Impact of Induced Therapeutic Hypothermia by Intravenous Infusion of Ice-Cold Fluids After Hospital Arrival in Comatose Survivors of Out-of-Hospital Cardiac Arrest With Initial Shockable Rhythm.

BACKGROUND: The effect of in-hospital rapid cooling by intravenous ice-cold fluids for comatose survivors of out-of-hospital cardiac arrest (OHCA) is unclear.Methods and Results:From the J-PULSE-HYPO study registry, data for 248 comatose survivors with return of spontaneous circulation (ROSC) who were treated with therapeutic hypothermia (34℃ for 12-72 h) after witnessed shockable OHCA were extracted. Patients were divided into 2 groups by the median collapse-to-ROSC interval (18 min), and then into 2 groups by cooling method (rapid cooling by intravenous ice-cold fluids vs. standard cooling). The primary endpoint was favorable neurological outcome (Cerebral Performance Category of 1 or 2) at 30 days after OHCA. In the whole cohort, the shorter collapse-to-ROSC interval group had significantly higher favorable neurological outcome than the longer collapse-to-ROSC interval group (78.2% vs. 46.8%, P<0.001). In the shorter collapse-to-ROSC interval group, no significant difference was observed in favorable neurological outcome between the 2 cooling groups (rapid cooling group: 79.4% vs. standard cooling group: 77.0%, P=0.75). In the longer collapse-to-ROSC interval group, however, favorable neurological outcome was significant higher in the rapid cooling group than in the standard cooling group (60.7% vs. 33.3%, P<0.01) and the adjusted odds ratio after rapid cooling was 3.069 (95% confidence interval 1.423-6.616, P=0.004). CONCLUSIONS: In-hospital rapid cooling by intravenous ice-cold fluids improved neurologically intact survival in comatose survivors whose collapse-to-ROSC interval was delayed over 18 min after shockable OHCA.

Association between rewarming duration and neurological outcome in out-of-hospital cardiac arrest patients receiving therapeutic hypothermia.

AIM: The European Resuscitation Council guidelines recommend a slow rate of rewarming of 0.25 °C/h-0.5 °C/h for out-of-hospital cardiac arrest (OHCA) patients receiving therapeutic hypothermia (TH). Conversely, a very slow rewarming of 1 °C/day is generally applied in Japan. The rewarming duration ranged from less than 24 h up to more than 50 h. No randomized control trials have examined the optimal rewarming speed for TH in OHCA patients. Therefore, we examined the association between the rewarming duration and neurological outcomes in OHCA patients who received TH. METHODS: This study was a secondary analysis of the Japanese Population-based Utstein-style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia (J-PULSE-HYPO) study registry, a multicenter prospective cohort study. Patients suffering from OHCA who received TH (target temperature, 34 °C) after the return of spontaneous circulation from 2005 to 2011 in 14 hospitals throughout Japan were enrolled. The rewarming duration was defined as the time from the beginning of rewarming at a target temperature of 34 °C until reaching 36 °C. The primary outcome was an unfavorable neurological outcome at hospital discharge, i.e., a cerebral performance category of 3-5. RESULTS: The J-PULSE-HYPO study enrolled 452 OHCA patients. Of these, 328 were analyzed; 79.9% survived to hospital discharge, of which 56.4% had a favorable neurological outcome. Multivariable logistic regression analysis revealed that the rewarming duration was independently associated with unfavorable neurological outcomes [odds ratio (per 5 h), 0.89; 95% confidence interval, 0.79-0.99; p =  0.032]. CONCLUSION: A longer rewarming duration was significantly associated with and was an independent predictor of favorable neurological outcomes in OHCA patients who received TH.

Paget-Schroetter syndrome accompanied by pulmonary thromboembolism: A case report.

A 17-year-old male, who was involved in a baseball club, presented to our emergency department with the complaint of gradual onset of swelling of his right arm. Contrast-enhanced computed tomography showed obstruction of the proximal portion of the right subclavian vein and pulmonary thromboembolism. Venography confirmed an occluded right subclavian vein. The patient was diagnosed with right subclavian vein thrombosis, which is referred to as Paget-Schroetter syndrome (PSS). An ultrasonography for the affected subclavian vein was helpful not only for making an accurate diagnosis of PSS, but also for verifying dynamic venous flow changes depending on the forearm position. .

The Impact of Heart Rate Response During 48-Hour Rewarming Phase of Therapeutic Hypothermia on Neurologic Outcomes in Out-of-Hospital Cardiac Arrest Patients.

