Association of delayed diagnosis of pulmonary arterial hypertension with its prognosis.

BACKGROUND: Currently, pulmonary hypertension-targeted therapy has been shown to improve the survival of patients with pulmonary artery hypertension (PAH). However, the importance of early diagnosis has not been investigated. Therefore, this study aimed to investigate whether a delayed diagnosis of PAH is associated with its prognosis. METHODS AND RESULTS: A total of 66 consecutive untreated patients were diagnosed with PAH from January 2008 to December 2021 at the Kagoshima University Hospital. The time from symptom onset to diagnosis correlated with brain natriuretic peptide levels (p < 0.001), right ventricle (RV) Tei index (p < 0.001), and the tricuspid annular plane systolic excursion/systolic pulmonary artery pressure ratio (p = 0.003). These findings suggest that in patients with PAH, RV function declines with increasing time from symptom onset to diagnosis. Furthermore, older patients with PAH appeared to have a longer time from symptom onset to diagnosis. Next, patients were divided into delayed diagnosis (>3 months) and early diagnosis (≤3 months) groups based on the time from symptom onset to diagnosis. Patients were categorized into three groups according to the European Society of Cardiology (or the European Respiratory Society) risk stratification guidelines. Patients diagnosed with PAH within 3 months of symptom onset were significantly in the low- or intermediate-risk groups (p < 0.001). A Kaplan-Meier analysis revealed that the cumulative event-free rate was significantly lower (p < 0.01) in the delayed diagnosis group than in the early diagnosis group. A delayed diagnosis was significantly associated with a worse outcome than an early diagnosis, after adjusting for different sets of confounding factors. CONCLUSIONS: A delayed PAH diagnosis is associated with a poor prognosis. Early diagnosis of PAH may lead to a low-risk treatment. Furthermore, older patients need more careful screening for PAH.

Adult-onset idiopathic peripheral pulmonary artery stenosis.

BACKGROUND: Peripheral pulmonary artery stenosis (PPS) refers to stenosis of the pulmonary artery from the trunk to the peripheral arteries. Although paediatric PPS is well described, the clinical characteristics of adult-onset idiopathic PPS have not been established. Our objectives in this study were to characterise the disease profile of adult-onset PPS. METHODS: We collected data in Japanese centres. This cohort included patients who underwent pulmonary angiography (PAG) and excluded patients with chronic thromboembolic pulmonary hypertension or Takayasu arteritis. Patient backgrounds, right heart catheterisation (RHC) findings, imaging findings and treatment profiles were collected. RESULTS: 44 patients (median (interquartile range) age 39 (29-57) years; 29 females (65.9%)) with PPS were enrolled from 20 centres. In PAG, stenosis of segmental and peripheral pulmonary arteries was observed in 41 (93.2%) and 36 patients (81.8%), respectively. 35 patients (79.5%) received medications approved for pulmonary arterial hypertension (PAH) and 22 patients (50.0%) received combination therapy. 25 patients (56.8%) underwent transcatheter pulmonary angioplasty. RHC data showed improvements in both mean pulmonary arterial pressure (44 versus 40 mmHg; p<0.001) and pulmonary vascular resistance (760 versus 514 dyn·s·cm-5; p<0.001) from baseline to final follow-up. The 3-, 5- and 10-year survival rates of patients with PPS were 97.5% (95% CI 83.5-99.6%), 89.0% (95% CI 68.9-96.4%) and 67.0% (95% CI 41.4-83.3%), respectively. CONCLUSIONS: In this study, patients with adult-onset idiopathic PPS presented with segmental and peripheral pulmonary artery stenosis. Although patients had severe pulmonary hypertension at baseline, they showed a favourable treatment response to PAH drugs combined with transcatheter pulmonary angioplasty.

Protocol for a multicentre, double-blind, randomised, placebo-controlled trial of riociguat on peak cardiac index during exercise in patients with chronic thromboembolic pulmonary hypertension after balloon pulmonary angioplasty (THERAPY-HYBRID-BPA trial).

