Regional extracellular volume within late gadolinium enhancement-positive myocardium to differentiate cardiac sarcoidosis from myocarditis of other etiology: a cardiovascular magnetic resonance study.

BACKGROUND: Cardiovascular magnetic resonance (CMR) plays a pivotal role in diagnosing myocardial inflammation. In addition to late gadolinium enhancement (LGE), native T1 and T2 mapping as well as extracellular volume (ECV) are essential tools for tissue characterization. However, the differentiation of cardiac sarcoidosis (CS) from myocarditis of other etiology can be challenging. Positron-emission tomography-computed tomography (PET-CT) regularly shows the highest Fluordesoxyglucose (FDG) uptake in LGE positive regions. It was therefore the aim of this study to investigate, whether native T1, T2, and ECV measurements within LGE regions can improve the differentiation of CS and myocarditis compared with using global native T1, T2, and ECV values alone. METHODS: PET/CT confirmed CS patients and myocarditis patients (both acute and chronic) from a prospective registry were compared with respect to regional native T1, T2, and ECV. Acute and chronic myocarditis were defined based on the 2013 European Society of Cardiology position paper on myocarditis. All parametric measures and ECV were acquired in standard fashion on three short-axis slices according to the ConSept study for global values and within PET-CT positive regions of LGE. RESULTS: Between 2017 and 2020, 33 patients with CS and 73 chronic and 35 acute myocarditis patients were identified. The mean ECV (± SD) in LGE regions of CS patients was higher than in myocarditis patients (CS vs. acute and chronic, respectively: 0.65 ± 0.12 vs. 0.45 ± 0.13 and 0.47 ± 0.1; p < 0.001). Acute and chronic myocarditis patients had higher global native T1 values (1157 ± 54 ms vs. 1196 ± 63 ms vs. 1215 ± 74 ms; p = 0.001). There was no difference in global T2 and ECV values between CS and acute or chronic myocarditis patients. CONCLUSION: This is the first study to show that the calculation of regional ECV within LGE-positive regions may help to differentiate CS from myocarditis. Further studies are warranted to corroborate these findings.

Patient-Reported Long-Term Outcome of Balloon Pulmonary Angioplasty for Inoperable CTEPH.

BACKGROUND: Balloon pulmonary angioplasty (BPA) is a promising interventional treatment for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Evidence in favor of BPA is growing, but long-term data remain scarce. The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is validated for the assessment of patients with pulmonary hypertension within three domains: symptoms, activity, and quality of life (QoL). The aim of the present study was to evaluate the long-term effects of BPA on these domains in patients with inoperable CTEPH. METHODS: Between March 2014 and August 2019, technically inoperable patients with target lesions for BPA were included in this prospective, observational study. CAMPHOR scores were compared between baseline (before the first BPA) and 6 months after the last intervention and also for scores assessed at annual follow-ups. RESULTS: A total of 152 patients had completed a full series of BPA interventions and a 28 (interquartile range [IQR]: 26-32) week follow-up. Further follow-up assessments including the CAMPHOR score were performed 96 (IQR: 70-117) weeks, 178 (IQR: 156-200) weeks, and 250 (IQR: 237-275) weeks after the last intervention. From baseline to the last follow-up, CAMPHOR scores for symptoms, activity, and QoL improved from 9 (IQR: 6-14) to 3 (IQR: 0-9) (p < 0.001), 8 (IQR: 5-12) to 4 (IQR: 2-8) (p < 0.001), and 5 (IQR: 2-9) to 1 (IQR: 0-5) (p < 0.001). CONCLUSION: BPA leads to long-lasting, significant improvement of symptoms, physical capacity, and QoL in inoperable CTEPH patients.

Does Age Matter? Pulmonary Endarterectomy in the Elderly Patient with CTEPH.

