Efficacy and Safety of Balloon Pulmonary Angioplasty for Patients With Chronic Thromboembolic Pulmonary Hypertension and Comorbid Chronic Obstructive Pulmonary Disease.

Background Balloon pulmonary angioplasty (BPA) is a promising treatment modality for nonoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, BPA for atypical CTEPH with concurrent chronic obstructive pulmonary disease (COPD) remains controversial owing to the risk of exacerbation of ventilation-perfusion mismatch. We aimed to evaluate the efficacy and safety of BPA for CTEPH with moderate or severe COPD. Methods and Results Data from 149 patients with CTEPH, who underwent BPA from March 2011 to June 2021, were retrospectively analyzed. Patients were divided based on COPD comorbidity: the COPD group (n=32, defined as forced expiratory volume in 1 second/forced vital capacity <70% and forced expiratory volume in 1 second <80% predicted) and the non-COPD group (n=101); patients with mild COPD (n=16) were excluded. Hemodynamic and respiratory parameters were compared between the groups. Hemodynamics improved similarly in both groups (reduction in pulmonary vascular resistance): -55.6±29.0% (COPD group) and -58.9±21.4% (non-COPD group); P=nonsignificant. Respiratory function and oxygenation improved in the COPD group (forced expiratory volume in 1 second/forced vital capacity [61.8±7.0% to 66.5±10.2%, P=0.02] and arterial oxygen partial pressure [60.9±10.6 mm Hg to 69.3±13.6 mm Hg, P<0.01]). Higher vital capacity (P=0.024) and higher diffusing capacity for lung carbon monoxide (P=0.028) at baseline were associated with greater improvement in oxygenation in the multivariable linear analysis. Lung injury per BPA session was 1.6% in the COPD group. Conclusions The efficacy and safety of BPA for nonoperable CTEPH in patients with comorbid COPD were similar to those in patients without COPD. Oxygenation and forced expiratory volume in 1 second/forced vital capacity improved in patients with COPD. BPA should be considered in patients with CTEPH with concurrent COPD.

Microvasculopathy Evaluated by Dual-Energy Computed Tomography in Patients with Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Arterial Hypertension.

Background: Poor subpleural perfusion (PSP) on dual-energy computed tomography (DE-CT) suggests microvasculopathy in chronic thromboembolic pulmonary hypertension (CTEPH). However, whether the microvasculopathy findings are equivalent to those in pulmonary arterial hypertension (PAH) remains unclear. The aim of this study was to elucidate the characteristics of microvasculopathy in CTEPH compared to those of that in PAH. Methods: We retrospectively reviewed subpleural perfusion on DE-CT and the hemodynamics of 23 patients with PAH and 113 with inoperable CTEPH. Subpleural perfusion on DE-CT was classified as poor (subpleural spaces in all segments with little or no perfusion) or normal. Results: PSP was observed in 51% of patients with CTEPH and in 4% of those with PAH (p < 0.01). CTEPH patients with PSP had poorer baseline hemodynamics and lower diffusing capacity for carbon monoxide divided by the alveolar volume (DLCO/VA) than those with CTEPH with normal perfusion (pulmonary vascular resistance [PVR]: 768 ± 445 dynes-sec/cm5 vs. 463 ± 284 dynes-sec/cm5, p < 0.01; DLCO/VA, 60.4 ± 16.8% vs. 75.9 ± 15.7%, p < 0.001). Despite the existence of PSP, hemodynamics improved to nearly normal in both groups after balloon pulmonary angioplasty. Conclusions: PSP on DE-CT, which is one of the specific imaging findings in CTEPH, might suggest a different mechanism of microvasculopathy from that in PAH.

Untying relaxed circular DNA of hepatitis B virus by polymerase reaction provides a new option for accurate quantification and visualization of covalently closed circular DNA.

