysiology of myocardial damage in the setting of ischemic cardiomyopathy is complicated by the fact that the process of restoring blood flow to the ischemic cardiomyocytes can itself induce injury to the myocardium. This phenomenon, termed reperfusion injury, reduces the benefits of vessel recanalization and contributes to the damage initiated by occlusion. The interest on techniques aiming at protecting the heart from ischemia-reperfusion (IR) injury has constantly grown over the last two decades. Three main actors of IR injury can be identified: 1) cardiomyocite-related damage, 2) vascular-related injury and 3) inflammatory-related injury. Ideally targeting the series of molecular events that take place during myocardial reperfusion, this area of research focuses on the different strategies that may help to render the heart more resistant to the ischemic insult. The aim of this article is to highlight the clinical relevance of IR injury, how IR-injury can be assessed clinically as well as to review the current strategies, both pharmacological and non pharmacological, that show promise for translation to clinical practice.

Relationship of plasma neuropeptide Y with angiographic, electrocardiographic and coronary physiology indices of reperfusion during ST elevation myocardial infarction.

OBJECTIVES: The co-transmitter neuropeptide Y (NPY) is released during high levels of sympathetic stimulation and is a potent vasoconstrictor. We defined the release profile of plasma NPY during acute ST elevation myocardial infarction, and tested the hypothesis that levels correlate with reperfusion measures after treatment with primary percutaneous coronary intervention (PPCI). DESIGN: Prospective observational study. SETTING: University hospital heart centre. PATIENTS: 64 patients (62.6±11.7 years-old, 73% male) presenting throughout the 24-h cycle of clinical activity with ST elevation myocardial infarction. INTERVENTIONS: PPCI. MAIN OUTCOME MEASURES: NPY was measured (ELISA) in peripheral blood taken before and immediately after PPCI and at 6, 24 and 48 h post-PPCI. Reperfusion was assessed by angiographic criteria, ST segment resolution, invasive measurement of coronary flow reserve and the index of microcirculatory resistance. RESULTS: Plasma NPY levels were highest before PPCI (17.4 (8.8-42.2) pg/ml, median (IQR)) and dropped significantly post-PPCI (12.4 (6.5-26.7) pg/ml, p<0.0001) and after 6 h (9.0 (2.6-21.5) pg/ml, p=0.008). Patients with admission NPY levels above the median were significantly more hypertensive and tachycardic and were more likely to have diabetes mellitus. Patients with angiographic no-reflow (less than thrombolysis in myocardial infarction 3 flow and myocardial blush grade >2, n=16) or no electrocardiographic ST resolution (<70%, n=30) following PPCI had significantly higher plasma NPY levels. Patients with a coronary flow reserve <1.5 or index of microcirculatory resistance >33 also had significantly higher plasma NPY levels pre-PPCI and post-PPCI. CONCLUSIONS: Plasma NPY levels correlate with indices of reperfusion and coronary microvascular resistance.

Effects of late REopening of Coronary total Occlusion on micRovascular perfusion and myocarDial function: the RECORD study.

AIMS: The effects of the reopening of a coronary total occlusion (CoTO) on microvascular perfusion in subacute or chronic coronary syndromes are actually unclear. We aimed at evaluating the microvascular perfusion pattern by myocardial contrast echocardiography (MCE), in addition to contractile function, before and after CoTO reopening. METHODS: Twenty four patients with subacute and chronic coronary syndromes and CoTO datable >7 days underwent evaluation of microvascular perfusion and left ventricular (LV) function by MCE (Acuson Sequoia, with Sonovue, Bracco) before the reopening of the CoTO and at 9 ± 3 months of follow-up. Microvascular perfusion was semi-quantitatively assessed by the contrast score index (CSI), whereas the endocardial length of the perfusion defect [contrast defect length (CDL)], measured in three apical views and averaged, was expressed as a percentage of the total LV endocardial border. The wall motion score index (WMSI), LV volumes, and ejection fraction were also calculated. RESULTS: At baseline, a mild impairment of LV contractile function was observed, which corresponded to a similar impairment of the coronary microvascular perfusion in the overall study population. At follow-up, a significant reduction of CDL% [8.23 (0-19.63) vs. 0 (0-3.68), P = 0.005], improvement of the CSI (1.41 ± 0.29 vs. 1.12 ± 0.17, P = 0.001) and the WMSI (1.73 ± 0.41 vs. 1.33 ± 0.34, P = 0.0004), and increase in the ejection fraction (47.48% ± 8.66 vs. 55.60% ± 8.29, P = 0.0001) were found. CONCLUSION: Reopening of a CoTO in patients with clinical indications to myocardial revascularization is associated with the improvement of coronary microvascular perfusion and the recovery of contractile function.

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.

Axial deformation during coronary stenting: an extreme case.

