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Background: The aim of the study is to evaluate the subclinical alterations of cardiac mechanics detected using speckle-tracking echocardiography and compare these data with the coronary angiography indices used during coronary angiography in a population of patients diagnosed with ischemia with no obstructive coronary artery (INOCA) and microvascular angina (MVA). Methods: The study included 85 patients admitted to our center between November 2019 and January 2022 who were diagnosed with INOCA compared with a control group of 70 healthy patients. A collection of anamnestic data and a complete cardiovascular physical examination, and echocardiogram at rest with longitudinal strain were performed for all patients. Furthermore, the TIMI frame count (TFC) for the three coronary vessels was calculated according to Gibson's indications. All parameters were compared with a control population with similar characteristics. Results: Patients with INOCA compared to the control population showed statistically significant changes in the parameters assessed on the longitudinal strain analysis. In particular, patients with INOCA showed statistically significant changes in GLS (−16.71) compared to the control population (−19.64) (p = 0.003). In patients with INOCA, the total TIMI frame count (tTFC) correlated with the GLS value with a correlation coefficient of 0.418 (p = 0.021). Conclusions: In patients with angina, documented myocardial ischemia, the absence of angiographically significant stenosis (INOCA) and LVEF > 50%, the prevalence of microvascular dysfunction documented by TFC was extremely represented. A statistically significant reduction in GLS was observed in these patients. TFC and longitudinal strain, therefore, appear to be two reliable, sensitive and easily accessible methods for the study of alterations in coronary microcirculation and the characterization of patients with INOCA and microvascular angina. [ABSTRACT FROM AUTHOR]

Background: Myocarditis have variable clinical presentation, evolution and prognosis. Aim of our study was to evaluate the value of speckle tracking echocardiography and cardiac magnetic resonance (CMR) in the short‐term prediction of supraventricular arrhythmias (SVA) in patients with acute myocarditis. Methods: Seventy patients (mean age 31±14 years old) with acute myocarditis and preserved left ventricular ejection fraction (LVEF) were enrolled. Longitudinal systolic strain (LS) of the left ventricle (LV), mechanical dispersion (MD) and CMR with quantitative measurement of delayed enhancement (DE) were performed in a subset of 43 patients. Logistic regression and ROC analysis were used to identify predictors of SVA Results: Only LS measured at sup‐epicardial, mid‐wall and sub‐endocardial level of the apical 4‐chamber view was significantly lower in patients with SVA, while MD was marginally prolonged in this setting. A value of LS > ‐ 16.1% measured at LV mid‐wall in the apical 4‐chamber view (ROC‐AUC.75, Sensitivity 63%, Specificity 85%) was the most accurate measure to identify patients with SVA. DE mass was also helpful with a ROC‐AUC.76; a DE‐Mass > 18.9 gr. had a Sensitivity 63% and a Specificity 77%, to identify patients at risk of SVA. Conclusions: Both DE mass and LS were associated with higher risk of SVA in patients with acute myocarditis and preserved LVEF. However, LS measured at the mid‐wall level and limited to LV segments included in the apical 4‐chamber view was the most accurate measure and did not show interaction with DE mass. [ABSTRACT FROM AUTHOR]

Several studies have shown that endothelial dysfunction plays a role in the pathogenesis of Takotsubo syndrome (TTS). Given the potential benefit of statin therapy on endothelial dysfunction, we hypothesized that such treatment could improve outcome. Aim of our study was to evaluate clinical characteristics and outcome of TTS patients treated with statin therapy. Patients were enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry. Demographic data, clinical features and drug therapy at discharge were recorded. Primary study outcome was the occurrence of all-cause death at follow-up. Study population included 2429 consecutive TTS patients: 1293 (53.2%) discharged on statin and 1136 (46.8%) without statin. Patients with statin were older (age 72 ± 11 vs 69 ± 13 years, p < 0.001), with higher prevalence of hypertension (74.3% vs 60.3%, p < 0.001), diabetes (21.1% vs 14.7%, p < 0.001), dyslipidemia (56.1% vs 23.3%, p < 0.001), history of coronary artery disease (13.3% vs 6.3%, p < 0.001) and lower rates of in-hospital complications (14.7% vs 19.3%, p = 0.003). Survival analysis showed similar mortality rates between groups (log rank p = 0.803). At univariable analysis, statin therapy at discharge was not associated with lower mortality (HR: 0.97, 95% CI 0.74–1.26, p = 0.803). At multivariable analysis age (HR: 1.06 95% CI 1.04–1.08, p < 0.001), male sex (HR: 1.83, 95% CI 1.20–2.80, p = 0.005), diabetes (HR: 2.55, 95% CI 1.83–3.54 p < 0.001), malignancies (HR: 2.41, 95% CI 1.68–3.44, p < 0.001) and physical trigger (HR: 2.24, 95% CI 1.62–3.10, p < 0.001) were associated with increased mortality. Statin therapy after a TTS event was not associated with better prognosis at follow-up. [Display omitted] • Endothelial dysfunction is implicated in Takotsubo pathogenesis. • Statins improving endothelial function are investigated for their impact on Takotsubo. • GEIST Registry explores statin treatment in 2429 Takotsubo patients. • Statins at discharge are not associated with improved survival in Takotsubo patients. [ABSTRACT FROM AUTHOR]

Background: Target therapy can cause various cardiovascular complications. The aim of this study was to evaluate the burden of cardiovascular complications related to treatment with anti-BCR-ABL tyrosine kinase inhibitors (TKIs) and to determine if there are differences between the latest- and first-generation TKIs. Methods: A retrospective observational study was carried out on 55 patients (39 men, 16 women; mean age ± SD: 58 ± 11 years) treated with TKIs targeting Bcr-Abl for a median period of 3.5 years. Patients were divided in two groups according to the type of treatment. Group A included patients treated with latest-generation TKI (nilotinib, dasatinib, and ponatinib), while group B included patients treated with first-generation TKI (imatinib). Cardiological evaluation included electrocardiogram, echocardiogram with global longitudinal strain of left ventricle (GLS), and carotid ultrasound scan with arterial stiffness measurement (pulse wave velocity, PWV). Adverse cardiovascular events were recorded in both groups. Results: Statistical analysis showed that cardiovascular adverse events (myocardial ischemia, peripheral artery disease, deep vein thrombosis, and pleural effusion) were significantly more frequent in group A than group B (p value = 0.044). Moreover, there was a significant reduction in GLS and PWV in group A when compared to group B (respectively, p = 0.03 and p = 0.004). Conclusions: Our study confirms that imatinib is a relatively safe drug, while it reveals that the latest-generation TKIs may cause a burden of cardiovascular complications. GLS and PWV allow detection of early signs of cardiac and vascular toxicity in oncohematologic patients treated with TKI, and their use is advisable. [ABSTRACT FROM AUTHOR]

