Mutation Analysis of PRKAR1A Gene in a Patient with Atrial Myxoma.

BACKGROUND: Intracardiac myxomas are frequent benign tumors of the heart and typically localize in the left atri- um and interatrial septum. When myxomas generate at other sites, they are designated as atypical. Mutations in the PRKAR1A gene (a tumor suppressor gene that encodes a protein kinase A [PKA] regulatory 1-alpha subunit) have been identified in both syndromic and non-syndromic cardiac atypical myxomas. METHODS: We report the case of a 33-year old woman suffering from night fever, weight loss, asthenia, and progressive dyspnea. RESULTS: The blood laboratory tests revealed microcytic anemia, leukocytosis, thrombocytosis, increased serum levels of C-reactive protein level, and negative blood cultures. Physical examination also demonstrated a 2/6 systolic murmur. Transthoracic and trans-esophageal echocardiography showed a voluminous, mobile mass in the left atrium with a secondary dynamic obstruction of the left cardiac chamber and a significant functional mitral stenosis. A myxoma was supposed and the patient underwent surgery. Histologically, the lesion was identified as myxomatous tumor with gelatinous pattern. No germline mutations of the PRKAR1A gene were detected. The postoperative course did not present any complications, and the patient was discharged on the sixth postoperative day in good clinical condition. Accordingly, there was an improvement in the laboratory tests' results and a resolution of symptoms. CONCLUSIONS: The patient presented an atrial giant gelatinous myxoma with peculiarity of fever of unknown origin, without PRKAR1A gene germline mutations.

The Diagnosis of Acute Myocarditis in Emergency (DAME) score: improving diagnostics within the emergency department.

PURPOSE: . The final diagnosis of myocarditis is challenging. The aim of our study was to provide the D.A.M.E. (Diagnosis of Acute Myocarditis in Emergency) Score for the fast identification of patients suffering from myocarditis at Emergency Department (ED). METHODS: . This was a multicenter, retrospective study involving three centers. All medical records from January 2010 to December 2014 reporting a final discharge diagnosis of myocarditis were considered. One hundred-four patients (mean age: 40.2±16.5 years) were enrolled. Clinical, biochemical and instrumental data were gathered. Data were analysed by means of logistic regression model and factorial analysis. A validation cohort from a fourth center was enrolled. RESULTS: . The final determinants of the DAME score were six: fever, chest pain, erythrocyte sedimentation rate (ESR) > 20 mm/h, C-reactive protein (hs-CRP) >3 mg/L, troponin serum levels >3 ng/L, and left ventricle ejection fraction < 50%. All of them received a specified score ranging from 0 to 4. A score > 4 was related to 75% probability of myocarditis; a final score ranging between 1 and 4 was related to 57% probability of myocarditis. ROC curve on the validation cohort (289 patients, 27 with myocarditis) demonstrated the best cut-off to be 7: AUC 0.958 (p< 0.001), sensibility: 100%, specificity: 85.11%, PPV: 40.9%, NPV: 100% (LR+: 6.72; LR-: 0.00). Logistic regression analysis revealed Odds Ratio equal to 2.83 (95% CI 1.90 - 4.20, p < 0.0001). CONCLUSIONS: . DAME score can offer a reliable tool in ED setting for the evaluation of patients suffering from suspected myocarditis.

Frequency, predictors and prognostic impact of implantable cardioverter defibrillator shocks in a primary prevention population with heart failure and reduced ejection fraction.

AIMS: The role of the implantable cardioverter defibrillator (ICD) in primary prevention real-world population is debated. We sought to evaluate the incidence, predictors and prognostic impact of ICD shocks in consecutive heart failure patients implanted for primary prevention at our tertiary institution. METHODS AND RESULTS: We retrospectively selected a sample of 497 patients (mean age 64.8 years, 82.1% men, average left ventricular ejection fraction, LVEF, 27.1%). At long-term follow-up (median time 70.4 months), total mortality was 40.8%, and 16.5% of patients had received at least one appropriate shock (3.12%/year). Inappropriate shock [odds ratio (OR) 1.93, 95% confidence interval (95% CI) 1.08-3.47; P = 0.027] and length of follow-up (1 year, OR 1.01, 95% CI 1.00-1.01; P = 0.0031) were associated with the occurrence of appropriate shock, whereas atrial fibrillation (OR 2.65, 95% CI 1.55-4.51, P < 0.001), length of follow-up (1-year OR 1.01, 95% CI 1.00-1.01, P < 0.001) and appropriate shock (OR 1.93, 95% CI 1.08-3.47, P = 0.027) were associated with the occurrence of inappropriate shock. Neither appropriate nor inappropriate shock independently increased mortality risk, whereas older age (hazard ratio 1.05; 95% CI 1.04-1.07; P < 0.001), atrial fibrillation (hazard ratio 2.25; 95% CI 1.67-3.02; P < 0.001) and lower LVEF (hazard ratio 0.97; 95% CI 0.94-0.99; P = 0.004) did. CONCLUSION: Incidence of shocks in real-world primary prevention ICD recipients might be lower than expected, and the association between ICD shocks and prolongation of survival is not as clear-cut as might be perceived. Further investigations from larger real-world samples are warranted.