OBJECTIVES: Bradycardia during therapeutic hypothermia has been reported to be a predictor of favorable neurologic outcomes in out-of-hospital cardiac arrests. However, bradycardia occurrence rate may be influenced by the target body temperature. During therapeutic hypothermia, as part of the normal physiologic response, heart rate decreases in the cooling phase and increases during the rewarming phase. We hypothesized that increased heart rate during the rewarming phase is another predictor of favorable neurologic outcomes. To address this hypothesis, the study aimed to examine the association between heart rate response during the rewarming phase and neurologic outcomes in patients having return of spontaneous circulation after out-of-hospital cardiac arrest. DESIGN: A secondary analysis of the Japanese Population-based Utstein style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia registry, which was a multicenter prospective cohort study. SETTING: Fourteen hospitals throughout Japan. PATIENTS: Patients suffering from out-of-hospital cardiac arrest who received therapeutic hypothermia after the return of spontaneous circulation from 2005 to 2011. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: This study enrolled 452 out-of-hospital cardiac arrest patients, of which 354 were analyzed, and 80.2% survived to hospital discharge, of which 57.3% had a good neurologic outcome. Heart rate response was calculated using heart rate data recorded during therapeutic hypothermia in the abovementioned registry. Heart rate response in the rewarming phase (heart rate response-rewarming) was calculated as follows: (heart rate [post rewarming]-heart rate [pre rewarming])/heart rate (pre rewarming) × 100. The primary outcome was an unfavorable neurologic outcome at hospital discharge, that is, a Cerebral Performance Category of 3-5. Multivariable logistic regression analysis was performed to determine the association between heart rate response-rewarming and unfavorable neurologic outcomes. Multivariable logistic regression analysis showed that heart rate response-rewarming was independently associated with unfavorable outcomes (odds ratio [per 10% change], 0.86; 95% CI, 0.78-0.96; p = 0.004). CONCLUSIONS: Increased heart rate in the approximately 48-hour rewarming phase during therapeutic hypothermia was significantly associated with and was an independent predictor of favorable neurologic outcomes during out-of-hospital cardiac arrest.

Accelerated Atherogenicity in Tangier Disease.

We report a case of Tangier disease with Leriche syndrome and bleeding tendency. In this male patient, nasal hemorrhage had been observed frequently throughout childhood. At 46 years old, he experienced effort angina, and coronary angiography demonstrated 75% stenosis in the right coronary artery. Orange-colored tonsils, mild hepatosplenomegaly and very low levels of serum high-density lipoprotein cholesterol (HDL-C) were observed, and the patient was diagnosed with Tangier disease. At 52 years old, effort angina recurred. Coronary angiography revealed 75% stenosis of the left main trunk, left anterior descending, and right coronary arteries. Stenosis of the brachiocephalic and right common iliac arteries was also recorded. Stents were implanted, and coronary artery bypass surgery was performed. At 53 years old, 15 months after surgery, the patient reported intermittent claudication, coldness of feet, and impotence. Aortic angiography showed progression of the stenosis at the bifurcation of the common iliac artery. The patient was diagnosed with Leriche syndrome, and aorta-left external iliac artery graft bypass surgery was performed. After surgery, oozing from subcutaneous tissue and leaking from the anastomotic region were observed. Additional analysis revealed two single-nucleotide polymorphisms (V825I and N935T) in the ATP-binding cassette transporter A1 (ABCA1) gene, and accumulation of small dense low-density lipoprotein together with low levels of HDL-C. In Tangier disease, HDL-C is markedly decreased because of ABCA1 deficiency. However, this is the first reported case to exhibit extensive atherosclerosis and bleeding tendency. This patient had atypical extensive and multiple atherosclerotic lesions, accompanied by Leriche syndrome and uncontrollable bleeding.

Effect of Admission Glasgow Coma Scale Motor Score on Neurological Outcome in Out-of-Hospital Cardiac Arrest Patients Receiving Therapeutic Hypothermia.

