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Research reveals that social anxiety may be predictive of bullying victimization, but it is not clear whether this relation stands for different groups of youth. The present study examines this association by employing a longitudinal design over 1 year and including the moderating role of developmental period (childhood vs. early adolescence) and students’ immigrant status (native vs. non-native). T1 sample included 506 children (46.44% girls, mean age M = 8.55 years, SD = 0.55) and 310 early adolescents (50% girls, mean age = 12.54 years, SD = 0.59) recruited in schools in Northern Italy. Due to missing cases and drop-outs from T1 to T2, the final sample comprised 443 and 203 students from primary and middle school, respectively. Social anxiety and peer victimization were assessed through self-reported questionnaires. Results indicated that victimization at T2 was predicted by a 3-way interaction between T1 social anxiety, immigrant status, and developmental period. In particular, socially anxious early adolescents with an immigrant background were the most victimized. The results are discussed in terms of group dynamics and intergroup processes. The findings highlight the importance of personal variables in the cumulation of risks: social anxiety is more predictive of bullying victimization for immigrant early adolescents than for children or native early adolescents.

Background: Echocardiographic surrogates of right ventricle–to–pulmonary artery (RV-PA) coupling have been reported to be associated with outcomes in patients with secondary tricuspid regurgitation (STR). However, pulmonary artery systolic pressure (PASP) is difficult to estimate using echocardiography in patients with severe STR. The aim of the present study was to evaluate the predictive power of a surrogate of RV-PA coupling obtained using right ventricular (RV) volumes measured on three-dimensional echocardiography. Methods: One hundred eight patients (mean age, 73 ± 13 years; 61% women) with moderate or severe STR were included. Results: At a median follow-up of 24 months (interquartile range, 2-48 months), 72 patients (40%) had reached the composite end point of death of any cause and heart failure hospitalization. RV-PA coupling was computed as the ratio between RV forward stroke volume (SV) (i.e., RV SV − regurgitant volume) and RV end-systolic volume (ESV). RV forward SV/ESV was significantly more related to the composite end point than RV ejection fraction (area under the curve, 0.85 [95% CI, 0.78-0.93] vs 0.73 [95% CI, 0.64-0.83], respectively; P = .03). A value of 0.40 was found to best correlate with outcome. On multivariate Cox regression, RV forward SV/ESV, tricuspid annular plane systolic excursion/PASP, and RV free wall longitudinal strain/PASP were all independently associated with the occurrence of the composite end point when added to a group of parameters including STR severity (severe vs moderate), atrial fibrillation, pulmonary arterial hypertension, right atrial volume, RV end-diastolic volume, and RV free wall longitudinal strain. RV forward SV/ESV < 0.40 (HR, 3.36; 95% CI, 1.49-7.56; P < .01) carried higher related risk than RV free wall longitudinal strain/PASP < −0.42%/mm Hg (HR, 3.1; 95% CI, 1.26-7.84; P = .01) and tricuspid annular plane systolic excursion/PASP < 0.36 mm/mm Hg (HR, 2.69; 95% CI, 1.29-5.58; P = .01). RV eject

Aims: The HFA-PEFF algorithm (Heart Failure Association-Pre-test assessment, Echocardiography and natriuretic peptide score, Functional testing in cases of uncertainty, Final aetiology) is a three-step algorithm to diagnose heart failure with preserved ejection fraction (HFpEF). It provides a three-level likelihood of HFpEF: low (score < 2), intermediate (score 2–4), or high (score > 4). HFpEF may be confirmed in individuals with a score > 4 (rule-in approach). The second step of the algorithm is based on echocardiographic features and natriuretic peptide levels. The third step implements diastolic stress echocardiography (DSE) for controversial diagnostic cases. We sought to validate the three-step HFA-PEFF algorithm against a haemodynamic diagnosis of HFpEF based on rest and exercise right heart catheterization (RHC). Methods and results: Seventy-three individuals with exertional dyspnoea underwent a full diagnostic work-up following the HFA-PEFF algorithm, including DSE and rest/exercise RHC. The association between the HFA-PEFF score and a haemodynamic diagnosis of HFpEF, as well as the diagnostic performance of the HFA-PEFF algorithm vs. RHC, was assessed. The diagnostic performance of left atrial (LA) strain < 24.5% and LA strain/E/E′ < 3% was also assessed. The probability of HFpEF was low/intermediate/high in 8%/52%/40% of individuals at the second step of the HFA-PEFF algorithm and 8%/49%/43% at the third step. After RHC, 89% of patients were diagnosed as HFpEF and 11% as non-cardiac dyspnoea. The HFA-PEFF score resulted associated with the invasive haemodynamic diagnosis of HFpEF (P < 0.001). Sensitivity and specificity of the HFA-PEFF score for the invasive haemodynamic diagnosis of HFpEF were 45% and 100% for the second step of the algorithm and 46% and 88% for the third step of the algorithm. Neither age, sex, body mass index, obesity, chronic obstructive pulmonary disease, or paroxysmal atrial fibrillation influenced the performance o