Hepatitis B virus (HBV) is a small hepatotropic DNA virus that replicates via an RNA intermediate. After entry, the virus capsid carries relaxed circular DNA (rcDNA) into the nucleus where the viral genome is converted into covalently closed circular DNA (cccDNA), which serves as the template for all viral transcripts. To monitor cccDNA levels, preprocessing methods to eliminate rcDNA have emerged for quantitative PCR, although Southern blotting is still the only method to discriminate cccDNA from other DNA intermediates. In this study, we have established a robust method for untying mature rcDNA into double stranded linear DNA using specific polymerases. Untying rcDNA provides not only an alternative method for cccDNA quantification but also a sensitive method for visualizing cccDNA. We combined this method with plasmid-safe DNase and T5 exonuclease preprocessing and revealed that accurate quantification requires cccDNA digestion by a restriction enzyme because heat stability of cccDNA increases after T5 exonuclease treatment. In digital PCR using duplex TaqMan probes, fewer than 1000 copies of cccDNA were successfully visualized as double positive spots that were distinct from single positives derived from untied rcDNA. This method was further applied to the infection model of primary hepatocytes treated with nucleoside analogues and a core protein allosteric modulator to monitor cccDNA levels. Relative quantification of cccDNA by human genome copy demonstrated the possibility of precise evaluation of cccDNA level per nucleus. These results clearly indicate that the sequential reaction from untying rcDNA is useful to investigate cccDNA fates in a small fraction of nuclei.

Rescue balloon pulmonary angioplasty for life-threatening acute pulmonary embolism on chronic thromboembolic pulmonary hypertension patients.

We report the cases of two patients with life-threatening acute pulmonary embolism (PE) on chronic thromboembolic pulmonary hypertension (CTEPH) who were treated with rescue balloon pulmonary angioplasty (BPA). These cases highlight the effect of rescue BPA on acute PE on CTEPH, which requires veno-arterial extracorporeal membrane oxygenation.

Assessment of oxygenation after balloon pulmonary angioplasty for patients with inoperable chronic thromboembolic pulmonary hypertension.

BACKGROUND: The efficacy of balloon pulmonary angioplasty (BPA) in patients with inoperable chronic thromboembolic pulmonary hypertension would be promising. However, some patients showed residual dyspnea or symptoms, despite normalized hemodynamics. We aimed to clarify the clinical impact of oxygenation parameters on BPA outcome. METHOD: Ninety-nine consecutive patients who underwent BPA from September 2011 to December 2019 were enrolled. We evaluated hemodynamics with right heart catheterization, arterial blood gas examination, New York Heart Association functional class (NYHA-FC), respiratory function tests, nocturnal oximetry, and exercise capacity (6-min walk test and cardiopulmonary exercise testing) at baseline and after BPA. RESULT: Nearly normal hemodynamics was achieved after BPA (mean pulmonary artery pressure (PAP): 37.5 ± 10.0 to 20.6 ± 4.9 mmHg, p < 0.01). Oxygenation slightly improved (partial pressure of arterial oxygen; 61.5 ± 12.3 to 67.7 ± 12.7 mmHg, p < 0.01). Exertional desaturation remained unchanged (-8.1 ± 4.8 to -7.8 ± 5.1, p = 0.59), and this was associated with residual symptom (NYHA-FC ≥ 2) after BPA (OR 0.591, 95% CI 0.416-0.840, p = 0.003) in multivariate regression analyses. Lower vital capacity (r2 = 0.03, p = 0.01), higher mean PAP (r2 = 0.08, p = 0.02), and higher minute ventilation/carbon dioxide production (VE/VCO2) slope (r2 = 0.18, p < 0.01), the marker of ventilatory inefficiency, were correlated with exertional desaturation after BPA in multivariate linear analyses. CONCLUSION: Although hemodynamics nearly normalized, oxygenation did not. Moreover, exertional desaturation remained unchanged. This might cause residual symptom after BPA. Residual pulmonary hypertension suggesting incurable arteriopathy, and higher VE/VCO2 slope suggesting ventilation-perfusion mismatch might be related to exertional desaturation. Domiciliary oxygen therapy should be continued, if necessary.

