Pulmonary arterial hypertension (PAH) is a life-threatening condition characterised by the excessive proliferation of pulmonary artery vessels. Despite significant advancements in treatment strategies over recent years, mortality rates remain high. The current treatment strategy focuses on risk assessment both at the time of diagnosis and during follow-up. It involves the initial use of combination therapies targeting PAH. These therapies regulate vascular tone through 3 main pathways: the endothelin pathway, the nitric oxide/cyclic guanosine monophosphate pathway, and the prostacyclin pathway. Sotatercept, a fusion protein that binds to ligands of the transforming growth factor-β superfamily, rebalances the pro- and anti-proliferative signalling of activin receptor type II (A/B), thus targeting a unique pathogenic pathway and promoting anti-proliferative effects on the pulmonary vasculature. Recently, it received approval from the European Medicines Agency for patients with PAH classified as World Health Organisation functional class II or III. Proceedings from the latest World Symposium on Pulmonary Hypertension stress the importance of adding sotatercept to the treatment regimen for the majority of patients during follow-up, including those at high risk. In anticipation of upcoming scientific guidelines and with the hope of improved outcomes for patients with PAH, an expert opinion for the treatment of Greek patients has been developed, focusing on the integration of this novel agent into the therapeutic algorithm.

Combined post- and precapillary pulmonary hypertension (CpcPH) comprises the most severe form of postcapillary PH. A severe precapillary component (pulmonary vascular resistance [PVR] > 5 WU) is critical for therapeutic decisions. Current treatment guidelines focus on optimizing underlying cardiac disease, while there are conflicting data regarding the efficacy and safety of pulmonary arterial hypertension (PAH) drugs in selected patients. This study examines the impact of PVR > 5 WU on survival in heart failure with preserved ejection fraction (HFpEF) and CpcPH and evaluates the effect of treatment with phosphodiesterase 5 inhibitors (PDE5is) on clinical and hemodynamic parameters and on prognosis. The Hellenic Pulmonary Hypertension Registry (HOPE) enrolls patients from all PH groups in Greece. This study focuses on Group 2 CpcPH patients with HFpEF. Propensity score matching was performed to reduce the risk of bias in the treatment selection and potential confounders. Kaplan-Meier curve was used to estimate 5-year survival, and the log-rank test was used for the comparisons. A total of 98 patients were included, with a median follow-up of 2.9 years. PVR > 5 WU and age were independently associated with worse survival ([HR 2.15, 95% CI 1.13-4.83, p = 0.04], [HR 1.07, 95% CI 1.03-1.13, p = 0.003], respectively). Propensity-matched cohort analysis indicated that PDE5i treatment was associated with a significant reduction in PVR at follow-up (from median [IQR] 4.89 [1.9] WU to 3.1 [2.0] WU, p = 0.04) and a trend towards improved survival. Severe precapillary component is associated with impaired prognosis in CpcPH. While PDE5i treatment shows promise in improving hemodynamic outcomes, its effect on long-term survival requires further investigation.

BACKGROUND:Pulmonary arterial hypertension (PAH) is a severe complication among adult patients with congenital heart disease (ACHD). This study presents real-world data on risk stratification, pharmacotherapy and survival rates in PAH-ACHD. METHODS:Data from PAH-ACHD patients were analyzed using The Hellenic Pulmonary Hypertension Registry (HOPE), spanning eight specialized centers between 2015 and 2023. Patients were categorized into low, intermediate, and high-risk groups using the ESC/ERS three-strata model to assess 1-year mortality risk. RESULTS:A total of 93 PAH-ACHD patients were included (median age 38.5 years, 60.2 % women). Most patients had an atrial septal defect (37.6 %) or a ventricular septal defect (35.5 %), with 11.8 % presenting with complex ACHD. Eisenmenger syndrome was present in 35.5 % of patients. The proportion of low-risk patients nearly doubled from first to last assessment (24.7 % vs. 40.9 %, p = 0.001). Initially, 52.7 % of patients were on PAH monotherapy, with a subsequent shift towards combination therapy (73.1 %) during follow-up. Over a median follow-up of 5.9 years, 29 patients (31.1 %) died, with 1- and 5-year survival rates of 95.5 % and 81.9 %, respectively. Compared to the high-risk group, low- and intermediate-risk patients exhibited a 70 % and 50 % lower hazard of death, respectively. The lowest survival rates were observed in patients with Eisenmenger physiology. CONCLUSION:Survival prospects were favorable for the non-high risk patients in this nationwide cohort of PAH-ACHD patients. The observed shift towards combination therapy use may have contributed to the improvement in 1-year ESC mortality risk, underscoring the importance of timely combination therapy with PAH drugs.

