Signs Of Right Heart Failure Research Articles

Definition, classification and diagnosis of pulmonary hypertension.

Pulmonary hypertension (PH) is a haemodynamic condition characterised by elevation of mean pulmonary arterial pressure (mPAP) >20 mmHg, assessed by right heart catheterisation. Pulmonary arterial wedge pressure (PAWP) and pulmonary vascular resistance (PVR) distinguish pre-capillary PH (PAWP ≤15 mmHg, PVR >2 Wood Units (WU)), isolated post-capillary PH (PAWP >15 mmHg, PVR ≤2 WU) and combined post- and pre-capillary PH (PAWP >15 mmHg, PVR >2 WU). Exercise PH is a haemodynamic condition describing a normal mPAP at rest with an abnormal increase of mPAP during exercise, defined as a mPAP/cardiac output slope >3 mmHg/L/min between rest and exercise. The core structure of the clinical classification of PH has been retained, including the five major groups. However, some changes are presented herewith, such as the re-introduction of "long-term responders to calcium channel blockers" as a subgroup of idiopathic pulmonary arterial hypertension, the addition of subgroups in group 2 PH and the differentiation of group 3 PH subgroups based on pulmonary diseases instead of functional abnormalities. Mitomycin-C and carfilzomib have been added to the list of drugs with "definite association" with PAH. For diagnosis of PH, we propose a stepwise approach with the main aim of discerning those patients who need to be referred to a PH centre and who should undergo invasive haemodynamic assessment. In case of high probability of severe pulmonary vascular disease, especially if there are signs of right heart failure, a fast-track referral to a PH centre is recommended at any point during the clinical workup.

Primary tricuspid regurgitation: a rare case report

Tricuspid regurgitation is no longer a forgotten valve as TR can be clinical challenge for the treating physician especially patients with moderate to severe tricuspid regurgitation. The aetiology can be primary and secondary TR of which secondary TR is more common with female predominance. Another entity called isolated TR is now seen. Primary TR due to infective endocarditis is a rare condition. Clinical examination must look for signs of right heart failure. Investigations like Transthoracic and transesophageal echocardiogram has to meticulously done to grade the severity of TR and look for morphological changes. Medical management must be tailored made for patients based upon the severity and the clinicians must know when to refer to the valve team for appropriate intervention.

Giant right and left atrium: spectrum of rheumatic triple valve disease (double hit with double impact): a case report and review of the literature

BackgroundRheumatic heart disease (RHD) continues to pose a significant burden on global health, particularly in socioeconomically disadvantaged populations. We present the case of a 38-year-old woman with severe multivalvular RHD and giant atria, highlighting the challenges and complexities of managing this condition.Case presentationThe patient presented with progressively worsening dyspnoea, signs of right heart failure, and severe valvular abnormalities. Diagnostic evaluations revealed severe mixed mitral valve disease in the form of mitral stenosis and regurgitation, along with involvement of the aortic and tricuspid valves, leading to significant enlargement of both atria. Despite facing socioeconomic constraints and poor adherence to treatment, the patient underwent successful surgical intervention, resulting in remarkable symptomatic improvement.ConclusionsThrough this case, we emphasise the importance of early detection, comprehensive management strategies, and multidisciplinary care in addressing the complexities of RHD. Despite the challenges posed by socioeconomic disparities, positive outcomes can be achieved with timely diagnosis and appropriate intervention. This case underscores the need for targeted efforts to improve access to healthcare resources and reduce the global burden of RHD.

Contemporary diagnosis and treatment of tricuspid regurgitation: from neglected valve to primetime

Tricuspid insufficiency has long been considered an entity with low prognostic importance and associated with symptoms and signs only secondarily to left heart pathology. Scientific research in recent years has debunked this myth, demonstrating a key role in determining symptoms and signs of right heart failure, even in advanced stages. In parallel, advances in transcatheter technologies have opened up treatment options even for patients with increased surgical risk, who were previously excluded from traditional surgical options, with increasingly convincing results in reducing symptoms and improving the quality of life of our patients. The contemporary challenge is to translate these messages into everyday clinical practice and to encourage the centralization of patients in centers that currently have the expertise for feasibility evaluation and subsequent treatment. In this Review, we will analyze the most recent evidence on the pathophysiology and diagnosis of tricuspid insufficiency, the latest recommendations from European guidelines, and we will try to illustrate the most common technologies for percutaneous treatment and the abundant evidence supporting them.

