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.

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.

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.

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.

Right heart failure in left heart disease: imaging, functional, and biochemical aspects of right ventricular dysfunction.

For decades, cardiologists have largely underestimated the role of the right heart in heart failure due to left heart disease. Nowadays, the importance of evaluating right ventricular (RV) structure and function in left heart failure is well documented and this concept has been emphasized in the most recent heart failure guidelines. However, several relevant questions remain unanswered such as the following: (a) which imaging technique (standard or 3D echocardiography or strain imaging or cardiac magnetic resonance) and, more, which parameters should be used to grade the severity of RV dysfunction? (b) do less widespread and less applied diagnostic tools such as cardiopulmonary stress testing and bioelectrical impedance analysis play a role in this field? (c) are there specific biochemical aspects of RV failure? (d) why notion of pathophysiology of heart and lung interaction are so well appreciated at an academic level but are not applied in the clinical setting? The present review has been prepared by the Heart Failure (HF) working group of the Italian Society of Cardiology and its main objective is to improve our understanding on RV dysfunction in heart failure.

BMPR2 mutations and response to inhaled or parenteral prostanoids: a case series.

Whether mutations in the BMPR2 gene may influence the response to PAH-specific therapies has not yet been investigated. In this study, in 13 idiopathic, heritable or anorexigen-associated PAH patients, in whom treatment escalation was performed by adding a prostanoid, a greater haemodynamic improvement was observed in BMPR2-negative than in BMPR2-positive patients.

Acute pericarditis, Graves' disease, and thymic hyperplasia: a case report.

BACKGROUND: Acute pericarditis as a sign of mediastinal mass is rare and aetiological diagnosis can be challenging without adequate imaging. CASE SUMMARY: An 18-year-old woman came to our attention describing acute sharp chest pain radiated to the left arm, exacerbated with supine positioning and attenuated while sitting or leaning forward. The electrocardiogram showed diffuse ST elevation and PR depression, with sinus tachycardia. Cardiac biomarkers and D-dimer were negative; echocardiography showed no abnormalities and the absence of pericardial effusion. Her blood work revealed no sign of inflammation or bacterial infection (PCR and procalcitonin were normal); thyroid-stimulating hormone plasma levels were suppressed, showing decompensated thyrotoxicosis. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Epstein-Barr virus, human immunodeficiency virus, hepatitis C virus, Enterovirus, Parvovirus B19, and Adenovirus tests were normal. Her past medical history was silent, apart from Grave's disease on treatment with methimazole. Chest computed tomography (CT) was performed and showed the presence of slightly increased density pericardial effusion, with a maximum thickness of 15 mm in the upper mediastinum. Finally, cardiac magnetic resonance (MR) identified a mass of 73 × 51 mm located in the upper mediastinum. The mass was subsequently biopsed with video-assisted thoracoscopic surgery and the histological analysis showed thymic hyperplasia. DISCUSSION: This case shows the importance of an adequate clinical suspicion of thymic hyperplasia in the context of acute pericarditis symptoms and known Graves' disease. In this case, a negative chest CT finding may not be sufficient to rule out the diagnosis and cardiac MR imaging is necessary.

Long-Term Effects of the Replacement of Calcineurin Inhibitors With Everolimus and Mycophenolate in Patients With Calcineurin Inhibitor-Related Nephrotoxicity.

BACKGROUND: There is little evidence on the long-term effects of calcineurin inhibitor (CNI) withdrawal and substitution with everolimus and mycophenolate mofetil in maintenance therapy of patients who have received heart transplants and have concurrent CNI nephrotoxicity. Aims of this study were to evaluate the progression of renal dysfunction after discontinuation of CNIs and to monitor for major adverse events after therapy change. METHODS: Data from 41 patients who underwent heart transplant and have different degrees of renal dysfunction (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2), without evidence of proteinuria, and in whom CNI therapy was replaced by everolimus, were analyzed. At the time of CNI withdrawal, clinical parameters, echocardiographic data, blood tests of renal function, and monitoring of adverse events were recorded. The median follow-up period was 5 years ± 28 months. RESULTS: In 52% of patients, there was a clear improvement in renal function (10.5 mL/min/1.73 m2 of extra eGFR on average). The former were characterized by less advanced age and a short time from the heart transplant. The echocardiographic parameters showed a significant reduction in septum thickness (11.58 ± 2 mm vs 10.29 ± 2 mm; P = .0001) and in left ventricle posterior wall thickness (10.74 ± 1 mm vs 9.74 ± 1 mm; P = .0004). The incidence of late acute rejection and cardiac allograft vasculopathy was similar in our population compared to literature data. CONCLUSIONS: A therapeutic switch from CNIs to everolimus and mycophenolate mofetil can improve renal function in patients with CNI nephrotoxicity, especially in those with a shorter time period from transplantation, without exposing them to a higher incidence of late acute rejection and cardiac allograft vasculopathy.