Combination of F-ASO and Targeted Medical Therapy in Patients With Secundum ASD and Severe PAH

ObjectivesThis study was conducted to investigate the combined use of fenestrated atrial septal occluder (F-ASO) and targeted medical therapy (TMT) in patients with secundum atrial septal defect (ASD) and severe pulmonary arterial hypertension (PAH).BackgroundTreatment of patients with ASD and severe PAH is still challenging.MethodsAfter ethical approval was obtained, 56 consecutive patients with ASD with severe PAH were included (7 men, 49 women; median age 50.5 years; mean ASD size 26.9 ± 4.6 mm). After 3 months of TMT, transcatheter closure was performed using F-ASO in patients with ratios of pulmonary to systemic blood flow ≥1.5. TMT was continued post-operatively together with 6 months of dual-antiplatelet therapy. The hemodynamic variables during baseline, TMT alone, and combined treatment with F-ASO were compared.ResultsAfter only TMT, systolic pulmonary arterial pressure (−14.5 mm Hg; p < 0.001), pulmonary vascular resistance (−3.9 Wood units; p < 0.001), and exercise capacity (+72.0 m; p < 0.001) improved. Ratio of pulmonary to systemic blood flow increased by 0.9 (p < 0.001), with adverse cardiac remodeling (right ventricular dimension +3.5 mm; p < 0.001). Closure with F-ASO (median size 34.0 mm) led to further decrease in systolic pulmonary artery pressure (−6.0 mm Hg; p < 0.001). Follow-up (median duration 10 months) revealed further improvement in exercise capacity (+60.5 m; p < 0.001), with favorable cardiac remodeling (right ventricular dimension −9.9 mm; p < 0.001). In addition, all fenestrations were stable (p = 0.699), with negligible shunt (median ratio of pulmonary to systemic blood flow 1.1) and no complications. One year later, pulmonary artery pressure was normalized in 8 of 19 patients, and PAH recurred in 5 patients after discontinuation of TMT.ConclusionsIn patients with ASD and severe PAH, combination of F-ASO and TMT was a safe and effective procedure. Compared with TMT alone, the combined treatment further improved exercise capacity, with favorable cardiac remodeling.     

A suggested protocol for the endocrine postoperative management of patients undergoing pituitary surgery

PurposeEndocrine disorders are the most frequent postoperative complications in patients undergoing pituitary surgery. Given the absence of recent guidelines on the postoperative care following pituitary surgery, this article summarizes the available evidence on the topic.MethodWe conducted a systematic search of PubMed up to 2021 and updated the search in December 2022. We retrieved 119 articles and included 53 full-text papers.ResultsThe early postoperative care consists of the assessment for cortisol deficiency and diabetes insipidus (DI). Experts suggest that all patients should receive a glucocorticoid (GC) stress dose followed by a rapid taper. The decision for GC replacement after discharge depends on the morning plasma cortisol level on day 3 after surgery. Experts suggest that patients with a morning plasma cortisol < 10 mcg/dL should receive GC replacement at discharge, and those with 10–18 mcg/dL a morning dose only, with formal assessment of the hypothalamic-pituitary-adrenal axis at week 6 postoperatively. When the cortisol level is > 18 mcg/dL, the patient can be discharged safely without GC, as suggested by observational studies. Postoperative care also includes a close monitoring of water balance. If DI develops, desmopressin is used only in case of uncomfortable polyuria or hypernatremia. The assessment of other hormones is indicated at 3 months postoperatively and beyond.ConclusionThe evaluation and treatment of patients following pituitary surgery are based on expert opinion and a few observational studies. Further research is needed to provide additional evidence on the most appropriate approach.     

Cardiopulmonary Hemodynamic Profile Predicts Mortality After Transcatheter Tricuspid Valve Repair in Chronic Heart Failure