Summary: Background: Cirrhosis is associated with morpho‐functional cardiovascular alterations. Aims: To detect early features of cardiovascular damage in HCV‐compensated cirrhotic patients using myocardial deformation indices and carotid arterial stiffness, and, further, to evaluate their short‐term behaviour after HCV eradication with direct antiviral agents (DAAs). Methods: Thirty‐nine consecutive patients with HCV cirrhosis, without previous cardiovascular events, were studied and matched for age, gender and cardiovascular risk factors to 39 controls without liver or cardiovascular disease. Patients and controls underwent a baseline echocardiographic evaluation including global longitudinal strain and ultrasound scan of carotid arteries. HCV‐cirrhotics were reassessed by echocardiography and carotid ultrasound after obtaining sustained virological response (SVR) on DAAs. Results: HCV‐cirrhotics showed at baseline a significantly reduced global longitudinal strain compared to controls −18.1 (16.3‐20.5) vs −21.2 (20.4‐22.3), P < 0.001. They also had a significantly higher pulse wave velocity 8.6 (7.7‐9.1) m/s vs 6.6 (6.0‐7.1) m/s, P = 0.0001, and β‐stiffness index 12.4 (11.1‐13.5) vs 8.6 (8.0‐9.2) P = 0.0001. At multiple regression analysis, diabetes and HCV cirrhosis were independent predictors of global longitudinal strain. All HCV‐cirrhotic patients had SVR on DAAs. Follow‐up available in 32 of 39 (82%) at 9 (8‐10) months showed a significant improvement of tricuspid annular plane systolic excursion (P = 0.01) and lateral E’ velocity compared to baseline (P = 0.001). Conclusions: HCV‐cirrhotics show a significant rate of subclinical cardiac and vascular abnormalities. At a time when their survival is less linked to progression of liver disease, due to viral eradication on DAAs, cardiovascular morbidity and mortality may take a significant role. [ABSTRACT FROM AUTHOR]

Background Insulin resistance (IR), constitutes an important cardiovascular risk factor and can cause ischemic heart disease. It can lead to left ventricular dysfunction with a mechanism independent of ischemic heart disease and it is closely associated with impaired vascular function. The aim of our study was to explore the impact of IR on cardiac and vascular function, in patients with cardiovascular risk factors but angiographically undamaged coronary arteries. Methods We studied 32 patients (62.06 ± 11.19 years) with cardiovascular risk factors. All patients underwent coronary angiography, echocardiography, Doppler ultrasound of carotid arteries and laboratory tests. Exclusion criteria were coronary artery disease detected by coronary angiography, diabetes mellitus, creatinine above 1.5 mg/dl, atrial fibrillation or malignant arrhythmias, left-ventricular hypertrophy, valvular heart disease, ejection fraction below 50%. The presence of insulin resistance was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Each patient underwent a complete echocardiographic examination including Global Longitudinal Strain assessment and carotid artery ultrasound scan including measurement of arterial stiffness. Results The patients were divided into two groups based on the median value of HOMA-IR, the first group for values < 4.14 and, the second, for values ≥ 4.14. Ejection fraction and diastolic function did not significantly differ between the two groups, whether in patients with higher levels of HOMA-IR (≥ 4.14) we observed a Global Longitudinal Strain (GLS) that was significantly reduced (− 16.50 ± 1.37% vs. − 20.73 ± 1.84%, p = 0.0015) vascular stiffness, measured in the carotid arteries as pulse wave velocity (PWV) (9.70 ± 1.75 m/s vs. 7.40 ± 1.89 m/s, p = 0.00148) that was increased. At multivariate analysis HOMA-IR was an independent predictor of myocardial dysfunction (GLS: coefficient 0.1156, p < 0.0001). Conclusion Insulin resistance is associated with subclinical myocardial and vascular alterations in patients without significant coronary artery disease, measured as a reduction of Global Longitudinal Strain, and increased arterial stiffness. Our results underscore the importance of studying the interaction between ventricular function and vessels, in the perspective of more effective preventive and therapeutic interventions. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The relationship between whole blood fatty acids and myocardial infarction (MI) risk has not been analyzed in detail, especially in Mediterranean countries. The AGE-IM (Acidi Grassi Essenziali e Infarto Miocardico) study was planned to examine the relationships between MI, whole blood fatty acids and the diet in an Italian cohort. Methods: 119 Patients with a recent MI and 103 control subjects were enrolled in the study. The whole blood fatty acid composition was determined; information on anthropometrics, biochemical parameters and blood pressure values were also obtained. Diet composition was assessed using a validated food frequency questionnaire from 86 cases and 72 controls. Results: Total PUFA, omega-6 and omega-3 PUFA (as percentage of whole blood fatty acids) were significantly lower in MI patients than in matched controls, whereas saturated and monounsaturated fatty acids were higher in cases. MI infarction risk significantly and steadily decreased with increasing levels of total PUFA (OR: 0.14) and of total omega-6 and omega-3 (OR: 0.15 and 0.37, respectively). No correlation was identified between dietary fats and MI risk or between whole blood fatty acid levels and dietary nutrients and fats. Conclusion: Percentage levels of total PUFA, total omega-3 PUFA and total omega-6 PUFA are lower in MI patients than in matched control subjects in the AGE-IM cohort. These data support a favorable association not only of whole blood percentage levels of total omega-3, but also of total omega-6, with cardiovascular risk. [Copyright &y& Elsevier]

Abstract: Objective: Degenerative aortic stenosis shows similarities with atherosclerosis. To confirm the hypothesis that aortic stenosis is an “atherosclerosis-like” disease, we investigated the association between degenerative aortic stenosis and atherosclerosis of carotid arteries. Methods: We studied 270 consecutive patients, 135 with degenerative aortic stenosis (trans-aortic peak velocity ≥ 2 m/sec) and other 135 subjects without aortic valve disease. All patients underwent echocardiography and ultrasound scan of the supra-aortic trunks to assess the presence of plaque and/or intima-media thickening (IMT). Results: Atherosclerosis of carotid arteries (IMT and plaque) was significantly more frequent in patients with aortic stenosis than in controls (95.5% vs. 66.6%, p < 0.0001). The same result was confirmed as concerns carotid plaques (69.6% vs. 42.2%, p < 0.0001). In addition, there was a significant association between aortic stenosis and degenerative carotid plaque (OR = 3.13; 95% C.I. = 1.90–5.17). Thus the presence of a linear correlation between the trans-aortic peak velocity of the cases and the thickness of the plaques and IMT was evaluated by calculating the coefficient of correlation (R = 0.15 for plaque and R = 0.53 for IMT). Conclusions: The presence of carotid atherosclerosis is associated with degenerative aortic stenosis and the severity of aortic stenosis corresponds to an increase of the thickness of plaque and IMT. This relationship is quite new. Our result strengthens the pathogenetic hypothesis “atherosclerosis-like” of degenerative aortic stenosis and suggest the ultrasound scan as a non invasive method for risk stratification in patient with aortic stenosis, with therapeutic implications especially for higher risk subgroups. [Copyright &y& Elsevier]

