Renal Outcomes Following Transcatheter Mitral Valve Repair - Analysis of COAPT Trial Data.

The prevalence of valvular heart disease in the United States has been estimated at 4.2-to-5.6 million, with mitral regurgitation (MR) being the most common lesion. Significant MR is associated with heart failure (HF) and death if left untreated. When HF is present, renal dysfunction (RD) is common and is associated with worse outcomes (ie, it is a marker of HF disease progression). Additionally, a complex interplay exists in patients with HF who also have MR, as this combination further impairs renal function, and the presence of RD further worsens prognosis and often limits guideline-directed management and therapy (GDMT). This has important implications in secondary MR because GDMT is the standard of care. However, with the development of minimally invasive transcatheter mitral valve repair, mitral transcatheter edge-to-edge repair (TEER) has become a new treatment option for secondary MR that is now incorporated into current guidelines published in 2020 that listed mitral TEER as a class 2a recommendation (moderate recommendation with benefit >> risk) as an addition to GDMT in a subset of patients with left ventricular ejection fraction <50%. The Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial, which demonstrated favorable outcomes in secondary MR by adding mitral TEER to GDMT versus GDMT alone, was the evidence base for these guidelines. Considering these guidelines and the understanding that concomitant RD often limits GDMT in secondary MR, there is emerging research studying the renal outcomes from the COAPT trial. This review analyzes this evidence, which could further influence current decision-making and future guidelines.

The Dicrotic Notch: Mechanisms, Characteristics, and Clinical Correlations.

PURPOSE OF REVIEW: The dicrotic notch (DN) has long been considered a marker of arterial stiffness and compliance. Herein, we explored the recent developments in vascular medicine research in an attempt to assess the DN utility in clinical cardiovascular medicine. RECENT FINDINGS: Since its discovery, several studies have attempted to measure the changes in different parameters of the DN in physiological and pathological states. Despite the significance of their findings, the clinical role of the DN remained limited. This may have been related to the difficulty of measuring the DN via indwelling arterial catheters in the past. However, over the past two decades, several non-invasive methods have been developed, which may re-ignite interest in DN research. The DN may have broader applications in clinical cardiovascular medicine. Further research is needed to establish the accuracy of DN non-invasive measurement methods and compare its prognostic value to other circulatory parameters.

Problems with interpreting troponins in chronic kidney disease patients for ruling out acute coronary syndrome.

Chest pain is one of the most common reasons for emergency department visits worldwide, and troponins play a central role in diagnosing acute coronary syndrome (ACS) in these patients. Hence, the tests for these molecules are imperative in triage for ACS. Presently, multiple high-sensitivity troponin tests are available, including those for troponin T and I. However, in the presence of physiological and pathological alterations such as chronic kidney disease (CKD) and muscle dysfunction, these tests lose their sensitivity and specificity, especially if not interpreted in the right clinical background. Further, no guidelines exist for interpreting the results in patients with CKD. We identified studies that compared the relative efficacy, sensitivity, and specificity of tests for troponin T and I in patients with CKD to understand the practical problems in the clinical interpretation of these results in the specific setting of CKD and highlight the measures to be taken into consideration.

The Impact of Cocaine Use and the Obesity Paradox in Patients With Heart Failure With Reduced Ejection Fraction Due to Non-ischemic Cardiomyopathy.

Background Obesity and illicit drugs are independent risk factors for developing heart failure (HF). However, recent studies have suggested that patients who already have HF and are obese have better clinical outcomes. We aim to study the effect of cocaine use on this obesity paradox phenomenon as it pertains to HF readmissions. Methodology In a retrospective chart analysis, we reviewed patients with a diagnosis of HF with reduced ejection fraction (HFrEF) admitted to Metropolitan Hospital in New York. We studied the association between body mass index (BMI) categories, namely, non-obese (<30 kg/m2) and obese (≥30 kg/m2), cocaine use, and the primary outcome (time to readmission for HF within 30 days after discharge). The interaction between cocaine and obesity status and its association with the primary outcome was also assessed. Results A total of 261 patients were identified. Non-obese status and cocaine use were associated with an increased hazard of readmission in 30 days (hazard ratio (HR) = 2.28, p = 0.049 and HR = 3.12, p = 0.004, respectively). Furthermore, cocaine users who were non-obese were over six times more likely to be re-admitted in 30 days compared to non-cocaine users who were obese (HR = 6.45, p = 0.0002). Conclusions Non-obese status and continued use of cocaine have a negative additive effect in impacting HF readmissions.

