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.

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.

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.

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.

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.

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.

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.

Exercise MR-proANP unmasks latent right heart failure in CTEPH.

OBJECTIVE: The present study was designed to investigate the dynamics of right atrial pressure (RAP) and mid-regional pro-atrial natriuretic peptide (MR-proANP) during physical exercise in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and to determine whether these parameters might serve as a tool to measure exercise-dependent atrial stress as an indicator of right heart failure. METHODS: This prospective observational cohort study included 100 CTEPH patients who underwent right heart catheterization during physical exercise (eRHC). Blood samples for MR-proANP measurement were taken prior, during, and after eRHC. MR-proANP levels were correlated to RAP levels at rest, at peak exercise (eRAP), and during recovery. RAP at rest ≤7 mmHg was defined as normal and eRAP >15 mmHg as suggestive of right heart failure. RESULTS: During eRHC mean RAP increased from 6 mmHg (standard deviation, SD 4) to 16 mmHg (SD 7; p < 0.001). MR-proANP levels and dynamics correlated with RAP at rest (rs = 0.61; p < 0.001) and at peak exercise (rs = 0.66; p < 0.001). Logistic regression analysis revealed the peak MR-proANP level (B = 0.058; p = 0.004) and the right atrial area (B = 0.389; p < 0.001) to be associated with eRAP dynamics. A peak MR-proANP level ≥139 pmol/L (AUC = 0.81) and recovery level ≥159 pmol/L (AUC = 0.82) predicted an eRAP >15 mmHg. Physical exercise unmasked right heart failure in 39% of patients with normal RAP at rest; these patients were also characterized by a more distinct increase in MR-proANP levels (p = 0.005) and higher peak (p < 0.001) and recovery levels (p < 0.001). CONCLUSIONS: RAP and MR-proANP dynamics unmask manifest and latent right heart failure in CTEPH patients.

Complications of balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension: Impact on the outcome.

BACKGROUND: Balloon pulmonary angioplasty (BPA) is an emerging interventional treatment for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) that targets subsegmental branches of the pulmonary artery. As the reported complication rates are high, the aim of the present study was to evaluate the effects of certain complications on the outcome after treatment. METHODS: From March 2014 to December 2019, a total of 235 patients with inoperable CTEPH underwent BPA. Of these patients, 140 were included who completed a follow-up examination 6 months after the last intervention; another 2 patients deceased due to complications of BPA. RESULTS: A high baseline pulmonary vascular resistance (PVR) >6.6 WU correlated with a higher rate of complications (mostly pulmonary artery perforations). Wire perforation during BPA did not correlate with worse outcome in terms of PVR reduction. The complication rate per intervention decreased from 21% to 14% during the 5 year period of the study. CONCLUSIONS: Complications are frequently observed in BPA, but the mortality rate is very low in expert centers. Importantly, the occurrence of complications does not portend a worse outcome.

Prognostic Power of Pulmonary Arterial Compliance Is Boosted by a Hemodynamic Unloading Test With Glyceryl Trinitrate in Heart Failure Patients With Post-capillary Pulmonary Hypertension.

Background: Pulmonary hypertension (PH) is an established risk factor in patients with heart failure (HF). However, right heart catheterisation (RHC) and vasoreactivity testing (VRT) are not routinely recommended in these patients. Methods: The primary objective of the present study was to explore the impact of VRT using sublingual glyceryl trinitrate (GTN) on transplant/ventricular assist device-free survival in HF patients with post-capillary PH. RHC parameters were correlated retrospectively with the primary outcome. Results: The cohort comprised 154 HF patients with post-capillary PH undergoing RHC with GTN-VRT at a tertiary heart failure centre. Multiple parameters were associated with survival. After adjustment for established prognosis-relevant clinical variables from the MAGGIC Score, variables with the most relevant odds ratios (OR) obtained after GTN-VRT were: calculated effective pulmonary arterial (PA) elastance (adjusted OR 2.26, 95%CI 1.30-3.92; p = 0.004), PA compliance (PAC-GTN; adjusted OR 0.45, 95%CI 0.25-0.80; p = 0.006), and total pulmonary resistance (adjusted OR 2.29, 95%CI 1.34-3.93; p = 0.003). Forest plot analysis including these three variables as well as PAC at baseline, delta PAC, and the presence of combined post- and pre-capillary PH revealed prognostic superiority of PAC-GTN, which was confirmed by Kaplan-Meier analysis. Conclusions: In our cohort of symptomatic HF patients with post-capillary PH, improved PAC after administration of GTN was associated with survival independent of established hemodynamic and clinical risk factors. VRT using GTN may be better described as unloading test due to GTN's complex effects on the circulation. This could be used for advanced prognostication and should be investigated in further studies.