ObjectivesThis study was designed to assess hemodynamic changes in response to transcatheter tricuspid valve edge-to-edge repair (TTVR) and to identify hemodynamic predictors associated with mortality.BackgroundSevere tricuspid regurgitation (TR) is associated with high mortality. TTVR effectively alleviates heart failure symptoms, but comprehensive hemodynamic characterization of patients undergoing TTVR is currently lacking.MethodsThis international, multicenter study included 236 patients undergoing TTVR. Data from clinical assessment, echocardiography, intraprocedural right heart catheterization, and noninvasive cardiac output measurement were analyzed. Hemodynamic predictors for mortality were identified using linear Cox regression analysis and were used for stratification of patients with subsequent analysis of survival time.ResultsPatients (median age 78 years, 53% women) were symptomatic (89% in New York Heart Association functional class III or IV) because of severe TR (grade ≥3+ in 100%). TTVR significantly reduced TR at discharge (grade ≥3+ in 16%; p < 0.001), with a corresponding 19% reduction of the right atrial v wave (21 mm Hg vs. 16 mm Hg; p < 0.001) and an improvement in cardiac output (from 3.5 to 4.0 l/min; p < 0.01). Invasive mean pulmonary artery pressure, transpulmonary gradient, pulmonary vascular resistance, and right ventricular stroke work were significant predictors of 1-year mortality (p < 0.05 for all). Hemodynamic stratification by mean pulmonary artery pressure and transpulmonary gradient best predicted 1-year survival (p < 0.001). Although patients with pre-capillary dominant pulmonary hypertension showed an unfavorable prognosis (1-year survival 38%), patients without or with post-capillary pulmonary hypertension had favorable outcome (1-year survival 92% or 78%, respectively).ConclusionsInvasive assessment of cardiopulmonary hemodynamic status predicts survival after TTVR. Invasive hemodynamic characterization may help identify patients profiting most from TTVR.     

Serum cytokine changes induced by direct hemoperfusion with polymyxin B-immobilized fiber in patients with acute respiratory failure

BackgroundPolymyxin B-immobilized Fiber therapy (PMX-DHP) may improve the prognosis of patients with rapidly progressive interstitial lung diseases (ILDs). However, the mechanisms by which PMX-DHP ameliorates oxygenation are unclear. The present study aimed to clarify the changes in serum cytokine concentrations during PMX-DHP with steroid pulse therapy.MethodsPatients with acute respiratory failure (ARF) and rapidly progressive ILDs, acute exacerbation of idiopathic pulmonary fibrosis (IPF), or acute respiratory distress syndrome (ARDS), and treated with PMX-DHP were assessed, including patients with IPF. The serum concentrations of 38 cytokines were compared between the ARF and IPF groups before treatment. In the ARF group, cytokine levels were compared before, immediately after PMX-DHP, and the day after termination of steroid pulse therapy.ResultsFourteen ARF and eight IPF patients were enrolled. A comparison of the cytokine levels before treatment initiation revealed that EGF, GRO, IL-10, MDC, IL-12p70, IL-15, sCD40L, IL-7, IP-10, MCP-1, and MIP-1β were significantly different between the two groups. In the ARF group treated with PMX-DHP, the concentrations of MDC, IP-10, and TNF-α continuously decreased during treatment (P < 0.01). Further, the cytokine levels of GRO, IL-10, IL-1Ra, IL-5, IL-6, and MCP-1 decreased after the entire treatment period, with no change observed during the steroid-only period (P < 0.01, except GRO and MCP-1). Although PMX-DHP significantly reduced eotaxin and GM-CSF serum levels (P < 0.01 and P < 0.05), these levels did not change after treatment.ConclusionsPMX-DHP combined with steroid pulse therapy might reduce GRO, IL-10, IL-1Ra, IL-5, IL-6, and MCP-1 levels in ARF, contributing to better oxygenation in the disorder.     

COAPT-Like Profile Predicts Long-Term Outcomes in Patients With Secondary Mitral Regurgitation Undergoing MitraClip Implantation

ObjectivesThe aim of this study was to evaluate whether fulfilling COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) criteria identifies patients with better outcomes after MitraClip treatment for secondary mitral regurgitation (SMR).BackgroundTo date, COAPT is the only trial showing a prognostic benefit of MitraClip implantation compared with conservative management.MethodsThree hundred four patients with SMR undergoing MitraClip placement in addition to optimal medical therapy at 3 European centers were analyzed. A COAPT-like profile was defined as absence of all the following criteria: severe left ventricular impairment, moderate to severe right ventricular dysfunction, severe tricuspid regurgitation, severe pulmonary hypertension, and hemodynamic instability. Freedom from all-cause death and from a composite endpoint (cardiovascular death and heart failure hospitalization) were evaluated at 2- and 5-year follow-up.ResultsA COAPT-like profile was observed in 65% of the population. Compared with non-COAPT-like patients, those fulfilling COAPT criteria had greater survival free from all-cause death and from the composite endpoint at both 2 year (75% vs. 55% and 67% vs. 47%; p < 0.001 for both) and 5-year (49% vs. 25% and 40% vs. 19%; p < 0.001 for both) follow-up. Among the non-COAPT-like patients, similar outcomes were observed in those fulfilling 1 or ≥1 criterion. Left ventricular impairment had a late impact on outcomes, while right ventricular impairment, pulmonary hypertension, and hemodynamic instability had early effects. COAPT-like profile was an independent predictor of long-term outcomes, as well as administration of neurohormonal antagonists, European System for Cardiac Operative Risk Evaluation II score, and previous heart failure hospitalization.ConclusionsA COAPT-like profile, including specific echocardiographic and clinical criteria, identifies patients with SMR who have a better prognosis after MitraClip implantation.     