BACKGROUND: The gold standard treatment of patients with chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary endarterectomy (PEA). Little is known about the influence of advanced age on surgical outcome. Therefore, the aim of this study was to investigate the impact of patient's age on postoperative morbidity, mortality, and quality of life in a German referral center. METHODS: Prospectively collected data from 386 consecutive patients undergoing PEA between 01/2014 and 12/2016 were analyzed. Patients were divided into three groups according to their age: group 1: ≤ 50 years, group 2: > 50 ≤ 70 years, group 3: > 70 years. RESULTS: After PEA, distinct improvements in pulmonary hemodynamics, physical capacity (World Health Organization [WHO] functional class and 6-minute walking distance) and quality of life were found in all groups. There were more complications in elderly patients with longer time of invasive ventilation, intensive care, and in-hospital stay. However, the in-hospital mortality was comparable (0% in group 1, 2.6% in group 2, and 2.1% in group 3 [p = 0.326]). Furthermore, the all-cause mortality at 1 year was 1.1% in group 1, 3.2% in group 2, and 6.3% in group 3 (p = 0.122). CONCLUSIONS: PEA is an effective treatment for CTEPH patients of all ages accompanied by low perioperative and 1-year mortality. CTEPH patients in advanced age carefully selected by thorough preoperative evaluation should be offered PEA in expert centers to improve quality of life, symptoms, and pulmonary hemodynamics.

CILP1 as a biomarker for right ventricular maladaptation in pulmonary hypertension.

The aim of our study was to analyse the protein expression of cartilage intermediate layer protein (CILP)1 in a mouse model of right ventricular (RV) pressure overload and to evaluate CILP1 as a biomarker of cardiac remodelling and maladaptive RV function in patients with pulmonary hypertension (PH).Pulmonary artery banding was performed in 14 mice; another nine mice underwent sham surgery. CILP1 protein expression was analysed in all hearts using Western blotting and immunostaining. CILP1 serum concentrations were measured in 161 patients (97 with adaptive and maladaptive RV pressure overload caused by PH; 25 with left ventricular (LV) hypertrophy; 20 with dilative cardiomyopathy (DCM); 19 controls without LV or RV abnormalities)In mice, the amount of RV CILP1 was markedly higher after banding than after sham. Control patients had lower CILP1 serum levels than all other groups (p<0.001). CILP1 concentrations were higher in PH patients with maladaptive RV function than those with adaptive RV function (p<0.001), LV pressure overload (p<0.001) and DCM (p=0.003). CILP1 showed good predictive power for maladaptive RV in receiver operating characteristic analysis (area under the curve (AUC) 0.79). There was no significant difference between the AUCs of CILP1 and N-terminal pro-brain natriuretic peptide (NT-proBNP) (AUC 0.82). High CILP1 (cut-off value for maladaptive RV of ≥4373 pg·mL-1) was associated with lower tricuspid annular plane excursion/pulmonary artery systolic pressure ratios (p<0.001) and higher NT-proBNP levels (p<0.001).CILP1 is a novel biomarker of RV and LV pathological remodelling that is associated with RV maladaptation and ventriculoarterial uncoupling in patients with PH.

Prospective validation of an acoustic-based system for the detection of obstructive coronary artery disease in a high-prevalence population.

Recent guidelines recommend a risk-adjusted, non-invasive work-up in patients presenting with chest discomfort to exclude coronary artery disease (CAD). However, a risk-adjusted diagnostic approach remains challenging in clinical practice. An acoustic detection device for analyzing micro-bruits induced by stenosis-generated turbulence in the coronary circulation has shown potential for ruling out CAD in patients with low-to-intermediate likelihood. We examined the diagnostic value of this acoustic detection system in a high-prevalence cohort. In total, 226 patients scheduled for clinically indicated invasive coronary angiography (ICA) were prospectively enrolled at two centers and examined using a portable, acoustic detection system. The acoustic analysis was performed in double-blinded fashion prior to quantitative ICA and following percutaneous coronary intervention (PCI). An acoustic detection result (CAD score) was obtained in 94% of all patients. The mean baseline CAD score was 41.2 ± 11.9 in patients with obstructive CAD and 33.8 ± 13.4 in patients without obstructive CAD (p < 0.001). ROC analysis revealed an AUC of 0.661 (95% CI 0.584-0.737). Sensitivity was 97.6% (95% confidence interval (CI) 91.5-99.7%), specificity was 14.5% (CI 9.0-21.7%), negative predictive value was 90.5% (CI 69.6-98.8%), and positive predictive value was 41.7% (CI 34.6-49.0%). Following PCI, the mean CAD score decreased from 40.5 ± 11.2 to 38.3 ± 13.7 (p = 0.039). Using an acoustic detection device identified individuals with CAD in a high-prevalence cohort with high sensitivity but relatively low specificity. The negative predictive value was within the predicted range and may be of value for a fast rule-out of obstructive CAD even in a high-prevalence population.

