The association of early naloxone use with outcomes in non-shockable out-of-hospital cardiac arrest.

STUDY OBJECTIVE: Evaluate the association between early naloxone use and outcomes after out-of-hospital cardiac arrest (OHCA) with initial non-shockable rhythms. METHODS: This study was a secondary analysis of data collected in the Portland Cardiac Arrest Epidemiologic Registry, a database containing details of emergency medical services (EMS)-treated OHCA cases in the Portland, Oregon metropolitan region. Eligible patients had non-traumatic OHCA with an initial non-shockable rhythm and received naloxone by EMS or law enforcement prior to IV/IO access (exposure group). The primary outcome was ROSC at emergency department (ED) arrival. Secondary outcomes included survival to admission, survival to hospital discharge, and cerebral performance category score ≤2 at discharge (good neurologic outcome). We performed multivariable logistic regressions adjusting for age, sex, arrest location, witness status, bystander interventions, dispatch to EMS arrival time, initial rhythm, and county of arrest. RESULTS: There were 1807 OHCA cases from 2018 to 2021 meeting eligibility criteria, with 57 receiving naloxone before vascular access. Patients receiving naloxone prior to vascular access attempts had higher adjusted odds (aOR [95% CI]) of ROSC at any time (2.14 [1.20-3.81]), ROSC at ED arrival (2.14 [1.18-3.88]), survival to admission (2.86 [1.60-5.09]), survival to discharge (4.41 [1.78-10.97]), and good neurologic outcome (4.61 [1.74-12.19]). CONCLUSIONS: Patients with initial non-shockable OHCA who received law enforcement or EMS naloxone prior to IV/IO access attempts had higher adjusted odds of ROSC at any time, ROSC at ED arrival, survival to admission, survival to discharge, and good neurologic outcome.

Out-of-hospital cardiac arrest outcomes when law enforcement arrives before emergency medical services.

BACKGROUND: Law enforcement (LE) professionals are often dispatched to out-of-hospital cardiac arrests (OHCA) to provide early cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) application with mixed evidence of a survival benefit. Our objective was to comprehensively evaluate LE care in OHCA. METHODS: This is a secondary analysis of adults with non-traumatic OHCA not witnessed by EMS and without bystander AED use from 2018-2021. Our primary outcome was survival with Cerebral Perfusion Category score ≤ 2 (functional survival). Our exposures included: LE On-scene Only (without providing care); LE CPR Only (without applying an AED); LE Ideal Care (ensuring CPR and AED application). Our control group had no LE arrival before EMS. We performed multivariable logistic regression analyses adjusting for confounders and stratified our analyses by patients with and without bystander CPR. RESULTS: There were 2569 adult, non-traumatic OHCAs from 2018-2021 meeting inclusion criteria. There were no differences in the odds of functional survival for LE On-scene Only (adjusted odds ratio [95% CI]: 1.28 [0.47-3.45]), LE CPR Only (1.26 [0.80-1.99]), or LE Ideal Care (1.36 [0.79-2.33]). In patients without bystander CPR, LE Ideal Care had significantly higher odds of functional survival (2.01 [1.06-3.81]) compared to no LE on-scene, with no significant associations for LE On-scene Only or LE CPR Only. There were no significant differences by LE care in patients already receiving bystander CPR. CONCLUSIONS: LE arrival before EMS and ensuring both CPR and AED application is associated with significantly improved functional survival in OHCA patients not already receiving bystander CPR.

Utility of end-tidal carbon dioxide to guide resuscitation termination in prolonged out-of-hospital cardiac arrest.

