Pilot study to assess the early cardiac safety of carbon ion radiotherapy for intra- and para-cardiac tumours.

PURPOSE: Modern photon radiotherapy effectively spares cardiac structures more than previous volumetric approaches. Still, it is related to non-negligible cardiac toxicity due to the low-dose bath of surrounding normal tissues. However, the dosimetric advantages of particle radiotherapy make it a promising treatment for para- and intra-cardiac tumours. In the current short report, we evaluate the cardiac safety profile of carbon ion radiotherapy (CIRT) for radioresistant intra- and para-cardiac malignancies in a real-world setting. METHODS: We retrospectively analysed serum biomarkers (TnI, CRP and NT-proBNP), echocardiographic, and both 12-lead and 24-hour Holter electrocardiogram (ECG) data of consecutive patients with radioresistant intra- and para-cardiac tumours irradiated with CIRT between June 2019 and September 2022. In the CIRT planning optimization process, to minimize the delivered doses, we contoured and gave a high priority to the cardiac substructures. Weekly re-evaluative 4D computed tomography scans were carried out throughout the treatment. RESULTS: A total of 16 patients with intra- and para-cardiac localizations of radioresistant tumours were treated up to a total dose of 70.4 Gy relative biological effectiveness (RBE) and a mean heart dose of 2.41 Gy(RBE). We did not record any significant variation of the analysed serum biomarkers after CIRT nor significant changes of echocardiographic features, biventricular strain, or 12-lead and 24-hour Holter ECG parameters during 6 months of follow-up. CONCLUSION: Our pilot study suggests that carbon ion radiotherapy is a promising radiation technique capable of sparing off-target side effects at the cardiac level. A larger cohort, long-term follow-up and further prospective studies are needed to confirm these findings.

Glucagon-like Peptide 1 Receptor Agonists in Cardio-Oncology: Pathophysiology of Cardiometabolic Outcomes in Cancer Patients.

Cancer patients, especially long cancer survivors, are exposed to several cardio-metabolic diseases, including diabetes, heart failure, and atherosclerosis, which increase their risk of cardiovascular mortality. Therapy with glucagon-like peptide 1 (GLP1) receptor agonists demonstrated several beneficial cardiovascular effects, including atherosclerosis and heart failure prevention. Cardiovascular outcome trials (CVOTs) suggest that GLP-1 RA could exert cardiorenal benefits and systemic anti-inflammatory effects in patients with type-2 diabetes through the activation of cAMP and PI3K/AkT pathways and the inhibition of NLRP-3 and MyD88. In this narrative review, we highlight the biochemical properties of GLP-1 RA through a deep analysis of the clinical and preclinical evidence of the primary prevention of cardiomyopathies. The overall picture of this review encourages the study of GLP-1 RA in cancer patients with type-2 diabetes, as a potential primary prevention strategy against heart failure and atherosclerosis.

The paradox of pulmonary arterial hypertension in Italy in the COVID-19 era: is risk of disease progression around the corner?

OBJECTIVE: The coronavirus disease 2019 (COVID-19) outbreak has led to significant restrictions on routine medical care. We conducted a multicentre nationwide survey of patients with pulmonary arterial hypertension (PAH) to determine the consequences of governance measures on PAH management and risk of poor outcome in patients with COVID-19. MATERIALS AND METHODS: The present study, which included 25 Italian centres, considered demographic data, the number of in-person visits, 6-min walk and echocardiographic test results, brain natriuretic peptide/N-terminal pro-brain natriuretic peptide test results, World Health Organization functional class assessment, presence of elective and non-elective hospitalisation, need for treatment escalation/initiation, newly diagnosed PAH, incidence of COVID-19 and mortality rates. Data were collected, double-checked and tracked by institutional records between March 1 and May 1, 2020, to coincide with the first peak of COVID-19 and compared with the same time period in 2019. RESULTS: Among 1922 PAH patients, the incidences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 were 1.0% and 0.46%, respectively, with the latter comparable to that in the overall Italian population (0.34%) but associated with 100% mortality. Less systematic activities were converted into more effective remote interfacing between clinicians and PAH patients, resulting in lower rates of hospitalisation (1.2% versus 1.9%) and related death (0.3% versus 0.5%) compared with 2019 (p<0.001). A high level of attention is needed to avoid the potential risk of disease progression related to less aggressive escalation of treatment and the reduction in new PAH diagnoses compared with 2019. CONCLUSION: A cohesive partnership between healthcare providers and regional public health officials is needed to prioritise PAH patients for remote monitoring by dedicated tools.

