Frequency, characteristics and risk assessment of pulmonary arterial hypertension with a left heart disease phenotype.

AIM: To obtain real-world evidence about the features and risk stratification of pulmonary arterial hypertension (PAH) with a left heart disease (LHD) phenotype (PAH-LHD). METHODS AND RESULTS: By reviewing the records of consecutive incident PAH patients at 7 tertiary centers from 2001 to 2021, we selected 286 subjects with all parameters needed to determine risk of death at baseline and at first follow-up with COMPERA and COMPERA 2.0 scores. Fifty seven (20%) had PAH-LHD according to the AMBITION definition. Compared with no-LHD ones, they were older, had higher BMI, more cardiovascular comorbidities, higher E/e' ratio and left atrial area, but lower BNP concentrations and better right ventricular function and pulmonary hemodynamics. Survival was comparable between PAH-LHD and no-LHD patients, although the former were less commonly treated with dual PAH therapy. Both COMPERA and COMPERA 2.0 discriminated all-cause mortality risk of PAH-LHD at follow-up, but not at baseline. Risk profile significantly improved during follow-up only when assessed by COMPERA 2.0. At multivariable analysis with low-risk status as reference, intermediate-high and high-risk, but not LHD phenotype, were associated with higher hazard of all-cause mortality. Results were comparable in secondary analyses including patients in the last 10 years and atrial fibrillation and echocardiographic abnormalities as additional criteria for PAH-LHD. CONCLUSIONS: In real life, PAH-LHD patients are frequent, have less severe disease and are less likely treated with PAH drug combinations than no-LHD. The COMPERA 2.0 model may be more appropriate to evaluate their mortality risk during follow-up and how it is modulated by therapy.

INFLA-score: A new diagnostic paradigm to identify pericarditis.

BACKGROUND: Diagnosis of pericarditis may be challenging because not all patients meet the conventional criteria. An overlooked diagnosis implies a longer course of symptoms and an increased risk of recurrences. C-reactive protein (CRP), widely used as an inflammation marker, has some limitations. This study aimed to assess the usefulness and prognostic value of INFLA-score, a validated index assessing low-grade inflammation, in the definite diagnosis of pericarditis. METHODS: Patients with suspected pericarditis were included. The INFLA-score was computed based on white blood cells and platelet count, neutrophil-to-lymphocyte ratio, and CRP, ranging from -16 to +16. An INFLA-score > 0 was considered positive for the presence of pericardial inflammation. The primary end point was the association of INFLA-score with diagnosis of pericarditis according to conventional criteria. The recurrence of pericarditis at 6 months was the secondary end point. RESULTS: A total of 202 patients were included, aged 47 ± 17 years, and 57% were females. Among 72 (36%) patients with a diagnosis of pericarditis, an INFLA-score > 0 was observed in 86% (vs. 36%, p < 0.001), abnormal CRP in 42% (vs. 10%, p < 0.001), pericardial effusion in 44% (vs. 19%, p < 0.001), abnormal electrocardiogram in 56% (vs. 24%, p < 0.001), and rubs in 5% (vs. 0.1%, p = 0.072). INFLA-score > 0 had the strongest predictive value for the diagnosis of pericarditis (hazard ratio 8.48, 95% confidence interval [CI] 3.39-21.21), with 86% sensitivity and 64% specificity, as opposed to CRP (hazard ratio 1.72, non-significant 95% CI 0.69-4.29). Recurrent pericarditis at 6 months was more frequent in patients with a positive INFLA-score (37% vs. 8%, p < 0.001, rate ratio 4.15, 95% CI 2.81-6.12). In patients with normal CRP, INFLA-score-confirmed ongoing inflammation in 78% of the cases. Compared with the conventional criteria, the INFLA-score had the highest accuracy (area under the curve = 0.82). Different cutoffs were valuable to rule out (INFLA-score > 0, sensitivity 86%, and negative likelihood ratio 0.22) or rule in (INFLA-score ≥ 10, specificity 97%, and positive likelihood ratio 13) the diagnosis. CONCLUSIONS: The INFLA-score is a useful diagnostic tool to assess the probability of pericarditis, with a strong prognostic value for further recurrences, outperforming CRP.

