The Role of New Imaging Technologies in the Diagnosis of Cardiac Amyloidosis.

Cardiac amyloidosis is an infiltrative disorder caused by transthyretin or immunoglobulin free light-chain deposition, which determines clinical disease with similar phenotype but different time course, prognosis and therapy. Multimodality imaging is the cornerstone for disease diagnosis and management. Multimodality imaging has revolutionized the approach to the disease favoring its awareness and simplifying its diagnosis, especially in ATTR cardiac amyloidosis. This describes the different imaging tools, from the traditional to the more novel ones, and highlights the different approach in each different setting (prognosis, subtyping, prognosis, monitoring disease progression, and response to therapy).

Lights and shadows of long-term dual antiplatelet therapy in "real life" clinical scenarios.

Dual antiplatelet therapy (DAPT) is a cornerstone of treatment for patients with acute coronary syndromes (ACS). Mounting evidences have opened the debate about the optimal DAPT duration. Considering the ACS-pathophysiology, the most recent guidelines recommend DAPT in all ACS patients for at least 12 months unless there are contraindications such as excessive risk of bleeding. Thus, it can be considered acceptable earlier discontinuation if the risk of morbidity from bleeding outweighs the anticipated benefit. On the other hand, several studies have clearly indicated that a significant burden of platelet related-events, such as stroke and new ACS might occur after this period, suggesting that potential benefits might derive by prolonging DAPT beyond 12 months (Long DAPT). Indeed, although current guidelines give some indications about patients eligible for Long DAPT, they do not embrace several real-life clinical scenarios. Thus, in such scenarios, how to decide whether a patient is eligible for Long DAPT or not might be still challenging for clinicians. This position paper presents and discusses various "real-life" clinical scenarios in ACS patients, in order to propose several possible recommendations to overcome guidelines potential limitations.

The mitral-to-aortic flow-velocity integral ratio in the real world echocardiographic evaluation of functional mitral regurgitation before and after percutaneous repair.

INTRODUCTION: Percutaneous mitral valve repair (PMVR) using MitraClip system has emerged as a therapeutic option for patients with functional severe mitral regurgitation (FMR) at prohibitive risk for surgery. In this setting, the echocardiographic assessment of FMR severity is challenging because the traditional echocardiographic methods have important limitations. The aim of this study was to assess the accuracy and reliability of a simple Doppler index, the mitral/aortic flow velocity integral ratio (MAVIR), to evaluate residual FMR severity after PMVR. METHODS: Eighty-five heart failure patients with functional MR and LV dysfunction (LVEF ≤ 40%) were included. FMR was quantified on the basis of traditional quantitative parameters of MR severity. MAVIR was expressed as the ratio of mitral and aortic time velocity integral (TVI) values. According to MR severity, 25 patients underwent MC implantation and at 6 months a complete echocardiographic follow-up was performed. RESULTS: A significant linear relationship was found between MAVIR and both VC and EROA. A MAVIR ≥1.02 identified pts with severe MR with a sensitivity of 86.7% and a specificity of 90.9%. At the 6 months echocardiographic follow-up after the MitraClip implantation, we observed a significant reduction of LAVI, LVED and LVES volume, while LVEF improved. Furthermore, MAVIR significantly decreased its decrease showed a significant linear relationship with LAVI reduction. CONCLUSION: Our data show a close relationship between MAVIR and traditional indexes of MR severity in patients with FMR. This Doppler-derived index seems applicable after PMVR where traditional echocardiographic index of MR severity shows significant limitations.

Incremental Value of Pocket-Sized Echocardiography in Addition to Physical Examination during Inpatient Cardiology Evaluation: A Multicenter Italian Study (SIEC).

