Neurological recovery after out-of-hospital cardiac arrest: hospital admission predictors and one-year survival in an urban cardiac network experience.

AIM: The aim of the study was to detect early predictors of neurological recovery and evaluate one year survival related to neurological status at discharge in patients (pts) admitted after out of hospital cardiac arrest (OHCA). METHODS: Sixty-three consecutive pts with OHCA from any cardiac cause, admitted to our cardiac intensive care unit, were classified according to survival and cerebral performance category (CPC) scale from 1 to 4 at hospital discharge. Pre-hospital and emergency room (ER) variables were analyzed to identify early predictors of neurological recovery as defined CPC=1-2. RESULTS: Overall in-hospital survival was 60%. Sixty-eight and 32% of survivors were classified as CPC 1-2 and CPC 3-4 respectively. During one year follow-up 96% of patients classified as CPC 1-2 survived and 100% of CPC 3-4 died. Emergency crew witnessing, performance of cardio pulmonary resuscitation (CPR) by witnesses, the call for chest pain, no history of heart disease and a Glasgow coma scale (GCS) of ≥9 on arrival to the ER, were more frequent in patients classified as CPC 1-2 and times from "OHCA to return of spontaneous circulation (ROSC)", from "emergency medical system (EMS) arrival to ROSC" and "first DC shock to ROSC" were also significantly shorter in these patients. The time of first DC shock to ROSC in pts who presented with rhythm in ventricular fibrillation and the time from OHCA to ROSC in pts with witnessed OHCA were an independent predictors of neurological recovery. CONCLUSION: Forty-one percent of pts admitted to our tertiary centre after OHCA were discharged with CPC 1-2 and at one year follow-up 96% of these were alive, while all pts classified as CPC 3-4 died. Easily documented information such as the time from OHCA to ROSC and the time of first shock to ROSC are early independent predictors of neurological recovery.

Mid-term prognostic value of coronary artery disease in patients undergoing transcatheter aortic valve implantation: a meta-analysis of adjusted observational results.

AIMS: Coronary artery disease (CAD) negatively affects prognosis in patients undergoing surgical aortic valve replacement, being currently evaluated in the most common used risk score. Our meta-analysis aims to clarify the prognostic role of CAD on mid-term survival in patients undergoing TAVI. METHODS AND RESULTS: Studies reporting multivariate predictors of adverse outcomes in patients undergoing TAVI were systematically searched for and pooled, when appropriate, using a random-effect method. 960 citations were first screened and finally 7 studies (2472 patients) were included. Diagnosis of CAD was reported in 52%(42-65) of patients and 1169 Edwards SAPIEN and 1303 CoreValve prostheses were implanted. After a median follow up of 452 days (357-585) 24% of patients (19-33) died, and 23 (14-32) for cardiovascular death. At pooled analysis of multivariate approach, diagnosis of coronary artery disease did not increase risk of death (OR 1.0, 95% CI, confidence interval, 0.67-1.50 I(2) 0%). CONCLUSION: CAD does not affect mid-term TAVI outcome: this finding should be weighted to accurately evaluate risk and strategies for patients with severe aortic stenosis.

Predictors of mortality in patients undergoing percutaneous aortic valve implantation.

