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.

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.

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.

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.

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.

Dipyridamole thallium-201 imaging very early after uncomplicated acute myocardial infarction in patients treated with thrombolytic therapy.

The aim of this study was to assess the safety and prognostic value of dipyridamole 201T1 imaging very early after acute myocardial infarction in patients treated with thrombolytic therapy. Fifty-two consecutive patients with an uncomplicated clinical course underwent quantitative planar dipyridamole 201T1 imaging 2 5 days after acute myocardial infarction. The patients were followed for 14 +/- 7 months after discharge. No major complications occurred during the test. Of the 30 patients with redistribution, five (16.6%) developed in-hospital unstable angina as against none of the 22 patients without redistribution. During follow-up, a total of live late cardiac events were observed: two deaths and two cases of unstable angina in the group with reversible defects and one reinfarction in the group with fixed defects. The 1-year actuarial probability of being free of cardiac events was, respectively, 66 +/- 10% and 94 +/- 5% in the patients with and without redistribution (P < 0.01). In conclusion, in patients treated with thrombolysis, dipyridamole-201T1 imaging very early after uncomplicated acute myocardial infarction is a feasible and safe test. Patients with fixed defects appear to be at low risk and may be candidates for early discharge; the presence of redistribution identifies a subgroup of patients who may benefit from further careful clinical evaluation.

[Clinical and instrumental elements predictive of left ventricular insufficiency in acute myocardial infarct: multivariate analysis in patients treated with thrombolytic therapy]. / Elementi clinico-strumentali predittivi di insufficienza ventricolare sinistra in corso di infarto miocardico acuto: analisi multivariata in pazienti trattati con terapia trombolitica.

BACKGROUNDS: During the course of acute myocardial infarction (AMI), the appearance of signs of left ventricular failure (LVF) (cardiogenic shock, acute pulmonary edema, congestive heart failure) is a prognostically negative event which is still relatively frequent even in patients receiving fibrinolytic therapy. The early identification of patients exposed to such a risk would allow adequate diagnostic and therapeutic preventive measures to be taken. AIM: To evaluate, in a population of AMI patients undergoing thrombolysis and without any serious complications at the moment of hospitalisation, which anamnestic, clinical and instrumental data obtained within the first 24 hours best identify those who will subsequently develop full-blown LVF. Secondary aim is to evaluate the role that extension of coronary disease plays in determining the occurrence of LVF. METHODS: The study involved 104 consecutive patients aged < 75 years admitted to hospital for AMI with ST-segment elevation, within 12 hours of the onset of symptoms, in Killip class 1-2 upon entry to the CCU, and treated with thrombolytic therapy. The study design included the collection of anamnestic and clinical data upon admission to the CCU; an enzymatic curve during the first 4 days; the ECG at entry, and 4 and 24 hours after the beginning of fibrinolysis; the chest X-ray, the 2D-echocardiography (2D-echo) and the hemodynamic measurements within the first 24 hours; a coronary angiography on the tenth day (or earlier if clinically necessary). RESULTS: Seventeen patients (16%) presented signs of LVF; 8 (7.6%) with cardiogenic shock, 9 with congestive heart failure: 3 died (3%), all for shock. Univariate analysis correlated LVF with: 1) the indices of the extension of ischemic/necrotic damage: number of derivations with ST elevation (p < 0.04) and Q waves (p < 0.05) at first ECG, maximum peak of myocardial enzyme (p < 0.02), wall motion score index (p < 0.001), percentage extension of asynergy (p < 0.001), presence of remote asynergy (p < 0.001), left ventricular (LV) end-systolic (p < 0.001) and end-diastolic volume (p < 0.01), and LV ejection fraction (EF) (p < 0.001) at 2D-echo; 2) the indices of hemodynamic involvement: Killip class 2 at entry (p < 0.02), pulmonary venous flow diversion at chest X-ray (p < 0.001), systolic (p < 0.05), diastolic (p < 0.01) and mean (p < 0.01) pulmonary pressure, capillary wedge pressure (p < 0.01), and the LV systolic work index (p < 0.05). Multivariate analysis showed that the only independent variable predictive of LVF was the EF at 2D-echo (p < 0.001): the sensitivity and specificity of EF was respectively 36% and 97% at cut-off value of 0.30, and 93% and 69% at cut-off value of 0.45. Multivessel coronary disease was found more frequently in patients who developed LVF (p < 0.05) and was correlated with 2D-echo LV involvement: presence of remote asynergies (p < 0.0001), lower EF (p < 0.01), higher wall motion score index (p < 0.001) and percentage extension of asynergy (p < 0.01). CONCLUSIONS: The incidence of LVF in patients with AMI, without serious complications at onset, is still relatively high (16%) even if they are treated with thrombolysis. Of all evaluated clinical and instrumental indices, multivariate analysis showed that EF at 2D-echo was the only independent variable predictive of LVF. Extension of coronary disease correlated with development of LVF. Moreover, worse LV performance and greater regional contractility involvement at 2D-echo correlated with extension of coronary disease. Consequently, echocardiography would appear to be bed-side, simple, reliable and accurate mean of establishing a prognosis from the moment a patient with AMI is admitted to a CCU.

