Perioperative management of a double valve replacement and coronary artery bypass graft in a patient with carcinoid syndrome; a case report and literature review.

INTRODUCTION: Carcinoid tumors are rare neuroendocrine tumors; about 5% of patients develop the carcinoid syndrome. We present the case of a patient with carcinoid syndrome undergoing cardiac surgery. CASE REPORT: A 74-year-old patient with carcinoid heart disease and hepatic metastases underwent double valve replacement and CABG. The patient was on octreotide therapy and antihypertensive medication. An octreotide infusion was commenced perioperatively. Pharmaceutical agents that could potentially precipitate histamine release or exacerbate catecholamine secretion and carcinoid crises were avoided. Postoperatively, recovery was complicated by atrial fibrillation, chest infection, pleural effusions, acute kidney injury and delirium. DISCUSSION: Hepatic metastases cause systemic hormones' secretion, which cause a carcinoid crisis. Perioperative administration of octreotide is used, while vigilance is required to differentiate between hemodynamic effects related to the operation or disease specific factors. CONCLUSION: No carcinoid crisis was evident perioperatively. High vigilance with appropriate monitoring, aggressive management combined with meticulous choice of pharmaceutical agents led to this outcome.

Post-Operative Thoracic Epidural Analgesia and Incidence of Major Complications according to Specific Safety Standardized Documentation: A Large Retrospective Dual Center Experience.

(1) Background: Thoracic epidural analgesia is considered the gold standard in post-operative pain management following thoracic surgery. This study was designed to explore the safety of thoracic epidural analgesia and to quantify the incidence of its post-operative complications and side effects in patients undergoing thoracotomy for major surgery, such as resection of lung malignancies and lung transplantation. (2) Methods: This is a retrospective, dual-center observational study including patients that underwent major thoracic surgery including lung transplantation and received concurrent placement of thoracic epidural catheters for post-operative analgesia. An electronic system of referral and documentation of complications was used, and information was retrieved from our electronic critical care charting system. (3) Results: In total, 1145 patients were included in the study. None of the patients suffered any major complication, including hematoma, abscess, or permanent nerve damage. (4) Conclusions: the present study showed that in experienced centers, post-operative epidural analgesia in patients with thoracotomy is a safe technique, manifesting minimal, none-serious complications.

Temporal Trends in Diagnostic Hemodynamics and Survival of Patients with Pulmonary Hypertension: A Single-Center Study.

Advances in the diagnosis and treatment of pulmonary hypertension (PH) have gradually improved the disease course. This retrospective cohort study aims to explore the diagnostic hemodynamic profile and survival of PH patients and their temporal changes, as well as investigate potential prognostic factors. Overall, 257 adult patients were diagnosed with PH following right heart catheterization (RHC) from January 2008 to June 2023 according to the hemodynamic cut-off values proposed by the corresponding ESC/ERS guidelines at the time RHC was performed. Of these patients, 46.3% were Group 1, 17.8% Group 2, 14.0% Group 3, 18.0% Group 4, and 3.0% Group 5 PH. Temporal improvement in both diagnostic hemodynamic profile and survival of patients with PH and pulmonary arterial hypertension (PAH) was identified after 2013. Survival analysis demonstrated 5-year survival rates of 65% in Group 1 PH (90.3% in idiopathic PAH) and 77% in Group 4 PH. PAH patients being at low risk at diagnosis presented a similar 1-year all-cause mortality rate (12.4%) with high-risk ones (12.8%), primarily due to non-PH-related causes of death (62%), while high-risk patients died mostly due to PH (67%). The observed improvements in diagnostic hemodynamic profiles and overall survival highlight the importance of timely diagnosis and successful treatment strategies in PH.

Haemodynamic effects of initial combination therapy in pulmonary arterial hypertension: a systematic review and meta-analysis.

