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Dronedarone is the antiarrhythmic drug with the most complete and wide literature preceding its marketing. Most of these studies showed a good efficacy along with an excellent risk profile, especially in low- and medium-risk patients. Recently, updates of European, American and even Italian guidelines gave dronedarone its own spot into the antiarrhythmic armamentarium, recommending its use both for rhythm control and rate control in non-permanent atrial fibrillation. In Italy, however, dronedarone prescription is still possible only when amiodarone is not tolerated, making dronedarone a mere second choice of its older "relative". Moreover, patients taking dronedarone must undergo a strict alanine aminotransferase and bilirubin follow-up, which usefulness in predicting drug-induced liver damage (probably idiosyncratic in nature and therefore unpredictable) is far from demonstrated. The aim of this review is to sum up actual evidences on dronedarone, describe how these evidences had been differently transposed by panel of experts and drug agencies into guidelines and recommendations, and define the current difficulties encountered by the cardiologist in the correct use of this new antiarrhythmic agent in clinical practice.

Background: In X-linked dilated cardiomyopathy due to dystrophin mutations which abolish the expression of the M isoform (5'-XLDC), the skeletal muscle is spared through the up-regulation of the Brain (B) isoform, a compensatory mechanism that does not appear to occur in the heart of affected individuals., Methods: We quantitatively studied the expression topography of both B and M isoforms in various human heart regions through in-situ RNA hybridization, Reverse-Transcriptase and Real-Time PCR experiments. We also investigated the methylation profile of the B promoter region in the heart and quantified the B isoform up regulation in the skeletal muscle of two 5'-XLDC patients., Results: Unlike the M isoform, consistently detectable in all the heart regions, the B isoform was selectively expressed in atrial cardiomyocytes, but absent in ventricles and in conduction system structures. Although the level of B isoform messenger in the skeletal muscle of 5'-XLDC patients was lower that of the M messenger present in control muscle, it seems sufficient to avoid an overt muscle pathology. This result is consistent with the protein level in XLDC patients muscles we previously quantified. Methylation studies revealed that the B promoter shows an overall low level of methylation at the CG dinucleotides in both atria and ventricles, suggesting a methylation-independent regulation of the B promoter activity., Conclusions: The ventricular dilatation seen in 5'-XLDC patients appears to be functionally related to loss of the M isoform, the only isoform transcribed in human ventricles; in contrast, the B isoform is well expressed in heart but confined to the atria. Since the B isoform can functionally replace the M isoform in the skeletal muscle, its expression in the heart could potentially exert the same rescue function. Methylation status does not seem to play a role in the differential B promoter activity in atria and ventricles, which may be governed by other regulatory mechanisms. If these mechanisms could be deduced, de-silencing of the B isoform may represent a therapeutic strategy in 5'-XLDC patients., (© 2012 Neri et al; licensee BioMed Central Ltd.)

Objective: Prediction of aortic dissection or rupture is extremely difficult in patients with bicuspid aortic valve. We aimed to identify clinical and echocardiography predictors of histological abnormalities of the aortic wall in patients with bicuspid aortic valve undergoing aortic surgery., Methods: We assessed the histology of the aortic wall and clinical and echocardiography variables in a cohort of patients with bicuspid aortic valve (n = 127) and a wide spectrum of valvar disease who underwent replacement of the ascending aorta (with or without aortic valve surgery). Histology was classified using a 5-grade system developed by Larson and Edward., Results: Histological alterations of the aortic wall were absent/mild (grade 0-1) in 77 patients (61%) and moderate/severe (grade 2-3) in 50 (39%). Patients with moderate/severe histological alterations were younger (47 ± 17 vs 53 ± 16; p = 0.042). Eighteen patients out of 48 (38%) with an ascending aorta diameter ≤ 4.5 cm had grade 2-3 aortic wall disease as did 8 out of 18 (44%) with a diameter ≤ 4 cm. Nineteen out of 46 (41%) patients with a maximal ascending aortic area/height ratio < 10 cm(2) m(-1) had moderate/severe histological alterations. Multivariate logistic regression analysis showed that the indexed diameter of the aortic annulus was significantly associated with grade 2-3 aortic wall disease (odds ratio (OR): 12.22, 95% confidence interval (CI): 1.65-90.38, p = 0.014)., Conclusions: A high proportion of patients with bicuspid aortic valve and mild to moderate aortic dilatation have severe histological abnormalities of the aortic wall that are not predictable by clinical and echocardiographic findings. These observations suggest that risk stratification for aortic dissection or rupture in patients with bicuspid aortic valve is so far quite suboptimal and future investigations are warranted.

Background: Many ICD carriers experience inappropriate shocks, but the relative merits of dual- /single-chamber devices for arrhythmia discrimination still remain unclear. We explored possible advantages of the atrial data provided by dual-chamber implantable defibrillators (ICD) for discrimination of real-life supraventricular/ventricular tachyarrhythmias (SVT/VT)., Methods: 100 dual-chamber traces from 24 ICD were blindly reviewed in dual-chamber and simulated single-chamber (with/without discriminator data) reading modes by five electrophysiologists who determined chamber of origin and provided Likert-scale "confidence" ratings. We assessed 1) intra/interobserver concordance; 2) diagnostic accuracy, using expert diagnoses as a reference standard; 3) ROC curves of sensitivity/specificity of "likelihood perception" scores, generated by combining chamber-of-origin diagnostic judgments with Likert-scale "confidence" ratings. We also assessed diagnostic accuracy of automated discrimination by all possible dual-/single-chamber algorithm configurations., Results: Interobserver concordance was "substantial" (modified Cohen kappa-test values for dual-/single-chamber, 0.79/0.68); intraobserver concordance "almost complete" (kappa ≥ 0.89). Dual-chamber mode provided best diagnostic sensitivity/specificity (99%/92%) and highest reader confidence (p<0.001). Area under ROC curves of sensitivity/specificity values for the "likelihood perception" score (representing electrophysiologists' perceptions of the likelihood that an episode was of ventricular origin) was highest in dual-chamber mode (0.98 vs. 0.93 for both single-chamber modes; p<0.001). Regarding automated discrimination, all four dual-chamber configurations conferred 100% sensitivity (specificity values ranged 39%-88%), whereas single-chamber configurations appeared inferior (best sensitivity/specificity combination, 89%/64%)., Conclusions: Availability of the atrial channel helps in reducing inappropriate ICD therapies by providing relevant advantages in terms of both appropriate cardiologist's post-hoc discrimination of SVT/VT (improving program tailoring) and automated arrhythmia discrimination., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