Truncus arteriosus from prenatal diagnosis to clinical outcome: a single-centre experience.

The aim of this study was to review our institution's experience with truncus arteriosus from prenatal diagnosis to clinical outcome. and results: We conducted a single-centre retrospective cohort study for the years 2005-2020. Truncus arteriosus antenatal echocardiographic diagnostic accuracy within our institution was 92.3%. After antenatal diagnosis, five parents (31%) decided to terminate the pregnancy. After inclusion from referring hospitals, 16 patients were offered surgery and were available for follow-up. Right ventricle-to-pulmonary artery continuity was preferably established without the use of a valve (direct connection), which was possible in 14 patients (88%). There was no early or late mortality. Reinterventions were performed in half of the patients at latest follow-up (median follow-up of 5.4 years). At a median age of 5.5 years, 13 out of 14 patients were still without right ventricle-to-pulmonary artery valve, which was well tolerated without signs of right heart failure. The right ventricle demonstrated preserved systolic function as expressed by tricuspid annular plane systolic excursion z-score (-1.4 ± 1.7) and fractional area change (44 ± 12%). The dimensions and function of the left ventricle were normal at latest follow-up (ejection fraction 64.4 ± 6.2%, fractional shortening 34.3 ± 4.3%). This study demonstrates good prenatal diagnostic accuracy of truncus arteriosus. There was no mortality and favourable clinical outcomes at mid-term follow-up, with little interventions on the right ventricle-to-pulmonary artery connection and no right ventricle deterioration. This supports the notion that current perspectives of patients with truncus arteriosus are good, in contrast to the poor historic outcome series. This insight can be used in counselling and surgical decision-making.

Gestion de la péricardite constrictive : à travers l’étude de 43 cas opérés

Chronic constrictive pericarditis is a rare condition characterized by clinical signs of right heart failure, due to the symphysis of the two pericardial leaflets.Our study focused on a retrospective analysis of 43 CCP surgery observations collected over an 11-year period (2003–2013).The mean age of the patients was 32 years; 65% were male; exercise dyspnea (95%) was the most frequent sign. Two main etiologies were observed: tuberculosis 58% and idiopathic causes 42%. All of our patients received a subtotal pericardectomy per median sternotomy, of which 95% had no cardiopulmonary bypass.

PULMONARY EMBOLISM MANAGEMENT CHALLENGES IN DIAGNOSTIC AND TREATMENT OF 81 YEAR OLD MAN IN THE SETTING OF RURAL AREA WITH LIMITED RESOURCES : A CASE REPORT

Background: Pulmonary embolism is a cardiology emergency with a high mortality rate that is hard to diagnose for its symptoms. The adequate diagnosis of pulmonary embolism requires advanced laboratory and imaging facilities which are not widely available in Indonesia. The lack of facilities and pharmacological availability is an important problem for the delay of treatment and diagnosis of pulmonary embolism will increase the mortality number. This case reports on a patient with pulmonary embolism, managed in a limited healthcare facility. Case Illustration: A-81-year-old Man came with sudden dyspnea and hemoptoe. Physical examination showed mild tachycardia, a drop of blood saturation, and signs of right heart failure. His ECG showed deep S wave in lead I, Q wave in lead III (McGinn-white sign), P pulmonary in lead II, III, aVF, inverted T in inferior and anterior lead. Diagnosis were determined by the clinical score and the ECG pattern. The patient showed hemodynamic instability and was included as a high-risk pulmonary embolism, therefore systemic thrombolysis should be the goal therapy for this patient. Due to the unavailability of systemic thrombolysis, systemic anticoagulant therapy using fondaparinux sodium was initiated and hemodynamic support was given. The patient developed refractory shock despite the usage of the hemodynamic support and died after 5 days of hospitalization. Conclusion: The limitation of diagnostic tools and therapy is one of the biggest challenges in rural hospitals for it can increase the mortality rate of PE Patients. The procurement of diagnostic modalities and pharmacology therapies should be carried out in all hospitals in Indonesia to provide the best management for the patient.