Tell-a provider about tele: Reducing overuse of telemetry across 10 hospitals in a safety net system.

BACKGROUND: Telemetry is often a scarce resource at hospitals and is important for arrhythmia and myocardial ischemia detection. Overuse of telemetry monitoring leads to alarm fatigue resulting in failure to respond to arrhythmias, patient harm, and possible unnecessary testing. METHODS: This quality improvement initiative was implemented across NYC Health and Hospitals, an 11-hospital urban safety net system. The electronic health record intervention involved the addition of a mandatory indication in the telemetry order and a best practice advisory (BPA) that would fire after the recommended time period for reassessment had passed. RESULTS: The average telemetry hours per patient encounter went from 60.1 preintervention to 48.4 postintervention, a 19.5% reduction (p < .001). When stratified by the 11 hospitals, decreases ranged from 9% to 30%. The BPA had a 53% accept rate and fired 52,682 times, with 27,938 "discontinue telemetry" orders placed. The true accept rate was 50.4%, as there was a 2.6% 24-h reorder rate. There was variation based on clinician specialty and clinician type (attending, fellow, resident, physician associate, nurse practitioner). CONCLUSION: We successfully reduced telemetry monitoring across a multisite safety net system using solely an electronic health record (EHR) intervention. This expands on previous telemetry monitoring reduction initiatives using EHR interventions at single academic sites. Further study is needed to investigate variation across clinician type, specialty, and post-acute sites.

Utility of Multidetector Computed Tomographic Angiography as an Alternative to Transesophageal Echocardiogram for Preoperative Transcatheter Mitral Valve Repair Planning.

BACKGROUND: Three-dimensional (3D) transesophageal echocardiogram (TEE) is the gold standard for the diagnosis of degenerative mitral regurgitation (dMR) and preoperative planning for transcatheter mitral valve repair (TMVr). TEE is an invasive modality requiring anesthesia and esophageal intubation. The severe acute respiratory syndrome coronavirus 2 pandemic has limited the number of elective invasive procedures. Multi-detector computed tomographic angiography (MDCT) provides high-resolution images and 3D reconstructions to assess complex mitral anatomy. We hypothesized that MDCT would reveal similar information to TEE relevant to TMVr, thus deferring the need for a preoperative TEE in certain situations like during a pandemic. METHODS: We retrospectively analyzed data on patients who underwent or were evaluated for TMVr for dMR with preoperative MDCT and TEE between 2017 and 2019. Two TEE and 2 MDCT readers, blinded to patient outcome, analyzed: leaflet pathology (flail, degenerative, mixed), leaflet location, mitral valve area (MVA), flail width/gap, anterior-posterior (AP) and commissural diameters, posterior leaflet length, leaflet thickness, presence of mitral valve cleft and degree of mitral annular calcification (MAC). RESULTS: A total of 22 (out of 87) patients had preoperative MDCT. MDCT correctly identified the leaflet pathology in 77% (17/22), flail leaflet in 91% (10/11), MAC degree in 91% (10/11) and the dysfunctional leaflet location in 95% (21/22) of patients. There were no differences in the measurements for MVA, flail width, commissural or AP diameter, posterior leaflet length, and leaflet thickness. MDCT overestimated the measurements of flail gap. CONCLUSIONS: For preoperative TMVr planning, MDCT provided similar measurements to TEE in our study.

Three-Year Outcomes of Balloon-Expandable Transcatheter Aortic Valve Implantation According to Annular Size.

