A Very Late Atrial Septal Erosion After an Ostium Secundum Percutaneous Closure.

Complications after device closure of ostium secundum defects are rare but possible. We present a very late erosion of the interatrial septum after a percutaneous closure of an ostium secundum defect. Identification of early clinical and imaging clues associated with this condition is fundamental for a timely diagnosis and treatment. (Level of Difficulty: Intermediate.).

Echocardiographic Patterns of Abnormal Septal Motion: Beyond Myocardial Ischemia.

Abnormal septal motion (ASM), which often is associated with myocardial ischemia, is also observed in other diseases. Owing to the position of the interventricular septum (IVS) in the heart, its movement not only relies on contractile properties but is also affected by the pressure gradient between the 2 ventricles and by the mode of electrical activation. Echocardiography allows the operator to focus on the motion of the IVS, analyzing its characteristics and thereby gaining information about the possible underlying pathophysiological mechanism. In this review, we focused on the main echocardiographic patterns of ASM that are not related to a failure of contractile properties of the septum (i.e., acute coronary syndrome and cardiomyopathies), showing their pathophysiological mechanisms and underlining their diagnostic usefulness in clinical practice.

Incremental Value of Left Atrial Function Analysis in the Assessment of Left Ventricular Filling Pressures in Patients with ST-Elevation Myocardial Infarction.

Background: Left atrial (LA) reservoir strain provides interesting information about left ventricular (LV) filling pressure. However, the advantages of atrial reservoir strain in comparison with conventional parameters in patients with myocardial infarction are not clear yet. Methods: Fifty patients with ST-elevation myocardial infarction (STEMI) prospectively underwent echocardiographic assessment of LV systolic and diastolic function by conventional parameters and two-dimensional speckle tracking longitudinal strain of left atrium. LV filling pressure was estimated by brain natriuretic peptide (BNP) levels. Results: Systolic and conventional diastolic parameters did not show significant differences between patients with increased and normal BNP values, whereas LA reservoir strain was reduced (33.1 ± 8% vs. 46.5 ± 9.8%; P = 0.001) in patients with higher BNP levels. LA reservoir strain had higher area under curve value (0.880) than the other parameters in identifying patients with elevated BNP and a cut-off value of 40.5% reached sensitivity and specificity values of 93% and 86% and positive and negative predictive values of 92% and 85%. LA reservoir strain reclassified 23 patients with increased BNP values, which were previously estimated to have normal (16 patients) and undeterminable LA pressure (seven patients) by using the recommended algorithm for diastolic function. Conclusions: LA reservoir strain is a useful tool for the evaluation of diastolic function and seems to be more sensitive than conventional parameters in the detection of subtle increase of LV filling pressure in patients with STEMI. It allows physicians to reclassify patients with undeterminable diastolic function according to conventional algorithm.

Lipomatous Hypertrophy of the Interatrial Septum: A Case Report and Insights from the Literature.

Lipomatous hypertrophy of the interatrial septum (LHIS) is a histologically benign cardiac lesion that is defined by excessive fat accumulation in the area of the interatrial septum (IAS) that does not include the fossa ovalis. Another unusual illness is lipomatosis, which is defined as a broad overgrowth of mature adipose tissue that involves a large portion of an extremity or trunk. We describe a rare case with significant LHIS accompanied by subcutaneous lipomatosis. Echocardiography revealed a mass in the right atrium in this patient. Magnetic resonance imaging revealed that this mass was composed of the adipose tissue and was an extension of a huge thickened IAS. Furthermore, this significant hypertrophy of the IAS was in direct continuation with the excessive mediastinal and epicardial fat.

Anthracyclines and regional myocardial damage in breast cancer patients. A multicentre study from the Working Group on Drug Cardiotoxicity and Cardioprotection, Italian Society of Cardiology (SIC).