AIM: Transcatheter aortic valve implantation (TAVI) became an attractive alternative to surgery for patients with severe aortic stenosis and high operative risk. The first multicenter randomized trial, conducted in such high risk cohort, showed 20% reduction in mortality in the group treated with TAVI compared to those treated with medical therapy (30.7% vs. 50.7% P=0.001) and a non-inferiority of TAVI compared to traditional valve surgical replacement for all-cause mortality at 1 year with, similar improvement of symptoms and physical performance. However, mortality rate of TAVI remains high (20-30% at one year). The purpose of this prospective single center study was to identify predictors of mortality and adverse events in patients undergoing TAVI in order to be able to select the ones who benefit most from the procedure. METHODS: Between June 2009 and June of 2011, 118 patients with severe aortic stenosis treated with TAVI at IRCCS Humanitas Clinical Institute were included in a prospective registry. Pre procedural clinical and ecocardiographic evaluations, surgical risk estimation, and procedural complications, defined by VASC criteria, were recorded. Clinical and echocardiographic evaluations were performed at 1, 6 and 12 months after the implants. To investigate the predictors of mortality, clinical and anatomical characteristics of alive patients were compared with those of death ones at one month and one year follow-up. RESULTS: The procedural success occurred in 92.4% of procedures; vascular complications (33%), bleeding complications (22%), postimplant paravalvolar grade ≥2 AR (20.4%) a new permanent pacemaker implant (19.7%), were the most common complications. Survival for the whole cohort at 30 days was 6.8%, survival at one year was 82.2%. In the logistic regression test, one month mortality was significantly adversely affected by the renal functional status (odd ratio 0.9356), by a previous history of coronary artery bypass grafting (odd ratio 39) and by the mean aortic annular diameter (odd ratio 0.512) (P=0.0005). One year mortality was influenced by high EuroSCORE (odd ratio 1.0399) and the presence of hemodynamically significant prosthetic regurgitation (odd ratio 3.8438). CONCLUSION: TAVI procedure, in high risk patients with critical aortic stenosis, can be accomplished with low procedural mortality. The worst outcome affects particularly patients with renal insufficiency and previous coronary bypass. However, the long-term mortality remains high due to the poor baseline conditions, mainly related to co-morbidity and to the presence of residual post-procedural aortic insufficiency.

Multivessel disease in primary percutaneous coronary intervention.

Primary percutaneous coronary intervention (PCI) is currently the preferred revascularization strategy in acute trasmural myocardial infarction (AMI). In this setting, about one half of patients will be diagnosed with concomitant multivessel (MV) coronary artery disease, associated with a multitude of negative prognostic factors but also still an independent predictor of adverse cardiac events and increased long-term mortality. Since additional "angiographic" lesions found at primary PCI are not directly responsile for the acute presentation, their treatment represents a difficult decision-making problem in cardiology. The article summarizes available clinical data on treatment in this setting and also review our current understanding of short-term progression of atherosclerosis after AMI.

Percutaneous aortic valve in severe valvular regurgitation caused by infective endocarditis.

Recently, the feasibility and safety of percutaneous aortic valve replacement (PAVR) have been reported in the treatment of degenerative aortic valve stenosis in patients at high-risk for surgical aortic valve replacement (AVR). However, so far this therapy has been limited to patients with severe stenosis of the native valve. We report the case of an 84 year old patient with severe aortic regurgitation caused by infective endocarditis who was successfully treated by implantation of a CoreValve (CoreValve Inc, Irvine. Calif) prosthesis with a totally percutaneous approach.

Variable effect of P2Y12 inhibition on platelet thrombus volume in flowing blood.

BACKGROUND AND OBJECTIVES: Patients treated with percutaneous coronary intervention receive aspirin and P2Y12 ADP receptor inhibitors to reduce thrombotic complications. The choice of methodology for monitoring the effects of treatment and assessing its efficacy is still a topic of debate. We evaluated how decreased P2Y12 function influences platelet aggregate (thrombus) size measured ex vivo. METHODS AND RESULTS: We used confocal videomicroscopy to measure in real time the volume of platelet thrombi forming upon blood perfusion over fibrillar collagen type I at a wall shear rate of 1500 s(-1). The average volume was significantly smaller in 31 patients receiving aspirin and clopidogrel (19) or ticlopidine (12) than in 21 controls, but individual values were above the lower limit of the normal distribution, albeit mostly within the lower quartile, in 61.3% of cases. Disaggregation of platelet thrombi at later perfusion times occurred frequently in the patients. Vasodilator-stimulated phosphoprotein phosphorylation, reflecting P2Y12 inhibition, was also decreased in the patient group, and only 22.6% of individual values were above the lower normal limit. We found no correlation between volume of thrombus formed on collagen fibrils and level of P2Y12 inhibition, suggesting that additional and individually variable factors can influence the inhibitory effect of treatment on platelet function. CONCLUSIONS: Measurements of platelet thrombus formation in flowing blood reflects the consequences of antiplatelet therapy in a manner that is not proportional to P2Y12 inhibition. Combining the results of the two assays may improve the assessment of thrombotic risk.