Efficacy of colchicine in addition to anakinra in patients with recurrent pericarditis.

AIM: Anakinra, an anti IL-1 agent targeting IL-1 alfa and beta, is available for the treatment of recurrent pericarditis in cases with corticosteroid dependence and colchicine resistance after failure of conventional therapies. However, it is unclear if the combination with colchicine, a non-specific inhibitor of the inflammasome targeting the same inflammatory pathway of IL-1, could provide additional benefit to prevent further recurrences. The aim of the present observational study is to assess whether the addition of colchicine on top of anakinra could prolong the time to first recurrence and prevent recurrences better than anakinra alone. METHODS: International, all-comers, multicentre, retrospective observational cohort study analysing all consecutive patients treated with anakinra for corticosteroid-dependent and colchicine-resistant recurrent pericarditis. The efficacy endpoint was recurrence rate and the time to the first recurrence. RESULTS: A total of 256 patients (mean age 45.0±15.4 years, 65.6% females, 80.9% with idiopathic/viral aetiology) were included. 64 (25.0%) were treated with anakinra as monotherapy while 192 (75.0%) with both anakinra and colchicine. After a follow-up of 12 months, 56 (21.9%) patients had recurrences. Patients treated with colchicine added to anakinra had a lower incidence of recurrences (respectively, 18.8% vs 31.3%; p=0.036) and a longer event-free survival (p=0.025). In multivariable analysis, colchicine use prevented recurrences (HR 0.52, 95% CI 0.29 to 0.91; p=0.021). CONCLUSIONS: The addition of colchicine on top of anakinra treatment could be helpful to reduce recurrences and prolong the recurrence-free survival.

Efficacy and safety of colchicine for the treatment of myopericarditis.

OBJECTIVE: Clinical trials have evaluated the efficacy and safety of colchicine only in simple pericarditis, excluding cases of concomitant myocarditis. The aim of this paper is to evaluate the efficacy and safety of colchicine for the treatment of the first attack of acute pericarditis with concomitant myocardial involvement. METHODS: Double-centre retrospective cohort study analysing consecutive patients admitted for first attack of pericarditis with myocarditis and treated with or without colchicine. The primary efficacy end point was the time to the first recurrence. Propensity score matching was used to generate two groups of patients with similar baseline characteristics. Colchicine-associated side effects were analysed as safety end-point. RESULTS: A total of 175 patients (mean age 46.2±20.1 years, 25.1% females, 88.6% with idiopathic/viral aetiology) were included. Seventy-nine (45.1%) patients were treated with colchicine. After a median follow-up of 25.3 (IQR 8.3-45.6) months, 58 (33.1%) patients had recurrences. The propensity score generated two groups of 73 patients with similar baseline characteristics but the use of colchicine. Patients treated with colchicine had a lower incidence of recurrences (respectively, 19.2% vs 43.8%; p=0.001) and a longer event-free survival (p=0.005). In multivariable analysis, women (HR 1.97, 95% CI 1.04 to 3.73; p=0.037) and corticosteroid use (HR 2.27, 95% CI 1.15 to 4.47; p=0.018) were independent risk factors for recurrences. Colchicine-associated side effects were mild and occurred in 3 (1.7%) patients. CONCLUSION: In patients with first attack of pericarditis associated with myocardial involvement, colchicine was safe and efficacious for the reduction of recurrences.

Eosinophilic myocarditis: comprehensive update on pathophysiology, diagnosis, prognosis and management.

