Calcium channel blockers in patients with pulmonary arterial hypertension receiving PAH-specific treatment.

BACKGROUND: Calcium channel blockers (CCB) are the first effective therapy for vasoreactive patients with idiopathic pulmonary arterial hypertension (IPAH). However, the advent of modern PAH-specific drugs may undermine the role of vasoreactivity tests and CCB treatment. We aimed to clarify the effect of acute vasoreactivity testing and CCB on patients with IPAH receiving PAH-specific treatment. METHODS: We retrospectively investigated consecutive patients with IPAH (n = 136) diagnosed between 2000 and 2020 and collected data from patients who underwent acute vasoreactivity testing using inhaled nitric oxide (NO). The effects of vasoreactivity testing and CCB therapy were reviewed. Long-term survival was analysed using the Kaplan-Meier method. RESULTS: Acute vasoreactivity testing was performed in 49% of patients with IPAH (n = 67), including 23 patients (34%) receiving PAH-specific therapy without vasoreactivity testing. Eight patients (12%), including three patients (4.4%) receiving PAH-specific therapy, presented acute responses at vasoreactivity testing. They received high-dose CCB therapy (CCB monotherapy for five patients [7.5%] and CCB therapy and PAH-specific therapy for three patients [4.4%]). They presented a significant improvement in clinical parameters and near-normalisation of haemodynamics (mean pulmonary arterial pressure decreased from 46 [interquartile range: 40-49] to 19.5 [interquartile range: 18-23] mmHg [P < .001] at 1-year follow-up). All eight vasoreactive responders receiving CCB therapy showed better long-term survival than non-responders treated with PAH-specific therapy (P < .001). CONCLUSIONS: CCB therapy benefited patients with IPAH who showed acute response to vasoreactivity testing using inhaled NO, even when receiving modern PAH-specific therapy. Acute vasoreactive responders may benefit more from CCB than from PAH-specific therapy.

Depressive symptoms, right ventricular function, and muscular strength are associated with peak oxygen uptake in patients with implantable left ventricular assist devices.

BACKGROUND: Left ventricular assist device (LVAD) implantation is among the most effective treatment options for patients with severe heart failure. Although previous studies have examined the factors related to peak oxygen uptake (peak VO2 ), they were limited by the few patients involved and their focus on medical and physical functions. Therefore, this study comprehensively examined the factors associated with peak VO2 , which is an important prognostic factor in patients with implantable LVADs. METHODS: Eighty-nine patients who underwent initial LVAD implantation and were eligible for cardiopulmonary exercise testing (CPX) between May 2014 and September 2021 were included. The patients' mean age was 48 ± 12 years, and 70% were males. Based on previous studies, the cut-off was set at 12 and 14 mL/kg/min for patients taking ß-blocker and those not taking ß-blockers, respectively. Furthermore, factors associated with peak VO2 were examined using multivariate logistic regression analysis. RESULTS: The mean time from surgery to CPX administration was 73 ± 40 days. The high group had a higher cardiac index, right ventricular stroke work index (RVSWI), and isometric knee extensor muscular strength and lower Patient Health Questionnaire-9 (PHQ-9) and B-type natriuretic peptide values than the low group. Multivariate logistic regression analysis showed that RVSWI and KEMS were positively correlated, whereas PHQ-9 was negatively associated with peak VO2 . CONCLUSION: Right ventricular function, depressive symptoms, and lower limb muscular strength were associated with exercise capacity in patients with implantable LVADs.

Recurrent pulmonary hypertension after balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension.