This article presents an overview of clinical and molecular genetics of myocardial infarction (MI). Discussion includes the partial overlapping of risk factors for myocardial infarction and atherosclerosis, the impact of a positive family history on the risk of MI, the "familial" nongenetic, environmental factors, the inherited risk associated with the low-dose input of many genes, and a simple approach to stratify the individual risk in genetic counseling., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Statins are recommended in heart transplantation regardless of lipid levels. However, it remains unknown whether dosing should be maximized or adjusted toward a pre-defined cholesterol threshold., Methods: This pilot, randomized, open-label study compares an early maximal dose of fluvastatin (80 mg/day) with a strategy based on 20 mg/day subsequently titrated to target low-density lipoproteins (LDL) <100 mg/dl. Efficacy outcomes consisted of achieving an LDL level of <100 mg/dl at 12 months after transplant, and change in intracoronary ultrasound parameters., Results: Fifty-two patients were randomized. Overall safety, and efficacy in achieving LDL targets (13 [50%] vs 14 [54%]; p = 0.8) were comparable between study arms, but 17 (65%) patients needed a dose increase in the titrated-dosing arm. Early LDL levels and average LDL burden were lower in the maximal-dosing arm (p < 0.05). Few patients developed an increase in maximal intimal thickness of >0.5 mm, with numerical prevalence in the titrated-dosing arm (3 [12.5%] vs 1 [5%]; p = 0.3). Intimal volume increased in the titrated-dosing (p < 0.01) but not in the maximal-dosing arm (p = 0.1), which accordingly showed a higher prevalence of negative remodeling (p = 0.02)., Conclusions: Despite being as effective as the titrated-dosing approach in achieving LDL <100 mg/dl at 12 months after transplant, the maximal-dose approach was associated with a more rapid effect and with potential advantages in preventing pathologic changes in graft coronary arteries., (Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

The term cardiac amyloidosis refers to the involvement of the heart as a result of amyloid deposition in heart tissue either in the context of a systemic disease or as a localized form. Several proamyloid proteins can produce amyloid deposits in the heart. Each of these amyloidoses has characteristic clinical (cardiac and extracardiac) features, its own course, and a specific diagnosis and treatment. Since cardiac involvement may be the first-manifestation of amyloidosis, the cardiologist may be the first healthcare professional to see the patient and must always consider this diagnosis. In this review, we consider the amyloidosis characteristics that may present with cardiac involvement, from the cardiologist's viewpoint and in light of our experience. We review in detail when and how to establish the diagnosis and how to treat these patients' cardiac involvement and the underlying amyloid disease., (Copyright © 2011 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.)

We sought to evaluate the prognostic significance of ST-segment elevation (STE) in lead aVR in unselected patients with non-STE acute coronary syndrome (NSTE-ACS). We enrolled 1,042 consecutive patients with NSTE-ACS. Patients were divided into 5 groups according to the following electrocardiographic (ECG) patterns on admission: (1) normal electrocardiogram or no significant ST-T changes, (2) inverted T waves, (3) isolated ST deviation (ST depression [STD] without STE in lead aVR or transient STE), (4) STD plus STE in lead aVR, and (5) ECG confounders (pacing, right or left bundle branch block). The main angiographic end point was left main coronary artery (LM) disease as the culprit artery. Clinical end points were in-hospital and 1-year cardiovascular death defined as the composite of cardiac death, fatal stroke, and fatal bleeding. Prevalence of STD plus STE in lead aVR was 13.4%. Rates of culprit LM disease and in-hospital cardiovascular death were 8.1% and 3.8%, respectively. On multivariable analysis, patients with STD plus STE in lead aVR (group 4) showed an increased risk of culprit LM disease (odds ratio 4.72, 95% confidence interval [CI] 2.31 to 9.64, p <0.001) and in-hospital cardiovascular mortality (odds ratio 5.58, 95% CI 2.35 to 13.24, p <0.001) compared to patients without any ST deviation (pooled groups 1, 2, and 5), whereas patients with isolated ST deviation (group 3) did not. At 1-year follow-up 127 patients (12.2%) died from cardiovascular causes. On multivariable analysis, STD plus STE in lead aVR was a stronger independent predictor of cardiovascular death (hazard ratio 2.29, 95% CI 1.44 to 3.64, p <0.001) than isolated ST deviation (hazard ratio 1.52, 95% CI 0.98 to 2.36, p = 0.06). In conclusion, STD plus STE in lead aVR is associated with high-risk coronary lesions and predicts in-hospital and 1-year cardiovascular deaths in patients with NSTE-ACS. Therefore, this promptly available ECG pattern could be useful to improve risk stratification and management of patients with NSTE-ACS., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Mean platelet volume (MPV) has been proposed as a marker of platelet reactivity and cardiovascular risk. Its prognostic significance has not been thoroughly investigated in patients with non-ST elevation acute coronary syndrome (NSTE-ACS). We included 1,041 consecutive patients with NSTE-ACS. Patients were divided in quartiles according to the MPV value on admission (fl) i.e. Q1<7.5; Q2=7.5-8.0; Q3=8.1-8.8; Q4≥8.9. The primary study endpoint was the composite of cardiovascular death and re-myocardial infarction (MI) at one year. Secondary study endpoints were individual cardiovascular death and re-MI. Patients in Q4 were older, had a higher prevalence of previous MI, peripheral artery disease and advanced Killip class compared to patients in Q1-Q3. Elevated MPV levels (Q4) was independently associated with gender, smoking status, platelet count and creatinine level. Overall, 210 patients (20.2%) reached the primary endpoint, 124 (12.1%) died from cardiovascular causes and 125 (12.0%) suffered from re-MI. On multivariable analysis patients in Q4 were at higher risk of primary endpoint (HR=1.41; 95%CI 1.06-1.89; p=0.02) whilst the association with cardiovascular death and re-MI was attenuated. MPV as continuous variable was independently associated with both primary endpoint (HR=1.19; 95%CI 1.06-1.33; p=0.003) and cardiovascular death (HR=1.23; 95%CI 1.06-1.42, p=0.006). The incorporation of MPV into a comprehensive model of risk significantly increased the likelihood ratio chi-square for prediction of both the composite endpoint (p=0.004) and cardiovascular death (p=0.009). Therefore, MPV may be useful to improve risk stratification in NSTE-ACS patients and should be included in future prospective studies evaluating the role of platelet function in promoting cardiovascular events.

