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Hyponatremia is a frequent electrolyte disorder. It is often found in congestive cardiac failure, liver cirrhosis, plasma volume contraction and in SiADH. In these disorders hyponatremia is caused by nonosmotic vasopressin and sustained fluid intake. This provides a rationale for V2 vasopressin receptor antagonists in the treatment of hyponatremia. There is now convincing evidence from different animal models of congestive cardiac failure that peptide and non-peptide V2 vasopressin antagonists effectively increase renal water diuresis and plasma sodium concentration. In addition, several of the experimental studies also showed an improvement of hemodynamic changes of cardiac failure in response to V2 antagonists. Data in patients indicated that oral non-peptide V2-antagonists correct hyponatremia and may improve hemodynamic derangements in cardiac failure. In addition, experimental and clinical studies of V2 antagonists have been undertaken in liver cirrhosis and SiADH. In those studies hyponatremia was improved or corrected, too. Taken together, V2 vasopressin antagonists promise to become therapeutic agents in hyponatremic disorders. [ABSTRACT FROM PUBLISHER]

Chronic heart failure is one of the most debilitating chronic conditions affecting millions of people and adding a significant financial burden to health care systems worldwide. Despite the significant therapeutic advances achieved over the last decade, morbidity and mortality remain high. Multiple catheter-based interventional therapies targeting different physiological and anatomical targets are already under different stages of clinical investigation. The present paper provides a technical overview of the most relevant catheter-based interventional therapies under clinical investigation., Competing Interests: Dr Latib has served as a consultant and/or on the advisory board of Medtronic, Abbott, Boston Scientific, Edwards Lifesciences, Neochord, Nuvera, Supira, and Coramaze. Dr Burkhoff has received institutional research grant support from Ancora Heart; and received consultant fees from preCARDIA, Revamp Medical, and Corvia Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

Background: Although balloon pulmonary angioplasty (BPA) improves symptoms and pulmonary hemodynamics in patients with chronic thromboembolic pulmonary hypertension (CTEPH), the effects of riociguat on hemodynamics and exercise capacity in patients after BPA remain to be elucidated., Methods and Results: This study was a single-center, prospective, randomized, open-label trial. From November 2015 to November 2018, we prospectively examined 21 patients with CTEPH (65 ± 9 years old, M/F 2/19) who showed hemodynamic improvement with mean pulmonary arterial pressure (mPAP) < 30 mmHg after BPA without any vasodilators. We performed hemodynamic evaluation and expired gas analysis both at rest and during exercise in supine position using cycle ergometer. After right heart catheterization during exercise, they were randomly assigned to 2 groups with minimized method, using age, sex, and resting mPAP; riociguat (N = 10) and control (N = 11) groups. After 6 months, exercise capacity evaluated by 6-min walk distance and cardiopulmonary exercise testing, and resting hemodynamic parameters were comparable in both groups. However, cardiac output (CO) (6.0 ± 1.7-7.4 ± 1.6, P < 0.01) and pulmonary vascular resistance (4.8 ± 1.8-3.2 ± 0.7 Wood units, P = 0.02) at peak workload were significantly improved in the riociguat group as compared with the control group. The slope of linearized mPAP-CO relationship was significantly decreased in the riociguat group [14.5 (7.8, 14.7) to 6.41 (5.1, 11.4), P < 0.01] but not in the control group., Conclusions: These results indicate that riociguat exerts beneficial effects on hemodynamic response to exercise in CTEPH patients even after hemodynamic improvement by BPA., (© 2020 The Author(s).)