We describe a case of longitudinal stent compression induced by withdrawal of a "buddy wire," which we managed by crushing the retracted struts using another stent. To the best of our knowledge, this is one of the first reports of this complication induced by wire manipulation.

Critical evaluation of the efficacy and tolerability of azilsartan.

Appropriate control of blood pressure (BP) in hypertensive patients still represents the major therapeutic goal in the treatment of hypertension. Despite the growing attention and wide range of antihypertensive agents available in the clinical scenario, the target of BP below the advised thresholds of 140/90 mmHg is, unfortunately, often unreached. For this reason, the search for new antihypertensive agents is still ongoing. Azilsartan medoxomil, a new angiotensin receptor blocker that has been recently introduced in the clinical arena, represents the eighth angiotensin receptor blocker currently available for BP control. The aim of this paper is to describe the efficacy and safety profile of this new compound, reviewing available data obtained from both pre-clinical and clinical studies.

Prevention and treatment of coronary distal embolization in the setting of acute myocardial infarction: pharmacologic approach.

Distal embolization (DE) of atherothrombotic debris into the coronary microcirculation occurs both in stable and unstable coronary syndromes. Despite the well recognized clinical significance of periprocedural myocardial infarction (MI) in stable percutaneous coronary intervention (PCI), the impact of DE has a much higher prognostic impact in the acute setting, and especially in ST-elevation myocardial infarction, where DE is a main determinant of no-reflow phenomenon. The present review aims to describe the pathophysiology of DE and to summarize the currently available pharmacological strategies to prevent and treat DE in the setting of MI, especially focusing on antithrombotic, antiinflammatory and vasodilator agents.

Positron emission tomography in acute coronary syndromes.

Several imaging techniques have been used to assess cardiac structure and function, to understand pathophysiology, and to guide clinical decision making in the setting of acute coronary syndromes (ACS). Over the last years, cardiac positron emission tomography (PET) has affirmed its role in this setting. Indeed, the combined quantitative assessment of myocardial metabolism and perfusion has allowed to better understand the functional status of infarcted and non-infarcted myocardium, thus improving our knowledge of myocardial response to necrosis. More recently, several studies, taking advantage of previous observations in patients with cancer, have shown that PET could also provide important information on the mechanisms of vascular instability through the early identification of activated inflammatory cells in the atherosclerotic plaque. These findings are opening the way to more effective forms of prevention of acute vascular syndromes in high-risk patients; furthermore, new more sensitive and specific tracers for the identification of vascular inflammation are under development. In this review, we describe the potential and limitations of PET in the assessment of ACS.

Characterization of microvascular and myocardial damage within perfusion defect area at myocardial contrast echocardiography in the subacute phase of myocardial infarction.

AIMS: The anatomical correlates of perfusion defect (PD) at myocardial contrast echocardiography (MCE) in the subacute phase of ST-elevation myocardial infarction (STEMI) are currently unknown. The study aimed at assessing whether, in the subacute phase of STEMI, within MCE PD microvessels are anatomically damaged or if some vasodilation can be still elicited and if the PD correlates with the extent of myocardial necrosis. METHODS AND RESULTS: Twenty-two post-percutaneous coronary intervention (PCI) patients underwent MCE 7 ± 1 days after STEMI, at baseline and after adenosine (ADN) administration. An area of completely non-opacified myocardium, corresponding to the area of the PD, was quantitated by planimetry. The area of the PD on MCE was compared with biochemical and imaging measures of myocardial necrosis: cardiac Troponin T peak (cTnT peak) and hyperenhanced area at gadolinium-enhanced cardiac magnetic resonance (Gd-CMR), respectively. After vasodilator stimulus, the area of the PD remained significantly unchanged when compared with the baseline value (P = 0.09 vs. baseline). The MCE index correlated at baseline with cTnT peak and Gd-CMR assessments of myocardial necrosis (P < 0.001). Also after ADN infusion, correlations between PD and extent of myocardial necrosis were similar to that assessed at baseline. CONCLUSION: When assessed in the subacute phase of STEMI, the extent of the PD on MCE represents an area of both myocardial and microvascular necrosis.

Optimal reperfusion in ST-elevation myocardial infarction--the role of the coronary microcirculation.

Coronary microcirculation plays a crucial role for the outcomes of patients with STEMI. Although PPCI improves outcomes compared to thrombolysis, a substantial amount of STEMI patients do not achieve optimal myocardial reperfusion. Angiographic methods for assessment of reperfusion like TIMI Flow and MBG are easy to use but new, catheter laboratory based techniques to assess reperfusion have a lot of potential to assess and potentially guide management of patients with STEMI.