STUDY OBJECTIVE: To evaluate if the change in end-tidal carbon dioxide (ETCO2) over time has improved discriminatory value for determining resuscitation futility compared to a single ETCO2 value in prolonged, refractory non-shockable out-of-hospital cardiac arrest (OHCA). METHODS: This is a retrospective analysis of adult refractory non-shockable, non-traumatic OHCA patients in the Portland Cardiac Arrest Epidemiologic Registry (PDX Epistry) from 2018 to 2021. We defined refractory non-shockable OHCA cases as patients with lack of a shockable rhythm at any time or return of spontaneous circulation at any time prior to 30-min of on-scene resuscitation. We abstracted ETCO2 values first recorded after advanced airway placement and nearest to the 30-min mark of on-scene resuscitation (30 min-ETCO2) from EMS charts. The primary outcome was survival to hospital discharge. We compared 30 min-ETCO2 cutoffs of 10 mmHg and 20 mmHg to the trend (increasing or not) from initial to 30 min-ETCO2 (delta-ETCO2) using sensitivity, specificity, and area under the receiver operating curves (AUROC). RESULTS: Of 3837 adult OHCA, 2850 were initially non-shockable, and there were 617 (16.1%) cases of refractory non-shockable OHCA at 30-min. We excluded 320 cases without at least two ETCO2 recordings in the EMS chart, leaving 297 cases that met inclusion criteria. Of these, 176 (59.3%) were transported and 2 (0.7%) survived to discharge. Using absolute 30 min-ETCO2 cutoffs, both survivors were in the >10 mmHg group (sensitivity 100.0%, specificity 12.5%), whereas only one survivor was identified in the >20 mmHg group (sensitivity 50.0%, specificity 32.5%). Using delta-ETCO2, both survivors were in the increasing ETCO2 group (sensitivity 100.0%, specificity 60.7%). In comparing the two tests that did not misclassify survivors, the AUROC [95% CI] was higher when using delta-ETCO2 (0.803 [0.775-0.831]) compared to an absolute cutoff of 10 mmHg (0.563 [0.544-0.582]). CONCLUSIONS: Nearly one-sixth of EMS-treated adult OHCA patients had refractory non-shockable arrests after at least 30 min of ongoing resuscitation. In this group, the ETCO2 trend following advanced airway placement may be more accurate in guiding termination of resuscitation than an absolute ETCO2 cutoff of 10 or 20 mmHg.

Outcomes with Tibial and Humeral Intraosseous Access Compared to Peripheral Intravenous Access in Out-of-Hospital Cardiac Arrest.

BACKGROUND: The optimal initial vascular access strategy for out-of-hospital cardiac arrest (OHCA) remains unknown. Our objective was to evaluate the association between peripheral intravenous (PIV), tibial intraosseous (TIO), or humeral intraosseous (HIO) as first vascular attempt strategies and outcomes for patients suffering OHCA. METHOD: This was a secondary analysis of the Portland Cardiac Arrest Epidemiologic Registry, which included adult patients (≥18 years-old) with EMS-treated, non-traumatic OHCA from 2018-2021. The primary independent variable in our analysis was the initial vascular access strategy, defined as PIV, TIO, or HIO based on the first access attempt. The primary outcome for this study was the return of spontaneous circulation (ROSC) at emergency department (ED) arrival (a palpable pulse on arrival to the hospital). Secondary outcomes included survival to: admission, discharge, and discharge with a favorable outcome (Cerebral Perfusion Category score of ≤2). We conducted multivariable logistic regressions, adjusting for confounding variables and for clustering using a mixed-effects approach, with prespecified subgroup analyses by initial rhythm. RESULTS: We included 2,993 patients with initial vascular access strategies of PIV (822 [27.5%]), TIO (1,171 [39.1%]), and HIO (1,000 [33.4%]). Multivariable analysis showed lower odds of ROSC at ED arrival (adjusted odds ratio [95% CI]) with TIO (0.79 [0.64-0.98]) or HIO (0.75 [0.60-0.93]) compared to a PIV-first strategy. These associations remained in stratified analyses for those with shockable initial rhythms (0.60 [0.41-0.88] and 0.53 [0.36-0.79]) but not in patients with asystole or pulseless electrical activity for TIO and HIO compared to PIV, respectively. There were no statistically significant differences in adjusted odds for survival to admission, discharge, or discharge with a favorable outcome for TIO or HIO compared to the PIV-first group in the overall analysis. Patients with shockable initial rhythms had lower adjusted odds of survival to discharge (0.63 [0.41-0.96] and 0.64 [0.41-0.99]) and to discharge with a favorable outcome (0.60 [0.39-0.93] and 0.64 [0.40-1.00]) for TIO and HIO compared to PIV, respectively. CONCLUSIONS: TIO or HIO as first access strategies in OHCA were associated with lower odds of ROSC at ED arrival compared to PIV.

Survival by time-to-administration of amiodarone, lidocaine, or placebo in shock-refractory out-of-hospital cardiac arrest.