[The resolution of right atrial thrombosis of recent onset during the intravenous infusion of rtPA: a report of 3 cases with continuous echocardiographic monitoring]. / Risoluzione della trombosi atriale destra di recente insorgenza durante infusione endovenosa di rtPA: descrizione di tre casi con monitoraggio continuo ecocardiografico.

We performed continuous echocardiographic examination during the i.v. administration of rtPA in three patients with recent-onset, mobile right atrial thrombosis, in order to assess both the timing and mode of thrombus resolution. In all these cases, right atrial thrombus disappeared before the scheduled dose (100 mg i.v. within three hours) was completed: 60 mg of rtPA were required in the first patient, and 50 mg in the other two. In the first case, the thrombus divided into numerous smaller fragments chaotically moving in the right chambers before disappearing; in the second, the echo reflectivity of the thrombus gradually diminished and the mass showed multiple echo-lucent cavities before disappearing; in last case, the atrial mass migrated from the right atrium to the right ventricle before disappearing. None of the patients experienced any symptoms at the dissolving of the thrombus; bleeding complications occurred in all three (in one, at the site of previous PTCA; in another, at the site of arterial and venous puncture; in the third the haematoma was localized at the site of a previous orthopedic operation) but only two required blood transfusion. In patients with right atrial thrombosis, continuous echocardiographic examination allows us to identify both the timing and mode of thrombus resolution, and the occurrence of new-onset peripheral pulmonary embolization. This information can help in optimizing the dosage of the drug in patients in whom bleeding complications can be suspected to occur after thrombolytic therapy.

[A prospective study of the evolution of coronary lesions: clinico-morphologic correlations]. / Studio prospettico sulla evolutività delle lesioni coronariche: correlazioni clinico-morfologiche.

In order to evaluate the evolution (progression and regression) of coronary atherosclerosis, 61 patients (8 with stable angina, 9 with unstable angina, 15 with a recent myocardial infarction, 29 with multivessel coronary artery disease and treated with successful one-vessel angioplasty) were enrolled in a prospective study. In the angioplasty group, only untreated vessels were considered for the analysis. All patients underwent coronary angiography before hospital discharge and after one year, in accordance with the study protocol. In 13 patients (21%) a repeat angiography was performed at 6.3 +/- 2.7 months for clinical reasons (myocardial infarction, changing pattern angina, angina recurrence). All patients were asymptomatic or mildly symptomatic on medical therapy between the angiographic studies. Progression (decrease in internal luminal diameter at the site of stenosis greater than or equal to 20%; new onset of lesions, new episodes of total occlusions) was found in 16 out of 216 stenoses (7%) and in 14 out of 61 patients (23%). Regression (increase greater than or equal to 20% in internal luminal diameter; reopening of a previously occluded vessel) was found in 11 out of 227 lesions (5%) and in 7 out 61 patients (11%). At repeat angiography, the increase in severity was found more frequently in stenoses greater than 5 mm in length and with a reduction of greater than or equal to 75% in luminal diameter. Regression was more frequent in the occluded vessel supplying a recently infarcted area. No significant relationship was observed between lesion morphology (concentric, eccentric, with plaque ulceration, thrombi, border irregularities) and progression or regression. Lesions with plaque ulceration (with or without superimposed thrombi) were found only in patients submitted to coronary angiography close to an acute ischemic attack. Morphologic regression (disappearance of ulceration, border irregularities, thrombi) was also observed, without any significant changes occurring in the severity of the underlying stenosis. Progression may occur independently of worsening in the clinical status; on the contrary, regression was only found in patients without new cardiac events. Nevertheless, clinical status does not seem to be closely correlated to progression, regression, or changes in plaque morphology.

Exercise testing and dipyridamole echocardiography test before and 48 h after successful coronary angioplasty: prognostic implications.

The purpose of the present study was to determine the value of exercise testing (ET) and dipyridamole echocardiography test (DET) in the early functional evaluation after a successful coronary angioplasty (PTCA) and in the prediction of angina recurrence. 52 patients underwent ET and DET before and 48 h after a successful PTCA. During a 6-12 month follow-up period they all underwent clinical evaluation. Before PTCA, ET was positive in 49 of 52 patients (94%) and new asynergies were detected by DET in 47 of 52 patients (90%). 48 h after PTCA 23 patients (44%) had positive ET results and 10 had a positive DET response. During the follow-up, 17 patients experienced recurrence of angina. Positive predictive value (PPV) for angina recurrence of ET and DET performed early after the PTCA were, respectively, 57 and 80%. The PPV of ET increased to 88% when electrocardiographic (ECG) positivity was accompanied by angina. Negative predictive values of ET and DET were, respectively, 86% and 79%. Early after PTCA, exercise ECG positivity was not predictive of symptom recurrence while ECG positivity associated with angina revealed a high PPV, similar to that of DET.