Empagliflozin in Patients With Heart Failure,Reduced Ejection Fraction,and Volume Overload: EMPEROR-Reduced Trial

BackgroundInvestigators have hypothesized that sodium-glucose cotransporter 2 (SGLT2) inhibitors exert diuretic effects that contribute to their ability to reduce serious heart failure events, and this action is particularly important in patients with fluid retention.ObjectivesThis study sought to evaluate the effects of the SGLT2 inhibitor empagliflozin on symptoms, health status, and major heart failure outcomes in patients with and without recent volume overload.MethodsThis double-blind randomized trial compared the effects of empagliflozin and placebo in 3,730 patients with heart failure and a reduced ejection fraction, with or without diabetes. Approximately 40% of the patients had volume overload in the 4 weeks before study enrollment.ResultsPatients with recent volume overload were more likely to have been hospitalized for heart failure and to have received an intravenous diuretic agent in an outpatient setting in the previous 12 months, and to experience a heart failure event following randomization, even though they were more likely to be treated with high doses of a loop diuretic agent as an outpatient (all p < 0.001). When compared with placebo, empagliflozin reduced the composite risk of cardiovascular death or hospitalization for heart failure, decreased total hospitalizations for heart failure, and improved health status and functional class. Yet despite the predisposition of patients with recent volume overload to fluid retention, the magnitude of these benefits (even after 1 month of treatment) was not more marked in patients with recent volume overload (interaction p values > 0.05). Changes in body weight, hematocrit, and natriuretic peptides (each potentially indicative of a diuretic action of SGLT2 inhibitors) did not track each other closely in their time course or in individual patients.ConclusionsTaken together, study findings do not support a dominant role of diuresis in mediating the physiological changes or clinical benefits of SGLT2 inhibitors on the course of heart failure in patients with a reduced ejection fraction. (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977)     

Impact of Pulmonary Hypertension Hemodynamic Status on Long-Term Outcome After Transcatheter Aortic Valve Replacement

ObjectivesThe aim of this study was to investigate the prognostic impact and development of pulmonary hypertension (PH) in the different hemodynamic subtypes of PH in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR).BackgroundPH is a frequent finding in patients with severe AS and predicts outcome after TAVR. Nevertheless, outcomes among PH subtypes and the impact of residual PH after TAVR are controversial.MethodsA total of 1,400 patients with symptomatic AS and full invasive hemodynamic assessment before and after TAVR were included. Patients were stratified into 4 groups: no PH (n = 658); isolated pre-capillary PH (n = 139), isolated post-capillary PH (Ipc-PH; n = 534), and combined post-capillary and pre-capillary PH (n = 69).ResultsThe mean overall patient age was 81.5 ± 6.8 years, and 46.3% were men. Acute device success was achieved in 94.9%. Patients without PH showed significantly lower mortality rates compared with patients with PH (1 year, 13.8% vs. 22.4% [p < 0.001]; 4 years, 37.2% vs. 51.5% [p < 0.001]). Patients with pre-capillary PH showed 1.9-fold increased 1-year mortality and those with Ipc-PH showed 1.5-fold increased 1-year mortality compared with patients without pH (p = 0.001). No differences regarding survival were found among the subgroups. Only in patients with Ipc-PH, residual PH was associated with 2.1-fold increased mortality (p = 0.010). All patients benefited in terms of functional capacity after TAVR.ConclusionsPatients with pre-capillary PH and those with Ipc-PH showed significantly higher risk for death after TAVR compared with those without PH. Reversible PH had no benefit for survival except in patients with Ipc-PH. Hemodynamic stratification of PH is helpful for risk and response prediction in patients with AS undergoing TAVR.     