Untreated Right Ventricle Myxoma with Pericardial Effusion in Young Men: A Case Report

Myxomas are benign cardiac tumors that are mostly found in the left atrium. We present a case of a 20-year-old male patient who presented with worsening dyspnea and signs of right heart failure. The echocardiography shows an untreated giant intracardiac mass in a rare place in the right ventricle, obstructing the blood flow, and massive pericardial effusion. We do a pericardiocentesis first to manage the pericardial effusion. Pericardiocentesis was done in different normal locations due to ascites permagna. Nevertheless, our patient needs emergency surgical excision as soon as possible to prevent sudden death caused by obstruction, embolic, and other complications.

Neoplastic Pericardial Effusion in Malignant Solid Tumors: Clinical Features, Diagnosis and Management

Introduction: Neoplastic pericardial effusion (NPE) poses a significant challenge in medical pathology, particularly due to its association with secondary involvement by malignancies originating in various organs. Timely management of NPE is pivotal for both overall survival and the patients' quality of life. However, there is a scarcity of data on NPE in our country. This study aims to provide a comprehensive description of the clinical, diagnostic, and therapeutic characteristics of consecutive Moroccan patients with NPE. Methods: A retrospective cohort study was conducted at Ibn Rochd Cardiology Department and Oncology Unit in Casablanca, covering a period of three years (January 2020 to December 2022). The study included patients diagnosed with NPE based on clinical, biological, histological, and echocardiographic criteria. Data collection encompassed sociodemographic information, performance status, clinical manifestations, ECG and echocardiography findings, grade of pericardial effusion, cytology of pericardial fluid, and details of therapeutic protocols administered. Results: Between 2020 and 2022, 49 NPE patients were admitted, with a gender distribution of 51% men and 49% women. The median age was 42 years. Most patients presented with symptomatic pericardial effusion (81%), and 61.2% had NPE at the first diagnosis of metastatic disease. Lung, breast, and other solid tumors were common etiologies. Cytology of pericardial fluid was positive in 23 patients. Clinical examination and diagnostic imaging revealed diverse presentations, including signs of right heart failure, ECG abnormalities, and echocardiographic findings indicative of significant pericardial effusion. Pericardiocentesis and drainage were performed in the majority of patients, often combined with pleuropericardial window placement. Systemic treatments, tailored to the primary tumor type, were administered, with a 60% overall mortality rate, rising to 88% in lung cancer cases. Conclusion: This study provides crucial insights into the clinical spectrum and management of NPE in Moroccan patients. The high mortality rate, particularly in lung cancers, underscores the importance of early detection and targeted therapeutic interventions in improving outcomes for patients with NPE.