Risk Reduction and Hemodynamics with Initial Combination Therapy in Pulmonary Arterial Hypertension.

Rationale: An initial oral combination of drugs is being recommended in pulmonary arterial hypertension (PAH), but the effects of this approach on risk reduction and pulmonary vascular resistance (PVR) are not known.Objectives: To test the hypothesis that a low-risk status would be determined by the reduction of PVR in patients with PAH treated upfront with a combination of oral drugs.Methods: The study enrolled 181 treatment-naive patients with PAH (81% idiopathic) with a follow-up right heart catheterization at 6 months (interquartile range, 144-363 d) after the initial combination of endothelin receptor antagonist + phosphodiesterase-5 inhibitor drugs and clinical evaluation and risk assessments by European guidelines and Registry to Evaluate Early and Long-Term PAH Disease Management scores.Measurements and Main Results: Initial combination therapy improved functional class and 6-minute-walk distance and decreased PVR by an average of 35% (median, 40%). One-third of the patients had a decrease in PVR <25%. This poor hemodynamic response was independently predicted by age, male sex, pulmonary artery pressure and cardiac index, and at echocardiography, a right/left ventricular surface area ratio of greater than 1 associated with low tricuspid annular plane systolic excursion of less than 18 mm. A low-risk status at 6 months was achieved or maintained in only 34.8% (Registry to Evaluate Early and Long-Term PAH Disease Management score) to 43.1% (European score) of the patients. Adding criteria of poor hemodynamic response improved prediction of a low-risk status.Conclusions: A majority of patients with PAH still insufficiently improved after 6 months of initial combinations of oral drugs is identifiable at initial evaluation by hemodynamic response criteria added to risk scores.

Right ventricular time intervals - Comparison between pulsed wave Doppler and tissue Doppler imaging.

BACKGROUND: Cardiac time intervals are used as indices of systolic and diastolic function. Echocardiographic assessment of these intervals is based on either pulsed wave Doppler (PWD) or tissue Doppler imaging (TDI). We investigated the agreement between the two techniques in the evaluation of right ventricular (RV) time intervals in healthy adults. METHODS: In 123 healthy volunteers we used both PWD and TDI to assess RV time intervals (filling time - RVFT, ejection time - RVET), heart rate-corrected intervals (total filling time - t-FT, total ejection time - t-ET) and RV performance indices (total isovolumic time - t-IVT, myocardial performance index - MPI). Intraclass correlation coefficient (ICC) and Pearson analysis (r coefficient) were used to evaluate the agreement and correlation between the two techniques. RESULTS: PWD and TDI had excellent agreement and correlation in measuring RVFT (ICC 0.94 [95% CI 0.85 - 0.97], r 0.91) whereas a good agreement was found for RVET (ICC 0.63[95% CI - 0.14 - 0.84]; r 0.68). Good agreement and strong correlation were found for both t-FT (ICC 0.67 [95% CI 0.36 - 0.82]; r 0.59) and t-ET (ICC 0.71 [95% CI - 0.06-0.88]; r 0.74). The two methods had lower agreement in assessing RV t-IVT (ICC 0.52 [95% CI 0.3187-0.6622]; r 0.57) and MPI (ICC 0.36 [95% CI - 0.05-0.43]; r 0.50). CONCLUSION: In healthy adults, PWD and TDI are interchangeable in measuring RVFT, RVET, RV t-FT and RV t-ET. Lower agreement between the two techniques was found for RV t-IVT and MPI.

Right ventricular total isovolumic time: Reference value study.

BACKGROUND: There is lack of noninvasive indices to detail the right side cardiovascular physiology. Total isovolumic time (tIVT) is a sensitive marker of left ventricular electromechanical efficiency and systolic-diastolic interaction. The aim of the study was to evaluate normal reference value of the right ventricular tIVT with increasing age. METHODS AND RESULTS: One hundred and eighty-one healthy volunteers (51% male) underwent transthoracic echocardiography. The population was divided into four categories according to age: A < 30 years; B 30-39 years; C 40-49 years; and C ≥ 50 years old. tIVT was computed in seconds/minutes as: 60 - (tET + tFT). tET and tFT are the total ejection and filling time adjusted by the heart rate, measured, respectively, from the onset to the end of the right ventricle (RV) forward flow through the pulmonary valve and from the onset of the E-wave and the end of the A-wave at the level of the tricuspid valve. The mean RV tIVT was 7 ± 1.1 s/min and increased significantly with age, from a 3.4 to 9.7 s/min(P < 0.0001). Significant correlation was found between tIVT and trans-tricuspid E/E' (P < 0.0001; 0.78 (95% CI: 0.715-0.831) while weaker between tIVT and E/A (P = 0.001; -0.283 95% CI: -0.413 to -0.143). CONCLUSION: The normal values of RV tIVT increase with age and correlate significantly with Doppler diastolic parameters.