[Appropriateness criteria for the management of lipid-lowering therapy with alirocumab in high cardiovascular risk patients. The opinion of a multidisciplinary group of Italian experts]. / Criteri di appropriatezza nella gestione della terapia ipocolesterolemizzante con alirocumab nel paziente ad alto rischio cardiovascolare. L'opinione di un gruppo multidisciplinare di esperti italiani.

High levels of LDL cholesterol (LDL-C) represent a causal factor for cardiovascular diseases on an atherosclerotic basis, with a direct correlation between these and mortality or cardiovascular events, such that the reduction of both is associated proportionally and linearly with the reduction of LDL-C.Statins and ezetimibe are used for LDL-C lowering but may not be sufficient to achieve the targets defined by the ESC/EAS guidelines, which recommend use of PCSK9 inhibitors for further LDL-C reduction in patients not at goal.This project submitted 86 clinical scenarios to a group of experts, cardiologists, internists and lipidologists, collecting their opinion on the appropriateness of different behaviors and decisions. We used the RAND/UCLA method of assessing the appropriateness of clinical interventions, validated to combine the best scientific evidence available with expert judgment. To this end, the benefit-risk ratio was evaluated in the proposed clinical scenarios. Each indication was classified as "appropriate", "uncertain" or "inappropriate" based on the average score given by the participants.This document presents the results of a consensus process that led to the development of recommendations for the management of clinical scenarios on the treatment of patients with dyslipidemia, which cannot always be solved with scientific evidence alone.

Causes and impact on survival of underuse of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in heart failure.

Guidelines recommend angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) for treatment of heart failure with reduced ejection fraction (HFrEF), but these medications are underprescribed in clinical practice. We reviewed the records of HF patients receiving a first visit in a tertiary outpatient clinic from January 1st 2004 to May 31st 2015, and selected those with a serum creatinine concentration (sCr) available at both the first and last visit and < 3.5 mg/dL at baseline, and a left ventricular ejection fraction (LVEF) < 50% at the first visit. Of 570 eligible patients, 92 (16.1%) never received ACEi/ARB. Compared to ACEi/ARB users, never-users were older, more often women, had higher sCr and lower systolic blood pressure, were less commonly on beta-blocker, and had more frequently anemia. Current or prior cancer also tended to be more common in ACEi/ARB never-users. ACEi/ARB users displayed an improvement in LVEF by ≥ 10% of the baseline value more often than ACEi/ARB never-users (33.7% vs. 20.7%, respectively, P = 0.01), whereas no difference in percent variation of sCr levels was found between the two groups (8.2% vs. 3.1%, respectively; P = 0.13). Over a median follow-up of 56 months (range 1-137 months), 215 (37.7%) patients died. After multiple adjustments, ACEi/ARB never-use was associated with an almost twofold increased risk of all-cause mortality (HR 1.97, 95%CI 1.39-2.80). ACEi/ARB underuse in HFrEF is a standing issue with dramatic prognostic consequences. Efforts are needed to eliminate perceived contraindications to these drugs and ensure their implementation in real-life cardiology.

Trends in management and outcome of patients with non-ST elevation acute coronary syndromes and peripheral arterial disease.

OBJECTIVE: Patients with non ST-segment elevation acute coronary syndromes (NSTE-ACS) and peripheral arterial disease (PAD) present a worse prognosis compared to those without PAD. We sought to describe contemporary trends of in-hospital management and outcome of patients admitted for NSTE-ACS with associated PAD. METHODS: We analyzed data from 6 Italian nationwide registries, conducted between 2001 and 2014, including consecutive NSTE-ACS patients. RESULTS: Out of 15,867 patients with NSTE-ACS enrolled in the 6 registries, 2226 (14.0%) had a history of PAD. As compared to non-PAD patients, those with PAD had significantly more risk factors and comorbidities (all p < 0.0001) that increased over time. Patients with PAD underwent less frequently coronary angiography (72.0% vs 79.2%, p < 0.0001) and percutaneous coronary intervention (PCI, 42.9% vs 51.8%, p < 0.0001), compared to patients without PAD. Over the years, a progressive and similar increase occurred in the rates of invasive procedures both in patients with and without PAD (both p for trend <0.0001). The crude in-hospital mortality rate did not significantly change over time (p for trend = 0.83). However, as compared to 2001, the risk of death was significantly lower in all other studies performed at different times, after adjustment for multiple comorbidities.. At multivariable analysis, PAD on admission was an independent predictor of in-hospital mortality [odds ratio (OR): 1.75; 95% confidence intervals (CI): 1.35-2.27; p < 0.0001]. CONCLUSIONS: Over the 14 years of observation, patients with PAD and NSTE-ACS exhibited worsening baseline characteristics and a progressive increase in invasive procedures. Whereas crude in-hospital mortality did not change over time, we observed a significant reduction in comorbidity-adjusted mortality, as compared to 2001.