OBJECTIVES: Balloon pulmonary angioplasty (BPA) and medical therapy, such as soluble guanylate cyclase stimulators, are recommended treatments for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are ineligible for pulmonary endarterectomy (PEA). However, monotherapy with BPA or medical therapy cannot always eliminate symptoms such as exertional dyspnoea. Thus, this study aims to clarify the efficacy of continuous treatment with riociguat in inoperable CTEPH patients with normalised haemodynamics after BPA. METHODS AND ANALYSIS: This is a double-blind, multicentre, randomised, placebo-controlled trial. Participants with CTEPH who are ineligible for PEA will receive riociguat followed by BPA. Subsequently, participants will be randomised (1:1) into either riociguat continuing or discontinuing groups and will be observed for 16 weeks after randomisation. The primary endpoint will be the change in peak cardiac index (CI) during the cardiopulmonary exercise test. In the primary analysis, the least square mean differences and 95% CIs for the change in peak CI at 16 weeks between the groups will be estimated by a linear mixed-effects model with baseline value as a covariate, treatment group as a fixed effect and study institution as a random effect. ETHICS AND DISSEMINATION: National Hospital Organisation Review Board for Clinical Trials (Nagoya) and each participating institution approved this study and its protocols. Written informed consent will be obtained from all participants. The results will be disseminated at medical conferences and in journal publications. REGISTRATION DETAILS: Japan Registry of Clinical Trials: jRCT no. 041200052. CLINICALTRIALS: gov by National Library of Medicine Registry ID: NCT04600492. TRIAL REGISTRATION NUMBER: NCT04600492.

Pulmonary artery hypertension-associated with human immunodeficiency virus infection with attenuated effect of subcutaneous treprostinil injection during long-term observation: A case report.

Pulmonary artery hypertension associated with human immunodeficiency virus infection (PAH-HIV) is known to be caused by HIV infection. Antiretroviral therapy and PAH-specific drugs improve the prognosis of patients with PAH-HIV, but the pathophysiology of PAH-HIV remains unclear. We report a case of PAH-HIV treated with upfront combination therapy including subcutaneous injection of treprostinil. One year after treatment initiation, the patient's PAH improved significantly. However, it worsened over time due to reduced efficacy of subcutaneous injection of treprostinil. Learning objective: The etiology and pathophysiology of pulmonary artery hypertension associated with human immunodeficiency virus infection (PAH-HIV) remain unclear, and there are few case reports of PAH-HIV in Japan because the HIV prevalence is low. We encountered a case of PAH-HIV in which the efficacy of subcutaneous treprostinil injection was attenuated. It was unclear whether the reduced efficacy was associated with the pathophysiology of PAH-HIV. When PAH control deteriorates, early alteration of medication choice and administration route is important.

Unknown atrial septal defect was diagnosed during the course of treatment for portopulmonary hypertension: A case report.

Portopulmonary hypertension (POPH) is a condition defined by the development of pulmonary arterial hypertension (PAH) that is associated with liver disease or portal hypertension. Untreated POPH has a poor prognosis. POPH can be treated with PAH-targeted therapy and can sometimes resolve with liver transplantation (LT); however, poorly controlled POPH can preclude LT owing to an increased peri-operative risk. We report a case of POPH that was diagnosed as an unknown atrial septal defect during PAH-targeted therapy. As observed in our case, the same patient may have several causes of PAH. It is important to confirm an unknown shunt disease using echocardiography during PAH-targeted therapy. Learning objective: It is difficult to detect unknown shunt disease in patients who are diagnosed with pulmonary arterial hypertension (PAH) owing to other causes. We report a case of portopulmonary hypertension that was diagnosed as an unknown atrial septal defect during PAH-targeted therapy. This report highlights the same patient may have several causes of PAH. It is important to confirm an unknown shunt disease using echocardiography during PAH-targeted therapy.

Different characteristics of mitochondrial dynamics-related miRNAs on the hemodynamics of pulmonary artery hypertension and chronic thromboembolic pulmonary hypertension.