Pregnancy-associated plasma protein A - a new indicator of pulmonary vascular remodeling in chronic thromboembolic pulmonary hypertension?

BACKGROUND: In chronic thromboembolic pulmonary hypertension (CTEPH) impaired pulmonary hemodynamics lead to right heart failure. Natriuretic peptides reflect hemodynamic disease severity. Pregnancy-associated plasma protein-A (PAPP-A) might address another aspect of CTEPH - chronic tissue injury and inflammation. This study assessed dynamics of PAPP-A in CTEPH patients who undergo therapy with pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA). METHODS: The study included a total of 125 CTEPH patients scheduled for treatment (55 PEA/ 70 BPA) and a control group of 58 patients with pulmonary hypertension other than CTEPH. Biomarker measurement was performed at baseline and follow-up in the CTEPH cohort, prior to each BPA in the BPA cohort and once in the control group. RESULTS: The median PAPP-A level was slightly higher (p = 0.05) in CTEPH patients [13.8 (11.0-18.6) mU/L], than in the control group [12.6 (8.6-16.5) mU/L], without a difference between the BPA and PEA group (p = 0.437) and without a correlation to mean pulmonary artery pressure (p = 0.188), pulmonary vascular resistance (p = 0.893), cardiac index (p = 0.821) and right atrial pressure (p = 0.596). PEA and BPA therapy decreased the mean pulmonary artery pressure (p < 0.001) and pulmonary vascular resistance (p < 0.001) and improved the WHO-functional-class (baseline: I:0/II:25/III:80/IV:20 vs. follow-up: I:55/II:58/III:10/IV:2). PAPP-A levels decreased after PEA [13.5 (9.5-17.5) vs. 11.3 (9.8-13.6) mU/L; p = 0.003) and BPA treatment [14.3 (11.2-18.9) vs. 11.1 (9.7-13.3) mU/L; p < 0.001). The decrease of PAPP-A levels is delayed in comparison to N-terminal pro-B-type natriuretic peptide. CONCLUSION: PAPP-A is overexpressed in CTEPH and decrease significantly after surgical or interventional therapy, however without association to hemodynamics. Further investigation is needed to define the underlying mechanism of PAPP-A expression and changes after therapy in CTEPH.

Galectin-3, GDF-15, and sST2 for the assessment of disease severity and therapy response in patients suffering from inoperable chronic thromboembolic pulmonary hypertension.

PURPOSE: This study examined sST2, GDF-15, and galectin-3 as indicators of disease severity and therapy response in chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: This study included 57 inoperable CTEPH patients who underwent balloon pulmonary angioplasty and 25 controls without cardiovascular disease. Biomarker levels were examined in relation to advanced hemodynamic impairment [tertile with worst right atrial pressure (RAP) and cardiac index], hemodynamic therapy response [normalized hemodynamics (meanPAP ≤25 mmHg, PVR ≤3 WU and RAP ≤6 mmHg) or a reduction of meanPAP ≥25%; PVR ≥ 35%, RAP ≥25%]. RESULTS: GDF-15 [820 (556-1315) pg/ml vs. 370 (314-516) pg/ml; p < 0.001] and sST2 [53.7 (45.3-74.1) ng/ml vs. 48.7 (35.5-57.0) ng/ml; p = 0.02] were higher in CTEPH patients than in controls. At baseline, a GDF-15 level ≥1443 pg/ml (AUC 0.88; OR 31.4) and a sST2 level ≥65 ng/ml (AUC 0.80; OR 10.9) were associated with advanced hemodynamic impairment. At follow-up GDF-15 ≤ 958 pg/ml (AUC = 0.74, OR 18) identified patients with optimal hemodynamic therapy response and ≤760 pg/ml (AUC = 0.79, OR 14). CONCLUSION: GDF-15 and sST2 levels are higher in CTEPH and identified patients with advanced hemodynamic impairment. Further, decreased GDF-15 levels at follow-up were associated with hemodynamic therapy response. The diagnostic strength was not superior to NT-proBNP.

SPARCL1 as a biomarker of maladaptive right ventricular remodelling in pulmonary hypertension.

