Mai Kimura

Report of the American Heart Association (AHA) Scientific Sessions 2015, Orlando

The American Heart Association Scientific Sessions were held in Orlando on November 7-15, 2015. The meeting attracted more than 18,000 participants, including physicians, research scientists, students, and paramedical personnel, from more than 100 countries. Sessions over the 5 days included a comprehensive and unparalleled education delivered via more than 5,000 presentations, with 1,000 invited faculty members and 4,000 abstract presentations from the world leaders in cardiovascular disease. It also displayed the newest cardiovascular technology and resources by more than 200 exhibitors. There were 19 trials scheduled in 6 late-breaking clinical trial sessions. The Systolic Blood Pressure Intervention Trial (SPRINT) aimed to determine the most appropriate targets for the systolic blood pressure among persons without diabetes. A total of 9,361 persons with systolic blood pressure of ≥130 mmHg and an increased cardiovascular risk, but without diabetes, were randomly assigned to a target systolic blood pressure of <120 mmHg (intensive treatment) or a target of <140 mmHg (standard treatment). A significantly lower rate of the primary composite outcome and all-cause mortality in the intensive-treatment group than in the standard-treatment group was observed. Summaries and overviews of the late-breaking trials, clinical science special report sessions, and sessions to which members of the Japanese Circulation Society contributed are presented.

Balloon pulmonary angioplasty attenuates ongoing myocardial damage in patients with chronic thromboembolic pulmonary hypertension

Age, y Female sex, n (%) WHO functional class, n (%) II III IV Number of patients previously treated with PEA eGFR, mL/min/1.73 m BNP, pg/mL Six-minute walk distance, m Drugs, n (%) Phosphodiesterase type-5 inhibitor Endothelin-receptor antagonist Prostacyclin analogue Soluble guanylate cyclase stimulator Warfarin Diuretics Mean RAP, mm Hg Mean PAP, mm Hg CO, L/min PCWP, mm Hg PVR, dynes·sec·cm SvO2, %

Usefulness of Circulating Amino Acid Profile and Fischer Ratio to Predict Severity of Pulmonary Hypertension

Plasma amino acid concentrations (aminogram) show distinct patterns under various pathologic conditions. However, the plasma aminogram pattern in patients with pulmonary hypertension (PH) has not been elucidated. We sought to examine whether an aminogram could be predictive of clinical severity in patients with PH. We attained fasting plasma aminograms for 140 patients with PH and then compared the patient plasma amino acid levels with those of age- and gender-matched healthy control subjects. Aminograms revealed that the plasma concentrations of many amino acids were significantly different between patients with PH and healthy control subjects. We focused on the Fischer ratio (branched-chain amino acids/aromatic amino acids) as an integrated parameter. In all enrolled patients, Fischer ratio was negatively correlated with New York Heart Association functional class (ρ = -0.37, p <0.001), plasma B-type natriuretic peptide (ρ = -0.35, p <0.001), and pulmonary vascular resistance (ρ = -0.27, p = 0.002) and positively correlated with venous oxygen saturation (ρ = 0.27, p = 0.002) and 6-minute walk distance (ρ = 0.23, p = 0.016). Time course changes in Fischer ratio and in cardiac output were significantly correlated (ρ = 0.39, p = 0.024). The aminogram is changed in patients with PH, and in these patients, Fischer ratio decreases in proportion to the clinical severity of PH.

A genome-wide association analysis identifies PDE1A | DNAJC10 locus on chromosome 2 associated with idiopathic pulmonary arterial hypertension in a Japanese population

Pulmonary arterial hypertension (PAH) is a lethal disease that often affects the young. Although Bone Morphogenetic Protein Receptor Type 2 gene (BMPR2) mutations are related with idiopathic and heritable PAH, the low penetrance and variable expressivity in PAH suggest the existence of other genetic and/or environmental factors. In this study, we aimed to identify novel genetic factors associated with PAH, irrespective of BMPR2 mutation. We performed genome-wide association study (GWAS) in a Japanese population comprising 44 individuals with idiopathic and heritable PAH, and 2,993 controls. Seven loci identified in the genome-wide study were submitted to the validation study, and a novel susceptibility locus, PDE1A|DNAJC10, was identified that maps to 2q32.1 (rs71427857, P = 7.9 × 10-9, odds ratio in the validation study = 5.18; 95% CI 1.86 – 14.42). We also found the augmentation of PDE1A protein in distal remodeled pulmonary artery walls in idiopathic PAH patients. Given that phosphodiesterase 5 inhibitors are effective for the treatment of idiopathic and heritable PAH, our findings suggest that PDE1A could be a novel therapeutic target of PAH.

