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Aim To assess the prevalence and prognostic significance of NI-LGE in patients undergoing stress-CMR. Methods Stress-CMR with either dipyridamole or adenosine was performed in 283 patients (228 men, 81%) including perfusion imaging, wall motion evaluation and LGE. Follow-up was completed in all enrolled patients (median time: 1850 days; interquartile range: 1225-2705 days). Composite endpoint included cardiac death, ventricular tachycardia, myocardial infarction, stroke, hospitalization for cardiac cause and coronary revascularization performed beyond 90 days from stress-CMR scans. Results One hundred and twelve patients (40%) had negative LGE (no-LGE), 140 patients (49%) I-LGE and 31 patients (11%) NI-LGE. Twenty-five events occurred in the no-LGE group, 68 in I-LGE and 11 in the NI-LGE group. On survival curves, patients with NI-LGE had worse prognosis than patients with no-LGE regardless of the presence of inducible perfusion defects. No significant prognostic differences were found between I-LGE and NI-LGE. Conclusion NI-LGE can be detected in 11% of patients during stress-CMR providing a diagnosis of nonischemic cardiac disease. Patients with NI-LGE have worse prognosis than those with no-LGE.

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.

Worldwide population ageing is partly due to advanced standard of care, leading to increased incidence and prevalence of geriatric syndromes such as frailty and disability. Hence, the age at the onset of acute coronary syndromes (ACS) keeps growing as well. Moreover, ageing is a risk factor for both frailty and cardiovascular disease (CVD). Frailty and CVD in the elderly share pathophysiological mechanisms and associated conditions, such as malnutrition, sarcopenia, anemia, polypharmacy and both increased bleeding/thrombotic risk, leading to a negative impact on outcomes. In geriatric populations ACS is associated with an increased frailty degree that has a negative effect on re-hospitalization and mortality outcomes. Frail elderly patients are increasingly referred to cardiac rehabilitation (CR) programs after ACS; however, plans of care must be tailored on individual’s clinical complexity in terms of functional capacity, nutritional status and comorbidities, cognitive status, socio-economic support. Completing rehabilitative intervention with a reduced frailty degree, disability prevention, improvement in functional state and quality of life and reduction of re-hospitalization are the goals of CR program. Tools for detecting frailty and guidelines for management of frail elderly patients post-ACS are still debated. This review focused on the need of an early identification of frail patients in elderly with ACS and at elaborating personalized plans of care and secondary prevention in CR setting.

Patent foramen ovale (PFO) is a common abnormality that occurs in about 25% of the adult population. In most cases is a benign finding, but sometimes the communication between the right and the left atria can be a conduit for thrombi.

Atherosclerosis is a dynamic process driven by all cardiovascular risk factors that can be briefly divided into an early and a late phase. Inflammation is one of the fundamental substrates that initiates the atherosclerotic process in the early stages and promotes and maintains it in the final stages. In the last decades, clinical and experimental data have shown that inflammation is supported by mediators that respond to physical activity. The present review aims at investigating the effect of physical exercise on inflammatory mediators, both the positive ones that therefore have a pro-inflammatory effect (interleukin 6, c-reactive protein and tumor necrosis factor alpha, interferon gamma, high-mobility group box-1), and the negative ones which have an anti-inflammatory effect (interleukin 10). Pooled data support the evidence that physical exercise is able to directly modulate the activity of inflammatory cytokines slowing down or preventing the formation of the atherosclerotic stage.

Background. The variation between rest and peak stress end-systolic pressure-volume relation (ΔESPVR) is an index of myocardial contractility, easily obtained during routine stress echocardiography and never tested during dipyridamole stress-cardiac magnetic resonance (CMR). We assessed the ΔESPVR index in patients with known/suspected coronary artery disease (CAD) who underwent dipyridamole stress-CMR.Methods. One-hundred consecutive patients (24 females, 63.76±10.17 years) were considered. ESPVR index was evaluated at rest and stress from raw measurement of systolic arterial pressure and end-systolic volume by biplane Simpson’s method. Results. The ΔESPVR index showed a good inter-operator reproducibility. Mean ΔESPVR index was 0.48±1.45 mmHg/mL/m2. ΔESPVR index was significantly lower in males than in females. ΔESPVR index was not correlated to rest left ventricular end-diastolic volume index or ejection fraction. Forty-six of 85 patients had myocardial fibrosis detected by the late gadolinium enhancement technique and they showed significantly lower ΔESPVR values. An abnormal stress CMR was found in 25 patients and they showed significantly lower ΔESPVR values. During a mean follow-up of 56.34±30.04 months, 24 cardiovascular events occurred. At receiver-operating characteristic curve analysis, a ΔESPVRConclusions. The noninvasive assessment of the ΔESPVR index during a dipyridamole stress-CMR exam is feasible and reproducible. The ΔESPVR index was independent from rest LV dimensions and function and can be used for a comparative assessment of patients with different diseases. ΔESPVR by CMR can be a useful and simple marker for additional prognostic stratification.