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.

Exercise hemodynamics in heart failure patients with preserved and mid-range ejection fraction: key role of the right heart.

OBJECTIVE: We sought to explore whether classification of patients with heart failure and mid-range (HFmrEF) or preserved ejection fraction (HFpEF) according to their left ventricular ejection fraction (LVEF) identifies differences in their exercise hemodynamic profile, and whether classification according to an index of right ventricular (RV) function improves differentiation. BACKGROUND: Patients with HFmrEF and HFpEF have hemodynamic compromise on exertion. The classification according to LVEF implies a key role of the left ventricle. However, RV involvement in exercise limitation is increasingly recognized. The tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure (TAPSE/PASP) ratio is an index of RV and pulmonary vascular function. Whether exercise hemodynamics differ more between HFmrEF and HFpEF than between TAPSE/PASP tertiles is unknown. METHODS: We analyzed 166 patients with HFpEF (LVEF ≥ 50%) or HFmrEF (LVEF 40-49%) who underwent basic diagnostics (laboratory testing, echocardiography at rest, and cardiopulmonary exercise testing [CPET]) and exercise with right heart catheterization. Hemodynamics were compared according to echocardiographic left ventricular or RV function. RESULTS: Exercise hemodynamics (e.g. pulmonary arterial wedge pressure/cardiac output [CO] slope, CO increase during exercise, and maximum total pulmonary resistance) showed no difference between HFpEF and HFmrEF, but significantly differed across TAPSE/PASP tertiles and were associated with CPET results. N-terminal pro-brain natriuretic peptide concentration also differed significantly across TAPSE/PASP tertiles but not between HFpEF and HFmrEF. CONCLUSION: In patients with HFpEF or HFmrEF, TAPSE/PASP emerged as a more appropriate stratification parameter than LVEF to predict clinically relevant impairment of exercise hemodynamics. Stratification of exercise hemodynamics in patients with HFpEF or HFmrEF according to LVEF or TAPSE/PASP, showing significant distinctions only with the RV-based strategy. All data are shown as median [upper limit of interquartile range] and were calculated using the independent-samples Mann-Whitney U test or Kruskal-Wallis test. PVR pulmonary vascular resistance; max maximum level during exercise.

Application and Validation of the Tricuspid Annular Plane Systolic Excursion/Systolic Pulmonary Artery Pressure Ratio in Patients with Ischemic and Non-Ischemic Cardiomyopathy.

The main aim of this study was to assess the prognostic utility of TAPSE/PASP as an echocardiographic parameter of maladaptive RV remodeling in cardiomyopathy patients using cardiac magnetic resonance (CMR) imaging. Furthermore, we sought to compare TAPSE/PASP to TAPSE. The association of the echocardiographic parameters TAPSE/PASP and TAPSE with CMR parameters of RV and LV remodeling was evaluated in 111 patients with ischemic and non-ischemic cardiomyopathy and cut-off values for maladaptive RV remodeling were defined. In a second step, the prognostic value of TAPSE/PASP and its cut-off value were analyzed regarding mortality in a validation cohort consisting of 221 patients with ischemic and non-ischemic cardiomyopathy. A low TAPSE/PASP (<0.38 mm/mmHg) and TAPSE (<16 mm) were associated with a lower RVEF and a long-axis RV global longitudinal strain (GLS) as well as higher RVESVI, RVEDVI and NT-proBNP. A low TAPSE/PASP, but not TAPSE, was associated with a lower LVEF and long-axis LV GLS, and a higher LVESVI, LVEDVI and T1 relaxation time at the interventricular septum and the RV insertion points. Furthermore, in the validation cohort, low TAPSE/PASP was associated with a higher mortality and TAPSE/PASP was an independent predictor of mortality. TAPSE/PASP is a predictor of maladaptive RV and LV remodeling associated with poor outcomes in cardiomyopathy patients.