Abstract Whereas younger female patients were diagnosed with idiopathic pulmonary arterial hypertension (IPAH) in 1980s, it is now frequently encountered in elderly patients with cardiovascular comorbidities (CVCs) associated with increased risk for left heart disease. We present data until November 2019 regarding specific features and clinical outcomes of IPAH population from the Hellenic Pulmonary Hypertension Registry (HOPE). Patients were divided into two groups based on the presence of ≥ or <3 CVCs, arterial hypertension, diabetes mellitus, obesity, presence of coronary artery disease, or atrial fibrillation. Overall, 77 patients with IPAH (55.1 [interquartile range, IQR: 24.1] years, 62.8% women) have been recorded. Fifteen patients (19.2%) had ≥3 CVCs, while 25 (32%) were over 65 years old. Patients with ≥3 CVCs were older, presented an almost equal female to male ratio, walked less in 6‐min walk test, and had lower mean arterial pulmonary pressure and pulmonary vascular resistance at baseline than patients with less CVCs. Fewer patients with ≥3 CVCs received PAH‐specific treatment compared to patients with less comorbidities (n = 11 [73.3%] versus n = 58 [95.5%], p = 0.02). During a median follow‐up period of 3.8 (IQR: 2.7) years, 18 patients died (all‐cause mortality 24.3%). Male sex and older age were independent predictors of mortality and/or lung transplantation, while CVCs did not have a significant impact on clinical outcomes. In this nationwide, register‐based study, the epidemiology of IPAH involves older patients with CVCs, who seem to have less hemodynamic compromise, but worse functional impairment and are treated less aggressively with PAH pharmacotherapy.

Pericardial effusion (PE) prognosis depends on the underlying etiology. We sought to assess the outcome of patients with chronic (>3 months), large (diastolic echo-free space >2 cm), idiopathic (without apparent etiology), C-reactive protein (CRP) negative PE, a topic where data are lacking. A total of n = 74 patients were enrolled in this study. Patients were treated by pericardiocentesis (n = 39) or surgical pericardial "window" (PW) (n = 13) or conservatively (n = 22). The median follow-up was 24 months (interquartile range: 15 to 38). Among those patients who had PE drained (n = 52), PE re-accumulation occurred in 32 cases (61.5%) and the rate was significantly higher in the pericardiocentesis subgroup (76.9% for pericardiocentesis vs 15.4% for PW group, p <0.001). Patients with reaccumulation had longer disease duration (32.1 +/- 25.7 months vs 19.5 +/- 23.8 months, p = 0.01), higher maximum PE diameter (32.2 +/- 9.4 mm vs 26.1 +/- 4.9 mm, p = 0.003) and larger PE volume drained at baseline (1,912 +/- 707 mL vs 1,508 +/- 387 mL, p = 0.04). Large PE re-accumulation occurred in 41% of patients who underwent pericardiocentesis and in 7.7% of those who underwent PW. In Cox survival analysis the only independent predictor of fluid re-accumulation was the type of intervention, with PW being associated with significantly reduced risk (hazard ratio 0.115, 95% confidence interval 0.015 to 0.875, p = 0.037). Major complications needing treatment were recorded in 12.8% and 15.4% (p = 0.999) of patients who underwent pericardiocentesis and PW, respectively. Moreover, invasive procedures were not helpful in establishing new diagnoses and guide treatment. In conclusion, in asymptomatic patients with chronic, large, hemodynamically insignificant, CRP negative, idiopathic PE, conservative management seems a more reasonable approach in most cases. (C) 2020 Elsevier Inc. All rights reserved.