A case of platypnea-orthodeoxia syndrome caused by the interaction between the presence of corrected transposition of the great arteries and patent foramen ovale.

A 42-year-old was admitted to our institution for recurrent episodic dyspnea on exertion. The patient had also a history of recurrent transient ischemic attacks. Careful history taking revealed that she developed dyspnea in an upright position, whereas the symptoms were relieved in a supine position (platypnea). The patient was given the diagnosis of platypnea-orthodeoxia syndrome. Transthoracic echocardiography showed cardiac situs solitus levocardia with great artery transposition with intact interventricular septum, patent foramen ovale (PFO) and moderate right atrial dilatation. Agitated saline contrast injection demonstrated the presence of spontaneous right-to-left shunt. The patient underwent transcatheter closure of PFO. After percutaneous closure of PFO patient became asymptomatic and hypoxemia induced by orthostatic conditions did not appear again. A transthoracic echocardiography performed after two months, showed the complete closure of PFO, without residual shunt.

Anatomical patterns of patent foramen ovale (PFO): do they matter for percutaneous closure?

AIM: The aim of this study was to describe and classify the various anatomical pattern of patent foramen ovale (PFO) with transesophageal echocardiography (TEE) and to relate such classification to the selection of PFO closure devices. METHODS: This study enrolled 216 PFO patients (118 females) mostly with previous cryptogenic stroke or transitory ischemic attack (TIA) who underwent percutaneous closure of PFO with deep sedation under TEE control. Anatomical patterns were classified as follows: simple: PFO characterised by central/superior eccentric shunt or with a valve mechanism (45%); reduse: widely redundant septum primum (22%); ASA: atrial septal aneurysm (11%); EASA: entire atrial septal aneurysm (1.4%); CRIB: cribriform septum primum (9%); tunnel: tunnel between septum primum and secundum >10 mm (11%). Degree of right-to-left shunt, either at basal condition or at Valsalva manoeuvre, was classified as: 1=mild (45%); 2=moderate (42%); 3=severe (13%). Additional right-atrium anatomical features are also described. RESULTS: Procedure was successful in 100% of the cases. At follow-up recurrent TIA occurred in two patients. Residual shunts were present in 4.9% of the patients after Valsalva manoeuvre. Palpitations were reported in 4%. CONCLUSIONS: Closing the PFO choosing the device following strict anatomical criteria based on TEE assessment allowed excellent immediate and late results minimizing residual shunts.

Admission glycemia and markers of inflammation are independent outcome predictors in primary PCI in non-diabetic patients.

AIM: To assess the prognostic value of admission plasma glucose (APG) respect to clinical variables and inflammatory markers in a selected population of non-diabetic patients with ST elevation myocardial infarction (STEMI) treated with primary angioplasty (primary coronary intervention, PCI). METHODS: A total of 188 consecutive non-diabetic STEMI patients undergoing primary PCI were divided into four quartiles based on APG (<117, 117-140, 141-170, >170 mg/dL). Combined end-point of major adverse cardiac events (MACE) was defined as death, acute heart failure, re-infarction, unstable angina or inducible ischemia. RESULTS: Event-free survival from MACE was significantly (P<0.001) correlated with APG quartiles and decrease from the lowest to the highest: 6 months event-free survival was 89.3%, 77.4%, 59.1%, 42.5%. Patients with higher APG were characterized by a significantly higher Killip class (P<0.001), higher serum creatinine (P<0.05) on admission, and a lower rate of thrombolysis in myocardial infarction (TIMI) 3 flow after PCI (P<0.05). Multivariate analysis showed APG>170 mg/dL (hazard ratio [HR] 2.39, 95% confidence interval [CI] 1.24 to 4.65, P<0.01), admission high-sensitivity C-reactive protein level (HR 1.19, 95% CI 1.07 to 1.31, P<0.001), white blood cells count (HR 1.07, 95% CI 1.00 to 1.14, P<0.04) and heart rate (HR 1.02, 95% CI 1.00 to 1.04, P<0.02) to be independent predictors of MACE. CONCLUSION: Admission glycemia and inflammatory markers are independent predictors of MACE in the mid-term follow-up in non-diabetic STEMI treated with primary PCI. Further investigations are needed to study the pathogenesis of stress hyperglycaemia, interactions with mechanisms of inflammation and whether early and aggressive treatment with insulin may influence outcome of primary PCI.

