Angiotensin Receptor Research Articles

The influence of the daily salt-intake on the antihypertensive action and atrial natriuretic peptide level in patietns with angiotensin receptor neprilysin inhibition

Abstract Background The angiotensin receptor–neprilysin inhibitor (ARNI) is a drug which acts through angiotensin receptor blocking effect and the increase in atrail natriuretic peptide (ANP) through neprilysin inhibitor in hypertension (HT). These combined effects result in a reduced risk of hospitalization for heart failure or death from cardiovascular causes. ANP is also known for its various cardioprotective effects including vasodilator and natriuretic action. Acording to Guyton's pressure-natriuresis curve, the efficacy of angiotensin receptor blocker drugs is diminished in HT cases with high daily salt inatke. However, whether the effect of ARNI on HT is attenuated in patients with high daily salt intake remains unclear. Purpose The present study investigated the influence of a daily salt intake on the antihypertensive action and ANP level in patients with ARNI. Methods Fourty-four consecutive essential HT patients on ARNI were enrolled. Blood pressure and ANP level were measured at baseline (before taking ARNI) and 3 weeks later. ARNI (200mg) was prescribed and maintained during the study. In addtion, the daily salt intake was calculated using creatinine and natrium levels in urine, age, and body weight according to Japanese hypertensive guideline at baseline and 3 weeks later. Results The average age was 70±8 years old. About 50% (N=23) was male. The mean sytolic and diastolic blood pressure was 148±14mmHg and 89±10mmHg, respectively. The mean daily salt intake was 9.5±2.2 g/day at baseline. The mean ANP level was 529±300pg/ml. At follow up (3 weeks later), the mean systolic and diastolic blood pressure significanly went down to 132± 18 mmHg and 70± 9 mmHg, respectively (p=0.03). ANP level also increased from 529±300pg/ml to 793±580pg/ml. However, the mean daily salt intake was almost same as the baseline at 9.4±3.2 g/day. The patients were divided into 2 groups; high daily salt intake (N=20 with mean daily salt intake 10.5±1.7g/day)) and low daily salt intake (N=24 with 8.4±3.1g/day) groups compared to the baseline. The absolute and percentage changes in systolic blood pressure were almost same in the high and low daily salt intake groups (-12.7±15.8mmHg vs -13.7±14.2mmHg, p=0.75; -5.8±6.5% vs.-7.0±9.6%, p=0.58, respectively). However, the change rate in ANP level was significantly higer in the high daily salt intake group than in the low daily salt intake group (155±63 vs. 12±16%, p=0.01). Conclusion ARNI demonstrates effectiveness in lowering the blood pressure even in patients with higher salt intake, unlike angiotensin receptor blocker. In cases with high salt intake, the notable increase in ANP levels may contribute to decreasing blood pressure through vasodilator and natriuretic action.

Elegibility for Sacubitril/Valsartan in italian clinical practice: insights from the OPTIMA-HF registry

Abstract Background/Introduction Guidelines strongly recommend patients with heart failure with reduced ejection fraction (HFrEF) be treated with multiple medications proven to improve clinical outcomes, as tolerated. Among them, angiotensin receptor blocker/neprylisin inhibitor (ARNi) are the foundation of neuro-hormonal blockade in patients with HFrEF, however the degree to which gaps in this medication use and dosing persist in outpatient practice is unclear. Purpose To assess the proportion of patients with HFrEF who are eligible for ARNi based on the PARADIGM-HF trial criteria and the association between eligibility and baseline characteristics. Methods The OPTIMA-HF (Optimization of Therapy in the Italian Management of Heart Failure) registry included outpatients in Italy with chronic HFrEF receiving at least 1 oral medication for management of HF. Patients were characterized by baseline use and dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB)/ARNI, beta-blocker, mineralocorticoid receptor antagonist (MRA) and sodium glucose co-transporter II inhibitor (SGLT2i). Patient-level factors associated with medication use were examined. Results Outpatients with HFrEF from 29 ambulatory cardiology practices and university hospitals in the OPTIMA-HF registry recruited between January 2022 and September 2023 were included. Of 1291 patients, 1018 (79%) met the PARADIGM-HF criteria and 949 of them (93%) were on ARNi. Of the enrolled patients, 342 (27%) were not on ARNi, however only 129 (38%) did not met the PARADIGM-HF inclusion criteria for ARNi prescription. Reasons for not meeting PARADIGM-HF criteria were no beta-blocker background therapy (22%), hyperkalemia (4%), hypotension (15%), chronic kidney disease (65%) and hyperkalemia (79%). In a logistic regression model not being on ARNi was associated with older age, chronic kidney disease, not being on cardiac resynchronization therapy, lower systolic blood pressure, lower BMI, and higher PAPs (Figure), representing the picture of a more fragile patient net of compliance with the PARADIGM-HF criteria. Conclusions Among outpatients with HFrEF in the OPTIMA-HF Registry, 79% met the PARADIGM-HF criteria. Strategies to improve guideline-directed use of HFrEF medications remain urgently needed, and these findings may inform targeted approaches to optimize outpatient medical therapy.

Angiotensin-II receptor type 1 and endothelin-1 receptor type A agonistic autoantibodies in patients with STEMI: new kids on the block