BACKGROUND: Because the initial (on admission) Glasgow Coma Scale (GCS) examination has not been fully evaluated in comatose survivors of cardiac arrest (CA) who receive therapeutic hypothermia (TH), the aim of the present study was to determine any association between the admission GCS motor score and neurologic outcomes in patients with out-of-hospital CA who receive TH. METHODS AND RESULTS: In the J-PULSE-HYPO study registry, patients with bystander-witnessed CA were eligible for inclusion. Patients were divided into 3 groups based on GCS motor score (1, 2-3, and 4-5) to assess various effects on neurologic outcome. Univariate and multivariate analyses were performed to identify independent predictors of good neurologic outcome at 90 days. Of 452 patients, 302 were enrolled. There was a significant difference among the 3 patient groups with regard to neurologic outcome at 90 days in the univariate analysis. Multiple logistic regression analyses showed that the GCS motor score on admission, age >65 years, bystander cardiopulmonary resuscitation, the time from collapse to return of spontaneous circulation, and pupil size <4 mm were independent predictors of a good neurologic outcome at 90 days in cases of CA (GCS motor score, 4-5: odds ratio, 8.18; 95% confidence interval: 1.90-60.28; P<0.01). CONCLUSIONS: GCS motor score is an independent predictor of good neurologic outcome at 90 days in patients sustaining out-of-hospital CA who receive TH.

Effectiveness of lower target temperature therapeutic hypothermia in post-cardiac arrest syndrome patients with a resuscitation interval of ≤30 min.

BACKGROUND: Therapeutic hypothermia (TH) is a standard strategy to reduce brain damage in post-cardiac arrest syndrome (PCAS) patients. However, it is unknown whether the target temperature should be adjusted for PCAS patients in different states. METHODS: Participants in the J-PULSE-Hypo study database were divided into lower (32.0-33.5 °C; Group L) or moderate (34.0-35.0 °C; Group M) temperature groups. Primary outcome was a favourable neurological outcome (proportion of patients with a Glasgow-Pittsburgh Cerebral Performance Category [CPC] of 1-2 on day 30). We compared between the two groups and in subgroups of patients divided by age and resuscitation interval (interval from collapse to return of spontaneous circulation) by propensity score (PS) analysis. RESULTS: Overall, 467 participants were analysed. The proportions of patients with favourable neurological outcomes were as follows (Group L vs. Group M) (OR; Odds ratio): all patients, 64 % (n = 42) vs. 55 % ((n = 424) (PS; OR 1.381 (0.596-3.197)), P = 0.452) and resuscitation interval ≤ 30 min, 88 % (n = 24) vs. 64 % ((n = 281) (PS; OR 7.438 (1.769-31.272)), P = 0.007). CONCLUSIONS: PCAS patients with a resuscitation interval of <30 min may be candidates for TH with a target temperature of <34 °C. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) Clinical Trials Registry UMIN000001935; available at: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000002348&language=J.

Relation of estimated glomerular filtration rate to the presence of coronary plaque and obstructive coronary artery disease in a zero or low coronary artery calcium score.

OBJECTIVES: Although renal dysfunction is associated with the presence of atherosclerosis, little is known about the relationship between reduced estimated glomerular filtration rate (eGFR) and the presence of atherosclerosis detected by coronary computed tomographic angiography (CCTA). This study evaluated the relation of eGFR to the presence of coronary plaque and obstructive coronary artery disease (CAD) in patients with a zero or low coronary artery calcium score (CACS). METHODS: Coronary artery calcium scoring and CCTA were performed with CT scanners. Serum creatinine was measured before CCTA, and GFR was estimated. A total of 720 patients with a CACS ≤ 10 were enrolled. RESULTS: Coronary plaque was detected in 118 patients. Of the 118 patients, 36 had a diagnosis of obstructive CAD. The multiple-adjusted odds ratios of presenting with coronary plaque and obstructive CAD were 1.82 (95% CI 1.06-3.12, p = 0.030) and 1.79 (95% CI 0.71-4.49, p = 0.217) for the lowest tertile of eGFR compared with the highest tertile, respectively. CONCLUSIONS: Lower eGFR levels were associated with the presence of coronary plaque in patients with a zero or low CACS. However, the association between eGFR and the presence of obstructive CAD was not statistically significant.

Neurological benefit of therapeutic hypothermia following return of spontaneous circulation for out-of-hospital non-shockable cardiac arrest.

