Cardiopulmonary Death Research Articles

Tricuspid regurgitation in pulmonary arterial hypertension: a right ventricular volumetric and functional analysis.

The consequences of tricuspid regurgitation (TR) for right ventricular (RV) function and prognosis in pulmonary arterial hypertension (PAH) are poorly described and effects of tricuspid valve repair on the RV are difficult to predict. In 92 PAH patients with available cardiac magnetic resonance (CMR) studies, TR volume was calculated as the difference between RV stroke volume and forward stroke volume, i.e. pulmonary artery (PA) stroke volume. Survival was estimated from the time of the CMR scan to cardiopulmonary death or lung transplantation. In a subgroup, pressure-volume loop analysis including two-parallel elastances was applied to evaluate effective elastances, including net afterload (effective arterial elastance (E a)), forward afterload (effective pulmonary arterial elastance (E pa)) and backward afterload (effective tricuspid regurgitant elastance (E TR)). The effects of tricuspid valve repair were simulated using the online software package Harvi. 26% of PAH patients had a TR volume ≥30 mL. Greater TR volume was associated with increased N-terminal pro-brain natriuretic peptide (p=0.018), mean right atrial pressure (p<0.001) and RV end-systolic and -diastolic volume (both p<0.001). TR volume ≥30 mL was associated with a poor event-free survival (p=0.008). In comparison to E a, E pa correlated better with indices of RV dysfunction. Lower end-systolic elastance (E es) (p=0.002) and E TR (p=0.030), higher E pa (p=0.001) and reduced E es/E pa (p<0.001) were found in patients with a greater TR volume. Simulations predicted that tricuspid valve repair increases RV myocardial oxygen consumption in PAH patients with severe TR and low E es unless aggressive volume reduction is accomplished. In PAH, TR has prognostic significance and is associated with low RV contractility and RV-PA uncoupling. However, haemodynamic simulations showed detrimental consequences of tricuspid valve repair in PAH patients with low RV contractility.

Predicting Peri-Operative Cardiorespiratory Adverse Events in Children with Idiopathic Pulmonary Arterial Hypertension Undergoing Cardiac Catheterization Using Echocardiography: A Cohort Study.

General anesthesia in children with idiopathic pulmonary arterial hypertension (PAH) carries an increased risk of peri-operative cardiorespiratory complications though risk stratifying individual children pre-operatively remains difficult. We report the incidence and echocardiographic risk factors for adverse events in children with PAH undergoing general anesthesia for cardiac catheterization. Echocardiographic, hemodynamic, and adverse event data from consecutive PAH patients are reported. A multivariable predictive model was developed from echocardiographic variables identified by Bayesian univariable logistic regression. Model performance was reported by area under the curve for receiver operating characteristics (AUCroc) and precision/recall (AUCpr) and a pre-operative scoring system derived (0-100). Ninety-three children underwent 158 cardiac catheterizations with mean age 8.8 ± 4.6years. Adverse events (n = 42) occurred in 15 patients (16%) during 16 catheterizations (10%) including cardiopulmonary resuscitation (n = 5, 3%), electrocardiographic changes (n = 3, 2%), significant hypotension (n = 2, 1%), stridor (n = 1, 1%), and death (n = 2, 1%). A multivariable model (age, right ventricular dysfunction, and dilatation, pulmonary and tricuspid regurgitation severity, and maximal velocity) was highly predictive of adverse events (AUCroc 0.86, 95% CI 0.75 to 1.00; AUCpr 0.68, 95% CI 0.50 to 0.91; baseline AUCpr 0.10). Pre-operative risk scores were higher in those who had a subsequent adverse event (median 47, IQR 43 to 53) than in those who did not (median 23, IQR 15 to 33). Pre-operative echocardiography informs the risk of peri-operative adverse events and may therefore be useful both for consent and multi-disciplinary care planning.

Effectiveness of mRNA Booster Vaccine Against Coronavirus Disease 2019 Infection and Severe Outcomes Among Persons With and Without Immune Dysfunction: A Retrospective Cohort Study of National Electronic Medical Record Data in the United States.