BACKGROUND: We prospectively assessed the incremental value of a pocket-sized echocardiography (PSE) device during cardiology consultations, in addition to physical examination, ECG reading, and chest x-ray. METHODS: A total of 443 consecutive patients (53% men), referred for bedside consultations, underwent physical examination, ECG, and CXR, followed by PSE examination. The physician completed a detailed questionnaire (clinical and echocardiographic data, scanning time, abnormal results). Receiver operating characteristic (ROC) curve analysis was generated to test the predictive discrimination value of the different methods. The incremental value of PSE examination compared to clinical visit alone or combined with ECG results was expressed as a global chi-square value. RESULTS: The PSE examination did not influence the definitive diagnosis in only 23.5% of cases, while 25.3% of the diagnoses were confirmed and verified by PSE. The clinical diagnosis was enriched by PSE in 21.9% of cases, and the diagnosis was changed in 26.2%. The area under curve (AUC) of physical examination + ECG results (sensitivity: 80%; specificity: 67%) was significantly higher than physical examination alone (sensitivity: 75%; specificity: 62%) (P < 0.0002), and the AUC of PSE results (sensitivity: 88%; specificity: 86%) was significantly higher than physical examination + ECG results (P < 0.0001). The PSE results, combined with clinical and ECG results, had a significant incremental diagnostic value during cardiology consultation when compared to the clinical visit alone or with ECG results (P < 0.0001). CONCLUSIONS: PSE had an incremental diagnostic value during bedside cardiology consultation, increasing the number of appropriate diagnoses and reducing the routine use of echocardiography.

Left atrium by echocardiography in clinical practice: from conventional methods to new echocardiographic techniques.

Although often referred to as "the forgotten chamber", compared with left ventricle (LV), especially in the past years, the left atrium (LA) plays a critical role in the clinical expression and prognosis of patients with heart and cerebrovascular disease, as demonstrated by several studies. Echocardiographers initially focused on early detection of atrial geometrical abnormalities through monodimensional atrial diameter quantification and then bidimensional (2D) areas and volume estimation. Now, together with conventional echocardiographic parameters, new echocardiographic techniques, such as strain Doppler, 2D speckle tracking and three-dimensional (3D) echocardiography, allow assessing early LA dysfunction and they all play a fundamental role to detect early functional remodelling before anatomical alterations occur. LA dysfunction and its important prognostic implications may be detected sooner by LA strain than by volumetric measurements.

Left atrial volume index in healthy subjects: clinical and echocardiographic correlates.

Left atrial (LA) size is related to cardiovascular morbidity and mortality. The relative role of multiple determinants of LA morphology in healthy subjects remains incompletely defined. The aim of this study is to define normal ranges for LA diameters and volume index (LAVi), and to investigate clinical and echocardiographic correlates. A total of 1480 healthy individuals (mean age 36.1 ± 15.5 years, range 20-80; 61% males) underwent a comprehensive transthoracic echocardiography exam including assessment of LAVi calculated using the biplane area-length method at the apical four-chamber and two-chamber views at ventricular end systole (maximum LA size) and indexed for body surface area (BSA). Mean LAVi in the overall population was 29.5 ± 10.8 mL/m(2) (range: 26.1-41.8 mL/m(2) ). Distinct higher values were found in subjects ≥50 years as compared with those <50 years of age (33.4 ± 12.5 vs. 29.1 ± 13.5; P < 0.001). On univariate analysis, LA volume was significantly associated with age (r = 0.48, P < 0.0001), male gender (r = 0.28, P < 0.05), BSA (r = 0.51, P < 0.0001), mitral E/E' (r = 0.47, P < 0.0001), LV end-diastolic volume (r = 0.52, P < 0.0001), and LV mass index (r = 0.31, P < 0.05). Multivariable analysis identified age, BSA, LV end-diastolic volume, and mitral E/E' ratio as the only independent determinants of LA volume (model R(2) = 0.54, P < 0.0001). Gender was an independent predictor of most absolute LA volume, but following normalization to BSA, some associations became nonsignificant. In healthy individuals LAVi vary significantly by age, BSA, diastolic function, and LV dimensions, with lesser effects of gender.

[Endocarditis complicated by anterior myocardial infarction: a case report. What the guidelines do not say]. / Endocardite infettiva complicata da infarto anteriore: un caso clinico. Quello che le linee guida non dicono.

Acute myocardial infarction is an uncommon complication of infective endocarditis, burdened by high mortality and often underdiagnosed. Due to its reduced frequency, current guidelines do not always highlight this condition or provide clear indications regarding treatment. We present a case of acute coronary syndrome induced by the occlusion of the anterior descending artery, due to a septic embolus and treated by aspiration of the embolic material. The clinical-instrumental aspects necessary to raise the suspicion of endocarditis and make the diagnosis are then examined. Subsequently, all the possible therapeutic strategies and any complications of the traditional treatment of acute coronary syndromes during infectious valve disease are analyzed. Since clinical presentation may be extremely variable, the establishment of a multidisciplinary team would allow, in these cases, a more appropriate and complete diagnostic and therapeutic management.