BACKGROUND: Mitochondria are dynamic organelles that undergo fission or fusion. These mitochondrial dynamics are reported to be associated with pulmonary hypertension (PH). PH is divided into 5 groups, including pulmonary artery hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), based on its pathogenesis. However, it is still unknown whether and how miRNAs related to mitochondrial dynamics (MD) affect PAH and CTEPH. METHODS: We investigated patients who underwent right heart catheterization between October 2016 and January 2019. Out of 34 PH patients, 12 were diagnosed with PAH, and 22 were diagnosed with CTEPH. In addition, there were 30 patients diagnosed with left heart disease. We enrolled the 34 PH patients as the PH group and 30 left heart disease patients as the control group. RESULTS: Among MD-related miRNAs, the circulating levels of miR-140-3p were higher, and those of miR-485-5p were lower in the PH group than in the control group (p < 0.01), suggesting that miRNAs inducing mitochondrial fission are related to PH. The miR-140-3p levels in the PAH and CTEPH groups were higher than those in the control group (p < 0.01). The levels of miR-140-3p and miR-485-5p in the PAH group correlated with pulmonary vascular resistance (r = 0.582, p = 0.046) and cardiac index (r = -0.36, p = 0.04), respectively. The miR-485-5p levels in the CTEPH group correlated with right atrium pressure (r = -0.456, p = 0.049). CONCLUSION: MD-related miRNAs levels change to induce fission and are closely related to the hemodynamics of PAH and CTEPH.

Effects of Dual Initial Combination Therapy With Macitentan Plus Riociguat or Macitentan Plus Selexipag on Hemodynamics in Patients With Pulmonary Arterial Hypertension (SETOUCHI-PH Study)　- Protocol of a Multicenter Randomized Control Trial.

Background: The latest guideline from the European Society of Cardiology and European Respiratory Society recommends initial combination therapy with oral pulmonary arterial hypertension (PAH)-specific drugs in PAH patients with World Health Organization functional class (WHO-FC) II or III. However, whether this initial combination therapy improves hemodynamics and clinical failure events regardless of the combination of PAH-specific drugs remains unknown. This study was designed to evaluate whether the initial combination therapy with macitentan plus riociguat or macitentan plus selexipag showed equal efficacy in reducing pulmonary vascular resistance (PVR) 8 months after administration. Methods and Results: This study is a multicenter randomized control trial. PAH subjects with WHO-FC II or III will be randomized (1 : 1) into initial combination therapy with either macitentan plus riociguat or macitentan plus selexipag, and will be observed 8 months after the initiation of treatment. The primary endpoint will be the difference in the change ratio of PVR from baseline to after 8 months of treatment. Conclusions: The SETOUCHI-PH study will clarify whether initial combination therapy with macitentan plus riociguat or macitentan plus selexipag results in equal reductions in PVR 8 months after administration.

The potential for early diagnosis of pulmonary arterial hypertension using lung iodine-123-metaiodobenzylguanidine (123I-MIBG) uptake: A case report.

Previous reports have found evidence that the lung uptake of iodine-123-metaiodobenzylguanidine (123I-MIBG) represents pulmonary vascular endothelial function. Therefore, it was believed that the reduced lung uptake of 123I-MIBG in patients with pulmonary artery hypertension may indicate poor pulmonary vascular endothelial function in those patients. In our previous report, we analyzed the lung uptake of 123I-MIBG in patients with pulmonary hypertension, and demonstrated that it is lower in patients with pulmonary arterial hypertension (PAH) than in those with chronic thromboembolic pulmonary hypertension and controls, suggesting that reduced uptake of 123I-MIBG in patients with PAH indicates endothelial dysfunction of the pulmonary artery. In the current report, we describe a 46-year-old woman diagnosed with scleroderma whose lung uptake of 123I-MIBG was decreased on admission, but she was not diagnosed with pulmonary artery hypertension at that time because her pulmonary artery pressure during right heart catheterization was not elevated. However, she was diagnosed with borderline PAH 2 years later. The lung uptake of 123I-MIBG was reduced before a reduction in %DLCO was observed. This report suggests that the lung uptake of 123I-MIBG may be useful for the early diagnosis of pulmonary artery hypertension.

Geriatric Nutritional Risk Index Is Associated With Prognosis in Patients With Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension.