Background: Although the initial use of combination treatment has been proven to be beneficial for patients' clinical outcomes, there are scarce data on its haemodynamic effects. The objective of the present study was to evaluate the effect of an initial combination of pulmonary arterial hypertension (PAH)-targeted therapies on haemodynamic parameters in treatment-naïve PAH patients. Methods: A systematic search of PubMed, Cochrane Central Register of Controlled Trials and Web of Science was performed. We considered eligible studies with an intervention of initial PAH-targeted combination therapy in treatment-naïve PAH patients with or without monotherapy control. A random-effects meta-analysis was performed for the difference between baseline and follow-up in pulmonary vascular resistance (PVR) and other haemodynamic parameters. Results: In 880 patients receiving initial combination therapy PVR was reduced by -6.5 Wood Units (95% CI -7.4--5.7 Wood Units) or by -52% (95% CI -56%--48%, I2=0%) compared to baseline. Initial triple therapy including a parenteral prostanoid resulted in significantly greater PVR reduction (-67% versus -50% with all other combination therapies, p=0.01). The effect was more pronounced in younger patients (p=0.02). Compared to baseline, there was -12.2 mmHg (95% CI -14.0--10.4 mmHg) decrease in mean pulmonary artery pressure, 0.9 L·min-1·m-2 (95% CI 0.8-1.1 L·min-1·m-2) increase in cardiac index, -3.2 mmHg (95% CI -4.1--2.3 mmHg) decrease in right atrial pressure and 8.6% (95% CI 6.9-10.3%) increase in mixed venous oxygen saturation. In the controlled studies, initial combination therapy reduced PVR by -4.2 Wood Units (95% CI -6.1--2.4 Wood Units) compared to monotherapy. Conclusion: Initial combination therapy leads to remarkable haemodynamic amelioration. Parenteral prostanoids should be considered early, especially in more severely affected patients, to enable right ventricular reverse remodelling.

Balloon Pulmonary Angioplasty in Patients with Chronic Thromboembolic Pulmonary Hypertension in Greece: Data from the Hellenic Pulmonary Hypertension Registry.

Balloon pulmonary angioplasty (BPA) is a novel and promising treatment option for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are ineligible for pulmonary endarterectomy (PEA) and for those with persistent or recurrent pulmonary hypertension after PEA. We present the results of BPA procedures in CTEPH patients included in the Greek Pulmonary Hypertension Registry, evaluating the real-life efficacy and safety. We analyzed data from 180 BPA procedures (2−17/patient, mean 8 ± 4/patient, 1248 dilated vessels, 0−18/session). Significant improvements were observed in mean pulmonary arterial pressure (a reduction by 44%, p < 0.001), pulmonary vascular resistance (reduction by 60%, p < 0.001), and NT-proBNP (decrease by >70%, p: 0.003), while cardiac index improved modestly (9% increase, p = 0.143). We had 37 BPA-related non-fatal complications (20.6% in all interventions), predominantly including hemoptysis. Overall survival was 91%, 75% and 62% at 3, 4 and 5 years, respectively. Therefore, BPA may be a promising therapeutic option in patients with CTEPH in Greece.

Long-Term Effect of an Exercise Training Program on Physical Functioning and Quality of Life in Pulmonary Hypertension: A Randomized Controlled Trial.

