Changes in REVEAL Lite 2 risk status are associated with long-term outcomes in patients with pulmonary arterial hypertension: A post-hoc analysis of the GRIPHON study.

BACKGROUND: Mortality risk assessment informs clinical management of pulmonary arterial hypertension (PAH). The Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) Lite 2 is a simplified risk calculator discriminating 1-year mortality risk. METHODS: This post-hoc analysis of the phase 3 GRIPHON study assessed changes in REVEAL Lite 2 risk score with selexipag versus placebo and whether changes were prognostic or predictive of time to first morbidity/mortality (M/M) event. RESULTS: REVEAL Lite 2 risk category discriminated M/M risk (landmark concordance indices: 0.68-0.76, selexipag; 0.65-0.70, placebo). Across baseline risk categories, hazard ratios supported a lower risk of M/M events with selexipag versus placebo: low, 0.573 (95% confidence interval [CI] 0.361-0.908; p = 0.0178); intermediate, 0.423 (95% CI 0.274-0.655; p = 0.0001); and high, 0.711 (9% CI 0.520-0.972; p = 0.0326). Odds ratios for risk improvement were 2.0 (95% CI 1.50-2.65), 1.8 (95% CI 1.38-2.43), and 2.0 (95% CI 1.43-2.72) for selexipag versus placebo at 16, 26, and 52 weeks, respectively (all p < 0.001). REVEAL Lite 2 risk improvement at week 16 explained 19.1% of the treatment effect in all patients and 47.0% in patients with REVEAL Lite 2 baseline risk score of ≥7. CONCLUSIONS: REVEAL Lite 2 can monitor PAH M/M risk and facilitate treatment optimization. Baseline REVEAL Lite 2 risk score was prognostic of M/M risk in patients with PAH and mediates treatment effect up to 47% for those at higher risk. Lower M/M risk with selexipag versus placebo occurred irrespective of baseline risk category (ClinicalTrials.gov identifier: NCT01106014).

Improved diagnosis of arrhythmogenic right ventricular cardiomyopathy using electrocardiographic deep learning.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare genetic heart disease associated with life-threatening ventricular arrhythmias. Diagnosis of ARVC is based on the 2010 Task Force Criteria (TFC), application of which often requires clinical expertise at specialized centers. OBJECTIVE: The purpose of this study was to develop and validate an electrocardiogram (ECG) deep learning (DL) tool for ARVC diagnosis. METHODS: ECGs of patients referred for ARVC evaluation were used to develop (n = 551 [80.1%]) and test (n = 137 [19.9%]) an ECG-DL model for prediction of TFC-defined ARVC diagnosis. The ARVC ECG-DL model was externally validated in a cohort of patients with pathogenic or likely pathogenic (P/LP) ARVC gene variants identified through the Geisinger MyCode Community Health Initiative (N = 167). RESULTS: Of 688 patients evaluated at Johns Hopkins Hospital (JHH) (57.3% male, mean age 40.2 years), 329 (47.8%) were diagnosed with ARVC. Although ARVC diagnosis made by referring cardiologist ECG interpretation was unreliable (c-statistic 0.53; confidence interval [CI] 0.52-0.53), ECG-DL discrimination in the hold-out testing cohort was excellent (0.87; 0.86-0.89) and compared favorably to that of ECG interpretation by an ARVC expert (0.85; 0.84-0.86). In the Geisinger cohort, prevalence of ARVC was lower (n = 17 [10.2%]), but ECG-DL-based identification of ARVC phenotype remained reliable (0.80; 0.77-0.83). Discrimination was further increased when ECG-DL predictions were combined with non-ECG-derived TFC in the JHH testing (c-statistic 0.940; 95% CI 0.933-0.948) and Geisinger validation (0.897; 95% CI 0.883-0.912) cohorts. CONCLUSION: ECG-DL augments diagnosis of ARVC to the level of an ARVC expert and can differentiate true ARVC diagnosis from phenotype-mimics and at-risk family members/genotype-positive individuals.

Treatment algorithm for pulmonary arterial hypertension.