Anxiety, Depression, and Quality of Sleep Vary in Their Correlation to Postoperative Outcomes of Rotator Cuff Repair: A Prospective Study.

Background/Objectives: Recent studies imply that psychological factors and sleep quality play a role in the outcomes of surgical procedures, including in orthopedic surgery. The aim of the present study is to evaluate possible correlations between preoperative depression, anxiety, and quality of sleep and functional 6-month postoperative scores in patients having undergone rotator cuff repair (RCR). Methods: All patients included in the study performed the Hospital Anxiety and Depression Scale (HADS) and Pittsburgh Sleep Quality Index (PSQI) questionnaires preoperatively and 36-item Short-Form Health Survey (SF-36), Oxford Shoulder Score (OSS), Shoulder Pain and Disability Index (SPADI), and PSQI questionnaires at the six-month postoperative follow-up. A total of 47 patients were included in the analysis. Results: Statistically significant differences between preoperative anxious and not-anxious groups were found in the postoperative SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores and PSQI score. The correlation of the preoperative depression score to postoperative outcome measures revealed a strong positive correlation between the preoperative HADS-D score and the 6-month PCS, MCS, and OSS scores. The correlation of preoperative sleep quality to postoperative outcome measures revealed a strong positive correlation between the preoperative PSQI score and 6-month MCS score. Conclusions: Anxious patients had worse postoperative RCR outcomes. Depression may be influenced by factors related to RC pathology; however, there were no statistically significant correlations. Sleep quality generally improves postoperatively, and no significant association was found between bad preoperative sleepers and worse outcomes.

The influence of sex on heart failure mortality.

AIMS: Little research has investigated how sex may affect the prognosis of patients with chronic heart failure (HF). The present study was aimed at exploring sex-specific differences in prognosis in a cohort of patients with chronic HF, categorized according to severity of left ventricular dysfunction (HFrEF, HFmrEF and HFpEF), right ventricular (RV) dysfunction and ischemic (IHD) or nonischemic (no-IHD) etiology. METHODS: This retrospective analysis included 1640 HF patients of whom 24% were females, 759 patients had IHD, 1110 patients had HFrEF, 147 patients had HFmrEF and 383 patients had HFpEF. The median follow-up period was 63 months (25th-75th 27-93). RESULTS: In the no-IHD group, no statistically significant sex differences emerged regarding survival, regardless of age and severity of cardiac dysfunction. In contrast, in the IHD group, females had a significantly lower event rate than males in the age group between 65 and 79 years [hazard ratio (HR) 0.39; 95% confidence interval (CI): 0.86-0.18; P  < 0.01]; in addition, a lower event rate was observed in females compared with males among patients with HFrEF (HR 0.47; 95% CI: 0.88-0.25; P  < 0.01), among patients without RV dysfunction (HR 0.58; 95% CI: 1.02-0.33; P  = 0.048) and among patients without diabetes (HR 0.44; 95% CI: 0.84-0.23; P  < 0.01). CONCLUSION: In nonischemic patients there was no difference between males and females in terms of survival whereas in patients with ischemic etiology survival was better in females among elderly patients, in HFrEF patients, in the absence of RV dysfunction and in the absence of diabetes.

DAPAGLIFLOZIN EFFECTS ON LEFT VENTRICULAR REMODELING AND FILLING PRESSURES IN HEART FAILURE WITH REDUCED EJECTION FRACTION.