The aim of this study was to evaluate the effects of a 6-month combined aerobic and strength exercise training program on functional and psychological aspects and health-related quality of life in patients with PH and to evaluate its longer-term impact. In total, 22 stable patients (mean age 53.9 ± 13.8, 13 female) with pulmonary hypertension of World Health Organization (WHO) class I-III participated in a nine-month study. They were randomly assigned into two groups: Group A participated in a 6-month combined aerobic and strength exercise training program, whereas Group B remained untrained. All patients underwent physical and psychological assessment at baseline and at month 6 (after completing the exercise program) and physical assessment after 9 months (3 months posttraining). After the 6-month exercise training program, patients of Group A significantly improved their physical (6MWD, STS 10 rep, STS 20 rep, TUG, lower limb strength, cardiopulmonary exercise time, METs, peak VO2, VCO2, and VE/VCO2 slope) and psychological aspects (SF-36, STAI, and BDI). Between the two groups, differences were observed at the 6MWD (95% CI: 36.2-64.6, η 2 = 0.72), STS 10 rep (95% CI: 6.6-2.2, η 2 = 0.4), STS 20 rep (95% CI: 10.8-2.4, η 2 = 0.34), lower limb strength (95% CI: 7.2-3.6, η 2 = 0.38), cardiopulmonary exercise time (95% CI: 0.1-3.3, η 2 = 0.2), and VCO2 (95% CI: 0.1-0.5, η 2 = 0.2). Additionally, psychological changes were noted at SF-36, PCS (95% CI: 3.6-14.8, η 2 = 0.35), MCS (95% CI: 1.3-16.1, η 2 = 0.22), TCS (95% CI: 1.3-16.1, η 2 = 0.22), and STAI (95% CI: 1.8-28.2, η 2 = 0.18). The favorable results of exercise were maintained at the 3-month posttraining follow-up assessment. No exercise-induced complications were observed throughout the study. In conclusion, a long-term exercise training program is a safe and effective intervention to improve functional status, psychological aspects, and health-related quality of life in patients with PH.

Prediction Models and Scores in Pulmonary Hypertension: A Review.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a serious disease with increased morbidity and mortality. The need for an individualized patient treatment approach necessitates the use of risk assessment in PAH patients. That may include a range of hemodynamic, clinical, imaging and biochemical parameters derived from clinical studies and registry data. OBJECTIVE: In the current systematic review, we summarize the available data on risk prognostic models and scores in PAH and we explore the possible concordance amongst different risk stratification tools in PAH. METHODS: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines aided the performance of this systematic review. Eligible studies were identified through a literature search in the electronic databases PubMed, Science Direct, Google Scholar and Cochrane with the use of various combinations of MeSH and non-MeSH terms, with a focus on PAH. RESULTS: Overall, 25 studies were included in the systematic review; out of them, 9 were studies deriving prognostic equations and risk scores and 16 were validating studies of an existing score. The majority of risk stratification scores use hemodynamic data for the assessment of prognosis, while others also include clinical and demographic variables in their equations. The risk discrimination in the overall PAH population was adequate, especially in differentiating the low versus high-risk patients, but their discrimination ability in the intermediate groups remained lower. Current ESC/ERS proposed risk stratification score utilizes a limited number of parameters with prognostic significance, whose prognostic ability has been validated in European patient populations. CONCLUSION: Despite improvement in risk estimation of prognostic tools of the disease, PAH morbidity and mortality remain high, necessitating the need for the risk scores to undergo periodic re-evaluation and refinements to incorporate new data into predictors of disease progression and mortality and, thereby, maintain their clinical utility.

Rationale and design of a prospective, observational, multicentre study on the safety and efficacy of apixaban for the prevention of thromboembolism in adults with congenital heart disease and atrial arrhythmias: the PROTECT-AR study.

INTRODUCTION: The risk for stroke in adults with congenital heart disease (ACHD) is increased, especially in the setting of commonly ensuing atrial arrhythmias (AA), namely atrial fibrillation, atrial flutter or intra-atrial re-entrant tachycardia. Data are limited regarding treatment with non-vitamin K oral anticoagulants in long-term studies involving patients with ACHD and AA. METHODS AND ANALYSIS: PReventiOn of ThromboEmbolism in Adults with Congenital HearΤ disease and Atrial aRrhythmias is a prospective, multicenter, single-arm, non-interventional cohort study designed to investigate the safety and efficacy of apixaban for the prevention of thromboembolism in ACHD with AA in a 'real-world' setting. Eligible patients will be evaluated by the means of available registries and clinical counter. The study aims to accumulate approximately 500 patient-years of exposure to apixaban as part of routine care. Enrolment will take place at four ACHD centres in Greece. The first patient was enrolled in July 2019. The primary efficacy endpoint is a composite of stroke, systemic or pulmonary embolism and intracardiac thrombosis. The primary safety endpoint is major bleeding, according to the International Society on Thrombosis and Haemostasis bleeding criteria. ETHICS AND DISSEMINATION: The study protocol has been approved by the institutional review board/independent ethics committee at each site prior to study commencement. All patients will provide written informed consent. Results will be disseminated at scientific meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03854149; Pre-results.