Impact of synchronous atrioventricular delay optimization on left ventricle flow force angle evaluated by echocardiographic particle image velocimetry.

PURPOSE: To evaluate the improvement in electrical synchrony and left ventricle (LV) hemodynamics provided by combining the dynamic atrioventricular delay (AVD) of SyncAVTM CRT and the multiple LV pacing sites of MultiPoint pacing (MPP). METHODS: Patients with LBBB and QRS duration (QRSd) > 140 ms implanted with a CRT-D or CRT-P device and quadripolar LV lead were enrolled in this prospective study. During a post-implant follow-up visit, QRSd was measured from 12-lead surface electrograms by experts blinded to pacing configurations. QRSd reduction relative to intrinsic rhythm was evaluated during biventricular pacing (BiV) and MPP for two AVDs: nominal (140/110 ms paced/sensed) and SyncAV (patient-optimized SyncAV offset [10-60 ms] minimizing QRSd). Echocardiography particle imaging velocimetry (Echo-PIV) analysis was performed for each configuration. The resulting hemodynamic force LV flow angle (φ) was analyzed, which ranges from 0o (predominantly base-apex forces) to 90o (predominantly transverse forces). Higher angles indicate more energy dissipation at lateral walls due to transverse flow; lower angles indicate healthier flow aligned with the longitudinal base-apex path of the pressure gradient. RESULTS: Twelve patients (58% male, 17% ischemic, 32±7% ejection fraction, 165 ± 18 ms intrinsic QRSd) completed QRSd and Echo-PIV assessment. Relative to intrinsic rhythm, BiV and MPP with nominal AVD reduced QRSd by 10 ± 9% and 12 ± 9%, respectively. BiV+SyncAV and MPP+SyncAV further reduced QRSd by 19 ± 8%, (p < 0.05 vs. BiV with nominal AVD) and 23 ± 9% (p < 0.05 vs BiV+SyncAV), respectively. Echo-PIV showed similar sequential hemodynamic improvements. LV flow angular orientation during intrinsic activation (46 ± 3o) reduced with BiV+SyncAV (37 ± 4o, p < 0.05 vs intrinsic) and further with MPP+SyncAV (34 ± 4o, p < 0.05 vs BiV+SyncAV). CONCLUSION: These results suggest that SyncAV may improve electrical synchrony and influence LV flow patterns in patients suffering from heart failure compared to conventional CRT with a fixed AVD, with further improvement observed by combining with MPP.

The Impact of the COVID-19 Outbreak on Patients' Adherence to PCSK9 Inhibitors Therapy.

PCSK9 inhibitors (PCSK9i) are monoclonal antibodies that have been shown to be effective in reducing both LDL cholesterol (LDL-C) values and major cardiovascular events in patients at high cardiovascular risk. Adherence to PCSK9i is critical for the success of the treatment. The aim of the present study is to evaluate patients' adherence to PCSK9i during the COVID-19 pandemic. Patients referred to the Cardiac Diagnostic Unit of the University of Campania "Luigi Vanvitelli" Naples, taking PCSK9i, and who missed the cardiological follow-up visit during the first national COVID-19 lockdown (9 March-17 May 2020), were included. Each patient underwent medical teleconsultation to collect current clinical conditions, adherence to drug treatments, and lipid profile laboratory tests. Among 151 eligible patients, 20 were excluded for missing or untraceable telephone numbers and one for refusing to join the interview. The selected study population consisted of 130 patients (64 ± 9 years, 68% males), of whom 11 (8.5%) reported a temporary interruption of the PCSK-9 therapy for a mean period of 65 ± 1.5 days. The non-adherent patients showed a marked increase in LDL-C than in the pre-pandemic period (90.8 ± 6.0 vs. 54.4 ± 7.7 mg/dL, p < 0.0001), and 82% of patients moved out of the LDL-C therapeutic range. The non-adherent group was more likely to have a very high cardiovascular risk compared to the adherent group (81.8 vs. 33.6%, p < 0.001). Causes of interruption included drug prescription failure (63.6%) due to temporary interruption of the non-urgent outpatient visits and failure in drug withdrawal (36.4%) due to patients' fear of becoming infected during the pandemic. The COVID-19 lockdown caused a remarkable lack of adherence to PCSK9i therapy, risking negative implications for the health status of patients at high cardiovascular risk. Facilitating patients' access to PCSK9i and enhancing telemedicine seem to be effective strategies to ensure the continuity of care and appropriate management of these patients.