AIMS: In breast cancer (BC) patients treated with anthracyclines-based therapies, we aim at assessing whether adjuvant drugs impact cardiac function differently and whether their cardiotoxicity has a regional pattern. METHODS AND RESULTS: In a multicentre study, 146 BC patients (56 ± 11 years) were prospectively enrolled and divided into three groups according to the received treatments: AC/EC-Group (doxorubicin or epirubicin + cyclophosphamide), AC/EC/Tax-Group (AC/EC + taxanes), FEC/Tax-Group (fluorouracil + EC + taxanes). Fifty-six patients of the total cohort also received trastuzumab. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were calculated before starting chemotherapy (T0), at 3 months (T3), at 6 (T6), and 12 months (T12). A ≥10% drop of EF, while remaining within the normal range, was reached at T6 in 25.3% of patients from the whole cohort with an early decrease only in FEC/Tax-Group (P = 0.04). A ≥15% GLS reduction was observed in many more (61.6%) patients. GLS decreased early both in the whole population (P < 0.001) and in the subgroups. The FEC-Tax Group showed the worst GLS at T6. Trastuzumab further worsened GLS at T12 (P = 0.031). A significant reduction of GLS was observed in all LV segments and was more relevant in the anterior septum and apex. CONCLUSIONS: The decrease of GLS is more precocious and pronounced in BC patients who received FEC + taxanes. Cardiac function further worsens after 6 months of adjuvant trastuzumab. All LV segments are damaged, with the anterior septum and the apex showing the greatest impairments.

Assessment of Intra and Extra-Hospital Outcome after Takotsubo Syndrome in a Single-Center Population.

Objectives: To evaluate short- and long-term outcome in a single prospective cohort of Takotsubo syndrome (TTS) patients, trying to early identify those with better prognosis and to assess the prevalence of left ventricular ejection fraction (LVEF) recovery over time. Methods: Forty-nine patients prospectively enrolled underwent to assessment of demographic, clinical, and echocardiographic characteristics, and later were followed to identify the outcomes during a mean follow-up (FU) of 93 months. At the end of the FU phase, a subgroup of patients underwent to a clinical and echocardiographic re-evaluation. As major adverse cardiac events (MACE) were considered: Intra and extra-hospital death, re-hospitalizations for acute heart failure or atrial fibrillation (AF) or acute myocardial infarction (AMI) and TTS recurrence; minor events were considered minor symptoms of heart failure and angina not requiring hospitalization. Results: The prevalence of re-hospitalizations (MACE) over time was: 41% (n = 12) for HF; 6.8% (n = 2) for AMI; 3.4% (n = 1) for TTS relapse and 20% (n = 6) for AF. Minor events were the symptoms of chest pain and dyspnea not requiring hospitalization in 6 (20.7%) and 12 (34.4%) patients, respectively. LVEF at the time of admission was predictor for MACE. Stratifying patients on the LVEF admission median value (40%). Patients with LVEF <40% at admission had a significantly lower survival free from adverse cardiac events compared to patients with LVEF ≥40%. Twenty-seven (93%) patients underwent to a clinical reassessment with electrocardiogram and echocardiographic examination. LVEF value showed a statistically significant increase (P = 0.004) at the end of FU. Conclusions: At admission, "high-risk" patients (LVEF <40%) can be easily detected, allowing an appropriate pharmacological and/or mechanical support strategy and a more "careful" FU.

Bicuspid aortic valve and aortopathy: novel prognostic predictors for the identification of high-risk patients.

AIMS: Bicuspid aortic valve (BAV) may be complicated by aortic aneurysms and dissection. This study aimed to evaluate the prognostic efficacy of markers from cardiac imaging, as well as genetic and new biomarkers, to early predict aortic complications. METHODS AND RESULTS: We re-evaluated after a mean time of 48 ± 11 months 47 BAV patients who had undergone previous echocardiography for evaluation of aortic stiffness and 2D aortic longitudinal strain (LS) (by speckle-tracking analysis), and who had given a blood sample for the assessment of a single-nucleotide polymorphism of elastin gene (ELN rs2 071307) and quantification of elastin soluble fragments (ESF). Surgical treatment of aortic aneurysm/dissection was the primary endpoint, and an aortic dimension increase (of one or more aortic segments) ≥1 mm/year was the secondary endpoint. Nine patients underwent surgical treatment of ascending aorta (AA) aneurysms. Out of the 38 patients who did not need surgical intervention, 16 showed an increase of aortic root and/or AA dimension ≥1 mm/year. At multivariate Cox regression analysis, an impaired AA LS was an independent predictor of aortic surgery [P = 0.04; hazard ratio (HR) 0.961; 95% confidence interval (CI) 0.924-0.984] and aortic dilatation (P = 0.007; HR 0.960; 95% CI 0.932-0.989). An increased quantity of ESF was correlated (P = 0.015) with the primary endpoint at univariate Cox regression analysis but it did not keep statistical significance at multivariate analysis. CONCLUSION: In BAV patients, impairment of elastic properties of the AA, as assessed by 2D LS, is an effective predictor of aortic complications.