Discrete subaortic stenosis in elderly women.

Discrete subaortic stenosis (DSS) is likely an acquired cardiac disorder which requires anatomic precursors and a genetic background. DSS occurs usually within the first decade, provoking rapidly progressive left ventricular outflow tract obstruction and secondary aortic regurgitation. DSS has been considered for a long time exclusively a disease of infancy and childhood and few reports and small series have described DSS in adulthood and only two cases are reported in elderly. Our case describes a discrete subaortic membranous ridge in an elderly woman with recent onset of dyspnea.

Recent trends in management and outcome of patients with acute coronary syndromes and atrial fibrillation.

AIMS: To describe the clinical characteristics, contemporary trends of in-hospital management and outcome of patients admitted for an acute coronary syndrome (ACS) with associated atrial fibrillation (AF). METHODS: We analyzed data from four Italian nationwide prospective registries, conducted between 2001 and 2014, including consecutive ACS patients. RESULTS: Out of 16,803 ACS patients, 1019 (6.1%) presented with concomitant AF: 668 with non-ST elevation (NSTE)-ACS and 351 with ST-elevation myocardial infarction (STEMI). As compared to no-AF patients, those with AF were older and had significantly more prior cardiac events and comorbidities (all p<0.005). A progressive increase occurred over time in the rates of coronary angiography and percutaneous coronary intervention, both in NSTE-ACS (p for trend=0.0002 and 0.0008, respectively) and STEMI patients with AF at admission (both p for trend <0.0001), with trends similar to those observed in non-AF patients. Among STEMI patients, in-hospital mortality decreased by 50% in those without AF (7.5% in 2001 to 3.3% in 2014, p<0.0001), with a similar decrease in those with AF (20% vs 10.7%, p=0.20), even though not statistically significant. At multivariable analysis, AF on admission was not an independent predictor of in-hospital mortality [odds ratio (OR): 0.82; 95% confidence intervals (CI): 0.52-1.30; p=0.41 for NSTE-ACS, and OR: 1.07; 95% CI: 0.73-1.57; p=0.74 for STEMI]. CONCLUSIONS: Over the last 14years, the in-hospital management of ACS patients with AF has significantly improved as for patients without AF, with comparable effect in terms of outcome.

Hydrotherapy in advanced heart failure: the cardio-HKT pilot study.

BACKGROUND: In-water exercise, hydrotherapy, may offer an attractive alternative to conventional training in markedly compromised patients with advanced HF. This Pilot Study evaluates the safety and efficacy of Cardio-Hydrokinesitherapy (Cardio-HKT) in patients with advanced HF on optimal medical therapy. Cardio-HKT is a novel rehabilitation program that includes training sessions in warm water (31 degrees C), integrated by educational and psycho-behavioural sessions to promote healthy life style modifications. METHODS: We studied 18 adult patients with advanced HF, LVEF < 35%, NYHA functional class > II and peak oxygen uptake (peak VO2) < 18 ml/kg/min. Cardio-HKT consisted of a 3 weeks daily in-water training, combined to educational and psycho-behavioural sessions. Patients underwent a six-minute-walking-test (6mWT), a cardiopulmonary exercise test at baseline and after 3 weeks of Cardio-HKT. Quality of life was assessed with the Minnesota Living with Heart Failure Questionnaire (MLHF). RESULTS: All patients completed the Cardio-HKT rehabilitation program without complications. The 6mWT improved from 453 +/- 172 m to 571 +/- 120 m (p < 0.01), peak VO2 from 13.0 +/- 3.1 to 14.5 +/- 2.9 ml/kg/min (p = 0.03), whereas VE/ CO2 slope declined from 37 +/- 10 to 33 +/- 9 (p = 0.01). MLHF markedly improved from 56 (68-27) to 18 (40-7) (p < 0.01). CONCLUSIONS: Our results support the safety and efficacy of the innovative Cardio-HKT rehabilitation program in patients with advanced HF.