Abstract Background The Prognosis after ST-elevation myocardial infarction (STEMI) remains poor. Angiotensin-II and endothelin-1 contribute to adverse prognosis after STEMI through molecular mechanisms that lead to myocardial inflammation, fibrosis and, ultimately, adverse myocardial remodeling. Functional autoantibodies against angiotensin II type 1 (AT1R-AAs) and endothelin-1 type A (ETAR-AAs) receptors bind to the same receptors as natural ligands, eliciting similar (and amplified) responses. In patients with STEMI, AT1R-AAs and ETAR-AAs have been associated with a higher risk of developing microvascular obstruction and left ventricular remodeling. Both microvascular obstruction and left ventricular remodeling are associated with a poor prognosis. Purpose To assess the prognostic role of AT1R-AAs and ETAR-AAs after STEMI. Methods Consecutive STEMI patients who underwent primary percutaneous coronary intervention within 12 h after pain onset were enrolled in this prospective study. The levels of AT1R-AAs and ETAR ETAR-AAs at the time of hospital admission were measured using an enzyme-linked immunosorbent assay (ELISA) in all patients. The incidence of major adverse cardiovascular events (MACE, defined as a composite of cardiovascular mortality, myocardial re-infarction, and hospitalizations for heart failure) during follow-up was the primary outcome. Autoantibody seropositivity was defined according to ELISA’s kit manufacturer’s instructions (levels > 10 U/mL). Results Two hundred patients with STEMI were enrolled. The baseline characteristics of the patients are shown in Table 1. Of these, 110 (55%) were seronegative for both autoantibodies, 44 (22%) were seropositive for one autoantibody (but not both), and 46 (23%) were seropositive for both autoantibodies. The incidence of MACE over a 14-month median follow-up was higher in patients with double (31%) and single (25%) seropositivity than in seronegative patients (13%, p=0.009 and p=0.06, respectively). Survival free from MACE was significantly different across the different degrees of autoantibody seropositivity (Figure 1). In the multivariable Cox regression analysis, adjusted for the variables that were significant in the univariate analysis (highlighted in bold in Table 1), double seropositivity was independently associated with an increased risk of MACE (hazard ratio 2.386, 95 % CI 1.471-3.864, p<0.001). Conclusions The degree of seropositivity for AT1R-AAs and ETAR-AAs is associated with an increased risk of MACE after STEMI. Our findings provide valuable mechanistic insights into the pathophysiology of STEMI and pave the way for future therapies focused on the improvement of long-term prognosis after acute coronary syndromes.

Prognostic determinants in patients with heart failure with reduced ejection fraction after a first hospitalisation for acute heart failure. COMFE registry

Abstract Introduction The clinical characteristics and determinants for prognosis of patients with a first hospitalisation for heart failure (HF) with reduced left ventricular ejection fraction (LVEF <40%) are poor described and show heterogeneous results that need major investigation. Purpose The aim of our study was to identify the clinical characteristics, prognosis and their main determinants in a prospective registry of patients with HF and reduced LVEF with a first hospital admission for acute heart failure, prognosis and their main determinants in a prospective registry in these patients. Methods We carried out a prospective registry in 2 University Hospitals of patients admitted to cardiology department due to first-time HF hospitalisation with reduced LVEF. 231 admitted consecutively between March 2021 and September 2022 were included, with a mean follow-up of 381 days. Continuous variables were represented as median (interquartile range) and categorical variables as percentage %. A multivariate logistic regression was performed in which age, sex, comorbidities, treatment, rhythm at discharge and improvement in LVEF were included; and using the Wald method, the predictors of rehospitalization and/or death were identified. Data were analysed using SPSS v. 25.0. Results The main baseline characteristics are shown in Table 1. The population had a median age of 71 years, 75% were men, with a high prevalence of arterial hypertension (HBP) (69%) and hyperlipidemia (57%). Quadruple therapy (Na-Glucose cotransporter 2 inhibitor [SGLT2i], Beta-Blocker, mineralocorticoid receptor antagonist [MRA] and angiotensin receptor-neprilysin inhibitor [ARNI], angiotensin converting enzyme inhibitor [ACEi] or Angiotensin-II receptor blocker [ARB]) was achieved in 57% at discharge. The dynamics of NTproBNP was studied from admission to completed up-titration, observing an average reduction of 37% and 32% met the criteria for improved LVEF after. The etiology is described in Figure 1a, with ischemic heart disease being the most represented (31%). Multivariate Cox regression for the combined event of readmission/death from any cause showed that treatment with SGLT2i (OR 0,48 [CI 95%: 0,23-0,98 p:0,04]) and Beta-Blocker (OR 0,35 [CI 95%: 0,14-0,87 p:0,02]) at discharge and improved LVEF (OR 0,33 [CI 95%: 0,15-0,72 p:0,006]) were protective predictors against the event; but diabetes mellitus (DM) was a predictor of a worse prognosis (OR 2,9 [CI 95%: 1,52-5,5 p:0,001]) Fig. 1b. Conclusions Patients with a first admission for HF with reduced LVEF constitute a heterogeneous clinical group. Improvement in LVEF after drug up-titration and treatment with SGLT2i and Beta-blocker are independently associated with a better prognosis. Our findings may have implications for their clinical management.Table 1Figure 1

5-year valve academic research consortium-3 outcomes and predictors of mortality in a 10-year Asian transcatheter aortic valve implantation registry

Abstract Background Transaortic valvular implantation (TAVI) has revolutionised the management of aortic stenosis (AS). Uptake in Asia has caught up in recent years, after an initial lag due to expensive cost, limited subsidies, and scarce accessibility. Hence, longitudinal outcomes of TAVI remain largely unknown in Asian patients. Purpose This study aims to present the 5-year mortality endpoints in an Asian cohort followed up over a decade. Methods 253 patients with symptomatic severe aortic stenosis status post TAVI were retrospectively enrolled at a tertiary academic hospital from 2010-2021. The main outcomes were defined as short-term (30-day), mid-term (1-year) and long-term (5-year) all-cause mortality. Baseline demographics, procedural findings and clinical outcomes were analysed. Kaplan-Meier curves and multiple Cox regression analyses were constructed. Results The mean age was 75.2 + 10.2 years. 120 (47.4%) patients were female and 167 (66%) were Chinese. 168 patients (66.7%) received balloon-expandable valves, 80 patients (31.7%) underwent self-expandable valves, and 4 patients (1.6%) had mechanical-expandable valves. Malignancy was associated with worse short-term mortality at 30-days (HR 3.65, p = 0.054), while pulmonary disease and previous stroke were associated with worse long-term mortality at 5-years (HR 2.27, p = 0.012 and HR 2.02, p = 0.064). Worse all-cause mortality at 30-days, 1-year and 5-years were associated with high NT-Pro BNP levels (HR 1.04, p = 0.046; HR 1.05, p = 0.002 and HR 1.04, p < 0.001), the presence of peripheral arterial disease (PAD) (HR 4.32, p = 0.056; HR 4.48, p = 0.006 and HR 2.43, p = 0.023) and chronic kidney disease (CKD) (HR 6.19, p = 0.006; HR 6.77, p < 0.001 and HR 2.09, p = 0.008). Society of Thoracic Surgery (STS) score (HR 1.11, p = 0.001; HR 1.13, p < 0.001 and HR 1.12, p < 0.001) and Valve Academic Research Consortium (VARC) III endpoints of acute kidney injury (AKI) (HR 6.68, p = 0.047, HR 10.8, p < 0.001 and HR 6.99, p < 0.001), cardiogenic shock (HR 26.3, p < 0.001, HR 12.0, p < 0.001 and HR 4.29, p = 0.011) and structural complications (HR 40.3, p < 0.001, HR 18.1, p < 0.001 and HR 5.18, p = 0.008) were associated with worse all –cause mortality at time-points of 30-days, 1-year and 5-years respectively. On multivariate analyses adjusted for comorbidities and outcomes, STS score and structural complications were independent predictors of 30-day, 1-year, and 5-year all-cause mortality (HR 1.16; p = 0.003, HR 1.09, p = 0.003 and HR 1.10, p < 0.001) and (HR 62.7, p < 0.007; HR 18.9, p < 0.001 and HR 10.6, p = 0.001) respectively. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) use was protective of survival within 1-year (HR 0.37, p = 0.022). Conclusions STS score and VARC III endpoints of structural complications were reliable predictors of all-cause mortality in Asian patients with TAVI. ACE inhibitor and ARB use was protective against mortality at 1-year.Cox regression analysesKaplan-Meier curves