Aim: This study assessed the utility of SPARC-like protein 1 (SPARCL1) as a biomarker of maladaptive right ventricular (RV) function in patients with pulmonary hypertension (PH).Methods: In this prospective study, we examined SPARCL1 levels in 105 patients with adaptive (n = 34) and maladaptive RV (n = 32) pressure overload caused by PH, dilated cardiomyopathy (DCM, n = 18) with LVEF < 35% and preserved RV function and controls without LV or RV abnormalities (n = 21).Results: The median SPARCL1 concentration in patients with maladaptive RV function was higher than in those with adaptive RV function (p < 0.01), DCM (p < 0.001) or controls (p < 0.001). Patients with adaptive RV function had higher SPARCL1 concentrations than controls (p < 0.05), whereas there was no difference between adaptive RV and DCM. SPARCL1 showed good predictive power for maladaptive RV (AUC 0.77, p < 0.001) with an optimal cut-off value of 9.66 ng/ml. The TAPSE/PASP ratio was the only independent predictor of SPARCL1 ≥ 9.66 ng/ml in multivariable logistic regression analysis.Conclusion: SPARCL1 shows potential as novel biomarker of RV pathological remodelling and is associated with RV maladaptation and ventriculoarterial uncoupling in PH.

Development of renal function during staged balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension.

Balloon pulmonary angioplasty (BPA), for chronic thromboembolic pulmonary hypertension, improves pulmonary and systemic hemodynamics. The kidney might benefit from this effect. However, staged BPA therapy comes along with repetitive administration of contrast agent. This study examined the overall effect of BPA therapy on renal function. This study included consecutive patients who underwent BPA treatment and completed a 6-month follow-up between March 2014 and March 2017. Biomarker-based evaluation of renal function was performed at baseline, consecutively prior to and after each BPA and at 6-month follow-up. The 51 patients underwent an average of 5 (±2) BPA sessions. In this course, patients received 133 (±48; 21-300) mL of contrast agent per session and 691 (±24; 240-1410) mL during the whole sequence. Acute kidney injury occurred after 6 (2.3%) procedures. The creatinine [80.1 (IQR 67.8-96.8) µmol/L vs. 77.4 (IQR 66.9-91.5) µmol/L, p = .02] and urea level [13.7 (IQR10.7-16.6) mmol/L vs. 12.5 (IQR 10.0-15.5) mmol/L, p = .02] decreased from baseline to the 6-month follow-up. The estimated glomerular filtration rate (eGFR) [79 (IQR 59-94) mL/min/m2 vs. 79.6 (IQR 67.1-95.0) mL/min/m2, p = .11] did not change. The Chronic kidney disease (CKD) stages at baseline were: G1:15; G2:23; G3a:10; G3b:2; G4:1; G5:0. Among patients with a CKD-stage ≥2, analysis revealed an increase of eGFR, decrease of creatinine and urea from baseline to 6-month follow-up. Among those patients, the baseline-CKD-stage improved in 14 (41.2%) patients. BPA therapy improves pulmonary and systemic hemodynamics, with positive effects on renal function. Repetitive administration of contrast agent seems not to be harmful regarding renal function.

Outcome of thrombus aspiration in STEMI patients: a propensity score-adjusted study.

The use of thrombus aspiration (TA) prior to primary percutaneous coronary intervention (PPCI) has undergone a radical change in intervention guidelines. The clinical implications, however, are still under scrutiny. This study investigated the clinical effects and outcome of TA before PPCI in patients with ST-segment elevation myocardial infarction (STEMI). Overall 1027 patients with STEMI were analyzed in this retrospective, propensity score-adjusted, multicenter study. The primary endpoints were in-hospital and long-term mortality. There were 418 patients in the TA group and 609 in the conventional PPCI group. The in-hospital mortality rate was significantly higher in the TA group (8.7 vs. 5.0%; P = 0.03). During long-term follow-up [median follow-up duration 689 days (IQR 405-959)] the mortality rates were similar (TA 14.3%, conventional PPCI 15.0%; P = 0.85). Survival analysis for the complete observation period revealed no significant benefit of TA [hazard ratio (HR) 1.12; 97.5% CI 0.90-0.71; P = 0.63]. There were also no significant differences between the groups in the following secondary endpoints: composite of cardiovascular death and non-fatal reinfarction at discharge (P = 0.39), post-PPCI thrombolysis in myocardial infarction flow-grade-3 (P = 0.14), left ventricular ejection fraction (P = 0.47), and non-fatal reinfarction during follow-up (P = 0.17). Rehospitalization rate (1.82 vs. 10.3%; P < 0.0001) and Canadian Cardiovascular Society (CCS) grading (P = 0.02) during follow-up were significantly lower in the TA group. In our cohort the in-hospital mortality rate was significantly higher for TA patients, but during long-term follow-up the mortality rates did not differ. The incidence of rehospitalization and CCS grading were lower in the TA-treated patients.

