Coronary Vasospasm in a Patient With Argininosuccinic Aciduria.

A 39-year-old male was referred for treatment of hypertension. He had been treated for argininosuccinic aciduria since 8 months of age. Therapeutic drugs, including l-arginine, sodium phenylbutyrate, and antiepileptic drugs, had been prescribed. A detailed medical history revealed that he complained of chest discomfort under psychologic stress. A 12-lead electrocardiogram showed abnormal q waves in lead III and aVF. Transthoracic echocardiography showed hypokinesia of the left ventricular posterior wall. The patient was diagnosed with myocardial infarction because of coronary vasospastic angina by intracoronary acetylcholine provocation test. Argininosuccinic aciduria is a genetic disorder of the urea cycle caused by a deficiency of argininosuccinate lyase. Reduction of the enzymatic activity leads to a decrease in nitric oxide production, even if arginine is supplemented. Our case report supports the significance of endothelial function in the pathogenesis of coronary vasospasm.

Development of anti-thrombotic vaccine against human S100A9 in rhesus monkey.

In post-stroke patients, a decreased adherence to antiplatelet drugs is a major challenge in the prevention of recurrent stroke. Previously, we reported an antiplatelet vaccine against S100A9 in mice, but the use of Freund's adjuvant and the difference in amino acid sequences in epitopes between mice and humans were problematic for clinical use. Here, we redesigned the S100A9 vaccine for the common sequence in both humans and monkeys and examined its effects in cynomolgus monkeys with Alum adjuvant. First, we assessed several candidate epitopes and selected 102 to 112 amino acids as the suitable epitope, which could produce antibodies. When this peptide vaccine was intradermally injected into 4 cynomolgus monkeys with Alum, the antibody against human S100A9 was successfully produced. Anti-thrombotic effects were shown in two monkeys in a mixture of vaccinated serum and fresh whole blood from another cynomolgus monkey. Additionally, the anti-thrombotic effects were partially inhibited by the epitope peptide, indicating the feasibility of neutralizing anti-thrombotic effects of produced antibodies. Prolongation of bleeding time was not observed in vaccinated monkeys. Although further studies on increasing the effect of vaccine and safety are necessary, this vaccine will be a promising approach to improve adherence to antiplatelet drugs in clinical settings.

Associations between corrected serum calcium and phosphorus levels and outcome in dialysis patients in the Kumamoto Prefecture.

INTRODUCTION: Mortality in hemodialysis patients is relatively high; thus, its risk stratification is very important. There are insufficient data describing the current status of the management of serum phosphate and calcium levels. METHODS: We conducted a multicenter, prospective, registry study throughout the Kumamoto Prefecture in Japan. We enrolled 1993 patients at 58 facilities with complete explanatory data, including serum phosphate, corrected calcium, and intact parathyroid hormone levels. We categorized subjects into nine categories according to low, normal, and high levels of phosphate and corrected calcium levels. The endpoint was all-cause mortality. RESULTS: Of the total number of subjects, 56.1% of the patients were in the normal phosphate and calcium category, and 72% and 77.1% had controlled serum phosphate and calcium levels, respectively. Two hundred twenty-six deaths occurred during the follow-up period. In the nine categories, the highest mortality rates were observed in the highest corrected calcium and lowest phosphate categories. Stepwise backward multivariate regression analyses identified the serum corrected calcium level (OR, 1.38; 95% CI, 1.06-1.79; P = 0.016) and the serum phosphate level (OR, 1.26; 95% CI, 1.08-1.48; P = 0.003) as significant and independent predictors of all-cause mortality. CONCLUSIONS: The corrected serum calcium and phosphate levels are associated with mortality in our dialysis population, with poorest survival in patients with high corrected serum calcium and low serum phosphorus.

Cognitive function in post-cardiac intensive care: patient characteristics and impact of multidisciplinary cardiac rehabilitation.