Cardiovascular mortality with oral potassium-binders in patients with CKD and heart failure

Abstract Introduction Hyperkalemia is an inherent consequence of advancing chronic kidney disease (CKD) as a result of the kidney’s decreased ability to excrete potassium. Heart failure patients with concomitant CKD may not tolerate maximum doses of guideline-directed medical therapies (GDMT) like ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), angiotensin receptor/neprilysin inhibitors (ARNI) and mineralocorticoid receptor antagonists (MRA) due to dose-limiting hyperkalemia. Many randomized controlled trials in heart failure exclude patients with advanced CKD. Two oral therapies exist to manage hyperkalemia - patiromer sorbitex calcium and sodium zirconium cyclosilicate. This study aims to identify the potassium-binder with better outcomes as defined by less readmissions, hyperkalemia episodes, and death. Purpose This project was undertaken to better understand the impact of using potassium-binders in CKD patients with heart failure. Improved management of hyperkalemia will be an avenue for optimization of GDMT in this population. Methods and materials The TriNetX research network was used for this study. Two cohorts of patients were created by using International Classification of Disease 10 (ICD-10) codes and CPT codes. Both cohorts consisted of patients with no prior history of hyperkalemia within 30 days of hospital discharge at which time one cohort was prescribed patiromer and the other received sodium zirconium cyclosilicate. Each cohort was prohibited from exposure to the other medication. The cohorts were balanced by propensity score matching and the greedy nearest neighbor algorithm for age, race, gender, ethnicity. They were also balanced for systolic and diastolic heart failure diagnoses, and for each individual stage of CKD (1 through 5 and end stage). They were also balanced for use of ACEi, ARBs, and MRAs. This resulted in 8,921 patients in each arm. They were then evaluated for the outcomes of hospital readmission, hyperkalemia episodes (>6.1 mmol/L), and death within 12 months. Results Patients treated with patiromer were more likely to be hospitalized over the following twelve months (44% vs 40%, RR 1.11, 95% CI (1.07,1.15), p value <0.0001). They were also more likely to experience hyperkalemia (11.7% vs 9.2%, RR 1.27, 95% CI (1.16,1.38), p value <0.0001). Patiromer was also associated with slightly greater all cause mortality (27% vs 25%, RR 1.08, 95% CI (1.03,1.13), p value 0.0021). Discussion This study demonstrates patiromer has more readmissions and hyperkalemia episodes along with greater mortality. In conclusion, sodium zirconium cyclosilicate was found to have better outcomes compared to that of patiromer. Further studies are necessary to better understand the utility of using sodium zirconium cyclosilicate as maintenance therapy for hyperkalemia in order to maximize GDMT in CKD patients with heart failure.

Long-term continuation to pharmacological treatment for secondary prevention after a myocardial infarction: a register study

Abstract Background Pharmacological treatment for secondary prevention after acute myocardial infarction (MI) is crucial to prevent new events. Several studies report inconsistence and need for improvement of pharmacological treatment. Study follow-up is often less than 10 years and showing that continuation to drug treatment decreases with time. Objective To study long-term follow-up of nationally guideline recommended medical therapy (GDMT) for secondary prevention after a myocardial infarction. Method The study population consisted of individuals aged 18-84 years, who were hospitalized for a MI between January 2006 and December 2022 and were followed up to 16 years. The study subjects were identified through the National Inpatient Register and linked to the Prescribed Drug Register. Four classes of drugs were analyzed: antiplatelet/anticoagulant therapy, lowering therapy, betablockers and angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB). Time-updated survival analyses were used to investigate the relationship between continuation of preventive pharmacological treatment and mortality and recurrent MI after an acute MI. Results A total number of 139 413 individuals (mean age 69.1±10.6) were included and 33.3% were female. At baseline 51.2% had hypertension, 21.5% diabetes mellitus and 15.2% heart failure. All prescriptions of GDMT were decreased significantly after hospitalization after MI and during first years and remained plateau (figure 1). During follow-up 55487 persons died (39.8%, event rate 5.81 per 100 person years [95% CI 5.76-5.86]). Medication with antiplatelets/anticoagulantia, ACEi/ARB and statins decreased risk of all cause-mortality and myocardial infarction [HR 0.83 [95% CI 0.79-0.86], p-value <0.001, HR 0,79 [95% CI 0.77-0.83], p-value <0.001, HR 0.70 [95% CI 0.67-0.73], p-value <0.001) respectively. Conclusion Pharmacological treatment as a part of secondary prevention remained greatly underutilized both shortly and during long-term after MI. Usage of antiplatelets or antigulantia, ACEi or ARB and statins decreased the risk of all-cause mortality and recurrent myocardial infarction.