Background: The Geriatric Nutritional Risk Index (GNRI) is a simple tool for assessing nutritional risk that predicts prognosis in patients with heart failure. This study evaluated associations between the GNRI at first hospitalization and prognosis in patients with pulmonary artery hypertension (PAH) and those with chronic thromboembolic pulmonary hypertension (CTEPH). Methods and Results: This retrospective investigation included 104 patients with either PAH or CTEPH who were treated at Kagoshima University Hospital in Japan. Patients were divided into a high (≥92) and low (<92) GNRI groups. Body mass index and serum albumin levels were significantly lower in the low GNRI group (P<0.001). Over a median follow-up period of 24 months, the incidence of pulmonary hypertension rehospitalization was higher in the low GNRI group (P=0.04). Kaplan-Meier analysis revealed that the cumulative event-free rate was significantly lower in the low GNRI group (P=0.002). Low GNRI was significantly associated with a poorer outcome after adjusting for different sets of confounding factors, including: age and sex (P=0.004); age, sex, and PAH (P=0.043); and age, sex, and mean pulmonary artery pressure (P=0.003). Conclusions: The GNRI at first hospitalization is useful for predicting prognosis in PAH and CTEPH patients.

Correlation of Right Ventricular Wall Stress With Plasma B-Type Natriuretic Peptide Levels in Patients With Pulmonary Hypertension.

BACKGROUND: This study was designed to investigate the relationship between right ventricular wall stress (RVWS) and plasma B-type natriuretic peptide (BNP) levels in patients with pulmonary hypertension (PH). Methods and Results: The 57 consecutive PH patients and 8 control subjects were enrolled. Right heart catheterization (RHC), echocardiography, and BNP measurements were performed, and RVWS and left ventricular wall stress (LVWS) were calculated with the formula based on Laplace's law. Systolic RVWS and end-diastolic RVWS were higher in PH patients compared with controls (systolic RVWS: 77±41 vs. 17±5 kdynes/cm2(P<0.0001), end-diastolic RVWS: 15±12 vs. 8±2 kdynes/cm2(P<0.0005)). Univariate analyses showed that logBNP at baseline correlated with systolic RVWS (r=0.58, P<0.0001) and end-diastolic RVWS (r=0.61, P<0.0001). We performed multivariate regression analysis and determined that end-diastolic RVWS was an independent determinant of logBNP in patients with PH. In addition, change in plasma BNP levels after treatment correlated with change in systolic RVWS (r=0.70, P<0.0001) and change in end-diastolic RVWS (r=0.68, P<0.0001). CONCLUSIONS: Both systolic and end-diastolic RVWS were elevated in patients with PH, and correlated with the symptoms of PH. End-diastolic RVWS was an independent determinant of plasma BNP levels in PH patients.

Predictors of exercise-induced pulmonary hypertension in patients with connective tissue disease.

Screening and early detection of pulmonary arterial hypertension (PAH) in connective tissue disease (CTD) are currently recommended for early treatment. Exercise-induced pulmonary hypertension (EIPH) is thought to be a potential risk of developing resting pulmonary hypertension. However, accurate diagnosis of EIPH is needed hemodynamics by right heart catheterization during exercise. Therefore, we compared various parameters of EIPH group with non-EIPH group in patients with CTD. This study aimed to investigate noninvasive predictors of EIPH. A total of 162 consecutive patients with CTD who received screening of PAH was studied. Thirty-four patients with suspected PAH received right heart catheterization (RHC) at rest. Twenty-four patients without PAH underwent RHC during exercise, and they were divided into the EIPH group (n = 7) and the non-EIPH group (n = 17). Exercise tolerance such as 6-min walk distance and peak VO2/kg in the EIPH group was lower than that in the non-EIPH group. For hemodynamics, pulmonary artery pressure, right atrial pressure, and vascular resistance in the EIPH group were significantly higher than those in the non-EIPH group. In echocardiography, RV Tei index in the EIPH group was significantly higher than that in the non-EIPH group (EIPH vs non-EIPH = 0.42 [0.41, 0.47] vs 0.25 [0.20, 0.32], P = 0.007). The receiver operating characteristics curve showed a cutoff value of RV Tei index (0.41) with a sensitivity of 0.857 and specificity of 0.882. In conclusion, RV Tei index might be a feasible predictor of EIPH in patients with CTD.