Impaired myocardial strain in early stage of Duchenne muscular dystrophy: its relation with age and motor performance.

Duchenne muscular dystrophy (DMD) is complicated by an early and progressive left ventricular (LV) dysfunction. Despite the reduction of ejection fraction (EF) usually manifests in the second decade, subtle alterations in LV mechanics can be detected earlier. Longitudinal and circumferential LV deformation, evaluated by speckle tracking echocardiography (STE), are considered sensitive markers of early dysfunction. We retrospectively examined clinical and echocardiographic data of 32 DMD children with preserved LV function. According to the median age, patients were then divided into younger and older than 9 years, and compared to 24 age-matched healthy subjects. Six-minute-walk test (6MWT), North Star Ambulatory Assessment (NSAA), and a comprehensive cardiac evaluation were performed. Although EF was within the normal range, DMD patients had significantly lower values than healthy controls, and the same occurred for the remaining conventional systolic and diastolic indices. Global longitudinal strain (GLS) was reduced in all patients (older and younger, both p < 0.001). Global circumferential strain (GCS) was reduced only in older patients (< 0.001). Both GLS and GCS worsened with age in DMD patients (GLS p = 0.005; GCS p = 0.024). GLS was significantly worse in the apical segments and in the postero-lateral wall. GCS in the antero-septal, anterior and antero-lateral segments was significantly reduced in older patients, with a prevalent involvement of the sole septal wall in the younger boys. 6MWT appeared to be correlated inversely to GLS and directly to EF. A longitudinal evaluation should be scheduled in DMD boys to assess the global cardiac performance over time and to evaluate the impact of therapies.

Arterial stiffness and mitral regurgitation in arterial hypertension: an intriguing pathophysiological link.

BACKGROUND: We examined the relative impact of arterial stiffness on the presence and/or severity of chronic mitral regurgitation (MR) in hypertensive patients. METHODS: We prospectively enrolled 141 untreated hypertensive patients (mean age 56.6 ±â€¯11.5 years): 94 with MR, 47 without MR. As a measure of arterial stiffness, pulse wave velocity (PWV) was assessed by applanation tonometry. Assessment of MR severity was obtained through calculation of effective regurgitant orifice area (EROA) and vena contracta by standard two-dimensional transthoracic echocardiography. RESULTS: PWV appears to progressively increase according to the presence and severity of MR (no MR = 7.3 ±â€¯1.1 m/s, mild MR = 7.9 ±â€¯1.3 m/s, moderate MR = 9.0 ±â€¯1.7 m/s, severe MR = 13.3 ±â€¯4.1 m/s; P < 0.001 for all comparisons). EROA was positively correlated with age (P = 0.011), left atrial volume index (P = 0.023), PWV (P < 0.001) and augmentation index (P < 0.001), and negatively correlated with left ventricular ejection fraction (P = 0.002) and heart rate (HR) (P = 0.018). On stepwise multivariate logistic regression analysis, only PWV (OR = 2.87, 95% CI 1.750-4.738, P < 0.001) and HR (OR = 0.94, 95% CI 0.895-0.994, P = 0.02) appeared to be independent predictors of severe MR. Receiver operating characteristic curves showed that a cutoff of 9 m/s for PWV provided the best sensitivity/specificity for predicting both the presence of any degree of MR (sensitivity 73%, specificity 87%, AUC = 0.863; P < 0.001) and MR severity (sensitivity 100%, specificity 81%, AUC = 0.954; P < 0.001). CONCLUSION: Reduced arterial elasticity because of increased stiffness may be an important marker for the presence and severity of MR in hypertensive patients.