Background The variation between rest and peak stress end-systolic pressure-volume relation is an afterload-independent index of left ventricular contractility. This index is easily obtained during routine stress echocardiography but can be derived also during a stress cardiovascular magnetic resonance (CMR) exam, that is the gold standard for the quantification of biventricular volumes. Purpose The aim of this study was to assess for the first time the prognostic value ofdelta rest-stress ESPVR (DESPVR) by dipyridamole stress-CMR in patients with known or suspected coronary artery disease (CAD). Methods One hundred and sixty-six consecutive patients (37 females, main age 61.96 ± 10.05 years) who underwent dipyridamole stress-CMR in a high volume CMR Laboratory were considered. Abnormal wall motion and perfusion at rest and after dipyridamole were analysed. Macroscopic myocardial fibrosis was detected by the late gadolinium enhancement (LGE) technique. The ESPVR was evaluated at rest and peak stress from raw measurement of systolic arterial pressure by cuff sphygmomanometer and end-systolic volume by biplane Simpson method. Results An abnormal stress CMR was found in 39 (23.5%) patients; 24 patients had a reversible stress perfusion defect in at least one myocardial segment and 15 a reversible stress perfusion defect plus worsening of stress wall motion in comparison with rest. Myocardial fibrosis was detected in 69 patients (41.6%). A DESPVR During a median follow up of 55.51 months (IQ range 33.20 months), 54 patients (32.5%) experienced major cardiac events: 5 deaths, 2 ventricular arrhythmias, 18 coronary syndromes, and 29 heart failure hospitalization.Reversible perfusion deficit, DESPVR Conclusions DESPRV assessed by CMR provides a prognostic stratification in patients with known or suspected coronary artery disease, in addition to that supplied by reversible perfusion deficit and diabetes. Abstract 1177 Figure 1

Background in the recent years, survival of cancer patients increased enormously through the use of new anticancer drugs such as molecular target drugs (tyrosine kinase inhibitors- TKIs, immunotherapy). Immunotherapy includes anti-BRAF and anti-MEK drugs (although evidences are scarce, these drugs seem to be capable of causing cardiovascular toxicity too); TKIs includes inhibitors of VEGF, VEGFR and other kinases. Purpose to assess cardiovascular toxic effects of TKIs and immunotherapy, to identify early signs of cardiac and vascular toxicity using speckle tracking echocardiography and arterial stiffness measurement. Methods a prospective study was carried out evaluating 45 patients treated with immunotherapy or TKIs. Population was divided into 2 groups: Group A (17 patients with melanoma treated with anti- BRAF and anti-MEK) and Group B (28 patients with solid cancer treated with TKIs-anti VEGF). Cardiological evaluation including electrocardiogram, conventional echocardiogram with tissue Doppler imaging (TDI) and left ventricular global longitudinal strain (GLS) measurement and carotid ultrasound scan was carried out before starting therapy and at a follow-up time of 6 and 12 months. Cardiovascular events such as heart failure, arterial hypertension, arrhythmias, Qtc interval prolongation, stroke, arterial and venous thrombosis were assessed during follow-up. Results mean follow-up was 7 months for anti-BRAF and 13 months for TKI. Neither cardiovascular adverse events nor significant reductions in LVEF or other echocardiographic parameters during follow-up were observed in Group A: we did not observe significant changes in GLS (-18,4 [RI -19,9 a -15,8] vs. -18,3 [RI -18,9 a -16,1] or in vascular parameters (PWV 7,3 ± 1,4 vs. 6,7 ± 1,5, β mean wave 8,5 [RI 6,3-12] vs. 7,4 [RI 4,9-9,4]; α mean wave 6,8 [RI 3,1-6,2] vs. 9,6 [RI 2,4-4,6]). As regards Group B, new onset of arterial hypertension in 35% of population but no significant changes in LVEF or other echocardiographic parameters including GLS ( -18,6 ± 2,3 vs. -18,3 ± 3,3) were observed. Significant changes were furthermore found in vascular parameters with increased arterial stiffness during follow-up (PWV 7,82 ± 1,23 vs. 10,02 ± 2,73; p = 0,04, β mean wave 5,33 ± 1,98 vs. 8,43 ± 3,03; p = 0,02, α mean wave 10,79 ± 4,03 vs.16,82 ± 6,38; p = 0,03). Conclusions according to the literature data, immunotherapy seems to have a safe cardiovascular profile. Anti-VEGF drugs seem to predominantly cause vascular damage, early identifiable through arterial stiffness measurement.

BACKGROUND Speckle-tracking echocardiography (STE) can be applied in a large variety of clinical conditions. Global longitudinal strain (GLS) shows high diagnostic accuracy for the detection of myocardial ischemia as it reflects changes in subendocardial fibers deformation that are more exposed to ischemic damage, even before alterations in segmental kinetics are revealed. PURPOSE Aim of our study was to assess whether the measurement of global longitudinal strain during stress-echo can provide additional information compared to the assessment of conventional parameters such as left ventricular ejection fraction (LVEF) and wall motion abnormalities. We also evaluated the added value of strain in patients with complete (CRP) and incomplete revascularization (IRP). METHODS We enrolled 69 patients, 39 with known (IHD) and 30 with suspected ischaemic heart disease (SIHD) with indication to perform a stress echocardiogram. Inclusion criteria were: known or suspected CAD, age 18, adeguate acoustic window. Cardiological evaluation and stress echo were performed in all patients. Primary end point was evaluating whether in patients with negative stress test the presence of reduced GLS identifies patients with an adverse prognosis at follow up and to assess if in IRP and negative stress test there is evidence of left subclinical ventricular dysfunction identifiable by GLS analysis compared to CRP. RESULTS LVEF was significantly reduced in IHD patients compared to SIHD patients (54 ± 7vs 60 ± 4 at rest; 55 ± 8vs62 ± 3 at peak; p compared to SIHD patients (-16.7 ± 4,3vs-19 ± 2.2 - p = 0.07 at rest, -18 ± 4.6vs22 ± 3.4-p = 0.004 at peak). In CRP patients GLS did not change significantly with a tendency to improve (-17.6 ± 4 at rest vs -19 ± 4.5 at peak - p = 0.4). Instead in IRP patients, significant reduction of GLS was observed at peak (17.5 ± 0.7 at rest vs 14.2 ± 0.3 at peak, p value 0,03). LVEF did not significantly differ in CRP (54 ± 5 at baseline vs 55 ± 7 at peak, p = 0.5) and IRP (52 ± 9 at baseline vs. 52 ± 9 at peak, p = 0.9) . CONCLUSIONS Our study shows that strain analysis during stress echocardiography can provide additional information in identifying a subclinical reduction of myocardial function at baseline and a reduction in contractile reserve under stress, secondary to coronary flow reduction. Being GLS a powerful prognostic marker probably patients with negative stress test and incomplete revascularization, reduced baseline GLS and reduction of GLS at peak exercise represent a population at higher risk of coronary artery disease progression and development of left ventricular dysfunction who need a closer follow up. To verify our hypothesis we plan to increase our sample size and to prospectively follow up our patients.

