Sacubitril/valsartan for cardioprotection in breast cancer (MAINSTREAM): design and rationale of the randomized trial.

AIMS: In recent years, survival in patients with breast cancer has increased. Despite the improvement in outcomes of those patients, the risk of treatment-related cardiotoxicity remains high, and its presence has been associated with a higher risk of treatment termination and thus lower therapeutic efficacy. Prior trials demonstrated that a preventive initiation of heart failure drugs, including the renin-angiotensin-aldosterone inhibitors, might reduce the risk of treatment-related cardiotoxicity. However, to date, no study investigated the efficacy of sacubitril/valsartan, a novel antineurohormonal drug shown to be superior to the previous therapies, in the prevention of cardiotoxicity in patients with early-stage breast cancer, which is the aim of the trial. METHODS AND RESULTS: MAINSTREAM is a randomized, placebo-controlled, double-blind, multicentre, clinical trial. After the run-in period, a total of 480 patients with early breast cancer undergoing treatment with anthracyclines and/or anti-human epidermal growth factor receptor 2 drugs will be randomized to the highest tolerated dose of sacubitril/valsartan, being preferably 97/103 mg twice daily or placebo in 1:1 ratio. The patients will be monitored, including routine transthoracic echocardiography (TTE) and laboratory biomarker monitoring, for 24 months. The primary endpoint of the trial will be the occurrence of a decrease in left ventricular ejection fraction by ≥5% in TTE within 24 months. The key secondary endpoints will be the composite endpoint of death from any cause or hospitalization for heart failure, as well as other imaging, laboratory, and clinical outcomes, including the occurrence of the cancer therapy-related cardiac dysfunction resulting in the necessity to initiate treatment. The first patients are expected to be recruited in the coming months, and the estimated completion of the study and publication of the results are expected in December 2027, pending recruitment. CONCLUSIONS: The MAINSTREAM trial will determine the efficacy and safety of treatment with sacubitril/valsartan as a prevention of cardiotoxicity in patients with early breast cancer (ClinicalTrials.gov number: NCT05465031).

Impact of diabetes mellitus on disease severity and patient survival in idiopathic pulmonary arterial hypertension: data from the Polish multicentre registry (BNP-PL).

BACKGROUND: Recent studies revealed that alterations in glucose and lipid metabolism in idiopathic pulmonary arterial hypertension (IPAH) are associated with disease severity and poor survival. However, data regarding the impact of diabetes mellitus (DM) on the prognosis of patients with IPAH remain scarce. The aim of our study was to determine that impact using data from a national multicentre prospective pulmonary hypertension registry. METHODS: We analysed data of adult patients with IPAH from the Database of Pulmonary Hypertension in the Polish population (BNP­PL) between March 1, 2018 and August 31, 2020. Upon admission, clinical, echocardiographic, and haemodynamic data were collected at 21 Polish IPAH reference centres. The all-cause mortality was assessed during a 30-month follow-up period. To adjust for differences in age, body mass index (BMI), and comorbidities between patients with and without DM, a 2-group propensity score matching was performed using a 1:1 pairing algorithm. RESULTS: A total of 532 patients with IPAH were included in the study and 25.6% were diagnosed with DM. Further matched analysis was performed in 136 patients with DM and 136 without DM. DM was associated with older age, higher BMI, more advanced exertional dyspnea, increased levels of N-terminal pro-brain natriuretic peptide, larger right atrial area, increased mean right atrial pressure, mean pulmonary artery pressure, pulmonary vascular resistance, and all-cause mortality compared with no DM. CONCLUSIONS: Patients with IPAH and DM present with more advanced pulmonary vascular disease and worse survival than counterparts without DM independently of age, BMI, and cardiovascular comorbidities.

Impact of the COVID-19 Pandemic on Pulmonary Hypertension Patients: Insights from the BNP-PL National Database.