Risk stratification for a primary prevention ICD: Performance of the MADIT-ICD Benefit Score in contemporary real world patients

Abstract Background We have recently developed the MADIT-ICD Benefit Score to improve risk stratification for primary implantable cardioverter defibrillator (ICD) implantation by assessing the competing risk of life-threatening ventricular tachyarrhythmia (VTA) vs. non-arrhythmic mortality based using simple clinical variables. Patients with a MADIT-ICD Benefit Score of < 50 are more likely to experience non-arrhythmic mortality than life-threatening VTA, and therefore derive limited benefit from a prophylactic ICD. Purpose We aimed to provide data on the performance of the MADIT-ICD Benefit Score in a real world population, comprising patients with HFrEF and either ischemic or nonischemic cardiomyopathy (ICM/NICM) who are treated with contemporary guideline-directed medical therapy (GDMT). Methods The study population comprised 2875 patients who were implanted with a primary prevention ICD and prospectively followed in a large tertiary healthcare system (the University of Rochester Medical Center, including 3 affiliated hospitals in Upstate New York) between 2017 through 2023. Arrhythmic events were captured from device interrogation data, which were blindly adjudicated by 2 electrophysiologists. Results Among the 2875 study patients, mean age was 62 ± 15 years, 1265 (44%) were women, and 1667 (58%) had ICM. Guideline-directed medical therapies, including angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, angiotensin receptor/neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose transport protein 2 (SGLT2) inhibitors, were prescribed to 43%, 36%, 96%, 67% and 32% of study patients, respectively. The 2-year cumulative incidence of VTA, after accounting for the competing risk of death, was 19% vs. 11% in patients with a Score of ≥50 vs. <50, respectively (p<0.001; Figure 1A). Findings regarding ICD shocks were consistent (8% vs. 4%, respectively, p<0.001; Figure 1B) The rate of VTA events at 4 years was directly correlated with increasing quartiles of the MADIT-ICD Benefit Score, while the corresponding rates of non-arrhythmic mortality were inversely correlated with score quartiles (Figure 1C). A similar direct correlation with increasing Benefit Score quartiles was observed when the endpoint of ICD shocks was assessed (Figure 1D). Accordingly, the benefit of the ICD (calculated as the difference between predicted rates of VTA/shock events and corresponding rates of non-arrhythmic mortality) was attenuated with decreasing quartiles of the MADIT-ICD Benefit Score (Figures 1C and 1D; right column). Conclusions We show good performance of the MADIT-ICD Benefit Score in a large cohort of real world ICD recipients who are treated with contemporary GDMT. These data support the use of the MADIT-ICD Benefit Score for improved risk stratification and for shared decision-making in contemporary candidates for a primary prevention ICD.

Temporal trends and regional differences of initial oral antiarrhythmic drug options in patients with new-onset atrial fibrillation: a report from the GLORIA-AF registry

Abstract Background New-onset atrial fibrillation (AF) is common and antiarrhythmic drugs (AADs) are commonly used for treating such patients. However, whether there are temporal changes and regional differences in the choice of AADs in direct acting non-vitamin K oral anticoagulants (DOACs) era is less studied. Purpose The present study aimed to analyze the temporal trends and regional differences of initial oral AAD options in patients with new-onset AF in the GLORIA-AF registry, based on a proposed modernized classification of AADs in 2018 (Circulation, 2018, PMID: 30354657). AADs involved in the present study included traditional Vaughn-Williams Class I to Class IV AAD, Class IId AAD (digoxin), and Class VII AAD, which acts on the upstream of arrhythmia including angiotensin converting enzyme inhibition, angiotensin receptor blocker, and stains. Methods Temporal changes regarding the AAD use between the two phases of GLORIA-AF and regional differences of AADs choice were investigated. Factors associated with the choice of different AADs were established by multivariate logistic regression. Results Among the 36,617 participants in the GLORIA-AF registry, 33,208 (90.7%) were prescribed with AADs: 74.0% were rate control and 10.2% were rhythm control, and among the prescribed AADs, single and dual AADs were used in 73.3% and 24.9%, respectively. Moreover, 70.5% patients received upstream target modulators (Class VII AAD). Class IIa AADs (beta-blockers) were the most commonly prescribed AAD and slightly increased from Phase II (60.58%) to Phase III (62.91%) while the use of Class IId AAD (e.g. digoxin) decreased regardless of single or combined use. AADs use varied significantly among regions but the temporal trends and regional differences were similar with that of the overall cohort. Age, gender, comorbidities, admission signs, region, and concomitant medications (e.g. anticoagulants) were associated with the choices of different AADs. Conclusions In the DOAC era, new-onset AF patients receiving AAD commonly included upstream therapy. Rate control was still the dominant strategy for patients with new-onset AF but the use of Class IId AAD significantly decreased with the increased use of Class IIa AAD. The choice of AADs demonstrated significant regional differences and concomitant anticoagulants played important roles.Temporal trends in GLORIA-AFComparisons of AADs use in GLORIA-AF

Marfan syndrome in children: large, single centre experience on management and outcome

Abstract Introduction Beta-blockers (BBs) and angiotensin receptor blockers (ARBs) have been proved to decrease the growth rate of the aortic root in Marfan patients, we describe our single centre experience at a large tertiary paediatric institution. Methods This is a retrospective longitudinal study of a large, paediatric only, Marfan cohort through review of medical notes for clinical data and treatment and assessment of serial echocardiograms. Results 167 patients were included, mean age at first assessment was 4.05 ± 3.12 years, 86 (51.50%) were males. 41 pts (24.55%) had a de novo FBN1 mutation. A 35.32% had a cysteine loss mutation. Median follow up was 9.54±4.37 years. 2 patients had a clinical and molecular diagnosis of early-onset Marfan, they both underwent mitral valve surgery in infancy and one of them died at 7 years old. No other deaths or acute aortic events in our cohort until transition to adult services at 18 years old. Of the entire study population 12 pts (7.2%) underwent aortic surgery at a median age of 13±7.02 years, 1 patient had a mitral valve repair. Chemoprophylaxis (currently only evaluated in a subgroup of our youngest 65 patients) was offered to all patients, 27.69% declined medicines. The remining 47 subjects are on treatment which was started at a mean age of 4.88 ±2.96 years, surveillance data available for a mean follow up of 2.75±2.41 years. 50 received BB (58.50% atenolol [average dose 0.79 mg/kg/day] and 19.15% bisoprolol [average dose 0.087 mg/kg/day]), 5 (8.51%) losartan [average dose 0.763 mg/kg/day], and 10 (15.38%) double therapy with BB and ARBs. The Sinus of Valsalva (SOV) z-scores, as assessed on echocardiograms and normalised according to Lopez dataset, showed a reduction over time in children treated with chemoprophylaxis (see figure 1). SOV mean z-score at starting treatment was 3.38 ± 2.06 which reduced to 2.79± 1.81, however, differences were not statistically significant (paired T-student p-value 0.078). In non-treated patients, initial SOV z-score was 1.89 ± 1.05. When comparing evolution there was a trend towards decreased average SOV z-score over the years in the treated group, not seen in the non-treated patients (see figure 2). No statistical differences in the SOV z-score reduction change were found when comparing different treatment groups (ANOVA p-value 0.851), but a tendency to more profound decrease in the losartan groups was observed. Reduction in blood pressure or heart rate did not differ amongst the treatment groups. Conclusions We present one of the largest single centre reviews on management of paediatric Marfan patients. Our data confirm a decrease in SOV z-score with chemoprophylaxis in a real-world cohort. This is in line with current evidence and corroborates clinical practice.SOV Z-SCORE EVOLUTION AFTER TREATMENTSOV Z-SCORE GROUP AVERAGE CHANGE