AIMS: The benefits of sodium glucose cotransporter 2 inhibitors in patients with heart failure with reduced ejection fraction (HFrEF) have been clearly demonstrated in randomized clinical trails. However, the mechanisms of the observed beneficial effects remain incompletely understood. This study aimed to assess morpho-functional cardiac changes following dapagliflozin introduction in stable outpatients with HFrEF and to investigate whether these changes were determinants of the improved clinical outcome. METHODS AND RESULTS: In this multicenter, prospective observational study, 300 consecutive HFrEF patients ≥ 18 years old on optimized medical therapy (OMT) and eligible for dapagliflozin therapy were enrolled between april 2022 and January 2023. Laboratory and echocardiographic assessments were performed at baseline and after a median of 6 months. Following dapagliflozin initiation, 47% of patients achieved a target of improvement in left ventricular end-diastolic volume (Δ EDVi < -10%) and/or end-systolic volume (Δ ESVi <-15%) and/or ejection fraction (Δ EF% > 10%) at 6 months. The proportion of patients with elevated left ventricular filling pressures decreased from 26% to 3% at 6 months (p<0.001). The combination of left ventricular remodeling (LVRR) and filling pressures improvements was associated with absence of HF-related hospitalizations and significant natriuretic peptides (NPs) reduction at 12 months. CONCLUSIONS: Dapagliflozin detemined LVRR and improved left ventricular filling pressures in a high proportion of patients with stable HFrEF patients already on OMT. These improvements were associated with absence of HF-related hospitalizations and a significant NPs reduction at 12 months.

Prognostic value of deep echocardiographic phenotyping in pulmonary arterial hypertension.

Background: A novel approach to derive prognostic information from echocardiography in pulmonary arterial hypertension (PAH) is to define a phenotype of right heart function combining standard echocardiographic parameters which describe right ventricular pump function and systemic venous congestion. We tested the hypothesis that the combination of advanced strain imaging parameters could yield high prognostic accuracy. Methods: This was a prospective observational study with a single centre derivation cohort and a second centre validation cohort. The derivation cohort included 49 naive PAH patients who underwent right heart catheterisation and echocardiographic evaluation at baseline and 4-12 months after diagnosis. The validation cohort included 83 prevalent PAH patients who underwent the same examinations at 12 months after diagnosis. We stratified the risk of the derivation cohort according to three models: Model 1, based on haemodynamic parameters; Model 2, based on standard echocardiographic parameters; and Model 3, based on advanced echocardiographic parameters. The median follow-up period was 21 months; the end point of the analysis was clinical worsening. Results: In the derivation cohort, haemodynamic and echocardiographic parameters obtained at diagnosis were not associated with outcome, whereas a significant association was observed at first reassessment. Model 3 yielded a better predictive accuracy (Harrell's C index 0.832) as compared to Model 2 (Harrell's C index 0.667), and to Model 1 (Harrell's C index 0.713). The validation cohort confirmed the accuracy of Model 3. Conclusions: A comprehensive assessment of right heart function using right ventricular strain, right atrial reservoir strain and degree of tricuspid regurgitation provides accurate prognostic information in prevalent PAH patients.

Cancer incidence in immigrants by geographical area of origin: data from the Veneto Tumour Registry, Northeastern Italy.

Objective: We investigated whether there are differences in cancer incidence by geographical area of origin in North-eastern Italy. Methods: We selected all incident cases recorded in the Veneto Tumour Registry in the period 2015-2019. Subjects were classified, based on the country of birth, in six geographical areas of origin (Italy, Highly Developed Countries-HDC, Eastern Europe, Asia, Africa, South-central America). Age-standardized incidence rates and incidence rate ratio (IRR) were calculated, for all cancer sites and for colorectal, liver, breast and cervical cancer separately. Results: We recorded 159,486 all-site cancer cases; 5.2% cases occurred in subjects born outside Italy, the majority from High Migratory Pressure Countries (HMPC) (74.3%). Incidence rates were significantly lower in subjects born in HMPC in both sexes. Immigrants, in particular born in Asia and Africa, showed lower rates of all site cancer incidence. The lowest IRR for colorectal cancer was observed in males from South-Central America (IRR 0.19, 95%CI 0.09-0.44) and in females from Asia (IRR 0.32, 95%CI 0.18-0.70). The IRR of breast cancer appeared significantly lower than Italian natives in all female populations, except for those coming from HDC. Females from Eastern Europe showed a higher IRR for cervical cancer (IRR 2.02, 95%CI 1.57-2.61). Conclusion: Cancer incidence was found lower in subjects born outside Italy, with differences in incidence patterns depending on geographical area of origin and the cancer type in question. Further studies, focused on the country of birth of the immigrant population, would help to identify specific risk factors influencing cancer incidence.