Takotsubo cardiomyopathy: queries of the current era.

: Takotsubo cardiomyopathy (TTS), also known as left ventricular apical ballooning syndrome, is an acute, usually reversible heart failure syndrome that most often affects postmenopausal women experiencing an emotionally stressful event. It is characterized by sudden left ventricular dysfunction and wall motion abnormalities involving the apical and mid segments. TTS has been increasingly recognized in recent years, and more and more information about the pathophysiology, diagnosis, and treatment of these patients has been reported. However, much is still unknown. TTS has a wide variety of clinical subtypes and has been described in several clinical contexts. Moreover, TTS simulates ST-segment elevation myocardial infarction and acute myocarditis, and it can be difficult to obtain a certain diagnosis. As a result, clinical decisions are challenging, and many patients currently receive an inappropriate management strategy. The aim of this review is to critically analyze the evidence about this disease reported in the literature, with particular focus on the pathophysiological processes, the diagnostic elements that can help the clinician differentiate it from other diseases, and the best management of these patients.

Ten Years of 2D Longitudinal Strain for Early Myocardial Dysfunction Detection: A Clinical Overview.

In recent years, the role of left ventricular ejection fraction (EF) as the gold standard parameter for the evaluation of systolic function has been questioned, and many efforts have been concentrated in the clinical validation of new noninvasive tools for the study of myocardial contractility. Improvement in the accuracy of speckle-tracking echocardiography has resulted in a large amount of research showing the ability of two-dimensional strain to overcome EF limitations in the majority of primary and secondary heart diseases. Currently, global longitudinal strain (GLS) is considered the most accurate and sensitive parameter for the assessment of early left ventricular dysfunction. This review summarizes the advantages that this measurement can provide in several clinical settings. Moreover, the important cautions that should be considered in making the choice to use GLS also are addressed. Finally, a special focus on bull's-eye polar maps for the assessment of regional changes of longitudinal function and the usefulness of these maps in the differential diagnosis of several diseases is provided.

Cardiovascular maladaptation to exercise in young hypertensive patients.

BACKGROUND: Impairment of the adaptive mechanisms that increase cardiac output during exercise can translate to a reduced functional capacity. We investigated cardiovascular adaptation to exertion in asymptomatic hypertensive patients, aiming to identify the early signs of cardiac and vascular dysfunction. METHODS AND RESULTS: We enrolled 54 subjects: 30 patients (45.1±11.9years, 19 males) and 24 age-matched healthy controls (44.4±9.6years, 14 males). Speckle-tracking echocardiography (STE) and echo-tracking were performed at rest and during exertion to assess myocardial deformation and arterial stiffness. RESULTS: E/E' increased from rest to peak exercise more in patients than in controls (peak stage: p=0.024). Global longitudinal strain increased significantly from rest to peak stage in controls (p=0.011) whereas it remained unchanged in patients (p=0.777). Left atrial (LA) reservoir was significantly increased throughout the exercise only in controls (p=0.001) whereas it was almost unchanged in patients (p=0.293). LA stiffness was significantly higher in patients than in controls both at rest (p=0.023) and during exercise (p<0.001). Beta index and pulse wave velocity (PWV) increased during exercise in both groups, showing higher values in patients in each step. CONCLUSIONS: Our study showed a more pronounced maladaptation during exercise, with respect to rest, of the cardiovascular system with impaired cardiac-vessel coupling in hypertensive patients compared to healthy subjects. Exercise echocardiography implemented by STE and echo-tracking is invaluable in the early detection of these cardiovascular abnormalities.

Takotsubo syndrome and estrogen receptor genes: partners in crime?