Impact of Oral Health Status on Postoperative Complications and Functional Recovery After Cardiovascular Surgery.

BACKGROUND: Poor oral health status can lead to a deteriorated level of general health and is common among patients undergoing cardiovascular surgery. However, the effect of oral health status on postoperative outcomes in cardiovascular surgery patients remains unclear. Thus, we investigated the effect of preoperative oral health status on postoperative complications and functional recovery after cardiovascular surgery. METHODS: This single-centre retrospective cohort study included 884 inpatients undergoing elective cardiovascular surgery. Oral health status was assessed based on the number of remaining teeth, use of dentures, occlusal support, and periodontal status. We investigated postoperative complications related to surgery and postoperative functional recovery by measuring the reacquisition of walking ability, activities of daily living, and length of postoperative hospital stay. RESULTS: In this cohort (age 66.9 ± 13.4 years), the mean number of remaining teeth was 18.7 ± 9.4. Patients were grouped based on tertiles of the data distribution of remaining teeth: ≥ 20 teeth (470 patients); 10-19 teeth (137 patients); < 10 teeth (185 patients). The number of missing teeth was associated with age (P < 0.001). The prevalence of postoperative pneumonia and reintubation after surgery was 3.2% and 2.5%, respectively, which was significantly higher in patients with severe tooth loss (P < 0.05 for both). After adjusting for age and other confounding factors, the number of remaining teeth was a statistically significant predictor of functional recovery (P < 0.05). CONCLUSIONS: Preoperative oral health status was related to postoperative respiratory complications and independently associated with functional recovery. Preoperative oral intervention may improve functional recovery after cardiovascular surgery.

CONTEXTE: Une mauvaise santé buccodentaire peut avoir des répercussions néfastes sur la santé générale et est fréquemment observée chez les patients subissant une intervention chirurgicale cardiovasculaire. Cependant, l'effet de l'état de santé buccodentaire sur les issues postopératoires chez les patients ayant subi une telle intervention est mal connu. Nous avons donc étudié l'effet de l'état de santé buccodentaire avant l'intervention sur les complications postopératoires et le rétablissement fonctionnel après une intervention chirurgicale cardiovasculaire. MÉTHODOLOGIE: Cette étude de cohorte rétrospective menée dans un seul centre réunissait 884 patients subissant une intervention chirurgicale cardiovasculaire non urgente. L'état de santé buccodentaire des patients a été évalué en fonction du nombre de dents restantes, du recours à des prothèses dentaires, de la présence d'appuis occlusaux et de la santé parodontale. Nous avons examiné les cas de complications postopératoires liées à l'intervention chirurgicale ainsi que le rétablissement fonctionnel après l'intervention en évaluant la réacquisition de la capacité de marcher, la capacité d'accomplir les activités de la vie quotidienne et la durée du séjour à l'hôpital après l'intervention. RÉSULTATS: Dans cette cohorte (âge moyen : 66,9 ± 13,4 ans), les sujets avaient en moyenne 18,7 ± 9,4 dents restantes. Les patients ont été répartis en trois groupes en fonction du nombre de dents restantes : ≥ 20 dents (470 patients); de 10 à 19 dents (137 patients); < 10 dents (185 patients). Il y avait un lien entre le nombre de dents manquantes et l'âge (p < 0,001). La prévalence des cas de pneumonie postopératoire et de réintubation après l'intervention s'établissait à 3,2 % et à 2,5 %, respectivement, et était significativement plus élevée chez les patients à qui il restait très peu de dents (p < 0,05 dans les deux cas). Après correction pour tenir compte de l'âge et d'autres facteurs de confusion, le nombre de dents restantes s'est révélé être un facteur de prédiction statistiquement significatif du rétablissement fonctionnel (p < 0,05). CONCLUSIONS: L'état de santé buccodentaire avant l'intervention chirurgicale était lié à des complications respiratoires postopératoires et associé de manière indépendante au rétablissement fonctionnel. Des soins buccodentaires préopératoires pourraient améliorer le rétablissement fonctionnel après une intervention chirurgicale cardiovasculaire.