Background Speckle tracking echocardiography with assessment of left ventricular global longitudinal strain (GLS) allows to identify early signs of cardiac dysfunction. The superiority of GLS in the prediction of all-cause mortality in the general population compared with LVEF is well known; in addiction GLS improves risk stratification and recognize early left ventricular dysfunction in several clinical setting. Purpose the aim of this study was to assess the diagnostic and prognostic role of global and segmental strain in the early identification of cardiac dysfunction in patients with myocardial infarction without persistent ST segment elevation (NSTEMI) and without obvious wall motion abnormalities and to assess the ability to predict the presence/extension of coronary artery disease in this population. Methods an observational study was carried out enrolling 56 patients (median age 66 ± 11,7 years) admitted for NSTEMI. Electrocardiogram, echocardiogram with global and segmental strain measurement (GE’s Automated Function Imaging) and coronary angiography were performed in all patients. In addition we measured territorial longitudinal strain (TLS) defined as the mean of peak systolic strain of the segments pertinent to the perfusion territories of each epicardial coronary arteries in a 17-segment LV model. Results mean LVEF was 53%. We found a significant relationship between GLS values and coronary artery disease extension: GLS -19,1 % ±5,7% in patients without significant coronary artery stenosis, -18,74% ±4,85% in patients with one coronary artery disease, -15,6% ±4,3% in patients with two coronary artery disease, -14,2% ±5,4% in patients with 3 coronary artery disease (p = 0,03). We also found a correlation between territorial strain value and corresponding coronary artery stenosis. TLS was significantly reduced in patients with significant coronary disease of the perfused territory for each artery (LAD TLS 15,1% ± 6,74 % vs -20,73± 4,47 p = 0,002; CX TLS -11,42 % ± 6,59 %,vs -17,06 ± 7,1, p = 0,0 05 , RCA -14,02 % ± 6,00 % vs-17,6 ± 5,21 p = 0,02). At ROC analysis we identified a TLS value of -16,9 % to identify patients with significant stenosis of LAD (sensibility 58,3% and specificity 89,4%, AUC = 0,74, P Conclusions global and segmental strain measurement in patients with NSTEMI help to identify the presence and extension of significant coronary artery disease.

Iron deficiency (ID) is recognized as an important comorbidity in patients undergoing cardiac surgery; however, it still remains under-diagnosed and under-treated in clinical practice. This study aims at comparing efficacy and the effects on exercise capacity of intravenous ferric carboxymaltose (FCM) versus ferric gluconate (FG) in patients with ID anemia (IDA) resulting from cardiac surgery. We retrospectively analyzed data from our records of in-hospital patients with IDA after cardiac surgery undergoing cardiac rehabilitation. Group I was treated with FG, group II with FCM. Efficacy measures included changes (baseline vs discharge) in hemoglobin (Hb) and in distance traveled at six-minutes walking test (6MWT). Data from 74 in-patients (mean age 67.5±10.4 years, 43% women) were analyzed. At discharge, patients treated with FCM showed higher levels of Hb (11.1±1.2g/dl vs 10.2±1.1 g/dl; p=0.001), greater distance traveled at 6MWT (279.2±108.8 meters vs 236.3±72.7 meters; p=0.048), and lower in-hospital rehabilitation length of stay (20.3±7 vs 25.3±11.7 days; p=0.043) as compared to FG group. At multivariate analysis, the most powerful predictors of Hb increase >1 g/dl at discharge were transferrin levels (p=0.019) and treatment with FCM (p100 meters) at discharge (p=0.13 and p=0.003, respectively). In patients with IDA following cardiac surgery, intravenous FCM is effective in restoring Hb levels and in improving exercise capacity after cardiac surgery.