Background: Among patients with heart failure with preserved ejection fraction (HFpEF), a distinct hemodynamic phenotype has been recently described, ie, latent pulmonary vascular disease (HFpEF-latentPVD), defined by exercise pulmonary vascular resistance (PVR) >1.74 WU. Objectives: This study aims to explore the pathophysiological significance of HFpEF-latentPVD. Methods: The authors analyzed a cohort of patients who had undergone supine exercise right heart catheterization with cardiac output (CO) measured by direct Fick method, between 2016 and 2021. HFpEF-latentPVD patients were compared with HFpEF control patients. Results: Out of 86 HFpEF patients, 21% qualified as having HFpEF-latentPVD, 78% of whom had PVR >2 WU at rest. Patients with HFpEF-latentPVD were older, with a higher pretest probability of HFpEF, and more frequently experienced atrial fibrillation and at least moderate tricuspid regurgitation (P < 0.05). PVR trajectories differed between HFpEF-latentPVD patients and HFpEF control patients (Pinteraction = 0.008), slightly increasing in the former and reducing in the latter. HFpEF-latentPVD patients displayed more frequent hemodynamically significant tricuspid regurgitation during exercise (P = 0.002) and had more impaired CO and stroke volume reserve (P < 0.05). Exercise PVR was correlated with mixed venous O2 tension (R2 = 0.33) and stroke volume (R2 = 0.31) in HFpEF-latentPVD patients. The HFpEF-latentPVD patients had had higher dead space ventilation during exercise and higher PaCO2 (P < 0.05), which correlated with resting PVR (R2 = 0.21). Event-free survival was reduced in HFpEF-latentPVD patients (P < 0.05). Conclusions: The results suggest that when CO is measured by direct Fick, few HFpEF patients have isolated latent PVD (ie, normal PVR at rest, becoming abnormal during exercise). HFpEF-latentPVD patients present with CO limitation to exercise, associated with dynamic tricuspid regurgitation, altered ventilatory control, a

Background: Right heart failure (RHF) is associated with a dismal prognosis in patients with pulmonary hypertension (PH). Exercise right heart catheterization may unmask right heart maladaptation as a sign of RHF. We sought to (1) define the normal limits of right atrial pressure (RAP) increase during exercise; (2) describe the right heart adaptation to exercise in PH owing to heart failure with preserved ejection fraction (PH-HFpEF) and in pulmonary arterial hypertension (PAH); and (3) identify the factors associated with right heart maladaptation during exercise. Methods and results: We analyzed rest and exercise right heart catheterization from patients with PH-HFpEF and PAH. Right heart adaptation was described by absolute or cardiac output (CO)-normalized changes of RAP during exercise. Individuals with noncardiac dyspnea (NCD) served to define abnormal RAP responses (>97.5th percentile). Thirty patients with PH-HFpEF, 30 patients with PAH, and 21 patients with NCD were included. PH-HFpEF were older than PAH, with more cardiovascular comorbidities, and a higher prevalence of severe tricuspid regurgitation (P < .05). The upper limit of normal for peak RAP and RAP/CO slope in NCD were >12 mm Hg and ≥1.30 mm Hg/L/min, respectively. PH-HFpEF had higher peak RAP and RAP/CO slope than PAH (20 mm Hg [16-24 mm Hg] vs 12 mm Hg [9-19 mm Hg] and 3.47 mm Hg/L/min [2.02-6.19 mm Hg/L/min] vs 1.90 mm Hg/L/min [1.01-4.29 mm Hg/L/min], P < .05). A higher proportion of PH-HFpEF had RAP/CO slope and peak RAP above normal (P < .001). Estimated stressed blood volume at peak exercise was higher in PH-HFpEF than PAH (P < .05). In the whole PH cohort, the RAP/CO slope was associated with age, the rate of increase in estimated stressed blood volume during exercise, severe tricuspid regurgitation, and right atrial dilation. Conclusions: Patients with PH-HFpEF display a steeper increase of RAP during exercise than those