We aimed to evaluate the clinical course and impact of the SARS-CoV-2 pandemic on the rate of diagnosis and therapy in the complete Polish population of patients (pts) with pulmonary arterial hypertension (PAH-1134) and CTEPH (570 pts) treated within the National Health Fund program and reported in the national BNP-PL database. Updated records of 1704 BNP-PL pts collected between March and December 2020 were analyzed with regard to incidence, clinical course and mortality associated with COVID-19. Clinical characteristics of the infected pts and COVID-19 decedents were analyzed. The rates of new diagnoses and treatment intensification in this period were studied and collated to the proper intervals of the previous year. The incidence of COVID-19 was 3.8% (n = 65) (PAH, 4.1%; CTEPH, 3.2%). COVID-19-related mortality was 28% (18/65 pts). Those who died were substantially older and had a more advanced functional WHO class and more cardiovascular comorbidities (comorbidity score, 4.0 ± 2.1 vs. 2.7 ± 1.8; p = 0.01). During the pandemic, annualized new diagnoses of PH diminished by 25-30% as compared to 2019. A relevant increase in total mortality was also observed among the PH pts (9.7% vs. 5.9% pre-pandemic, p = 0.006), whereas escalation of specific PAH/CTEPH therapies occurred less frequently (14.7% vs. 21.6% pre-pandemic). The COVID-19 pandemic has affected the diagnosis and treatment of PH by decreasing the number of new diagnoses, escalating therapy and enhancing overall mortality. Pulmonary hypertension is a risk factor for worsened course of COVID-19 and elevated mortality.

Exhaled Air Metabolome Analysis for Pulmonary Arterial Hypertension Fingerprints Identification-The Preliminary Study.

Pulmonary arterial hypertension (PAH) is a rare disease with a serious prognosis. The aim of this study was to identify biomarkers for PAH in the breath phase and to prepare an automatic classification method to determine the changing metabolome trends and molecular mapping. A group of 37 patients (F/M: 8/29 women, mean age 60.4 ± 10.9 years, BMI 27.6 ± 6.0 kg/m2) with diagnosed PAH were enrolled in the study. The breath phase of all the patients was collected on a highly porous septic material using a special patented holder PL230578, OHIM 002890789-0001. The collected air was then examined with gas chromatography coupled with mass spectrometry (GC/MS). The algorithms of Spectral Clustering, KMeans, DBSCAN, and hierarchical clustering methods were used to perform the cluster analysis. The identification of the changes in the ratio of the whole spectra of biomarkers allowed us to obtain a multidimensional pathway for PAH characteristics and showed the metabolome differences in the four subgroups divided by the cluster analysis. The use of GC/MS, supported with novel porous polymeric materials, for the breath phase analysis seems to be a useful tool in selecting bio-fingerprints in patients with PAH. The four metabolome classes which were obtained constitute novel data in the PAH population.

An expert opinion of the Polish Cardiac Society Working Group on Pulmonary Circulation and the Polish Society for Rheumatology on the diagnosis and treatment of pulmonary hypertension in patients with connective tissue disease.

Systemic connective tissue diseases (CTDs) comprise a large group of diseases that are auto-immune in nature and characterized by the involvement of multiple systems and organs. Pul-monary hypertension (PH) of various etiologies may develop in the course of CTD, including pulmonary arterial hypertension (PAH), PH secondary to the lung disease, postcapillary PH in the course of left heart disease, and chronic thromboembolic pulmonary hypertension (CTEPH). In addition, the different forms of PH may coexist with each other. Among patients with CTD, PAH occurs most commonly in those with systemic sclerosis, where it affects ap-proximately 8%-12% of patients. The prognosis in patients with untreated PAH is very poor. It is particularly important to identify the high-risk CTD-PAH population and to perform effi-cient and accurate diagnostics so that targeted therapy of the pulmonary arteries can be intro-duced. Echocardiography is used to screen for PH, but clinical and echocardiographic suspicion of PH always requires confirmation by right heart catheterization. Confirmation of PAH ena-bles the initiation of life-prolonging pharmacological treatment in this group of patients, which should be administered in referral centers. Drugs available for pharmacological management include endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostacyclins.

Characteristics and outcomes of patients with chronic thromboembolic pulmonary hypertension in the era of modern therapeutic approaches: data from the Polish multicenter registry (BNP-PL).

BACKGROUND: Significant achievements in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) have provided effective therapeutic options for most patients. However, the true impact of the changed landscape of CTEPH therapies on patients' management and outcomes is poorly known. We aimed to characterize the incidence, clinical characteristics, and outcomes of CTEPH patients in the modern era of CTEPH therapies. METHODS: We analyzed the data of CTEPH adults enrolled in the prospective multicenter registry. RESULTS: We enrolled 516 patients aged 63.8 ± 15.4 years. The incidence rate of CTEPH was 3.96 per million adults per year. The group was burdened with several comorbidities. New oral anticoagulants (n = 301; 58.3%) were preferred over vitamin K antagonists (n = 159; 30.8%). Pulmonary endarterectomy (PEA) was performed in 120 (23.3%) patients and balloon pulmonary angioplasty (BPA) in 258 (50%) patients. PEA was pretreated with targeted pharmacotherapy in 19 (15.8%) patients, and BPA in 124 (48.1%) patients. Persistent CTEPH was present in 46% of PEA patients and in 65% of patients after completion of BPA. Persistent CTEPH after PEA was treated with targeted pharmacotherapy in 72% and with BPA in 27.7% of patients. At a mean time period of 14.3 ± 5.8 months, 26 patients had died. The use of PEA or BPA was associated with better survival than the use of solely medical treatment. CONCLUSIONS: The modern population of CTEPH patients comprises mostly elderly people significantly burdened with comorbid conditions. This calls for treatment decisions that are tailored individually for every patient. The combination of two or three methods is currently a frequent approach in the treatment of CTEPH. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov/ct2/show/NCT03959748.