Evaluation of microvasculopathy using dual-energy computed tomography in patients with chronic thromboembolic pulmonary hypertension.

The existence of microvasculopathy in patients with chronic thromboembolic pulmonary hypertension has been suggested. Recently, dual-energy computed tomography has been used to produce a sensitive iodine distribution map in lung fields to indicate microvasculopathy according to poor subpleural perfusion. Our aim was to evaluate the impact of microvasculopathy on pathophysiology in chronic thromboembolic pulmonary hypertension. According to the extent of poor subpleural perfusion, ninety-three interventional treatment-naïve patients were divided into poorly perfused (n = 49) or normally perfused group (n = 44). We assessed cardiopulmonary exercise test, right heart catheterization, and dual-energy computed tomography parameters for quantitative evaluation of lung perfusion of blood volume score. Lung perfusion of blood volume score in normally perfused group was significantly inversely correlated with pulmonary vascular resistance (pulmonary vascular resistance = 6816.1 × lung perfusion of blood volume score-0.793, R2 = 0.225, p < 0.01), but lung perfusion of blood volume score in poorly perfused group was not. Poorly perfused group had higher pulmonary vascular resistance (879 ± 409 dynes-s/cm5 vs. 574 ± 279 dynes-s/cm5, p < 0.01) and lower lung perfusion of blood volume score (22.1 ± 5.4 vs. 26.4 ± 6.6, p < 0.01) and % diffusing capacity for carbon monoxide divided by the alveolar volume (59.9 ± 15.4% vs. 78.8 ± 14.2%, p < 0.01). Perfusion of blood volume score in the normally perfused group showed an inverse correlation with pulmonary vascular resistance; however, that in poorly perfused group did not. Microvasculopathy might contribute to severe hemodynamics, apart from pulmonary vascular obstruction. In our experience, more than half of treatment-naïve chronic thromboembolic pulmonary hypertension patients have microvasculopathy.

Preoperative frailty affects postoperative complications, exercise capacity, and home discharge rates after surgical and transcatheter aortic valve replacement.

Assessment of frailty is important for risk stratification among the elderly with severe aortic stenosis (AS) when considering interventions such as surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR). However, evidence of the impact of preoperative frailty on short-term postoperative outcomes or functional recovery is limited. This retrospective study included 234 consecutive patients with severe AS who underwent SAVR or TAVR at Kobe University Hospital between Dec 2013 and Dec 2019. Primary outcomes were postoperative complications, postoperative 6-min walking distance (6MWD), and home discharge rates. The mean age was 82 ± 6.6 years. There were 169 (SAVR: 80, TAVR: 89) and 65 (SAVR: 20, TAVR: 45) patients in the non-frail and frail groups, respectively (p = 0.02). The postoperative complication rates in the frail group were significantly higher than those in the non-frail group [30.8% (SAVR: 35.0%, TAVR: 28.9%) vs. 10.7% (SAVR: 15.0%, TAVR: 6.7%), p < 0.001]. The home discharge rate in the non-frail group was significantly higher than that in the frail group [85.2% (SAVR: 81.2%, TAVR: 88.8%) vs. 49.2% (SAVR: 55.0%, TAVR: 46.7%), p < 0.001]. The postoperative 6MWD in the non-frail group was significantly longer than that in the frail group [299.3 ± 87.8 m (SAVR: 321.9 ± 90.8 m, TAVR: 281.1 ± 81.3 m) vs. 141.9 ± 92.4 m (SAVR: 167.8 ± 92.5 m, TAVR: 131.6 ± 91.3 m), p < 0.001]. The TAVR group did not show a decrease in the 6MWD after intervention, regardless of frailty. We report for the first time that preoperative frailty was strongly associated with postoperative complications, 6MWD, and home discharge rates following both SAVR and TAVR. Preoperative frailty assessment may provide useful indications for planning better individualized therapeutic interventions and supporting comprehensive intensive care before and after interventions.