Introduction: High-sensitivity C-Reactive Protein (hsCRP) levels are correlated with vulnerable carotid plaques, although their impact on the outcome of carotid revascularization is unknown. The aim of our study was to investigate the correlation between hsCRP and embolization during carotid artery stenting (CAS)., Methods: Patients with symptomatic carotid stenosis were submitted to CAS with distal protection filters. Serum hsCRP was analysed prior to CAS and patients were divided into two groups: Class I, patients presenting hsCRP < 5 mg/l and, Class II, patients presenting hsCRP≥5 mg/l. Plaques were categorised by ultrasound grey scale measurement as homogenous and dishomogenous. Afterwards CAS filters were analyzed microscopically and ultrastructurally to determine the type and the amount of debris present, based on percentage of surface involvement (SI) and pore occluded (PO) by embolic material., Results: Fourteen patients underwent uneventful CAS, with a mean hsCRP of 11.5±18.4 mg/l. Eight patients were in Class I and six in Class II. All filters had microscopic debris. SI was 25.4% in Class I and 33.3% in Class II (p=ns), PO 22.9% and 33.3% respectively (p=0.049). Patients in Class II who also had a dishomogenous plaque showed greater SI and PO compared with patients in Class I with homogenous plaque (35.0% vs. 21.8% and 40.4% vs. 22.7% respectively, p<0.05). Microscopically embolic material was identified as atherosclerotic plaque fragments and platelet aggregates and was similar in both groups., Discussion: High hsCRP levels are associated with significantly greater embolization during CAS in symptomatic patients, particularly in dishomogenous plaque. Although these results need further investigation due to the limited number of enrolled patients, this study suggests that CAS may not be indicated as a method of carotid revascularization in this setting.

Objectives: In a cohort of patients with hereditary transthyretin-related amyloidosis (ATTR), we aimed to assess the role of (99m)Tc-3,3-diphosphono-1,2-propanodicarboxylic acid ((99m)Tc-DPD) in detecting myocardial amyloid infiltration across a wide spectrum of cardiac involvement and in predicting major adverse cardiac events (MACE)., Background: Hereditary transthyretin-related amyloidosis is a challenging and underdiagnosed condition where both early diagnosis and prognosis remain problematic., Methods: We evaluated 63 patients with ATTR: 40 with and 23 without echocardiographically diagnosed amyloidotic cardiomyopathy (AC). Myocardial uptake of (99m)Tc-DPD scintigraphy was semiquantitatively and visually assessed at 5 min and 3 h., Results: All patients with AC showed moderate-to-severe myocardial tracer uptake (i.e., visual score ≥2). Within the subgroup without AC, only 4 patients (with Ala36Pro, Gly47Ala, Thr49Ala, and Glu89Gln transthyretin mutations) showed myocardial tracer uptake and abnormal heart/whole body retention (H/WB) values: in all these cases endomyocardial biopsies showed amyloidotic infiltration. The H/WB was positively correlated with left ventricular (LV) mean wall thickness (Pearson's r=0.695, p<0.001) and negatively with LV ejection fraction (r=-0.368, p=0.004). The H/WB was an unfavorable predictor of MACE-free survival at Cox univariate analysis and contributed to the multivariate model. Notably, LV wall thickness >12 mm in combination with H/WB >7.5 was associated with the highest event rate., Conclusions: In ATTR, (99m)Tc-DPD scintigraphy can identify myocardial infiltration across a wide spectrum of morphologic/functional cardiac involvement, allowing an early diagnosis of the disease (even before the appearance of echocardiographic abnormalities). The (99m)Tc-DPD myocardial uptake is a prognostic determinant of "cardiac" outcome in ATTR, either alone or in combination with LV wall thickness., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: We previously reported in a small series of patients that (99m)Tc-3,3-diphosphono-1,2-propanodicarboxylic acid ((99m)Tc-DPD) scintigraphy tested positive in transthyretin-related (TTR) (both mutant and wild-type) but not in primary (AL) amyloidotic cardiomyopathy (AC). We extended our study to a larger cohort of patients with AC., Methods: We evaluated (1) 45 patients with TTR-related AC (28 mutant and 17 wild-type), (2) 34 with AL-related AC and (3) 15 non-affected controls. Myocardial uptake of (99m)Tc-DPD (740 MBq i.v.) was semiquantitatively and visually assessed at 5 min and at 3 h., Results: Heart retention (HR) and heart to whole-body retention ratio (H/WB) of late (99m)Tc-DPD uptake were higher among TTR-related AC (HR 7.8%; H/WB 10.4) compared with both unaffected controls (HR 3.5%; H/WB 5.7; p < 0.0001) and AL-related AC (HR 4.0%; H/WB 6.1; p < 0.0001). For the diagnosis of TTR-related AC, positive and negative predictive accuracy of visual scoring of cardiac retention were: 80 and 100% (visual score ≥1); 88 and 100% (visual score ≥2); and 100 and 68% (visual score = 3). At adjusted linear regression analysis, TTR aetiology turned out to be the only positive predictor of increasing (99m)Tc-DPD uptake in terms of both HR [β 2.5, 95% confidence interval (CI) 1.5-3.5; p < 0.0001] and H/WB (β 3.5, 95% CI 2.1-4.9; p < 0.0001)., Conclusion: While (99m)Tc-DPD scintigraphy was confirmed to be useful for differentiating TTR from AL-related AC, diagnostic accuracy was lower than previously reported due to a mild degree of tracer uptake in about one third of AL patients. (99m)Tc-DPD scintigraphy can provide an accurate differential diagnosis in cases of absent or intense uptake evaluated by visual score.

Objective: To compare the effects of cardiac resynchronisation therapy (CRT) on left ventricular (LV) reverse remodelling in patients with dilated cardiomyopathy (DCM) associated or not with isolated ventricular non-compaction (IVNC)., Methods and Results: 52 patients with heart failure, candidates for CRT, were recruited: 20 patients with IVNC associated with DCM (IVNC-DCM) without other coexisting cardiac diseases and 32 patients with DCM without IVNC matched for age, gender, body surface area and LV systolic function. Standard and contrast echocardiography were used to assess LV volumes and function and to optimise visualisation of the endocardial border at baseline and at 6 months' follow-up. Patients with heart failure were subsequently classified as CRT negative responders, non-responders, responders or super-responders based on different LV reverse remodelling 6 months after CRT implantation. Different types of CRT response were observed in IVNC-DCM and DCM patients. In particular, in IVNC-DCM patients the percentage of super-responders was significantly higher than for patients with DCM (60% vs 28%, respectively, p = 0.023). In addition, the number of IVNC segments had a trend towards reduction with respect to baseline (4 (3-6)) at 6 months' follow-up (3 (1-5); p = 0.067). Finally, in IVNC-DCM, the patients with a higher number of IVNC segments at baseline (>4) were more likely to be responders or super-responders than patients with ≤ 4 IVNC segments (p = 0.003)., Conclusions: Patients with IVNC-DCM had greater LV reverse remodelling after CRT than patients with DCM. The greater the area of non-compaction (higher number of IVNC segments) the greater the chance of achieving CRT response and greater LV reverse remodelling.