BACKGROUND: Amiodarone and lidocaine have not been shown to have a clear survival benefit compared to placebo for out-of-hospital cardiac arrest (OHCA). However, randomized trials may have been impacted by delayed administration of the study drugs. We sought to evaluate how timing from emergency medical services (EMS) arrival on scene to drug administration affects the efficacy of amiodarone and lidocaine compared to placebo. METHOD: This is a secondary analysis of the 10-site, 55-EMS-agency double-blind randomized controlled amiodarone, lidocaine, or placebo in OHCA study. We included patients with initial shockable rhythms who received the study drugs of amiodarone, lidocaine, or placebo before achieving return of spontaneous circulation. We performed logistic regression analyses evaluating survival to hospital discharge and secondary outcomes of survival to admission and functional survival (modified Rankin scale score ≤ 3). We evaluated the samples stratified by early (<8 min) and late administration groups (≥8 min). We compared outcomes for amiodarone and lidocaine compared to placebo and adjust for potential confounders. RESULTS: There were 2802 patients meeting inclusion criteria, with 879 (31.4%) in the early (<8 min) and 1923 (68.6%) in the late (≥8 min) groups. In the early group, patients receiving amiodarone, compared to placebo, had significantly higher survival to admission (62.0% vs. 48.5%, p = 0.001; adjusted OR [95% CI] 1.76 [1.24-2.50]), survival to discharge (37.1% vs. 28.0%, p = 0.021; 1.56 [1.07-2.29]), and functional survival (31.6% vs. 23.3%, p = 0.029; 1.55 [1.04-2.32]). There were no significant differences with early lidocaine compared to early placebo (p > 0.05). Patients in the late group who received amiodarone or lidocaine had no significant differences in outcomes at discharge compared to placebo (p > 0.05). CONCLUSIONS: The early administration of amiodarone, particularly within 8 min, is associated with greater survival to admission, survival to discharge, and functional survival compared to placebo in patients with an initial shockable rhythm.

Utilization and Effect of Direct Medical Oversight during Out-of-Hospital Cardiac Arrest.

STUDY OBJECTIVE: Direct medical oversight (DMO), where emergency medical services (EMS) clinicians contact a physician for real-time medical direction, is used by many EMS systems across the United States. Our objective was to characterize the recommendations made by DMO during out-of-hospital cardiac arrests (OHCA) and to determine their effect on EMS transport decisions and patient outcomes. METHODS: This is a secondary analysis of DMO call recordings from OHCA cases in the Portland, Oregon metropolitan area from January 1, 2018 to February 28, 2021. Data extracted from the audio recordings were linked to OHCA cases in the Portland Cardiac Arrest Epidemiologic Registry (PDX Epistry). The primary outcomes are recommendations made by DMO: transport, continued field resuscitation, or termination of resuscitation (TOR). Secondary outcomes include EMS transport decisions, survival to hospital admission, and survival to hospital discharge. We used descriptive statistics, unpaired t-tests, and chi-square tests as appropriate for data analysis. RESULTS: There were 239 OHCA cases for which DMO was contacted by EMS. The median time from EMS arrival to DMO contact was 25.6 min, and EMS requested TOR for 72.0% of patients. Compared to patients where EMS requested further treatment advice, patients for whom EMS requested TOR had poor prognostic signs including older age, asystole as an initial rhythm, and lower rates of transient return of spontaneous circulation prior to DMO call compared with cases where EMS did not request TOR. DMO recommended transport, continued field resuscitation, or TOR in 21.8%, 18.0%, and 60.2% of patients, respectively. Of the 239 patients, 59 (24.7%) were ultimately transported by EMS to the hospital, 14 (5.9%) survived to admission, and only 1 patient (0.4%) survived to hospital discharge and had an acceptable neurologic outcome (Cerebral Performance Category score of 2). CONCLUSIONS: Patients for whom EMS contacts DMO for further treatment advice or requesting field TOR after prolonged OHCA resuscitation have poor outcomes, even when DMO recommends transport or further resuscitation, and may represent opportunities to reduce unnecessary DMO contact or patient transports. More research is needed to determine which OHCA patients benefit from DMO contact.

Development of a clinical decision rule for the early prediction of Shock-Refractory Out-of-Hospital cardiac arrest.