Increased hepatic T1 values are correlated with right ventricular involvement and congestion after ST-segment elevation myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: None. Background ST-segment elevation myocardial infarction (STEMI) may have a multiorgan impact. Due to its proximity to the heart, a large portion of the liver is imaged during T1 mapping in Cardiovascular Magnetic Resonance (CMR) and recently higher T1 have been found associated with signs of right heart failure (RHF) in patients with non-ischemic cardiomyopathy, but no data are available in STEMI population. Purpose To evaluate the role of early hepatic native T1 in detecting the presence of right ventricle (RV) involvement after STEMI. Methods 133 patients with STEMI who underwent early CMR after primary angioplasty (PPCI) were enrolled. Patients with known hepatic disease were excluded from the study. Hepatic T1 was evaluated considering the mean value obtained from three regions of interest, free from fat and blood vessels. RV involvement was diagnosed in the presence of RV ejection fraction (EF) reduction according to current guidelines, RV wall motion abnormalities and the presence of necrosis in late gadolinium enhancement (LGE) sequences. Results Overall, the mean age was 59.72 ± 13.32 years and 28.2% were female. Fifty-two (39.1%) patients had an anterior myocardial infarction. The median time from PPCI to CMR was 3 [IQR 2.00–5.00] days. T1 mapping was available in all patients and mean hepatic T1 value of the population was 622.91 ± 100.14 ms. According to the Youden index the optimal hepatic T1 cut-off value to predict RV involvement was 605 ms. A total of 72 (54.1%) patients presented high hepatic T1 values (>605 ms). No significant correlations were found between high hepatic T1 values and left ventricle EF, infarct size, area at risk and the presence of microvascular obstruction. High hepatic T1 values were correlated with larger RV end-diastolic volume index (RVEDVi) (median 83.03 ml/m2 vs 53.16 ml/m2, p<0.001), lower RVEF (median 39.4% vs 57.62%, p<0.001) and presence of LGE in RV (26.5% vs 9.8%, p = 0.015). White blood cells (WBC), C-reactive protein and hs-Tn T peak values did not differ in the two study groups but NT-proBNP values were significantly higher in patients with high hepatic T1 (median 3531.22 vs 111.25 pg/mL, p<0.001). A strong positive correlation was found between hepatic T1 and NTproBNP (r = 0.754, p<0.001, Figure 1). At the univariable analysis, RV EF (OR 0.848, 95%CI 0.806–0.893, p<0.001), RVEDVi (OR 1.026, 95%CI 1.013–1.038, p<0.001) and the presence of RV infarct at the CMR evaluation (OR 3.286, 95%CI 1.218–8.865, p = 0.019) were found predictors of high hepatic T1 values. On multivariable logistic regression, RVEDVi (OR 1.022, 95%CI 1.006–1.038, p = 0.008) and RV-EF (OR 0.854, 95%CI 0.809–0.902, p<0.001) resulted as independent predictors of increased hepatic T1 values. Conclusions RV involvement after STEMI may lead to hepatic congestion and high hepatic T1 values are associated with early RV dysfunction parameters (RVEDVi, RV-EF and LGE) at CMR and higher levels of NT-proBNP.

Diagnosis and surgical management of pericardial constriction after cardiac surgery

ObjectivesPrevious cardiac surgery is an increasingly common etiology of constrictive pericarditis, but there is a paucity of data on clinical presentation and outcome of surgical treatment. MethodsWe reviewed data of 263 patients who underwent pericardiectomy for postoperative constriction from January 1, 1993, through July 1, 2017. Outcomes of interest were early and late mortality, as well as features of clinical presentation. ResultsMedian patient age was 64 (56-72) years, and the median interval between previous operation and pericardiectomy was 2.7 years (range, 0-54 years). Previous operations included coronary artery bypass grafting in 114 (43%), valve surgery in 85 (32%), combined coronary artery bypass grafting and valve surgery in 33 (13%), and other procedures in 31 (12%). Common presentations were symptoms of right heart failure in 221 (84%) or dyspnea in 42 (16%). Moderate-to-severe tricuspid valve regurgitation was present in 108 (41%) patients. There were 14 (5.5%) deaths within 30 days postoperatively, and survival at 5 and 10 years postoperatively was 61% and 44%. On multivariate analysis, older age (P = .013), diabetes (P = .019), and nonelective pericardiectomy within 2 years of cardiac surgery (P < .001) were associated with decreased long-term survival. ConclusionsPericardial constriction after cardiac surgery can present at any interval postoperatively. Symptoms and signs of right heart failure in patients with previous cardiac surgery should alert physicians to the possibility of pericardial constriction followed by a correct diagnosis. Pericardiectomy performed urgently following cardiac operation has poor long-term outcomes.

Transcatheter tricuspid valve edge-to-edge repair after a heart transplant: a single-centre experience with a novel therapy†.