Many are the open issues around the atherosclerotic disease still requiring definite answers. Why do involved arteries some times undergo a wall dilatation process and other times a progressive lumen narrowing? Why does a systemic disease like atherosclerosis "favour" different vascular districts in different patients and/or ages? Why are atherosclerotic lesions proximally or distally located in relation to different vascular beds? This paper reviews the major clinical implications of these issues mainly considering three clinical situations: the cardiological assessment of the patient after a neurological event, the cardiological visit in the patient undergoing a vascular intervention, the search of a renal artery stenosis in the patient undergoing a coronary arteriography.

Objective: Subendocardial and subepicardial layers have opposite orientation of the myofibres and they are differently affected by coronary artery disease. This study investigated the differences in subendocardial and subepicardial left ventricular (LV) twist in patients with coronary artery disease., Methods: 214 patients were included in the study: 60 with first ST elevation myocardial infarction (STEMI), 111 with chronic ischaemic heart failure (HF) and 43 normal subjects. Real-time three-dimensional echocardiography provided LV volumes and function. Two-dimensional speckle tracking echocardiography differentiating the subendocardial and subepicardial layers was used for the assessment of LV twist. Patients with STEMI were divided into two groups (small and large STEMI)., Results: Compared with normal subjects, peak subendocardial LV twist was significantly impaired in patients with STEMI (11.2 ± 6.0° vs 15.3 ± 2.7°, p<0.001). In patients with chronic HF, peak subendocardial LV twist was even more impaired (4.6 ± 3.4°, p<0.001 vs normal subjects and patients with STEMI). Conversely, peak subepicardial LV twist was not statistically different between normal subjects and patients with STEMI (8.9 ± 1.9° vs 8.4 ± 4.4°, p=0.98), whereas it was significantly impaired in patients with chronic HF (2.6 ± 2.5°, p<0.001 vs normal subjects and patients with STEMI). Peak subendocardial LV twist was not statistically different between large and small STEMI, whereas peak subepicardial LV twist was significantly lower in large STEMI than in small STEMI (7.1 ± 4.8° vs 9.6 ± 3.6°, p=0.025)., Conclusions: Subendocardial LV twist is reduced in patients with STEMI and chronic ischaemic HF whereas subepicardial LV twist is reduced only in chronic ischaemic HF. When STEMI are divided into large and small infarctions, it becomes evident that subepicardial LV twist is only reduced in large infarctions.

Advances in molecular genetics present new opportunities and challenges for cardiologists who manage patients and families with cardiomyopathies. The aims of this position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases are to review the general issues related to genetic counselling, family screening and genetic testing in families with a cardiomyopathy, and to provide key messages and suggestions for clinicians involved in their management.

Antisense-mediated exon skipping has proven to be efficacious for subsets of Duchenne muscular dystrophy mutations. This approach is based on targeting specific splicing motifs that interfere with the spliceosome assembly by steric hindrance. Proper exon recognition by the splicing machinery is thought to depend on exonic splicing enhancer sequences, often characterized by purine-rich stretches, representing potential targets for antisense-mediated exon skipping. We identified and functionally characterized two purine-rich regions located within dystrophin intron 11 and involved in splicing regulation of a pseudo-exon. A functional role for these sequences was suggested by a pure intronic DMD deletion causing X-linked dilated cardiomyopathy through the prevalent cardiac incorporation of the aberrant pseudo-exon, marked as Alu-exon, into the dystrophin transcript. The first splicing sequence is contained within the pseudo-exon, whereas the second is localized within its 3' intron. We demonstrated that the two sequences actually behave as splicing enhancers in cell-free splicing assays because their deletion strongly interferes with the pseudo-exon inclusion. Cell-free results were then confirmed in myogenic cells derived from the patient with X-linked dilated cardiomyopathy, by targeting the identified motifs with antisense molecules and obtaining a reduction in dystrophin pseudo-exon recognition. The splicing motifs identified could represent target sequences for a personalized molecular therapy in this particular DMD mutation. Our results demonstrated for the first time the role of intronic splicing sequences in antisense modulation with implications in exon skipping-mediated therapeutic approaches.

More than a century after it was invented, standard ECG is enjoying a renaissance of sorts. With regard to acute ischemic heart disease, this phenomenon is due mainly to the availability of large databases that in an ordered and predefined manner collect patient ECG patterns along side their clinical and coronary angiography details as well as outcome data. The present review critically analyses the diagnostic role of standard ECG in acute coronary syndromes with or without ST-segment elevation (STEMI and NSTEMI, respectively) and focuses on interpretation pitfalls and patterns that can contribute to therapeutic decision-making. In front of a patient with a clinical presentation suggestive of acute myocardial infarction the ECG can help answer many questions. In case a STEMI is suspected: are we sure we can exclude an infarction? (the problem of false negatives); are we sure it is a real infarction and not a false positive? Which is the obstructed coronary artery and at what level? Has there been reperfusion? In case an NSTEMI is suspected: are we sure it is a real myocardial infarction, rather than a pulmonary embolism or an aortic dissection? Are we sure it is NSTEMI rather than a "masked" dorsal STEMI? Which coronary substrate and what ischemia extension can we hypothesize in this patient? In particular, is the substrate of such high risk suggesting an emergency invasive approach?

Cardiac resynchronization therapy (CRT) can improve global left ventricular (LV) function. However, limited data are available on regional LV contractility at rest and during exercise. The aim of the present study was to prospectively investigate the effects of CRT on regional LV ejection fraction (EF), global LVEF, and dyssynchrony, during rest and exercise, using radionuclide angiography. A total of 32 consecutive patients with heart failure and nonischemic cardiomyopathy underwent technetium-99m radionuclide angiography with bicycle exercise immediately after CRT implantation (during spontaneous rhythm and after CRT activation) and 3 months later. The regional EF was assessed in the interventricular septum and the lateral wall (LW). Intraventricular dyssynchrony was evaluated using Fourier phase analysis. During spontaneous rhythm, the EF was severely depressed in the septum compared to in the LW. CRT improved septal EF at rest and during exercise both at baseline (p <0.001) and after 3 months (p <0.05). The basal LW EF decreased during CRT (p <0.05, both at rest and during exercise). LV dyssynchrony decreased both at baseline and during follow-up, and the global LVEF showed improvement only at 3 months (p <0.001). In conclusion, in patients with nonischemic cardiomyopathy, CRT affects regional LV function by increasing the septal EF and reducing LW contractility, both at rest and during exercise. This was associated with an improvement in global LVEF and dyssynchrony., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

A nonhereditary form of systemic amyloidosis associated with wild-type transthyretin causes heart involvement predominantly in elderly men (systemic senile amyloidosis, or SSA). However, hereditary transthyretin-related amyloidosis (ATTR) is the most frequent form of familial systemic amyloidosis, a group of severe diseases with variable neurological and organ involvement. ATTR remains a challenging and widely underdiagnosed condition, owing to its extreme phenotypic variability: the clinical spectrum of the disease ranges from an almost exclusive neurologic involvement to a strictly cardiac presentation. Such heterogeneity principally results from differential effects of the various reported transthyretin mutations, the geographic region the patient is from and, in the case of the most common mutation, Val30Met, whether or not large foci of cases occur (endemic versus nonendemic aggregation). Genetic or environmental factors (such as age, sex, and amyloid fibril composition) also contribute to the heterogeneity of ATTR, albeit to a lesser extent. The existence of exclusively or predominantly cardiac phenotypes should lead clinicians to consider the possibility of ATTR in all patients who present with an unexplained increase in left ventricular wall thickness at echocardiography. Assessment of such patients should include an active search for possible red flags that can point to the correct final diagnosis.