Real-world evidence of coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) booster effectiveness among patients with immune dysfunction are limited. We included data from patients in the United States National COVID Cohort Collaborative (N3C) who completed ≥2 doses of mRNA vaccination between 10 December 2020 and 27 May 2022. Immune dysfunction conditions included human immunodeficiency virus infection, solid organ or bone marrow transplant, autoimmune diseases, and cancer. We defined incident COVID-19 BTI as positive results from laboratory tests or diagnostic codes 14 days after at least 2 doses of mRNA vaccination; and severe COVID-19 BTI as hospitalization, invasive cardiopulmonary support, and/or death. We used propensity scores to match boosted versus nonboosted patients and evaluated hazards of incident and severe COVID-19 BTI using Cox regression after matching. Among patients without immune dysfunction, the relative effectiveness of booster (3 doses) after 6 months from the primary (2 doses) vaccination against BTI ranged from 69% to 81% during the Delta-predominant period and from 33% to 39% during the Omicron-predominant period. Relative effectiveness against BTI was lower among patients with immune dysfunction but remained statistically significant in both periods. Boosted patients had lower risk of COVID-19-related hospitalization (hazard ratios [HR] ranged from 0.5 [95% confidence interval {CI}, .48-.53] to 0.63 [95% CI, .56-.70]), invasive cardiopulmonary support, or death (HRs ranged from 0.46 [95% CI, .41-.52] to 0.63 [95% CI, .50-.79]) during both periods. Booster vaccines remain effective against severe COVID-19 BTI throughout the Delta- and Omicron-predominant periods, regardless of patients' immune status.

Slowly moving the needle away from Fistula First

ObjectiveIn 2019, the management of end-stage kidney disease (ESKD) shifted away from “Fistula First” (FF) to “ESKD Life-Plan: Patient Life-Plan First then Access Needs.” Indeed, some patients exhibit such excessive comorbidity that even relatively minor vascular surgery may be complicated. The purpose of this study was to retrospectively assess complications and mortality (and delineate operative futility) in patients undergoing arteriovenous fistula (AVF) creation in the FF era. MethodsConsecutive AVFs created in a single institution before 2021 were retrospectively reviewed. Operative futility was defined as never-accessed fistula, no initiation of dialysis, failure of access maturation (despite secondary intervention), hemodialysis access-induced distal ischemia requiring ligation, early loss of secondary patency, and/or patient mortality within the first 6 postoperative months. ResultsA total of 401 AVFs were created including radial-cephalic (44%), brachial-cephalic (41%), and brachial-basilic (15%) constructions. Patients exhibited a mean age of 69 ± 15 years; 63% were male, and most (74%) were already being hemodialyzed at the time of fistula creation. Forty-five patients (11%) suffered a cardiac event, and five patients died (1%) within 90 days of their access surgery. Perioperative cardiac events were significantly more common after age 80 (19% vs 8%; P = .004); age >80 years was an independent predictor of major 90-day complications (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.04-3.39; P = .036) and the sole independent predictor of major morbidity defined as cardiopulmonary complications, stroke, or death within the first year (OR, 2.01; 95% CI, 1.24-3.25; P = .004). Operative futility was encountered in 52% of the cohort (n = 208 patients): 40% (n = 160) of primary AVFs failed to mature despite assistance, 19% (n = 77) had lost secondary patency by 6 months, 13% of patients (n = 53) were never started on dialysis after access creation, 4% (n = 16) were dead by 6 months, 2% of AVFs (n = 10) matured but were never accessed, and 2% (n = 9) required ligation for hemodialysis access-induced distal ischemia. Not surprisingly, the sole independent protector against operative futility was that catheter-based dialysis had been established prior to AVF creation (OR, 0.36; 95% CI, 0.22-0.59; P < .01). ConclusionsApproximately 50% of primary AVF operations performed in the aggressive FF era were deemed futile. Octogenarians were particularly prone to futility and complications during this era. A paradigm shift, from FF to an “ESKD Life-Plan” will, hopefully, more thoughtfully match vascular access strategies to individual patient needs.