Pharmacokinetics and pharmacodynamics of ticagrelor in the treatment of cardiac ischemia.

INTRODUCTION: After acute coronary syndromes (ACS), the so-called dual antiplatelet therapy (DAPT), which usually consists of low-dose of aspirin in combination with a thienopyridine (clopidogrel, prasugrel) or with a cyclopentyltriazolopyrimidine (ticagrelor), reduces the risk of ischemic events. Ticagrelor, un particular, is an effective drug as it isn' a prodrug, doesn't require metabolic activation and demonstrates a rapid onset and faster offset of action. Areas covered: This article evaluates the pharmacokinetics, efficacy, safety and tolerability of ticagrelor during DAPT after ACS and its potential use beyond the canonical twelve months after PCI. The review discusses studies comparing: ticagrelor and clopidogrel (DISPERSE, DISPERSE-2, PLATO, RESPOND Trial, ONSET/OFFSET Trials), ticagrelor and placebo (PEGASUS TIMI 54 Trial). Expert opinion: For ACS patients, the PLATO trial showed that ticagrelor was superior to clopidogrel in the reduction of cardiovascular death, myocardial infarction and stroke. PEGASUS TIMI 54 showed that patients in whom ischemic events and cardiovascular death outweigh the risk of life-threatening bleeding, may benefit from prolonged ticagrelor-based dual antiplatelet therapy, over 12 months. This strategy has been recently approved by the ACC/AHA guidelines. Further studies are needed to evaluate and eventually validate the role of the prolonged DAPT in patients treated with new generation stents.

Clinical characteristics and prognostic impact of atrial fibrillation in patients with chronic heart failure.

AIM: To assess the prevalence, clinical characteristics and independent prognostic impact of atrial fibrillation (AF) in chronic heart failure (CHF) patients, and the potential protective effect of disease-modifying medications, particularly beta-blockers (BB). METHODS: We retrospectively reviewed the charts of patients referred to our center since January 2004, and collected all clinical information available at their first visit. We assessed mortality to the end of June 2015. We compared patients with and without AF, and assessed the association between AF and all-cause mortality by multivariate Cox regression and Kaplan-Meyer analysis, particularly accounting for ongoing treatment with BB. RESULTS: A total of 903 patients were evaluated (mean age 68 ± 12 years, 73% male). Prevalence of AF was 19%, ranging from 10% to 28% in patients ≤ 60 and ≥ 77 years, respectively. Besides the older age, patients with AF had more symptoms (New York Heart Association II-III 60% vs 44%), lower prevalence of dyslipidemia (23% vs 37%), coronary artery disease (28% vs 52%) and left bundle branch block (9% vs 16%). On the contrary, they more frequently presented with an idiopathic etiology (50% vs 24%), a history of valve surgery (13% vs 4%) and received overall more devices implantation (31% vs 21%). The use of disease-modifying medications (i.e., BB and ACE inhibitors/angiotensin receptor blockers) was lower in patients with AF (72% vs 80% and 71% vs 79%, respectively), who on the contrary were more frequently treated with symptomatic and antiarrhythmic drugs including diuretics (87% vs 69%) and digoxin (51% vs 11%). At a mean follow-up of about 5 years, all-cause mortality was significantly higher in patients with AF as compared to those in sinus rhythm (SR) (45% vs 34%, P value < 0.05 for all previous comparisons). However, in a multivariate analysis including the main significant predictors of all-cause mortality, the univariate relationship between AF and death (HR = 1.49, 95%CI: 1.15-1.92) became not statistically significant (HR = 0.98, 95%CI: 0.73-1.32). Nonetheless, patients with AF not receiving BB treatment were found to have the worst prognosis, followed by patients with SR not receiving BB therapy and patients with AF receiving BB therapy, who both had similarly worse survival when compared to patients with SR receiving BB therapy. CONCLUSION: AF was highly prevalent and associated with older age, worse clinical presentation and underutilization of disease-modifying medications such as BB in a population of elderly patients with CHF. AF had no independent impact on mortality, but the underutilization of BB in this group of patients was associated to a worse long-term prognosis.