Cerebellar syndrome associated with legionellosis: A case report and literature review

IntroductionLegionnaire's disease is a community-acquired pneumonia caused by the Gram-negative bacterium Legionella pneumophila. This disease is often associated with neurological symptoms, the clinical presentation of which can be very varied.Case reportWe report a 47-year-old female patient who developed Legionnaires’ disease with cerebellar symptoms (ataxia, dysarthria and hypermetria). Laboratory tests revealed a biological inflammatory syndrome. The cerebrospinal fluid was sterile. Urinary antigen test and serology were positive for L. pneumophila. An interstitial syndrome of the right upper lobe was detected on chest computed tomography (CT) scan. Brain imaging (magnetic resonance imaging and CT angiography) showed no abnormalities. The outcome was favourable after treatment with spiramycin, levofloxacin and corticosteroids.DiscussionFew cases only (n = 110) of Legionnaires’ disease with cerebellar symptoms have been reported in the literature. The pathogenic mechanism behind neurological dysfunction in patients with Legionnaires’ disease is unknown. Neurological symptoms improve with antibiotic therapy and corticosteroids. Extra-pulmonary forms of Legionnaires’ disease are frequent, with neurological symptoms being the most common symptoms. Cerebellar dysfunction may be underestimated and requires appropriate management with antibiotic therapy and corticosteroid therapy. Recommendations for the management of Legionnaire's disease with severe extra-pulmonary symptoms are needed.     

Gastroesophageal reflux-like symptoms are associated with hyposalivation and oropharyngeal problems in patients with asthma

BackgroundPrevious studies have suggested a significant relationship between hyposalivation and inhalation therapy-induced oropharyngeal problems. However, salivary secretion tests are not widely performed in daily clinical practice. In fact, xerostomia, the complaint of dry mouth, may not indicate hyposalivation. Therefore, we determined the clinical factors associated with hyposalivation in patients with asthma.MethodsThis study is a post-hoc analysis of our previous studies. Adult patients with asthma on maintenance inhalation therapy were enrolled. The participants completed questionnaires on oropharyngeal symptoms and underwent a salivary secretion test. Symptom severity was evaluated using a numerical rating scale (NRS), and salivary secretion was measured using the modified cotton roll method. Using logistic regression analysis, we identified the clinical factors associated with hyposalivation.ResultsIn total, 531 patients completed the questionnaire (43.8 ± 16.9 years and male/female = 171/360), and 234 patients successfully performed a salivary secretion test, of which 126 (53.8%) were diagnosed with hyposalivation (<0.25 g/min). The patients with hyposalivation were significantly older (p < 0.0001) and had severe xerostomia and/or gastroesophageal reflux-like symptoms (GERLS) (p < 0.0001). Many of these patients had also used inhaled long-acting beta agonists (p = 0.012) and high-dose inhaled corticosteroids (p = 0.024). Multivariate analysis revealed that advanced age (odds ratio [OR] 1.05, p < 0.0001), severe xerostomia (OR 1.02, p = 0.0006) and severe GERLS (OR 1.02, p = 0.001) were independently and significantly associated with hyposalivation.ConclusionsAge, xerostomia, and GERLS were significantly related to hyposalivation in patients with asthma. To identify oropharyngeal problems in these patients, a careful assessment of the suspected symptoms of gastroesophageal reflux may be useful.     

Prognostic Impact of Extra–Mitral Valve Cardiac Involvement in Patients With Primary Mitral Regurgitation

BackgroundIn patients with severe primary mitral regurgitation (MR), the indication for surgery is currently based on the presence of symptoms, left ventricular dilatation and dysfunction, atrial fibrillation, and pulmonary hypertension.ObjectivesThe aim of this study was to evaluate the prognostic impact of the presence of extra–mitral valve cardiac involvement (including known risk factors but also severe left atrial [LA] dilatation and right ventricular [RV] dysfunction) in a large multicenter study of patients with primary MR.MethodsPatients with severe primary MR undergoing surgery were included and categorized according to the extent (highest) of cardiac involvement: group 0, no cardiac involvement; group 1, left ventricular involvement; group 2, LA involvement; group 3, pulmonary vasculature or tricuspid valve involvement; or group 4, RV involvement. The outcome was all-cause mortality.ResultsA total of 1,106 patients were included (mean age 63 ± 12 years, 68% male). In total, 377 patients (34%) were classified in group 0, 239 (22%) in group 1, 213 (19%) in group 2, 180 (16%) in group 3, and 97 (9%) in group 4. Kaplan-Meier curve analysis revealed significantly worse survival (log-rank chi-square = 43.4; P < 0.001) with higher group. On multivariable analysis, age, male sex, chronic obstructive pulmonary disease, kidney function, and group of cardiac involvement were independently associated with all-cause mortality. For each increase in group, a 17% higher risk for all-cause mortality was observed (95% CI: 1.051-1.313; P = 0.005) during a median follow-up time of 88 months.ConclusionsIn patients with severe primary MR, a novel classification system based on extra–mitral valve cardiac involvement may help refine risk stratification and timing of surgery, particularly including severe LA dilatation and RV dysfunction in the assessment.     