Tricuspid regurgitation in pulmonary arterial hypertension: relations with right ventricular function and prognosis

Abstract Background Pulmonary arterial hypertension (PAH) is a devastating disease characterized by progressive pulmonary vascular remodeling and increased pulmonary vascular resistance (PVR), subsequent right ventricular (RV) failure and premature death (1). Progressive RV overload leads to RV dilatation, which in turn induces tethering of the tricuspid valve and functional valvular regurgitation (2,3). As such, severity and the progression of tricuspid regurgitation (TR), as evaluated by echocardiographic qualitative analysis, are reported to associate with a poor prognosis in PAH (4,5). However, it has remained unclear to what extent the severity of TR directly impacts RV hemodynamics and prognosis of PAH patients. Purpose This study aimed to explore the consequences of TR for RV function and prognosis in PAH using a volumetric analysis by cardiac magnetic resonance (CMR). Methods 92 PAH patients, mean pulmonary arterial pressure (mPAP) ≥25 mmHg and pulmonary artery wedge pressure ≤15 mmHg, with available CMR data from January 1st 2010 to August 31st 2021 were included in this study. TR volume was calculated as the difference between the stroke volume (SV) of RV and pulmonary artery (PA). TR severity was graded as no or mild (TR&amp;lt;30 mL), moderate (30≤TR&amp;lt;45 mL) and severe (TR≤45 mL). Hemodynamic assessment was performed by right heart catheterization. Event free survival was estimated from the time of the CMR scan to cardiopulmonary death or lung transplantation. Results In the studied cohort, 74% of PAH patients had no or mild TR, 16% had moderate TR, and 10% had severe TR (Table 1). A greater TR volume was characterized by increased NT-proBNP, increased mPAP, PVR and mean right atrial pressure (mRAP), and increased RV volume. Additionally, RVSV was higher while PASV was lower. There was no difference in RV ejection fraction (RVEF). Pearson correlation analysis showed a good correlation between TR volume and parameters of PAH severity, such as NT-proBNP, RV end-systolic volume (RVESV), mRAP and cardiac index (CI) (Figure 1). ROC curves analysis revealed that the optimal cut-off value of TR volume was 30 mL. Kaplan-Meier survival analysis demonstrated that TR volume ≥30 mL was strongly associated with a poor event free survival (Figure 2). Conclusion 26% of PAH patients had a TR volume 30 ≥mL. TR severity showed a good correlation with PAH disease severity. TR volume 30 ≥mL, i.e. moderate or severe TR, was strongly associated with a poor prognosis in PAH patients.TableFigure

Abstract 19059: Risk Factors for the First Cardiopulmonary Hospitalization Differ From Those of Recurrent Cardiopulmonary Hospitalizations in Patients With Cardiovascular Disease Vaccinated Against Influenza — A Secondary Analysis of the INVESTED Trial

Background: Influenza vaccines are recommended for patients with CVD due to their protective effects and favorable safety profile. Patients with recent MI/HF hospitalization are at high risk of multiple events, but it is not known which flu vaccine type can mitigate recurrent events. Research Questions: What are predictors of recurrent cardiopulmonary hospitalization and death in patients with CVD and does the high-dose trivalent flu vaccine reduce the rate of recurrent events compared with standard-dose quadrivalent vaccine? Methods: In this pragmatic, active comparator trial, patients with recent MI/HF hospitalization across 157 sites were randomized to either vaccine type and revaccinated each enrolled season (2016-2019). Recurrent event analysis with a Markov multistate model, negative binomial, and Lin-Wei-Yang-Ying regression models was applied, adjusting for clinical and sociodemographic factors, flu infection and vaccine history, with vaccine type as the main exposure. Cardiopulmonary hospitalization and all-cause death comprised the multistate model’s main states and the composite primary outcome for remaining analyses. Results: Among 5260 patients (mean age 65.5 years; 28% women; 63% with recent HF), 12% were readmitted ≥1 for cardiopulmonary causes, accounting for half of total cardiopulmonary hospitalization. In the multistate model, a history of comorbidities (e.g., low LVEF and COPD) was associated with recurrent hospitalization (Figure), whereas age and frailty primarily determined a higher rate of death, particularly after a first hospitalization. There were no significant differences between the vaccines on the rate of recurrent events and death in the multistate and negative binomial regression models. Conclusions: As hospitalizations accrue, the association of certain predictors changes in this population. Alternative strategies beyond vaccine type are needed to mitigate the total burden of cardiopulmonary disease.