AIMS: We aimed to analyze genetic polymorphism of estrogen receptor (ESR) 1 and ESR2 in a series of postmenopausal women with Takotsubo syndrome (TS). METHODS: In total, 81 consecutive white women were prospectively enrolled: 22 with TS (TS group; mean age 71.2 ±â€Š9.8 years), 22 with acute myocardial infarction (MI group; mean age 73.2 ±â€Š8 years), and 37 asymptomatic healthy controls (CTRL group; mean age 69 ±â€Š4.2 years). Genotyping of ESR1 -397C>T (rs2234693) and -351A>G (rs9340799) and ESR2 -1839G>T (rs 1271572) and 1082G>A (rs1256049) genetic variants was performed. We estimated the odds ratio (OR) between the genotype of each examined locus with the occurrence of TS or MI. RESULTS: The risk of experiencing TS was higher for those study participants carrying the T allele at the rs2234693 locus of the ESR1 gene [OR: 2.0, 95% confidence interval (CI): 0.973-4.11, P = 0.04, TS vs. MI + CTRL; OR: 2.79, 95% CI: 1.17-6.64, P = 0.016, TS vs. MI alone]. Women carrying a T allele at the rs1271572 locus of the ESR2 gene demonstrated an even higher risk (OR: 3.23, 95% CI: 1.55-6.73, P = 0.0019, TS vs. MI + CTRL; OR: 9.13, 95% CI: 2.78-29.9, P = 0.0001, TS vs. MI alone). CONCLUSION: The study reports preliminary findings suggesting a possible link between ESR polymorphisms and the occurrence of TS. Larger studies are needed to confirm our results.

PFO: Button me up, but wait Comprehensive evaluation of the patient.

Patent foramen ovale (PFO) is a slit or tunnel-like communication in the atrial septum occurring in approximately 25% of the population. A wide number of pathological conditions have been linked to its presence, most notably, cryptogenic stroke (CS) and migraine. However, in the setting of a neurological event, it is not often clear whether the PFO is pathogenically related to the index event or an incidental finding. Therefore, a detailed analysis of several clues is needed for understanding PFO's clinical significance, with a frequent case-by-case decision about destination therapy. Indeed, the controversy about PFO's pathogenicity prompted a paradigm shift of research interest from medical therapy with antiplatelets or anticoagulants to percutaneous transcatheter closure, in secondary prevention. Observational data and meta-analysis of observational studies had previously suggested that PFO closure with a device was a safe procedure with a low recurrence rate of stroke. To date, however, recent randomized controlled trials have not shown the superiority of PFO closure over medical therapy. Thus, the optimal strategy for secondary prevention of paradoxical embolism in patients with a PFO remains unclear. Moreover, the latest guidelines for the prevention on stroke restricted indications for PFO closure to patients with deep vein thrombosis and high-risk of its recurrence. Given these recent data, in the present review, we critically discuss current treatment options, pointing out the role of a comprehensive patient evaluation in overcoming PFO closure restrictions and planning the best management for each patient.

Usefulness of atrial function for risk stratification in asymptomatic severe aortic stenosis.

AIM: We aimed to evaluate the usefulness of left atrial (LA) mechanics and stiffness over global left ventricular (LV) longitudinal strain (GLS) for risk stratification in severe aortic stenosis (AS). METHODS: From a cohort of 89 prospective asymptomatic patients with severe AS and normal LV ejection fraction, 82 (32 men, mean age 73±10 years) truly asymptomatic patients, scheduled after a negative exercise echocardiogram, were enrolled. Forty age- and gender-matched prospective, asymptomatic subjects served as controls. Predefined end points were the occurrence of symptoms (dyspnea, angina, syncope), and death during follow-up. RESULTS: At study entry, patients had: impaired LV GLS (p=0.001), reduced LA reservoir (p<0.001), high LA stiffness (p<0.001), and increased valvulo-arterial impedance (p<0.001) compared to controls. During follow-up [16±14.9 months (ranging from 1 month to 4.2 years)], 53 patients (64.6%) reached one of the endpoints. Patients with events showed lower LV GLS (p>0.001), lower LA reservoir (p<0.001), and greater LA stiffness (p<0.001) than those asymptomatic. On univariate Cox regression analysis, LV GLS (p<0.001), LA reservoir (p<0.001), and LA stiffness (p=0.004) were strong predictors of adverse events. Kaplan-Meier curves showed that event-free survival was significantly higher in patients with a LV GLS ≥16.8% [p<0.001; area under the curve (AUC)=0.922; sensitivity=86%, specificity=80%], a LA reservoir ≥19.8% (p=0.001; AUC=0.860, sensitivity=71%, specificity=84%), and a LA stiffness <0.78 (p<0.001; AUC 0.819, sensitivity 70%, specificity 89%). On multivariate analysis, only LV GLS remained significantly associated with patients' prognosis (hazard ratio=1.49, 95% CI=1.11-2.01, p=0.008). CONCLUSIONS: In asymptomatic patients with severe AS, an efficient cardiovascular system is based on an effective atrial-ventricular interplay. LA function assessment is useful for early identification of risk in these patients. LV GLS however was confirmed to be the best predictor of patients' outcome.