Tricuspid regurgitation (TR) in patients who had heart transplants is associated with poor outcome. The increased risk for surgical and postoperative complications might be reduced in these vulnerable patients by transcatheter therapies. All patients with a prior heart transplant (HTX) undergoing transcatheter edge-to-edge repair in the tricuspid position (T-TEER) were prospectively enrolled in an institutional registry. Seven patients who had heart transplants (5/7 female) at a mean age of 53 [48; 64] and median TRI-SCORE of 14 [7; 22] underwent T-TEER to treat symptomatic TR ≥ IV in an elective (n = 6) and urgent (n = 1) setting, respectively. The median time from HTX to T-TEER was 13 years. A total of 2 (n = 4) and 3 (n = 3) clips were implanted with a technical success in 6/7 (one single- device detachment). TR reduction was effective and durable within a median echocardiographic follow-up time of 10 months (TR baseline vs last follow-up: P = 0.03). Further, significant right ventricular remodelling (right ventricular end-diastolic diameter: 50 mm-36 mm, P = 0.02), decrease in the inferior vena cava diameter (24 mm-18 mm, P = 0.04) and in the gamma-glutamyl-transferase (255 U/l-159 U/l, P = 0.04) was found. Four of 7 patients were free of cardiovascular death (n = 1, 267 days after T-TEER), cardiac redo surgery (n = 1) and heart failure hospitalization (n = 2) and had no further clinical signs of right heart failure. T-TEER after HTX is feasible and effective regarding TR reduction in a short-term follow-up. The initial results may pave the way for a novel approach in TR management in patients having HTX.

0980 A Child with Achondroplasia, Cervicomedullary Junction Compression, Severe Obstructive Sleep Apnea and Pulmonary Hypertension

Abstract Introduction Achondroplasia is a short stature autosomal dominant skeletal dysplasia. Children with Achondroplasia are at risk for multiple medical comorbidities including sleep disordered breathing due to midface hypoplasia and craniocervical junction compression. Recent guidelines from American Academy of Pediatrics on health supervision of children with achondroplasia recommend routine clinical screening for symptoms of obstructive sleep apnea (OSA) and craniocervical junction compression in which case a polysomnogram should be considered. Report of case(s) The patient is a now 15 month old male who was initially seen in sleep medicine clinic at age 4 months for snoring and respiratory distress while awake. Polysomnogram 2 days later demonstrated severe OSA. The study demonstrated an oAHI of 25.1/hour, O2 nadir of 77%, and TcCO2 with evidence of significant hypoventilation with TcCO2 max of 67mmHg. This was adequately treated with supplemental oxygen. The patient subsequently presented to the emergency department at age 7 months with hypoxemic respiratory failure and signs of right heart failure and was started on CPAP. Echocardiogram demonstrated significant pulmonary hypertension. Subsequent CPAP titration study during admission demonstrated adequate treatment of OSA and his pulmonary hypertension significantly improved with the patient requiring no pulmonary hypertension treatment at discharge. At age 9 months, the patient was again admitted with hypoxemic respiratory failure and subsequent brain MRI demonstrated foramen magnum stenosis requiring subsequent surgical decompression. He was discharged on CPAP, however, was not tolerating this at home. Therefore, repeat polysomnogram was obtained that demonstrated severe OSA that was not responsive to supplemental oxygen. The patient was then started on BPAP therapy which he has since been tolerating well. Conclusion Children with achondroplasia are at increased risk for sleep disordered breathing and craniocervical junction compression. Our patient experienced significant complications from OSA at a young age. His sleep apnea worsened significantly in a short period making it unresponsive to previous treatment recommendations. There is a need for further studies to determine better screening guidelines for craniocervical junction narrowing and OSA. This case highlights the dynamic nature of sleep disordered breathing in achondroplasia and need for close follow up and monitoring of symptoms at all clinical encounters. Support (if any)

Immediate right chambers remodelling after orthotopic transcatheter valve tricuspid replacement.