Antihypertensive treatment during pregnancy and maternal and fetal outcomes

Abstract Introduction Arterial hypertension affects about 5-10% of pregnancies and has detrimental effects on pregnancy outcomes in both the mother and fetus. The study aimed to analyse the outcomes of pregnancy in women treated for arterial hypertension in pregnancy in the Czech Republic. Methodology Nationwide data on all births and abortions in the period 2012-2022 in the Czech Republic were obtained from the National Registry of Reproductive Health (NRRZ) and the National Registry of Reimbursable Health Services (NRHZS). Women who had the diagnosis I10 within one year before pregnancy and were prescribed any antihypertensive drug from selected ATC groups (C02, C03, C07, C08, C09) were classified as pre-existing hypertension. Women diagnosed with O13 or I10 during pregnancy were classified as pregnancy induced hypertension. Hypoxia in the new-born was defined as pH <7.1 or Apgar score <8 present after delivery. For all factors, univariate logistic regression was used to calculate the odds ratios (OR) of adverse outcomes. Results There were total of 1,154,648 deliveries in the 11-year period. 95,215 women had hypertension in pregnancy, out of these 21,094 (22.2%) were treated with antihypertensive drugs. Odds ratios for caesarean section, pre-term delivery, low birth weight, new-born hypoxia and pre-eclampsia in women using different antihypertensive classes and drugs are shown in the Table. Risk of maternal and fetal complications was found to be higher with calcium channel blockers (mainly amlodipine) compared to methyldopa and beta blockers. Among beta blockers, bisoprolol had the most favourable safety profile. Although used in limited numbers, diuretics, verapamil, ACE-inhibitors and angiotensin receptor blockers (ARBs) appeared to be comparably safe to methyldopa. Combination of multiple antihypertensive drugs was associated with higher risk of adverse outcomes. Conclusion Bisoprolol, verapamil and diuretics seem to have the risk of adverse maternal and fetal outcomes comparable to methyldopa. Amlodipine and multiple antihypertensive drug combinations are associated with increased risk.Table

Real world evidence of Sacubitril/Valsartan in octogenarian patients with heart failure. Results From the PARACHUTE-HF Study

Abstract Introduction The beneficial effects of Angiotensin Receptor Neprilysin Inhibitors (ARNI) on heart failure (HF) patients, particularly those with reduced left ventricular ejection fraction (LVEF), have been highlighted in several randomized controlled trials. Since 2020, ARNI has been available for HF treatment in Japan, a country known for its aging population. However, the inclusion of octogenarians in previous trials has been limited, leaving a gap in evidence regarding ARNI's effectiveness in the elderly. Objective This study aims to explore the real-world efficacy and safety of ARNI treatment among octogenarian HF patients in Japan, reflecting its status as a leading aging society. Methods The Prospective Area Registry of ARNI for Congestive Heart failUre in Tokyo East (PARACHUTE) trial, a multicenter registry, was conducted. It involved patients newly prescribed ARNI for chronic HF regardless of LVEF between 2020 and 2021. We compared patient backgrounds, changes in NT-proBNP levels at 6 months, and the rate of ARNI discontinuation between groups aged below and above 80 years. Results The study enrolled 105 patients, with an average age of 75 years. Forty-six patients (44%) were over 80 years old, and the majority (72%) were male. Among the younger group, 50% had preserved LVEF, compared to 32% in the octogenarian group (p=0.01). Median NT-proBNP levels across all patients decreased significantly from 2,540 pg/mL at baseline to 998 pg/mL at 6 months. The reduction in NT-proBNP was similar between the two age groups, with no significant interaction (p=0.46). Discontinuation rates due to any cause were not significantly different between younger and older patients (7% vs. 13%, p=0.28). Conclusion ARNI treatment resulted in significant reductions in NT-proBNP levels in HF patients, both under and over 80 years of age, with comparable discontinuation rates. These findings highlight the effectiveness and safety of ARNI in the management of chronic HF in the elderly, offering valuable real-world evidence from Japan's unique demographic context.

What does routinely-collected electronic health record data tell us about the use of heart failure medication among older people in Wales? Making progress but could do better