Contemporary Trends and Age-Specific Sex Differences in Management and Outcome for Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Age- and sex-specific differences exist in the treatment and outcome of ST-elevation myocardial infarction (STEMI). We sought to describe age- and sex-matched contemporary trends of in-hospital management and outcome of patients with STEMI. METHODS AND RESULTS: We analyzed data from 5 Italian nationwide prospective registries, conducted between 2001 and 2014, including consecutive patients with STEMI. All the analyses were age- and sex-matched, considering 4 age classes: <55, 55 to 64, 65 to 74, and ≥75 years. A total of 13 235 patients were classified as having STEMI (72.1% men and 27.9% women). A progressive shift from thrombolysis to primary percutaneous coronary intervention occurred over time, with a concomitant increase in overall reperfusion rates (P for trend <0.0001), which was consistent across sex and age classes. The crude rates of in-hospital death were 3.2% in men and 8.4% in women (P<0.0001), with a significant increase over age classes for both sexes and a significant decrease over time for both sexes (all P for trend <0.01). On multivariable analysis, age (odds ratio 1.09, 95% CI 1.07-1.10, P<0.0001) and female sex (odds ratio 1.44, 95% CI 1.07-1.93, P=0.009) were found to be significantly associated with in-hospital mortality after adjustment for other risk factors, but no significant interaction between these 2 variables was observed (P for interaction=0.61). CONCLUSIONS: Despite a nationwide shift from thrombolytic therapy to primary percutaneous coronary intervention for STEMI affecting both sexes and all ages, women continue to experience higher in-hospital mortality than men, irrespective of age.

[Acute coronary syndromes in Italy: observations from the BLITZ-2 study]. / Sindromi coronariche acute in Italia: osservazioni dallo studio BLITZ-2.

The hospital admission of patients with acute coronary syndromes without ST-segment elevation is increasing in the real world. The aim of the BLITZ-2 study, carried out in May 2003, was to investigate the epidemiology and management of patients admitted with a diagnosis of non-ST-elevation myocardial infarction. The study enrolled 1888 patients with a mean age of 68 years. Among the involved hospitals a cath-lab was available in 67.7% in northern Italy vs 37 and 39.8% in central and southern Italy, respectively. Only 44 and 55% of patients underwent coronary angiography during the first hospital admission in central and southern Italy, respectively, against 68% of patients in northern Italy. The type of strategy was more influenced by the availability of a cath-lab than by the TIMI risk score. A conservative strategy was applied in 45% of patients (26% in hospitals with a cath-lab) whereas an invasive approach was used in 55% of patients (74% in hospitals with a cath-lab). There was no difference in the TIMI risk score between the groups. Age was predictor of coronary angiography: 71% in patients < 55 years, 63% in patients 55-74 years, and 44% in patients > or = 75 years. The in-hospital mortality was 1.2% (1% in northern Italy, 1.4% in central Italy, 1.4% in southern Italy) and was higher in high-risk patients (1.5% with TIMI risk score > 5) and in older patients (3% in those > or = 75 years). The 1-month mortality and reinfarction was 2.4 and 3.6%, respectively. The total in-hospital stay was 8.8 days (coronary care unit stay 3.9 days). The contemporary management of Italian patients with acute coronary syndrome turned out to be influenced by resource availability, and elderly patients and subjects at higher risk are undertreated.

Clinical characteristics and outcome of diabetic patients with acute myocardial infarction. Data from the BLITZ-1 study.

BACKGROUND: The determinants of a worse outcome in diabetic patients after an acute myocardial infarction (AMI) are controversial. They include delayed hospital admission, worse clinical presentation and lesser efficacy of accepted therapeutic interventions. Therefore, to improve our knowledge, we aimed to describe the clinical characteristics, treatment options and short-term outcomes of diabetic patients in a survey of consecutive AMI subjects admitted to the Italian coronary care unit (CCU) network in the current era of reperfusion. METHODS: The BLITZ study prospectively enrolled patients with AMI, within 48 hours of symptom onset, admitted to 296 out of the 341 existing Italian CCUs from October 15 to 29, 2001. Diabetic status was recorded by collecting clinical history. In-hospital and post-discharge management and outcomes were collected up to 30 days from admission. RESULTS: Overall, 434 of 1959 enrolled patients (22%) had a clinical diagnosis of diabetes. Diabetic patients were older, more frequently women, had a worse coronary risk profile, and an unfavorable clinical presentation compared to non-diabetics. Among 1275 patients with ST-elevation AMI, diabetics (20%) received a similar proportion of any reperfusion therapy (61 vs 66%, p = 0.10), but significantly less primary percutaneous coronary angioplasty (9 vs 16%, p = 0.003). Diabetic patients were treated less often with oral beta-blockers than non-diabetics both during hospitalization (56 vs 64%, p = 0.003) and at discharge (54 vs 61%, p = 0.01). In contrast, in-hospital use of angiotensin-converting enzyme inhibitors (76 vs 67%, p = 0.0003), digitalis (10 vs 5%, p = 0.0005), and diuretics (54 vs 36%, p < 0.0001) was more frequent among diabetics. During their index admission, subjects with diabetes had higher in-hospital mortality (11 vs 6%, p = 0.0004), as well as higher rates of reinfarction (6 vs 2%, p = 0.0003), new congestive heart failure (28 vs 14%, p < 0.0001), cardiogenic shock (10 vs 5%, p = 0.0005) or recurrent angina (22 vs 16%, p = 0.0034). A similar pattern was observed at 30-day follow-up. At multivariate analysis, diabetic status was not confirmed to be an independent predictor of 30-day mortality. CONCLUSIONS: Although diabetic patients with AMI admitted to the Italian CCU network have a higher in-hospital and 30-day morbidity and mortality rates compared to non-diabetics, a clinical diagnosis of diabetes has no independent predictive value on short-term outcome.