Development of Cognitive and Physical Exercise Systems, Clinical Recordings, Large-Scale Data Analytics, and Virtual Coaching for Heart Failure Patients: Protocol for the BioTechCOACH-ForALL Project.

BACKGROUND: Heart failure is a chronic disease affecting patient morbidity and mortality. Current guidelines for heart failure patient treatment are focused on improving their clinical status, functional capacity, and quality of life. However, these guidelines implement numerous instructions including medical treatment adherence, physical activity, and self-care management. The complexity of the therapeutic instructions makes them difficult to follow especially by older adults. OBJECTIVE: The challenge of this project is to (1) measure real-life adherence to a regular physical exercise program and (2) attempt to influence older adult patients with heart failure toward embracing a more physically active self-care lifestyle. METHODS: This research consists of two studies, including a lab experiment and a pragmatic evaluation of technology at patients' homes. The lab experiment aims at exploring in an objective way (measuring neurophysiological responses to stimuli) patient engagement with different characteristics of virtual agents, while the home study is a 3-phase prospective study where the developed technology platform is tested by heart failure patients in their own home environments. Patients undergo evaluation of their physical activity and cognitive status using standard evaluation methods (6-minute walk test, questionnaires) and receive wearable devices to accurately measure everyday life activity levels (home study phases 1-3). During home study phases 2 and 3, exergames (serious games for physical exercise) to provide a physical exercise plan as a joyful activity are delivered to patients' private households and e-coaching techniques are implemented in the final phase (home study phase 3) of the protocol, to influence patient attitudes toward a more healthy and recommended lifestyle. RESULTS: The trial is still ongoing. Recruitment is ongoing, and the project has progressed for some participants through phase 2 of the home study. The sample size for both studies is 28 participants; 10 have already been included in the study, and both baseline clinical and patient-reported outcome data are retrieved. Phases 2 and 3 of the home pilot study are expected to be completed within 6 months. CONCLUSIONS: The main challenge of the project is the change of attitude of older age heart failure patients through an e-coaching system. Given the adoption of a cocreation and living lab approach and the main objective for real-life evaluation, the project is ready to react to any collected feedback, even during the implementation of the research plan. Clinical assessment and objective evaluation are expected to provide all required information for reliable findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT03877328; https://clinicaltrials.gov/ct2/show/NCT03877328. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/17714.

Transition protocol from subcutaneous treprostinil to intravenous epoprostenol in deteriorating patients with pulmonary arterial hypertension.

BACKGROUND: Despite advantages in the treatment options of pulmonary arterial hypertension, continuous parenteral prostanoid administration, although often complicated by serious side effects, remains the treatment of choice for patients with advanced disease. The need of transitioning from one parenteral prostanoid agent to the other is often faced in the daily clinical practise. Up to today, there is no established transition protocol from subcutaneous treprostinil to intravenous epoprostenol. METHODS: A staggered approach to subcutaneous treprostinil down-titration with simultaneous epoprostenol up-titration is described. Subcutaneous treprostinil is down-titrated by 5 ng/kg/min every 5 h while intravenous epoprostenol is up-titrated by 2 ng/kg/min every 2 h. RESULTS: The designed protocol was implemented in 4 patients with pulmonary arterial hypertension (3 women, median age 70.5 (range 38-79) years). Median starting subcutaneous treprostinil dose was 44.5 (range 37-100) ng/kg/min and median treprostinil down-titration time was 32.5 (range 25-85) hours. The median maximal epoprostenol dose was 36 (range 28-90) ng/kg/min, achieved in 36 (range 30-90) hours. Only mild prostanoid-related side effects were reported. CONCLUSIONS: The proposed staggered transition protocol from subcutaneous treprostinil to intravenous epoprostenol was safe in a limited number of patients with pulmonary arterial hypertension.