BACKGROUND: Although therapeutic hypothermia is an effective therapy for comatose adults experiencing out-of-hospital shockable cardiac arrest, there is insufficient evidence that is also applicable for those with out-of-hospital non-shockable cardiac arrest. METHODS AND RESULTS: Of 452 comatose adults treated with therapeutic hypothermia after return of spontaneous circulation (ROSC) subsequent to an out-of-hospital cardiac arrest of cardiac etiology, 372 who had a bystander-witnessed cardiac arrest, target core temperature of 32-34°C and cooling duration of 12-72 h were eligible for this study (75 cases of non-shockable cardiac arrest, 297 cases of shockable cardiac arrest). The median collapse-to-ROSC interval was significantly longer in the non-shockable group than in the shockable group (30 min vs. 22 min, P=0.008), resulting in a significantly lower frequency of 30-day favorable neurological outcome in the non-shockable group compared with the shockable group (32% vs. 66%, P<0.001). However, an analysis of data in quartiles assigned to varying lengths of collapse-to-ROSC interval revealed a similar frequency of 30-day favorable neurological outcome among both groups when the collapse-to-ROSC interval was ≤16 min (90% non-shockable group vs. 92% shockable group; odds ratio 0.80, 95% confidence interval 0.09-7.24, P=0.84). CONCLUSIONS: Post-ROSC cooling is an effective treatment for patients with non-shockable cardiac arrest when the time interval from collapse to ROSC is short.

Relation of cardiovascular risk factors and angina status to obstructive coronary artery disease according to categorical coronary artery calcium score.

Coronary artery calcium (CAC) is associated with the presence of coronary artery disease (CAD) and cardiovascular risk factors. However, the relation between cardiovascular risk factors and CAD has not yet been fully elucidated in patients with a zero or low coronary artery calcium score (CACS). The purpose of this study was to evaluate the relation of cardiovascular risk factors and angina status to obstructive CAD according to categorical CACS. A total of 753 patients were enrolled in this study. CAC scoring and coronary computed tomographic angiography (CCTA) were performed with dual-source 64-slice CT scanners. The number of patients with a CACS ≤10 and ≤100 were 358 and 528, respectively. Patients with a higher CACS were older and more frequently male, and had a greater frequency of hypertension, diabetes, and hypercholesterolemia. The prevalence of obstructive CAD increased with the CACS. Among patients with a CACS ≤100, age, male gender, diabetes, hypercholesterolemia, and typical angina pectoris were related to obstructive CAD. The presence of hypercholesterolemia was relatively strongly associated with obstructive CAD (OR 6.67, 95% CI 2.91-15.3, p < 0.001) on multivariate analysis. Among patients with a CACS ≤10, men, hypercholesterolemia, and typical angina pectoris were significantly more frequent in patients with than in those without obstructive CAD (p < 0.01). Our data suggest that neither the absence nor low of coronary calcium burden may reliably exclude obstructive CAD in typical symptomatic male patients with hypercholesterolemia. This result may be useful to interpret the relation of CACS to obstructive CAD.

Impact of therapeutic hypothermia in the treatment of patients with out-of-hospital cardiac arrest from the J-PULSE-HYPO study registry.

BACKGROUND: Mild hypothermia is an effective therapy for patients with return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest. However, evidence of the effectiveness of therapeutic hypothermia (TH) remains unclear. METHODS AND RESULTS: A multicenter registry in Japan (J-PULSE-HYPO study registry) was conducted to investigate the effectiveness of TH for post-resuscitation neurological dysfunction developing after out-of-hospital cardiac arrest from 14 institutions, between January 2005 and December 2009. The committee entrusted each hospital with the timing of cooling, cooling methods, target temperature, duration, and rewarming. There were 452 patients (375 men) enrolled into the registry. The mean age was 58.6 ± 13.5 years. Initial electrocardiogram rhythm at the time of occurrence of the cardiac arrest showed 68.9% had ventricular fibrillation or pulseless ventricular tachycardia, 13.7% had pulseless electrical activity, and 9.1% had asystole. The median interval from the occurrence of cardiac arrest to ROSC was 26 min. The target core temperature during TH was 33.9 ± 0.4°C and the mean duration of cooling was 31.5 ± 13.9 h. Intra-aortic balloon pumping was used in 40.1% and percutaneous cardiopulmonary support in 22.6% of patients. At 30 days after cardiac arrest, the proportion of survival was 80.1% and the proportion of patients with favorable neurological functions, with a cerebral performance category score of 1 or 2, was 55.3%. CONCLUSIONS: The J-PULSE-HYPO study registry showed a clinical aspect of TH.

An autopsy case of left ventricular apical ballooning probably caused by pheochromocytoma with persistent ST-segment elevation.

We describe the autopsy case of an 86-year-old man who experienced left ventricular (LV) apical ballooning with pheochromocytoma. During the follow-up period, his electrocardiogram (ECG) showed persistent ST-segment elevation in leads V3 to V6, and an echocardiogram revealed persistent LV dysfunction in the apical region. He died 64 days after admission. Pathological findings suggested catecholamine-induced cardiomyopathy and pheochromocytoma. This is the report of a rare autopsy case of LV apical ballooning.