Effects of acute-phase multidisciplinary rehabilitation on unplanned readmissions after cardiac surgery.

OBJECTIVES: The provision of inpatient programs that reduce the incidence of readmission after cardiac surgery remains challenging. Investigators have focused on multidisciplinary cardiac rehabilitation (CR) because it reduces the postoperative readmission rate; however, most previous studies used outpatient models (phase II CR). We retrospectively investigated the effect of comprehensive multidisciplinary interventions in the acute inpatient phase (phase I CR) on unplanned hospital readmission. METHODS: In a retrospective cohort study, we compared consecutive patients after cardiac surgery. We divided them into the multidisciplinary CR (multi-CR) group or conventional exercise-based CR (conv-CR) group according to their postoperative intervention during phase I CR. Multi-CR included psychological and educational intervention and individualized counseling in addition to conv-CR. The primary outcome was unplanned readmission rates between the groups. A propensity score-matching analysis was performed to minimize selection biases and the differences in clinical characteristics. RESULTS: In our cohort (n = 341), 56 (18.3%) patients had unplanned readmission during the follow-up period (median, 419 days). Compared with the conv-CR group, the multi-CR group had a significantly lower unplanned readmission rate (multivariable regression analysis; hazard ratio, 0.520; 95% confidence interval, 0.28-0.95; P = .024). A Kaplan-Meier analysis of our propensity score-matched cohort showed that, compared with the conv-CR group, the multi-CR group had a significantly lower incidence of readmission (stratified log-rank test, P = .041). CONCLUSIONS: In phase I, compared to conv-CR alone, multi-CR reduced the incidence of unplanned readmission. Early multidisciplinary CR can reduce hospitalizations and improve long-term prognosis after cardiac surgery.

Relationship between oral health and physical frailty in patients with cardiovascular disease.

BACKGROUND: Oral health is important for maintaining general health and is associated with components of physical frailty among the elderly. Oral health problems are common in hospitalized patients; however, no reports on oral health problems pertain to patients with cardiovascular diseases (CVD). The present study aimed to evaluate the association between oral health and physical frailty in these patients. METHODS: In this retrospective cohort study, we included consecutive patients admitted for CVD to our hospital between May 2014 and December 2018. Physical frailty was assessed using the Short Physical Performance Battery (SPPB). Oral health characteristics, such as the number of remaining teeth, denture use, occlusal support, and periodontal status, were assessed. RESULTS: In our cohort (n = 457), 111 (24.3%) patients had physical frailty. Univariate linear regression showed that the number of teeth present and the prevalence of occlusal support were significantly lower in patients with than without physical frailty. Pearson correlation indicated that the number of teeth significantly correlated with the nutritional status (r = 0.27) and SPPB score (r = 0.24), grip strength (r = 0.33), and 6-minute walking distance (r = 0.26). Multiple linear regression analysis showed that the number of teeth was independently associated with physical frailty after adjusting for confounders. CONCLUSIONS: Oral health was closely associated with physical frailty, and nutritional status in patients with CVD; thus, it could be an important screening marker for early frailty symptoms and a predictor of future malnutrition risk.

Efficacy of preoperative amino acid supplements on postoperative physical function and complications in open heart surgery patients: A study protocol for a randomized controlled trial.