Background: Isolated ventricular noncompaction (IVNC) is characterized by multiple prominent trabeculations and deep intertrabecular recesses. Some reports prove that the chronic heart failure may occur in approximately half of the patients. In this report we investigate the correlation between the number of non compacted segments and entity of systolic dysfunction from the registry and subregistries of the SIEC., Method: To identify the correlation between ventricular dysfunction and number of segments involved in non compaction we evaluated a consecutive series of 238 patients affected by non compaction, from the SIEC (Società Italiana di Ecografia Cardiovascolare) registry. The average age of patients was 41.5 years (range: 1-92 years), 137 were males and 101 females. In 122 cases we found ventricular systolic dysfunctions with an EF average of 34.6%. The number of affected segments by non-compactation and diastolic dysfunction were found to be non-independent predictors of LV systolic dysfunction., Conclusion: From the analyses we carried out, it seems that ventricular dysfunction seems to be completely independent from the segment numbers of non compacted segments., (Copyright (c) 2009. Published by Elsevier Ireland Ltd.)

Apical hypertrophic cardiomyopathy (HC) is an uncommon variant of nonobstructive HC with peculiar characteristics. The investigators report a series of 13 consecutive Caucasian patients with a suspicion or diagnosis of apical HC on the basis of electrocardiographic and/or echocardiographic findings who prospectively underwent magnetic resonance imaging with late gadolinium enhancement (LGE) evaluation. All but 1 patient presented T-wave inversion in the anterolateral leads on electrocardiogram, with a mean maximum negative T wave of 7.0 +/- 3.9 mm. Echocardiography provided correct diagnoses in 9/13 patients (69%), while in 4 patients echocardiographic results were normal or inconclusive. Magnetic resonance imaging showed a spadelike morphology of the left ventricle in 6 patients and identified an apical aneurysm in 4. Eleven patients (85%) presented LGE with a mean percentage of 2.3 +/- 2.6% of total left ventricular mass. In 9 (69%) patients LGE was limited to the hypertrophic segments while in 6 (46%) patients it was also present in nonhypertrophic segments. In conclusion, magnetic resonance imaging in patients with apical HC showed a high incidence of apical aneurysms and a peculiar distribution of LGE, that was not limited to hypertrophic segments., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Randomized controlled trials have generated strong evidence on the efficacy of electrical device therapy in selected patients with heart failure (HF). The enrolment criteria of these three trials generated patient profiles that helped to shape current guidelines on chronic heart failure (CHF) treatment and sudden cardiac death (SCD) prevention. We investigated the prevalence of trial-generated profiles for implantable defibrillator or cardiac resynchronization therapy candidacy among HF outpatients; we explored differences between real-world and trial populations and we evaluated 1-year survival without device treatment., Methods: We reviewed Italian Network on Congestive Heart Failure (IN-CHF) registry patients (n = 4977) enrolled in a period (1995-2000) roughly concurrent with the MADIT-II and SCD-HeFT trials., Results: Regarding device eligibility, 14.5% IN-CHF patients at entry satisfied MADIT-II criteria, 6.8% satisfied CARE-HF criteria and as many as 47.9% fulfilled SCD-HeFT criteria. One-year overall mortality among non-implanted patients was 1.5 to 2-fold higher in each of these subgroups than in control arms of the corresponding trials. Among registry patients, different trial-profile combinations were associated with a wide range of 1-year outcomes (mortality, 8-35%; SCD/total mortality ratio, 0.35-0.57). Despite clear differences between registry and trial patients in pharmacological therapy (and clinical characteristics), none of the main drug classes independently predicted 1-year mortality in any of the IN-CHF subgroups., Conclusions: As many as half the IN-CHF outpatients fulfilled current criteria for device implantation. Various subgroups had higher 1-year mortality than patients in trial control arms - a finding that may not be entirely attributable to differences in drug therapy (especially beta blockers).

Aim of the Study: To compare three different methods for obtaining interventricular-(VV) interval optimization., Methods: A total of 30 patients undergoing cardiac resynchronization therapy (CRT) were enrolled. All the patients underwent VV-interval optimization performed with three different echocardiographic methods at seven different settings: simultaneous right (RV) and left (LV) ventricular pacing, LV stimulation only, LV preexcitation (LV+20,+40,+60 ms, respectively), RV preexcitation (RV+20 and+40 ms, respectively). Optimal VV delay was selected by: (1) measuring the aortic velocity time integral (VTI method); (2) measuring the time to maximum delay between septal and lateral longitudinal motion in the four-chamber view (velocity method); and (3) measuring the segment with maximal temporal difference of peak circumferential strain in short-axis view at papillary muscles level, (strain method). Velocity and strain methods measurements were obtained relying on two-dimensional ultrasound border tracking algorithm thus providing angle-independent measurements., Results: Immediately after CRT, VTI, maximum peak circumferential strain delay and maximum septal-to-lateral delay were significantly improved (P < 0.001). Particularly, VV-interval optimization determined a further improvement of these indices as compared to the other VV settings (P < 0.001). Furthermore, a substantial concordance was found between the optimal VV interval obtained according to the VTI method and velocity method (k = 0.68), between the optimal VV interval obtained according to the VTI method and strain method (k = 0.63); and between the optimal VV interval obtained according to the velocity method and strain method (k = 0.71)., Conclusions: VV-interval optimization was shown to determine a further benefit beyond CRT. A significant concordance was present between VV programming based on different echocardiographic methods.