Temporal trends in the epidemiology, management, and outcome of patients with cardiogenic shock complicating acute coronary syndromes.

AIMS: Despite advances in the management of patients with acute coronary syndrome (ACS), cardiogenic shock (CS) remains the leading cause of death in these patients. We describe the evolution of clinical characteristics, in-hospital management, and outcome of patients with CS complicating ACS. METHODS AND RESULTS: We analysed data from five Italian nationwide prospective registries, conducted between 2001 and 2014, including consecutive patients with ACS. Out of 28 217 ACS patients enrolled, 1209 (4.3%) had CS: 526 (44%) at the time of admission and 683 (56%) later on during hospitalization. Over the years, a reduction in the incidence of CS was observed, even though this was not statistically significant (P for trend = 0.17). The proportions of CS patients with a history of heart failure declined, whereas the proportion of those with hypertension, renal dysfunction, previous PCI, and AF significantly increased. The use of PCI considerably increased from 2001 to 2014 [19% to 60%; percentage change 41, 95% confidence interval (CI) 29-51]. In-hospital mortality of CS patients decreased from 68% (95% CI 59-76) in 2001 to 38% (95% CI 29-47) in 2014 (percentage change -30, 95% CI -41 to -18). Compared with 2001, the risk of death was significantly lower in all of the registries, with reductions in adjusted mortality between 45% and 66%. CONCLUSIONS: Over the last 14 years, substantial changes occurred in the clinical characteristics and management of patients with CS complicating ACS, with a greater use of PCI and a significant reduction in adjusted mortality rate.

Quantitative Texture Analysis in Two-Dimensional Echocardiography: Application to the Diagnosis of Myocardial Hemochromatosis.

BACKGROUND: Myocardial reflectivity is abnormally increased in patients with thalassemia major under transfusion treatment, probably due to myocardial iron deposits and/or secondary structural changes. Such increased reflectivity has been detected by both qualitative and subjective analysis of two-dimensional echocardiographic (2-D echo) images and quantitative assessment of integrated backscatter amplitude with noncommercially available ultrasound prototypes. The purpose of this study was to assess the acoustic properties of myocardium in patients with beta-thalassemia major and iron overload by means of quantitative computerized offline textural analysis of conventionally recorded 2-D echo images, and to compare textural data with other qualitative (visual assessment) and quantitative (ultrasound backscatter analysis) approaches for myocardial ultrasound tissue characterization simultaneously applied to these patients. METHODS AND RESULTS: Thirty-five young patients with thalassemia major, without clinical signs of cardiac failure, and 20 age and sex matched normal controls were studied by echocardiography. Each patient was receiving blood transfusion every 2-3 weeks. Two-dimensional echo images, obtained with a commercially available echocardiograph using the parasternal long-axis view, were digitized off line and analyzed by first and second order texture algorithms applied to regions of interest in the myocardium (septal and posterior wall). The mean gray level value was higher in thalassemic patients than in controls on both the septum (110 +/- 25 vs 57 +/- 13, arbitrary units on a 0-255 scale; P < 0.01) and posterior wall (91 +/- 25 vs 67 +/- 18; P < 0.01). Among second order statistical parameters, contrast and angular second moment significantly (P < 0.01) differentiated septal and posterior walls of patients and controls. In thalassemic patients, no consistent correlation was found between wall texture parameters and hematologic (years of transfusions and chelation, number of transfusions), 2-D echo (posterior wall thickness, left ventricular end-diastolic diameter), and Doppler (transmitral E/A waves ratio) parameters. Myocardial walls with visually assessed increased echo reflectivity showed a trend toward higher values of mean gray level when compared with myocardial segments with qualitatively assessed normal reflectivity (septum: 121 +/- 26 vs 106 +/- 24; posterior wall: 105 +/- 23 vs 87 +/- 23). Although radiofrequency integrated backscatter has been demonstrated to be capable of identifying thalassemic patients, no significant correlation was found between mean gray level (by texture analysis) and radiofrequency data (septum: r = 0.03; posterior wall: r = 0.09; P = NS for both). CONCLUSIONS: Myocardial walls affected by hemochromatosis show ultrasound image texture alterations that may be quantified with digital image analysis techniques and appear mostly unrelated to hematologic and conventional, as well as radiofrequency-based, echocardiographic parameters. These changes in quantitatively evaluated echo reflectivity are present even before the development of clinical and echocardiographic signs of cardiac dysfunction. (ECHOCARDIOGRAPHY, Volume 13, January 1996)

In-hospital and one-year outcomes of patients with high-risk acute myocardial infarction treated with thrombolysis or primary coronary angioplasty.