We assessed whether macrophage colony-stimulating factor (M-CSF) levels are associated with left ventricular systolic dysfunction (LVSD) in patients with acute myocardial infarction (AMI). We studied 56 patients with AMI (mean age: 67 ± 12 years) and identified those with clinical (Killip class >II) or echocardiographic signs (ejection fraction ≤45%) of LVSD. We evaluated the established cardiovascular risk factors and measured several cardiovascular biomarkers, including M-CSF. Serum M-CSF concentrations (pg/mL) were significantly increased in patients with both clinical and echocardiographic signs of LVSD (460 ± 265 vs 290 ± 210, P = .0103 and 493 ± 299 vs 287 ± 174, P = .0028, respectively). We found a significant inverse association between M-CSF and ejection fraction (r = −.351, P = .0079). Logistic regression analysis revealed that, among all evaluated clinical and biochemical parameters, the stronger predictor of LVSD was M-CSF (odds ratios 2.1, 95% confidence interval 1.1-2.9, P = .0168). This is the first study reporting plasma M-CSF levels as independent determinants of low LV ejection fraction and clinical LV dysfunction in patients with AMI. [ABSTRACT FROM PUBLISHER]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Atrial fibrillation (AF) is the most common rhythm disturbance in medical practice. • AF can be managed with the prevention of thromboembolism and either a rate control or rhythm control strategy; however, as both treatment strategies have important limitations, a preventative strategy could be a more attractive option. • Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin-II receptor blockers (ARBs) may play a role in preventing AF recurrence. WHAT THIS STUDY ADDS • The aim of the present review was to analyse evidence supporting the usefulness of renin–angiotensin system (RAS) inhibition in patients with AF and to focus on which specific subset of patients it most favours. • Although many studies and meta-analysis have supported the advantage of RAS block in preventing AF recurrence, it is not possible to recommend the use of ACE-Is and ARBs in routine clinical practice specifically to prevent AF. • As these drugs are safe and manageable, they should be considered the drugs of choice in patients with AF and coexisting clinical conditions such as hypertension, coronary disease, heart failure and diabetes mellitus. Atrial fibrillation (AF) is the most common rhythm disturbance in medical practice and represents a very expensive health problem. AF can be managed with the prevention of thromboembolism and either a rate control or rhythm control strategy. As both strategies have important limitations, probably a preventative strategy in patients at risk of developing arrhythmia can be a more attractive option. The renin–angiotensin system (RAS) seems to be involved in the genesis of arrhythmia by the following two mechanisms: 1 the induction of atrial fibrosis and structural remodelling by mitogen-activated protein kinase (MAPK) expression and reduction of collagenase activity; 2 the induction of electrical remodelling by shortening of the atrial effective refractory period (AERP) and of the action potential duration. For these reasons it has been hypothesized that angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin-II receptor blockers (ARBs) may play a role in preventing AF recurrence. The aim of the present review was to analyse evidence supporting the usefulness of RAS inhibition in patients with AF in order to focus on which specific subset of patients it would most favour. After reviewing the literature, we conclude that, although many studies and meta-analyses have supported the advantage of RAS block in preventing AF recurrence, it is premature to recommend the use of ACE-Is and ARBs specifically for the prevention of AF. However we believe that as these drugs are safe and manageable, they should be considered the drugs of choice in patients with AF and coexisting clinical conditions such as hypertension, coronary disease, heart failure and diabetes mellitus. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases represent the leading cause of death in the world and are subject to limitations in prevention strategies despite the use of very effective drugs. The concept of residual risk (RR) is intrinsically related to that of global risk of which it represents a very significant percentage. In the cardiovascular field, the term RR refers to the probability of incurring a major cardiovascular event, despite adequate control of the risk factors present in the individual patient. A significant portion of the RR in the cardiovascular field results from the underestimation of additional risk factors not subjected to adequate intervention such as, for example, triglyceride levels in patients treated for the presence of hypertension and/or hypercholesterolemia. The control of the RR therefore appears as an essential condition for the effective reduction of the global risk profile and is based on an integrated intervention that combines all the different prevention strategies derived from the available evidence and capable of interacting on the basis of a strengthening reciprocal between lifestyle and pharmacological and nutraceutical intervention methods. [ABSTRACT FROM AUTHOR]

Abstract: Non-compaction of the ventricular myocardium (LCVM) is a rare disorder of myocardial morphogenesis usually diagnosed in paediatric age. The diagnosis was echocardiographically made on the basis of a reported spongeous/compacted ratio >2 in one or more segments of the left ventricle during the diastolic period. We aimed to test the diagnostic accuracy of cardiovascular magnetic resonance (CMR) imaging in distinguishing pathological left ventricular non-compaction. Methods: We collected a consecutive series of 8 patients, 5 males and 3 females, with a mean age of 14.9 years with non-compaction of left ventricular myocardium. All patients were admitted in our divisions of cardiology. In all cases the diagnosis was performed by echocardiography. The diagnosis was obtained when the spongeous/compacted ratio was >2 in one or more segments of left ventricle, evaluated in systolic and diastolic period. In the end we completed the diagnosis by scanning with a Signa HD 1.5 T (GE, Milwaukee, USA) the same 8 patients affected by non compaction of ventricular myocardium. In all patients cardiac-gated T1 and T2 black-blood FSE images in short axis and in four-chamber horizontal long axis were obtained. Breath hold cine MR sequences (FIESTA) were performed, covering the whole left ventricle in short-axis plane and in four-chamber view. A segmented inversion-recovery fast gradient echo sequence (IR-FGE) was performed in the short-axis plane of the LV and in four-chamber-view after Gadolinium injection in 8 patients affected by non compaction of left ventricle. At the end of examination the spongeous/compacted ratio >2 was calculated in all involved segments of the left ventricle in diastole. Results: In all cases we demonstrated by echocardiography an involvement of the ventricular apex. In 3 cases the structural alterations involved also lateral wall of left ventricle. Magnetic resonance evaluation showed that involvement demonstrated by the echocardiogram was the same: ventricular apex involved in every patient, lateral wall in 3 and all segments in 2. However the spongeous/compacted ratio was >>2 in all patients, with a mean value of 3,1. Conclusions: Although our data refer to a small population of patients and need further confirmation, they suggest that it seems reasonable increase the cut-off for spongeous/compacted ratio from a value of 2 to 2.5 for non-compaction diagnosis when high-resolution magnetic resonance is used. [Copyright &y& Elsevier]

Abstract: Noncompaction of the ventricular myocardium (LVNC) is a rare congenital cardiomyopathy resulting from an arrest in normal endomyocardial embryogenesis. In 2002 Jenni et al. [Jenni R, Wyss CA, Oechslin EN, Kaufmann PA. Isolated ventricular noncompaction is associated with coronary microcirculatory dysfunction. J Am Coll Cardiol 2002; 39:450-454.] reported a microvascular dysfunction in 12 patients affected by non compaction: areas of restricted myocardial perfusion have been documented by scintigraphy, suggesting a reduction of Coronary flow reserve. McMahon et al reported in a recent article a reduction of TD velocities in children with noncompaction of the left ventricle, compared with normal controls. The authors concluded their work saying that the reduction of lateral mitral Ea velocity helps to predict children with LVNC who are at risk of adverse clinical outcomes including death and need for cardiac transplantation. In a precedent report our group reported a strong correlation between pathological tissue Doppler and reduction of ejection fraction. Recently we scanned with a Signa HD 1.5 T (GE, Milwaukee, USA) 8 patients affected by non compaction. Transmural Gd-enhancement was detected in 5/8 patients (62%). In all patients with late enhancement a reduction of EF has demonstrated. In our opinion the late enhancement can depend on a CFR, and is the determinant of the tissue Doppler alterations. So the TD alteration is associated with EF, and is an indirect index of poor clinical outcome, like EF. [Copyright &y& Elsevier]