The Doppler echocardiographic pattern of restrictive left ventricular (LV) filling has proved to be an important predictor of clinical course and prognosis in dilated cardiomyopathy. However, the relation between restrictive filling pattern and clinical course has not been systematically investigated in hypertrophic cardiomyopathy (HC). We assessed the prognostic implications of the Doppler restrictive filling pattern in 239 consecutive patients with HC in whom Doppler measurements of LV filling had been systematically recorded at initial evaluation and during follow-up. Restrictive LV filling was identified in 14 patients (5.9%) at initial evaluation and developed in 22 (9.2%) during follow-up. A close relation was identified between restrictive filling pattern and end-stage HC, with patients with restrictive filling showing a sixfold increase in risk of developing end-stage HC (hazard ratio 6.25, 95% confidence interval 1.90 to 20.57, p = 0.003). Over a median follow-up of 9.7 years, 22 patients (9.2%) died suddenly or received appropriate cardioverter-defibrillator interventions, and 54 (22.6%) had HC-related death or underwent heart transplantation. In a set of univariate and multivariate analyses including each of the generally accepted risk factors for cardiac death in HC, the restrictive filling pattern was a strong and independent marker of increased risk (hazard ratio for sudden cardiac events 3.51, 95% confidence interval 1.37 to 8.95, p = 0.009; hazard ratio for HC-related death or heart transplantation 3.54, 95% confidence interval 1.91 to 6.57, p <0.001) compared to patients without restrictive filling. In conclusion, in our study cohort, the Doppler pattern of restrictive LV filling proved to be a strong predictor of sudden death and HC-related death, independently of other markers for unfavorable prognosis in this disease.

Many large-scale studies demonstrated in aggregate that high-sensitivity C-reactive protein (hsCRP) levels are a strong, independent predictor of future vascular events and that hsCRP adds prognostic information on risk at all levels of LDL cholesterol, at all levels of the Framingham risk score, and at all levels of the metabolic syndrome. Moreover, hsCRP predicts risk of recurrent coronary events and has important prognostic value in acute coronary ischemia and after coronary interventions. The JUPITER study was aimed to determine whether long-term treatment with rosuvastatin (20 mg/die) will reduce the rate of major adverse cardiovascular events, defined as the combined endpoint of cardiovascular death, stroke, myocardial infarction, hospitalization for unstable angina, or arterial revascularization among individuals with LDL cholesterol levels < 130 mg/dl (3.36 mmol/I) who are at high risk because of an enhanced inflammatory response as indicated by hsCRP levels > 2 mg/I.

Background: Most studies of amyloidotic cardiomyopathy consider as a single entity the 3 main systemic cardiac amyloidoses: acquired monoclonal immunoglobulin light-chain (AL); hereditary, mutated transthyretin-related (ATTRm); and wild-type transthyretin-related (ATTRwt). In this study, we compared the diagnostic/clinical profiles of these 3 types of systemic cardiac amyloidosis., Methods and Results: We conducted a longitudinal study of 233 patients with clear-cut diagnosis by type of cardiac amyloidosis (AL, n=157; ATTRm, n=61; ATTRwt, n=15) at 2 large Italian centers providing coordinated amyloidosis diagnosis/management facilities since 1990. Average age at diagnosis was higher in AL than in ATTRm patients; all ATTRwt patients except 1 were elderly men. At diagnosis, mean left ventricular wall thickness was higher in ATTRwt than in ATTRm and AL. Left ventricular ejection fraction was moderately depressed in ATTRwt but not in AL or ATTRm. ATTRm patients less often displayed low QRS voltage (25% versus 60% in AL; P<0.0001) or low voltage-to-mass ratio (1.1+/-0.5 versus 0.9+/-0.5; P<0.0001). AL patients appeared to have greater hemodynamic impairment. On multivariate analysis, ATTRm was a strongly favorable predictor of survival, and ATTRwt predicted freedom from major cardiac events., Conclusions: AL, ATTRm, and ATTRwt should be considered 3 different cardiac diseases, probably characterized by different pathophysiological substrates and courses. Awareness of the diversity underlying the cardiac amyloidosis label is important on several levels, ranging from disease classification to diagnosis and clinical management.

The Italian Scientific Associations of Cardiologists and Cardiovascular Pathologists have produced this consensus document on the diagnostic role of endomyocardial biopsy (EMB) in terms of techniques, analysis and reporting. The document is intended for clinical cardiologists, hemodynamic experts, electrophysiologists, surgical pathologists, and cardiac surgeons. It has three main aims: a) to collocate EMB in the context of currently available tools for diagnosis of heart diseases; b) to provide recommendations for rational implementation; c) to outline key characteristics (standards) for Italian cardiology and surgical pathology centers that perform and analyze EMB. A general lack of prospective, controlled studies addressing EMB prohibited the use of traditional evidence-based recommendations that rely on classes of available evidence. Thus, it was agreed that three key points should be taken into account: a) the specific pathology to be diagnosed (or excluded); b) the existence of any alternative, non-invasive diagnostic techniques; c) the overall consequences of reaching a definite diagnosis on patients' clinical management. Accordingly, we propose recommendations for EMB based on the following levels of diagnostic value: level 1: no alternative method exists to reach a definite diagnosis that can have obvious consequences for clinical management; level 2a: no alternative method exists to reach a definite diagnosis; however, the implications for clinical management are uncertain; level 2b: no alternative method exists to reach a definite diagnosis; however, the diagnosis would not influence clinical management; level 3: an alternative method exists to reach a definite diagnosis. The second part of the document proposes current protocols for the preparation, analysis and reporting of EMB in the context of each main pathologic entity. Particular attention is given to tissue characterization and implementation of molecular tests.

Whereas it is well known that idiopathic HCM can present in newborns and infants, little information is available on HT in this very young age group. We report a series of 17 infants with idiopathic HCM, including two neonates with rapidly progressive severe HF for whom HT was necessary. When HF manifests in a newborn/infant with idiopathic HCM and extreme cavity size reduction, the possibility of a rapidly progressive clinical course should be anticipated and HT may become the only available therapeutic solution.

Aim: This study investigated the fate of the stent inner surface in carotid artery stenting (CAS). In addition, the occurrence of late cerebral micro-embolism after CAS has been studied in order to identify predictors and correlate it with a possible neo-intimal layer., Methods: A series of patients were evaluated before CAS through aortic arch trans-oesophageal echocardiography. Six months after CAS, the stent coverage by neo-intima and the possible presence of uncovered plaques were determined by high-resolution duplex scanning (5-17-Hz probe and 3D reconstruction). Possible micro-embolic signals (MESs) were evaluated through transcranial duplex scanning (30-min analysis of ipsilateral middle cerebral artery with a 1-4-Hz probe) and correlated with patients' characteristics, intimal media thickness (IMT) (>0.9mm vs. <0.9mm) and uncovered proximal plaques, type of stent (closed vs. open cells) and aortic arch complicated plaques (>4mm). Fisher's and Wilcoxon tests were used to evaluate differences across groups for categorical and continuous variables, respectively., Results: In the 68 CASs examined (40 closed cells and 28 open cells), the stent was completely covered by neo-intima in 52 cases (76.4%). Complete coverage was significantly correlated with IMT<0.9mm and the absence of a proximal plaque uncovered by the stent (100% vs. 0%, p<0.001). Hypertension was an independent predictor of complete intimal coverage (p=0.002), while the stent type did not influence this process. The MESs were significantly more frequent in patients with complicated aortic arch plaques (62.5% vs. 23.8%, p<0.012), independently from all other factors., Conclusions: The extent of the stent neo-intimal formation is independent of stent type, but it is correlated with proximal plaque coverage. Six months after CAS, MESs are still possible and are not prevented by complete neo-intimal stent coverage. Complicated aortic arch atherosclerosis is an independent predictor of late MES, thus underlying its importance in cerebral ischaemia onset.