BACKGROUND: Elderly patients undergoing cardiac surgery often show poor nutritional status, muscle wasting, and sarcopenia, which are reported to affect postoperative functional recovery and incidence of complications. Amino acids are essential in maintaining nutritional status, synthesizing muscle protein, and promoting beneficial energy balance of the heart muscle. ß-Hydroxy ß-methylbutyric acid (HMB) is a leucine metabolite known to increase muscle protein synthesis and inhibit protein catabolism; it has been used to more effectively support patients with muscle wasting due to wearing diseases. However, the efficacy of amino acid administration comprising HMB in patients undergoing open heart surgery remains unclear. This study aims to examine whether preoperative short-term aggressive amino acid administration helps support postoperative recovery of physical function and prevent complications. METHODS: This is a single-center prospective randomized controlled trial (UMIN000030490). Patients aged ≥65 years who will be hospitalized for medical examination before cardiac surgery will be recruited. The participants will be randomly assigned to the experimental or control group. The experimental group will be administered with an amino acid supplement with HMB 1200mg, l-glutamine 7000mg, and l-arginine 7000mg once or twice per day depending on the degree of renal dysfunction, for 14-28 days preoperatively. The control group will not receive any nutritional intervention. The main outcome will be a change in the 6-min walking test distance pre- and postoperatively as a sign of functional recovery. Secondary outcomes such as the incidence of complications; physical, nutritional, and psychological states; mortality; and length of hospital stay will also be evaluated. CONCLUSION: This clinical study will determine the effects of preoperative short-term oral amino acid supplementation with HMB, l-glutamine, and l-arginine on postoperative physical function in elderly patients undergoing cardiac surgery.

Pulmonary Endarterectomy and Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension　- Similar Effects on Health-Related Quality of Life.

Background: While hemodynamics and exercise capacity in patients with chronic thromboembolic pulmonary hypertension (CTEPH) can be improved by invasive therapy such as pulmonary endarterectomy (PEA) and balloon pulmonary angioplasty (BPA), there has been little data on the health-related quality of life (HRQOL) in such patients. Methods and Results: This single-center and observational study compared the impact of invasive therapy on HRQOL. We utilized the Medical Outcome Study 36-Item Short Health Survey (SF-36) to measure HRQOL and compared HRQOL changes after PEA and BPA. A total of 48 patients were diagnosed with CTEPH. Of these, 39 patients completed questionnaires before and after invasive therapy. The PEA group (n=15) and the BPA group (n=24) had similar improvements in clinical parameters. With regard to HRQOL score, both groups had fairly low scores in physical functioning (PF), role physical (RP), general health (GH), social functioning (SF), role emotional (RE), and physical component summary (PCS) at baseline. PF, GH, vitality (VT), mental health (MH), and PCS had significant improvements in the PEA group while PCS and all subscales except for bodily pain (BP) had significant improvements in the BPA group. Furthermore, changes between baseline and follow-up were not significantly different between the 2 groups. Conclusions: BPA for patients who are ineligible for PEA can recover HRQOL to a similar level to that achieved by PEA.

Sequential Hybrid Therapy With Pulmonary Endarterectomy and Additional Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Residual symptoms after pulmonary endarterectomy (PEA) remain as the clinical issues to be solved. Additional balloon pulmonary angioplasty (BPA) after PEA showed its efficacy with symptoms in a case series, although long-term spontaneous recovery of exercise ability after PEA was also reported. However, no studies have validated the clinical efficacy of additional BPA by directly comparing PEA with and without BPA. The aim of this study was to retrospectively evaluate the efficacy of additional BPA as a sequential hybrid therapy for chronic thromboembolic pulmonary hypertension after PEA. METHODS AND RESULTS: Among 44 patients with chronic thromboembolic pulmonary hypertension, 20 patients had residual symptoms after PEA. Of those, 10 patients underwent additional BPA (hybrid group) and were compared with the other 10 patients, who were followed up without BPA (PEA group). The period from PEA to additional BPA was 7.3±2.3 months. In hybrid group, mean pulmonary arterial pressure was significantly improved by PEA (40.6±1.8 to 26.9±3.1 mm Hg, P=0.001) and improved further (to 16.7±1.8 mm Hg, P=0.002) with additional BPA, which resulted in remarkable improvement in World Health Organization (WHO) functional class (pre- to post-BPA: class I/II/III/IV, 0/5/4/1 to 7/3/0/0; P<0.001). Compared with the PEA group at follow-up, the hybrid group achieved better mean pulmonary arterial pressure (18.7±1.7 versus 30.2±3.2 mm Hg, P=0.008), WHO functional class (class I/II/III/IV, 7/3/0/0 versus 0/8/2/0; P=0.001), and 6-minute walking distance (429±38 versus 319±22 m, P=0.028). CONCLUSIONS: A sequential hybrid strategy improved residual symptoms and exercise capacity compared with single-PEA therapy.