New/worsening cognitive and physical impairments following critical care pose significant problems. Multidisciplinary cardiac rehabilitation (CR) can improve physical function after cardiac intensive care (CIC). This observational study aimed to evaluate cognitive function in patients participating in multidisciplinary CR and to identify correlates of impaired cognitive function after CIC. We analyzed 111 consecutive patients admitted to our comprehensive care ward at least 7 days after CIC and assessed factors associated with cognitive function using the Functional Independence Measure (FIM). Patients were stratified into two groups based on the median FIM-Cognitive scores: impaired (n = 56) and preserved cognition (n = 55) groups. Multiple logistic regression analysis identified age [odds ratio (OR) 1.06; 95% confidence interval (CI) 1.00-1.13; p = 0.042], Mini-Nutrition Assessment-Short Form (MNA-SF; OR 0.73; 95% CI 0.56-0.95; p = 0.017), and FIM-Physical scores (OR: 0.94; 95% CI 0.90-0.99; p = 0.012) as significant and independent factors associated with impaired cognition. The median length of hospital stay was 28 (interquartile range: 18, 43) days. The FIM-Cognitive and FIM-Physical scores significantly increased from admission to discharge [32.0 (27.0, 35.0) vs. 34.0 (29.0, 35.0) points; p < 0.001; 67.0 (53.0, 75.0) vs. 85.0 (73.5, 89.0) points; p < 0.001, respectively]. On subgroup analysis within the impaired cognition group, increased FIM-Cognitive scores positively and significantly correlated with increased FIM-Physical scores (ρ = 0.450; p = 0.001). Multiple linear regression analysis identified atrial fibrillation (AF; ß = - 0.29; p = 0.016), ln(glycated hemoglobin; HbA1c) (ß = 0.29; p = 0.018), and ln(high-sensitivity C-reactive protein; hs-CRP) (ß = - 0.26; p = 0.034) as significant and independent factors correlated with increased FIM-Cognitive scores. In conclusion, advanced age, low MNA-SF score, and FIM-Physical score were independent factors associated with impaired cognition in post-CIC patients. Multidisciplinary CR improved both physical and cognitive functions, and AF, HbA1c, and hs-CRP were independent factors correlated with increased FIM-Cognitive score.

Analysis of the preferable site and stability of rotational reentry: its role for the maintenance of atrial fibrillation.

It remains unclear whether AF is maintained by rotor. We evaluated the significance of rotor during atrial fibrillation (AF). Prevalence, location, and stability of rotational reentry (RR) in the left atrium were clarified by endocardial non-contact mapping in 66 AF patients. RR was classified into three categories: RR continued at stable site (Stable-RR), RR observed intermittently at the same site (Intermittent-RR), and RR observed at different locations (Different-RR). Catheter ablation was performed in a stepwise fashion (linear roof lesion and complex fractionated atrial electrogram ablation following pulmonary vein isolation) until AF termination and elucidated the consequence of radiofrequency lesion delivered within RR site on AF termination and recurrence. One hundred and nineteen RRs were observed. There were 54 patients with RR (RR Group) and 22 patients without RR (Non-RR Group). Prevalence of Different-RR (n = 81) was significantly higher than Stable-RR (n = 16, p < 0.001) and Intermittent-RR (n = 22, p < 0.001). The intervals involved in RR occupied only 22.4% of total activation time. There was no significant difference in the prevalence of AF termination nor AF/atrial tachycardia recurrence between RR and non-RR Groups (46 vs. 9 patients, p = 0.317, and 13 vs. 1 patients, p = 0.271) and between patients in whom radiofrequency lesion was involved in RR and those was not (24 vs. 22 patients, p = 0.210, and 6 vs. 7 patients, p = 0.506). In conclusion, most RRs were observed transiently and often shifted its locations. Radiofrequency lesion delivered within RR site did not correlate with AF termination nor recurrence, suggesting that RR is not a driving source during AF.

Slow Potential at the Entrance of the Slow Conduction Zone in the Reentry Circuit of a Verapamil-Sensitive Atrial Tachycardia Originating From the Atrioventricular Annulus.

BACKGROUND: Slow conduction zone in a verapamil-sensitive reentrant atrial tachycardia originating from atrioventricular annulus is composed of calcium channel-dependent tissue. We examined whether there was a slow potential (SP) at the entrance of the slow conduction zone. METHODS AND RESULTS: We first identified the pacing site from where manifest entrainment and orthodromic capture of the earliest atrial activation site were demonstrated in 40 atrioventricular annulus patients with atrioventricular annulus. Radiofrequency energy was then delivered 2 cm proximal to the earliest atrial activation site in the direction of entrainment pacing site and gradually advanced toward the earliest atrial activation site until atrial tachycardia termination to localize the entrance of the slow conduction zone. Electrogram characteristics were analyzed at successful and unsuccessful ablation sites. During sinus rhythm, SP was observed at all 40 successful sites, but was observed at only 12 unsuccessful sites (P<0.0001). During sinus rhythm, there was no significant difference in electrogram amplitude nor width of atrial electrogram between successful and unsuccessful sites (0.407±0.281 versus 0.487±0.447 mV [P=0.1989] and 37.0±9.2 versus 38.9±8.0 ms [P=0.1773]); however, SP amplitude and width at successful sites were significantly greater than those at unsuccessful sites (0.110±0.049 versus 0.025±0.046 mV [P<0.0001] and 38.8±13.4 versus 8.1±13.2 ms [P<0.0001]). During atrial tachycardia, SP amplitude was significantly attenuated (0.088±0.042 versus 0.110±0.049 mV, P<0.001) and SP width was significantly prolonged (47.8±14.1 versus 38.8±13.4 ms, P<0.0001) at successful sites. CONCLUSIONS: SP was observed during sinus rhythm at the entrance of the slow conduction zone; however, SP amplitude was attenuated and SP width was prolonged during atrial tachycardia, suggesting that SP reflects the characteristics of calcium channel-dependent tissue involved in atrioventricular annulus reentry circuit.