Background: The prognostic significance of syncope has not been investigated systematically in hypertrophic cardiomyopathy, and treatment strategies have been based largely on intuition and experience., Methods and Results: We assessed the relationship between syncope and sudden death in 1511 consecutive patients with hypertrophic cardiomyopathy. Unexplained (n=153) or neurally mediated (n=52) syncope occurred in 205 patients (14%). Over a 5.6+/-5.2-year follow-up, 74 patients died suddenly. Relative risk of sudden death was 1.78 (95% confidence interval 0.88 to 3.51, P=0.08) in patients with unexplained syncope and 0.91 (95% confidence interval 0.00 to 3.83, P=1.0) in those with neurally mediated syncope compared with patients without syncope. In multivariable analysis, the temporal proximity of unexplained syncope to initial patient evaluation was independently associated with risk of sudden death (P=0.006). Patients with unexplained syncope within 6 months before the initial evaluation showed a 5-fold increase in risk compared with patients without syncope (adjusted hazard ratio 4.89, 95% confidence interval 2.19 to 10.94), a relationship that was maintained throughout all age groups (<18, 18 to 39, and > or =40 years). Older patients (> or =40 years of age) with remote episodes of syncope (>5 years before initial evaluation) did not show an increased risk of sudden death (adjusted hazard ratio 0.38, 95% confidence interval 0.05 to 2.74)., Conclusions: In the present large cohort of patients with hypertrophic cardiomyopathy, unexplained syncope was a risk factor for sudden death. Patients with syncopal events that occurred in close temporal proximity to the initial evaluation showed a substantially higher risk of sudden death than patients without syncope. Older patients with remote syncopal events did not show an increased risk.

Aims: Cardiac resynchronization therapy (CRT) improves functional capacity and survival in heart failure. However, one-third of patients fail to respond to CRT. Resting left ventricular (LV) dyssynchrony assessed by echocardiography (ECHO) showed discordant results in identifying CRT responders. LV dyssynchrony can totally change during exercise. Aim of this study was to evaluate whether exercise dyssynchrony could select responders to CRT., Methods and Results: Sixty-four patients scheduled for CRT implantation performed bicycle exercise ECHO in semi-supine position on an exercise tilting table before and 6 months after CRT implantation. Tissue Doppler imaging (TDI) was acquired both at rest and during exercise to detect LV mechanical dyssynchrony. Predictive values for CRT response were 70% for rest TDI and 89% for exercise TDI (P = 0.01). Exercise LV dyssynchrony was the only parameter independently associated with follow-up improvement of rest ejection fraction and LV volume during multivariable analysis (P < 0.001). Functional improvement at 6-min walking test was statistically higher in patients with exercise dyssynchrony (P = 0.005), and not different considering rest dyssynchrony (P = 0.30)., Conclusion: Exercise intraventricular dyssynchrony assessed by exercise TDI ECHO is a strong independent predictor of CRT response. It could be used to select candidates for CRT, thus reducing ineffective implantations of biventricular pacemakers.

Background: Carotid artery stenting (CAS) leads to frequent embolic brain lesions; their source has not been clearly identified yet. In order to investigate this phenomenon, we have evaluated embolic brain lesions (BL) after CAS and correlated them with aortic arch (AA) characteristics., Methods: The AAs of 59 patients undergoing CAS under distal protection were evaluated by angiography and transesophageal echocardiography (TEE). AAs were stratified according to morphology (type I and II "simple" vs type III and bovine "difficult"), atherosclerotic arch lesions (complicated: >5 mm or with mobile debris vs uncomplicated: <5 mm), and tortuosity index (TI; sum of all angles diverging from ideal carotid axis, <150 vs >150). Diffusion weighted imaging (DWI) was performed before and within 24 hours from CAS. New BL were considered ipsilateral (IL) if ipsilateral to the site of CAS and non-ipsilateral (CL) if contralateral to it or bilateral. Normality distribution was by Shapiro-Wilk test (variables reported as medians +/- interquartile range) and statistical significance (P < .05) by Wilcoxon and Fisher's exact test., Results: Difficult arches were present in 17 patients (28.8%), complicated aortic plaque in 21 (35.5%), and TI > 150 in 34 (57.6%). New BL appeared in 34 or 57.6% patients (6 or 18% IL and 28 or 82% CL). The mean number of BL was 5.7 (range, 0 to 20), 4.7 IL, and 5.7 CL, with a median volume of 560.95 +/- 1677.7 mm(3). Type of arch and TI were not correlated with mean number of BL. Mean volume of BL were greater in patients with difficult AA, complicated plaques, and TI > 150 (258 (572) mm(3) vs 15.6 (353) mm(3), P = .2; and 86 (828) mm(3) vs 85.9 (352) mm(3), P = .4 172 (766) mm(3) vs 0 (228) mm(3), P = .06, respectively). In patients with all three AA characteristics, mean number and volume of BL was significantly greater compared with other patients. Specifically, this increase was due mainly to CL (IL 0 (117) mm(3) vs 0 (172) mm(3), P = .9; CL 564 (687) mm(3) vs 0 (133) mm(3), P = .001). None of the technical details considered was correlated with either IL or CL., Conclusion: BL are frequent after protected CAS and are correlated with AA characteristics, thus underlining the role of catheterization maneuvers in determining embolic events. TEE may be useful in patient's selection for CAS.