Abstract Background European Society of Cardiology 2021 guidelines recommend 4 pillars of treatment to reduce mortality for those with heart failure (HF) and reduced ejection fraction (HFrEF): pillar 1) angiotensin converting enzyme inhibitor (ACE-I)/angiotensin receptor blocker (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), pillar 2) beta-blocker (BB), pillar 3) mineralocorticoid receptor antagonist (MRA), pillar 4) sodium-glucose co-transporter 2 inhibitor (SGLT2i). When there is heart failure with preserved ejection fraction (HFpEF), guidelines recommend diuretics to alleviate congestion and treatment of risk factors such as hypertension and diabetes. Prior to 2021, United Kingdom guidelines did not include SGLT2i. Purpose To examine how HF treatment is recorded in routinely-collected electronic health record (EHR) data for older people in Wales, and to explore how that has changed since 2015. Methods We conducted a retrospective, population-level, observational study using linked anonymised EHR data in Wales (2015-22). 737,230 individuals were aged 65y+ in the study period (21.5% of population in 2022). Of these, 65,010 had a code for heart failure in their primary or secondary care records. We excluded 13,990 individuals with fewer than 12 months data pre- or post-diagnosis. We looked forward, from HF diagnosis, for codes associated with specific medications. Results The final cohort comprised 51,020 individuals aged 65y and over with a diagnosis of heart failure between 2015-2022. Incidence and prevalence of heart failure increased across the study period (1.4-1.5% and 8.5-9.1% respectively). Preceding cardiovascular diagnoses included hypertension (69.5%), atrial fibrillation (36.7%), myocardial infarction (30.5%), coronary artery disease (25.7%), and valve disease (17.7%). Diabetes (41.7%), chronic kidney disease (30.9%) and cancer (26.4%) were the most common comorbidities. The subtype of HF (HFrEF or HFpEF) was only evident in 5,850. Treatments recorded most often were loop diuretics, ACE-I, and BB (Table 1). SGLT2i codes increased in 2020/2021(Figure 1). At 10-12 months post diagnosis, the proportion with simultaneous pillar combinations was; 27.4% 1 + 2, 12.5% 1, 2 + 3, and only 2% 1, 2, 3 + 4. Conclusions In Wales, there is a need to improve the coding of HF subtype in primary care records. We suggest interpreting data with the assumption that approximately half of the cohort are likely to have HFrEF. While the cohort proportion on ACE-I or beta-blockers may be appropriate, the proportion with more than 1 simultaneous pillar of treatment recorded appears low. The use of SGLT2i in codes is increasing. These results are important in evaluating health service delivery and in establishing baseline data from which to monitor improvements.

Sex-differences in prescription patterns of secondary prevention pharmacotherapy in patients with acute myocardial infarction: a 20-year perspective

Abstract Background Recent studies have demonstrated sex-related differences in secondary prevention pharmacotherapy in patients with acute myocardial infarction (AMI), although guidelines recommend the same preventive approach in both women and men. Purpose This study extends earlier work by examining temporal trends of prescribing practices of secondary prevention medications using contemporary data from a long-term period in Switzerland, with particular regard to sex inequalities. Methods For the purpose of this retrospective analysis of prospectively collected data in the Acute Myocardial Infarction in Switzerland (AMIS) Plus registry, optimal medical therapy (OMT) was defined as the combination of all five guideline-recommended medications in AMI at discharge: aspirin, P2Y12 inhibitors, lipid-lowering drugs, beta blockers, and angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Uni- and multivariable logistic regression analyses were performed. Results A total of 34'612 patients (men n=25’913, 75%) hospitalised with AMI between 2003 and 2022 were included in the analysis. The mean age was 66±13 years and women were on average 7 years older than men. Despite having more comorbidities, women benefited less frequently from OMT than men (51% vs. 60%) across all age groups (all p<0.001), with the greatest gap occurring in patients <50 years of age. Within the 20-year study period, significant increases over time were observed in the singular prescription of all OMT components, except for beta blockers (p=0.2). This translated into a marked increase in OMT prescription irrespective of age and sex (from 36% to 60%), mainly due to greater prescription of dual antiplatelet therapy (DAPT, from 71% to 91%) and lipid-lowering drugs (LLD, from 69% to 93%). The sex-related gap in OMT disfavoring women showed a uctuating trend over the years (getting reduced from 14% in 2003 to 0.7% in 2016 to widen again to 12% in 2022) whereas there was a continuous narrowing over time regarding the combination of DAPT plus LLD, from 18% to 10% at the beginning and the end of the observation, respectively (Figure 1). In multivariable analysis, age (OR 0.99, 95%CI 0.98-0.99, p<0.001) and female sex (OR 0.90, 95%CI 0.85-0.95, p<0.001) were independent predictors of deficient OMT prescription, while the performance of percutaneous coronary intervention was identified as the strongest positive predictor favoring it (OR 4.85, 95%CI 4.49-5.24, p<0.001). Conclusion Although there has been a gradual increase in the prescription of OMT over time among both women and men, concerning sex disparities disfavoring women, and particularly young women, remained. Targeted programs to reduce sex-related differences in secondary prevention care are warranted.

Heart failure burden among adults with congenital heart disease

Abstract Background Adult congenital heart disease (ACHD) is associated with high rates of healthcare utilization and mortality. Data on Heart failure (HF) burden among ACHD patients are limited. Purpose To study the association between HF and healthcare utilization and mortality among ACHD patients in the community. Methods The retrospective cohort study comprised 11,653≥ 18 year old ACHD patients insured by two large Israeli healthcare providers between January 2007 and December 2011. We used multivariable Cox proportional hazard and negative binomial models to study the associations of HF with mortality and healthcare utilization, respectively. Inverse treatment probability weighting accounted for drug indication. Results ACHD-HF patients (N=908; 7.8%) were older (median: 69 vs. 45 years), more likely men (53% vs. 45%), with complex congenital heart disease (14% vs. 4%), and higher comorbidity rates than ACHD patients without HF. HF was associated with higher healthcare utilization. Compared to patients without HF, ACHD-HF patients had higher adjusted relative rates (RR) of primary care (1.26, 95% confidence interval [CI]: 1.17-1.3), and cardiology clinic visits (1.9, 95% CI: 1.7-2.0), higher hospitalization rates (RR=2.0, 95% CI: 1.7-2.1), and higher risk of death (mortality hazard ratio [HR]: 1.9, 95% CI: 1.5-20.) over the study period. Among ACHD-HF patients, Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and diuretics were associated with a lower mortality risk (treated vs. untreated HR=0.56, 95% CI: 0.48-0.65; HR=0.7, 95% CI: 0.6-0.8; HR=0.84, 95% CI: 0.73-0.97; respectively). Conclusions HF presents a major burden on ACHD patients and health care systems. Drugs recommended to the general HF patient population are also associated with lower risk of hospitalization and mortality in ACHD patients. Clinical trials are needed to establish the benefit of HF pharmacotherapy in ACHD patients.Age adjusted ACHD patient survival by HF

Clinical characteristics and treatment patterns of new users of dapagliflozin for heart failure with reduced ejection fraction: an observational study programme across 12 countries (EVOLUTION HF)