BACKGROUND: Balloon pulmonary angioplasty improves the hemodynamics of patients with inoperable chronic thromboembolic pulmonary hypertension; however, the clinical impact of recurrent pulmonary hypertension after balloon pulmonary angioplasty remains unclear. METHODS: We retrospectively reviewed 262 consecutive patients with chronic thromboembolic pulmonary hypertension who underwent balloon pulmonary angioplasty between July 2009 and December 2020; 158 (65 ± 12 years; males, 20%; median follow-up period, 45 [26, 66] months) with follow-up right heart catheterization and no residual pulmonary hypertension were included. Recurrent pulmonary hypertension was defined as mean pulmonary arterial pressure <25 mm Hg at the first evaluation after balloon pulmonary angioplasty and ≥25 mm Hg at follow-up evaluation requiring additional treatment with balloon pulmonary angioplasty or pulmonary vasodilators. RESULTS: Recurrent pulmonary hypertension was observed in 11 patients; the state occupation probability of recurrence at 5 years was 9.0% (95% confidence interval: 5.0%-18.9%). Only 1 case (0.6%) of recurrent pulmonary hypertension showed vascular restenosis and reocclusion of previously treated lesions, with more significant hemodynamic and exercise capacity deterioration than the other cases. Additional treatments for recurrent pulmonary hypertension (balloon pulmonary angioplasty in 9 patients, pulmonary vasodilators in 4 patients) improved the mean pulmonary arterial pressure from 27 [26, 29] to 22 [19, 23] mm Hg (p < 0.01). Recurrence had a low probability of transitioning to death in an illness-death model. No specific risk factors for recurrent pulmonary hypertension were identified. CONCLUSIONS: Symptomatic recurrent pulmonary hypertension due to vascular restenosis or reocclusion after balloon pulmonary angioplasty was extremely rare. Most cases of recurrent pulmonary hypertension were mild, did not worsen clinically, and had favorable prognoses.

Disease management using home-based cardiac rehabilitation for patients with heart failure.

Home-based cardiac rehabilitation (HBCR) is expected to address the low participation rate in cardiac rehabilitation; however, it is not covered by insurance in Japan, and the optimal method for monitoring a patient's condition during exercise has not been determined. Patients hospitalized for heart failure often deteriorate soon after discharge and require appropriate disease monitoring. In this report, we describe cases in which real-time monitoring of exercise intensity, electrocardiography, and video chat during HBCR was useful in the management of heart failure. Furthermore, the use of HBCR enabled frequent disease monitoring, even during the coronavirus disease 2019 pandemic, and timely medicine adjustment. Learning objective: Clinicians cannot perform radiography, blood tests, or physical examinations at home during home-based cardiac rehabilitation (HBCR). Therefore, it is particularly important to reconsider the appropriate monitoring indicators for HBCR and apply them to disease management. Our cases suggest that real-time monitoring of the following three indicators is useful for disease management using HBCR: (1) exercise intensity, (2) electrocardiography, and (3) shortness of breath.

Inhaled nitric oxide testing in predicting prognosis in pulmonary hypertension due to left-sided heart diseases.

AIMS: The pathophysiology of pulmonary hypertension (PH) due to left-sided heart disease (Group 2 PH) is distinct from that of other groups of PH, yet there are still no approved therapies that selectively target pulmonary circulation. The increase in pulmonary capillary pressure due to left-sided heart disease is a trigger event for physical and biological alterations of the pulmonary circulation, including the nitric oxide (NO)-soluble guanylate cyclase-cyclic guanosine monophosphate axis. This study investigated inhaled NO vasoreactivity tests for patients with Group 2 PH and hypothesized that these changes may have a prognostic impact. METHODS AND RESULTS: This was a single-centre, retrospective study with a median follow-up of 365 days. From January 2011 to December 2015, we studied 69 patients with Group 2 PH [age, 61.5 ± 13.0 (standard deviation) years; male:female, 49:20; left ventricular ejection fraction, 50.1 ± 20.4%; mean pulmonary arterial pressure, ≥25 mmHg; and pulmonary arterial wedge pressure (PAWP), >15 mmHg]. No adverse events were observed after NO inhalation. Thirty-four patients with Group 2 PH showed increased PAWP (ΔPAWP: 3.26 ± 2.22 mmHg), while the remaining 35 patients did not (ΔPAWP: -2.11 ± 2.29 mmHg). Multivariate analysis revealed that increased PAWP was the only significant predictor of all-cause death or hospitalization for heart failure (HF) after 1 year (hazard ratio 4.35; 95% confidence interval, 1.27-14.83; P = 0.019). The acute response of PAWP to NO differed between HF with preserved and reduced ejection fractions. CONCLUSIONS: Patients with Group 2 PH were tolerant of the inhaled NO test. NO-induced PAWP is a novel prognostic indicator.

