Breath variability increases in the minutes preceding obstructive sleep apneic events.

PURPOSE: It is unclear if there is a consistent signature in breath patterns prior to an impending obstructive apneic event in patients with sleep-disordered breathing (SDB). OBJECTIVE: To use continuous recordings of ambient sound in sleep using a smartphone to track auditory signatures of breaths and measure their regularity preceding apneic events. METHODS: We studied 50 patients evaluated for SDB in whom sound was recorded using smartphones concurrently with polysomnography (PSG). Whole-night sound files were analyzed for time and frequency domain analyses of breath periodicity during periods of normal and sleep-disordered breathing. RESULTS: Fifty patients (44% women, 42.0 ± 9.4 years old, BMI 32.8 ± 10.8 kg/m2) recorded sound, of whom 30 were diagnosed with OSA and 20 were not. We analyzed a total of 497 apneic (≥10 s) and 481 non-apneic intervals, confirmed by PSG. Interbreath intervals were 3.75 ± 0.62 s for 1 min in quiet breathing, with SD 1.11 ± 0.48 s that increased to 4.16 ± 3.06 s in successive 60-s epochs up to apnea (p < 0.001). Interbreath SD in the 60 s immediately preceding apnea was higher than the SD in random non-apneic periods (p < 0.01, ANOVA). Interbreath SD ≥1.49 s gave 87.3% sensitivity and 86.5% specificity for predicting apnea in the next minute (c-statistic 0.94). CONCLUSIONS: Breaths increase in variability minutes before proven obstructive apnea in patients with suspected SDB. These results suggest that it may be possible to predict and thus potentially avert apneic events and provide insights into events leading to SDB. TRIAL REGISTRATION: NCT03288376, clinicaltrials.org.

Noncontact identification of sleep-disturbed breathing from smartphone-recorded sounds validated by polysomnography.

PURPOSE: Diagnosis of obstructive sleep apnea by the gold-standard of polysomnography (PSG), or by home sleep testing (HST), requires numerous physical connections to the patient which may restrict use of these tools for early screening. We hypothesized that normal and disturbed breathing may be detected by a consumer smartphone without physical connections to the patient using novel algorithms to analyze ambient sound. METHODS: We studied 91 patients undergoing clinically indicated PSG. Phase I: In a derivation cohort (n = 32), we placed an unmodified Samsung Galaxy S5 without external microphone near the bed to record ambient sounds. We analyzed 12,352 discrete breath/non-breath sounds (386/patient), from which we developed algorithms to remove noise, and detect breaths as envelopes of spectral peaks. Phase II: In a distinct validation cohort (n = 59), we tested the ability of acoustic algorithms to detect AHI < 15 vs AHI > 15 on PSG. RESULTS: Smartphone-recorded sound analyses detected the presence, absence, and types of breath sound. Phase I: In the derivation cohort, spectral analysis identified breaths and apneas with a c-statistic of 0.91, and loud obstruction sounds with c-statistic of 0.95 on receiver operating characteristic analyses, relative to adjudicated events. Phase II: In the validation cohort, automated acoustic analysis provided a c-statistic of 0.87 compared to whole-night PSG. CONCLUSIONS: Ambient sounds recorded from a smartphone during sleep can identify apnea and abnormal breathing verified on PSG. Future studies should determine if this approach may facilitate early screening of SDB to identify at-risk patients for definitive diagnosis and therapy. CLINICAL TRIALS: NCT03288376; clinicaltrials.org.

Thinking outside the Box: Rotor Modulation in the Treatment of Atrial Fibrillation.