Pulmonary arterial hypertension (PAH) is a heterogenous clinical entity with poor prognosis, despite recent major pharmacological advances. To increase awareness about the pathophysiology, epidemiology, and management of the disease, large national registries are required. The Hellenic pulmOnary hyPertension rEgistry (HOPE) was launched in early 2015 and enrolls patients from all pulmonary hypertension subgroups in Greece. Baseline epidemiologic, diagnostic, and initial treatment data of consecutive patients with PAH are presented in this article. In total, 231 patients with PAH were enrolled from January 2015 until April 2018. At baseline, about half of patients with PAH were in World Health Organization functional class II. The majority of patients with PAH (56.7%) were at intermediate 1-year mortality risk, while more than one-third were low-risk patients, according to an abbreviated risk stratification score. Half of patients with PAH were on monotherapy, 38.9% received combination therapy, while prostanoids were used only in 12.1% of patients. In conclusion, baseline data of the Greek PAH population share common characteristics, but also have some differences with other registries, the most prominent being a better functional capacity. This may reflect earlier diagnosis of PAH that in conjunction with the increased proportion of patients with atypical PAH could partially explain the preference for monotherapy and the limited use of prostanoids in Greece. Nevertheless, early, advanced specific therapy is strongly recommended.

Objective Despite the progress in the management of patients with adult congenital heart disease (ACHD), a significant proportion of patients still develop pulmonary hypertension (PH). We aimed to highlight the rate of the complications in PH-ACHD and the predicting factors of cumulative mortality risk in this population. Methods Data were obtained from the cohort of the national registry of ACHD in Greece from February 2012 until January 2018. Results Overall, 65 patients receiving PH-specific therapy were included (mean age 46.1±14.4 years, 64.6% females). Heavily symptomatic (New York Heart Association (NYHA) class III/IV) were 53.8% of patients. The majority received monotherapy, while combination therapy was administered in 41.5% of patients. Cardiac arrhythmia was reported in 30.8%, endocarditis in 1.5%, stroke in 4.6%, pulmonary arterial thrombosis in 6.2%, haemoptysis in 3.1% and hospitalisation due to heart failure (HF) in 23.1%. Over a median follow-up of 3 years (range 1–6), 12 (18.5%) patients died. On univariate Cox regression analysis history of HF hospitalisation emerged as a strong predictor of mortality (HR 8.91, 95% CI 2.64 to 30.02, p<0.001), which remained significant after adjustment for age and for NYHA functional class. Conclusions Long-term complications are common among patients with PH-ACHD. Hospitalisations for HF predict mortality and should be considered in the risk stratification of this population.

Transcatheter aortic valve replacement has emerged as an alternative to surgical aortic valve replacement for high-risk and inoperable patients. Although transcatheter aortic valve replacement avoids the use of extracorporeal circulation and sternotomy, it is nonetheless associated with inherent complications. We aim to present an embolized valve-in-valve complex in the ascending aorta, which required emergency surgery with deep hypothermic circulatory arrest and proximal aortic cannulation.

Background Androgens are known to influence the risk of developing cardiovascular diseases. This study aims at investigating the possible association between G1733A polymorphism in the coding region of androgen receptor ( AR ) gene and premature coronary artery disease (CAD). Methods A total of 460 Greek subjects were investigated for the G1733A polymorphism. The patient group consisted of 250 CAD individuals, aged less than 58 years, while 210 healthy individuals served as controls. Genotyping was performed using the PCR‐RFLP method. Results Significant differences in genotype distribution ( P = 0.0067) and allele frequencies ( P = 0.0060) have been observed between patients and controls in the women's subgroup. Conversely, the genotype/allele frequencies were similar between patients and controls in the subgroup of men. Conclusion We may conclude that the G1733A polymorphism of AR gene could be a useful genetic marker for the assessment of a woman's risk for CAD in our Caucasian Greek population.

