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Concept: Cardiac arrest

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Background Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever. Methods In an international trial, we randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33°C or 36°C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale. Results In total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33°C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36°C group (225 of 466 patients) (hazard ratio with a temperature of 33°C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33°C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36°C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar. Conclusions In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C. (Funded by the Swedish Heart-Lung Foundation and others; TTM ClinicalTrials.gov number, NCT01020916 .).

Concepts: Cardiac arrest, Modified Rankin Scale, Therapeutic hypothermia, Barthel scale

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Background Targeted temperature management is recommended for comatose adults and children after out-of-hospital cardiac arrest; however, data on temperature management after in-hospital cardiac arrest are limited. Methods In a trial conducted at 37 children’s hospitals, we compared two temperature interventions in children who had had in-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose children older than 48 hours and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a score of 70 or higher on the Vineland Adaptive Behavior Scales, second edition (VABS-II, on which scores range from 20 to 160, with higher scores indicating better function), was evaluated among patients who had had a VABS-II score of at least 70 before the cardiac arrest. Results The trial was terminated because of futility after 329 patients had undergone randomization. Among the 257 patients who had a VABS-II score of at least 70 before cardiac arrest and who could be evaluated, the rate of the primary efficacy outcome did not differ significantly between the hypothermia group and the normothermia group (36% [48 of 133 patients] and 39% [48 of 124 patients], respectively; relative risk, 0.92; 95% confidence interval [CI], 0.67 to 1.27; P=0.63). Among 317 patients who could be evaluated for change in neurobehavioral function, the change in VABS-II score from baseline to 12 months did not differ significantly between the groups (P=0.70). Among 327 patients who could be evaluated for 1-year survival, the rate of 1-year survival did not differ significantly between the hypothermia group and the normothermia group (49% [81 of 166 patients] and 46% [74 of 161 patients], respectively; relative risk, 1.07; 95% CI, 0.85 to 1.34; P=0.56). The incidences of blood-product use, infection, and serious adverse events, as well as 28-day mortality, did not differ significantly between groups. Conclusions Among comatose children who survived in-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a favorable functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute; THAPCA-IH ClinicalTrials.gov number, NCT00880087 .).

Concepts: Heart, Relative risk, Cardiac arrest, Asystole, Therapeutic hypothermia, Harshad number, Hebrew numerals, Drowning

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Sudden cardiac death exhibits diurnal variation in both acquired and hereditary forms of heart disease, but the molecular basis of this variation is unknown. A common mechanism that underlies susceptibility to ventricular arrhythmias is abnormalities in the duration (for example, short or long QT syndromes and heart failure) or pattern (for example, Brugada’s syndrome) of myocardial repolarization. Here we provide molecular evidence that links circadian rhythms to vulnerability in ventricular arrhythmias in mice. Specifically, we show that cardiac ion-channel expression and QT-interval duration (an index of myocardial repolarization) exhibit endogenous circadian rhythmicity under the control of a clock-dependent oscillator, krüppel-like factor 15 (Klf15). Klf15 transcriptionally controls rhythmic expression of Kv channel-interacting protein 2 (KChIP2), a critical subunit required for generating the transient outward potassium current. Deficiency or excess of Klf15 causes loss of rhythmic QT variation, abnormal repolarization and enhanced susceptibility to ventricular arrhythmias. These findings identify circadian transcription of ion channels as a mechanism for cardiac arrhythmogenesis.

Concepts: Cardiology, Heart, Sleep, Cardiac arrest, Cardiac electrophysiology, Long QT syndrome, Circadian rhythm, Sudden cardiac death

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Approximately 300,000 people suffer sudden cardiac arrest (SCA) annually in the United States. Less than 30% of out-of-hospital victims receive cardiopulmonary resuscitation (CPR) despite the American Heart Association training over 12 million laypersons annually to conduct CPR. New engaging learning methods are needed for CPR education, especially in schools. Massively multiplayer virtual worlds (MMVW) offer platforms for serious games that are promising learning methods that take advantage of the computer capabilities of today’s youth (ie, the digital native generation).

Concepts: Cardiac arrest, Cardiopulmonary resuscitation, Asystole, Drowning, Respiratory arrest, American Heart Association

168

BACKGROUND: Heart failure (HF) patients have a high risk of death, and implantable cardioverter defibrillators (ICDs) are effective in preventing sudden cardiac death (SCD). However, a certain percentage of patients may not be immediate candidates for ICDs, particularly those having a short duration of risk or an uncertain amount of risk. This includes the newly diagnosed patients, as well as those on the cardiac transplant list or NYHA class IV heart failure patients who do not already have an ICD. In these patients, a wearable cardioverter defibrillator (WCD) may be used until long term risk of SCD is defined. The purpose of this study was to determine the incidence of SCD in this population, and the efficacy of early defibrillation by a WCD. METHODS: Ten enrolling centers identified 89 eligible HF patients who were either listed for cardiac transplantation, diagnosed with dilated cardiomyopathy, or receiving inotropic medications. Data collected included medical history, device records, and outcomes (including 90 day mortality). RESULTS: Out of 89 patients, final data on 82 patients has been collected. Patients wore the device for 75+/-58 days. Mean age was 56.8+/-13.2, and 72% were male. Most patients (98.8%) were diagnosed with dilated cardiomyopathy with a low ejection fraction (<40%) and twelve were listed for cardiac transplantation. Four patients were on inotropes. There were no sudden cardiac arrests or deaths during the study. Interestingly, 41.5% of patients were much improved after WCD use, while 34.1% went on to receive an ICD. CONCLUSIONS: In conclusion, the WCD monitored HF patients until further assessment of risk. The leading reasons for end of WCD use were improvement in left ventricular ejection fraction (LVEF) or ICD implantation if there was no significant improvement in LVEF.

