Exercise pulmonary hypertension in patients with systemic sclerosis based on updated guidelines.

Recent European guidelines have introduced the concept of exercise pulmonary hypertension (ex-PH). However, the clinical characteristics of ex-PH in systemic sclerosis (SSc) remains unknown. We aimed to investigate the characteristics of exercise pulmonary hypertension (ex-PH) in patients with systemic sclerosis (SSc), which are unknown. We retrospectively examined 77 patients with SSc who underwent symptom-limited exercise testing using a cycle ergometer with right heart catheterization at our hospital. Nineteen patients with postcapillary PH were excluded. Fifty-eight patients (median age, 63 years; 55 women) were divided into the overt-PH (n = 18, mean pulmonary arterial pressure [PAP] > 20 mmHg and pulmonary vascular resistance > 2 Wood units at rest), ex-PH (n = 19, mean PAP/cardiac output slope > 3), and non-PH (n = 21) groups. Exercise tolerance and echocardiography results were compared among the groups. Peak oxygen consumption was high in the non-PH group, intermediate in the ex-PH group, and low in the overt-PH group (14.5 vs. 13.0 vs. 12.5 mL/kg/min, p = 0.043), and the minute ventilation/peak carbon dioxide production slope was also intermediate in the ex-PH group (32.2 vs. 32.4 vs. 43.0, p = 0.003). The tricuspid annular plane systolic excursion/systolic PAP ratio decreased from non-PH to ex-PH to overt-PH (0.73 vs. 0.69 vs. 0.55 mm/mmHg, p = 0.018). In patients with SSc, exercise PH may represent an intermediate condition between not having PH and overt PH, according to the new guidelines.

Renin-angiotensin system inhibitors for patients with mild or moderate chronic kidney disease and heart failure with mildly reduced or preserved ejection fraction.

BACKGROUND: Renin-angiotensin system inhibitors (RASI) reduce adverse cardiovascular events in patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤40% and mild or moderate chronic kidney disease (CKD). However, RASI administration rate and its association with long-term outcomes in patients with CKD complicated by HF with LVEF >40% remain unclear. METHODS: We analyzed 1923 consecutive patients with LVEF >40% registered within the multicenter database for hospitalized HF. We assessed RASI administration rate and its association with all-cause mortality among patients with mild or moderate CKD (estimated glomerular filtration rate [eGFR]: 30-60 mL/min/1.73 m2). Exploratory subgroups included patients grouped by age (<80, ≥80 years), sex, previous HF hospitalization, B-type natriuretic peptide (higher, lower than median), eGFR (30-44, 45-59 mL/min/1.73 m2), systolic blood pressure (<120, ≥120 mmHg), LVEF (41-49, ≥50%), and mineralocorticoid receptor antagonists (MRA) use. RESULTS: Among patients with LVEF >40%, 980 (51.0%) had mild or moderate CKD (age: 81 [74-86] years; male, 52.6%; hypertension, 69.7%; diabetes, 25.9%), and 370 (37.8%) did not receive RASI. RASI use was associated with hypertension, absence of atrial fibrillation, and MRA use. After multivariable adjustments, RASI use was independently associated with lower all-cause mortality over a 2-year median follow-up (hazard ratio: 0.58, 95% confidence interval: 0.43-0.79, P = 0.001), and the mortality rate difference was predominantly due to cardiac death, consistent in all subgroups. CONCLUSIONS: Approximately one-third of HF patients with mild or moderate CKD and LVEF >40% were discharged without RASI administration and demonstrated relatively guarded outcomes.

Characteristics of cardiopulmonary exercise testing in patients with combined post- and pre-capillary pulmonary hypertension due to left heart disease.