Abstract Background Clinical trials have shown that dapagliflozin, a sodium–glucose cotransporter-2 inhibitor (SGLT-2i), reduces cardiovascular mortality and worsening heart failure (HF). Adoption of new therapies has historically been slow despite robust evidence. Furthermore, treatment profiles of patients in real-world settings are scarce. Purpose EVOLUTION HF is a multinational study programme that aims to describe clinical characteristics and treatment patterns among patients initiating dapagliflozin for HF with reduced ejection fraction (HFrEF) in routine clinical practice. Methods The EVOLUTION HF primary data study programme consists of prospective, observational, descriptive studies of new users of dapagliflozin for HFrEF in 12 countries (Italy, Portugal, UK and the Central and Eastern Europe and Baltic [CEEBA] region [Bulgaria, Croatia, Estonia, Hungary, Latvia, Lithuania, Poland, Romania and Slovenia]). Patients with type 1 diabetes or prior SGLT-2i treatment were excluded. Clinical characteristics were obtained from electronic health records. A total of 2170/2555 (85%) patients were enrolled from November 2021 to November 2023; 1736 patient profiles were assessed using descriptive statistics in this interim analysis. Results In total, 256, 228, 125 and 1127 new dapagliflozin users were analysed from Italy, Portugal, the UK and the CEEBA region, respectively (Table 1). Across the 12 countries, mean patient age in the studies was 65–70 years. Patients were predominantly male (67–76%) and generally had HF with an ischaemic aetiology (35–56%) and New York Heart Association functional class II (52–85%). Mean left ventricular ejection fraction in the studies was 29–32% and estimated glomerular filtration rate was 61–77 mL/min/1.73m². Hypertension and atrial fibrillation were common comorbidities. Mean time between HF diagnosis and dapagliflozin initiation in the studies was 23–52 months. Background therapy included angiotensin receptor-neprilysin inhibitors (36–72%), angiotensin receptor blockers (4–12%) and angiotensin-converting enzyme inhibitors (9–33%). At 6 and 12 months after dapagliflozin initiation, respectively, treatment discontinuation rates across the CEEBA region were 5.22% (59/1131) and 4.66% (50/1072). Conclusions The EVOLUTION HF primary data study programme provides novel insights into clinical characteristics and treatment patterns in patients with HFrEF initiating dapagliflozin in real-world practice across a broad European population. At dapagliflozin initiation, a large proportion of patients were receiving other HF therapeutics, suggesting dapagliflozin is one of the later therapies to be initiated. Indeed, this study identified a substantial delay (23–52 months) in dapagliflozin initiation following HF diagnosis. Treatment discontinuation rates following dapagliflozin initiation were also low, reinforcing the findings of the EVOLUTION HF secondary data studies.

Association of ticagrelor vs clopidogrel with net adverse clinical events in patients with mild thrombocytopenia undergoing PCI

Abstract Backgrounds Current guidelines recommend aspirin plus ticagrelor as the preferred dual antiplatelet therapy (DAPT) for managing ST-elevation myocardial infarction (STEMI). However, there is a lack of consensus or guidelines to direct clinicians on managing patients with mild thrombocytopenia, defined as a platelet count of 100~150×109/L, undergoing percutaneous coronary intervention (PCI). Purpose This study aims to investigate the association between ticagrelor and clopidogrel with ischemic and hemorrhagic events for patients with mild thrombocytopenia undergoing PCI. Methods A retrospective cohort study of patients with mild thrombocytopenia undergoing PCI who received DAPT consisting of aspirin and a P2Y12 receptor antagonist (includinig clopidogrel or ticagrelor) was conducted using Health and Medical Big Data Super Platform from January 2010 to June 2023. All patients meeting the criteria were included in the analysis, with a follow-up of at least one year. Propensity Score Matching (PSM) was performed to equalize the effects of following characteristics: age, sex, hypertension, diabetes, dyslipidemia, stroke, atrial fibrillation, Killip class, percutaneous coronary intervention (PCI), beta-blockers, statins, calcium channel blockers (CCB), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEI or ARB), angiotensin receptor-neprilysin inhibitor (ARNI), diuretic, organic nitrates, and oral anticoagulation. The primary endpoint was net adverse clinical events (NACE) at 1 year, composed of ischemic events (recurrent myocardial infarction or ischemic stroke), Bleeding Academic Research Consortium (BARC) classification ≥ 3, and cardiac death. Secondary outcomes included the components of NACE. Results A total of 3647 patients met the inclusion criteria, with 2684 receiving aspirin plus clopidogrel and 963 receiving aspirin plus ticagrelor, matched by a 1:3 ratio using the PSM method. Demographic characteristics were well balanced between the clopidogrel and ticagrelor groups. The 1-year risk of NACE did not significantly differ between ticagrelor and clopidogrel (11.1% vs. 8.4%, p=0.370). Similarly, there was no significant difference in the risk of cardiac death (7.3% vs. 4.2%, p=0.720), recurrent myocardial infarction (9.3% vs. 5.8%, p=0.550), ischemic stroke (8.8% vs. 6.7%, p=0.055), or BARC type ≥ 3 bleeding (7.9% vs. 4.5%, p=0.990). Conclusion In routine clinical practice, among patients with a platelet count of 100~150×109/L undergoing PCI, ticagrelor compared with clopidogrel was not associated with a significant difference in the risk of NACE at 1 year. Further research is warranted to assess whether ticagrelor is more effective than clopidogrel in this setting, considering potential unmeasured confounders.

Optimizing aldosterone receptor antagonist therapy by sodium zirconium cyclosilicate in heart failure - OPRA-HF trial