Linear lesions for treating the recurrence of persistent atrial tachyarrhythmia after cryoballoon ablation of atrial fibrillation

Overall, 133 patients underwent 170 procedures for the treatment of persistent ATa following an index cryoballoon pulmonary vein isolation (n = 715). After all the procedures, > 90% of the patients had a roof line, a mitral isthmus and/or septal line, and a cavotricuspid isthmus line. Ninety-two patients (69.2%) were in sinus rhythm after a median of 36 months since the index cryoballoon PVI. ATa: atrial tachyarrhythmia; cryo: cryoballoon; CTI: cavotricuspid isthmus; LSPV: left superior pulmonary vein; LIPV: left inferior pulmonary vein; PVI: pulmonary vein isolation; RF: radiofrequency; RSPV: right superior pulmonary vein; RIPV: right inferior pulmonary vein.

     

Solving the Pulmonary Hypertension Paradox in Patients With Severe Tricuspid Regurgitation by Employing Artificial Intelligence

ObjectivesThis study aimed to improve echocardiographic assessment of pulmonary hypertension (PH) in patients presenting with severe tricuspid regurgitation (TR).BackgroundEchocardiographic assessment of PH in patients with severe TR carries several pitfalls for underestimation, hence concealing the true severity of PH in very sick patients in particular, and ultimately obscuring the impact of PH on survival after transcatheter tricuspid valve intervention (TTVI).MethodsAll patients in this study underwent TTVI for severe TR between 2016 and 2020. To predict the mean pulmonary artery pressure (mPAP) solely based on echocardiographic parameters, we trained an extreme gradient boosting (XGB) algorithm. The derivation cohort was constituted by 116 out of 162 patients with both echocardiography and right heart catheterization data, preprocedurally obtained, from a bicentric registry. Moreover, 142 patients from an independent institution served for external validation.ResultsSystolic pulmonary artery pressure was consistently underestimated by echocardiography in comparison to right heart catheterization (40.3 ± 15.9 mm Hg vs 44.1 ± 12.9 mm Hg; P = 0.0066), and the assessment was most discrepant among patients with severe defects of the tricuspid valve and impaired right ventricular systolic function. Using 9 echocardiographic parameters as input variables, an XGB algorithm could reliably predict mPAP levels (R = 0.96, P < 2.2 × 10^-16). Moreover, patients with elevations in predicted mPAP levels ≥29.9 mm Hg showed significantly reduced 2-year survival after TTVI (58.3% [95% CI: 41.7%-81.6%] vs 78.8% [95% CI: 68.7%-90.5%]; P = 0.026). Importantly, the poor prognosis associated with elevation in predicted mPAP levels was externally confirmed (HR for 2-year mortality: 2.9 [95% CI: 1.5-5.7]; P = 0.002).ConclusionsPH in patients with severe TR can be reliably assessed based on echocardiographic parameters in conjunction with an XGB algorithm, and elevations in predicted mPAP levels translate into increased mortality after TTVI.     