Analysis of Biphasic Right Ventricular Outflow Doppler Waveform in Patients with Pulmonary Hypertension.

Pulmonary hypertension (PH) with pulmonary vascular disease (PVD) is a progressive and debilitating disease associated with increased pulmonary vascular resistance (PVR). Biphasic right ventricular outflow tract (RVOT) Doppler flow is frequently seen in severe PH patients with PVD. In association with hemodynamics, the precise analysis of biphasic RVOT Doppler flow (RVDF) has not been fully elucidated. Therefore, the purpose of the present study is to analyze the relation between the hemodynamics and indices of biphasic RVDF in PH patients with PVD.Seventy PH patients with biphasic RVDF were analyzed. All patients underwent transthoracic echocardiography and right heart catheterization. For the analysis of biphasic RVDF, the early waveform was determined as P1 while the late waveform was determined as P2. For each P1 and P2, the duration (D, seconds) and peak flow velocity (PFV, in m/second) were measured.P1D and P2PFV were significantly correlated with PVR (P1D: r = -0.542, P < 0.0001, P2PFV: r = -0.513, P < 0.0001). Therefore, we propose a novel RVDF formula for estimation of PVR, as follows. PVR = 26 - 77 × P1D - 14 × P2PFV. The PVR could be estimated by this proposed formula (r = 0.649, P < 0.0001), which is derived from one Doppler image only unlike previously used PVR prediction formula.P1D and P2PFV were associated with PVR. Moreover, this simple RVDF formula proposed herein can estimate PVR in PH patients with PVD.

Significant Clinical Indexes of Exercise-Induced Pulmonary Hypertension in Patients With Connective Tissue Disease.

Background: Pulmonary hypertension (PH) is an important cause of morbidity in patients with connective tissue disease (CTD), and an early stage of PH could present as exercise-induced PH (EIPH). This study investigated the significant clinical indexes of EIPH in patients with CTD. Methods and Results: We enrolled 63 patients with CTD who did not have PH at rest. All patients underwent the 6-min walk test (6MWT), and systolic pulmonary artery pressure (SPAP) was evaluated on echocardiography before and after 6MWT. EIPH was defined as SPAP ≥40 mmHg after 6 WMT. Thirty-five patients had EIPH. On univariate logistic analysis, SPAP at rest, log brain natriuretic peptide (BNP), vital capacity (VC), and forced expiratory volume in 1 s (FEV1.0) were significantly correlated with EIPH. On multiple logistic analysis, SPAP at rest and VC were independent predictors of EIPH, whereas FEV1.0 and log BNP were not significantly associated with EIPH. The area under the receiver operating characteristics curve between EIPH and BNP, SPAP at rest, VC or FEV1.0 was 0.67, 0.76, 0.74, and 0.75, respectively. Conclusions: SPAP at rest and respiratory function, especially VC, could be independent predictors of EIPH in patients with CTD.

[Successful treatment of POEMS syndrome-associated pulmonary hypertension with lenalidomide and dexamethasone therapy].

POEMS syndrome is often complicated by pulmonary hypertension. The standard therapy for patients with POEMS syndrome is high-dose chemotherapy followed by autologous stem cell transplantation. However, the safety of high-dose chemotherapy for patients complicated with pulmonary hypertension remains unclear, and the optimal therapy for these patients is yet to be establishment. Herein, we report the case of a 54-year-old woman with POEMS syndrome accompanied by pulmonary hypertension. We successfully and safely performed lenalidomide and dexamethasone (Ld) therapy followed by high-dose chemotherapy and autologous stem cell transplantation, which improved her pulmonary hypertension. Thus, Ld can be considered as safe and effective for pulmonary hypertension with POEMS syndrome.

Impairment of Iodine-123-Metaiodobenzylguanidine (123I-MIBG) Uptake in Patients with Pulmonary Artery Hypertension.