Data on the association between annular size and transcatheter aortic valve implantation (TAVI) outcomes beyond 1 year are limited. The present study assessed the association between the aortic annulus size and TAVI clinical and hemodynamic outcomes at 3 years of follow-up. Patients were classified according to the aortic annulus size as having small, intermediate, and large annuli (size <400, 400 to 574, and ≥575 mm2, respectively). The co-primary endpoints were all-cause mortality and heart failure hospitalization. Further, the changes in hemodynamic outcomes over the follow-up period (median 37, interquartile range: 26 to 45 months) were assessed. The present analysis included 850 patients, with 182 patients (21.4%), 538 patients (63.3%), and 130 patients (15.3%) in the small, intermediate, and large-sized aortic annulus groups, respectively. The groups had comparable age and pre-TAVI pressure gradients; however, patients with small annuli had higher Society of Thoracic Surgeons risk scores. Adjusted Cox regression analysis showed that compared to patients with intermediate-sized annuli, patients with small and large annuli had similar all-cause mortality (hazard ratio [HR] = 1.11, 95% confidence interval [CI] 0.72 to 1.69 and HR = 0.74, 95% CI 0.48 to 1.16, respectively) and heart failure hospitalization rates (HR = 0.96, 95% CI 0.55 to 1.69 and HR = 1.26, 95% CI 0.73 to 2.17, respectively). However, patients with small annuli had consistently higher mean and peak pressure gradients and a higher risk of patient-prosthesis mismatch. The risks of moderate-to-severe regurgitation and structural valve deterioration were similar between the three groups. In conclusion, although patients with small annuli had higher transvalvular gradients, there was no significant association between the aortic annulus size and TAVI clinical outcomes at 3 years of follow-up. Future studies should compare the performance of transcatheter valve types in patients with different aortic annulus sizes.

Is Periodontitis a Risk Factor for Lung Cancer? A Meta-Analysis and Detailed Review of Mechanisms of Association.

Background: Numerous studies have explored the correlation of periodontal disease (PD) with the risk of lung cancers, but the findings were inconsistent. Therefore, we did a meta-analysis to ascertain the correlation of PD with the risk of incident lung cancer. Methods: The authors searched relevant studies in databases (PubMed, Web of Science, Scopus, Embase, and MEDLINE) till November 2020. We registered the study at the International database of Prospectively Registered Systemic Reviews under the CRD42020198119. The summary relative risk (RR) along with a 95% confidence interval (CI) was calculated using fixed-effects models. Results: Twelve studies were included in the qualitative synthesis. The pooled analysis revealed that PD was significantly associated with an increased risk of lung cancer (RR 1.71; 95%CI 1.61-1.81; P < 0.01). Subgroup analysis was performed based on gender distribution, geographic location, and type of studies. Conclusion: From this current evidence, PD is a potential risk factor for the development of lung cancer. The risk for incidence of lung cancer is surged twice in the patients with PD, even though age and smoking are controlled in the studies.

Tolvaptan add-on therapy and its effects on efficacy parameters and outcomes in patients hospitalized with heart failure.

INTRODUCTION: Even with the adequate use of diuretics and vasodilators, volume overload and congestion are the major causes of morbidity and mortality in patients hospitalized with acute heart failure (HF). We aim to evaluate the additive effect of tolvaptan on efficacy parameters as well as outcomes in hospitalized patients with HF. METHODS: We searched PubMed, EMBASE, Cochrane library, and Web of Science databases for randomized controlled trials that studied the effects of tolvaptan versus placebo in hospitalized patients with HF. Studies were included if they had any of the following endpoints: mortality, re-hospitalization, and in-hospital parameters like dyspnea relief, change in weight, sodium, and creatinine. RESULTS: The meta-analysis analyzed data from 14 studies involving 5945 patients. The follow up duration ranged from 30 days to 2 years. Between tolvaptan and placebo groups, there was no difference in mortality and rehospitalization. HF patients had a better dyspnea relief score (Likert score) in tolvaptan group and mean reduction in weight in the first 48 h (short-term). However, at 7 days (medium-term) the mean difference in weight was not significant. Serum sodium increased significantly in tolvaptan group. There was no difference in creatinine among the two groups. CONCLUSIONS: Our meta-analysis shows that tolvaptan helps in short-term symptomatic dyspnea relief and weight reduction, but there are no long term benefits including reduction in mortality and rehospitalization.

Right ventricular systolic pressure - Non-invasive bedside predictor of mortality and readmission in heart failure with reduced and preserved ejection fraction hospitalization.