[Atherosclerosis, cancer and immune checkpoint inhibitors]. / Aterosclerosi, cancro e inibitori dei checkpoint immunitari.

Immunotherapy has revolutionized the treatment of various cancers leading to a clear survival benefit with cured or long-surviving patients. Atherosclerosis and cancer share risk factors and molecular mechanisms and have as their common thread a state of chronic inflammation linked to a deregulation of the immune system. A growing body of evidence is accumulating on the potential worsening effect of immune checkpoint inhibitors on atherosclerosis, with subsequent worsening of patients' long-term cardiovascular risk. The molecular pathways implicated in the growth and deregulation of atherosclerotic plaques seem to be the same (CTLA-4, PD-1, PD-L1) as those on which the anti-tumor effect is exerted. Owing to the increasing number of cancer patients treated with immunotherapy and the improved survival with the possibility of prolonged disease control, it is necessary to know the potential increase in cardiovascular risk for atherosclerosis-related events and to establish all prevention measures to reduce it.

Right ventricular phenotyping in incident patients with idiopathic pulmonary arterial hypertension.

BACKGROUND: Right ventricular (RV) imaging has not a definite role in risk stratification of pulmonary arterial hypertension (PAH) patients. We tested the hypothesis that echocardiography-derived phenotypes, depicting different degrees of RV remodeling and dysfunction, may provide additional prognostic information to current risk stratification tools. METHODS: Consecutive incident PAH patients aged ≥18 years, diagnosed between January 2005 and December 2021, underwent clinical assessment, right heart catheterization, standard echocardiography. Simple echocardiographic variables were combined in order to define a priori four phenotypes representing different degrees of RV dilatation and RV-pulmonary arterial (PA) coupling: Phenotype 1 with mildy dilated right ventricle and preserved RV-PA coupling (n = 152 patients); phenotype 2 with mildly dilated right ventricle and poor RV-PA coupling (n = 143 patients); phenotype 3 with severely dilated right ventricle and preserved RV-PA coupling (n = 201 patients); phenotype 4 with severely dilated right ventricle and poor RV-PA coupling, with or without severe tricuspid regurgitation (n = 519 patients). Risk stratification was based on the European Society of Cardiology/European Respiratory Society (ESC/ERS) 3-strata model and Registry to Evaluate Early and Long-Term PAH disease Management (REVEAL) 2.0 score. RESULTS: These phenotypes were present in all risk groups. Notably, regardless of the ESC/ERS risk stratum assigned to the patient, phenotype 4 was associated with a 2-fold increase of the odds of death (HR 2.1, 95% CI 1.6-2.8, p < 0.001), while phenotype 1 was associated with a 71% reduction in the odds of dying (HR 0.29, 95% CI 0.18-0.47, p < 0.001). CONCLUSIONS: Echocardiography-derived phenotypes describing RV remodeling and dysfunction may provide prognostic information which is independent of and additional to the clinically defined risk in incident PAH patients.

Supervised versus unsupervised rehabilitation following total knee arthroplasty: A systematic review and meta-analysis.

BACKGROUND: Outcomes after total knee arthroplasty (TKA) are strongly influenced by the adequacy of rehabilitation and the consequent functional recovery. The economic impact of rehabilitation it is not negligible. Inpatient rehabilitation can be 5 to 26 times more expensive than the home-based rehabilitation. This topic is extremely relevant as the COVID-19 pandemic has highlighted the importance of unsupervised rehabilitation in orthopedic surgery. The aim of this review and meta-analysis is to investigate the scientific evidence regarding the comparison between supervised and unsupervised rehabilitation following TKA. MATERIALS AND METHODS: Following PRISMA guideline, a comprehensive search of PubMed, Cochrane and Scopus databases using combinations of keywords and MeSH descriptors: "total "Knee replacement," "Arthroplasty", "Rehabilitation" was performed from inception to December 2021. All relevant articles were retrieved, and their bibliographies were searched for further relevant references. Only English written randomized controlled trials comparing supervised and unsupervised rehabilitation following TKA were included in this systematic review. The outcomes considered were long-term pain, physical function, knee flexion and extension ROM, 6 minute walking test (6MWT) and timed up and go test (TUG). RESULTS: 11 studies (2.181 patients in total) were included in this systematic review. The long-term pain outcome showed no significant differences (Std. Mean Difference [SMD] = 0.00, 95 % confidence interval [CI] -0.16, 0.017) between the supervised (n = 397) and unsupervised (n = 255). Physical function showed no significant differences among the two groups (mean difference [MD] = 0.84, 95 % CI = -1.82, 3.50). Non-significant differences were also found for knee ROM flexion (mean difference [MD] = -0.46, 95 % CI = -2.95, 2.04) and for knee extension (mean difference [MD] = 0.54, 95 % CI = -0.89, 1.97). At the 52-week follow-up, the unsupervised group showed significant better results in 6MWT (mean difference [MD] = -26.10, 95 % CI = -47.62, -4.59) and in Timed up and go test (mean difference [MD] = 1.33, 95 % CI = 0.50, 2.15). CONCLUSION: This systematic review did not show a significant clinical difference in improving pain, function, and mobility outcomes after TKA between supervised PT and unsupervised PT. Therefore, it would appear that supervised rehabilitation did not had additional benefits compared to unsupervised rehabilitation.