BACKGROUND: Pulmonary hypertension (PH) is a common and morbid complication of left heart disease (LHD), comprising two subtypes: (1) isolated post-capillary pulmonary hypertension (Ipc-PH) and (2) combined post-capillary and pre-capillary pulmonary hypertension (Cpc-PH). Knowledge regarding the physiological characteristics that distinguish Cpc-PH, which has a worse prognosis, from Ipc-PH remains limited. Therefore, this study aimed to assess the utility of cardiopulmonary exercise testing (CPET) variables in detecting Cpc-PH. METHODS AND RESULTS: Among 105 consecutive patients with LHD (age: 55 ± 13 years; male/female = 79/26) who underwent right heart catheterization and CPET, 45 (43%) were classified as PH-LHD (mean pulmonary artery pressure >20 mmHg). Ipc-PH (n = 24) was defined as pulmonary vascular resistance (PVR) ≤ 3 WU and Cpc-PH (n = 21) as PVR > 3 WU. Patients with Cpc-PH had a significantly lower peak partial pressure of carbon dioxide (PETCO2) (Non-PH/Ipc-PH/Cpc-PH = 38.2 ± 6.6 vs. 38.3 ± 6.0 vs 33.0 ± 4.4 mmHg, p = 0.006), higher VE vs. VCO2 slope (Non-PH/Ipc-PH/Cpc-PH = 33.0 [28.3, 36.6] vs. 32.5 [28.1, 37.8] vs. 40.6 [33.6, 46.1], p = 0.007), and lower ΔVO2/ΔWR (Non-PH/Ipc-PH/Cpc-PH = 8.5 ± 1.4 vs. 8.0 ± 1.7 vs. 6.8 ± 2.0 mL/min/watt, p = 0.001) than those with Ipc-PH and non-PH. Using multivariable logistic regression analysis, CPET variables were found to be independent predictors of Cpc-PH (lower peak PETCO2: odds ratio, 0.728 [95% confidence interval {CI}: 0.616-0.840], p = 0.003 and lower ΔVO2/ΔWR: odds ratio, 0.747 [95% CI: 0.575-0.872], p = 0.003). CONCLUSION: From our exploratory analysis, CPET variables, especially in the lower peak PETCO2 and lower ΔVO2/ΔWR, were associated with Cpc-PH in patients with left heart disease.

Low blood pressure and guideline-directed medical therapy in patients with heart failure with reduced ejection fraction.

BACKGROUND: Patients with heart failure (HF) presenting with low blood pressure (BP) have been underrepresented in large-scale clinical trials. We investigated the characteristics and implementation of conventional guideline-directed medical therapy (GDMT; renin-angiotensin system inhibitors and ß-blockers) in patients with low BP hospitalized for HF with systolic dysfunction. METHODS: Conventional GDMT was evaluated by discharge BP among 2043 consecutive patients with HF and left ventricular ejection fraction (LVEF) < 50% in the WET-HF registry. Among the 708 (34.7%) patients with lower discharge BP (≤ 100 mmHg; the lower tertiles), exploratory subgroups included patients with previous HF hospitalization, inotrope use, New York Heart Association (NYHA) III-IV class, and lower estimated glomerular filtration rate (eGFR) and LVEF (lower than median value). We evaluated the risk-adjusted association between GDMT implementation and 2-year adverse events (all-cause mortality or HF rehospitalization). RESULTS: Among the 2043 patients (age 74 [63-82] years), the median systolic BP was 108 (98-120) mmHg. Among patients with lower BP, GDMT prescription rate was 62.7%, and GDMT use was associated with decreased adverse events (HR:0.74, 95%CI:0.58-0.94). GDMT prescription rates were lower among higher-NYHA class and lower-eGFR subgroups compared with their reference subgroups, and directionally similar outcomes were noted in all subgroups (favoring GDMT use); however, this association was somewhat attenuated in the lower-eGFR group (HR:0.87, 95%CI:0.64-1.17). CONCLUSIONS: Conventional GDMT use was associated with decreased adverse outcomes in most patients with HF compounded by systolic dysfunction and low BP, albeit caution is warranted in patients with renal dysfunction.

Malnutrition in real-world patients hospitalized for heart failure with preserved ejection fraction and its potential impact on generalizability of EMPEROR-Preserved trial.