Pulmonary arterial hypertension leads to significant impairment in haemodynamics, right heart function, exercise capacity, quality of life and survival. Current therapies have mechanisms of action involving signalling via one of four pathways: endothelin-1, nitric oxide, prostacyclin and bone morphogenetic protein/activin signalling. Efficacy has generally been greater with therapeutic combinations and with parenteral therapy compared with monotherapy or nonparenteral therapies, and maximal medical therapy is now four-drug therapy. Lung transplantation remains an option for selected patients with an inadequate response to therapies.

Four-Strata Risk Assessment in Patients with Pulmonary Arterial Hypertension Treated with Selexipag in Real-World Settings (EXPOSURE Study).

INTRODUCTION: Risk assessment can aid management of pulmonary arterial hypertension (PAH) and clinical decision-making. This analysis describes characteristics, treatment patterns and outcomes of patients with PAH, categorised by risk status at time of treatment escalation with selexipag in clinical settings. METHODS: Patients initiating selexipag in the ongoing multicentre, prospective EXPOSURE (EUPAS19085) study were grouped as low, intermediate-low, intermediate-high or high risk of 1-year mortality according to the ESC/ERS 4-strata method. RESULTS: As of November 2022, 77% (535/698) of patients initiating selexipag had data allowing for risk calculation; 14% (N = 76) were low, 31% (N = 168) intermediate-low, 34% (N = 182) intermediate-high and 20% (N = 109) high risk of 1-year mortality. Overall, patients were predominantly female (71%), with idiopathic/heritable PAH (56%) or PAH associated with connective tissue disease (CTD-PAH; 27%), median age of 60 years and prevalent (2 years) disease. From low to high risk, proportion of CTD-PAH and age increased (from 12%-40% and 46-68 years, respectively); time from diagnosis decreased and presence of cardiovascular risk factors increased. Most patients across risk groups (74-81%) initiated selexipag as part of triple oral combination therapy. Overall median (Q1, Q3) selexipag exposure duration was 10.1 (3.5, 24.1) months. Proportions of hospitalised patients increased with increasing risk group (16-42% from low to high, respectively); more hospitalisations were PAH-related for the high risk (71%) versus other risk groups (47-54%). Kaplan-Meier survival estimates were 98%, 98%, 93% and 80% at 1-year and 98%, 92%, 81% and 67% at 2-years, from low to high risk, respectively. CONCLUSIONS: In clinical settings, selexipag is initiated across all risk groups, predominantly as triple therapy. Only 45% of patients being at low/intermediate-low risk at selexipag initiation suggests an opportunity for more frequent patient monitoring and earlier treatment escalation, given that 4-strata risk assessment was prognostic for hospitalisations and survival in this contemporary PAH cohort. A graphical abstract is available with this article.

Pulmonary arterial hypertension (PAH) is a disease that gets worse over time. To make decisions about treatment, we need to know the stage of the disease. We can do this by measuring the patient's risk of death during the next few years. Selexipag is a medication for PAH. This analysis included patients living in Europe and Canada who started treatment with selexipag for their PAH disease. Our findings suggest that the monitoring of patients' health and the timing of starting selexipag can be improved. This analysis includes 698 patients taking part in the EXPOSURE study (EUPAS19085), which looks at the real-life treatment of patients with PAH. Overall, 71% of patients were female, the median age was 60 years, most had been diagnosed with PAH for around 2 years and were already taking two other medications for their PAH disease. At the beginning of selexipag treatment, 14% of patients were classified as low risk, 31% as intermediate-low risk, 34% as intermediate-high risk and 20% as high risk of mortality within the next year. More high-risk patients were hospitalised compared with the lower risk groups. After 1 year of treatment, more patients in the low (98%) and intermediate-low groups (98%) were alive than those in the intermediate-high (93%) and high risk groups (80%). The same was true after 2 years of treatment with selexipag (98%, 92%, 81% and 67%, respectively). This study confirms that assessing patients' risk levels can indicate how well they will do over time and shows that earlier treatment with selexipag should be considered to potentially prevent worsening of the disease.

Selexipag in patients with pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD): Real-world experience from EXPOSURE.