Background: Both secondary tricuspid regurgitation (STR) and heart failure with preserved ejection fraction (HFpEF) are relevant public health problems in the elderly population, presenting with potential overlaps and sharing similar risk factors. However, the impact of severe STR on hemodynamics and cardiorespiratory adaptation to exercise in HFpEF remains to be clarified. Aim: To explore the impact of STR on exercise hemodynamics and cardiorespiratory adaptation in HFpEF. Methods: We analyzed invasive hemodynamics and gas-exchange data obtained at rest and during exercise from HFpEF patients with severe STR (HFpEF-STR), compared with 1:1 age-, sex-, and body mass index (BMI)- matched HFpEF patients with mild or no STR (HFpEF-controls). Results: Twelve HFpEF with atrial-STR (mean age 72 years, 92% females, BMI 28 Kg/m2) and 12 HFpEF-controls patients were analyzed. HFpEF-STR had higher (p < 0.01) right atrial pressure than HFpEF-controls both at rest (10 ± 1 vs. 5 ± 1 mmHg) and during exercise (23 ± 2 vs. 14 ± 2 mmHg). Despite higher pulmonary artery wedge pressure (PAWP) at rest in HFpEF-STR than in HFpEF-controls (17 ± 2 vs. 11 ± 2, p = 0.04), PAWP at peak exercise was no more different (28 ± 2 vs. 29 ± 2). Left ventricular transmural pressure and cardiac output (CO) increased less in HFpEF-STR than in HFpEF-controls (interaction p-value < 0.05). This latter was due to lower stroke volume (SV) values both at rest (48 ± 9 vs. 77 ± 9 mL, p < 0.05) and at peak exercise (54 ± 10 vs. 93 ± 10 mL, p < 0.05). Despite these differences, the two groups of patients laid on the same oxygen consumption isophlets because of the increased peripheral oxygen extraction in HFpEF-STR (p < 0.01). We found an inverse relationship between pulmonary vascular resistance and SV, both at rest and at peak exercise (R2 = 0.12 and 0.19, respectively). Conclusions: Severe STR complicating HFpEF impairs SV and CO reserve, leading to pulmonary vascular de-recruitment and relative

The outbreak of novel coronavirus-19 disease (COVID-19) was classified as a global pandemic thanks to the rapid viral spread, and restrictive policy measures of infection containment, including "lockdown" periods and self-isolation, were first instituted in Belgium from March to June 2020. The consequent reduction in physical activity could have a negative impact on exercise capacity, especially in frail patients with pre-existing chronic diseases, such as pulmonary arterial hypertension (PAH). With the aim to define the impact of COVID-19 lockdown on functional status, we included in our observational analysis clinically stable PAH patients, who had performed at least four consecutive 6-min walking tests (6MWT) during 2019-2020, to compare their exercise performance before and after the lockdown. In the 63 patients included, a comparison between the distance covered at 6MWT after the lockdown period and the pooled mean of the previous three 6MWTs showed a mean reduction of 14 m after the lockdown (p = 0.004). Moreover, the mean distance covered at 6MWT went from 447 m in March 2020 to 434 m in June 2020, with a significant average loss of 13 m (p = 0.024). Our results showed that PAH patients were less performing at 6MWT after 3 months of reduced physical activity, despite constant clinical stability and the absence of signs of disease progression, suggesting that this confounding factor should be kept in mind when evaluating changes in 6MWT during or after COVID-19 pandemic.

Pulmonary hypertension (PH) is associated with a poor prognosis in left heart disease (LHD). We sought to provide an updated analysis on the association of hemodynamic variables, such as pulmonary vascular resistance (PVR), pulmonary artery compliance (PAC), and diastolic pressure gradient (DPG), with prognosis in PH-LHD, through a systematic literature review. Sixteen articles were identified, including 9600 patients with LHD, heterogeneous in terms of age, sex, and etiology of cardiac disease. In this large population, PVR (hazard ratio [HR], 1.07; 95% confidence interval [CI]: 1.05−1.0), DPG (HR, 1.02; 95% CI: 1.01−1.02) and PAC (HR, 0.76; 95% CI: 0.69−0.84) were associated with an increased risk of adverse outcome, albeit with a less solid performance of DPG. Similar results were found when hemodynamic variables were analyzed according to the thresholds commonly applied in clinical practice, or subdividing cohorts according to the underlying LHD. Furthermore, cumulative metanalysis indicated that these results are consistently stable since 2018. Thus, PVR, DPG and PAC have an established prognostic value in PH-LHD. These results are consistent through the years and unlikely to change with further studies.