BACKGROUND: Nearly half of ventricular fibrillation or ventricular tachycardia (VF/VT) out-of-hospital cardiac arrest (OHCA) patients receive three or more shocks, often referred to as refractory VF/VT. Our objective was to derive a clinical decision rule (CDR) for the early stratification of patients into risk categories for refractory VF/VT. METHODS: We included adults with non-traumatic OHCA in the Resuscitation Outcomes Consortium Epistry (2011-2015) with ≥ 1 EMS shock. We used Classification and Regression Tree analysis for CDR building using variables known at initial EMS rhythm analysis including age, sex, witness, location, bystander interventions, initial EMS rhythm, obvious non-cardiac etiology, and dispatch to arrival times. The outcome was refractory VF/VT (≥3 shocks). We calculated sensitivity, specificity, area under the receiver operating curve (AUROC), and odds ratios (OR). The rule was validated using the Portland Cardiac Arrest Epidemiologic Registry (2018-2020). RESULTS: There were 17,140 eligible patients and 8,146 (47.5%) had refractory VF/VT. The optimal CDR (AUROC = 0.671) defined three groups: high-risk were any patients requiring an EMS shock after a bystander AED shock; moderate-risk were any non-EMS witnessed arrests with shockable initial EMS rhythms; and the remainder were low-risk. Refractory VF/VT increased across the low (30.7%), moderate (58.5%) and high-risk (84.8%) groups. Compared to low-risk, being moderate-risk or higher (OR [95% CI]:3.37 [3.16-3.59]; sensitivity 72.7%; specificity 55.9%) or high-risk (OR:12.63 [9.89-16.13]; sensitivity 5.4%; specificity 99.1%) had higher odds of refractory VF/VT. Results was similar in the validation cohort (n = 765, AUROC = 0.672). CONCLUSIONS: Patients at higher risk for refractory VF/VT can be identified early in EMS care.

Non-transport after Prehospital Naloxone Administration Is Associated with Higher Risk of Subsequent Non-fatal Overdose.

Objective: U.S. opioid overdoses increased nearly sixfold from 1999 to 2018, and greater than 1% of all emergency medical services (EMS) encounters now involve naloxone administration. While "treat and release" protocols may have low short-term mortality, the risk of subsequent non-fatal overdoses is not known. This study compares the risk of repeat overdose encounters between patients transported to an emergency department (ED) and those who refused transport after prehospital naloxone administration. Methods: All EMS charts within a large single-tier fire-based urban EMS system between January 1 and August 31, 2018 were reviewed if either naloxone administration or a clinical impression related to opioid overdose was documented. Charts were excluded if there was no documented evidence of an opioid toxidrome (respiratory depression or altered mental status), if there was another clear explanation for the symptoms (e.g., hypoglycemia), or if naloxone was not administered. Ten percent of charts were reviewed by a second author to assess reliability. Cox regression (survival analysis) was used to estimate the risk of a subsequent EMS encounter with naloxone administration following an index encounter with naloxone administration. Results: Of the 2143 charts reviewed, 1311 unique patients with 1600 overdose encounters involving naloxone administration were identified. Inter-rater reliability for chart inclusion was strong [κ = 0.83 (95% CI: 0.72-0.90)]. Police/bystanders administered naloxone in 208/1600 (13.0%) encounters. A substantial proportion of encounters resulted in transport refusal (674/1600, 42.1%). The final Cox model included only refusal vs. acceptance of transport to an ED during the index EMS encounter. Patient age, gender, and naloxone administration prior to EMS arrival were not statistically significant in univariate or multivariable analyses, nor were they significant confounders. Refusal of transport was associated with a hazard ratio of 1.66 (95% CI: 1.23-2.23) for subsequent EMS encounters with naloxone administration. Conclusions: Non-transport after prehospital naloxone administration is associated with an increased risk of subsequent non-fatal overdose requiring EMS intervention. Limitations include the use of a single EMS agency as patients may have had uncaptured overdose encounters in neighboring municipalities.

Prehospital Airway Management: A Systematic Review.