DES implantation in saphenous vein and left internal mammary grafts.

Forty percent of patients treated with CABG need further revascularizations after 10 years mainly due to saphenous--more than arterial--graft disease. In this issue, the Authors make a critical review of current available literature on the treatment of saphenous and arterial graft disease, a subset of lesions for which a clear consensus for DES use is still lacking. The Authors examine both the positive and negative aspects of DES use in this setting. Percutaneous revascularizations with DES are feasible and safe. The antiproliferative properties of DES seem to be effective even in the treatment of bypass disease, in particular in saphenous grafts. The clinical efficacy of a treatment with DES is expressed mainly in the reduction of in-stent restenosis and, therefore, in the rates of target lesion revascularization (TLR). Moreover, the use of DES is not associated to higher rates of stent thrombosis and, in case of reintervention, recurrence rates seem to be limited. However, the benefit provided by DES in prevention of restenosis may be limited by the progression of the disease in other segments than those treated with stents. Percutaneous treatment of arterial bypass with DES is feasible and safe. Most of available data on DES are on anastomotic disease (data on bypass ostium and shaft are too scarce to draw any conclusion). In this case, where the use of stents is imperative, there is no evidence of advantages gained by the use of DES over BMS in terms of new revascularizations. Some unanswered questions on DES use in this setting still remain. For this reason new randomized trials are required to definitively give a reliable answer on DES efficacy in this subset of lesions.

Endovascular intervention in the treatment of congenital heart disease in adults.

Over the last years, endovascular intervention have become an important part of treatment in patients with congenital heart disease particularly for residual defects after surgery done in infancy. These transcatheter procedures can be described as dilatation of stenotic sites (angioplasty, endovascular stenting and valvuloplasty) or as a closure of anomalous openings (device closure defects and vascular embolisation). Balloon valvuloplasty, without or with stent, is the procedure of choice in adults with pulmonary valve stenosis, pulmonary arteries stenosis, bicuspid aortic valve stenosis without calcification, aortic re-coarctation. Treatment of native aortic coarctation is still under debate. Devices for closing atrial and ventricular septal defects or patent ductus arteriosus have been developed and are now widely used. Transcatheter, plug or coil occlusion is nowadays the goal treatment in a wide range of arterial and venous vascular connections. This review describes the current role of each major catheter-directed therapy in the treatment of congenital heart disease in adults.

Drug-eluting stents: towards new endpoints.

Drug-eluting stents (DES) have significantly reduced the rates of in-stent restenosis (ISR). As previously observed with bare-metal stents (BMS), either patient's clinical characteristics and lesion morphology may influence the risk of recurrence even with DES. In this review we will focus on the most recent available data on clinical settings where DES efficacy on long-term outcomes are largely unknown. In particular, we report on very complex lesions (bifurcations, small vessels, chronic total occlusions, in-stent restenosis) myocardial infarction, multivessel disease, treatment of bypass graft and of unprotected left main disease. Several issues are still open on DES routinary use for these indications, mainly as far as stent thrombosis is concerned. Recent pathological studies show that DES are characterized by chronic inflammatory infiltrates and delayed endothelialization. Therefore, this effect could translate in a ''vulnerable period'' for thromboses longer than with BMS. Even though large meta-analysis have excluded higher rates of stent thrombosis with DES rather than with BMS, few cases of unusual very late stent thrombosis have been described, pointing out that this problem seems to be still unsolved. Although DES provide better angiographic outcomes in each clinical setting, further randomized studies are running to assess their safety and efficacy on currently off-label indications.