Dual phosphodiesterase type 5 inhibitor therapy for refractory pulmonary arterial hypertension: a pilot study

BackgroundRecent vasodilating drugs have improved prognosis of Pulmonary arterial hypertension (PAH). Some reports describe the merits of combination therapies for PAH, and this study evaluated the efficacy and safety of phosphodiesterase type 5 inhibitors (PDE5i) combination therapy, using sildenafil and tadalafil, for multi-drug-resistant PAH.MethodsWe retrospectively analyzed 7 consecutive refractory patients with PAH administered either sildenafil 60 mg or tadalafil 40 mg as well as both ERA and prostanoid as combination therapies. All were started on the dual PDE5i (sildenafil and tadalafil at maximum dose).ResultsTreatment was generally well tolerated without severe adverse events. On completion of the study, the seven patients received right heart catheterization and the 6-minute walk test (6WMT) 9.6 ± 1.4 months after initiation of the dual PDE5i therapy, showing significant improvements in hemodynamic parameters and exercise tolerance. Mean pulmonary arterial pressure and pulmonary vascular resistance decreased from 47.9 ± 9.7 to 41.7 ± 9.2 mmHg (P = 0.004) and 9.3 ± 2.7 to 6.7 ± 2.9 mmHg (P = 0.018), respectively. Cardiac index and 6MWT also increased from 2.8 ± 0.9 to 3.1 ± 0.8 L/min/m2 (P = 0.026) and 353 ± 60 to 382 ± 62 m (P = 0.014), respectively.ConclusionThe findings support dual PDE5i therapy as a new treatment option for refractory PAH.

Coexistence of two distinct fascinating cardiovascular disorders: Heterotaxy syndrome with left ventricular non-compaction and vasospastic angina

Coexistence of two distinct fascinating cardiovascular disorders: Heterotaxy syndrome with left ventricular non-compaction and vasospastic angina Toru Egashira ⁎, Shinsuke Yuasa , Mai Kimura , Mitsuaki Sawano , Atsushi Anzai , Kentaro Hayashida , Akio Kawamura , Takehiro Kimura , Nobuhiro Nishiyama , Yoshiyasu Aizawa , Seiji Takatsuki , Hikaru Tsuruta , Mitsushige Murata , Yoshitake Yamada , Takashi Kohno , Yuichiro Maekawa , Motoaki Sano , Kenjiro Kosaki , Keiichi Fukuda a

A Novel SCN5A Mutation Found in a Familial Case of Long QT Syndrome Complicated by Severe Left Ventricular Dysfunction

A 16-year-old boy with long QT syndrome type 3 (LQT3) was admitted for decompensated heart failure resulting from dilated cardiomyopathy (DCM). His brother was also diagnosed with LQT3 and DCM. A comprehensive genetic analysis identified a novel SCN5A missense mutation-p.Q371E-in these 2 affected living family members. It might be important to suspect the coexistence of DCM and LQT3 (which is rare according to previous articles) in cases with this novel SCN5A missense mutation.

Oral Nitrate Administration Ameliorates Cardiogenic Shock due to Eclipsed Mitral Regurgitation.

Eclipsed mitral regurgitation (MR) has been reported as transient massive functional MR caused by a sudden coaptation defect in the absence of left ventricular remodeling or epicardial coronary artery stenosis. Coronary spasm or microvascular dysfunction has been suggested to be associated with the pathogenesis. Here, we present a 68-year-old woman with eclipsed MR with cardiogenic shock ameliorated by nitrate. She was admitted for transient shock with massive functional MR. Transient MR was associated with a complete absence of mitral leaflet coaptation owing to tethering of the lateral posterior mitral leaflet. The leaflet tethering was triggered by transient myocardial ischemia around the anterolateral papillary muscle, which could have been caused by coronary spasm and/or microvascular dysfunction. During admission, she experienced similar repeated episodes, which were ameliorated by oral nitrate administration. This is the first described case of eclipsed MR with shock ameliorated by nitrate. Although eclipsed MR, a cause of life-threatening shock, is uncommon, we need to keep in mind that nitrate administration could be a treatment option even in patients with cardiogenic shock.