Preoperative exercise capacity is associated with the prevalence of postoperative delirium in elective cardiac surgery.

BACKGROUND: Postoperative delirium (POD) is a critical complication that is closely associated with mortality and major morbidity in elective cardiac surgery. The identification of patients at risk for POD is crucial but has not been fully explored. AIMS: The aim of this study was to determine the predictive value of the assessment of preoperative exercise capacity for POD. METHODS: We enrolled 313 consecutive patients (mean age, 68.6 ± 14.8 years) undergoing elective cardiac surgery. We measured physical functions such as the 6-minute walking distance (6MWD) and Timed Up-and-Go test (TUG) before surgery. The assessment of delirium was conducted every 8 h from the day of surgery to 5 days after surgery using the Intensive Care Delirium Screening Checklist. RESULTS: POD occurred in 46 patients (14.6%). Age, 6MWD, TUG, serum hemoglobin, estimated glomerular filtration rate, and length of intensive care unit stay were significantly different based on the presence or absence of POD (p < 0.05 for each). After multivariate analysis, 6MWD remained a statistically significant indicator for developing POD (OR 0.98; p = 0.02). The cut-off value of 6MWD for predicting POD was 345 m (AUC = 0.75; p = 0.001). CONCLUSIONS: Poor exercise capacity was found to be an independent predictor of POD following elective cardiac surgery. This finding suggests the importance of preoperative functional evaluation in the prevention and management of POD in cardiac surgery patients.

Extensive revascularisation by balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension beyond haemodynamic normalisation.

AIMS: Balloon pulmonary angioplasty (BPA) improves hemodynamics and exercise capacity in patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, even after BPA many patients still suffered from exertional dyspnea. Our purpose is to clarify the clinical validity of extensive revascularization by BPA (ERBPA) beyond hemodynamic normalization. METHODS AND RESULTS: 35 CTEPH patients with normalized or borderline mean pulmonary arterial pressure (mPAP) after BPA were retrospectively analyzed. We evaluated the clinical efficacy of ERBPA strategy in 15 patients (ERBPA group) by comparing with the natural course of 20 patients who could be followed without additional BPA (conventional BPA group). ERBPA reduced the number of pulmonary arterial segments with residual stenoses from 11.7±0.4 to 5.3±0.5 segments. Symptoms, six-minute walking distance, and VE/VCO2 slope were significantly improved in the ERBPA group but not the conventional BPA group, which indicated that this improvement was due to ERBPA and not merely a natural progression after hemodynamic normalization. Complications accompanied with ERBPA were fewer than that of the initial BPA therapy. CONCLUSION: ERBPA targeting residual stenoses can safely ameliorate symptoms and exercise capacity by additional improvement of hemodynamics. The results encourage us to optimize the current BPA goal to be more aggressive.

Impact of delirium on postoperative frailty and long term cardiovascular events after cardiac surgery.