Selexipag is indicated for the treatment of pulmonary arterial hypertension (PAH), including PAH associated with connective tissue disease (CTD), and further insights into the management of selexipag-treated PAH-CTD patients in clinical settings are needed. These analyses of the ongoing, multicenter, prospective EXPOSURE (EUPAS19085) study describe characteristics, treatment patterns, tolerability, and outcomes of PAH-CTD patients initiating selexipag in Europe/Canada. All analyses were descriptive, with idiopathic PAH patients who typically display better prognosis included for context. Six hundred ninety-eight selexipag-treated patients had follow-up information; 178 (26%) had PAH-CTD. The median age was 68 years, patients were predominantly female (88%), and with WHO functional class III symptoms (63%); the median time since diagnosis was 1.7 years. There were 5% patients at low, 25% intermediate-low, 40% intermediate-high, and 30% high risk of 1-year mortality, according to the ESC/ERS 4-strata risk score. Most (80%) initiated selexipag as a triple oral therapy, and most of these (62%) remained on triple therapy 6 months post-baseline. Over a median (Q1-Q3) selexipag exposure period of 8.6 (2.5-17.2) months, 79 (44%) patients discontinued selexipag; 36 (20%) due to tolerability/adverse events. Sixty (34%) patients were hospitalized at least once; 120 hospitalizations occurred, with 49 (48%) deemed PAH-related. Survival at 1 year was 85%, and at 2 years was 71%; 29 (16%) patients died. These results describe the use of combination therapy with selexipag for patients with PAH-CTD. These findings suggest an opportunity to optimize the benefits of selexipag among patients with PAH-CTD by moving from escalating after years in response to clinical deterioration to escalating sooner to prevent clinical deterioration.

Pulmonary Hypertension in Systemic Sclerosis.

Systemic sclerosis is a multisystem connective tissue disease that is associated with substantial morbidity and mortality. Visceral organ involvement is common in patients with systemic sclerosis and occurs independently of skin manifestations. Pulmonary hypertension (PH) is an important and prevalent complication of systemic sclerosis. The clinical classification of PH cohorts conditions with similar pathophysiological mechanisms into one of five groups. While patients with systemic sclerosis can manifest with a spectrum of pulmonary vascular disease, notable clinical groups include group 1 pulmonary arterial hypertension (PAH) associated with connective tissues disease, PAH with features of capillary/venous involvement, group 2 PH associated with left heart disease, and group 3 PH associated with interstitial lung disease. Considerable efforts have been made to advance screening methods for PH in systemic sclerosis including the DETECT and ASIG (Australian Scleroderma Interest Group) composite algorithms. Current guidelines recommend annual assessment of the risk of PAH as early recognition may result in attenuated hemodynamic impairment and improved survival. The treatment of PAH associated with systemic sclerosis requires a multidisciplinary team including a PH specialist and a rheumatologist to optimize immunomodulatory and PAH-specific therapies. Several potential biomarkers have been identified and there are several promising PAH therapies on the horizon such as the novel fusion protein sotatercept. This chapter provides an overview of PH in systemic sclerosis, with a specific focus on group 1 PAH.

Real-World Management of Patients with Pulmonary Arterial Hypertension: Insights from EXPOSURE.

INTRODUCTION: Further insights into real-world management and outcomes of patients with pulmonary arterial hypertension (PAH) are needed. This interim analysis of the ongoing, multicentre, prospective EXPOSURE (EUPAS19085) observational study describes characteristics, treatment patterns and outcomes of patients with PAH initiating a new PAH-specific therapy in Europe/Canada. METHODS AND RESULTS: All analyses were descriptive. In total, 1944 patients with follow-up information were included; the majority were female, with World Health Organization functional class II/III symptoms and with idiopathic PAH or connective tissue disease-associated PAH. Most incident patients (N = 1100; diagnosed for ≤ 6 months) initiated treatment as monotherapy (48%) or double therapy (43%). Of those initiating monotherapy, 38% (199/530) escalated to double therapy (median [Q1, Q3] time to escalation 3.4 [1.9, 6.6] months), and of those initiating double therapy, 17% (78/457) escalated to triple therapy (median [Q1, Q3] time to escalation 7.0 [3.4, 12.7] months) during the observation period (median [Q1, Q3]: 17.0 [7.5, 29.9] months). The majority of the 834 prevalent patients (diagnosed > 6 months) entered the study on initiation of combination therapy and most did not change treatment regimen during the observation period (median [Q1, Q3]: 19.6 [10.2, 32.2] months). One-year survival was 88% for incident patients and 90% for prevalent patients. CONCLUSIONS: Results from EXPOSURE suggest a shift towards combination therapy and the alignment of real-world treatment patterns with current guideline recommendations. While survival estimates are encouraging, the extent of monotherapy use at treatment initiation and follow-up highlight an opportunity for further improvements through optimisation of treatment strategies in line with current guidelines. A graphical abstract is also available with this article. TRIAL REGISTRATION NUMBER: EUPAS19085.