OBJECTIVE: To study the prognostic role of right ventricular systolic pressure (RVSP) in patients with heart failure (HF). BACKGROUND: Although RVSP is a readily available echocardiographic parameter, it is often underused. Its prognostic role in patients with heart failure is not well established compared with pulmonary artery pressure measured by right heart catheterization. METHODS: This single-center retrospective cohort study included patients with acute heart failure hospitalization admitted to the hospital from January 2005 to December 2018. The primary predictor was right ventricular systolic pressure (RVSP) obtained from bedside transthoracic echocardiography at admission. We divided RVSP into two groups, RVSP <40 mm Hg (reference group) and RVSP ≥40 mm Hg. Primary outcome was all-cause mortality. Secondary outcomes were all-cause readmission and cardiac readmission. We conducted propensity-score matching and applied cox-proportional hazard model to compute hazard ratio (HR) with 95% confidence interval (CI). RESULTS: Out of 972 HF patients, 534 patients had RVSP <40 mm Hg and 438 patients had RVSP ≥40 mm Hg. Patients with RVSP ≥40 mm Hg compared with RVSP <40 mm Hg were associated with higher rates of death [HR: 1.60, 95% CI: 1.22-2.09, P-value = 0.001], all-cause readmissions [HR: 1.37, 95% CI: 1.09-1.73, P-value = 0.008] and cardiac readmissions [HR: 1.41, 95% CI: 1.07-1.85, P-value = 0.014]. CONCLUSION: Higher RVSP (≥40 mm Hg) in HF patients was associated with higher rates of death, all-cause readmissions, and cardiac readmissions. RVSP can be considered as a prognostic marker for mortality and readmission.

Absolute lymphocyte count as a predictor of mortality and readmission in heart failure hospitalization.

Background: There is renewed interest in pursuing frugal and readily available laboratory markers to predict mortality and readmission in heart failure. We aim to determine the relationship between absolute lymphocyte count (ALC) and clinical outcomes in patients with heart failure hospitalization. Methods: This was a retrospective cohort study of patients with heart failure. Patients were divided into two groups based on ALC, less than or equal to 1500 cells/mm3 and > 1500 cells/ mm3. The primary outcome was all-cause mortality. We did subgroup analysis based on ejection fraction and studied the association between ALC categories and clinical outcomes. Both ALC groups are matched by propensity score, outcomes were analyzed by Cox regression, and estimates are presented in hazard ratios (HR) and 95% confidence intervals (CI). Results: We included 1029 patients in the pre-matched cohort and 766 patients in the propensity-score matched cohort. The median age was 64 years (IQR, 54-75), and 60.78% were male. In the matched cohort, ALC less than or equal to 1500 cells/mm3 had a higher risk of mortality compared with ALC > 1500 cells/mm3 (HR 1.51, 95% CI: 1.17-1.95; P = 0.002). These results were reproducible in subgroups of heart failure. When ALC was divided into four groups based on their levels, the lowest group of ALC had the highest risk of mortality. Conclusions: In patients with heart failure and both subgroups, ALC less than or equal to 1500 cells/mm3 had a higher risk of mortality. Patients in lower groups of the ALC categories had a higher risk of mortality.

Network Meta-analysis of Trials Comparing Intravascular Ultrasound, Optical Coherence Tomography, and Angiography-Guided Technique for Drug-Eluting Stent Implantation.

Background: The current advances in coronary imaging with the introduction of intravascular ultrasound (IVUS), and more recently, optical coherence tomography (OCT) have overcome the limitations of coronary angiography. Objective: This study aimed to conduct a comprehensive network meta-analysis of randomized clinical trials to report clinical outcomes among patients undergoing drug-eluting stent (DES) implantation either by IVUS- or OCT-guided technique or angiography alone. Methods: PubMed/MEDLINE and EMBASE databases were searched systematically for all relevant published randomized clinical trials from the inception of the respective database to October 15th, 2021. The outcomes of interest assessed in this meta-analysis were major adverse cardiac events, myocardial infarction, target vessel revascularization, all-cause mortality, and cardiovascular mortality. All the endpoints were expressed as odds ratio (OR) with 95% CI. The network diagrams were computed using the OR as an effective measure. All statistical analyses were carried out in R statistical software version 4.0.3. Results: A total of 14 randomized clinical trials were included in our meta-analysis. In patient undergoing DES implantation, angiography alone was associated with higher odds of major adverse cardiac events (OR, 1.62; 95% CI, 1.17-2.24), target vessel revascularization (OR, 1.60; 95% CI, 1.21-2.13) and cardiovascular mortality (OR, 1.97; 95% CI, 1.25-3.11). However, OCT demonstrated similar odds of major adverse cardiac events, cardiovascular mortality, and target vessel revascularization compared with IVUS. The odds of myocardial infarction and all-cause mortality were similar among all the 3 groups. Conclusions: Although angiography alone was associated with worse outcomes than IVUS in a patient undergoing DES implantation, no difference in outcome was noted between patients undergoing DES implantation with OCT compared with IVUS. Advanced intracoronary imaging use should be encouraged to prevent excess mortality and morbidity.