Objective: The current experience with combination therapy in chronic thromboembolic pulmonary hypertension (CTEPH) is limited. We present the first survival results up to 5 years for dual combination therapy versus monotherapy in CTEPH., Methods: All consecutive, non-operated CTEPH or residual PH after pulmonary endarterectomy patients treated with PH-specific medical therapy between January 2002 and November 2019 were included. We report and compare survival between monotherapy and (upfront or sequential) dual combination therapy until five years after medication initiation., Results: In total, 183 patients (mean age 65 ± 14 years, 60% female, 66% WHO FC III/IV, 86% non-operated) were included, of which 83 patients received monotherapy and 100 patients received dual combination therapy. At baseline, patients receiving combination therapy had a higher NT-proBNP (p = 0.02) mean pulmonary artery pressure (p = 0.0001) and pulmonary vascular resistance (p = 0.02), while cardiac index was lower (p = 0.03). Total follow-up duration was 3.3 ± 1.8 years, during which 31 (17%) patients died. Estimated 1-, 3- and 5-year survival for monotherapy were 99%, 92% and 79%, respectively. For combination therapy percentages were 98%, 89% and 70%, respectively. Survival did not significantly differ between both groups (p = 0.22)., Conclusion: Survival up to 5 years for patients treated with combination therapy, regardless of the combination strategy, was similar as patients with monotherapy, despite worse clinical and haemodynamic baseline characteristics., (© 2020 The Authors.)

Background: Several cardiopulmonary exercise test (CPET) parameters (peak VO 2 , PetCO 2 and VE/VCO 2 ) emerged as tools for the prediction of pulmonary arterial hypertension (PAH). Less is known on ventilatory power (VP) in patients with suspect PAH., Aim: To ascertain possible correlations between VP derived at CPET and hemodynamic parameters at right heart catheterization (RHC) indicative of PH., Methods: Forty-seven consecutive outpatients with suspect of PAH were assessed by CPET and RHC; VP was defined as peak SBP divided by the minute ventilation-CO2 production slope at CPET and Diastolic Pressure Gradient (DPG), Trans-pulmonary Pressure Gradient (TPG), mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) at RHC were also assessed and compared with VP., Results: VP values were inversely related to mPAP (r -0.427, p 0.003), DPG (r -0.36, p 0.019), TPG (r: -0.43, p 0.004), and PVR (r -0.52, p 0.001). Correlations remained significant even after correction at multivariate analysis for age and gender. VP values below median identified subjects with mPAP ≥ 25 mmHg with an odds ratio of 4.5 (95% confidence interval 1.05-19.36, p < 0.05), an accuracy of 0.712 at ROC curve analysis (95% confidence interval 0.534-0.852, p < 0.05) and a positive predictive power 82%., Conclusions: In patients with suspected PAH, VP assessed at CPET might provide further information in predicting PAH at RHC. Correlations with PVR and DPG may be helpful in differentiating patients with isolated post-capillary PH from those with combined post-capillary and pre-capillary., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.)

Objective: To evaluate the safety and efficacy of balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) seen at a US medical center., Patients and Methods: Patients with inoperable or residual postendarterectomy CTEPH who underwent BPA at Mayo Clinic in Rochester, Minnesota, between August 11, 2014, and May 17, 2018, were included. Invasive hemodynamic, clinical, laboratory, and echocardiographic data were collected and analyzed retrospectively., Results: We identified 31 patients (26 with inoperable CTEPH and 5 with residual postendarterectomy CTEPH) who underwent 75 BPA procedures performed in a staged manner to reduce complications. The median number of sessions was 2 (interquartile range [IQR], 1-3) per patient, and the number of vessels treated per session was 3 (IQR, 2-3). Of the 31 patients, 24 (77.4%) were taking pulmonary vasodilators and 22 (71.0%) were taking riociguat. The mean pulmonary arterial pressure decreased from 40 mm Hg (IQR, 29-48 mm Hg) to 29 mm Hg (IQR, 25-37 mm Hg; P <.001); pulmonary vascular resistance decreased from 5.5 Wood units (WU) (IQR, 3.0-7.6 WU) to 3.3 WU (2.2-5.2 WU; P <.001). The follow-up 6-minute walk test was performed in 13 patients and improved from 402 m (IQR, 311-439 m) to 439 m (366-510 m; P =.001). Of the 31 patients, 19 (61.3%) had improvement in New York Heart Association functional class. The mean ± SD nadir of minute ventilation/carbon dioxide production decreased by 3.4±5.5 ( P =.03), reflecting improved ventilatory efficiency. Complications included hemoptysis requiring overnight intensive care unit observation (n=1) and cardiac tamponade requiring pericardiocentesis (n=1). One patient had reperfusion injury requiring intubation, recovered, and was dismissed to home but died unexpectedly within less than 30 days of the procedure. Serious complications occurred in 3 of the 75 BPA procedures (4.0%)., Conclusion: Our experience with BPA revealed that this procedure has acceptable risk and improves hemodynamics, functional class, and exercise tolerance in patients with inoperable or residual CTEPH.