Three Cases of Unprovoked Venous Thromboembolism with Prothrombin p.Arg596Gln Variant and a Literature Review of Antithrombin Resistance.

Antithrombin resistance (ATR) is a newly identified strong genetic predisposition to venous thromboembolism (VTE) caused by genetic variations in prothrombin with substitutions of Arg at position 596 with either Leu, Gln, or Trp. In the present report, we identified a missense variant p.Arg596Gln in 3 patients from 2 families with unprovoked VTE who each experienced their first VTE event at 19, 67, and 19 years old. The three patients did not show any positive markers for thrombophilia on routine testing, suggesting that patients with unprovoked VTE who have negative findings on thrombophilia tests may carry a prothrombin variant with ATR.

Long-term outcomes of combined pulmonary endarterectomy and additional balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension.

BACKGROUND: The early and long-term outcomes after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) have been established by several high-volume centers, but the impact of postoperative residual pulmonary hypertension affecting postoperative clinical parameters remains unclear. This study aims to investigate the institutional surgical results of PEA and to evaluate the efficacy of additional balloon pulmonary angioplasty (BPA) for residual pulmonary hypertension. PATIENTS AND METHODS: We retrospectively reviewed 222 patients (57.7 ± 12.9 years old, 141 female) who underwent PEA for CTEPH at the National Cerebral and Cardiovascular Center between 2000 and 2020. RESULTS: The preoperative mean pulmonary artery pressure (mPAP) was 45.6 ± 9.7 mmHg and pulmonary vascular resistance (PVR) was 1062 ± 451 dyne*sec/cm-5. Postoperative mPAP (23.4 ± 11 mmHg, 204 patients, P < 0.001) and PVR (419 ± 291 dyne*sec/cm-5, 199 patients, P < 0.001) significantly improved after PEA. Since 2011, 62 patients (28%) underwent BPA after PEA for "catecholamine dependent" residual PH 1 month after PEA in 14, "scheduled" BPA with residual PH 1 year after PEA in 32, and 16 "symptomatic" patients without residual PH. Their mPAP had significantly improved by PEA (48.1 ± 7.7 to 32.0 ± 10.2 mmHg, P < 0.001), and further improved (33.8 ± 11.1 to 26.5 ± 9.1 mmHg, P < 0.001) after BPA. CONCLUSIONS: PEA provided immediate and substantial improvements in pulmonary hemodynamics and favorable long-term survival. In addition, postoperative BPA improved postoperative clinical parameters for eligible patients regardless of the presence of residual PH.

Balloon Pulmonary Angioplasty in the Management of Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH), which is classified as group 4 pulmonary hypertension (PH) in the 2015 European Society of Cardiology/European Respiratory Society guidelines for the diagnosis and treatment of PH, is regarded as a complication of pulmonary embolism and is caused by the transformation of incompletely resolved thrombi into fibrous tissue that occludes the pulmonary arteries. The current established reference standard curative therapy for CTEPH is pulmonary endarterectomy (PEA), which provides good long-term outcomes with a low mortality rate. For patients with inoperable disease with inaccessible lesions and risk factors for surgery or patients who are diagnosed with residual or recurrent PH after PEA, medical therapy with riociguat is recommended. Balloon pulmonary angioplasty (BPA) is an emerging alternative treatment option for patients with inoperable disease or those with residual or recurrent PH after PEA. BPA has been reported to improve hemodynamics, cardiac function, exercise capacity, and symptoms, as well as PEA. A detailed assessment of thromboembolic lesions in pulmonary arteries by using multiple imaging techniques and treatment strategies with multiple staged procedures based on the patient's condition is important for safe and effective BPA. However, this new technique may still induce life-threatening complications, such as reperfusion pulmonary edema, wire perforation, vessel dissection, and vessel rupture. Meticulous attention to technique is mandatory to minimize serious complications owing to the nature of the anatomic territory involved. The authors summarize the current roles, goals, and complications of BPA in patients with CTEPH and demonstrate ways to formulate an effective and safe treatment strategy. The future perspective of BPA is also discussed. Online supplemental material is available for this article. ©RSNA, 2022.