Drug eluting stents in acute myocardial infarction.

Routine stent-implantation in primary coronary intervention (PCI) for acute myocardial infarction (AMI) has been shown to have a better clinical outcome than balloon angioplasty mainly because of reduction in restenosis rate and reocclusion. Drug eluting stents (DES) have recently been proven to further reduce restenosis and revascularization rate in comparison to bare metal stent (BMS) in elective procedures. Delayed endothelialization of these stents raises concern about a possible increase of thrombotic complications in the setting of AMI. Randomized studies with DES in the treatment of elective patients have shown at 9-12 months follow-up a thrombosis rate of 0-2% comparable to the one of BMS. Sirolimus eluting stents (SES) in AMI have been used in small series of consecutive pts not randomized or in registries with very high successful rate and a stent thrombosis varying between 0 and 4.7%. Paclitaxel eluting stent (PES) have also shown in small series a good immediate performance with a thrombosis rate between 0 and 4.8%. Predictors of acute and subacute stent thrombosis are the same than for BMS: residual dissection, long or overlapping stents, biforcation lesions and discontinuation of antiplatelets treatment. Providing effective mechanical reperfusion with similar results to the current therapeutic standard and decreasing the incidence of late complications, DES appear as an attractive approach for patients admitted with AMI.

Clinical utility of IVUS in 2005.

Intravascular ultrasounds (IVUS) allowed an innovative visualization of coronary artery disease. This technique developed first in the research field and, then, it was introduced in clinical practice as a supplement to coronary angiography in diagnosis of the severity of ischemic heart disease. The characteristic tomographic view of coronary plaque supplied by IVUS allowed to overcome the limitations of coronary angiography and to add important supplemental information in understanding the mechanism of action of several interventional devices. In this review we analyze current indications of use of IVUS in clinical practice and the future applications of IVUS-related techniques for the diagnosis of coronary artery disease.

Phenotype commitment in vascular smooth muscle cells derived from coronary atherosclerotic plaques: differential gene expression of endothelial nitric oxide synthase.

Unstable angina and myocardial infarction are the clinical manifestations of the abrupt thrombotic occlusion of an epicardial coronary artery as a result of spontaneous atherosclerotic plaque rupture or fissuring, and the exposure of highly thrombogenic material to blood. It has been demonstrated that the proliferation of vascular smooth muscle cells (VSMCs) and impaired bioavailabilty of nitric oxide (NO) are among the most important mechanisms involved in the progression of atherosclerosis. It has also been suggested that a NO imbalance in coronary arteries may be involved in myocardial ischemia as a result of vasomotor dysfunction triggering plaque rupture and the thrombotic response. We used 5' nuclease assays (TaqMan PCRs) to study gene expression in coronary plaques collected by means of therapeutic directional coronary atherectomy from 15 patients with stable angina (SA) and 15 with acute coronary syndromes (ACS) without ST elevation. Total RNA was extracted from the 30 plaques and the cDNA was amplified in order to determine endothelial nitric oxide synthase (eNOS) gene expression. Analysis of the results showed that the expression of eNOS was significantly higher (p<0.001) in the plaques from the ACS patients. Furthermore, isolated VSMCs from ACS and SA plaques confirmed the above pattern even after 25 plating passages. In situ RT-PCR was also carried out to co-localize the eNOS messengers and the VSMC phenotype. The eNOS gene was more expressed in ACS plaques and VSMCs cultured from them, thus indicating that: a) the expression of the most important differentiation markers is retained under in vitro conditions; and b) NO may play a pivotal role in coronary artery disease. Our findings suggest a new cell system model for studying the pathophysiology of unstable angina and myocardial infarction.