Pulmonary arterial hypertension (PAH) is a progressive disease. Clinical guidelines recommend that most patients start treatment with a combination of different PAH medications. While there is no cure for PAH, these medications help to control symptoms and slow disease worsening. To understand treatments currently used in clinical practice, we analysed data from EXPOSURE (EUPAS19085), an ongoing study collecting information from patients starting a new PAH medication in Europe and Canada. Most patients in the study were female, with World Health Organization functional class II/III symptoms, and idiopathic (unknown cause) PAH or PAH associated with connective tissue disorders. Among 1100 patients who were 'recently diagnosed' (diagnosed with PAH in the past 6 months), 88% were alive after 1 year. We found that 48% started treatment with one PAH medication, and 38% of those patients had a second medication prescribed within a median period of 3 months. Among the 457 'recently diagnosed' patients treated with two PAH medications when they entered the study, 17% had a third medication prescribed within a median period of 7 months. Among 834 patients with 'established PAH' (diagnosed more than 6 months ago), 90% were alive after 1 year. Most entered the study when they started a third medication and did not have further changes in treatment. Our findings show that patients with PAH are often treated with one medication in clinical practice as well as a combination of medications. While survival rates are encouraging, the extent to which one PAH medication is used suggests there is room for treatment improvement.

Safety, feasibility and effectiveness of the remotely delivered Pulmonary Hypertension and Home-Based (PHAHB) physical activity intervention.

Background: Pulmonary hypertension (PH) is a heterogeneous condition, associated with a high symptom burden and a substantial loss of exercise capacity. Despite prior safety concerns regarding physical exertion, exercise training as a supportive therapy is now recommended for PH patients. Currently, most programmes are hospital-based, which limits accessibility. There is a need to provide alternative approaches for physical activity engagement for PH patients. The aim of this research was to develop, implement and evaluate the safety, feasibility and effectiveness of home-based physical activity intervention for PH. Methods: An entirely remotely delivered home-based physical activity intervention underpinned by behaviour change theory and informed by end-users, was assessed using a single-arm feasibility study design. Participants (n=19; 80% female) with a mean±sd age of 49.9±15.9 years with a diagnosis of PH undertook a 10-week, home-based physical activity intervention with induction training, support materials, telecommunication support, health coaching, exercise training and assessments, all remotely delivered. Training involved respiratory training along with a combination of aerobic and resistance exercises. Results: The intervention was deemed safe as no adverse events were reported. A high level of feasibility was demonstrated as the protocol was implemented as intended, sustained a high level of engagement and adherence and was well accepted by participants in terms of enjoyment and utility. There was a significant improvement in functional capacity, physical activity, exercise self-efficacy and quality of life, between baseline and post-training. Conclusion: The study demonstrates that an entirely remotely delivered home-based physical activity programme is safe, feasible and effective in improving functional capacity, physical activity and quality of life in PH patients.