Hypereosinophilic syndromes are a group of disorders secondary to the accumulation of eosinophils leading to the injury of one or more organs. Among them, eosinophilic myocarditis (EM) is a rare form of inflammatory cardiomyopathy characterized by eosinophilic infiltration into myocardial tissue and subsequent release of substances with cell membrane damage and cell destruction. The degree of infiltration is thought to depend on the underlying condition, as well as the degree and duration of eosinophil exposure and ranges from mild localized disease to diffuse multifocal infiltrates associated with myocardial necrosis, thrombotic complications and endomyocardial fibrosis. The main causes of EM are hypersensitivity reactions, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome variants, infections and cancer. Clinical presentation can be variable, ranging from asymptomatic forms to life-threatening conditions, to chronic heart failure due to progression to chronic restrictive cardiomyopathy. Marked eosinophilia in peripheral blood, elevated serum eosinophilic cationic protein concentration and multimodality imaging may suggest the etiology of EM, but in most cases an endomyocardial biopsy must be performed to establish a definitive diagnosis. Systemic treatment varies greatly depending on the underlying cause, however the evidence of an eosinophilic infiltrate allows initiation of immunosuppressive therapy, which is the mainstay of treatment in idiopathic and in most forms of EM. Patients with helminthic infection benefit from anti-parasitic therapy, those with myeloid clone often need a tyrosine kinase inhibitor, while anticoagulant therapy should be undertaken in case of possible thrombotic complications.

Performance of risk stratification scores and role of comorbidities in older vs younger patients with pulmonary arterial hypertension.

BACKGROUND: Risk scores are important tools for the prognostic stratification of pulmonary arterial hypertension (PAH). Their performance and the additional impact of comorbidities across age groups is unknown. METHODS: Patients with PAH enrolled from 2001 to 2021 were divided in ≥65 years old vs <65 years old patients. Study outcome was 5-year all-cause mortality. French Pulmonary Hypertension Network (FPHN), FPHN noninvasive, Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) and Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL 2.0) risk scores were calculated and patients categorized at low, intermediate and high risk. Number of comorbidities was calculated. RESULTS: Among 383 patients, 152 (40%) were ≥65 years old. They had more comorbidities (number of comorbidities 2, IQR 1-3, vs 1, IQR 0-2 in <65 years patients). Five-year survival was 63% in ≥65 vs 90% in <65 years. Risk scores correctly discriminated the different classes of risk in the overall cohort and in the older and younger groups. REVEAL 2.0 showed the best accuracy in the total cohort (C-index 0.74, standard error-SE- 0.03) and older (C-index 0.69, SE 0.03) patients, whereas COMPERA 2.0 performed better in younger patients (C-index 0.75, SE 0.08). Number of comorbidities was associated with higher 5-year mortality, and consistently increased the accuracy of risk scores, in younger but not in older patients. CONCLUSIONS: Risk scores have similar accuracy in the prognostic stratification of older vs younger PAH patients. REVEAL 2.0 had the best performance in older patients and COMPERA 2.0 had it in younger patients. Comorbidities increased the accuracy of risk scores only in younger patients.

New Developments in the Management of Recurrent Pericarditis.

Recurrent pericarditis is a common and troublesome complication that affects 15%-30% of patients with a previous episode of pericarditis. However, the pathogenesis of these recurrences is not well understood, and most cases remain idiopathic. Recent advances in medical therapy, including the use of colchicine and anti-interleukin-1 agents like anakinra and rilonacept, have suggested an autoinflammatory rather than an autoimmune mechanism for recurrences with an inflammatory phenotype. As a result, a more personalized approach to treatment is now recommended. Patients with an inflammatory phenotype (fever and elevated C-reactive protein level) should receive colchicine and anti-interleukin-1 agents as first-line therapy, whereas those without systemic inflammation should receive low to moderate doses of corticosteroids (eg, prednisone 0.2-0.5 mg/kg/d as an initial dose) and consider azathioprine and intravenous human immunoglobulins in the case of corticosteroid failure. Tapering of corticosteroids should be slow after achieving clinical remission. In this article, we review the new developments in the management of recurrent pericarditis.