Objective: To assess comparative benefits and harms across three airway management approaches (bag valve mask [BVM], supraglottic airway [SGA], and endotracheal intubation [ETI]) used by prehospital emergency medical services (EMS) to treat patients with trauma, cardiac arrest, or medical emergencies, and how they differ based on techniques and devices, EMS personnel and patient characteristics. Data sources: We searched electronic citation databases (Ovid® MEDLINE®, CINAHL®, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus®) from 1990 to September 2020. Review methods: We followed Agency for Healthcare Research and Quality Effective Health Care Program Methods guidance. Outcomes included mortality, neurological function, return of spontaneous circulation (ROSC), and successful advanced airway insertion. Meta-analyses using profile-likelihood random effects models were conducted, with analyses stratified by study design, emergency type, and age. Results: We included 99 studies involving 630,397 patients. We found few differences in primary outcomes across airway management approaches. For survival, there was no difference for BVM versus ETI or SGA in adult and pediatric patients with cardiac arrest or trauma. For neurological function, there was no difference for BVM versus ETI and SGA versus ETI in pediatric patients with cardiac arrest. There was no difference in BVM versus ETI in adults with cardiac arrest, but improved neurological function with BVM or ETI versus SGA. There was no difference in ROSC for patients with cardiac arrest for BVM versus ETI or SGA in adults and pediatrics, or SGA versus ETI in pediatrics. There was higher frequency of ROSC in adults with SGA versus ETI. For successful advanced airway insertion, there was higher first-pass success with SGA versus ETI for all patients except adult medical patients (no difference), and no difference in overall success using SGA versus ETI in adults. Conclusions: The currently available evidence does not indicate benefits of more invasive airway approaches based on survival, neurological function, ROSC, or successful airway insertion. Strength of evidence was low or moderate; most included studies were observational. This supports the need for high-quality randomized controlled trials to advance clinical practice and EMS education and policy, and improve patient-centered outcomes.

Fatal Sodium Nitrite Poisoning: Key Considerations for Prehospital Providers.

Sodium nitrite is a powerful oxidizing agent that causes hypotension and limits oxygen transport and delivery in the body through the formation of methemoglobin. Clinical manifestations can include cyanosis, hypoxia, altered consciousness, dysrhythmias, and death. The majority of reports on sodium nitrite poisonings have been the result of unintentional exposures. We report a case of an intentional fatal overdose of sodium nitrite. A 17-year-old female reportedly drank approximately one tablespoon of sodium nitrite in a self-harm attempt. The patient was hypotensive and cyanotic upon EMS arrival. The patient decompensated rapidly into a bradycardic arrest during transport despite intubation, push-dose epinephrine, and intravenous fluid resuscitation. In the Emergency Department (ED), she received methylene blue and packed red cells but could not be resuscitated despite a prolonged effort. EMS professionals should consider sodium nitrite toxicity in patients with a suspected overdose who present with a cyanotic appearance, pulse oximetry that remains around 85% despite oxygen, and dark brown blood seen on venipuncture. Early prehospital contact with the Poison Control Center and ED prenotification in poisoned patients is encouraged.

Ventilation in Simulated Out-of-Hospital Cardiac Arrest Resuscitation Rarely Meets Guidelines.

OBJECTIVE: The American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care recommend ventilation rates of eight to ten breaths per minute or two ventilations every 30 compressions, and tidal volumes between 500-600 ml. However, compliance with these guidelines is mainly unknown. The objective of this study is to estimate the proportion of simulated adult OHCA cases that meet guideline-based ventilation targets. METHODS: We conducted a blinded prospective observational study of standardized simulated cases of EMS-witnessed adult OHCA. During scheduled training sessions, resuscitations were performed by high-quality CPR trained EMS teams composed of four on-duty, full-time EMT/Paramedics from a large urban fire-based EMS agency. A high-fidelity simulation center allowed complete audio and video monitoring from a control room. Rescuers were unaware of the study, or that ventilation practices were being observed. All interventions, including airway and ventilation strategies, were at the discretion of the clinical team. A calibrated Laerdal SimMan 3 G manikin and associated Laerdal Debrief Viewer software recorded ventilation rate, tidal volume, and minute ventilation. Simulations achieving median ventilation rate 7-10 breaths/min, tidal volume 500-600 ml, and minute ventilation 3.5-6 liters/min were considered meeting guideline-based targets. RESULTS: A total of 106 EMS teams were included in the study. Only 3/106 [2.8% (95% CI: 0.6-8.0)] of the EMS teams demonstrated ventilation characteristics meeting all guideline-based targets. The median ventilation rate was 5.8 breaths/min (IQR 4.4-7.7 breaths/min) with 26/106 [24.5% (95% CI: 17.2-33.7)] between 7-10 breaths/min. The median tidal volume was 413.5 ml (IQR 280.5-555.4 ml), with 18/106 [17.0% (95% CI: 10.9-25.5)] between 500-600 ml. The median minute ventilation was 2.4 L/min (IQR 1.2-3.6 L/min) with 16/106 [15.1% (95% CI: 9.4-23.3)] between 3.5-6.0 L/min. CONCLUSION: During simulated adult OHCA resuscitation attempts, ventilation practices rarely met guideline-based targets, despite being performed by well-trained EMS providers. Methods should be developed to monitor and ensure high-quality ventilation during actual OHCA resuscitation attempts.