BACKGROUND The structural heart modifications especially for left chambers, in chronic hypertensive status are well known but recently, an increased interest in a global assessment of cardiac dysfunction in arterial hypertension is developing especially concerning the preclinical cardiac damage. The two-dimensional speckle tracking echocardiography (2D STE) is a promising technique to detect the preclinical myocardial dysfunction in different circumstances included hypertension. PURPOSE Our aim was to detect and investigate the early changes in myocardial deformation index in hypertensive patients without evident signs of organ damage, using speckle tracking echocardiography. METHOD We enrolled 92 subjects referred to our outpatient clinic for suspected hypertension without history of previous cardiovascular disease. The blood pressure measurements were always gotten with the patients seated after 5 minutes of rest. Among the selected patients 49 were finally diagnosed with essential hypertension (average office blood pressure (BP) ≥ 140/90 mmHg for at least 3 times or valid 24 hours ambulatory blood pressure measurement (ABPM) with an average BP ≥ 135/85 mmHg) while 43 subjects were not and their data were used as controls. A 2D conventional echocardiography was performed prior to other analysis for an internal protocol to exclude all the subjects with structural pathologic findings and all the patients underwent the echocardiography before the starting of any kind of therapy active on BP. Patients with chronic diseases and pregnant women were considered not eligible. We perform STE analysis of LA, LV, RV free wall, and a multilayer STE analysis for LV and RV (epicardial, mid-wall myocardial, endocardial) using specifics offline software. RESULTS All the patients had always conventional echocardiographic parameters in range of normality without particularly difference between the groups except for IVS thickness and E/E’ratio (P The STE analysis show worsening in myocardial deformation index both for LV GLS (P CONCLUSION Our study suggest that 2D STE can be considered a useful method to identify early alterations of myocardial dysfunction in hypertensive patients without a clinical organ damage. All ventricular myocardial layers are involved in arterial hypertension likewise the LA walls. A layer specific pattern of alteration looks to be present in the early phases of arterial hypertension however its predictive value needs more investigation first to become of clinical use.

BACKGROUND Heart failure with preserved ejection fraction (HFpEF) is characterized by heart failure symptoms despite preserved LV systolic function together with at least one among left ventricle hypertrophy/left atrial enlargement plus diastolic dysfunction (DD) and increased brain natriuretic peptide levels. Rest echocardiography could still be normal despite patients experience HF symptoms. Speckle tracking analysis (STE) analyzes myocardial deformation and is able to identify subtle left ventricular dysfunction. PURPOSE to analyze the added value of stress echocardiography to improve diagnostic accuracy in patients with normal ejection fraction and unexplained dyspnoea by evaluating DD, lung B lines and STE. METHODS Main inclusion criteria were: suspected heart failure, EF > 40%, DD up to moderate at rest (E/e"18 years, satisfactory acoustic window. Exclusion criteria were: comorbidities limiting the prognosis, valvulopathy more than moderate, coronary artery disease, moderate to severe DD at rest (E/e"≥14; E/A≥2), pregnancy or lactation. Each patient underwent physical stress echo and STE by GE Vivid 7, (AFI). RESULTS After measuring diastolic function parameters variation with stress, HFpEF was diagnosed in 8 patients, who had baseline non-diagnostic echocardiogram (Table 1). In the remaining 20 patients a non-cardiac etiology of dyspnoea was diagnosed (NCD). EF did not significantly change from rest to stress either in HFpEF group (58 ± 6 vs 61 ± 8.7 p:0.62) or in DNC group (59 ± 8 vs 62.2 ± 7.4; p:0.26). GLS values tended to decrease in patients with HFpEF (-18.5 ± 2.2 at baseline vs -15.96 ± 6.67 at peak stress; p:0.33), and it was stable in DNC (-17.69 ± 1.15 at baseline vs - 18.04 ± 2.02 at peak stress; p:0.64). CONCLUSIONS Study of diastolic function during stress echocardiography is a useful diagnostic tool to reveal HFpEF in patients with dyspnea and unremarkable baseline echocardiogram. STE could offer useful adjunctive diagnostic information but further studies are needed to confirm its value. Table 1 HFpEF NCD p HFpEF NCD p GLS -18,5 ± 2,2 -17,6 ± 1,15 0,23 -15,96 ± 6,67 18,04 ± 2,02 0,26 E/A 0,8 ± 0,1 1 ± 0,7 0,55 1,67 ± 0,7 1,26 ± 0,6 0,07 E/e’ 10,1 ± 2,2 9,9 ± 3,7 0,4 16,4 ± 0,9 13,8 ± 5 0,16 PAP 25,6 ± 4,1 22,33 ± 0,55 0,57 49,8 ± 9,65 28,27 ± 4,35 0,001 LA 35,5 ± 8,5 23,44 ± 4,9 0,001 34,45 ± 4,88 27,32 ± 7,33 0,018 EF 58 ± 6 59 ± 8 0,6 61 ± 8,7 62,2 ± 7,4 0,7 Echocardiographic parameters at baseline and at peak stress in patients with HFpEF and with NCD