Rapid Initiation of Intravenous Epoprostenol Infusion Is the Favored Option in Patients with Advanced Pulmonary Arterial Hypertension

Background Intravenous infusion (IVI) of epoprostenol is an effective treatment for patients with advanced pulmonary arterial hypertension (PAH). However, there is no widely accepted standard method for initiating the IVI therapy. This study evaluated the hemodynamic improvements achieved with IVI epoprostenol to determine the optimal protocol for treatment initiation. Methods and Results We retrospectively analyzed 42 consecutive PAH patients who underwent IVI epoprostenol in Keio University Hospital from 2001 to 2013. The study group comprised 30 women with a mean age of 34.3 ± 1.9 years. The etiology of PAH was idiopathic or heritable PAH (I/HPAH) in 38 cases, PAH associated with connective tissue disease in 3, and Eissenmenger’s syndrome in the remaining case. We divided the patients into rapid- and slow-initiation therapy groups according to the cumulative epoprostenol dose administered during the first 180 days, and compared the hemodynamic changes between the groups. The median cumulative doses were 6142 ± 165 μg/kg and 3998 ± 132 μg/kg epoprostenol, respectively. While there were no significant differences in mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), or cardiac index (CI) between the groups before the IVI epoprostenol therapy, the rapid-initiation therapy group achieved significant improvements in these hemodynamic data compared with the slow-initiation therapy group (P < 0.005) at the follow-up right-heart catheterization (RHC). Conclusion Rapid initiation of IVI epoprostenol therapy achieved the optimal hemodynamic improvements in patients with severe PAH.

Moderate-to-severe obstructive sleep apnea is associated with subclinical myocardial injury and impaired hemodynamics in pulmonary hypertension patients

BACKGROUND The clinical significance of obstructive sleep apnea (OSA) in pulmonary hypertension (PH) patients remains unclear. We investigated the hemodynamics and serum troponin T concentrations associated with OSA in PH patients. METHODS Cross-sectional study was performed on data from 97 clinically stable PH patients. Using overnight sleep study, we evaluated apnea-hypopnea index (AHI) and divided patients into two groups: none-to-mild OSA (AHI < 15/h, N = 81) and moderate-to-severe OSA (AHI ≥ 15/h, N = 16). Clinical, hemodynamic, and laboratory data were compared with OSA severity. RESULTS Moderate-to-severe OSA patients had higher pulmonary vascular resistance (PVR; 6.5 [5.7-12.9] vs 4.4 [2.9-6.4] Wood units, p = 0.001) and mean pulmonary artery pressure (mPAP; 37 [30-49] vs 30 [22-37] mmHg, p = 0.045), and a lower cardiac index (2.2 [1.6-2.6] vs 2.8 [2.3-3.5] L/min/m2, p = 0.001) than those without. There was no association between plasma B-type natriuretic peptide (BNP) or serum C-reactive protein levels and OSA. However, high-sensitivity troponin T (hs-TnT) level was significantly higher in moderate-to-severe OSA patients (13 [8-18] vs 6 [4-10] ng/L, p <0.001). The hs-TnT level positively correlated with the plasma BNP level, mPAP, PVR, AHI, obstructive apnea index, and 6-min walking distance. After adjustment for age, estimated glomerular filtration rate, hypertension, smoking, and plasma BNP level, moderate-to-severe OSA was an independent factor for determining the plasma level of log hs-TnT level (β = 0.419, 95% confidence interval 0.119-0.718, p = 0.007). CONCLUSIONS Moderate-to-severe OSA is associated with impaired hemodynamics and subclinical myocardial damage in PH patients. Thus, OSA-related myocardial injury may play a role in hemodynamic destabilization with its associated poor prognosis.