According to recent studies, lung uptake of iodine-123-metaiodobenzylguanidine (123I-MIBG) is impaired in many lung diseases and low lung uptake of 123I-MIBG suggests endothelial dysfunction of the pulmonary artery. 123I-MIBG scintigraphy in patients with pulmonary hypertension (PH) has not yet been clinically evaluated. We hypothesized that the lung uptake of 123I-MIBG is reduced in patients with PH and differs among PH subtypes. The purpose of the present study was to analyze the lung uptake of 123I-MIBG in patients with PH and compare it with the data obtained by echocardiography or right heart catheterization. 123I-MIBG scintigraphy was performed in 286 consecutive patients from 2003 to 2014. We enrolled 21 patients with PH and 8 control patients. The 21 patients with PH were categorized into those with pulmonary artery hypertension (PAH, n = 12) and those with chronic thromboembolic pulmonary hypertension (CTEPH, n = 9). The mean pulmonary artery pressure was not significantly different between patients with CTEPH and PAH (37.7 ± 6.8 versus 32.3 ± 5.3 mmHg respectively; P = 0.054). There were no significant differences in any other hemodynamic parameters between the two groups. The lung uptake of 123I-MIBG in PAH patients (early image: 1.54 ± 0.18, delayed image: 1.41 ± 0.16) was significantly lower than that of CTEPH patients (early image: 2.17 ± 0.25, P < 0.0001; delayed image: 1.99 ± 0.20, P = 0.0001, adjusted for age and World Health Organization classification) and controls (early image: 2.32 ± 0.27, P = 0.0007; delayed image: 1.92 ± 0.19, P = 0.0007). In conclusion, we found for the first time that the lung uptake of 123I-MIBG in patients with PAH is lower than that in patients with CTEPH and controls.

Successful antemortem diagnosis and treatment of pulmonary tumor thrombotic microangiopathy.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal cancer-related complication with rapid progression. Although the underlying molecular mechanisms of PTTM remain unclear, platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) may play important roles in the pathogenesis of PTTM. We herein report a case of PTTM that was diagnosed antemortem by pathology using pulmonary wedge aspiration. The patient was treated with a combination therapy of imatinib (PDGF receptor antagonist), bevacizumab (VEGF receptor inhibitor), S-1, and cisplatin. These findings suggest that molecular-target drugs are effective for the treatment of PTTM.

Prosthetic tricuspid valve dysfunction assessed by three-dimensional transthoracic and transesophageal echocardiography.

A 39-year-old male who had undergone tricuspid valve replacement for severe tricuspid regurgitation was admitted with palpitation and general edema. Two-dimensional (2D) echocardiography showed tricuspid prosthetic valve dysfunction. Additional three-dimensional (3D) transthoracic and transesophageal echocardiography (TEE) could clearly demonstrate the disabilities of the mechanical tricuspid valve. Particularly, 3D TEE demonstrated a mass located on the right ventricular side of the tricuspid prosthesis, which may have caused the stuck disk. This observation was confirmed by intra-operative findings.

Left ventricular dysfunction assessed by cardiac time interval analysis among different geometric patterns in untreated hypertension.

BACKGROUND: Left ventricular (LV) hypertrophy is a powerful independent predictor of morbidity and mortality in hypertensive patients. Abnormal LV geometric patterns are also associated with hypertensive complications, and concentric hypertrophy is associated with the highest mortality in hypertensive patients. However, the relationship between geometric patterns and cardiac dysfunction is not fully established. We hypothesized that the Tei index, which is a measure of global cardiac function, is a feasible parameter for estimating cardiac dysfunction among the different LV geometric patterns in hypertensive patients. METHODS AND RESULTS: We enrolled 60 consecutive patients with untreated essential hypertension. Subjects were divided into 4 groups: normal geometry, concentric remodeling, eccentric hypertrophy and concentric hypertrophy. We measured ejection fraction, mitral E/A ratio, Tei index, ejection time, and isovolumic contraction and relaxation times. There were significant correlations between LV mass index and systolic blood pressure (P<0.01), ejection fraction (P<0.05), mitral E/A ratio (P<0.05) and Tei index (P<0.0001). In multiple regression analysis, only the Tei index independently correlated with LV mass index (P<0.01). Concentric hypertrophy significantly increased the Tei index compared with the other 3 groups. CONCLUSIONS: The Tei index provides a better marker for LV dysfunction by hypertensive hypertrophy than conventional parameters. LV function in concentric hypertrophy was most impaired among all the geometric patterns in untreated hypertensive patients.