Pulmonary arterial hypertension sensitive to calcium channel blocker, but not advanced pulmonary hypertension treatment: a case report.

Background: Calcium channel blockers (CCB), the first accepted treatment, is effective only in a small number of idiopathic pulmonary arterial hypertension (I-PAH) patients with vasoreactivity [these patients are identified by a positive acute pulmonary vasoreactive test (AVT) response]. While the majority of I-PAH patients is non-vasoreactive and CCB non-responders, modern advanced pulmonary hypertension (PH)-specific therapies, which act on one of the three different mechanistic pathways-endothelin, nitric oxide (NO), and prostacyclin pathways, are effective. Treatment response to advanced PH-specific vasodilators in PAH patients with vasoreactivity is unknown. Case summary: A 30-year-old woman with I-PAH was referred to our centre with worsening symptoms and deteriorating PH. She was being administered oral triple combination of advanced PH-specific treatment including a phosphodiesterase-5 inhibitor, an endothelin receptor antagonist, and a long-acting prostacyclin analogue. The patient showed positive AVT with NO inhalation while on these advanced PH-specific drugs. We added high-dose CCB, which dramatically normalized her pulmonary blood pressure without further symptoms, and she has remained stable for 5 years. Discussion: Our case describes a PAH patient with vasoreactivity, who was resistant to three different types of advanced PH-specific vasodilators but was exclusively sensitive to CCB treatment. Some CCB responders may have a specific CCB-sensitive PAH phenotype refractory to other pulmonary vasodilators. This case highlights the role of identifying CCB responders in this era of use of modern, advanced PH-specific vasodilators. The investigation of the mechanisms underlying CCB sensitivity in PAH is necessary.

Prognostic impact of follow-up pulmonary vascular resistance in pulmonary arterial hypertension.

OBJECTIVE: Pulmonary arterial hypertension (PAH), caused by pulmonary artery remodelling and increased pulmonary vascular resistance (PVR) due to an unknown mechanism, is an intractable disease with a poor prognosis. The recent development of PAH-specific treatment medications may allow for higher PVR reduction than previously achieved. This study aimed to identify the prognostic significance of follow-up PVR levels achieved shortly after the initiation of targeted treatment in patients with idiopathic/heritable pulmonary arterial hypertension (I/H-PAH). METHODS: We analysed the data of all patients with I/H-PAH admitted to our hospital between 1998 and 2019. We collected data at baseline and during the first invasive haemodynamic evaluation. The primary outcome was death or lung transplantation. RESULTS: Of the 133 treatment-naïve patients enrolled in this study, 47 experienced adverse events during a median follow-up period of 6.4 (IQR 3.5-11.5) years. The median time interval to first follow-up from diagnosis was 162 (IQR 117-253) days. Incidence of the primary outcome was significantly lower in patients who achieved low PVR at follow-up. Of risk factors evaluated at follow-up, the multivariate Cox regression analysis revealed PVR as an independent predictor of the primary outcome (HR 1.103, 95% CI 1.029 to 1.183; p=0.006). The results were consistent across risk profiles according to the simplified risk stratification recommended by the European Society of Cardiology and European Respiratory Society guidelines. CONCLUSION: Follow-up PVR was an independent predictor of transplant-free survival in patients with I/H-PAH. Evaluation of haemodynamic status shortly after initiating treatment may help predict long-term prognosis.