Duration of interventricular septal shift toward the left ventricle is associated with poor clinical outcome in precapillary pulmonary hypertension: A cardiac magnetic resonance study.

BACKGROUND: Right ventricular pressure overload results in interventricular septal shift toward the left ventricle in patients with precapillary pulmonary hypertension (PH). We aimed to investigate the predictive role of the duration of septal curvature configuration during the cardiac cycle, as expressed by the novel marker curvature duration index (CDi) in precapillary PH. METHODS: This was a prospective study. All patients underwent cardiac magnetic resonance (CMR). CDi was defined by the number of CMR frames in which septal curvature configuration toward left ventricle is observed *100/total number of frames per cardiac cycle. Time from enrollment to first clinical failure event (death, hospitalization due to PH, and disease progression) was recorded. RESULTS: The study included 36 patients with precapillary PH. During a median follow-up of 20 months (IQR 4-37 months), 14 clinical failure events were observed. Survival ROC analysis showed that the optimal cutoff value of CDi, which predicted clinical failure, was 67%. Kaplan-Meier survival analysis showed that CDi≥67% was associated with a 9.4-fold increase in the risk for clinical failure. Addition of CDi to baseline models including six-minute walk test distance (c-statistic = 0.65 vs. c-statistic = 0.79), NT-proBNP (c-statistic = 0.72 vs. c-statistic = 0.83), and WHO functional class (c-statistic = 0.76 vs. c-statistic = 0.81) improved risk stratification. CONCLUSION: Ventricular septal shift toward the left ventricle lasting for more than the two thirds of the cardiac cycle is associated with worse prognosis in precapillary PH.

Quality of Life is Related to Haemodynamics in Precapillary Pulmonary Hypertension.

BACKGROUND: Precapillary pulmonary hypertension (PH) is characterised by compromised functional capacity and impaired quality of life. Assessment of haemodynamics is routinely used for initial diagnosis, follow-up, and risk stratification in these patients. The purpose of this study was to investigate the relation of health-related quality of life (HRQoL) as assessed by emPHasis-10 score, a self-assessment questionnaire assessing breathlessness, fatigue, control, and confidence, to haemodynamic and neurohormonal indices in patients with precapillary PH. METHOD: This was a prospective cross-sectional study which included stable patients with precapillary PH. All patients underwent right heart catheterisation, 6-minute walk test, N-terminal pro-brain natriuretic peptide (NT-proBNP) measurement, and assessment of HRQoL with the emPHasis-10 scale. RESULTS: Overall, 54 patients were included (32 women; mean age, 58.4 ± 14.6 yr). Mean emPHasis-10 score was 19.2 ± 12.0. EmPHasis-10 score correlated with World Health Organization functional class (r = 0.52, p < 0.001), 6-minute walk distance (r=-0.56, p < 0.001), and log10(NT-proBNP) (r = 0.41, p < 0.01). A positive correlation of emPHasis-10 score with mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) and a negative correlation with mixed venous oxygen saturation and cardiac index was observed, after adjustment for age, sex, body mass index, and PH group. In a subgroup analysis of patients with pulmonary arterial hypertension (n = 34) there was a stronger correlation of emPHasis-10 score with mPAP (r = 0.86, p < 0.001) and PVR (r = 0.69, p < 0.01), but no correlation with cardiac index and mixed venous oxygen saturation. CONCLUSIONS: Self-assessment of quality of life with the use of the emPHasis-10 score reflects functional capacity and is correlated with haemodynamic and neurohormonal indices of right heart dysfunction in patients with precapillary PH.

Right Atrial Function Predicts Clinical Outcome in Patients with Precapillary Pulmonary Hypertension.