An 84-year-old man with atrial fibrillation, ischemic heart disease with surgical and percutaneous revascularization, complained about effort abdominal pain and dyspnoea (NYHA III), with asthenia and peripheral oedema. Transoesophageal echocardiography showed torrential atrial tricuspid regurgitation and dilated right ventricle with preserved ejection fraction (Panels A–C). Invasive systolic pulmonary pressure was 30 mmHg. The TRI-SCORE was 30%. Considering the symptoms and signs of right heart failure despite optimal medical treatment and the prohibitive surgical risk, the patient was selected for tricuspid transcatheter valve replacement with Cardiovalve (VenusMedtech, Hangzhou, China) according to Heart Team evaluation. Repair percutaneous techniques were rejected, transcatheter annuloplasty due to right coronary artery proximity and thin tissue, and edge-to-edge approach because of the gap of 1 cm. The 32-F Large Cardiovalve system was inserted via surgically exposed femoral vein and was advanced into the right atrium. Under transesophageal echocardiographic and fluoroscopic guidance, the device legs were opened in the atrium and advanced into ventricle and grasp the 3 native leaflets by pulling the system (Panel D). Finally, the atrial followed the ventricular flanges that were released (Panel E). There was a posterior mild paravalvular regurgitation (Panels F and G, Supplementary data online, Videos S1 and S2). After 1 month, the patient is NYHA class I, neither having effort abdominal pain nor peripheral oedema. CT scan showed a significant reduction of the right ventricular diastolic volume from 256 to 216 mL, and the right atrium from 89 to 71 mL, even persisting atrial fibrillation (Panel H, Supplementary data online, Video S3).

Electrical, Echocardiographic and Coronary Artery Characteristics of Right Ventricular Infarction: Experience of the Cardiology Department of the CHU Mohammed VI Marrakech

Introduction: Coronary heart disease is the main cause of morbidity and mortality worldwide. Right ventricular (RV) infarction is often difficult to diagnose and has a poor prognosis due to rhythmic and hemodynamic complications.&#x0D; Objective: The study of electrical, ultrasonographic, and coronarographic features of the VD Infarction.&#x0D; Materials and Methods: Retrospective study of patients hospitalized in the Cardiology Department of the Mohammed VI University Hospital in Marrakech over a period of 24 months for MDI extended to the RV.&#x0D; Results: 120 patients were hospitalized during this period for MI with extension to the VD. Atypical clinical presentation was noted in 10% of cases. Clinical examination on admission revealed signs of right heart failure in 18% of cases, including 6% complicated by cardiogenic shock. Thrombolysis was performed in 10% of the patients, 67% of them successfully. The ECG found an isolated extension to the V3R leads in 76% of the cases and in association with a V4R overshoot in 45% of the cases, conduction disorders were noted in 28% of the cases, presented essentially by first degree auriculoventricular block. Echocardiography showed impaired LV function in 82% of cases, and longitudinal systolic dysfunction of the LV in 65%. Coronary angiography was performed in 91% of the cases, half of which underwent coronary angioplasty. The combination of both CD and IVA damage was found in 40% of the cases, and damage to the middle DC was the most common in almost half of the cases. The most frequent complications were rhythmic and conductive disorders in 38% of cases, and the evolution was fatal in 8% of cases.&#x0D; Conclusion: Involvement of the RV during MI is characterized by a very critical initial phase, once overcome, the overall prognosis becomes favorable in the long term.

Fetal pulmonary valvuloplasty for pulmonary atresia with intact ventricular septum: a single-center clinical experience.

Fetal pulmonary valvuloplasty for pulmonary atresia with intact ventricular septum: a single-center clinical experience.

Obstructive sleep apnea and pulmonary hypertension: the pendulum swings again.

Obstructive sleep apnea and pulmonary hypertension: the pendulum swings again.

Clinical Profile, Immediate- and Short-term Outcome of Patients with Intermediate-risk Acute Pulmonary Thromboembolism.