Glycosylated hemoglobin is a predictor of major adverse cardiac events after drug-eluting stent implantation in patients with diabetes mellitus.

OBJECTIVES: Diabetes mellitus is associated with the risk of restenosis and mortality after coronary stenting, but the relation between glycosylated hemoglobin (hemoglobin A1c) and prognosis has not yet been fully elucidated in patients with diabetes mellitus. The purpose of this study was to evaluate whether hemoglobin A1c is associated with a risk of major adverse cardiac events (MACE) after successful drug-eluting stent (DES) implantation in patients with diabetes mellitus. METHODS: In a retrospective study with a prospective follow-up, 206 patients with diabetes mellitus undergoing successful DES implantation were enrolled in this study. Hemoglobin A1c levels were measured within 1 month before coronary stenting. RESULTS: During a period of 4,811 person-months, we confirmed 40 cases of MACE. Higher hemoglobin A1c levels increased the incidence of MACE. Based on multivariate analysis, hemoglobin A1c was a significant predictor of MACE. The multiple-adjusted hazard ratio for a 1% increase in hemoglobin A1c levels was 1.40 (95% CI: 1.13-1.74, p = 0.002) for MACE after adjustment for age, gender, ejection fraction, chronic renal failure on hemodialysis, and statins. CONCLUSIONS: Hemoglobin A1c is associated with an increased risk of MACE after successful DES implantation in patients with diabetes mellitus.

Effect of culprit-lesion remodeling versus plaque rupture on three-year outcome in patients with acute coronary syndrome.

To investigate intravascular ultrasound predictors of long-term clinical outcome in patients with acute coronary syndrome, 94 patients with a first acute coronary syndrome with both preintervention intravascular ultrasound imaging and long-term follow-up were enrolled in this study. Remodeling index was defined as external elastic membrane cross-sectional area at the target lesion divided by that at the proximal reference. Arterial remodeling was defined as either positive (PR: remodeling index >1.05) or intermediate/negative remodeling (remodeling index < or =1.05). Clinical events were death, myocardial infarction, and target-lesion revascularization. Patients were followed up for a mean of 3 years. PR was observed in 50 (53%), and intermediate/negative remodeling, in 44 (47%). During the 3-year follow-up, there were 20 target-lesion revascularization events and 5 deaths (2 cardiac and 3 noncardiac), but no myocardial infarctions. Patients with PR showed significantly lower major adverse cardiac event (MACE; death, myocardial infarction, and target-lesion revascularization)-free survival (log-rank p = 0.03). However, patients with plaque rupture showed a nonsignificant trend toward lower MACE-free survival (p = 0.13), but there were no significant differences in MACE-free survival between those with single versus multiple plaque ruptures. Using multivariate logistic regression analysis, only culprit lesion PR was an independent predictor of MACEs (p = 0.04). In conclusion, culprit-lesion remodeling rather than the presence or absence of culprit-lesion plaque rupture was a strong predictor of long-term (3-year) clinical outcome in patients with acute coronary syndrome.

[Perioperative multivessel coronary vasospasm as a cause of cardiogenic shock immediately after off-pump coronary artery bypass grafting surgery: a case report].

Perioperative coronary vasospasm has been recognized as a possible cause of myocardial infarction or low output syndrome after open heart operations. A 57-year-old male suffered cardiogenic shock immediately after off-pump coronary artery bypass grafting surgery. Emergent angiography performed under intraaortic balloon pumping and percutaneous cardiopulmonary support revealed severe multivessel coronary vasospasm which was effectively treated with a high dose intracoronary administration of isosorbide dinitrate. Emergent angiography for patients with cardiogenic shock after open heart operation is feasible and effective for the diagnosis and treatment of perioperative coronary vasospasm.

[Young woman with repeated late stent thrombosis: a case report].

A 34-year-old woman with hypertension, obesity, and history of smoking presented with unstable angina and severe stenosis of the proximal left anterior descending artery. Percutaneous coronary intervention was performed with stent implantation resulting in adequate expansion. She was treated with aspirin and ticlopidine for 1 month, then only aspirin for 1 month. One year after stenting, she presented with acute myocardial infarction and total occlusion at the stent. Balloon angioplasty was performed. She took ticlopidine and aspirin for 9 months. Two months later, she presented with acute myocardial infarction with reocclusion at the stent. Blood examination showed no manifest collagen disease or thrombophilia. This case of repeated late stent thrombosis occurred in a young woman not treated by brachytherapy.