Aim: We sought to evaluate the differences in prognosis between the atrial (A-STR) and the ventricular (V-STR) phenotypes of secondary tricuspid regurgitation. Materials and methods: Consecutive patients with moderate or severe STR referred for echocardiography were enrolled. A-STR and V-STR were defined according to the last ACC/AHA guidelines criteria. The primary endpoint was the composite of all-cause death and heart failure (HF) hospitalizations. Results: A total of 211 patients were enrolled. The prevalence of A-STR in our cohort was 26%. Patients with A- STR were significantly older and with lower NYHA functional class than V-STR patients. The prevalence of severe STR was similar (28% in A-STR vs. 37% in V-STR, p = 0.291). A-STR patients had smaller tenting height (TH) (10 ± 4 mm vs. 12 ± 7 mm, p = 0.023), larger end-diastolic tricuspid annulus area (9 ± 2 cm2 vs. 7 ± 6 cm2/m2, p = 0.007), smaller right ventricular (RV) end-diastolic volumes (72 ± 27 ml/m2 vs. 92 ± 38 ml/m2; p = 0.001), and better RV longitudinal function (18 ± 7 mm vs. 16 ± 6 mm; p = 0.126 for TAPSE, and −21 ± 5% vs. −18 ± 5%; p = 0.006, for RV free-wall longitudinal strain, RVFWLS) than V-STR patients. Conversely, RV ejection fraction (RVEF, 48 ± 10% vs. 46 ± 11%, p = 0.257) and maximal right atrial volumes (64 ± 38 ml/m2 vs. 55 ± 23 ml/m2, p = 0.327) were similar between the two groups. After a median follow-up of 10 months, patients with V-STR had a 2.7-fold higher risk (HR: 2.7, 95% CI 95% = 1.3–5.7) of experiencing the combined endpoint than A-STR patients. The factors related to outcomes resulted different between the two STR phenotypes: TR-severity (HR: 5.8, CI 95% = 1, 4–25, P = 0.019) in A-STR patients; TR severity (HR 2.9, 95% CI 1.4–6.3, p = 0.005), RVEF (HR: 0.97, 95% CI 0.94–0.99, p = 0.044), and RVFWLS (HR: 0.93, 95% CI 0.85–0.98, p = 0.009) in V-STR. Conclusion: Almost one-third of patients referred to the echocardiography laboratory for significant STR have A-STR. A-STR patie

Editorial of the special issue "Novel Developmental Perspectives on the Link Between Morality and Social Outcomes".

Background: Although the assessment of left atrial (LA) mechanics has been reported to refine atrial fibrillation (AF) risk prediction, it doesn't completely predict AF recurrences. The potential added role of right atrial (RA) function in this setting is unknown. Accordingly, this study sought to evaluate the added value of RA longitudinal reservoir strain (RASr) for the prediction of AF recurrence after electrical cardioversion (ECV). Methods: We retrospectively studied 132 consecutive patients with persistent AF who underwent elective ECV. Complete two-dimensional and speckle-tracking echocardiography analyses of LA and RA size and function were obtained in all patients before ECV. The endpoint was AF recurrence. Results: During a 12-month follow-up of, 63 patients (48%) showed AF recurrence. Both LA and RASr were significantly lower in patients experiencing AF recurrence than in patients with persistent sinus rhythm (LASr 10±6 vs 13±7%, and RASr 14±10 vs 20±9 %, respectively, p<0.001 for both). RASr (AUC=0.77, 95%IC 0.69-0.84, p<0.0001) was more strongly associated with the recurrence of AF after ECV than LASr (AUC=0.69 (95%IC 0.60-0.77), p<0.0001]. Kaplan-Meier curves showed that patients with both LASr≤10% and RASr ≤15% had a significantly increased risk for AF recurrences (log-rank, p<0.001). However, at multivariable Cox regression, RASr [HR 3.26, 95%CI (1.73-6.13), p< 0.001] was the only parameter independently associated with the AF recurrence. RASr was more strongly associated with the occurrence of AF relapse after ECV than LASr, LA and RA volumes. Conclusions: RASr was independently and more strongly associated than LASr with AF recurrence after elective ECV. This study highlights the importance of assessing the functional remodeling of both RA and LA in patients with persistent AF.