Ablation for atrial fibrillation (AF) is an important and exciting therapy whose results remain suboptimal. Although most clinical trials show that ablation eliminates AF more effectively than medications, it is disappointing that the continued single procedural success remains ≈50% despite the substantial advances that have taken place in imaging, catheter positioning and energy delivery. Focal impulse and rotor modulation (FIRM), on the other hand, offers the opportunity to precisely define and then ablate patient-specific sustaining mechanisms for AF, rather than trying to eliminate all possible AF triggers. For over a decade, electrophysiologists have described cases in which AF terminates after only limited ablation - usually that cannot be explained by 'random' meandering wavelets. Indeed, recent studies from several laboratories show that all forms of clinical AF are typically 'driven' by stable electrical rotors and focal sources, not by multiple meandering waves. FIRM mapping enables an operator to place a catheter at typically 1-3 predicted sites in the atria, and with <5-10 minutes of RF ablation, terminate AF and potentially render it non-inducible. Several independent laboratories have now shown that such FIRM ablation alone can terminate or substantially slow AF in >80% of patients with persistent and paroxysmal AF and increase the single procedure rate of AF elimination from 50% with PV isolation alone to >80%. Ongoing studies hint that FIRM only ablation, enabling ablation times in the range observed for typical atrial flutter, may also achieve these high success rates without subsequent trigger ablation. This review summarizes the current state-of-the-art on FIRM mapping and ablation.

Contemporary outcome measures in acute stroke research: choice of primary outcome measure.

BACKGROUND AND PURPOSE: The diversity of available outcome measures for acute stroke trials is challenging and implies that the scales may be imperfect. To assist researchers planning trials and to aid interpretation, this article reviews and makes recommendations on the available choices of scales. The aim is to identify an approach that will be universally accepted and that should be included in most acute trials, without seeking to restrict options for special circumstances. METHODS: The article considers outcome measures that have been widely used or are currently advised. It examines desirable properties for outcome measures such as validity, relevance, responsiveness, statistical properties, availability of training, cultural and language issues, resistance to comorbidity, as well as potential weaknesses. Tracking and agreement among outcomes are covered. RESULTS: Typical ranges of scores for the common scales are described, along with their statistical properties, which in turn influence optimal analytic techniques. The timing of recovery on scores and usual practice in trial design are considered. CONCLUSIONS: The preferred outcome measure for acute trials is the modified Rankin Scale, assessed at 3 months after stroke onset or later. The interview should be conducted by a certified rater and should involve both the patient and any relevant caregiver. Incremental benefits at any level of the modified Rankin Scale may be acceptable. The modified Rankin Scale is imperfect but should be retained in its present form for comparability with existing treatment comparisons. No second measure should be required, but correlations with supporting scales may be used to confirm consistency in direction of effects on other measures.

First experience with remote left ventricular mapping and transendocardial cell injection with a novel integrated magnetic navigation-guided electromechanical mapping system.

AIMS: The purpose of this preclinical feasibility study was to evaluate a novel integrated platform in which magnetic navigation is used to remotely guide electromechanical mapping of the left ventricle (LV) and transendocardial cell injections. Using an integrated remote system would greatly facilitate intramyocardial delivery of stem cells for treating ischaemic heart disease. METHODS AND RESULTS: We used the computer-controlled Stereotaxis magnetic navigation system to guide the NOGA electromechanical mapping system in mapping viable myocardium in the LV of seven pigs. We then tested the feasibility of this system to perform transendocardial injections in three of the pigs and to deliver mesenchymal precursor cells (MPCs) to targeted myocardial segments in four of the pigs. The success or failure of each injection was determined by myocardial contrast staining in the first group and by histopathologic analysis in the last group. The mean time (+/-SD) spent mapping the LV for each pig was 49.3+/-10.6 min. The success rate for transendocardial injections was 94.4%, as indicated by myocardial contrast staining. There was a 95.8% success rate for targeted injections of MPCs, and 4',6-diamidino-2-phenylindole-labeled MPCs were detected in all but one segment of one pig. No epicardial haemorrhage or injury was observed, although there was some venous drainage. CONCLUSIONS: The integrated Stereotaxis/NOGA system has excellent remote navigability inside the LV cavity while sparing the operator from radiation exposure. This system also allows transendocardial cell injections to be performed with a high success rate. Further studies are needed to define the safety profile of this system for clinical use.

Adverse events associated with lay emergency response programs: the public access defibrillation trial experience.