Dual aortic and ventricular thrombi are rare following myocardial infraction. We report the case of a 56-year-old man who initially denied primary percutaneous coronary intervention as a result of psychological phobia. Initial pharmacological management by thrombolysis and heparin was followed by multiple arterial thromboses including those of the left ventricle and right iliac artery with a subsequent diagnosis of heparin-induced thrombocytopaenia. Ensuing surgical management revealed the unanticipated finding of an additional aortic sinus thrombosis that was excised. The left ventricular thrombus was removed endoscopically to prevent ventricular incisions. This case emphasizes the technical advantages of video-endoscopic management of intracardiac thrombi and highlights the unexpected nature of multiple thromboses associated with heparin-induced thrombocytopaenia.

AIMS AND OBJECTIVES:To evaluate the one-year prognosis of a lifestyle counselling intervention (diet, smoking cessation and exercise) among patients who had open heart surgery.BACKGROUND:Cardiovascular disease is the leading cause of morbidity worldwide in both developing and developed countries. Lifestyle modification plays an important role for patients who are at a high risk of developing cardiovascular disease and for those with an established cardiovascular disease.DESIGN:Randomised, nonblind and lifestyle counselling intervention study with a one-year follow-up.METHODS:A randomised, nonblind intervention study was performed on 500 patients who had open heart surgery. After hospital discharge, 250 patients (intervention group) were randomly allocated lifestyle counselling according to the recent guidelines provided by the European Society of Cardiology (European Journal Preventive Cardiology, 19, 2012, 585). The remaining 250 patients (control group) received the regular instructions. Primary end-point was the development of a cardiovascular disease (nonfatal event) during the first year; secondary end-points included fatal events, smoking abstinence, dietary habits and a physical activity evaluation.RESULTS:According to the primary end-point, the odds of having a nonfatal cardiovascular disease event are 0·56-times (95%CI 0·28, 0·96, p = 0·03) lower for the intervention group compared to the control group. One-year after surgery, it was found that participants in the intervention group were 1·96-times (95%CI 1·31, 2·93, p < 0·001) more likely to achieve dietary recommendations, 3·32-times (95%CI 2·24, 4·91, p < 0·001) more likely to achieve physical activity recommendations and 1·34-times (95%CI 1·15, 1·56, p < 0·001) more likely to return to work.CONCLUSION:Lifestyle counselling intervention following open heart surgery can improve health outcomes and reduce the risk of a new cardiac event. Health care services must recommend and organise well-structured cardiac rehabilitation programmes adjusted to the patient's needs.RELEVANCE TO CLINICAL PRACTICE:A well-structured cardiac rehabilitation programme adjusted to the patient's profile is a safe and cost-effective way to improve patients' outcome.

The aim of this study was to evaluate the gender-oriented differences in the outcomes of a lifestyle intervention trial (diet, smoking cessation, and exercise) among patients who had open heart surgery. A randomized, nonblind intervention study was performed on 500 patients who had open heart surgery. Immediately after hospital discharge, 250 patients were randomly allocated lifestyle intervention by receiving oral and written information in the form of a booklet with specific educational information for postoperative rehabilitation. The remaining 250 patients received the regular oral instructions. The applied lifestyle intervention proved to be beneficial only in men as far as quitting smoking (relative risk [RR]: 0.36, confidence interval [CI]: 0.16-0.80; P = .01) and returning to work (RR: 0.35, CI: 0.13-0.92; P = .03) are concerned. For both genders, no significant associations between dietary and physical activity recommendations were observed. Conclusion: Lifestyle nursing intervention immediately after open heart surgery had a beneficial effect on men 1 year after the surgery but not on women. Thus, there is a need for gender-specific studies among women.