3-Year Outcome in Patients With Combined Precapillary and Postcapillary Pulmonary Hypertension: Results From PADN-5 Trial

BackgroundLong-term benefits of pulmonary artery denervation (PADN) for patients with combined precapillary and postcapillary pulmonary hypertension (CpcPH) secondary to left heart failure are unknown. ObjectivesThe authors sought to report the 3-year clinical results of PADN for patients with CpcPH. MethodsA total of 98 patients with CpcPH, defined as having mean pulmonary arterial pressure of ≥25 mm Hg, pulmonary capillary wedge pressure of >15 mm Hg, and pulmonary vascular resistance of >3.0 WU, were randomly assigned to receive the sham + sildenafil or PADN. The primary endpoint was the occurrence of clinical worsening defined as cardiopulmonary death, rehospitalization or heart/lung transplantation at 3-year follow-up. Changes in the 6-minute walk distance and N-terminal pro–B-type natriuretic peptide served as secondary points. ResultsAt the 3-year follow-up, clinical worsening was reported in 49 (50.0%) patients, with 31 (62.0%) in the sham + sildenafil group and 18 (37.5%) in the PADN group (HR: 2.13 [95% CI: 1.19-3.81]; P = 0.011), largely driven by a higher rate of rehospitalization in the sham + sildenafil group (56.2% vs 35.4%; HR: 1.96 [95% CI: 1.07-3.58]; P = 0.029) by Cox proportional hazards regression. At the end of the study, cardiopulmonary-related deaths occurred in 16 (32.0%) patients in the sham and 9 (18.8%) (P = 0.167) patients in the PADN group. PADN also resulted in a more profound increase in the 6-minute walk distance and reduction in N-terminal pro–B-type natriuretic peptide. ConclusionsPADN is associated with significant improvements in exercise capacity, cardiac function, and clinical outcomes. Further study without approved drugs for pulmonary arterial hypertension is required to confirm the benefits of PADN for patients with CpcPH. (Pulmonary Arterial Denervation in Patients With Pulmonary Hypertension Associated With the Left Heart Failure [PADN-5]; NCT02220335)

Heart Rate Change as a Potential Digital Biomarker of Brain Death in Critically Ill Children With Acute Catastrophic Brain Injury.

To determine whether HRC, calculated using numeric HR measurements sampled every 5 seconds, can identify patients with BD among patients with catastrophic brain injury (CBI). Single-center, retrospective study (2008-2020) of critically ill children with acute CBI. Patients with CBI had a neurocritical care consultation, were admitted to an ICU, had acute neurologic injury on presentation or during hospitalization based on clinical and/or imaging findings, and died or survived with Glasgow Coma Scale (GCS) less than 13 at hospital discharge. Patients meeting BD criteria (BD group) were compared with those with cardiopulmonary death (CD group) or those who survived to discharge. HRC was calculated as the interquartile range of HR divided by median HR using 5-minute windows with 50% overlap for up to 5 days before death or end of recording. HRC was compared among the BD, CD, and survivor groups. Of 96 patients with CBI (69% male, median age 4 years), 28 died (8 BD, 20 CD) and 20 survived (median GCS 9 at discharge). Within 24 hours before death, HRC was lower in BD compared with CD patients or survivors (0.01 vs 0.03 vs 0.04, p = 0.001). In BD patients, HRC decreased at least 1 day before death. HRC discriminated BD from CD patients and survivors with 90% sensitivity, 70% specificity, 44% positive predictive value, 96% negative predictive value (area under the receiver operating characteristic curve 0.88, 95% CI, 0.80-0.93). HRC is a novel digital biomarker that, with further validation, may be useful as a classifier for BD in the overall course of patients with CBI.

Disputing death: brain death in the courts

AbstractDeath by neurological criteria (DNC) has remained controversial since its introduction over 50 years ago. Objections to the diagnosis of DNC have been coming before the courts in various jurisdictions, including at least seven recent challenges before the UK courts. In responding to these challenges, the UK courts have expressed no doubts as to the status of DNC and have affirmed that following a diagnosis of DNC, the matter of best interests is no longer relevant. Yet, the courts have also, tacitly, acknowledged that DNC is not quite the same as cardio-pulmonary death.This paper begins by setting out the origins of DNC as a medico-legal construction, and its ongoing controversies. It then analyses the treatment of DNC, including authorisation of DNC testing, by the UK courts. It shows that the courts have been operating a form of ad hoc reasonable accommodation of different views of DNC but have done so without normative engagement. The paper argues that the courts should recognise that DNC disputes are not simply concerned with whether, as a matter of fact, DNC has been correctly diagnosed, but also raise profound questions about rights and interests, both of families and of the DNC dead.