Association between haematological parameters and outcomes following transcatheter aortic valve implantation at mid-term follow-up.

BACKGROUND: Patients undergoing transcatheter aortic valve implantation (TAVI) often have multiple comorbidities, such as anaemia and chronic inflammatory disorders. We sought to investigate the association between preoperative and postoperative haematological parameters and clinical outcomes in TAVI patients at mid-term follow-up. METHODS: In the present study, consecutive patients (N=908) who underwent TAVI at the Cleveland Clinic between 2017 and 2019 with available complete blood counts were studied. Data were collected on preoperative and postoperative anaemia and elevations in neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Survival analysis was used to study the association of haematologic parameters with all-cause mortality and major adverse cardiac and cerebrovascular events (MACCE). RESULTS: We found that preoperative anaemia and elevated NLR were significantly associated with a higher risk of all-cause mortality (aHR=1.6 (95% CI: 1.1 to 2.0) and 1.4 (95% CI: 1.1 to 1.6), respectively) and MACCE (aHR=1.9 (95% CI: 1.3 to 2.8) and 1.6 (95% CI: 1.1 to 2.4), respectively). While an elevated preoperative PLR was not associated with increased mortality risk, it had a significant association with MACCE risk (aHR: 1.6 (95% CI: 1.1 to 2.4)). Further, postoperative anaemia, elevated NLR and PLR were associated with increased risks of all-cause mortality and MACCE. CONCLUSION: Pathological alterations in haematological parameters were associated with higher risks of post-TAVI mortality and MACCE at mid-term follow-up. Our findings advocate for further incorporating haematological parameters in the preoperative evaluation of TAVI candidates.

Utilization and outcomes of aortic valve replacements (from the United States readmissions database).

Study objective: Assess the utilization of aortic valve replacements (AVR). Design: Retrospective analysis of the Nationwide Readmissions Database (2016-2018). Setting: Nationwide. Participants: Heart failure patients with concomitant aortic stenosis (CHF + AS cohort) or aortic stenosis with aortic regurgitation (CHF + AS+AR cohort). Interventions: Transcatheter aortic valve implantation (TAVI), surgical aortic valve replacement (SAVR), no-AVR. Main outcome measures: Utilization of treatment interventions. Results: In the CHF + AS cohort, TAVI, SAVR and no-AVR were done in 9.3 %, 10.8 % and 79.9 % of patients respectively. Similarly, majority of CHF + AS+AR patients were managed with no-AVR (53.2 %). Of patients managed with no-AVR in the first six months of each year, only 7.9 % of CHF + AS and 11.8 % of CHF + AS+AR patients underwent AVR in the subsequent six months of the year. No-AVR patients had worse short-term outcomes in comparison to AVR recipients. Conclusion: More studies are needed to understand the timing, indications and utilization of AVR in this population.

Mitral regurgitation following PASCAL mitral valve repair system: A single arm meta-analysis.

Major consequences of untreated severe mitral regurgitation (MR) includes heart failure, ventricular remodeling and pulmonary hypertension leading to significant morbidity and mortality. MitraClip is the most widely used device for treatment of severe MR. To overcome some of the shortcomings of MitraClip, novel devices like PASCAL mitral valve repair system are developed. We performed a single arm meta-analysis for patients with severe mitral regurgitation (MR) undergoing PASCAL mitral valve repair system. The results showed that 93.8% patients had reduction in MR grade, with an average operative time of 88 min and an average increase of 86.33 m in 6-min walk test.

Transient Left Bundle Branch Block in the Setting of Hyperkalemia.