Diagnostic pitfalls in patients referred for arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: The diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) is challenging because of nonspecific clinical findings and lack of conclusive answers from genetic testing (ie, an ARVC-related variant is neither necessary nor sufficient for diagnosis). Despite the revised 2010 Task Force Criteria, patients are still misdiagnosed with ARVC. OBJECTIVE: In patients referred for ARVC, we sought to identify the clinical characteristics and diagnostic confounders for those patients in whom ARVC was ultimately ruled out. METHODS: Patients who were referred to our center with previously diagnosed or suspected ARVC (between January 2011 and September 2019; N = 726) were included in this analysis. RESULTS: Among 726 patients, ARVC was ruled out in 365 (50.3%). The most common presenting symptoms in ruled-out patients were palpitations (n = 139, 38.1%), ventricular arrhythmias (n = 62, 17.0%), and chest pain (n = 53, 14.5%). On the basis of outside evaluation, 23.8% of these patients had received implantable cardioverter-defibrillators (ICDs) and device extraction was recommended in 9.0% after reevaluation. An additional 5.5% had received ICD recommendations, all of which were reversed on reevaluation. The most frequent final diagnoses were idiopathic premature ventricular contractions/ventricular tachycardia/ventricular fibrillation (46.6%), absence of disease (19.2%), and noncardiac presyncope/syncope (17.5%). The most common contributor to diagnostic error was cardiac magnetic resonance imaging, including mistaken right ventricular wall motion abnormalities (33.2%) and nonspecific fat (12.1%). CONCLUSION: False suspicion or misdiagnosis was found in the majority of patients referred for ARVC, resulting in inappropriate ICD implantation or recommendation in 14.5% of these patients. Misdiagnosis or false suspicion was most commonly due to misinterpretation of cardiac magnetic resonance imaging.

Antiarrhythmic Drug Therapy in Arrhythmogenic Right Ventricular Cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable progressive myocardial disorder that predisposes patients to ventricular arrhythmias and sudden cardiac death. Antiarrhythmic medications have an important role in reducing the frequency of ventricular arrhythmias and the morbidity associated with recurrent implantable cardioverter-defibrillator (ICD) shocks. Although several studies have examined the use of antiarrhythmic drugs in ARVC, these have been mostly retrospective in nature and inconsistent in their methodology, patient population and endpoints. Thus, current prescribing practices are largely based on expert opinion and extrapolation from other diseases. Herein, we discuss the major studies of the use of antiarrhythmics in ARVC, present the current approach employed at the Johns Hopkins Hospital and identify areas where further research is needed. Most notably, there is a great need for high-quality studies with consistent methodology and randomized controlled trial data into the use of antiarrhythmic drugs in ARVC. This would improve management of the condition and ensure antiarrhythmic prescribing is based on robust evidence.

New trends in pulmonary hypertension.

Pulmonary hypertension (PH) is a prevalent disease of the pulmonary vasculature that is characterised by considerable morbidity and mortality. Substantial efforts have been made in recent years to improve disease recognition, diagnosis and management, and this is reflected in current guidelines. The haemodynamic definition of PH has been revised and a definition for exercise PH has been provided. Risk stratification has been refined and the importance of comorbidities and phenotyping have been highlighted. These changes provide an opportunity to potentially identify pulmonary vascular disease at an earlier stage and to enhance patient-centred, goal-orientated treatment decisions. A promising fourth treatment pathway for pulmonary arterial hypertension and potential targeted therapies for group 3 PH are on the horizon, concepts which seemed inconceivable only a few years ago. Beyond medication, there is a greater appreciation for the importance of supervised training in stable PH and the possible role of interventional therapies in select cases. The landscape of PH is changing and it is characterised by progress, innovation and opportunities. In this article, we highlight some of the new trends in PH, with a specific focus on the revised European Society of Cardiology/European Respiratory Society 2022 guidelines for the diagnosis and management of PH.

Early selexipag initiation and long-term outcomes: insights from randomised controlled trials in pulmonary arterial hypertension.

Further understanding of when to initiate therapies in pulmonary arterial hypertension (PAH) is important to improve long-term outcomes. Post hoc analyses of GRIPHON (NCT01106014) and exploratory analyses of TRITON (NCT02558231) suggested benefit of early selexipag initiation on long-term outcomes, despite no additional benefit versus initial double combination on haemodynamic and functional parameters in TRITON. Post hoc analyses investigated the effect of early selexipag initiation on disease progression and survival in a large, pooled PAH cohort. Data from newly diagnosed (≤6 months) PAH patients from GRIPHON and TRITON were pooled. Patients on active therapy with selexipag (pooled selexipag group) were compared with those on control therapy with placebo (pooled control group). Disease progression end-points were defined as per the individual studies. Hazard ratios (HR) and 95% CI for time to first disease progression event up to end of double-blind treatment (selexipag/placebo) +7 days and time to all-cause death up to end of study were estimated using Cox regression models. The pooled dataset comprised 649 patients, with 44% on double background therapy. Selexipag reduced the risk of disease progression by 52% versus control (HR: 0.48; 95% CI: 0.35-0.66). HR for risk of all-cause death was 0.70 (95% CI: 0.46-1.10) for the pooled selexipag versus control group. Sensitivity analyses accounting for the impact of PAH background therapy showed consistent results, confirming the appropriateness of data pooling. These post hoc, pooled analyses build on previous insights, further supporting selexipag use within 6 months of diagnosis, including as part of triple therapy, to delay disease progression.