BACKGROUND: Although the primary role of right atrial (RA) size in the diagnosis and risk stratification of precapillary pulmonary hypertension (PH) has been studied, little is known about the clinical significance of RA function. In line with studies assessing left atrial function in heart failure, the aim of this study was to introduce the RA function index (RAFi) and to explore its prognostic power in precapillary PH. METHODS: RA emptying fraction was calculated as (RA end-systolic volume - RA end-diastolic volume) × 100/(RA end-systolic volume). RAFi was calculated as (RA emptying fraction × right ventricular outflow tract velocity-time integral)/(RA end-systolic volume index). Patients were followed for the end point of clinical failure, which was defined as death, hospitalization because of PH, or disease progression. RESULTS: In total, 47 patients with precapillary PH were included. Mean RAFi was 16.1 ± 22.3%. Over a median follow-up period of 25 months (interquartile range, 9.5-41.1 months), 29 patients experienced clinical failure. Univariate Cox proportional-hazard analysis showed that RAFi was a predictor of clinical failure (hazard ratio, 0.935; 95% CI, 0.890-0.981; P = .007). Addition of RAFi to established predictors of outcomes, including 6-minute walk distance, N-terminal pro-B-type natriuretic peptide, and RA area, improved their prognostic power. CONCLUSIONS: RAFi is an easily assessed echocardiographic parameter, which is strongly predictive of clinical outcomes in patients with precapillary PH. Further studies are needed to validate RAFi and define its role in clinical practice.

Epidemiology and management of chronic thromboembolic pulmonary hypertension: experience from two expert centers.

OBJECTIVES: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, distinct pulmonary vascular disease, and therefore, there is a lack of data regarding its clinical presentation, diagnosis, and management at a national basis. We aimed to describe the demographics and management of patients with CTEPH in Northern Greece. METHODS: We conducted a retrospective, observational study by a joint collaboration between two pulmonary hypertension expert centers in Greece, and the study included patients diagnosed with CTEPH. The patient population was divided into two groups depending on their operability. RESULTS: Overall, 27 consecutive patients were included (59% female, mean age 59.3±15.1 years). Dyspnea and fatigue were the most common presenting symptoms. History of pulmonary embolism was present in 82%. Of patients, 18 (67%) were assessed as operable, of whom 10 (55%) finally underwent pulmonary endarterectomy (PEA). There were no differences in symptoms, WHO functional class, 6-min walking test distance, and hemodynamics between the operable and nonoperable groups. At the end of follow-up, all non-operable and operable patients who did not receive surgical treatment were treated with at least one pulmonary hypertension-specific drug. CONCLUSION: This is the first report that presents data of patients diagnosed with CTEPH in Greece. The percentage of patients who underwent surgical treatment is lower but approaches the reported rates in large registries. Considering that PEA is a relatively safe and potentially curative surgical procedure, we emphasize the need for establishing a designated PEA center in Greece.

Atrial septostomy and disease targeting therapy in pulmonary hypertension secondary to neurofibromatosis.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a rare multisystem genetic disorder. During the course of the disease it can be rarely complicated with pulmonary hypertension (PH) which confers a dismal prognosis. CASE PRESENTATION: We describe the case of a 57-year-old female patient with NF1 complicated by severe precapillary PH despite dual disease-specific oral combination therapy. The patient was treated with initial atrial septostomy followed by administration of high-dose subcutaneous treprostinil with a favorable medium-term clinical and hemodynamic response. CONCLUSIONS: PH secondary to NF1 may be successfully treated with the combination of atrial septostomy and PH targeted therapy in selected patients.

Intra--and Intercellular Calcium Handling in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a serious life threatening disease that leads to right heart failure and death. Elevated pulmonary vascular resistance (PVR) is the main pathophysiological component that leads to elevated pulmonary arterial pressures and increased right ventricular afterload. Increased PVR is related to different mechanisms that include vasoconstriction, proliferative and obstructive remodeling of the pulmonary vessel wall and in situ thrombosis. Numerous molecular, genetic and humoral abnormalities have been proposed to play an important role in pulmonary vasoconstriction and remodeling. Of those, calcium (Ca(+2)) is a well recognized parameter involved in the pathogenetic mechanisms of PAH, because of its twofold role in both vasoconstriction and pulmonary artery smooth muscle cell (PASMC) proliferation. The aim of this review is to focus on Ca(+2) handling and dysregulation in PASMC of PAH patients.