Cardiovascular diseases (CVDs) are a leading global cause of mortality and are primarily driven by atherosclerotic coronary artery disease. Their pathogenesis involves multi-factorial mechanisms, among which low-density lipoprotein (LDL) plays a causative role. Recent ESC/EAS guidelines advocate for a shift toward new risk estimation algorithms that better emphasize non-fatal cardiovascular events, lifetime risk prediction, and tailored pharmacological approaches, including statin + ezetimibe and triple therapy, in specific cases. Intensive lipid-lowering therapy has been shown to be pivotal, especially in post-acute coronary events. Intracoronary imaging has revealed insights into the composition of plaque and demonstrated the significant regression that can be achieved through the use of statins such as rosuvastatin and atorvastatin. The positive effects of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors, particularly alirocumab and evolocumab, on plaque regression, have been demonstrated. Inclisiran, which targets PCSK9 gene expression, significantly reduces LDL cholesterol. The associated challenges include hesitancy to prescribe intensive regimens and limited treatment adherence, highlighting the need for pharmacological combinations to improve therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Serum biomarkers represent a reproducible, sensitive, minimally invasive and inexpensive method to explore possible adverse cardiovascular effects of antineoplastic treatments. They are useful tools in risk stratification, the early detection of cardiotoxicity and the follow-up and prognostic assessment of cancer patients. In this literature review, we aim at describing the current state of knowledge on the meaning and the usefulness of cardiovascular biomarkers in patients with cancer; analyzing the intricate relationship between cancer and cardiovascular disease (especially HF) and how this affects cardiovascular and tumor biomarkers; exploring the role of cardiovascular biomarkers in the risk stratification and in the identification of chemotherapy-induced cardiotoxicity; and providing a summary of the novel potential biomarkers in this clinical setting. [ABSTRACT FROM AUTHOR]

Background and purpose: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv‐PN) is caused by mutations in the TTR gene, leading to misfolded monomers that aggregate generating amyloid fibrils. Methods: A prospective systematic genetic screening for ATTRv‐PN was proposed in patients presenting with a sensory–motor idiopathic polyneuropathy and two or more "red flags" among the following: family history of polyneuropathy or cardiopathy, bilateral carpal tunnel syndrome, cardiac insufficiency, renal amyloidosis, lumbar tract stenosis, autonomic dysfunction, idiopathic gastrointestinal disease, amyloid deposits on biopsy, and vitreous opacities. The detection rate was calculated, and nonparametric analyses were carried out to underline differences among screened positive versus negative patients. Results: In the first step, 145 suspected patients underwent genetic testing, revealing a diagnosis of ATTRv‐PN in 14 patients (10%). Then, cascade screening allowed early recognition of 33 additional individuals (seven symptomatic ATTRv‐PN patients and 26 presymptomatic carriers) among 84 first‐degree relatives. Patients with a positive genetic test presented a higher frequency of unexplained weight loss, gastrointestinal symptoms, and family history of cardiopathy. Conclusions: A systematic screening for ATTRv‐PN yielded an increased recognition of the disease in our neurological clinic. Unexplained weight loss associated with axonal polyneuropathy had the highest predictive value in the guidance of clinical suspicion. A focused approach for the screening of ATTRv‐PN could lead to an earlier diagnosis and identification of asymptomatic carriers, who will be promptly treated after a strict follow‐up at the clinical onset. [ABSTRACT FROM AUTHOR]

Background: Hereditary transthyretin amyloidosis is a rare disease caused by transthyretin (TTR) gene mutations. The aim of our study was to identify early signs of cardiac involvement in patients with a TTR gene mutation in order to differentiate carriers from patients with neurological or cardiac disease. Methods: A case–control study was carried out on 31 subjects with the TTR mutation. Patients were divided into three groups: 23% with cardiac amyloidosis and polyneuropathy (group A), 42% with only polyneuropathy (group B) and 35% carriers (group C). Speckle-tracking echocardiography (left-ventricular global longitudinal strain—GLS, atrial stiffness) was performed in all patients. The apical/basal longitudinal strain ratio (SAB) and relative apical sparing (RAS) were assessed in all subjects. Results: Analyzing groups C and B, we only found a significant difference in the SAB (p-value 0.001) and RAS (p-value 0.039). These parameters were significantly more impaired in group A compared to group B (SAB p-value 0.008; RAS p-value 0.002). Also, atrial stiffness was significantly impaired in groups A and B compared to group C. Conclusions: Our study suggests the diagnostic role of the SAB and RAS in cardiac amyloidosis. The SAB and RAS showed a gradual increase from carriers to patients with neurological and cardiac diseases. Thus, these parameters, in addition to atrial stiffness, could be used to monitor carriers. More extensive data are needed. [ABSTRACT FROM AUTHOR]

Left ventricular global longitudinal strain (GLS) has an important role in the diagnosis of cancer therapy-related cardiac dysfunction (CTRCD). Little is known about the role of atrial function in diagnosing CTRCD. The aim of our study was to assess the impact of anti-cancer drugs on atrial function measured by speckle-tracking echocardiography in breast cancer women. A prospective multicenter study was conducted enrolling 169 breast cancer women treated with anthracyclines. A cardiological evaluation including an electrocardiogram and echocardiogram with an analysis of GLS, left atrial (LA) strain, and LA stiffness (LASi) was performed at baseline (T0), 3 (T1), and 6 months (T2) after starting chemotherapy. The patients were divided into two groups: patients with asymptomatic mild cardiotoxicity at T1 (with a relative reduction in GLS > 15%; Group 1) and those without (Group 2). We did not find a significant change in left ventricular ejection fraction (LVEF) at T1 and T2; we found a significant change in GLS (p-value < 0.0001) in the peak atrial longitudinal strain (PALS) and in LASi (p-value < 0.0001). Impairment of atrial function was greater in Group 1 compared to Group 2. A PALS variation > 20.8% identified patients who were most likely to develop asymptomatic mild cardiotoxicity [AUC 0.62; CI (0.51–0.73) p = 0.06, sensitivity 45%, specificity 69.5%]. Conclusions: PALS and LASi significantly change during chemotherapy in association with GLS. Atrial strain is an additional parameter that could be measured together with GLS to detect cardiotoxicity early. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to assess clinical outcomes and quality of life after PFO closure in patients with previous stroke/TIA of undetermined cause and in patients with other complex PFO-associated clinical conditions. Methods: Between July 2009 and December 2019 at our University Cardiology Department, 118 consecutive patients underwent a thorough diagnostic work-up including standardized history taking, clinical evaluation, full neurological examination, screening for thrombophilia, brain magnetic resonance imaging (MRI), ultrasound–Doppler sonography of supra-aortic vessels and 24 h ECG Holter monitoring. Anatomo-morphological evaluation using 2D transthoracic/transesophageal echocardiography (TTE/TEE) color Doppler and functional assessment using contrast TTE (cTTE) in the apical four-chamber view and contrast transcranial Doppler (cTCD) using power M-mode modality were performed to verify the presence, location and amount of right-to-left shunting via PFO or other extracardiac source. Completed questionnaires based on the Quality-of-Life Short Form-36 (QoL SF-36) and Migraine Disability Assessment (MIDAS) were obtained from the patients before PFO closure and after 12 months. Contrast TTE/TEE and cTCD were performed at dismission, 1, 6 and 12 months and yearly thereafter. Brain MRI was performed at 1-year follow-up in 54 patients. Results: Transcatheter PFO closure was performed in 106 selected symptomatic patients (mean age 41.7 ± 10.7 years, range 16–63, 65% women) with the following conditions: ischemic stroke (n = 23), transient ischemic attack (n = 22), peripheral and coronary embolism (n = 2), MRI lesions without cerebrovascular clinical events (n = 53), platypnea–orthodeoxia (n = 1), decompression sickness (n = 1) and refractory migraine without ischemic cerebral lesions (n = 4). The implanted devices were Occlutech Figulla Flex I/II PFO (n = 99), Occlutech UNI (n = 3), Amplatzer PFO (n = 3) and CeraFlex PFO occluders (n = 1). Procedures were performed under local anesthesia and rotational intracardiac monitoring (Ultra ICE) alone. The devices were correctly implanted in all patients. The mean fluoroscopy time was 15 ± 5 min (range = 10–45 min) and the mean procedural time was 55 ± 20 min (range = 35–90 min). The total occlusion rate at follow-up (mean 50 months, range 3–100) was 98.1%. No recurrent neurological events were observed in the long-term follow-up. Conclusions: The data collected in this study demonstrate that percutaneous PFO closure is a safe and effective procedure, showing long-term prevention of recurrent cerebrovascular events, significant reduction in migraine symptoms and substantial improvement in quality of life. [ABSTRACT FROM AUTHOR]