Forced Organ Harvesting

Forced Organ Harvesting

Early outcomes of "low-risk" patients undergoing lung resection assessed by cardiopulmonary exercise testing: Single-institution experience.

Cardiopulmonary exercise testing (CPET) is currently recommended for all patients undergoing lung resection with either respiratory comorbidities or functional limitations. The main parameter evaluated is oxygen consumption at peak (VO2peak). Patients with VO2peak above 20 ml/kg/min are classified as low risk surgical candidates. The aims of this study were to evaluate postoperative outcomes of low-risk patients, and to compare their outcomes with those of patients without pulmonary impairment at respiratory function testing. Retrospective monocentric observational study was designed, evaluating outcomes of patients undergoing lung resection at San Paolo University Hospital, Milan, Italy, between January 2016 and November 2021, preoperatively assessed by CPET, according to 2009 ERS/ESTS guidelines. All low-risk patients undergoing any extent surgical lung resection for pulmonary nodules were enrolled. Postoperative major cardiopulmonary complications or death, occurring within 30 days from surgery, were assessed. A case-control study was nested, matching 1:1 for type of surgery the cohort population with control patients without functional respiratory impairment consecutively undergoing surgery at the same centre in the study period. A total of 80 patients were enrolled: 40 subjects were preoperatively assessed by CPET and deemed at low risk, whereas 40 subjects represented the control group. Among the first, 4 patients (10%) developed major cardiopulmonary complications, and 1 patient (2.5%) died within 30 days from surgery. In the control group, 2 patients (5%) developed complications and none of the patients (0%) died. The differences in morbidity and mortality rates did not reach statistically significance. Instead, age, weight, BMI, smoking history, COPD incidence, surgical approach, FEV1, Tiffenau, DLCO and length of hospital stay resulted significantly different between the two groups. At a case-by-case analysis, CPET revealed a pathological pattern in each complicated patient, in spite of VO2peak above target for safe surgery. Postoperative outcomes of low-risk patients undergoing lung resections are comparable to those of patients without any pulmonary functional impairment; nonetheless the formers represent a dramatically different category of individuals from the latter and may harbour few patients with worse outcomes. CPET variables overall interpretation may add to the VO2peak in identifying higher risk patients, even in this subgroup.

Social and ethical-moral considerations in cardiopulmonary death donation

The sociocultural perception of Cardiopulmonary Death Donation by the population is an important issue, especially at this time when this type of donation is growing. However, the data that are currently available are insufficient to draw definitive conclusions on public reactions. Controlled organ donation after cardiocirculatory determination of death has generated an ethical and social debate since its implementation. The objective is to analyze the most relevant ethical-moral and social issues that involve this type of donation.We were selected the 30 articles about this area with the PRISMA methodology. 72.2% of the articles that analyze the ethical conflicts on the withdrawal of life support treatment state that the staff that carries it out must be separate from the donation staff. 38.9% believe that it should be done in the ICM and 44.4% that it should be done by the ICM staff themselves. Regarding who should suggest controlled organ donation after cardiocirculatory determination of death, they all agree that it should be totally unrelated to ICM staff. 71.4% of the articles that analyze the use of premortem procedures justify their use based on scientific evidence and declare that they do not harm the potential donor. 42.1% accept the use of permanent circulatory cessation in determining death and 78.9% believe that a consensus should be reached on the waiting time in asystole. Despite some detractors, the use of ECMO is fully justified. Christian and Jewish culture are in favor of non-heart beating donation, but religious and economic objections continue to be raised in the Middle East. 80% of the articles that mention euthanasia classify it as a subject completely unrelated to controlled organ donation after cardiocirculatory determination of deathIn conclusion, Organ donation after cardiocirculatory determination of death has experienced a boom in recent years and continues to lead to ethical-moral and social debate.

Cardiac Children Hospital Early Warning ScoreVersus the Inadequate Oxygen Delivery Index for the Detection of Early Warning Signs of Deterioration.