BACKGROUND: Despite the benefits of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin, its suitability for patients with heart failure (HF) in the real-world setting remains unclear. Considering the unique pharmacological profile of SGLT2i (e.g., glucose excretion leading to calorie loss) and increasingly aging patients with HF, applicability of trials' finding in patients with malnutrition is important. METHODS: We examined 1633 consecutive patients with a preserved left ventricular ejection fraction (LVEF; >40%) enrolled in a multicenter-based acute HF registry. After applying the EMPEROR-Preserved eligibility criteria, we compared the baseline characteristics of trial-eligible and actual trial participants, and patients with and without malnutrition among the trial-eligible group. Malnutrition was assessed by the geriatric nutritional risk index (GNRI). The trial-eligible patients were divided into high (GNRI≥92) and low (GNRI<92) nutritional groups, and a composite endpoint comprising all-cause death and HF rehospitalization was evaluated. RESULTS: Majority (70.2%) of the analyzed patients were eligible for the EMPEROR-Preserved trial (age: 77 ± 12 years and body mass index [BMI]: 22.0 ± 4.1 kg/m2), but were older and had lower BMIs than the actual trial participants. Notably, 51.9% of the eligible patients were at high risk for malnutrition and had a higher rate of the composite endpoint than non-malnourished counterparts (HR 1.27, 95%CI 1.04-1.56, P = 0.020). The difference in outcomes was predominantly due to mortality from non-cardiac causes. CONCLUSIONS: Mostly patients with HF in a real-world setting met the EMPEROR-Preserved criteria; however, approximately half were at high risk for malnutrition with poorer outcomes owing to non-cardiac-related causes.

Multimorbidity, guideline-directed medical therapies, and associated outcomes among hospitalized heart failure patients.

AIMS: Multimorbidity is common among heart failure (HF) patients and may attenuate guideline-directed medical therapy (GDMT). Multimorbid patients are under-represented in clinical trials; therefore, the effect of multimorbidity clustering on the prognosis of HF patients remains unknown. We evaluated the prevalence of multimorbidity clusters among consecutively registered hospitalized HF patients and assessed whether GDMT attenuated outcomes. METHODS AND RESULTS: We examined 1924 hospitalized HF patients with reduced left ventricular ejection fraction (<50%) in a multicentre registry (West Tokyo HF Registry: WET-HF). Ten comorbid conditions in the WET-HF were abstracted: coronary artery disease, atrial fibrillation, stroke, anaemia, chronic obstructive pulmonary disease, renal dysfunction, obesity, hypertension, dyslipidaemia, and diabetes. Patients were divided into three groups (0-2: n = 451; 3-4: n = 787; and ≥5: n = 686) based on the number of comorbid conditions. The primary composite endpoint was all-cause mortality and HF rehospitalization. The most prevalent comorbidities were renal dysfunction (67.9%), hypertension (66.0%), and anaemia (53.8%). Increased comorbidity was associated with increased adverse outcomes [3-4: hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.13-1.77, P = 0.003; ≥5: HR 2.12, 95%CI 1.69-2.65, P < 0.001; and reference: 0-2] and lower GDMT prescription rate (0-2: 69.2%; 3-4: 57.7%; and ≥5: 57.6%). GDMT was associated with decreased adverse outcomes; this association was maintained even as the comorbidity burden increased but tended to weaken (0-2: HR 0.53, 95%CI 0.35-0.78; P = 0.001; 3-4: HR 0.82, 95%CI 0.65-1.04, P = 0.095; and ≥5: HR 0.81, 95%CI 0.65-1.00, P = 0.053; P for interaction = 0.156). CONCLUSIONS: Comorbidity clusters were prevalent and associated with poorer outcomes. GDMT remained beneficial regardless of the comorbidity burden but tended to weaken with increasing comorbidity burden. Further research is required to optimize medical care in these patients.

A penetrating atherosclerotic ulcer rapidly growing into a saccular aortic aneurysm during treatment of leukaemia: a case report.

BACKGROUND: The clinical course of penetrating atherosclerotic ulcers is variable and can be complicated with intramural haematomas, dissection, pseudoaneurysms, or aortic rupture. Because it can lead to life-threatening conditions, it needs to be managed carefully. CASE SUMMARY: A 68-year-old woman, who was treated for acute myeloid leukaemia (subtype: M0-FAB) approximately 1 year before presentation, visited the hospital with complaints of a headache and lumbar pain. After hospitalization, investigations revealed miliary tuberculosis. On the same day, she developed a Stanford type A acute aortic dissection (AAD) with cardiac tamponade; during the course of the previous leukaemia treatment, a small ulcerative lesion at the distal aortic arch grew into a small saccular aortic aneurysm (SAA) that expanded rapidly and finally developed into a Stanford type A AAD. However, the relationship between the SAA and aortic dissection could not be confirmed. DISCUSSION: The chronological changes in the atherosclerotic lesion at the distal aortic arch could be clearly observed because computed tomography scans were repeatedly obtained until just before the onset of AAD. The rapid progression of atherosclerotic lesions in the unique context of leukaemia treatment and miliary tuberculosis was considered to be a pathological characteristic, and the mechanism underlying this process was investigated. Clinicians should be aware of the aortic complications that may progress under special circumstances, such as anthracycline use or immunodeficiency. Careful observation is mandatory for patients with aortic disease.