UNLABELLED: The adverse event (AE) profile of lay volunteer CPR and public access defibrillation (PAD) programs is unknown. We undertook to investigate the frequency, severity, and type of AE's occurring in widespread PAD implementation. DESIGN: A randomized-controlled clinical trial. SETTING: One thousand two hundred and sixty public and residential facilities in the US and Canada. PARTICIPANTS: On-site, volunteer, lay personnel trained in CPR only compared to CPR plus automated external defibrillators (AEDs). INTERVENTION: Persons experiencing possible cardiac arrest receiving lay volunteer first response with CPR+AED compared with CPR alone. MAIN OUTCOME MEASURE: An AE is defined as an event of significance that caused, or had the potential to cause, harm to a patient or volunteer, or a criminal act. AE data were collected prospectively. RESULTS: Twenty thousand three hundred and ninety six lay volunteers were trained in either CPR or CPR+AED. One thousand seven hundred and sixteen AEDs were placed in units randomized to the AED arm. There were 26,389 exposure months. Only 36 AE's were reported. There were two patient-related AEs: both patients experienced rib fractures. There were seven volunteer-related AE's: one had a muscle pull, four experienced significant emotional distress and two reported pressure by their employee to participate. There were 27 AED-related AEs: 17 episodes of theft involving 20 devices, three involved AEDs that were placed in locations inaccessible to the volunteer, four AEDs had mechanical problems not affecting patient safety, and three devices were improperly maintained by the facility. There were no inappropriate shocks and no failures to shock when indicated (95% upper bound for probability of inappropriate shock or failure to shock = 0.0012). CONCLUSIONS: AED use following widespread training of lay-persons in CPR and AED is generally safe for the volunteer and the patient. Lay volunteers may report significant, usually transient, emotional stress following response to a potential cardiac arrest. Within the context of this prospective, randomized multi-center study, AEDs have an exceptionally high safety profile when used by trained lay responders.

Automated external defibrillator program does not impair cardiopulmonary resuscitation initiation in the public access defibrillation trial.

OBJECTIVES: To evaluate whether automated external defibrillator (AED) training and AED availability affected the response of volunteer rescuers and performance of cardiopulmonary resuscitation (CPR) in presumed out-of-hospital cardiac arrest (OOH-CA) during the multicenter Public Access Defibrillation Trial. METHODS: The Public Access Defibrillation Trial recruited 1,260 facilities in 24 North American regional sites to participate in a trial addressing survival from OOH-CA when AED training and availability were added to a volunteer-based emergency response team. Volunteers at each facility were trained to perform either CPR alone (CPR) or CPR in conjunction with AED use (CPR+AED) according to randomized assignments. This study reports the frequency of response and initiation of CPR actions (chest compressions and/or ventilations) by volunteers in the CPR and CPR+AED study groups. RESULTS: A total of 314 presumed OOH-CA episodes occurred in CPR facilities, and 308 occurred in CPR+AED facilities. The volunteers were matched well for age, gender, and other features. Overall, ventilations (23.1% vs. 13.1%), chest compressions (24.4% vs. 12.1%), and both actions (19.8% vs. 10.5%; all p < 0.05) were more commonly performed in OOH-CA cases in the CPR+AED group. However, when only OOH-CA cases with volunteers responding were analyzed, the rates of CPR actions were similar. In the subgroup of CPR+AED cases with a responding volunteer, the AED was turned on for only 47% of cases. Volunteers initiated a CPR action more commonly when the AED was turned on (60.7% vs. 39.3%; p = 0.003). CONCLUSIONS: In the Public Access Defibrillation Trial, rates of CPR actions for presumed OOH-CA victims were low but similar for CPR and CPR+AED responding volunteer rescuers. Factors associated with volunteer response, CPR action initiation, and AED activation warrant further investigation.

How well are cardiopulmonary resuscitation and automated external defibrillator skills retained over time? Results from the Public Access Defibrillation (PAD) Trial.