BACKGROUND: The aim of this study was to observe the outcomes of high-risk patients with acute myocardial infarction treated with primary angioplasty and intravenous thrombolysis in a community setting. METHODS: A prospective study of the in-hospital and 12-month outcomes was conducted in 17 cardiology centers where primary angioplasty was available, and in 30 where it was not. Three thousand seventy-four patients in the first 12 hours of an evolving infarction were recruited; among these, 2227 patients who met one or more pre-defined criteria of increased risk were included in the study. RESULTS: Thrombolysis and primary angioplasty were respectively performed in 1090 and in 721 patients; 416 patients (18.7%) received no reperfusion treatment. The incidence of the primary combined in-hospital endpoint (death, non-fatal reinfarction and stroke) was similar in patients treated with thrombolysis (9.2%) and with primary angioplasty (10.7%) (odds ratio--OR 1.19, 95% confidence interval--CI 0.86-1.63, p = NS), and was higher (22.6%) in patients receiving no reperfusion treatment as compared to thrombolysis (OR 3.30, 95% CI 2.36-4.63, p < 0.0001). The occurrence of the 12-month endpoint (death, reinfarction, congestive heart failure and recurrent angina) was lower after primary angioplasty than after thrombolysis (26.8 vs 35.0%, OR 0.68, 95% CI 0.55-0.84, p = 0.0003), due to a lower incidence of angina. At multivariate analysis, older age, anterior infarction, Killip class > 1, high heart rate, and low systolic blood pressure on admission were all significantly associated with a higher incidence of both endpoints. The adjusted analysis confirmed that, despite similar in-hospital results after both reperfusion treatments, primary angioplasty was independently associated with better 1-year outcomes (relative risk 0.66, 95% CI 0.56-0.79, p < 0.0001). CONCLUSIONS: In this observation in the community setting, a strategy of primary angioplasty in patients with high-risk myocardial infarction was not better than thrombolysis in terms of mortality or recurrent infarction, but was associated with less angina at 1 year.

The new definition of myocardial infarction: analysis of the ESC/ACC Consensus Document and reflections on its applicability to the Italian Health System.

The recent document of the ESC/ACC Committee for the redefinition of myocardial infarction (MI) has introduced the measurement of cardiac troponin as the biochemical standard for the diagnosis of MI. This change has been mainly driven by the demonstration that any amount of myocardial damage, as detected by cardiac troponins, implies a worse long-term outcome of the patient. The results of several studies consistently show that there is a continuous relationship between the degree of troponin elevation and the patient's prognosis. The new definition has important consequences on the diagnostic and therapeutic approaches to patients with acute coronary syndromes; in fact, patients with increased troponins, i.e. patients with MI, necessitate more aggressive treatment than those without troponin elevations, i.e. patients with unstable angina. The application of the new definition is expected to increase the number of cases of MI by about 30% and to decrease mortality. We believe that several aspects of the new definition need to be discussed before the new criteria for MI are used in clinical practice in Italy. The most relevant issues are the following: 1) the definition of troponin elevation should meet the analytical performance of the available assays, the diagnostic cutoff of which is frequently too imprecise. We propose that troponin elevations be defined as values exceeding the concentration corresponding to a total analytical imprecision of 10%. We disclose such a concentration for the currently available assays and suggest its use in clinical practice to mitigate the possibility of false-positive values; 2) the number of samples required for the diagnosis should be sufficient for the assessment of the changes in concentration over time. When only one sample is available, or when the temporal pattern of the changes in marker concentration is not consistent with the time elapsed from the onset of symptoms, we suggest that objective evidence that myocardial ischemia is the likely cause of myocardial damage should be obtained; 3) the diagnosis of MI after a percutaneous coronary intervention represents a unique situation. In contrast with myocardial damage occurring during spontaneous ischemia, available data do not support the concept that any troponin elevation is associated with an adverse prognosis. In the absence of conclusive studies, we suggest that the diagnosis of MI after a percutaneous coronary intervention be based on conventional criteria. Finally, we propose this summary with the aim of overcoming some of the more controversial aspects of the ESC/ACC redefinition of MI: Criteria for acute, evolving or recent MI. Either one of the following criteria satisfies the diagnosis for an acute, evolving or recent MI: 1) elevation of biochemical markers of myocardial necrosis (preferably troponin) with at least one of the following: a) ischemic symptoms; b) development of pathologic Q waves on the ECG; c) ECG changes indicative of ischemia (ST segment elevation or depression); d) coronary artery intervention (e.g., coronary angioplasty). Marker elevations should be accompanied by objective evidence that myocardial ischemia is the likely cause of myocardial damage when: a) only one blood sample is available; b) marker changes over time are not consistent with the onset of symptoms; 2) pathologic findings of an acute MI. Criteria for established MI. Anyone of the following criteria satisfies the diagnosis for established MI: 1) development of new pathologic Q waves on serial ECGs. The patient may or may not remember previous symptoms. Biochemical markers of myocardial necrosis may have normalized, depending on the length of time that has passed since the infarct developed; 2) pathologic findings of a healed or healing MI.