Systemic-pulmonary collateral supply associated with clinical severity of chronic thromboembolic pulmonary hypertension: a study using intra-aortic computed tomography angiography.

OBJECTIVES: To assess whether systemic-pulmonary collaterals are associated with clinical severity and extent of pulmonary perfusion defects in chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: This prospective study was approved by a local ethics committee. Twenty-four patients diagnosed with inoperable CTEPH were enrolled between July 2014 and February 2017. Systemic-pulmonary collaterals were detected using pulmonary vascular enhancement on intra-aortic computed tomography (CT) angiography. The pulmonary enhancement parameters were calculated, including (1) Hounsfield unit differences (HUdiff) between pulmonary trunks and pulmonary arteries (PAs) or veins (PVs), namely HUdiff-PA and HUdiff-PV, on the segmental base; (2) the mean HUdiff-PA, mean HUdiff-PV, numbers of significantly enhanced PAs and PVs, on the patient base. Pulmonary perfusion defects were recorded and scored using the lung perfused blood volume (PBV) based on intravenous dual-energy CT (DECT) angiography. Pearson's or Spearman's correlation coefficients were used to evaluate correlations between the following: (1) segment-based intra-aortic CT and intravenous DECT parameters (2) patient-based intra-aortic CT parameters and clinical severity parameters or lung PBV scores. Statistical significance was set at p < 0.05. RESULTS: Segmental HUdiff-PV was correlated with the segmental perfusion defect score (r = 0.45, p < 0.01). The mean HUdiff-PV was correlated with the mean pulmonary arterial pressure (PAP) (r = 0.52, p < 0.01), cardiac output (rho = - 0.41, p = 0.05), and lung PBV score (rho = 0.43, p = 0.04). And the number of significantly enhanced PVs was correlated with the mean PAP (r = 0.54, p < 0.01), pulmonary vascular resistance (r = 0.54, p < 0.01), and lung PBV score (rho = 0.50, p = 0.01). CONCLUSIONS: PV enhancement measured by intra-aortic CT angiography reflects clinical severity and pulmonary perfusion defects in CTEPH. KEY POINTS: • Intra-aortic CT angiography demonstrated heterogeneous enhancement within the pulmonary vasculature, showing collaterals from the systemic arteries to the pulmonary circulation in CTEPH. • The degree of systemic-pulmonary collateral development was significantly correlated with the clinical severity of CTEPH and may be used to evaluate disease progression. • The distribution of systemic-pulmonary collaterals is positively correlated with perfusion defects in the lung segments in CTEPH.

Association of adherence to a 3 month cardiac rehabilitation with long-term clinical outcomes in heart failure patients.