BACKGROUND: The current standard for cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) retraining for laypersons is a four-hour course every two years. Others have documented substantial skill deterioration during this time period. OBJECTIVES: To evaluate 1) the retention of core CPR and AED skills among volunteer laypersons and 2) the time required to retrain laypersons to proficiency as a function of time since initial training. METHODS: This was an observational follow-up study evaluating CPR and AED skill retention and testing/retraining time up through 17 months after initial training. The study took place at 1,260 facilities recruited by 24 North American clinical research centers, and included 6,182 volunteer laypersons participating in the Public Access Defibrillation (PAD) Trial. Training to proficiency in either CPR only (N = 2,426) or CPR+AED (N = 3,756) was followed by testing/retraining provided three to 17 months later. Retraining was done in brief, one-on-one, individualized, interactive sessions. The outcome studied was instructors' global assessments of performance of CPR and AED skill adequacy, i.e., whether CPR actions would likely result in perfusion (yes/no) and whether AED actions would result in a shock through the heart (yes/no). RESULTS: For global CPR performance, 79%, 73%, and 71% of volunteers tested for the first time since initial training three to five, six to 11, and 12 to 17 months after initial training, respectively, were judged by their instructors as having adequate performance (p < 0.001, chi-square for linear trend). For global AED performance, 91%, 86%, and 84% of volunteers, respectively, were judged as having adequate performance (p < 0.001). The mean (+/- standard deviation) times required to test and retrain volunteers to proficiency were 5.7 (+/- 4.0) minutes for CPR skills and 7.7 (+/- 4.6) minutes for CPR+AED skills. CONCLUSIONS: Among PAD Trial volunteer laypersons participating in a simulated resuscitation, the proportions of volunteers judged by instructors to have adequate CPR and AED skills demonstrated small declines associated with longer intervals between initial training and subsequent testing. However, based on instructors' judgment, large majorities of volunteers still retained both CPR and AED core skills through 17 months after initial training. Furthermore, individual testing and retraining for CPR and AED skills were usually accomplished in less than 10 minutes per volunteer. Additional research is essential to identify training and evaluation techniques that predict adequate CPR and AED skill performance of laypersons when applied to an actual cardiac arrest.

Performance of a new cardiac cryoablation system in the treatment of cavotricuspid valve isthmus-dependent atrial flutter.

We sought to evaluate prospectively the safety and efficacy of cryothermal energy to ablate typical atrial flutter (AFL). Ablation of cardiac tissue using cryothermal energy has recently been developed as an alternative to radiofrequency energy, which may offer certain advantages in the treatment of AFL. This prospective, multicenter nonrandomized study of a new catheter-based system for the treatment of cavotricuspid isthmus (CTI)-dependent AFL enrolled patients between 18 and 75 years of age. The CTI dependence of AFL was confirmed at electrophysiologic study with activation mapping and/or entrainment. Patients with atrial septal defect, recent myocardial infarction, left ventricular ejection fraction <0.30, or prior AFL ablation were excluded. Cryoablation of AFL was performed in 48 patients from 11 centers. The procedure was immediately successful in 45 patients (94%), and effective in 30 of 40 patients with complete data available at 6 months. Cryoablation is a promising new treatment of CTI-dependent AFL refractory to medical therapy. Further improvements in catheter design and intravascular sheaths will be tested in a larger multicenter trial.

Transvenous catheter cryoablation for treatment of atrial fibrillation: results of a feasibility study.

Pulmonary vein (PV) isolation using radiofrequency (RF) ablation can induce PV stenosis. Cryoablation may offer a safer alternative energy source for PV isolation. PV isolation with cryoablation was attempted in 31 patients with paroxysmal atrial fibrillation (AF). Event monitors were used to measure the AF episode burden. Serial spiral CT scans were obtained to monitor PV stenosis pre- and postcryoablation. Cryoablation was immediately successful for PV isolation in 29 of 31 patients (94%), with 5.9 +/- 1.2 months of follow-up. Additional RF ablation was performed for AF recurrences in seven patients. The remaining 22 patients with a single cryoablation procedure demonstrated a time-dependent, long-term reduction in the frequency of AF episodes. At 6 months of follow-up, 18 of 22 of cryo-treated only patients (82%) were free of symptomatic AF episodes, and antiarrhythmic drugs were discontinued in 12 of 22 patients. Serial spiral CT scans demonstrated no change in the cryo-treated PV ostial diameter. PV cryoablation was effective to control paroxysmal AF in most patients. Early recurrences of AF postcryoablation were common, though tended to resolve within 6 months postablation, consistent with a process of reverse atrial remodeling. Cryoablation of the PVs did not cause PV stenosis or other serious adverse events.