Incidence and characteristics of acute aortic dissection in patients with out-of-hospital cardiopulmonary arrest evaluated by non-contrast computed tomography.

BACKGROUND: The exact epidemiology of acute aortic dissection, including cases of out-of-hospital cardiopulmonary arrest, is unclear. We aimed to investigate the incidence and characteristics of acute aortic dissection in patients with out-of-hospital cardiopulmonary arrest transferred to our institution and validate the related factors to out-of-hospital cardiopulmonary arrest in Stanford type A acute aortic dissection. METHODS: We retrospectively reviewed the acute-phase computed tomography data of patients with out-of-hospital cardiopulmonary arrest who visited our hospital between 1 January 2015 and 31 December 2017. RESULTS: Among 1011 consecutive patients with out-of-hospital cardiopulmonary arrest, excluding those aged 17 years and younger and exogenous out-of-hospital cardiopulmonary arrest, such as suicide and trauma, 934 underwent computed tomography examination and 71 (7.6%) were diagnosed with acute aortic dissection: 66 with Stanford type A and five with type B acute aortic dissection (out-of-hospital cardiopulmonary arrest group). Seventy-five patients without out-of-hospital cardiopulmonary arrest with Stanford type A acute aortic dissection visited our institution during the same period (non-out-of-hospital cardiopulmonary arrest group). Age, incidence of massive bloody pericardial effusion and massive intrathoracic haemorrhage were significantly higher in the out-of-hospital cardiopulmonary arrest than in the non-out-of-hospital cardiopulmonary arrest group (78 ± 8 years, 72.7% and 24.2% vs. 70 ± 13 years, 26.7% and 1.3%, respectively; all P < 0.01). These variables were independently related to out-of-hospital cardiopulmonary arrest. CONCLUSIONS: There may be more patients with acute aortic dissection with out-of-hospital cardiopulmonary arrest than previously thought. Aortic rupture into the pericardial space or thoracic cavity is the major cause of out-of-hospital cardiopulmonary arrest in these cases. Non-contrast computed tomography can be used to diagnose acute aortic dissection in patients with out-of-hospital cardiopulmonary arrest. Our study is one of a few to evaluate the real circumstances surrounding acute aortic dissection and its epidemiology.

Reducing radiation exposure during atrial fibrillation ablation using lectures to promote awareness.

Objective: Recently, concern has increased regarding the hazards of radiation exposure in patients and laboratory staff. Since the numbers of complex catheter ablations (CA) performed, duration of procedure times, and need for multiple sessions have increased, radiation exposure during each session needs to be minimised. Our study aimed to assess the impact of awareness on radiation exposure during CA for atrial fibrillation (AF). Methods: Mini-course lectures was delivered to the physicians and staff in the electrophysiology division. Its effect on the fluoroscopic time and radiation dose during AF ablation before (Group I, n=70), shortly after (Group II: n=70) and remotely after the mini-lecture (Group III, n=70) were evaluated. Patient demographics, preoperative testing and procedural parameters were collected. Results: The fluoroscopic time significantly reduced after the lecture (Group I and II: 25.1±10.0 and 15.1±7.3 min, respectively (p<0.0001)), and remained so in Group III (13.0±5.4 min), despite the increase in the number of persistent AFs. The radiation dose also significantly reduced (Groups I, II, III: 295.0±263.0, 109.6±103.5 and 110.1±89.6 mGy, respectively (p<0.0001)). Conclusion: Awareness on radiation exposure led to a significant reduction in fluoroscopic time and radiation dose during CA for AF, the effect of which persisted even to remote periods following the procedure.

Non-contrast computed tomography of type A acute aortic dissection in patients with out-of-hospital cardiopulmonary arrest: a case series.