INTRODUCTION Sex hormones are well known to increase the risk of coronary artery disease (CAD). The CYP17 gene encodes the enzyme cytochrome P450c17, which functions at key steps during the process of human sex steroid hormone synthesis. A T/C polymorphism in the 5 promoter region of the CYP17 gene influences its expression and the resulting serum levels of androgens and estrogens. The aim of this casecontrol study was to investigate the role of a T/C CYP17 polymorphism in premature CAD and the occurrence of myocardial infarction (MI) in the Caucasian Greek population. METHODS Our study group consisted of 230 CAD patients, aged less than 58 years, while 200 healthy individuals served as controls. The genotyping of the T/C CYP17 polymorphism was carried out using the PCRRFLP method. RESULTS The frequencies of TT, TC, and CC genotypes were 0.38, 0.42, and 0.20, respectively, in the patient group, and 0.35, 0.44, and 0.21, respectively, in the control group. Allele frequencies for the patient group were 0.58 and 0.42 for T and C, respectively, and 0.57 and 0.43, respectively, for the control group. Statistical analysis revealed no significant differences between patients and controls in genotype frequencies (p=0.8746) or allele frequencies (p=0.6783). CONCLUSIONS These findings do not support the hypothesis that the genetic variation T/C of the promoter of the CYP17 gene is an important contributing factor in the aetiology of premature CAD or occurrence of MI in the Caucasian Greek population.

BACKGROUND: Connective tissue growth factor (CTGF) has been reported to be upregulated in experimental models of chronic cardiac allograft rejection. We investigated the contribution of CTGF to the development of cardiac allograft vasculopathy (CAV), a surrogate marker for chronic rejection.METHODS: This prospective study included 72 adult heart allograft recipients. Genotyping of the rs6918698 polymorphism was performed by sequence-specific primer polymerase chain reaction (PCR). CTGF protein levels were measured in serum. CTGF messenger RNA (mRNA) from myocardial biopsy specimens was quantified by quantitative real-time PCR.RESULTS: Recipient genotype was associated with the development of CAV (p = 0.014) and the carriers of the C allele (CC and CG genotype) were high-risk recipients for the development of CAV (odds ratio, 3.30; 95% confidence interval, 1.12-9.74; p = 0.044). Serum CTGF protein levels could not be associated with the presence of the C allele but were significantly lower in the patients that had developed CAV (p = 0.038). This was attributed to the addition of everolimus to their immunosuppression scheme. Myocardial relative CTGF mRNA expression was estimated to be approximately twice as much in the CAV patients than in the patients without CAV (p = 0.013).CONCLUSIONS: The important role of CTGF during the development of CAV in heart transplantation was supported by the association of CAV with the recipient CTGF-945 CC/CG genotypes. The CAV patients, who were all receiving everolimus treatment, displayed elevated myocardial CTGF mRNA transcription levels, while everolimus has been observed to reduce serum CTGF protein levels. J Heart Lung Transplant 2012;31:881-7 (C) 2012 International Society for Heart and Lung Transplantation. All rights reserved.

The precise localization of bone marrow stem cells (SCs) into the necrotic tissue after intracoronary infusion (ICI) may be important for the therapeutic outcome. This study aims to examine the correlation between Tl-201 and Tc-99m-hexa-methyl-propylene-amine-oxime (HMPAO) images.

INTRODUCTION:In this prospective, single-center study we assessed the long-term results after drug-eluting stent implantation in non insulin-dependent diabetic patients compared to insulin-dependent patients.METHODS:A total of 610 consecutive diabetic patients (mean age 65 ± 9 years) underwent percutaneous coronary intervention with drug-eluting stent implantation. They were classified into 2 groups according to their diabetic treatment: 1) non insulin-dependent patients (477); 2) insulin-dependent patients (133). The primary endpoint was the composite of death, non-fatal myocardial infarction, bypass surgery and target lesion revascularization.RESULTS:Clinical follow up for more than 12 months (median 29 months) was achieved in 597/610 patients (98%). The insulin-dependent group had more women (29% vs. 18%, p=0.003), as well as a higher incidence of multivessel disease (84% vs. 65%, p<0.0001) and ejection fraction <40% (16% vs. 9%, p=0.037) compared to the non insulin-dependent group. The in-hospital results were almost the same in both groups, except for the incidence of non-Q myocardial infarction and bleeding complications, which were more frequent in the insulin-dependent group (9.8% vs. 4.8%, p=0.03, and 1.5% vs. 0%, p=0.047, respectively). During clinical follow up, no significant differences in the incidence of death or non-fatal myocardial infarction were observed, but target lesion revascularization and bypass surgery were more frequent in the insulin-dependent group (8.5% vs. 3.4%, p=0.01, and 4.7% vs. 1.3%, p=0.01, respectively). The event-free survival was lower in the insulin-dependent group (hazard ratio: 0.52; 95% confidence interval, 0.31-0.85, p=0.01).CONCLUSION:The implantation of drug-eluting stents in diabetics is associated with excellent in-hospital and long-term results. However, the long-term effectiveness in insulin-dependent patients is lower, because of the greater risk of new revascularization.