Background Myocarditis is an inflammatory disease of the myocardium predominantly caused by infection with subsequent immunological response. Cardiac magnetic resonance (CMR) is the currently best imaging modality to confirm a suspected diagnosis of myocarditis. Conventional echocardiography can detect regional or global wall motion abnormalities but it could also be negative. Speckle tracking echocardiography can help to identify subtle systolic dysfunction, in patients with myocardits and apparently negative echocardiogram. Purpose the aim of this study was to identify cardiac imaging parameters predictive of cardiovascular events in patients with acute myocarditis. Methods a prospective study was carried out using 76 patients with acute myocarditis. Cardiological evaluation including echocardiogram and CMR with quantitative analysis of edema and delayed enhancement (DE) was performed in all patients at the hospital admission. In 43 patients we assessed multilayer 2D speckle tracking analysis measuring GLS at three levels (mid-wall layer, endocardial and epicardial) and mechanical dispersion (MD). We assessed cardiovascular events during hospitalization in all patients (arrhythmias, heart failure, cardiogenic shock, syncope). Results we found significant higher value of DE mass in patients with cardiovascular events compared to patients without cardiovascular events (20,23 ± 11,47gr vs 11,58 ± 9,54gr; p = 0,021). GLS and multilayer strain at each level was significantly lower in patients with events than in patients without events (GLS epicardial -16,29 ± 1,76% vs -14,54 ± 2,19%; p = 0,013; GLS mid-wall -18,22 ± 1,94% vs -16,27 ± 2,48%; p = 0,013; GLS endocardial -19,83 ± 1,91% vs -17,81 ± 2,65%; p = 0,011). MD was significantly higher in patients with cardiovascular events (48.50 ± 15.79 ms vs 34.12 ± 6.22ms; p With segmental analysis, inferior and lateral walls seemed to be more predictive of events. Segment 9 had a good predictability in all layers (epicardial: ROCarea 0,8-OddsRatio 1,69; mid wall: ROCarea 0,83- OddsRatio 1,77; endocardial: ROC area 0,82-OddsRatio 1,69). MD was a slight predictor of events with ROC area < 0,7. Conclusions Speckle tracking echocardiography could be used in addiction to cardiac magnetic resonance to get more information about prognosis and events risk stratification in patients with acute myocarditis.

Anthracyclines are the cornerstone for many oncologic treatments, but their cardiotoxicity has been recognized for several decades. Female subjects, especially before puberty and adolescence, or after menopause, seem to be more at increased risk, with the prognostic impact of this sex issue being less consistent compared to other cardiovascular risk factors. Several studies imply that sex differences could depend on the lack of the protective effect of sex hormones against the anthracycline-initiated damage in cardiac cells, or on differential mitochondria-related oxidative gene expression. This is also reflected by the results obtained with different diagnostic methods, such as cardiovascular biomarkers and imaging techniques (echocardiography, magnetic resonance, and nuclear medicine) in the diagnosis and monitoring of cardiotoxicity, confirming that sex differences exist. The same is true about protective strategies from anthracycline cardiotoxicity. Indeed, first studied to withstand oxidative damage in response to ischemia/reperfusion (I/R) injury, cardioprotection has different outcomes in men and women. A number of studies assessed the differences in I/R response between male and female hearts, with oxidative stress and apoptosis being shared mechanisms between the I/R and anthracyclines heart damage. Sex hormones can modulate these mechanisms, thus confirming their importance in the pathophysiology in cardioprotection not only from the ischemia/reperfusion damage, but also from anthracyclines, fueling further cardio-oncologic research on the topic.

Background The variation between rest and peak stress end-systolic pressure-volume relation (ESPVR; the Suga index) is easily obtained during routine stress echocardiography and has been established as a reasonably load-independent index of myocardial contractile performance that provides prognostic information above and beyond regional wall motion. Purpose This is the first study assessing the delta rest-stress ESPVR (DESPVR) by stress Cardiovascular Magnetic Resonance (CMR). Methods Eighty-five consecutive patients (19 females, main age 62.99±9.26 years) who underwent dipyridamole stress-CMR in a high volume CMR Laboratory were considered. The ESPVR was evaluated at rest and peak stress from raw measurement of systolic arterial pressure by cuff sphygmomanometer and end-systolic volume by biplane Simpson method. Results Mean ESPVR index at rest and peak stress was, respectively, 4.52±2.26 mmHg/mL/m2 and 4.62±2.32 mmHg/mL/m2 and mean DESPVR was 0.11±1.19 mmHg/mL/m2. DESPVR was not associated to age or sex. An inverse relationship between rest left ventricular end-diastolic volume index (LVEDVI) and both rest and peak ESPVR was present (R=-0.805 P An abnormal stress CMR was found in 22 patients and the DESPVR was comparable between patients with normal and abnormal stress exam. During a median follow-up of 60.62 months (IQ range 36.78 months), 27 cardiovascular events occurred: 3 deaths, 1 ventricular arrhythmias, 9 coronary syndromes, 14 heart failure hospitalization. At receiver-operating characteristic (ROC) curve analysis, a DESPVR Conclusions We showed for the first time that dipyridamole stress CMR can be used for the assessment of DESPVR. DESPVR was shown to be independent from chamber size and, as a consequence, can be used for a comparative assessment of patients with different diseases. DESPVR by CMR can provide a prognostic stratification and the optimal cutoff for relevant events was 0.009.