Introduction: Limited information is available on blood pressure (BP) behavior in workers exposed to chronic intermittent hypoxia (CIH), and even less is known regarding effects of CIH on 24-h ambulatory BP in those affected by arterial hypertension at sea level (SL). The aims of this study were to assess clinic and 24-h ambulatory BP at SL and at high altitude (HA; 3,870 m above SL) in workers exposed to CIH, and to compare BP response to HA exposure between normotensive and hypertensive workers. Methods: Nineteen normotensive and 18 pharmacologically treated hypertensive miners acclimatized to CIH were included, whose work was organized according to a “7 days-on−7 days-off” shift pattern between SL and HA. All measurements were performed on the second and seventh day of their HA shift and after the second day of SL sojourn. Results: Compared to SL, 24-h systolic BP (SBP) and diastolic BP (DBP) increased at HA [+14.7 ± 12.6 mmHg (p < 0.001) and +8.7 ± 7.2 mmHg (p < 0.001), respectively], and SBP nocturnal fall decreased consistently (−4.1 ± 9.8%; p < 0.05) in all participants, with hypertensives showing higher nocturnal DBP than normotensives (p < 0.05) despite the current therapy. Also, heart rate (HR) nocturnal fall tended to be reduced at HA. In addition, the 24-h SBP/DBP hypertension threshold of ≥130/80 mmHg was exceeded by 39% of workers at SL and by 89% at HA. Clinic HR, SBP, and DBP were significantly higher on the second day of work at HA compared with SL, the increase being more pronounced for SBP in hypertensives (p < 0.05) and accompanied by, on average, mild altitude sickness in both groups. These symptoms and the values of all cardiovascular variables decreased on the seventh day at HA (p < 0.05) regardless of CIH exposure duration. Conclusion: Long history of work at HA according to scheduled CIH did not prevent the occurrence of acute cardiovascular changes at HA during the first days of exposure. The BP response to HA tended to be

High altitude is an extreme environment that challenges human beings exposed because of work, recreational activities, or habitat. Exposure to hypobaric hypoxia results in physiological adaptations in response to the geography and the associated extreme environmental conditions. These acclimatization responses can be diverse and result from evolutionary changes and comorbidities. In this context, this review aims to identify the available evidence on the effects of high altitude on blood pressure-from the physiological to clinical aspects at rest and during exercise-and the underlying mechanisms and possible clinical implications of acute and chronic intermittent hypoxia., La gran altitud es un ambiente extremo que impone fuertes desafíos para el ser humano que se expone por actividades laborales, recreativas o que vive en esta condición. La exposición a hipoxia hipobárica genera una serie de adaptaciones fisiológicas dadas por el entorno geográfico y las condiciones ambientales extremas asociadas. Estas respuestas de aclimatación pueden ser heterogéneas, siendo el resultado de cambios evolutivos y de la existencia de comorbilidades o patologías asociadas. En este contexto, el objetivo de este artículo es identificar la evidencia científica acerca de los efectos de la altitud geográfica en la presión arterial, desde los aspectos fisiológicos a las implicaciones clínicas en reposo y ejercicio. Asimismo, se abordan los mecanismos subyacentes y las posibles implicaciones clínicas en hipoxia aguda e hipoxia intermitente crónica.

Introduction: The tricuspid valve (TV) and the right heart chambers are complex three-dimensional structures that are difficult to assess using tomographic imaging techniques. The progressive aging of the general population and the advancements in treating left-sided heart diseases by transcatheter procedures have contributed to the tricuspid regurgitation (TR) becoming a major public health problem associated with progression to refractory heart failure and poor outcome. Recent advances in multimodality cardiac imaging allow a better understanding of the pathophysiology of TR that may translate in better management of patients. Areas covered: Three-dimensional echocardiography, cardiac magnetic resonance, and computed tomography provide complementary information to i. assess the TV complex; ii. identify the etiology and the mechanisms of TR; iii. evaluate its severity and hemodynamic consequences; iv. explore the remodeling of the right heart chambers; and v. properly plan, guide, and monitor the transcatheter interventions aimed to reduce the severity of TR. Expert opinion: We need thorough understanding of both the TV and the right heart chamber geometry and function to understand the pathophysiology of TR. The integrated use of multimodality cardiac imaging is pivotal to assess patients with TR and to identify tailored and timely treatment of TR in properly selected patients.

Heart Failure with preserved Ejection Fraction (HFpEF) is an increasingly prevalent clinical condition associated with cardiovascular aging, characterized by different pathophysiological mechanisms and poor outcomes. In this manuscript, we analysed the main differences in terms of updated diagnostic criteria and patients' selection in the most recent HFpEF trials. Recent algorithm purposed for HFpEF diagnosis, does not reflect common criteria adopted in clinical trials. Patients included in the larger studies experienced different characteristics in terms of clinical presentation and echocardiographic features. Current concerns complicate results interpretation and could hypothesize different stages of disease progression, rather than different cardiac phenotypes. Both the lack of diagnostic standardization and the population heterogeneity, might explain why trials investigating the effects of different therapeutic interventions failed to show improved outcomes for patients with HFpEF. Accordingly, we propose to exceed current view mainly based on the morphological adaptations evaluating patients' characterisation, their cardiovascular risk, associated diseases, and structural features consistent with disease progression. Detailed clinical, imaging and biological characterisation of this population, along with the identification of mechanisms linked with disease progression and prognosis, would allow for tailored treatments and provide important mechanistic insights into the complex HFpEF pathophysiology.