Cardiac biomarkers as indicators of right ventricular dysfunction and recovery in chronic thromboembolic pulmonary hypertension patients after balloon pulmonary angioplasty therapy - a cardiac magnetic resonance imaging cohort study.

BACKGROUND: In chronic thromboembolic pulmonary hypertension, right heart failure determines outcome. Balloon pulmonary angioplasty therapy allows right heart recovery, which can be monitored by cardiac magnetic resonance imaging. This study evaluates whether cardiac biomarkers (NT-proBNP, MR-proANP, sST2, and PAPP-A) are associated with cardiac magnetic resonance imaging findings prior to and after balloon pulmonary angioplasty therapy. METHODS: This observational cohort study enrolled 22 chronic thromboembolic pulmonary hypertension patients who underwent balloon pulmonary angioplasty therapy and completed a six-month follow-up including cardiac magnetic resonance imaging. Biomarker levels were compared with findings for right heart morphology and function derived from cardiac magnetic resonance imaging. RESULTS: Pulmonary hemodynamics improved after balloon pulmonary angioplasty therapy [pulmonary vascular resistance: 7.7 (6.0-9.0) vs. 4.7 (3.5-5.5) wood units, p < 0.001; mean pulmonary artery pressure 41 (38-47) vs. 32 (28-37) mmHg, p < 0.001]. Cardiac magnetic resonance imaging findings indicated right heart maladaptation at baseline and recovery after therapy [right ventricular end-diastolic volume 192 (141-229) ml vs. 143 (128-172) ml, p = 0.002; right ventricular end-systolic volume 131 (73-157) ml vs. 77 (61-99) ml (p < 0.001); right ventricular ejection fraction (RVEF) 34 (28-41) % vs. 52 (41-54) %; p < 0.001]. Biomarker level cut-offs [NT-proBNP 347 ng/L (area under the curve (AUC) 0.91), MR-proANP 230 pg/L (AUC 0.78), PAPP-A 14.5 mU/L (AUC 0.81), and sST2 48.0 ng/ml (AUC 0.88)] indicated a RVEF ≤ 35% at baseline. The dynamics of NT-proBNP (rs = -0.79; p < 0.001), MR-proANP (rs = -0.80; p < 0.001), and sST2 (rs = -0.49; p = 0.02) correlated inversely with the improvement in RVEF after therapy. A relative decrease of NT-proBNP < 53% (AUC 0.86) and MR-proANP < 24% (AUC 0.82) indicated a limited RVEF response. CONCLUSIONS: In chronic thromboembolic pulmonary hypertension patients, cardiac magnetic resonance imaging findings illustrate right heart failure and recovery after balloon pulmonary angioplasty therapy. Cardiac biomarker levels correlate with right heart parameters at baseline and their dynamics after therapy.

Noninvasive prediction of pulmonary hemodynamics in chronic thromboembolic pulmonary hypertension by electrocardiogram-gated computed tomography.

PURPOSE: The aim of the study was to investigate the potential of electrocardiogram (ECG)-gated computed tomography pulmonary angiography (CTPA) as a predictor of disease severity in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHOD: Forty-five CTEPH patients with a mean age of 63.8 years±12.7 y (±standard deviation) who had undergone ECG-gated CTPA and right heart catheterization (RHC) were included in the study. Right ventricular to left ventricular volume ratio (RVV/LVV), diameter ratio on 4-chamber view (RVD4CH/LVD4CH), pulmonary trunk (PT) diameter, PT to aortic diameter ratio (PT/A), and septal angle were correlated to mean pulmonary artery pressure (mPAP). Moreover, RVV/LVV and RVD4CH/LVD4CH were adjusted to pulmonary diameter index (PADi) and PT/A index. Areas under the curve (AUC) for predicting mPAP above 40 mmHg, 35 mmHg, and 30 mmHg were calculated. RESULTS: RVD4CH/LVD4CH revealed the strongest correlation to mPAP before (r = 0.6507) and after (r = 0.7650; p < 0.0001) PT/A adjustment. The AUCs for predicting pH with mPAP over 40 mmHg and 30 mmHg were 0.9229 and 0.864, respectively. A cutoff value of 1.298 enabled prediction of pH with mPAP over 40 mmHg with a sensitivity, specificity, positive predictive, and negative predictive value of 80.00 %, 95.83 %, 88.46 %, and 94.12 %, respectively. Intra- and interobserver variability were excellent for all parameters. CONCLUSION: Combining different and easily evaluable ECG-gated CTPA parameters enables excellent prediction of pulmonary hemodynamics in CTEPH patients. Ventricular diameter ratio on 4-chamber view adjusted by the PT/A ratio yielded the best correlation to mPAP.