Long-Term Outcome of Aortic Root Remodeling for Patients With and Without Acute Aortic Dissection.

BACKGROUND: Valve-preserving aortic surgery is increasingly used in acute aortic dissection type A (AADA). The object of this study was to compare the long-term results of aortic root remodeling (remodeling) for patients with and without AADA.Methods and Results:Between October 1995 and December 2013, 776 patients underwent valve-preserving root replacement, of whom 59 patients with AADA (<2 weeks from onset, 56±16 years, 48 male) underwent remodeling (the remodeling-group); 7 patients had bicuspid anatomy (12%), 3 had Marfan syndrome (5%), and 1 had undergone previous cardiac surgery (2%). For this analysis the control group of patients who underwent remodeling for stable aneurysm (n=59) was generated using a propensity score matching. The long-term outcomes regarding survival and reoperation on the aortic valve were compared between the 2 groups. Pre- and intraoperative patients' characteristics were comparable between groups. Early death was 7% in the AADA group and 3% in the control group (P=0.40). Actuarial survival at 10 years of the AADA group (72±6%) was insignificantly lower than that of the control group (83±5%) (P=0.16). Freedom from reoperation at 10 years was similar (AADA group: 98±2%, control group: 97±3%, P=0.99). Multivariable Cox's proportional hazards model could not identify an independent predictor for late reoperation but advanced age for late death. CONCLUSIONS: Long-term stability of remodeling was comparable between patients with and without AADA.

Native T1 is predictive of cardiovascular death/heart failure events and all-cause mortality irrespective of the patient's volume status.

Background: Native T1 has become a pivotal parameter of tissue composition that is assessed by cardiac magnetic resonance (CMR). It characterizes diseased myocardium and can be used for prognosis estimation. Recent publications have shown that native T1 is influenced by short-term fluctuations of volume status due to hydration or hemodialysis. Methods: Patients from a prospective BioCVI all-comers clinical CMR registry were included, and native T1 and plasma volume status (PVS) were determined according to Hakim's formula as surrogate markers of patient volume status. The primary endpoint was defined as combined endpoint of cardiovascular death or hospitalization for heart failure events, the secondary endpoint was defined as all-cause mortality. Results: A total of 2,047 patients were included since April 2017 [median (IQR); age 63 (52-72) years, 33% female]. There was a significant although weak influence of PVS on native T1 (ß = 0.11, p < 0.0001). Patients with volume expansion (PVS > -13%) showed significantly higher values for tissue markers than non-volume-overloaded patients [PVS ≤ -13%; median (IQR); native T1 1,130 (1,095-1,170) vs. 1,123 (1,086-1,166) ms, p < 0.003; and T2 39 (37-40) vs. 38 (36-40) ms, p < 0.0001]. In Cox regression analysis both native T1 and PVS were independently predictive of the primary endpoint and all-cause mortality. Conclusion: Despite a weak effect of PVS on native T1, its predictive power was not affected in a large, all-comers cohort.

Native T2 Predicts Myocardial Inflammation Irrespective of a Patient's Volume Status.

Myocardial inflammation and edema are major pathological features in myocarditis. Myocardial tissue water content and myocardial edema can be quantified via T2 mapping. Thus, cardiac magnetic resonance (CMR) is the noninvasive gold standard for diagnosing myocarditis. Several studies showed an impact of short-term volume changes on T2 relaxation time. Plasma volume status (PVS) is a good surrogate parameter to quantify a patient's volume status, and it is simple to use. The aim of this study was to determine the effect of PVS on the diagnostic value of T2 relaxation time in myocardial inflammation. Between April 2017 and December 2022, patients who were indicated for cardiac CMR were included in our prospective clinical registry. Patients with myocardial inflammation and those with unremarkable findings were analyzed in the present study. A blood sample was drawn, and PVS was calculated. Patients were separated into PVS tertiles to explore a possible nonlinear dose-response relationship. Logistic regression analysis was used to determine whether T2 is an independent predictor of myocardial inflammation. A total of 700 patients (47.43% female) were eligible for analysis. Of these, 551 patients were healthy (78.7%), while 149 (21.3%) showed signs of myocardial inflammation. The T2 relaxation time was elevated in patients with myocardial inflammation (40 ms [IQR 37-42 ms] vs. 38.0 ms [IQR 36-39 ms], p < 0.001). PVS showed no difference between the groups (-12.94 [IQR -18.4--7.28] vs.-12.19 [IQR -18.93--5.87], p = 0.384). T2 showed a clear dose-response relationship with PVS, with increasing T2 values along the PVS tertiles. In spite of this, T2 was found to be an independent marker of myocardial inflammation in logistic regression (OR T2 1.3 [95% CI 1.21-1.39], p < 0.001), even after adjusting for PVS (OR T2 [adj. PVS] 1.31 [95% CI 1.22-1.40], p < 0.001). Despite a dose-response relationship between T2 and the volume status, T2 was found to be an independent indicator of myocardial inflammation.