Comparative non-persistence in the first year of treatment with oral anticoagulants in patients with atrial fibrillation: A French comprehensive nationwide study

BackgroundDirect oral anticoagulants (DOACs) were developed as an alternative to vitamin K antagonists (VKAs) and are commonly used for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Unlike VKAs, DOACs do not require Internal Normalized Ratio (INR) monitoring, but regular intake is as important for effective anticoagulation.ObjectivesThis study examined treatment persistence among patients receiving oral anticoagulants (OACs) for NVAF.MethodsWithin the French healthcare claims database (SNDS), we assessed and compared the rates of non-persistence (≥ 30-day treatment gap) among patients with NVAF initiating an OAC between January 2014 and December 2016. The time-to-event of non-persistence was computed and plotted using a cumulative incidence function accounting for the competing risk of mortality. After adjusting on confounding factors, the risk for non-persistence was compared between apixaban and each other OACs using a Cox proportional hazard model, or Fine and Gray models.ResultsIn a cohort of 321,501 OAC-naive patients with NVAF, the cumulative incidence of non-persistence at 12 months considering competing risk was 44.3%, 31.0%, 41.3% and 46.8% for VKAs, apixaban, rivaroxaban and dabigatran, respectively. Median therapy duration before non-persistence ranged between 70 and 121 days. Non-persistence was lower with apixaban compared with VKAs (HR = 0.63, 95%CI = [0.62–0.64]), rivaroxaban (HR = 0.71, 95%CI = [0.70–0.73]), and dabigatran (HR = 0.60, 95%CI = [0.59–0.62]).ConclusionsIn this nationwide observational study, non-persistence rates of oral anticoagulant treatment were high in patients treated for NVAF. Apixaban-treated patients seem to experience lowest discontinuation rates 12 months after treatment initiation compared to patients treated with any other OAC.     

Predictive models assessing the response to ustekinumab highlight the value of therapeutic drug monitoring in Crohn’s disease

BackgroundDespite the therapeutic efficacy of Ustekinumab (UST) in Crohn's disease (CD), loss of response (LOR) is observed over time. This study aims to evaluate the impact of the UST pharmacokinetics (PK) at induction on clinical and endoscopic outcomes, as well as to find predictive markers of UST response.MethodsThis retrospective study included 80 CD patients. Pharmacokinetics data (trough levels (TLs)) combined with clinical and biological parameters were fed into tailored logistic regression and tree-based ensemble techniques to predict clinical and endoscopic outcomes at one year of follow-up.ResultsTLs at week 16 were significantly lower among patients with moderate to severe endoscopic activity during the follow-up (p = 0.04). The best model to predict endoscopic outcome was obtained at week 16 by Random Forest with an area under the receiver operating characteristic curve of 0.92 ± 0.08, sensitivity 91% and specificity 75%, with key inputs such as lymphocyte and monocyte counts at week 8, and UST TLs and CRP at week 16.ConclusionsThis real-world study confirms the relationship between early UST TLs and both clinical and endoscopic outcomes. Models were developed for the task of predicting clinical and endoscopic remission in CD patients treated with UST, highlighting the clinical relevance of UST TLs at week 16.     

Efficacy of immunoglobulin replacement therapy and azithromycin in severe asthma with antibody deficiency

BackgroundAlthough antibody deficiency (AD) is a well-known cause of recurrent respiratory infections, there are few data on its impact in adults with asthma. The objective of the present study was to assess outcomes in adults with severe asthma and AD after treatment with either azithromycin or subcutaneous immunoglobulins (SCIg).MethodsWe performed a 5-year, prospective, observational, two-centre study of adults with severe asthma and AD in France. Bronchiectasis was ruled out by high-resolution computed tomography. Patients were treated for one year with either azithromycin (250 mg every other day) or SCIg (0.4–0.6 g/kg/months, weekly). All patients were evaluated for exacerbations, asthma control and lung function at baseline and then one year after treatment initiation.ResultsThirty-nine patients with severe asthma were included in the study: 14 had been treated with azithromycin and 25 had been treated with SCIg. Before the initiation of treatment for AD, all patients had an Asthma Control Questionnaire (ACQ-7) score > 1.5 (mean ± SD: 2.71 ± 0.53) despite treatment at GINA step 4 or 5, and had a high exacerbation rate requiring oral corticosteroids and/or rescue antibiotics (∼7.2 ± 2.1/patient/year). One year after treatment initiation, we observed a significantly higher FEV1 (mean: 0.18 ± 0.22 L) and ACQ-7 score (1.26 ± 0.68), and a significantly lower exacerbation rate (1.63 ± 1.24/patient/year).ConclusionsTreatment of AD dramatically improved asthma outcomes - suggesting that adults with severe asthma and recurrent respiratory infections should be screened and (if appropriate) treated for AD.     