Single-center longitudinal pilot study. Pediatric cardiac ICU (PCICU), Aga Khan University. C-CHEWS and Inadequate Oxygen Delivery (IDO2) Index calculation every 2 hours. A total of 60 children (0 d to 18 yr old). A single-center longitudinal pilot study was conducted at PCICU. All postoperative extubated patients were assessed and scored between 0 and 11, and these scores were then correlated with the IDO2 index data available from the T3 platform. Adverse events were defined as a need for cardiopulmonary resuscitation, or reintubation, and death. A total of 920 C-CHEWS and IDO2 scores were analyzed on 60 patients during the study period. There were 36 males and 24 females, and the median age of the study population was 34 months (interquartile range, 9.0-72.0 mo). Fourteen patients (23.3%) developed adverse events; these included 9 reintubations and 5 cardiopulmonary arrests, resulting in 2 deaths. The area under the curve (AUC) for C-CHEWS scores fell in an acceptable range of 0.956 (95% CI, 0.869-0.992), suggesting an optimal accuracy for identifying early warning signs of cardiopulmonary arrest. Whereas, IDO2 showed no discriminatory power to detect the adverse events with an AUC of 0.522 (95% CI, 0.389-0.652). The C-CHEWS tool provides a standardized assessment and approach to deteriorating congenital cardiac surgery patients in recognizing early postoperative deterioration.

Türkiye'de Beyin Ölümü Vakalarında Klinik Etik, Kişisel Değerler, Yasal Belirsizlikler ve Olası Çatışmalar: Bir Uygulamalı Çalışma

Both clinically and legally, brain death has long been recognized as death. However, many people including patient relatives still equate death with cardiopulmonary death (irreversible cessation of heartbeat and breathing), and thus may oppose withdrawal of life-support technologies and refuse to consider organ donation in brain death. Such reactions may lead to problematic or dilemmatic situations in relation to the norms and practices of justice, beneficence, paternalism, futile care, defensive medicine, due care, consideration of personal beliefs and values and financial and emotional burdens, etc. Although the determination of brain death and procedures of organ donation have been legally regulated in Türkiye since the late twentieth century, there have also been legal uncertainties about the decision to terminate care, particularly the extent to which the decision depends on the agreement of patient relatives. With consideration of historical developments, legal documents, ethical issues, and personal attitudes, the present study aimed to analyze the nature of such conflicts between patient relatives (agents that act with subjective priorities) and health-care providers (agents that should act within certain standards) as the two parties in a typical case of brain death. For particular emphasis on the pivotal role of information and communication in the resolution of potential conflicts in real cases of brain death, the discussion was made with application in a hypothetical case.

Abstract 12837: A Novel Index to Predict Post-Operative Left Atrioventricular Valve Morbidity in Atrioventricular Septal Defects

Introduction: Morbidity of the left atrioventricular valve (LAVV) remains the leading indication for reoperation on atrioventricular septal defects (AVSDs). While qualitative 2D and quantitative 3D risk factors have been identified, no quantitative 2D measurement yet exists to predict poor postoperative outcomes. The aim of this study was to evaluate objective measurements of the LAVV and subvalvar apparatus in relation to postoperative outcomes. Methods: A retrospective review was performed on 2D echocardiograms of patients undergoing surgical repair of an AVSD from January 1, 2014 to December 31, 2021. Demographic and perioperative data were collected from the electronic medical record. The hingepoint-to-hingepoint length of the superior, mural and inferior bridging leaflets in early diastole, as well as LAVV chordal length at end-diastole were measured and indexed to body surface area. A poor outcome was defined by significant LAVV regurgitation (moderate or greater), LAVV stenosis (5mmHg or greater), need for second cardiopulmonary bypass run, postoperative ECMO, reoperation, or death. LAVV measurements were compared to composite outcome by Wilcoxon rank sum test. Results: Of 120 patients with adequate perioperative imaging, 47 (39.2%) had a poor outcome. Indexed LAVV chordal length was significantly different between those who experienced a poor outcome and those who did not, with shorter chordal length predictive of a poor outcome. Interestingly, mural leaflet size was not associated with a poor outcome. Conclusions: Indexed LAVV chordal length is a novel measurement shown to predict a poor postoperative outcome in AVSD. Additional analysis is necessary to assess whether short chords are more predictive of LAVV regurgitation or stenosis, and to determine a numeric cut-off of indexed chordal length for predicting poor outcome.