In acute aortic dissection (AAD), timely diagnosis is challenging. However, dedicated studies of the entity and determinants of delay are currently lacking. We surveyed pre-/in-hospital time to diagnosis and explored risk factors for diagnostic delay. We analyzed the dedicated database of a metropolitan AAD network (161 patients diagnosed since 1996; 115 Stanford type A) in terms of hospital arrival times (from pain to presentation at any hospital) and in-hospital diagnostic times (presentation to final diagnosis). Median (interquartile range) in-hospital diagnostic times were approximately twofold greater than hospital arrival times (177 minutes, 644, vs 75 minutes, 124, p = 0.0001, Wilcoxon test). Median annual in-hospital diagnostic times were most often approximately 3 hours (spread was wide, but decreased after 2001; rho = -0.94, p = 0.005). Risk factors (univariate analysis) for in-hospital diagnostic time >75th percentile (12 hours) included pleural effusion (odds ratio 3.96, 95% confidence interval 1.80 to 8.69), dyspneic presentation (odds ratio 3.33, 95% confidence interval 1.93 to 8.59), and age <70 years (odds ratio 2.34, 95% confidence interval 1.03 to 5.36). Systolic arterial pressure < or =105 mm Hg decreased the likelihood of lengthy diagnosis (odds ratio 0.08, 95% confidence interval 0.01 to 0.59). In patients (n = 82) with routine values (since 2000), troponin positivity (odds ratio 3.63, 95% confidence interval 1.12 to 11.84) and an acute coronary syndrome-like electrocardiogram (odds ratio 2.88, 95% confidence interval 1.01 to 8.17) were also risk factors. In conclusion, in a metropolitan setting, most of the diagnostic delay may occur in hospital. At presentation, pleural effusion, troponin positivity, acute coronary syndrome-like electrocardiogram, and dyspnea are possible "clinical confounders" associated with particularly long in-hospital diagnostic times.

Takotsubo cardiomyopathy is a syndrome characterized by acute regional systolic dysfunction of the left ventricle, frequently related to psycho-physical acute stress, and usually reversible. This rare syndrome involves more often the female sex with the highest frequency of occurrence between the seventh and eighth decade of life. Etiology has not been clarified yet and several hypotheses have been postulated: multiple epicardial coronary artery damage, abnormal coronary microcirculation, catecholamine-mediated cardiac toxicity, and neurogenic stunning. Clinical presentation is not easy to distinguish from an acute coronary syndrome: chest pain at rest or dyspnea, new-onset electrocardiographic changes, characterized by ST-segment elevation or T-wave inversion. Coronary angiography, which should be performed within 48 h of symptom onset in order to be diagnostic, excludes the presence of significant atherosclerotic stenosis or plaque rupture. Ventricular angiography shows the typical regional wall motion abnormalities (apical akinesia and hyperkinesia of the mid-basal segments) that give to the syndrome its name (takotsubo is a traditional Japanese octopus trap or pot). Echocardiography performed in the acute phase also evidences wall motion abnormalities that characteristically regress in the following days. There is no specific treatment for this syndrome, but supportive and symptomatic therapy is usually administered.

Background: Noncompaction of left ventricular myocardium is a rare congenital cardiomyopathy resulting from an incomplete myocardial morphogenesis that leads to the persistence of the embryonic myocardium. This condition is characterized by a thin compacted epicardial and an extremely thickened endocardial layer with prominent trabeculations and deep intertrabecular recesses. It is not clear, in noncompaction of myocardium, whether intertrabecular recesses could be responsible for thrombi formation and thromboembolic complications., Methods: The prevalence of stroke and echocardiographic finding of thrombus was evaluated in a continuous series of 229 patients (men and women) affected by noncompaction of the left ventricular myocardium, who were included in the SIEC registry. We excluded patients affected by atrial fibrillation., Results: The mean age of the patients was 49.5 years. Fifty percent of the patients were affected by a ventricular systolic dysfunction. The mean period of follow-up was 7.3 years. Only four patients had a history of ischemic stroke. A large thrombus into the left ventricular chamber was observed in a 1-year-old child affected by Behcet's disease (high risk of thrombi formation)., Conclusion: Noncompaction of the left ventricular myocardium, by itself, does not seem to be a risk factor for stroke or embolic results, so there is no indication for oral anticoagulant therapy.

Objectives: The aim of this study was to analyze the long-term follow-up of dilated cardiolaminopathies., Background: Lamin A/C (LMNA) gene mutations cause a variety of phenotypes. In the cardiology setting, patients diagnosed with idiopathic dilated cardiomyopathy (DCM) plus atrioventricular block (AVB) constitute the majority of reported cases., Methods: Longitudinal retrospective observational studies were conducted with 27 consecutive families in which LMNA gene defects were identified in the probands, all sharing the DCM phenotype., Results: Of the 164 family members, 94 had LMNA gene mutations. Sixty of 94 (64%) were phenotypically affected whereas 34 were only genotypically affected, including 5 with pre-clinical signs. Of the 60 patients, 40 had DCM with AVB, 12 had DCM with ventricular tachycardia/fibrillation, 6 had DCM with AVB and Emery-Dreifuss muscular dystrophy type 2 (EDMD2), and 2 had AVB plus EDMD2. During a median of 57 months (interquartile range 36 to 107 months), we observed 49 events in 43 DCM patients (6 had a later event, excluded from the analysis). The events were related to heart failure (15 heart transplants, 1 death from end-stage heart failure) and ventricular arrhythmias (15 sudden cardiac deaths and 12 appropriate implantable cardioverter-defibrillator interventions). By multivariable analysis, New York Heart Association functional class III to IV and highly dynamic competitive sports for >or=10 years were independent predictors of total events. By a bivariable Cox model, splice site mutations and competitive sport predicted sudden cardiac death., Conclusions: Dilated cardiomyopathies caused by LMNA gene defects are highly penetrant, adult onset, malignant diseases characterized by a high rate of heart failure and life-threatening arrhythmias, predicted by New York Heart Association functional class, competitive sport activity, and type of mutation.

Objectives: To evaluate implementation of low-density lipoprotein cholesterol (LDL-C) control recommendations in secondary care and explore key points in the decisional workup., Methods and Results: In a nationwide survey of secondary-care outpatients (n=11,124), we studied prevalence/predictors of (1) LDL-C value availability; (2) ongoing treatment with statins; (3) achievement of US National Cholesterol Education Program III target LDL-C values. Agreement between US National Cholesterol Education Program III risk category and physicians' personal risk assessments was also studied. LDL-C values were available for 78% evaluable patients; 71% of the patients with dyslipidema were undergoing treatment with statins; 34% patients undergoing treatment had target LDL-C values. At regression analysis, non-availability of LDL-C values was predicted by absence of diabetes, presence of normotension, and advancing age; lack of statins treatment by female sex, diabetes, overweight and northern location (southern location predicted treatment); non-achievement of target LDL-C values by age, diabetes, attending a diabetic clinic, cigarette smoking, history of cardiovascular disease, and taking less than six pills per day. Physicians provided underestimates of patients' risk (39% high-risk patients were rated as intermediate-risk patients and a further 10% as low-risk patients)., Conclusion: Suboptimal prevention practice seems to be associated with various factors acting at different levels within the complex process running from individual risk-level ascertainment to LDL-C target achievement. Multicomponent interventions that target the different key steps need to be considered.

Despite meaningful progress in the identification of risk factors and the development of highly effective prevention tools, the residual risk of cardiovascular events remains high (about 60-70% in the major outcome trials dealing with statins). Awareness of this problem can properly orient the search for new effective and efficient preventive strategies.