Exercise Hemodynamic Profiling Is Associated With Outcome in Patients Undergoing Percutaneous Mitral Valve Repair.

[Figure: see text].

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.

Balloon pulmonary angioplasty in the treatment of chronic thromboembolic pulmonary hypertension: recent advances and future perspectives.

Chronic thromboembolic pulmonary hypertension constitutes a significant late sequela of pulmonary embolism. It is defined by precapillary pulmonary hypertension with mismatched perfusion defects and pulmonary arterial lesions after at least 3 months of effective anticoagulation. Symptomatic patients who do not have pulmonary hypertension yet fulfill all other criteria are diagnosed with chronic thromboembolic disease. The treatment of chronic thromboembolic pulmonary hypertension is based on 3 pillars: pulmonary endarterectomy, pulmonary arterial hypertension-targeted medication, and balloon pulmonary angioplasty. Surgical pulmonary endarterectomy is the standard of care and can be performed in 2/3 of all patients. Targeted medication with or without balloon pulmonary angioplasty is reserved for inoperable patients or those with residual pulmonary hypertension after surgical treatment. Despite the lack of profound evidence, the treatment of chronic thromboembolic disease is similar to that of patients with pulmonary hypertension: pulmonary endarterectomy is offered to operable individuals, whereas balloon pulmonary angioplasty is considered in inoperable patients. Since therapeutic strategies are complex, and diagnostic and therapeutic procedures-demanding, treatment in a specialized, experienced center is mandatory.

Mid-regional pro-atrial natriuretic peptide and copeptin as indicators of disease severity and therapy response in CTEPH.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) leads to right heart failure. Pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) restore pulmonary haemodynamics and allow cardiac recovery. This study examined the relationship of copeptin and mid-regional pro-atrial natriuretic peptide (MR-proANP) levels to disease severity and therapy response. METHODS: This observational cohort study included 125 patients (55 PEA/70 BPA) who underwent treatment and completed a 6-/12-month follow-up. Biomarkers, measured at baseline, prior to every BPA and at follow-up, were compared to 1) severe disease at baseline (right atrial pressure (RAP) ≥8 mmHg and cardiac index ≤2.4 L·min-1·m-2) and 2) optimal therapy response (no persistent pulmonary hypertension combined with a normalised RAP (mean PAP ≤25 mmHg, pulmonary vascular resistance (PVR) ≤3 WU and RAP ≤6 mmHg) or a reduction in mean PAP ≥25%, PVR ≥35% and RAP ≥25%). RESULTS: Severely diseased patients had higher levels of MR-proANP (320 (246-527) pmol·L-1 versus 133 (82-215) pmol·L-1; p=0.001) and copeptin (12.7 (7.3-20.6) pmol·L-1 versus 6.8 (4.4-12.8) pmol·L-1; p=0.015) at baseline than the rest of the cohort. At baseline, MR-proANP (area under the curve (AUC) 0.91; cut-off value 227 pmol·L-1; OR 56, 95% CI 6.9-454.3) and copeptin (AUC 0.70; cut-off value 10.9 pmol·L-1; OR 1.5, 95% CI 1.2-1.9) identified severely diseased patients. After PEA/BPA, levels of MR-proANP (99 (58-145) pmol·L-1; p<0.001) and copeptin (6.3 (3.7-12.6) pmol·L-1; p=0.009) decreased and indicated optimal therapy response (MR-proANP <123 pmol·L-1 (AUC 0.70) and copeptin <10.1 pmol·L-1 (AUC 0.58)). CONCLUSION: MR-proANP and copeptin levels are affected in CTEPH and decrease after therapy. MR-proANP identifies a severe disease status and optimal therapy response.

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.