[Myocardial infarction redefined based on the consensus document of the ESC/ACC]. / L'infarto miocardico ridefinito a proposito del documento di consenso dell'ESC/ACC.

An expert committee of the European Society of Cardiology and the American College of Cardiology has recently proposed new and more precise criteria for the diagnosis of myocardial infarction, entailing both relevant implications in clinical practice and scientific, epidemiological and organizational aspects. The Board of the Emergency Area of the National Association of Hospital Cardiologists (ANMCO) will review the document and analyze the issues of major concern.

[New definition of myocardial infarction: analysis of the consensus document ESC/ACC and thoughts about applicability to the Italian health situation]. / La nuova definizione di infarto miocardico: analisi del documento di consenso ESC/ACC e riflessioni sull'applicabilità alla realtà sanitaria italiana.

The recent document of the ESC/ACC Committee for the redefinition of myocardial infarction (MI) has introduced the measurement of cardiac troponin as the biochemical standard for the diagnosis of MI. This change has been mainly driven by the demonstration that any amount of myocardial damage, as detected by cardiac troponins, implies a worse long-term outcome of the patient. The results of several studies consistently show that there is a continuous relationship between the degree of troponin elevation and the patient's prognosis. The new definition has important consequences on the diagnostic and therapeutic approaches to patients with acute coronary syndromes; in fact, patients with increased troponins, i.e. patients with MI, necessitate more aggressive treatment than those without troponin elevations, i.e. patients with unstable angina. The application of the new definition is expected to increase the number of cases of MI by about 30% and to decrease mortality. We believe that several aspects of the new definition need to be discussed before the new criteria for MI are used in clinical practice in Italy. The most relevant issues are the following: 1) the definition of troponin elevation should meet the analytical performance of the available assays, the diagnostic cut-off of which is frequently too imprecise. We propose that troponin elevations be defined as values exceeding the concentration corresponding to a total analytical imprecision of 10%. We disclose such a concentration for the currently available assays and suggest its use in clinical practice to mitigate the possibility of false-positive values; 2) the number of samples required for the diagnosis should be sufficient for the assessment of the changes in concentration over time. When only one sample is available, or when the temporal pattern of the changes in marker concentration is not consistent with the time elapsed from the onset of symptoms, we suggest that objective evidence that myocardial ischemia is the likely cause of myocardial damage should be obtained; 3) the diagnosis of MI after a percutaneous coronary intervention represents a unique situation. In contrast with myocardial damage occurring during spontaneous ischemia, available data do not support the concept that any troponin elevation is associated with an adverse prognosis. In the absence of conclusive studies, we suggest that the diagnosis of MI after a percutaneous coronary intervention be based on conventional criteria. Finally, we propose this summary with the aim of overcoming some of the more controversial aspects of the ESC/ACC redefinition of MI: Criteria for acute, evolving or recent MI. Either one of the following criteria satisfies the diagnosis for an acute, evolving or recent MI: 1) elevation of biochemical markers of myocardial necrosis (preferably troponin) with at least one of the following: a) ischemic symptoms; b) development of pathologic Q waves on the ECG; c) ECG changes indicative of ischemia (ST segment elevation or depression); d) coronary artery intervention (e.g., coronary angioplasty). Marker elevations should be accompanied by objective evidence that myocardial ischemia is the likely cause of myocardial damage when: a) only one blood sample is available; b) marker changes over time are not consistent with the onset of symptoms; 2) pathologic findings of an acute MI. Criteria for established MI. Anyone of the following criteria satisfies the diagnosis for established MI: 1) development of new pathologic Q waves on serial ECGs. The patient may or may not remember previous symptoms. Biochemical markers of myocardial necrosis may have normalized, depending on the length of time that has passed since the infarct developed; 2) pathologic findings of a healed or healing MI.