Feasibility and safety of guidewire navigation using a magnetic navigation system in coronary artery stenoses.

AIM: Few studies are available on magnetic navigation system (MNS) for coronary artery disease. The present investigation was conducted to evaluate the feasibility and safety of guidewire navigation with a MNS in diseased coronary arteries. METHODS AND RESULTS: Between February 2004 and August 2005, a total of 59 patients (68 target vessels) underwent magnetic-assisted guidewire navigation in coronary arteries with stenoses amenable to coronary intervention. Patients were excluded if any of the following conditions applied: pacemakers or cardioverter defibrillator implanted; acute myocardial infarction; thrombotic lesions; chronic total occlusion; claustrophobia; and renal dysfunction with serum creatinine > 2.5mg/dl. Procedural success was defined as successful guidewire passage distal to the stenoses with no procedural events, defined as either perforation or dissection. Magnetic guidewires successfully crossed 60 (88%) lesions. Only 1 patient experienced a minor dissection of vessel wall in a circumflex lesion and was treated with a coronary stent. There was no other complication related to the magnetic guidewire. Nineteen (27.3%) coronary interventions were performed with magnetic guidewires. In 4 complex lesions (a lesion located in saphenous vein graft with proximal severe tortuosity; 3 approaches to stent-jailed side branch), where conventional wires failed to cross the culprit lesions, magnetic navigation achieved successful guidewire passage. CONCLUSIONS: Guidewire navigation using a MNS was feasible and safe. In the four complex cases, magnetic navigation enabled crossing of lesions in which conventional attempts failed. Further studies are needed to better evaluate the efficacy of MNS compared with conventional manual navigation.

Effect of a selection and postoperative care protocol on survival of infants with hypoplastic left heart syndrome.

BACKGROUND: We report the development and implementation of a program designed to assign patients preoperatively to either transplant or Norwood procedure based on a score derived from known risk factors and to enhance postoperative care of infants undergoing the Norwood procedure. METHODS: A weighted score for each of six variables comprised the scoring system: ventricular function, tricuspid regurgitation, ascending aortic diameter, atrial septal defect blood flow characteristics, blood type, and age. The scoring system was used to prospectively assign mortality risk and lead to recommendation of either Norwood procedure or transplantation. RESULTS: Survival following the Norwood procedure significantly improved after the management program was implemented (88% versus 40% at 48 hours, 57% versus 10% at 30 days, and 50% versus 10% at 1 year, p < 0.0001 at each time point). The survival of the group that received a score of 7 or less (high risk) who underwent the Norwood procedure was 78% at 48 hours, 44% at 30 days, and 33% at 1 year; survival rates among patients considered lower risk (greater than 7) were 100% at 48 hours and 80% at 30 days and 1 year. Transplant outcomes remained unchanged. CONCLUSIONS: We report improved survival following the Norwood procedure after the implementation of an institutional management approach aimed at improving the outcome of infants with hypoplastic left heart syndrome and may help neutralize historical biases toward Norwood procedure or transplantation.

Cardiac troponin I as a predictor of respiratory failure in children hospitalized with respiratory syncytial virus (RSV) infections: a pilot study.