BACKGROUND: Postoperative delirium (POD) is a common and critical complication after cardiac surgery. However, the relationship between POD and postoperative physical frailty and the effect of both on long-term clinical outcomes have not been fully explored. OBJECTIVE: We aimed to examine the associations among POD, postoperative frailty, and major adverse cardiac events (MACE). DESIGN: This was a prospective cohort study. METHODS: We studied 329 consecutive patients undergoing elective cardiac surgery. The intensive care delirium screening checklist was used to assess POD. Postoperative frailty was defined by handgrip strength and walking speed. Patients were subsequently followed-up to detect MACE. RESULTS: POD was present in 13.2%, while the incidence of postoperative frailty was 27.0%. POD was independently associated with development of postoperative frailty (adjusted odds ratio = 2.98). During follow-up, MACE occurred in 14.1% of all participants. On multivariate Cox proportional hazard analysis, POD (adjusted hazard ratio (HR) = 3.36), postoperative frailty (HR = 2.21), postoperative complications (HR = 1.54), and left ventricular ejection fraction (HR = 0.95) were independently associated with increased risk of MACE. LIMITATIONS: It is a single-center study with a risk of bias. We did not investigate follow up cognitive function. CONCLUSIONS: POD was a predictor of postoperative frailty after cardiac surgery. Both postoperative frailty and POD were associated with the incidence of MACE, while POD was the stronger predictor of MACE. Thus, POD and frailty play critical roles in the risk stratification of patients undergoing cardiac surgery.

Associations of Exercise Tolerance With Hemodynamic Parameters for Pulmonary Arterial Hypertension and for Chronic Thromboembolic Pulmonary Hypertension.

PURPOSE: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are the main subgroups of pulmonary hypertension (PH). Despite differences in their etiologies, both diseases are characterized by vascular remodeling, resulting in progressive right heart failure. Noninvasive periodic evaluation of exercise tolerance has become increasingly important. Cardiopulmonary exercise testing (CPET) and a 6-minute walk test (6MWT) are now both recommended for evaluating exercise tolerance, but there is insufficient knowledge about possible differences in the associations of exercise tolerance with right heart catheterization (RHC) data for patients with PAH and CTEPH. METHODS: A retrospective study was performed with 57 patients with PH (24 with PAH and 33 with CTEPH) all of whom underwent echocardiography, CPET, 6MWT, and RHC. RESULTS: For both patients with PAH and CTEPH, peak heart rate during CPET was significantly higher than that from 6MWT, whereas minimum peripheral oxygen saturation during CPET and 6MWT was similar. For patients with PAH, significant correlations were observed between peak (Equation is included in full-text article.)O2 and cardiac index (CI) (r = 0.59; P = .002) and between (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 slopes and CI (r =-0.46, P = .02), as well as a nonsignificant correlation tendency for peak (Equation is included in full-text article.)O2 and pulmonary vascular resistance (PVR) and for (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 and PVR (r =-0.39; P = .05; and r = 0.39; P = .06, respectively). For patients with CTEPH, however, a significant correlation was observed only between (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 slopes and CI (r =-0.38; P = .02). CONCLUSION: PH etiology should be considered when assessing exercise tolerance, whereas CPET can be effective in addition to hemodynamic assessment by means of RHC for periodic evaluation during followup.

Practical synthesis of (20S)-10-(3-aminopropyloxy)-7-ethylcamptothecin, a water-soluble analogue of camptothecin.

A robust, practical synthesis of (20S)-10-(3-aminopropyloxy)-7-ethylcamptothecin (T-2513, 5), which is a water-soluble analogue of camptothecin, has been developed. The key step in this synthesis is a highly diastereoselective ethylation at the C20 position by using N-arylsulfonyl-(R)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid ester as a chiral auxiliary, which affords the key intermediate ethyl-(S)-2-acyloxy-2-(6-cyano-5-oxo-1,2,3,5-tetrahydroindolizin-7-yl)butanoate (8k) in 93% yield and 87% de. Optically pure compound 8k was obtained by a single recrystallization from acetone and its further elaboration through Friedlander condensation afforded compound 5. This synthesis does not require any chromatographic purification steps and can provide compound 5 on a multi-gram scale in 6.3% overall yield (16 steps).