Value of Right and Left Ventricular T1 and T2 Blood Pool Mapping in Patients with Chronic Thromboembolic Hypertension before and after Balloon Pulmonary Angioplasty.

BACKGROUND: Parametric imaging has taken a steep rise in recent years and non-cardiac applications are of increasing interest. Therefore, the aim of our study was to assess right (RV) and left ventricular (LV) blood pool T1 and T2 values in patients with chronic thromboembolic pulmonary hypertension (CTEPH) compared to control subjects and their correlation to pulmonary hemodynamic. METHODS: 26 patients with CTEPH (mean age 64.8 years ± 12.8 SD; 15 female), who underwent CMR and right heart catheterization (RHC) before and 6-months after balloon pulmonary angioplasty (BPA), were retrospectively included. Ventricular blood pool values were measured, compared to control subjects (mean age 40.5 years ± 12.8 SD; 16 female) and correlated to invasive measures (CI, mPAP, PVR). RESULTS: In both, control subjects and CTEPH patients, RVT1 and RVT2 were significantly reduced compared to LVT1 and LVT2. Compared to control subjects, RVT2 was significantly reduced in CTEPH patients (p = 0.0065) and increased significantly after BPA (p = 0.0048). Moreover, RVT2 was positively correlated with CI and negatively correlated with mPAP and PVR before (r = 0.5155, r = -0.2541, r = -0.4571) and after BPA (r = 0.4769, r = -0.2585, r = -0.4396). CONCLUSION: Ventricular blood pool T2 mapping might be novel non-invasive CMR imaging marker for assessment of disease severity, prognosis, follow-up and even therapy monitoring in PH.

Evaluation of diagnostic accuracy of dual-energy computed tomography in patients with chronic thromboembolic pulmonary hypertension compared to V/Q-SPECT and pulmonary angiogram.

Purpose: The relevance of dual-energy computed tomography (DECT) for the detection of chronic thromboembolic pulmonary hypertension (CTEPH) still lies behind V/Q-SPECT in current clinical guidelines. Therefore, our study aimed to assess the diagnostic accuracy of DECT compared to V/Q-SPECT with invasive pulmonary angiogram (PA) serving as the reference standard. Methods: A total of 28 patients (mean age 62.1 years ± 10.6SD; 18 women) with clinically suspected CTEPH were retrospectively included. All patients received DECT with the calculation of iodine maps, V/Q-SPECT, and PA. Results of DECT and V/Q-SPECT were compared, and the percent of agreement, concordance (utilizing Cohen's kappa), and accuracy (kappa2) to PA were calculated. Furthermore, radiation doses were analyzed and compared. Results: In total, 18 patients were diagnosed with CTEPH (mean age 62.4 years ± 11.0SD; 10 women) and 10 patients had other diseases. Compared to PA, accuracy and concordance for DECT were superior to V/Q-SPECT in all patients (88.9% vs. 81.3%; k = 0.764 vs. k = 0.607) and in CTEPH patients (82.4% vs. 70.1%; k = 0.694 vs. k = 0.560). Furthermore, the mean radiation dose was significantly lower for DECT vs. V/Q-SPECT (p = 0.0081). Conclusion: In our patient cohort, DECT is at least equivalent to V/Q-SPECT in diagnosing CTEPH and has the added advantage of significantly lower radiation doses in combination with simultaneous assessment of lung and heart morphology. Hence, DECT should be the subject of ongoing research, and if our results are further confirmed, it should be implemented in future diagnostic PH algorithms at least on par with V/Q-SPECT.