Procedural and long-term results of sirolimus-eluting stent in patients at high risk for restenosis.

AIM: In-stent restenosis still affects 10-50% of long-term outcome after percutaneous coronary intervention (PCI). Large clinical trials have shown that sirolimus-eluting stents (SES) have reduced restenosis rate to 0-9% in lesions at low-moderate risk. The aim of this study was to evaluate long-term clinical and angiographic outcome of SES in a real world population, at very high risk of restenosis. METHODS: Ninety lesions at high risk of restenosis (lesion length >20 mm, target vessel diameter <2.5 mm, in-stent diffuse restenosis, total occlusions and complex lesions on bypass grafts and bifurcations) were treated in 75 patients. A follow-up was scheduled at 6 months. RESULTS: Restenosis rate was 16.6% with a focal pattern of presentation in most cases. Subacute in-stent thrombosis occurred in 2.2%. Resteno-sis occurred mainly in small vessels, diabetic patients and in vessels previously treated with brachytherapy. CONCLUSION: The treatment of lesions at high risk of restenosis with SES is safe with a low restenosis rate at follow-up. An aggressive and prolonged antiplatelet regimen is mandatory because of high subacute in-stent thrombosis rates.

Partial anomalous left pulmonary venous return.

We report the case of a 52-year-old woman with partial left anomalous pulmonary venous return who was successfully treated surgically without the use of extracorporeal circulation by diverting the anomalous left vertical vein into the left atrium through a postero-lateral thoracotomy.

[Drug-eluting stents do they make the difference? ]. / Gli stent ricoperti di farmaci fanno davvero la differenza?

The main limitation to further expansion of PTCI (percutaneous transluminal coronary intervention) is restenosis that occurs in 30% of the patients within 6-months after the procedure. Coronary stenting decreases the percent of restenosis due to arterial remodeling after PTCI but proliferation of smooth muscle cells due to vascular injury still remains. A mechanical approach the only treatment up to now (further balloon expansion, plaque removal with rotablator or directional atherectomy) failed. Because the restenotic process is due to a complex series of biological events which start with platelet aggregation, grow-factors and cytochine release, the use of antiflammatory, antithrombotic and antiproliferative drugs were attempted. Cortisone and heparin showed low benefits in clinical trial. New drugs (rapamycin, taxol, actinomycin D, tacrolimus, estradiol, dexamethazone) with antiproliferative and antiflammatory activities are under evaluation. They act as inhibitors of the cell migration and of the cell cicle progression with different specific molecular mechanisms. The first pilot study performed in 45 patients with sirolimus-eluting stents has shown a sustained suppression (25% in the fast release group and 23% in the slow release group) of neointimal formation at 12 months after procedure with absence of restenosis. The Ravel study, a randomized trial, has enrolled 238 patients treated with sirolimus coated stent vs a control group: the results confirm the previous data with a complete suppression of intimal hyperproliferation and restenosis at six months follow-up. The first 400 patients treated in the Sirius trial a similar study which will randomize 1100 pts show a low, but not a complete inhibition of the restenotic process probably due to a more complexity of the lesions treated in comparison to Ravel trial (9.2% of restenosis). Another very promising drug is taxol (paclitaxel). It is an antiproliferative and antinflammatory molecule tested in a series of clinical trials called Taxus. The still unpublished data of TAXUS I and TAXUS II randomized trial show extremely low restenosis rate. Other drugs (actinomycin D, estradiol, tacrolimus, dexamethazone) show to have a potential effect on restenosis and neointimal proliferation and are under investigation. Is very important to maintain lessons learned from the past. The design, the type, the smooth surface of the stent still remains very important as it is a good expansion and a full coverage of the lesions with a "good stent" in the attempt to reduce restenosis. Drug-eluting stents will add further improvement.