Background Several studies have investigated the association between native QRS duration (QRSd) or QRS narrowing and response to biventricular pacing. However, their results have been conflicting. The aim of our study was to determine the association between the relative change in QRS narrowing index (QI) and clinical outcome and prognosis in patients who undergo cardiac resynchronization therapy (CRT) implantation. Methods and results We included 311 patients in whom a CRT device was implanted in accordance with current guidelines for CRT. On implantation, the native QRS, the QRSd and the QI during CRT were measured. After 6months, 220 (71%) patients showed a 10% reduction in LVESV. The median [25th–75th] QI was 14.3% [7.2–21.4] and was significantly related to reverse remodeling (r=+0.22; 95%CI: 0.11–0.32, p=0.0001). The cut-off value of QI that best predicted LV reverse remodeling after 6months of CRT was 12.5% (sensitivity=63.6%, specificity=57.1%, area under the curve=0.633, p=0.0002). The time to the event death or cardiovascular hospitalization was significantly longer among patients with QI>12.5% (log-rank test, p=0.0155), with a hazard ratio (HR) of 0.3 [95%CI: 0.11–0.78]. In the multivariate regression model adjusted for baseline parameters, a 10% increment in QI (HR=0.61[0.44–0.83], p=0.002) remained significantly associated with CRT response. Conclusions Patients with a larger decrease in QRSd after CRT initiation showed greater echocardiographic reverse remodeling and better outcome from death or cardiovascular hospitalization. QI is an easy-to-measure variable that could be used to predict CRT response at the time of pacing site selection or pacing configuration programming.

Hypertrophic obstructive cardiomyopathy (HOCM) is the most frequently inherited cardiovascular disease (prevalence in the general population of 1/500) and is characterized by significant left ventricular hypertrophy, especially in the interventricular septum, combined with small-volume cardiac cavities. Transaortic surgical septal myectomy is the most commonly used technique to treat HOCM, and is associated with low operative morbidity and mortality and a reduction of the outflow gradients. The composite operative mortality of only 0.4% (17/3695 patients) from 5 major high-volume centers in North America highlights the role of dedicated HOCM units. The involvement of the mitral valve in the pathophysiology of HOCM has been addressed as systolic anterior motion (SAM)-related left ventricular outflow tract obstruction. Hypertrophic cardiomyopathy mitral malformations include leaflet elongation and a wide array of malformations of the papillary muscles and chordae that can be detected by transthoracic and transesophageal echocardiography and by cardiac magnetic resonance. Because they participate fundamentally in the predisposition to SAM, they have increasingly been repaired surgically.

Background. Sacubitril/valsartan in heart failure (HF) with reduced ejection fraction (HFrEF) was shown to be superior to enalapril in reducing the risk of death and hospitalization for HF. Our aim was to evaluate the cardiopulmonary effects of sacubitril/valsartan in patients with HFrEF. Methods. We conducted an observational study. Ninety-nine ambulatory patients with HFrEF underwent serial cardiopulmonary exercise tests (CPET) after initiation of sacubitril/valsartan in addition to recommended therapy. Results. At baseline, 37% of patients had New York Heart Association (NYHA) class III. After a median follow-up of 6.2 months (range 3&ndash, 14.9 months) systolic blood pressure decreased from 117 &plusmn, 14 to 101 &plusmn, 12 mmHg (p &lt, 0.0001), left ventricular ejection fraction (LVEF) increased from 27 &plusmn, 6 to 29.7 &plusmn, 7% (p &lt, 0.0001), peak oxygen consumption (VO2) improved from 14.6 &plusmn, 3.3 (% of predicted = 53.8 &plusmn, 14.1) to 17.2 &plusmn, 4.7 mL/kg/min (% of predicted = 64.7 &plusmn, 17.8) (p &lt, 0.0001), minute ventilation/carbon dioxide production relationship (VE/VCO2 Slope) decreased from 34.1 &plusmn, 6.3 to 31.7 &plusmn, 6.1 (p = 0.006), VO2 at anaerobic threshold increased from 11.3 &plusmn, 2.6 to 12.6 &plusmn, 3.5 mL/kg/min (p = 0.007), oxygen pulse increased from 11.5 &plusmn, 3.0 to 13.4 &plusmn, 4.3 mL/kg/min (p &lt, 0.0001), and ∆VO2/∆Work increased from 9.2 &plusmn, 1.5 to 10.1 &plusmn, 1.8 mL/min/watt (p = 0.0002). Conclusion. Sacubitril/valsartan improved exercise tolerance, LVEF, peak VO2, and ventilatory efficiency at 6.2 months follow-up. Further studies are necessary to better clarify underlying mechanisms of this functional improvement.

Sudden cardiac death (SCD) is the most life-threating complication of hypertrophic cardiomyopathy. Guidelines of the European Society of Cardiology (ESC) suggest the implantation of an implantable cardioverter defibrillator in primary prevention according to a 5-year risk SCD score >= 6%. The aim of the study is to evaluate the prognostic role of late gadolinium enhancement (LGE) in patients with a 5-year risk SCD score = 4 and = 10% was the best threshold to predict major arrhythmic events (area under the curve: 0.74). Kaplan-Meier curves showed that patients with LGE >= 10% had a worse prognosis than those with lower extent (p < 0.0001). LGE extent was the best independent predictor of hard cardiac events (hazard ratio 1.05; 95% confidence interval [CI] 1.03 to 107; p < 0.0001). The estimates 5-year risk of hard cardiac event was 2.5% (95% CI 0.8 to 4.2) in patients with LGE extent = 10%. In conclusion, this study demonstrates as the extent of LGE >= 10% is able to recognize additional patients at increased risk for malignant arrhythmic episodes in a population with low-to-intermediate ESC SCD risk score. (C) 2019 Elsevier Inc. All rights reserved.