The Diagnostic Value of Bedside Echocardiography and Lower Extremity Blood Vessels in Acute Pulmonary Embolism.

Objective The study aimed to evaluate the value of bedside echocardiography (TTE) and lower extremity blood vessels in diagnosis and prognosis of acute pulmonary embolism (APE). Methods A retrospective study was performed on 53 patients with APE diagnosed by CT pulmonary angiography (CTPA) (systemic systolic blood pressure was >90 mmHg at time of consultation, and systemic systolic blood pressure decreased by <40 mmHg compared with basic value in those with hypertension). All patients underwent TTE examination before treatment. The high-risk factors, clinical manifestations, laboratory tests, and prognosis were retrospectively analyzed. Results The rate of PE-related deterioration (cardiopulmonary resuscitation, tracheal intubation, cardiogenic shock, and death) within 14 days of hospitalization in RVD was 28%, and mortality rate (sudden death) was 20%, compared with non-RVD (both 0%). TTE examination showed that RVD as a predictor of pulmonary embolism-related death had a sensitivity of 100%, a specificity of 58%, a positive predictive value of 20%, and a negative predictive value of 100%. Conclusions (1) TTE has increasingly shown obvious advantages in diagnosis of APE. It can detect direct or indirect signs of pulmonary embolism, confirm diagnosis or suspected diagnosis, and noninvasively and dynamically observe hemodynamic changes of heart in patients with acute PTE before and after treatment.. (2) The PE-related exacerbation rate (28%) or mortality (20%) of APE patients in normotensive with RVD was higher without RVD (0%). RVD is an independent predictor of poor prognosis in normotensive acute PTE. TTE tests allow people to identify people at risk of early death. The short-term prognosis of patients without RVD was better (14 days).

Causes of Death in Long-Term Nasopharyngeal Carcinoma Survivors.

PurposeTo assess the causes of death (COD) and long-term survival after nasopharyngeal carcinoma (NPC) diagnosis.MethodsUsing linked data from the Surveillance, Epidemiology, and End Results program, patients with NPC diagnosed from 1990 to 2010 and followed up >5 years were identified. Chi-squared test, the Kaplan–Meier method, and the Cox proportional hazard model were used for analyses.ResultsAmong the 3,036 long-term NPC survivors, 1,432 survived for >5–10 years and 1,604 survived for >10 years. The most common COD was primary NPC (36.9%), followed by other causes (28.7%), other cancers (15.3%), cardiac disease (12.9%), and non-malignant pulmonary disease (6.2%). With a median follow-up of 125 months, deaths from NPC decreased with increasing time from diagnosis, while death because of cardiac disease and other causes increased. In those aged <50 years, death due to NPC remained the main COD over time, while cardiopulmonary disease-related death was the leading COD in patients aged ≥50 years. In White patients, death due to NPC decreased, and death due to cardiac disease increased over time. Death from NPC remained significant in Black and Asian patients even 15 years after the diagnosis of NPC, while death due to cardiac disease significantly increased after 9 years of diagnosis in Black patients. Multivariate analyses showed that the independent factors associated with inferior NPC-specific survival were older age, Asians, American Indian/Alaska Native, regional stage, distant stage, and diagnosis in the early years.ConclusionsThe probability of death from primary NPC remains significant even 15 years after the NPC diagnosis. Our study advocates continued surveillance for NPC survivors beyond the traditional 5 years. Individualized follow-up strategies are required for patients with NPC of different ages and races.

Identification of a novel binding inhibitor that blocks the interaction between hSCARB2 and VP1 of enterovirus 71.