BACKGROUND: The prognosis of patients admitted for acute aortic dissection (AAD) has remarkably improved. However, we must also consider out-of-hospital cardiopulmonary arrest (OHCPA) patients while assessing the prognosis. In recent years, autopsy imaging has become more common as an alternative to conventional autopsy. Therefore, we reviewed our OHCPA patients with type A AAD using acute phase non-contrast computed tomography (CT). CASE SUMMARY: Here, we report a case series of three patients who developed OHCPA and were diagnosed with type A AAD using non-contrast CT. Although the direct causes of death varied in each case, we could easily determine the direct causes of death from clinical course of the condition and from non-contrast CT. DISCUSSION: Although non-contrast CT does not completely replace autopsy, if its convenience and non-invasiveness make it possible for more patients to undergo the procedure, the real prognosis (including morbidity and mortality) may be better understood. Therefore, we considered it significant to use non-contrast CT for investigating the cause of sudden death.

Idiopathic Ventricular Arrhythmia Ablation Using Non-Fluoroscopic Catheter Visualization System.

A novel, sensor-based, electromagnetic, non-fluoroscopic catheter visualization (NFCV) system shows tracked catheters directly on pre-acquired fluoroscopy or cine loops. We aimed to evaluate the effectiveness of this system in the setting of catheter ablation for idiopathic premature ventricular contractions/ventricular tachycardia (i-PVC/VT).A total of 30 i-PVC/VT ablation procedures were performed using the NFCV system in conjunction with three-dimensional electroanatomic mapping system (3D-EMS) between January 2013 and April 2017. At the beginning of the procedure, cine loops of right and left anterior oblique views were obtained and replayed for subsequent mapping and ablation. Right ventriculography, aortography, or coronary angiography was performed, depending on the chamber of interest. We reviewed procedural parameters, comparing with the i-PVC/VT ablation procedure using conventional fluoroscopy (CvF) system (pre-, and post-NFCV implementation; 20 and 11 cases, respectively).I-PVC/VTs were successfully eliminated in 26 patients (87%) in the NFCV group and in 26 (84%) in the CvF group (P = 1.000). The procedure time in the NFCV group was comparable to that in the CvF group (119.8 versus 125.0 minutes, respectively, P = 0.868); the total fluoroscopy time was significantly shorter in the NFCV group (3.3 versus 16.6 minutes, P < 0.001). One patient in the CvF group experienced cardiac tamponade, requiring pericardial drainage. No major complications were encountered in the NFCV group.NFCV system, in conjunction with 3D-EMS, was safe and feasible for i-PVC/VT mapping and ablation. The system contributed to dramatically reduced fluoroscopy time, compared with CvF.

Sounding-rocket microgravity experiments on alumina dust.

Alumina (Al2O3) is believed to be the first major condensate to form in the gas outflow from oxygen-rich evolved stars because of the refractoriness and that α-Al2O3 (corundum, most stable polymorph) is a potential origin of a 13 µm feature that appears close to stars. However, no one has directly reproduced the 13 µm feature experimentally, and it has remained as a noteworthy unidentified infrared band. Here, we report nucleation experiments on Al2O3 nanoparticles monitored by a specially designed infrared spectrometer in the microgravity environment of a sounding rocket. The conditions approximate to those around asymptotic giant branch (AGB) stars. The measured spectra of the nucleated Al2O3 show a sharp feature at a wavelength of 13.55 µm and comparable in width to that observed near oxygen-rich AGB stars. Our finding that α-Al2O3 nucleates under certain condition provides a solid basis to elaborate condensation models of dust around oxygen-rich evolved stars.

Pure iron grains are rare in the universe.

The abundant forms in which the major elements in the universe exist have been determined from numerous astronomical observations and meteoritic analyses. Iron (Fe) is an exception, in that only depletion of gaseous Fe has been detected in the interstellar medium, suggesting that Fe is condensed into a solid, possibly the astronomically invisible metal. To determine the primary form of Fe, we replicated the formation of Fe grains in gaseous ejecta of evolved stars by means of microgravity experiments. We found that the sticking probability for the formation of Fe grains is extremely small; only a few atoms will stick per hundred thousand collisions so that homogeneous nucleation of metallic Fe grains is highly ineffective, even in the Fe-rich ejecta of type Ia supernovae. This implies that most Fe is locked up as grains of Fe compounds or as impurities accreted onto other grains in the interstellar medium.