Early left ventricular longitudinal systolic dysfunction and cardiovascular risk factors in 1,371 asymptomatic subjects with normal ejection fraction: a tissue Doppler study.

BACKGROUND: Nowadays early diagnosis of left ventricular (LV) dysfunction represents a major challenge in asymptomatic subjects with cardiovascular (CV) risk factors. Tissue Doppler imaging (TDI) recently emerged as an important tool with clinical relevance in several cardiac diseases. AIM: To evaluate the ability of TDI in detecting early longitudinal ventricular dysfunction in asymptomatic subjects, with LV ejection fraction >55%, normal diastolic function, and its relationship with CV risk factors. METHODS: A total of 1,371 subjects (median age 60 years, 595 males) formed our study population: Controls, 265 healthy subjects; Group I, 434 subjects with one CV risk factor; Group II, 401 subjects with two CV risk factors; Group III, 271 subjects with ≥ 3 CV risk factors. All subjects underwent a comprehensive standard echo Doppler evaluation, including PW-TDI study. RESULTS: Diastolic parameters such as (E\A, A-wave, Em\Am; E\Em) were able to discriminate the number of CV risk factors. The only systolic parameter that progressively reduced by increasing the number of CV risk factors was LV global longitudinal systolic function (Sm), (P < 0.0001). At multivariate analysis, the only functional parameter able to predict the increasing number of CV risk factors was Sm (P < 0.001). CONCLUSIONS: TDI is able to identify early longitudinal LV systolic abnormalities in presence of apparently normal systolic and diastolic function and progressively impairs with increasing CV risk factors. These findings could be clinically relevant in identifying asymptomatic subjects who need a early tailored preventive treatment.

Impact of obesity on left ventricular geometry and function in pediatric patients after successful aortic coarctation repair.

AIMS: To evaluate if obesity has an additional negative impact on left ventricular (LV) geometry and function in normotensive pediatric patients >12 months after successful treatment of aortic coarctation (CoA). METHODS AND RESULTS: We studied 40 CoA patients (mean age 14 ± 3 years, and male sex 70%), of them 10 were obese and 30 lean. Both groups were age and sex comparable. The entire studied sample underwent 24-ambulatory blood pressure (BP) monitoring, standard echocardiographic evaluation, and speckle tracking study. Both office and 24-hour diastolic BP were significantly increased in obese patients. Obese CoA patients showed increased LV mass (52 ± 13 g/m(2.7) vs. 43 ± 9 g/m(2.7) , P = 0.02), and significant reduction in E/A compared with lean CoA patients. Myocardial deformation properties were significantly reduced in obese CoA patients in all the three studied planes (longitudinal, radial, and circumferential) compared with CoA lean patients. LV twist values showed a significant reduction in the obese CoA group (9.9° ± 2.2° vs. 14.5° ± 2.3°, P < 0.0001). CONCLUSIONS: Our study shows that obesity in successfully treated CoA children, has an additional negative effect on BP, LV mass, and cardiac function. These findings are of particular concern, since life expectancy in CoA patients is limited mainly by atherosclerosis, and all the obesity-associated abnormalities found are harbingers of higher cardiovascular risk.

Regulation of Inflammation and Oxidative Stress by Formyl Peptide Receptors in Cardiovascular Disease Progression.

G protein-coupled receptors (GPCRs) are the most important regulators of cardiac function and are commonly targeted for medical therapeutics. Formyl-Peptide Receptors (FPRs) are members of the GPCR superfamily and play an emerging role in cardiovascular pathologies. FPRs can modulate oxidative stress through nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent reactive oxygen species (ROS) production whose dysregulation has been observed in different cardiovascular diseases. Therefore, many studies are focused on identifying molecular mechanisms of the regulation of ROS production. FPR1, FPR2 and FPR3 belong to the FPRs family and their stimulation triggers phosphorylation of intracellular signaling molecules and nonsignaling proteins that are required for NADPH oxidase activation. Some FPR agonists trigger inflammatory processes, while other ligands activate proresolving or anti-inflammatory pathways, depending on the nature of the ligands. In general, bacterial and mitochondrial formylated peptides activate a proinflammatory cell response through FPR1, while Annexin A1 and Lipoxin A4 are anti-inflammatory FPR2 ligands. FPR2 can also trigger a proinflammatory pathway and the switch between FPR2-mediated pro- and anti-inflammatory cell responses depends on conformational changes of the receptor upon ligand binding. Here we describe the detrimental or beneficial effects of the main FPR agonists and their potential role as new therapeutic and diagnostic targets in the progression of cardiovascular diseases.