Abstract Many new drugs have appeared in last years in the oncological treatment scenario. Each drug carries an important set of adverse events, not less, cardiovascular adverse events. This aspect is even more important considering the increasing use of combination therapies with two drugs, or three drugs as in some ongoing clinical trials. Besides it represents a growing problem for Cardiologists, that face it in every day clinical practice and that will face it probably more and more in the coming years. This work reviews the mechanism of action of BRAF-inhibitors and MEK-inhibitors used together, the pathophysiological mechanisms that lead to cardiovascular toxicity. Particularly, it focuses on hypertension and ejection fraction reduction development. Then, it follows the examination of published data for each combination therapy. A Literature research was carried out using Pubmed selecting review articles, original studies and clinical trials, but mainly focusing on phase 3 studies. This work aims to summarize the knowledge about BRAF-inhibitor and MEK-inhibitor treatment and its cardiovascular toxicity to make it usable and give the basic tools to Cardiologists and Oncologists for a better management of cancer patient undergoing this treatment. Besides a deeper knowledge of the cardiovascular adverse events linked to this treatment and the magnitude of their expression and frequency can lead to a targeted cardiological treatment. [ABSTRACT FROM AUTHOR]

Abstract: For neurological disorders we consider every possible affection of the central nervous system or neuro-muscular junction, in the presence of complex syndromes as well, such as Cornelia De Lange syndrome or any other. In our experience the incidence of neurological or neuromuscular envolment in patients affected by noncompaction is low. An incidence of comorbidities higher than 20% is not recorded in any centre, in published experiences. Data of the Vienna group could be likely influenced by selection bias (second level centre) or territorial genetic factors, or could depend on higher sensibility of used diagnostic techniques of neurological disease. But, if it was so, in our opinion, let me assert that patients routinely underwent so sensible and accurate neurological tests only for cognitive purpose, without practical implications. [ABSTRACT FROM AUTHOR]

Abstract: In many reports Finsterer and Stöllberger reported a strong association between non compaction of the left ventricle and neuromuscular disorders. In the same report the authors described a neurological involvement in more than 50%. Recently we published our personal experience, about 21 paediatric patients: only 4 patients (19%) showed a neuromuscular disorder, and only 1 of them showed an increased plasmatic level of CK, and in particular of MM isoform, with a normal level of CK-MB. None presented high levels of troponine. Through the experience of 3 centres we collected 61 patients affected by non compaction that performed a neurological control, and only 14 (21%) were affected by neuromuscular disorders. A correlation between neuromuscular disorders and cardiac non compaction is present, even if, until today, genetic involvement has not been identified clearly. However, in our opinion, an estimated incidence of 50% of neuromuscular disorders in this population of patients could be too exaggerated. About the prognostic value of the CK elevation, it is interesting to consider that an increasing of CK plasmatic level is an expression of muscular disorders and not of cardiac alterations. In our experience only 1 patient in 21 patients (4%) with neuromuscular disorders showed an increasing of CK-MM plasmatic value. [Copyright &y& Elsevier]

Abstract: Takotsubo Cardiomyopathy is characterized by a reversible systolic left ventricular apical ballooning. A new pattern of dyskinesia in the absence of angiographic evidence of coronary artery stenosis has been indicated like a variant of takotsubo cardiomiopathy: mid-ventricular akinesis with preservation of apical and basal contractilities revealed at echocardiograms and ventriculographies. We report the case of a 65 years old patient with this pattern, reverted in 4 weeks. [Copyright &y& Elsevier]

Background: Early detecting AMI in individuals presenting to the ED with chest pain continues to be a challenge. cTn is the gold standard for AMI diagnosis but early presenters (<1 hours from symptom onset) maybe cTn negative on admission. We analysed the diagnostic value of h-FABP and hs-TnI in patients presenting to ED with chest pain and no cTnI elevations.Methods: 28 AMI and 28 no-AMI individuals both presented to ED within one hour from pain onset were included. Blood donors were analysed for h-FABP cut-off identification. Among AMI patients, 55% were positive for h-FABP and 34.6% were positive for hs-TnI (p = .015), thus 21% were positive only for h-FABP. The diagnostic accuracy was assessed by ROC curve. h-FABP showed a higher sensitivity but lower specificity than hs-TnI.Conclusions: In our study, the frequency of h-FABP positivity among AMI patients was higher than that of hs-TnI, which would have missed six of them; however, hs-TnI AUC was superior to that of h-FABP. These preliminary findings might confirm that h-FABP may be a good candidate for AMI rule-in/rule-out within the ED context. [ABSTRACT FROM AUTHOR]

Abstract: In a recent report about noncompaction Nemes et al. reported that systolic left ventricular (LV) dysfunction assessed using the wall motion score during 2D echocardiography in noncompaction is not confined to noncompacted LV segments. These results confirmed some published reports of our group. Recently we analyzed a population of 238 patients affected by noncompaction, and demonstrated that the number of noncompacted segment is uncorrelated with the degree of systolic dysfunction. It is an attractive hypothesis that the systolic dysfunction could be depend on the fibrosis of the left ventricle, itself a consequence of microcirculatory dysfunction, which has been confirmed by reports that describe microvascular dysfunction using myocardial scintigraphy. [Copyright &y& Elsevier]

Objective The aim of this study was to evaluate in patients with cardiac syndrome X (CSX), using validated angiography indices, coronary blood flow and myocardial perfusion of the microcirculation to assess whether there is greater microvascular dysfunction in patients with increase of carotid intima media thickness (C-IMT), compared to those who do not have. Methods Our study was performed on a population 124 patients with CSX that underwent coronary angiography and carotid ultrasound. We divided the sample into two categories: patients with increase of C-IMT and those without increase. We calculated Gibson and Yusuf indices for each patient based on angiographic images, including TIMI Frame Count (TFC), Myocardial Blush Grade (MBG) and Total Myocardial Blush Score (TMBS). Results Our sample compared two groups: patients with increase of C-IMT (n-63) and patients without increase of C-IMT (n-61). We showed that patients with increase C-IMT had a longest TFC of three major coronary arteries (TFC LAD 44.7 ± 12.5; TFC RCA 26.2 ± 6.9; TFC CX 27 ± 5.9), than control group. We found lower MBG on three coronary arteries (MBG LAD 2.5 ± 0.3; MBG RCA 2.3 ± 0.3; MBG CX 2.1 ± 0.32) in patients with increase of C-IMT than control group, with good statistical significance. Conclusion Analysis of microcirculation trough angiography indexes in patients with CSX with increase of C-IMT and without has led to asses that patients with increase of C-IMT population has a greater involvement of microcirculation than patients without. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to evaluate myocardial perfusion and coronary blood flow through validated angiography indices to assess whether there is greater MVD in patients with microvascular angina and HFPEF compared to those who do not have. Methods Our study was performed on a population of 286 patients with stable angina that underwent coronary angiography and echocardiography. They showed epicardial coronary arteries free from stenosis. We divided the sample into two categories: patients with HFPEF and those without. We calculated indices for each patient based on angiographic images, including TFC, MBG, and TMBS. Results Our sample compared two groups: HFPEF ( n = 155) and non-HFPEF ( n = 135) patients. We showed that patients with HFPEF had a longest TFC of three major coronary arteries (TFC LAD 44.7 ± 12.5; TFC RCA 26.2 ± 6.9; TFC CX 27 ± 5.9) than non-HFPEF patients (TFC LAD 40.7 ± 11.6; TFC RCA 25 ± 6.3; TFC CX 21 ± 4.7). On the other hand, we found lower MBG on three coronary arteries (MBG LAD 2.1 ± 0.3; MBG RCA 2.1 ± 0.3; MBG CX 2.0 ± 0.32) in HFPEF than non-HFPEF patients (MBG LAD 2.6 ± 0.5; MBG RCA 2.2 ± 0.47; MBG CX 2.3 ± 0.4). Conclusion Analysis of microcirculation through angiography indices in patients with and without HFPEF has led to assess that the HFPEF population has a greater involvement of microcirculation than patients without HFPEF. [ABSTRACT FROM AUTHOR]