This pilot study was performed to assess the use of cardiac troponin I to predict respiratory failure in children admitted to the hospital with respiratory syncytial virus (RSV) infections. We enrolled a prospective convenience sample of children under 5 years of age who were admitted to our university-based, tertiary care children's hospital from December 1, 2000, to February 1, 2002, with RSV infections. A cardiac troponin I was drawn at admission. We assessed the test characteristics for positive cardiac troponin I (defined as >0.3 ng/mL, the manufacturer's upper limit of normal) in correctly identifying children who had respiratory failure as evidenced by the need for endotracheal intubation. Twenty-five children from 9 days to 38 months of age were included. Ten children had a positive cardiac troponin I and 3 of these children had respiratory failure. A positive cardiac troponin I demonstrated a sensitivity of 100%, specificity 68%, positive predictive value of 30%, negative predictive value of 100%, and accuracy of 72%. The area under the receiver operating characteristic curve was 0.939 (95% confidence interval, 0.820-1.0), suggesting a high degree of discriminatory power in selecting children with respiratory failure. A sample size calculation revealed that a follow-up study of 359 patients is needed before the clinical use of cardiac troponin I for this purpose.

Myocardial injury in children following resuscitation after cardiac arrest.

BACKGROUND: Myocardial dysfunction occurs immediately after successful cardiac resuscitation. Our purpose was to determine whether measurement of cardiac troponin I in children with acute out-of-hospital cardiac arrest predicts the severity of myocardial injury. METHODS AND RESULTS: This prospective, observational study was performed in the Pediatric Intensive Care Unit (PICU) on 24 patients following arrest, ranging in age from 8 months to 17 years. Troponin measurements were obtained on admission, and at 12, 24, and 48 h. Transthoracic echocardiograms were performed within 24 h after admission. Survival to hospital discharge was 29% (7/24). The mean age was 5.9+/-4.6 years for survivors and 4.2+/-5.3 years for non-survivors. The median (range) duration of cardiac arrest times for survivors was 6 min (3 to 63 min) versus 34 min (4 to 70 min) for nonsurvivors (P=0.02). Survivors received 1.3+/-2.2 doses of epinephrine (adrenaline) compared with 2.9+/-1.6 doses for non-survivors (P=0.02). Only one patient had ventricular fibrillation and defibrillation was unsuccessful. The ejection fraction for survivors averaged 73.2+/-11.2%, but for nonsurvivors only 55.4+/-19.8% (P=0.04). Ejection fraction correlated inversely with troponin at 12 h (r=-0.54, P=0.01) and at 24 h (r=-0.59, P=0.02). Circumferential fiber shortening for survivors was 37.5+/-7.8 and 25.5+/-10.7% for nonsurvivors (P=0.02). It also correlated inversely with troponin (r=-0.46, P=0.03 for survivors and r=-0.65, P=0.01, for nonsurvivors). CONCLUSION: After cardiac arrest and resuscitation in pediatric patients, the severity of myocardial dysfunction was reflected in troponin I levels.

End tidal CO2 is a quantitative measure of cardiac arrest.

PURPOSE OF THE STUDY: Predictors of severity of cardiac arrest or efficacy of cardiopulmonary resuscitation are few. Respiratory end tidal CO2 (ETCO) is a marker of pulmonary blood flow and, possibly, cardiac arrest. The purpose of this study was to evaluate ETCO as a quantitative marker of cardiac arrest in a human model of ventricular fibrillation (VF). METHODS: Thirty-one cardiac arrest/VF episodes (mean BP < 40 mmHg) in 8 men and 3 women mean age = 42 +/- 24 years, mean left ventricular ejection fraction = 39%) undergoing defibrillator (ICD) implant for ventricular tachycardia or previous cardiac arrest were evaluated with continuous ETCO monitoring during defibrillation threshold testing. All patients but one were intubated. RESULTS: Significant differences (P < 0.001) were noted between ETCO values prior (mean 37.2 +/- 6.8 mmHg) versus during VF (mean 27.1 +/- 5.9 mmHg), and during VF versus return of spontaneous circulation (mean 36.6 +/- 6.6 mmHg). ETCO decreased by 23% +/- 8% from pre-VF to during VF. It increased by 37% +/- 16% during VF to return of spontaneous circulation. These changes were significantly different (P < 0.001). CONCLUSION: Significant changes in ETCO were measured during VF arrest. ETCO can predict acute cardiac arrest in a quantitative manner.