Riociguat and balloon pulmonary angioplasty improve prognosis in patients with inoperable chronic thromboembolic pulmonary Hypertension.

BACKGROUND: The combination of riociguat and interventional balloon pulmonary angioplasty (BPA) is currently used to treat patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). The aim of the present study was to evaluate the impact of this combination therapy on the prognosis of inoperable CTEPH patients by comparing the long-term survival rates of patients undergoing combination therapy with riociguat and BPA with those of inoperable patients from the first international CTEPH registry who did not receive specific treatment. METHODS: Between March 2014 and August 2019, 138 technically inoperable patients were included in the present prospective, observational cohort study when they were treated with riociguat and BPA at a single CTEPH referral center. Long-term survival of this cohort was compared using propensity score matching with that of inoperable patients recruited between 2007 and 2009 in the first international CTEPH registry. Kaplan-Meier methods were used to evaluate differences in outcomes. RESULTS: Whereas the survival rate in the historical group was 84.6% in the first year, 76.6% in the second, 68.5% in the third, and 58.5% in the fifth year after diagnosis, implementation of riociguat/BPA led to survival rates of 100%, 96.7%, 92.9%, and 90% in the respective follow-up periods. In a comparison of 83 well-matched pairs from the 2 cohorts, survival was markedly better in the group treated with riociguat and BPA than in the historical cohort (HR = 0.145, 95% CI 0.05, 0.421). CONCLUSION: The combination of riociguat and BPA for the treatment of inoperable CTEPH is associated with excellent 5-year survival rates.

Echocardiographic pressure-strain loop-derived stroke work of the right ventricle: validation against the gold standard.

AIMS: Commercially available integrated software for echocardiographic measurement of stroke work (SW) is increasingly used for the right ventricle, despite a lack of validation. We sought to assess the validity of this method [echo-based myocardial work (MW) module] vs. gold-standard invasive right ventricular (RV) pressure-volume (PV) loops. METHODS AND RESULTS: From the prospectively recruiting EXERTION study (NCT04663217), we included 42 patients [34 patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) and 8 patients with absence of cardiopulmonary disease] with RV echocardiography and invasive PV catheterization. Echocardiographic SW was assessed as RV global work index (RVGWI) generated via the integrated pressure-strain MW software. Invasive SW was calculated as the area bounded by the PV loop. An additional parameter derived from the MW module, RV global wasted work (RVGWW), was correlated with PV loop measures. RVGWI significantly correlated with invasive PV loop-derived RV SW in the overall cohort [rho = 0.546 (P < 0.001)] and the PAH/CTEPH subgroup [rho = 0.568 (P < 0.001)]. Overall, RVGWW correlated with invasive measures of arterial elastance (Ea), the ratio of end-systolic elastance (Ees)/Ea, and end-diastolic elastance (Eed) significantly. CONCLUSIONS: Integrated echo measurement of pressure-strain loop-derived SW correlates with PV loop-based assessment of RV SW. Wasted work correlates with invasive measures of load-independent RV function. Given the methodological and anatomical challenges of RV work assessment, evolution of this approach by incorporating more elaborated echo analysis data and an RV reference curve might improve its reliability to mirror invasively assessed RV SW.

Fibroblast growth factor 23 as a biomarker of right ventricular dysfunction in pulmonary hypertension.

BACKGROUND: Fibroblast growth factor 23 (FGF-23) has been associated with left ventricular hypertrophy (LVH) and heart failure. However, its role in right ventricular (RV) remodeling and RV failure is unknown. This study analyzed the utility of FGF-23 as a biomarker of RV function in patients with pulmonary hypertension (PH). METHODS: In this observational study, FGF-23 was measured in the plasma of patients with PH (n = 627), dilated cardiomyopathy (DCM, n = 59), or LVH with severe aortic stenosis (n = 35). Participants without LV or RV abnormalities served as controls (n = 36). RESULTS: Median FGF-23 plasma levels were higher in PH patients than in healthy controls (p < 0.001). There were no significant differences between PH, DCM, and LVH patients. Analysis across tertiles of FGF-23 levels in PH patients revealed an association between higher FGF-23 levels and higher levels of NT-proBNP and worse renal function. Furthermore, patients in the high-FGF-23 tertile had a higher pulmonary vascular resistance (PVR), mean pulmonary artery pressure, and right atrial pressure and a lower cardiac index (CI) than patients in the low tertile (p < 0.001 for all comparisons). Higher FGF-23 levels were associated with higher RV end-diastolic diameter and lower tricuspid annular plane systolic excursions (TAPSE) and TAPSE/PASP. Receiver operating characteristic analysis revealed FGF-23 as a good predictor of RV maladaptation, defined as TAPSE < 17 mm and CI < 2.5 L/min/m2. Association of FGF-23 with parameters of RV function was independent of the glomerular filtration rate in regression analysis. CONCLUSION: FGF-23 may serve as a biomarker for maladaptive RV remodeling in patients with PH.