Leadless pacemaker (LPs) is a safe device and the implantation rates of this device is increasing. The device extraction and replacement are today a challenging procedures especially in case of infections, fragile and older patients or in unfavorable venous anatomy; LPs can be a valid alternative strategy in these cases. We report a case of management of a patient with multiple previous device replacements and extractions, with malfunction of transvenous pacemaker and with a fibrous membrane between the walls of the ventricular lead and the superior vena cava (SVC), who underwent a successful LP implantation. [ABSTRACT FROM AUTHOR]

Background: Male sex in takotsubo syndrome (TTS) has a low incidence and it is still not well characterized.Objectives: The aim of the present study is to describe TTS sex differences.Methods: TTS patients enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry were analyzed. Comparisons between sexes were performed within the overall cohort and using an adjusted analysis with 1:1 propensity score matching for age, comorbidities, and kind of trigger.Results: In total, 286 (11%) of 2,492 TTS patients were men. Male patients were younger (age 69 ± 13 years vs 71 ± 11 years; P = 0.005), with higher prevalence of comorbid conditions (diabetes mellitus 25% vs 19%; P = 0.01; pulmonary diseases 21% vs 15%; P = 0.006; malignancies 25% vs 13%; P < 0.001) and physical trigger (55 vs 32% P < 0.01). Propensity-score matching yielded 207 patients from each group. After 1:1 propensity matching, male patients had higher rates of cardiogenic shock and in-hospital mortality (16% vs 6% and 8% vs 3%, respectively; both P < 0.05). Long-term mortality rate was 4.3% per patient-year (men 10%, women 3.8%). Survival analysis showed higher mortality rate in men during the acute phase in both cohorts (overall: P < 0.001; matched: P = 0.001); mortality rate after 60 days was higher in men in the overall (P = 0.002) but not in the matched cohort (P = 0.541). Within the overall population, male sex remained independently associated with both in-hospital (OR: 2.26; 95% CI: 1.16-4.40) and long-term mortality (HR: 1.83; 95% CI: 1.32-2.52).Conclusions: Male TTS is featured by a distinct high-risk phenotype requiring close in-hospital monitoring and long-term follow-up. [ABSTRACT FROM AUTHOR]

The current gold standard for diagnosis of coronary microvascular dysfunction (CMD) in the absence of myocardial diseases, whose clinical manifestation is microvascular angina (MVA), is reactivity testing using adenosine or acetylcholine during coronary angiography. This invasive test can be difficult to perform, expensive, and harmful. The identification of easily obtainable blood biomarkers which reflect the pathophysiology of CMD, characterized by high reliability, precision, accuracy, and accessibility may reduce risks and costs related to invasive procedures and even facilitate the screening and diagnosis of CMD. In this review, we summarized the results of several studies that have investigated the possible relationships between blood biomarkers involved with CMD and MVA. More specifically, we have divided the analyzed biomarkers into 3 different groups, according to the main mechanisms underlying CMD: biomarkers of "endothelial dysfunction," "vascular inflammation," and "oxidative stress." Finally, in the last section of the review, we consider mixed mechanisms and biomarkers which are not included in the 3 major categories mentioned above, but could be involved in the pathogenesis of CMD. [ABSTRACT FROM AUTHOR]

Purpose: Only a few studies are available on dose-related effects of sacubitril/valsartan (angiotensin receptor neprilysin inhibition (ARNI)) in real-life patients with heart failure and reduced ejection fraction (HFrEF). We sought to investigate clinical and functional effects in real-life HFrEF patients receiving ARNI at a different cumulative dose. Methods: This was an observational study in consecutive outpatients admitted for HFrEF from October 2017 to June 2019. The PARADIGM criteria were needed for enrolment. ARNI was uptitrated according to blood pressure, drug tolerability, renal function and kaliemia. At least 10-month follow-up was required in each patient. Clinical assessment, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, 6-min walk test and strain echocardiography were performed in each patient on a regular basis during the observational period. At the end of the study, patients were divided into two groups based on the median yearly dose of the ARNI medication. Results: A total of 90 patients, 64 ± 11 years, 82% males, were enrolled. The cut-off dose was established in 75 mg BID, and the study population was divided into group A (≤ 75 mg), 52 patients (58%), and group B (> 75 mg), 38 patients (42%). The follow-up duration was 12 months (range 11–13). NYHA class, KCCQ score and 6MWT performance ameliorated in both groups, with a quicker time to benefit in group B. The proportion of patients walking > 350 m increased from 21 to 58% in group A (p < 0.001), and from 29 to 82% in group B (p < 0.001). A positive effect was also disclosed in the left ventricular remodelling, strain deformation and diastolic function. Conclusion: One-year ARNI treatment was effective in our real-life HFrEF patient population, leading to clinical and functional improvement in both study groups, slightly greater and with a shorter time to benefit in group B. [ABSTRACT FROM AUTHOR]

Abstract: 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 &y& Elsevier]

Objectives: Although cardiovascular magnetic resonance (CMR) is widely used in the assessment of left ventricular non-compaction (LVNC), there are no universally accepted diagnostic criteria and limited data regarding their prognostic value. We assessed the long-term prognostic role of the planimetric global Grothoff's criteria and of the CMR findings in predicting adverse cardiovascular events (CE). Methods: We prospectively enrolled 78 patients (46.7 ± 18.7 years, 33.3% females) with documented positive Jenni's echocardiographic criteria for LVNC. Cine images were used to quantify function parameters and to assess for the presence of all four quantitative Grothoff's criteria (global Grothoff's criteria). Late gadolinium enhancement (LGE) images were acquired to detect the presence of replacement myocardial fibrosis. Results: Petersen's CMR criterion for LVNC (NC/C ratio > 2.3 in at least one myocardial segment) was fulfilled in the whole population. Twenty-six patients fulfilled the global Grothoff's criteria (four out of four). The mean duration of the follow-up was 44.2 ± 27.4 months and 28 CE were registered: 10 ventricular tachycardias, 12 episodes of heart failure (HF), four strokes, and two cardiac deaths. In the multivariate analysis, the independent predictive factors for CE were positive global Grothoff's criteria (hazard ratio, HR = 3.33, 95% CI = 1.52–7.29; p = 0.003) and myocardial fibrosis (HR = 2.41, 95% CI = 1.08–5.36; p = 0.032). Conclusions: Positive global Grothoff's criteria and myocardial fibrosis were powerful predictors of CE in patients with a diagnosis of LVNC by CMR Petersen's criterion. Thus, we strongly suggest a step approach confirming the diagnosis of LVNC by using the global planimetric Grothoff's criteria, which showed a prognostic impact. Key Points: • Positive global Grothoff's criteria and replacement myocardial fibrosis were powerful predictors of cardiovascular events in patients with a diagnosis of LVNC by CMR Petersen's criterion. • Positive global Grothoff's criteria were associated with a higher frequency of ventricular arrhythmias in patients with a diagnosis of LVNC by CMR Petersen's criterion. [ABSTRACT FROM AUTHOR]