Plasma levels of brain natriuretic peptide (BNP) have been shown to correlate to aortic stenosis severity and are predictive of symptom development and survival. They also predict postoperative outcomes after valve replacement in patients with aortic stenosis. The early evolution of N-terminal-pro-BNP (NT-pro-BNP) levels after 50 aortic balloon valvuloplasty procedures performed in 45 patients was investigated. The mean NT-pro-BNP concentration decreased from 7,048 +/- 7,636 pg/ml at baseline to 5,309 +/- 6,150 pg/ml at 1 to 3 days after the procedure (mean difference 1,739 pg/ml, 95% confidence interval 804 to 2,675, p = 0.001). The absolute reduction in NT-pro-BNP levels correlated to the reductions in the maximum and mean transvalvular pressure gradients (on echocardiography: c = 0.57, p = 0.004, and c = 0.54, p = 0.012, respectively; invasively: c = 0.54, p = 0.025, and c = 0.39, p = 0.019). In conclusion, NT-pro-BNP levels decrease early after aortic balloon valvuloplasty in patients with severe aortic stenosis at high surgical risk. (C) 2009 Elsevier Inc. All rights reserved. (Am J Cardiol 2009;104:846-849)

INTRODUCTIONThe aim of this study was to record the results from a modern diagnostic and therapeutic approach to patients with pulmonary arterial hypertension.METHODSWe studied the clinical characteristics and the treatment of 69 patients (50 women, 72.5%), aged 44 +/- 17 years, who were diagnosed with pulmonary hypertension (World Health Organisation categories I, IV and V). The patients' outcomes were recorded over 14 years' operation of our Pulmonary Hypertension Unit.RESULTSTwenty-seven patients (39.1%) suffered from idiopathic pulmonary hypertension, 12 (17.4%) from thromboembolic obstructive disease, 14 (20.3%) from congenital heart diseases, 11 (15.9%) from connective tissue diseases, 3 (4.3%) from portal hypertension, 2 (2.9%) from sarcoidosis, and 1 (1.4%) from pulmonary veno-occlusive disease. Six patients (8.7%) were in New York Heart Association (NYHA) functional class I, 28 (40.6%) were in class II, 30 (43.5%) were in class III, and 5 (7.2%) were in class IV. Thirty-four patients completed a 6-minute walk test and covered a mean distance of 352 +/- 137 m. N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were measured in 18 patients, with a mean value of 1665 +/- 1935 pg/ml. A vasoreactivity test in 41 patients had a positive response in 10 (24.4%). Twenty-six patients (37.7%) were treated with combination therapy, whereas 16 (23.2%) either did not comply with or were not given specific medication. The mortality over a mean follow-up period of 5 +/- 4 years was 26%, significantly lower than that reported before the introduction of new drugs. An advanced NYHA class was an independent predictor of mortality (p=0.004), while elevated NT-proBNP levels were also associated with poor survival (p=0.013).CONCLUSIONSPulmonary arterial hypertension is a severe disease that leads to right heart failure and death. Despite the latest advances, vigilance and continuous investigation are needed in order to achieve a prompt diagnosis and the most suitable treatment.