Hemodynamic markers of pulmonary vasculopathy for prediction of early right heart failure and mortality after heart transplantation.

BACKGROUND: Elevated pulmonary vascular resistance (PVR) is broadly accepted as an imminent risk factor for mortality after heart transplantation (HTx). However, no current HTx recipient risk score includes PVR or other hemodynamic parameters. This study examined the utility of various hemodynamic parameters for risk stratification in a contemporary HTx population. METHODS: Patients from seven German HTx centers undergoing HTx between 2011 and 2015 were included retrospectively. Established risk factors and complete hemodynamic datasets before HTx were analyzed. Outcome measures were overall all-cause mortality, 12-month mortality, and right heart failure (RHF) after HTx. RESULTS: The final analysis included 333 patients (28% female) with a median age of 54 (IQR 46-60) years. The median mean pulmonary artery pressure was 30 (IQR 23-38) mm Hg, transpulmonary gradient 8 (IQR 5-10) mm Hg, and PVR 2.1 (IQR 1.5-2.9) Wood units. Overall mortality was 35.7%, 12-month mortality was 23.7%, and the incidence of early RHF was 22.8%, which was significantly associated with overall mortality (log-rank HR 4.11, 95% CI 2.47-6.84; log-rank p < .0001). Pulmonary arterial elastance (Ea) was associated with overall mortality (HR 1.74, 95% CI 1.25-2.30; p < .001) independent of other non-hemodynamic risk factors. Ea values below a calculated cutoff represented a significantly reduced mortality risk (HR 0.38, 95% CI 0.19-0.76; p < .0001). PVR with the established cutoff of 3.0 WU was not significant. Ea was also significantly associated with 12-month mortality and RHF. CONCLUSIONS: Ea showed a strong impact on post-transplant mortality and RHF and should become part of the routine hemodynamic evaluation in HTx candidates.

Effects of BPA on right ventricular mechanical dysfunction in patients with inoperable CTEPH - A cardiac magnetic resonance study.

PURPOSE: The aim of this study was to assess effects of balloon pulmonary angioplasty (BPA) on right ventricular (RV) mechanical dysfunction in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) via MRI. METHOD: MRI at 1.5 Tesla and right heart catheterization were performed before and 6 months after BPA in 30 CTEPH patients (mean age 63.4 ± 10.6 years; 17 female). Feature-tracking strain analysis, including global longitudinal (GLS), circumferential (GCS), and radial (GRS) strain, was performed and compared with right ventricular function, myocardial remodelling (assessed by native T1 times), and pulmonary haemodynamics (mean pulmonary arterial pressure and pulmonary vascular resistance). RESULTS: RVEF (35.9% to 48.4%) increased and mPAP (42.1 mmHg to 33.1 mmHg) and PVR (551.8 to 377.7 dyn∙s/cm5) decreased after BPA (all p < 0.0001). Moreover, RV strain increased (GLS -19.9 to -24.0%, p = 0.0003; GCS -9.4 to -11.0%, p = 0.0022; GRS 38.2 to 50.7%, p = 0.001) and septal native area-adjusted T1 time (AA-T1) decreased (1019.4 to 988.7 ms, p < 0.0001). GLS revealed the best correlations with RVEF (before BPA r = -0.75; after BPA r = -0.54), mPAP (r = 0.36; r = 0.52), PVR (r = 0.49; r = 0.48), and AA-T1 (r = 0.44; 0.19). CONCLUSION: RV mechanical dysfunction, pulmonary haemodynamics, and myocardial remodelling are markedly improved by BPA. Moreover, RV strain values showed good correlations with RV function, pulmonary haemodynamics, and myocardial remodelling. Therefore, strain analysis might provide new insights regarding therapy outcome, monitoring, and prognosis.