Global Left Ventricular Myocardial Work Efficiency in Heart Failure Patients with Cardiac Amyloidosis: Pathophysiological Implications and Role in Differential Diagnosis.

INTRODUCTION: Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy and a common cause of heart failure with preserved and mid-range ejection fraction (HFpEF and HFmrEF). Left ventricular (LV) systolic assessment is pivotal in differential diagnostic and prognostic stratification in CA. However, nondeformation and deformation-based parameters classically implied had many limitations. Myocardial work (MW) has been recently introduced for the evaluation of myocardial performance, in a load-independent fashion, in patients with cardiomyopathies. AIMS: This study aimed to evaluate MW parameters in LV performance assessment in CA and their possible role in differential diagnosis between AL and ATTR forms, compared with other echocardiographic parameters, also exploring the possible association between MW parameters and blood biomarkers. MATERIALS AND METHODS: The study population consisted of 25 patients with CA (10 with AL amyloidosis and 15 with wild-type ATTR [ATTRwt] form) and HFpEF or HFmrHF, enrolled between March 2018 and December 2019, undergoing a comprehensive clinical, biochemical, and imaging evaluation. Ten healthy individuals were studied as controls. ATTR patients had a noninvasive diagnosis of wtATTR-CA (positive 99mTc-hydroxy methylene-diphosphonate scintigraphy with a negative hematological screening), while AL patients underwent endomyocardial biopsy. All patients underwent standard transthoracic echocardiography. MW and related indices were estimated using a vendor-specific module. RESULTS: Compared to the ATTRwt group, patients in the AL group showed a more pronounced myocardial performance impairment assessed by Global Word Efficiency (GWE: 83.5% ± 6.3% vs. 88.2% ± 3.6%; P = 0.026). In multiple linear regression analysis, cardiac troponin I (Β = -0.55; P < 0.0001), global longitudinal strain (Β =0.35; P < 0.008), and regional relative strain ratio (Β = -0.30; P < 0.016) were significant predictors of GWE reduction in CA patients. At receiver operating characteristics curve analysis, among all other deformation-based and nondeformation-based echocardiographic parameters, GWE showed the highest area under the curve (AUC) (AUC 0.74; 95% CI: 0.55-0.96; P < 0.04). The optimal cutoff was determined by sensitivity/specificity analysis: a GWE < 86.5% identified patients with AL amyloidosis with a sensitivity and specificity, respectively, of 80.0% and 66.7%. CONCLUSIONS: The results of our pivotal study seem to highlight the importance of new deformation parameters to study myocardial performance in patients with CA, and to differentiate between AL CA and ATTR CA.

Left atrial volume index in highly trained athletes.

BACKGROUND: Increase of left atrial (LA) diameter in trained athletes has been regarded as another component of the "athlete's heart". AIMS: To evaluate the possible impact of competitive training on LA volume and to define reference values of LA volume index in athletes. METHODS AND RESULTS: Six hundred fifteen consecutive elite athletes (370 endurance- [ATE] vs 245 strength-trained athletes [ATS]; 385 men; 28.4 +/- 10.2 years, range 18-40 years) underwent a comprehensive transthoracic echocardiography exam. LA maximal volume was measured at the point of mitral valve opening using the biplane area-length method, and corrected for body surface area. LA mild dilatation was defined as a LA volume index between 29 and 33 mL/m(2), while a moderate dilatation was identified by a LA volume index > or =34 mL/m(2). Left ventricular (LV) mass index and ejection fraction did not significantly differ between the 2 groups. Conversely, ATS showed increased body surface area, sum of wall thickness (septum + LV posterior wall), LV circumferential end-systolic stress (ESSc) and relative wall thickness, whereas LA volume index, LV stroke volume and LV end-diastolic volume were greater in ATE. The range of LA volume index was 26 to 36 mL/m(2) (mean 28.2 +/- 9.2) in men and 22 to 33 mL/m(2) (mean 26.5 +/- 7.2) in women (P < .01). LA volume index was mildly enlarged in 150 athletes (24.3%) and moderately enlarged only in 20, all males (3.2%). Mild mitral regurgitation was observed in 64 athletes (10.3%). LA volume index was significantly greater in ATE (P < .01). By multivariate analysis, the overall population type (P < .01) and duration (P < .01) of training and LV end-diastolic volume (P < .001) were the only independent predictors of LA volume index. CONCLUSIONS: In a large population of highly trained athletes, a mild enlargement of LA volume index was relatively common and may be regarded as a physiologic adaptation to exercise conditioning.