Background: The presence of left ventricular diastolic dysfunction (LVDD) in patients with cirrhosis leads to a restriction of activities and a poor health related quality of life (HRQoL), which should be taken into consideration when treating them for liver and cardiac complications., Aims: The prevalence, complications, predictors of HRQoL and survival in cirrhotic patients with LVDD were studied., Methods: We report a prospective cohort study of 145 consecutive cirrhotic patients with LVDD who were evaluated for cardiac functional status at enrollment and followed up for hepatic complications, cardiac events, outcome and HRQoL using the Minnesota Living With Heart Failure Questionnaire (MLHFQ) over a period of 2 years., Results: In total, 145 (mean age 61 years, 59% male) patients were included. Seventeen patients died with 10.5%, 22.5% and 40% mortality rates in patients with Grades 1, 2 and 3 LVDD respectively over 24 months. The parameters that were significant for predicting mortality on bivariate analysis were MELD, MELDNa, hepatic venous pressure gradient, MLHFQ, and left ventricular (LV) diastolic function (e' and E/e' ratio), but only MELD, MELDNa and E/e' remained significant on multivariate analysis. The E/e' ratio (8.7 ± 3.3 in survivors vs. 9.1 ± 2.3 in non-survivors) predicted outcome. On univariate analysis, the predictors of poor HRQoL were the Child-Pugh score ≥9.8 (OR 2.6; 95% confidence intervals (CI) 2.3-9.1, P  = 0.041), MELD score ≥ 15.7 (OR 2.48; 95% CI 1.4-3.9, P  = 0.029), refractory ascites (OR 1.9; 95% CI 1.1-6.1, P  = 0.050), and E/e' ratio ≥7.6 (OR 1.9; 95% CI 1.8-7.1, P  = 0.036) The presence of Class II/III ( P  = 0.046) symptoms of heart failure and MLHFQ≥ 45 ( P  = 0.042) were predictors of mortality at 24 months., Conclusion: The grade of LVDD correlates with liver function, clinical events, risk of renal dysfunction and HRQoL. Evaluation of novel therapies which target symptomatic improvement in LVDD, should be done with suitable outcome measures, including HRQoL assessment.

Background: To improve clinical outcome, patients with inoperable and residual chronic thromboembolic pulmonary hypertension (CTEPH) can be treated with riociguat. The aim of this study is to explore long-term outcomes and to compare our 'real world' data with previous research., Methods: We included all consecutive patients with technical inoperable and residual CTEPH, in whom riociguat therapy was initiated from January 2014 onwards, with patients followed till January 2019. Survival, clinical worsening (CW), functional class (FC), N-terminal pro brain natriuretic peptide (NT-proBNP) and 6-minute walking distance (6MWD) were described yearly after riociguat initiation., Results: Thirty-six patients (50% female, mean age 64.9 ± 12.1 years, 54% WHO FC III/IV and 6MWD 337 ± 138 m could be included, with a mean follow-up of 2.3 ± 1.2 years. Survival and CW-free survival three years after initiation of riociguat were 94% and 78%, respectively. The 6MWD per 10 m at baseline was a significant predictor (HR 0.90 [0.83-0.97], p  = 0.009) for CW. At three years follow-up the WHO FC and 6MWD improved and NT-proBNP decreased compared to baseline., Conclusion: Our study confirms that riociguat is an effective treatment in patients with technical inoperable and residual CTEPH at long-term follow-up. Although our results are consistent with previous studies, more 'real world' research is necessary to confirm long-term results.