A review of ventilation in adult out-of-hospital cardiac arrest.

Out-of-hospital cardiac arrest continues to be a devastating condition despite advances in resuscitation care. Ensuring effective gas exchange must be weighed against the negative impact hyperventilation can have on cardiac physiology and survival. The goals of this narrative review are to evaluate the available evidence regarding the role of ventilation in out-of-hospital cardiac arrest resuscitation and to provide recommendations for future directions. Ensuring successful airway patency is fundamental for effective ventilation. The airway management approach should be based on professional skill level and the situation faced by rescuers. Evidence has explored the influence of different ventilation rates, tidal volumes, and strategies during out-of-hospital cardiac arrest; however, other modifiable factors affecting out-of-hospital cardiac arrest ventilation have limited supporting data. Researchers have begun to explore the impact of ventilation in adult out-of-hospital cardiac arrest outcomes, further stressing its importance in cardiac arrest resuscitation management. Capnography and thoracic impedance signals are used to measure ventilation rate, although these strategies have limitations. Existing technology fails to reliably measure real-time clinical ventilation data, thereby limiting the ability to investigate optimal ventilation management. An essential step in advancing cardiac arrest care will be to develop techniques to accurately and reliably measure ventilation parameters. These devices should allow for immediate feedback for out-of-hospital practitioners, in a similar way to chest compression feedback. Once developed, new strategies can be established to guide out-of-hospital personnel on optimal ventilation practices.

Ruptured Ectopic Pregnancy in the Presence of an Intrauterine Device.

Ruptured ectopic pregnancy is the leading cause of first trimester maternal mortality. The diagnosis of ectopic pregnancy should always be suspected in patients with abdominal pain, vaginal bleeding or syncope. While the use of an intrauterine device (IUD) markedly reduces the incidence of intrauterine pregnancy, it does not confer equal protection from the risk of ectopic pregnancy. In this report we discuss the case of a female patient who presented with a ruptured ectopic pregnancy and hemoperitoneum despite a correctly positioned IUD.

Acute hand pain resulting in spontaneous thenar compartment syndrome.

Compartment syndrome is a potentially limb-threatening disease process, leading to decreased tissue perfusion and cellular death [1]. The following presentation is believed to be the first reported case of thenar compartment syndrome, which occurred without an identifiable cause. A 67-year-old male presented with 12 h of left-hand pain, located at the base of the thumb and worsened with movement. Firmness of the thenar eminence, along with pallor, poikilothermia, and paresthesias of the first and second digits lead to the increased suspicion for compartment syndrome. The diagnosis was confirmed and successfully managed in the operating room. While relatively uncommon, clinicians should consider the diagnosis of compartment syndrome of the hand when patients present with acute hand pain. A missed or delayed diagnosis can lead to severe morbidity, which can profoundly affect patients' functional outcomes and quality of life.

Progressive anatomical closure of foramen ovale in normal neonatal mouse hearts.

In the prenatal heart, right-to-left atrial shunting of blood through the foramen ovale is essential for proper circulation. After birth, as the pulmonary circulation is established, the foramen ovale functionally closes as a result of changes in the relative pressure of the two atrial chambers, ensuring the separation of oxygen depleted venous blood in the right atrium from the oxygenated blood entering the left atrium. Little is known regarding the process of anatomical closure of the foramen ovale in the postnatal heart. Genetically engineered mouse models are powerful tools to study heart development and to reveal mechanisms underlying cardiac anomalies, including defects in atrioventricular septation. Using three-dimensional reconstructions of serial sectioned hearts at early postnatal Days 2-7, we show a progressive reduction in the size of the interatrial communication throughout this period and complete closure by postnatal Day 7. Furthermore we demonstrate that fusion of the septum primum and septum secundum occurs between 4 weeks and 3 months of age. This study provides a standard timeline for morphological closure of the right-left atrial communication and fusion between the atrial septa in normal mouse hearts.