Enterovirus 71 (EV-A71) infection causes severe hand-foot-and-mouth disease that leads to cardiopulmonary complications and death in young children under 5 years of age. Although there are available vaccines for EV-A71 C4, however, there are no efficient drugs for severe cases. Thus, there is an urgent need to find new direct-antiviral agents (DAAs) to control EV-A71 infection. In this study, we report our discovery of the EV-A71 capsid inhibitor PTC-209HBr, a small-molecule Bmi-1 inhibitor and an anticancer agent, and its derivatives that inhibit multiple enteroviruses with an EC50 at a submicromolar efficacy. The mechanism of action of PTC-209HBr was confirmed by time-of-addition, resistance selection and reverse genetics experiments, microscale thermophoresis (MST), viral binding and entry assays, coimmunoprecipitation (Co-IP) and immunofluorescence experiments (IF). Mechanistic studies indicated that PTC-209HBr inhibited EV-A71 infection by impeding the binding between VP1 and the receptor hSCARB2 during the early stage of EV-A71 infection through hindering viral entry into host cells. Collectively, these findings indicated that PCT-209HBr is a novel inhibitor of enteroviruses with a confirmed mechanism of action that can be further developed into EV-A71 DAAs.

Milrinone effects on cardiac mitochondria, hemodynamics, and death in catecholamine-infused rats.

BackgroundCatecholamine-storm is considered the major cause of enterovirus 71-associated cardiopulmonary death. To elucidate the effect of milrinone on cardiac mitochondria and death, a rat model of catecholamine-induced heart failure was investigated.MethodsYoung male Spray-Dawley rats received a continuous intravenous infusion of norepinephrine then followed by co-treatment with and without milrinone or esmolol. Vital signs were monitored and echocardiography was performed at indicated time points. At the end of experiments, hearts were extracted to study mitochondrial function, biogenesis, and DNA copy numbers.ResultsHypernorepinephrinemia induced persistent tachycardia, hypertension, and high mortality and significantly impaired the activities of the electron transport chain and suppressed mitochondrial DNA copy number, mitochondrial transcription factor A and peroxisome proliferator-activated receptor-gamma coactivator 1-α. Norepinephrine-induced hypertension could be significantly suppressed by milrinone and esmolol. Milrinone improved but esmolol deteriorated the survival rate. The left ventricle was significantly enlarged shortly after norepinephrine infusion but later gradually reduced in size by milrinone. The impairment and suppression of mitochondrial function could be significantly reversed by milrinone but not by esmolol.ConclusionsMilrinone may protect the heart via maintaining mitochondrial function from hypernorepinephrinemia. This study warrants the importance of milrinone and the preservation of mitochondrial function in the treatment of catecholamine-induced death.Impact Milrinone may protect the heart from hypernorepinephrinemia-induced death via maintaining myocardial mitochondrial activity, function, and copy number.Maintenance of cardiac mitochondrial function may be a potential therapeutic strategy in such catecholamine-induced heart failure.

ETIOLOGY AND CLINICAL PROFILE OF PERICARDIAL EFFUSION PATIENTS

Background Pericardial effusion is one of the most prevalent disorders . Pericardial effusion can create substantial symptoms and a lower quality of life, but its also linked to a higher risk of cardiopulmonary failure, mortality, and death. Pericardial effusion has a variety of causes that are related to the relative occurrence of certain diseases in different parts of the world. Methods:it was a retrospective study that includes data from all pericardial effusion cases diagnosed . Echocardiography was used to diagnose a total of 50 cases with pericardial effusion. Complete blood count with ESR, blood urea, serum creatinine, tuberculin skin test, chest X-ray, ECG, Thyroid profile, ANA, Rheumatoid factor, CT chest / MRI, and pericardiocentesis were all used to determine the source of the pericardial effusion. Cells, proteins, LDH, malignant cells, ADA, PCR (for Mycobacterium tuberculosis), gram staining, AFB staining, and cultures were all examined in the pericardial fluid. Iatrogenic (cardiac surgery, catheterization) and post-traumatic cases were excluded . Results: The majority of the patients were between the ages of 50 and 70. Thirty patients (60%) were men and 20 patients (40%) were women. Tuberculosis was the most prevalent cause of pericardial effusion, accounting for 28 % of cases, followed by Idiopathic 18%, Uremia 12 %, and Malignant 14 %. HIV infection was the least common cause of pericardial effusion, accounting for 2% of cases. Tachycardia was the most common clinical symptom, in 70% of patients, followed by Breathlessness (60%), and fever (56 %). Conclusions:Tachycardia, shortness of breath, fever, heaviness of chest, cough, chest pain, and other symptoms of pericardial effusion have been noted in this study. Tuberculosis, idiopathic/viral, uremic, neoplastic, CCF, hypothyroidism, post-MI, etc. are all major factors for the development of pericardial effusion.