Lugar de acceso y tipo de anticoagulante en pacientes con síndrome coronario agudo en clase Killip avanzada o con parada cardiaca extrahospitalaria / Choice of access site and type of anticoagulant in acute coronary syndromes with advanced Killip class or out-of-hospital cardiac arrest

INTRODUCCIÓN Y OBJETIVOS: A menudo se excluye de los ensayos clínicos a los pacientes hemodinámica o eléctricamente vulnerables, por lo que escasea la información sobre el acceso vascular y el tratamiento antitrombótico óptimos. En este trabajo se estudia la evolución de los pacientes vulnerables con síndrome coronario agudo tratados invasivamente según el acceso fuera radial o femoral y el tratamiento fuera con bivalirudina o con heparina no fraccionada (HNF). MÉTODOS: El estudio MATRIX aleatorizó a 8.404 pacientes a acceso radial o femoral y a 7.213 pacientes a bivalirudina o a HNF. Se consideró vulnerables a 934 pacientes (11,1%) debido a clase Killip avanzada (808), parada cardiaca (168) o ambas a la vez (42). El objetivo primario compuesto a 30 días fueron los eventos cardiovasculares y cerebrovasculares mayores (MACE: muerte, infarto de miocardio e ictus) y los eventos clínicos adversos netos (NACE: MACE o hemorragia grave). RESULTADOS: El acceso radial, comparado con el femoral, redujo los MACE y NACE de modo similar en pacientes vulnerables y no vulnerables. El acceso radial se asoció con un claro beneficio relativo en la mortalidad total y cardiovascular y las hemorragias BARC 3 o 5, con mayor beneficio absoluto en los pacientes vulnerables. Los efectos de la bivalirudina comparada con la HNF en MACE y NACE concuerdan entre pacientes vulnerables y no vulnerables. La bivalirudina se asoció con menores mortalidad cardiovascular y por todas las causas en pacientes vulnerables, pero no en los no vulnerables, con test de interacción en el límite. La bivalirudina redujo las hemorragias en ambos grupos de pacientes, con un beneficio absoluto mayor en el caso de los pacientes vulnerables. CONCLUSIONES: En pacientes con síndrome coronario agudo sometidos a tratamiento invasivo, los efectos de los tratamientos aleatorizados fueron concordantes entre los pacientes vulnerables y los no vulnerables, pero la reducción del riesgo absoluto del acceso radial y bivalirudina fue mayor en los vulnerables, con una reducción de 5 a 10 veces en el número de pacientes que es necesario tratar

INTRODUCTION AND OBJECTIVES: Patients who are vulnerable to hemodynamic or electrical disorders (VP) are often excluded from clinical trials and data on the optimal access-site or antithrombotic treatment are limited. We assessed outcomes of transradial vs transfemoral access and bivalirudin vs unfractionated heparin (UFH) in VP with acute coronary syndrome undergoing invasive management. METHODS: The MATRIX trial randomized 8404 patients to radial or femoral access and 7213 patients to bivalirudin or UFH. Among them, 934 (11.1%) were deemed VP due to advanced Killip class (n = 808), cardiac arrest (n = 168), or both (n = 42). The 30-day coprimary outcomes were major adverse cardiovascular and cerebrovascular events (MACE: death, myocardial infarction, or stroke) and net adverse clinical events (NACE: MACE or major bleeding). RESULTS: MACE and NACE were similarly reduced with radial vs femoral access in VP and non-VP. Transradial access was also associated with consistent relative benefits in all-cause and cardiovascular mortality or Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding with greater absolute benefits in VP. The effects of bivalirudin vs UFH on MACE and NACE were consistent in VP and non-VP. Bivalirudin was associated with lower all-cause and cardiovascular mortality in VP but not in non-VP, with borderline interaction testing. Bivalirudin reduced bleeding in both VP and non-VP with a larger absolute benefit in VP. CONCLUSIONS: In acute coronary syndrome patients undergoing invasive management, the effects of randomized treatments were consistent in VP and non-VP, but absolute risk reduction with radial access and bivalirudin were greater in VP, with a 5- to 10-fold lower number needed to treat for benefits

Patent foramen ovale and hypercoagulable state in the pathogenesis of acute thrombotic myocardial infarction.

Patent foramen ovale (PFO) is a known cause of cryptogenic stroke and, when associated with a condition of thrombophilia, its closure has been shown to reduce the recurrence of cerebral embolic events. Here we present a case of a young man, with a history of previous recurrent cerebral ischaemic episodes, that developed an inferior acute myocardial infarction (AMI) with angiographic evidence of thrombotic occlusion of the right coronary artery (RCA). Thrombus aspiration followed by balloon angioplasty was performed and, after 24 h of glycoprotein IIb/IIIa inhibitor infusion, thrombus was no longer evident at coronary angiography. Screening for thrombophilia revealed heterozygosis for prothrombin G20210A polymorphism. At transoesophageal echocardiography (TOE), a large PFO with right-to-left atrial shunt was present. Given the history of multiple thrombotic clinical events and the associated state of thrombophilia, transcatheter PFO closure was successfully performed. At 12 months of follow-up the patient was completely asymptomatic.