Coronavirus disease 2019 vaccination-related pericarditis: a single tertiary-center experience.

AIMS: Vaccination represents a cornerstone of prevention in the COVID-19 pandemic. Rare adverse events including acute pericarditis and myopericarditis have been reported. METHODS: All consecutive patients referred to our referral center for pericardial diseases following COVID-19 vaccination from 1 April 2021 to 15 April 2022 were included. Acute pericarditis and myopericarditis were diagnosed according to ESC guidelines. Patients with SARS-CoV-2 infection were excluded from the study. RESULTS: Twenty-four patients (79% men) aged 39.7 ±â€Š19.8 years were referred to our center with pericarditis after receiving COVID-19 vaccination. Thirteen (54%) patients were diagnosed with myopericarditis. The mean time between vaccination and symptoms onset was 7.0 ±â€Š4.9 days, and the most frequent symptom was pericarditic chest pain (83%). Respectively, 50 and 33% of patients presented after the second and the third dose of the vaccine. Almost all patients were treated with both nonsteroidal anti-inflammatory drugs and colchicine. Five patients (21%) experienced a recurrence of pericarditis. No patient died or developed constrictive pericarditis. Mean follow-up was 8.0 ±â€Š3.2 months. CONCLUSION: COVID-19 vaccine-related pericarditis typically manifest with mild clinical signs, in young male individuals, a few days after the second or third vaccine dose and are commonly characterized by a rapid complete recovery.

Leflunomide-induced pulmonary arterial hypertension: Case report and review of literature.

Leflunomide, an isoxazole derivative, is a disease-modifying antirheumatic drug, that has successfully been used for the treatment of rheumatoid arthritis and psoriatic arthritis as a feasible alternative to methotrexate. Among side effects, pulmonary arterial hypertension (PAH) has been described in a few case reports.We present a 55-year-old woman treated with leflunomide for psoriatic spondyloarthritis who consulted our hospital because of progressive exertional dyspnea. Clinical examination found signs of right heart failure and severe pre-capillary pulmonary hypertension (PH) was diagnosed by right heart catheterization. All investigations for pre-capillary PH were negative and a diagnosis of severe PAH was thus established. Due to previous evidence of the association of leflunomide with PAH, the drug was stopped and upfront dual combination therapy with pulmonary vasodilators was initiated. The patient's condition rapidly improved with significant improvement in exercise tolerance and normalization of echocardiographic right ventricular systolic pressure within three months of treatment. Learning objective: Pulmonary arterial hypertension (PAH) is a rare disease and drug-induced causes account for only a small percentage of these patients. In recent years, new drugs have been identified or suspected as potential risk factors for PAH. Among these, leflunomide, a disease-modifying antirheumatic drug, has been associated with PAH only in a few case reports. An accurate drug history is strongly recommended for all patients in which a PAH is newly diagnosed.

From Goliath to David: Interventricular fibroma.

We describe an interventricular septum mass in 1 years old child, followed during 14 years. The mass did not grow up over time, the patient did not experienced any arrythmia, and did not developed heart failure. A complete diagnosis of interventricular Fibroma was made at the age of 14 years old when the patient underwent to cardiac MRI. A close follow up was in this case the winner strategy, saving him from an early unnecessary cardiac surgery.

Advanced Heart Failure in Special Population: Cardiomyopathies and Myocarditis.

Cardiomyopathies are a heterogeneous group of heart muscle diseases and an important cause of heart failure (HF) in young populations. The variety of causes, multiple underlying pathophysiological mechanisms, and different phenotypic expressions influence their presentation and response to treatment. Dilated cardiomyopathy is the most prevalent cause of HF. Advanced HF in hypertrophic, restrictive, and arrhythmogenic cardiomyopathies is rare, but its development portends a poor prognosis. The active phase of fulminant myocarditis may result in acute HF requiring advanced strategies to support the systemic circulation or may determine an irreversible persisting left ventricular failure with end-stage HF.