Two professions against two killer diseases: the rationale, organization, and initial experience of a cardio-oncology service.

BACKGROUND: Cardiovascular diseases are the most common factor affecting prognosis in cancer survivors. Cardio­oncology (CO) services have been developed to solve this issue. The outcomes regarding patient demographics and clinical findings are limited and the available data include CO services evaluating patients undergoing only chemotherapy as opposed to those also undergoing radiation therapy. AIMS: We aimed to show initial experiences of the CO service implemented in a tertiary oncology center. METHODS: The CO service was designed to include 2 major domains, general CO and electrotherapy consultations. This observational study included patients referred to the CO service with the following data: baseline demographics, cancer type, reasons for referral, cardiac evaluation, and initial clinical outcomes. RESULTS: All patients with cancer referred to our CO service between March 2016 and December 2019 were included in the study. A total of 2762 patients (77% women) at the mean (SD) age of 62 (12) years were referred (63% on an out­patient basis) for general consultations. The most frequent diagnosis was breast cancer (66%). A total of 18% of patients were referred to the CO service due to cardiovascular complications related to cancer treatment. The CO-cardiac implantable electronic device (CIED) team evaluated 652 patients (515 patients with CIEDs who were qualified for radiotherapy, 48 patients with CIEDs who were assessed with magnetic resonance imaging, and 89 patients with CIEDs who underwent cancer surgery). In the total of 5872 radiotherapy sessions, there were 2 harmful interactions; no other complications during magnetic resonance imaging and surgery were recorded. CONCLUSIONS: The CO­service established within the cancer center seems to be safe and feasible.

Characterization of Patients with Pulmonary Arterial Hypertension: Data from the Polish Registry of Pulmonary Hypertension (BNP-PL).

Current knowledge of pulmonary arterial hypertension (PAH) epidemiology is based mainly on data from Western populations, and therefore we aimed to characterize a large group of Caucasian PAH adults of Central-Eastern European origin. We analyzed data of incident and prevalent PAH adults enrolled in a prospective national registry involving all Polish PAH centers. The estimated prevalence and annual incidence of PAH were 30.8/mln adults and 5.2/mln adults, respectively and they were the highest in females ≥65 years old. The most frequent type of PAH was idiopathic (n = 444; 46%) followed by PAH associated with congenital heart diseases (CHD-PAH, n = 356; 36.7%), and PAH associated with connective tissue disease (CTD-PAH, n = 132; 13.6%). At enrollment, most incident cases (71.9%) were at intermediate mortality risk and the prevalent cases had most of their risk factors in the intermediate or high risk range. The use of triple combination therapy was rare (4.7%). A high prevalence of PAH among older population confirms the changing demographics of PAH found in the Western countries. In contrast, we found: a female predominance across all age groups, a high proportion of patients with CHD-PAH as compared to patients with CTD-PAH and a low use of triple combination therapy.

[Thrombo-embolic pulmonary hypertension--do not spoil a chance for effective surgery!]. / Zakrzepowo-zatorowe nadcisnienie plucne--nie marnujmy szansy na skuteczne leczenie operacyjne!

Chronic thromboembolic pulmonary hypertension (CTEPH) can be defined as pulmonary hypertension with persistent pulmonary perfusion defects causes by unresolved thrombi. All symptomatic CTEPH patients with documented pulmonary vascular resistance > 300 dyn*sec*cm(-5) and proximal lesions should be considered for surgical treatment--pulmonary endarterectomy. The role of pharmacological treatment remains controversial and should be restricted to inoperable cases and persistent pulmonary hypertension after pulmonary endarterectomy. Every year about 30 procedures is performed in two specialised centers in Poland with 1 year mortality at 8-9%. Number of procedures done gives the frequency of pulmonary endarterectomy at 0.7/million of population/year. Current data from UK indicate the actual ratio of surgical treatment of CTPH at 2/million/year. The article discusses reasons for CTEPH is underdiagnosed and why rate of surgical therapy in Poland is too low.