Aims: Interstitial pneumonia due to coronavirus disease 2019 (COVID-19) is often complicated by severe respiratory failure. In addition to reduced lung compliance and ventilation/perfusion mismatch, a blunted hypoxic pulmonary vasoconstriction has been hypothesized, that could explain part of the peculiar pathophysiology of the COVID-19 cardiorespiratory syndrome. However, no invasive haemodynamic characterization of COVID-19 patients has been reported so far. Methods and results: Twenty-one mechanically-ventilated COVID-19 patients underwent right heart catheterization. Their data were compared both with those obtained from non-mechanically ventilated paired control subjects matched for age, sex and body mass index, and with pooled data of 1937 patients with ‘typical’ acute respiratory distress syndrome (ARDS) from a systematic literature review. Cardiac index was higher in COVID-19 patients than in controls [3.8 (2.7–4.5) vs. 2.4 (2.1–2.8) L/min/m2, P < 0.001], but slightly lower than in ARDS patients (P = 0.024). Intrapulmonary shunt and lung compliance were inversely related in COVID-19 patients (r = −0.57, P = 0.011) and did not differ from ARDS patients. Despite this, pulmonary vascular resistance of COVID-19 patients was normal, similar to that of control subjects [1.6 (1.1–2.5) vs. 1.6 (0.9–2.0) WU, P = 0.343], and lower than reported in ARDS patients (P < 0.01). Pulmonary hypertension was present in 76% of COVID-19 patients and in 19% of control subjects (P < 0.001), and it was always post-capillary. Pulmonary artery wedge pressure was higher in COVID-19 than in ARDS patients, and inversely related to lung compliance (r = −0.46, P = 0.038). Conclusions: The haemodynamic profile of COVID-19 patients needing mechanical ventilation is characterized by combined cardiopulmonary alterations. Low pulmonary vascular resistance, coherent with a blunted hypoxic vasoconstriction, is associated with high c

Neprilisin and angiotensin receptor inhibition (Sacubitril/Valsartan, i.e. ARNI) is recommended in heart failure guidelines for patients in NYHA class II-III with reduced left ventricular ejection fraction (LVEF). ARNI increase survival and quality of life; due to their hemodynamic effects, ARNI could also affect exercise tolerance. We studied the effects of ARNI on cardiopulmonary test (CPET) after six months of treatment in 35 patients [67 ± 11 years; LVEF 31 ± 6%; NT-proBNP 1822 ± 1651 pg/ml; ICD/CRT since at least 6 months in 26/35], treated with increasing doses of Sacubitril/Valsartan up to 318 ± 36 mg/die. In addition, levels of NT-proBNP, renal function, electrolytes, and echocardiocolorDoppler were assessed in the same time periods. No variations of renal function and/or potassium levels were observed; NT-proBNP decreased. Most CPET variables were improved by ARNI (p <.05): peak VO2 and O2 pulse increased (from 15.8 ± 3.4 to 17.0 ± 4.0 ml/kg/min and from 11.5 ± 2.5 to 12.6 ± 2.4 ml/beat, respectively), while VEVCO2 slope decreased from 35.2 ± 11.2 to 33.1 ± 12.3. A significant relationship (p <.05) was observed between the amount of increase in LVEF and that of O2 pulse in all patients, and between the amount of decrease in PAPs and that of VEVCO2 slope in patients showing pulmonary hypertension in baseline. In a subgroup of 22 patients who already completed A 1 year follow-up, overall CPET improvement was maintained. In conclusion, already in the short term ARNI favourably affect cardiopulmonary response to exercise in heart failure patients; such a change seems to be preserved on a longer period.

Heart failure (HF) with preserved ejection fraction (HFpEF) is a chronic cardiac condition whose prevalence continues to rise, with high social and economic burden, but with no specific approved treatment. Patients diagnosed with HFpEF have a high prevalence of comorbidities and exhibit a high misdiagnosis rate. True HFpEF is likely to have multiple pathophysiological causes – with these causes being clinically ill-defined due to limitations of current measurement techniques. Myocyte, interstitium, microvascular, and metabolic abnormalities have been regarded as key components of the pathophysiology and potential therapeutic targets. Cardiac magnetic resonance (CMR) has the capability to look deeper with a number of tissue characterization techniques which are closer to the underlying specific abnormalities and which could be linked to personalized medicine for HFpEF. This review aims to discuss the potential role of CMR to better define HFpEF phenotypes and to infer measurable therapeutic targets.