Recommendations for echocardiography use in the diagnosis and management of cardiac sources of embolism: European Association of Echocardiography (EAE) (a registered branch of the ESC).

Embolism of cardiac origin accounts for around 15-30% of ischaemic strokes. Strokes due to cardioembolism are generally severe and early and long-term recurrence and mortality are high. The diagnosis of a cardioembolic source of stroke is frequently uncertain and relies on the identification of a potential cardiac source of embolism in the absence of significant autochthone cerebrovascular occlusive disease. In this respect, echocardiography (both transthoracic and/or transoesophageal) serves as a cornerstone in the evaluation, diagnosis, and management of these patients. A clear understanding of the various types of cardiac conditions associated with cardioembolic stroke and their intrinsic risk is therefore very important. This article reviews potential cardiac sources of embolism and discusses the role of echocardiography in clinical practice. Recommendations for the use of echocardiography in the diagnosis of cardiac sources of embolism are given including major and minor conditions associated with the risk of embolism.

Right ventricular myocardial involvement in either physiological or pathological left ventricular hypertrophy: an ultrasound speckle-tracking two-dimensional strain analysis.

AIMS: To analyse right ventricular (RV) myocardial deformation in patients with left ventricular (LV) hypertrophy secondary to either hypertrophic cardiomyopathy (HCM) or athlete's competitive endurance training. METHODS AND RESULTS: Standard Doppler echo, exercise stress echo, and 2D speckle-tracking strain echocardiography (2DSE) of RV longitudinal deformation in RV septal and lateral walls were performed in 50 top-level endurance athletes and in 35 patients with HCM, all men, having evidence of LV hypertrophy. Right ventricular global longitudinal strain (GLS) was calculated by averaging local strains along the entire right ventricle. The two groups were comparable for age and blood pressure, whereas athletes showed lower heart rate and increased body surface area than HCM. Interventricular septal thickness was higher in HCM, whereas both LV and RV end-diastolic diameters (LVEDD and RVEDD) and LV stroke volume were increased in athletes. Right ventricular tricuspid annulus systolic excursion was comparable between the two groups. Conversely, RV GLS and regional peaks of RV myocardial strain were significantly impaired in patients with HCM (all P < 0.001). Multiple linear regression models detected an independent association between RV GLS and LVEDD (beta-coefficient = -0.68, P < 0.0001) in athletes, as well as an independent correlation of the same RV GLS with septal thickness (beta = 0.63, P < 0.0001) in HCM. An RV GLS cut-off value of -0.16% differentiated athletes and HCM with an 86% sensitivity and a 92% specificity. Furthermore, in the overall population, RV GLS (beta = 0.51, P < 0.0001) was a powerful independent predictor of maximal workload during exercise stress echo. CONCLUSION: Right ventricular myocardial systolic deformation is positively influenced by preload increase in athletes and negatively associated with increased septal thickness in HCM. Therefore, 2DSE may represent a useful tool in the differential diagnosis between athlete's heart and HCM, underlining the different involvement of RV myocardial function in either physiological or pathological LV hypertrophy.

Ventricular mechanical asynchrony in patients with different degrees of systolic dysfunction: results from AVE Registry by the Italian Society of Cardiovascular Echography (SIEC).

OBJECTIVE: The aim of the study was to compare the prevalence of interventricular and intraventricular asynchrony in patients with different degrees of left ventricular (LV) dysfunction. METHODS: We enrolled 182 patients (male 79%, mean age 64 +/- 11 years) with LV ejection fraction (EF) < 50% and identified two groups: Group A (n = 79) with mild-to-moderate LV dysfunction (EF between 36% and 49%) and Group B (n = 103) with severe dysfunction (EF 102 msec) did not differ between groups either (29.9% vs. 35.9%; P = 0.39). CONCLUSIONS: The prevalence of intraventricular asynchrony is independent of the LV systolic dysfunction severity. This could indicate the potential role of cardiac resynchronization therapy in patients with mild-moderate systolic dysfunction.