Left ventricular global systolic dysfunction has a significant role in the development of diastolic heart failure in patients with systemic hypertension.

Regional left ventricular (LV) systolic dysfunction has been identified in diastolic heart failure (DHF). However, the relationship between regional or global LV systolic function and heart failure symptoms in DHF has not been evaluated in detail. The present study evaluates such relationships in patients with systemic hypertension (HT) and DHF. We assessed LV systolic and diastolic function in 220 consecutive patients with systemic HT and in 30 normal individuals (Control) using Doppler echocardiography. Patients with HT were assigned to groups with DHF, asymptomatic diastolic dysfunction (ADD) and no diastolic dysfunction (Simple HT). Ejection fraction in DHF was significantly decreased (63±8%) compared with the Control, Simple HT and ADD groups (67±5, 66±7 and 68±8%, respectively). Isovolumetric contraction time in DHF (70±30 msec) was significantly increased compared with those in the ADD, Simple HT and Control groups (31±17, 31±15 and 30±19 msec, respectively). Mitral annular systolic velocities were significantly decreased in the DHF and ADD groups (6.4±1.5 and 7.2±1.3 cm sec⁻¹, respectively) compared with those in the Simple HT and Control groups (8.5±1.8 and 8.4±3.0 cm sec⁻¹, respectively), and in the DHF group compared with the ADD group. LV global systolic dysfunction has a significant role in the development of heart failure symptoms associated with DHF in patients with systemic HT.

Functional mitral stenosis after surgical annuloplasty for ischemic mitral regurgitation: importance of subvalvular tethering in the mechanism and dynamic deterioration during exertion.

OBJECTIVE: Diastolic subvalvular mitral leaflet tethering by left ventricular remodeling that restricts leaflet opening in the presence of annular size reduction by surgery for ischemic mitral regurgitation potentially causes functional mitral stenosis in the absence of organic leaflet lesions. Exercise, known to worsen systolic tethering and ischemic mitral regurgitation, might also dynamically exacerbate such mitral stenosis by increasing tethering. This study evaluates the mechanism and response of such mitral stenosis to exercise. METHODS: We measured the diastolic mitral valve area, annular area, and peak and mean transmitral pressure gradient by echocardiography in 20 healthy individuals and 31 patients who underwent surgical annuloplasty for ischemic mitral regurgitation. RESULTS: Although the mitral valve area and annular area did not significantly differ in healthy individuals (4.7 +/- 0.6 cm(2) vs 5.2 +/- 0.6 cm(2), not significant), mitral valve area was significantly smaller than the annular area in patients after annuloplasty (1.6 +/- 0.2 cm(2) vs 3.3 +/- 0.5 cm(2), P < .01). The mitral valve area was less than 1.5 cm(2) only after the surgery (P < .01) and was significantly correlated with restricted leaflet opening (r(2) = 0.74, P < .001), left ventricular dilatation (r(2) = 0.17, P < .05), and New York Heart Association functional class (P < .05). Exercise stress echocardiography of 12 patients demonstrated dynamic worsening in functional mitral stenosis (mitral valve area: 2.0 +/- 0.5 cm(2) to 1.4 +/- 0.2 cm(2), P < .01; mean pressure gradient: 1.5 +/- 0.9 mm Hg to 6.0 +/- 2.2 mm Hg, P < .01). CONCLUSIONS: Persistent subvalvular leaflet tethering in the presence of annular size reduction by surgery in ischemic mitral regurgitation frequently causes functional mitral stenosis at the leaflet tip level, which is related to heart failure symptoms and can be dynamic with significant exercise-induced worsening.