Sacubitril/valsartan effects on arrhythmias and left ventricular remodelling in heart failure: An observational study.

AIMS: Conflicting results have been reported in the literature on the potential antiarrhythmic effect of sacubitril/valsartan in heart failure patients with reduced ejection fraction (HFrEF). The objectives of this study were: 1- to evaluate the long term effects of sacubitril/valsartan on arrhythmic burden in HFrEF patients; 2- to evaluate the correlation between the reduction of premature ventricular complexes during f-up and reverse remodelling. METHODS: We identified 255 consecutive HFrEF patients treated with sacubitril/valsartan between March 2017 and May 2020 and followed by the Heart Failure and Cardiac Transplant Unit of IRCCS San Matteo Hospital in Pavia (Italy). Within this subgroup, 153 patients underwent 24 h-Holter-ECG or implantable cardioverter defibrillators (ICD) interrogation at baseline, at 12 months (t1) and at 24 months (t2) and transthoracic echocardiography at baseline and after 12 months after the beginning of sacubitril/valsartan. Cardiac-related hospitalizations were analyzed in the 12 months preceding and during 24 months following the drug starting date. RESULTS: Global burden of 24-h premature ventricular complexes (PVC) was significantly reduced at 12 months (t1) and at 24 months (t2) as compared to the same period before treatment (1043 [304-3360] vs 768 [82-2784] at t1 vs 114 [9-333] at t2, P = 0.000). In the subgroup of patients implanted with biventricular ICD (n = 30), the percentage of biventricular pacing increased significantly (96% [94-99] vs 98% [96-99] at t1 vs 98%[97-100] at t2; P = 0.027). The burden of non-sustained ventricular tachycardia and sustained ventricular tachycardia did not change from baseline to t1 and t2, but a reduction of patients with at least one ICD appropriate shock was reported. The correlations between reduction in 24 h PVC and reduction in LV-ESVi or improvement in LVEF were not statistically significant (respectively R = 0.144, P = 0.197 and R = -0.190, P = 0.074). Heart failure related hospitalizations decreased during follow up (11.1% in the year before treatment vs 4.6% at t1 and 4.6% at t2; P = 0.040). CONCLUSION: Sacubitril/valsartan reduced the number of premature ventricular complexes and increased the percentage of biventricular pacing in a cohort of HFrEF patients already on optimal medical therapy. PVC reduction did not correlate with reverse left ventricular remodelling. Whether sacubitril/valsartan has any direct antiarrhythmic effects is an issue to be better explored in future studies.

Role of cardiac magnetic resonance in the differential diagnosis between arrhythmogenic cardiomyopathy with left ventricular involvement and previous infectious myocarditis.

AIMS: Arrhythmogenic cardiomyopathy with left ventricular involvement (ACM-LV), particularly in case of isolated left ventricular involvement (i.e. left dominant arrhythmogenic cardiomyopathy, LDAC) and previous infectious myocarditis (pIM) may have overlapping clinical and cardiac magnetic resonance (CMR) features. To date, there are no validated CMR criteria for the differential diagnosis between these conditions. The present study aimed to identify CMR characteristics to distinguish ACM-LV from pIM. METHODS AND RESULTS: This observational, retrospective, single-centre study included 30 pIM patients and 30 ACM-LV patients. In ACM-LV patients CMR was performed at diagnosis; in patients with pIM, CMR was performed six months after acute infection. CMR analysis included quantitative assessment of left ventricle (LV) volumes, systolic function and wall thicknesses, qualitative and quantitative assessment of late gadolinium enhancement (LGE) sequences. Compared with pIM, ACM-LV patients showed slightly larger LV volumes, more frequent regional wall motion anomalies and reduced wall thicknesses. ACM-LV patients had higher amounts of LV LGE and extension. Notably, the LDAC subgroup had the highest amount of LV LGE. LV LGE amount > 15 g and a LV LGE percentage > 30% of LV mass discriminated ACM-LV from pIM with a 100% specificity. LGE segmental distribution was superimposable among the groups, except for septal segments that were more frequently involved in ACM-LV and LDAC patients. CONCLUSIONS: A great extension of LV LGE (a cut-off of LGE >15 g and a percentage above 30% of LV LGE in relation to total myocardial mass) discriminates ACM-LV from pIM with extremely high specificity.