AIMS: Although comprehensive cardiac rehabilitation (CCR) is recommended for patients with heart failure (HF), participants often show low adherence. The aim of this study was to evaluate the association of CCR completion and response with long-term clinical outcomes. METHODS AND RESULTS: We screened 824 HF patients who participated in a 3 month CCR programme and underwent baseline assessment, including cardiopulmonary exercise testing (CPX). After excluding 52 participants who experienced all-cause death or HF hospitalization within 180 days, long-term outcomes were compared between those who attended 3 month follow-up assessment including CPX (completers) and those who did not (non-completers). We also compared the prognostic value of the changes in peak oxygen uptake (VO2 ) vs. quadriceps muscle strength (QMS) during the 3 month CCR programme. Among the 772 study patients, there were no significant differences in baseline characteristics, including left ventricular ejection fraction, B-type natriuretic peptide levels, and peak VO2 , between the completers (n = 561) and non-completers (n = 211), except for a higher age (63.2 ± 14.2 vs. 59.4 ± 16.2 years; P = 0.0015) and proportion of females (27% vs. 17%; P = 0.0030) among the completers. During a median follow-up of 55.4 months, the completers had lower rates of the composite of all-cause death or HF hospitalization (34.4% vs. 44.6%; P = 0.0015) and all-cause death (16.9% vs. 24.6%; P = 0.0037) than the non-completers. After adjustment for prognostic baseline characteristics, including age and sex, CCR completion was associated with 34% and 44% reductions in the composite outcome and all-cause death, respectively. Among the completers, peak VO2 and QMS increased significantly (8.9 ± 15.8% and 10.5 ± 17.9%, respectively) over 3 months. Patients who had an increase in peak VO2  ≥ 6.3% (median value) during the CCR programme had significantly lower rates of the composite outcome (27.0% vs. 33.8%; P = 0.048) and all-cause mortality (10.0% vs. 17.4%; P = 0.0069) than those who did not. No statistically significant difference was observed in the composite outcome (30.5% vs. 30.4%; P = 0.76) or all-cause mortality (13.0% vs. 14.4%; P = 0.39) between those with and without an increase in QMS ≥8.3% (median value). CONCLUSIONS: In HF patients who participated in a 3 month CCR programme, its completion was associated with lower risks of subsequent HF hospitalization and death. Within the group of patients who completed the programme, the improvement in exercise capacity, but not in skeletal muscle strength, over the 3-month period was associated with better outcomes. These findings highlight the importance of the post-CCR follow-up assessment, including CPX, to identify a patient's adherence and response to the CCR programme.

Quantification of vortex flow in pulmonary arteries of patients with chronic thromboembolic pulmonary hypertension.

PURPOSE: This study proposes an objective method of quantifying the vortex flow in pulmonary arteries to compare the duration of its presence before and after balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Thoracic 4D-flow magnetic resonance imaging was performed in 28 CTEPH patients before and after BPA. Planes were set in pulmonary arteries to evaluate volume flow rate (VFR), the duration, and area of backward flow in the pulmonary trunk, which is a component of the vortex flow. The full width at half maximum (FWHM) of the peak of the time course of VFR of backward flow was assessed to quantify the duration of the vortical flow. RESULTS: Although overall flow patterns after BPA appeared to be the same as the one before BPA, significant decreases in the FWHM, area, and VFR of the backward flow after BPA were found (FWHM: before, 1.88 × 10-1 ± 1.51 × 10-2 [cardiac cycle] vs. after, 1.65 × 10-1 ± 1.86 × 10-2 [cardiac cycle]; area ratio: before, 2.67 × 10-1 ± 1.30 × 10-2 vs. after, 2.38 × 10-1 ± 1.31 × 10-2; VFR: before, 13.6 ± 2.21 [mL/s] vs. after, 11.3 ± 2.36 [mL/s]). CONCLUSION: BPA promoted significant decreases in the FWHM, area, and VFR of backward flow in the pulmonary trunk, thereby facilitating efficient blood transport. The tendencies for these changes were to be larger for cases where BPA more greatly decreased the pressure. The results suggest that the FWHM, area, and VFR are useful indicators for the noninvasive evaluation of the therapeutic effects of BPA.

Sex-related Differences in Exercise Capacity Trends and Determinants after Cardiac Rehabilitation in Patients with Acute Myocardial Infarction.