Dipyridamole-thallium 201 scintigraphy in the early post-infarction period. (Safety and accuracy in predicting the extent of coronary disease and future recurrence of angina in patients suffering from their first myocardial infarction).

To evaluate the safety and usefulness of myocardial thallium-201 scintigraphy after intravenous dipyridamole during the early post-infarction period, 35 patients under 60 years of age and with recent first transmural uncomplicated myocardial infarction (27 inferior, 8 anterior) were examined between the 5th and 13th day of hospitalization. Although four patients experienced angina and transient ischemic ST depression during the test, there were no serious complications. Patients were followed for a mean period of 11.4 +/- 6.3 months after hospital discharge. None of the patients experienced recurrent infarction and there were no cardiac deaths. In 11 patients there were reversible perfusion defects in areas different from those of myocardial infarction. Of these patients, seven (one with infarct vessel stenosis only and six with multivessel coronary disease) developed angina during the follow-up: five underwent coronary surgery because of severe angina refractory to full medical therapy. Out of the 24 patients without reversible perfusion defects, only two (with multivessel coronary disease) showed typical angina symptoms. The presence of redistribution on thallium scans was significantly more frequent in patients who developed a recurrence of angina over a period of 11.4 +/- 6.3 months of follow-up (P less than 0.0005). Thus dipyridamole-thallium 201 scintigraphy is a safe, non-invasive stress test which may be used early following uncomplicated myocardial infarction in order to identify patients at risk for the recurrence of angina.

The effects on exercise tolerance of a new transdermal therapeutic system containing nitroglycerine, in patients with stable angina pectoris.

In two randomized, double blind, placebo-controlled, within patient, studies, the effects of 4 doses of a new transdermal therapeutic system containing nitroglycerin (TTS-NTG) were studied in a total of 15 patients with stable exercise-induced angina pectoris. A single 24-hour application of TTS-NTG 10 cm2, TTS-NTG 20 cm2 and TTS placebo (1st study: 6 patients) and of TTS-NTG 40 cm2, TTS-NTG 80 cm2 and TTS placebo (2nd study: 9 patients) was applied on 3 different days, and a symptom-limited cycloergometric exercise test was performed 3, 12 (only in the 2nd study) and 24 hours after the application of each treatment. In comparison with placebo, the doses tested in the 1st study induced, at the 3rd hour post-dosing, a decrease in standing systolic blood pressure and an improvement in exercise tolerance which, however, were not statistically significant while the effects at the 24th hour were similar to those of placebo. In the 2nd study, in comparison with placebo, both TTS-NTG doses induced, 3 hours post-dosing, a significant decrease in both lying and standing systolic (P less than 0.01) blood pressure at rest, and a significant (P less than 0.01) improvement in exercise tolerance throughout the 24 hours of application. It is concluded that, in patients with exercise-induced angina pectoris due to coronary artery disease, a single application of TTS-NTG 40 cm2 or 80 cm2 results in a 24-hour increase in exercise tolerance.

[Assessment of coronary stenosis by myocardial scintigraphy with thallium-201 after dipyridamol infusion]. / Evidenziazione di stenosi coronariche mediante scintigrafia miocardica con tallio-201 dopo infusione di dipiridamolo.

After a 4 minute i.v. dipyridamole infusion (0.14 mg/Kg/min) serial Thallium-201 scans were obtained in 45 patients, without myocardial necrosis, undergoing coronarography. Twelve patients had effort angina, 6 rest angina, 14 effort associated with rest angina, 13 had atypical chest pain. Thirty-two patients had a 50% or greater stenosis of 1 or more coronary artery (8 had three vessels disease, 7 two vessels, 17 one vessel); 13 patients had no significant coronary stenosis ("control group"). The test induced electrocardiographic signs of ischemia in 18 patients, all with significant coronary stenosis, 15 of them experienced angina too. Sensitivity of Thallium-201 for detecting coronary artery stenosis was 94% (30 of 32) and specificity was 85% (11 of 13). In the group of the 17 patients with one vessel disease we obtained a sensitivity and specificity of 100% (17 of 17). We conclude that Thallium-201 myocardial imaging after pharmacologic vasodilatation with dipyridamole is a highly sensitive and specific test for detecting coronary artery stenoses without necessary overt ischemia. In fact dipyridamole, as consequence of its important coronary vasodilatation, produces differences in myocardial perfusion with relative perfusion defects detectable with Thallium-201 imaging.