Hyperkalemia is a potentially life-threatening condition that can lead to sudden cardiac death. We report a case of transient left bundle branch block (LBBB) pattern on an electrocardiogram (EKG) secondary to hyperkalemia in a patient with a history of end-stage renal disease. A 48-year-old female presented to the emergency department (ED) with chief complaints of weakness and shortness of breath after a missed hemodialysis session. A 12-lead EKG in the ED showed the LBBB pattern with left axis deviation, prolonged PR interval, and peaked T-waves in the precordial leads. The initial serum potassium level was 8.5 mEq/L. EKG changes resolved after correcting the serum potassium level.

Infective Endocarditis and Intravenous Drug Users: Never Was and Never Will Be Taken Lightly.

Infective endocarditis (IE) is the infection of the endocardial surface (innermost layer - valves, chordae tendineae, and papillary muscles) of the heart. It usually refers to infection of one or more of the heart valves which may be native or prosthetic. The definition also includes infection on indwelling cardiac devices. Over time, the etiology, as well as causes of IE, have evolved and doubled in numbers because of a greater number of patients with indwelling cardiac devices and central lines. Some characteristic features have remained the same, including intravenous drug users (IVDU) and right-sided IE, fever, or peripheral signs of IE. However, there are instances where the clinical presentation is unique. Here we describe an unusual case of an IVDU patient developing acute decompensated heart failure following acute aortic regurgitation (AR) from IE without fever and right-sided heart or tricuspid valve involvement.

Intestinal Tuberculosis: A Diagnostic Challenge.

Diagnosing intestinal tuberculosis (TB) with uncommon clinical manifestations is often challenging. Here, we report a case of an alcoholic patient who presented with vague symptoms and was later diagnosed with intestinal TB. This patient experienced multiorgan failure causing hemodynamic instability requiring ionotropic support; acute hypoxic respiratory failure managed with non-invasive positive pressure ventilation, hepatic failure, transudative peritoneal effusion, and transudative pleural effusion. These conditions clouded our judgment to pursue colonoscopy for a definite diagnosis and delayed the anti-tuberculosis treatment. When intestinal tuberculosis TB is suspected, the differential diagnosis must be established with other gastrointestinal involving diseases, including mycobacterium avium complex (MAC) and Crohn's disease (CD). MAC can show overlapping features with intestinal TB or coexist with it; Acid-fast stain and tissue culture are the key tests to differentiate these two. In the presence of diagnostic uncertainty between intestinal TB and CD, a therapeutic trial with anti-tuberculous therapy may be warranted.

Meta-Analysis of Early Intervention Versus Conservative Management for Asymptomatic Severe Aortic Stenosis.

The main objective was to determine the optimal strategy for managing asymptomatic severe aortic stenosis between early intervention versus conservative management. We performed a systematic electronic search of the PubMed and Cochrane databases from the inception of the database to May 31, 2020. The Mantel Haenszel method with the Paule-Mandel estimator of Tau2 and Hartung-Knapp adjustment were used to calculate relative risk (RR) with a 95% confidence interval (CI) and 95% prediction interval. P curve analysis was used to assess publication bias and estimate the true effect of an intervention. All analysis was carried out using R version 3.6.2. A total of 9 studies were included in the final analysis, consisting of 1,775 patients with early intervention and 3,040 patients with conservative management. Early intervention as compared with conservative management was associated with reduced risk of all-cause mortality (RR 0.36, 95% CI 0.24 to 0.53), cardiac mortality (RR 0.36, 95% CI 0.27 to 0.48) and noncardiac mortality (RR 0.40, 95% CI 0.28 to 0.56). There was no difference in the risk of sudden cardiac death (RR 0.46, 95% CI 0.15 to 1.40), stroke (RR 0.79, 95% CI 0.17 to 3.64), myocardial infarction (RR 0.44, 95% CI 0.01 to 16.82) or heart failure hospitalization (RR 0.18, 95% CI 0.01 to 5.29) with early intervention compared with conservative management. In conclusion, early intervention is associated with reduced all-cause, cardiovascular, and noncardiovascular mortality without increasing any procedure-related clinical outcomes among asymptomatic severe AS patients. Hence, this meta-analysis supports early intervention instead of watchful waiting for the management of asymptomatic severe AS. This systematic review and meta-analysis was registered with PROSPERO- CRD42020188439.