Background: The short- and long-term prognosis of Takotsubo syndrome (TTS) presenting with right ventricular (RV) involvement remains poorly understood.Research Question: What is the incidence and clinical outcome of RV involvement in TTS?Study Design and Methods: This study analyzed 839 consecutive patients with TTS (758 female subjects and 81 male subjects) in a multicenter registry. RV involvement was defined as wall motion abnormality of the RV free wall, with or without apical involvement. The median long-term follow-up was 2.1 years (interquartile range, 0.3-4.5 years). The primary outcome was in-hospital and out-of-hospital all-cause mortality. The secondary end point was a composite of in-hospital death, thromboembolic events, cardiogenic shock, pulmonary edema, and malignant arrhythmias.Results: The incidence of RV involvement in TTS was 11% (n = 93). More often patients with RV involvement were male compared with patients without RV involvement (P = .02). There was a slight difference in the left ventricular ejection fraction measured in patients with RV involvement vs those patients with isolated left ventricular TTS (38 ± 10% vs 40 ± 10%; P = .03). No major differences in terms of comorbidities were observed between groups except regarding a history of cancer, which was significantly more prevalent in patients with TTS presenting with RV involvement (P = .03). Physical stressors were more prevalent in the RV group (P < .01), whereas emotional stressors were less prevalent (P < .01). Patients with RV involvement had a higher incidence of in-hospital cardiogenic shock (P = .02). The primary outcome (in- and out-of-hospital all-cause mortality) was observed in 12.8% of patients without RV involvement compared with 29% of patients with RV involvement. Although the in-hospital mortality rate was similar in both groups, a higher out-of-hospital all-cause mortality rate (log-rank test, P = .008) was observed in the RV involvement group. The Cox multivariable regression analysis showed that physical triggers were independent predictors of RV involvement.Interpretation: RV involvement defines a high-risk cohort of patients with TTS.Clinical Trial Registration: ClinicalTrials.gov; No.: NCT04361994; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Linked Content This article is linked to Novo et al and He et al papers. To view these articles visit https://doi.org/10.1111/apt.14934 and https://doi.org/10.1111/apt.15003. [ABSTRACT FROM AUTHOR]

Clinical presentation of Takotsubo syndrome (TTS) may range from acute chest pain to dyspnea: the prognostic role of clinical onset is still controversial. Aim of this study was therefore to investigate the prognostic relevance of dyspnea at presentation in patients with TTS. We analyzed 1,071 TTS patients (median age 72 years, 90% female) enrolled in the international multicenter GEIST registry. Patients were divided according to the presence or absence of dyspnea at hospital admission, as clinically assessed by the accepting physician. The primary endpoint was occurrence of in-hospital complications defined as a composite of pulmonary edema, cardiogenic shock and death. Overall, 316 (30%) patients presented with dyspnea at hospital admission. Diabetes, lower left ventricular ejection fraction and presence of pulmonary disease or atrial fibrillation were independently associated with dyspnea. In-hospital pulmonary edema, cardiogenic shock and death (17% vs. 3%, p < 0.001; 12% vs. 7%, p = 0.009; 5% vs. 2%, p = 0.004 respectively) and long-term overall mortality (22% vs. 11%, p < 0.001) occurred more frequently in patients with dyspnea than in those without. At multivariable analysis, dyspnea at presentation remained independently associated to both the composite primary endpoint [odds ratio 2.98 (95% confidence interval (CI) 1.95–4.59, p < 0.001] and all-cause mortality [hazard ratio 2.03 (95% CI 1.37–2.99), p < 0.001]. Dyspnea at presentation is common in TTS and is independently associated with in-hospital complications and impaired long-term prognosis. Thorough symptom assessment including dyspnea therefore represents a valuable tool to potentially optimize risk-stratification models for TTS patients. [ABSTRACT FROM AUTHOR]

Objectives: To analyze left ventricular (LV) myocardial deformation and contractile reserve (CR) in asymptomatic patients with severe aortic regurgitation (AR) at rest and during exercise, and their correlation with functional capacity. Background: The natural history of chronic AR is characterized by a prolonged silent phase before onset of symptoms and overt LV dysfunction. Assessment of LV systolic function and contractile reserve has an important role in the decision‐making of AR asymptomatic patients. Methods: Standard echo, lung ultrasound, and LV 2D speckle tracking strain were performed at rest and during exercise in asymptomatic patients with severe AR and in age‐ and sex‐comparable healthy controls. Results: 115 AR patients (male sex 58.2%; 52.3 ± 18.3 years) and 55 controls were enrolled. Baseline LV ejection fraction was comparable between the groups. Resting LV global longitudinal strain (GLS) and myocardial work efficiency (MWE) were significantly reduced in AR (GLS‐15.8 ± 2.8 vs −21.4 ± 4.4; P <.001). Patients with AR and CR− showed reduced resting LV GLS and MWE and increased B‐lines. MWE was closely related to peak effort watts, VO2, LV E/e′, and B‐lines, at a multivariable analysis. Both GLS and MWE were strong independent predictors of CR. A resting LV GLS cutoff of −12% differentiated CR+ and CR− (78% sensitivity and 84% specificity). Conclusions: The lower resting values of LV GLS and MWE in severe AR asymptomatic patients suggest an early subclinical myocardial damage that seems to be closely associated with lower exercise capacity, greater pulmonary congestion, and blunted LV contractile reserve during stress. [ABSTRACT FROM AUTHOR]

Sacubitril/valsartan has been shown to reduce cardiovascular mortality and hospitalizations in patients with HFrEF when compared to enalapril. There are also some evidences of its potential antiarrhythmic effects. We present a report where we found a relation between reverse ventricular remodeling and arrhythmic reduction in a patient treated with sacubitril/valsartan. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate in patients with microvascular angina and heart failure with preserved ejection fraction, the speckle‐tracking echocardiography, and longitudinal myocardial strain to evaluate the possible presence of alterations in heart failure with preserved ejection fraction patients compared with a control population. We also investigated the correlation between the longitudinal strain analysis and the TIMI frame count after coronary angiography. Methods: Our study was performed on a population 41 patients with microvascular angina that underwent coronary angiography and speckle‐tracking echocardiography. We divided the sample into two categories: patients with heart failure with preserved ejection fraction (n‐21) and patients without heart failure with preserved ejection fraction (n‐20). We calculated TIMI frame count indices for each patient based on angiographic images. Results: Patients with heart failure with preserved ejection fraction had reduced global longitudinal strain values (−17.88) compared with the total control population, and this reduction was statistically significant (P =.028). This reduction was more marked in patients who had a significantly increased TIMI frame count. Therefore, a statistically significant correlation was observed between TIMI frame count and global longitudinal strain. Conclusion: Our results show that cardiac contractile mechanics are altered in patients with heart failure with preserved ejection fraction at a subclinical level hard to identifiable with conventional echocardiography. The dysfunction of the microcirculation and the consequent alteration of the TIMI frame count probably results in a reduction of myocardial performance. [ABSTRACT FROM AUTHOR]