OBJECTIVE: This study aimed to investigate whether longitudinal changes in exercise capacity in patients with acute myocardial infarction (AMI) differ by sex and clarified what contributed to these differences. METHODS: We retrospectively examined the differences in each variable between men and women in 156 patients with AMI (mean age: 65 ± 12 years; 82.0% male) who participated in a 3-month cardiac rehabilitation (CR) program and could be followed-up for exercise capacity 12-months after AMI onset. Sex-related differences in the change in peak oxygen uptake (peak VO2) at baseline, 3-months, and 12-months after AMI were analyzed. RESULTS: Male patients with AMI were younger and had higher body mass index and employment rate than women. The attendance of the CR program was higher in women (men vs. women; 10 [3-15] vs. 14 [11-24] sessions, p = 0.0002). Women showed a significant lower %change in peak VO2 after 12 months (men vs. women; 7.8% [-0.49% to 14.6%] vs. 1.3% [-5.7% to 7.5%], p = 0.013). In multiple linear regression analysis, age (ß = -0.76, 95% confidence interval [CI] = -1.0 to -0.50, p <0.0001) and female sex (ß = -6.3, 95% CI = -9.1 to -3.5, p <0.0001) were negative independent predictors of change in peak VO2 over 12 months, while CR attendance (ß = 0.21, 95% CI = 0.0032-0.42, p = 0.047) and recommended exercise habit after the CR program (ß = 2.1, 95% CI = 0.095-4.1, p = 0.040) were positive independent predictors of change in peak VO2 over 12 months. CONCLUSION: In female patients, exercise capacity improved during the CR program but decreased to AMI onset levels after 12 months.

Prognostic value of right ventricular native T1 mapping in pulmonary arterial hypertension.

BACKGROUND: Right ventricular function is an important prognostic marker for pulmonary arterial hypertension. Native T1 mapping using cardiovascular magnetic resonance imaging can characterize the myocardium, but accumulating evidence indicates that T1 values of the septum or ventricular insertion points do not have predictive potential in pulmonary arterial hypertension. We aimed to elucidate whether native T1 values of the right ventricular free wall (RVT1) can predict poor outcomes in patients with pulmonary arterial hypertension. METHODS: This retrospective study included 30 patients with pulmonary arterial hypertension (median age, 45 years; mean pulmonary artery pressure, 41±13 mmHg) and 16 healthy controls (median age, 43 years) who underwent native T1 mapping. RVT1 was obtained from the inferior right ventricular free wall during end systole. RESULTS: Patients with pulmonary arterial hypertension had significantly higher native RVT1 than did controls (1384±74 vs. 1217±57 ms, p<0.001). Compared with T1 values of the septum or ventricular insertion points, RVT1 correlated better with the effective right ventricular elastance index (R = -0.53, p = 0.003), ventricular-arterial uncoupling (R = 0.46, p = 0.013), and serum brain natriuretic peptide levels (R = 0.65, p<0.001). Moreover, the baseline RVT1 was an accurate predictor of the reduced right ventricular ejection fraction at the 12-month follow-up (delta -3%). RVT1 was independently associated with composite events of death or hospitalization from any cause (hazard ratio = 1.02, p = 0.002). CONCLUSIONS: RVT1 was predictive of right ventricular performance and outcomes in patients with pulmonary arterial hypertension. Thus, native T1 mapping in the right ventricular free wall may be an effective prognostic method for pulmonary arterial hypertension.

Long term prognosis in patients with pulmonary hypertension undergoing catheter ablation for supraventricular tachycardia.

Various forms of supraventricular tachycardia (SVT) occur in patients with severe pulmonary hypertension (PH). Despite the high efficacy of radiofrequency catheter ablation (RFCA) for SVT, insufficient data exist regarding patients with PH. Thirty SVTs in 23 PH patients (age 47 [35-60] years; mean pulmonary artery pressure 44 [32-50] mmHg) were analyzed. Procedural success rate, short- and long-term clinical outcomes, were evaluated during a median follow-up of 5.1 years. Single-procedure success rate was 83%; 94% (17/18) in typical atrial flutter, 73% (8/11) in atrial tachycardia (AT), and 100% (1/1) in atrioventricular nodal reentrant tachycardia. Antiarrhythmic drugs, serum brain natriuretic peptide levels and number of hospitalizations significantly decreased after RFCA than that before (p = 0.002, 0.04, and 0.002, respectively). Four patients had several procedures. After last RFCA, 12 patients had SVT and 8 patients died. Kaplan-Meier curves showed that patients with SVT after the last RFCA had a lower survival rate compared to those without (p = 0.0297). Multivariate analysis identified any SVT after the last RFCA as significant risk factor of mortality (hazard ratio: 9.31; p = 0.016). RFCA for SVT in patients with PH is feasible and effective in the short-term, but SVT is common during long-term follow-up and associated with lower survival.