Oxidative stress and mitochondrial dysfunction are hallmarks of heart failure (HF). Coenzyme Q10 (CoQ10) is a vitamin-like organic compound widely expressed in humans as ubiquinol (reduced form) and ubiquinone (oxidized form). CoQ10 plays a key role in electron transport in oxidative phosphorylation of mitochondria. CoQ10 acts as a potent antioxidant, membrane stabilizer and cofactor in the production of adenosine triphosphate by oxidative phosphorylation, inhibiting the oxidation of proteins and DNA. Patients with HF showed CoQ10 deficiency; therefore, a number of clinical trials investigating the effects of CoQ10 supplementation in HF have been conducted. CoQ10 supplementation may confer potential prognostic advantages in HF patients with no adverse hemodynamic profile or safety issues. The latest evidence on the clinical effects of CoQ10 supplementation in HF was reviewed.

Heart failure (HF) and left ventricular (LV) dysfunction are the most concerning and serious cardiovascular complications of cancer therapies and cause an increase in morbidity and mortality. Some cancer treatments induce left ventricular dysfunction that appears early after exposure and therefore may adversely affect oncological therapy, while others generate cardiac injuries resulting in clinical problems only years later.

Early detection and quantification of cardiac damage in cancer patients are essential to readily intervene with cardioprotective strategies and avoid the need of the discontinuation of antineoplastic treatment.

Infective endocarditis is a disease associated with high mortality and severe complications. We report a case of a young shepherd affected by valvular endocarditis on a bicuspid aortic valve, complicated by a pseudoaneurysm with periaortic abscess. Thanks to the use of multimodality diagnostic imaging (particular echocardiogram, Magnetic Risonance Imaging, Computed tomography-scan and coronary angiography), it was possible to make a correct diagnosis, in order to plan a tailored surgical strategy and to reduce the perioperative risks. The operation consisted of myocardial revascularization, closure of the annular pseudoaneurysm and aortic valve replacement with mechanical prosthesis. The patient maintained normal inflammation indices and was discharged at home in the absence of relevant clinical events. Infective endocarditis is a deadly disease. Multimodality imaging is crucial to clarify anatomical distorsions that can occur in complicated cases.

Background Cirrhotic cardiomyopathy has been characterized by impaired contractile response to stress and/or altered diastolic relaxation, with electrophysiological abnormalities in the absence of known cardiac disease. However, the clinical significance of diastolic dysfunction (DDF) in cirrhotic patients has not been clarified. Methods We studied 84 cirrhotic patients with normal systolic function to evaluate the prevalence of DDF using tissue Doppler imaging, and to investigate the possible correlation of DDF with outcomes (hospitalization, death) and with the specific causes of death. Results The mean follow-up was 10±8months. DDF was diagnosed in 22 patients (26.2%). Patients with DDF more frequently had ascites (90.9% vs. 64.5 %; p =0.026), lower levels of albumin (OR: 5.39; p =0.004), higher NT-proBNP levels, and longer QTc interval (464±23ms vs. 452±30ms; p =0.039). At follow-up, patients with DDF did not have a higher incidence of adverse events in terms of hospitalization and death. Conclusions The presence of diastolic dysfunction has not been found to be clearly associated with outcome, and prognosis has been determined primarily by the severity of liver disease.

Cardiovascular diseases are possible complications of antineoplastic treatment and may lead to premature morbidity and mortality among cancer survivors. A symptom-based follow-up is ineffective, and there are growing evidences that early detection of myocardial damage in patients treated with antineoplastic drugs is the key point to prevent the occurrence of damage and improve the prognosis of these patients. Different techniques have been proposed to monitor cardiac function in oncologic patients such as cardiac imaging (echocardiography, nuclear imaging, and cardiac magnetic resonance) and biomarkers (troponin and natriuretic peptides). The European Association of Cardiovascular Imaging/American Society of Echocardiography consensus document encourages an integrated approach to early detect cardiotoxicity.

Chest pain is one of the chief presenting complaints among patients attending Emergency department. The diagnosis of acute myocardial infarction may be a challenge. Various tools such as anamnesis, blood sample (with evaluation of markers of myocardial necrosis), ultrasound techniques and coronary computed tomography could be useful. However, the interpretation of electrocardiograms of these patients may be a real concern. The earliest manifestations of myocardial ischemia typically interest T waves and ST segment. Despite the high sensitivity, ST segment deviation has however poor specificity since it may be observed in many other cardiac and non-cardiac conditions. Therefore, when ST–T abnormalities are detected the physicians should take into account many other parameters (such as risk factors, symptoms and anamnesis) and all the other differential diagnoses. The aim of our review is to overview of the main conditions that may mimic a ST segment Elevation Myocardial Infarction (STEMI).

A 47-year–old asymptomatic woman underwent routine follow-up of Takayasu aortitis with cardiovascular magnetic resonance. She had undergone aortic valve replacement 7 years before because of aortic root aneurysm. She was normotensive and on chronic therapy with steroids and tocilizumab. In addition, she had undergone yearly clinical follow-ups and a previous cardiovascular magnetic resonance 1 year before, showing mild dilation of the postprosthetic ascending aorta and aortic arch, as well as wall thickening and inflammation of the descending aorta (Figure 1). Her current cardiovascular magnetic resonance scan disclosed a large pseudoaneurysm of the descending aorta, with …