Hypertrophic Cardiomyopathy and Atrial Fibrillation: A Systematic Review and Meta-analysis of Anticoagulation Strategy.

BACKGROUND: Atrial fibrillation (AF) frequently complicates hypertrophic cardiomyopathy (HCM), and anticoagulation significantly decreases the risk of stroke in this population. To date, no randomized controlled trials (RCTs) have compared direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs). The present study aimed to systematically compare the two anticoagulation strategies in terms of effectiveness and safety. METHOD: We performed a systematic literature search and meta-analysis in the PubMed, MEDLINE, and EMBASE databases for studies reporting all-cause mortality, major bleeding, or thromboembolic events (TEs). Since no RCTs were available, we included observational studies only. The overall hazard ratio (HR) and 95% confidence interval (CI) for each analyzed parameter were pooled using a random-effects model. RESULTS: Five observational studies including 6919 patients were eligible for inclusion. Compared with VKAs, DOACs were associated with statistically significant lower rates of all-cause mortality (HR 0.64, 95% CI 0.35-0.54; p < 0.00001), comparable major bleeding events (HR 0.64, 95% CI 0.40-1.03; p = 0.07), and TEs (HR 0.94, 95% CI 0.73-1.22; p = 0.65). CONCLUSIONS: Compared with VKAs, a DOAC-based strategy might represent an effective and safe strategy regarding all-cause mortality, major/life-threatening bleeding complications, and TEs in HCM patients with concomitant AF. However, further prospective studies are necessary to reinforce a DOAC-based anticoagulation strategy in this population.

Exploring the association between specific genes and the onset of idiopathic scoliosis: a systematic review.

BACKGROUND: Idiopathic Scoliosis (IS) is the most common spinal deformity in adolescents, accounting for 80% of all spinal deformities. However, the etiology remains uncertain in most cases, being identified as Adolescent Idiopathic Scoliosis (AIS). IS treatments range from observation and sport to bracing or surgery. Several risk factors including sex and familiarity, have been linked with IS. Although there are still many uncertainties regarding the cause of this pathology, several studies report a greater incidence of the defect in families in which at least one other first degree relative is affected. This study systematically reviews the available literature to identify the most significant genes or variants related to the development and onset of IS. METHODS: The research question was formulated using a PIOS approach on the following databases: Medline, Embase, Cinahl, Scopus, Web of Science and Google Scholar. The search was performed from July to August 2021, and articles from the inception of the database to August 2021 were searched. RESULTS: 24 of the 919 initially identified studies were included in the present review. The 24 included studies observed a total of 16,316 cases and 81,567 controls. All the considered studies stated either the affected gene and/or specific SNPs. CHD7, SH2B1, ESR, CALM1, LBX1, MATN1, CHL1, FBN1 and FBN2 genes were associated with IS development. CONCLUSIONS: Although association can be found in some candidate genes the field of research regarding genetic association with the onset of IS still requires more information.

When you hear hoofbeats, think zebras - pulmonary veno-occlusive disease: A case report.

Pulmonary veno-occlusive disease (PVOD) is a rare disease. It may be idiopathic or associated, in particular, with connective tissue disease, or it may develop after radiation exposure; in heritable forms of PVOD, the inheritance is autosomal recessive due to the presence of homozygous or compound heterozygous pathogenic variants in the EIF2AK4 gene. We describe the case of a young man whose PVOD was initially misdiagnosed as chronic thromboembolic pulmonary hypertension despite worsening after riociguat, nonspecific computed tomography pulmonary angiogram findings, and parental consanguinity could suggest an autosomal recessive disease. The correct diagnosis and the correct treatment are crucial given the high mortality rate of this disease.