Exploration of physical activity knowledge, preferences and support needs among pulmonary hypertension patients.

OBJECTIVE: Physical activity (PA) is an established adjunct therapy for pulmonary hypertension (PH) patients to mitigate PH symptoms and improve quality of life. However, PA engagement within this population remains low. This study investigated PH patients' knowledge of PA, recalled advice, exercise preferences and PA support needs. METHODS: Semi-structured interviews were conducted with 19 adults (mean age 50 years; SD ±12 years) diagnosed with PH, living in Ireland. Interview scripts were digitally recorded and transcribed verbatim. Thematic analysis was used to analyse the data. RESULTS: Four key themes were identified: Lack of PA knowledge; exercise setting preference; accountability and monitoring; and clinician delivered PA information and guidance. CONCLUSION: This study found that PH clinicians provide suboptimal PA advice, yet patients desired clinician-delivered PA guidance. Home-based exercise was preferred with monitoring and external accountability deemed as important to facilitate sustained engagement. PRACTICE IMPLICATIONS: PH clinicians are well positioned to play a critical role in assisting and empowering PH patients to engage in PA. Providing training and education to PH clinicians regarding exercise prescription may be beneficial. Further research is needed to evaluate the feasibility and efficacy of home-based exercise interventions to improve quality of life and physical activity in PH.

Eicosapentaenoic acid vs. docosahexaenoic acid for the prevention of cardiovascular disease.

PURPOSE OF REVIEW: Populations with greater fatty fish intake have lower risk of coronary heart disease. However, trials testing omega-3 fatty acids (FA) on cardiovascular outcomes have yielded inconsistent results. In this review, we summarize the major cardiovascular trials examining omega-3 FA supplementation, and compare differences with eicosapentaenoic acid (EPA) alone vs. docosahexaenoic acid (DHA) combined with EPA. RECENT FINDINGS: The JELIS and REDUCE-IT trials both demonstrated significant reduction in cardiovascular events with high dose EPA in the form of icosapent ethyl (IPE), with a similar trend seen in the RESPECT-EPA trial. In contrast, the ASCEND, VITAL, STRENGTH, and OMEMI trials examining EPA+DPA combinations failed to demonstrate benefit. Beyond the difference in omega-3 FA formulations (IPE vs. omega-3 carboxylic acid), other differences between REDUCE-IT and STRENGTH include the achieved EPA levels, differing properties that EPA and DHA have on membrane stabilization, and the comparator oils tested in the trials. SUMMARY: The totality of evidence suggests EPA alone, administered in a highly-purified, high-dose form, improves cardiovascular outcomes among patients with elevated triglycerides at high cardiovascular risk, but EPA and DHA together does not. Current guidelines endorse the use of IPE in statin-treated patients at high cardiovascular risk who have triglycerides >135 mg/dl.

New Strategies for Lowering Low Density Lipoprotein Cholesterol for Cardiovascular Disease Prevention.