Functional tricuspid regurgitation (FTR) is a strong and independent predictor of patient morbidity and mortality if left untreated. The development of transcatheter procedures to either repair or replace the tricuspid valve (TV) has fueled the interest in the pathophysiology, severity assessment, and clinical consequences of FTR. FTR has been considered to be secondary to tricuspid annulus (TA) dilation and leaflet tethering, associated to right ventricular (RV) dilation and/or dysfunction (the “classical”, ventricular form of FTR, V-FTR) for a long time. Atrial FTR (A-FTR) has recently emerged as a distinct pathophysiological entity. A-FTR typically occurs in patients with persistent/permanent atrial fibrillation, in whom an imbalance between the TA and leaflet areas results in leaflets malcoaptation, associated with the dilation and loss of the sphincter-like function of the TA, due to right atrium enlargement and dysfunction. According to its distinct pathophysiology, A-FTR poses different needs of clinical management, and the various interventional treatment options will likely have different outcomes than in V-FTR patients. This review aims to provide an insight into the anatomy of the TV, and the distinct pathophysiology of A-FTR, which are key concepts to understanding the objectives of therapy, the choice of transcatheter TV interventions, and to properly use pre-, intra-, and post-procedural imaging.

Aims: Exercise right heart catheterization (RHC) is considered the gold-standard test to diagnose heart failure with preserved ejection fraction (HFpEF). However, exercise RHC is an insufficiently standardized technique, and current haemodynamic thresholds to define HFpEF are not universally accepted. We sought to describe the exercise haemodynamics profile of HFpEF cohorts reported in literature, as compared with control subjects. Methods and results: We performed a systematic literature review until December 2020. Studies reporting pulmonary artery wedge pressure (PAWP) at rest and peak exercise were extracted. Summary estimates of all haemodynamic variables were evaluated, stratified according to body position (supine/upright exercise). The PAWP/cardiac output (CO) slope during exercise was extrapolated. Twenty-seven studies were identified, providing data for 2180 HFpEF patients and 682 controls. At peak exercise, patients with HFpEF achieved higher PAWP (30 [29–31] vs. 16 [15–17] mmHg, P < 0.001) and mean right atrial pressure (P < 0.001) than controls. These differences persisted after adjustment for age, sex, body mass index, and body position. However, peak PAWP values were highly heterogeneous among the cohorts (I2 = 93%), with a relative overlap with controls. PAWP/CO slope was steeper in HFpEF than in controls (3.75 [3.20–4.28] vs. 0.95 [0.30–1.59] mmHg/L/min, P value < 0.0001), even after adjustment for covariates (P = 0.007). Conclusions: Despite methodological heterogeneity, as well as heterogeneity of pooled haemodynamic estimates, the exercise haemodynamic profile of HFpEF patients is consistent across studies and characterized by a steep PAWP rise during exercise. More standardization of exercise haemodynamics may be advisable for a wider application in clinical practice.

AIMS: In functional tricuspid regurgitation (FTR) patients, tricuspid leaflet tethering and relatively low jet velocity could result in proximal flow geometry distortions that lead to underestimation of TR. Application of correction factors on two-dimensional (2D) proximal isovelocity surface area (PISA) equation may increase its reliability. This study sought to evaluate the impact of the corrected 2D PISA method in quantifying FTR severity. METHODS AND RESULTS: In 102 patients with FTR, we compared both conventional and corrected 2D PISA measurements of effective regurgitant orifice area [EROA vs. corrected (EROAc)] and regurgitant volume (RegVol vs. RegVolc) with those obtained by volumetric method (VM) using three-dimensional echocardiography (3DE), as reference. Both EROAc and RegVolc were larger than EROA (0.29 ± 0.26 vs. 0.22 ± 0.21 cm2; P < 0.001) and RegVol (24.5 ± 20 vs. 18.5 ± 14.25 mL; P < 0.001), respectively. Compared with VM, both EROAc and RegVolc resulted more accurate than EROA [bias = -0.04 cm2, limits of agreement (LOA) ± 0.02 cm2 vs. bias = -0.15 cm2, LOA ± 0.31 cm2] and RegVol (bias = -3.29 mL, LOA ± 2.19 mL vs. bias = -10.9 mL, LOA ± 13.5 mL). Using EROAc and RegVolc, 37% of patients were reclassified in higher grades of FTR severity. Corrected 2D PISA method led to a higher concordance of TR severity grade with the VM method (ĸ = 0.84 vs. ĸ = 0.33 for uncorrected PISA, P < 0.001). CONCLUSION: Compared with VM by 3DE, the conventional PISA underestimated FTR severity in about 50% of patients. Correction for TV leaflets tethering angle and lower velocity of FTR jet improved 2D PISA accuracy and reclassified more than one-third of the patients.