Cardiovascular outcomes and conventional risk factors in non-diabetic adult patients with GH deficiency: A long-term retrospective cohort study.

PURPOSE: To investigate the association between cardiovascular (CV) risk factors and cumulative CV events in patients with growth hormone deficiency (GHD) receiving GH replacement therapy (GHRT). METHODS: 53 non-diabetic adult GHD patients, aged 45.4±14.3years, 31 females, with a median follow up of 140months, were divided into two groups based on the presence (group A) or absence (group B) of systemic hypertension. Tertiles of age and LDL-cholesterol were considered as further potential prognosticators. Cumulative CV event rates were recorded and analyzed by Kaplan-Mayer method. Differences between patients with and without events were also evaluated. RESULTS: Seventeen patients (32%) entered the group A and 36 (68%) the group B. A composite of fatal and non-fatal CV events occurred in 22.6% of patients, 47.1% in group A and 11% in group B (p=0.01), CV deaths in 3 patients (5.7%; annual death rate 0.49%), 2 of whom were in group A. At Kaplan-Mayer analysis, hypertension and age>55years were major prognosticators. The odds ratio was 7.1 (95% CI: 1.74-29.12, p<0.003) and 6.2 (95% CI: 1.54-25.04, p<0.006), respectively. LDL-cholesterol showed borderline statistical significance. Patients with CV events also had high prevalence of left ventricular hypertrophy, left atrial enlargement and subclinical systolic dysfunction. CONCLUSIONS: In this study, outcomes were mainly related to hypertension and age (partially to LDL-cholesterol), confirming that management of GHD patients must be inclusive of treatment of conventional risk factors, being as important as GHRT. Optimal blood pressure control is crucial when a target organ damage is present and in patients older than 55years.

Usefulness of Left Atrial Reservoir Size and Left Ventricular Untwisting Rate for Predicting Outcome in Primary Mitral Regurgitation.

The present study proposed to evaluate whether analysis of cardiac mechanics through speckle-tracking imaging is useful for risk stratification in asymptomatic patients with chronic primary mitral regurgitation (MR). We prospectively enrolled 67 patients (mean age 57 ± 18 years) and followed them over time. MR was mild in 20 patients (30%), moderate in 24 (36%), and severe in 23 (34%). After a mean time of 24.8 ± 17 months, 34 patients (51%) remained asymptomatic, whereas 33 (49%) developed events (19 underwent mitral valve surgery, 9 required hospitalization for acute heart failure, and 5 patients died). Compared to asymptomatic patients, those with events at baseline showed more severe MR, larger and spherical ventricles, diastolic dysfunction, and greater systolic pulmonary arterial pressure. Moreover, patients with events had decreased left atrial (LA) reservoir (p <0.001) and left ventricular (LV) untwisting rate (p <0.001). On univariate Cox regression analysis, effective regurgitant orifice area (p <0.001), vena contracta (p <0.001), systolic pulmonary arterial pressure (p = 0.003), LV end-systolic diameter (p <0.001), E/E' ratio (p = 0.004), LA volume (p = 0.001), LA reservoir (p <0.001), and LV untwisting rate (p <0.001) were associated with an increased risk of events. On multivariate analysis, only LA reservoir (p = 0.013) and LV untwisting rate were independent predictors (p = 0.017) of outcome. Moreover, LA reservoir evaluation significantly improved (p = 0.013) risk stratification compared to recommended parameters. In conclusion, impaired cardiac mechanics is more closely associated than severity of MR with the occurrence of events in asymptomatic chronic primary MR.