Purpose of review: The primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) relies on optimizing cardiovascular health and appropriate pharmacotherapy, a mainstay of which is low-density lipoprotein-cholesterol (LDL-C) lowering. Typically, statin therapy remains the first line approach. Advances in technology and understanding of lipid metabolism have facilitated the development of several novel therapeutic targets and medications within the last decade. This review focuses on medications recently approved by the U.S. Food and Drug Administration (FDA) for the reduction of LDL-C and ASCVD risk, as well as new therapies in the pipeline. Recent findings: Novel lipid therapies aim to lower risk of ASCVD by targeting reduction of atherogenic compounds, such as LDL, lipoprotein(a) (Lp(a)), and triglyceride-rich lipoproteins. Evolocumab and alirocumab, monoclonal antibody proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors which lower LDL-C by approximately 60%, have emerged as important therapies for use in patients with ASCVD as well as familial hypercholesterolemia (FH). Bempedoic acid, an ATP citrate lyase inhibitor, is an oral medication recently approved that can lower LDL-C by approximately 18% alone and 38% when combined with ezetimibe. Inclisiran, a small-interfering RNA (siRNA) molecule which inhibits the translation of PCSK9, is the most recently FDA-approved LDL-C lowering medication, and can reduce LDL-C by approximately 50% with twice yearly subcutaneous dosing. The cardiovascular outcome trials for bempedoic acid and inclisiran are still on-going. Evinacumab, a monoclonal antibody which targets angiopoietin-like protein 3 (ANGPTL3), has been approved for use in patients with homozygous FH. SiRNAs and anti-sense oligonucleotides (ASO) facilitating selective inhibition of the production of targeted proteins including Lp(a) and ANGLPTL3 are active areas of clinical investigation. Summary: Recently several novel LDL-C lowering medications have been approved. New therapeutic targets have been identified and present additional means of lowering LDL-C and other atherogenic compounds for patients who remain at high ASCVD risk.

Multimodality Imaging in the Detection of Ischemic Heart Disease in Women.

Women with coronary artery disease tend to have a worse short and long-term prognosis relative to men and the incidence of atherosclerotic cardiovascular disease is increasing. Women are less likely to present with classic anginal symptoms when compared with men and more likely to be misdiagnosed. Several non-invasive imaging modalities are available for diagnosing ischemic heart disease in women and many of these modalities can also assist with prognostication and help to guide management. Selection of the optimal imaging modality to evaluate women with possible ischemic heart disease is a scenario which clinicians often encounter. Earlier modalities such as exercise treadmill testing demonstrate significant performance variation in men and women, while newer modalities such as coronary CT angiography, myocardial perfusion imaging and cardiac magnetic resonance imaging are highly specific and sensitive for the detection of ischemia and coronary artery disease with greater parity between sexes. Individual factors, availability, diagnostic performance, and female-specific considerations such as pregnancy status may influence the decision to select one modality over another. Emerging techniques such as strain rate imaging, CT-myocardial perfusion imaging and cardiac magnetic resonance imaging present additional options for diagnosing ischemia and coronary microvascular dysfunction.

Incidence and outcomes of pulmonary hypertension in the Ireland.

INTRODUCTION: Pulmonary hypertension (PH) is a progressive disease of the pulmonary vasculature, which is characterised by premature morbidity and mortality. The aim of this study is to define the characteristics of PH in the national PH unit (NPHU) in Ireland between 2010 and 2020. METHODS: Cases of PH which were referred to the NPHU between 2010 and 2020 were included. PH was defined as a mean pulmonary artery pressure ≥25 mm Hg at right heart catheterisation. RESULTS: Four hundred and fifteen cases of PH were identified during the study period. Group 1 pulmonary arterial hypertension (PAH) accounted for 39% (n=163) of cases, with a calculated annual incidence of 3.11 per million population (95% CI 1.53 to 4.70). The leading PAH subgroup was connective tissue disease-associated PAH (CTD-PAH), which was responsible for 49% of PAH referrals. This was followed by idiopathic PAH, with an estimated annual incidence of 0.63 cases per million population. The mean age at PAH diagnosis was 56±15 years and 86% (n=111) received double-combination or triple-combination therapy within the first 12 months of diagnosis. The 1-year, 3-year and 5-year transplant-free survival for PAH was 89%, 75% and 65%. This was significantly lower for individuals with CTD-PAH relative to other PAH subgroups (p<0.05). DISCUSSION: This study describes the incidence and outcomes of PH in Ireland. While the outcomes are comparable to other centres, the incidence of PAH and specific subgroups appears low, suggesting that improved disease awareness and case recognition are required. Furthermore, the survival of individuals with CTD-PAH is poor and requires additional exploration.