Post-discharge arrhythmic risk stratification of patients with acute myocarditis and life-threatening ventricular tachyarrhythmias.

AIMS: The outcomes of patients presenting with acute myocarditis and life-threatening ventricular arrhythmias (LT-VA) are unclear. The aim of this study was to assess the incidence and predictors of recurrent major arrhythmic events (MAEs) after hospital discharge in this patient population. METHODS AND RESULTS: We retrospectively analysed 156 patients (median age 44 years; 77% male) discharged with a diagnosis of acute myocarditis and LT-VA from 16 hospitals worldwide. Diagnosis of myocarditis was based on histology or the combination of increased markers of cardiac injury and cardiac magnetic resonance (CMR) Lake Louise criteria. MAEs were defined as the relapse, after discharge, of sudden cardiac death or successfully defibrillated ventricular fibrillation, or sustained ventricular tachycardia (sVT) requiring implantable cardioverter-defibrillator therapy or synchronized external cardioversion. Median follow-up was 23 months [first to third quartile (Q1-Q3) 7-60]. Fifty-eight (37.2%) patients experienced MAEs after discharge, at a median of 8 months (Q1-Q3 2.5-24.0 months; 60.3% of MAEs within the first year). At multivariable Cox analysis, variables independently associated with MAEs were presentation with sVT [hazard ratio (HR) 2.90, 95% confidence interval (CI) 1.38-6.11]; late gadolinium enhancement involving ≥2 myocardial segments (HR 4.51, 95% CI 2.39-8.53), and absence of positive short-tau inversion recovery (STIR) (HR 2.59, 95% CI 1.40-4.79) at first CMR. CONCLUSIONS: Among patients discharged with a diagnosis of myocarditis and LT-VA, 37.2% had recurrences of MAEs during follow-up. Initial CMR pattern and sVT at presentation stratify the risk of arrhythmia recurrence.

Identification of the Novel Variants in Patients With Chronic Thromboembolic Pulmonary Hypertension.

Background Although chronic thromboembolic pulmonary hypertension (CTEPH) and acute pulmonary embolism (APE) share some clinical manifestations, a limited proportion of patients with CTEPH have a history of APE. Moreover, in histopathologic studies, it has been revealed that pulmonary vasculature lesions similar to pulmonary arterial hypertension existed in patients with CTEPH. Thus, it remains unknown whether these 3 disorders also share genetic backgrounds. Methods and Results Whole exome screening was performed with DNA isolated from 51 unrelated patients with CTEPH of Japanese ancestry. The frequency of genetic variants associated with pulmonary arterial hypertension or APE in patients with CTEPH was compared with those in the integrative Japanese Genome Variation Database 3.5KJPN. Whole exome screening analysis showed 17 049 nonsynonymous variants in patients with CTEPH. Although we found 6 nonsynonymous variants that are associated with APE in patients with CTEPH, there was no nonsynonymous variant associated with pulmonary arterial hypertension. Patients with CTEPH with a history of APE had nonsynonymous variants of F5, which encodes factor V. In contrast, patients with CTEPH without a history of APE had a nonsynonymous variant of THBD, which encodes thrombomodulin. Moreover, thrombin-activatable fibrinolysis inhibitor, which is one of the pathogenic proteins in CTEPH, was significantly more activated in those who had the variants of THBD compared with those without it. Conclusions These results provide the first evidence that patients with CTEPH have some variants associated with APE, regardless of the presence or absence of a history of APE. Furthermore, the variants might be different between patients with CTEPH with and without a history of APE.