According to the Pathologic Adaptation Model of community violence exposure, repeated experiences of violence within the community lead youth to accept violence as a normative and legitimate strategy to cope with conflict, thus increasing their involvement in aggressive behaviors. This hypothesis has been under-investigated with reference to bullying at school. Using a person-centered analytical approach (latent profile analysis), this study examines the mediating role of moral disengagement as a type of normalizing cognition about violence, in the relationship between profiles of community violence exposure and perpetration of bullying. Eight hundred and two adolescents (11–18 years; 43.4% girls) from two different urban and societal contexts in Italy (Milan vs. Naples) participated in the study. Four profiles of exposure to community violence emerged. Context site and age influenced belonging to the four profiles. Being moderately exposed to violence, both as a victim and as a witness, was significantly associated with higher levels of moral disengagement and bullying perpetration. Being exposed as a witness and as a victim, and being exposed only as a witness were associated with bullying perpetration via the increase of moral disengagement. These findings support the Pathologic Adaptation Model and indicate that adolescents who experience higher levels of community violence, as a witness or both as a witness and a victim, are more likely to develop morally disengaged beliefs about violence, which in turn would increase the likelihood to perpetrate bullying. Results are also discussed in the context of social diversity.

The present study investigated the extent to which moral disengagement and the tendency to consider moral rules as socio-conventional rules are distinct dimensions of morality, and their association with three different forms of participation in bullying (perpetrating bullying, defending the victim and passive bystander behavior). These two types of moral cognitions have been theorized in different models of morality and are usually studied independently, even if research on moral shifts (the interpretation of a moral rule transgression as a socio-conventional rule transgression) suggests some possible overlaps. A group of 276 Italian students from primary and middle school (aged 8–15) completed self-reports assessing moral disengagement, socio-conventional perception of moral rules, and participation in bullying as bully, defender of the victim and passive bystander. Results from structural equation modeling analysis confirmed that moral disengagement and socio-conventional comprehension of aggressions are separate and moderately connected morality dimensions. Controlling for age, gender and SES, only moral disengagement was positively associated with perpetrating bullying. These results point to moral disengagement as the critical component of moral cognitions to be addressed in interventions.

Bullying constitutes a serious risk factor for the psychosocial adjustment of young people in both the general population and minority groups. Among minorities, international adoptees are likely to show a specific vulnerability to the experience of being bullied, moderated by specific risk and protective factors. This study aimed to investigate the association between adoptees' experience of bullying victimization and their psychosocial adjustment, and to explore the moderating role of adoptive identity and reflected minority categorization. An online, anonymous self-report questionnaire was completed by 140 adolescents (13-17 years), who were internationally adopted by Italian families. Findings showed that being victimized was associated with higher levels of emotional and behavioral difficulties, but that the strength of this relation varied according to the levels of adoptive identity and reflected minority categorization. Specifically, victimization was found to have a more detrimental and negative impact on psychological adjustment for adoptees who were highly identified with the adoptive group, and reported to be less perceived by others as members of the minority group. Results are discussed in relation to recommendations for further research as well as for professionals working with internationally adopted adolescents.

AIMS: Atrial functional tricuspid regurgitation (A-FTR) is a recently defined phenotype of functional tricuspid regurgitation (FTR) associated with persistent/permanent atrial fibrillation. Differently from the classical ventricular form of FTR (V-FTR), patients with A-FTR might present with severely dilated right atrium and tricuspid annulus (TA), and with preserved right ventricular (RV) size and systolic function. However, the geometry and function of the right ventricle, right atrium, and TA in patients with A-FTR and V-FTR remain to be systematically evaluated. Accordingly, we sought to: (i) study the geometry and function of the right ventricle, right atrium, and TA in A-FTR by two- and three-dimensional transthoracic echocardiography; and (ii) compare them with those found in V-FTR. METHODS AND RESULTS: We prospectively analysed 113 (44 men, age 68 ± 18 years) FTR patients (A-FTR = 55 and V-FTR = 58) that were compared to two groups of age- and sex-matched controls to develop the respective Z-scores. Severity of FTR was similar in A-FTR and V-FTR patients. Z-scores of RV size were significantly larger, and those of RV function were significantly lower in V-FTR than in A-FTR (P < 0.001 for all). The right atrium was significantly enlarged in both A-FTR and V-FTR compared to controls (P < 0.001, Z-scores > 2), with similar right atrial (RA) maximum volume (RAVmax) between A-FTR and V-FTR (P = 0.2). Whereas, the RA minimum volumes (RAVmin) were significantly larger in A-FTR than in V-FTR (P = 0.001). CONCLUSION: Despite similar degrees of FTR and RAVmax size, A-FTR patients show larger RAVmin and smaller TA areas than V-FTR patients. Conversely, V-FTR patients show dilated, more elliptic and dysfunctional right ventricle than A-FTR patients.