Lower dose of ethambutol may reduce ocular toxicity without radiological deterioration for Mycobacterium avium complex pulmonary disease

BackgroundEthambutol ocular toxicity is a major problem during combination chemotherapy for Mycobacterium avium complex (MAC) pulmonary disease (MAC-PD) due to years-long therapy for MAC.ObjectivesThis study aimed to identify the lower dose of daily ethambutol that can reduce ocular toxicity.MethodsWe retrospectively reviewed the medical records of 312 patients who visited The University of Tokyo Hospital between January 2007 and December 2017 for nontuberculous mycobacterial pulmonary disease. Seventy-six patients with MAC-PD who were treated with combination chemotherapy for the first time were analyzed in this study.ResultsEthambutol was discontinued because of visual symptoms in 13 patients (17%), 7 of whom were diagnosed with ethambutol ocular neuropathy. The dose per body weight was significantly higher in patients who developed ocular neuropathy than in those who did not (15.4 mg/kg/d vs. 12.5 mg/kg/d, respectively; p = 0.048). We assigned patients to higher or lower dose groups according to the median dose of 12.5 mg/kg/d. Although ocular neuropathy developed in 6 out of 38 patients in the higher dose group, ocular neuropathy developed in 1 out of 38 patients in the lower dose group (16% vs. 3%, respectively; p = 0.038). The failures of sputum culture conversion and radiological improvement were not significantly different between the two groups (p = 0.638 and 0.305, respectively). Macrolide resistance developed in one patient per group during follow-up (3% per group, p = 0.945).ConclusionsA lower dose of ethambutol may reduce ocular toxicity without radiological deterioration for pulmonary MAC infection.     

Impact of Coronary Artery Tortuosity on Outcomes Following Stenting: A Pooled Analysis From 6 Trials

ObjectivesThe authors sought to determine whether coronary artery tortuosity negatively affects clinical outcomes after stent implantation.BackgroundCoronary artery tortuosity is a common angiographic finding and has been associated with increased rates of early and late major adverse events after balloon angioplasty.MethodsIndividual patient data from 6 prospective, randomized stent trials were pooled. Outcomes at 30 days and 5 years following percutaneous coronary intervention of a single coronary lesion were analyzed according to the presence or absence of moderate/severe vessel tortuosity, as determined by an angiographic core laboratory. The primary endpoint was target vessel failure (TVF) (composite of cardiac death, target vessel–related myocardial infarction [TV-MI], or ischemia-driven target vessel revascularization [ID-TVR]).ResultsA total of 6,951 patients were included, 729 of whom (10.5%) underwent percutaneous coronary intervention in vessels with moderate/severe tortuosity. At 30 days, TVF was more frequent in patients with versus without moderate/severe tortuosity (3.8% vs. 2.4%; hazard ratio [HR]: 1.64; 95% confidence interval [CI]: 1.09 to 2.46; p = 0.02), a difference driven by a higher rate of TV-MI. At 5 years, TVF remained increased in patients with moderate/severe tortuosity (p = 0.003), driven by higher rates of TV-MI (p = 0.003) and ID-TVR (p = 0.01). Definite stent thrombosis was also greater in patients with versus without moderate/severe tortuosity (1.9% vs. 1.0%; HR: 1.86; 95% CI: 1.02 to 3.39; p = 0.04). After adjustment for baseline covariates, moderate/severe vessel tortuosity was independently associated with TV-MI and ID-TVR at 5 years (p = 0.04 for both).ConclusionsStent implantation in vessels with moderate/severe coronary artery tortuosity is associated with increased rates of TVF due to greater rates of TV-MI and ID-TVR.     

Transfemoral Tricuspid Valve Replacement in Patients With Tricuspid Regurgitation: TRISCEND Study 30-Day Results