Long-term outcomes of acute pulmonary thromboembolism (PTE) have been reported. However, the immediate- and short-term outcomes have not been reported adequately. Primary objective was to determine the patient characteristics, and immediate- and short-term outcomes of intermediate-risk PTE, and the secondary objective was to evaluate the benefit of thrombolysis in normotensive PTE patients. This study included patients diagnosed with acute intermediate PTE. Patient's electrocardiography (ECG) parameters along with echocardiography (echo), etc., conducted at the time of admission, during their stay in hospital, at the time of discharge, and during follow-up were recorded. The patients were treated using thrombolysis or anticoagulants depending on hemodynamic decompensation. During follow-up, they were reassessed for echo parameters-right ventricular (RV) function and pulmonary arterial hypertension (PAH). Among 55 patients, 29 (52.73%) were diagnosed with intermediate high-risk PTE and 26 (47.27%) with intermediate low-risk PTE. They were normotensive and most of them had a simplified pulmonary embolism severity index (sPESI) score <2. Typical ECG pattern S1Q3T3 along with echo patterns and elevated cardiac troponin levels were observed in most of the patients. Patients treated with thrombolytic agents showed a reduction in hemodynamic decompensation as opposed to patients treated with anticoagulants who had clinical signs of right heart failure (RHF) on follow-up after 3 months. This study contributes to the existing literature on outcomes of intermediate-risk PTE and the effect of thrombolysis on patients with hemodynamic stability. Thrombolysis reduced the incidence and progression of RHF in patients with hemodynamic instability. Mathiyalagan P, Rajangam T, Bhargavi K, Gnanaraj R, Sundaram S. Clinical Profile, Immediate- and Short-term Outcome of Patients with Intermediate-risk Acute Pulmonary Thromboembolism. Indian J Crit Care Med 2022;26(11):1192-1197.

Concomitant initiation of combination therapy with macitentan and tadalafil in pulmonary arterial hypertension (PAH) patients with comorbidities: real-world data from OPUS and OrPHeUS

Abstract Background Guidelines for the management of pulmonary arterial hypertension (PAH) recommend early combination therapy of an endothelial receptor antagonist (ERA) and a phosphodiesterase type-5 inhibitor (PDE5i) [1]. There is, however, limited guidance about the management of PAH patients with comorbidities. Purpose To describe the demographics, clinical characteristics, safety, tolerability, and outcomes associated with initiation of the ERA macitentan and the PDE5i tadalafil in patients with comorbidities in the US OPsumit® USers (OPUS) and the OPsumit® Historical USers cohort (OrPHeUS) combined dataset. Methods This analysis reports data from the OPUS registry (Apr 2014–Jun 2020) and OrPHeUS medical chart review (Oct 2013–Mar 2017) on PAH patients initiating macitentan and tadalafil (M+T) combination therapy, in any order, as concomitant initiation (≤60 days apart, concomitant initiation group). The index date was defined as the start date of the second therapy (i.e., the start of combination therapy). Patients were further grouped by the number of comorbidities present prior to or at macitentan initiation: systemic hypertension, diabetes, renal insufficiency, BMI ≥30 kg/m2, other signs of right heart failure and atrial fibrillation. Results are presented descriptively alongside results for all PAH patients receiving M+T combination therapy (overall M+T group). Results Of the 1336 PAH patients that received M+T combination therapy, 431 (32%) were in the concomitant initiation group. In the concomitant initiation and overall M+T groups, respectively: 72% and 68% had ≥1 comorbidity, and the most common were systemic hypertension (47% and 47%), obesity (32% and 26%) and diabetes (23% and 22%). Patients were more likely to be older, male and have idiopathic/heritable PAH with increasing comorbidity burden (Table 1). Patients in the concomitant initiation group were more likely to be incident (median time from diagnosis: 1–2 months vs 9–24 months in the overall M+T group; Table 1). Most patients had ≥1 adverse event (AE); in both groups, patients with a high comorbidity burden (≥3) were more likely to have had an AE and to have discontinued treatment (Table 2). The incidence rate of first all-cause hospitalisation and mortality by comorbidity was comparable between the concomitant initiation and overall M+T groups. Conclusions In the real-world, concomitant initiation of M+T is used in PAH patients with comorbidities, usually shortly after diagnosis. Patient characteristics were similar for the concomitant initiation and overall M+T groups, with the exception of time from diagnosis. At index date, age, gender proportion, and PAH aetiology differed between the comorbidity groups. The safety profile of M+T combination therapy in the concomitant initiation group was consistent with that in the overall M+T group. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Actelion Pharmaceuticals Ltd, a Janssen Pharmaceutical Company of Johnson &amp; Johnson

ACUTE PULMONARY HYPERTENSION AFTER BORTEZOMIB THERAPY

ACUTE PULMONARY HYPERTENSION AFTER BORTEZOMIB THERAPY