The rationale for cardiac resynchronization therapy (CRT) in patients with heart failure (HF) is based on the possibility of inducing substantial left ventricular reverse remodeling. It is well known that some of these patients don't benefit from this therapy (the so-called non-responders) [1,2]. No better predictors of a positive answer to CRT than pre-CRT QRS duration (QRSd) were found [3,4]. The aim of our study was to identify a parameter for an easy and early identification of responders to CRT. In this regard, according to Rickard et al., we identified and observed QRS index (QI), as an expression of electrical remodeling after CRT, and its relation with anatomic reverse remodeling, ecocardiographically assessed at six months [5]. We enrolled 39 patients who underwent CRT implantation. The following inclusion criteria were applied: New York Heart Association (NYHA) functional classes II–IV, left ventricular ejection fraction (LVEF) ≤ 35% and pre-CRT QRSd N 120 ms. The procedure was performed according to the current technique. The preand post-CRT ECGs were the last ECG recorded prior to and after CRT implantation, respectively. QRS morphologies were classified in two categories: left bundle branch block (LBBB) and non-LBBB, which included right bundle branch block (RBBB) and nonspecific intraventricular conduction delay (NSIVCD). QI was defined as the relative reduction of the post-CRT QRSd and was determined through the following formula: QI = [(QRSd post CRT− QRSd pre CRT) / QRSd pre CRT] × 100 with a negative value corresponding to a higher reverse remodeling [5]. All patients were followed up at 1, 3, 6 and 12 months. At 6 months, patients were classified as responders to reverse remodeling if left ventricular end-systolic volume (LVESV) decreased by N10% from baseline according to Yu criteria [6]. Atrioventricular interval optimization was performed, if possible, soon after the implantation; interventricular interval optimization was performed at six months, only in the case of non-responders. Among 39 patients, 26 (66%) were considered responders to CRT with a significant QRS narrowing and QI decrement compared to nonresponders ones (127 ± 17 vs 141 ± 17 msec, P b 0.01; −14 ± 7 vs −6.8 ± 7%, P b 0.004, respectively). In univariate analysis, the presence of ischemic cardiomyopathy (19.2% in responders vs 30.7% in non-responders, P b 0.003) was associated with non responders to CRT (P = 0.004), while no statistically significant differences were found for atrial fibrillation (7.6% vs 23%) and glomerular filtration rate. No significant differences between responders and non-responders were found for pre-CRT QRSd and pre-CRT LVEF, LVESV and LVEDV. Both groups, responders and non-responders, showed an increase of post-CRT LVEF, which was higher among responders both as absolute value (32 ± 7 vs 22 ± 4%, P b 0.0001) and as an index of variation between preand post-CRT (8.7 ± 8 vs 0.3 ± 3%, P0.0005). Using multivariate analysis we found that QI could be a short-term predictor of response to CRT [Odds ratio di 1.5 (1.1–2.1), P = 0.03]. Spearman correlation analysis showed that QI was positively correlated with Yu index (Fig. 1). Because of the small sample size it is not possible to identify a cut-off value of QI but in our population this value was empirically considered about −10% (Fig. 2). Even if twenty years have passed since CRT was introduced, the number of responders to this therapy and how to get to an early identification of responders is still a matter of discussion. In our study, we identify responders, according to Yu criteria [6]. After CRT, LVEF improved in both categories, with a higher increase in responders. However, we registered an increase of left ventricular function in all patients who underwent CRT, independently from baseline LVEF and LVESV. This evidence stands for the absolute benefit of biventricular stimulation in patients with HF and overt left ventricular dysfunction. Besides this, in our populationwe observed a better outcome, in terms of response to CRT, in patients with LBBB [2]. However, the main unsolved problem is a fast identification of possible non-responders in order to provide, soon after the procedure, all the measures to obtain the best result from CRT. We chose QI because of its immediate availability and reproducibility. At 6 months follow-up, 66% of our populationwas responder to CRT, having shown signs of reverse remodeling; an improvement of ≥1 in NYHA functional class was registered in all patients and none of responders was admitted to the hospital at one year follow-up. Our study is important because it shows not only an association between QRSd reduction and responders but also between responders and QI (Figs. 1–2). Moreover it demonstrates the relation between QI and Yu index that is another example of the strong relationship between electrical and anatomic remodeling [6]. This suggests the possible role of QI as a fast and easy to obtain parameter for an early prediction of CRT response. In this way we could optimize the device or drug therapy during or soon after implantation looking for a possible reduction of nonresponder population considering a different position or pacing configuration of the left catheter during implantation, echocardiographic optimization of the interventricular interval or a best titration of drug therapy.

☆ This statement is to certify that all authors have seen being submitted, have contributed significantly to the w legitimacy of the data and its interpretation, and ag International Journal of Cardiology. We attest that the artic has not received prior publication and is not under elsewhere. We adhere to the statement of ethical pub (Shewan LG et al 2013 in press). ☆☆ On behalf of all co-authors, the corresponding author the submission. ⁎ Corresponding author at: Division of Cardiology II, D and Cardiovascular Diseases, University Hospital Paolo Gi 90127 Palermo, Italy. Tel.: +39 1 6554303; fax: +39 1 65 E-mail address: odisseos86@alice.it (V. Sucato).

Pulmonary embolism is a rare clinical onset of chronic myeloproliferative diseases. Early diagnosis is very important because medical therapy reduces both mortality and morbility. We describe a case of pulmonary embolism as clinical onset of an unknown myeloproliferative disorder. On the basis of our experience is very important early diagnosis and therapy to reduce incidence of later major thrombotic complications.

The term metabolic syndrome defines a cluster of risk factors for cardiovascular diseases and diabetes. This syndrome is very frequent in general population. However, despite the efforts to define the diagnostic criteria, nowadays its clinical utility is object of a lively debate.