Network Medicine: A Clinical Approach for Precision Medicine and Personalized Therapy in Coronary Heart Disease.

Early identification of coronary atherosclerotic pathogenic mechanisms is useful for predicting the risk of coronary heart disease (CHD) and future cardiac events. Epigenome changes may clarify a significant fraction of this "missing hereditability", thus offering novel potential biomarkers for prevention and care of CHD. The rapidly growing disciplines of systems biology and network science are now poised to meet the fields of precision medicine and personalized therapy. Network medicine integrates standard clinical recording and non-invasive, advanced cardiac imaging tools with epigenetics into deep learning for in-depth CHD molecular phenotyping. This approach could potentially explore developing novel drugs from natural compounds (i.e. polyphenols, folic acid) and repurposing current drugs, such as statins and metformin. Several clinical trials have exploited epigenetic tags and epigenetic sensitive drugs both in primary and secondary prevention. Due to their stability in plasma and easiness of detection, many ongoing clinical trials are focused on the evaluation of circulating miRNAs (e.g. miR-8059 and miR-320a) in blood, in association with imaging parameters such as coronary calcifications and stenosis degree detected by coronary computed tomography angiography (CCTA), or functional parameters provided by FFR/CT and PET/CT. Although epigenetic modifications have also been prioritized through network based approaches, the whole set of molecular interactions (interactome) in CHD is still under investigation for primary prevention strategies.

[ANMCO/SICI-GISE/SIC/SIECVI/SIRM Consensus document: Appropriateness of multimodality imaging in cardiovascular disease]. / Documento di consenso ANMCO/SICI-GISE/SIC/SIECVI/SIRM: Appropriatezza dell'imaging multimodale nelle patologie cardiovascolari.

The complexity of cardiovascular diseases has led to an extensive use of technological instruments and the development of multimodality imaging. This extensive use of different cardiovascular imaging tests in the same patient has increased costs and waiting times.The concept of appropriateness has changed over time. Appropriateness criteria address the need for specific cardiovascular imaging tests in well-defined clinical scenarios, and define the kind of cardiovascular imaging that is appropriated for each clinical scenario in different stages of the disease. The concept of appropriateness criteria has replaced the old idea of appropriate use criteria and reflects the increasing effort of the international Scientific Societies to create and review in a critical way the management of diagnostic tests used by clinicians.The aim of this Italian consensus document is to address the use of multimodality imaging in the diagnosis and management of the major cardiovascular clinical scenarios, taking into consideration not only the international guidelines and scientific documents already published, but also the reality of Italian laws as well as the various professional profiles involved in patient management and availability of technological diagnostic instruments.

Effects of global longitudinal strain and total scar burden on response to cardiac resynchronization therapy in patients with ischaemic dilated cardiomyopathy.

AIMS: To evaluate whether quantification of the extent of scarred left ventricular (LV) tissue by speckle-tracking strain echo (2DSE) can predict response to cardiac resynchronization therapy (CRT) in patients with ischaemic dilated cardiomyopathy (DCM). METHODS AND RESULTS: Forty-five patients (58.3 +/- 8.3 years; 24 males) with ischaemic DCM scheduled for CRT, and 25 controls were studied. A week before implantation all the patients underwent standard Doppler echo, 2DSE, and contrast-enhanced magnetic resonance (MR). Clinical and echocardiographic evaluation was repeated 6 months after CRT. The patients were considered as responders to CRT if LV end-systolic volume decreased by 15%. In DCM patients, LV ejection fraction was 29.2 +/- 5.1%. By evaluating the 765 segments with MR, subendocardial infarct was identified in 17.0% and transmural infarct in 18.3%. With 2DSE, the average global longitudinal strain (GLS) was -23.1 +/- 3.6% in controls and -15.1 +/- 5.1% in DCM (P = 0.001). GLS showed a close correlation with total scar burden using MR (r = 0.64, P < 0.001). At follow-up, patients were subdivided into responders (n = 30; 66.7%) and non-responders (n = 15; 33.3%) to CRT. GLS was significantly different in non-responders than in responders (GLS: -10.4 +/- 5.1 in non-responders vs. -18.4 +/- 14% in responders, P < 0.001). In a multivariable analysis, GLS (P < 0.0001) and radial intraventricular dyssynchrony (P < 0.001) were powerful independent determinants of response to CRT. CONCLUSION: GLS is strongly associated with total scar burden assessed by MR, and is an excellent independent predictor of response to CRT.