Cardiovascular (CV) adverse events are considered common complications of ponatinib treatment. Recently, it has been demonstrated that ponatinib dose reductions in definite settings can obtain optimal responses and lower ponatinib-related CV events. In this study, we describe the management of 5 patients with chronic myeloid leukemia treated with ponatinib, from second to fourth line of tyrosine kinase inhibitor therapy, carrying high pre-ponatinib CV risk, who obtained optimal molecular response and developed no CV adverse event during follow-up. Among these 5 patients, 2 had diagnosis of ischemic heart disease and underwent percutaneous angioplasty, 2 had type 2 diabetes and arterial hypertension, and 1 had only arterial hypertension. Median follow-up for ponatinib therapy is 1,039 days (34.6 months). Median dosage administered is 30 mg a day. SCORE charts were used to estimate risk of CV death in 10 years and Charlson Comorbidity Index was applied to estimate age-adjusted risk of death related to comorbidities. Strict cardiologic follow-up (complete evaluation every 3 to 6 months) and maximum effort in the control of CV modifiable risk factors are strongly recommended in the management of ponatinib treatment in patients at high risk for CV events and may allow the use of ponatinib in patients belonging to CV risk category. [ABSTRACT FROM AUTHOR]

Significance: Antineoplastic therapies have significantly improved the prognosis of oncology patients. However, these treatments can bring to a higher incidence of side-effects, including the worrying cardiovascular toxicity (CTX). Recent Advances: Substantial evidence indicates multiple mechanisms of CTX, with redox mechanisms playing a key role. Recent data singled out mitochondria as key targets for antineoplastic drug-induced CTX; understanding the underlying mechanisms is, therefore, crucial for effective cardioprotection, without compromising the efficacy of anti-cancer treatments. Critical Issues: CTX can occur within a few days or many years after treatment. Type I CTX is associated with irreversible cardiac cell injury, and it is typically caused by anthracyclines and traditional chemotherapeutics. Type II CTX is generally caused by novel biologics and more targeted drugs, and it is associated with reversible myocardial dysfunction. Therefore, patients undergoing anti-cancer treatments should be closely monitored, and patients at risk of CTX should be identified before beginning treatment to reduce CTX-related morbidity. Future Directions: Genetic profiling of clinical risk factors and an integrated approach using molecular, imaging, and clinical data may allow the recognition of patients who are at a high risk of developing chemotherapy-related CTX, and it may suggest methodologies to limit damage in a wider range of patients. The involvement of redox mechanisms in cancer biology and anticancer treatments is a very active field of research. Further investigations will be necessary to uncover the hallmarks of cancer from a redox perspective and to develop more efficacious antineoplastic therapies that also spare the cardiovascular system. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the long-term outcome of patients with Takotsubo syndrome (TTS) and severely reduced left ventricular ejection fraction (LVEF ≤ 35%) at presentation.Methods and Results: The study population included 326 patients (mean age 69.5 ± 10.7 years, 28 male) with TTS enrolled in the Takotsubo Italian Network, divided into two groups according to LVEF (≤ 35%, n = 131; > 35%, n = 195), as assessed by transthoracic echocardiography at hospital admission. In-hospital events were recorded in both groups. At long-term follow-up (median 26.5 months, interquartile range 18-33), composite major adverse cardiac events (MACE: cardiac death, acute myocardial infarction, heart failure, and TTS recurrence) and rehospitalization were investigated. Compared to patients with LVEF > 35%, patients with LVEF ≤ 35% were older (71.2 ± 10.8 vs. 68.4 ± 10.6 years; P = 0.026) and experienced more frequently cardiogenic shock (16% vs. 4.6%; P < 0.001), acute heart failure (28.2% vs. 12.8%; P = 0.001), and intra-aortic balloon pump support (11.5% vs. 2.6%; P = 0.001) in the acute phase. At long-term follow-up, higher rates of composite MACE (25.2% vs. 10.8%; P = 0.001) and rehospitalization for cardiac causes (26% vs. 13.3%; P = 0.004) were observed in these patients. LVEF ≤ 35% at admission [hazard ratio (HR) 2.184, 95% confidence interval (CI) 1.231-3.872; P = 0.008] and age (HR 1.041, 95% CI 1.011-1.073; P = 0.006) were independent predictors of MACE. Patients with LVEF ≤ 35% also had a significant lower freedom from composite MACE during long-term follow-up (χ2 = 11.551, P = 0.001).Conclusion: Left ventricular ejection fraction ≤ 35% at presentation is a key parameter to identify TTS patients at higher risk not only in the acute phase but also at long-term follow-up. [ABSTRACT FROM AUTHOR]

Abstract The great therapeutical success achieved by oncology is counterbalanced by growing evidences of cardiovascular (CV) toxicity due to many antineoplastic treatments. Cardiac adverse events may cause premature discontinuation of effective oncologic treatments or occur as late events undermining the oncologic success. Arterial hypertension is both the most common comorbidity in cancer patients and a frequent adverse effect of anticancer therapies. A pre-existing hypertension is known to increase the risk of other cardiac adverse events due to oncologic treatments, in particular heart failure. Moreover, as a strict association between cancer and CV diseases has emerged over the recent years, various analyses have shown a direct relationship between hypertension and cancer incidence and mortality. Finally, many antineoplastic treatments may cause a rise in blood pressure (BP) values, particularly the novel anti VEGF agents, this possibly compromising efficacy of chemotherapy. Aim of this review is to revise the topic and the many aspects linking arterial hypertension and cancer, and to provide a comprehensive and practical guide of the current treatment approaches. Highlights • Arterial hypertension is the most common comorbidity of cancer patients. • It is significantly associated with both cancer incidence and mortality. • Arterial hypertension is a risk factor for cancer therapy-related heart failure. • Arterial hypertension is a common adverse effect of many anticancer drugs. • Anti-hypertensive therapy prevents from premature discontinuation of cancer therapy. [ABSTRACT FROM AUTHOR]

Objective: In view of low prevalence rates, diabetes is discussed as a protective factor for the occurrence of Takotsubo syndrome (TTS). Furthermore, it was associated with improved outcome in a small single-center analysis. Therefore, this study assessed the prevalence and prognostic relevance of concomitant diabetes in TTS.Research Design and Methods: A total of 826 patients with TTS were enrolled in an international, multicenter, registry-based study (eight centers in Italy and Germany). All-cause mortality was compared between patients with diabetes and patients without diabetes, and the independent predictive value of diabetes was evaluated in multivariate regression analysis.Results: The prevalence of diabetes was 21.1% (n = 174). TTS patients with diabetes were older (P < 0.001), were more frequently male (P = 0.003), had a higher prevalence of hypertension (P < 0.001), physical triggers (P = 0.041), and typical apical ballooning (P = 0.010), had a lower left ventricular ejection fraction (P = 0.008), had a higher rate of pulmonary edema (P = 0.032), and had a longer hospital stay (P = 0.009). However, 28-day all-cause mortality did not differ between patients with diabetes and patients without diabetes (6.4% vs. 5.7%; hazard ratio [HR] 1.11 [95% CI 0.55-2.25]; P = 0.772). Longer-term follow-up after a median of 2.5 years revealed a significantly higher mortality among TTS patients with diabetes (31.4% vs. 16.5%; P < 0.001), and multivariate regression analysis identified diabetes as an independent predictor of adverse outcome (HR 1.66 [95% CI 1.16-2.39]; P = 0.006).Conclusions: Diabetes is not uncommon in patients with TTS, is associated with increased longer-term mortality rates, and is an independent predictor of adverse outcome irrespective of additional risk factors. [ABSTRACT FROM AUTHOR]