Abstract Background Heart failure remains a significant health burden, characterized by disabling symptoms and mortality rates comparable to cancer. Mineralocorticoid antagonists (MRAs), pivotal in treating heart failure with reduced ejection fraction (HFrEF), are underutilized due to concerns of hyperkalemia. Sodium Zirconium Cyclosilicate (SZC) enables optimized MRA therapy by reducing hyperkalemia. However, prospective studies on the efficacy and safety of SZC in patients with HFrEF and high hyperkalemia risk are lacking, particularly in the context of contemporary heart failure quadruple-therapy including angiotensin receptor neprilysin inhibitor (ARNI) and Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitors. Purpose The OPRA-HF trial aims to assess the efficacy and safety of SZC in optimizing MRA treatment in symptomatic patients with HFrEF with risk for hyperkalemia on top of optimal guideline-directed medical therapy including ARNI and SGLT2 Inhibitors. Methods This investigator-initiated multicentred, randomized, placebo-controlled, and double-blinded trial include patients with HFrEF on suboptimal MRA treatment due to (1) history of hyperkalemia due to MRA, or (2) risk of hyperkalemia due to reduced renal function (eGFR 30-45 ml/min/m2) and current potassium 4.5-5-0 mmol/L. Patients undergo a Run-In phase with SZC, initiating or up-titrating MRA to target doses for 4-7 weeks and SZC was initiated in those patients that became hyperkalemic (K+>5 mEq/L. Those normokalemic and tolerating MRA ≥ 25 mg daily or at least 25 mg dose increase vs before run-in were randomized to SZC (5g or 10g) or placebo for 6 months. Study is powered to randomize 110 patients. Primary outcomes include maintaining daily MRA dose ≥ 25 mg or dose increase by 25 mg with normal potassium levels without rescue therapy. Secondary outcomes include evaluating the safety and tolerability of SZC as well as impact of SZC on quality of life. Results In this ongoing trial, so far 40 patients have been randomized. Of these, mean age was 74.3 years, 88.9% men. Most patients had ischemic etiology (54.2%), 36.1% had diabetes mellitus, 52.8% had hypertension.n. At screening 94.4% had beta-blockers, 35% ACEI/ARB, 60% ARNI and 72.2% had SGLT2 inhibitors, 33.3% had no MRAs and 35,6% of patients had less than 25 mg MRA daily,62,2% had 25 mg MRA daily, mean p-potassium was 4.7+0.4 mmol/L, and eGFR was 57.3 ml/min/1.73m². After run-in, 85.2% were on 50 mg MRA daily. A substantial number (51.2%) of eligible patients with previous hyperkalemia had Run-In failure as they now successfully tolerated target dose of MRA at 50 mg daily without recurrent hyperkalemia. SZC dosing was 5g once daily in 78.9% of patients. Conclusion This ongoing trial will provide evidence for the use of SZC to optimize MRA treatment in contemporary HFrEF patients. Preliminary findings suggest SZC effectively maintains normokalemia, enabling MRA optimization, potentially improving patients’ otcome.

ACE inhibitor and angiotensin receptor blocker use during pregnancy: data from the ESC Registry of pregnancy and cardiac disease (ROPAC)

Abstract Background and Aims Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) are not recommended during the second and third trimester due to the significant risk of congenital anomalies associated with their use. However, data are scarce, especially regarding their use in the first trimester. Our study illustrates the profile of the women who used ACE-Is or ARBs during pregnancy and to evaluate the impact on perinatal outcomes. Methods The Registry of Pregnancy and Cardiac disease (ROPAC) is a prospective, global registry of pregnancies in women with structural heart disease. Outcomes were compared between women who used ACE-Is or ARBs and those who did not. Multivariable regression analysis was performed to assess the effect of ACE-I or ARB use on the occurrence of congenital anomalies. In addition, the perinatal outcomes of patients who stopped ACE-Is and/or ARBs before pregnancy were assessed. Results ACE-I (n=35) and/or ARB (n=8) were used in 42 (0.7%) of the 5739 ROPAC pregnancies. Women who used ACE-Is or ARBs more often came from a low-or-middle-income country (57% vs 40%, p=0.021), had chronic hypertension (31% vs 6%, p<0.001), or a left ventricular ejection fraction <40% (33% vs 4%, p<0.001). No pregnancy terminations due to fetal anomaly were reported. ACE-I use during the first trimester was independently associated with an increased risk of congenital anomaly (OR 3.1; 95% CI 1.0-9.3). No adverse fetal or neonatal effects were seen when ACE-I and/or ARB were discontinued prior to pregnancy. Conclusions ACE-Is and ARBs are seldom used during pregnancy and based on our data, ACE-Is should also be avoided in the first trimester due to a higher risk of congenital anomalies. Preconception counseling is crucial to discuss the potential risks of these medications, and to evaluate the clinical condition and, if possible, the woman can be switched to an alternative medication.

Combined ARNI and SGLT2i impacts on peak tricuspid regurgitant velocity and echocardiographic probability of pulmonary hypertension

Abstract Background In heart failure with reduced ejection fraction (HFrEF), the development of pulmonary hypertension (PH) is associated with poor prognosis. Recent medical advancements have substantially improved both survival rates and HF hospitalization. However, the impact of combining angiotensin receptor neprilysin inhibitor (ARNI) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) on peak tricuspid regurgitant velocity (TRV) and PH echocardiographic probability remains unexplored. Purpose We aimed to evaluate the effect of ARNI alone versus ARNI combined with SGLT2i on peak TRV and PH probability in a real-life population of outpatients with HFrEF. Methods This was an observational monocentric study including patients treated with either ARNI alone or with SGLT2i on top of ARNI. Echocardiographic examinations were performed by fully accredited operators and all parameters were analysed offline by expert operators blinded to clinical data. We performed echocardiographic evaluation in all patients before initiating treatment and at 12 months follow-up. We excluded patients who discontinued ARNI within 6 months of introduction and those who did not complete at least 6 months of follow-up with both drugs. Results 80 HFrEF patients were included, 41 receiving ARNI+SGLT2i and 39 receiving ARNI alone. Baseline mean peak TRV was similar between the two groups (280±44 cm/s and 259±48 cm/s respectively, p=0.09). At follow-up, mean peak TRV was 232±32 cm/s in ARNI+SGLT2i group and 258±45 cm/s in ARNI alone group (p=0.02). The decrease in peak TRV was significant in ARNI+SGLT2i group, p=0.0004 (Table). At baseline the echocardiographic probability of PH was comparable between both groups, p=0.53 (Figure). Nevertheless, during follow-up, the proportion of patients with high probability of PH decreased in the ARNI+SGLT2i group (from 22% to 2%), while in the ARNI alone group it did not change (Figure). Conclusions In HFrEF the combination of ARNI+SGLT2i demonstrates high effectiveness in TRV reduction, downgrading PH probability class. In our population, this evidence is primarily driven by the decrease TRV. These results may suggest the positive effect of SGLT2i on pulmonary vascular remodelling and right heart hemodynamic worth of full investigation in further studies aimed at targeting left-sided PH and its prevention strategies.