ObjectivesThe TRISCEND study (Edwards EVOQUE Tricuspid Valve Replacement: Investigation of Safety and Clinical Efficacy after Replacement of Tricuspid Valve with Transcatheter Device) is evaluating the safety and performance of transfemoral transcatheter tricuspid valve replacement in patients with clinically significant tricuspid regurgitation (TR) and elevated surgical risk.BackgroundTranscatheter valve replacement could lead to a paradigm shift in treating TR and improving patient quality of life.MethodsIn the prospective, single-arm, multicenter TRISCEND study, patients with symptomatic moderate or greater TR, despite medical therapy, underwent percutaneous transcatheter tricuspid valve replacement with the EVOQUE system. A composite rate of major adverse events, echocardiographic parameters, and clinical, functional, and quality-of-life measures were assessed at 30 days.ResultsFifty-six patients (mean age of 79.3 years, 76.8% female, 91.1% TR severe or greater, 91.1% atrial fibrillation, and 87.5% New York Heart Association functional class III or IV) were treated. At 30 days, TR was reduced to mild or less in 98%. The composite major adverse events rate was 26.8% at 30 days caused by 1 cardiovascular death in a patient with a failed procedure, 2 reinterventions after device embolization, 1 major access site or vascular complication, and 15 severe bleeds, of which none were life-threatening or fatal. No myocardial infarction, stroke, renal failure, major cardiac structural complications, or device-related pulmonary embolism were observed. New York Heart Association significantly improved to functional class I or II (78.8%; P < 0.001), 6-minute walk distance improved 49.8 m (P < 0.001), and Kansas City Cardiomyopathy Questionnaire score improved 19 points (P < 0.001).ConclusionsEarly experience with the transfemoral EVOQUE system in patients with clinically significant TR demonstrated technical feasibility, acceptable safety, TR reduction, and symptomatic improvement at 30 days. The TRISCEND II randomized trial (NCT04482062) is underway.     

Unsupervised clustering of patients with severe aortic stenosis: A myocardial continuum

BackgroundTraditional statistics, based on prediction models with a limited number of prespecified variables, are probably not adequate to provide an appropriate classification of a condition that is as heterogeneous as aortic stenosis (AS).AimsTo investigate a new classification system for severe AS using phenomapping.MethodsConsecutive patients from a referral centre (training cohort) who met the echocardiographic definition of an aortic valve area (AVA) ≤ 1 cm² were included. Clinical, laboratory and imaging continuous variables were entered into an agglomerative hierarchical clustering model to separate patients into phenogroups. Individuals from an external validation cohort were then assigned to these original clusters using the K nearest neighbour (KNN) function and their 5-year survival was compared after adjustment for aortic valve replacement (AVR) as a time-dependent covariable.ResultsIn total, 613 patients were initially recruited, with a mean ± standard deviation AVA of 0.72 ± 0.17 cm². Twenty-six variables were entered into the model to generate a specific heatmap. Penalized model-based clustering identified four phenogroups (A, B, C and D), of which phenogroups B and D tended to include smaller, older women and larger, older men, respectively. The application of supervised algorithms to the validation cohort (n = 1303) yielded the same clusters, showing incremental cardiac remodelling from phenogroup A to phenogroup D. According to this myocardial continuum, there was a stepwise increase in overall mortality (adjusted hazard ratio for phenogroup D vs A 2.18, 95% confidence interval 1.46–3.26; P < 0.001).ConclusionsArtificial intelligence re-emphasizes the significance of cardiac remodelling in the prognosis of patients with severe AS and highlights AS not only as an isolated valvular condition, but also a global disease.     

Clinical characteristics,outcomes, and factors associated with mortality in Nocardia pneumonia: 18 years' real-world data from a tertiary care hospital in Karachi,Pakistan

BackgroundPulmonary nocardiosis is a rare pulmonary infection with high morbidity and mortality. Limited real-world data on pulmonary nocardiosis patients are available from developing countries like Pakistan.MethodsThis retrospective observational study was conducted at the Aga Khan University Hospital, Karachi, Pakistan, from August 2003 to June 2020. Demographics, immune status, underlying diseases, laboratory data, treatment, and outcomes of all nocardiosis patients were recorded in predesigned proforma.ResultsSixty-six patients with smear/culture-proven pulmonary nocardiosis were identified. Most patients (83.3%) were treated with trimethoprim-sulfamethoxazole alone or in combination with other medicines. The overall mortality rate in our study was 33.3% (n = 22/66). Factors significantly associated with mortality were respiratory failure (p < 0.001), raised procalcitonin levels (p = 0.01), concomitant fungal infections (p = 0.01), concomitant TB (p = 0.03), and patients on combination therapy (p < 0.001).Respiratory failure (odds ratio [OR] 46.94 [95% confidence intervals [CI]: 5.01–439.03] p < 0.001), concomitant fungal infection (OR 17.09 [95% CI: 1.47–197.88] p- = 0.02) and patients on combination therapy (OR 6.90 [95% CI: 1.23–38.61] p = 0.02) were also identified as independent risk factors for mortality on multivariate analysis.ConclusionsThis study provides essential information on the clinical characteristics and risk factors, outcomes, and factors associated with mortality for pulmonary nocardial infections.