Concepts: Myocardial infarction, Cardiology, Cardiomyopathy, Heart failure, Ejection fraction, Implantable cardioverter-defibrillator, Cardiac arrest, Ventricular fibrillation

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Anomalies of coronary number and course represent an opinion-dividing topic in cardiopathology, particularly for their relationship with sudden cardiac death. To the best of our knowledge, we herein report the first fatal case of a young female whose coronary anatomy was characterised by the absence of any septal perforator branch in the proximal segment of the LAD. This case could be useful for pathologists, coronary angiographers, and interventional cardiologists in detecting this infrequent anomaly, thus providing a more accurate estimation of its incidence. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3570015858473043.

Concepts: Atherosclerosis, Cardiology, Heart, Cardiac arrest, Artery, Coronary circulation, Interventional cardiology, Sudden cardiac death

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Mechanical chest compression devices have the potential to help maintain high-quality cardiopulmonary resuscitation (CPR), but despite their increasing use, little evidence exists for their effectiveness. We aimed to study whether the introduction of LUCAS-2 mechanical CPR into front-line emergency response vehicles would improve survival from out-of-hospital cardiac arrest.

Concepts: Cardiac arrest, Cardiopulmonary resuscitation, Asystole

156

The Brugada syndrome (BrS) is a malignant, genetically-determined, arrhythmic syndrome manifesting as syncope or sudden cardiac death (SCD) in individuals with structurally normal hearts. The diagnosis of the BrS is mainly based on the presence of a spontaneous or Na + channel blocker induced characteristic, electrocardiographic (ECG) pattern (type 1 or coved Brugada ECG pattern) typically seen in leads V1 and V2 recorded from the 4th to 2nd intercostal (i.c.) spaces. This pattern needs to be distinguished from similar ECG changes due to other causes (Brugada ECG phenocopies). This review focuses mainly on the ECG-based methods for diagnosis and arrhythmia risk assessment in the BrS. Presently, the main unresolved clinical problem is the identification of those patients at high risk of SCD who need implantable cardioverter-defibrillator (ICD), which is the only therapy with proven efficacy. Current guidelines recommend ICD implantation only in patients with spontaneous type 1 ECG pattern, and either history of aborted cardiac arrest or documented sustained VT (class I), or syncope of arrhythmic origin (class IIa) because they are at high risk of recurrent arrhythmic events (up to 10% or more annually for those with aborted cardiac arrest). The majority of BrS patients are asymptomatic when diagnosed and considered to have low risk (around 0.5% annually) and therefore not indicated for ICD. The majority of SCD victims in the BrS, however, had no symptoms prior to the fatal event and therefore were not protected with an ICD. While some ECG markers such as QRS fragmentation, infero-lateral early repolarisation, and abnormal late potentials on signal-averaged ECG are known to be linked to increased arrhythmic risk, they are not sufficiently sensitive or specific. Potential novel ECG-based strategies for risk stratification are discussed based on computerised methods for depolarisation and repolarisation analysis, a composite approach targeting several major components of ventricular arrhythmogenesis, and the collection of large digital ECG databases in genotyped BrS patients and their relatives.

Concepts: Cardiology, Implantable cardioverter-defibrillator, Cardiac arrest, Cardiac electrophysiology, Ventricular fibrillation, Sudden cardiac death, Brugada syndrome, Cardiac dysrhythmia

152

increasing number of people living in high-rise buildings presents unique challenges to care and may cause delays for 911-initiated first responders (including paramedics and fire department personnel) responding to calls for out-of-hospital cardiac arrest. We examined the relation between floor of patient contact and survival after cardiac arrest in residential buildings.

Concepts: Patient, Cardiac arrest, Ambulance, Storey, Residential area, High-rise

150

The introduction of the so-called newer-generation transcatheter aortic valve implantation (TAVI) devices has led to a dramatic reduction in the incidence of complications associated with the procedure. However, preliminary data suggest that conduction abnormalities (particularly new-onset atrioventricular block and left bundle branch block) remain a frequent complication post TAVI. Although inconsistencies across studies are apparent, new-onset conduction abnormalities post TAVI may be associated with higher incidences of mortality, sudden cardiac death and left ventricular dysfunction. Strategies intended both to reduce the risk and to improve the management of such complications are clearly warranted. In fact, the indication and timing of permanent pacemaker implantation are frequently individualised according to centre and/or operator preference. Currently, studies assessing the impact of these complications and the optimal indications for permanent cardiac pacing are underway. In this article, we review the data available on the incidence and impact of conduction disturbances following TAVI, and propose a strategy for the management of such complications.

Concepts: Cardiology, Heart, Cardiac arrest, Cardiac electrophysiology, Left ventricle, Cardiac pacemaker, Sinoatrial node, Transcutaneous pacing